Central and peripheral contributions to control of heart rate during heat acclimation

The contributions of the autonomic nervous system and the cardiac pacing cells in the development of heat-acclimation-induced bradycardia were analyzed, and the effect of heat acclimation on the chronotropic response of the heart to heat stress (40° C) was studied. Rats were acclimated at 34° C for 0, 5, 14, 30 and 60 days. Heart rate (HR) was measured in conscious animals, using chronic subcutaneous electrodes. Sympathetic and parasympathetic influences were studied by IP administration of 0.1 and 1 mg/100 g body weight atropine and propranolol respectively, while intrinsic HR (HR_i) was measured following administration of both drugs simultaneously. The effects of carbamylcholine and norepinephrine on the beating rate of isolated rat atria were investigated to study pacemaker responsiveness to neutrotransmitters. Up to day 14 of heat acclimation, bradycardia was attained by tonic parasympathetic acceleration (18%) and temporal sympathetic withdrawal (0.8% on day 14), to compensate for the gradually augmented HR_i (2.5% and 8% on days 5 and 14, respectively). Following long-term acclimation HR_i declined below pre-acclimation rate. This was associated with resumed sympathetic activity (16% and 10% on days 30 and 60 respectively) while parasympathetic activity continued to be high (18%). Tachycardia, known to occur with severe uncontrolled body hyperthermia, was attenuated following heat acclimation by 42%. It was concluded that during the initial phase of heat acclimation bradycardia is achieved primarily by changes in autonomic influences, while following long-term acclimation, changes in the intrinsic properties of the pacing cells (HR_i) and the autonomic system both play a role.     

The procoagulant activity of red blood cells from patients with severe preeclampsia

OBJECTIVE: Our purpose was to determine whether red blood cells from patients with severe preeclampsia may exhibit increased membrane exposure of procoagulant phospholipids (i.e., phosphatidylserine), which may initiate intravascular clotting and platelet activation. STUDY DESIGN: The study group comprised 28 women: 9 with severe preeclampsia in the third trimester of pregnancy, 10 normotensive with uncomplicated pregnancies, and 9 age-matched, nonpregnant, healthy women. The exposure of phosphatidylserine on the outer membrane phospholipid layer was analyzed with use of isolated, washed red blood cells that were added as a source of phospholipids to a “prothrombinase” coagulation complex. RESULTS: The resultant thrombin formed was measured by an amidolytic assay. Thrombin generation significantly increased on the addition of red blood cells from women with preeclampsia (741 ± 132 mU/ml/min) compared with red blood cells from normotensive pregnant (422 ± 228 mU/ml/min) and nonpregnant women (316 ± 268 mU/ml/min, p = 0.0008). CONCLUSION: This study indicates that in patients with preeclampsia the red blood cells exhibit a significant procoagulant surface that may trigger thrombin formation, thereby playing a role in the hypercoagulable state.(Am J Obstet Gynecol 1997;177:6)     

Targeted disruption of GAP-43 in P19 embryonal carcinoma cells inhibits neuronal differentiation. As well as acquisition of the morphological phenotype

GAP-43 is expressed in proliferating neuroblasts in vivo and in vitro, but its role during early neurogenesis has not been investigated. Here we show that neuroectodermal differentiation stimulated by retinoic acid (RA) in the embryonal carcinoma (EC) line P19 is accompanied by upregulation of GAP-43 expression in neuroepithelial precursor cells. In contrast, when upregulation of GAP-43 expression was prevented in 3 independent P19 lines because of a targeted insertion into the gene, generation of neuroepithelial precursors was inhibited. Consequently, neuronal number was significantly decreased, neuronal morphology was abnormal and fewer than 20% of all neurons were able to initiate neuritogenesis. Extracellular matrix (ECM) was unable to rescue initiation of neuritogenesis in the mutant cells, however those neurites that were extended responded normally to ECM-stimulated neurite outgrowth-promoting signals. These data suggest that GAP-43 function is required for commitment to a neuronal phenotype as well as initiation of neurite extension. However, stimulation of neurite outgrowth by ECM in P19s occurs independently of GAP-43.     

Treatment with lecinoxoids attenuates focal and segmental glomerulosclerosis development in nephrectomized rats

Focal segmental glomerulosclerosis (FSGS) is a scarring process associated with chronic low‐grade inflammation ascribed to toll‐like receptor (TLR) activation and monocyte migration. We developed synthetic, small‐molecule lecinoxoids, VB‐201 and VB‐703, that differentially inhibit TLR‐2‐ and TLR‐4‐mediated activation and monocyte migration. The efficacy of anti‐inflammatory lecinoxoid treatment on FSGS development was explored using a 5/6 nephrectomy rat model. Five‐sixths of nephrectomized rats were treated with lecinoxoids VB‐201, VB‐703 or PBS, for 7 weeks. Upon sacrifice, albumin/creatinine ratio, glomerulosclerosis, fibrosis‐related gene expression and the number of glomerular and interstitial monocyte were evaluated. Treatment of nephrectomized rats with lecinoxoids ameliorated glomerulosclerosis. The percentage of damaged glomeruli, glomerular sclerosis and glomeruli fibrotic score was significantly reduced following VB‐201 and VB‐703 treatment. VB‐703 attenuated the expression of fibrosis hallmark genes collagen, fibronectin (FN) and transforming growth factor β (TGF‐β) in kidneys and improved albumin/creatinine ratio with higher efficacy than did VB‐201, but only VB‐201 significantly reduced the number of glomerular and interstitial monocytes. These results indicate that treatment with TLR‐2, and more prominently, TLR‐4 antagonizing lecinoxioids, is sufficient to significantly inhibit FSGS. Moreover, inhibiting monocyte migration can also contribute to treatment of FSGS. Our data demonstrate that targeting TLR‐2‐TLR‐4 and/or monocyte migration directly affects the priming phase of fibrosis and may consequently perturb disease parthogenesis.     

Correction to: Detection of acute rib fractures on CT images with convolutional neural networks: effect of location and type of fracture and reader’s experience

Emergency Radiology -     

Effects of nerve compression on fast axonal transport in streptozotocin-induced diabetes mellitus

Summary The hypothesis that nerves in diabetes mellitus exhibit an increased susceptibility to compression was experimentally tested. Inhibition of fast axonal transport was induced by local compression in sciatic nerves of rats with streptozotocin-induced diabetes mellitus. Fast anterograde axonal transport was measured after application of³H-leucine to the motor neurone cell bodies in the spinal cord. The sciatic nerve as subjected to local, graded compression in vivo by a small compression chamber. The amount of accumulation of proteins was quantified by calculation of a transport block ratio. Compression at 30 mm Hg for 3 h induced a significantly greater (p<0.05) accumulation of axonally transported proteins at the site of compression in nerves of diabetic animals (transport block ratio: 1.01±0.35; n=7) than in nerves of controls (0.67±0.16;n=7). Accumulation was significantly higher in ligature experiments of both control (1.34±0.44;n=8;p< 0.01) and diabetic animals (1.45±0.30;n=8 ;p< 0.05), indicating that the block of transport in compressed nerves was incomplete. Neither sham compressed diabetic (0.50±0.09;n=6) nor control (0.49±0.11;n=6) nerves showed any block of axonal transport. The possible causes of the increased inhibition of fast axonal transport in diabetic rats are discussed. The results indicate that diabetes may lead to an increased susceptibility of peripheral nerves to compression.