Background-Ischemia/reperfusion (I/R) injury complicates myocardial infarction and stroke by exacerbating tissue damage and increasing risk of mortality. We have recently identified C-type natriuretic peptide (CNP) as an endothelium-derived hyperpolarizing factor in the mesenteric resistance vasculature and described a novel signaling pathway involving activation of natriuretic peptide receptor C (NPR-C), which plays a pivotal role in the regulation of local blood flow. We tested the hypothesis that CNP/NPR-C signaling is a novel regulatory pathway governing coronary blood flow and protecting against I/R injury. Methods and Results-CNP and (Cys18)-atrial natriuretic factor (4-23) amide (cANF 4 -23 ) elicited dose-dependent decreases in coronary perfusion pressure (CPP) that were blocked by Ba 2ϩ and ouabain in the isolated Langendorff rat heart. The endothelium-dependent vasodilator acetylcholine elicited the release of CNP from the coronary endothelium. CNP and cANF 4 -23 reduced infarct size after 25 minutes of global ischemia and 120 minutes of reperfusion, maintaining CPP and left ventricular pressure at preischemic values. The vasorelaxant and protective activity of CNP and cANF 4 -23 were enhanced in the absence of endothelium-derived nitric oxide. Conclusion-Endothelium-derived CNP is involved in the regulation of the coronary circulation, and NPR-C activation underlies the vasorelaxant activity of this peptide. Moreover, this newly defined pathway represents a protective mechanism against I/R injury and a novel target for therapeutic intervention in ischemic cardiovascular disorders. Key Words: endothelium-derived factors Ⅲ myocardial infarction Ⅲ natriuretic peptides Ⅲ cardiovascular diseases Ⅲ ischemia R estoration of blood flow, or reperfusion, of ischemic tissues is essential for limiting the damage caused by acute myocardial infarction and salvaging organ function. However, reperfusion per se exerts detrimental effects by extending cell death and loss of myocardial and coronary function beyond that achieved by the ischemic insult itself; this phenomenon has been termed ischemia/reperfusion (I/R) injury. 1,2 I/R injury is characterized by microvascular dysfunction, in particular, the loss of endothelium-derived dilators, such as nitric oxide (NO) and prostacyclin, that results in capillary constriction and decreased perfusion, increased fluid and cellular extravasation, and leukocyte plugging. 1,2 Hence, considerable attention has focused on identifying endogenous pathways and therapeutic interventions that prevent or reverse microvascular dysfunction and thereby minimize I/R injury. 1,2 C-type natriuretic peptide (CNP) represents the paracrine element of the natriuretic peptide axis, complementing the endocrine actions of atrial natriuretic peptide and brain natriuretic peptide to lower blood volume and pressure. We have recently identified CNP as an endothelium-derived hyperpolarizing factor (EDHF) in mesenteric resistance arteries 3 and defined a novel signaling pathway, important in the regul...

A Safety Maturity Model was developed for use in UK coal mining operations in order to assess the level of compliance and effectiveness with a recently introduced standards based safety management system. The developed model allowed for a "self-assessment" of the maturity to be undertaken by teams from the individual sites. Assessments were undertaken at all sites (surface and underground) and in some cases within each site (e.g., underground operations, surface coal preparation plant). Once the level of maturity was established, improvement plans were developed to improve the maturity of individual standards that were weaker than the average and/or improve the maturity as a whole. The model was likened to a journey as there was a strong focus on continual improvement and effectiveness of the standards, rather than pure compliance. The model has been found to be a practical and useful tool by sites as a means of identifying strengths and weaknesses within their systems, and as a means of assurance with the safety management system standards.

years, with symptomatic achalasia proven by manometry and radiology were studied. Twelve patients were newly diagnosed as having achalasia and had received no previous treatment while the remaining five had previously undergone pneumatic dilatation of the cardia on one or more occasions but had developed recurrence of dysphagia.All patients were admitted to hospital for their pretreatment assessment and this allowed the diagnosis of achalasia to be confirmed in new patients. After an overnight fast the patients underwent 24 hour oesophageal pH monitoring using a pH sensitive radio telemetric capsule and portable receiving equipment (MR 1000 solid state system, Oxford Medical Systems Ltd).4 The capsule was placed 5 cm above the proximal end of the lower oesophageal sphincter as identified manometrically and tethered using a fine nylon thread taped to the cheek. Signals from the capsule were detected by an aerial belt around the chest connected to a solid state recorder. For the duration of the study patients were encouraged to be fully ambulant in the hospital 883 Smart, Foster, Evans, Slevin, and Atkinson environment and food with a pH value of less than 5 was avoided. At the end of the study the data was played back using a micro processor controlled playback unit linked to a standard digital printer. Data were analysed by calculating the time below pH5 and below pH4 expressing each as a percentage of the total, day and night recording period thus obtaining a percentage acid exposure time (%AET).After a 12 hour fast the patients underwent endoscopy and pneumatic dilatation of the cardia using the Rider-Moeller bag under general anaesthesia.5 The presence of food residue in the oesophagus was noted and a sample collected for measurement of its pH, titratable acidity and organic acid content using gas liquid chromatography.One week after pneumatic dilatation the 24 hour oesophageal pH study was repeated. STATISTICAL ANALYSISThe %AET was calculated for patients before and after pneumatic dilatation. The values were compared between groups of patients using the Mann Whitney U test for non-parametric data. ResultsFor purposes of analysis and comparison the patients were divided into two groups; the nine with oesophageal food residue at endoscopy and the remaining (Fig. 1). Analysis of the oesophageal residue obtained from patients with retained food revealed this to be acidic (median pH 3-8, range 3.5-4.0). The acidity of the residue was found to be largely caused by the lactic acid content which accounted for between 91 and 97% of the total acid.After pneumatic dilatation no food residues remained and acid exposure tended to be greater in patients with than in those without initial food residue but this difference was only significant for nocturnal pH measurement (Fig. 2). Those patients with initial food residue showed a fall in total %AET for both pH values after pneumatic dilatation. These changes were less marked at night than during the day (Fig. 3). In those patients without initial food residue, pneumatic d...

Kratom use as a herbal supplement is on the rise in the United States, with reported medical outcomes and lethal effects suggesting a public health threat. Even though the Drug Enforcement Administration has included kratom on its drugs of concern list and the FDA has published a press release to identify it as an opioid with a potential for abuse, its therapeutic and side effects are still not well defined in the literature. Here, we present a case of a 32-year-old man with a history of kratom use who became acutely ill with a brief prodromal illness, followed by jaundice and elevated liver enzymes showing a cholestatic picture, and his successful treatment. In this case, we emphasize the need for awareness of kratom exposure as a key contributor in the expansion of the opioid crisis, with therapeutic benefits earned at the expense of potentially lethal side effects.

An 87-year-old Caucasian woman with hypertension, diabetes mellitus type 2, and COPD was admitted with 1-week duration of back pain and weight gain. The physical examination revealed jugular venous distention, rales in the left lower lung field, and severe pitting edema over lower extremities. As workup for leukocytosis, blood cultures grew Gemella haemolysans. Subsequently, a transthoracic echocardiogram revealed vegetation on the non-coronary aortic leaflet and mild aortic stenosis. She was treated with ampicillin and gentamicin. After further investigation, the patient was diagnosed with plasma cell myeloma, the monoclonal lambda type. This is the first reported case of G. haemolysans endocarditis in a multiple myeloma patient.