ascorbic-acid and Edema

The recently published European Venous Forum (EVF) Guidelines 2018 update on the management of chronic venous disorders of the lower limbs has focused on several new aspects: a new place for early symptoms, new data on microcirculation alterations, and a re-evaluation of veno-active drugs (VADs), based on new criteria. The symposium "Chronic Venous Disease (CVD): From Symptoms to Microcirculation", held at the annual meeting of the EVF on 28 June 2018 in Athens, Greece, highlighted this perspective by answering three questions: What do symptoms mean and how do they influence our choice of investigations? Is there a link between symptoms and microcirculation alterations? How to choose the right VAD for the right patient based on the updated EVF guidelines? The answers given led the speakers to three conclusions: early symptoms reveal the initial stage of CVD and patients with C0S disease should be properly diagnosed, investigated, and treated; damage to the microcirculation is likely to be the first evidence of the onset of venous disease; Ruscus+HMC+VitC has proven efficacy in randomized controlled trials, and has been given a strong recommendation (Grade 1A) by the 2018 EVF guidelines for treatment of pain, heaviness, feeling of swelling, paresthesia, and edema, and should be considered as one of the preferred treatments to relieve these symptoms in CVD patients.

Topics: Ascorbic Acid; Chronic Disease; Congresses as Topic; Edema; Greece; Humans; Microcirculation; Phytotherapy; Plant Extracts; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Ruscus; Vascular Diseases; Veins

Venoactive drugs (VADs) are considered an important component of the medical (conservative) treatment of chronic venous disorders (CVDs). However, the efficacy of certain VADs on one or more individual leg symptoms may have not been extensively studied to justify a high level or grade of recommendation in guidelines on CVD. The aim of the present systematic review and meta-analysis was to study the effectiveness of VADs containing Ruscus across the spectrum of defined venous symptoms.. On November 14 2016, a literature search of the databases MEDLINE and Scopus was performed, supplemented by hand searching, to identify randomized double-blind placebo-controlled trials on Ruscus extracts in patients with CVD.. The main outcome measures were the effects of Ruscus on individual symptoms and leg edema, which were expressed as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). Trial quality of evidence was graded using the GRADE system. We identified 10 trials, mostly with low risk of bias, on 719 patients. On qualitative analysis, Ruscus significantly improved seven defined leg symptoms, including pain, heaviness, fatigue, feeling of swelling, cramps, itching and paresthesia compared to placebo. On quantitative analysis, Ruscus compared with placebo, assessed as a categorical variable, reduced leg pain (RR=0.35, P=0.01, number needed to treat [NNT] 5, with no heterogeneity), heaviness (RR=0.26, P<0.00001, NNT=2.4, with a small amount of heterogeneity), feeling of swelling (RR=0.53, P<0.0001, NNT=4, with considerable heterogeneity, minimized after sensitivity analysis), paresthesia (RR=0.27, P<0.0001, NNT=1.8), global symptoms (RR=0.54, P<0.00001, NNT=4.3) and the total number of venous symptoms (RR 0.41, P=0.002). Similarly, Ruscus compared to placebo, assessed as a continuous variable reduced pain (SMD=-0.80, 95% CI: -1.21 to -0.39), heaviness (SMD=-1.23, 95% CI: -1.60 to -0.86), fatigue (SMD -1.16, 95% CI: -1.71 to -0.61), feeling of swelling (SMD=-2.27, 95% CI: -3.83 to -0.70), and paresthesia (SMD=-0.86, 95% CI: -1.51 to -0.21). Regarding objective assessments of leg edema, the use of Ruscus compared with placebo reduced ankle circumference (SMD=-0.74, 95% CI: -1.01 to -0.47) and leg or foot volume (SMD=-0.61, 95% CI: -0.91 to -0.31). The existing evidence, where sufficient, was mostly of high quality.. Based on high quality evidence, Ruscus extracts are highly effective in reducing symptoms and edema of patients with CVD.

Topics: Ascorbic Acid; Edema; Humans; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Ruscus; Vascular Diseases; Veins

Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation.

Topics: Administration, Inhalation; Animals; Antioxidants; Ascorbic Acid; Brain; Carbon Tetrachloride; Carrageenan; Edema; Free Radicals; Gases; Inflammation; Mice; Radon; Reactive Oxygen Species; Reperfusion Injury; Superoxide Dismutase; Vitamin E; X-Rays

Topics: Animals; Anura; Ascorbic Acid; Blood Vessels; Bradykinin; Calcium; Capillary Fragility; Capillary Permeability; Drug Synergism; Edema; Epinephrine; Flavonoids; Guinea Pigs; Histamine; Hot Temperature; Iodine Radioisotopes; Rabbits; Radiation Effects; Radioisotopes; Serotonin; Sodium Isotopes

To evaluate changes on cutaneous microangiopathy in chronic venous disorder (CVD) after use of Cirkan [venotonic drug containing Ruscus aculeatus (plant extract), hesperidine methylchalcone (flavonoid) and vitamin C], elastic compression stockings (ECS) or no treatment for four weeks.. Fifty-five female patients (85 legs), 25 to 57 years, with at least one limb classified as C2,s or C2,3,s (CEAP classification), were allocated consecutively, according to entrance order, in these three groups. Ten healthy women age-matched were also investigated. Using orthogonal polarization spectral technique (noninvasive method), measurements of functional capillary density (FCD, number of capillaries with flowing red blood cells/mm(2)), capillary morphology (CM, % of abnormal capillaries/mm(2)) and diameters (mum) of dermal papilla (DDP), capillary bulk (DCB) and capillary limb (CD) were obtained on the medial perimalleolar region and later analyzed using CapImage software.. CVD patients showed significant changes on CD and CM compared to healthy subjects in agreement with our previous findings (J Vasc Surg 43:1037-1044, 2006). On Cirkan-treated patients, after 4 weeks, CD decreased on both limbs and CM improved on the left one, suggesting an amelioration of the chronic venous hypertension. No significant changes could be detected on other patient groups. These results confirm the existence of microcirculatory dysfunction in early stages of CVD, probably due to post-capillary hypertension, and further support the venotonic action of Cirkan.

Topics: Adult; Ascorbic Acid; Capillaries; Chymotrypsin; Combined Modality Therapy; Drug Combinations; Edema; Female; Hesperidin; Humans; Leg; Microcirculation; Middle Aged; Phytosterols; Plant Extracts; Stockings, Compression; Treatment Outcome; Trypsin; Venous Insufficiency; Venous Thrombosis

The inflammation which follows cryotherapy is a significant disadvantage of this therapeutic modality. To date, the only treatment shown to reduce this inflammation is application of topical corticoids. We have therefore conducted a pilot study to investigate whether pretreatment with the free radical scavengers, vitamins C and E might alleviate the signs and symptoms of inflammation following liquid nitrogen cryotherapy of common warts. We undertook a randomized, double-blind, placebo-controlled, parallel group study. We recruited 40 adult patients, of whom 38 returned for evaluation. Treatments comprised vitamin C (2000 mg) and vitamin E (800 IU) daily or matching placebo for 7 days prior to cryotherapy to a hand wart. Oedema volume, erythema level, pain intensity and the presence or absence of blistering were assessed 24 h after cryotherapy. There were no significant differences between the two treatment groups in any of the parameters assessed. This study yielded no suggestion of benefit from the use of pretreatment with free radical scavengers in conjunction with liquid nitrogen cryotherapy.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Blister; Cryotherapy; Dermatitis; Double-Blind Method; Edema; Erythema; Female; Humans; Male; Middle Aged; Pain, Postoperative; Pilot Projects; Vitamin E; Warts

High-dose ascorbic acid (vitamin C) therapy (66 mg/kg per hour) attenuates postburn lipid peroxidation, resuscitation fluid volume requirements, and edema generation in severely burned patients.. A prospective, randomized study at a university trauma and critical care center in Japan.. Thirty-seven patients with burns over more than 30% of their total body surface area (TBSA) hospitalized within 2 hours after injury were randomly divided into ascorbic acid and control groups. Fluid resuscitation was performed using Ringer lactate solution to maintain stable hemodynamic measurements and adequate urine output (0.5-1.0 ml/kg per hour). In the ascorbic acid group (n = 19; mean burn size, 63% +/- 26% TBSA; mean burn index, 57 +/- 26; inhalation injury, 15/ 19), ascorbic acid was infused during the initial 24-hour study period. In the control group (n = 18; mean burn size, 53% +/- 17% TBSA; mean burn index, 47 +/- 13; inhalation injury, 12/18), no ascorbic acid was infused. We compared hemodynamic and respiratory measurements, lipid peroxidation, and fluid balance for 96 hours after injury. Two-way analysis of variance and Tukey test were used to analyze the data.. Heart rate, mean arterial pressure, central venous pressure, arterial pH, base deficit, and urine outputs were equivalent in both groups. The 24-hour total fluid infusion volumes in the control and ascorbic acid groups were 5.5 +/- 3.1 and 3.0 +/- 1.7 mL/kg per percentage of burn area, respectively (P<.01). In the first 24 hours, the ascorbic acid group gained 9.2% +/- 8.2% of pretreatment weight; controls, 17.8% +/- 6.9%. Burned tissue water content was 6.1 +/- 1.8 vs 2.6 +/- 1.7 mL/g of dry weight in the control and ascorbic acid groups, respectively (P<.01). Fluid retention in the second 24 hours was also significantly reduced in the ascorbic acid group. In the control group, the ratio of PaO2 to fraction of inspired oxygen at 18, 24, 36, 48, and 72 hours after injury was less than that of the ascorbic acid group (P<.01). The length of mechanical ventilation in the control and ascorbic acid groups was 21.3 +/- 15.6 and 12.1 +/- 8.8 days, respectively (P<.05). Serum malondialdehyde levels were lower in the ascorbic acid group at 18, 24, and 36 hours after injury (P<.05).. Adjuvant administration of high-dose ascorbic acid during the first 24 hours after thermal injury significantly reduces resuscitation fluid volume requirements, body weight gain, and wound edema. A reduction in the severity of respiratory dysfunction was also apparent in these patients.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Burns; Dose-Response Relationship, Drug; Edema; Female; Fluid Therapy; Humans; Infusions, Intravenous; Isotonic Solutions; Lipid Peroxidation; Male; Middle Aged; Prospective Studies; Resuscitation; Ringer's Lactate; Water-Electrolyte Balance

Topics: Adolescent; Adult; Ascorbic Acid; Aspirin; Edema; Humans; Mouth; Phenylbutazone; Postoperative Complications

Topics: Ascorbic Acid; Capillary Fragility; Capillary Permeability; Capillary Resistance; Clinical Trials as Topic; Drug Synergism; Edema; Flavonoids; Humans; Phlebitis; Placebos; Varicose Veins; Vascular Resistance

No reflow in capillaries (no reflow) is the lack of tissue perfusion that occurs once central hemodynamics are restored. This prevents oxygen transfer and debt repayment to vital tissues after shock resuscitation. Since metabolic swelling of cells and tissues can cause no reflow, it is a target for study in shock. We hypothesize no reflow secondary to metabolic cell swelling causes the problem not addressed by current strategies that increase central hemodynamics alone.. Anesthetized swine were bled until plasma lactate reached 7.5 mM to 9 mM. Intravenous low volume resuscitation solutions were administered (6.8 mL/kg over 5 minutes) consisting of; (1) lactated Ringer (LR), (2) autologous whole blood, (3) high-dose vitamin C (200 mg/kg), or (4) 10% PEG-20k, a polymer-based cell impermeant that corrects metabolic cell swelling. Outcomes were macrohemodynamics (MAP), plasma lactate, capillary flow in the gut and tongue mucosa using orthogonal polarization spectral imaging (OPSI), and survival to 4 hours.. All PEG-20k resuscitated swine survived 240 minutes with MAP above 60 mm Hg compared with 50% and 0% of the whole blood and LR groups, respectively. The vitamin C group died at just over 2 hours with MAPs below 40 and high lactate. The LR swine only survived 30 minutes and died with low MAP and high lactate. Capillary flow positively correlated ( p < 0.05) with survival and MAP. Sublingual OPSI correlated with intestinal OPSI and OPSI was validated with a histological technique.. Targeting micro-hemodynamics in resuscitation may be more important than macrohemodynamics. Fixing both is optimal. Sublingual OPSI is clinically achievable to assess micro-hemodynamic status. Targeting tissue cell swelling that occurs during ATP depletion in shock using optimized osmotically active cell impermeants in crystalloid low volume resuscitation solutions improves perfusion in shocked tissues, which leverages a primary mechanism of injury.

