Mahmuda Haque

Detoxification of Carbonyl Compounds by Carbonyl Reductase in Neurodegeneration

Oxidative stress in the brain is the major cause of neurodegenerative disorders, including Alzheimers, Parkinsons, Huntingtons, and Creutzfeldt-Jakob diseases or amyotrophic lateral sclerosis. Under conditions of oxidative stress, the production of highly reactive oxygen species (ROS) overwhelms antioxidant defenses, resulting in the modification of macromolecules and their deposition in neuronal cell tissues. ROS plays an important role in neuronal cell death that they generate reactive aldehydes from membrane lipid peroxidation. Several neuronal diseases are associated with increased accumulation of abnormal protein adducts of reactive aldehydes, which mediate oxidative stress-linked pathological events, including cell growth inhibition and apoptosis induction. Combining findings on neurodegeneration and oxidative stress in Drosophila with studies on the metabolic characteristics of the human enzyme CBR1, it is clear now that CBR1 has a potential physiological role of neuroprotection in humans. Several studies suggest that CBR1 represents a significant pathway for the detoxification of reactive aldehydes derived from lipid peroxidation and that CBR1 in humans is essential for neuronal cell survival and to confer protection against oxidative stress-induced brain degeneration. Recently, it was discovered that HIF1alpha, AP-1, and Nrf2 could all regulate CBR1 at the transcriptional level. Nrf2 is known to regulate the transcription of antioxidant enzymes, and CBR1 functions as an antioxidant enzyme, suggesting that transcriptional regulation of CBR1 is a major contributor to the control of oxidative stress in neurodegeneration.

Role of Polyunsaturated Fatty Acids and Their Metabolites on Stem Cell Proliferation and Differentiation

The nervous system is highly enriched with long-chain polyunsaturated fatty acids (PUFAs). Essential fatty acids, namely, ω-6 (n - 6) and ω-3 (n - 3) PUFA, and their metabolites are critical components of cell structure and function and could therefore influence stem cell fate. The available supporting experimental data reveal that n - 6 and n - 3 PUFA and their metabolites can act through multiple mechanisms to promote the proliferation and differentiation of various stem cell types. PUFAs and their mediators regulate several processes within the brain, such as neurotransmission, cell survival and neuroinflammation, and thereby mood and cognition. PUFA levels and the signaling pathways that they regulate are altered in various neurological disorders, including Alzheimers disease and major depression. Therefore, elucidating the role of PUFAs and their metabolites in stem cell fate regulation is important for stem cell biology as well as stem cell therapy. PUFA-based interventions to generate a positive environment for stem cell proliferation or differentiation might be a promising and practical approach to controlling stem cell fate for clinical applications.

Serum and intracellular levels of ionized sodium, potassium, and magnesium in type 2 diabetic subjects

Background and Aims: Alterations of ionized sodium, potassium, and magnesium in the serum or within erythrocytes have been reported in diabetes mellitus (DM) subjects, both as causes and consequences. There is also increasing evidence that electrolyte imbalances are early biochemical events responsible for long-term diabetic complications. Considerable variations in the electrolyte metabolism may exist in populations depending on the genetic constitution, nutritional status, and environmental situation. The present study was undertaken to investigate the serum and erythrocyte levels of Na + , K + , and Mg 2+ , and also to explore their relationship to glycemic status in a group of Bangladeshi type 2 diabetic patients without any complications. Materials and Methods: There were 30 newly-diagnosed type 2 diabetic subjects [age in years 45.17 ± 1.66; body mass index (BMI) 27.26 ± 1.59, M ± SD] who were studied with 30 age- and BMI-matched control subjects (age 46.30 ± 2.41; BMI 26.50 ± 1.78). Serum and intracellular concentration of Na + , K + , and Mg 2+ were estimated by the ion sensitive electrode (ISE) method using an Auto Analyzer (Nova Biomedical Corporation, 200 Prospect Street, Waltham, MA 02254-9141, USA). Serum glucose and lipid profile were measured by enzymatic colorimetric method. Results: The serum levels of ions (mmol/L, M ± SD) in the control subjects were as follows: Na + - 145 ± 1, K + - 3.78 ± 0.25, and Mg 2+ - 0.47 ± 0.02. In diabetic subjects, significantly lower value of Na + (143 ± 2, P < 0.0001) and Mg 2+ (0.44 ± 0.03, P < 0.0001) and higher value of K + (4.19 ± 0.41, P < 0.0001) were observed. Serum Na + and Mg 2+ showed negative correlation (P < 0.0001 for both ions) and serum K + showed positive correlation (P < 0.0001) with serum glucose only in the diabetic group. In these diabetic subjects, erythrocyte Na + was higher [(values in mmol/L, M ± SD): 11.20 ± 5.40 in diabetic subjects vs. 10.40 ± 4.77 in control subjects, P < 0.0001] and erythrocyte K + [(values in mmol/L, M ± SD): 139 ± 4.8 in control subjects vs. 133.06 ± 3.71 in diabetic subjects, P < 0.0001] and Mg 2+ [(values in mmol/L, M ± SD): 1.82 ± 0.22 in control subjects vs. 1.75 ± 0.20 in diabetic subjects, P < 0.0001] were found to be significantly lower as compared to control subjects. A significantly positive correlation between erythrocyte Na + (P < 0.0001) and a negative correlation between erythrocyte K + and Mg 2+ (P < 0.0001) were observed with serum glucose. Conclusions: These data confirm the existence of hyponatremia, hyperkalemia, and hypomagnesemia, paralleled by a reverse change of Na + and K + in erythrocytes of type 2 diabetic subjects. The study also demonstrates that hyperglycemia-induced effects on cellular transport process play a major role in mediating the electrolyte imbalances in diabetes.

