Role of fructose concentration on cataractogenesis in senile diabetic and non-diabetic patients.

BACKGROUND: Fructose intake has increased steadily during the past 2 decades. Fructose, like other reducing sugar, can react with proteins, which may account for aging and cataract formation. Fructose participates in glycation (fructation) and advanced glycation endproducts (AGE) formation some ten times faster than glucose. This study aims to determine the fructose concentration and correlate with antioxidant status in senile diabetic and non-diabetic cataract patients. METHODS: The study included 124 subjects. Of them, 31 were normal senile subjects, 33 were senile diabetic patients without cataract, 30 were senile diabetic patients with cataract, and 30 were senile non-diabetic patients with cataract. The patients were selected on clinical grounds from Eye Ward, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. RESULTS: Serum fructose was significantly increased (P < 0.001) in senile diabetic patients with and without cataract and senile non-diabetic patients with cataract as compared with senile control subjects. Negative significant correlation was observed between serum fructose and serum total antioxidant status in diabetic and non-diabetic patients with cataract. Positive significant correlation was observed between serum fructose and s-AGEs in diabetic and non-diabetic patients with cataract. Serum total antioxidant status was found to be significantly decreased (P < 0.001) in senile diabetic patients with and without cataract and senile non-diabetic patients with cataract as compared with senile control subjects. Fasting blood glucose, HbA(1C) and serum fructosamine were significantly increased (P < 0.001) in senile diabetic patients with or without cataract as compared with senile non-diabetic patients with cataract and senile control subjects. CONCLUSIONS: The results indicate that the increased fructose concentration which induces oxidative stress in diabetic and non-diabetic patients with cataract may be a predictor for cataractogenesis.

Antioxidant status in diabetic and non-diabetic senile patients, with cataract or cardiovascular complications.

OBJECTIVE: To assess the total antioxidant status in diabetic and non-diabetic senile patients, with cataract or cardiovascular complications, and without complications. METHODS: A comparative study on 186 senile patients and control subjects was carried out from March 2004 to November 2006 on patients from Ziauddin University Hospital, Karachi, Pakistan. Among them, 33 were diabetic patients without any clinical evidence of chronic diabetic complications, 32 with cardiovascular complications, 30 non-diabetic patients with cardiovascular complications, 30 diabetic patients with cataract, 30 non-diabetic patients with cataract, and 31 apparently normal, age, gender, and weight matched control subjects were investigated. All patients were selected on clinical grounds. RESULTS: Total antioxidant status was significantly decreased (p<0.001) in all diabetic patients with and without complications, and non-diabetic patients with same complications (155 patients) as compared with control subjects (31 subjects). Fasting plasma glucose was increased (p<0.001) in all diabetic patients with and without complications (95 patients), and correlated significantly with glycosylated hemoglobin (HbA1C) and serum fructosamine concentrations. Fasting plasma glucose, HbA1C, and serum fructosamine were not different in diabetic patients with and without complications. Fasting plasma glucose, HbA1C, serum fructosamine, and total serum protein were not different in non-diabetic patients with the same complications, as compared with control subjects. CONCLUSION: Total antioxidant status is decreased in diabetic and non-diabetic senile patients with the same complication as compared with control subjects. Some other factors may be responsible for decrease antioxidant status.

Potential role of amino acids in pathogenesis of schizophrenia.

Schizophrenia is a syndrome of inconclusive etiopathogenesis with a prevalence of about 1% in general population. Underlying factors include genetic predisposition and defected neurodevelopment in early stages of life. The role of amino acids has been indicated in some reports. However, very few workers have detailed the effect of each amino acid in the pathophysiology of schizophrenia. Thus, in the present review, we aimed to provide an insight into the potential role of amino acids levels during schizophrenia. Any single amino acid defect cannot lead to the development of the disease. Higher concentration of glycine, serine, glutamate, homocysteine, and arginine are reported by many scientists in blood samples of patients of schizophrenia. Levels of rest of the amino acids show inconsistent results. Involvement of glutamate in pathophysiology of schizophrenia was hypothesized as early as the 1980s. It was demonstrated that dissociative anesthetics which are N-methyl-D-aspartate (NMDA) receptor antagonists can produce all negative, psychotic, cognitive, and physiological features of schizophrenia in healthy controls. This led to the development of hypothesis of NMDA receptor hypofunctioning in the pathophysiology of schizophrenia. Later on, it was also found that agents enhancing functioning of NMDA receptor at glycine modulatory site, improved symptoms in patients of schizophrenia receiving antipsychotic medications. Thus, the relationship of perturb amino acid levels with the biological basis and pathophysiology of schizophrenia is an important area to be further explored for effective management of schizophrenic patients.