Topics: Animals; Ascorbic Acid; Crystalloid Solutions; Edema; Hemodynamics; Isotonic Solutions; Lactates; Microcirculation; Perfusion; Resuscitation; Ringer's Lactate; Shock, Hemorrhagic; Swine

Novel N-substituted Indole derivatives with various hetero-cyclic moieties were synthesized via an ethyl linker in order to obtain highly potent anti-inflammatory and antioxidant agents. The structure of the obtained chemical compounds was determined using IR,

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Ascorbic Acid; Carrageenan; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Edema; Formaldehyde; Humans; Indoles; Inflammation; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship

Scurvy is a rare disease in developed countries and few cases have been reported in adults within the last years. We aimed to report and discuss a case of a 35-year-old male with a medical history of irritable bowel syndrome (IBS) who initially presented to the emergency department with complaints of right leg pain, swelling, and weakness. Physical exam revealed low degree fever associated with right knee and ankle ecchymosis and edema, in addition to a well healing laceration on the anterior tibia with hyperpigmentation. Laboratory results showed elevated inflammatory markers. Due to the high suspicion of bone or soft tissue infection, antibiotic treatment was started without improvement. Upon reassessment and closer inspection of the skin, the patient was noted to have follicular hyperkeratosis and perifollicular hemorrhage; that in combination with a restrictive diet due to IBS, raised the suspicion of scurvy. Vitamin C levels were.

Topics: Adult; Ascorbic Acid; Diagnostic Errors; Edema; Humans; Irritable Bowel Syndrome; Male; Scurvy; Skin

Topics: Ascorbic Acid; Bone Marrow; Edema; Humans; Scurvy

Children are at high risk of injuries and wounds. The application of medical grade honey is a promising approach to improving the healing of wounds of various origin and severity. However, the use of medical grade honey in young paediatric patients remains limited. The aim of this study is to show the safety, efficacy and usefulness of medical grade honey in abdominal wounds, of different causes, in paediatric patients.. This was a prospective, observational case series evaluating five young infants with abdominal wounds at the General Hospital in Thessaloniki. All wounds were treated in the same manner with daily medical grade honey applied to the wound area and closely monitored.. All treated wounds rapidly presented granulation tissue formation and underwent re-epithelialisation. Peripheral oedema and inflammation decreased upon initial application. Necrotic tissue was effectively debrided when present. Slough was removed and no signs of infection were detected, irrespective of initial wound presentations. Scar formation was minimal and the full range of motion was preserved in all cases.. Based on this case study, medical grade honey is safe and effective in treating different abdominal wounds, including infected or dehisced wounds as well as burns. The easy application and broad applicability make medical grade honey recommendable as a first-line treatment in paediatric patients.

Topics: Abdominal Injuries; Apitherapy; Appendectomy; Appendicitis; Ascorbic Acid; Bacteroides Infections; Burns; Burns, Chemical; Child; Child, Preschool; Dermatologic Agents; Drug Resistance, Multiple, Bacterial; Edema; Female; Gastrostomy; Greece; Honey; Humans; Infant; Infant, Newborn; Inflammation; Klebsiella Infections; Lanolin; Male; Neuroblastoma; Oils, Volatile; Ointments; Prospective Studies; Re-Epithelialization; Retroperitoneal Neoplasms; Surgical Wound Dehiscence; Surgical Wound Infection; Vitamin E; Vitamins; Zinc Oxide

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has adverse effects on the development and function of the heart in zebrafish eleutheroembryos (embryos and larvae). We previously reported that TCDD reduced blood flow in the mesencephalic vein of zebrafish eleutheroembryos long before inducing pericardial edema. In the present study, we compared early edema (pre-cardiac edema), reduction of deduced cardiac output and reduction of blood flow in the dorsal aorta and cardinal vein caused by TCDD. In the same group of eleutheroembryos, TCDD (1.0 ppb) caused pre-cardiac edema and circulation failure at the cardinal vein in the central trunk region with the similar time courses from 42 to 54 h post fertilization (hpf), while the same concentration of TCDD did not significantly affect aortic circulation in the central trunk region or cardiac output. The dependence of pre-cardiac edema on TCDD concentration (0-2.0 ppb) at 55 hpf correlated well with the dependence of blood flow through the cardinal vein on TCDD concentration. Several treatments that markedly inhibited TCDD-induced pre-cardiac edema such as knockdown of aryl hydrocarbon receptor nuclear translocator-1 (ARNT1) and treatment with ascorbic acid, an antioxidant, did not significantly prevent the reduction of cardiac output at 55 hpf caused by 2.0 ppb TCDD. TCDD caused hemorrhage and extravasation of Evans blue that was intravascularly injected with bovine serum albumin, suggesting an increase in endothelium permeability to serum protein induced by TCDD. The results suggest that the blood vessels are primary targets of TCDD in edema formation in larval zebrafish.

Topics: Animals; Antioxidants; Aryl Hydrocarbon Receptor Nuclear Translocator; Ascorbic Acid; Edema; Edema, Cardiac; Embryo, Nonmammalian; Larva; Polychlorinated Dibenzodioxins; Receptors, Aryl Hydrocarbon; Water Pollutants, Chemical; Zebrafish; Zebrafish Proteins

Cytotoxic edema is the initial and most important step in the sequence that almost inevitably leads to brain damage. Exploring the neurochemical disturbances in this process is of great significance in providing a measurable biological parameter for signaling specific pathological conditions. Here, we present an electrochemical system that pinpoints a critical neurochemical involved in cytotoxic edema. Specially, we report a molecularly tailored brain-implantable ascorbate sensor (CFE

Topics: Animals; Ascorbic Acid; Brain; Edema; Electrochemical Techniques; In Vitro Techniques; N-Methylaspartate; Rats

The cyclic enaminone moiety has been identified as a new scaffold for selective inhibition of cyclooxygenase-2 with anti-inflammatory and analgesic activities. The designed cyclic enaminones have been synthesized conveniently through the development of a new catalyst-free methodology and evaluated for cyclooxygenase (COX-1 and COX-2) inhibitory activities. Three compounds 7d, 8, and 9 predominantly inhibited COX-2 with selectivity index of 74.09, 19.45 and 108.68, respectively, and were assessed for in vivo anti-inflammatory activity in carrageenan induced rat paw edema assay. The anti-inflammatory activity of 7d was comparable to that of celecoxib at a dose of 12.5 mg/kg. However, the compounds 8 and 9 were more/equally effective as anti-inflammatory agent compared to celecoxib at the doses of 12.5 mg/kg and 25 mg/kg and also exhibited anti-inflammatory activity comparable to that of diclofenac. The therapeutic potential of the most active compound 9 was further assessed by performing in vivo thermal and mechanical hyperalgesia tests using various models that revealed its analgesic activity. The in vivo non-ulcerogenicity of 9 revealed the gastrointestinal safety as compared to the non-selective COX inhibitor indomethacin. The in vitro antioxidant activity and in vivo experiments on heart rate and blood pressure provided the cardiovascular safety profile of 9. The molecular docking studies rationalize the COX-2 selectivity of the newly found anti-inflammatory compounds 7d, 8, and 9.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Carrageenan; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Edema; Heterocyclic Compounds; Humans; Male; Molecular Docking Simulation; Molecular Structure; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship

One of the most important aspects of postsurgical care is finding an efficient way for the management of pain. Third molar extractions/surgical impaction is one of the most frequent surgical procedures in dental hospitals, and it is most often associated with postoperative complications like severe pain, oedema and reduced mouth opening. This study was aimed to evaluate the efficacy of 2 g intravenous (IV) vitamin C compared to 100 mg aceclofenac on postsurgical pain, swelling and trismus after the surgical removal of third molars. A total of 101 patients were recruited for the study, and theywere divided into two treatment groups; group A (n = 51) received 2 g IV vitamin C and group B (n = 50) received 100 mg aceclofenac. Pain intensity, facial swelling and mouth opening were assessed till day 3 post-surgically. Statistical analysis of pain intensity revealed that IV vitamin C performed slightly better but not significantly different (p>0.05) from aceclofenac group at the end of day 3. No significant difference for facial swelling and mouth opening between the two treatment protocols was seen (p>0.05). Our results concluded that both treatment groups were overall similar in analgesic efficacy, postoperative oedema and reduction in mouth opening. It was also determined that the method devised administering 2 g IV vitamin C intravenously was well suited to the treatment of postoperative pain, swelling and trismus following the surgical extraction of impacted third molars.

