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Diabetes mellitus (DM) is a metabolic disease, which causes an increase in the proinflammatory cytokines tumor necrosis factor-? (TNF-?) and interleukin 1? (IL-1?), and also proliferation of monocyte chemotactic protein. In the present study, the potential effects of melatonin on proinflammatory cytokines, hematological values, and lymphoid tissues were investigated in diabetic rats. In the study, 36 male rats were randomly divided into 4 groups as follows: Control, Mel (melatonin), DM, and DM-Mel. For 15 days, an isotonic saline solution was given to the Control and DM groups; melatonin was administered to the Mel and DM-Mel groups intraperitoneally. At the end of the study, all animals were sacrificed by drawing the blood from their hearts under deep anesthesia. Samples of the spleen, thymus, and lymph nodes were fixed in 10 % formaldehyde for histologic analysis. Increases in proinflammatory serum cytokine concentrations, mast cells, and total white blood cell counts as well as tissue destruction in the lymphoid organs were determined in the DM group via biochemical, hematological, and histologic analyses. However, the findings for the DM-Mel group revealed decreases in serum IL-1? concentration and mast cell densities, and destructions in lymphoid tissues by the melatonin administration. The present study suggests that melatonin treatment may control immune system regulation and inhibit the production of proinflammatory cytokines and tissue mast cell accumulation by preventing the destruction of lymphoid organs in the diabetic process. [ABSTRACT FROM AUTHOR]

The article investigates the clinical signs, venous blood gases and cytokine production in naturally infected calves with bovine respiratory disease (BRD). The researchers detected bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), and infectious bovine rhinotracheitis virus (IBRV) in the diseased calves. Bacteria such as Mannheimia hemolytica, Streptococcus and Staphylococcus were detected in the lungs of infected calves, while respiration rate and rectal temperature significantly increased. Findings showed the respiratory acidosis as well as the presence of serum concentrations of tumor necrosis factor-α and interleukin-6 in infected calves. Clinical recovery of the affected calves were induced by tulathromycin and carprofen treatment.

The article discusses a study which determined body condition scores (BCS) and metabolic blood parameters among non-pregnant dairy cows at a farm in Erzurum, Turkey. Researchers showed the variance in BCS between thin cows and normal cows and its correlation with levels of aspartate aminotransferase activity AST and blood urea nitrogen (BUN). The study cited the advantage of using BCS to determine energy reserves in many kinds of animals. It also concluded that periparturient cows had a significant association between their BCS and low density lipoprotein (LDL) concentrations.

The article provides information about a study on the role of blood transfusion in treating cattle with severe Leptospirosis. It specifically aims to determine the efficacy of a whole blood transfusion as an adjunct to antibiotic and B vitamins in cattle with leptospirosis. The researchers evaluated 42 cattle shedding urinary spirochetes and manifesting clinical symptoms of Leptospirosis. Based on the results, it was concluded that the administration of dihydrostreptomycin-penicillin can remove the urinary shedding of spirochetes. Moreover, blood transfusion is said to have helped in repairing the present collapses, like anemia, hemorrhagic diathesis, and septicemia.

The aim of the study was to evaluate the measurement of total calcium levels in sera of sheep with and without milk fever by using a commercial water hardness test kit. Thirty sheep with findings of milk fever from 9 different farms were used in the present study. Total serum calcium concentrations were determined by using a commercial water hardness test kit and a laboratory automated biochemical analyzer. Results of the test kit and laboratory methods were significantly (P < 0.00 1) correlated (Spearman's p = 0.896). In conclusion, it has been determined that total calcium levels in sheep sera may be determined with a water hardness test kit as used in this study, and that data are in concordance with the clinical findings and the other laboratory results. [ABSTRACT FROM AUTHOR]

