Concomitant Administration Of Vitamin Research Articles

Effect of Maternal Panadol Extra Exposure on Embryonic Heart of Rat’s Offspring and Possible Protective Effect of Vitamin D

Introduction: excessive use of paracetamol with caffeine in Panadol extra during pregnancy increase the risk of spontaneous abortion. Vitamin D stimulates cardiomyocyte proliferation and protects against injury. Aim of Work: To investigate the effect of maternal exposure to large doses of Panadol extra on the development of the embryonic hearts of rat’s offspring and possible protective effects of vitamin D.Material and Methods: Forty-five albino rats; 30 adult females and 15 adult males were used in this study. The pregnant rats were divided into Group I as a control group, Group II (treated group; Panadol extra) received the maximum daily dose (4000mg paracetamol/ 520 mg caffeine) / kg/ day and Group III (protective group; Panadol extra + vitamin D) received previously mentioned dose of Panadol extra plus vitamin D at a dose of 400 IU/kg/day. All the treatments were given by oral gavage from the 1st day of pregnancy until day 19. Pregnant rats from all groups were sacrificed on day 19 of pregnancy and their pups were extracted & weighted, then sacrificed. Blood samples were taken for biochemical assessment. Sections from the hearts were stained (H&E, Eosin & Mallory’s trichrome stain), Immunohistochemical (alpha-smooth muscles) for histopathological and morphometric studies.Results: group (II) revealed changes of blood gases as PH, increase in PCO2, decrease PO2, high lipid profile, and increase Creatinine kinase-MB. There were different histopathological changes as cardiomyocyte damage, necrosis, and inflammation with increased fibrosis by Mallory stain. The morphometric results revealed an enlarged size of cardiac cells, decreased proliferation, and maturation. All these results were greatly improved in the group (III) when concomitant administration of vitamin D in the last protective group. Conclusion: prolonged and excessive maternal use of Panadol extra greatly affect heart development. Vitamin D has a potential effect on cardiac regeneration and development.

Molecular and hormonal changes caused by long-term use of high dose pregabalin on testicular tissue: the role of p38 MAPK, oxidative stress and apoptosis.

In 1990, pregabalin was introduced as a novel antiepileptic drug that acts by binding selectively to the alpha-2-delta subunits of voltage-gated calcium channels resulting in increasing neuronal GABA levels and inhibiting the release of exciting neurotransmitters. The aim of our study is to assess the hazardous effects of prolonged high-dose pregabalin (like that abused by addicts) on testes and to clarify the potential causative mechanisms. The current study was conducted on 70 adult male Wistar albino rats which were divided into 7 groups. In our study we evaluated the effect of pregabalin, at concentrations 150 and 300mg/kg/day for 90 days, on hormones; FSH, LH, testosterone and prolactin secretion. Our study also evaluated the expression of apoptosis-related genes BAX and BCL2 in testicular tissue in addition to the western blotted analysis of p38 Mitogen activated protein kinases (p38 MAPK). The levels of reduced glutathione, malondialdehyde and superoxide dismutase were also measured. Pregabalin decreased testosterone level while FSH, LH and prolactin showed a significant increase. It also produced genotoxicity through reversal of the BAX/BCL2 ratio; increased p38 MAPK level and induction of oxidative stress markers. The concomitant administration of vitamin E significantly reduced all the previously mentioned biochemical and hormonal adverse effects caused by pregabalin. Pregabalin can adversely affect male fertility particularly in addicts and patients who are being treated with it for long periods as those suffering from neuropathies and seizures. Antioxidants like vitamin E could have a role in amelioration.

