SMAD2 rs4940086 heterozygosity increases the risk of cervical cancer development among the women in Bangladesh.

SMAD2 is a critical signal transducer molecule in the TGFß- SMAD pathway which is also known for its tumor suppressor role. Genetic variations in SMAD2 render cells insensitive to its anti-proliferative signals leading to tumor formation. In this study, we demonstrate the impact of single nucleotide polymorphisms (SNPs) of SMAD2 (rs4940086 and rs8085335) on cervical cancer risk development in Bangladeshi population. 132 cervical cancer patients and 98 control volunteers were enrolled in the study and genotyped utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between cervical cancer susceptibility and the chosen SNPs were evaluated through multiple logistic regression. SMAD2 rs4940086 heterozygous genotype (T/C) was associated with a 3.89 times higher risk of cervical cancer development (P = 0.001, AOR 3.89, 95% CI 1.777-8.513). The T/C and C/C genotypes in combination also significantly elevated cervical cancer risk (P = 0.035, AOR 1.876, 95% CI 1.047-3.364). Urban cancer patients had a significantly higher chance of carrying the rs4940086 polymorphism as compared to rural cancer patients (P = 0.045, OR 2.59 95% CI 1.02-6.59). SMAD2 rs8085335 heterozygous variant (A/G) demonstrated modest effects in increasing cervical cancer susceptibility (P = 0.594, AOR 1.247, 95% CI 0.554-2.809). Our results suggest that polymorphic variations in SMAD2, particularly rs4940086, can potentially elevate cervical cancer susceptibility in Bangladeshi women.

Genetic polymorphisms of GSTP1, XRCC1, XPC and ERCC1: prediction of clinical outcome of platinum-based chemotherapy in advanced non-small cell lung cancer patients of Bangladesh.

Inter-individual genetic makeup can trigger variability in platinum-based chemotherapeutic responses and corresponding adverse drug reactions and toxicities. Exploring the genetic causes behind these inter-individual variabilities in platinum-based chemotherapeutic responses by investigating the effects of GSTP1 (rs1695), XRCC1 (rs25487), XPC (rs2228001) and ERCC1 (rs11615) genetic polymorphisms on toxicity and therapeutic response of this treatment among Bangladeshi advanced non-small cell lung cancer (NSCLC) patients was the aim of this study. 285 Clinically proven either stage IIIB or IV (advanced) NSCLC patients aging not less than 18 years old and receiving platinum-based chemotherapy were recruited to assess the influence of these four single nucleotide polymorphisms (SNPs) on peripheral leukocytes. Toxicity and response were evaluated by multivariate regression analyses using SPSS statistical software (version 17.0). XRCC1 (rs25487) polymorphism was found to act as a predictive factor for not only grade 3 and 4 anemia (p = 0.008), neutropenia (p = 0.010), thrombocytopenia (p = 0.025) and gastrointestinal toxicity (p = 0.002) but also for therapeutic response (p = 0.012) in platinum-based chemotherapy. Although GSTP1 (rs1695) polymorphism might serve as prognostic factor regarding grade 3 or 4 neutropenia, a significant (p = 0.044) improvement in response to platinum-based chemotherapy was observed. However, XPC (rs2228001) and ERCC1 (rs11615) polymorphisms could not establish any significant relation with toxicity or therapeutic response. XRCC1 (rs2228001) and GSTP1 (rs1695) polymorphisms might explain platinum-induced clinical outcomes in terms of both toxicity and therapeutic response variations among Bangladeshi advanced NSCLC patients.

Evaluation of serum amino acids and non-enzymatic antioxidants in drug-naïve first-episode major depressive disorder.

