nystatin-a1 and Inflammation

Thienopyrimidine scaffold is a fused heterocyclic ring system that structurally can be considered as adenine, the purine base that is found in both DNA and RNA-bioisosteres. Thienopyrimidines exist in three distinct isomeric forms. The current review discusses thieno[2,3-d]pyrimidine as a one of the opulent heterocycles in drug discovery. Its broad range of medical applications such as anticancer, anti-inflammatory, anti-microbial, and CNS protective agents has inspired us to study its structure-activity relationship (SAR), along with its relevant synthetic strategies. The present review briefly summarizes synthetic approaches for the preparation of thieno[2,3-d]pyrimidine derivatives. In addition, the promising biological activities of this scaffold are also illustrated with explanatory diagrams for their SAR studies.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Chemistry, Pharmaceutical; Humans; Inflammation; Neoplasms; Pyrimidines; Structure-Activity Relationship

Intracellular viscosity abnormalities can lead to diabetes, neurodegenerative diseases and cancer. In this work, we developed a mitochondria-targetable fluorescent probe (EIMV) for discriminating normal and inflammatory models by viscosity changes. It was found that EIMV showed excellent properties, including high photostability, low cytotoxicity, red emission and favorable biocompatibility. In view of these unique features, this probe could successfully identify normal and cancer cells via viscosity changes. Furthermore, the EIMV probe successfully identified zebrafish with different viscosities by the same method. Moreover, EIMV exhibited different fluorescence signals in normal and inflammatory mice due to changes in viscosity. Therefore, the probe provides a new method to study the relationship between diseases and viscosity in the fields of biology and medicine.

Topics: Animals; Cell Line, Tumor; Female; Fluorescence; Fluorescent Dyes; Humans; Indoles; Inflammation; Ionophores; Mice; Mice, Inbred BALB C; Mitochondria; Monensin; Neoplasms; Nystatin; RAW 264.7 Cells; Viscosity; Zebrafish

Vulvovaginal candidiasis (VVC) affects approximately 75% of all women of during their reproductive years. Previously, we reported that recombinant human IFN α-2b (rhIFNα-2b) protects vaginal epithelial cells from candidal injury in vitro. In the current study, we examined the effects of rhIFNα-2b (1.25 mg/mL, 10% inhibition concentration) on fungal clearance, immunocompetent cytokine responses, non-B IgG production, and tissue repair in a rat model of VVC. Following rhIFNα-2b treatment, the negative pathogen conversion rate reached 50.0% (3/6). Although rhIFNα-2b exhibited a limited ability to decrease inflammation and injury progression (P > 0.05), the Flameng mitochondrial injury scores were significantly reduced (P < 0.001) compared with those of the Model rats. After rhIFNα-2b treatment, the levels of IFN-γ and epithelial-derived IgG (tested by RP215) in vaginal tissues were significantly increased with those in the Control and Model groups (both P < 0.001), while there were no significant differences in the levels of IL-4 and IL-17 (P > 0.05). This is the first study to address the efficacy of rhIFNα-2b in treating VVC in a rat model, providing a theoretical basis for development of this promising treatment for clinical use.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis, Vulvovaginal; Cytokines; Disease Models, Animal; Epithelial Cells; Female; Humans; Immunoglobulin G; Inflammation; Interferon alpha-2; Interferon Type I; Interleukin-17; Interleukin-4; Nystatin; Rats; Rats, Sprague-Dawley; Vagina

Chronic, non-healing wounds are often characterised by an excessive, and detrimental, inflammatory response. We review our experience of using a combined topical steroid, antibiotic and antifungal preparation in the treatment of chronic wounds displaying abnormal and excessive inflammation.. A retrospective review was undertaken of all patients being treated with a topical preparation containing a steroid (clobetasone butyrate 0.05%), antibiotic and antifungal at a tertiary wound healing centre over a ten-year period. Patients were selected as the primary treating physician felt the wounds were displaying excessive inflammation. Healing rates were calculated for before and during this treatment period for each patient. Changes in symptom burden (pain, odour and exudate levels) following topical application were also calculated.. Overall, 34 ulcers were identified from 25 individual patients (mean age: 65 years, range: 37-97 years) and 331 clinic visits were analysed, spanning a total time of 14,670 days (7,721 days 'before treatment' time, 6,949 days 'during treatment' time). Following treatment, 24 ulcers demonstrated faster rates of healing, 3 ulcers showed no significant change in healing rates and 7 were healing more slowly (p=0.0006). Treatment generally reduced the burden of pain and exudate, without affecting odour.. In normal wound healing, inflammation represents a transient but essential phase of tissue repair. In selected cases, direct application of a steroid containing agent has been shown to improve healing rates, presumably by curtailing this phase. Further evaluation is required to establish the role of preparations containing topical steroids without antimicrobials in the management of chronic wounds.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Chronic Disease; Clobetasol; Drug Combinations; Female; Glucocorticoids; Humans; Inflammation; Male; Middle Aged; Nystatin; Ointments; Oxytetracycline; Retrospective Studies; Wound Healing