Vitamin E supplementation ameliorates the hepatotoxicity induced by Tramadol: toxicological, histological and immunohistochemical study

Several deleterious effects of Tramadol including deaths were reported especially when used in large doses. Being metabolized mainly in the liver, Tramadol have serious hepatotoxic effects. This study investigates the effect of vitamin E on Tramadol-induced hepatotoxicity in rats by evaluating the antioxidant biochemical markers, the histopathological and immunohistochemical changes.Thirty adult mature male albino rats were divided into five groups (Gs); G1: negative control; G2: received Tramadol 150 mg/kg, G 3–5: received Tramadol plus vitamin E in concentrations of 50 mg/kg, 100 mg/kg and 200 mg/kg respectively. Liver function parameters and oxidative markers in liver tissue (CAT, SOD, GSH, and MDA) were estimated. Liver samples were processed for histopathological and immunohistochemical (Caspase 3 and TNF) examinations. The results indicated that Sub-chronic administration of Tramadol resulted in impaired liver functions, increased oxidative stress parameters with decreased antioxidant capacity of liver tissues, severe hepatocellular damage (hydropic degeneration, steatosis and apoptosis) and strong immunoexpression to TNF and Caspase 3. All these effects were ameliorated with concomitant administration of vitamin E especially with high doses. The co-treatment of Tramadol-intoxicated rats with Vitamin E, especially in high doses, protects against hepatic toxicity.

Cardio-protective Effect of Vitamin E on Doxorubicin-Induced Cardiotoxicity in Adult Male Albino Rats: A Histological and Biochemical Study

Background: Doxorubicin (Dox) is a powerful and greatly effective drug in cancer. However, its clinical usefulness is still restricted due to its specific toxicity to the cardiac tissue. Vitamin E is a well-known antioxidant used as a dietary supplement.Aim of the work: To evaluate the possible protective effects of vitamin E against Dox-induced cardiotoxicity.Material and Methods: Forty 3-months adult male albino rats weighing 200-250 gm were divided into four equal groups: Group (I): served as a negative control and received no treatment. Group (II): served as a positive control and treated with an intraperitoneal injection of 0.9% sodium chloride saline once daily for one week. Group (III): treated with 4mg Dox/kg b.w./day intraperitoneally for one week. Group (IV): was pretreated with 100mg vitamin E/kg body weight/day orally for 2 weeks followed by a combination of an intraperitoneal injection of Dox and oral vitamin E for one week in the same previous doses. Then, the animals were anaesthetized and blood samples were utilized for measurement of lactate dehydrogenase (LDH), creatine kinase (CK), triglyceride, total cholesterol and high-density lipoprotein (HDL-C). Animals were sacrificed, and a portion of each heart was taken from all groups for determination of the levels of total cardiac antioxidant capacity (TAC). The remaining portions of the heart muscle were prepared for light and electron microscopic studies.Results: Administration of Dox resulted in histological alterations in the form of vacuolated disorganized cardiac muscle fibers, degenerated mitochondria and congested dilated blood vessels. Also, significant decreases of cardiac TAC and serum HDL-C and increases of serum levels of LDH, CK, triglyceride and total cholesterol of Dox-treated group were noticed in comparison with the control ones. Pre and concomitant administration of vitamin E with Dox improved these alterations.Conclusion: Vitamin E ameliorates the cardiac damage induced by Dox.

VITAMIN E AMELIORATES THE TOXIC EFFECT OF AMIODARONE ON THYROID GLAND IN RATS: A HISTOLOGICAL AND ULTRASTRUCTURAL STUDY

Background: Amiodarone is a highly effective and class III antiarrhythmic drug. It can be used to treat wide range of arrhythmias. However, it is markedly concentrated in tissues leading to multiple adverse effects mainly on thyroid gland. The concomitant use of vitamin E with amiodarone in treatment of arrhythmias can ameliorate the hazardous effects of amiodarone on thyroid glandAim of work: The aim of this work is to study the histological and ultrastructural effects of amiodarone as antiarrhythmic drug on the thyroid gland, as well as the ability of vitamin E to protect against amiodarone induced thyroid damage.Material and methods: Thirty adult male albino rats (weighing 150-200 g), were used in the study. Rats were divided into three groups (10 per group): Group A (Control group); Group B (Amiodarone treated group) and Group C (Amiodarone + Vitamin E treated group). Rats were sacrificed after 6 weeks of amiodarone administration. Thyroid gland was examined histologically and ultrastructurally.Results: Histological and ultrastructure examination of thyroid glands of rats treated with amiodarone showed disorganized follicles. Follicular epithelium showed focal disruption and desquamation. The interfollicular tissue showed increased collagen deposition. Electron microscopic examination revealed irregular nuclei, dilated rough endoplasmic reticulum and swollen mitochondria. Concomitant administration of vitamin E showed marked amelioration of hazardous effects of amiodarone with improved histologic and ultrastructural signsConclusion: Amiodarone induces damage of the thyroid gland. Administration of vitamin E protects the thyroid gland and attenuates histopathological changes induced by amiodarone.

