Effects of the nonsteroidal anti-inflammatory drug mefenamic acid on energy metabolism in the perfused rat liver

The action of mefenamic acid, a nonsteroidal anti-inflammatory drug, on energy metabolism in the isolated perfused rat liver was investigated. Mefenamic acid in the range between 0.1 and 1.0 mM was infused to livers from well-fed rats and from 24-hr fasted rats. The former were perfused with substrate-free Krebs/Henseleit-bicarbonate buffer, allowing the measurement of glycogenolysis and glycolysis from endogenous glycogen. The livers from 24-hr fasted rats, on the other hand, were perfused with Krebs/Henseleit-bicarbonate buffer containing fructose, thus allowing the measurement of fructolysis and glucose synthesis. Oxygen consumption was measured in both cases. When present in the range between 0.1 and 0.5 mM, mefenamic acid increased glycolysis, oxygen uptake, glycogenolysis and fructolysis. Higher concentrations, depending on the perfusion conditions, were inhibitory. Glucose production from exogenous fructose, on the other hand, was inhibited at low mefenamic acid concentrations. In general terms, the effects of mefenamic acid on energy metabolism seemed to be the primary consequence of its uncoupling action on the respiratory chain. This conclusion is supported mainly by the opposite effects on glucose synthesis (inhibition) and oxygen consumption (activation). The intracellular concentration of mefenamic acid is much higher than the extracellular one, a phenomenon which may represent binding to intracellular membrane or proteins.     

Impact of a community health promotion program on existing organizations: the Minnesota Heart Health Program.

A community organization strategy was used in the delivery of health education programs by the Minnesota Heart Health Program (MHHP). The effectiveness of the approach was evaluated to determine whether an enhanced health promotion delivery system had developed in MHHP communities by the end of the intervention period or whether the intervention had suppressed community efforts. 'Social connectedness' among providers, as measured by health promotion network size, also was expected to be higher in intervention communities. Six Midwestern communities were studied: the MHHP communities of Mankato, MN and Fargo, ND--Moorhead, MN with two matched comparison communities for each (Winona, MN, St Cloud, MN and Eau Claire, WI, Sioux Falls, SD). Nine areas of health promotion were assessed, including the five heart disease risk factor areas where education campaigns had been implemented (smoking cessation, weight loss, eating patterns, exercise, and heart disease education and screening) and four other areas where community programs are common (chemical dependency; home, personal and drivers' safety; stress management; and cancer education and screening). Indicators of the health promotion delivery system were developed (program options and program participation), and data were collected in separate surveys of 438 community organization providers and 320 larger worksites in the six communities. Results showed no suppression of health promotion delivery systems in MHHP communities. Instead, the survey of larger worksites showed that there was greater participation in heart disease health promotion and greater 'social connectedness' among worksites in both intervention communities. Also, there were more heart disease health promotion programs in the larger intervention community of Fargo-Moorhead. In the community organization survey, results favored the larger intervention community over its comparison communities in heart disease health promotion program options and in 'social connectedness' but not in program participation. However, survey results favored one of the comparison communities (Winona) over the smaller intervention community (Mankato) on all indicators in this survey. The greater impact of the MHHP intervention at worksites suggests that institutionalization may be more likely in stable organizations whose current needs and interests fit the goals of the intervention activity.     

Angeborenes linksventrikul?res Aneurysma bei einem 17-j?hrigen Leistungssportler

We present the case of a 17-year-old competitive athlete with an asymptomatic left ventricular aneurysm (LVA). Echocardiography demonstrated hypoplasia of the septum and a large apical LVA. Magnetic resonance imaging (MRI) detected a very thin and fibrotic wall of the LVA. Due to the potential risk of rupture the LVA was surgically resected and the apex of the left ventricle was covered with a patch plasty. The patient had an event-free postoperative course. Because of the potential risk of arrhythmia, the patient was recommended not to participate further in competitive sport.     