In cystic fibrosis (CF), the absence of functional CFTR leads to dysregulated Na(+) absorption across airway epithelia. We established an in vitro model of dysregulated Na(+) absorption by treating polarized normal human bronchial epithelial cells (HBEs) with nystatin (Nys), a polyene antibiotic that enables monovalent cations to permeate biological membranes. Acute mucosal Nys produced a rapid increase in short circuit current (I(sc)) that reflected increased transepithelial Na(+) absorption and required Na(+)/K(+)ATPase activity. The acute increase in I(sc) was associated with increased mucosal liquid absorption. Prolonged mucosal Nys treatment resulted in sustained Na(+) hyperabsorption, associated with increased mucosal liquid absorption in comparison with naïve (nontreated, kept under air-liquid interface conditions) or vehicle-treated cultures. Nys treatment was not toxic. Increased lactate accumulation in Nys-treated culture media suggested a higher metabolic rate associated with the higher energy demand for Na(+) transport. After chronic Nys treatment, the increased I(sc) was rapidly lost when the cultures were mounted in Ussing chambers, indicating that Nys could be rapidly removed from the apical membrane. Importantly, chronic Nys treatment promoted sustained mucosal liquid depletion and caused mucus dehydration, compaction, and adhesion to the apical surface of Nys-treated cultures. We conclude that mucosal Nys treatment of HBEs provides a simple in vitro model to recapitulate the Na(+) and volume hyperabsorptive features of CF airway epithelia.

Topics: Absorption; Biological Transport; Cell Membrane Permeability; Cell Polarity; Cells, Cultured; Dehydration; Electric Conductivity; Epithelial Cells; Gene Expression Regulation; Humans; Inflammation; Lactic Acid; Models, Biological; Mucous Membrane; Nystatin; Organ Size; Respiratory System; RNA, Messenger; Serous Membrane; Sodium; Sodium-Potassium-Exchanging ATPase

Sepsis, an overwhelming inflammatory response to infection, is a major cause of morbidity and mortality worldwide and has no specific therapy. Phospholipid metabolites, such as lysophospholipids, have been shown to regulate inflammatory responses in sepsis, although their mechanism of action is not well understood. The phospholipid-metabolizing enzymes, lysophospholipid acyltransferases, control membrane phospholipid composition, function, and the inflammatory responses of innate immune cells. Here, we show that lysophosphatidylcholine acyltransferase (LPCAT) regulates inflammatory responses to LPS and other microbial stimuli. Specific inhibition of LPCAT down-regulated inflammatory cytokine production in monocytes and epithelial cells by preventing translocation of TLR4 into membrane lipid raft domains. Our observations demonstrate a new regulatory mechanism that facilitates the innate immune responses to microbial molecular patterns and provide a basis for the anti-inflammatory activity observed in many phospholipid metabolites. This provides the possibility of the development of new classes of anti-inflammatory and antisepsis agents.

Topics: 1-Acylglycerophosphocholine O-Acyltransferase; Cell Line; Cell Membrane; Down-Regulation; Enzyme Inhibitors; Humans; Inflammation; Lipopolysaccharides; Lysophospholipids; Membrane Microdomains; Nystatin; Protein Transport; Pyridines; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Nystatin is an antifungal compound with potent proinflammatory properties. Herein, we demonstrate that nystatin induces interleukin (IL)-1beta, IL-8, and tumor necrosis factor alpha secretion through its activation of toll-like receptor 1 (TLR1) and TLR2. Hence, a TLR-dependent mechanism could serve as the molecular basis for the proinflammatory properties of nystatin.