Topics: Administration, Intravenous; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Diclofenac; Double-Blind Method; Edema; Humans; Molar, Third; Pain, Postoperative; Tooth Extraction; Tooth, Impacted

A series of 5-methanesulphonamido benzimidazole derivatives were designed by combining the structural features of clinically useful anti-inflammatory drugs (nimesulide and rofecoxib) and antiulcer drugs (lansoprazole, omeprazole, etc.) based on physicochemical and 3D similarity studies. The compounds were evaluated for their anti-inflammatory activity in carrageenan induced rat paw edema model taking rofecoxib and indomethacin as standard drugs. In vitro antioxidant activity of the compounds was assessed by potassium ferricyanide reducing power (PFRAP) assay. The compounds 9, 10 and 11 showed anti-inflammatory activity comparable to the standard group and were also non-ulcerogenic at the test doses. Compounds 6-11 exhibited good antioxidant effect in the concentration range (1.0-50.0µmol/ml. Preliminary theoretical ADME profiling of the compounds based on computation of selected physicochemical properties showed an excellent compliance with Lipinski's rule.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Antioxidants; Benzimidazoles; Carrageenan; Dose-Response Relationship, Drug; Edema; Molecular Structure; Rats; Stomach Ulcer; Structure-Activity Relationship; Sulfonamides

Syzygium jambos has been used as a traditional medicine for the treatment of inflammatory diseases in Bangladesh. The study investigates the high performance liquid chromatography (HPLC) profiling of phenolic compounds, and evaluates the antioxidant and anti-inflammatory activities of ethanol extract of S. jambos available in Bangladesh.. The extract was subjected to HPLC for the identification and quantification of the major bioactive polyphenols present in S. jambos. Antioxidant activity was determined using 2, 2'-azino bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging, reducing power assay, total antioxidant capacity, total phenolic and flavonoid content. Furthermore, the anti-inflammatory effect of the extract in rats for two different test models: carrageenan and histamine-induced paw edema was inspected.. High levels of catechin hydrate and rutin hydrate (99.00 and 79.20 mg/100 g extract, respectively) and moderate amounts of ellagic acid and quercetin (59.40 and 69.30 mg/100 g extract, respectively) were quantified in HPLC. Catechin hydrate from this plant extract was determined for the first time through HPLC. For ABTS scavenging assay, the median inhibition concentration (IC50) value of S. jambos was 57.80 µg/ml, which was significant to that of ascorbic acid (12.01 µg/ml). The maximum absorbance for reducing power assay was found to be 0.4934. The total antioxidant capacity, phenolic and flavonoid contents were calculated to be 628.50 mg/g of ascorbic acid, 230.82 mg/g of gallic acid and 11.84 mg/g of quercetin equivalent, respectively. At a dose of 400 mg/kg, a significant acute anti-inflammatory activity (P < 0.01) was observed in rats for both the test models with a reduction in the paw volume of 58.04 and 53.95 %, in comparison to those of indomethacin (62.94 and 65.79 %), respectively.. The results suggest that the phenolic and flavonoid compounds are responsible for acute anti-inflammatory and antioxidant activities of S. jambos.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Bangladesh; Benzothiazoles; Chromatography, High Pressure Liquid; Edema; Ethanol; Flavonoids; Free Radical Scavengers; Histamine; Indomethacin; Male; Oxidation-Reduction; Plant Extracts; Polyphenols; Rats, Wistar; Sulfonic Acids; Syzygium

Some N-[(N-benzoyldehydrophenylalalnyl)glycinyl/cysteinyl]-N,N'-dicyclohexylurea analogs (3a-3o) were synthesized by conjugating different substituted N-benzoyldehydrophenylalanyl glycines/cysteines (differing substitutions on benzylidene ring) and dicyclohexyl carbodiimide (DCC) using base as a catalyst. The synthesized compounds were characterized and evaluated for biological activities. Compounds 3a and 3h with unsubstituted dehydrophenylalanyl glycinyl/cysteinyl moiety exhibited moderate anti-inflammatory and analgesic activities. Compound 3j bearing 4-hydroxy substitution on benzylidene ring of dehydrophenylalanyl cysteinyl moiety displayed potent antimicrobial and antioxidant activities. The results obtained from docking studies on compound 3j with penicillin binding protein and protease supported the results.

Topics: Acetic Acid; Analgesics; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Bacteria; Carrageenan; Dose-Response Relationship, Drug; Edema; Fungi; Mice; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Pain; Rats; Structure-Activity Relationship; Urea

In the present study, an efficient synthesis of some Mannich base of 5-methyl-2-[(2-oxo-2H-chromen-3-yl)carbonyl]-2,4-dihydro-3H-pyrazol-3-one (4a-j) have been described by using conventional and non-conventional (microwave) techniques. Microwave assisted reactions showed that require shorter reaction time and good yield. The newly synthesized compounds were screened for their anti-inflammatory, analgesic activity, antioxidant, and antibacterial effects were compared with standard drug. Among the compounds studied, compound (4f) showing nearly equipotent anti-inflammatory and analgesic activity than the standard drug (indomethacin), along with minimum ulcerogenic index. Compounds (4b and 4i) showing 1.06 times more active than ciprofloxacin against tested Gram-negative bacteria.

Topics: Acetic Acid; Analgesics; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bacteria; Carrageenan; Dose-Response Relationship, Drug; Edema; Mice; Microbial Sensitivity Tests; Microwaves; Molecular Structure; Pain; Pyrazolones; Rats; Structure-Activity Relationship

Leea macrophylla (Leeaceae) is a wild edible plant with ethomedicinal importance as anti-inflammatory agent. However, no systematic studies on its anti-inflammatory activity and mechanisms have been reported. Present study was undertaken to evaluate anti-inflammatory activity of methanol extract of L. macrophylla leaves. Phytochemical investigation revealed presence of sterols, triterpenoids and ascorbic acid in extract. Methanol extract inhibited lipopolysaccharide stimulated production of inflammatory mediators viz. prostaglandin E2, tumor necrotic factor-α, interleukin-6 and interleukin-1β in vitro in mouse peritoneal macrophages. Additionally, the in vivo anti-inflammatory activity of this extract was evaluated by using carrageenan induced paw edema and cotton pellet granuloma assays in experimental rats. Oral administration of extract (100 and 200 mg/kg) exhibited dose dependant inhibition of carrageenan induced inflammation (p<0.05) and the reduction of the granuloma tissue formation (p<0.05-0.01). The extract (100 and 200 mg/kg, orally) exhibited significant central and peripheral analgesic activity in hot-plate test (p<0.01) and acetic acid induced writhing test (p<0.05-0.01) respectively in experimental mice. Treatment with extract (100 and 200 mg/kg, orally) significantly reduced the yeast provoked elevated body temperature (p<0.05-0.01) in experimental rats. These results confirmed the traditional anti-inflammatory indication of L. macrophylla leaves.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Cells, Cultured; Dietary Supplements; Edema; Ethnopharmacology; Granuloma; India; Macrophages, Peritoneal; Medicine, Traditional; Mice; Mice, Inbred Strains; Phytosterols; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Toxicity Tests, Acute; Toxicity Tests, Subacute; Triterpenes; Vitaceae

A novel series of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines (5a-o) has been synthesized and the structures of newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their in vitro and in vivo anti-inflammatory activity, and also for their antioxidant activity. Compounds 5b, 5c, 5d and 5n were found to be selective COX-2 inhibitors. Compound 5c was found to potent inhibitor of the carrageenin induced paw edema in rats. Most of the compounds exhibited good DPPH and superoxide radical scavenging activity, while compounds 5c, 5d, 5i and 5k exhibited good hydroxyl radical scavenging activity. Molecular docking result, along with the biological assay data, suggested that compound 5c was a potential anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biphenyl Compounds; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Edema; Free Radical Scavengers; Models, Molecular; Molecular Structure; Picrates; Pyrazoles; Rats; Stereoisomerism; Structure-Activity Relationship; Superoxides

Euadenia eminens Hook f. (Capparaceae) has traditional uses in the management of conjunctivitis, iritis, ophthalmia, tuberculosis, otalgia and rectal prolapse. The fruit pulp is also eaten as an aphrodisiac. In this paper, we report on the anti-inflammatory, antioxidant and antibacterial effects of its roots. A 70 % ethanol extract was tested for anti-inflammatory effect using the carrageenan-induced oedema in chicks. Free radical scavenging, total antioxidant and total phenol content were assessed spectrophotometrically. The extract was tested for antibacterial activity using the agar well diffusion method and micro dilution assays. The 70% ethanol extract gave a maximal inhibition of oedema by 74.18 % at 30 mg/kg. The total antioxidant capacity expressed in terms of ascorbic acid was 0.609 mg/g dry weight. The total phenol in terms of tannic acid was 7.25 mg/g dry weight. The extract also demonstrated free radical scavenging activity yielding IC50 value of 1.175 mg/mL. The root extract however, showed selective antibacterial activity, inhibiting growth of two microorganisms; Bacillus subtilis and Bacillus thurigiensis. The MICs were 500 and 1000 µg/mL respectively. These results may account in part for the ethnopharmacological use of the plant.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Bacillus; Capparaceae; Carrageenan; Chickens; Edema; Free Radical Scavengers; Inhibitory Concentration 50; Male; Microbial Sensitivity Tests; Phenols; Plant Bark; Plant Extracts; Plant Roots; Tannins

Thermal injuries with more than 20% of burned body surface area (BSA) lead to systemic shock with generalised oedema in addition to local tissue destruction. This condition, known as burn injury, is caused by immunmodulative mediators whose individual significance is not known in detail. We present an experimental model where plasma of burned animals (burn plasma) is transmitted to healthy animals, to trigger burn iniury without performing direct burn trauma.. The systemic oedema is measured by extravasation of fluorescent albumin in mesenterial venules of Wistar rats. In addition, leukocyte-endothelial interactions ("leukocyte rolling and sticking") is examined.. The systemic capillary leak is induced by both direct thermal trauma as well as by infusion of burn plasma. This is evident even after plasma dilution (1% in Ringer's lactate) of the burn plasma. In addition, topical therapy for burned animals (donors) with cerium nitrate led to a significant reduction of plasma extravasation in receiver animals. In addition, systemic antioxidant therapy with high-dose vitamin C of receiver animals, led to a significant reduction of the capillary leak. Leukocyte-endothelial interactions are not significantly affected in either case.. In summary, for the first time a reliable model of burn injury has been established, which eliminates mediator-independent effects. In addition, our studies show that antioxidant therapy with high doses of vitamin C and topical treatment with cerium nitrate both reduce the systemic capillary leak in receiver animals. Their positive influence could therefore soon be integrated in clinical treatment algorithms.

Topics: Animals; Anti-Infective Agents, Local; Antioxidants; Ascorbic Acid; Blood Flow Velocity; Burns; Capillary Leak Syndrome; Cell Adhesion; Cerium; Cytokines; Disease Models, Animal; Edema; Extravasation of Diagnostic and Therapeutic Materials; Leukocytes; Male; Mesenteric Veins; Microcirculation; Plasma; Rats; Rats, Wistar; Shock; Venules

The aim of this study was to investigate a new flavone triglycoside, together with eleven phenolic metabolites from 80% aqueous methanol extract of S. splendens leaves (AME) and assessment of its hypoglycemic and antiinflammatory activities along with in vitro antioxidant effect.. The phenolic composition of S. splendens leaves was analyzed using UV, 1D and 2D NMR and negative ESI-MS spectroscopy. Hypoglycemic activity of AME was assessed by measuring blood glucose in streptozotocin induced-diabetic rats. Antiinflammatory activity was evaluated using the carrageenan-induced paw oedema test. Antioxidant activity was evaluated in vitro using DPPH test..  Twelve phenolic metabolites including three phenolic acids, namely caffeic acid 1, rosmarinic acid 2 and methyl rosmarinate 3; four flavone glycosides viz the new compound luteolin 7-O-(4″,6″-di-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside 4, apigenin 7-O-β-D-rutinoside 5, cosmosiin 6 and cinaroside 7, together with four flavones aglycone, luteolin 8, apigenin 9, pedalitin 10 and crisiliol 11 in addition to one coumarin, 6,7-dihydroxycoumarin 12 were isolated from the leaves of S. splendens Sellow ex Roem & Schult. The AME of S. splendens was non toxic to mice up to 5 g/kg b.wt. it exhibited a significant hypoglycemic activity at 250 and 500 mg/kg as compared with control pre-drug (zero time) for each group as well as the diabetic control. Moreover, AME exhibited a significant antiinflammatory activity only at 1000 mg/kg in comparison to indomethacin. Finally, AME exhibited a marked significant scavenging activity against DPPH; the maximum reactive reaction rate after 5 min was 62.9, 82.5, 83.7, 84.3 and 85.1% for the concentrations 10, 20, 30, 40 and 50 mg/ml, respectively in comparison to L-ascorbic acid (86.8%)..  This is the first study reporting the identification of a new flavone triglycoside, along with eleven known phenolic metabolites from AME of S. splendens. It showed significant hypoglycemic and antiinflammatory effects in dose dependant manner. Moreover it showed an in vitro antioxidant activity.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Hypoglycemic Agents; Indomethacin; Inflammation; Magnetic Resonance Spectroscopy; Male; Mice; Plant Extracts; Plant Leaves; Polyphenols; Rats; Rats, Sprague-Dawley; Salvia; Spectrometry, Mass, Electrospray Ionization

