Real-World Observational Study on Vildagliptin With Insulin (VIL-INS) or Vildagliptin and Metformin With Insulin (VIL-MET-INS) Therapy in Indian Patients With Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVE:  The therapeutic use of vildagliptin and insulin (VIL-INS) or vildagliptin and metformin in combination with insulin (VIL-MET-INS) in the Indian scenario has yet to be explored by generating real-world evidence. Therefore, the present study aimed to evaluate the demographic, clinical characteristics, and treatment patterns of patients with type 2 diabetes mellitus (T2DM) in Indian settings in the above context. METHODOLOGY:  This observational study conducted at 600 healthcare centers in India retrospectively analyzed data of adult patients with T2DM who had been treated with either vildagliptin with insulin or a combination of vildagliptin and metformin with insulin. Data were collected from medical records and analyzed by appropriate statistical tests. RESULTS:  A total of 12,603 patients with T2DM were included with a mean age of 53.4 years of which 63.8% were males. The majority of patients (n=6511; 51.7%) received a combination of vildagliptin and metformin on top of insulin. A significantly high proportion of patients in the age group of 18-40 years received this treatment compared to patients who were initiated on insulin treatment after vildagliptin and metformin combination (11.6% vs. 9.7%; P<0.001). Of all the patients, 70.0% were able to achieve target glycemic control with either VIS-INS or VIL-MET-INS. After treatment with VIL-INS or VIL-MET-INS, the mean glycated hemoglobin (HbA1c) levels significantly decreased with a mean change of 1.46%. Out of all patients, 13.5% experienced weight changes during treatment, with 67.4% of them showing weight loss. A total of 68 patients reported hypoglycemic events and among them, 49 patients had mild hypoglycemic events. Physician global evaluation of efficacy and tolerability showed a majority of patients rated their experience as good to excellent (86.3% and 86.0%, respectively). CONCLUSION:  Both treatment regimens were effective in terms of reduced HbA1c to achieve glycemic control. Furthermore, it is well tolerated without an increase in the risk of hypoglycemia or weight gain. Hence, this therapy has favorable outcomes for T2DM management in Indian clinical settings.

Hymenolepiosis in a group of albino rats (Rattus albus): a study.

A study was carried out on adult albino Wistar laboratory rats to know the incidence of hymenolepiosis, a zoonotic disease which were brought for experiment purpose. Faecal samples of 95 rats examined for parasitic infection by simple floatation technique in which 32 were positive (33.68 %) for hymenolepiosis. Identification of species of Hymenolepis was done based on morphology of egg. The highest prevalence of Hymenolepis diminuta (23.15 %) was recorded followed by Hymenolepis nana (10.52 %). Heavy infection with Hymenolepis in rats draws attention in view of public health importance in contact persons.

Turpentine oil induced inflammation decreases absorption and increases distribution of phenacetin without altering its elimination process in rats.

Plasma concentrations and pharmacokinetics of phenacetin, a CYP1A2 substrate were determined in normal and experimentally induced inflamed rats by turpentine oil to know the role of inflammation on the pharmacokinetics of phenacetin and formation of its active metabolite (paracetamol) by CYP1A2 in wistar albino rats, weighing about 200-250 g that were randomly divided into two groups consisting six in each group. Rats in group I (control) received phenacetin (150 mg kg(-1), PO) where as group II received phenacetin 12 h after induction of inflammation by turpentine oil (0.4 mL, i.m). Blood samples were collected from retro orbital plexus at pre-determined time intervals prior to and at 0.166, 0.33, 0.67, 1.5, 2, 4, 8 and 12 h post-administration of phenacetin. Plasma was separated and analyzed for phenacetin and its metabolite paracetamol by HPLC assay. Based on plasma concentrations of phenacetin and its metabolite paracetamol, the pharmacokinetic parameters were determined by compartmental methods. C(max) of phenacetin was significantly (p < 0.01) decreased to 19.50 ± 2.74 µg mL(-1) in inflamed conditions compared to 38.13 ± 2.20 µg mL(-1) obtained in normal rats. Except, for significant (p < 0.001) increase in volume of distribution at steady state (V(dss)) from 2.87 ± 0.37 to 8.03 ± 1.26 L kg(-1) and increased the rate of absorption with shorter absorption half-life (t(1/2ka)) for phenacetin in inflammation. None of the pharmacokinetic parameters of either phenacetin or its metabolite paracetamol were affected. It can be concluded that turpentine oil induced inflammation has no role on the activity of CYP1A2 in rats, as the plasma concentrations and pharmacokinetic parameters of paracetamol were found unaltered.

