ascorbic-acid and Hemorrhage

The World Health Organization set the recommended daily vitamin C intake, henceforth referred to as ascorbic acid (AA), on the basis of scurvy prevention. Double-blind AA depletion-repletion studies suggest that this recommended AA dose may be too low to prevent microvascular fragility.. (1) To conduct a systematic review and meta-analysis of controlled clinical trials on whether AA supplementation leads to a reduced gingival bleeding tendency, a manifestation of microvascular fragility; and (2) to relate AA plasma levels to retinal hemorrhaging, another manifestation of microvascular fragility.. Data were reviewed from 15 trials conducted in 6 countries with 1140 predominantly healthy participants with measures of gingival bleeding tendency, and from the National Health and Nutrition Examination Survey (NHANES) III of 8210 US residents with measures of retinal hemorrhaging.. In clinical trials, AA supplementation reduced gingival bleeding tendency when estimated baseline AA plasma levels were < 28 μmol/L (standardized mean difference [SMD], -0.83; 95%CI, -1.16 to -0.49; P < 0.002). Supplementation with AA did not unequivocally reduce gingival bleeding tendency when baseline estimated AA plasma levels were >48  μmol/L or unknown (respective standardized mean differences: -0.23, 95%CI, -0.45 to -0.01, P < 0.05; and -0.56; 95%CI: -1.19 to 0.06, P < 0.08). In NHANES III, prevalence of both retinal hemorrhaging and gingival bleeding tendency increased when AA plasma levels were within the range that protects against scurvy (11-28 μmol/L; respective prevalence ratios adjusted for age and sex: 1.47; 95%CI: 1.22-1.77; and 1.64; 95%CI: 1.32-2.03; P < 0.001 for both).. Consistent evidence from controlled clinical trials indicates that setting human AA requirements based on scurvy prevention leads to AA plasma levels that may be too low to prevent an increased gingival bleeding tendency. Gingival bleeding tendency and retinal hemorrhaging coincide with low AA plasma levels and thus may be reflective of a systemic microvascular pathology that is reversible with an increased daily AA intake.

Topics: Ascorbic Acid; Gingiva; Hemorrhage; Humans; Nutrition Surveys; Randomized Controlled Trials as Topic

Topics: Antioxidants; Ascorbic Acid; Burns; Hemorrhage; Humans; Sepsis; Wounds and Injuries

Topics: Animals; Ascorbic Acid; Child; Female; Gingival Diseases; Hemorrhage; Humans; Infant; Joint Diseases; Nutritional Requirements; Scurvy

Topics: Adult; Age Factors; Anemia; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Diseases, Developmental; Capillaries; Child; Collagen Diseases; Connective Tissue; Creatinine; Dentin; Gingival Hemorrhage; Hemorrhage; Humans; Hydroxyproline; Infant; Scurvy; Skin Diseases; Species Specificity

Topics: Acid-Base Equilibrium; Adaptation, Psychological; Ascorbic Acid; Dermatitis; Follow-Up Studies; Hemorrhage; Humans; Hydrogen-Ion Concentration; Ileum; Postoperative Care; Postoperative Complications; Surgical Wound Dehiscence; Surgical Wound Infection; Urinary Catheterization; Urinary Diversion

Topics: Adult; Ascorbic Acid; Flavonoids; Hemorrhage; Hemostasis; Humans; Male; Prothrombin; Vitamin K; Vitamin K Deficiency; Vitamins

Previous studies mentioned the beneficial effects of vitamin C on the hemorrhage and wound healing. We evaluated the effects of vitamin C on the hemorrhage, hemoglobin concentration, and wound complications in total abdominal hysterectomy.. In this randomized, double-blind, placebo-controlled trial, 80 patients with total abdominal hysterectomy were randomly divided into the study and control groups to receive either intravenous 2 g of vitamin C in normal saline or solely normal saline therapy. The first 1-g dose of ascorbic acid was administrated the night before surgery, and the second 1 g was administrated during surgery.. The mean age of the participants was 37.8 ± 4.8 years with a mean preoperative plasma vitamin C concentration of 5.07 ± 2.1 mg/dL, close to the subclinical deficiency. The basal characteristics of both groups were the same. The hemorrhage volume was slightly higher in the control group (345.2 ± 31.8 ml vs. 388.1 ± 28.3 ml, P < 0.001).. Intravenous vitamin C administration had a positive effect on reducing hemorrhage during total abdominal hysterectomy.. Clinicaltrials.gov.identifier: NCT03965637.

Topics: Adult; Ascorbic Acid; Female; Hemorrhage; Humans; Hysterectomy; Prospective Studies; Saline Solution; Vitamins

Vitamin C is an immune-relevant micronutrient, which is depleted in viral infections and this deficiency seems to play a critical role in the pathogenesis of herpes infections and in the development of postherpetic neuralgia. The objective of this observational multicenter study was to evaluate the utilization, safety and efficacy of intravenously administrated vitamin C in patients with shingles.. Between April 2009 and December 2010 16 general practitioners recorded data of 67 participants with symptomatic herpes zoster who received vitamin C intravenously (Pascorbin® 7.5 g/50 ml) for approximately 2 weeks in addition to standard treatment. The assessment of pain (VAS) and the dermatologic symptoms of shingles such as hemorrhagic lesions and the number of efflorescences were investigated in a follow-up observation phase of up to 12 weeks.. Mean declines of pain scores (VAS), number of affected dermatomes and efflorescences, and the presence of hemorrhagic vesicles between the baseline and follow-up assessments at 2 and 12 weeks were statistically significant. Overall, 6.4% of the participants experienced post-herpetic neuralgia. Common complaints such as general fatigue and impaired concentration also improved during the study. The effects and the tolerability of the treatment were evaluated positively by the physicians. The risk of developing PHN was reduced.. The data presented here provide evidence that concomitant use of intravenously administered ascorbic acid may have beneficial effects on herpes zoster-associated pain, dermatologic findings and accompanying common complaints. To confirm our findings, randomized, placebo-controlled clinical studies are necessary.