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1-11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID₅₀ 77 μg/cm²) as well compounds 1-11 (ID₅₀ 0.31-0.60 μmol/cm²) exhibited topical antiedematous properties comparable to those of indomethacin (ID₅₀ 0.29 μmol/cm²) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NF-κB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E₂ synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate 5-Lipoxygenase; Austria; Benzofurans; Cyclooxygenase 1; Edema; Intramolecular Oxidoreductases; Krameriaceae; Lignans; Male; Mice; NF-kappa B; Plant Roots; Prostaglandin-E Synthases

Topics: Ascorbic Acid; Canada; Edema; Female; Humans; Lower Extremity; Magnetic Resonance Imaging; Middle Aged; Pain; Purpura; Scurvy; Vitamins

L-ascorbic acid upon condensation with palmitic acid in the presence of sulphuric acid results in L-ascorbic acid-6-palmitate (AP). The effect of L-ascorbic acid derivative, AP on the pharmacological activities of purified basic multi-toxic PLA2 enzyme, VRV-PL-VIIIa from Vipera russelli snake venom along with in vitro activities is described. AP inhibited VRV-PL-VIIIa enzyme activity in a concentration dependent manner with IC50 value of 48.85 μM and the inhibition is found to be independent of substrate and calcium concentration. Upon investigating the in vivo pharmacological activities, it has been found that AP inhibited VRV-PL-VIIIa induced mouse paw edematogenic activity in a dose dependant manner. Intramuscular co-injection of AP with VRV-PL-VIIIa (1:10 w:w) neutralized the VRV-PL-VIIIa induced myotoxocity. Sections of mouse thigh muscle showed normal intact musculature with normal levels of serum creatine kinase and lactate dehydrogenase. Histopathological studies showed that administration of VRV-PL-VIIIa (i.p) along with AP mixture inhibited VRV-PL-VIIIa induced lung haemorrhage in mouse indicated that enzyme activity is responsible for all these observed pathological and pharmacological activities. The biophysical interaction studies showed that AP interacted directly with the enzyme and decreased the relative intrinsic fluorescence intensity. CD spectral analysis showed an apparent shift in the far UV-CD spectra of VRV-PL-VIIIa with AP. Docking study also confirmed the interaction of AP with enzyme directly. These results demonstrate that AP neutralizes VRV-PL-VIIIa induced pharmacological activities by inhibiting the enzyme with direct interactions. This compound along with other inhibitors of snake venom hydrolytic enzymes might be of use to neutralize local toxicity of V. russelli venom where antivenoms have failed.

Topics: Animals; Antivenins; Ascorbic Acid; Circular Dichroism; Creatine Kinase; Daboia; Dose-Response Relationship, Drug; Edema; Group II Phospholipases A2; Hemorrhage; Inhibitory Concentration 50; L-Lactate Dehydrogenase; Lung; Mice; Models, Molecular; Muscles; Palmitates; Snake Bites; Spectrometry, Fluorescence; Viper Venoms

To explore the efficacy of n-hexane extract of Emilia sonchifolia (E. sonchifobia) against ethanol induced pancreatic dysfunction in the young Wistar albino rats.. The rats were divided into four groups. Control rats in group received distilled water orally, group received oral administration of 20% (w/v) ethanol dissolved in drinking water, group received oral administration of 20% (w/v) ethanol in distilled water+n-hexane extract of E. sonchifolia (250 mg/kg body weight), and group received oral administration of n-hexane extract of E. sonchifolia (250 mg/kg body weight) alone. Liver marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), pancreatic enzymatic antioxidants superoxide dismutase, lipid peroxidation, catalase, glutathione peroxidase, non-enzymatic antioxidants glutathione and vitamin C were measured and compared.. Administration of 20% ethanol for 16 weeks significantly increased the liver marker enzymes AST, ALT(P<0.05), reduced the pancreatic enzymatic antioxidants superoxide dismutase, lipid peroxidation, catalase, glutathione peroxidase, glutathione and vitamin C(P<0.05). Histopathological examination showed that the ethanol provoked the oxidative stress which was demonstrated as pancreatic necrosis and oedema. Simultaneous administration of n-hexane extract of E. sonchifolia (250 mg/kg body weight) protected the pancreas against the damage induced by ethanol which was confirmed by the histopathological studies and the normalization of biochemical parameters.. Thus n-hexane extract of E. sonchifolia shows a promise in therapeutic use in alcohol induced oxidative stress.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Catalase; Edema; Ethanol; Glutathione; Glutathione Peroxidase; Lipid Peroxidation; Liver; Male; Necrosis; Oxidative Stress; Pancreas; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Sonchus; Superoxide Dismutase

A series of symmetric and asymmetric spermine (SPM) conjugates with all-trans-retinoic acid (ATRA), acitretin (ACI), (E)-3-(trioxsalen-4'-yl)acrylic acid (TRAA) and L-DOPA, amides of ACI, l-DOPA and TRAA with 1-aminobutane, benzylamine, dopamine and 1,12-diaminobutane as well as hybrid conjugates of O,O'-dimethylcaffeic acid (DMCA) with TRAA or N-fumaroyl-indole-3-carboxanilide (FICA) and 2-(2-aminoethoxy)ethanol were synthesized and their antioxidant properties were studied. The reducing activity (RA)% of the compounds were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay and found to be in the range 0-92(20 min)%/96(60 min)% at 100μM, the most powerful being the conjugates L-DOPA-SPM-L-DOPA (8, RA=89%/96%) and L-DOPA-dopamine (13, RA=92%/92%). Conjugate DMCA-NH(CH₂CH₂O)₂-FICA (14) was the most powerful LOX inhibitor with IC₅₀ 33.5μM, followed by the conjugates ACI-NHCH₂Ph (10, IC₅₀ 40.5μM), ACI-SPM-TRAA (7, IC₅₀ 41.5μM), DMCA-NH(CH₂CH₂O)₂-TRAA (15, IC₅₀ 65μM), 13 (IC₅₀ 81.5μM) and ACI-dopamine (11, IC₅₀ 87μM). The most potent inhibitors of lipid peroxidation at 100μM were the conjugates 15 (98%) and ACI-SPM-ACI (4, 97%) whereas all other compounds showed activities comparable or lower than trolox. The most interesting compounds, namely ATRA-SPM-ATRA (3), 4, 10, 11 and 15, as well as unconjugated compounds such as ATRA and dopamine, were studied for their anti-inflammatory activity in vivo on rat paw oedema induced by Carrageenan and found to exhibit, for doses of 0.01 mmol/mL of conjugates per Kg of rat body weight, weaker anti-inflammatory activities (3.6-40%) than indomethacin (47%) with conjugate 3 being the most potent (40%) in this series of compounds. The cytocompatibility of selected compounds was evaluated by the viability of RAMEC cells in the presence of different concentrations (0.5-50μM) of the compounds. Conjugates 3 (IC₅₀ 2.6μM) and 4 (IC₅₀ 4.7μM) were more cytotoxic than the corresponding unconjugated retinoids ATRA (IC₅₀ 18.3μM) and ACI (IC₅₀ 14.6μM), whereas conjugate 15 (IC₅₀ 12.9μM) was less cytotoxic than either DCSP (IC₅₀ 11.3μM) or the tert-butyl ester of TRAA (IC₅₀ 2.9μM).

Topics: Acitretin; Animals; Anti-Inflammatory Agents; Antioxidants; Edema; Levodopa; Lipid Peroxidation; Rats; Spermine; Tretinoin

The halo 6-fatty acid esters of L-ascorbic acid 3a, 3b and 6-fatty acid esters of L-ascorbic acid 5a-g were achieved from L-ascorbic acid 1. Compounds 3a, 3b and 5a-g were evaluated for anti-oxidant, anti-lipid peroxidation, and secretory phospholipase A(2) (sPLA(2)) inhibition in vitro, and sPLA(2) induced mouse paw edema. All the derivatives retained their anti-oxidant property compared to ascorbic acid at 6 × 10(-4)M and are good inhibitors of lipid peroxidation at 1 mg ml(-1) as evaluated by 2, 2-Diphenyl-1-picrylhydrazyl radical and thio-barbituric acid methods, respectively. Compounds 5e and 5f significantly inhibited purified group I sPLA(2) from Naja naja and group II sPLA(2) from Vipera russelli, human synovial fluid and human pleural fluid with IC(50) value ranging from 64 ± 1.95 to 82 ± 1.3 and 48 ± 2.27 to 61 ± 2.23 μM, respectively. The compounds 5e and 5f also showed varying degree of potency in neutralizing indirect hemolytic activity of sPLA(2) at 50 μM concentration, and sPLA(2) induced mouse paw edema at the dose 3 mg/kg. Further docking studies also confirmed that compounds 5e and 5f have maximum interaction with increasing negative energy value. Single molecule possessing both anti-oxidant and anti-inflammatory activities is of great therapeutic significance in inflammatory disorders.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Drug Evaluation, Preclinical; Edema; Fatty Acids; Hemolysis; Humans; Hydrophobic and Hydrophilic Interactions; Lipid Peroxidation; Mice; Phospholipases A2, Secretory; Protein Binding; Snake Venoms; Structure-Activity Relationship

The 5,10-dihydro-2-thioxo-pyrimido[4,5-b]quinolines (2a-c) and its oxidized form 3 were prepared and used as key intermediates for the synthesis of thiazolo[3',2':1,2]pyrimido[4,5-b]-quinolines (5a-c), isoxazolo[5'',4'':4',5']thiazolo[3',2':1,2]pyrimido[4,5-b]quinolines (6a-c), 4-chloro-2-methylthio-pyrimido[4,5-b]quinoline, its amino derivatives (19-21) and 10,11,12,13-tetrahydro-5H-quino[2',3':4,5]pyrimido[6,1-b]quinazoline (22). The newly synthesized compounds were characterized by IR, NMR (1H, 13C) and mass spectral studies. Representative of the synthesized compounds was tested and evaluated for anti-oxidant, anti-inflammatory and analgesic activities. Compounds 2a-c showed the highest inhibitory anti-oxidant activity either using erythrocyte hemolysis or ABTS methods. Compounds 2a, 10b, 16, and 17a manifested the best protective effect against DNA damage induced by bleomycin. Compounds 2c, 5a, 20a, 2a, and 2b exhibited a potent anti-inflammatory activity using carrageenan-induced paw edema test in rats.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Brain; DNA Damage; Drug Design; Edema; Erythrocytes; Hemolysis; Kidney; Quinolines; Rats; Spectrum Analysis

Synthesis of 2-thioxopyrimido[4,5-b]quinoline 3a-c by microwave oven was used as a base to synthesis acyclic nucleosides analogue of types, 3-(penta-O-acetyl-glycosyl)-6-(4-chlorophenyl)-10-(4-chlorophenylmethylene)-7,8,9,10-tetrahydro[1,2,4]triazolo[4',3':1,2]-pyrimido[4,5-b]quinolin-4-ones (7a-c), 2-tetra-O-acetyl-glycosylhydrazon-N3-acetyl-5-(4-chlorophenyl)-9-(4-chlorophenylmethylene)-6,7,8,9-pentahydro-1H-pyrimido[4,5-b]-quinolin-4-ones (10a-c) and 3-(glycosyl)-6-(4-chlorophenyl)-10-(4-chlorophenylmethylene)-7,8,9,10-tetrahydro[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-b]quinolin-4-ones (8a-c), (12a-c). The title compounds were investigated for analgesic, anti-inflammatory, anti-oxidant and anti-microbial activities. Compounds 8a,b and 12a,b exhibited highly significant activity towards gram-negative and gram-positive bacteria, showed more potent anti-inflammatory and analgesic activities than the acetylated glycoside derivatives 7a,b and 10a,b and exhibited high anti-oxidant activity when compared to the ascorbic acid.

