Predictors of breast self-examination performance among Jordanian university female students.

Breast cancer is considered one of the main types of cancer among female worldwide and in Jordan also. Early detection of it will improve the prognosis and decrease the mortality rate also. Thus, this study was conducted to assess the predictors of breast self-examination performance among Jordanian university female students. Across-sectional design was utilised in this study. A sample of 100 participants was completed the study survey (The Champion's Health Belief Model Scale). The main results or regression analysis showed that confidence (ß = .71, p < .0001) and perceived barriers (ß = -.061, p = .0004) were significant predictors of breast self-examination performance. In summary, other variables of Health belief model were found not be significant indicators of BSE performance in this study. However, the HBM is considered a valid framework to assess the predictors of breast self-examination knowledge, attitude, beliefs and barriers among Jordanian college female students.

Activation of cardiomyocytes depending on their proximity to human bone marrow stem cells.

Our study aimed to elucidate whether bone marrow stem cell (BMC) treatment might result in a cellular response in cardiomyocytes IN VITRO. Subconfluent neonatal rat cardiomyocyte cultures were cocultured for three days with Vybrant CM-DiI labeled BMC from human sternal bone marrow and underwent immunohistological staining for the proto-oncogene c-Myc and the cell cycle proteins CDK2, CDK4 and ATF-3. ß-adrenoceptor density was analyzed using [125I]-iodocyanopindolol (ICYP) histoautoradiography. Quantitative analysis of immunohistochemical images revealed significantly increased expression and upregulation of c-Myc, and its downstream targets ATF-3, CDK2 and CDK4 in neighboring cardiomyocytes to BMC, depending on their distance to the BMC compared to cardiomyocytes far from the BMC. Histoautoradiography revealed a significantly higher ß-adrenoceptor density in cardiomyocytes in the immediate vicinity to the BMC. With increasing distance to the BMC, ß-adrenoceptor density in cardiomyocytes declined. Thus, a small number of BMC can affect a larger number of cardiomyocytes by activating an intracellular signaling cascade and enhancing ß-adrenoceptor density.

Translation and validation of the Arabic version of the quality of oncology nursing care scale (QONCS): Psychometric testing in three Arabic countries.

BACKGROUND: In the Arab world, little is known about cancer patient's satisfaction with the care provided by the oncology nurses. The only explanation for this dearth of knowledge is lack of a specified, valid and reliable tool that can be utilized with all types of cancer. This regional study was conducted to translate and validate the Arabic version of quality of oncology nursing care scale (QONCS). METHODS: Brislin's model of translation was used with a cross-sectional, cross-cultural and psychometric design. A convenience sample of 517 from three countries (Jordan, Oman and Egypt) completed the study's surveys. RESULTS: The results indicated that the total QONCS-Ar was reliable with Cronbach's alpha 0.88 and 0.84, 0.87, 0.83, 0.89 and 0.86 for being supported and confirmed, with the religious and spiritual care, belonging, being valued and being respected domains respectively. Exploratory factor analysis supported the dimensional structure of the 34-item scale with five domains with Kaiser-Meyer-Oklin (KMO) measuring 0.872 and Bartlett's Test of Sphericity being significant (significant p<0.001) CONCLUSION: QONCS-Ar is a relatively short, valid, reliable and easy to use instrument that can be applied with all types of cancer, research and educational institutions in the Arabic region.

Subchronic alpha- and beta-adrenergic regulation of cardiac gap junction protein expression.

Gap junction channels are essential for intercellular electrical communication in the heart. The most important cardiac gap junction proteins are connexin43 (predominantly) (Cx43), connexin40 (Cx40), and in early developmental stages connexin45. Since catecholamines play an important role in cardiac (patho)physiology, we wanted to elucidate whether catecholamines may affect expression of Cx43 and Cx40. Cultured neonatal rat cardiomyocytes were exposed for 24 h to increasing concentrations of noradrenaline (1-10000 nM) (physiological agonist at alpha and beta-adrenoceptors), resulting in significantly increased Cx43-expression, while Cx40 was unaffected. In further experiments cells were incubated with either phenylephrine (alpha-adrenergic agonist) or isoproterenol (beta-adrenergic agonist) (0.1-1000 nM) for 24 h. Both catecholamines lead to a concentration-dependent increase in Cx43 protein and mRNA expression (EC50: 10-20 nM). Inhibition experiments showed that the phenylephrine effect was transduced via PKC, while the isoproterenol effect was mediated by PKA. Dual whole-cell voltage clamp demonstrated that increased Cx43-expression was accompanied by significant increases in gap junction current. In additional in vivo experiments, adult rats were subjected to 24-h infusion of isoproterenol or phenylephrine showing again significant increase in Cx43 but not Cx40. Adrenergic stimulation of cardiomyocytes can enhance Cx43 expression thereby increasing cellular coupling, indicating a possible role for catecholamines in the regulation of cardiac gap junction expression in cardiac disease.

Lung protection in cardio-pulmonary bypass.

