We investigated the effects of general receptor for phosphoinositides-1
(GRP1), a recently cloned protein that binds 3,4,5-phosphatidylinositol
PtdIns(3,4,5)P3 with high affinity, but not ...PtdIns(3,4)P2 nor
PtdIns(3)P, on insulin and insulin-like growth factor I (IGF-I)-induced
cytoskeletal rearrangement, glucose transporter-4 (GLUT4)
translocation, and DNA synthesis. GRP1 consists of an
NH2-terminally located coiled coil domain followed by a
Sec7 domain and a COOH-terminal pleckstrin homology (PH) domain that is
required for PtdIns binding. We used microinjection of
glutathione-S-transferase fusion proteins containing
residues 239–399 (PH domain), residues 52–260 (Sec7 domain), residues
5–71 (N-terminal domain), full-length GRP1, and an antibody (AB)
raised against full-length GRP1 coupled with immunofluorescent
detection of actin filament rearrangement, GLUT4 translocation, and
3′-bromo-5′-deoxyuridine incorporation. Microinjection of these
constructs and the AB had no effect on insulin-induced GLUT4
translocation or DNA synthesis. However, microinjection of the GRP1-PH
and the GRP1-Sec7 domain as well as the α-GRP1-AB significantly
inhibited insulin- and IGF-I-stimulated actin rearrangement in an
insulin receptor-overexpressing cell line (HIRcB) compared with that in
control experiments. Coinjection of GRP1-Sec7 along with constitutively
active Rac (Q67L) did not inhibit Rac-induced actin rearrangement.
Furthermore, GRP1 is not able to bind and act as a nucleotide exchange
factor for the small GTP-binding proteins of the Rho family. As GRP1
acts as a guanine nucleotide exchange factor for ARF6 proteins, we
propose a signaling pathway distinct from the small GTP-binding protein
Rac, connecting PtdIns(3,4,5)P3 via GRP1 to ARF6, leading to insulin-
and IGF-I-induced actin rearrangement.
To elucidate the metabolism of islet amyloid polypeptide (IAPP) with respect to a possible renal elimination we investigated IAPP levels in 20 lean, nondiabetic patients with renal failure maintained ...on chronic hemodialysis (HD) and in 20 healthy controls. The basal levels of IAPP were significantly higher in uremic patients than in controls (15.1 +/- 3.2 vs. 3.2 +/- 0.2 pM, P < 0.001) suggesting renal excretion of IAPP. To investigate the impact of chronically elevated levels of endogenous IAPP on insulin secretion and insulin sensitivity, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed in a subset of patients on hemodialysis and in age-matched healthy controls (C) and obese patients with normal (NGT) and with impaired glucose tolerance (IGT). Insulin sensitivity index (SI) was 8.7 +/- 1.5 in C (P < 0.05 vs. NGT, P < 0.01 vs. IGT), 5.4 +/- 0.9 in HD (P < 0.05 vs. IGT), 3.1 +/- 1.0 in NGT, and 2.0 +/- 0.5 in IGT. First phase insulin secretion was increased in patients on HD compared with those of several control groups. The results of this study therefore indicate a renal route of metabolism of IAPP. Increased endogenous circulating IAPP levels over a long period of time do not lead to a decrease in insulin release in patients on HD and do not cause the insulin resistance commonly seen in obesity and diabetes. Increased levels of circulating IAPP therefore are not likely to be a pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM).
Lipoprotein(a) (Lp(a)) is an independent risk factor for atherosclerotic disease. However, information concerning the site of Lp(a) catabolism and breakdown is scarce. Several studies have shown ...that, in renal insufficiency, plasma Lp(a) levels are elevated, and that after normalisation of kidney function they return to normal. We have recently shown that fragments of apo(a) are found in the urine of healthy individuals. Despite this evidence that apo (a) is excreted into the urine, the mode of excretion of apo(a) remains unclear. Since it has been reported that intravenous infusion of somatostatin can reduce glomerular filtration rate (GFR) and renal plasma flow (RPF), we analysed urinary apo(a) excretion in ten healthy volunteers receiving somatostatin infusions. The infusion of somatostatin led to reversible changes in GFR and RPF. Apo(a) excretion was constant in all 10 individuals over the entire time course when normalised for creatinine. There was a highly significant correlation between plasma Lp(a) levels and urinary apo(a) values. Changes in renal plasma flow and glomerular filtration rate did not alter urinary apo(a) excretion. We conclude that a constant amount of apo(a) is excreted into urine, depending on plasma Lp(a) levels, and that urinary apo(a) excretion is not altered by changes in GFR and RPF in healthy males.
NT-proBNP and cardiac events in older diabetic patients Resl, Michael; Neuhold, Stephanie; Riedl, Michaela ...
European journal of cardiovascular prevention and rehabilitation,
06/2011, Letnik:
18, Številka:
3
Journal Article
NT-proBNP is an excellent predictor of adverse events in patients with diabetes mellitus. Due to an aging population it is of interest to determine whether NT-proBNP can predict cardiac events with ...equal precision in subgroups with different ages.
1395 outpatients with diabetes mellitus were recruited for this prospective observational study. NT-proBNP, renal function, lipid status and other demographic variables were measured at baseline. The cohort was divided into three groups: Group I (609 patients under 60 years of age), group II (634 patients ranging from 60–75) and group III (152 patients older than 75). Patients were followed during a mean observation period of 11 months, 75 patients reached the defined endpoint, which was unplanned hospitalization due to a cardiac event.
Mean age was 60 ± 30 years, mean HbA1c was 7.6% and mean NT-proBNP was 242 ± 437 pg/ml. In a multiple Cox regression model, age (hazard ratio (HR) 11.18, p < 0.01) and the absence of a cardiac disease (HR 0.49, p < 0.01) were important variables for short-term prognosis. The addition of the logarithm of NT-proBNP provided independent prognostic information (HR 1.81 p < 0.01) and significantly increased the explained variance of the model (χ2 = 22.93; d.f. = 1; p < 0.01). More importantly, the predictive power of this model was similar in different age-groups.
The prognostic information of NT-proBNP was not influenced by age and this biomarker remained a reliable predictor of short-term cardiac events in patients with diabetes mellitus aged 75 years or older.
In vitro and in vivo studies in rodents and human suggested an immunostimulatory effect of prolactin. The aim of the present study was to determine the impact of chronically elevated serum prolactin ...concentrations on the immune system in patients with prolactinomas. For this purpose parameters of the humoral and cellular immune system were studied in seven patients with prolactinomas on two occasions (1) when their serum prolactin concentration had been normalized through treatment with dopamine agonists and (2) when their serum prolactin concentration was high. Serum concentrations of immunoglobulines, interleukin 1, 3 and 6, TNF-alpha, interferon-gamma and the soluble interleukin 2 receptor, leukocyte subsets and the natural killer cell activity were found to be within the normal range on both occasions, i.e. at normal and at high serum prolactin concentrations. The assumption could be made that long-lasting elevation of serum prolactin concentration induces adaptive changes when the acute stimulatory effects of prolactin on several parameters of the immune system have subsided.
Summary
Background
Coronary artery disease (CAD) is the most common cause of sudden cardiac arrest (SCA). Although coronary angiography (CAG) should be performed also in the absence of ST-elevation ...(STE) after sustained return of spontaneous circulation (ROSC), this recommendation is not well implemented in daily routine.
Methods
A retrospective database analysis was conducted in a tertiary care center between January 2005 and December 2014. We included all SCA patients aged ≥ 18 years with presumed cardiac cause and sustained ROSC in the absence of STE at hospital admission. The rate and timing of CAG were defined as the primary endpoints. As secondary endpoints, the reasons pro and contra CAG were analyzed. Furthermore, we observed if the signs and symptoms used for decision making occurred more often in patients with treatable CAD.
Results
We included 645 (53.6%) of the 1203 screened patients, CAG was performed in 343 (53.2%) patients with a diagnosis of occlusive CAD in 214 (62.4%) patients. Of these, 151 (71.0%) patients had occlusive CAD treated with coronary intervention, thrombus aspiration, or coronary artery bypass grafting. In an adjusted binomial logistic regression analysis, age ≥ 70 years, female sex, non-shockable rhythms, and cardiomyopathy were associated with withholding of CAG. In patients diagnosed and treated with occlusive CAD, initially shockable rhythms, previously diagnosed CAD, hypertension, and smoking were found more often.
Conclusion
Although selection bias is unavoidable due to the retrospective design of this study, a high proportion of the examined patients had occlusive CAD. The criteria used for patient selection may be suboptimal.
Transoesophageal echocardiography (TOE) has increasingly been described as a possible complementary and point-of-care approach for patients with cardiac arrest (CA). It provides information about ...potentially reversible causes and prognosis and allows monitoring of resuscitation efforts without affecting ongoing chest compressions. The aim of this study was to assess the feasibility of TOE performed by emergency physicians (EPs) during CA in an emergency department (ED).
This prospective study was performed at the Department of Emergency Medicine at the Medical University of Vienna from February 2020 to February 2021. All patients of ≥18 years old presenting with ongoing resuscitation efforts were screened. After exclusion of potential contraindications, a TOE examination was performed and documented by EPs according to a standardized four-view imaging protocol. The primary endpoint represents feasibility defined as successful probe insertion and acquisition of interpretable images. Of 99 patients with ongoing non-traumatic CA treated in the ED, a total of 62 patients were considered to be examined by TOE. The examination was feasible in 57 patients (92%) females, 14 (25%), mean age 53 ± 13, and witnessed collapse 48 (84%). Within these, the examiners observed 51 major findings in 32 different patients (66%). In 21 patients (37%), these findings led to a direct change of therapy. In 18 patients (32%), the examiner found ventricular contractions without detectable pulse. No TOE-related complications were found.
Our findings suggest that EPs may be able to acquire and interpret TOE images in the majority of patients during CA using a standardized four-view imaging protocol.
Since CD4+ lymphocytopenia can be caused by disturbed thymic T-cell maturation, we investigated the T-cell subsets of a 9-year-old boy fulfilling the diagnostic criteria for CD4+ lymphocytopenia in a ...follow-up period of 4 years. We found (I) reduced CD45RA expression, (II) enhanced CD45RO expression and (III) a significant increase in gamma delta TCR-bearing T cells. An accelerated apoptosis (11%) was observed in the CD45RO+, but not CD45RA+ subset. These findings provide evidence that a disturbed thymic T-cell maturation process might play a role in the pathogenesis of CD4+ lymphocytopenia.
PDF