Study of the Protective Effect of Vitamin C on Monosodium Glutamate Induced Cardiotoxicity in Adult Male Albino Rats

Introduction: Monosodium glutamate (MSG) is worldwide used food flavoring agent. Its safety as food additive is controversial. Vitamin C is a water soluble vitamin with antioxidant activities Aim of the study: The aim of this study was to evaluate the possible toxic effect of MSG on the heart and to evaluate the potential protective effect of concomitant administration of vitamin C together with MSG on the heart of adult male albino rats. Material and methods: The current study was conducted on 60 adult male albino rats. Rats were divided into six equal groups. The first group was used as control group. Group II was treated with vitamin C (100mg/kg/day). Group III was treated with MSG (100mg/kg/day). Group IV was treated with MSG (4g/kg/day). Group V was treated with MSG (100mg/kg/day) together with vitamin C (100mg/kg/day). Group VI was treated with MSG (4g/kg/day) together with vitamin C (100mg/kg/day). All drugs were given orally for 45 days. The weight of the heart was recorded. The level of cardiac troponin I (cTnI) enzyme and the activity of creatine kinase MB (CK- MB) enzyme in serum were assessed. Histopathological examination of heart tissue was carried out. Results: Administration of MSG led to significant increase in the heart weight with significant elevation in the serum cTnI levels and serum CK-MB activity. Sections from low dose MSG treated rats revealed cloudy swelling, while sections form high dose MSG treated rats revealed extensive cloudy swelling with fiber separation and vascular congestion. Concomitant administration of vitamin C together with MSG significantly protected against all these changes Conclusion: It was concluded that MSG is cardiotoxic and that concomitant administration of vitamin C is protective against MSG cardiotoxicity. Recommendations: The current study recommends that the use of MSG should be restricted to very small amounts and should be under supervision of health authorities. The use of vitamin C as a natural and cheap dietary supplement is highly recommended especially in persons who consume diets reach in flavoring agents such as MSG.

The Effects of Valproic Acid on the Skeletal Development and the Ameliorative Effects of Combined Use of Folic Acid and Vitamin E in Pregnant Albino Rats

Objectives: To evaluate skeletal developmental defects secondary to chronic valproic acid (VPA) use during pregnancy and the extent of ameliorative effect of combined use of vitamin E and folic acid (FA) during VPA therapy. Materials and Methods: Thirty virgin female albino rats were allowed to get pregnant and were divided into three equal groups: Control group received no medications; VPA group received oral VPA 400 mg/kg body weight (BW) starting on gestational day (GD) 1 till GD20 and Prophylaxis group received oral VPA (400 mg/kg BW) and vitamin E 250 mg/kg BW and folic acid 100 µg/kg BW using gastric tube starting on GD1 till GD20. At GD20, uterine horns were examined for resorption sites, alive or dead fetuses. Extracted living fetuses were examined for BW, crown-rump length (CRL), and antero-posterior (AP) and biparietal diameters and for congenital malformations. Results: VPA significantly reduced all body measurements of living dams compared to control dams. Prophylaxis therapy significantly increased BW, CRL and AP skull diameter compared to VPA dams. The GD20 fetus of VPA group showed delayed ossification of skull bones with wide anterior fontanel (AF) and widely separated parietal bones, very small ossification center (OC) for hyoid bone. Caudal vertebrae were unossified or showed very small OC with no evident OC for calcaneous, metatarsal bones or distal phalanges. Fetuses of prophylaxis group showed slightly wide AF than that of control animals and parietal bones are separated to lesser extent than VPA group. Mandible is developed, with an OC for hyoid bone and sternebrae are seen. Six caudal vertebrae and few OC in phalanges are seen, but no OC in calcaneous. Conclusion: VPA chronic administration during pregnancy showed deleterious effects on fetal body measurements and skeletal system development. Concomitant administration of vitamin E and FA significantly ameliorated these changes.

