Morphology and physiology of lamina I neurons of the caudal part of the trigeminal nucleus

It has been suggested that in mammals, trigeminal lamina I neurons play a role in the processing and transmission of sensory information from the orofacial region. We investigated the physiological and morphological properties of trigeminal subnucleus caudalis (Sp5C) lamina I neurons in slices prepared from the medulla oblongata of 13- to 15-day-old postnatal rats using patch-clamp recordings and subsequent biocytin-streptavidin-Alexa labeling. Twenty-five neurons were recorded and immunohistochemically stained. The Sp5C lamina I consisted of several types of neurons which, on the basis of their responses to somatic current injection, can be classified into four groups: tonic neurons, which fired throughout the depolarizing pulse; phasic neurons, which expressed an initial burst of action potentials; delayed onset neurons, which showed a significant delay of the first action potential; and single spike neurons, characterized by only one to five action potentials at the very beginning of the depolarizing pulse even at high levels of stimulation intensity. Electrical stimulation of the spinal trigeminal tract evoked AMPA receptor-mediated excitatory postsynaptic currents (EPSC) exhibiting a strong polysynaptic component. AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSC) were characterized by a 10-90% rise time of 0.50+/-0.06 ms and a decay time constant of 2.5+/-0.5 ms. The kinetic properties of NMDA receptor-mediated EPSCs were measured at +40 mV. The 10-90% rise time was 8+/-2 ms and the deactivation time constants were 94+/-31 and 339+/-72 ms, respectively. Intracellular staining and morphological analysis revealed three groups of neurons: fusiform, pyramidal, and multipolar. Statistical analysis indicated that the electrophysiological properties and morphological characteristics are correlated. Tonic and phasic neurons were fusiform or pyramidal and delayed onset and single spike neurons were multipolar. Our results show that both the physiological and morphological properties of Sp5C lamina I neurons exhibit significant differences, indicating their specific integration in the processing and transmission of sensory information from the orofacial region.     

Pulmonary delivery of polyplexes for combined PAI-1 gene silencing and CXCR4 inhibition to treat lung fibrosis

This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.     

Reproducibility of sonographic measurement of the substantia nigra

The aim of this study was to evaluate inter-reader, intra-investigator and inter-investigator reproducibility and correlations in the assessment of substantia nigra (SN) echogenicity and area measurement by a physician-sonographer (PS), a sonographic laboratory assistant (SLA) and a physician without sonographic experience (PN). A total of 22 patients with extrapyramidal symptoms were examined using transcranial sonography (TCS). SN images were encoded and evaluated by the three readers. A second TCS examination was performed after 7+/-2 d. A second investigator performed TCS examination 1 mo later. Spearman rank correlation and Pearson's correlation coefficient were used when assessing the agreement between readers. All three readers identified the same 15 patients with SN echogenicity III or more. Inter-reader SN echogenicity and area measurement correlations were r=0.55 to 0.82 and r=0.31 to 0.74 between PS and SLA and r=0.55 to 0.77 and 0.49 to 0.62 between PS and PN, respectively (p<0.05 in all cases). Intra-reader echogenicity and area measurement correlations (r=0.85 to 0.96 and r=0.51 to 0.69) were statistically significant only for PS (p<0.001). All intra- and inter-investigator correlations of SN area measurement (r=0.69 to 0.88 and r=0.5 to 0.61) and SN echogenicity (r=0.64 to 0.92 and r=0.51 to 0.69) were statistically significant (p<0.05). Semiquantitative evaluation of SN echogenicity and area using TCS is highly dependent on the experience of the sonographer. Only an experienced sonographer was able to produce very reproducible results with statistically significant correlations; SLA and PN intra-reader correlations were poor.     

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism,Cancer Cell Invasion,and DNA Transfection

Purpose

To determine the effect of PEG modification on pharmacologic and gene delivery properties of polymeric CXCR4 antagonist based on Plerixafor.

Methods

Polymeric Plerixafor (PAMD) was synthesized from Plerixafor (AMD3100) and grafted with different amounts of PEG (2 kDa). CXCR4 antagonism of the synthesized polymers was determined using receptor redistribution assay. Inhibition of cancer cell invasion by the polyplexes of the synthesized polymers was assessed using Boyden-chamber method. Transfection activity of DNA polyplexes formed with the synthesized polymers was evaluated in U2OS osteosarcoma and B16F10 melanoma cells.

Results

Our results demonstrate that modification of PAMD with PEG decreased toxicity of the polymers, while preserving their CXCR4 antagonism. Polyplexes prepared with PEG-PAMD inhibited invasion of cancer cells to an extent similar to the commercial CXCR4 antagonist Plerixafor. Negative effect of PEG on transfection activity of PEG-PAMD polyplexes could be overcome by using polyplexes formulated with a mixture of PAMD and PEG-PAMD.

Conclusion

Modification of PAMD with PEG is a viable strategy to preserve the desirable CXCR4 antagonism and ability to inhibit cancer cell invasion of PAMD, while improving safety and colloidal stability of the PAMD polyplexes.     

Parenting styles and alcohol use among children and adolescents: A systematic review

Introduction: Research studies have been focusing on the prevalence of alcohol use among children and adolescents since the 1990s. There are many individual, family, and social factors that can influence this kind of risk behaviour. The present review is focused on the influence of parenting styles.

