Anaesthesia and the acute phase protein response in children undergoing circumcision

Concentrations of acute phase proteins (CRP: C-reactive protein, albumin) change during surgery. We investigated the acute phase response to circumcision and the effects of anaesthesia on this response. The children were divided into four groups; group 1 (intratracheal general anaesthesia, n=40), group 2 (general anaesthesia with mask, n=20), group 3 (ketamine, n=20), group 4 (local anaesthesia, n=35). Blood samples were obtained, 24 hours before circumcision, after premedication, and 24 hours after circumcision. CRP and albumin before circumcision were comparable for all groups. There was no increase in CRP, and albumin remained steady throughout the study. No difference was observed among the groups, and related to anaesthesia. No responsiveness may be explained with the size of injured tissue or anatomical and histological type of preputium.     

Synthesis of novel 5-aryl-2-thio-1,3,4-oxadiazoles and the study of their structure-anti-mycobacterial activities

The preparation of novel 5-aryl-2-thio-1,3,4-oxadiazoles 4a-41 and the computer-aided study of their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) are reported. The average accuracy of the electronic-topological method and neural network methods applied to the activity prediction in leave-one-out cross validation is 80%.     

Stable spiro-endoperoxides by sunlight-mediated photooxygenation of 1,2-O-alkylidene-5(E)-eno-5,6,8-trideoxy-alpha-D-xylo-oct-1,4-furano-7-uloses

Sunlight-mediated photooxygenation of 3-O-acetyl and 3-O-methyl derivatives of 1,2-O-alkylidene-5(E)-eno-5,6,8-trideoxy-α-d-xylo-oct-1,4-furano-7-uloses (1a-e) in carbon tetrachloride solution gave stable 4,7-epidioxy derivatives in 4R (2a-e) and 4S (3a-e) configurations. The presence of an endo alkyl, on the 1,2-O-alkylidene group and its size, resulted in an increase of the yield of the 4S isomers. 3-O-Acetyl derivatives yielded products as a mixture of C-7 anomers, whereas 3-O-methyl derivatives gave pure single stereoisomers.     

Tripeptides with ionizable side chains adopt a perturbed polyproline II structure in water

The present paper reports the conformations of the acidic and basic homotripeptides triglutamate, triaspartate, and trilysine in aqueous solution to better understand their relevance for the structure of disordered proteins and protein segments and for a variety of protein binding processes. The determination of the dihedral angles of the central amino acid residue was achieved by analyzing the amide I band profile of the respective polarized visible Raman, Fourier transform infrared (FT-IR), and vibrational circular dichroism (VCD) spectra by means of recently developed algorithms [Schweitzer-Stenner, R. (2002) Biophys. J. 83, 523-532; Eker et al. (2002) J. Am. Chem. Soc. 124, 523-532]. The results were validated by measuring the UV electronic circular dichroism (ECD) spectra of the peptides. The analyses revealed that a polyproline II-like conformation is predominant at room temperature. For triaspartate and triglutamate the dihedral angles of phi = -70 degrees, psi = 165 degrees and phi = -60 degrees, psi = 160 degrees were obtained, respectively. A similar conformation, i.e., phi = -50 degrees, psi = 170 degrees, was obtained for trilysine, which is at variance with the earlier reported left-handed turn structure. The ECD spectrum of charged tripeptides displayed symmetric negative and positive couplets at 190 and 210 nm, which are interpreted as indicating a somewhat, perturbed polyproline II conformation, in agreement with the obtained dihedral angles. Comparison with literature data shows that the investigated tripeptides are ideal model systems for understanding the local conformation of functionally relevant K3, K2X, E3, and D3 segments in a variety of different proteins.     

Abeta(1-28) fragment of the amyloid peptide predominantly adopts a polyproline II conformation in an acidic solution

To structurally characterize the nonaggregated state of the amyloid beta peptide, which assembles into the hallmark fibrils of Alzheimer disease, we investigated the conformation of the N-terminal extracellular peptide fragment Abeta(1-28) in D(2)O at acidic pD by utilizing combined FTIR and isotropic and anisotropic Raman spectra measured between 1550 and 1750 cm(-1). Peptide aggregation is avoided under the conditions chosen. The amide I' band was found to exhibit a significant noncoincidence effect in that the first moment of the anisotropic Raman and of the IR band profile appears red-shifted from that of the isotropic Raman scattering. A simulation based on a coupled oscillator model involving all 27 amide I' modes of the peptide reveals that the peptide adopts a predominantly polyproline II conformation. Our results are inconsistent with the notion that the monomeric form of Abeta(1-28) is a totally disordered, random-coil structure. Generally, they underscore the notion that polyproline II is a characteristic motif of the unfolded state of proteins and peptides.     

Polyol pathway-dependent osmotic and oxidative stresses in aldose reductase-mediated apoptosis in human lens epithelial cells: role of AOP2

Aldose reductase (AR) has been implicated as a major contributor to the pathogenesis of diabetic cataracts. AR activation generates osmotic and oxidative stresses via the polyol pathway and induces cell death signals. Antioxidant protein 2 (AOP2) protects cells from oxidative stress. We investigated the effect of AR overexpression on polyol accumulation and on hyperglycemic oxidative stress and osmotic stress, as well as the effects of these stresses on human lens epithelial cell (hLEC) survival. hLECs overexpressing the AR became apoptotic during hyperglycemia and showed elevated levels of intracellular polyols. Glutathione and AOP2 levels were significantly decreased in these cells. Interestingly, supply of AOP2 and/or the AR inhibitor fidarestat protected the cells against hyperglycemia-induced death. Overexpression of AR increased osmotic and oxidative stresses, resulting in increased apoptosis in hLECs. Because AOP2 protects hyperglycemia-induced hLEC apoptosis, this molecule may have the potential to prevent hyperglycemia-mediated complications in diabetes.     