Topics: Ascorbic Acid; Attention; Fatigue; Female; Hemorrhage; Herpes Zoster; Herpesvirus 3, Human; Humans; Injections, Intravenous; Male; Middle Aged; Pain Measurement; Prospective Studies; Treatment Outcome

Topics: Adult; Ascorbic Acid; Carbon Isotopes; Clinical Trials as Topic; Diet; Electrocardiography; Electroencephalography; Enteral Nutrition; Eye Diseases; Feces; Glucose Tolerance Test; Hematology; Hemorrhage; Humans; Keratosis; Male; Nutritional Physiological Phenomena; Nutritional Requirements; Oral Hemorrhage; Scurvy; Skin Diseases; Urine

Topics: Ascorbic Acid; Hematemesis; Hemorrhage; Humans; Scurvy

Scurvy is a rare entity in developed countries and the diagnosis may often be delayed resulting in unnecessary investigations and/or potentially severe complications. A recent increase in the number of patients diagnosed with scurvy in our hematology clinics indicated the need to review the literature on the diagnosis and optimal management of similar patients.. We conducted a retrospective chart review of patients referred to hematology at our tertiary care centre between 2010 and 2018, who were ultimately diagnosed with scurvy. Data collected from electronic medical records included baseline characteristics, clinical features on presentation, bloodwork results from initial consultation, treatment plan as well as response to treatment.. Twenty-two adults patient had a diagnosis of scurvy with a mean vitamin C level of 6 μmol/L. Iron deficiency anemia (54%) and gastrointestinal disorders (54%) were the most common comorbidities noted in our cohort. Proton-pump inhibitors use was noted in 54% of patients. Bleeding (45%) and bruising (45%) were the most commonly reported clinical features. Eleven patients received oral supplementation, five had intravenous (IV) vitamin C and six were not treated. Two patients required a transition from oral to IV supplementation. Vitamin C dosing ranged between 250 and 2000 mg and the frequency varied from daily for oral therapy to every few weeks or months for IV.. Awareness of scurvy and its associated risk factors and clinical presentation is important in the evaluation of a patient with bleeding tendency. Treatment plan should be individualized, and a careful review of patients' diet, medial history and medications is warranted.

Topics: Adult; Ascorbic Acid; Contusions; Diet; Hemorrhage; Humans; Medical History Taking; Precision Medicine; Proton Pump Inhibitors; Retrospective Studies; Scurvy

Topics: Adolescent; Ascorbic Acid; Chest Pain; Cholecalciferol; Dietary Supplements; Echocardiography; Gingiva; Hemorrhage; Humans; Hypertension, Pulmonary; Iron; Leg; Male; Pain; Scurvy; Wounds and Injuries

Endosulfan, a chlorinated hydrocarbon insecticide/acaricide, is a member of a cyclodiene sub-group of poisons to a wide variety of insects and mites. It is also toxic to humans and animals, but there is limited knowledge about endosulfan-related splenic and overall immunotoxicity. The aim of this study was to review pathological findings of endosulfan toxicity in the spleen and to examine potential protective effects of the anti-oxidant Vitamin C (Vit C). Here, after 6-week exposures, the spleens of New Zealand White rabbits were examined grossly and histopathologically and tissue caspase-3 activity was assessed immunohistochemically. Rabbits in four groups were used: Group END were given by oral gavage a sub-lethal dose of endosulfan (1 mg/kg) in corn oil daily for 6 weeks; Group END + C received the same dose of endosulfan daily and Vit C (20 mg/kg) every other day by gavage during this period; Group Vit C received oral corn oil daily and 20 mg/kg Vit C every other day; and Group OIL received corn oil daily for 6 weeks. Analyses of the tissues collected 1 week after the final dosing revealed lymphocyte depletion and necrosis in spleens of the hosts that received the pesticide (END only and END + C); hemorrhage and slight neutrophilic infiltration was also noted. Caspase-3 immunoreactivity was marked in lymphocytes in all spleens of rabbits in both END groups. Overall, these toxicities were mitigated by Vit C co-treatment; in END + C hosts, markedly decreased depletion of lymphocytes, inflammation and caspase-3 immunoreactivity were observed. However, even with mitigation, the level of toxicity present was still greater than any seen in the spleens of hosts that received OIL or Vit C alone. These results revealed endosulfan could cause toxicity in the rabbit spleen, characterized by depletion of lymphocytes, inflammation, necrosis and hemorrhage, and that this toxicity could begin to be mitigated by Vit C co-treatment.