Antibacterial and Cytotoxic Activities of Alocasia fornicata (Roxb.)

Objectives: The aim of the study was to investigate the antibacterial activity, with minimum inhibitory concentration (MIC) and cytotoxic activities of petroleum-ether, chloroform, and ethyl acetate extracts of leaves, stolons and ethanol extract of the roots of the plant Alocasia fornicata (Roxb.) from the family Araceae. Materials and Methods: The antimicrobial activity was evaluated using the disk diffusion method and then MIC was detected using the serial dilution technique. The various parts of the plant were also assessed for cytotoxic activity using the brine shrimp lethality bioassay. Results: All crude extracts, except petroleum ether extract of the leaf and stolon showed moderate-to-good levels of antimicrobial activity against most of the tested bacteria, with an average zone of inhibition of 8-20 mm. The MICs were detected using the serial dilution method and the results ranged from 64 μg/ml to 256 μg/ml. All crude extracts displayed considerable general toxicity toward brine shrimps. The chloroform extract of the leaf, ethyl acetate extract of the stolon, and ethanol extract showed good cytotoxic activity and the LC 50 values were found to be 13.98 μg/ml, 12.26 μg/ml, and 12.81 μg/ml, respectively. Conclusion : From the above context, it may be concluded that the plant A. fornicate may be a potential source for the development of traditional medicine, such as, a safer antibiotic and also as an anticancer agent.

Role of measurement of blood ketone bodies in the management of diabetic ketoacidosis

Objective: The present study was designed to investigate whether early detection of blood ketone bodies help in diagnosing Diabetic ketoacidosis (DKA) and also to explore whether early changes in blood β-hydroxybutyrate is associated with serum electrolytes and acid-base abnormalities. Research Design and Methods: A total of 122 consecutive type 2 diabetic patients (age 39 ± 15 yrs and body mass index 20.3 ± 2.4 kg/m 2 , mean ± SD) were included in the study. Plasma glucose was measured by glucose oxidase method, glycosylated haemoglobin (HbA 1C ) by high-performance liquid chromatography method, blood β-hydroxybutyrate by biosensor method; urinary acetone was measured by strip based on nitroprusside reaction. Serum urea and creatinine were measured by enzymatic method. Serum electrolytes were measured by ion sensitive electrode technique. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for urinary ketone method were calculated against the blood ketone. Results: The relative frequencies of DKA, using urinary ketone and blood ketone criteria, were 15.6% (19 out of 122) and 13.9% (17 out of 122), respectively. In contrast, 50% (61 out of 122) patients showed hyperketonemia. Using blood ketone as the reference method, the sensitivity of urinary ketone measurement was found to be 32.6% and specificity was 93.7%. PPV and NPV of urinary ketone against blood ketone were 73.68% and 71.84%, respectively. The DKA subjects, diagnosed by blood ketone criteria, showed significant biochemical derangements as compared to Non-DKA subjects [serum urea (P < 0.001), creatinine (P = 0.02), sodium (P < 0.001), potassium (P < 0.001), total carbon dioxide (P = 0.02), and osmolality (P = 0.02)]. Correlation analysis shows that electrolytes, blood gas, and acid-base status have highly significant correlation with blood ketone levels (Na + - r = −0.303, P < 0.001; K + - r = 0.449, P < 0.001; Mg 2+ - r = −0.174, P < 0.05; TCO 2 - r = −0.573, P < 0.001; venous blood pH- r = −0.659, P < 0.001, and osmolality- r = −0.273, P < 0.002). No such correlation was found with plasma glucose except that for serum sodium (r = −0.301, P < 0.001). Conclusions: Measurement of ketonuria by nitroprusside reaction has considerable limitations with an error of about 25-30% in detecting the ketonemic status of type 2 diabetic patients. The present data also demonstrated that severity of hyperketonemia, but not that of hyperglycemia, reflects the underlying biochemical derangements in type 2 diabetic patients better.

