Effect of maternal fasting on uterine arterial blood flow

AIM: To determine the effect maternal diet pattern on the uterine artery Doppler flow velocimetry. METHODS: This is a cross-sectional observational study. The uterine artery Doppler flow velocimetry was measured between 20 and 24 weeks' gestation in healthy pregnant women observing Ramadan. For each fasting mother, a non-fasting healthy pregnant woman was recruited as a control. Maternal blood glucose level was measured. RESULTS: A total of 106 pregnant women were studied. The mean hours since last oral intake were significantly longer, and the maternal glucose level was significantly lower in the study group than in the control group. The Mean (95% CI) of the uterine artery pulsatility index, resistance index, peak systolic velocity, end diastolic velocity and systolic/diastolic ratio was similar in both groups. CONCLUSION: Maternal fasting is not associated with significant changes in the uterine artery Doppler flow velocimetry.     

Optical,Electrochemical, Magnetic,and Conductive Properties of New Polyindolocarbazoles and Polydiindolocarbazoles

Summary: New polyindolocarbazoles (PIC) and polydiindolocarbazoles (PDIC) have been synthesized using Yamamoto polymerization reaction. These polymers have been investigated by cyclic voltammetry, UV‐Vis‐NIR spectroelectrochemistry, electrochemical quartz crystal microbalance, in situ electron spin resonance, and in situ conductivity techniques. Two redox oxidation processes, each involving one electron per repeat unit, produce radical cations (free or π‐dimerized) and dications. Each one‐electron redox process is generally split into two due to the stabilization of mixed‐valence states. The oxidative charge is delocalized over the polyconjugated backbone with neutral‐polaron conductivities in the range 0.002–0.04 S · cm^?1 and polaron‐bipolaron conductivities in the range 0.04–0.5 S · cm^?1. Conductivities are higher when nitrogen atoms are involved in the conjugation pathway.

Structure of P3IC, P3DIC, P2IC, and P2DIC.     

A founder truncating variant in GDF1 causes autosomal‐recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds

The genetic basis of congenital heart malformations associated with disruption of left–right (L–R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left–right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab‐Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left–right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.     

Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor-alpha and transforming growth factor-beta mRNA production

There is now good evidence that cytokines contribute to the regulation of tumor growth. The cytokine-driven modulation of tumor growth was investigated during the progression of a hepatocellular carcinoma (HCC) in SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of liver growth correlated with increased transforming growth factor (TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis factor (TNF)-alpha mRNA were detected earlier during tumor development. Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2, IL-4 and IFN-gamma mRNA production could be reported. In vitro, hepatocyte-like tumor cell lines established at two stages, either before or after HCC differentiation, were characterized. The early-stage-derived cell line produced TNF-alpha mRNA, but had barely detectable expression of TGF-beta 1 mRNA, while later-stage- derived cell lines showed the reciprocal pattern. All cell lines displayed a lack of sensitivity to TNF-alpha, although some degree of sensitivity to TNF-alpha could be observed in the presence of actinomycin-D or after treatment with IFN-gamma. The early-stage- derived cell line was sensitive to the growth inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines displayed a loss of sensitivity to TGF-beta 1 which correlated with the increased expression of TGF-beta 1 mRNA. Altogether, this suggests that tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression patterns during HCC progression. This model of HCC could be of valuable interest to assess the impact of various immunotherapeutic strategies on modulation of tumor growth.      

Contribution of phage typing and ribotyping in investigating a typhoid fever outbreak in Tunisia

A study was carried out to investigate an outbreak of typhoid fever that occurred in Sousse city and in the vicinity of Sousse (Tunisia) during summer 1999. Twenty four isolates of Salmonella enterica serotype Typhi were isolated in hospitalized patients with a typhoid fever in two hospitals (Farhat Hached Sousse and M'saken) and were studied with the help of two molecular typing methods: phage typing and automated ribotyping. Twenty one isolates with the Vi antigen had profile DVS (Degraded Vi Strain), one isolate with the Vi antigen belonged to phage type A and two isolates were non phage typable (no Vi antigen). The same ribotype was found in 22 out of 24 isolates. The results suggested that ribotyping is more discriminative than phage typing in this case in distinguishing strains and the strains shared the same source of the contamination. Unfortunately the precise source of the contamination could not be determined.     

