Effects of repeated bouts of squatting exercise on sub-maximal endurance running performance

It is well established that exercise-induced muscle damage (EIMD) has a detrimental effect on endurance exercise performed in the days that follow. However, it is unknown whether such effects remain after a repeated bout of EIMD. Therefore, the purpose of this study was to examine the effects of repeated bouts of muscle-damaging exercise on sub-maximal running exercise. Nine male participants completed baseline measurements associated with a sub-maximal running bout at lactate turn point. These measurements were repeated 24–48 h after EIMD, comprising 100 squats (10 sets of 10 at 80 % body mass). Two weeks later, when symptoms from the first bout of EIMD had dissipated, all procedures performed at baseline were repeated. Results revealed significant increases in muscle soreness and creatine kinase activity and decreases in peak knee extensor torque and vertical jump performance at 24–48 h after the initial bout of EIMD. However, after the repeated bout, symptoms of EIMD were reduced from baseline at 24–48 h. Significant increases in oxygen uptake $ (\dot{V}{\text{O}}_{2} ) $ , minute ventilation $ (\dot{V}_{\text{E}} ) $ , blood lactate ([BLa]), rating of perceived exertion (RPE), stride frequency and decreases in stride length were observed during sub-maximal running at 24–48 h following the initial bout of EIMD. However, following the repeated bout of EIMD, $ \dot{V}{\text{O}}_{2} ,\;\dot{V}_{\text{E}} , $ [BLa], RPE and stride pattern responses during sub-maximal running remained unchanged from baseline at all time points. These findings confirm that a single resistance session protects skeletal muscle against the detrimental effects of EIMD on sub-maximal running endurance exercise.     

A role for IL-27p28 as an antagonist of gp130-mediated signaling

The heterodimeric cytokine interleukin 27 (IL-27) signals through the IL-27Rα subunit of its receptor, combined with gp130, a common receptor chain used by several cytokines, including IL-6. Notably, the IL-27 subunits p28 (IL-27p28) and EBI3 are not always expressed together, which suggests that they may have unique functions. Here we show that IL-27p28, independently of EBI3, antagonized cytokine signaling through gp130 and IL-6-mediated production of IL-17 and IL-10. Similarly, the ability to generate antibody responses was dependent on the activity of gp130-signaling cytokines. Mice transgenic for expression of IL-27p28 showed a substantial defect in the formation of germinal centers and antibody production. Thus, IL-27p28, as a natural antagonist of gp130-mediated signaling, may be useful as a therapeutic for managing inflammation mediated by cytokines that signal through gp130.     

Gabapentin is not a GABAB receptor agonist.

Recent experiments have demonstrated that formation of functional type B gamma-aminobutyric acid (GABA_B) receptors requires co-expression of two receptor subunits, GABA_B1 and GABA_B2. Despite the identification of these subunits and a number of associated splice variants, there has been little convincing evidence of pharmacological diversity between GABA_B receptors comprising different subunit combinations. However, Ng et al. [Mol. Pharmacol., 59 (2000) 144] have recently suggested a novel and important pharmacological difference between GABA_B receptor heterodimers expressing the GABA_B1a and GABA_B1b receptor subunits. This study suggested that the antiepileptic GABA analogue gabapentin (Neurontin) is an agonist at GABA_B receptors expressing the GABA_B1a but not the GABA_B1b receptor subunit. The importance of this finding with respect to identifying novel GABA_B receptor subunit specific agonists prompted us to repeat these experiments in our own [³⁵S]−GTPγS binding and second messenger assay systems. Here we report that gabapentin was completely inactive at recombinant GABA_B heterodimers expressing either GABA_B1a or GABA_B1b receptor subunits in combination with GABA_B2 receptor subunits. In addition, in both CA1 and CA3 pyramidal neurones from rodent hippocampal slices we were unable to demonstrate any agonist-like effects of gabapentin at either pre- or post-synaptic GABA_B receptors. In contrast, gabapentin activated a GABA_A receptor mediated chloride conductance. Our data suggest that gabapentin is not a GABA_B-receptor agonist let alone a GABA_B receptor subunit selective agonist.     

Epidemiology of Early Monkeypox Virus Transmission in Sexual Networks of Gay and Bisexual Men,England, 2022

After community transmission of monkeypox virus was identified in Europe, interviews of 45 case-patients from England indicated transmission in international sexual networks of gay and bisexual men since April 2022. Interventions targeting sex-on-premises venues, geospatial dating applications, and sexual health services are likely to be critical for outbreak control.     

Deficits of neuronal density in CA1 and synaptic density in the dentate gyrus, CA3 and CA1, in a mouse model of Down syndrome