Outcomes Associated With Prothrombin Complex Concentrate for International Normalized Ratio Reversal in Patients on Oral Anticoagulants With Acute Bleeding.

Management of bleeding in patients on oral anticoagulants (OACs) is crucial in optimizing outcomes. No large studies examine 3-factor prothrombin complex concentrate (PCC) for OAC reversal. To assess outcomes after administration of 3-factor PCC for reversal of international normalized ratio (INR). We conducted an institutional review board-approved retrospective cohort study in all patients admitted to our level II trauma center over a 5-year period from 2007 to 2012 who received PCC for INR reversal and bleeding management. The primary outcome was assessment of efficacy as measured by achievement of INR < 1.5. Secondary objectives were to evaluate: factors associated with achievement of target INR, cessation of bleeding, mortality, outcome differences with or without fresh frozen plasma (FFP) or protocol utilization, safety, and cost. A total of 403 patients were evaluated. Target INR was achieved in 88.8% of patients and was influenced by baseline INR. Associated factors were younger age (P = 0.02), utilization of the institution's protocol (P < 0.01), and concomitant administration of vitamin K (P < 0.01). Concomitant FFP did not affect achievement. Bleeding cessation occurred in 333 (82.6%) patients, and 68 (16.9%) patients died. Patients who achieved target INR were more likely to have bleeding cessation (P < 0.01). The odds of survival for those who reached target INR was 3.8 times greater (P < 0.01). The incidence of thromboembolism was 3.7%. Three-factor PCC administration with IV vitamin K was effective for INR reversal and bleeding cessation and should continue to be a mainstay of therapy pending head-to-head outcome and cost comparisons with 4-factor products.

Cytotoxicity and mutagenicity of fluoxetine hydrochloride (Prozac), with or without vitamins A and C, in plant and animal model systems

Fluoxetine, commonly known as Prozac, is the first representative of the so-called new generation of antidepressants that promise efficacy, with few side effects, against deep depression, nervous bulimia, and anxiety. As there is a growing number of people suffering from anxiety and depression; consequently, the use of fluoxetine is also increasing. Verifying absence of drug effects such as cytotoxicity or mutagenicity is of great importance. Certain vitamins, such as vitamin A (retinol, retinoids) and vitamin C (ascorbic acid) protect and are extremely active against mutagens. We evaluated the cytotoxic and mutagenic activity of fluoxetine, with and without concomitant administration of vitamin A or C, in Allium cepa meristem cells and Wistar rat bone marrow cells. The A. cepa meristem cells showed fluoxetine cytotoxicity; concomitant treatment with vitamin A or C proved non-protective. Treatment of Wistar rats with fluoxetine intraperitoneally or via gavage did not affect cell division or cause clastogenic effects. Vitamin A and C did not affect the cytotoxicity or mutagenicity of fluoxetine in the rat cells.

