Variability in the therapeutic response of metformin treatment in patients with type 2 diabetes mellitus

Objective: To assess the glycemic response of metformin in patients with Type-2 Diabetes Mellitus [T2DM] as well as to see its association with reductions in BMI and GIT intolerance

Methods: This Quasi, Experimental study was conducted at Jinnah-Allama Iqbal Institute of Diabetes and Endocrinology [JAIDE] Jinnah Hospital, Lahore from 1st March 2016 to 30th September 2016. Newly diagnosed T2DM patients were given metformin for duration of three months and later on they were categorized into Responders and Non-Responders on the basis of HbA1c [A1C] reductions, which were estimated by Hemoglobin [A1C] analyzer [TD4611A TAIDoc Tech. Taiwan] through photometry. Similarly, baseline BMI and BMI after three months therapy with metformin was also recorded

Results: Among total of 200 patients, 40.5% of the patients were classified as Non-Responders whereas; 59.5% of the patients as Responders. The baseline BMI [26.09 kg/m2] was also decreased significantly after metformin therapy [25.40 kg/m2]. It was found that metformin reduced the A1C in all the patients. However, the glycemic control was much better in patients with higher baseline A1C [1.13% ± 0.08] as compared to lower baseline levels [0.61% ± 0.07]. Regarding GIT intolerance, 140 patients lacked the symptoms, out of which 60.7% were responders and 39.3% were non-responders

Conclusions: Metformin lead to improvement in glycemic control in 59.5% of newly diagnosed T2DM patients after taking metformin for three months but in 40.5% it did not which may be because of combined effects of various gene polymorphisms and their interaction with non-genetic factors. Metformin reduced the BMI in all the patients; however, BMI lowering activity of metformin was same regardless of its effect on HbA1C. Moreover, the signs and symptoms of GIT intolerance did not differ between the two groups

Phenolic acid profiling and antiglycation studies of leaf and fruit extracts of tyrosine primed Momordica charantia seeds for possible treatment of diabetes mellitus

The increasing risk of variety of fatal diseases including diabetes mellitus is imposing serious challenge to chemist, biologists and clinicians. Due to the side effects of the chemotherapy, worldwide it is thinking that phytomedicine are more effective to cope continuously increasing risk of fatal diseases without any side effect. Seed priming is a strategic pre-sowing semi-bioengineering technique which has ability to improve the growth rate and biologically active compounds in short time. Among seed priming techniques, tyrosine seed priming most frequently used because amino acids provide best growth media for nutritional food crops. Seeds of Momordica charantia were subjected to the pre-sowing tyrosine solution. Different growth parameters including growth emergence rate, seedling vigor, growth and weight of root, shoot and leaf were studied. The results showed positive effect on Momordica charantia seed growth and phenolic acids production i.e. ferulic acid - 43.95 ppm and sinapic acid - 18.39 ppm. The antiglycation assay showed 23.45 +/- 1.23% antiglycation activity of primed-seed fruit extract as compare to control seed fruit extract [0.87 +/- 0.03%]. On the basis of the results, it is concluded that tyrosine primed seed fruit extract could effectively be further tested for pre-clinical and clinical studies to manage diabetes mellitus disease

Homozygous mutations in NTRK1 gene underlie congenital insensitivity to pain with anhidrosis in Pakistani families

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder presenting with loss of pain sensation, thermal sensation defects, and self-mutilating behavior. In the present study, we recruited two consanguineous pedigree showing pain insensitivity symptoms from Pakistan for clinical and molecular investigations. In family A, one female patient displayed classical CIPA symptoms along with microcephaly and severe intellectual disability. During course of the disease, her right foot was amputated and had remarkable dental degeneration and teeth shedding. In family B, one boy presented with classical symptoms of congenital insensitivity to pain with anhidrosis. Blood was collected from both families for molecular studies. Sequencing with the Ilumina Trusight One Sequencing Panel covering 4813 OMIM genes revealed a known homozygous mutation c.2084C>T; p.P695L of NTRK1 in family A and a novel truncated mutation c.2025C>G; p.Y681X in family B. Protein modeling analysis of both mutations (p.P695L and p.Y681X) predicted loss of the rigidity in tyrosine kinase domain of NTRK1 that led to conformational changes as well as deleterious effect on protein function. The known mutation was reported more than a decade ago in a family from Northern Israel and other non-sense mutation is newly identified. It is interested that most of NTRK1 mutations are associated with this domain. This is first ever report of NTRK1 variants in congenital insensitivity to pain with anhidrosis patients from Pakistan.

