Tania Shakoori

Research shows that serum Vitamin B12 levels are reduced in diabetes including gestational diabetes. We sought to compare serum cobalamin between pregnant females diagnosed with gestational diabetes mellitus (GDM) and healthy controls and to propose a cut off value for serum B12 levels as a predictive biomarker for GDM. Study design was Quantitative cross-sectional study. This study was carried out at Lady Atchison Hospital/Mayo Hospital Lahore, Pakistan from January to December 2016. Cobalamin levels were measured in women diagnosed with GDM (n=59) and controls (n=41). GDM was diagnosed when fasting blood sugar levels were 95 mg/dL or above. The levels were compared using Mann Whitney U test. Multiple linear regression was used to investigate the association of cobalamin with fasting blood sugar level after adjusting for gestational age and gravidity. ROC curve analysis was conducted to assess the suitability cobalamin as a predictive biomarker for GDM. Median cobalamin were significantly reduced in cases (108.95±92 pg/mL) as compared to controls (173±90 pg/mL) at p<0.001. Low vitamin B12 levels (β =-0.29, p=0.004) significantly predicted high fasting blood sugar levels in pregnancy even after adjusting for gestational age and gravidity. ROC curve analysis revealed the optimal cutoff point of serum cobalamin for predicting gestational diabetes to be 113 pg/mL at which sensitivity and specificity were was 56.9% (95%CI 44.1-68.8%) and 80.5 % (95%CI 65.6-89.9%) at P<0.0001. It was concluded that low serum cobalamin levels may be a risk factor and may predict the development of GDM.

Sirt1/AMPK and Akt/mTOR axes regulate cellular energy homeostasis and metabolism. Sodium butyrate (NaB) is a product of healthy gut microbiota and a histone deacetylase inhibitor. Recent studies have shown that NaB activates the intracellular pathways involving key metabolic regulator molecules. However, the effect of NaB on Sirt1/AMPK and Akt/mTOR axes is not reported. We compared genetic expression of Sirt1, AMPK, Akt, and mTOR in adipose tissue from mice treated with NaB versus placebo. Four groups of mice (n=27) mice were administered oral NaB, intraperitoneal (i.p) NaB, oral placebo or i.p placebo for 16 days. RNA was isolated from the epididymal fat pads and relative genetic expression of AMPK, Sirt1, mTOR and Akt was measured using real time PCR. Oral NaB group showed decreased genetic expression of AMPK (0.04 fold, p<0.001), mTOR (0.30 fold, p=0.04), Akt (0.29 fold, p=0.67) and Sirt1 (0.83 fold, p=0.18). In the I/P group AMPK (2.26 fold, p=0.33), Akt (1.3 fold, p=0.59) and Sirt1 (1.69, p=0.45) were increased while mTOR was unchanged (0.99 fold, p=0.81). Our study for the first time reports on change in genetic expression of Sirt1/AMPK and Akt/mTOR axes in adipose tissue of mice given oral and intraperitoneal NaB treatment.

Acute exacerbations are important events in the natural history of chronic obstructive pulmonary disease (COPD). Their frequency is directly related to the prognosis of the disease. The objective of this study was to identify the 'frequent exacerbator' phenotype and determine the risk factors for increased frequency of acute exacerbations in local chronic obstructive pulmonary disease (COPD) patients in a cross sectional analytical study design. For this purpose 137 patients were included in the study after obtaining necessary permissions from the ethical board of the hospital. COPD was diagnosed on the basis of clinical symptoms and a post bronchodilator values of FEV1/FVC<0.70 on spirometry. Frequent exacerbator's were defined as patients experiencing 2 or more exacerbation episodes per year, which merited visited to the hospital. Average number of hospital visits for exacerbations per year, smoking history, family history of smoking related chronic lung disease in first degree relatives and presence of comorbidities were recorded from patient history and medical records. Body mass index was calculated and complete pulmonary function tests were recorded using electronic spirometer. Three multiple linear regression models were created with mid maximal expiratory flow, FEV1, and FVC as surrogate markers for lung function in different models. We found that 28 (20.4%) of our COPD patients were frequent exacerbators. All three multiple linear regression models for identifying risk factors for frequent exacerbations were significant (p< 0.001). The model in which mid maximal expiratory flow was used as a surrogate marker for lung function, accounted for the change in the dependent variable to the greatest degree (Adjusted R 2 = 0.38, p< 0.001). Overall the three models consistently showed that positive family history, high body mass index, heavy smoking, poor lung function (mid maximal expiratory flow/FEF2575, FEV1 and FVC), older age and requirement of steroid therapy predicted increased frequency of exacerbations. To conclude lung function (FEF2575%, FEV1 % predicted and FVC% predicted), longer smoking history, higher body mass index, succumbing to COPD at a younger age, and a positive family history of chronic lung disease in first degree relatives are important risk factors for frequent exacerbations of COPD.