Topics: Animals; Antioxidants; Ascorbic Acid; Caspase 3; Endosulfan; Hemorrhage; Immunohistochemistry; Inflammation; Lymphocytes; Necrosis; Neutrophil Infiltration; Pesticides; Rabbits; Spleen

To investigate the roles of epithelial-dendritic cell transformation (EDT) characterized by the expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in the occurrence of tissue inflammation induced by hemorrhagic hypotension (HH), the protective effect of vitamin C (VitC), and the potential mechanisms.. We conducted an in vitro study using the rat intestinal epithelial cells (IEC-6). After hypoxic culture with or without VitC for 2, 6, 24, and 48 h (n = 3 per group), the expression levels of DC-SIGN, E-cadherin, and Glycogen synthase kinase-3β-S9 (GSK-3β-S9) in IEC-6 cells, IL-1β, and IL-6 concentrations in the cell culture medium were measured. To investigate the potential mechanism, we inhibited E-cadherin expression by siRNA and GSK-3β activity by TDZD-8, respectively. The in vivo study was conducted by establishing SD rat HH model. We observed the expression levels and location of DC-SIGN in the intestines. We also showed histological damage, TNF-α and IL-6 concentrations, and organ injury scores at 2, 6, and 24 h after HH (n = 6 per group), with or without VitC pretreatment.. Hypoxia-induced DC-SIGN expression in IEC-6 cells in a time-dependent manner and the inflammatory factors were also increased. VitC inhibited all these phenomena. Hypoxia inhibited GSK-3β activity and E-cadherin expression. VitC could ease these inhibitions. The inhibitory effect of VitC on DC-SIGN was diminished when E-cadherin expression was inhibited in advance. TDZD-8 diminished the protective effect of VitC on E-cadherin and abolished inhibitory effect of VitC on DC-SIGN expression. HH-induced DC-SIGN expression in rat intestine epithelial cells and the histological damage scores and pro-inflammatory cytokine levels were also increased.. HH induces EDT in rat intestine epithelial cells. VitC maintains GSK-3β activity, attenuates the suppression of E-cadherin caused by hypoxia, and ultimately decreases DC-SIGN expression.

Topics: Animals; Ascorbic Acid; Cadherins; Cell Adhesion Molecules; Cell Hypoxia; Cell Transdifferentiation; Cells, Cultured; Dendritic Cells; Epithelial Cells; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hemodynamics; Hemorrhage; Hypotension; Inflammation Mediators; Intestinal Mucosa; Lectins, C-Type; Male; Rats, Sprague-Dawley; Receptors, Cell Surface; Resuscitation; Systemic Inflammatory Response Syndrome

Scurvy results from a dietary deficiency of vitamin C (ascorbic acid) and is rarely thought of in modern day medicine. It now almost always occurs in pediatric patients with behavioral diagnoses, nutritionally restricted diets, and food allergies. Symptoms of scurvy include ecchymoses, bleeding gums, and arthralgias. Here, we present a 17-year-old male with autism spectrum disorder and a diet severely deficient in ascorbic acid due to textural aversion and food preferences. He presented with recurrent arthritis, hemarthrosis, bruising, and anemia. His vitamin C level was low, and his symptoms improved promptly after treatment with ascorbic acid.

Topics: Adolescent; Ascorbic Acid; Autism Spectrum Disorder; Hemorrhage; Humans; Male; Scurvy

Dysfunctional inflammation following traumatic hemorrhage can lead to multiple-organ failure and death. In our polytrauma swine model, lyophilized plasma (LP) reconstituted with sterile water and ascorbic acid suppressed systemic inflammation and attenuated DNA damage. However, it remains unknown whether the inflammatory response is affected by the type of fluid used to reconstitute LP. We hypothesized that common resuscitation fluids such as normal saline (LP-NS), lactated Ringer's solution (LP-LR), Hextend (LP-HX), or sterile water (LP-SW) would yield similar inflammation profiles and DNA damage following LP reconstitution and transfusion.. This was a randomized, prospective, blinded animal study. LP was reconstituted to 50% of original volume with NS, LR, HX, or SW buffered with 15-mM ascorbic acid. Forty swine were subjected to a validated model of polytrauma, hemorrhagic shock, and Grade V liver injury and resuscitated with LP. Serum interleukin 6 (IL-6), IL-10, plasma C-reactive protein, and 8-hydroxy-2-deoxyguanosine concentrations were assessed for systemic inflammation and DNA damage at baseline, 2 hours, and 4 hours following liver injury. Lung inflammation was evaluated by Real Time Polymerize Chain Reaction (RT-PCR).. Reconstituted LP pH was similar between groups before resuscitation. IL-6 and IL-10 increased at 2 hours and 4 hours compared with baseline in all groups (p < 0.017). DNA damage increased at 2 hours and 4 hours compared with baseline and from 2 hours to 4 hours in the LP-NS, LP-LR, and LP-SW groups (all p < 0.017). Animals resuscitated with LP-HX not only demonstrated increased DNA damage at 4 hours versus baseline but also had the lowest C-reactive protein level at 2 hours and 4-hours (p < 0.017). Overall, differences between groups were similar for DNA damage and lung inflammation.. Reconstitution fluid type does not affect inflammatory cytokine profiles or DNA damage following LP transfusion in this swine polytrauma model. Based on universal availability, these data suggest that sterile water is the most logical choice for LP reconstitution in humans.. Prognostic, level II.

