Approaches towards the development of chimeric DPP4/ACE inhibitors for treating metabolic syndrome

Designing drug candidates exhibiting polypharmacology is one of the strategies adopted by medicinal chemists to address multifactorial diseases. Metabolic disease is one such multifactorial disorder characterized by hyperglycaemia, hypertension and dyslipidaemia among others. In this paper we report a new class of molecular framework combining the pharmacophoric features of DPP4 inhibitors with those of ACE inhibitors to afford potent dual inhibitors of DPP4 and ACE.     

Hypothalamic GABA receptor functional regulation and liver cell proliferation

The influence of carbohydrate utilisation on the growth of three strains of Vittad. mycelium (1BO, 17BO and 10RA) in culture was assessed using culture media containing glucose (control), mannose or mannitol. Mannose was the best substrate for growth of the strains and this was particularly evident for strain 17BO. Mannitol instead was metabolized only by 10RA and 1BO. In order to explain the different growth trends, analyses of enzyme levels, kinetic parameters, protein patterns and the morphology of the three strains were carried out. Our results show that these strains of mycelium were affected by the substrates used in the media. The aim of the present work was to optimise the in vitro production of T. borchii mycelium for use in experiments which require the fungus in precise and reproducible conditions, such as mycorrhizal synthesis or protein and nucleic acid extractions.     

Brain Stem GABA Receptor Functional Regulation During Rat Liver Cell Proliferation

GABAergic alterations in brain stem during compensatory hyperplasia after partial hepatectomy (PH), lead nitrate (LN)-induced direct hyperplasia, and N-nitrosodiethylamine (NDEA)-induced neoplasia in liver were investigated. GABA content decreased in brain stem of PH- and NDEA-treated rats while it increased in LN-treated rats. GABA_A receptor number and affinity in brain stem membrane preparations of rats showed a significant decrease in PH- and NDEA-treated rats. The GABA_B receptor number increased in PH- and NDEA-treated rats with an increase in affinity. The results of the present study indicate that liver cell proliferation is influencing the brain stem GABAergic neurotransmission and these changes regulate the hepatic proliferation through the sympathetic stimulation.     

Molecular-genetic analysis of two cases with retinoblastoma: Benefits for disease management

Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of the world. We studied histopathological, chromosomal and molecular-genetic data of two retinoblastoma patients from India. The two patients, one with bilateral and the other with unilateral retinoblastoma, underwent complete ophthalmic examination, cytogenetic study, retinoblastoma gene (RB1) mutational analysis andRB1 promoter region methylation screening. In the bilateral retinoblastoma patient deletion of chromosome region 13q14 in peripheral blood lymphocytes and a hemizygous novel 8-bp deletion in exon 4 ofRB1 in tumour sample were observed. In the unilaterally affected patient CGA to TGA transition protein truncation mutations were observed in exons 8 and 14 ofRB1.     

Amazonian invaders in an Asian biodiversity hotspot: Understanding demographics for the management of the armoured sailfin catfish,Pterygoplichthys pardalis in Kerala,India

Invasion of armoured catfish, Pterygoplichthys spp., is a major threat to global aquatic biodiversity, and developing effective strategies for their control and eradication is both a concern and a research priority. A length-based population assessment of invasive Pterygoplichthys pardalis in southern India, a hotspot for endemic aquatic biodiversity, indicated that rapid growth, high growth performance index and continuous recruitment have aided their successful invasion. Increasing fishing pressure on the adults is not adequate for population management, and only targeting young individuals (<30 cm) will result in overexploitation and population collapse.     

Improved Clinical Outcomes of High Risk β Thalassemia Major Patients Undergoing a HLA Matched Related Allogeneic Stem Cell Transplant with a Treosulfan Based Conditioning Regimen and Peripheral Blood Stem Cell Grafts

Improving clinical outcomes among high risk Class III β thalassemia major patients (Class IIIHR) receiving an allogeneic SCT remains a challenge. From October, 2009 a treosulfan based regimen (TreoFluT) was used for all consecutive Class III patients (n = 50). The clinical outcomes were compared with the historical conventional busulfan (BuCy) based regimen (n = 139). Use of TreoFluT was associated with a significantly reduced incidence of sinusoidal obstruction syndrome (SOS) among Class IIIHR cases (78% to 30%; P = 0.000) and early TRM (46% to 13%; p = 0.005). There was also a trend towards better engraftment in the Class IIIHR subset (P = 0.055). However, the use of bone marrow (BM) as source of stem cells along with the TreoFluT regimen was associated with 50% early mixed chimerism which reduced to 8.5% with the use of a peripheral blood stem cell graft (PBSC). Use of a PBSC graft was not associated with a significant increase in the incidence of acute or chronic graft versus host disease (GVHD). The overall and event free survival was significantly better among the Class IIIHR subset with the use of TreoFluT Vs. BuCy (86.6±7.3 Vs. 39.4±6.8%; P = 0.002 and 77.8±8.8 Vs. 32.4±6.5%; P = 0.003 respectively). A TreoFluT conditioning regimen with a PBSC graft can significantly improve clinical outcomes of Class IIIHR patients.     

Whole-genome sequence of the transformable Neisseria meningitidis serogroup A strain WUE2594

Serogroup A meningococci are a leading cause of bacterial meningitis in children and young adults worldwide. However, the genetic basis of serogroup A strains' virulence and their epidemiological properties remain poorly understood. Therefore, we sequenced the complete genome of the transformable Neisseria meningitidis serogroup A strain WUE2594.