Topics: Analgesics; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antioxidants; Bacteria; Carrageenan; Drug Discovery; Edema; Female; Lipid Peroxidation; Male; Mice; Microwaves; Nucleosides; Quinolines; Rats

Topics: Adult; Arthralgia; Ascorbic Acid; Ascorbic Acid Deficiency; Edema; Epistaxis; Gastrointestinal Hemorrhage; Humans; Knee Joint; Male; Pigmentation Disorders; Scurvy

We have previously shown oxidative stress and oedema, caused by both xanthine oxidase-derived oxidants and infiltrating neutrophils, within skeletal muscle after contractile-induced claudication. The purpose of this study was to determine whether supplementation with antioxidant vitamins attenuates the oxidative stress, neutrophil infiltration and oedema associated with an acute bout of contractile-induced claudication. Rats received vehicle, vitamin C, vitamin E or vitamin C + E for 5 days prior to contractile-induced claudication. Force production was significantly reduced in the claudicant limbs of all groups compared with the control (sham) limb of control animals. Contractile-induced claudication caused a significant increase in protein oxidation, lipid peroxidation, neutrophil infiltration and oedema compared with sham muscles. Supplementation with vitamin C, E or C + E prevented the increases in each of these, and there were no differences between groups. These findings suggest that, in an animal model of exercise-induced claudication, neutrophil chemotaxis is caused by oxidizing species and that antioxidant supplementation can prevent oxidative damage, neutrophil infiltration and oedema following an acute bout of contractile-induced claudication.

Topics: Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Edema; Electric Stimulation; Intermittent Claudication; Ischemia; Lipid Peroxidation; Male; Muscle Contraction; Muscle, Skeletal; Neutrophil Infiltration; Neutrophils; Oxidative Stress; Peroxidase; Protein Carbonylation; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Vitamin E

Topics: Airway Obstruction; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Ascorbic Acid; Child, Preschool; Edema; Fentanyl; Gingivitis; Hemorrhage; Humans; Intubation, Intratracheal; Laryngeal Masks; Leg; Male; Methyl Ethers; Propofol; Scurvy; Sevoflurane; Vitamins

A series of new tetrasubstituted thiophenes (4a-4i, 5a-5i and 6a-6f) have been synthesized as novel anti-inflammatory agents and were evaluated for their anti-inflammatory activity in carrageenin-induced rat hind paw oedema model at the doses of 10, 20 and 40mg/kg body weight. Among ester series, the best compound 4c showed 71% protection at 10mg/kg, 72% at 20mg/kg, and 76% at 40mg/kg to inflamed paw; while in acid series 5a showed 79% protection at 10mg/kg, 80% at 20mg/kg, and 70% at 40mg/kg, and 5c showed 72% protection at 10mg/kg, 75% at 20mg/kg, and 69% at 40mg/kg, to inflamed paw. In case of oxime series 6a-6f, the anti-inflammatory activities of the candidates were found to be poor as compared to acid and ester series. It was found on the basis of SAR studies of target compounds, that the presence of OCH(3) at R(2) position and H, OCH(3) at R(1) are one of the requirements for eliciting comparable anti-inflammatory activity in both tetrasubstituted thiophenes' ester and acid series. Compounds 4a-4i, 5a-5i were investigated for their analgesic activity in acetic acid induced writhing response model at 10mg/kg dose. Among the ester series compound 4e showed maximum protection of 60%, while 4a, 4b, and 4i exhibited 55%, 45%, and 43% protection, respectively. The result showed that presence of H, Cl at R(1) and OCH(3), CH(3) at R(2) in tetrasubstituted thiophene ester series enhances their analgesic activity. The candidates of acid series 5a-5i showed poor analgesic activity as compared to the standard drug ibuprofen. Compounds 4a-4i, 5a-5i were evaluated for their in vitro antioxidant nitric oxide radical scavenging assay. Among the ester series 4a showed maximum in vitro nitric oxide radical scavenging activity having IC(50) value 30.08microg/ml while in acid series 5a has IC(50) value 25.20microg/ml. The results showed that the presence of R(1)=H, R(2)=OCH(3) and R(1)=R(2)=OCH(3) enhances nitric oxide radical scavenging property in tetrasubstituted thiophenes' acid series.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Rats; Structure-Activity Relationship; Thiophenes

Ascorbic acid (vitamin C) is necessary for the formation of collagen, reducing free radicals, and aiding in iron absorption. Scurvy, a disease of dietary ascorbic acid deficiency, is uncommon today. Indeed, implementation of dietary recommendations largely eradicated infantile scurvy in the US in the early 1900s. We present a case of an otherwise healthy 2-year-old Caucasian girl who presented with refusal to walk secondary to pain in her lower extremities, generalized irritability, sleep disturbance, and malaise. The girl's parents described feeding the patient an organic diet recommended by the Church of Scientology that included a boiled mixture of organic whole milk, barley, and corn syrup devoid of fruits and vegetables. Physical examination revealed pale, bloated skin with edematous, violaceous gums and loosening of a few of her teeth. Dermatologic findings included xerosis, multiple scattered ecchymoses of the extremities, and perifollicular hemorrhage. Laboratory and radiographic evaluation confirmed the diagnosis of scurvy. The patient showed dramatic improvement after only 3 days of treatment with oral ascorbic acid and significant dietary modification. In this case report, we revisit the old diagnosis of scurvy with a modern dietary twist secondary to religious practices. This case highlights the importance of taking a detailed dietary history when evaluating diseases involving the skin.

Topics: Administration, Oral; Ascorbic Acid; Child, Preschool; Diet; Edema; Female; Gingival Diseases; Humans; Religion; Scurvy; Tooth Mobility; Vitamins

Antioxidant potential of Aspergillus candidus MTCC 2202 broth filtrate extract was studied using different antioxidant models, whereas anti-inflammatory potential was studied using carrageenan-induced rat paw oedema model. The ethyl acetate extract at 1000 microg/ml showed maximum scavenging activity of the stable radical 1,1-diphenyl,2-picryl hydrazyl upto 96.65% (IC50=430.36 microg/ml) and scavenging of the radical cation, 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) upto 92.25% (IC50=606.29 microg/ml) at the same concentration. The extract had good reducing power, however showed moderate inhibition for conjugated dienes and thiobarbituric acid reactive acid substances (59.56 and 51.45%). The total phenolic content of various extracts of A. candidus broth filtrate was measured and a correlation between radical scavenging activities of extracts with total phenolic content was observed. The ethyl acetate extract (125 mg/kg ip) showed significant anti-inflammatory activity in carrageenan-induced rat paw oedema model. The exhibited antioxidant activity of ethyl acetate extract of A. candidus broth filtrate was comparable with BHA and ascorbic acid, while anti-inflammatory activity was comparable with standard diclofenac sodium.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Aspergillus; Biphenyl Compounds; Butylated Hydroxyanisole; Cations; Culture Media; Diclofenac; Edema; Free Radicals; Hydrazines; Phenol; Picrates; Rats

Fluid resuscitation to maintain adequate tissue perfusion while reducing edema in the severely burned patient remains a challenge. Recent studies suggest that reactive oxygen species generated by thermal injury are involved in edema formation associated with burn. The present study tested the hypothesis that adding a free radical scavenger to the resuscitation fluid would reduce total fluid requirements in the treatment of severe thermal injury. Anesthetized chronically instrumented sheep received a 40% total body surface area full-thickness flame burn. At 1 h after injury, animals were resuscitated with lactated Ringer's (LR, n = 14) as control, LR containing high doses of vitamin C (VC, n = 6), 1000 mOsM hypertonic saline (HS, n = 7), or 1000 HS containing VC (HS/VC, n = 7) in coded bags so that investigators were blinded to the treatment. Fluids were infused at an initial Parkland rate of 10 mL/kg/h, adjusted hourly to restore and maintain urine output at 1 to 2 mL/kg/h. Sheep in the VC or HS/VC group received 250 mg/kg VC in the first 500 mL of LR or HS, and then 15 mg/kg/h thereafter. Hemodynamic variables and indices of antioxidant status were measured. At 48 h postburn, sheep were euthanized, and heart, liver, lung, skeletal muscle, and ileum were evaluated for antioxidant status. All fluid resuscitation regimens were equally effective in restoring cardiac output to near baseline levels; no treatment effects were apparent on arterial pressure or heart rate. VC infusion significantly reduced fluid requirements and, therefore, net fluid balance (fluid in, urine out) by about 30% at 6 h and about 50% at 48 h in comparison with the LR group (P < 0.05). HS and HS/VC reduced fluid requirements by 30% and 65%, respectively, at 6 h, but the volume-sparing effect of HS was not observed after 36 h and that of HS/VC was lost after 12 h. Plasma total antioxidant potential increased about 25-fold (P < 0.05) at 2 and 3 h in response to VC infusion compared with the LR and HS groups, and remained about 5- to 10-fold higher throughout the rest of the study. VC infusion also prevented the 4-fold increase in plasma thiobarbituric acid reactive substances seen in the LR group early after burn (P < 0.05). Tissue antioxidant status was similar between groups. In this sheep burn model, continuous high-dose VC infusion reduced net fluid balance, reduced indices of plasma lipid peroxidation, and maintained overall antioxidant status in comparison with standard-of-care LR

Topics: Animals; Antioxidants; Arteries; Ascorbic Acid; Burns; Edema; Female; Fluid Therapy; Free Radical Scavengers; Hematocrit; Hemodynamics; Lipid Peroxidation; Resuscitation; Saline Solution, Hypertonic; Sheep; Shock, Traumatic; Sodium Chloride; Thiobarbituric Acid Reactive Substances; Time Factors; Tissue Distribution

The aim of this study was to ascertain the possibility of diminishing ischemia-reperfusion injury by intravenous application of the chosen antioxidants: vitamin C, mannitol, and N-acetylcysteine.. The study was performed on New Zealand Red male rabbits, which were divided into 6 groups of 8. In group 1, 5 segments of the small intestine were taken for histopathologic examination (normal intestine). In group 2, segments of the small intestine were taken for histopathologic examination after 3 hours of closure of the superior mesenteric artery (ischemic intestine). In group 3, after 3 hours of closure of the superior mesenteric artery, 1 hour of reperfusion took place. In this group, blood flow in the superior mesenteric artery was measured within the first 30 minutes, and segments of the small intestine were taken for histopathologic examination after 60 minutes of the reperfusion. In groups 4, 5, and 6 the procedure was similar to that in group 3, but additionally the rabbits were given antioxidants intravenously: in group 4, vitamin C, 250 mg/kg; in group 5, 20% mannitol, 3 mL/kg; and in group 6, N-acetylcysteine, 100 mg/kg.. All the chosen antioxidants had a beneficial influence on the blood flow in the superior mesenteric artery. The blood flow in the groups with antioxidants after 30 minutes of the reperfusion was 53% to 57% of initial values compared with 27% of initial values in group 3. In histopathologic evaluation, protective action of the antioxidants was seen in the groups with vitamin C and mannitol.. Application of the chosen antioxidants reduces injury of the rabbit small intestine caused by reperfusion after 3 hours of closure of the superior mesenteric artery.