The traumatic reticuloperitonitis (TRP) model was used to investigate the acute phase biomarkers (APBs) in the inflammatory response of dairy cows. Fourteen Swiss Brown cows were diagnosed with TRP based on the clinical findings, ferroscopy and ultrasonography as well as positive responses to pain tests. Four of the cows were necropsied and TRP was confirmed. Additionally, 10 healthy cows were used as the control group. Blood samples were obtained from cows during the clinical stage of TRP. Mean serum haptoglobulin (Hp) (1.19±0.37 vs. 0.03±0.01 mg/mL) (P<0.05) and plasma fibrinogen (Fb) (205.1±18.1 vs. 101.1±17.6 ηg/ mL) (P<0.001) concentrations of TRP group were found higher compared to control group. There was an insignificant increase in mean serum amyloid A (SAA) (165±63 vs. 67.9±34 μg/mL) and α-1 acid glycoprotein (α-1 AGP) (1069±220 vs. 663±121 μg/mL) levels (P>0.05). Mean total white blood cell (WBC) count of TRP group (10.8±1.4 vs. 6.9±0.6 ×103/μL) was significantly higher compared to control group (P<0.001). Moreover, neutrophil counts of the TRP group showed a tendency to increase compared to the control group, however no statistical difference was detected (P>0.05). While positive correlation was detected between WBC count and Hp concentration of TRP group (r=0.636; P=0.01); there was no correlation between WBC count and Fb concentration (r=0.395; P>0.05). There was no statistical difference (P>0.05) between groups for routine biochemical parameters. In conclusion, significant increases in Fb and Hp values were found to be related to the inflammatory response of dairy cows with TRP. The tendency of increase in the SAA and α-1 AGP were evaluated as nonspecific for the response. In addition, high Hp values were consistent with the correlation of high WBC counts due to the inflammatory response. [ABSTRACT FROM AUTHOR]

Background: The metabolic impacts of including soya meal, wheat gluten and corn gluten in the diet of male lambs could influence their reproductive performance., Objectives: An experiment was carried out to assess the effects of corn gluten, wheat gluten and soya meal on the reproductive system of male lambs., Methods: Twenty-four male Morkaraman lambs, aged 9 months, were utilized in this study and were fed experimental diets for 56 days. The lambs were divided into a control group (soybean meal + safflower meal), a corn group (corn gluten) and a wheat group (wheat gluten)., Results: The serum follicle-stimulating hormone level of the control group was significantly higher and tumour necrosis factor-alpha (TNF-α) level was lower than the wheat and corn gluten groups (p < 0.05). The lowest malondialdehyde level in testicular tissue was observed in the control group, whereas the highest was in the wheat gluten group (p < 0.05). The glutathione level in the control group was significantly higher than in the other groups (p < 0.05). The corn gluten group showed the highest CHOP and IRE1 levels; the lowest Bcl-2 levels and the highest IL-1B and P2 × 7R levels were found in the wheat group; and the lowest TNF-α levels were in the control group (p < 0.05). Additionally, the study revealed that diet had a significant impact on spermatological parameters of the testis such as diameter, volume and weight (p < 0.05)., Conclusions: These results concluded that the inclusion of different protein sources in the diet of reproductive male lambs affects the metabolism of testicular tissue., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Monosodium glutamate (MSG, E621) is a flavor-enhancing food additive used widely in the food preparation industry and consumed regularly. It is considered that long-term consumption of MSG causes metabolic syndrome and obesity. Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood sugar, polyuria, polydipsia, and polyphagia, in which insulin secreted from pancreatic β cells is inadequate for maintaining blood glucose homeostasis. Rats were application 65 mg/kg streptozotocin (STZ) solution intraperitoneally and a diabetes model was created. For this purpose, freshly prepared STZ was injected into the peritoneum. Tumor necrosis factor-α, interleukin (IL)-10, IL-6, and IL-1β levels in STZ, MSG, and STZ + MSG groups were found to be significantly increased in inflammation parameters measured on the 28th day of administration when compared to the Control Group (p < 0.001). Also, although malondialdehyde (MDA) levels increased significantly in the STZ + MSG group when compared to the control group (p < 0.001), glutathione (GSH), and superoxide dismutase (SOD) levels were significantly decreased in the STZ, MSG, and STZ + MSG groups when compared to the control group (p < 0.001). Also, although glucose levels increased significantly in STZ and STZ + MSG at the end of the 28th day (p < 0.01), insulin levels decreased in STZ, MSG, and STZ + MSG groups when compared to the control groups (p < 0.01). As a result, it was found that STZ and MSG application significantly increased cytokine production, increased MDA, which is an oxidant parameter in pancreatic tissue, and decreased antioxidants (GSH and SOD) when compared to the control groups. It was also found that MSG disrupted the normal histological structure in pancreatic cells, and the damage was much more in both exocrine and endocrine pancreatic areas in the STZ + MSG group when compared to the STZ and MSG groups. It was considered that with the increased use of MSG, the susceptibility to DM might increase along with tissue damage significantly in diabetic groups, therefore, MSG must be used in a limited and controlled manner., (© 2023 The Authors. Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC.)

