The detrusor electromyogram and purinergic mechanisms in the bladders of guinea-pig and man.

It has been said that a technique capable of recording a urinary bladder electromyogram could be useful in the clinical evaluation of the detrusor neuropathies and myopathies implicated in the generation of lower urinary tract symptoms. However, in contrast to electromyography of skeletal and cardiac muscle, detrusor smooth muscle electromyography has remained in its infancy despite fifty years of scientific effort. The principal problems appear to be isolation of the real signal from artifacts, and uncertainties surrounding the existence of electromyographic activity during parasympathetically mediated muscle contraction. The discovery of purinergic neuromuscular transmission in overactive human bladder samples has renewed interest in detrusor electromyography as, in contrast to cholinergic mechanisms, purinergically mediated contractions can generate extracellular electrical activity. This thesis describes the development and validation of a novel technique for recording electrical activity from neurologically intact guinea-pig bladders and human detrusor in vitro. We characterise a purinergic electromyographic signal and show that detrusor taken from overactive human bladders has a greater propensity to generate electromyographic activity than normal by virtue of an aberrant purinergic mechanism. We discuss the potential role of electromyography in the clinical evaluation of a putative purinergic detrusor myopathy

Autophagy Exacerbates Muscle Wasting in Cancer Cachexia and Impairs Mitochondrial Function

Cancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss and muscle wasting that impairs patients' quality of life and survival. Aim of this work was to evaluate the impact of either autophagy inhibition (knocking-down beclin-1) or promotion (overexpressing TP53INP2/DOR) on cancer-induced muscle wasting. In C26 tumor-bearing mice, stress-induced autophagy inhibition was unable to rescue the loss of muscle mass and worsened muscle morphology. Treating C26-bearing mice with formoterol, a selective β2-agonist, muscle sparing was paralleled by reduced static autophagy markers although the flux was maintained. Conversely, the stimulation of muscle autophagy exacerbated muscle atrophy in tumor-bearing mice. TP53INP2 further promoted atrogene expression and suppressed mitochondrial dynamics-related genes. Excessive autophagy might impair mitochondrial function through mitophagy. Consistently, tumor-induced mitochondrial dysfunction was detected by reduced ex vivo muscle fiber respiration. Overall, the results evoke a central role for muscle autophagy in cancer-induced muscle wasting

Targeting mitochondria by ss-31 ameliorates the whole body energy status in cancer-and chemotherapy-induced cachexia

Objective: Cachexia is a complex metabolic syndrome frequently occurring in cancer patients and exacerbated by chemotherapy. In skeletal muscle of cancer hosts, reduced oxidative ca-pacity and low intracellular ATP resulting from abnormal mitochondrial function were described. Methods: The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiv-ing chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not. Results: Mitochondrial dysfunction in C26-bearing (C26) mice associated with alterations of cardiolipin fatty acid chains. Selectively targeting cardiolipin with SS-31 partially counteracted body wasting and prevented the reduction of glycolytic myofiber area. SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity and rescued intracellular ATP levels, although it was unable to counteract mitochondrial protein loss. Progressively increased dosing of SS-31 to C26 OXFU mice showed transient (21 days) beneficial effects on body and muscle weight loss before the onset of a refractory end-stage condi-tion (28 days). At day 21, SS-31 prevented mitochondrial loss and abnormal autophagy/mitophagy. Skeletal muscle, liver and plasma metabolomes were analyzed, showing marked energy and protein metabolism alterations in tumor hosts. SS-31 partially modulated skeletal muscle and liver metab-olome, likely reflecting an improved systemic energy homeostasis. Conclusions: The results suggest that targeting mitochondrial function may be as important as targeting protein anabolism/catabo-lism for the prevention of cancer cachexia. With this in mind, prospective multi-modal therapies including SS-31 are warranted

Targeting Mitochondria by SS-31 Ameliorates the Whole Body Energy Status in Cancer- and Chemotherapy-Induced Cachexia

Cachexia is a complex metabolic syndrome frequently occurring in cancer patients and exacerbated by chemotherapy. In skeletal muscle of cancer hosts, reduced oxidative capacity and low intracellular ATP resulting from abnormal mitochondrial function were described. : The present study aimed at evaluating the ability of the mitochondria-targeted compound SS-31 to counteract muscle wasting and altered metabolism in C26-bearing (C26) mice either receiving chemotherapy (OXFU: oxaliplatin plus 5-fluorouracil) or not. : Mitochondrial dysfunction in C26-bearing (C26) mice associated with alterations of cardiolipin fatty acid chains. Selectively targeting cardiolipin with SS-31 partially counteracted body wasting and prevented the reduction of glycolytic myofiber area. SS-31 prompted muscle mitochondrial succinate dehydrogenase (SDH) activity and rescued intracellular ATP levels, although it was unable to counteract mitochondrial protein loss. Progressively increased dosing of SS-31 to C26 OXFU mice showed transient (21 days) beneficial effects on body and muscle weight loss before the onset of a refractory end-stage condition (28 days). At day 21, SS-31 prevented mitochondrial loss and abnormal autophagy/mitophagy. Skeletal muscle, liver and plasma metabolomes were analyzed, showing marked energy and protein metabolism alterations in tumor hosts. SS-31 partially modulated skeletal muscle and liver metabolome, likely reflecting an improved systemic energy homeostasis. : The results suggest that targeting mitochondrial function may be as important as targeting protein anabolism/catabolism for the prevention of cancer cachexia. With this in mind, prospective multi-modal therapies including SS-31 are warranted

Is there a relationship between weather conditions and aortic dissection?

BACKGROUND: Bleeding and rupture of blood vessels has been correlated with weather conditions in the past. This is the first study in the world literature with the aim of investigating the relationship between atmospheric pressure and temperature with the presentation of aortic dissection. METHODS: The dates of all emergency aortic dissection repairs from 1996–2002 in a regional cardiothoracic unit at Blackpool Victoria Hospital were obtained. Hourly temperature and pressure data from a regional weather station for this time period was supplied by the Meteorological Office. The mean and standard deviation of hourly temperature and pressure data for that month were compared to the mean and standard deviation of the data 24 and 48 hours prior to the aortic dissection. RESULTS: 26 patients were found to have been operated on during the time period studied. There was no statistically significant correlation between temperature or atmospheric pressure readings, and the incidence of aortic dissection, using a Bonferonni-corrected significance p-value of 0.005 CONCLUSION: This study is the first to examine the relationship between atmospheric pressure, temperature and dissecting thoracic aorta. No statistically significant relationship was demonstrable

Acute colonic pseudo-obstruction after total hip replacement.

Acute colonic pseudo-obstruction is a poorly recognised and potentially fatal complication of hip surgery. Between 1991 and 1994 six patients were observed who required laparotomy after failure of medical management. In three the indication was signs of peritonism, while in the other three exploration was required to exclude segmental ischaemia and to decompress the bowel. In all, there was no evidence of mechanical obstruction. Patients having total hip replacement are at risk of developing pseudo-obstruction due to their age, comorbidity, high doses of analgesics and the nature of the operation. If postoperative ileus persists for more than 48 hours acute colonic pseudo-obstruction should be suspected and confirmed by plain radiography. Prompt recognition and treatment with early referral to a colorectal unit are indicated. Laparotomy appears to carry less risk than that for patients with idiopathic pseudo-obstruction, but should be performed only if colonic ischaemia is suspected