BACKGROUND: The alterations of biological markers are thought to be effective tools to understand the pathophysiology and management of major depressive disorder (MDD). A lot of researches has implied many markers for depression, but any of them fully discovered the association between the markers and depression. The present study investigated the serum levels of amino acids and non-enzymatic antioxidants in major depression, and also explained their association with depression. METHODS: This study examined 247 MDD patients and 248 healthy controls (HCs) matched by age and sex. The Hamilton Depression Rating Scale (Ham-D) was used to all the participants to measure the severity of depression. Quantification of serum amino acids, vitamin A and E were carried out using the HPLC system whereas vitamin C levels were measured by UV-spectrophotometer. All the statistical analysis was performed by SPSS statistical software (version 23.0). The independent sample t-test, the Mann-Whitney U test, and the Fisher's exact test were applied to detect the group differences where a Bonferroni correction applied to the p value. RESULTS: It was observed that serum levels of four amino acids (methionine, phenylalanine, tryptophan, and tyrosine) along with three non-enzymatic antioxidants (vitamin A, E, and C) were significantly dropped in MDD patients compared to HCs (Cohen's d (d): - 0.45, - 0.50, - 0.68, - 0.21, - 0.27, - 0.65, and - 0.24, respectively). Furthermore, Ham-D scores of cases were negatively correlated with serum levels of methionine (r = - 0.155, p = 0.015) and tyrosine (r = - 0.172, p = 0.007). CONCLUSION: The present study suggests that lowered serum methionine, phenylalanine, tryptophan, tyrosine, and non-enzymatic antioxidants are associated with depression. The reduction of these parameters in MDD patients may be the consequence, and not the cause, of major depression.

Alterations of serum macro-minerals and trace elements are associated with major depressive disorder: a case-control study.

BACKGROUND: Major depressive disorder (MDD) is a mixed disorder with the highly irregular course, inconsistent response to treatment and has no well-known mechanism for the pathophysiology. Major causes of depression are genetic, neurobiological, and environmental. However, over the past few years, altered serum levels of macro-minerals (MM) and trace elements (TE) have been recognized as major causative factors to the pathogenesis of many mental disorders. The purpose of this study was to determine the serum levels of MM (calcium and magnesium) and TE (copper, iron, manganese, selenium, and zinc) in MDD patients and find out their associations with depression risk. METHODS: This prospective case-control study recruited 247 patients and 248 healthy volunteers matched by age and sex. The serum levels of MM and TE were analyzed by atomic absorption spectroscopy (AAS). Statistical analysis was performed with independent sample t-tests and Pearson's correlation test. RESULTS: We found significantly decreased concentrations of calcium and magnesium, iron, manganese, selenium, and zinc in MDD patients compared with control subjects (p < 0.05). But the concentration of copper was significantly increased in the patients than control subjects (p < 0.05). Data obtained from different inter-element relations in MDD patients and control subjects strongly suggest that there is a disturbance in the element homeostasis. CONCLUSION: Our study suggests that altered serum concentrations of MM and TE are major contributing factors for the pathogenesis of MDD. Alterations of these elements in serum levels of MDD patients arise independently and they may provide a prognostic tool for the assessment of depression risk.

Genetic variants of SULT1A1 and XRCC1 genes and risk of lung cancer in Bangladeshi population.

Lung cancer is one of the most frequently occurring cancers throughout the world as well as in Bangladesh. This study aimed to correlate the prognostic and/or predictive value of functional polymorphisms in SULT1A1 (rs9282861) and XRCC1 (rs25487) genes and lung cancer risk in Bangladeshi population. A case-control study was conducted which comprises 202 lung cancer patients and 242 healthy volunteers taking into account the age, sex, and smoking status. After isolation of genomic DNA, genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method and the lung cancer risk was evaluated as odds ratio that was adjusted for age, sex, and smoking status. A significant association was found between SULT1A1 rs9282861 and XRCC1 rs25487 polymorphisms and lung cancer risk. In case of rs9282861 polymorphism, Arg/His (adjusted odds ratio = 5.06, 95% confidence interval = 3.05-8.41, p < 0.05) and His/His (adjusted odds ratio = 3.88, 95% confidence interval = 2.20-6.82, p < 0.05) genotypes were strongly associated with increased risk of lung cancer in comparison to the Arg/Arg genotype. In case of rs25487 polymorphism, Arg/Gln heterozygote (adjusted odds ratio = 4.57, 95% confidence interval = 2.79-7.46, p < 0.05) and Gln/Gln mutant homozygote (adjusted odds ratio = 4.99, 95% confidence interval = 2.66-9.36, p < 0.05) were also found to be significantly associated with increased risk of lung cancer. This study demonstrates that the presence of His allele and Gln allele in case of SULT1A1 rs9282861 and XRCC1 rs25487, respectively, involve in lung cancer prognosis in Bangladeshi population.

Effect of VKORC1 and CYP2C9 polymorphisms on warfarin dose requirement in Bangladeshi population.

Warfarin, an oral anticoagulant is one of the most widely prescribed drugs in modern medicine. Large inter-individuals variability due to age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes make the management of warfarin therapy challenging and yet no study has been conducted on the Bangladeshi population. The aim of the study was to identify the role of VKORC1 and CYP2C9 polymorphisms in Bangladeshi population in dose requirement of warfarin. We studied 87 heart valve replacement patients who were prescribed warfarin for minimum of 6 months with a target International normalized ratio of 2.0-3.5. Genotyping of VKORC1rs9923231 (-1639 G>A), CYP2C9*2 and CYP2C9*3 was performed by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism. The frequencies of GG, AG and AA genotypes of VKORC1rs9923231 in the studied population were 87.4%, 8%, and 4.6% respectively whereas the frequencies of the CYP2C9*1/3 and CYP2C9*3/3 were 4.6% and 3.4% respectively. The CYP2C9*2 was not found in the studied population. The results of this study indicate that comparatively higher daily maintenance doses of warfarin were required to achieve the target INR for patients carrying both GG genotype of VKORC1rs9923231 and wild type variant of CYP2C9*3 whereas minimum dose were required for patient having AA genotype of VKORC1rs9923231 and *3/*3 variant of CYP2C9.

Breast cancer risk in relation to TP53 codon 72 and CDH1 gene polymorphisms in the Bangladeshi women.

Pharmacogenomic studies play a significant role in understanding the risk of breast cancer where genetic abnormalities are implicated as the etiology of cancer. Various polymorphisms of tumor suppressor gene TP53 and E-cadherin (CDH1) have been found to be associated with increased breast cancer risk worldwide. This study aimed to analyze the contribution of TP53 and CDH1 gene anomalies in breast cancer risk in the Bangladeshi breast cancer patients. For risk determination, 310 patients with breast cancer and 250 controls from Bangladeshi women were recruited who are matched up with age and use of contraceptives with patients. Genetic polymorphisms were detected by using polymerase chain reaction restriction fragment length polymorphism. A significant association was found between TP53Arg72Pro (rs1042522) and CDH1 -160 C/A (rs16260) polymorphisms and breast cancer risk. In case of P53rs1042522 polymorphism, Arg/Pro (P = 0.0053, odds ratio (OR) = 1.69) and Pro/Pro (P = 0.018, OR = 1.83) genotypes were associated with increased risk of breast cancer in comparison to the Arg/Arg genotype. Arg/Pro + Pro/Pro genotype and Pro allele also increased the risk of breast cancer (P = 0.002, OR = 1.73; P = 0.004, OR = 1.43, respectively). In case of CDH1rs16260 polymorphism, C/A heterozygote and combined C/A + A/A genotypes were found to be strongly associated (P = 0.005, OR = 1.67; P = 0.0037, OR = 1.68) with increased risk of breast cancer. The variant A allele also increased the breast cancer risk (P = 0.0058, OR = 1.52). The present study demonstrates that P53Arg72Pro and CDH1rs16260 polymorphisms are associated with elevated breast cancer risk in the Bangladeshi population.

Effect of GSTP1 and ABCC4 gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-5-fluorouracil-based chemotherapy in Bangladeshi breast cancer patients.

The most important cytotoxic drug namely, cyclophosphamide used in breast cancer along with epirubicin and 5-fluorouracil, is transported by ABCC transporters and detoxified by glutathione S-transferases (GSTs). The activities of these enzymes and transporters may vary in different population due to the presence of genetic polymorphisms. This study was aimed to evaluate the effects of GSTP1rs1695 and ABCC4rs9561778 polymorphisms on the response and toxicities produced by chemotherapy used in the treatment of Bangladeshi breast cancer patients. A total of 200 and 56 patients with invasive breast cancers were recruited from different public and private hospitals of Bangladesh of which 117 patients received neoadjuvant chemotherapy to examine the response as well as the toxicity, and another 139 patients received adjuvant chemotherapy to evaluate only the toxicity. Genetic polymorphisms of the mentioned genes were detected by using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR RFLP). Patients carrying AG and AG plus GG genotype of GSTP1rs1695 were more likely to have a good response, whereas no association of ABCC4rs9561778 was found with the chemotherapy response. Patients carrying GT and GT plus TT genotypes of ABCC4rs9561778 were found to be associated with anemia, neutropenia, leukopenia, and gastrointestinal toxicities when compared with GG genotype whereas no association was found with thrombocytopenia. GSTP1rs1695 was not associated with any type of toxicities investigated. Our result indicates that GSTP1rs1695 polymorphism was strongly associated with the response of chemotherapy, whereas ABCC4rs9561778 polymorphism was significantly related with chemotherapy-induced toxicities.

Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population.

The extent to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain due to considerable heterogeneity between studies. We used the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method for genotyping loss of function (LOF) allele, CYP2C19*2 and gain of function (GOF) allele, CYP2C19*17 in 163 patients undergoing PCI and 165 healthy volunteers from an ethnically distinctive Bangladeshi population. Thirty-eight patients took prasugrel and 125 patients took clopidogrel among whom 30 patients had their clopidogrel active metabolites (CAM) determined by LC-MS/MS 1-1.5 h after clopidogrel intake. All patients who underwent PCI had their P2Y12 per cent inhibition (PRI) measured by VerifyNow System. The impact of different genotypes on CAM and PRI were also determined. We did not find significant variation of CYP2C19*2 (P > 0.05) and CYP2C9*17 (P > 0.05) alleles among healthy volunteers and patients. CAM concentration as well as PRI by clopidogrel varied significantly (P < 0.05) based on genotypic variation of CYP2C19*2 and CYP2C19*17 individually. Such influence was not observed in case of prasugrel. Genotypic variation did not impact PRI but as a whole PRI by prasugrel was better than that of clopidogrel (P < 0.05). Due to presence of both of alleles the effect on PRI by clopidogrel could not be predicted, effectively indicating possible involvement of other factors. Genotype guided clopidogrel dose adjustment would be beneficial and therefore we propose mandatory genotyping before clopidogrel dosing. Prasugrel proved to be less affected by genotypic variability, but due to lack of sufficient long-term toxicity data, caution would be adopted before substituting clopidogrel.

Lung cancer risk in relation to TP53 codon 47 and codon 72 polymorphism in Bangladeshi population.

The objective of this study was to determine whether p53 codon 47 and codon 72 polymorphisms are associated with increased risk of lung cancer in Bangladeshi population. We carried out a case-control study and examined the genotype distribution Pro47Ser and Arg72Pro single-nucleotide polymorphisms along with tobacco smoking in the predisposition of lung cancer by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The study included 106 lung cancer patients and 116 control subjects from Bangladesh. Lung cancer risk was estimated as odds ratio (OR) and 95 % confidence interval (CI) using conditional logistic regression models adjusting for age, sex, and smoking. No significant association was found between Pro47Ser SNP and lung cancer. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in lung cancer were 25.5, 37.7, and 36.8 %, respectively; frequencies in the controls were 53.4, 30.2, and 16.4 %, respectively (p < 0.01). The Arg/Pro and Pro/Pro genotype were significantly associated with increased risk of lung cancer (OR = 2.51, 95 % CI = 1.38-4.82 and OR = 4.62, 95 % CI = 2.31-9.52, respectively) compared with the Arg/Arg genotype. The combined frequency of Arg/pro and Pro/Pro genotype was also found to be associated with elevated risk of lung cancer (OR = 3.36, 95 % CI = 1.90-5.94, p < 0.01). However, no significant relationship was found between age, sex, and histological subtypes of lung cancer with p53 codon 72 genotype distributions. When classified by smoking status, the effects of Arg72Pro polymorphism on lung cancer risk was only found to be significant (χ (2) = 33.94, p = 0.00000004) in case of heavy smokers (40 packs per year or more). We conclude that not Pro47Ser SNP but Arg72Pro SNP is involved in susceptibility to developing lung cancer, at least in Bangladeshi population.

Association of CYP3A4, CYP3A5 polymorphisms with lung cancer risk in Bangladeshi population.

The rate of direct smoking, second hand smoking, and smokeless tobacco users as well as the amount of environmental pollutant like polycyclic aromatic hydrocarons is increasing in Bangladesh. Therefore, the prevalence of lung cancer is increasing day by day. To the best of our knowledge, no pharmacogentic study of CYP3A4, CYP3A5 genes has been reported on Bangladeshi population relating those with lung cancer. The present study was conducted to determine the association of CYP3A4, CYP3A5 gene polymorphisms and tobacco smoking in the development of lung cancer in Bangladeshi population. A case-control study was carried out on 106 lung cancer patients and 116 controls to investigate three allelic variants-CYP3A4*1B, CYP3A5*3, and CYP3A5*6 using Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Risk of lung cancer was estimated as odds ratio (OR) and 95 % confidence interval (CI) using unconditional logistic regression models. The variant allele frequencies for CYP3A4*1B (*1A/*1B + *1B/*1B) were 2.83 % and 0.86 % and that of CYP3A5*3 (*1A/*3 + *3/*3) were 88.68 % and 85.34 % in cases and controls, respectively. Individual carrying at least one variant allele of CYP3A4*1B (CYP3A4*1A/1B + *1B/1B) has a 3.35 times more risk (OR = 3.35, 95 % Cl = 0.34-32.71, p = 0.271) for developing lung cancer whereas individual carrying at least one variant allele of CYP3A5 (CYP3A5*1A/3 + *3/3) has a 1.26 times more risk (OR = 1.35, 95 % Cl = 0.61-2.97) and both are statistically non-significant (p > 0.05). CYP3A5*6 was absent in the study population. No association of lung cancer with the mentioned polymorphisms was found both in heavy and light smokers. In the cases of all three major types of lung cancer-squamous cell carcinoma, adenocarcinoma, and small cell carcinoma-significantly strong relationships (p ˂ 0.05) have been found. To confirm the association of lung cancer with the mentioned polymorphisms, large number volunteers (patients and controls) will be required.

N-acetyltransferase 2 (NAT2) genotype as a risk factor for development of drug-induced liver injury relating to antituberculosis drug treatment in a mixed-ethnicity patient group.

PURPOSE: This study aims to assess whether NAT2 genotype affects susceptibility to moderate to severe liver injury in patients undergoing drug treatment for tuberculosis with isoniazid-containing regimens. METHODS: Twenty-six patients of European or South Asian ethnicity, who had suffered liver injury during treatment with isoniazid-containing drug regimens and 101 ethnically matched controls were genotyped for the NAT2*5, NAT2*6, and NAT2*7 alleles. Genotyping for additional polymorphisms in the NAT gene region was also performed on 20 of the 26 cases. NAT2 genotype frequency between cases and controls was compared. RESULTS: NAT2 genotypes predicting a slow acetylator phenotype were found to be associated with an increased risk of isoniazid-related liver injury (odds ratio (OR) = 4.25 (95% confidence interval (CI), 1.36-13.22); p = 0.012) with 85% of the cases being slow acetylators compared with 56% of the controls. There was no evidence for an increased risk for the slow acetylator genotype in patients with the most severe cases of liver injury, who underwent liver transplantation. CONCLUSIONS: The NAT2 slow acetylator genotype appears to be a significant risk factor for moderate and severe drug- induced liver injury. However, the overall effect size is modest and generally in line with effects described previously for this genotype in milder drug-induced liver injury. Additional genetic risk factors may also contribute.

Genotype-phenotype variability in human CYP3A locus in Nepalese people residing in Bangladesh.

OBJECTIVES: The study has been designed to phenotype 200 Nepalese people residing in Bangladesh by measuring urinary ratio of 6ß-hydroxycortisol/cortisol (metabolic ratio) and to genotype all the subjects for the presence of CYP3A4*1B, *2, *4, *5, *6, *10, *18, CYP3A5*3, and *6 alleles. METHODS: Cortisol and 6ß-hydroxycortisol were extracted and quantified from morning spot urine samples (n = 200) by HPLC. Genotyping was carried out using the extracted genomic DNA by amplification of target alleles by PCR. Amplified DNA was digested by appropriate restriction enzymes followed by gel electrophoresis and sequencing to identify the targeted alleles. RESULTS: A wide ratio of 6ß-hydroxycortisol/cortisol was found (0.71 - 10.61) with an average of 4.41. No sample (n = 200) was found positive for CYP3A4*1B, *2, *4, *5, *6, *10, *18, and CYP3A5*6 alleles. CYP3A5*1/*1, *1/*3, and *3/*3 genotype frequency were found to be 20%, 20%, and 60%, respectively. A significantly higher mean metabolic ratio (MR) ± SD (MR = 6.28 ± 3.43) was found for CYP3A5*1/*1 compared to both CYP3A5*1/*3 (MR = 3.68 ± 1.37) and CYP3A5*3/*3 (MR = 3.58 ± 1.95). CONCLUSION: This study demonstrates the absence of common CYP3A4 variant alleles in Nepalese people residing in Bangladesh whereas Nepalese people carrying the CYP3A5*1/*1 genotype appear to show a significantly higher 6ß-hydroxycortisol/cortisol ratios compared to those with CYP3A5*3/*3 genotype.

