Increased amino acid turnover and myofibrillar protein breakdown in advanced cancer are associated with muscle weakness and impaired physical function

Muscle wasting in cancer negatively affects physical function and quality of life. This study investigates amino acid metabolism and the association with muscle mass and function in patients with cancer.In 16 patients with advanced cancer undergoing chemotherapy and 16 healthy controls, we administered an intravenous pulse and prime of stable amino acid tracers. We took blood samples to measure the Rate of appearance (Ra), whole body production (WBP), clearance (Cl), and post absorptive whole body net protein breakdown (WBnetPB). Plasma amino acid concentrations and enrichments were analysed by LC-MS/MS. We assessed muscle mass, handgrip/leg/respiratory muscle strength and reported physical activity, quality of life, and physical function.Muscle strength was lower in cancer patients than in healthy controls. Total and limb muscle mass, reported physical activity and WBnetPB were comparable. WBP and Cl of tau-methylhistidine, leucine, glutamine and taurine were higher in cancer patients as well as glycine Cl. Amino acid metabolism was correlated with low muscle mass, strength, physical function and quality of life.Myofibrillar protein breakdown and production of amino acids involved in muscle contractility are up regulated in patients with cancer undergoing chemotherapy and related to muscle weakness and reduced physical outcomes

Chemical ecology of antibiotic production by actinomycetes

Actinomycetes are a diverse family of filamentous bacteria that produce a plethora of natural products relevant for agriculture, biotechnology and medicine, including the majority of the antibiotics we use in the clinic. Rather than as free-living bacteria, many actinomycetes have evolved to live in symbiosis with among others plants, fungi, insects and sponges. As a common theme, these organisms profit from the natural products and enzymes produced by the actinomycetes, for example, for protection against pathogenic microbes, for growth promotion or for the degradation of complex natural polymers such as lignocellulose. At the same time, the actinomycetes benefit from the resources of the hosts they interact with. Evidence is accumulating that these interactions control the expression of biosynthetic gene clusters and have played a major role in the evolution of the high chemical diversity of actinomycete-produced secondary metabolites. Many of the biosynthetic gene clusters for antibiotics are poorly expressed under laboratory conditions, but they are likely expressed in response to host-specific demands. Here, we review the environmental triggers and cues that control natural product formation by actinomycetes and provide pointers as to how these insights may be harnessed for drug discovery

Presence or Absence of Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease is Associated With Distinct Phenotypes

Introduction: Reduced skeletal muscle function and cognitive performance are common extrapulmonary features in Chronic Obstructive Pulmonary Disease (COPD) but their connection remains unclear. Whether presence or absence of skeletal muscle dysfunction in COPD patients is linked to a specific phenotype consisting of reduced cognitive performance, comorbidities and nutritional and metabolic disturbances needs further investigation. Methods: Thirty-seven patients with COPD (grade II–IV) were divided into two phenotypic cohorts based on the presence (COPD dysfunctional, n = 25) or absence (COPD functional, n = 12) of muscle dysfunction. These cohorts were compared to 28 healthy, age matched controls. Muscle strength (dynamometry), cognitive performance (Trail Making Test and STROOP Test), body composition (Dual-energy X-Ray Absorptiometry), habitual physical activity, comorbidities and mood status (questionnaires) were measured. Pulse administration of stable amino acid tracers was performed to measure whole body production rates. Results: Presence of muscle dysfunction in COPD was independent of muscle mass or severity of airflow obstruction but associated with impaired STROOP Test performance (p = 0.04), reduced resting O saturation (p = 0.003) and physical inactivity (p = 0.01), and specific amino acid metabolic disturbances (enhanced leucine (p = 0.02) and arginine (p = 0.06) production). In contrast, COPD patients with normal muscle function presented with anxiety, increased fat mass, plasma glucose concentration, and metabolic syndrome related comorbidities (hypertension and dyslipidemia). Conclusion: COPD patients with muscle dysfunction show characteristics of a cognitive – metabolic impairment phenotype, influenced by the presence of hypoxia, whereas those with normal muscle function present a phenotype of metabolic syndrome and mood disturbances

Invasive nasal histiocytic sarcoma as a cause of temporal lobe epilepsy in a cat

Case summary A 10-year-old neutered female domestic shorthair cat was presented with an acute onset of neurological signs suggestive of a right-sided forebrain lesion, temporal lobe epilepsy and generalised seizure activity. MRI of the head revealed an expansile soft tissue mass in the caudal nasal passages (both sides but predominantly right-sided) involving the ethmoid bone and extending through the cribriform plate into the cranial vault affecting predominantly the right frontal lobe and temporal lobe. Histopathological examination of the tumour revealed a histiocytic sarcoma. Relevance and novel information This is the first report of a cat with clinical signs of temporal lobe epilepsy due to an invasive, histiocytic sarcoma. Histiocytic sarcoma, although rare, should be included in the list of differential diagnoses for soft tissue masses extending through the cribriform plate. Other differential diagnoses are primary nasal neoplasia (eg, adenocarcinoma, squamous cell carcinoma, chondrosarcoma and other types of sarcomas), lymphoma and olfactory neuroblastoma. Temporal lobe epilepsy in cats can be the consequence of primary pathology of temporal lobe structures, or it can be a consequence of pathology with an effect on these structures (eg, mass effect or disruption of interconnecting neuronal pathways)

Evaluation of hypophysectomy for treatment of hypersomatotropism in 25 cats

Background: Successful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats. Objectives: To describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020. Animals: Twenty-five client-owned cats with spontaneous hypersomatotropism. Methods: Retrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin-like growth factor-1 (IGF-1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF-1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow-up information from owners and referring veterinarians. Results: Median postoperative hospital stay was 7 days (range, 3-18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0-101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6-13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF-1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14-240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900-1794 days; range, 11-3180 days) and the overall 1-, 2-, and 3-year all-cause survival rates were 76%, 76%, and 52%, respectively. Conclusions and Clinical Importance: This study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure