T.C. Mathew

Indications of the mechanisms involved in improved sperm parameters by zinc therapy.

Objective: To determine possible indications of the mechanisms involved in improved sperm parameters by zinc therapy in asthenozoospermic men. Subjects and Methods: Forty-five men with asthenozoospermia (≧40% immotile sperm) were randomized into four therapy groups: zinc only: n = 11; zinc + vitamin E: n = 12 and zinc + vitamins E + C: n = 14 for 3 months, and non-therapy control group: n = 8. Semen analysis was done according to WHO guidelines. Malone dialdehyde, tumour necrosis factor-α (TNF-α), total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase were determined in the semen and serum. Antisperm antibodies IgG, IgM and IgA were evaluated by immunobeads. Sperm chromatin integrity was determined by acid denaturation by acridine orange and sperm apoptosis by light and electron microscopy. The effect of zinc on in vitro induced sperm oxidative stress by NADH was evaluated. Results: Asthenozoospermia was significantly associated with oxidative stress with higher seminal malone dialdehyde (8.8 vs. 1.8 mmol/l, p < 0.001) and TNF-α (60 vs. 12 pg/l, p < 0.001), and low total antioxidant capacity (1.8 vs. 8.4, p < 0.01), SOD (0.8 vs. 3.1, p < 0.01) and glutathione peroxidase (1.6 vs. 4.2, p < 0.05), compared to normozoospermia. Zinc therapy alone, in combination with vitamin E or with vitamin E + C were associated with comparably improved sperm parameters with less oxidative stress, sperm apoptosis and sperm DNA fragmentation index (DFI). On the whole, there was no difference in the outcome measures between zinc only and zinc with vitamin E and combination of vitamins E + C. In the in vitro experiment zinc supplementation resulted in significantly lower DFI (14–29%, p < 0.05) compared to zinc deficiency. Conclusion: Zinc therapy reduces asthenozoospermia through several mechanisms such as prevention of oxidative stress, apoptosis and sperm DNA fragmentation.

Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes

OBJECTIVE Effective diabetic management requires reasonable weight control. Previous studies from our laboratory have shown the beneficial effects of a low-carbohydrate ketogenic diet (LCKD) in patients with type 2 diabetes after its long term administration. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. These studies have indicated that, in addition to decreasing body weight and improving glycemia, LCKD can be effective in decreasing antidiabetic medication dosage. Similar to the LCKD, the conventional low-calorie, high nutritional value diet is also used for weight loss. The purpose of this study was to understand the beneficial effects of LCKD compared with the low-calorie diet (LCD) in improving glycemia. METHODS Three hundred and sixty-three overweight and obese participants were recruited from the Al-Shaab Clinic for a 24-wk diet intervention trial; 102 of them had type 2 diabetes. The participants were advised to choose LCD or LDKD, depending on their preference. Body weight, body mass index, changes in waist circumference, blood glucose level, changes in hemoglobin and glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, urea and creatinine were determined before and at 4, 8, 12, 16, 20, and 24 wk after the administration of the LCD or LCKD. The initial dose of some antidiabetic medications was decreased to half and some were discontinued at the beginning of the dietary program in the LCKD group. Dietary counseling and further medication adjustment were done on a biweekly basis. RESULTS The LCD and LCKD had beneficial effects on all the parameters examined. Interestingly, these changes were more significant in subjects who were on the LCKD as compared with those on the LCD. Changes in the level of creatinine were not statistically significant. CONCLUSION This study shows the beneficial effects of a ketogenic diet over the conventional LCD in obese diabetic subjects. The ketogenic diet appears to improve glycemic control. Therefore, diabetic patients on a ketogenic diet should be under strict medical supervision because the LCKD can significantly lower blood glucose levels.

Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level

AbstractObjective: Various studies have convincingly shown the beneficial effect of ketogenic diet (in which the daily consumption of carbohydrate is less than 20 grams, regardless of fat, protein and caloric intake) in reducing weight in obese subjects. However, its long term effect on obese subjects with high total cholesterol (as compared to obese subjects with normal cholesterol level is lacking. It is believed that ketogenic diet may have adverse effect on the lipid profile. Therefore, in this study the effect of ketogenic diet in obese subjects with high cholesterol level above 6 mmol/L is compared to those with normocholesterolemia for a period of 56 weeks. Materials and methods: In this study, 66 healthy obese subjects with body mass index (BMI) greater than 30, having high cholesterol level (Group I; n = 35) and those subjects with normal cholesterol level (Group II; n = 31) were selected. The body weight, body mass index, total cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, glucose and triglycerides were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored at 8, 16, 24, 32, 40, 48 and 56 weeks of the treatment. Results: The body weight and body mass index of both groups decreased significantly (P < 0.0001). The level of total cholesterol, LDL cholesterol, triglycerides and blood glucose level decreased significantly (P < 0.0001), whereas HDL cholesterol increased significantly (P < 0.0001) after the treatment in both groups. Conclusion: This study shows the beneficial effects of ketogenic diet following its long term administration in obese subjects with a high level of total cholesterol. Moreover, this study demonstrates that low carbohydrate diet is safe to use for a longer period of time in obese subjects with a high total cholesterol level and those with normocholesterolemia.