Acetylcholinesterase inhibition and in vitro and in vivo antioxidant activities of Ganoderma lucidum grown on germinated brown rice.

In this study, the acetylcholinesterase inhibition and in vitro and in vivo antioxidant activities of Ganoderma lucidum grown on germinated brown rice (GLBR) were evaluated. In antioxidant assays in vitro, GLBR was found to have strong metal chelating activity, DPPH, ABTS, hydroxyl and superoxide radical scavenging activity. Cell-based antioxidant methods were used, including lipid peroxidation on brain homogenate and AAPH-induced erythrocyte haemolysis. In antioxidant assays in vivo, mice were administered with GLBR and this significantly enhanced the activities of antioxidant enzymes in the mice sera, livers and brains. The amount of total phenolic and flavonoid compounds were 43.14 mg GAE/g and 13.36 mg CE/g dry mass, respectively. GLBR also exhibited acetylcholinesterase inhibitory activity. In addition, HPLC analyses of GLBR extract revealed the presence of different phenolic compounds. These findings demonstrate the remarkable potential of GLBR extract as valuable source of antioxidants which exhibit interesting acetylcholinesterase inhibitory activity.

Development of nanozyme based sensors as diagnostic tools in clinic applications: a review.

Since 1970, many artificial enzymes that imitate the activity and structure of natural enzymes have been discovered. Nanozymes are a group of nanomaterials with enzyme-mimetic properties capable of catalyzing natural enzyme processes. Nanozymes have attracted great interest in biomedicine due to their excellent stability, rapid reactivity, and affordable cost. The enzyme-mimetic activities of nanozymes may be modulated by numerous parameters, including the oxidative state of metal ions, pH, hydrogen peroxide (H2O2) level, and glutathione (GSH) concentration, indicating the tremendous potential for biological applications. This article delivers a comprehensive overview of the advances in the knowledge of nanozymes and the creation of unique and multifunctional nanozymes, and their biological applications. In addition, a future perspective of employing the as-designed nanozymes in biomedical and diagnostic applications is provided, and we also discuss the barriers and constraints for their further therapeutic use.

Comparative pharmacokinetic and bioequivalence study of azithromycin 500 mg tablet in healthy Bangladeshi volunteers.

OBJECTIVE: Although several generic oral formulations of azithromycin (AZT; CAS 83905-01-5) are available in Bangladesh, information regarding the bioavailability of these formulations in the Bangladeshi population is unavailable. The purpose of this study was to compare the relative bioavailability and other pharmacokinetic properties of 2 formulations of AZT 500 mg tablet, namely Azomac® (General Pharmaceutical Ltd., Bangladesh) (Test formulation) and Zithromax® (Pfizer, Rome, Italy) (Reference product) and to evaluate whether these formulations meet the FDA criteria to assume bioequivalence in Bangladeshi volunteers. MATERIALS AND METHODS: A randomized, single-dose, two-way, cross-over, open-label pharmacokinetic study was performed in 24 healthy volunteers after administration of single dose of AZT 500 mg tablet under fasting condition following a washout period of 3 weeks. Blood samples were collected at pre-determined time points and analyzed for serum AZT concentration using a validated liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were determined by a noncompartmental method. RESULTS: From serum data, the obtained values given as mean (SD) for test and reference products were 382.41 (21.96), 392.31 (18.77) ng/ml for Cmax; 4.83(1.03), 4.83(1.03) h for tmax; 5,646.29 (912.19), 6,293.30 (966.76) h×ng/ml for AUC0-120; and 6,307.50 (863.40), 7,022.54 (961.28) h×ng/ml for AUC0-∞, respectively. The mean t1/2 was 41.44 (7.01), 41.16 (6.38) h for Test formulation and Reference product, respectively. The analysis of variance revealed no period or sequence effect for any pharmacokinetic property; however, a significant formulation effect was observed for Cmax, AUC0-120, AUC0-∞ and AUMC0-120. The 90% confidence intervals of the test/ reference mean ratios of the ln-transformed Cmax, AUC0-120 and AUC0-∞ were 87.89 - 89.36%, 87.40 - 91.70% and 87.47 - 92.07%, respectively, which fell within the predetermined FDA bioequivalence range. CONCLUSION: It can be concluded that the test formulation met the regulatory criteria for bioequivalence to the Reference tablet formulation in terms of both rate and extent of absorption.