Comparison of blood protein levels between diabetic and non-diabetic patients with retinopathy.

OBJECTIVE: To compare serum protein levels between diabetic and non-diabetic patients with retinopathy. STUDY DESIGN: Comparative study. PLACE AND DURATION: Ziauddin Medical University and Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from 2000 to 2002. PATIENTS AND METHODS: Sixty patients were selected. Among them, 21 were diabetic patients without any clinical evidence of chronic diabetic complications; 20 were diabetic patients with retinopathy and 19 were non-diabetic patients with retinopathy. Twenty-one apparently normal, age, gender and weight-matched control subjects were also inducted. All these patients were selected on clinical grounds. Blood values, fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, glycosylated plasma protein, hexosamine, sialic acid and total serum proteins were determined and compared. RESULTS: Fasting plasma glucose was high in all diabetic patients and correlated significantly with glycosylated hemoglobin, glycosylated plasma proteins and serum fructosamine concentrations. Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with retinopathy and diabetic patients without any complications. These values were not different in diabetic patients with retinopathy and diabetic patients without chronic complications as compared with control subjects. Alpha-1 and alpha-2 globulins were significantly increased in diabetic patients with retinopathy, diabetic patients without complications and non-diabetic patients with retinopathy as compared with control subjects. Beta globulin was significantly increased in diabetic patients with retinopathy as compared with non-diabetic patients with retinopathy, diabetic patients without complication and control subjects. Gamma globulin was significantly decreased in diabetic and non-diabetic patients with retinopathy. CONCLUSION: Fasting plasma glucose, glycosylated hemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein were increased in diabetic patients with and without complications but these parameters remained within normal limits in non-diabetic patients with retinopathy. The decrease in gamma globulins may be associated with a retinopathy.

Relationship of cytokines and AGE products in diabetic and non-diabetic patients with cataract.

OBJECTIVES: Cytokines are important mediators of inflammatory and immune responses. The aim of this study was to investigate the changes in cytokines concentration (IL-6, IL-8 and TNF-α) and serum advanced glycation end products (sAGEs) in senile diabetics with or without cataract and non-diabetic patients with cataract. METHODOLOGY: The study included 124 subjects (sixty or over sixty years age), distributed as four groups thirty senile diabetic patients with cataract (Group I) (16 female and 14 male), thirty senile non-diabetic patients with cataract (Group II) (15 female and 15 male), thirty three senile diabetic patients without any complication (Group III) (16 female and 17 male), thirty one apparently normal healthy individuals (Group IV) (16 female and 15 male), age, sex and weight matched with senile control subjects were investigated. Patients were selected on clinical grounds from Eye Ward Jinnah Postgraduate Medical Centre. RESULTS: Interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) levels were significantly increased (P < 0.001) in Group I and III as compared to Group II and IV. Fasting blood glucose, glycosylated hemoglobin, serum fructosamine, malondialdehyde (MDA), sAGEs, IL-6, IL-8 and TNF-α levels were significantly increased (P < 0.001) in Group I as compared to Group II and the levels were almost same in Group II and IV. There was a significant decrease in serum vitamin E and total antioxidant status (p< 0.001) in Group I and Group III as compared to Group II and Group IV. CONCLUSION: The results of the present study thus demonstrated that levels increased in both condition but are more severe in diabetic patients with cataract that may be a predictor for cataractogenesis and the levels were almost same in Group II and IV.

Changes in glycosylated proteins in type-2 diabetic patients with and without complications.