Topics: Acetylcysteine; Animals; Antioxidants; Ascorbic Acid; Edema; Hemorrhage; Intestinal Mucosa; Intestine, Small; Ischemia; Ligation; Male; Mannitol; Mesenteric Artery, Superior; Oxidative Stress; Rabbits; Reperfusion Injury

Compartment syndrome is a unique form of ischaemia of skeletal muscle which occurs despite patency of the large vessels. Decompression allows the influx of activated leucocytes which cause further injury. Vitamin C is a powerful antioxidant which concentrates preferentially in leucocytes and attenuates reperfusion-induced muscle injury. We have evaluated the use of pretreatment with oral vitamin C in the prevention of injury caused by compartment syndrome in a rat cremasteric muscle model. Acute and delayed effects of pretreatment with vitamin C were assessed at one and 24 hours after decompression of compartment syndrome. Muscle function was assessed electrophysiologically. Vascular, cellular and tissue inflammation was assessed by staining of intercellular adhesion molecule-1 (ICAM-1) and by determination of the activity of myeloperoxidase (MPO) in neutrophils and tissue oedema. Compartment syndrome impaired skeletal muscle function and increased the expression of ICAM-1, activity of MPO and muscle weight increased significantly. Pretreatment with vitamin C preserved muscle function and reduced the expression of ICAM-1, infiltration of the neutrophils and oedema.

Topics: Administration, Oral; Animals; Ascorbic Acid; Compartment Syndromes; Edema; Intercellular Adhesion Molecule-1; Muscle, Skeletal; Peroxidase; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Topics: Antioxidants; Ascorbic Acid; Bulgaria; Drug Industry; Edema; Escin; Flavonoids; Hemorrhagic Disorders; Hypocalcemia; Phytic Acid; Plant Preparations

The alcoholic extract of Trewia polycarpa roots (TPE), which exhibited significant anti-inflammatory activity, was evaluated for the possible mode of action by studying its antioxidant potential in adjuvant-induced arthritic rats. The biological defence system constituting the superoxide dismutase, glutathione peroxidase, ascorbic acid showed a significant increase while the lipid peroxide content was found to decrease to a large extent on TPE treatment thereby indicating the extracts free radical scavenging property. Histopathological studies too supported anti-arthritic potential of the roots of Trewia polycarpa.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Ascorbic Acid; Body Weight; Edema; Ethanol; Euphorbiaceae; Female; Free Radical Scavengers; Freund's Adjuvant; Glutathione; Glutathione Peroxidase; Indomethacin; Lipid Peroxidation; Medicine, Ayurvedic; Phytotherapy; Plant Extracts; Plant Roots; Rats; Superoxide Dismutase; Synovial Fluid; Toxicity Tests

We investigated the antioxidative activities and the effects on acute inflammation in mice of a novel diaminouracil derivative, CX-659S ((S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione). CX-659S showed potent scavenging activities against the hydroxyl radical and peroxynitrite and inhibited lipid peroxidation in rat brain homogenates in vitro. Topically applied CX-659S dose-dependently inhibited arachidonic acid- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. Consistent with its antioxidative properties in vitro, CX-659S dramatically attenuated the accumulation of lipid peroxides in the mouse ear elicited by repeated application of TPA. Previously, we reported the effectiveness of CX-659S against contact hypersensitivity reactions in both mouse and guinea pig models. These present results further suggest the therapeutic potential of CX-659S for acute skin inflammation that may involve oxidative tissue damage.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Ascorbic Acid; Chromans; Dose-Response Relationship, Drug; Ear; Edema; Lipid Peroxidation; Male; Mice; Mice, Inbred ICR; Oxidation-Reduction; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; Tetradecanoylphorbol Acetate; Uracil

edema formation after thermal injury is rapid and fulminant within the first hour after injury and increased microvascular permeability has been claimed to be the main responsible mechanism. An acute decrease in interstitial fluid hydrostatic pressure (P(if)) down to -150 mm Hg has recently been reported in dermal burns. This strong negative tissue pressure creates a 'suction' on the fluid in the capillaries. Furthermore, high dose vitamin C (VC) has been shown to reduce postburn edema and fluid requirements following major burn injuries. This led to the present study, aimed at investigating whether VC administered after thermal injury in rats, could attenuate the strongly negative P(if). Edema volume was measured by total tissue water content (TTW) and extravasation of albumin (Ealb).. a prospective, open experimental study.. pentobarbital-anesthetized rats received either a full-thickness burn injury covering 10% of total body surface area, or a sham burn. The rats were given VC or equal volumes normal saline (NS) either before the burn, 5 or 30 min after the injury. VC (25 mg/ml in NS, osmolality 272 mOsm/l) was administered as a bolus (66 mg/kg) followed by infusion (33 mg/kg/h). The animals were divided into 7 groups (6 animals in each) according to the timing of VC/NS administration: (1) VC-preburn, (2) VC-5 min postburn, (3) VC-30 min postburn, (4) NS-preburn, (5) NS-5 min postburn, (6) NS-30 min postburn and (7) VC-pre sham burn group. All groups were duplicated for series I and II.. in series I; P(if) was measured using a sharpened glass micropipette connected to a servo-controlled counter pressure system. Measurements were averaged in the following time periods: preburn, 5-20, 21-40, 41-60 and 61-90 min postburn. In series II; Ealb and TTW were measured in burned and non-burned skin by radio-labelled albumin and wet-dry weights, respectively.. in the sham control group (VC-pre-sham burn), P(if) ranged between -1 and -2 mm Hg and did not change throughout the experimental period. In the NS group (placebo), P(if) fell to -46.8 +/- 10.1 (1 S.D.) mm Hg at 5-20 min after the injury and were -23.1 +/- 13.4 and -11.6 +/- 4.1 mm Hg at 21-40 and 41-60 min postburn. P(if) returned to preburn values at 61-90 min post injury. In the VC groups, there was a marked attenuation of the negative P(if) to average -10.1 +/- 11.8 mm Hg at 5-20 min, -2 +/- 1.7 and -0.6 +/- 1.2 mm Hg at 21-40 and 41-60 min after injury, respectively (all p < 0.01 compared to NS). TTW in burned skin of the NS-5 min groups was 3.12 +/- 0.28, VC5-min group was 2.57+/-0.69 and VC sham was 1.77+/-0.19 ml/g DW, respectively (p < 0.01 compared to sham control for all values). In all the VC-groups TTW values were higher than sham control and lower than in the corresponding NS-groups (p > 0.05 both ways). No statistical significant differences were found between Ealb-values in the VC- and NS-groups.. high-dose vitamin C attenuates the development of strongly negative P(if) in burned dermis and reduces the edema as measured by TTW. No significant change in Ealb was found. Vitamin C was thus found to have potential beneficial effects on the acute postburn edema generation.

Topics: Analysis of Variance; Animals; Ascorbic Acid; Burns; Cell Membrane Permeability; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Extracellular Space; Hydrostatic Pressure; Rats; Rats, Wistar; Reference Values; Time Factors; Wound Healing

Topics: Albumins; Ascorbic Acid; Edema; Humans; Systemic Inflammatory Response Syndrome

We studied the hemodynamic effects of delayed initiation (6 h postburn) of antioxidant therapy with high-dose vitamin C in second-degree thermal injuries. Seventy percent body surface area burns were produced by subxiphoid immersion of 12 guinea pigs into 100 degrees C water for 3 s. The animals were resuscitated with Ringer's lactate solution (R/L) according to the Parkland formula (4 ml/kg/% burn during the first 24 h) from 6 h postburn, after which the resuscitation fluid volume was reduced to 25% of the Parkland formula volume. Animals were divided into two groups. The vitamin C group (n = 6) received R/L to which vitamin C (340 mg/kg/24 h) was added after 6 h postburn. The control group (n = 6) received R/L only. Both groups received identical resuscitation volumes. Heart rates, mean arterial blood pressure, cardiac output, hematocrit level, and water content of burned and unburned tissue were measured before injury and at intervals thereafter. No animals died. There were no significant differences in heart rates or blood pressures between the two groups throughout the 24-h study period. The vitamin C group showed significantly (P < 0.05) lower hematocrits 8 and 24 h postburn, and higher cardiac outputs after 7 h postburn. At 24 h postburn, the burned skin in the vitamin C group had a significantly (P < 0.05) lower water content (73.1 +/- 1.1) than that of the control group (76.0 +/- 0.8). In conclusion, delayed initiation of high-dose vitamin C therapy beginning 6 h postburn with 25% of the Parkland formula volume significantly reduced edema formation in burned tissue, while maintaining stable hemodynamics.

Topics: Animals; Ascorbic Acid; Blood Pressure; Burns; Cardiac Output; Edema; Fluid Therapy; Guinea Pigs; Heart Rate; Hematocrit; Isotonic Solutions; Ringer's Lactate; Time Factors

Triptolide (Tri) was isolated from Tripterygium wilfordii Hook f. Tri 0.1-0.2 mg.kg-1 sc or 0.15-0.3 mg.kg-1 ig inhibited markedly the increased vascular permeability induced by ip 0.7% HAc in mice. Tri 0.05-0.1 mg.kg-1 ip or 0.15-0.3 mg.kg-1 ig inhibited hind paws swelling induced by sc 0.15 ml carrageenan and also inhibited the same swelling induced by sc 2.5% formaldehyde 0.1 ml in rats. Tri 0.05-0.1 mg.kg-1 ip inhibited markedly proliferation of granuloma induced by sc implantation of cotton-pellets in rats, but 0.2 mg.kg-1 ip can not inhibit the same swelling induced by sc 0.15 ml carrageenan in adrenalectomized rats. Tri 0.2 mg.kg-1 ip decreased markedly weight of thymus. Tri 0.2 mg.kg-1 ip, but 0.1 mg.kg-1 ip did not reduced the content of ascorbic acid of adrenal gland in rats. Tri 0.2 mg.kg-1 ip did not decrease the pro-staglandin E content in inflammatory tissues. These results indicate that high dose of Tri can stimulate the pituitary-adrenal axis.