Topics: Animals; Antioxidants; Ascorbic Acid; C-Reactive Protein; Disease Models, Animal; DNA Damage; Female; Femoral Fractures; Fluid Therapy; Freeze Drying; Hemorrhage; Hydrogen-Ion Concentration; Inflammation; Liver; Lung; Oxidative Stress; Plasma; Prospective Studies; Random Allocation; Real-Time Polymerase Chain Reaction; Swine; Water

Traumatic brain injury (TBI) and hemorrhagic shock (HS) can be associated with coagulopathy and inflammation, but the mechanisms are poorly understood. We hypothesized that a combination of TBI and HS would disturb coagulation, damage the endothelium, and activate inflammatory and complement systems.. A total of 33 swine were allocated to either TBI + HS (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation). TBI + HS animals were left hypotensive (mean arterial pressure, 30-35 mm Hg) for 2 hours. Blood samples were drawn at baseline, 3 minutes and 15 minutes after injury, as well as following 2 hours of hypotension. Markers of coagulation, anticoagulation, endothelial activation/glycocalyx shedding, inflammation, complement, and sympathoadrenal function were measured.. The TBI + HS group demonstrated an immediate (3 minutes after injury) activation of coagulation (prothrombin fragment 1 + 2, 289 ng/mL vs. 232 ng/mL, p = 0.03) and complement (C5a, 2.83 ng/mL vs. 2.05 ng/mL, p = 0.05). Shedding of the endothelial glycocalyx (syndecan 1) was evident 15 minutes after injury (851.0 ng/ml vs. 715.5 ng/ml, p = 0.03) while inflammation (tumor necrosis factor α [TNF-α], 81.1 pg/mL vs. 50.8 pg/mL, p = 0.03) and activation of the protein C system (activated protein C, 56.7 ng/mL vs. 26.1 ng/mL, p = 0.01) were evident following the 2-hour hypotension phase.. The combination of TBI and shock results in an immediate activation of coagulation and complement systems with subsequent endothelial shedding, protein C activation, and inflammation.

Topics: Animals; Ascorbic Acid; Blood Coagulation Disorders; Brain Injuries; Complement Activation; Disease Models, Animal; Endothelium; Female; Fibrinolysis; Hemorrhage; Inflammation; Shock, Hemorrhagic; Swine

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

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

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

Topics: Ascorbic Acid; Hemorrhage; Humans; Meningitis, Meningococcal; Oxidative Stress; Scurvy

Diffuse hemorrhage in surgical patients with normal coagulation parameters may be caused by vitamin C deficiency and is rapidly reversed by vitamin C replacement.. Patients treated on a surgical service were entered into a clinical registry over a 12-month period if they experienced diffuse hemorrhage in the face of normal coagulation parameters and a plasma ascorbic acid level < 0.6 mg/dL (normal 0.6-2.0 mg/dL). Oral vitamin C replacement was administered after determination of plasma ascorbic acid level. Response to therapy, including subsequent bleeding events, need for blood transfusions, and demographic data including social and dietary history were retrospectively reviewed from hospital and outpatient clinic records.. Twelve patients with bleeding diatheses and low plasma ascorbic acid levels were identified. Plasma ascorbic acid levels were 0.1 to 0.5 mg/dL (mean, 0.3 mg/dL). There were 6 men and 6 women; age ranged from 46 to 90 years (mean, 78 years). Coagulation parameters were normal in all patients. Diffuse postoperative bleeding from nonsurgical causes was evident in 10 of 12 patients. Four patients, 2 of whom had operations, presented with chronic recurrent blood loss from the gastrointestinal tract. Each patient received 250 to 1000 mg of vitamin C replacement daily. Within 24 hours of vitamin C administration, there was no further evidence of clinical bleeding nor need for subsequent blood transfusions in any patient.. Vitamin C deficiency should be included in the differential diagnosis of nonspecific bleeding in surgical patients. Prolonged hospitalization, severe illness, and poor diet create vitamin C deficiency with significant clinical consequences. Oral vitamin C replacement rapidly reverses the effects of this disorder.

Topics: Abdomen; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Surgical Procedures; Diagnosis, Differential; Female; Hemorrhage; Humans; Male; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Retrospective Studies

The risk of vitamin C deficiency is underestimated in industrialized countries and is only disclosed in rare cases of severe scurvy.. We report three cases of scurvy presenting with ecchymotic purpura and hemorrhagic ulcerations of the lower limbs. Vitamin C supplementation led to rapid improvement of the skin lesions.. Clinical diagnosis of low-grade deficiency can be difficult. Biological diagnosis requires special care in sample taking and transport.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Diagnosis, Differential; Ecchymosis; Female; Hemorrhage; Humans; Leg Dermatoses; Leg Ulcer; Purpura; Risk Factors; Scurvy

Topics: Adult; Ascorbic Acid; Ecchymosis; Female; Fluvoxamine; Hemorrhage; Humans; Menorrhagia; Panic Disorder; Paroxetine

We report a case of scurvy, which is rarely encountered in Japan. A 75-year-old male was hospitalized with diffuse subcutaneous hemorrhaging of both feet, pain on walking, and shortness of breath. A remarkably low serum level of vitamin C was confirmed. Administration of ascorbic acid dramatically improved his clinical symptoms. Improvement paralleled the increase of serum vitamin C level. This case underscores the important role of vitamin C on the integrity function of the vessel wall.