Ultrastructural Changes in Rat’s Atrial Cardiomyocytes After Short Term Administration of Amiodarone and Possible Protective Role of Vitamin E

BackgroundAmiodarone chlorhydrate is a diiodated benzofuran derivative used to treat a variety of cardiac rhythm abnormalities. The use of amiodarone is associated with ultrastructural changes affecting body tissues, but its effect on the ultrastructure of the heart has not yet been fully elucidated.MethodsThe aim of this study is to test the adverse effects of amiodarone administration on cardiomyocytes and to study the possible protective role of vitamin E co-administration. A total of 18 adult male albino rats were used in this study. The rats were divided randomly into three groups of 6 rats each as follows: group I was considered the control group and was given vegetable oil; group II received 54 mg/kg of oral amiodarone; and group III received a single dose of combined vitamin E (50 mg/kg) and amiodarone (54 mg/kg). After 2 weeks, the rats were sacrificed, and the atrial tissues were harvested and processed for electron microscopic study.ResultsAdministration of amiodarone alone modified the atrial architecture, which was demonstrated by the following: mitochondrial enlargement and cristae lysis; marked heterogeneity of myofibril patterns with partial necrosis and disintegration of myofilaments; and irregularities of the sarcomere and less concentration of atrionatriuretic factor (ANF) granules, which localised in closed proximity to the nucleus with disrupted chromatin contents. Concomitant administration of vitamin E with amiodarone showed a considerable preservation of the atrial architecture.ConclusionsOral administration of amiodarone in rats resulted in ultrastructural changes in atria, which can be attenuated by vitamin E co-administration.

Effect of long-term administration of amiodarone on rat lung and the possible protective role of vitamin E

Introduction Amiodarone is gaining support as a first-line antiarrhythmic drug despite its potentially fatal pulmonary complications involving inflammation and fibrosis. Objective This study was undertaken to investigate the effect of long-term amiodarone administration and withdrawal on the histological structure of rat lung. In addition, the possible protective role of vitamin E supplementation was studied. Materials and methods This study was carried out on 36 adult male albino rats, which were divided into four groups: group I, which was considered as control; group II (amiodarone-treated group), which received amiodarone orally in a daily dose of 30 mg/kg body weight for 12 weeks; group III (withdrawal group), which received the same dose of amiodarone for 12 weeks and were sacrificed 6 weeks after withdrawal of the drug; and group IV (protected group), which received vitamin E orally in a daily dose of 100 mg/kg body weight simultaneously with amiodarone for 12 weeks. At the time of sacrifice, the lungs were dissected and tissue samples were processed for both light and electron microscopic studies. Immuohistochemical study using anti-CD68 for showing alveolar macrophages was also performed and the number of positively stained cells was morphometrically estimated and statistically analyzed. Results Administration of amiodarone alone showed an alteration in the lung architecture in the form of collapsed alveoli with evident proliferation and vacuolation of pneumocytes type II. Thickening of interalveolar septa, cellular infiltration, and collagen deposition associated with an increased number of macrophages as proved by the morphometric study were demonstrated. Intrabronchial cellular debris and vascular congestion were also observed. Coadministration of amiodarone with vitamin E showed a considerable degree of preservation of the pulmonary alveolar architecture; however, a mild improvement in the lung injury was observed in animals after amiodarone withdrawal. The alveoli were lined mainly by vacuolated pneumocytes type II with moderately thickened interalveolar septa. Conclusion From this study it could be concluded that prolonged administration of amiodarone in rats can induce severe lung damage. Withdrawal of the drug showed little improvement of this harmful effect but concomitant administration of vitamin E effectively protected the lung tissue. In addition, the increased number of alveolar macrophages associated with amiodarone administration has supported the concept that these cells may play a role in the pathogenesis of lung injury caused by amiodarone.

Comparative study on the effect of vitamin K versus combined Ca and vitamin D administration on the prevention of experimentally-induced osteoporosis in adult male albino rats