Topics: Adrenal Glands; Adrenalectomy; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Capillary Permeability; Carrageenan; Diterpenes; Edema; Epoxy Compounds; Granuloma, Foreign-Body; Male; Mice; Phenanthrenes; Prostaglandins E; Rats

Pilose antler peptide (PAP:MW:7200; amino acid residue:68) isolated from the antlers of Cervus nippon temminck 10 and 20 mg.kg-1 i.p. produced inhibitions towards acute and chronic inflammations in a dose-dependent manner. PAP reduced ascorbic acid and cholesterol contents in adrenal glands and decreased the serum hydrocortisone level of rats. The reduction of ascorbic acid and cholesterol contents were unaffected by the pretreatment of dexamethasone. PAP also showed an anti-inflammatory action on the swelling of carrageenan-induced hind paw in adrenalectomized rats. The results suggest that the anti-inflammatory effects of PAP do not depend absolutely on pituitary-adrenal system.

Topics: Adrenal Glands; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antlers; Ascorbic Acid; Cholesterol; Deer; Edema; Female; Hydrocortisone; Male; Materia Medica; Mice; Peptides; Rats; Rats, Wistar

The influence of maternal vitamin C deficiency on fetal development was studied in swine with a hereditary lack of ability to synthesize ascorbic acid (OD pigs). Thirteen pregnant sows homozygous (od/od) for the defect were depleted of ascorbic acid for 24 to 38 d at various stages of gestation. Six normal (OD/OD) sows were used as controls. Only a few experimental sows showed clinical symptoms of vitamin C deficiency. Nevertheless, severe pathological changes were seen in the uterus and fetuses. Characteristic findings were hemorrhages and hematomas in both fetal and maternal placenta, and general edema and subcutaneous hemorrhages in the fetuses. Similarities were noted to the abruptio placentae syndrome in women. Depletion of vitamin C resulted in a pronounced decline in ascorbic acid concentration in most maternal and fetal organs as well as in plasma and embryonic fluids. No morphological malformations were found in the fetuses, but the ossification of the skeleton was severely deranged. Macroscopically the lesions comprised swelling of the costochondral junction and separation of the epiphysial cartilage from the spongiosa in ribs and limb bones. Another characteristic finding was loosening of the periost from the cortex, often resulting in subperiosteal bleedings. Microscopically normal osteoblasts were few and the formation of osteoid defective.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Edema; Embryonic and Fetal Development; Female; Fetal Diseases; Fetus; Hematoma; Hemorrhage; Male; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Swine; Swine Diseases; Uterine Diseases; Uterus

Major symptoms and death from systemic Bacillus anthracis infections are mediated by the action of the pathogen's lethal toxin on host macrophages. High levels of the toxin are cytolytic to macrophages, whereas low levels stimulate these cells to produce cytokines (interleukin-1 beta and tumor necrosis factor-alpha), which induce systemic shock and death.. Experiments were performed to assess the possibility that the oxidative burst may be involved in one or both of lethal toxin's effects on macrophages. Toximediated cell lysis, superoxide anion and cytokine production were measured. Effects of antioxidants and macrophage mutations were examined.. RAW264.7 murine macrophages treated with high levels of toxin released large amounts of superoxide anion, beginning at about 1 hr, which correlates with the onset of cytolysis. Cytolysis could be blocked with various exogenous antioxidants or with N-acetyl-L-cysteine and methionine, which promote production of the endogenous antioxidant, glutathione. Mutant murine macrophage lines deficient in production of reactive oxygen intermediates (ROIs) were relatively insensitive to the lytic effects of the toxin, whereas a line with increased oxidative burst potential showed elevated sensitivity. Also, cultured blood monocyte-derived macrophages from a patient with Chronic Granulomatous Disease, a disorder in which the phagocyte's oxidative burst is disabled, were totally resistant to toxin, in contrast to control monocytes.. These results imply that the cytolytic effect of the toxin is mediated by ROIs. Additionally, cytokine production and consequent pathologies showed partial dependence on macrophage ROIs. Antioxidants moderately inhibited toxin-induced cytokine production in vitro, and BALB/c mice pretreated with N-acetyl-L-cysteine or mepacrine showed partial protection against lethal toxin. Thus ROIs are involved in both the cytolytic action of anthrax lethal toxin and the overall pathologic process in vivo.

Topics: Animals; Antigens, Bacterial; Antioxidants; Ascorbic Acid; Bacillus anthracis; Bacterial Toxins; Cell Membrane Permeability; Cells, Cultured; Dose-Response Relationship, Drug; Edema; Female; Glutathione; Humans; Macrophages; Male; Methionine; Mice; Mice, Inbred BALB C; NADPH Oxidases; Nitric Oxide; Oxidative Stress; Oxygen; Quinacrine; Reactive Oxygen Species

The aim of this study was to explore whether intraperitoneal administration of ascorbic acid (AA) at a dose of 500 mg/kg, once a day for 3 following days, affected the peroxidase (PO) activity in inflamed feet of mice. The foot inflammatory reaction induced by the carrageenan (CAR), n-formyl-methionyl-leucyl-phenylalanine (FMLP) and xanthine-xanthine oxidase was accompanied by suppression of PO activity. Administration of AA, having no effect on the degree of foot oedema, skin temperature and microscopic picture of tissue specimens significantly enhanced the decline in PO activity provoked by inflammatory agents. This activity decreased 2.0-, 1.6- and 1.9-fold (p < 0.001, p < 0.01, p < 0.05) when inflammatory response was induced with FMLP, CAR and X-XO, respectively. Also in vitro AA (50-100 micrograms/ml) inhibited PO activity of leukocyte lysate and foot extract obtained from untreated animals. In conclusion we found that AA, having no effect on inflammatory response, significantly enhanced inhibition of PO activity in inflamed tissues in mice which could be a result of direct action of AA on the enzyme molecule.

Topics: Animals; Ascorbic Acid; Carrageenan; Edema; Foot; Inflammation; Male; Mice; Mice, Inbred BALB C; N-Formylmethionine Leucyl-Phenylalanine; Peroxidase; Skin Temperature; Xanthine; Xanthine Oxidase; Xanthines

Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization.. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization.. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.

Topics: Allopurinol; Animals; Ascorbic Acid; Body Water; Cardiomyopathies; Coronary Disease; Dogs; Edema; Embolism; Free Radical Scavengers; Free Radicals; Microcirculation; Microspheres; Oxygen; Superoxide Dismutase; Theophylline

This work attempts to determine the influence of vitamin C on locally induced inflammation and arthritis in rat paws, as measured by rat paw swelling, polymorphonuclear leukocyte infiltration, pain, and surface skin temperature. Daily subcutaneous administration of 150 mg/kg of vitamin C over 20 days reduced arthritic swelling, increased pain tolerance, and decreased polymorphonuclear leukocyte infiltration, with no significant change in surface temperature. Vitamin C may provide podiatrists with a supplemental or alternative treatment for patients with rheumatoid arthritis.

Topics: Animals; Arthritis, Rheumatoid; Ascorbic Acid; Body Temperature; Disease Models, Animal; Edema; Male; Pain; Rats; Rats, Inbred Strains

The ability of ascorbic acid (AA) as an antioxidant to suppress the inflammatory reaction was investigated. Carrageenan-induced foot pad edema was produced in the right hind foot of anesthetized mice (n = 22). Subsequently, Group A (n = 11) received 25 mg AA in saline (IP) and Group B, an equal volume of saline. After 2 1/2 hrs the animals were sacrificed and increase in weight of the amputated right paw over the amputated left paw was expressed as percentage edema (PE). The PE in Group A was 43.8 +/- 5.9, and in Group B was 59.3 +/- 3.9 (p less than 0.05, unpaired t-test). The same experiment was repeated with the AA administered 10 minutes prior to injury. The change in edema was not statistically significant. It is concluded that high dose AA suppresses edema if given after but not before injury.

Topics: Animals; Ascorbic Acid; Carrageenan; Edema; Female; Male; Mice

Combinations of inhibitors of phospholipase A2, cyclooxygenase and lipoxygenase as the key enzymes of the arachidonic acid cascade were investigated with respect to their anti-inflammatory effectivity in the carrageenin paw edema and adjuvant arthritis of rats. Combinations of indometacin with butylhydroxytoluene, quinacrine, lidocaine or/and procaine gave additive or overadditive effects in the carrageenin edema. Addition of ascorbic acid decreased the effectivity. Similar results as with indometacin were obtained with dexamethasone. The "steroid saving effect" of the combination of a glucocorticoid with a non-steroidal anti-inflammatory analgesic was confirmed in the carrageenin edema. However, it could not be found in the adjuvant arthritic rat with dexamethasone and declofenac-Na. The fitness of the models is discussed.

Topics: Animals; Anti-Inflammatory Agents; Arachidonic Acids; Ascorbic Acid; Carrageenan; Cyclooxygenase Inhibitors; Edema; Female; Lipoxygenase Inhibitors; Male; Phospholipases; Phospholipases A; Phospholipases A2; Rats; Rats, Inbred Strains

Topics: Adrenal Cortex; Animals; Ascorbic Acid; Capillary Permeability; Carrageenan; Corticosterone; Edema; Eosinophils; Hindlimb; Inflammation; Insulin; Leukocyte Count; Male; Rats; Rats, Inbred Strains

Scurvy occurred in an elderly man with fatigue, dyspnea on exertion, and extensive ecchymoses and brawny edema of the legs. Platelet count, prothrombin time, and partial thromboplastin time were normal, but serum ascorbic acid level was very low. Other signs considered to be classic and almost pathognomonic for were absent: bleeding gums, hyperkeratotic follicles, coiled hairs, and perifollicular hemorrhages. Reliance on these well-known features of scurvy may obscure or delay diagnosis of an easily cured disorder Severe scurvy is most commonly suggested by tenderness, extensive ecchymoses, and brawny edema of the lower extremities.

Topics: Aged; Ascorbic Acid; Diet; Dyspnea; Ecchymosis; Edema; Fatigue; Humans; Male; Mouth, Edentulous; Scurvy

Anti-carrageenin paw edema effects of 1-(m-trifluoromethylphenyl)-3-(2-hydroxyethyl)-quinazoline-2, 4(1H, 3H)-dione [H-88] and 1-(m-trifluoromethylphenyl)-3-ethylpyridopyrimidine-2, 4(1H, 3H)-dione [HN-37] in rats were dissipated or reduced markedly by adrenalectomy. The effects of both compounds on the pituitary-adrenal axis were therefore investigated in male Wistar rats at 5-6 weeks of age. Oral treatments with H-88 in a dose of 100 mg/kg and HN-37 at 10 mg/kg induced the same degree of responses in intact animals, namely, a marked increase of blood corticosterone level at one hr of the peak time (360%), a decrease of adrenal ascorbic acid level at 3 hr (52-59%), an increase of blood glucose level at 6-12 hr (25-59%) and of liver glycogen level at 12-4 hr (97-153%). In addition, a significant hypertrophy of the pituitary and adrenals (p less than 0.05) at 6-12 hr and/or atrophy of the thymus and spleen at 3-24 hr were noted. The effect of HN-37 on blood corticosterone level was approximately 10 times as potent as that of H-88 as well as on the carrageenin paw edema. The effects of both compounds on blood corticosterone level were dissipated by adrenalectomy, and those on blood corticosterone level and adrenal ascorbic acid level were abolished by hypophysectomy. These results suggest that hypophysis-adrenal axis stimulation may play an important role in antiedematous effects of N-88 and HN-37.