Topics: Aged; Ascorbic Acid; Foot Diseases; Hemorrhage; Humans; Japan; Male; Pain; Scurvy; Skin

From a group of 118 patients with chronic idiopathic thrombocytopenic purpura (ITP), 43 were older than 60 years at diagnosis. In this report, we describe the clinical evolution and therapeutic response in young and old patients. The overal rate of hemorrhagic manifestations was similar in the two age groups, but a greater risk for severe bleeding was observed in elderly patients. There were no significant differences between old and young patients in response to steroids. In none of our patients was mortality associated with bleeding or side effects of the treatment. In conclusion, we have observed a more benign clinical course in elderly patients with chronic ITP as compared to previous reports.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Child; Child, Preschool; Combined Modality Therapy; Female; Follow-Up Studies; Hemorrhage; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Middle Aged; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Risk Factors; Splenectomy

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Hemophilia A; Hemorrhage; Humans

Antioxidants occasionally have become prooxidants when a large amount was ingested. The haemorrhagic toxicity of butylated hydroxytoluene, a synthetic antioxidant, may involve such a mechanism. This study investigated whether haemorrhage is induced by overdoses of tocopherols, beta-carotene, ubiquinone or L-ascorbic acid, which are representative biological antioxidants. Male Jcl:SD rats (six rats/group) were fed d-alpha, d-beta, d-gamma or d-delta-tocopherols, ubiquinone Q-10, beta-carotene or retinol acetate at a level of 0.5%, or L-ascorbic acid at 5% in the diet for 7 days. Only two rats given retinol acetate died with lung haemorrhages. Haemorrhages were observed in five or six, six, one, one, one or one of six surviving rats given d-alpha, d-beta or d-gamma-tocopherols, ubiquinone Q-10, beta-carotene or retinol acetate, respectively (except for a retinol group in which four rats survived). Major haemorrhages were noted in the epididymis. In the alpha-, beta- and gamma-tocopherol, ubiquinone Q-10, beta-carotene or retinol acetate-treated groups, prothrombin and kaoline-activated partial thromboplastin time indices were 26-28, 37, 59, 42, 63 and 65% or 27-28, 35, 65, 38, 59 and 28%, respectively, of the control values. Only the prothrombin index was significantly decreased to 67% in delta-tocopherol-administered rates, whereas controls and those receiving L-ascorbic acid showed no signs of bleeding or coagulation defect. The same tendency was also seen in the decreasing effect on vitamin K-dependent blood coagulation factors. These results suggest that the four naturally occurring tocopherols have a tendency to cause haemorrhage in the order of alpha > beta > gamma > delta, and ubiquinone Q-10 and beta-carotene als0o have relatively strong and weak haemorrhagic effects, respectively, with regard to prothrombin and partial thromboplastin time indices.

Topics: Adjuvants, Immunologic; Analysis of Variance; Animals; Anticarcinogenic Agents; Antineoplastic Agents; Ascorbic Acid; beta Carotene; Blood Coagulation; Carotenoids; Diterpenes; Epididymis; Exophthalmos; Eye; Hemorrhage; Male; Prothrombin Time; Rats; Rats, Sprague-Dawley; Retinyl Esters; Stereoisomerism; Thromboplastin; Ubiquinone; Vitamin A; Vitamin E

We report a 66 years-old man case that was admitted with abdominal wall hemorrhagic swelling ecchymosis on inferior extremities and perifollicular purpura with hyperkeratosis of the follicles, which gives it an appearance of palpable purpura, together with gingival hemorrhage and moderate anemia. He was a well-nourished sick man but who made a peculiar diet, practically free from fruit and vegetables which developed a pure and serious form of scurvy. We report this case because we consider that the features which appear are illustrative to provide the immediate clinical diagnosis of this uncommon disease, potentially mortal, but easy to diagnose, if we think about it in the adequate clinical contexts, and which it is quickly curable with the administration of ascorbic acid.

Topics: Abdominal Muscles; Aged; Ascorbic Acid; Avitaminosis; Ecchymosis; Feeding Behavior; Hematoma; Hemorrhage; Humans; Male; Scurvy

1. Single comb White Leghorn hens of an inbred line highly susceptible to fatty liver haemorrhagic syndrome (FLHS) were fed supplemented dietary ascorbic acid (200 mg/kg), alpha-tocopherol (75 mg/kg), or L-cysteine (3 g/kg, and 6 g/kg) for 28 d in order to evaluate the potential therapeutic effect of these compounds against the disease. 2. Supplementation of ascorbic acid, alpha-tocopherol, or a low level of L-cysteine (3 g/kg) did not significantly affect any of the hepatic variables evaluated. Hepatic glutathione was not increased by the supplementation of dietary L-cysteine. 3. L-cysteine supplemented at a level of 6 g/kg decreased hepatic dry matter and fat contents without affecting the hepatic malondialdehyde or the liver haemorrhagic score. 4. Because one of the predisposing factors of FLHS is a high hepatic fat content it was concluded that dietary supplementation of L-cysteine (6 g/kg) may be useful in the prevention of the disease.