Design and synthesis of novel isoxazole tethered quinone-amino Acid hybrids.

A new series of isoxazole tethered quinone-amino acid hybrids has been designed and synthesized involving 1,3-dipolar cycloaddition reaction followed by an oxidation reaction using cerium ammonium nitrate (CAN). Using this method, for the first time various isoxazole tethered quinone-phenyl alanine and quinone-alanine hybrids were synthesized from simple commercially available 4-bromobenzyl bromide, propargyl bromide, and 2,5-dimethoxybenzaldehyde in good yield.

Accuracy of glycated haemoglobin in screening for pre-diabetes in Asian Indians--a community survey: the Chandigarh Urban Diabetes Study (CUDS).

AIM: To compare American Diabetes Association and International Expert Committee recommended cut-off values of HbA(1c) for detecting the presence of pre-diabetes against plasma glucose values obtained from oral glucose tolerance tests in Asian Indians. METHODS: A cross-sectional randomly sampled population survey involving 2368 adults, aged ≥ 20 years. HbA(1c) was measured on a Bio-Rad 10 system in 1972 subjects. RESULTS: Of the 1972 subjects studied, 329 were detected to have pre-diabetes based on isolated impaired fasting glucose in 125 subjects (6.3%), isolated impaired glucose tolerance in 141 subjects (7.1%) and the presence of both in 63 subjects (3.2%). The HbA(1c) cut-off of 34 mmol/mol (5.7%), as recommended by the American Diabetes Association for detecting the presence of pre-diabetes, showed sensitivity of 62%, specificity 77%, with a positive predictive value of 34.7%, a negative predictive value of 89.5% and accuracy of 67.8%; whereas the HbA(1c) cut-off recommended by the International Expert Committee of 42 mmol/mol (6%) had a sensitivity of 36%, specificity of 90%, positive predictive value of 42.7%, negative predictive of 85.4% and an accuracy of 77%. However, both these HbA(1c) cut-offs underdiagnosed the presence of pre-diabetes in 38 and 64% of these subjects, respectively. CONCLUSIONS: The American Diabetes Association and the International Expert Committee recommended HbA(1c) cut-off values and oral glucose tolerance tests identify different pre-diabetes cohorts. Long-term prospective studies are required to define the usefulness of one over the other.

Colonic neoplasia in acromegaly: increased proliferation or deceased apoptosis?

Patients with acromegaly have higher prevalence of colorectal neoplasms. The pathogenetic mechanism is still unclear and may be related to sustained increase in serum GH-IGF1. We aimed to evaluate the proliferative and apoptotic markers in samples of colonic mucosa obtained during screening colonoscopic biopsy from patients with acromegaly and study their relationship to serum IGF-1 and GH levels. The study subjects included 32 patients with acromegaly (4 female), 10 healthy controls (irritable bowel syndrome) and 10 positive controls (non-acromegalic colonic adenocarcinoma). Patients with acromegaly were divided into two groups, active disease (AD) and disease in remission (AR). Two biopsies each were obtained during colonoscopy from the right colon, transverse colon and rectosigmoid region. All the polyps were biopsied and subjected to histopathological examination. Immunohistochemistry for proliferation marker (Ki-67) and apoptotic markers (caspase-3 and TdT-Mediated dUTP Nick-End Labeling (TUNEL) was carried out in the histopathological samples. Indices of proliferation were significantly different in patients with acromegaly as compared to healthy controls. The mean Ki-67 positivity was 45.1 ± 17.7% in AD and 45.6 ± 23.1% in AR, as compared to 10 ± 5% in healthy controls. While none of the healthy controls had Ki-67 positivity beyond the lower third of crypts, among patients with acromegaly 12/32 (37.5%) had mid-third positivity (P = 0.000) and 15/32 (46.8%) had full length of crypt positively (P = 0.00). Immunostaining for caspase-3 was negative in patients with acromegaly and healthy controls. TUNEL was strongly positive in patients with colonic adenocarcinoma but not in healthy controls and patients with acromegaly. IGF-1 levels were higher in those with Ki-67 positivity in the superficial mucosa. Patients with acromegaly have increased proliferation of colonic epithelial cells. Elevated levels of serum IGF1 are associated with increase proliferation in the superficial crypt cells.

