The Effects of Glycine Therapy on the Fetal Outcome of Diabetic Mice

The effect of glycine in preventing diabetes teratogenicity was studied in mice. Pregnant female animals were given an IP injection of 200 mg/kg of streptozotocin (STZ) on gestation day (GD) 7. Glycine was administered ad libitum from GD9 through GD19 (day of sacrifice) as a 1 and 2% drinking water solution. Nine whole-litter resorptions, a decreased number of live fetuses and fetal parameters, and an increase in HbA1C levels in diabetic dams were found. Malformations were limited. Glycine had a protective effect from hemoglobin glycation and embryotoxicity due to STZ-induced diabetes. Also, resorptions and malformed fetuses were positively correlated to HbA1C levels with a negative correlation to the number of live fetuses. The data suggest that glycine reduces the embryolethality of STZ-induced diabetes due to its anti-glycation effect.     

Microencapsulated macrophages releases conditioned medium able to prevent epithelial to mesenchymal transition

Epithelial to mesenchymal transition (EMT) has emerged as a key process in the development of renal fibrosis. In fact, EMT-derived fibroblasts contribute to the progression of chronic renal disease. In addition, anti-inflammatory M2 macrophages have exhibited a great influence on renal fibrosis. However, because of the high impact that the inputs of different environmental cytokines have on their phenotype, macrophages can easily lose this property. We aim to known if microencapsulated macrophages on M2-inducing alginate matrices could preserve macrophage phenotype and thus release factors able to act on epithelial cells to prevent the epithelial differentiation towards mesenchymal cells. We reproduced an in vitro model of EMT by treating adipose-derived stem cells with all-trans retinoic acid (ATRA) and induced their transformation toward epithelia. Dedifferentiation of epithelial cells into a mesenchymal phenotype occurred when ATRA was retired, thus simulating EMT. Results indicate that induction of M2 phenotype by IL-10 addition in the alginate matrix produces anti-inflammatory cytokines and increases the metabolic activity and the viability of the encapsulated macrophages. The released conditioned medium modulates EMT and maintains healthy epithelial phenotype. This could be used for in vivo cell transplantation, or alternatively as an external releaser able to prevent epithelial to mesenchymal transformation for future anti-fibrotic therapies.     

Identification and characterization of small molecules that inhibit intracellular toxin transport

Shiga toxin (Stx), cholera toxin (Ctx), and the plant toxin ricin are among several toxins that reach their intracellular destinations via a complex route. Following endocytosis, these toxins travel in a retrograde direction through the endosomal system to the trans-Golgi network, Golgi apparatus, and endoplasmic reticulum (ER). There the toxins are transported across the ER membrane to the cytosol, where they carry out their toxic effects. Transport via the ER from the cell surface to the cytosol is apparently unique to pathogenic toxins, raising the possibility that various stages in the transport pathway can be therapeutically targeted. We have applied a luciferase-based high-throughput screen to a chemical library of small-molecule compounds in order to identify inhibitors of Stx. We report two novel compounds that protect against Stx and ricin inhibition of protein synthesis, and we demonstrate that these compounds reversibly inhibit bacterial transport at various stages in the endocytic pathway. One compound (compound 75) inhibited transport at an early stage of Stx and Ctx transport and also provided protection against diphtheria toxin, which enters the cytosol from early endosomes. In contrast, compound 134 inhibited transport from recycling endosomes through the Golgi apparatus and protected only against toxins that access the ER. Small-molecule compounds such as these will provide insight into the mechanism of toxin transport and lead to the identification of compounds with therapeutic potential against toxins routed through the ER.     

Operation and calibration of the novel PTW 1600SRS detector for the verification of single isocenter stereotactic radiosurgery treatments of multiple small brain metastases

Objectives:The aim of this work was to evaluate the operation of the 1600SRS detector and to develop a calibration procedure for verifying the dose delivered by a single isocenter stereotactic radiosurgery (SRS) treatment of small multiple brain metastases (BM).Methods:14 clinical treatment cases were selected with the number of BM ranging from 2 to 11. The dosimetric agreement was investigated between the calculated and the measured dose by an OCTAVIUS 1600SRS array detector in an OCTAVIUS 4D phantom equipped with dedicated SRS top. The cross-calibration procedure deviated from the manufacturer’s as it applied field sizes and dose rates corresponding to the volumetric modulated arc therapy segments in each plan.Results:Measurements with a plan specific cross-calibration showed mean ± standard deviation (SD) agreement scores for cut-off values 50%, 80%, 95%, of 98.6 ± 1.7%, 96.5 ± 4.6%, 97.3 ± 4.4% for the 6 MV plans respectively, and 98.6 ± 1.5%, 96.6 ± 4.0% 96.4 ± 6.3%, for the 6 MV flattening filter free (FFF) plans respectively. Using the default calibration procedure instead of the plan specific calibration could lead to a combined systematic dose offset of 4.1% for our treatment plans.Conclusion:The 1600SRS detector array with the 4D phantom offers an accurate solution to perform routine quality assurance measurements of single isocenter SRS treatments of multiple BM. This work points out the necessity of an adapted cross-calibration procedure.Advances in knowledge:A dedicated calibration procedure enables accurate dosimetry with the 1600SRS detector for small field single isocenter SRS treatment of multiple brain metastases for a large amount of BM.     

mokeless tobacco use,tooth loss and oral health issues among adults in Cameroon

Background

Tobacco use in smokeless and smoked forms is preventable cause of mortality and morbidity worldwide.

