STUDIES ON THE Cx-REACTIVE PROTEIN : III. THE EFFECT OF IRRADIATION OF RABBITS ON THE ACUTE PHASE PROTEIN SYSTEM

Young adult rabbits (2 to 3 kg.) were subjected to a single total body exposure of x-radiation ranging from 50 to 1200 r and tested frequently for the presence of Cx-reactive protein in their blood. It usually appeared in two phases separated by an interval of several days. The primary phase occurred 24 to 48 hours after irradiation in almost all (92 of 97) rabbits exposed to 500 r or more and in 4 of 16 exposed to 300 r or less. The secondary phase occurred during the 2nd week in many of the rabbits irradiated with 900 r or more and in a few irradiated with 700 r. Autopsy cultures failed to demonstrate the presence of infection in rabbits which died or were sacrificed during the primary phase. Bacterial infection was demonstrated, however, in almost all (21 of 24) rabbits autopsied and cultured during the secondary phase. After the disappearance of the primary phase in rabbits exposed to 700 or 900 r, the secondary phase could be elicited by initiating bacterial infection. Within 6 to 24 hours after intravenous inoculation of E. coli, Cx-reactive protein reappeared in the blood and persisted until death or termination of the experiment. Reappearance of the protein also followed the intravenous injection of killed E. coli but it disappeared again 1 to 2 days later. The results indicate that the primary phase is elicited by radiation injury per se and the secondary phase by bacterial infection.     

Changes in myocardial electrical impedance in human heart graft rejection

BACKGROUND: Monitoring of post-transplant heart rejection is currently based on endomyocardial biopsy analysis. This study aimed to assess the effects of heart graft rejection on myocardial electrical impedance. METHODS AND RESULTS: Twenty-nine cardiac transplant patients and 9 controls underwent measurement of myocardial electrical impedance using a specifically designed amplifying system. The module and phase angle of myocardial impedance were measured. Histopathological rejection grading was performed according to ISHLT classification. Fifty impedance tests were performed in transplanted patients. Myocardial impedance (Z) was higher in controls than in transplanted patients (p<0.001) and followed a progressive decline at increasing current frequencies (p<0.001). Likewise, the phase angle of impedance in controls ranged from positive values at low frequencies to negative values at higher frequencies (from 2.5+/-0.9 degrees at 10 kHz to -3.8+/-2.1 degrees at 300 kHz, p<0.001). Rejection was associated with a significant decrease in myocardial impedance (Z) (15+/-6.6 Omega in grade 0, 13+/-6.0 Omega in grade 1A, and 3.3+/-0.9 Omega in grade 3A at 10 kHz, p<0.003). CONCLUSIONS: Mild degrees of cardiac graft rejection are associated with significant changes in myocardial electrical impedance in transplant patients. Further clinical investigation is warranted to assess the potential of cardiac impedance to detect heart graft rejection.     

Peripheral chemoreflex regulation of sympathetic vasomotor tone in apnea divers

Objectives

Involuntary apnea episodes in obstructive sleep apnea patients result in selective potentiation of peripheral chemoreceptor regulation of sympathetic vasomotor tone. Breath-hold diving is associated with repeated “voluntary” apnea episodes and massive arterial oxygen desaturation, which could also perturb chemoreflex function.

Methods

We measured ventilation, heart rate, blood pressure, cardiac stroke volume, and muscle sympathetic nerve activity (MSNA) during isocapnic hypoxia in 11 breath-hold divers and eleven matched control subjects. The study was carried out at least 1 month after intense apnea training.

Results

Baseline MSNA frequency was 30 ± 4 bursts/min in control subjects and 31 ± 7 bursts/min in divers (ns). During hypoxia MSNA frequency and total activity increased similarly in both groups (30 and 66% in controls and 27 and 60% in divers, respectively). MSNA remained increased after termination of hypoxia and approached baseline measurements after 20 min. Hypoxia-induced stimulation of minute ventilation was similar in both groups, although in divers it was maintained by higher tidal volumes and lower breathing frequency compared with control subjects. In both groups, hypoxia-induced tachycardia drove an increase in cardiac output whereas total peripheral resistance decreased. Blood pressure remained unchanged.