Topics: Adrenal Glands; Adrenalectomy; Animals; Ascorbic Acid; Circadian Rhythm; Corticosterone; Dose-Response Relationship, Drug; Edema; Hypophysectomy; Male; Organ Size; Pituitary-Adrenal System; Pyrimidinones; Quinazolines; Rats

Topics: Animals; Ascorbic Acid; Chymotrypsin; Drug Combinations; Edema; Flavonoids; Male; Peptide Hydrolases; Phytosterols; Rats; Trypsin

The action of a combination of chymotrypsin-trypsin + flavonoids + ascorbic acid (zymolean) has been compared with that of 7 non-steroid anti-inflammatory substances in 4 tests: a histamine induced wheal, dextran and carrageenin induced edemas, and permeability to Evans blue in the peritoneal cavity. 1. The non-steroid anti-inflammatory substances, which reduce markedly the carrageenin induced edema, are active against peritoneal permeability, but bring about almost no decrease in the effects of histamine and dextran. 2. The combination studied is effective in all of the techniques. 3. The reduction of capillary permeability induced by histamine is due to the action of flavonoids and ascorbic acid. 4. The action of the proteolytic enzymes, administered by duodenal route, on the one hand, and that of hesperidin-methylchalcone + methyl-4-esculetol + ascorbic acid on the other, accumulate to reduce the two types of edema. 5. The effect against permeability in the peritoneum seems to exerted by the combination of the flavonoids + ascorbic acid. 6. The combination studied, therefore, shows a more complete spectrum of action than the non-steroid anti-inflammatory substances against initial symptoms of inflammation.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Capillary Permeability; Drug Combinations; Edema; Flavonoids; Male; Mice; Peptide Hydrolases; Rats

1 Rat paws were injected with carrageenin, and their subcutaneous tissue perfused 135 min later. These perfusates were injected intravenously into receptor rats in which they caused an attenuation of inflammatory responses. 2 The effect was not observed in adrenalectomized receptor rats nor in receptors with electrolytic lesions in the median eminence of the hypothalamus but persisted in adrenal-demedullated animals. 3 The active perfusates also induced eosinopenia in normal or adrenal-demedullated animals, but not in adrenalectomized rats, and produced an increase in blood corticosterone with a concomitant decrease in the amounts of adrenal ascorbic acid. 4 The active perfusates did not affect the responses of isolated preparations to histamine, bradykinin, prostaglandins and 5-hydroxytryptamine neither did they elicit changes of the arterial blood pressure in receptor animals. 5 The anti-inflammatory activity present in perfusates from inflamed paws seems to be formed slowly at the site of the developing inflammatory reaction, since perfusates collected 30-65 min after the injection of carrageenin were ineffective, as was plasma taken from donor rats at various time intervals after carrageenin injections. 6 It is suggested that the anti-inflammatory factor present in the active perfusates exerts its action by stimulation of the hypothalamo-pituitary-adrenal axis.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Blood Pressure; Carrageenan; Corticosterone; Edema; Eosinophils; Hypothalamus; Inflammation; Male; Pituitary Gland; Rats; Stimulation, Chemical; Time Factors; Tissue Extracts

Topics: Adult; Ascorbic Acid; Edema; Favism; Female; Fetal Diseases; Glucosephosphate Dehydrogenase Deficiency; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications, Hematologic

Topics: Adult; Ascites; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiomegaly; Edema; Female; Humans; Leg; Scurvy

Topics: Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholelithiasis; Cholesterol; Disease Models, Animal; Edema; Female; Gallbladder; Guinea Pigs; Humans; Liver

Since oedema of adjacent tissue is a major factor in preventing healing of leg ulcers conservative treatment should aim to dry out the ulcer area before bandaging and to keep it dry afterwards. A method of postural drainage of oedema is described in which the patient lies supine with the legs raised vertically for two days. Non-stretch Viscopaste bandages are then applied and the patient allowed to move about normally, but instructed to continue vertical leg drainage for a period each day. Out of 106 cases treated by this method the leg ulcer healed within a year in 82 (77.4%). Relapses were apt to occur when the patient neglected to continue the vertical drainage regimen after the ulcer had healed. These results compare well with those reported for other methods of treatment. Vertical leg drainage treatment is inexpensive and the patient can continue at work.

Topics: Adult; Ascorbic Acid; Bandages; Edema; Female; Humans; Leg Ulcer; Male; Posture; Varicose Ulcer; Wound Healing

Topics: Adrenal Glands; Amino Acids; Animals; Ascorbic Acid; Blood Proteins; Body Weight; Brain Chemistry; Carbon Isotopes; Dietary Proteins; DNA; Edema; Guinea Pigs; Kwashiorkor; Liver; Male; Organ Size; Ribosomes; RNA

Topics: Adrenal Cortex Hormones; Adult; Aged; Arterial Occlusive Diseases; Ascorbic Acid; Cerebrovascular Disorders; Child; Chorioretinitis; Edema; Female; Humans; Ketones; Male; Middle Aged; Retinal Artery; Retinal Degeneration; Retinal Diseases; Retinal Vessels; Rutin; Vitamin B Complex; Xanthines

Topics: Adrenal Glands; Aminopyrine; Animals; Anti-Inflammatory Agents; Arthritis; Ascorbic Acid; Aspirin; Benzoates; Capillary Permeability; Chemical Phenomena; Chemistry; Drug Evaluation, Preclinical; Edema; Erythema; Flufenamic Acid; Gastric Mucosa; Granuloma; Mefenamic Acid; Phenylbutazone; Phenylenediamines; Prednisolone; Rats; Thymus Gland

Topics: Ascorbic Acid; Aspirin; Atrophy; Auscultation; Cellulitis; Drug Combinations; Edema; Humans; Leg Ulcer; Lymphatic System; Macrophages; Necrosis; Occlusive Dressings; Pigmentation Disorders; Posture; Respiration; Rest; Thrombophlebitis; Time Factors; Valsalva Maneuver; Varicose Veins; Venous Insufficiency; Venous Pressure

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Ascorbic Acid; Aspirin; Carrageenan; Disease Models, Animal; Edema; Erythema; Female; Freund's Adjuvant; Glucuronidase; Guinea Pigs; In Vitro Techniques; Liver; Lysosomes; Male; Phenylbutazone; Rats; Rats, Inbred Strains; Ultraviolet Rays

Topics: Aged; Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; Edema; Hematoma; Humans; Hydrarthrosis; Male; Middle Aged; Scurvy; Single Person

Topics: Animals; Ascorbic Acid; Cornea; Corneal Opacity; Edema; Glucose; Glycerol; Mannitol; Methylcellulose; Osmosis; Photography; Propylene Glycols; Rabbits; Semiconductors; Sodium Chloride; Sorbitol; Urea

Topics: Adult; Ascites; Ascorbic Acid; Benzothiadiazines; Child; Edema; Heart Failure; Humans

Topics: Adjuvants, Anesthesia; Adrenal Glands; Amines; Anesthetics, Local; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Blood Pressure; Butyrates; Chemical Phenomena; Chemistry; Edema; Mice; Rats

Topics: Ascorbic Acid; Edema; Female; Humans; Phytotherapy; Plants, Medicinal; Rutin; Thrombophlebitis

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Chronic Disease; Depression; Diet; Diet Therapy; Edema; Female; Hemorrhage; Humans; Keratosis; Middle Aged; Scurvy

Topics: Acute Disease; Adrenal Cortex Hormones; Ascorbic Acid; Burns, Chemical; Chronic Disease; Contact Lenses; Cornea; Corneal Injuries; Edema; Eye Diseases; Glaucoma; Glucose; Glycerol; Humans; Hypertonic Solutions; Idoxuridine; Intraocular Pressure; Keratitis, Dendritic; Keratoconus; Ophthalmic Solutions; Povidone; Silicones; Sodium Chloride; Surface-Active Agents; Tears

Topics: Adrenalectomy; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Axis, Cervical Vertebra; Dibenzylchlorethamine; Edema; Epinephrine; Hexamethonium Compounds; Iproniazid; Male; Metyrapone; Pituitary-Adrenal System; Rats; Sodium Salicylate; Time Factors

Topics: 17-Hydroxycorticosteroids; Abscess; Adrenal Glands; Adrenalectomy; Analgesics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antipyretics; Ascorbic Acid; Cholesterol; Dextrans; Edema; Formaldehyde; Granuloma; Histamine; Inflammation; Injections, Intraperitoneal; Phenylbutazone; Physiology; Rats; Serotonin; Sulfinpyrazone

Topics: Adrenal Cortex Hormones; Adrenal Glands; Adrenalectomy; Aesculus; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Biomedical Research; Cholesterol; Edema; Escin; Guinea Pigs; Hypophysectomy; Inflammation; Lipid Metabolism; Metabolism; Pharmacology; Pituitary Gland; Rats; Research; Saponins; Tryptophan

Topics: Animals; Ascorbic Acid; Aspirin; Cyproheptadine; Edema; Flavonoids; Inflammation; Mice; Phenylbutazone; Radiometry; Research; Serotonin; Serum Albumin; Serum Albumin, Radio-Iodinated; Sodium Salicylate

Topics: 17-Ketosteroids; Adrenalectomy; Ascorbic Acid; Catechols; Edema; Formaldehyde; Hyaluronoglucosaminidase; Inflammation; Pharmacology; Rats; Research; Tannins; Tea; Urine

Topics: Adrenocorticotropic Hormone; Aldosterone; Analgesics; Analgesics, Non-Narcotic; Antipyretics; Ascorbic Acid; Aspirin; Bradykinin; Corticosterone; Cortisone; Desoxycorticosterone; Edema; Oxyphenbutazone; Pharmacology; Phenylbutazone; Rats; Research; Sodium Salicylate; Sulfinpyrazone; Toxicology; Uricosuric Agents

Topics: Ascorbic Acid; Blood Chemical Analysis; Deficiency Diseases; Diuretics; Edema; Intestine, Small; Intestines; Liver Cirrhosis; Mineralocorticoid Receptor Antagonists; Prednisone; Spironolactone

Topics: Adrenocorticotropic Hormone; Aldosterone; Analgesics; Analgesics, Non-Narcotic; Antipyretics; Ascorbic Acid; Bradykinin; Corticosterone; Cortisone; Desoxycorticosterone; Edema; Pharmacology; Phenylbutazone; Rats; Research; Salicylates; Salicylic Acid; Sulfinpyrazone; Uricosuric Agents

Topics: Ascorbic Acid; Edema; Flavonoids; Humans; Postoperative Period; Prednisolone; Tooth Extraction; Vitamins

Topics: Adrenal Cortex; Adrenal Glands; Animals; Ascorbic Acid; Cholesterol; Cysteamine; Edema; Ethylamines; Formaldehyde; Rats

Topics: Adrenal Cortex; Adrenal Glands; Animals; Ascorbic Acid; Cholesterol; Edema; Formaldehyde; Lipid Metabolism; Rats; Vitamins

Topics: Animals; Ascorbic Acid; Carbohydrate Metabolism; Edema; Egg White; Rats

Topics: Albumins; Animals; Ascorbic Acid; Edema; Egg White; Hypersensitivity; Rats; Vitamins

Topics: Animals; Ascorbic Acid; Diuresis; Diuretics; Edema; Humans; Vitamins; Water