Objective

To determine the prevalence of smokeless tobacco use and the association with tooth loss and oral health problems among adults in Cameroon.

Methods

Adults dwelling in the Fokoue area of West Region of Cameroon were studied.

Results

Out of the 226 participants studied, 119 of them reported smokeless tobacco use giving a prevalence of 52.7% with majority-74 (62.2%) chewing it. Three-quarters (77.3%) of the respondents use it more than than thrice-daily and more than half of them respondents have been using it for 6–10 years. The smokeless tobacco users were more of those aged 50–59 years, females, farmers, those with less than post-primary education, non alcohol consumers and those that have not received previous dental care than smokeless tobacco users. However, it was only age (p=0.006) and educational attainment (p=0.009) that were significantly associated with smokeless tobacco use. Smokeless tobacco user were more likely to have poor oral hygiene, dental caries, gingival recession, leukoplakia, erythroplakia, abnormal growth, tooth wear lesion, experienced tooth loss and edentulousnss than non smokeless tobacco users. However, the significantly associated lesions with smokeless tobacco use were tooth loss (p=0.008), edentulousness (p=0.016), gingival recession (p=0.006) and leukoplakia (p=0.001).

Conclusion

The prevalence of smokeless tobacco use was high among adults in Cameroon and it was associated with more likelihood of oral health problems. There is therefore a need for health education on the health consequences of the smokeless tobacco use with demonstrations by the dentist.     

Evaluation of some anthropometric indices for the diagnosis of obesity in pregnancy in Nigeria: a cross-sectional study

Background

Obesity in pregnancy is a global health problem which is associated with poor pregnancy outcomes. The use of weight and height, measured at about ten weeks of gestation, to produce pre-gestational body mass index is recommended for the diagnoses of the condition but limitations abound in under resourced settings.

Objectives

To measure anthropometric indices such as mid upper arm circumference, calf circumference, waist circumference and waist to hip ratio, for identification of obesity in pregnancy.

Methods

Anthropometric measurements were carried out on cohorts of pregnant women from 4 hospitals in Enugu, South-eastern Nigeria.

Results

There were no significant difference in the mean mid upper arm circumference (MUAC) and calf circumference (CC) across the trimester groups. The mean values of waist circumferences, hip circumference and waist to hip ratios changed significantly across the trimesters. The 75^th percentile of MUAC (33 cm) and CC (39 cm) in all trimesters, had sensitivity and specificity of more than 70% for identifying obesity in pregnancy.

Conclusion

MUAC and CC values of 33cm and 39cm respectively might be reliable cut off points for diagnoses of obesity throughout pregnancy in Enugu, Nigeria     

Overexpression of cyclin D1 in the Dami megakaryocytic cell line causes growth arrest

The maturation of megakaryocytes in vivo requires polyploidization or repeated duplication of DNA without cytokinesis. As DNA replication and cytokinesis are tightly regulated in somatic cells by cyclins and cyclin-dependent kinases, we sought to determine the pattern of cyclin gene expression in cells that undergo megakaryocytic differentiation and polyploidization. The Dami megakaryocytic cell line differentiates and increases ploidy in response to phorbol 12-myristate 13-acetate (PMA) stimulation in vitro. We used Northern blotting to analyze mRNA levels of cyclins A, B, C, D1, and E in PMA-induced Dami cells and found that cyclin D1 mRNA levels increased dramatically (18-fold). Similar increases in cyclin D1 mRNA were obtained for other cell lines (HEL and K562) with megakaryocytic properties, but not in HeLa cells. The increase in cyclin D1 was confirmed by Western immunoblotting of PMA-treated Dami cells. This finding suggested that cyclin D1 might participate in megakaryocyte differentiation by promoting endomitosis and/or inhibiting cell division. To address these possibilities, we constructed two stable Zn+2-inducible, cyclin D1-overexpressing Dami cell lines. Cyclin D1 expression alone was not sufficient to induce polyploidy, but in conjunction with PMA-induced differentiation, polyploidization was slightly enhanced. However, unlike other cell systems, cyclin D1 overexpression caused cessation of cell growth. Although the mechanism by which cyclin D1 may affect megakaryocyte differentiation is not clear, these data demonstrate that cyclin D1 is upregulated in differentiating megakaryocytic cells and may contribute to differentiation by arresting cell proliferation.     

The insulin receptor substrate-1-related 4PS substrate but not the interleukin-2R gamma chain is involved in interleukin-13-mediated signal transduction

Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3- dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin- like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL- 13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4R alpha) and lack expression of the IL-2 receptor gamma subunit (IL-2R gamma), resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. These results indicate that IL-13 does not use the IL-2R gamma subunit in its receptor complex and that expression of IL-2R gamma enhances, but is not absolutely required for mediating IL-4-induced tyrosine phosphorylation of IRS-1/4PS.