Publications by authors named "A A Rahman"

3,739 Publications

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Association of Type 2 Diabetes and Hepatic Encephalopathy in Chronic Liver Disease Patients.

Cureus 2021 Aug 10;13(8):e17061. Epub 2021 Aug 10.

Department of Research, Saskatchewan Health Authority, Regina, CAN.

Background Hepatic encephalopathy (HE) is an important complication of hepatic cirrhosis and is an independent predictor of mortality in patients with cirrhosis. The prevalence of type 2 diabetes continues to increase at an alarming rate around the world, with even more people being affected by prediabetes. Diabetes leads to increased gastric transit and orocecal time, increased glutamase activity, and intestinal bacterial overgrowth, which may increase intestinal ammonia production. Thus, we speculated that diabetes mellitus (DM) might predispose cirrhotic patients to development and/or exacerbation of HE. The main purpose of this study is to determine the association of DM with severe HE in patients with chronic liver disease (CLD). Methods This case-control study (122 cases and 122 controls) was conducted for 6 months on patients who fulfilled the inclusion criteria and were selected from the Medical department, Abbasi Shaheed Hospital, Karachi, after taking informed consent. Demographic data were presented as simple descriptive statistics giving mean and standard deviation and qualitative variables were presented as frequency and percentages. Chi-square was applied and the odds ratio (OR) was calculated taking a p-value of ≤ 0.05 as statistically significant. Results Out of a total of 244 patients, 122 patients had CLD with DM (case group) and 122 participants had CLD without DM (control group). The mean and standard deviation of age in the case and control groups in our study was 43.29±3.79 and 45.49±5.40. The mean and standard deviation of the duration of disease in the case and control groups in our study was 3.18±1.22 and 3.72±1.36. Males were 53 (43.44%) and 56 (45.10%) in the case and control groups, whereas females were 69 (56.56%) and 66 (54.10%) in the case and control groups, respectively. Out of 122 patients in the case group, 73 (59.84%) and 49 (40.16%) patients developed and did not develop severe HE, respectively. Out of 122 patients in the control group, 50 (40.98%) and 72 (59.02%) patients developed and did not develop severe HE, respectively. Binary logistic regression analysis showed an association of severe HE with DM (p-value: 0.93, OR: 1.033, 95% CI: 0.586-1.599). Conclusion This study demonstrates that HE is a common occurrence in CLD patients. There was not a direct relationship of DM with the severity of HE was observed. However, further research with larger sample size and involving a multicenter setting is warranted.
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http://dx.doi.org/10.7759/cureus.17061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428321PMC
August 2021

Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis.

BMJ Glob Health 2021 Sep;6(9)

Center for Public Health Kinetics, New Delhi, India.

Background: Selenium (Se), an essential trace mineral, has been implicated in preterm birth (PTB). We aimed to determine the association of maternal Se concentrations during pregnancy with PTB risk and gestational duration in a large number of samples collected from diverse populations.

Methods: Gestational duration data and maternal plasma or serum samples of 9946 singleton live births were obtained from 17 geographically diverse study cohorts. Maternal Se concentrations were determined by inductively coupled plasma mass spectrometry analysis. The associations between maternal Se with PTB and gestational duration were analysed using logistic and linear regressions. The results were then combined using fixed-effect and random-effect meta-analysis.

Findings: In all study samples, the Se concentrations followed a normal distribution with a mean of 93.8 ng/mL (SD: 28.5 ng/mL) but varied substantially across different sites. The fixed-effect meta-analysis across the 17 cohorts showed that Se was significantly associated with PTB and gestational duration with effect size estimates of an OR=0.95 (95% CI: 0.9 to 1.00) for PTB and 0.66 days (95% CI: 0.38 to 0.94) longer gestation per 15 ng/mL increase in Se concentration. However, there was a substantial heterogeneity among study cohorts and the random-effect meta-analysis did not achieve statistical significance. The largest effect sizes were observed in UK (Liverpool) cohort, and most significant associations were observed in samples from Malawi.

Interpretation: While our study observed statistically significant associations between maternal Se concentration and PTB at some sites, this did not generalise across the entire cohort. Whether population-specific factors explain the heterogeneity of our findings warrants further investigation. Further evidence is needed to understand the biologic pathways, clinical efficacy and safety, before changes to antenatal nutritional recommendations for Se supplementation are considered.
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http://dx.doi.org/10.1136/bmjgh-2021-005856DOI Listing
September 2021

Molecular and Metabolomic Investigation of Celecoxib Antiproliferative Activity in Mono-and Combination Therapy Against Breast Cancer Cell Models.

Anticancer Agents Med Chem 2021 Sep 9. Epub 2021 Sep 9.

Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh, 11564. Saudi Arabia.

Background: Chronic inflammation plays a crucial role in the initiation, promotion, and invasion of tumors, and thus the antiproliferative effects of numerous anti-inflammatory drugs have been frequently reported in the literature. Upregulation of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) has been linked to various human cancers, including breast cancer.