Introduction Immobilization is one of the important causes of osteoporosis especially after cast application and in the elderly people who might be bedridden or suffering from joint diseases. The aim of this study To compare between the effects of vitamin K and the combined use of Ca and vitamin D on the prevention of experimentally-induced osteoporosis of the femur. Materials and methods This study included 24 adult male albino rats. They were divided into four groups: group 1 (control group), group 2 (immobilization group that were immobilized by casting of their right lower limb for 4 weeks), group 3 (immobilization group that concomitantly received 0.0009 mg/g body weight of vitamin K daily during the casting period), and group 4 [that was given Ca (0.09 mg/g body weight daily) and vitamin D (0.5 μg/kg alfacalcidol daily) during the casting period]. At the end of the experiment, the distal end of the femur of the immobilized limb was taken, processed, and examined by different histological techniques. A morphometric study was conducted to measure cancellous bone thickness, osteoid thickness, osteoid surface percentage, and the eroded surface percentage. The data were statistically analyzed. Results It was observed that immobilization caused marked thinning of the cancellous bone trabeculae. Erosion cavities were frequently seen in both compact and cancellous bones. Increased mean eroded surface percentage and decreased mean osteoid thickness and mean osteoid surface percentage were also noticed with immobilization when compared with the control group. Concomitant administration of vitamin K with casting resulted in significant improvement of most of the above-mentioned bone parameters. With combined administration of Ca and vitamin D with immobilization, erosion cavities were still seen in a few areas. Decreased mean cancellous bone thickness was also noticed when compared with groups 1 and 3. Conclusion According to the results of this experiment, vitamin K proved to be more effective, as a protective agent, than combined Ca and vitamin D administration in cases of immobilization osteoporosis. Level of evidence Level three in vitro (prospective case–control study in vitro).

Homocysteine alters glutamate uptake and Na+,K+-ATPase activity and oxidative status in rats hippocampus: protection by vitamin C

In the present study we investigate the effect of homocysteine on glutamate uptake, Na+,K+-ATPase, enzymatic antioxidant defenses, as well as reactive species levels in hippocampus of rats. The influence of vitamin C, a classic antioxidant, on the effects elicited by homocysteine was also tested. Results showed that chronic hyperhomocysteinemia decreased glutamate uptake and the activities of Na+,K+-ATPase, catalase and superoxide dismutase in hippocampus of rats. Reactive species levels were increased by chronic homocysteine administration. Concomitant administration of vitamin C significantly prevented these alterations caused by homocysteine. According to our results, it seems possible to suggest that the reduction in glutamate uptake and Na+,K+-ATPase activity may be mediated by oxidative stress, since vitamin C prevented these effects. We suggest that the administration of antioxidants should be considered as an adjuvant therapy to specific diet in homocystinuria.

Effects of interaction of vitamin A and Rauwolfia vomitoria root bark extract on marker enzymes of cardiac diseases

Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and aspartate aminotransferase (AST) are key players in the diagnostic study of cardiac complications. These enzymes are specific diagnostic markers of myocardial infarction and hypertension is a disease condition characterized with a wide range of complications, including myocardial infarction. In this study, we determined the effects of interaction of vitamin A and Rauwolfia vomitoria (RV) root bark extract on marker enzymes of cardiac diseases. CK and CK-MB activities had significant decrease in the group of animals with concomitant administration of vitamin A (40 IU/kg body wt.) and 150 mg/kg body wt. of RV root bark extract. At the interaction of vitamin A with 300 mg/kg body wt. RV root bark extract, CK-MB only showed significant (p ≥ 0.05) decrease while CK decreased insignificantly. Also at the interaction of vitamin A with 300 mg/kg body wt. RV root bark extract, AST increased significantly but decreased significantly at the interaction of vitamin A (40 IU/kg body wt.) and 150 mg/kg body wt. of RV root bark extract. Our findings showed that vitamin A dose did not lower the activities of cardiac marker enzymes. However, concomitant administration of RV root bark extract at 150 mg/kg body wt. with vitamin A shows significant reduction in the activities of CK, CK-MB and AST. These findings suggest that interaction of vitamin A with RV root bark extract would be a meaningful ethno-pharmaceutical approach in the management of myocardial infarction and treatment of hypertension.