Efficacy of differently applied tyrosine and tryptophan for modulation of phenolic metabolism in Trachyspermum ammi [L.] sprague seedlings

Phenolics are pharmaceutically important molecules. Tyrosine and tryptophan are precursors of phenolic metabolism. It was aimed to investigate the potential of exogenously introduced precursors on the phenolic contents in Trachyspermum ammi [L.] Sprague seedlings. The seeds of two local varieties [Chakwal and Desi] were grown in completely randomized design in a growth chamber at 19 +/- 2[degree]C with two amino acids [tyrosine and tryptophan] applied [priming and supplementation in rooting medium] at two treatment levels [0, and 1%]. Ten days old seedlings were harvested and subjected for growth [root and shoot length, fresh weight and dry weight] and phenolic estimation was done by HPLC method. Presence of seven phenolic acids including quercitin, chromatotropic acid, gallic acid, chlorogenic acid, sinnapic acid, trans 4 hydroxy 3 methoxy cinamic acid and P-courmeric acid was confirmed in both varieties with dissimilar fraction. Poor growth was observed by "Desi" under controlled conditions that were efficiently enhanced by tyrosine and tryptophan treatments. As precursors both amino acids differed for allosteric regulation of the pathway. That varied from application to application and variety to variety too for a pattern of phenolic accumulation. In conclusion, tyrosine and tryptophan application can be useful for farmers for improved growth of T. ammi and for pharmaceutical scientists to modulate metabolites of interest

Detection of extended-spectrum beta -lactamases in Klebsiella pneumoniae: comparison of phenotypic characterization methods

Extended-spectrum beta -lactamase producing K. pneumoniae is a serious threat to the patients. This manuscript shows the comparison of phenotypic characterization methods used for ESBL K. pneumoniae and frequency distribution of these isolates in various clinical samples. Eleven different types of pathological samples collected on various time intervals were analyzed. K. pneumoniae were identified with API 20E system [bioMerieux] and initial screening of ESBL K. pneumoniae was performed using the ceftazidime antimicrobial disc. Double-disc synergy test [DDST] and CLSI confirmatory test were compared for the phenotypic detection of ESBL K. pneumoniae. A total number of 214 ESBL producing K. pneumoniae were isolated from various clinical samples. Frequency distribution of ESBL producing K. pneumoniae was found to be highest among blood 117 [54.7%] and urine 46 [21.5%] samples. Data regarding the use of various interventions among these patients showed most common presence of intravenous line 209 [97.7%] and urinary catheters 46 [21.5%]. Comparison of DDST and CLSI confirmatory test showed that the DDST detected 145 [67.8%] isolates while 213 [99.5%] ESBL K. pneumoniae were characterized by CLSI confirmatory test. The use of CLSI confirmatory test is very efficient in the early detection of ESBL K. pneumoniae especially when the facilities for molecular characterization are not available

Clinicopathological features of transient myeloproliferative syndrome and congenital leukaemia

The objectives of the study were to determine the spectrum of the clinical and pathological findings, the management and prognosis of patients of transient myeloproliferative syndrome [TMS] and congenital leukaemia. Case series. The study was conducted over a period of 8 years, from January 2000 to December 2007, at the Children's Hospital and the Institute of Child Health, Lahore. Suspected patients presenting with fever, pallor, bruises and hepatosplenomegaly and diagnosed as either transient myeloproliferative disorder or congenital leukaemia were studied. The complete blood count, reticulocyte count, leukocyte alkaline phosphatase score, liver function tests, karyotyping studies and bone marrow aspiration biopsy were performed in all of those patients. Management and outcome was noted. Results were described as frequency percentages. Out of 10,000 patients presenting during this period, 24 patients were diagnosed as either of transient myeloproliferative syndrome or congenital leukaemia. Fifteen of these were diagnosed as patients of TMS and 9 as patients of congenital leukaemia. Down syndrome [DS] was diagnosed in 75% of these patients. TMS patients were put on supportive treatment and recovered spontaneously. One DS patient with congenital leukaemia went into spontaneous remission and 2 of DS patients with congenital leukaemia responded to chemotherapy while rest of them either died or lost to follow-up. TMS and congenital leukaemia were not very uncommon in the studied population. Majority had Down syndrome. It is important to differentiate their clinical and pathological presentations for proper management. TMS may resolve with supportive treatment while congenital leukaemia is a fatal condition requiring chemotherapy