BACKGROUND: Diabetes mellitus constitutes one of the most important problems in developing and developed countries. Increased glycosylation of various proteins in diabetic patients has been reported by many authors. The present study describes the changes in protein glycosylation in diabetic patients with and without diabetic complication. METHODS: The study included one hundred and three subjects. Among them 21 were type 2 diabetic patients without any clinical evidence of chronic diabetic complications, 21 were type 2 diabetic patients with cardiovascular complications, 20 were type 2 diabetic patients with cataract, 20 were type 2 diabetic patients with retinopathy and 21 apparently normal, age, sex and weight matched controls. The patients were selected from Ziauddin Medical University Hospital, Karachi and Jinnah Postgraduate Medical Centre, Karachi. RESULTS: Fasting plasma glucose was increased in all diabetic patients and correlated significantly with glycosylated hemoglobin, glycosylated plasma proteins and serum fructosamine concentrations. There was no significant difference in the levels of fasting plasma glucose, glycosylated plasma proteins, glycosylated hemoglobin, serum fructosamine, hexosamine or sialic acid between diabetic patients with or without chronic complications. Alpha-1 and alpha-2 globulin fraction were significantly increased in diabetic patients without complications, diabetic patients with cardiovascular complications and diabetic patients with cataract. Albumin was found to be decreased in diabetic patients with cataract while gamma globulin was increased in diabetic patients with cardiovascular complications and diabetic patients with cataract. CONCLUSIONS: In uncomplicated diabetic patients alpha-1 and alpha-2 glycoproteins were increased. In diabetic patients with cardiovascular complications alpha-1, alpha-2 and gamma globulin were increased while in diabetic patients with cataract alpha-1, alpha-2 and gamma globulin were increased but serum albumin was significantly decreased.

Influence of cimetidine and bromocriptine on prolactin levels in rat fertility.

The present study was designed to see the effects of parenterally administered drugs cimetidine and bromocriptine affecting serum prolactin upon the fertility of adult male albino rats. Ninety adult young male albino rats between the ages of 60 to 120 days were selected. The animals were divided into three groups. Cimetidine was administered in a dose of 200 mg/kg body weight to group B intramuscularly and in addition to cimetidine, bromocriptine in a dose of 2.5 mg/day intramuscularly was given to group C. Normal saline was administered intramuscularly to control group A. Plasma prolactin was measured by Enzyme Immunoassays. Spermatogonia, spermatocytes, and spermatids were studied under oil immersion. The final plasma prolactin level instead of being elevated was found slightly depressed though insignificant in case of group B while remained slightly elevated instead of being suppressed/depressed though insignificant in group C. In group B spermatogenesis was normal in almost all of the tubules but a few of them were seen lined with only Sertoli cells and all the other germ cells like spermatogonia, primary spermatocytes, spermatids early and late, and spermatozoa were absent indicating total atrophy with both Sertoli cells and Leydig cells hyperplasia. While in the moderately affected tubules different types of spermatogonia A/B or intermediate were seen near the basement membrane. In group C both normal and abnormal germinal epithelium was seen in same/different tubules but a few of them were seen lined with only Sertoli cells and all the other germ cells like spermatogonia, primary spermatocytes, spermatids early and late, and spermatozoa were absent. The process of spermatogenesis was variable and appeared to be normal in most but in some it was found to be suppressed. This study revealed that the toxic effect of the drugs contributes to the infertility. It has not shown to be mediated through hormones in present study for which further research work is needed using low dose and longer duration to see the role of prolactin in causing infertility.

Advanced glycation end products in senile diabetic and nondiabetic patients with cataract.

BACKGROUND: Advanced glycation end products (AGE) have been reported to contribute to aging and cataract formation in the lens. In the present study, AGE immunoreactivity in human serum samples of normal senile subjects (n=31), senile diabetic patients without cataract (n=33), senile diabetic patients with cataract (n=30), senile nondiabetic with cataract (n=30), and normal young subjects (n=31) was investigated. METHODS: A noncompetitive ELISA with polyclonal anti-AGE antibody was performed. The patients were selected on clinical grounds from Eye Ward, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. RESULTS: Fasting blood glucose, glycosylated hemoglobin, and serum fructosamine were estimated. Fasting blood glucose, HbA(1C), and serum fructosamine levels were significantly (P<.001) increased in senile diabetic patients with and without cataract as compared to nondiabetic senile patients with cataract and senile control subjects. However, the serum AGEs were found to be significantly (P<.001) increased in senile diabetic patients with cataract and senile nondiabetic patients with cataract followed by the diabetic patients without cataract as compared to senile control and young control subjects. In contrast to all four senile groups, the serum AGEs were significantly (P<.001) lower in young control subjects. CONCLUSIONS: The AGE distribution in the senile groups corroborates the hypothesis that the advanced glycation process might have a role in cataract formation, which in diabetic patients occurs vigorously as compared with nondiabetic cataract patients.

Advanced glycation end-products in senile diabetic and non-diabetic patients with cardiovascular complications.

