[show abstract][hide abstract] ABSTRACT: Hemozoin production makes it possible for intraerythrocytic malaria parasites to digest massive quantities of hemoglobin but still avoid potential ferriprotoporphyrin IX (FP) toxicity, which they cannot decompose further. Some antimalarial drugs, such as chloroquine, work by inhibiting this production, forcing the parasite to starve to death. As part of the efforts to identify possible biological mechanisms of FP polymerization, we have used normal human erythrocyte membranes as a model, to promote β-hematin (β-h) synthesis. Hemin in 35% aqueous dimethyl sulfoxide (DMSO) was reacted with isolated erythrocyte membranes and incubated overnight in sodium acetate buffer, pH 4.8, at 41°C. Infrared spectroscopy and electron microscopy showed that β-h was produced. Hemin in 10% was less effective as the substrate than when it was in 35% DMSO. A high malarial temperature seemed to be necessary, because FP polymerization was less at 37°C than at 41°C. Production was partially inhibited by chloroquine. These observations are of interest because other investigators have reported that membrane lipids mediated FP polymerization, but whole membranes were ineffective. On the other hand, our hypothesis is that the transport vesicles (TV) in malaria parasites could provide the receptor for FP and the lipids that promote hemozoin formation. Erythrocyte membranes may not be directly involved, but Plasmodium species transport hemoglobin in membrane-bound TV into food vacuoles, where hemoglobin catabolism is completed and hemozoin crystals are stored.
Experimental Biology and Medicine 08/2012; 237(8):884-93. · 2.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: Diabetes continues to be an overwhelmingly prevalent endocrine disorder that leads to several micro- and macrocomplications. It has been widely accepted that changes in dietary habits could induce or prevent the onset of diabetes. It is shown that low carbohydrate ketogenic diet (LCKD) is effective in the amelioration of many of the deleterious consequences of diabetes. However, its role in preventing the onset of diabetes is not understood. Therefore, this study is focused on the effect of LCKD in preventing the induction of diabetes using streptozotocin (STZ) in rats by biochemical and histological methods. Forty-two Wistar rats weighing 150-250 g were used in this study. The animals were divided into three groups: normal diet (ND), low carbohydrate ketogenic diet (LCKD), and high carbohydrate diet (HCD). Specific diets ad libitum were given to each group of animals for a period of 8 weeks. Each group was further subdivided into normal control, sham control and diabetic groups. Animals in the diabetic group were given a single intraperitoneal injection of STZ (55 mg/kg). All the animals were sacrificed 4 weeks after the injection of STZ. Daily measurements of food and water intake as well as weekly measurement of body weight were taken during the whole 12 weeks of the experiment. After injecting with STZ, the blood glucose level of all the groups increased significantly except for the group fed on LCKD (p value<0.01). Also, food intake, water intake and urine output were significantly increased in all groups except for the LCKD group (p value<0.01). There was also a significant decrease in the weight gain of the animals that were fed on a LCKD as compared to other groups (p value<0.05). Although, substantial decrease in the number of β cells was noticed in diabetic rats, there were no change in the number of β cells in the LCKD treated diabetic animals as compared to LCKD control group. The results presented in this study, therefore, suggests that LCKD prevents the development of diabetes using streptozotocin in rats.
Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 11/2011; 63(7-8):663-9. · 1.43 Impact Factor
[show abstract][hide abstract] ABSTRACT: The intestinal mucosa is known to be adversely affected by ischemia-reperfusion (I/R). Previously we showed that green tea protects the intestinal mucosa from fasting-induced damage. The aim of this study is to determine whether green tea has any protective role in I/R of the intestine.
Three groups of male rats were used in this study. Group I (I/R) underwent I/R of the intestine (30 min of ischemia followed by 1 h of reperfusion). Group II (green tea + I/R) was given green tea for 2 wk before inducing I/R. Group III (control) had sham I/R. After the experiments, the jejunum was removed and the tissues were processed for histopathologic examination and immunohistochemical analysis for cell proliferation markers and antioxidant enzymes.
The intestinal mucosa in group II was preserved compared with that in group I. The expressions of cellular proliferation markers (proliferating cell nuclear antigen and Ki-67) and cellular antioxidants (superoxide dismutase and catalase) in group II were similar to those in group III and much less than in group I, reflecting the protective effects of green tea in group II animals.
In this animal model, administration of green tea before inducing I/R protects the intestinal mucosa from injury.
[show abstract][hide abstract] ABSTRACT: Green tea has been shown to repair fasting-induced mucosal damage in rat intestine. The aim of this study was to elucidate the underlying mechanism.
Five groups of rats were used. Group 1 had free access to chow diet and water, and those in group 2 were fasted for 3 days. Animals in group 3 were fasted for 3 days, then were allowed drinking water for a further 7 days. Groups 4 and 5 were fasted for 3 days, then given drinking water containing green tea or vitamin E respectively for 7 days. Blood was collected for estimation of total plasma antioxidants, and jejunal samples were used for immunohistochemical analysis of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), and for estimation of myeloperoxidase (MPO) activity.
Use of green tea was associated with a significant increase in total plasma antioxidants (P < 0.001), and mucosal SOD (P < 0.001), catalase (P = 0.006) and GPx (P = 0.017), but a significant decrease in MPO activity (P < 0.001). Vitamin E produced similar changes, but the effects were smaller.
Green tea reverses the fasting-induced damage to the intestinal mucosa by its antioxidant and anti-inflammatory effect.
British Journal of Surgery 06/2009; 96(5):552-9. · 4.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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).
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.
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.
This study indicates that LCKD has a significant beneficial effect in ameliorating the diabetic state and helping to stabilize hyperglycemia.
