Influence of liver pathology on markers of postmortem brain tissue quality

Background: Postmortem brain tissue provides an important resource to investigate various brain disorders, including those resulting from the effects of alcohol abuse. Unlike the traditionally recognized confounders to tissue quality (e.g., coma, hypoxia), our understanding of the effects of liver disease is incomplete. The aim of this study was to determine the effects of liver pathology, and in particular cirrhosis resulting in hepatic encephalopathy (HE), on 2 postmortem brain tissue quality markers, brain pH and RNA integrity. Methods: We measured tissue quality markers in a cohort of alcohol abuse and control cases collected by the NSW Tissue Resource Centre. Cerebellar tissue was used to evaluate both brain pH and RNA quality (as indicated by the RNA integrity number: RIN). A histological assessment was performed on each case to exclude coexisting pathologies (e.g., cerebrovascular disease, hypoxic encephalopathy, neurodegenerative disease) and to assess the presence or absence of HE. Autopsy reports were reviewed for liver pathology and toxicology. Results: Analysis revealed that cases of alcohol abuse had a lower mean (±SD) brain pH, 6.46 (±0.3) as compared with the control mean 6.64 (±0.2). The mean RIN for the alcohol abuse group was 6.97 (±1.3) and controls 7.66 (±0.5). The severity of liver pathology affected both brain pH (p < 0.0001) and RIN (p < 0.0001). The comparison between cirrhotic cases highlighted increased degradation of RNA in cases with cirrhosis resulting in HE (p = 0.0095). A similar effect was seen on brain pH (p = 0.0019). Conclusions: The results show that the presence of cirrhosis and, more so, HE reduces the pH and RIN of postmortem brain tissue.     

An Ultrasensitive Radioligand Assay for IgC Using the Protein A on Staphylococcus aureau Bacteria

The purpose of this study was to develop a simple and sensitive assay to measure IgG. Human IgG was radiolabelled with ¹²⁵Iodine and 7.5 ng was incubated with heat-killed Staphylococcus aureus bacteria (Cowan 1 strain). To replicate sets of tubes, increasing amounts of a standard IgG preparation were added. The samples were incubated at room temperature for two hours and separated by centrifugation. Using this assay it was found that the IgG concentration could readily be determined in one nanoliter or less of human serum. There was no significant cross-reactivity with IgA, IgE and IgM or the F(ab')₂ fragment of IgG. Serial dilutions of normal human or SLE sera, rabbit or guinea pig sera, the Fc fragment of human IgG and a mouse monoclonal anti-human DNA antibody parallelled the dose response curve obtained with standard human IgG. The method correlated well (r=0.89) with a routinely used nephelometric method. The mean (±SD) IgG concentration in 20 normal subjects measured by this assay was 10 ± 3.6 g/L.     

Essentials of cell physiology

Cell physiology and molecular genetics now provide the basis for the fundamental understanding of the mechanisms involved in normal and pathological physiology, modes of drug action, and risks involved in surgical procedures. Some explanations, often involving a single mutation in a protein are straightforward (e.g. cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis). Others may involve a constellation of effects (e.g. obesity) and surprisingly there still remain important areas lacking comprehensive explanation (e.g. the mode of action of general anaesthetics) or close to resolution but still lacking detail (aldosterone controlling both K and Na regulation in the kidney). The present article presents a concise summary of regulation of cell function, concentrating on the cell membrane and important organelles. Signalling and second messengers, together with the role of membrane channels and transporters constitute an important aspect of this, mediated via kinases and phosphatases. Cell volume regulation, reflecting swelling and oedema, are an important aspect of organ transplantation and brain function.     

Polyvalent mechanical bacterial lysate for the prevention of recurrent respiratory infections: a meta-analysis

BackgroundRespiratory tract infections are common and remain a major source of morbidity, mortality and economic cost worldwide, despite advances in modern medicine. One treatment approach is to non-specifically increase the immune response or augment innate defense mechanisms through the use of bacterial lysates. Polyvalent Mechanical Bacterial Lysate (PMBL) is a bacterial lysate made from a wide range of pathogenic bacteria, including all of the most commonly occurring pathogens of the upper and lower respiratory tract obtained by mechanical lysis.AimTo test the available evidence that PMBL is able to prevent respiratory tract infections.MethodsA number of studies investigating randomized comparisons of PMBL (active) with placebo or no treatment (control) were selected for analysis. The primary outcome measure was the prevention of exacerbations or acute respiratory tract infection. The results were expressed as relative risk (RR) and the number of patients needed to treat for one to benefit (NNTB).ResultsData from 2557 patients from 15 randomized clinical trials (RCTs) was investigated. PMBL induced a significant reduction of infections vs placebo (RR ?0.513; 95% CI; ?0.722 – ?0.303; p = 0.00). The NNTB was 1.15. The RR was always in favor of PMBL (in recurrent respiratory infections other than COPD, chronic bronchitis and tuberculosis, RR ?0.502; 95% CI ?0.824 – ?0.181; in children RR ?2.204; 95% CI ?3.260 – ?1.147; in COPD or chronic bronchitis, RR ?0.404; 95% CI ?0.864–0.057; in tuberculosis, RR ?0.502; 95% CI ?0.890 – ?0.114).ConclusionsThe results of the present meta-analysis suggest that PBML is effective in both in children and in adults in preventing respiratory tract infections. Our current meta-analysis shows that there is a trend with PBML toward clinically significant results in patients with COPD but it did not quite achieve statistical significance due to the small number of COPD studies.