Objectives: This research aims to investigate the antiproliferative activity of different Non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 selective and non-selective agents, against various breast cancer cell lines and to elucidate possible molecular pathways involved in their activity.

Methods: The antiproliferative and combined effects of NSAIDs with raloxifene were evaluated by MTT assay. Cell migration was assessed using a wound-healing assay. The mechanism of cell death was determined using the Annexin V-FITC/ propidium iodide staining flow cytometry method. A mass spectrometry-based targeted metabolomics approach was used to profile the metabolomic changes induced in the T47d cells upon drug treatment.

Results: Our results have demonstrated that celecoxib, a potent and selective COX-2 inhibitor, resulted in significant antiproliferative activity against all examined breast cancer cell lines with IC50 values of 95.44, 49.50. and 97.70 μM against MDA-MB-231, T47d, and MCF-7, respectively. Additionally, celecoxib exhibited a synergistic effect against T47d cells combined with raloxifene, a selective estrogen receptor modulator. Interestingly, celecoxib treatment increased cell apoptosis and resulted in substantial inhibition of cancer cell migration. In addition, the metabolomic analysis suggests that celecoxib may have affected metabolites (n = 43) that are involved in several pathways, including the tricarboxylic acid cycle, amino acids metabolism pathways, and energy production pathways in cancer cells.

Conclusion: Celecoxib may possess potential therapeutic utility for breast cancer treatment as monotherapy or in combination therapy. The reported metabolic changes taking place upon celecoxib treatment may shed light on possible molecular targets mediating the antiproliferative activity of celecoxib in an independent manner of its COX-2 inhibition.
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http://dx.doi.org/10.2174/1871520621666210910101349DOI Listing
September 2021

A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow.

Dis Model Mech 2021 Sep 13. Epub 2021 Sep 13.

Mouse Imaging Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.

In hypoplastic left heart syndrome (HLHS), the mechanisms leading to left heart hypoplasia and their associated fetal abnormalities are largely unknown. Current animal models have limited utility in resolving these questions as they either do not fully reproduce the cardiac phenotype, do not survive to term, and/or have very low disease penetrance. Here, we report the development of a surgically-induced mouse model of HLHS that overcomes these limitations. Briefly, we microinjected the fetal left atrium of embryonic day (E) 14.5 mice with an embolizing agent under high-frequency ultrasound guidance, which partially blocks blood flow into the left heart and induces hypoplasia. At term (E18.5), all positively embolized mice exhibit retrograde aortic arch flow, non-apex forming left ventricles and hypoplastic ascending aortas. We thus report the development of the first mouse model of isolated HLHS with a fully penetrant cardiac phenotype and survival to term. Our method allows for the interrogation of previously intractable questions, such as determining the mechanisms of cardiac hypoplasia and fetal abnormalities observed in HLHS, as well as testing of mechanism-based therapies which are urgently lacking.
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http://dx.doi.org/10.1242/dmm.049077DOI Listing
September 2021

Lipoprotein(a) Concentrations Correlate With LDL-C in Children With Type 1 and 2 Diabetes.

J Endocr Soc 2021 Nov 18;5(11):bvab138. Epub 2021 Aug 18.

Division of Pediatric Endocrinology, Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL 35233, USA.

Context: Elevated levels of lipoprotein(a) (Lp[a]) is an independent risk factor for atherosclerotic cardiovascular disease especially in patients with diabetes. Adult levels of Lp(a) are thought to be is expressed by the second year of life.

Objective: We hypothesized that Lp(a) would be influenced by low density lipoprotein cholesterol (LDL-C), race, and HbA1C.

Methods: Retrospective electronic medical record review of children and adolescents with type 1 diabetes (T1D) (n = 607) and type 2 diabetes (T2D) (n = 93).

Results: Total of 700 subjects, ages 12-19 years with T1D (n = 607) and T2D (n = 93), 49% were male, mean age was 13.2 ± 3.08 years, and the median Lp(a) was 8.00 mg/dL, IQR 5.00-12.00. The Black subjects had an increased relative risk (RR) of higher Lp(a) compared with White subjects (RR 1.25,  < .0001). Among patients with T1D, Black people had an increased relative risk of higher Lp(a) than White people (RR 1.23,  = .0002). In T2D, Black subjects have 43% higher risk of having elevated Lp(a) than White subjects (RR 1.43,  = .268). In T1D, a 5 mg/dL increase in LDL-C results in 2% increase in Lp(a) ( < .0001). In T2D, a 5 mg/dL increase of LDL-C results in an increase of Lp(a) by 3%. LDL-C and BMI are independently associated with Lp(a) (RR = 1.02,  < .001; RR = 0.98,  < .001).

Conclusion: Our data suggest that Lp(a) is associated with LDL-C in children with diabetes. Lp(a) is differentially increased at higher concentrations of LDL-C. Black children with diabetes have a significant burden of Lp(a) concentrations compared with White children.
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http://dx.doi.org/10.1210/jendso/bvab138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428194PMC
November 2021
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