Impacts of calcium addition and different oil types and levels on in vitro rumen fermentation and digestibility

This in vitro study was designed to investigate the effects of calcium addition to substrates differing in source and level of oil on fermentation, gas production, and digestibility parameters. Substrates were made from basal mixtures containing three levels of calcium salt (0, 1, and 2% CaCl2) to contain three levels (3, 6, and 9%) of two types (sunflower and soy) of oil. After collecting from two Holstein bulls and mixing with buffer, rumen fluid was used to incubate the resulting 18 mixtures in duplicate. Ionizable calcium, pH and NH3-N concentration were measured during incubation. Gas production was measured at 6, 12, 24, and 48 h after incubation. Kinetics parameters of gas production and in vitro dry matter digestibility (IVDMD) were calculated from regression coefficients of an exponential equation and a linear equation, respectively. Data were analysed using 3-way ANOVA with repeated measure option in which the parameter time was a subplot. Oil type did not affect pH and ionizable calcium concentration. There were linear increases and decreases in pH and ionizable calcium concentration in response to increasing oil and calcium levels, respectively. However, with increasing oil levels there were no interactions between calcium addition and oil level on pH and ionizable calcium concentration. None of the treatments affected NH3-N concentration. The amount of gas produced from substrates containing sunflower oil was greater than soy oil (41.7 vs. 40.5 ml). Cumulative gas production and amount of gas production from insoluble but slowly fermentable portion of the supplemental mixtures linearly decreased and linearly increased as oil and calcium levels increased in the substrates, respectively. However, interactions of calcium addition and oil level on gas production and kinetics of gas production were lacking. Oil type did not affect IVDMD. Despite lacking main effects, interaction of calcium addition and oil level indicated that increasing calcium level alleviated depression in IVDMD resulting from increasing oil level. In conclusion, increasing oil level depressed, whereas calcium addition stimulated ruminal fermentation. Improvement in IVDMD may partially support that calcium addition alleviates the adverse effects of oil and that more calcium is needed when diets are supplemented with increasing amounts of oil.     

Effect of weight loss on P wave dispersion in obese subjects

Objective: The aim of this study was to investigate effect of loss weight on P wave dispersion in obese subjects. Research Methods and Procedures: After a 12‐week weight loss program (diet and medical therapy), a total of 30 (24 women and six men) obese subjects who had lost at least 10% of their original weight were included in the present study. All subjects underwent a routine standard 12‐lead surface electrocardiogram. Electrocardiograms were transferred to a personal computer by a scanner and then magnified 400 times by Adobe Photoshop software (Adobe Systems, Mountain View, CA). P wave dispersion, which is also defined as the difference between the maximum P wave duration and the minimum P wave duration, was also calculated. Results: After a 12‐week weight loss program, BMI (p < 0.001), maximum P wave duration (p < 0.001), and P wave dispersion (p < 0.001) significantly decreased. The mean percentage of weight loss was 13% (10% to 20.3%). The decrease in the level of P wave dispersion (21 ± 10 and 7 ± 12 ms, p < 0.002) was more prominent in Group II (≥12% loss of their original weight) than Group I (<12% loss of their original weight) after the weight loss program. A statistically significant correlation between decrease in the level of P wave dispersion and percentage of weight loss was found (r = 0.624, p < 0.001). Discussion: Substantial weight loss in obese subjects is associated with a decrease of P wave duration and dispersion. Therefore, these observations suggest that substantial weight loss is associated with improvement in atrial repolarization abnormalities in obese subjects.     

The intersection of social determinants of health,the microbiome,and health outcomes in immigrants: A scoping review

In the present scoping review, we explore whether existing evidence supports the premise that social determinants of health (SDoH) affect immigrant health outcomes through their effects on the microbiome. We adapt the National Institute on Minority Health and Health Disparities' research framework to propose a conceptual model that considers the intersection of SDoH, the microbiome, and health outcomes in immigrants. We use this conceptual model as a lens through which to explore recent research about SDoH, biological factors associated with changes to immigrants' microbiomes, and long-term health outcomes. In the 17 articles reviewed, dietary acculturation, physical activity, ethnicity, birthplace, age at migration and length of time in the host country, socioeconomic status, and social/linguistic acculturation were important determinants of postmigration microbiome-related transformations. These factors are associated with progressive shifts in microbiome profile with time in host country, increasing the risks for cardiometabolic, mental, immune, and inflammatory disorders and antibiotic resistance. The evidence thus supports the premise that SDoH influence immigrants' health postmigration, at least in part, through their effects on the microbiome. Omission of important postmigration social-ecological variables (e.g., stress, racism, social/family relationships, and environment), limited research among minoritized subgroups of immigrants, complexity and inter- and intra-individual differences in the microbiome, and limited interdisciplinary and biosocial collaboration restrict our understanding of this area of study. To identify potential microbiome-based interventions and promote immigrants' well-being, more research is necessary to understand the intersections of immigrant health with factors from the biological, behavioral/psychosocial, physical/built environment, and sociocultural environment domains at all social-ecological levels.