Antibacterial activity and cytotoxicity of stem bark of two common plants of Bangladesh

Aim: The emergence and spread of antimicrobial resistance is a growing problem in both developing and developed countries and threatens to become a global crisis. In recent years, attempts have been made to investigate indigenous medicines used against infectious diseases, to help in developing safer antimicrobial and anticancer drugs. As part of the further advancement of this research arena, an attempt has been made to study the stem barks of Carica papaya Linn. (C. papaya; family: Caricaceae) and Tamarindus indica Linn. (T. indica; family: Fabaceae), two common plants of Bangladesh. The petroleum-ether, chloroform, and ethyl acetate extracts of the stem bark of both plants were investigated for their antibacterial activity and cytotoxicity. Materials and Methods: The antibacterial activity was evaluated using the disk diffusion method. Cytotoxicity was determined against brine shrimp nauplii. In addition, the minimum inhibitory concentration (MIC) was determined using the serial dilution technique to evaluate antibacterial potency. Results: All crude extracts of T. indica and the chloroform extract of C. papaya appeared very potent in terms of both zones of inhibition and spectrum of activity. However, all the extractives were also subjected to brine shrimp lethality bioassay for preliminary cytotoxicity evaluation. Here, the chloroform extract of C. papaya revealed the strongest cytotoxicity, LC 50 of 10.46 μg/mL. Conclusion: The stem barks of both C. papaya and T. indica show broad-spectrum antibacterial activity and may be potential sources of natural antimicrobial compounds and anticancer agents to be used in the treatment of various infectious diseases caused by resistant microorganisms and of cancer, respectively.

Association of amylin in the development of impaired fasting glucose and impaired glucose tolerance

Objective: The present study was planned to explore the role of amylin in the pathogenesis of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) subjects. Subjects and Methods: In this study, 20 IFG and 25 IGT subjects along with 30 healthy subjects were included. Plasma glucose (fasting and 2 h after 75 g glucose) was measured by glucose oxidase method, serum triglyceride and total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) by enzymatic method. Serum insulin and amylin were measured by the enzyme-linked immunosorbent assay method. B-cell secretory capacity (Homeostasis model assessment [HOMA] %B) and insulin sensitivity (HOMA %S) were estimated by HOMA-CIGMA software. Results: Age and body mass index were matched among control and the hyperglycemic groups (IFG, IGT). Fasting total cholesterol, HDL and LDL was significantly higher in IGT subjects compared with control and IFG subjects. Plasma insulin was significantly higher in IFG and IGT compared with control subjects (median [range], pmol/l; control, 38 [28-55]; IFG, 49 [40-56] and IGT, 60 [20-91]). HOMA %B was significantly lower in IFG and significantly higher in IGT subjects compared with the controls (median [range], %; control, 81 [53-156]; IFG, 52 [40-63] and IGT, 95 [33-195]). HOMA %S was significantly decreased in IGT and also in IFG compared to controls (median (range), %; control, 137 [95-187]; IFG, 104 [88-127] and IGT, 86 [57-255]). Plasma amylin was significantly raised in IFG and IGT compared to control subjects (mean ± standard deviation, pmol/l; control, 5.0 ± 0.63; IFG, 6.43 ± 0.67 and IGT, 8.0 ± 1.18). In binary logistic regression analysis, it has been found that plasma amylin concentration is positively associated with impaired glucose regulation and in bivariate correlation analysis it has been found that plasma amylin is positively associated with HOMA %B and negatively associated with fasting glucose. Conclusion: The present data suggested that increased amylin concentration may be contributed to the development of pre-diabetic condition or vice versa.