The renal cell carcinoma lysis by a specific cytotoxic T cell clone is independent of the Fas/Fas-L cytotoxic pathway

The expression of Fas antigen at the surface of renal cell carcinoma and the susceptibility to Fas-mediated lysis by a tumor specific CTL clone were investigated. Renal cell carcinoma cell lines expressed Fas antigen and were susceptible to apoptosis mediated by antibodies to Fas/APO1. Using RT-PCR, we further showed that these cell lines expressed mRNA for Fas deleted transmembrane region, corresponding to a soluble form of Fas/APO-1. To investigate the role of the Fas/FasL pathway in the cytotoxic response against RCC cells, we analyzed the induction of Fas-L on a tumor specific T cell clone (CTL 8C2), previously generated against one RCC cell line. Fas-L expression on CTL 8C2 was detected by RT-PCR after stimulation with autologous tumor cells. However, the cytotoxic activity of CTL 8C2 was completely abolished when EGTA was added, suggesting that the cytolysis was mainly mediated by a Ca++-dependent pathway, perforin/granzyme-based.     

Protective effect of aqueous extract of Allium sativum against zearalenone toxicity mediated by oxidative stress

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. Several reports suggest that oxidative damage seems to be a key determinant of ZEN induced toxicity in vitro and in vivo.The aim of the current study was to evaluate the protective effects of aqueous extract of Allium sativum (AEA), against ZEN-induced cytotoxicity, reactive oxygen species (ROS) generation and DNA fragmentation in cultured Vero cells. Indeed, cytotoxicity effects were studied using MTT viability assay, ROS generation measurement and catalase activity induction. To check whether the oxidative stress induction was associated to DNA lesions, we looked for DNA fragmentation using Comet test.Our results indicated that ZEN induced several toxic effects and significant alterations mediated by oxidative stress mechanism. Treatment by ZEN combined to the lowest dose of AEA (250 μg/ml) showed a significant reduction of ZEN induced damages for all tested markers and a noticeable reduction of DNA fragmentation. It could be concluded that A. sativum aqueous extracts is effective in the protection against ZEN hazards. This could be relevant, particularly with the emergent demand for natural products which may counteract the detrimental toxic effects mediated by oxidative stress process and therefore prevents multiple human diseases.     

Dietary honey and ginseng protect against carbon tetrachloride-induced hepatonephrotoxicity in rats

Liver diseases are amongst the most serious health problems in the world today and hepatocellular carcinoma is one of the world's deadliest cancers. The aim of the current study was to evaluate the protective effect of sider honey and/or Korean ginseng extract (KGE) against carbon tetrachloride (CCl₄)-induced hepato-nephrotoxicity in rat. Eighty male Sprague-Dawley (SD) rats were allocated into different groups and over a 4-week period, they orally received honey and/or KGE or were treated either with CCl₄ alone (100 mg/kg b.w) or with CCl₄ after a pretreatment period with honey, KGE or a combination of both. Clinical, clinico-pathological and histopathological evaluations were done and CCl₄-treated groups were compared with rats receiving no treatment and with rats given honey, KGE or a combination of these substances. The results indicated that oral administration of CCl₄ induced severe hepatic and kidney injury associated with oxidative stress. The combined treatment with CCl₄ plus honey and/or KGE resulted in a significant improvement in all evaluated parameters. This improvement was prominent in the group receiving CCl₄ after combined pretreatment with honey and KGE. Animals receiving honey and/or KGE (without CCl₄-treatment) were comparable to the control untreated group. It could be concluded that honey and KGE protect SD rats against the severe CCl₄-induced hepatic and renal toxic effects. Our results suggest that the protective activity of honey and KGE may have been related to their antioxidant properties.