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Cell Line; Cytokines; Humans; Inflammation; Interleukin-1; Interleukin-8; Membrane Glycoproteins; Nystatin; Receptors, Cell Surface; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptors; Tumor Necrosis Factor-alpha

The anti-inflammatory effect of Arnica montana 6cH was evaluated using acute and chronic inflammation models. In the acute, model, carrageenin-induced rat paw oedema, the group treated with Arnica montana 6cH showed 30% inhibition compared to control (P < 0.05). Treatment with Arnica 6cH, 30 min prior to carrageenin, did not produce any inhibition of the inflammatory process. In the chronic model, Nystatin-induced oedema, the group treated 3 days previously with Arnica montana 6cH had reduced inflammation 6 h after the inflammatory agent was applied (P < 0.05). When treatment was given 6 h after Nystatin treatment, there was no significant inhibitory effect. In a model based on histamine-induced increase of vascular permeability, pretreatment with Arnica montana 6cH blocked the action of histamine in increasing vascular permeability.

Topics: Acute Disease; Analysis of Variance; Animals; Anti-Inflammatory Agents; Arnica; Carrageenan; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Foot Diseases; Granulation Tissue; Inflammation; Male; Nystatin; Phytotherapy; Plant Extracts; Random Allocation; Rats; Rats, Wistar; Time Factors

Expediency was studied of use of the drug terginan in a combined treatment of uterine neck pathologies in patients presenting with local inflammatory processes. The drug was found to be capable of dispelling an unspecific inflammatory process, normalizing the vaginal microbe landscape, promoting the postcryodestruction epithelization processes as evidenced by the analysis of the results obtained.

Topics: Adult; Anti-Inflammatory Agents; Bacterial Infections; Drug Combinations; Female; Humans; Inflammation; Male; Neomycin; Nystatin; Prednisolone; Uterine Cervical Diseases

Biological rhythms are detected in a variety of physiological and pathological conditions in man and animals, such as rheumatoid arthritis and asthma. Here we describe a circadian rhythm in experimental infectious and non-infectious granuloma. After 30 days of BCG (Bacillus Calmette-Guerin) or nystatin inoculation in the left hind foot of C57B1/6 mice, there is an oscillation with a period of approximately 24 hr in the variation of paw thickness, indicating a circadian rhythm. The acrophase occurred during the light phase, between 9:00 and 13:00 hr, while the nadir occurred in the dark phase, between 21:00 and 01:00 hr. The vascular permeability around the granulomatous lesions was higher at 12:00 hr than at 24:00 hr. This is in agreement with the observation that the thickness of a paw with granulomatous lesion is larger during the light phase. This rhythmic variation was eliminated by either pinealectomy or superior cervical ganglionectomy, which greatly reduce melatonin levels in the blood. Nocturnal replacement of melatonin in pinealectomized mice led to the re-establishment of the circadian rhythm. Thus, the rhythm of the granulomatous lesion is due to the rhythmic melatonin release by the pineal gland. This approach opens new questions regarding the modulation of chronic inflammation in inflammatory diseases that present rhythmic symptoms throughout the day.

Topics: Animals; Antioxidants; Capillary Permeability; Circadian Rhythm; Ganglionectomy; Granuloma; Inflammation; Male; Melatonin; Mice; Mice, Inbred C57BL; Mycobacterium bovis; Nystatin; Pineal Gland; Superior Cervical Ganglion

1. We investigated the effect of a persistent carrageenin- or nystatin-induced inflammatory reaction on heterotopic ossification produced by the subcutaneous implant of a demineralized bone matrix in female Swiss mice (25 to 35 g). 2. Subcutaneous carrageenin injection (0.3 ml of a 2% solution in saline) into mice induced an inflammatory reaction characterized by a mature granuloma predominantly of macrophages containing particles of the irritant in their cytoplasm and which remained unchanged until the end of the experiment (40th day). 3. Subcutaneous nystatin inoculation (30,000 IU in 0.3 ml saline) induced an inflammatory reaction consisting initially of macrophages (4th day) but later turning into an epithelioid granuloma (7th day) consisting predominantly of epithelioid cells and which was present up to the 21st day when it was gradually replaced by adipocytes up to the 30th day. 4. An intramuscular implant of demineralized bone matrix (DBM, approximately 10 mg) induced the formation of cartilage and bone tissue and of hemopoietic bone marrow (heterotopic ossification) in 100% of the control animals (N = 5). An intramuscular DBM implant in animals that received carrageenin (N = 19) or nystatin (N = 21) induced heterotopic ossification in 100 and 57% (P < 0.01) of the animals, respectively. 5. The response to a dorsal subcutaneous DBM implant was essentially negative in control animals (N = 5), whereas implants performed near the site injected with carrageenin (N = 28) or nystatin (N = 31) produced a response in 71 (P < 0.01) and 36% (P < 0.01) of the animals, respectively. A DBM implant into the contralateral (control) dorsal subcutaneous tissue of the same animals that received carrageenin (N = 25) or nystatin (N = 29) resulted in heterotopic ossification in 64 (P < 0.01) and 7% of the animals, respectively. 6. The results suggest that the macrophages present in the mature granuloma induced by carrageenin somehow favored the development of metaplastic plates after subcutaneous DBM implant and that this effect may be systemic since the same response was observed in contralateral subcutaneous tissue.

