Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Life events exposure before a treated major depressive episode depends on the number of past episodes.

A cross-sectional survey investigated the relationship between the number of previous depressive episodes and life events, testing the kindling hypothesis, in a sample of 13,377 treated patients with unipolar depression. A linear decline of average life events exposure is observed for more frequent past episodes, even when age, gender and severity are taken into account.     

Effect of short-term training cessation on performance measures in distance runners.

This study examined if measures associated with distance running performance were affected by short-term (14 d) training cessation in 12 distance runners. VO2max decreased by approximately 3 ml.kg-1.min-1 (mean +/- SE, 61.6 +/- 2.0 vs 58.7 +/- 1.8 ml.kg-1.min-1, p < 0.05) with training cessation. Time to exhaustion (TTE) during the incremental VO2max test decreased by 1.2 min (13.0 +/- 0.5 vs 11.8 +/- 0.5 min, p < 0.001) and maximal heart rate increased (p < 0.001) by 9 beats per minute (BPM). No changes in running economy (75 and 90% VO2max) were evident, although submaximal heart rate increased by 11 BPM (p < 0.001) at both running speeds. Other evidence for detraining were decreases in estimated resting plasma volume (-5.1 +/- 1.9%) and muscle citrate synthase activity (-25.3 +/- 2.6%, p < 0.05). Muscular atrophy (muscle fiber cross-sectional area) was not evident. TTE and submaximal heart rate exhibited relatively large percent changes (-9 and +6%, respectively) compared to VO2max (-4%). These findings indicate that the reduction in VO2max with short-term training cessation is relatively small. TTE and submaximal heart rate may be easily measured, yet more sensitive indicators of decrements in distance running performance.     

Rare anatomic coronary variant. Description of a case]

A case of a patient with post-infarction angina and peculiar abnormalities of the coronary arteries is reported. We describe the anatomic findings as well as the possible therapeutical options.     

Neuronal adrenergic and muscular cholinergic contractile hypersensitivity in canine jejunum after extrinsic denervation

Extrinsic denervation may be responsible for motor dysfunction after small bowel transplantation. The aim of this study was to examine the role of extrinsic innervation of canine jejunum on contractile activity. An in vitro dose response of cholinergic and adrenergic agonists was evaluated in canine jejunal strips of circular muscle at 0, 2, and 8 weeks in a control group and after jejunoileal extrinsic denervation (EX DEN). Neurons in circular muscle were quantitated by means of immunohistochemical techniques. Adrenergic and cholinergic responses did not differ at any time in the control group. However, at 2 and 8 weeks, extrinsic denervation caused an increased sensitivity to the procontractile effects of the cholinergic agonist bethanechol at the level of the smooth muscle cells, and increased sensitivity to the inhibitory effects of the adrenergic agent norepinephrine mediated at the level of the enteric nervous system. Immunohistochemical analysis showed a reduction in all neurons and a complete lack of adrenergic fibers in the EX DEN group after 2 and 8 weeks. Extrinsic denervation induces enteric neuronal cholinergic and adrenergic smooth muscle hypersensitivity in canine jejunal circular muscle. Presented in part at the annual meeting of the American Gastroenterological Association, Orlando, Florida, May 18, 1999 (poster presentation), and published as an abstract in Gastroenterology 116:A1075, 1999. Supported by United States Public Health Service grant DK39337 from the National Institutes of Health (M.G.S.); the Swiss National Science Foundation; the Swiss Society of Gastroenterology and Hepatology; the Swiss Foundation for Medical and Biological Science; the Novartis Foundation; Astra Zeneca Pharmaceuticals, Switzerland; and the Department of Visceral and Transplantation Surgery, University of Bern, Switzerland.     

Telomerase activity in prognostic histopathologic features of melanoma.

BACKGROUND: Telomerase activity (TA) is believed to play a role in the regulation of senescence and to limit the number of cell divisions. The deregulation of telomerase appears to contribute to oncogenesis and the formation of immortal cell lines. As a result, it is believed that it could be used as a prognostic marker in melanoma. METHODS: TA was assayed by the polymerase chain reaction PCR-ELISA-based telomeric repeat amplification protocol (TRAP assay). One hundred and eight samples were distributed in four histological groups: 30 samples from primary cutaneous melanomas, 24 from peritumoural skin sites, 28 from benign melanocytic lesions, and 26 from normal skin sites as a control. RESULTS: TA was different among the four tested groups (Kruskall-Wallis test p<0.001), and increasing values of TA were observed progressing from normal skin to benign and then to malignant lesions. Among melanoma samples, there was a significant association between TA and ulceration (p=0.025), TA and vascular invasion (p=0.018) and TA and mitotic rate (p=0.029) (Mann-Whitney test). A linear regression analysis showed significant associations between the increase of TA with Breslow thickness (p=0.004) and the presence of satellites (p=0.002). CONCLUSIONS: We observed that TA had increased from control skin to peritumoural skin, and then to benign melanocytic lesions and finally to melanoma, suggesting tumour progression. TA showed higher values in the presence of some important histopathologic parameters related to poor prognosis in cutaneous melanoma such as ulceration, vascular invasion, satellites, high rates of mitosis, and in thicker tumours.     

Improving emergency obstetric care in Mozambique: the story of Sofala.

OBJECTIVE: The 5-year project in the province of Sofala was designed to improve access, quality and utilization of emergency obstetric care (EmOC) by strengthening rural hospitals and health centers and ultimately the health system's capacity to respond to emergencies more quickly and effectively. METHODS: Implementation consisted of attention to infrastructure, human resource development, transportation and communication systems, and management. Specific management aspects that were targeted for improvement included: supportive supervision, logistics for supplies, equipment and drugs, record keeping, monitoring and evaluation, and quality improvement techniques such as maternal death audits. RESULTS: Access to EmOC improved with an increase in the number of fully functional EmOC facilities from 4 to 18. The number of women with obstetric complications who were admitted for treatment in participating facilities tripled, and the proportion of those women dying declined by half. CONCLUSIONS: Close collaboration and partnership with the provincial health directorate make the sustainability of many results likely while the replication of much of the Sofala model to other provinces is promising for the national strategy to reduce maternal mortality.     

A review of the effects of external pressure on skin blood flow

The human foot is a complex mechanical structure consisting of bones, ligaments and joints. They act together to provide a robust system capable of absorbing and dissipating the intermitted pressure that is subjected to its plantar surface during walking to prevent soft tissue breakdown. Current studies suggest that plantar foot pressure may lead to soft tissue breakdown (e.g. neuropathic ulceration) and hence research has so far concentrated on investigating the mechanical effects of plantar foot pressure on the foot’s integrity. This has been possible through the widely available pressure and force platforms as well as in-shoe pressure systems. However, to understand how plantar foot pressure causes soft tissue breakdown it is vital to investigate both the physiological–mechanical interactions between the skin and plantar foot pressure. This review suggests that with the current advances in technology, the physiological response of skin blood flow to mechanical plantar foot pressure should be investigated and correlated further, both during static and dynamic loading, by developing a new system capable of either measuring both variables simultaneously or by synchronising two systems in real time.