Changes in distribution spaces and cell permeability caused by ATP in the rat liver

AIMS/BACKGROUND: Cellular and extracellular volume changes caused by ATP were investigated in the liver as well as the possible formation of diffusion barriers, which could be responsible for some of its metabolic effects. METHODS: The experimental system was the bivascularly perfused rat liver. [(14)C]Sucrose and [(3)H]water were simultaneously injected into either the portal vein or the hepatic artery. Mean transit times, distribution spaces, variances and linear superimpositions were calculated. RESULTS: In the portal system, ATP reduced the transit time in the great vessels, had little or no effect on sinusoidal and cellular spaces, but impaired the flow-limited distribution of both [(14)C]sucrose and [(3)H]water. In the arterial bed ATP infused into either the portal vein or the hepatic artery produced vasodilation and increased the aqueous extra-sucrose space. These effects were inhibited by Nomega-nitro-L-arginine methyl ester infused into the hepatic artery. CONCLUSIONS: Sucrose and extra-sucrose space changes caused in the arterial bed by portally infused ATP are most probably analogous to the transhepatic vasodilation effect already described for the rabbit liver. Impairment of flow-limited distribution of tracers in the sinusoidal bed indicates that ATP induces the formation of permeability barriers, which could be responsible for some of its metabolic effects.     

Ausbildung eines koronaren Pseudoaneurysmas nach komplexer Koronarintervention mit Drug-eluting-Stentimplantation

We report on a 68-year-old woman with typical symptoms of angina pectoris and unspecific findings in the 12-lead surface electrocardiogram. Invasive diagnostics with coronary angiography revealed a severely calcified ostial filiform stenosis of the right coronary artery (RCA). Therefore, a complex coronary intervention was performed and a drug-eluting stent was implanted (Taxus? stent, Boston Scientific). After 6 weeks a control coronary angiography with intracoronary optical coherence tomography was performed and a new pseudoaneurysm before the RCA stent (proximal RCA) was visible. In a conference with cardiologists and cardiac surgeons (heart team) indications for cardiac surgery were confirmed. The pseudoaneurysm was removed by clipping and an aortocoronary RCA bypass was performed. The postoperative follow-up was without any complications.     

Incidence of low central venous oxygen saturation during unplanned admissions in a multidisciplinary intensive care unit: an observational study

Introduction  

It has been shown that early central venous oxygen saturation (ScvO₂)-guided optimization of hemodynamics can improve outcome in septic patients. The early ScvO₂ profile of other patient groups is unknown. The aim of this study was to characterize unplanned admissions in a multidisciplinary intensive care unit (ICU) with respect to ScvO₂ and outcome.     

Analysis of U2 Small Nuclear RNA Fragments in the Bile Differentiates Cholangiocarcinoma from Primary Sclerosing Cholangitis and Other Benign Biliary Disorders

Background and Objectives

Up to now the diagnosis of early stage cholangiocarcinoma (CC) has remained difficult, with low sensitivities reported for current diagnostic methods. Based on recent promising findings about circulating U2 small nuclear RNA fragments (RNU2-1f) as novel blood-based biomarkers for pancreatic and colorectal adenocarcinoma, we studied the utility of RNU2-1f as a diagnostic marker of CC in bile fluid.

Methods

Bile fluid was collected from patients with CC (n = 12), controls (patients with choledocholithiasis) (n = 11) and with primary sclerosing cholangitis (PSC; n = 11). RNU2-1f levels were measured by real-time polymerase chain reaction normalized to cel-54.

Results

Measurement of RNU2-1f levels in bile fluids enabled the differentiation of patients with CC from controls in all cases. Furthermore, RNU2-1f levels in bile fluids of patients with CC were significantly higher than in patients with PSC, resulting in a receiver-operating characteristic curve area of 0.856, with sensitivity of 67 % and specificity of 91 %.

Conclusions

Our data suggest that the measurement of RNU2-1 fragments detected in the bile fluid can be used as a diagnostic marker for CC and should be included in future prospective diagnostic studies for this disease entity.     

Central venous oxygen saturation and emergency intubation – another piece in the puzzle?

A recent multicentre observational study examined the effect of emergency intubation on central venous oxygen saturation (SCVo₂) in critically ill patients. The main finding was that SCVo₂ significantly increases 15 minutes after emergency intubation and institution of mechanical ventilation with 100% oxygen, especially in those patients with pre-intubation SCVo₂ values <70%, regardless of whether these patients suffered from severe sepsis. However, in only one-quarter of this subgroup was the SCVo₂ normalized to ≥70% solely by this intervention. In contrast, in patients with pre-intubation SCVo₂ ≥70%, the SCVo₂ failed to increase after intubation. A rise in SCVo₂ can be expected when whole body oxygen extraction remains unchanged after intubation and ventilation with pure oxygen.