Advanced glycation end products (AGEs) have been reported to contribute to aging and cardiovascular complications. In the present study, the immunoreactivity of AGEs in human serum samples of healthy older subjects (n = 31), senile diabetic patients without cardiovascular complications (n = 33), senile diabetic patients with cardiovascular complications (n = 32), senile non-diabetic patients with cardiovascular complications (n = 30) ,and healthy young subjects (n = 31) were investigated. The patients were selected on clinical grounds from the National Institute of Cardiovascular Disease, Karachi and the Jinnah Postgraduate Medical Centre, Karachi, Pakistan. Fasting blood glucose, HbA(1C) and serum fructosamine levels were significantly (P < 0.001) increased in senile diabetic patients with and without cardiovascular complications as compared to non-diabetic senile patients with cardiovascular complications and healthy older subjects. Additionally, serum AGEs were found to be significantly (P < 0.001) increased in senile diabetic patients with cardiovascular complications and senile non-diabetic patients with cardiovascular complications, followed by diabetic patients without cardiovascular complications as compared to healthy older subjects and young control subjects. However, no significant difference was found in the senile diabetic patients without cardiovascular complications and senile non-diabetic patients with cardiovascular complications. In contrast to all four senile groups, serum AGEs were significantly (P < 0.001) lower in young control subjects. The AGEs distribution in the senile groups corroborates the hypothesis that the advanced glycation process might play a role in the development of cardiovascular complications, which are more severe in diabetic patients compared with non-diabetic patients with cardiovascular complications.

Could oxidative stress associate with age products in cataractogenesis?

BACKGROUND: Oxidative stress has been reported to contribute to aging and cataract formation in the lens. The aim was to determine the association of oxidative stress with advanced glycation end products (AGEs) in elderly diabetic and non-diabetic patients with cataract. METHODS: In the present study, malondialdehyde, vitamin E, serum AGEs, and glycemic control were investigated. The study included 156 subjects. Out of them, 30 were normal elderly subjects, 31 were elderly diabetic patients without cataract, 33 were elderly diabetic patients with cataract, 32 were elderly non-diabetic with cataract, and 30 were normal young subjects. The patients were selected on clinical grounds from Eye Ward, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. RESULTS: Positive significant correlation was observed between s-AGEs and malondialdehyde in elderly diabetic and non-diabetic patients with cataract. Negative significant correlation was observed between s-AGEs and vitamin E in elderly diabetic and non-diabetic patients with cataract. However, the malondialdehyde and serum AGEs were found to be significantly increased (p < 0.001) in elderly diabetic and non-diabetic patients with and without cataract compared with elderly control subjects. In contrast to all four senile groups, the serum AGEs was significantly lower (p < 0.001) in young control subjects. Serum vitamin E was found to be significantly decreased (p < 0.001) in elderly diabetic patients with and without cataract compared with elderly control subjects. Fasting blood glucose, HbA(1C) and serum fructosamine levels were significantly increased (p < 0.001) in elderly diabetic patients with and without cataract compared with non-diabetic elderly patients with cataract and elderly control subjects. CONCLUSIONS: This study revealed that increased AGEs were associated with oxidative stress in the elderly groups. AGE, as a result of oxidative stress, might have a role in cataract formation, which, in diabetic patients, occurs vigorously as compared with non-diabetic cataract patients.

Changes in glycosylated proteins in diabetic and non-diabetic patients with and without cardiovascular complications.

The objective of this study was to find the changes in glycoprotein composition in both diabetic and non-diabetic patients with and without cardiovascular complications. The study was carried out in Ziauddin Medical University Karachi, Pakistan. Eighty-three patients and control subjects were selected. Among them twenty-one were diabetic patients without any clinical evidence of chronic diabetic complications, twenty-one were diabetic patients with cardiovascular complications, twenty were non-diabetic patients with cardiovascular complications and twenty-one apparently normal, age, sex and weight matched control subjects were investigated. All these patients were selected on clinical grounds from National Institute of Cardiovascular Disease, Karachi. Fasting plasma glucose was increased in all diabetic patients and correlated significantly with and without cardiovascular complications. Fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum protein and its fractions were increased in diabetic patients with and without cardiovascular complications. Fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid and hexosamine were not different in diabetic patients with cardiovascular complications and diabetic patients without chronic complications as compared with control subjects. In conclusion, fasting plasma glucose, glycosylated haemoglobin, glycosylated plasma proteins, serum fructosamine, sialic acid, hexosamine and total serum proteins and its fractions were increased in diabetic patients with and without complications, but these parameters remained within normal limits in non-diabetic patients with cardiovascular complications.