Back extensor muscle oxygenation and fatigability in healthy subjects and low back pain patients during dynamic back extension exertion

The purpose of this study was to assess if chronic low back pain patients have impaired paraspinal muscle O₂ turnover and endurance capacity as compared to healthy control subjects during dynamic exercise. Middle-aged healthy male subjects (n = 12, control) and male patients with chronic low back pain (n = 17, CLBP) participated in the study. L4–L5 level paraspinal muscle fatigue was objectively assessed during earlier validated 90 s dynamic back endurance test (spectral EMG, MPF_slope). Also EMG amplitude (EMG_amplitude) and initial MPF (MPF_initial) were assessed from the initial 5 s of the endurance contraction. Simultaneously near infrared spectroscopy (NIRS) was used for quantitative measurement of local L4–L5 paraspinal muscle O₂ consumption. Subcutaneous tissue thickness (ATT) was measured from the EMG and NIRS recording sites. The results indicated that control and CLBP groups were compatible as regarding anthropometric variables, paraspinal muscle activation levels (EMG_amplitude), initial MPF (MPF_initial) and ATT. When the ATT was used as a covariate in the ANOVA analysis, CLBP group did not show significantly greater paraspinal muscle fatigability (right MPF_slope – 12.2 ± 10.7%/min, left right MPF_slope – 12.6 ± 13.3%/min) or O₂ consumption (right NIRS_slope – 52.8 ± 79.6 μM/l/s) as compared to healthy controls (right MPF_slope – 11.9 ± 7.6%/min, left MPF_slope – 12.7 ± 8.6%/min, right NIRS_slope – 53.7 ± 95.2 μM/l/s). As a conclusion, these CLBP male patients did not show any impaired rate of paraspinal muscle oxygen consumption or excessive paraspinal muscle fatigability during dynamic exercise as compared with healthy controls. Subcutaneous tissue thickness has a strong influence on the NIRS and EMG amplitude measurements and, if unchecked, it could result in the false interpretation of the results.     

Alternating copolymerization of butadiene and propene with the catalyst VO(ONeo)2 Cl/Al(i-C4H9)3, 1

The influence of basic reaction parameters—the ratio of catalyst components, the composition of the monomer mixture and the temperature—on the progress of the copolymerization, the molecular weight and the molecular weight distribution as well as on the composition of the copolymers obtained is reported. Conversion data for the variation of the mole ratio of comonomers show a maximum for an [Al]/[V] mole ratio of approximately 7, whereas the molecular weight of copolymers is not significantly influenced. An increase in the molecular weight of the copolymers can be obtained by an increase of butadiene content in the monomer mixture. However, there is also an increasing incorporation of butadiene into the copolymer. Raising the temperature from ?60°C to 0°C results in a significant decrease in molecular weight, whereas the composition of the copolymers is not significantly changed.     

Bone marrow-derived mesenchymal stem cells in repair of the injured lung

We sought to determine whether an intact bone marrow is essential to lung repair following bleomycin-induced lung injury in mice, and the mechanisms of any protective effects conferred by bone marrow-derived mesenchymal stem cell (BMDMSC) transfer. We found that myelosupression increased susceptibility to bleomycin injury and that BMDMSC transfer was protective. Protection was associated with the differentiation of engrafted BMDMSC into specific and distinct lung cell phenotypes, with an increase in circulating levels of G-CSF and GM-CSF (known for their ability to promote the mobilization of endogenous stem cells) and with a decrease in inflammatory cytokines. In vitro, cells from injured, but not from normal, mouse lung produced soluble factors that caused BMDMSC to proliferate and migrate toward the injured lung. We conclude that bone marrow stem cells are important in the repair of bleomycin-injured lung and that transfer of mesenchymal stem cells protects against the injury. BMDMSC localize to the injured lung and assume lung cell phenotypes, but protection from injury and fibrosis also involves suppression of inflammation and triggering production of reparative growth factors.     