Interpretation

We conclude that after the end of intensive training/competition periods, apnea divers show normal peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone. Although voluntary apnea may not lead to sustained changes in sympathetic nervous system regulation, we cannot exclude the possibility that repeated sympathetic activation elicited by voluntary apnea imposes a burden on the cardiovascular system.     

Basement membrane protein nidogen‐1 shapes hippocampal synaptic plasticity and excitability

The basement membrane (BM) is a specialized form of extracellular matrix (ECM) underlying epithelia and endothelia and surrounding many types of mesenchymal cells. Nidogen, along with collagen IV and laminin, is a major component of BMs. Although certain ECM proteins such as laminin or reelin influence neuronal function via interactions with cell‐surface receptors such as integrins, behavioral neurological impairments due to deficits of BM components have been recognized only recently. Here, alterations in neuronal network function underlying these behavioral changes are revealed. Using nidogen‐1 knockout mice, with or without additional heterozygous nidogen‐2 knockout (NID1^−/−/NID2^+/+ or NID1^−/−/NID2^±), we demonstrate that nidogen is essential for normal neuronal network excitability and plasticity. In nidogen‐1 knockouts, seizurelike behavior occurs, and epileptiform spiking was seen in hippocampal in vivo EEG recordings. In vitro, hippocampal field potential recordings revealed that lack of nidogen‐1, while not causing conspicuous morphological changes, led to the appearance of spontaneous and evoked epileptiform activity, significant increase of the input/output ratio of synaptically evoked responses in CA1 and dentate gyrus, as well as of paired pulse accentuation, and loss of perforant‐path long‐term synaptic potentiation. Nidogen‐1 is thus essential for normal network excitability and plasticity. © 2009 Wiley‐Liss, Inc.     

Serum 25‐hydroxyvitamin D levels modulate the acute‐phase response associated with the first nitrogen‐containing bisphosphonate infusion

The acute‐phase response (APR) is the most frequent side effect after the first dose of intravenous nitrogen‐containing bisphosphonates (N‐BPs). It has been demonstrated in vitro that N‐BPs stimulate γδ T‐cell proliferation and production of cytokines and that vitamin D is able to modulate them. Therefore, we have studied the relationship between bone metabolism parameters, particularly for 25‐hydroxyvitamin D [25(OH)D], and APR in patients treated with 5 mg zoledronic acid intravenously. Ninety N‐BP‐naive osteoporotic women (63.7 ± 10.6 years of age) were stratified for the occurrence of APR (APR⁺) or not (APR^–) and quantified by body temperature and C‐reactive protein (CRP). The APR⁺ women had significantly lower 25(OH)D levels than the APR^– women. Levels of 25(OH)D were normal (>30 ng/mL) in 31% of APR⁺ women and in 76% of APR^– women. The odds ratio (OR) to have APR in 25(OH)D‐depleted women was 5.8 [95% confidence interval (CI) 5.30–6.29; p < .0002] unadjusted and 2.38 (95% CI 1.85–2.81; p < .028) after multiple adjustments (for age, body mass index, CRP, calcium, parathyroid hormone, and C‐telopeptide of type I collagen). Levels of 25(OH)D were negatively correlated with postdose body temperature (r = ?0.64, p < .0001) and CRP (r = ?0.79, p < .001). An exponential increase in fever and CRP has been found with 25(OH)D levels lower than 30 ng/mL and body temperature less than 37 °C, whereas normal CRP was associated with 25(OH)D levels above 40 ng/mL. The association between post‐N‐BPs APR and 25(OH)D suggests an interesting interplay among N‐BPs, 25(OH)D, and the immune system, but a causal role of 25(OH)D in APR has to be proven by a randomized, controlled trial. However, if confirmed, it should have some practical implications in preventing APR. © 2010 American Society for Bone and Mineral Research.     

The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures

Background  

During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery.