Anoxic disturbance of the isolated respiratory network of neonatal rats

Tissue oxygen (PO₂), K⁺ (aK_e), pH (pH_e) and Ca²⁺ ([Ca²⁺]_e) were measured in the region of the ventral respiratory group (VRG) in the in vitro brainstem-spinal cord preparation of neonatal rats. During tissue anoxia, elicited by superfusion of N₂-gassed solutions, an initial increase in the frequency of respiratory activity, lasting between 2 and 12 min, turned into a frequency depression. During anoxia periods of up to 60 min, respiratory activity persisted in solutions containing CO₂/bicarbonate, whereas a complete blockade was observed after 15–25 min in N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid- (Hepes)-buffered salines. After such anoxic apnea, respiratory rhythmicity could be reactivated by superfusion of hypoxic, CO₂/bicarbonate-buffered solutions. In both types of hypoxic solutions, aK_e increased by maximally 1.5mM, whereas an initial increase of pH_e by up to 0.05 pH units turned, after 2–4 min, into an acidification which could exceed 0.5 pH units. In contrast, [Ca²⁺]_e remained unaffected by anoxia. Addition of 2–5 mM cyanide (CN^-) to oxygenated Hepes-buffered saline evoked an increase in PO₂ in the VRG from 100 to more than 300 mmHg. The effects of CN^- on respiratory activity, aK_e and pH_e were almost identical to those during anoxia. In oxygenated, CO₂/bicarbonatefree solutions of different pH, however, an increase in pH_e in the VRG led to a decrease in respiratory frequency, whereas a fall of pH_e produced a frequency acceleration. A rise of aK_e in the VRG by more than 2 mM as induced by superfusion of a 7 mM K⁺ solution led to a sustained increase of respiratory frequency. The results indicate that blockade of aerobic metabolism does not severely perturb K⁺ and Ca²⁺ homeostasis and that the biphasic response to anoxia is not directly related to the observed changes in PO₂, aK_e, pH_e, or [Ca²⁺]_e. In the respiratory network of neonatal mammals, CO₂ might provide a stimulus for long-term maintenance of respiratory activity under oxygen depletion.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Visualisation of the extent of damage in a rat spinal cord injury model using MR microsopy of the water diffusion tensor

Magnetic Resonance Diffusion Tensor Imaging (DTI) of the control and traumatic injured spinal cord of a rat in vitro is reported. Experiments were performed on excised spinal cords from 10 Wistar rats, using a home-built 6.4 T MR microscope. MRI and histopathological results were compared. Presented results show that DTI of the spinal cord, perfused with formalin 10 minutes after the injury, can detect changes in water diffusion in white matter (WM) and in gray matter (GM), in areas extending well beyond the region of direct impact. Histology of neurons of the GM shows changes that can be attributed to ischemia. This is in agreement with the observed decrease of diffusion in the injured regions, which may be attributed to the cytotoxic edema due to ischemia. However, the diffusion changes in highly anisotropic WM seem to be caused by a direct action of mechanical force of impact, which significantly distorts the nerve fibers.     

Microembolic Renal Disease in Rats Induced with Sephadex: Hypertension, Lesions and Serum Urea Nitrogen

Sephadex particles (20-80 μ in size) were injected into the abdominal aorta of 134 male Sprague-Dawley rats near the renal arteries. In 31 rats, the right kidney was then removed. The Sephadex particles lodged in glomerular capillaries, afferent glomerular arterioles and interlobular arteries, creating renal infarcts, some of which were grossly visible. Shortly after injection, arterial blood pressure rose significantly in most animals. The hypertension in uninephrectomized rats was not demonstrably different from that in rats with two Kidneys. Severity and duration of hypertension (up to 8 months) were positively correlated with the number of Sephadex particles in renal vessels, and there was also a positive correlation between the degree of hypertension and serum urea nitrogen levels, and between degree of hypertension and degree of cardiac hypertrophy. The vascular permeability in acutely hypertensive rats was abnormal, as judged from penetration of iron-dextran into vessel walls. This experimental model resembles atheromatous microembolic renovascular disease, which may play a significant role in the pathogenesis of unexplained hypertension in patients with advanced aortic atherosclerosis.     

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.     

Immunoglobulin determinants on the surface of lymphoid cells of carps.

Immunoglobulin determinants were detected by indirect immunofluorescence on the surface of numerous lymphocytes of perpheral blood, spleen, and pronephros of craps. The most interesting finding was the high proportion (65–68 %) of Ig⁺ lymphocytes in the thymus of early adult carps, possibly related to thymus function.     

Treatment with continuous positive airway pressure may affect blood glucose levels in nondiabetic patients with obstructive sleep apnea syndrome

STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) is often associated with impaired glucose metabolism. Data on the effects of OSAS treatment with continuous positive airway pressure (CPAP) on blood glucose and insulin resistance are conflicting. The study aimed at assessing the immediate effect of CPAP on glucose control measured with a continuous glucose monitoring system (CGMS). PARTICIPANTS AND MEASUREMENTS: Nine non-diabetes subjects with OSAS (mean age 53.0 +/- 8.0 years; body mass index 34.8 +/- 5.3 kg/m2) underwent 2 overnight polysomnographic examinations: a diagnostic study and one with CPAP treatment. Continuous glucose monitoring system (CGMS) was applied overnight on both occasions. Glucose metabolism was assessed with a 75-g oral glucose tolerance test, plasma insulin and homeostatic model assessment of insulin resistance (HOMA-IR) index. RESULTS: The mean (+/- SD) apnoea-hypopnea index (AHI) at diagnostic polysomnography was 54.3 +/- 29.3 (range 16-81). Fasting plasma insulin levels in patients with OSAS was 84.3 +/- 43.4 pM at baseline, and the HOMA-IR was 3.6 +/- 2.2. CPAP treatment in the subjects with OSAS resulted in a significant reduction in the AHI to 4.5 +/- 7.1. All of the major saturation parameters improved significantly on CPAP. CGMS showed mean glucose values significantly higher during the CPAP night than during the diagnostic night: 80 +/- 11 mg/dL versus 63 +/- 7 mg/dL (P < .01). Fasting insulin and HOMA-IR measured after the CPAP night tended to be higher than at baseline (98.4 +/- 51.0 pmol vs 84.3 +/- 43.4 pmol and 3.9 pmol +/- 2.6 vs 3.6 +/- 2.2 pmol, respectively, P > .05). CONCLUSION: CPAP treatment in nondiabetic obese patients with OSAS may have an immediate elevating effect on blood glucose.     

Cells involved in the immune response. XXX. An evaluation of the different assays to demonstrate rabbit spleen plaque-forming cells. Enhancement of the assay by anti-target cell antibodies

Four different procedures for the detection of rabbit spleen plaque-forming cells (PFC) directed toward the sheep erythrocyte (SRBC) antigen were evaluated in terms of their sensitivity. These included the conventional localized hemolysis in gel (LHG) assay, the thin-layer LHG assay, the LH assay using a monolayer of the target SRBC erythrocytes and the localized hemolysis in liquid phase (Cunningham) assay. The latter assay consistently proved to be the most sensitive assay. The sensitivity of this latter assay was further improved by incorporating preformed IgG or IgM antibodies directed toward the target erythrocytes, in subhemolytic concentrations, into the assay. This antibody-enhanced plaque assay in liquid medium is 20-50 times more sensitive than the conventional LHG assay.