Escape efficiency of diploid and polyploid frogs: A comparison ofOdontophrynus cultripes (2n=22) andO. americanus (4n=44)

The escape efficiency of two closely related species of frogs,Odontophrynus cultripes(2n=22) and the tetraploidO. americanus (4n=44), were compared in a shuttle box and under simulated naturalistic conditions.O. americanus was generally superior toO. cultripes, and females tended to outperform males within both species. The relative inefficiency ofO. cultripes escape behavior was examined in light of the animals' having an elaborate, passive defense mechanism in the form of well-marked venom glands. Escape efficiency was highly variable in both species. Possessing twice the amount of DNA, the tetraploid behavioral variation was paradoxically less than that of the diploid, but compatible with what has been found for morphological characters in other organisms.This research was carried out at the Instituto Butantan with the support of ongoing grants from the Brazilian CNPq, FAPESP, FEDIB, and PNUD while the first author was a visiting professor in the Departamento de Genética Humana, Instituto de Biociências, Universidade de São Paulo, under the auspices of the Programa Multinacional de Genética, Organization of American States.     

Selective sequestration of X4 isolates by human genital epithelial cells: Implication for virus tropism selection process during sexual transmission of HIV

X4 and R5 HIV strains are present in the semen of men infected with HIV but R5 isolates are transmitted preferentially. The role of human epithelial cells in this selection is addressed. Three human cervical cell lines-CaSki, SiHa, and HEC1A-and normal human vaginal cells from HIV-negative donors were characterized for HIV receptor expression and incubated with X4 and R5 laboratory-adapted strains or primary isolates. The infection was assessed by detection of intracellular HIV DNA. The three cell lines were shown to express on their surface the CXCR4 and GalCer molecules, but not the CD4 and CCR5 ones. The three cell lines and normal human vaginal cells were found to be selectively permissive to X4 HIV entry; the preincubation of the cell lines with rhSDF-1 inhibited this infection. The detection of the intracellular proviral DNA in the cell lines and in normal human vaginal cells demonstrated a selective integration of X4 strains. Additional experiments showed that no extracellular RNA was detected in the supernatants of HEC1A cells infected by X4 isolates either after 18 days of culture or after incubation with PHA-stimulated PBMCs and that no transmission occurred after co-culture between infected HEC1A cells and PHA-stimulated PBMCs. These results suggest specific sequestration of X4 strains by genital epithelial cells, which could explain, at least in part, the HIV tropism selection process during sexual intercourse.     

GLP-1 signalling and effects on glucose metabolism in myocytes from type 2 diabetic patients

Changes in the activity of glycogen synthase a and related kinases (phosphatidylinositol-3-kinase, protein kinase B, p44/42 MAP kinases and p70s6 kinase) evoked by GLP-1 in human myocytes from normal subjects were recently implied in the effect of this hormone upon D-glucose transport and glycogen synthesis in the same cells. The major aims of the present study were i) to investigate the possible extension of this knowledge to myocytes obtained from type 2 diabetic patients, ii) to compare in these patients the response to GLP-1, insulin or the structurally related GLP-1 peptides, exendin (1-39)amide and exendin(9-39)amide, and iii) to explore possible differences in the responsiveness to these agents between normal and diabetic subjects. Apart from the much higher basal PI3K activity and impaired response to insulin of p44/42 MAP kinases in the diabetic patients, the changes in enzyme activity caused by either hormone or peptide, although not identical, were essentially comparable. Nevertheless, significant differences in glucose transport and metabolism parameters were observed in the diabetic patients vs. normal subjects: in the diabetic patients, basal 2-deoxy-glucose uptake and glycogen synthase a activity were lower, accompanied by a similar increasing effect of GLP-1 or insulin; yet, the basal value for glycogen synthesis was higher, coinciding with a lesser relative increment in response to GLP-1 or insulin.     