Objective: To see if single nucleotide polymorphisms of pulmonary innate immune molecule surfactant protein D were associated with poor lung function in smokers.
Methods: The study was conducted at Shaikh Zayed Hospital, Lahore, Pakistan, from April 2008 to August 2010, and comprised relatives and attendants of patients, as well as college and university students. Self-reported healthy smokers who demonstrated no airflow obstruction on spirometry were included. Deoxyribonucleic acid was extracted from their blood sample and genotyped for single nucleotide polymorphisms rs721917 and rs3088308 by polymerase chain reaction and restriction analysis. Serum was separated for measurement of surfactant protein D levels by a commercially available enzyme-linked immunosorbent assay based kit. Lung functions were compared between subjects possessing major and minor alleles using two-tailed Student's t-test. Multiple linear regression analysis was conducted to analyse the effect of age, smoking and the two single nucleotide polymorphisms on forced expiratory volume in 1 second.
Results: Of the 122 participants, all of whom were men, 98(80.33%) were smokers while 24(19.67%) had never smoked. Of the former, 90(91.84%) were current smokers and 8(8.16%) were ex-smokers. The overall mean age was 35.8±10.9 years. The mean surfactant protein D level was 121.4±61.6ng/ml. In case of rs3088308, all lung function variables were reduced in patients with a minor allele and the results for forced expiratory volume in 1 second (p=0.016), forced expiratory volume in 1 second (%) predicted (p=0.009), forced vital capacity (p=0.048) and forced vital capacity (%) predicted (p=0.048) were statistically significant. Age had the highest influence on lung function (p<0.001) followed by smoking status (p=0.04) and single nucleotide polymorphisms rs3088308 minor allele (p=0.04).
Conclusion: Single nucleotide polymorphisms rs3088308 was found to modulate serum surfactant protein D levels and may be a risk factor for development of chronic obstructive pulmonary disease among smokers.
Keywords: Smoking, Genetic polymorphism, Surfactant protein D, Risk of COPD. (JPMA 66: 1137; 2016)

A B S T R A C T Previous animal studies have shown that butyrate (sodium butyrate, NaB) administration can protect against diet-induced obesity. We investigated the effect of oral (1g/kg body weight/day) and intraperitoneal (0.5/kg body weight/day) administration of NaB on body weight and lipid profile of mice. Oral (400mg/kg body weight/day) and intraperitoneal (200mg/kg body weight/day) metformin was similarly administered as positive control. Placebo was the drug vehicle (phosphate saline buffer). Fifty seven mice (15-18 weeks old) were divided into three groups and administered freshly prepared NaB (n=19), metformin (n=16) and placebo (n=16), respectively for 16 days. Within each group half the mice were given the drug orally and half intraperitoneally. Weights were recorded daily and serum lipids were measured from blood samples obtained at the end of the study. Both oral (p=0.001) and intraperitoneal (p<0.001) metformin caused significant weight loss (7.56±2.47% and 8.72±2.75%, respectively) compared to placebo. Oral NaB also caused significant weight loss (4.77±3.49%) in mice as compared to placebo (1.81±2.89%) at p=0.04. However, there was no significant difference in weight change between intraperitoneal NaB (4.08±2.65%) and placebo (4.78±2.23%) at p=0.85. Additionally serum lipids were raised in all groups with significant weight loss. The most prominent change was elevated triglycerides (214.42±81.96 mg/dL) in NaB treated mice (p-0.01) and raised cholesterol (189.01±39.89 mg/dL at p=0.04) in metformin treated mice as compared to placebo. To conclude NaB, causes significant weight loss in mice along with raised lipids. However oral NaB seems to be more effective than intraperitoneal butyrate.

Inflammatory markers are being explored to aid in stroke diagnosis especially, to differentiate between clinical varieties of stroke. This study aimed to compare plasma tumour necrosis factor-alpha (TNF-alpha) and Interleukin-10 (IL-10) levels between stroke patients and controls, as well as between hemorrhagic and ischemic varieties of stroke. Stroke patients who were admitted to Shaikh Zayed Hospital Lahore and Services Hospital Lahore, Pakistan within 24 hours after the onset of stroke symptoms were consecutively asked to participate in this study from June 2011 to December 2011.Venous blood samples were collected within 24 hours of stroke symptoms onset. Plasma TNF-α levels and IL-10 were calculated using commercial enzyme-linked immune-sorbent assay (ELISA). Cytokines levels were dichotomized as detectable yes/no and were compared between different groups using chi square test. Continuous variables were compared using the student t-test. Logistic regression model was used to in...