The effect of Cannabis sativa on testosterone level and seminal fluid analysis of male Wistar rats

The effects of Cannabis sativa on the testosterone level and seminal fluid analysis were studied. A total of twenty-four adult male rats were randomly divided into four experimental groups. Group 1 (control) were fed on 5% ethanol. Group 2,3and 4 were fed 20mg of cannabis in 5% ethanol,20mg of cannabis in 5% ethanol +100mg Vitamin C, and 20mg cannabis in 5% ethanol +1ml honey respectively for 21 consecutive days. The result showed a statistically significant decrease in percentage motile sperm and an increase in the percentage dead sperm (p<0.05).The decrease in the sperm count were not statistically significant. Also the changes in Testosterone hormonal levels were not statistically significant. However, those adverse effects caused by cannabis were reversed by the concomitant administration of vitamin C and honey. Also Vitamin C improved the quality of seminal fluid more than Honey.

Effects of Vitamin K2 and Risedronate on Bone Formation and Resorption, Osteocyte Lacunar System, and Porosity in the Cortical Bone of Glucocorticoid-Treated Rats

The purpose of the present study was to examine the effects of vitamin K(2) and risedronate on bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of glucocorticoid (GC)-treated rats. Forty-nine female Sprague-Dawley rats, 3 months of age, were randomized into five groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K(2), risedronate, or vitamin K(2) + risedronate. At the end of the 8-week experiment, classical bone histomorphometric analysis was performed, and the osteocyte lacunar system and porosity were evaluated on the cortical bone of the tibial diaphysis. GC administration decreased percent cortical bone area and increased percent marrow area as a result of decreased periosteal bone formation, and increased endocortical bone erosion, and increased cortical porosity. Vitamin K(2) prevented a reduction in periosteal bone formation but did not affect percent cortical bone and marrow areas. Risedronate prevented a reduction in periosteal bone formation and an increase in endocortical bone erosion, resulting in prevention of alterations in percent cortical bone and marrow areas. Both vitamin K(2) and risedronate increased osteocyte density and lacunar occupancy and prevented a GC-induced increase in cortical porosity. Vitamin K(2) and risedronate had additive effects on osteocyte density and lacunar occupancy and a synergistic effect on cortical porosity. The present study showed the efficacy of vitamin K(2) and risedronate for bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of GC-treated rats.

Reactive oxygen metabolites and anti-oxidative defenses in aspirin-induced gastric damage in rats: Gastroprotection by Vitamin E

Objective It has been proposed that neutrophil infiltration and oxygen radicals may be the important prime events that lead to mucosal injury induced by aspirin. Vitamin E acts as a potent antioxidant, and is capable of scavenging free radicals. The aim of this study was to evaluate the oxygen metabolites and anti-oxidative defenses in acute gastric damage induced by aspirin and to find the effects of Vitamin E. Methods Ninety-six Wistar rats were divided into four groups of 24 rats each as follows: (1) the control group; (2) the ASA group that received 300 mg/kg of ASA; (3) the Vitamin E plus ASA group and (4) the Vitamin E group that received Vitamin E (75 units) alone. At 3, 6, 9 and 24 h after the drug administration, six rats were randomly selected from each group and gastric mucosal injury, prostaglandin E2, and the activities of myeloperoxidase, xanthine-oxidase, superoxide dismutase, glutathione peroxidase as well as glutathione level were measured and compared between the groups. Results Oral administration of ASA caused acute gastric erosions and an increase in myeloperoxidase activity. It also decreased prostaglandin E2, superoxide dismutase activity, glutathione peroxidase activity and glutathione level. Concomitant administration of Vitamin E and ASA restored all the changes toward the control levels. Conclusion Free radicals and suppression of anti-oxidizing enzymes play important roles in gastric damage induced by aspirin. Increased myeloperoxidase activity suggests that activated neutrophils may be a major source of free radicals. Vitamin E protects against ASA-induced damage due to its anti-oxidizing activity.