Regulatory volume decrease in a renal distal tubular cell line (A6) II. Effect of Na+ transport rate

A6 epithelia, a cell line originating from the distal tubular part of the kidney ofXenopus laevis, were cultured on permeable supports and mounted in an Ussing-type chamber. Cell thickness (T _c), short-circuit current (I _sc) and transepithelial conductance (G _t) were recorded while tissues were bilaterally incubated in NaCl solutions and the transepithelial potential was clamped to zero. Effects of inhibition and stimulation of transepithelial Na⁺ transport on cell volume and on its regulation during a hyposmotic challenge were investigated. Under control conditions a slow spontaneous decrease ofT _c described by a linear baseline was recorded. The reduction of the apical osmolality from 260 to 140 mosmol/kg did not alter cell volume significantly, demonstrating a negligible water permeability of the apical barrier. The inhibition of Na⁺ uptake by replacing apical Na⁺ byN-methyl-d-glucamine (NMDG⁺) did not affect cell volume under isotonic conditions. An increase ofT _c by 12.1% above the control baseline was recorded after blocking active transport with ouabain for 60 min. The activation of Na⁺ transport with insulin or oxytocin, which is known to activate the apical water permeability in other epithelia, did not alter cell volume significantly. The insensitivity of cell volume to alterations in apical Na⁺ uptake or Na⁺ pump rate confirms the close coupling between apical and basolateral transport processes. The blockage of basolateral K⁺ channels by 5 mM Ba²⁺ elicited a significant increase inT _c of 16.3% above control. Quinine, a potent blocker of volume-activated K⁺ channels, did not changeT _c significantly. Basolateral hypotonicity elicited a rapid rise inT _c followed by a regulatory volume decrease (RVD). An RVD was also recorded after blocking apical Na⁺ uptake as well as after stimulating apical Na⁺ uptake with oxytocin or insulin. Inhibition of active transport with ouabain as well as blocking K⁺ efflux at the basolateral side with Ba²⁺ or quinine abolished the RVD. The inhibition of the RVD by ouabain seems to be caused by a depletion of cellular K⁺, whereas the effects of Ba²⁺ and quinine are most likely due to the blockage of the basolateral K⁺ pathway.     

Shashi XLMR syndrome: report of a second family

This report describes a family with mental retardation in two brothers. The pedigree is consistent with either X-linked mental retardation or autosomal recessive inheritance. The clinical features consist of coarse face, prominent lower lip, large testes, and obesity. This same constellation of findings was observed in a family with X-linked mental retardation (XLMR) reported by Shashi et al. [2000: Am J Hum Genet 66:469-479]. Furthermore, haplotype analysis was consistent with localization of the Shashi XLMR syndrome in Xq26-q27. Thus, the family likely represents a second occurrence of the Shashi XLMR syndrome.     

Lectin histochemistry of the lymphoid organs of the chicken

Cellular interactions within the immune system are in part mediated via the carbohydrate-rich coat of the cell membrane, the glycocalyx, of which the terminal carbohydrate residues are of particular functional importance. Thus, these carbohydrate residues from thymus, bursa of Fabricius, spleen and bone marrow of 2- and 30-day-old chickens were investigated by lectin histochemistry. In the thymus, mannose as well as N-acetyl-glucosamine (glcNAc)-specific lectins labelled macrophages, epithelial reticulum cells and lymphocytes within the cortex. In the bursa of Fabricius, the brush border of the lining epithelium, the macrophages and the endothelium were labelled by mannose-specific lectins. The follicle-associated epithelium was labelled by a broad spectrum of lectins. Epithelial cells that separated the cortex from the medulla and large mononuclear cells in the cortex were only being labelled by N-acetyl-galactosamine (galNAc)-specific and glcNAc-specific lectins, respectively. In the spleen, lymphocytes of the peri-ellipsoid lymphocyte sheaths and macrophages of the red pulp were labelled by lectins of nearly all sugar specificities. In general, glycotopes of these organs were more intensively labelled in the 2-day-old chicken than in the 30-day-old chicken, indicating changes in glycotope expression during post-hatching development. Thus, cells of the avian immune system are as rich and diverse in their lectin binding sites as their mammalian counterparts, indicating that similar carbohydrate lectin interactions between cells and matrices take place in birds as well.     

Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV

BACKGROUND: Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia. METHODS: A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48. RESULTS: At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; -1.2%, 11.7%). Median CD4 cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm with atazanavir, 160 cells/mm with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels. CONCLUSIONS: For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.