[show abstract][hide abstract] ABSTRACT: It is generally known that the luminal surface of the choroidal epithelial cells is covered with a luxuriant coat of slender microvilli and cilia. However, extensive ultrastructural studies on the surface morphology of choroidal epithelial cells are lacking. This study, therefore, is focused on the detailed surface morphology of the choroid plexus of the lateral ventricle of adult Wistar rats using transmission and scanning electron microscopy. The animals were anesthetized, perfused with 0.9% oxygenated saline followed by 3% gluteraldehyde and the choroid plexus was processed for routine electron microscopy. The results of the ultrastructural observations presented in this study show that even the neighboring choroidal epithelial cells may express distinct morphology. In addition to the usually described morphology of choroidal epithelial cells, in this study, the presence of cells with uniform small blebs, crenulated or doughnut shaped structures, large mature blebs, or cells with an extensive network of fibers were observed. Although, dissimilar surface morphology of adjacent choroidal epithelial cells may indicate their distinct functional status, further studies are necessary to understand the physiological relevance of the varied surface morphology of choroidal epithelial cells.
Molecular and Cellular Biochemistry 08/2007; 301(1-2):235-9. · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Obesity is closely linked to the incidence of type II diabetes. It is found that effective management of body weight and changes to nutritional habits especially with regard to the carbohydrate content and glycemic index of the diet have beneficial effects in obese subjects with glucose intolerance. Previously we have shown that ketogenic diet is quite effective in reducing body weight. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. In this study the effect of ketogenic diet in obese subjects with high blood glucose level is compared to those with normal blood glucose level for a period of 56 weeks.
A total of 64 healthy obese subjects with body mass index (BMI) greater than 30, having high blood glucose level and those subjects with normal blood glucose level were selected in this study. The body weight, body mass index, blood glucose level, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, urea and creatinine were determined before and at 8, 16, 24, 48, and 56 weeks after the administration of the ketogenic diet.
The body weight, body mass index, the level of blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P < 0.0001), whereas the level of HDL-cholesterol increased significantly (P < 0.0001). Interestingly these changes were more significant in subjects with high blood glucose level as compared to those with normal blood glucose level. The changes in the level of creatinine were not statistically significant.
This study shows the beneficial effects of ketogenic diet in obese diabetic subjects following its long-term administration. Furthermore, it demonstrates that in addition to its therapeutic value, low carbohydrate diet is safe to use for a longer period of time in obese diabetic subjects.
Molecular and Cellular Biochemistry 08/2007; 302(1-2):249-56. · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
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 cardio-protective effect of an LCKD needs to be elucidated.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to assess the effects of alpha-interferon and alpha-tocopherol (vitamin E), or a combination of both, in reversing hepatic fibrosis following the induction of cirrhosis using thioacetamide by histological and biochemical analysis. Fifty male Wistar rats were used in this study. The animals were divided equally into five groups. Animals in group I were used as controls. The remaining animals (groups II-V) were provided with 0.5 g/L of thioacetamide in order to induce liver cirrhosis. Group II animals were used as the cirrhotic control. Animals of groups III, IV and V were given alpha-interferon, alpha-tocopherol and interferon together with alpha-tocopherol, respectively, for 30 days. After 30 days the animals were killed and following gross morphological examination of the liver, the hepatic tissues were processed for histological analysis and the serum was used for liver function tests. Morphological analysis showed a decrease in the number of nodules on the surface of the liver in both interferon- as well as vitamin E-treated cirrhotic rats. Histopathological analysis showed that the abnormalities of the cirrhotic liver were partially reversed and liver function tests showed an overall improvement following treatment of animals of groups III, IV and V. Combination therapy using both interferon and alpha-tocopherol did not have any substantial effect on the rats compared with that when they were given separately. These findings suggest that alpha-interferon and alpha-tocopherol may have therapeutic value in reversing liver cirrhosis.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
Molecular and Cellular Biochemistry 07/2006; 286(1-2):1-9. · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
Molecular and Cellular Biochemistry 05/2004; 260(1-2):1-5. · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although various studies have examined the short-term effects of a ketogenic diet in reducing weight in obese patients, its long-term effects on various physical and biochemical parameters are not known.
To determine the effects of a 24-week ketogenic diet (consisting of 30 g carbohydrate, 1 g/kg body weight protein, 20% saturated fat, and 80% polyunsaturated and monounsaturated fat) in obese patients.
In the present study, 83 obese patients (39 men and 44 women) with a body mass index greater than 35 kg/m(2), and high glucose and cholesterol levels were selected. The body weight, body mass index, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, fasting blood sugar, urea and creatinine levels were determined before and after the administration of the ketogenic diet. Changes in these parameters were monitored after eight, 16 and 24 weeks of treatment.
The weight and body mass index of the patients decreased significantly (P<0.0001). The level of total cholesterol decreased from week 1 to week 24. HDL cholesterol levels significantly increased, whereas LDL cholesterol levels significantly decreased after treatment. The level of triglycerides decreased significantly following 24 weeks of treatment. The level of blood glucose significantly decreased. The changes in the level of urea and creatinine were not statistically significant.
The present study shows the beneficial effects of a long-term ketogenic diet. It significantly reduced the body weight and body mass index of the patients. Furthermore, it decreased the level of triglycerides, LDL cholesterol and blood glucose, and increased the level of HDL cholesterol. Administering a ketogenic diet for a relatively longer period of time did not produce any significant side effects in the patients. Therefore, the present study confirms that it is safe to use a ketogenic diet for a longer period of time than previously demonstrated.
Experimental and clinical cardiology 01/2004; 9(3):200-5. · 1.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.