Ts65Dn mice are partially trisomic for the distal region of MMU16, which is homologous with the obligate segment of HSA21 triplicated in Down syndrome (DS). Ts65Dn mice are impaired in learning tasks that require an intact hippocampus. In order to investigate the neural basis of these deficits in this mouse model of Down syndrome, quantitative light and electron microscopy were used to compare the volume densities of neurons and synapses in the hippocampus of adult Ts65Dn (n=4) and diploid mice (n=4). Neuron density was significantly lower in the CA1 of Ts65Dn compared to diploid mice (p<0.01). Total synapse density was significantly lower in the dentate gyrus (DG; p<0.001), CA3 (p<0.05) and CA1 (p<0.001) of Ts65Dn compared to diploid mice. The synapse-to-neuron ratio was significantly lower in the DG (p<0.001), CA3 (p<0.01) and CA1 (p<0.001) of Ts65Dn compared to diploid mice. When the data were broken down by synapse type, asymmetric synapse density was found to be significantly lower in the DG (p<0.001), CA3 (p<0.05) and CA1 (p<0.001) of Ts65Dn compared to diploid mice, while such a difference in symmetric synapse density was only present in the DG (p<0.01). The asymmetric synapse-to-neuron ratio was significantly lower in the DG (p<0.001), CA3 (p<0.01) and CA1 (p<0.001) of Ts65Dn compared to diploid mice, but there were no such significant differences in symmetric synapse-to-neuron ratios. These results suggest that impaired synaptic connectivity in the hippocampus of Ts65Dn mice underlies, at least in part, their cognitive impairment.     

The effects of spinal anesthesia vs epidural anesthesia on 3 potential postoperative complications: pain,urinary retention,and mobility following inguinal herniorrhaphy

This study was conducted to determine the effects of spinal (n = 113) vs epidural (n = 31) anesthetic techniques on 3 common postoperative complications: pain, urinary retention, and mobility for patients undergoing inguinal herniorrhaphy. The study design was a retrospective chart review. Data were collected on 144 subjects who underwent herniorrhaphy between January 1 and December 31, 1999, had an ASA classification of I to III, and were older than 18 years. The local anesthetics used to provide spinal anesthesia were 5% lidocaine, 0.75% bupivacaine, and 1% tetracaine solutions. The anesthetics used to provide epidural anesthesia were a solution of 2% lidocaine with epinephrine or 3% chloroprocaine with epinephrine. Results revealed that pain was not significantly different between the 2 anesthetic groups (P = .65); however, subjects in the epidural anesthesia group were able to ambulate (P = .008) and void (P = .02) sooner than subjects in the spinal anesthesia group. This study demonstrates that epidural anesthesia results in less urinary retention and earlier mobility than spinal anesthesia in men undergoing inguinal herniorrhaphy. Minimizing postoperative complications is essential in order for the nurse anesthetist to provide a satisfactory anesthetic experience. This study's findings suggest that epidural anesthesia optimizes recovery for the patient undergoing inguinal herniorrhaphy.     

Reduced tumor necrosis factor signaling in primary human fibroblasts containing a tumor necrosis factor receptor superfamily 1A mutant

OBJECTIVE: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autoinflammatory syndrome associated with mutations in the gene that encodes tumor necrosis factor receptor superfamily 1A (TNFRSF1A). The purpose of this study was to describe a novel TNFRSF1A mutation (C43S) in a patient with TRAPS and to examine the effects of this TNFRSF1A mutation on tumor necrosis factor alpha (TNFalpha)-induced signaling in a patient-derived primary dermal fibroblast line. METHODS: TNFRSF1A shedding from neutrophils was measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Primary dermal fibroblast lines were established from the patient with the C43S TRAPS mutation and from healthy volunteers. Activation of NF-kappaB and activator protein 1 (AP-1) was evaluated by electrophoretic mobility shift assays. Cytokine production was measured by ELISA. Cell viability was measured by alamar blue assay. Apoptosis was measured by caspase 3 assay in the fibroblasts and by annexin V assay in peripheral blood mononuclear cells. RESULTS: Activation-induced shedding of the TNFRSF1A from neutrophils was not altered by the C43S TRAPS mutation. TNFalpha-induced activation of NF-kappaB and AP-1 was decreased in the primary dermal fibroblasts with the C43S TNFRSF1A mutation. Nevertheless, the C43S TRAPS fibroblasts were capable of producing interleukin-6 (IL-6) and IL-8 in response to TNFalpha. However, TNFalpha-induced cell death and apoptosis were significantly decreased in the samples from the patient with the C43S TRAPS mutation. CONCLUSION: The C43S TNFRSF1A mutation results in decreased TNFalpha-induced nuclear signaling and apoptosis. Our data suggest a new hypothesis, in that the C43S TRAPS mutation may cause the inflammatory phenotype by increasing resistance to TNFalpha-induced apoptosis.     

Isolation, purification, and heterogeneity of human lymphatic endothelial cells from different tissues

Relatively few attempts have been made in the past to isolate and expand lymphatic endothelial cells (LECs). Recently this task has become feasible thanks to the identification of new lymphatic markers such as Podoplanin, Lyve-1, Prox-1 and D2-40. Using a two-step purification method based on the sorting of endothelial cells with Ulex Europaeus Agglutinin 1-coated beads followed by purification with monoclonal antibody D2-40, we were able to purify and in vitro expand human derived LECs from tissues such as lymph node, spleen, thymus, palatine tonsil and iliac lymphatic vessels. The isolated LECs were expanded on collagen type 1 and fibronectin coated flasks for up to 8-10 passages and then analyzed for phenotypic and functional properties. LECs were able to form a capillary like network, when seeded on Cultrex BME, indicating their capability to form lymphatic vessels in vitro. Comparative studies were performed, and we found that specific lymphatic and vascular markers were differentially expressed by LECs prepared from different sources, clearly demonstrating the phenotypic heterogeneity of LECs from different organs and different segments of the lymphatic vasculature. We here propose a new technique to make available ready sources of abundant well-characterized human LECs to examine normal profiles and behavior to compare with abnormal conditions.