Sarpogrelate HCl, a selective 5-HT 2A antagonist, retards the progression of atherosclerosis through a novel mechanism

Although sarpogrelate HCl is widely used for the prevention of arterial thrombosis, its effect on atherosclerosis is unknown. Accordingly, we here investigated the effects of sarpogrelate HCl on a rabbit model of atherosclerosis. Male rabbits were fed a 0.5% cholesterol diet (HCD) (Gp 1), HCD with vitamin E (Gp 2), HCD with vitamin E and sarpogrelate (Gp 3), or HCD with sarpogrelate alone (Gp 4) for 8 weeks. The atherosclerotic area was decreased by feeding of vitamin E and sarpogrelate (16.9±2.0% in Gp 1 vs. 8.2±2.0% in Gp 3). Tone-related basal NO release was higher in Gps 3 and 4. Acetylcholine-induced relaxation tended to be improved in Gp 3. The amount of eNOS mRNA was increased in Gp 4, and aortic cyclic GMP concentration showed the same tendency. O 2 − release tended to be decreased in Gps 2 and 3. The matrix metalloproteinase-1 (MMP-1)-positive area was decreased, and the percentage ratio of cell numbers of smooth muscle cells/macrophages in the plaque was increased in Gp 3. The results demonstrated that sarpogrelate HCl retards the progression of atherosclerosis in rabbits, and that this effect is enhanced by concomitant administration of vitamin E. Although upregulation of eNOS may play a role as one of the underlying mechanisms, our results suggest that an additional mechanism—possibly involving the antiproliferative effects of sarpogrelate HCl on smooth muscle cells and macrophages—may also play an important role.

Novel aspects of erythropoietin response in renal failure patients.

The invention of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia was a hallmark in the care of patients with renal insufficiency. Recently published guidelines (European Best Practice Guidelines, NKF-DOQI) have set the target haemoglobin to be reached by treatment with rHuEpo to >11 g/dl. Normalizing haemoglobin levels may reduce morbidity and mortality and improve quality of life in haemodialysis patients. During long-term treatment, most patients will not respond adequately to therapy with rHuEpo alone. The most important confounding factor, limiting the effectiveness of rHuEpo, is absolute or functional iron deficiency, which is now recognized and treated in many dialysis units. However, there are several other adjuvant treatment options which may help to optimize the response to treatment with rHuEpo. A weekly dose of 2-3 mg of folic acid and 100-150 mg of vitamin B6 is recommended for haemodialysis patients on rHuEpo therapy. The addition of 0.25 mg/month of vitamin B12 may be necessary in selected patients. Vitamin C (1-1.5 g/week) was shown to overcome functional iron deficiency in patients with high ferritin levels. The potential increase of oxidative stress induced by intravenous iron therapy may be blunted by concomitant administration of vitamin E (1200 IU). There is clear evidence from the literature that treatment of secondary hyperparathyroidism by vitamin D improves erythropoiesis. The most recently discovered biological effects of rHuEpo include the induction of several genes in endothelial cells as well as a role for erythropoietin in the outcome of plasmodium infection. A new erythropoietin-like molecule is novel erythropoiesis stimulating protein (NESP), which is as effective and safe as rHuEpo, with the potential advantage of less frequent dosing.

Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: A randomized trial

Background: Isotretinoin treatment is frequently associated with reversible, dose-related side effects. Recent studies claimed that combining vitamin E with high-dose isotretinoin ameliorated isotretinoin-induced side effects. Objective: The purpose of this double-blind, randomized study was to determine the effects of a fixed dose of vitamin E on the side effects of isotretinoin for treatment-resistant acne vulgaris. Methods: One hundred forty subjects were randomly assigned to one of two treatment programs with isotretinoin (1 mg/kg) together with either vitamin E (800 IU/day) or a vitamin E placebo for 20 weeks. The incidence, severity, and duration of the side effects (eg, dry eyes, dry lips) were assessed. Results: A fixed 800 IU/day dose of vitamin E did not improve the incidence, severity, or duration of side effects associated with isotretinoin (1 mg/kg per day). Conclusion: Vitamin E did not significantly ameliorate retinoid side effects when combined with 1 mg/kg of isotretinoin in the treatment of acne. (J Am Acad Dermatol 2000;43:777-84.)