Tumor necrosis factor inhibits glucocorticoid receptor function in mice: a strong signal toward lethal shock

As glucocorticoid resistance (GCR) and the concomitant burden pose a worldwide problem, there is an urgent need for a more effective glucocorticoid therapy, for which insights into the molecular mechanisms of GCR are essential. In this study, we addressed the hypothesis that TNFα, a strong pro-inflammatory mediator in numerous inflammatory diseases, compromises the protective function of the glucocorticoid receptor (GR) against TNFα-induced lethal inflammation. Indeed, protection of mice by dexamethasone against TNFα lethality was completely abolished when it was administered after TNFα stimulation, indicating compromised GR function upon TNFα challenge. TNFα-induced GCR was further demonstrated by impaired GR-dependent gene expression in the liver. Furthermore, TNFα down-regulates the levels of both GR mRNA and protein. However, this down-regulation seems to occur independently of GC production, as TNFα also resulted in down-regulation of GR levels in adrenalectomized mice. These findings suggest that the decreased amount of GR determines the GR response and outcome of TNFα-induced shock, as supported by our studies with GR heterozygous mice. We propose that by inducing GCR, TNFα inhibits a major brake on inflammation and thereby amplifies the pro-inflammatory response. Our findings might prove helpful in understanding GCR in inflammatory diseases in which TNFα is intimately involved.     

Morphological differences in human zygotes and embryos cultured in different media

Summary Purpose: To compare the effects of four culture media on the quality of human zygotes and embryos. Methods: Prospective study analyzing 2289 human embryos cultivated simultaneously in two different culture media: HTF, the default medium, with either Universal IVF, Global or IVF-30 as the secondary media. The sibling oocytes by each patient were randomly divided between the two culture media following intracytoplasmic sperm injection (ICSI). On day 1 the pronuclear stage of zygotes were evaluated and on day 2 embryos were evaluated according to the number of cells, percentage of fragmentation and number of nuclei. Z-test and odds ratios were used in the statistical analysis. Results: There was a higher percentage (55.2%) of class A1 + A2 zygotes with IVF-30 compared with HTF, Global or Universal IVF media (49.1%, 44.7% and 44.2%, respectively). The percentage of Top embryos was significantly higher with Global (40.2%) compared with HTF (21.3%), IVF-30 (25.0%) or Universal IVF media (11.2%). Conclusions: Global medium produced more Top embryos evaluated on day 2 of development.     

Serum γ-glutamyl Transferase Levels,Insulin Resistance and Liver Fibrosis in Patients with Chronic Liver Diseases

Background and Aims

Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis.

Methods

843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT.

Results

By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120–6.564,p = 0.02), G1CHC (OR3.461,CI2.138–5.603,p<0.001) and CHB (OR2.778,CI1.042–7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079–15.970,p = 0.03 for NAFLD; OR2.250,CI1.211–4.181,p = 0.01 for G1CHC; OR3.096,CI2.050–34.220,p = 0.01 for CHB).

Conclusions

In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.     

Implications of Storing Urinary DNA from Different Populations for Molecular Analyses

Background

Molecular diagnosis using urine is established for many sexually transmitted diseases and is increasingly used to diagnose tumours and other infectious diseases. Storage of urine prior to analysis, whether due to home collection or bio-banking, is increasingly advocated yet no best practice has emerged. Here, we examined the stability of DNA in stored urine in two populations over 28 days.

Methodology

Urine from 40 (20 male) healthy volunteers from two populations, Italy and Zambia, was stored at four different temperatures (RT, 4°C, −20°C & −80°C) with and without EDTA preservative solution. Urines were extracted at days 0, 1, 3, 7 and 28 after storage. Human DNA content was measured using multi-copy (ALU J) and single copy (TLR2) targets by quantitative real-time PCR. Zambian and Italian samples contained comparable DNA quantity at time zero. Generally, two trends were observed during storage; no degradation, or rapid degradation from days 0 to 7 followed by little further degradation to 28 days. The biphasic degradation was always observed in Zambia regardless of storage conditions, but only twice in Italy.

Conclusion

Site-specific differences in urine composition significantly affect the stability of DNA during storage. Assessing the quality of stored urine for molecular analysis, by using the type of strategy described here, is paramount before these samples are used for molecular prognostic monitoring, genetic analyses and disease diagnosis.     

Sexual dimorphism in digital dermatoglyphic traits among Sinhalese people in Sri Lanka

Background

The purpose of this study was to evaluate gender-wise diversity of digital dermatoglyphic traits in a sample of Sinhalese people in Sri Lanka.