Topics: Animals; Antioxidants; Ascorbic Acid; Chickens; Cysteine; Fatty Liver; Female; Food, Fortified; Glutathione; Hemorrhage; Liver; Oviposition; Poultry Diseases; Syndrome; Vitamin E

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

Hemorrhage within the central nervous system (CNS) may be associated with subsequent development of seizure states or paralysis. Prior investigations indicate that hemoglobin, released from extravasated erythrocytes, may be toxic to the CNS by promoting peroxidation of lipids and inhibition of Na,K-ATPase. These deleterious effects are blocked both in vitro and in vivo by the Fe3+ chelator, desferrioxamine, indicating the involvement of free iron derived from hemoglobin. We now report that the Fe2+ chelator, ferene, also inhibits methemoglobin- and ferric iron-mediated CNS lipid oxidation, reflecting the reduction of Fe3+ by some component of the CNS. This reduction is apparent in the accumulation of the highly chromophoric ferene: Fe2+ chelate after the addition of Fe3+ salts to supernatants of murine brain homogenates. Because large amounts of ascorbic acid occur in mammalian CNS, we suspected that this reducing substance might be responsible. Indeed, the peroxidative effects of hemoglobin and iron on murine brain are blocked by washing of CNS membranes or by preincubation of crude homogenates with ascorbate oxidase. Furthermore, the addition of ascorbate to washed CNS membranes fully restores hemoglobin/iron-driven peroxidation. We conclude that posthemorrhagic CNS dysfunction may stem from damaging redox reactions between hemoglobin iron, ascorbic acid, and oxidizable components of the nervous system.

Topics: Animals; Ascorbic Acid; Brain; Cerebrovascular Circulation; Deferoxamine; Hemoglobins; Hemorrhage; Lipid Peroxides; Male; Mice; Oxidation-Reduction; Sodium-Potassium-Exchanging ATPase; Thiobarbiturates

Topics: Adult; Ascorbic Acid; Gingiva; Half-Life; Hemorrhage; Humans; Male

Concentrations of histamine and total ascorbic acid (L-ascorbic acid plus dehydroascorbic acid) in the antecubital vein blood of women in abruptio placentae (normally situated placentae) and placenta praevia have been measured. The results show that blood ascorbic acid in abruptio placentae is significantly (P less than 0.05) lower than the values found in placenta praevia. This may reflect impaired absorption and/or increased breakdown of ascorbic acid in abruptio placentae. Histamine levels in the two conditions are similar to one another.

Topics: Abruptio Placentae; Adult; Ascorbic Acid; Female; Hemorrhage; Histamine; Humans; Placenta Diseases; Placenta Previa; Pregnancy; Pregnancy Trimester, Third

A 9-year-old girl had the insidious development of lethargy, gingival erosions, and follicular hyperkeratosis with perifollicular hemorrhage. A dietary history disclosed that she consumed only one kind of sandwich and beverage and took no other foods. A skin biopsy specimen was consistent with the diagnosis of scurvy, and marked improvement occurred with ascorbic acid therapy. Although it is an uncommon disorder in the United States, scurvy may occur in persons with prolonged and peculiar dietary habits.

Topics: Ascorbic Acid; Child; Feeding Behavior; Female; Folliculitis; Gingiva; Gingivitis; Hemorrhage; Humans; Keratosis; Leg; Scurvy

Topics: Ascorbic Acid; Blood Platelet Disorders; Female; Hemorrhage; Humans; Middle Aged; Renal Dialysis; Scurvy

Topics: Adolescent; Adult; Anemia, Hypochromic; Ascorbic Acid; Female; Free Radicals; Hemorrhage; Humans; Male; Middle Aged; Niacinamide; Pyridoxine; Riboflavin; Thiamine; Vitamin B Complex

The hematic level of ascorbic acid was significantly lower with respect to that of healthy subjects in 55 patients with hemorrhagic ocular diseases. Experiments on albino guinea pigs showed that an induced hypovitaminosis C (2 weeks of scorbutigenic diet followed by a maintenance dose of 0,5 mg of ascorbic acid) caused the appearance of widespread retina hemorrhages and a significant decrease of the blood ascorbate levels with respect to the control groups. The present results suggest that a prolonged insufficient dietary intake of ascorbic acid may give rise to hemorrhagic ocular pathologies in humans.

Topics: Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Eye Diseases; Female; Guinea Pigs; Hemorrhage; Humans; Male; Middle Aged

Navel bleeding of newborn piglets was completely prevented by dosing the pregnant sows with ascorbic acid. The coagulation defect appeared to be caused by immature collagen which did not efficiently induce platelet plug formation. It seems that piglets depend upon their dams for their supply of vitamin C.

Topics: Administration, Oral; Animals; Ascorbic Acid; Female; Hemorrhage; Pregnancy; Swine; Swine Diseases; Time Factors; Umbilical Cord

Topics: Administration, Oral; Anemia, Hypochromic; Animals; Ascorbic Acid; Biological Transport; Body Weight; Diet; Erythropoietin; Female; Genetic Linkage; Hematocrit; Hemorrhage; Hypoxia; Injections, Intraperitoneal; Intestinal Absorption; Iron; Iron Radioisotopes; Male; Mice; Mice, Inbred Strains; Phenobarbital; Sex Chromosomes; Statistics as Topic

Topics: Administration, Oral; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Body Weight; Guinea Pigs; Hemorrhage; Hindlimb; Injections, Intraperitoneal; Joints; Liver; Male; Ribs; Scurvy; Structure-Activity Relationship; Sulfuric Acids

1. The rabbit rectum superfused with blood or Krebs solution was used to assay vasopressin in circulating blood and in plasma extracts respectively.2. Vasopressin was released by a rapid fall in diastolic pressure of as little as 5 mmHg, and the amount of vasopressin released was proportional to the magnitude of the fall in diastolic pressure in the range studied. These results would indicate that vasopressin release follows the magnitude of the fall in diastolic pressure more closely than the actual decrease in blood volume in haemorrhagic hypotension.3. It was shown that the time required to induce an increase in circulating vasopressin is inversely proportional to the severity of the fall in diastolic pressure; this suggested that the stimulation of neurosecretory reflex arc varies with the intensity of the stimulus.4. The slight changes in plasma renin activity as well as the pattern of renin release suggested the unlikeliness of the influence of renin upon vasopressin secretion under these circumstances. On the contrary, the results suggested that the secretion of large amounts of vasopressin tended to inhibit renin release.