Topics: Animals; Bone Matrix; Carrageenan; Female; Inflammation; Macrophages; Male; Mice; Nystatin; Ossification, Heterotopic; Time Factors

An isoproterenol-induced chloride current has been detected in ventricular myocytes from guinea pig and rabbit but has not been found in canine ventricular cells. This investigation was undertaken to determine whether canine atrial cells possessed such a current. Steady-state currents were examined with potassium currents blocked by cesium. In whole-cell patch-clamp experiments, an isoproterenol-induced chloride current could not be detected shortly after patch rupture. However, whole-cell current in the absence of isoproterenol increased over time after patch rupture. The spontaneously activating steady-state current was outwardly rectifying with a reversal potential of approximately -25 mV. The current that developed over time was sensitive to variation in extracellular chloride concentration and was partially blocked by anthracene-9-carboxylic acid. Isoproterenol could enhance the amplitude of this current once it developed. Although isosmotic pipette filling and extracellular solutions were used, cell swelling was found to be the cause of the increase in whole-cell conductance that was observed during whole-cell patch-clamp experiments. The development of the current and the associated cell swelling could be prevented with the addition of 50-75 mM mannitol to the extracellular solution. The current could be observed in perforated patch recordings with nystatin when extracellular osmolarity was low (221 mosm/kg) but not when the extracellular solution was isosmotic (293 mosm/kg). Cardiac chloride currents have the potential to depolarize the resting membrane potential and cause abnormal automaticity. Chloride currents can also decrease the refractory period through a reduction in action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Function; Chlorides; Cytological Techniques; Dogs; Electrophysiology; Heart Atria; In Vitro Techniques; Inflammation; Isoproterenol; Mannitol; Membrane Potentials; Myocarditis; Nystatin; Osmolar Concentration

We investigated the effect of the administration of rat parathyroid hormone-(1-34) on acute or chronic inflammatory processes in different experimental animal models. Fragment 1-34 of parathyroid hormone had an inhibitory effect in all inflammatory acute tests. The dose-response experiments showed that the maximal anti-inflammatory and anti-exudative effects appeared at the dose of 3.30 and 0.33 micrograms/kg, respectively. The anti-inflammatory effect was observed in the first phase of the inflammatory process. In the carrageenin-induced edema test the anti-inflammatory activity began to decline after 180 min. In contrast, this peptide was inactive in the inflammatory chronic test we used.

Topics: Acetates; Acetic Acid; Animals; Carrageenan; Edema; Inflammation; Male; Nystatin; Parathyroid Hormone; Peptide Fragments; Peritonitis; Rats; Rats, Inbred Strains; Serotonin; Substance P; Teriparatide

1. After inflammation was induced in the foot-pad of rats with nistatin or BCG, injection of "non-activated" homologous plasma at the inflamed site caused a significant increase in the vascular permeability of the lesions (Evans blue test), which was more intense in older lesions, increasing from 7.83 +/- 1.11 to 8.70 +/- 1.18 (nistatin, 4 and 21 days) and 7.30 +/- 0.66 to 7.54 +/- 0.80 (BCG, 4 and 21 days). 2. Steroidal (acetyltriamcinolone, 2 mg/kg) and non-steroidal (indomethacin, 25 mg/kg) [corrected] anti-inflammatory drugs markedly decreased this effect on 14-day old lesions induced by nistatin plus "non-activated" plasma (2.37 +/- 0.10 for acetyltriamcinolone treatment vs 8.15 +/- 1.22 for untreated animals; 3.34 +/- 0.41 for indomethacin treatment vs 8.15 +/- 1.22 for untreated animals) and BCG plus "non-activated" plasma (1.67 +/- 0.11 for acetyltriamcinolone treatment vs 10.27 +/- 0.52 for untreated animals; 5.87 +/- 0.35 for indomethacin treatment vs 9.14 +/- 0.23 for untreated animals). 3. These data suggest that an increase in exudation in chronic lesions might result in "reactivation" of the process as observed clinically, for example, in rheumatoid arthritis in man.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Capillary Permeability; Evans Blue; Female; Inflammation; Male; Mycobacterium bovis; Nystatin; Plasma; Rats; Rats, Inbred Strains; Steroids

ST 679 dose-dependently inhibited carrageenan-, concanavalin A-, and nystatin-induced oedema. Studies in rats with adjuvant arthritis showed that a long dosing regimen inhibited primary and secondary lesions. ST 679 was significantly active in reducing the severity of the already established disease and, when given in a short course at the time of adjuvant injection, permanently prevented the development of secondary lesions. Experimental allergic encephalomyelitis in guinea-pigs was not affected by ST 679.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Carrageenan; Concanavalin A; Dose-Response Relationship, Drug; Drug Administration Schedule; Edema; Female; Glycine; Inflammation; Nystatin; Pyrroles; Rats; Rats, Inbred Strains

In rats, the anti-inflammatory activity of parenteral S-adenosyl-L-methionine (SAMe) in carrageenin- and nystatin-induced oedemas and in carrageenin-induced pleurisy was tested. The capability of the drug to inhibit the production of PG-like material in sponge exudates and by peritoneal leukocytes during bacterial phagocytosis was also evaluated. Two of these experimental models were used to administer the compound by the oral route in order to see whether oral and injected SAMe had similar effects. The results obtained show that SAMe can exert anti-inflammatory activity by inhibiting the oedema and pleurisy in rats and PG-like material production in inflammatory exudates and in the phagocytosis process by leukocytes. The mechanism of action of SAMe is discussed.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Hydrocortisone; Indomethacin; Inflammation; Male; Nystatin; Pleurisy; Prostaglandins; Rats; Rats, Inbred Strains; S-Adenosylmethionine

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Experimental; Carrageenan; Copper; Edema; Inflammation; Mycobacterium tuberculosis; Nystatin; Rats

The effect of synthetic salmon calcitonin was studied on adjuvant arthritis, pertussis vaccine edema, tuberculin skin reaction, passive direct Arthus reaction and nystatin edema. The results show that calcitonin inhibits these inflammatory processes.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthus Reaction; Calcitonin; Dermatitis, Atopic; Disease Models, Animal; Edema; Inflammation; Nystatin; Pertussis Vaccine; Rats; Time Factors; Tuberculin

Cyclophosphamide (5 or 10 mg/kg p.o.) and Gold sodium thiomalate (0 or 40 mg/kg i.m.) inhibit after repeated administrations (5 days) all the phases of Nystatin edema, whereas a single administration is ineffective. D-Penicillamine (25 or 100 mg/kg p.9.) inhibits the early phases of Nystatin edema after a single administration whereas repeated administrations are almost ineffective. An early treatment with Cyclophosphamide (2.5 mg/kg p.o.) simply delays the appearance of the secondary lesions of adjuvant arthritis but inhibit the development of the primary lesions. A late treatment with Cyclophosphamide as both the types of treatment with Gold sodium thiomalate (10 mg/kg i.m.) are effective against primary and secondary lesions. The only effect of D-Penicillamine (50 mg/kg p.o.) in adjuvant arthritis is a significant increase of the intensity of secondary lesions during the late treatment. It is suggested that the anti-inflammatory activity of Cyclophosphamide does not depend exclusively upon its immunosuppressant activity and that D-Penicillamine is effective on some cell population committed in the inflammatory reactions.

Topics: Animals; Arthritis; Arthritis, Experimental; Cyclophosphamide; Disease Models, Animal; Female; Gold Sodium Thiomalate; Inflammation; Nystatin; Penicillamine; Rats; Time Factors

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Anti-Inflammatory Agents; Aspirin; Betamethasone; Carrageenan; Dexamethasone; Edema; Female; Glucuronidase; Hexosaminidases; Indomethacin; Inflammation; Lysosomes; Methotrexate; Nystatin; Phenylbutazone; Prednisolone; Rats; Time Factors

Topics: Animals; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Arthritis; Aspirin; Azathioprine; Chloramphenicol; Cyclophosphamide; Dexamethasone; Drug Antagonism; Edema; Hydrocortisone; Immunosuppressive Agents; Indomethacin; Inflammation; Male; Mefenamic Acid; Mercaptopurine; Nystatin; Phenylacetates; Phenylbutazone; Prednisolone; Rats; Rifampin; Triamcinolone

Topics: Animals; Disease Models, Animal; Edema; Female; Inflammation; Nystatin; Rats

Topics: Aged; Candida; Candidiasis, Oral; Cheilitis; Denture Bases; Denture Retention; Denture, Complete, Upper; Female; Humans; Inflammation; Male; Middle Aged; Mouth; Mouth Mucosa; Nystatin; Oral Health; Saliva; Stomatitis; Vertical Dimension; Vitamin B Deficiency