Sequencing, characterization and genetic variation of the Bos indicus glucose-6-phosphate-dehydrogenase gene.

The coding sequence of the bovine (Bos indicus) Glucose-6-phosphate-dehydrogenase (G6PD) gene was amplified by Reverse Transcriptase-PCR (RT-PCR), cloned, sequenced and characterized. The deduced amino acid sequence clustered the bovine G6PD sequence with the other mammalian G6PD proteins into a monophyletic group. The bovids (B. indicus and B. taurus) clustered clearly from the rodent (rat, mouse and hamster) subcluster and from humans. The multiple sequence alignment of the bovine G6PD with the mammalian species clearly revealed conservation of the substrate, coenzyme, catalytic and the dimer binding sites with the solved X-ray crystallographic structure of Homo sapiens. Also, four fragments of bovine (Bos indicus) G6PD gene viz. 118, 319, 683 and 408 bp were amplified and sequenced for the first time. A G/A and G/C single nucleotide polymorphisms in intron-9 and exon-10 were detected on PCR-RFLP of the 319 bp amplicon with Hae III and Pst I, respectively. This work is the first study on Bos indicus G6PD gene at the nucleotide level.

Synthesis and antidepressant activity of some 1,3,5-triphenyl-2-pyrazolines and 3-(2''-hydroxy naphthalen-1''-yl)-1,5-diphenyl-2-pyrazolines.

Five new 1,3,5-triphenyl-2-pyrazolines were synthesised by reacting 1,3-diphenyl-2-propene-1-one with phenyl hydrazine hydrochloride and another five new 3-(2''-hydroxy naphthalen-1''-yl)-1,5-diphenyl-2-pyrazolines were synthesised by reacting 1-(2'-hydroxynaphthyl)-3-phenyl-2-propene-1-one with phenyl hydrazine hydrochloride. The structures of the compounds were proved by means of their IR, (1)H NMR spectroscopic data, and microanalyses. The antidepressant activity of these compounds was evaluated by the 'Porsolt behavioural despair test' on Swiss-Webster mice.1-Phenyl-3-(2''-hydroxyphenyl)-5-(4'-dimethylaminophenyl)-2-pyrazoline, 5-(4'-dimethylaminophenyl)-1,3-diphenyl-2-pyrazoline, 1-phenyl-3-(2''-hydroxynaphthalen-1''-yl)-5-(3',4',5'-trimethoxyphenyl)-2-pyrazoline, 1-phenyl-3-(4''-methylphenyl)-5-(4'-dimethylaminophenyl)-2-pyrazoline and 1-phenyl-3-(4''-bromophenyl)-5-(4'-dimethyl amino phenyl)-2-pyrazoline reduced immobility times 25.63-59.25% at 100mg/kg dose level. In addition, it was found that the compounds possessing electron-releasing groups such as dimethyl amino, methoxy and hydroxyl substituents, on both the aromatic rings at positions 3 and 5 of pyrazolines, considerably enhanced the antidepressant activity when compared to the pyrazolines having no substituents on the phenyl rings.