Aims: The main aim is to provide a systematic review of studies published from 1995 until 2012 which investigate the relationship between alcohol use among adolescents and parenting styles.

Methods: A systematic search of literature employing the PRISMA method identified and evaluated 16 original studies published in the EBSCO, MEDLINE/PubMed, JSTOR, and ScienceDirect databases. The studies were classified according to their research design, the age group of the respondents, the participation of parents, the effects of parenting styles, and the sociocultural setting of the study.

Findings: The studies were subjected to quantitative evaluation according to their methodological criteria and forms of parenting styles. Qualitative evaluation showed a broader context and complexity of study results. While there is some evidence of the protective effect of an authoritative parenting style, there are many other individual, social, and environmental factors.

Conclusions: There is evidence of a connection between parenting styles and the forms of alcohol use among children and adolescents. Such conclusions should be reflected in national primary prevention strategies and family-based prevention programmes.     

Correlation of a change in the amplitude of the R wave during ergometry with the finding of significant stenosis of the coronary artery

The authors evaluated retrospectively 224 patients with ischaemic heart disease. These patients were subjected to an ergometric loading test on a bicycle ergometer followed by angiography of the coronary arteries. With regard to the site of the increased amplitude of R waves during the loading test the patients were divided into seven groups which were sub-divided further according to the coronarographic finding. The authors investigated the assumption that patients with pathological changes of R waves above the anterior wall suffer from afflictions of the ramus interventricularis anterior, patients with changes above the lateral wall of the ramus circuflexus and patients with increased R waves above the inferior wall of the right coronary artery. From the work ensues that no localization of increased amplitudes of R waves during the loading test has a statistically significant correlation with the coronarographic finding.     

Aspartate aminotransferase (AST) more than alanine aminotransferase (ALT) levels predict the progression of liver fibrosis in chronic HCV infection

The development and severity of liver fibrosis in patients with chronic HCV infection can be evaluated best according to the staging of fibrosis in blind liver biopsy. So far there is however no biochemical indicator suggesting advanced fibrosis or progression of fibrosis in chronic HCV infection. In 1997 - 1999 60 adult out-patients (32 women) with chronic HCV infection were examined by blind liver biopsy. The grading of hepatitis was scored according to Knodell and staging of fibrosis according to Desmet. All patients were anti-HCV positive, assessed by the ELISA-3 method and 48/60 had positive HCV RNA in serum. The main risk factor of HCV infection was blood transfusion (67%). Of 27 examined patients 20 (74%) had serotype HCV 1. Staging of fibrosis: histologically confirmed fibrosis was not recorded in 11 patients (18.3%), mild and medium fibrosis was recorded in 25 (42%), severe fibrosis in 14 (23%) and cirrhosis in 10 (17%). With confirmed fibrosis correlated more closely AST serum activity (p < 0.002) than ALT activity (p < 0.03). Steatosis of the liver was found in 25 (42%) patients. The mean age of patients with steatosis was significantly higher than that of patients without steatosis (p < 0.0008). Steatosis was more frequent in patients with fibrosis (p < 0.04), in particularin the age group above 60 years. The development of fibrosis in patients with chronic HCV infection is suggested by permanently elevated activity of both transaminases whereby AST has a higher predictive value than ALT activity. A total of 40% histologically tested patients had the highest staging of fibrosis (3 - 4). Steatosis is in chronic HCV infection a very frequent finding (42%), in particular in patients above 60 years and those with serious fibrosis. The finding of fibrosis should stimulate the initiation of antiviral treatment which can lead to regression of fibrosis and improvement of the histological finding.     

Anatomic variations of the paranasal sinus area in pediatric patients with chronic sinusitis

Endoscopic endonasal surgery has been performed in children. Therefore, we need to know the precise anatomy and anatomic variations of the lateral nasal wall. This is important in order to achieve better surgical results and avoid complications. We also need to know the relationship between the anatomic variations and sinonasal disease. For the purpose of this study we assessed the anatomic variations of the lateral nasal wall and the association of these variations with chronic sinusitis in children. Forty-seven children with chronic sinus disease were included in the study. There were 25 female and 22 male patients with ages ranging from 2 to 16 years (mean 10.5+/-3.8 years). On coronal and axial computed tomographic (CT) scans, the anatomic variations of the lateral nasal wall and sinusitis were assessed. A pneumatized middle concha (MC) was the most common anatomic variation, followed by pneumatization of the superior concha (SC), Haller cell and agger nasi cell. Secondary MC, large ethmoidal bulla, maxillary sinus hypoplasia, Onodi cell, and uncinate process pneumatization were relatively rare. Maxillary sinusitis was the most common sinus infection, followed by ethmoidal, sphenoidal and frontal sinusitis in that order. There was no significant relationship between the sinusitis and anatomic variations except for some minor associations. In conclusion, anatomic variations in the lateral nasal wall are common in children. Local, systemic or environmental factors appear to be more important in pediatric sinusitis than the anatomic variations. Due to the absence of a definitive relationship between the anatomic variations and sinus disease, aggressive surgical interventions should be avoided while performing endonasal endoscopic surgery in the children.