Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease.     

Glucose tolerance in pregnancy in South India: relationships to neonatal anthropometry

BACKGROUND: The incidence of type 2 diabetes is increasing worldwide, most rapidly in developing countries such as India. Exposure as a fetus to maternal gestational diabetes is thought to be a risk factor for developing the disease. This study was set up to determine the incidence of gestational diabetes mellitus in one urban maternity unit in South India and to examine its effect on the offspring's neonatal anthropometry, childhood growth, and glucose/insulin metabolism. This paper reports neonatal outcomes. METHODS: Seven hundred and eighty five women were recruited consecutively from the antenatal clinic of the Holdsworth Memorial Hospital, Mysore and underwent a 100 g, 3-hr oral glucose tolerance test at 30 +/- 2 weeks gestation. Gestational diabetes was defined using Carpenter and Coustan criteria. The babies were measured in detail at birth. RESULTS: Mean maternal age and body mass index were 23.6 years and 23.1 kg/m(2). The incidence of gestational diabetes was 6.2%. Mothers with gestational diabetes had babies that were heavier (3339 g compared with 2956 g for non-diabetic mothers) and larger in measurements of fat, muscle, and skeleton. Even in non-diabetic pregnancies, neonatal weight, head circumference, and ponderal index were positively related to maternal fasting glucose concentrations (P < or = 0.05 for all). CONCLUSIONS: The incidence of gestational diabetes was high in this unselected sample of mothers booking into one urban Indian maternity unit. Community-based studies are required to confirm this. The effect of maternal glucose concentrations on neonatal anthropometry is continuous and extends into the "normal" glycemic range.     

Anthropometry, glucose tolerance, and insulin concentrations in Indian children: relationships to maternal glucose and insulin concentrations during pregnancy

OBJECTIVE: The purpose of this study was to test the hypothesis that the environment experienced by fetuses of mothers with gestational diabetes mellitus (GDM) and mothers with higher glucose concentrations that are in the normal range causes increased adiposity and altered glucose/insulin metabolism in childhood. RESEARCH DESIGN AND METHODS: Children (n = 630) whose mothers were tested for glucose tolerance during pregnancy had detailed anthropometry performed at birth and annually thereafter. At 5 years, plasma glucose and insulin concentrations were measured in the children (2-h oral glucose tolerance test) and their fathers (fasting samples only). RESULTS: Newborns of diabetic mothers (n = 41) were larger in all body measurements than control newborns (babies with nondiabetic parents). At 1 year, these differences had diminished and were not statistically significant. At 5 years, female offspring of diabetic mothers had larger subscapular and triceps skinfold thicknesses (P = 0.01) and higher 30- and 120-min insulin concentrations (P < 0.05) than control children. Offspring of diabetic fathers (n = 41) were lighter at birth than control children (P < 0.001); they showed no differences in anthropometry at 5 years. In control children, skinfold thickness and 30-min insulin concentrations were positively related to maternal insulin area under the curve, and skinfold thicknesses were related to paternal fasting insulin concentrations independently of the parents' skinfold thickness and socioeconomic status. CONCLUSIONS: Maternal GDM is associated with adiposity and higher glucose and insulin concentrations in female offspring at 5 years. The absence of similar associations in offspring of diabetic fathers suggests a programming effect in the diabetic intrauterine environment. More research is needed to determine whether higher maternal glucose concentrations in the nondiabetic range have similar effects.     

Stability-Indicating RP-HPLC Method for the Simultaneous Estimation of Doxofylline and Terbutalinesulphate in Pharmaceutical Formulations

An isocratic, stability-indicating, reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the quantitative determination of doxofylline and terbutaline sulphate, used for the treatment of respiratory problems. The chromatographic separation was achieved on a Zorbax-SB Phenyl 250 × 4.6mm × 5 μm column with the mobile phase consisting of a mixture of 25 mM ammonium acetate (pH 5.0) : acetonitrile (85:15 %v/v) at a flow rate of 1.0 ml/min. The eluate was monitored at 274 nm using a PDA detector. Forced degradation studies were performed on the bulk sample of doxofylline and terbutaline sulphate using acid (0.1N HCl), base (0.1N NaOH), oxidation (10% hydrogen peroxide), photolytic, and thermal degradation conditions. Good resolution was observed between the degradants and analytes. Degradation products resulting from the stress studies did not interfere with the detection of doxofylline and terbutaline sulphate, thus the assay is stability-indicating. The method has the requisite accuracy, selectivity, sensitivity, and precision for the simultaneous estimation of doxofylline and terbutaline sulphate in bulk and pharmaceutical dosage forms. The limit of quantitation and limit of detection were found to be 1.16 μg/ml and 0.38 μg/ml for doxofylline, 2.08 μg/ml and 0.62 μg/ml for terbutaline sulphate, respectively.     

Synthesis, characterization and in vitro biological activity studies of Cu-M (M = Cu2+, Co2+, Ni2+, Mn2+, Zn2+) bimetallic complexes

Six new bimetallic complexes of the type CuCu, CuCo, CuNi, CuZn and CuMn were prepared. The structures of these complexes and the ligand have been proposed on the basis of FAB mass, elemental analysis, UV-vis, IR, EPR and CV studies. All the complexes completely cleave pBS (SK-) DNA at a concentration of 10 microM; however, even at lower concentrations of 2 microM and 0.1 microM, the complexes (I and Ia) showed partial cleavage. The results of the fluorescence binding studies of the metal complexes with CT-DNA showed that the presence of aliphatic ligands added additional binding effects including electrostatic, hydrogen binding and vander Waals interactions. Complexes (I, Ia) showed 50% inhibition of COX-1 and COX-2 activities at as low a concentration as 12.5 microM, 13.5 microM, 14 microM and 14.5 microM. Inhibition assay of top I and top II by different complexes in mutant yeast strains (JN394, JN394 t(-1) and JN394 t(2-5)) with all the complexes showed significant inhibition of topoisomerase at 5 microM concentration. Complexes I and Ia exhibited good anti-microbial activities against all human pathogens tested except Klebsiella pneumoniae. The following studies showed that among the synthesized bimetallic complexes, complexes I and Ia seem to be promising candidates possessing DNA cleavage activities besides anti-microbial and anti-inflammatory properties to serve as chemical nucleases and chemotherapeutic agents.     

Glucose tolerance and insulin resistance in Indian children: relationship to infant feeding pattern

Aims/hypothesis  

Our objective was to examine whether longer duration of breast-feeding and later introduction of complementary foods are associated with lower glucose concentrations and insulin resistance (IR-HOMA) in Indian children.