Zinc and liver cirrhosis: Biochemical and histopathologic assessment

Experimental liver cirrhosis was produced by administration of thioacetamide. Cirrhotic animals were divided into two groups: one group was given zinc sulphate and the second kept as cirrhotic control. Zinc-treated animals showed a restoration of normal hepatic and plasma zinc and copper levels. Similarly, plasma levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl aminotransferase, and total bilirubin decreased significantly. Light microscopic studies showed that most of the hepatocytes appeared normal in zinc-treated as compared with untreated cirrhotic animals. The amount of fibrin, reticulin, and collagen, which was high in the cirrhotic livers, decreased following zinc treatment. Staining with periodic acid Schiffs reagent showed the ability of hepatocytes to store glycogen after zinc treatment. These results revealed that zinc may have some beneficial effect in the treatment of liver cirrhosis.

SELENIUM AND LIVER CIRRHOSIS

Effects of selenium deficiency, induced by thioacetamide, were investigated in rats. Thioacetamide (0.3 g/L) given in drinking water, as expected, caused a significant loss of selenium from the liver. It was accompanied by liver cirrhosis and a significant increase in the liver weight as well as liver to body weight ratio. A significant loss of selenium from spleen was also accompanied by an increase in its weight. Weights of lungs, testis and kidney, however, were not affected by thioacetamide and there was no change in their selenium content. Plasma levels of selenium were significantly reduced in the thioacetamide treated group. All these changes were confirmed to be due to selenium deficiency caused by thioacetamide, as supplementation with selenium reversed these changes. The mode of action of selenium is unknown but may involve anti-oxidant defense mechanisms.

Effect of green tea in the prevention and reversal of fasting-induced intestinal mucosal damage

OBJECTIVE Epidemiologic studies have suggested that high consumption of green tea protects against the development of chronic active gastritis and decreases the risk of stomach cancer. The effect of green tea on the intestinal mucosa was not studied previously, so we examined the effects of green tea on the intestinal mucosa of fasting rats in a controlled experimental setting. METHODS Two sets of experiments were performed. In the recovery set, rats were fasted for 3 d, after which they were allowed free access to water, black tea, green tea, or vitamin E for 7 d. On day 8, the animals were killed, and small bowels were removed for histologic examination. In the pretreatment set, rats were allowed a normal diet, but the water supply was replaced with green tea, black tea, or vitamin E for 14 d. They were subsequently fasted for 3 d. On day 4, the rats were killed, and small bowels were removed for histologic examination. RESULTS In the recovery set, fasting for 3 d caused shortening of villi, atrophy, and fragmentation of mucosal villous architecture, with a significant (P < 0.0001) reduction in the length and surface area of the villi. Ingestion of green tea and, to a lesser extent, vitamin E for 7 d helped in the recovery of villi to normal. In the pretreatment set, drinking green tea, black tea, or vitamin E for 14 d before fasting protected intestinal mucosa from damage. CONCLUSION The mucosal and villous atrophy induced by fasting was reverted to normal by the ingestion of green tea and, to a lesser extent, vitamin E. Black tea ingestion had no effect. In addition, ingestion of black tea, green tea, and vitamin E before fasting protected the intestinal mucosa against atrophy.

Cholangiocarcinoma and liver cirrhosis in relation to changes due to thioacetamide

Different doses of thioacetamide (0.05, 0.1 and 0.15%) were used to induce liver cirrhosis in Wistar rats. Thioacetamide at 0.5% caused cirrhosis by the twelfth week of treatment. A severe bile duct proliferation and cholangiocarcinoma was seen at longer intervals. Animals treated with higher doses (0.1 and 0.15%) of thioacetamide developed more severe intense degenerative changes in the liver and died in the twelfth and eighth week respectively. The serum and tissue contents of Zn and Cu changed in a characteristic fashion that was consistent with the severity of the liver damage. Serum Zn and Cu concentrations were at their lowest in the animals that developed severe degenerative liver and died at higher dose (0.15%) of thioacetamide.This study indicates that treatment of rats with 0.05% thiocetamide is more effective and appropriate for the induction of liver cirrhosis. Continued administration of the drug at this dosage led to the development of further changes in the liver. This model may be suitable for studying these long term changes that occur in the liver and lead to cirrhosis. Events that precede the development of severe bile duct proliferation and cholangiocarcinoma may also be studied.

