Nitric oxide regulates skeletal muscle fatigue, fiber type, microtubule organization, and mitochondrial ATP synthesis efficiency through cGMP-dependent mechanisms

Aim: Skeletal muscle nitric oxide–cyclic guanosine monophosphate (NO-cGMP) pathways are impaired in Duchenne and Becker muscular dystrophy partly because of reduced nNOSμ and soluble guanylate cyclase (GC) activity. However, GC function and the consequences of reduced GC activity in skeletal muscle are unknown. In this study, we explore the functions of GC and NO-cGMP signaling in skeletal muscle. Results: GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSμ and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1−/− muscle. Functional analyses of GC1−/− muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA–IIX fiber balance. Force deficits in GC1−/− muscles were also not driven by defects in resting mitochondrial adenosine triphosphate (ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. Innovation: GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. Conclusions: These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency

Infected epidermal cyst of the clitoris in an infant

Clitoral enlargement in the pediatric population is a rare condition, usually related to problems of sexual differentiation, but malignant and benign clitoral lesions have also been described. We report the case of a newborn infant, investigated at birth for an intersex disorder because of clitoromegaly. Hormonal screening was normal and ultrasound (US) did not show a pelvic or abdominal mass. Three weeks later, the lesion was larger, tense and erythematous. An abscess was suspected. A drainage was then performed, and the bacteriological culture revealed the presence of Staphylococci aurei. A magnetic resonance imaging (MRI) performed to exclude a tumor of the soft tissue was normal. A diagnosis of infected epidermal cyst was confirmed by the pathology. Two months later, the external genital aspect was normal and the child asymptomatic

Soluble Guanylate Cyclase Generation of cGMP Regulates Migration of MGE Neurons

Here we have provided evidence that nitric oxide-cyclic GMP (NO-cGMP) signaling regulates neurite length and migration of immature neurons derived from the medial ganglionic eminence (MGE). Dlx1/2(-/-) and Lhx6(-/-) mouse mutants, which exhibit MGE interneuron migration defects, have reduced expression of the gene encoding the alpha subunit of a soluble guanylate cyclase (Gucy1A3). Furthermore, Dlx1/2(-/-) mouse mutants have reduced expression of NO synthase 1 (NOS1). Gucy1A3(-/-) mice have a transient reduction in cortical interneuron number. Pharmacological inhibition of soluble guanylate cyclase and NOS activity rapidly induces neurite retraction of MGE cells in vitro and in slice culture and robustly inhibits cell migration from the MGE and caudal ganglionic eminence. We provide evidence that these cellular phenotypes are mediated by activation of the Rho signaling pathway and inhibition of myosin light chain phosphatase activity

Lessons Learned: Recruiting Aging Adults for Research

Aging adults are the fastest-growing population in the United States, but they are underrepresented in health care research. Evidence-based decisions for aging adults need to be made using research done with this population. However, recruiting aging adults into research has many challenges. This article presents multiple cases of recruiting aging adults into nutrition research studies in 3 different US geographic locations. The challenges, successes, and lessons learned are presented. The lessons learned can provide guidance to others already doing research with aging adults and those clinical and community dietitians who want to start doing research with aging adults

Spitting cobra (Naja nigricincta nigricincta) bites complicated by rhabdomyolysis, possible intravascular haemolysis, and coagulopathy

Zebra snake (Naja nigricincta nigricincta) bite is a significant health problem in Namibia. Although fatalities are thought to be rare, the severe cytotoxic effects and debilitating consequences of neglected bites are well documented. The focus of our treatment has always been the urgent treatment of necrosis. Although there have been a few reports of infant fatalities, acute renal failure and mild coagulation problems, systemic effects after envenomation were not well documented. Three case reports of patients with rhabdomyolysis, intravascular haemolysis and coagulopathy following N. n. nigricincta bites are presented