Immunoglobulin levels in panic disorder patients.

The study was conducted to evaluate the serum immunoglobulin levels in patients suffering from panic disorder and to assess the relationship between the changes of immunoglobulin levels and the socioeconomic parameters, as well as nutritional status. 54 panic patients were randomly selected from the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital, Bangladesh. Fifty two, age and gender matched healthy volunteers (42 males and 10 females, mean age of 30 ± 6 yrs) were also enrolled in this study. Immunoglobulin levels were measured by turbidimetry method using immunoglobulin kits. It was found that the mean serum immunoglobulin concentrations of IgG, IgM and IgA of panic disorder patients were 0.999±0.26 (g/L), 0.1±0.028 (g/L) and 0.194±0.066 (g/L) respectively whereas the values were 1.24± 0.39 ( g/L ), 0.096±0.022 ( g/L) , 0.194±0.053 (g/L) in healthy volunteers. IgG level in panic disorder patient was found significantly (p <0.05) lower than that of the controls but the change in concentration of IgM and IgA were not significant (p=0.497, p=0.962). Socioeconomic data reveals that most of the patients were from lower income group and educated. BMI (Mean±SD) of the patients (22.62 ± 3.74 kg/m2) and controls (23.74 ± 2.71 kg/m2) were well within the normal range. From correlative analysis it has been found that income has significant effect (p=0 .047) on the change of the serum IgG level in panic disorder patient and it was also been justified by the regression analysis (p=0.049). This finding may play a key role in the diagnosis and treatment of the panic disorder patients. Further studies have been suggested with a large number of populations to confirm these findings.

The Association Between Mean Glycated Haemoglobin or Glycaemic Variability and the Development of Retinopathy in People with Diabetes: A Retrospective Observational Cohort Study.

INTRODUCTION: To determine the association between mean glycated haemoglobin (HbA1c) or glycaemic variability and the development of diabetic retinopathy (DR) in people with diabetes. METHODS: An observational cohort study with people registered with a DR eye screening service between October 2012 and October 2017. Those who had no DR at the start of the study were followed for a maximum of 5 years. HbA1c measures were used to calculate HbA1c variability and mean HbA1c to assess any relationship between these and the risk of developing new onset DR. RESULTS: A total of 2511 individuals were followed up for up to 5 years. Of these, 542 (21.6%) developed DR. After adjustment, HbA1c variability was not significantly associated with the development of DR (p = 0.3435). However, the mean HbA1c was (p < 0.0001). Those with type 1 diabetes had an odds of 1.63 (95% CI 1.11-2.40) of a retinopathy diagnosis compared to those with type 2 diabetes. CONCLUSIONS: We have shown that mean HbA1c is associated with an increased risk of developing diabetic retinopathy. However, after adjustment for sex, age, diabetes type and the mean, the HbA1c variability no longer remained significant. Our data suggest that optimizing long-term glycaemic control remains paramount.

It has been known for a long time that if an individual's diabetes is not as well controlled as it could be, then they are at increased risk of developing complications over many years. These complications include diabetes-related eye disease (retinopathy). For many years, the way of measuring how well someone's diabetes was controlled was by measuring glycated haemoglobin (HbA_1c) which looked at how much glucose was attached to a red cell. This study looked at whether variation in HbA_1c over 5 years of follow-up was associated with greater risk of developing retinopathy, and if this relationship was stronger than just measuring HbA_1c alone. Previous work has shown that people with greater variation in HbA_1c are at increased risk of poor wound healing in those with diabetes-related foot ulcers. The present study looked at 2511 people who had no diabetes-related eye disease at the start of the study and who had been followed for 5 years. We found that variability in HbA_1c was not associated with an increased risk of developing diabetes-related eye disease, but confirmed that the average HbA_1c had the strongest relationship. Our data confirm that the focus of preventing diabetes-related eye disease should be on lowering HbA_1c.

Altered serum elements, antioxidants, MDA, and immunoglobulins are associated with an increased risk of seborrheic dermatitis.

BACKGROUND: The exact mechanism for the pathophysiology of seborrheic dermatitis (SD) remains unknown. According to past knowledge, neuropsychiatric disorders, weak immune responses, fungal infections, antioxidants deficiencies, and inadequate nutrition might involve in SD. Here we evaluated serum trace elements, micronutrients, antioxidants, malondialdehyde (MDA), and immunoglobulins in SD patients. METHODS: This case-control study recruited 75 SD patients and 76 age-and sex-matched healthy controls (HCs). We measured serum micronutrients using atomic absorption spectroscopic methods. Similarly, we assessed serum antioxidants applying the RP-HPLC techniques. Also, serum MDA and immunoglobulins levels were evaluated by UV-spectrophotometric and turbidimetric methods, respectively. RESULTS: We observed higher serum levels of copper, manganese, iron, calcium, magnesium, and MDA in SD patients than HCs. Together with vitamin E, we noticed lower serum concentrations of immunoglobulin A, G, and M in SD patients than HCs. The present study detected a positive correlation between serum zinc and calcium levels (r = 0.365, p = 0.009) in SD patients. However, we identified a negative correlation between serum copper and calcium levels (r = -0.298, p = 0.035). CONCLUSION: The present study suggests that the altered levels of micronutrients, antioxidants, MDA, and immunoglobulins are associated with the pathophysiology of SD. These changes may not be the cause but the consequences of the disease. These findings might help to understand the etiopathology and management of SD.

Prevalence of CYP2C19 and ITGB3 polymorphisms among Bangladeshi patients who underwent percutaneous coronary intervention.

INTRODUCTION: Antithrombotic agents are the basic therapeutic option for patients with arterial thrombosis who underwent percutaneous coronary intervention (PCI). In Bangladesh, aspirin and clopidogrel are frequently prescribed as antithrombotics or platelet inhibitors. Studies reported the genetic polymorphisms of CYP2C19*2, CYP2C19*17, and ITGB3 cause an alteration of the pharmacodynamic and pharmacokinetic profile of aspirin and clopidogrel. Therefore, we aimed to assess the prevalence of CYP2C19*2, CYP2C19*17, and ITGB3 polymorphisms among Bangladeshi patients with cardiovascular disease (CVD) who underwent PCI. METHODS: Here we assessed a total of 1,000 CVD patients (male 782 and female 218) who underwent PCI and were treated with clopidogrel and/or aspirin. We performed genotyping of patients treated with clopidogrel and aspirin by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) methods. The PCR products of clopidogrel-treated patients were screened with agarose gel electrophoresis and then digested with SmaI and NsiI-HF for CYP2C19*2 and CYP2C19*17, respectively. We genotyped aspirin-treated patients with T-ARMS-PCR for missense rs5918 (PlA1/A1) polymorphism of the ITGB3 gene. Then we ran the digested PCR products on 2% agarose gel electrophoresis to detect the mentioned polymorphisms. RESULTS: Among the clopidogrel-treated patients, we observed 64.1% polymorphism (hetero + mutant) of CYP2C19*2 (loss-of-function allele) and 22.7% (hetero + mutant) of CYP2C19*17 (gain-of-function allele). On the other hand, among the aspirin-treated patients, polymorphisms of ITGB3 were 84.1% homozygous (PlA1/A1), 15.6% heterozygous (PlA1/A2), and 0.3% mutant homozygous. CONCLUSION: In the present study, we observed a high prevalence of genetic polymorphisms of CYP2C19 and ITGB3 genes. Therefore, we recommend genotyping of CVD patients before prescribing clopidogrel or aspirin to prevent coagulation. Based on the genotyping study, the adjustment of doses or alternative generics might require to avoid therapeutic failure or toxicity in some cases.