Findings

Four thousand and thirty-four digital prints of 434 Sinhalese individuals (217 males and 217 females) were examined for their digital dermatoglyphic pattern distribution. The mean age for the entire group was 23.66 years (standard deviation = 4.93 years). The loop pattern is observed more frequently (n = 2,592, 59.72%) compared to whorl (n = 1,542, 35.53%) and arch (n = 206, 4.75%) in the Sinhalese population. Females (n = 1,274, 58.71%) have a more ulnar loop pattern than males (n = 1,231, 56.73%). The plain whorl pattern is observed more frequently in males (n = 560, 25.81%) compared to females (n = 514, 23.69%).The double loop pattern is observed more frequently on the right and left thumb (digit 1) of both males and females. Pattern intensity index, Dankmeijer index and Furuhata index are higher in males.

Conclusions

Ulnar loop is the most frequently occurring digital dermatoglyphic pattern among the Sinhalese. All pattern indices are higher in males. To some extent, dermatoglyphic patterns of Sinhalese are similar to North Indians and other Caucasoid populations. Further studies with larger sample sizes are recommended to confirm our findings.     

ACUTE EFFECTS OF MOVEMENT VELOCITY ON BLOOD LACTATE AND GROWTH HORMONE RESPONSES AFTER ECCENTRIC BENCH PRESS EXERCISE IN RESISTANCE-TRAINED MEN

This study aimed to compare the effects of different velocities of eccentric muscle actions on acute blood lactate and serum growth hormone (GH) concentrations following free weight bench press exercises performed by resistance-trained men. Sixteen healthy men were divided into two groups: slow eccentric velocity (SEV; n = 8) and fast eccentric velocity (FEV; n = 8). Both groups performed four sets of eight eccentric repetitions at an intensity of 70% of their one repetition maximum eccentric (1RMecc) test, with 2-minute rest intervals between sets. The eccentric velocity was controlled to 3 seconds per range of motion for SEV and 0.5 seconds for the FEV group. There was a significant difference (P < 0.001) in the kinetics of blood lactate removal (at 3, 6, 9, 15, and 20 min) and higher mean values for peak blood lactate (P = 0.001) for the SEV group (9.1 ± 0.5 mM) compared to the FEV group (6.1 ± 0.4 mM). Additionally, serum GH concentrations were significantly higher (P < 0.001) at 15 minutes after bench press exercise in the SEV group (1.7 ± 0.6 ng · mL⁻¹) relative to the FEV group (0.1 ± 0.0 ng · mL⁻¹). In conclusion, the velocity of eccentric muscle action influences acute responses following bench press exercises performed by resistance-trained men using a slow velocity resulting in a greater metabolic stress and hormone response.     

Characterization of lipopeptides from <Emphasis Type="Italic">Paenibacillus</Emphasis> sp. (IIRAC30) suppressing <Emphasis Type="Italic">Rhizoctonia solani</Emphasis>

The main aim was to identify the active compound against Rhizoctonia solani produced by the cassava endophyte Paenibacillus sp. IIRAC-30. The compounds produced were extracted with ethyl acetate and purified by Sephadex column prior to analysis by Q-TOF mass spectrometry. A C₁₅-lipopeptide with an estimated molecular weight of 1036 Da and homologues were identified. The lipopeptide had a cyclic structure, which was deduced by interpreting the ESI–MS/MS spectra of main protonated homologues containing 15:0 FA, and the amino acid composition was Glu-Leu-Leu-Val-Asp-Leu-Leu. Therefore, the lipopeptides produced by isolate IIRAC-30 was characterized as a surfactin series. Thus, the main mechanism used by Paenibacillus sp. IIRAC-30 to suppress R. solani was elucidated. Furthermore, because lipopeptides active against phytopathogens generally show low toxicity to humans and the environment, the positive findings presented here suggest that the isolate IIRAC-30 could be a possible candidate for biocontrol of R. solani.     

Tactile sensitivity,tactile acuity,and affective touch: from childhood to early adolescence

The development of somatosensation and affective touch acquires a central role throughout our lives, for several reasons. In adults, these functions are driven by different, neuroanatomically and functionally segregated fibres. To date, very little is known about the basic features of these fibres in childhood and this lack of knowledge is mirrored in the affective touch domain, where there are no studies on the main physiological features of the tactile processes linked to the stimulation of the hairy skin, namely the preferential site of affective touch. Thus, our study aims to analyze (1) tactile sensitivity and tactile acuity of children’s hairy forearms; (2) a possible dissociation between somatosensation and the affective touch; and (3) the presence/absence of the perception of affective touch already in childhood. To these aims, participants (160 children, aged 6 to 14?years), were administered with the Von Frey (tactile sensitivity) and the 2 Point Discrimination (tactile acuity) tests. Affective touch was measured following the classic protocol and pleasantness ratings were recorded. Our findings showed a correlation between age and somatosensation, suggesting a progressive reduction of sensitivity and acuity as age grows. Further, there was no overlap between affective touch and somatosensation, suggesting a behavioural segregation. Lastly, we found higher pleasantness ratings for Affective versus Neutral stimulations at all ages and an enhanced preference for Affective as age grows. We concluded that both somatosensation and affective touch are already present as two separate components of touch in childhood and change as a function of age.