Background: Canine parvoviral enteritis (CPE) is a fatal disease worldwide. The treatment of CPE is based mainly on supportive and symptomatic treatment. Antiviral addition to the treatment may result in a higher survival., Objectives: This study evaluated the effects of antiviral treatments with a standardized treatment (ST) on the clinical and inflammatory response of dogs with naturally occurring CPE., Methods: Twenty-eight dogs with CPE caused by canine parvovirus type 2 were divided randomly into treatment groups. The ST group received fluid, antibiotic, antiemetic, and deworming treatments. The antiviral treatment groups received the same ST with an additional antiviral drug, recombinant feline interferon omega (rFeIFN-ω), oseltamivir (OSEL) or famciclovir (FAM)., Results: Compared to the healthy control, the tumor necrosis factor-α, interleukin-1β, interferon (IFN)-α, IFN-γ, haptoglobin, and C-reactive protein values were high ( p < 0.05) on day zero. At presentation, mild lymphopenia, neutropenia, and a high neutrophil to lymphocyte (LYM) ratio (NLR) were also observed. Adding rFeIFN-ω to the ST produced the best improvement in the clinical score with a decreased NLR, while leucocytes remained low and inflammatory markers stayed high on day three. The survival rates of the groups were 85.7% in ST+IFN, 71.4% in ST+OSEL, 71.4% in ST+FAM, and 57.1% in ST groups on day seven., Conclusions: Antiviral drugs may be valuable in treating CPE to improve the clinical signs and survival. In addition, the decrease in NLR in favor of LYM may be an indicator of the early prognosis before the improvement of leukocytes, cytokines, and acute phase proteins in CPE., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

