M. Ataur Rahman

Efficacy of daily vs. weekly supplementation of iron in schoolchildren with low iron status.

Iron deficiency anemia (IDA) is still a major nutritional and public health problem in developing countries. The prevalence among young children and pregnant women is particularly high. Daily oral supplementation with medicinal iron is considered an effective strategy for reducing the incidence of IDA but non-compliance is a major problem with this strategy. We undertook this study to compare the results of once-weekly vs. daily oral iron supplementation in schoolchildren. Sixty children ranging between 5 and 10 years with iron deficiency anemia were selected from a school in Karachi, Pakistan and were divided into two equal groups, i.e., daily and weekly supplementation groups. Hemoglobin (Hb), hematocrit (Hct), serum iron, total iron binding capacity (TIBC), and serum ferritin were determined before the start of the study. Ferrous sulfate (200 mg) was given daily to the daily supplementation group and once-weekly to the weekly supplementation group for 2 months. When post-supplementation values of the above-mentioned parameters were determined, a significant improvement was observed in all parameters in both groups. It is concluded that once-weekly iron supplementation is as effective as daily supplementation for the treatment of iron deficiency anemia. Moreover, weekly iron supplementation is cost effective and has no or fewer side-effects.

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, HbA1C 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.

Protein expression profiling of nuclear membrane protein reveals potential biomarker of human hepatocellular carcinoma

BackgroundComplex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes have been limited. Deciphering the molecular mechanism that differentiate between normal and disease state may lead to identification of biomarkers for carcinoma.ResultsMany proteins displayed differential expression when nuclear membrane proteome of hepatocellular carcinoma (HCC), fibrotic liver, and HepG2 cell line were assessed using 2-DE and ESI-Q-TOF MS/MS. From the down regulated set in HCC, we have identified for the first time a 15 KDa cytochrome b5A (CYB5A), ATP synthase subunit delta (ATPD) and Hemoglobin subunit beta (HBB) with 11, 5 and 22 peptide matches respectively. Furthermore, nitrosylation studies with S-nitrosocysteine followed by immunoblotting with anti SNO-cysteine demonstrated a novel and biologically relevant post translational modification of thiols of CYB5A in HCC specimens only. Immunofluorescence images demonstrated increased protein S-nitrosylation signals in the tumor cells and fibrotic region of HCC tissues. The two other nuclear membrane proteins which were only found to be nitrosylated in case of HCC were up regulated ATP synthase subunit beta (ATPB) and down regulated HBB. The decrease in expression of CYB5A in HCC suggests their possible role in disease progression. Further insight of the functional association of the identified proteins was obtained through KEGG/ REACTOME pathway analysis databases. String 8.3 interaction network shows strong interactions with proteins at high confidence score, which is helpful in characterization of functional abnormalities that may be a causative factor of liver pathology.ConclusionThese findings may have broader implications for understanding the mechanism of development of carcinoma. However, large scale studies will be required for further verification of their critical role in development and progression of HCC.

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

BackgroundFructose 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.MethodsThe 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.ResultsSerum 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, HbA1C 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.ConclusionsThe 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.

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, HbA1C 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.

Introducing differential expression of human heat shock protein 27 in hepatocellular carcinoma: moving toward identification of cancer biomarker

Previously, it has to be acknowledged that overexpressed heat shock protein B27 (HSPB27) have been implicated in the etiology of wide range of human cancers. However, the molecular mechanism leading to the disease initiation to progression in liver cancer is still unknown. Present work was undertaken to investigate the differentially expressed HSPB27 in association with those damages that lead to liver cancer development. For the identification of liver cancer biomarker, samples were subjected to comparative proteomic analysis using two-dimensional gel electrophoresis (2-DE) and were further validated by Western blot and immunohistochemical analysis. After validation, in silico studies were applied to demonstrate the significantly induced phosphorylated and S-nitrosylated signals. The later included the interacting partner of HSPB27, i.e., mitogen-activated protein kinase-3 and 5 (MAPK3 and 5), ubiquitin C (UBC), v-akt murine thymoma viral oncogene homolog 1 (AKT1), mitogen-activated protein kinase 14 (MAPK14), and tumor protein p53 (TP53), which bestowed with critical capabilities, namely, apoptosis, cell cycling, stress activation, tumor suppression, cell survival, angiogenesis, proliferation, and stress resistance. Taking together, these results shed new light on the potential biomarker HSPB27 that overexpression of HSPB27 did lead to upregulation of their interacting partner that together demonstrate their possible role as a novel tumor progressive agent for the treatment of metastasis in liver cancer. HSPB27 is a promising diagnostic marker for liver cancer although further large-scale studies are required. Also, molecular profiling may help pave the road to the discovery of new therapies.