Delayed development of humoral immunity in chickens following in ovo treatment with mibolerone

In order to determine if mibolerone causes rapid development of the humoral immune system as previously hypothesized, 12-day-old chicken embryos were injected with 0.1, 1, or 10 micrograms mibolerone. Mibolerone caused bursal atrophy in a dose-dependent manner with severe atrophy at the 10 micrograms dose, substantial atrophy at the 1 microgram dose, and very little or no atrophy at the 0.1 microgram dose. Mibolerone-treated chicks were subsequently challenged with sheep red blood cells (SRBC) and Brucella abortus at 1, 7, 14, or 21 days of age. When serum samples were analysed for agglutinins to SRBC and B. abortus, the results indicated that treated chickens had lower agglutinin titers to both antigens at younger ages. These responses improved with age in groups treated with 0.1 microgram and 1 microgram and were comparable to controls at 5 weeks of age except for low primary and secondary (IgG specific) titers to B. abortus in birds treated with 1 microgram. Chickens treated with 10 micrograms mibolerone still had considerably lower primary responses to SRBC and lower primary as well as secondary responses to B. abortus at 4 and 5 weeks of age. These results indicate that mibolerone causes delayed rather than rapid development of the humoral immune system. In control as well as in treated chickens, agglutinin responses to SRBC appeared earlier than responses to B. abortus.     

An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates.

The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-beta (IFN-beta ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-beta induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 microg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 microg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-beta, and the terminal half-life was 36-40 h compared with 8 h for IFN-beta. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2',5' mRNA expression. At a molar dose equivalent to one-half the dose of IFN-beta, Albuferon beta elicited comparable neopterin responses and significantly higher 2',5'-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-beta when fused to serum albumin suggest a clinical opportunity for improved IFN-beta therapy.     

All-cause and liver-related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank

Background

High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol.

Methods

We obtained information from the UK Biobank on approximately 500,000 participants aged 40–70 years at baseline assessment in 2006–2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis.

Results

Mortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89–2.17) for all causes, 1.89 (1.69–2.12) for any cancer, 1.87 (1.61–2.17) for any circulatory disease, and 9.40 (7.00–12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment.

Conclusions

People with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.     

Fracture Union in Closed Interlocking Nail in Humeral Shaft Fractures

Background:

Fracture shaft humerus is a major cause of morbidity in patients with upper extremity injuries. The aim of this study was to evaluate the outcome of interlocking nail in humeral shaft fractures.

Methods:

This study was conducted in the Department of Orthopedic Surgery in SMS and R Sharda University from January 2010 to November 2013. Seventy-eight patients were recruited from emergency and out-patient department having a close fracture of humerus shaft. All patients were operated under general anesthesia and closed reamed interlocking nailing was done. All patients were followed for 9 months.

Results:

Out of 78 patients, 69 patients underwent union in 90–150 days with a mean of 110.68 days. Complications found in four patients who had nonunion, and five patients had delayed union, which was treated with bone grafting. All the patients were assessed clinically and radiologically for fracture healing, joint movements and implant failure. The results were excellent in 88.46% and good in 6.41% patients. Complete subjective, functional, and clinical recovery had occurred in almost 100% of the patients.

Conclusions:

The results of the present study indicates that in the presence of proper indications, reamed antegrade intramedullary interlocked nailing appears to be a method of choice for internal fixation of osteoporotic and pathologic fractures.