Sepsis is a deadly systemic inflammatory response of the body against infection resulting in immune response, cell differentiation and organ damage. Endotoxemia is one of the causes of sepsis-related acute respiratory distress and respiratory burst is an important generator of oxidants. Inflammation may be aggravated by overexpression of ATP-gated purinergic receptors (i.e., P2X7R) following cell damage. We aimed to evaluate the effects of P2X7R antagonist A-438079 on lung oxidative status and the receptor expression in endotoxemia of sepsis. Rats were subjected to sepsis by E. coli lipopolysaccharide (LPS) and treated with 15 mg/kg A-438079. The increase in circulatory IL-1β and IL-8 concentrations in LPS group confirmed the systemic inflammatory response to endotoxemia compared with Control groups (p < 0.001). Besides, there was an increase in P2X7R expression in lung tissue after LPS administration. Compared with Control groups, there were significant increases in the values of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) (p < 0.001), and myeloperoxidase (MPO) (p < 0.05) in lung tissue of LPS group. P2X7R expression in lung and IL-1β level in blood did not increase in LPS + A-438079 group. A-438079 decreased the lung levels of MDA, GSH, CAT and SOD (p < 0.001), and MPO (p < 0.01) in septic rats. As a result, administration of pathogen-associated LPS led to increased P2X7R expression into lung tissue and elevated lipid peroxidation product MDA with regard to oxidative damage. The P2X7R antagonist A-438079 alleviated the oxidative stress of lung with a balance of tissue oxidant/antioxidant factors in experimental sepsis in rats., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The study aimed to investigate the hepatoprotective effects of purinergic receptor (P2X7R) antagonism by A438079 in liver damage. An experimental model of inflammation was performed by intraperitoneal (i.p.) lipopolysaccharide (LPS) administration in the rat. The groups were Control, A438079, dimethyl sulfoxide (DMSO), LPS, LPS + DMSO, and LPS + A438079. Following LPS (8 mg/kg) injection, A438079 (15 mg/kg) and DMSO (0.1 mL) were administrated (i.p) in the study groups. The blood and the liver tissues were removed for histological, biochemical, and western blot analyses. In the biochemical analysis, serum aspartate transaminase (AST) and alanine transaminase (ALT) concentrations, the tissue glutathione (GSH) level, and superoxide dismutase (SOD) activity dramatically decreased and malondialdehyde (MDA) level increased in the LPS and LPS + DMSO groups compared to the LPS + A438079 group. In the histological analysis, severe sinusoidal dilatation, necrotic hepatocytes, and inflammatory cell infiltration were observed in the LPS and LPS + DMSO groups while these effects were lessened in the LPS + A438079 group. The relative protein expression levels of P2X7R, Nf-kB-p65, IL-6, and Caspase-3 were significantly higher in the LPS and the LPS + DMSO groups than in the LPS + A438079 group. On the other hand, these protein expressions were considerably lower in the Control, A438079, and DMSO groups compared to the LPS + A438079 group. In addition, Bcl-2 protein expression was significantly lower in the LPS and the LPS + DMSO groups and higher in the LPS + A438079 group compared to the other groups. The protective effect of A438079 against LPS-induced hepatic inflammation may be related to P2X7R antagonism, inflammatory mediators, and apoptotic cell death., (© 2023 The Authors. Journal of Biochemical and Molecular Toxicology published by Wiley Periodicals LLC.)

Background: The aim of this study is to evaluate the effects of systemic melatonin treatment on serum oxidative stress index (OSI) and alveolar bone loss (ABL) in rats with diabetes mellitus (DM) and periodontitis., Methods: Seventy Sprague Dawley rats were divided into control, experimentally induced periodontitis (EP), DM, EP-DM, EP and melatonin treatment (EP-MEL), DM and melatonin treatment (DMMEL), and EP-DM-MEL groups. DM was induced by alloxan, after which periodontitis was induced by ligature for 4 weeks. After removal of the ligature, the rats in the melatonin groups (EP-MEL, DM-MEL, and EP-DM-MEL) were treated with a single dose of melatonin (10 mg/body weight) every day for 14 consecutive days. At the end of the study, all of the rats were euthanized, and intracardiac blood samples and mandible tissues were obtained for biochemical and histologic analyses. Serum levels of total oxidant status/total antioxidant status and OSI were measured. In addition, neutrophil and osteoclast densities and myeloperoxidase activities were determined in gingival tissue homogenates, and ABL was evaluated with histometric measurements., Results: Melatonin treatment significantly reduced fasting plasma glucose levels in the rats with DM. In addition, reduced OSI and ABL levels were detected in the EP-MEL and DM-MEL groups; the reductions in the EP-DM-MEL group were found to be more prominent. Melatonin also significantly decreased the increased myeloperoxidase activities and osteoclast and neutrophil densities in the EP, DM, and EP-DM groups., Conclusion: It is revealed in this experimental study that melatonin significantly inhibited hyperglycemia-induced oxidative stress and ABL through antiDM and antioxidant effects in rats with DM and periodontitis.

Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

The aim of this study was to evaluate the effects of systemic fucoxanthin treatment on alveolar bone resorption in rats with periodontitis. Thirty rats were divided into control, experimental periodontitis (EP), and experimental periodontitis-fucoxanthin (EP-FUCO) groups. Periodontitis was induced by ligature for four weeks. After removal of the ligature, the rats in the EP-FUCO group were treated with a single dose of fucoxanthin (200 mg/kg bw) per day for 28 consecutive days. At the end of the study, all of the rats were euthanized and intracardiac blood and mandible tissue samples were obtained for biochemical, immunohistochemical, and histometric analyses. Fucoxanthin treatment resulted in a slight decrease in tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels and a significant decrease in oxidative stress index. It was observed that fucoxanthin caused a significant reduction in receptor activator of nuclear factor kappa-β ligand (RANKL) levels and a statistically non-significant elevation in osteoprotegerin and bone-alkaline phosphatase levels. There were no significant differences in alveolar bone loss levels between the EP and EP-FUCO groups. This experimental study revealed that fucoxanthin provides a limited reduction in alveolar bone resorption in rats with periodontitis. One of the mechanisms underlying the mentioned limited effect might be related to the ability of fucoxanthin to inhibit oxidative stress-related RANKL-mediated osteoclastogenesis.

Extensive exercise induces inflammatory reactions together with high production of free radicals and subsequent liver and kidney tissues damage. This study was designed to investigate for effects of melatonin on liver and kidney tissues in the extensive exercise exposed rats and non-exercised rats. In this research, 24-male Sprague-Dawley rats were divided into four groups. For exercise rat model, the rats were exposed to slow pace running with the velocity of 10 m/min for 5 minutes for five days just before the study. And for last ten days after adaptation period, the exercise was improved as 15 min with the speed of 20 m/min and intra-peritoneal melatonin injection has been performed to the melatonin treated groups with the dose of 10 mg/kg. Biochemical results revealed a decrease in the parameters of kidney and liver enzymes in exercise-group and an increase in the parameters of serum, liver and kidney enzymes in the group that melatonin-exercise-group. As for histological analysis, while it is observed that there are cellular degenerations in the liver and kidney tissues with exercise application, a decrease has been observed in these degenerations in the group that melatonin was applied. At the end of the research, it has been determined that exercise application causes some damages on liver and kidney, and these damages were ameliorated with melatonin treatment.

This study was carried out to assess the protective bone-sparing effect of carnitine with anti-inflammatory properties on chronic inflammation-induced bone loss in ovariectomised (OVX) rats. A total of 64 rats were divided into eight groups. Sixteen rats were sham-operated (SH) while the others were ovariectomised (OVX). (1) SH, (2) sham + inflammation (SHinf), (3) OVX, (4) ovariectomy + inflammation (OVXinf), (5) OVX + CAR1, (6) OVX + CAR2, (7) OVXinf + CAR1, (8) OVXinf + CAR2. After the ovariectomy surgery, all the groups (3, 4, 5, 6, 7, and 8) were allowed to recover for two months. Sixty days after the OVX, inflammation was induced by subcutaneous injections of talc in groups 2, 4, 7, and 8. Group 5 and 7 were given 50 mg/kg CAR; Group 6 and 8 were given 100 mg/kg CAR from the 60th to the 80th day. Serum levels of TNF-α, IL-1, IL-6, OP, and OC were assessed to determine inflammation and to evaluate osteoblastic activity. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry in femur bones of rats. Carnitine administration was able to restore BMD up to values measured in both the OVX and the SH animals. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. In OVX rats, inflammation which is evaluated by serum cytokine levels exacerbated this bone loss, as supported by values of BMD of the total femur. The two different doses of carnitine reduced bone loss and improved inflammatory biomarkers.

Melatonin is an important antioxidant, and through its anti-inflammatory effects it can control immune responses, oxidative stress, and defense cell infiltration. Periodontitis is a disease of the oral cavity and the generation of free radicals is an important consideration in this disease. Therefore, we examined the immune-modulatory and antioxidant roles of melatonin in the treatment of periodontitis. In all, 30 male Wistar rats were randomly divided into three groups: the control group, the periodontitis-induced (PED) group, and the periodontitis+melatonin treatment (MEL+PED) group. The control group received no treatment, whereas periodontitis was induced in both the PED and the MEL+PED groups, with the MEL+PED group being treated with systemic melatonin. For the periodontitis-induced groups, the rats' mandibular first molar teeth were ligatured (3-0 cotton) in a submarginal position for 4 weeks, and then the ligature was removed. After removal of the ligature, melatonin was administered only to the MEL+PED group (an ip dose of 10mg/kg body wt for 15 days at 11:00 PM each day). In the histological examination, the MEL+PED group, which received the melatonin, showed reduced inflammatory cytokines (IL-1β, from 97.47 to 84.24pg/ml; TNF-α, from 0.22530 to 0.22519pg/ml), regulated oxidative stress parameters (MDA, from 41,458 to 30,708nmol/g; GSH, from 18,166 to 25,858nmol/mg), and less periodontal tissue destruction (CEJ-PL, lingual, from 244.54 to 140.57μm; buccal, from 235.6 to 158.93μm; and CEJ-BC, lingual, from 383.65 to 287.76μm; buccal, from 391.92 to 296.12μm). From these findings we conclude that, even when periodontitis was induced, melatonin reduced the oxidative damage in the rats' periodontal tissue by inhibiting the inflammatory effects and by restoring the antioxidants., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The protective effects of Panax ginseng (PG) on gentamicin sulphate (GS) induced acute nephrotoxicity were investigated in rats. A total of 32 adult Sprague-Dawley rats were randomly divided into 4 equal groups and treated by intraperitoneous route for 10 days with: 0.5 mL of isotonic saline (group C), GS 100 mg/kg/day (group GS), co treatment PG (100 and 200 mg/kg/day) plus GS (100 mg/kg/day). After the last injection, kidney markers (urea, creatinine and blood urea nitrogen-BUN) and hepatic markers (aspartate aminotransferase-AST, alanine aminotransferase-ALT, gama glutamil transferase-GGT), and biochemical parameters were analyzed using diagnostic kits. Also, kidney changes were evaluated by immunohistochemical and stereological methods. GS treatment induced significant elevation (P < 0.05) in kidney and hepatic markers, most of biochemical parameters, and Bax immunoreactivity as well. However, co treatments with both doses of PG (100 and 200 mg/kg/day) significantly alleviated (P < 0.05) the GS-induced elevations and have partially protected rats from nephrotoxicity (reduction of kidney damage, and of urea, creatinine and BUN concentrations, and of apoptotic index). Both biochemical results and immunohistochemical evidence showed that administration of PG reduced the gentamicin-induced nephrotoxicity.

Atherosclerotic heart diseases are universal problems in modern society. Oxidative damage to lipids is a primary cause of atherosclerosis. There are many choices for treatment, but no definite recommendations to prevent the occurrence of the disease. There is a relationship between atherosclerotic risk factors and increased vascular production of reactive oxygen species (ROS). Oxidized low-density lipoproteins (LDL) and ROS may directly cause endothelial dysfunction by reducing endothelial nitric oxide (NO) bioavailability. Vitamin E can to some degree prevent the consequences of oxidized LDL, and vitamin C provides NO synthase activity. Although prolonged use of vitamin A, C, and E supplementation in pharmaceutical forms has been proven to be effective in preventing atherosclerosis in animal experiments, this has not yet been demonstrated in clinical trials with human beings. It should be taken into account that the evidence has been gathered from young/adult experimental animals with early stages of arthrosclerosis and from in-vitro studies, while most of the clinical trials have involved older patients with late stages of the disease. Prolonged use of vitamins in the diet has not yet been recommended in human beings. There is some indication that a diet rich in antioxidant fruit and vegetables may be beneficial in the prevention of cardiovascular events.