The time-course of ribavirin-provoked changes of basal and AMPH-induced motor activities in rats

The time-course of changes of basal and amphetamine (AMPH)-induced locomotor and stereotypic activities in adult male Wistar rats after a single ribavirin injection was studied. In the first set of experiments, 10, 20 or 30 mg ribavirin/kg body weight (b.w.) were injected i.p. to rats and their basal motor activities were recorded every 10 min for 2 h and compared with those of saline-treated controls. In the second set of experiments, the animals were pretreated with ribavirin and 20 min later i.p. injected with AMPH (1.5 mg/kg b.w.). The controls received AMPH 20 min after the saline injection. Motor activity was recorded after the first injection and until 120 min after AMPH administration. Ribavirin did not significantly affect the time-course of either basal locomotor or stereotypic activities. Pretreatment with any of the applied ribavirin doses decreased the AMPH-induced hyperlocomotor response. However, the most pronounced effect was observed with ribavirin doses of 20 mg/kg and 30 mg/kg when administered during the first 10 min and 30 min after the AMPH injection respectively. In contrast, the stereotypic activities of these animals were only slightly changed. These results indicate a different susceptibility of regions in the basal ganglia to ribavirin.     

The effect of ventilation on spectral analysis of heart rate and blood pressure variability during exercise

Heart rate variability (HRV) and systolic blood pressure variability (BPV) during incremental exercise at 50, 75, and 100% of previously determined ventilatory threshold (VT) were compared to that of resting controlled breathing (CB) in 12 healthy subjects. CB was matched with exercise-associated respiratory rate, tidal volume, and end-tidal CO(2) for all stages of exercise. Power in the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, >0.15-0.4 Hz) for HRV and BPV were calculated, using time-frequency domain analysis, from beat-to-beat ECG and non-invasive radial artery blood pressure, respectively. During CB absolute and normalized power in the LF and HF of HRV and BPV were not significantly changed from baseline to maximal breathing. Conversely, during exercise HRV, LF and HF power significantly decreased from baseline to 100% VT while BPV, LF and HF power significantly increased for the same period. These findings suggest that the increases in ventilation associated with incremental exercise do not significantly affect spectral analysis of cardiovascular autonomic modulation in healthy subjects.     

Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas

Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.     

Food hypersensitivity in children

Food hypersensitivity affects children and adults with an increasing prevalence, and is therefore an important public health problem in the majority of developed countries. Moreover, self-reported reactions to food are of several times higher prevalence, compared to hypersensitivity diagnosed following well established evidence-based diagnostic guidelines. In children, allergic food reactions are more common compared to non-allergic food hypersensitivity reactions, and 90% of them are caused with only 8 food allergens: cow's milk, soya, egg, fish, shellfish, peanut, tree-nuts and gluten. Diagnosis should be based on challenge tests with the potentially offending food allergens. Concerning other, more conservative diagnostic procedures, negative serology and negative skin-prick tests can exclude IgE-mediated food allergy, but positive tests, due to high rate of false positive reactions are not sufficient for diagnosis. Strict dietary avoidance of incriminated allergens is the only well established management strategy. However, this should be applied only if food allergy is well documented - following the exposition tests. Introducing elimination diet in a paediatric population, particularly with the elimination of multiple foods, could cause inappropriate growth and disturb organ maturation. Concerning allergy prevention, avoidance of allergens is not efficacious either during pregnancy and lactation or weaning period, and is therefore, not recommended neither as a population preventive measure, nor in children at risk.     

Depression of Ca2+/calmodulin‐dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation

The enzyme calcium/calmodulin‐dependent protein kinase II (CaMKII) is associated with memory and its α isoform is critical for development of activity‐induced synaptic changes. Therefore, we hypothesized that CaMKII is involved in altered function of dorsal root ganglion (DRG) neurons after neuronal injury. To test this hypothesis, Sprague–Dawley rats were made hyperalgesic by L5 and L6 spinal nerve ligation (SNL), and changes in total phosphorylated and unphosphorylated CaMKII (tCaMKII) and phosphorylated form of its α isoform (pCaMKIIα) were analyzed using immunochemistry in different subpopulations of DRG. SNL did not induce any changes in tCaMKII between experimental groups, while the overall percentage of pCaMKIIα‐positive neurons in injured L5 DRG SNL (24.8%) decreased significantly when compared to control (41.7%). SNL did not change the percentage of pCaMKIIα/N52 colabeled neurons but decreased the percentage of N52‐negative nonmyelinated neurons that expressed pCaMKIIα from 27% in control animals to 11% after axotomy. We also observed a significant decrease in the percentage of small nonpeptidergic neurons labeled with IB4 (37.6% in control vs. 4.0% in L5 SNL DRG), as well as a decrease in the percentage of pCaMKIIα/IB4 colabeled neurons in injured L5 DRGs (27% in control vs. 1% in L5 DRG of SNL group). Our results show that reduction in pCaMKIIα levels following peripheral injury is due to the loss of IB4‐positive neurons. These results indicate that diminished afferent activity after axotomy may lead to decreased phosphorylation of CaMKIIα. J. Comp. Neurol. 518:64–74, 2010. © 2009 Wiley‐Liss, Inc.     

Mineralocorticoid receptor and heat shock protein expression levels in peripheral lymphocytes from war trauma-exposed men with and without PTSD

Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins.     

Comparison of facemask and mouthpiece interfaces for multiple breath washout measurements

Background

Different interfaces (mouthpiece/nose clip vs. facemask) are used during multiple breath washout (MBW) tests in young children.

Cardiologic predictors of sudden death in patients with myotonic dystrophy type 1

The aim of this study was to analyze survival, causes of death and cardiologic predictors of sudden death in a large cohort of patients with myotonic dystrophy type 1 (DM1). The study was comprised of 171 adult DM1 patients hospitalized at the Neurology Clinic in a 20-year period. Severe electrocardiographic (ECG) abnormality included at least one of the following: rhythm other than sinus, PR interval of ?240 ms, QRS complex duration of 120 ms or more, and second-degree or third-degree atrioventricular (AV) block. Survival data were analyzed by the Kaplan–Meier test, log–rank test and Cox regression analysis. During the mean follow-up period of 9.4 ± 5.4 years, a pacemaker was implanted in 5.8% of DM1 patients and 14% of patients died. The mean age at death was 55.6 ± 12.5 years. The most common causes of death in our cohort were sudden death (41.7%) and respiratory failure (29.2%). The presence of palpitations (hazard ratio [HR] = 4.7, p < 0.05) and increased systolic blood pressure (HR = 9.8, p < 0.05) were significant predictors of sudden death. Among ECG parameters, severe ECG abnormality (HR = 4.7, p < 0.05), right bundle branch block (RBBB; HR = 3.9, p < 0.05) and bifascicular block (HR = 5.8, p < 0.05) were significant predictors of sudden death.