Influence of corticotropin-releasing factor on pancreatic and islet blood flow in different regions of the rat pancreas

Corticotropin-releasing factor (CRF) has previously been shown to selectively dilate the mesenteric vascular bed, without affecting other vascular beds. Pancreatic blood flow and islet blood flow were therefore measured separately with a microsphere technique in the two regions of the rat pancreas perfused by the superior mesenteric artery (SMA) or celiac artery (CA) respectively. Intravenous infusion of CRF (0.25 microgram/kg b.w./min) caused an increase in both whole pancreatic blood flow and islet blood flow in the region of the pancreas perfused by the SMA. The fraction of whole pancreatic blood flow diverted through the islets in this part of the pancreas was, however, unaffected by CRF infusion (approximately 10%). CRF did not change either pancreatic or islet blood flow in the CA-perfused part of the pancreas, and did not affect the release of insulin.     

Effect of glutamine on protein synthesis in isolated intestinal epithelial cells

The purpose of this study was to determine the etiologic factors of denture stomatitis. Fifteen subjects with clinical evidence of localized simple denture stomatitis, fifteen subjects without clinical signs of denture stomatitis, and forty-five subjects with clinical evidence of generalized simple denture stomatitis were investigated clinically and mycologically. Subjects were evaluated according to age, sex, duration of denture usage, smoking habits, frequency of denture brushing, overnight denture wearing, pH level of saliva and degree of candidal colonization and candidal formation. Salivary samples and swabs were taken from the palate and the mucosal surfaces of the dentures investigated mycologically in order to identify the yeast colonies. Smears were taken from the palate and investigated in order to identify candidal formation. No statistically significant relationship was found between denture stomatitis and age, sex, duration of denture usage, frequency of denture brushing, overnight denture wearing or pH level of saliva. There was however, a statistically significant relationship between denture stomatitis and denture hygiene, smoking habits, candidal colonization and candidal formation.     

Lipoprotein(a) as a risk predictor for cardiac mortality in patients with acute coronary syndromes

AIMS: Raised lipoprotein(a) concentrations are considered to be a risk factor for atherothrombotic diseases. We examined whether baseline concentrations were a risk factor for an adverse outcome in patients admitted with acute coronary syndromes. METHODS AND RESULTS: Five hundred and nineteen patients admitted with suspected acute coronary syndromes were studied and followed prospectively for a median of 3 years. The prognostic significance of a baseline lipoprotein(a) concentration of > or = 30 mg x dl(-1) or lower for subsequent cardiac death was assessed in patients with myocardial infarction (266) and unstable angina (197) and compared with other variables in regression models. In patients with myocardial infarction, a baseline lipoprotein(a) concentration of > or =30 mg x dl(-1) was associated with a 62% increase in subsequent cardiac death compared to the lower concentration group (29.8% vs 18.6%, Log rank P=0.04). In a multivariate regression model a baseline lipoprotein(a) concentration of > or = 30 mg x dl(-1) retained its significance as an independent predictor of cardiac death (P=0.037). In patients with unstable angina, baseline concentrations of > or = 7.9 mg x dl(-1) were found to be significant predictors of cardiac death in univariate (P=0.021) and multivariate (P=0.035) regression models. CONCLUSION: Baseline lipoprotein(a) concentrations in patients admitted with acute coronary syndromes are associated with an increased risk of cardiac death. For patients with myocardial infarction a concentration of > or = 30 mg x dl(-1) appears appropriate as a risk discriminator; for patients admitted with unstable angina, however, much lower concentrations of lipoprotein(a) appear to be prognostically important.     

Conformational stability of factor VIIa: biophysical studies of thermal and guanidine hydrochloride-induced denaturation

The binding of the multidomain protein factor VIIa (fVIIa) to tissue factor provides the interprotein communication necessary to make fVIIa an efficient catalyst of the initial event in the extrinsic pathway of blood coagulation. We have investigated the stability of individual domains in fVIIa and the influence of Ca2+ and an irreversible active-site inhibitor (FFR-chloromethyl ketone). Equilibrium guanidine hydrochloride (GuHCl)-induced unfolding monitored by tryptophan fluorescence and far-UV circular dichroism (CD) demonstrated that the gamma-carboxyglutamic acid (Gla) domain unfolds at 0.3 M GuHCl and the serine protease (SP) domain at 3 M GuHCl and that Ca2+ is a prerequisite for the formation of an ordered, compact structure in the Gla domain. The loss of amidolytic activity coincides with the first transition, which is stabilized by the active-site inhibitor, and a change in the environment of the active site is demonstrated using a fluorescent inhibitor (DEGR-chloromethyl ketone). Thermal unfolding monitored by differential scanning calorimetry (DSC) reveals that Ca2+ stabilizes the SP domain slightly, increasing the unfolding temperature by 2.7 degrees C. In addition, Ca2+ is required for a large enthalpy change concomitant with unfolding of the Gla domain, and this unfolding enthalpy is only detectable in the presence of the SP domain, indicating some kind of interaction between these domains. Thermal unfolding measured by CD indicates secondary structural changes at the same temperature as the heat absorption in the DSC but only when both the Gla domain and the SP domain are present together with Ca2+ ions. Taken together, these results indicate a Ca2+-dependent interaction between the Gla domain and the SP domain, implying a high degree of flexibility of the domains in free fVIIa. It is also shown that the epidermal growth factor-like domains are stable at elevated temperatures and high GuHCl concentrations. Moreover, already at physiological temperature, subtle structural changes take place which influence the overall shape of fVIIa and are detrimental to its enzymatic activity.