Urocortin II treatment reduces skeletal muscle mass and function loss during atrophy and increases nonatrophying skeletal muscle mass and function

Two corticotropin-releasing factor 2 receptor (CRF2R)-selective peptides have been recently described, urocortin II (also known as stresscopin-related peptide) and urocortin III (stresscopin). We have used urocortin II to evaluate the effects of activation of the CRF2R on skeletal muscle-related physiological processes. Administration of urocortin II to mice prevented the loss of skeletal muscle mass resulting from disuse due to casting, corticosteroid treatment, and nerve damage. In addition, urocortin II treatment prevented the loss of skeletal muscle force and myocyte cross-sectional area that accompanied muscle mass losses resulting from disuse due to casting. Finally, we observed increased skeletal muscle mass and force in normal muscles when mice are treated with urocortin II. These results were confirmed using two additional CRF2R agonists, urocortin I and sauvagine. Thus, activation of the CRF2R modulates skeletal muscle mass in both normal and atrophying muscle. Therefore, CRF2R-selective agonists may find utility in the treatment of skeletal muscle wasting diseases including age-related muscle loss or sarcopenia.     

Self-efficacy for temptations is a better predictor of weight loss than motivation and global self-efficacy: Evidence from two prospective studies among overweight/obese women at high risk of breast cancer

Objectives

Identifying predictors of weight loss could help to triage people who will benefit most from programs and identify those who require additional support. The present research was designed to address statistical, conceptual and operational difficulties associated with the role of self-efficacy in predicting weight loss.

Methods

In Study 1, 115 dieting overweight/obese women at high risk of breast cancer were weighed and completed questionnaires assessing motivation, global self-efficacy and self-efficacy for temptations. The main outcome measure was weight, measured 3-months post-baseline. Study 2 was identical (n = 107), except changes in psychological variables were computed, and used to predict weight 6-months post-baseline.

Results

In Study 1, self-efficacy for temptations was a significant predictor of weight loss at 3-month follow-up. In Study 2, improved self-efficacy for temptations between baseline and four-weeks was predictive of lower weight at 6 months.

Conclusion

The key finding was that self-efficacy for temptations, as opposed to motivation and global self-efficacy, was predictive of subsequent weight loss.

Practice implications

The implication is that augmenting dieters’ capability for dealing with temptations might boost the impact of weight loss programs.     

The antimicrobial effect of Iseganan HCl oral solution in patients receiving stomatotoxic chemotherapy: analysis from a multicenter, double-blind, placebo-controlled, randomized, phase III clinical trial

J Oral Pathol Med (2012) 41 : 229–234 Background: Cytotoxic chemotherapy induces changes in the oral microflora that may cause oral and systemic infections in myelosuppressed cancer patients. These complications prompted us to assess the antimicrobial activity of a topical Iseganan HCl mouthwash vs. placebo on the aerobic and facultatively anaerobic oral flora in these patients. Methods: Two hundred and twenty‐five chemotherapy patients were recruited into a randomized, double‐blind, placebo‐controlled trial, conducted at multiple centers. The study compared the antimicrobial efficacy of Iseganan HCl vs. placebo (95% of the Iseganan and 97% of the control group received myeloablative chemotherapy). Iseganan HCl 9 mg/3 ml was administered as a swish and swallow solution, six times daily for 21–28 days. Microbial cultures were made before and after the daily Iseganan mouth rinse on the first and final days of chemotherapy. Results: The reduction in total microbial load after the first day of treatment was statistically significant (1.59 vs. 0.18 log10 CFU for the Iseganan HCl and placebo groups, respectively, P < 0.0001). Iseganan HCl rinse had a cumulative effect demonstrated by the significant difference between the two groups on the last day of the study (i.e. completion of Iseganan daily treatment) (P < 0.05). The reduction was mainly due to decreased densities of viridans streptococci, non‐hemolytic streptococci, and yeasts. The minimal inhibitory concentration (MIC) of Iseganan HCl remained the same throughout the course of treatment. Conclusions: Topical Iseganan HCl significantly reduces the total oral aerobic bacterial, streptococcal, and yeast load. Its potential as an oral antimicrobial agent in preventing these types of infections is clear.     