Topics: Animals; Ascorbic Acid; Blood Circulation; Chickens; Colon; Dose-Response Relationship, Drug; Hemorrhage; In Vitro Techniques; Muscles; Oxytocin; Rabbits; Rats; Rectum; Renin; Time Factors; Vasopressins

Topics: Acute Disease; Adrenal Glands; Animals; Ascorbic Acid; Dextrans; Growth Hormone; Hemorrhage; Infusions, Parenteral; Rabbits

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Dicumarol; Factor VII; Glycine max; Hemorrhage; Hemostatics; Humans; Pedigree; Phospholipids; Plasma; Prothrombin; Prothrombin Time; Rabbits; Thrombocytopenia; Thromboplastin; Vitamin K; Vitamin K Deficiency

Topics: Adenine Nucleotides; Adenosine Diphosphate; Ascorbic Acid; Aspirin; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Cell Membrane; Collagen; Epinephrine; Glass; Hemorrhage; Humans; In Vitro Techniques; Kaolin; Platelet Adhesiveness; Temperature; Thrombin

Topics: Adult; Antigens; Ascorbic Acid; Blood Glucose; Blood Protein Disorders; Body Weight; Carbon Isotopes; Cholesterol; Diet Therapy; Epinephrine; Epithelium; Fatigue; Gingival Diseases; Hemorrhage; Humans; Immunization; Insulin; Joint Diseases; Keratosis; Lipids; Male; Middle Aged; Muscular Diseases; Nutritional Requirements; Pain; Plasma; Scurvy; Time Factors; Typhoid Fever; Water

Topics: Adrenal Glands; Animals; Ascorbic Acid; Corticosterone; Electricity; Hemorrhage; Male; Pituitary-Adrenal System; Rats; Sodium Chloride; Stress, Physiological; Warfarin

Topics: Aged; Ascorbic Acid; Biopsy; Blood Vessels; Capillaries; Collagen; Endoplasmic Reticulum; Fibroblasts; Hemorrhage; Humans; Lysosomes; Male; Microscopy, Electron; Scurvy; Skin

Topics: Ascorbic Acid; Child, Preschool; Epiphyses, Slipped; Female; Femur; Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Male; Radiography; Scurvy

Topics: Adult; Albinism; Ascorbic Acid; Blood Transfusion; Bone Marrow Diseases; Cytoplasmic Granules; Hemorrhage; Histocytochemistry; Humans; Male; Mononuclear Phagocyte System; Oral Hemorrhage; Prednisone

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Capillary Resistance; Female; Forearm; Hemorrhage; Humans; Male; Methods; Middle Aged; Pressure; Skin

Topics: Anemia, Aplastic; Animal Feed; Animals; Ascorbic Acid; Blood Volume Determination; Chickens; Copper; Hemorrhage; Iron; Poultry Diseases; Quinoxalines; Vitamin B 12

Topics: Abnormalities, Drug-Induced; Animals; Ascorbic Acid; Brain; Brain Chemistry; Capillaries; Carotid Arteries; Depression, Chemical; Embryo, Mammalian; Embryonic and Fetal Development; Female; Glycogen; Hemoglobins; Hemorrhage; Histocytochemistry; Insecticides; Liver; Nucleic Acids; Osteogenesis; Placenta; Pregnancy; Rats; Stimulation, Chemical; Trophoblasts

Topics: Adult; Ascorbic Acid; Femoral Nerve; Hemorrhage; Humans; Male; Peripheral Nervous System Diseases; Scurvy

Topics: Achlorhydria; Adult; Aged; Ascorbic Acid; Blood Coagulation Tests; Extremities; Glomerular Filtration Rate; Hematoma; Hemorrhage; Humans; Male; Middle Aged; Oral Hemorrhage; Scurvy

Topics: Aged; Ascorbic Acid; Blood Sedimentation; Extremities; Hemorrhage; Humans; Male; Oral Manifestations; Periodontal Diseases; Scurvy; Skin Manifestations

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Haplorhini; Hematocrit; Hemorrhage

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

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinogens; Hemorrhage; Humans; Lymph Node Excision; Urinary Bladder; Urinary Bladder Neoplasms; Urinary Tract Infections

Topics: Animals; Ascorbic Acid; Bilirubin; Cats; Hematoporphyrins; Hemoglobins; Hemorrhage; Hemosiderin; Humans; Hyaluronic Acid; Light; Microscopy, Electron; Porphyrins; Retinal Degeneration; Vitreous Body

Topics: Anemia, Hypochromic; Animals; Ascorbic Acid; Gastrectomy; Hematocrit; Hemorrhage; Intestinal Absorption; Iron; Iron Isotopes; Iron-Dextran Complex; Male; Rats

Topics: Adrenal Glands; Animals; Ascorbic Acid; Body Weight; Guinea Pigs; Hemorrhage; Liver; Male; Spleen