Therapeutic role of low-carbohydrate ketogenic diet in diabetes

INTRODUCTION Changes in dietary habits influence the glycemic level. Preliminary studies using the low-carbohydrate ketogenic diet (LCKD) were found to be quite promising in controlling diabetes mellitus. Therefore, the objectives of this study are to investigate the therapeutic effects of LCKD in experimental diabetic rats following the administration of streptozotocin (STZ). MATERIALS AND METHODS Adult rats were divided into three groups: normal diet, LCKD, and high-carbohydrate diet. Each group was subdivided into normal, sham, and diabetic groups. Diabetes was induced by a single intraperitoneal injection of STZ (55mg/kg). Specific diets were given to each group of animals for a period of 8 wk and then the animals were sacrificed. The rats were monitored daily for food and water intake, whereas body weight, urine output, and blood glucose levels were monitored weekly. The histology of the islets of Langerhans was studied by histochemical methods. RESULTS The results showed that LCKD was effective in bringing blood glucose level close to normal (P<0.01). Food and water intake and urine output were increased in all groups except the LCKD group (P<0.01). The body weight was significantly reduced in all diabetic animals except in the LCKD group (P<0.01). Histologic studies showed significant decrease in the islet size and number of beta cells in all the diabetic groups. CONCLUSION This study indicates that LCKD has a significant beneficial effect in ameliorating the diabetic state and helping to stabilize hyperglycemia.

Low carbohydrate ketogenic diet enhances cardiac tolerance to global ischaemia.

Summary — The cardio-protective effects of a low carbohydrate ketogenic diet following global ischaemic injury as compared to rats fed a normal and high carbohydrate diet for a period of 19 weeks, were investigated.The reperfusion recovery of coronary flow was highly significant in the low carbohydrate ketogenic diet group. Although the initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups, after 15 minutes, the momentum for faster recovery was maintained in the low carbohydrate ketogenic diet group. Ultrastructural observations of the cardiac muscles have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group. This study demonstrates that a low carbohydrate ketogenic diet is cardio-protective functionally. Introduction — Ischaemia and reperfusion lead to cell death. These pathways are regulated and hence are subjected to therapeutic intervention. Previously, we have shown that a low carbohydrate ketogenic diet (LCKD) reduces the risk factors for heart disease in obese patients.This study is aimed at understanding the cardio-protective effects of LCKD following global ischaemic injury in rats. Materials and methods — Rats weighing 190-250 g were divided into normal diet (ND), LCKD and high carbohydrate diet (HCD) groups consisting of six animals in each group. Specific diets were given to each group for a period of 19 weeks. Changes in body weight, ultrastructure of the cardiac muscles and the cardio-protective effects of the LCKD group as compared to the ND and HCD groups were investigated in rats following global ischaemic injury. Results — Electron microscopic studies have shown that there was a decrease in the number of mitochondria in rats fed a high carbohydrate diet and an increase in the number of mitochondria in those fed a low carbohydrate ketogenic diet as compared to the normal diet group. Rats on LCKD had a remarkable tolerance to ischaemia and a faster recovery of cardiac function following reperfusion. The initial reperfusion recovery of the pressure developed in the left ventricle, Pmax was similar in all groups. However, after 15 minutes, the momentum for faster recovery was significantly maintained in the LCKD group (P < 0.05).The reperfusion recovery of coronary flow was highly significant (P < 0.05) in the LCKD regime.The increase in left ventricle end diastolic pressure, coronary vascular resistance and the changes in body weight were not significant between the experimental groups. Discussion and conclusion — This is a unique study showing ultrastructural variation in cardiac muscle in relation to cardio-protective function in rats fed a low carbohydrate ketogenic diet. This study suggests that the LCKD is cardio-protective functionally.The underlying mechanism of the cardioprotective effect of an LCKD needs to be elucidated.

Serum changes in trace elements during thyroid cancers

The objective was to examine changes in trace elements due to thyroid cancer in humans. Serum levels and tissue contents of trace elements (Zn, Cu, Mn, Mg, Fe and Se) were measured in 43 patients with thyroid cancer before and 4 days after surgery were compared to normal values. The serum levels of zinc in cancer patients were lower than those of normal subjects. Surgical removal of the cancer resulted in the restoration of these levels. Although serum Cu levels in patients were not different from normal, but post-operatively these levels rose significantly (p < 0.001). Levels of Fe, Mg and Mn were significantly lower (p < 0.001) post-operatively. There was no significant change in Serum Se levels. The thyroid tissue contents of these trace elements did not show a difference between the normal (Juxta-tumor) thyroid tissue and the cancerous lesion. Out of the six trace elements examined, the decrease of serum levels of zinc in cancer patients may be linked to the disease condition. It is suggested that this change: (a) may be used to demonstrate successful cancer surgery and (b) may have implications for a long-term follow-up of thyroid cancer patients.