Voltage-gated Na channels in chemoreceptor afferent neurons—Potential roles and changes with development

Carotid body chemoreceptors increase their action potential (AP) activity in response to a decrease in arterial oxygen tension and this response increases in the post-natal period. The initial transduction site is likely the glomus cell which responds to hypoxia with an increase in intracellular calcium and secretion of multiple neurotransmitters. Translation of this secretion to AP spiking levels is determined by the excitability of the afferent nerve terminals that is largely determined by the voltage-dependence of activation of Na⁺ channels. In this review, we examine the biophysical characteristics of Na⁺ channels present at the soma of chemoreceptor afferent neurons with the assumption that similar channels are present at nerve terminals. The voltage dependence of this current is consistent with a single Na⁺ channel isoform with activation around the resting potential and with about 60-70% of channels in the inactive state around the resting potential. Channel openings, due to transitions from inactive/open or closed/open states, may serve to amplify external depolarizing events or generate, by themselves, APs. Over the first two post-natal weeks, the Na⁺ channel activation voltage shifts to more negative potentials, thus enhancing the amplifying action of Na⁺ channels on depolarization events and increasing membrane noise generated by channel transitions. This may be a significant contributor to maturation of chemoreceptor activity in the post-natal period.     

Role of myeloid differentiation factor 88 in Rhesus rotavirus-induced biliary atresia

Background

Biliary atresia (BA) is a unique neonatal disease resulting from inflammatory and fibrosing obstruction of the extrahepatic biliary tree. Previous studies have demonstrated the critical role of innate immunity and the Th1 response to activated inflammatory cells and overexpressed cytokines in the pathogenesis of BA. Myeloid differentiation factor 88 (MyD88) is a critical adaptor molecule that has been shown to play a crucial role in immunity. We investigated the role of MyD88 in the inflammatory response and development of cholangiopathy in murine BA.

Methods

MyD88 knockout (MyD88^−/−) and wild-type (WT) BALB/c pups were injected with Rhesus rotavirus or saline on day 1 of life. The mice were monitored for clinical symptoms of BA, including jaundice, acholic stools, bilirubinuria, and death. The liver and extrahepatic bile ducts were harvested for histologic evaluation and the quantification of viral content, determination of cytokine expression, and detection of inflammatory cells.

Results

Rhesus rotavirus infection produced symptoms in 100% of both MyD88^−/− and WT pups, with survival of 18% of WT and 0% of MyD88^−/− mice. Histologic analysis demonstrated bile duct obstruction in both MyD88^−/− and WT mice. Viral titers obtained 7 d after infection and expression of interferon-γ and tumor necrosis factor-α at day 3, 5, 8, and 12 after infection revealed no significant differences between the WT and MyD88^−/− mice. Flow cytometry demonstrated similar levels of activated CD8+ T cells and natural killer cells.

Conclusions

The pathogenesis of murine BA is independent of the MyD88 signaling inflammatory pathway, suggesting alternative mechanisms are crucial in the induction of the model.     

Managing vaccines: defining the remit of primary care and specialist HIV clinics in the delivery of immunization to individuals with HIV infection

The British HIV Association (BHIVA) has published guidelines for immunization of HIV-infected adults. A chart review of 200 HIV-infected patients diagnosed was conducted to determine shortcomings in previous practice and determine which vaccines should routinely be given in specialist HIV clinics and which might be able to be delegated to primary care clinics. Data were collected on administration of three categories of vaccinations: (1) vaccines used in all individuals with chronic disease (pneumococcal, influenza, swine flu H1N1); (2) targeted vaccinations used in non-immune individuals with HIV who are at risk of exposure (hepatitis A and hepatitis B); (3) routine vaccines traditionally delivered to the whole population (measles/mumps/rubella [MMR], diphtheria/tetanus/pertussis and meningitis C/ACWY). Pneumococcal vaccine was delivered to 54% of eligible patients, 52% of eligible individuals completed a full hepatitis B programme of vaccination and 21% (42/200) were naturally immune; hepatitis A vaccine was delivered to 36% of eligible individuals. With increasing demands on resources, it seems likely that HIV services will have to harness resources of primary care in vaccine programmes in relation to routine vaccines. By improving communication between primary and secondary care mistakes with live vaccination decisions could be avoided; HIV services should continue to perform targeted and chronic disease vaccines, i.e. for category 1 and category 2 vaccines.