Topics: Ascorbic Acid; Drug Therapy; Eye Diseases; Gonioscopy; Hemorrhage; Hemostatics; Humans; Iris; Vitamin K

Topics: Absorption; Animals; Ascorbic Acid; Dogs; Duodenum; Feces; Hemorrhage; Ileum; Intestinal Absorption; Iron; Iron Isotopes; Jejunum; Rats; Research; Urine

Topics: Ascorbic Acid; Capillaries; Cataract Extraction; Drug Therapy; Eye Diseases; Flavonoids; Hemorrhage; Humans; Hyphema; Postoperative Complications; Postoperative Period; Preventive Medicine

Topics: Ascorbic Acid; Capillaries; Cardiovascular System; Contusions; Hemorrhage; Humans; Iron; Vascular Diseases

Topics: Ascorbic Acid; Eye Diseases; Eye Hemorrhage; Geriatrics; Hemorrhage; Humans; Scurvy

Topics: Ascorbic Acid; Biomedical Research; Hemorrhage; Humans; Promethazine; Rutin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ascorbic Acid; Capillary Permeability; Digestion; Hemorrhage; Humans; Liver; Peptic Ulcer Hemorrhage; Vitamins

Topics: Adrenal Glands; Animals; Ascorbic Acid; Chickens; Coccidiosis; Hemorrhage; Meat

Topics: Antifibrinolytic Agents; Ascorbic Acid; Flavonoids; Hemorrhage; Hemostatics; Urogenital System; Vitamin K; Vitamins

Topics: Ascorbic Acid; Calcium; Calcium, Dietary; Climacteric; Female; Hemorrhage; Humans; Menopause; Menorrhagia; Metrorrhagia

Topics: Anemia; Ascorbic Acid; Hemorrhage; Humans; Iron; Vitamins; Volunteers

Topics: Antifibrinolytic Agents; Ascorbic Acid; Flavonoids; Hemorrhage; Hemostasis; Hemostatics; Humans; Neurosurgery; Vitamin K; Vitamins

Topics: Adenosine; Animals; Ascorbic Acid; Brain; Carbohydrate Metabolism; Coenzymes; Hemorrhage; Nucleosides; Nucleotides; Phosphocreatine; Polyphosphates; Rats

Topics: Anticoagulants; Ascorbic Acid; Flavonoids; Hemorrhage; Humans; Vitamins

Topics: Antifibrinolytic Agents; Ascorbic Acid; Flavones; Flavonoids; Hemorrhage; Hemostatics; Humans; Otolaryngology; Vitamin K; Vitamins

Topics: Adrenal Cortex; Ascorbic Acid; Carbohydrate Metabolism; Hemorrhage

Topics: Adenoidectomy; Adenoids; Ascorbic Acid; Hemorrhage; Humans; Palatine Tonsil; Postoperative Hemorrhage; Tonsillectomy; Vitamin K

Topics: Ascorbic Acid; Capillaries; Capillary Permeability; Cardiovascular System; Cystitis; Flavones; Flavonoids; Hemorrhage; Humans; Vitamins

Topics: Antifibrinolytic Agents; Ascorbic Acid; Flavonoids; Hemorrhage; Hemostatics; Humans; Surgical Procedures, Operative; Vitamin K; Vitamins

Topics: Ascorbic Acid; Hemorrhage; Humans; Retina; Retinal Hemorrhage; Scurvy; Vitamins

Topics: Ascorbic Acid; Biomedical Research; Capillary Permeability; Flavonoids; Guinea Pigs; Hemorrhage; Humans; Vascular Diseases; Vitamins

Topics: Ascorbic Acid; Hemorrhage; Humans; Retina; Retinal Hemorrhage; Vitamins

Topics: Adrenocorticotropic Hormone; Ascorbic Acid; Hemorrhage; Pericardial Effusion; Pericarditis; Pericardium; Pulmonary Atelectasis; Vitamins

Topics: Ascorbic Acid; Hemorrhage; Humans; Pectins; Solutions; Syndrome; Vitamins

Topics: Ascorbic Acid; Cortisone; Hemorrhage; Humans; Neovascularization, Pathologic; Retina; Retinal Vasculitis; Streptomycin; Vitreous Body

Topics: Ascorbic Acid; Avitaminosis; Blood Pressure; Blood Pressure Determination; Epinephrine; Hemodynamics; Hemorrhage; Humans

Topics: Ascorbic Acid; Capillary Fragility; Erythrocytes; Flavones; Gingiva; Gingival Hemorrhage; Hemorrhage; Humans; Rutin; Vascular Diseases; Vitamins

Topics: Antifibrinolytic Agents; Ascorbic Acid; Epistaxis; Hemorrhage; Hemostatics; Humans; Nose; Prothrombin; Vitamin K; Vitamins

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Hemorrhage; Humans; Vitamins

Topics: Ascorbic Acid; Hemorrhage; Humans; Lymphatic Diseases; Palatine Tonsil; Pharynx

Topics: Ascorbic Acid; Deficiency Diseases; Hemorrhage; Humans; Infections; Metabolism; Niacin; Nicotinic Acids; Nutritional Sciences; Nutritional Status; Riboflavin; Thiamine; Vitamins; Wounds and Injuries

Topics: Ascorbic Acid; Guinea Pigs; Hemorrhage; Shock; Shock, Hemorrhagic

Topics: Adrenal Glands; Ascorbic Acid; Brain; Cholesterol; Hemorrhage; Humans; Liver; Plasma