Since the invention of the heart-lung machine paediatric cardiac surgery developed rapidly. For correction of complex cardiac malformations the application of a cardio-pulmonary bypass (CPB) has become indispensable but possible negative effects of this technique should not be neglected. Especially, both bypassed organs i.e. heart and lung are not perfused during the procedure and therefore are threatened by ischemia and reperfusion injury. Additionally, CPB was developed with a non-pulsatile flow but there are clinical observations that pulsatile flow might be superior with improved patient outcomes. Thus, the aim of our study was to evaluate the effect of CPB on lung structure and to assess whether different flow modalities (pulsatile vs. non-pulsatile flow) or application of the antibiotic minocycline might be advantageous. Thirty five piglets of four weeks age were examined and divided into five experimental groups: control (no CPB) without or with minocycline, CPB (non-pulsatile flow) without or with minocycline and CPB with pulsatile flow. CPB was performed for 90 min followed by a 120 min reperfusion and recovery phase. Thereafter, adenosine triphosphate-content of lung biopsies and histology was carried out. We found that CPB was associated with a significant thickening of alveolar wall accompanied by an infiltration of neutrophil leucocytes. Moreover, markers for hypoxia, apoptosis, nitrosative stress, inflammation and DNA damage were significantly elevated after CPB. These cellular damages could be partially inhibited by minocycline or pulsatile flow. Both, minocycline and pulsatile flow attenuate lung damage after CPB.

Relationship between achieved personalized glycaemic targets and monitoring of clinical events in elderly diabetic patients.

AIM: Recent guidelines for the management of type 2 diabetes (T2DM) in the elderly recommend adjusting the therapeutic target (HbA1c) according to the patient's health. Our study aimed to explore the association between achieving the recommended personalized HbA1c target and the occurrence of major clinical events under real-life conditions. METHODS: The T2DM S.AGES cohort was a prospective multicentre study into which 213 general practitioners recruited 983 non-institutionalized T2DM patients aged>65 years. The recommended personalized HbA1c targets were<7%, <8% and <9% for healthy, ill and very ill patients, respectively. Major clinical events (death from any cause, major vascular events and/or hospitalization) were recorded during the 3-year follow-up. Mixed-effects logistic regression models were used for the analyses. RESULTS: Of the 747 patients analyzed at baseline, 551 (76.8%) were at their recommended personalized HbA1c target. During follow-up, 391 patients (52.3%) experienced a major clinical event. Of the patients who did not achieve their personalized HbA1c target (compared with those who did), the risk (OR) of a major clinical event was 0.95 (95% CI: 0.69-1.31; P=0.76). The risk of death, major vascular event and hospitalization were 0.88 (95% CI: 0.40-1.94; P=0.75), 1.14 (95% CI: 0.7-1.83; P=0.59) and 0.84 (95% CI: 0.60-1.18; P=0.32), respectively. CONCLUSION: Over a 3-year follow-up period, our results showed no difference in risk of a major clinical event among patients, regardless of whether or not they achieved their personalized recommended HbA1c target. These results need to be confirmed before implementing a more permissive strategy for treating T2DM in elderly patients.

Efficient and heritable functional knock-out of an adult phenotype in Drosophila using a GAL4-driven hairpin RNA incorporating a heterologous spacer.

We have developed a modified RNA interference (RNAi) method for generating gene knock-outs in Drosophila melanogaster. We used the sequence of the yellow (y) locus to construct an inverted repeat that will form a double-stranded hairpin structure (y-IR) that is under the control of the upstream activating sequence (UAS) of the yeast transcriptional activator GAL4. Hairpins are extremely difficult to manipulate in Escherichia coli, so our method makes use of a heterologous 330 bp spacer encoding sequences from green fluorescent protein to facilitate the cloning steps. When the UAS-y-IR hairpin is expressed under the control of different promoter-GAL4 fusions, a high frequency of y pigment phenocopies is obtained in adults. Consequently this method for producing gene knock-outs has several advantages over previous methods in that it is applicable to any gene within the fly genome, greatly facilitates cloning of the hairpin, can be used if required with GAL4 drivers to avoid lethality or to induce RNAi in a specific developmental stage and/or tissue, is useful for generating knock-outs of adult phenotypes as reported here and, finally, the system can be manipulated to investigate the trans-acting factors that are involved in the RNAi mechanism.

Influence of chronic exposure to high concentrations of D-glucose and long-term beta-blocker treatment on intracellular calcium concentrations of porcine aortic endothelial cells.

Clinical observations indicate that diabetes leads to micro- and macroangiopathy involving endothelial dysfunction. Because recent studies indicate an antiangiopathic effect of celiprolol, but not of metoprolol, in type 1 diabetes, we investigated the direct influence of exposure to high D-glucose concentrations on endothelial cells and the possible effects of both beta-blockers. Nine different chronic treatments were carried out on cultured porcine aortic endothelial cells: 1) 5 mmol/l D-glucose ("normoglycemic" cells), 2) 5 mmol/l D-glucose plus 15 mmol/l L-glucose (osmotic control), 3) 5 mmol/l D-glucose plus 0.5 micromol/l celiprolol, 4) 5 mmol/l D-glucose plus 0.05 micromol/l metoprolol, 5) 5 mmol/l D-glucose plus 0.5 micromol/l celiprolol plus 5 micromol/l propranolol, 6) 20 mmol/l D-glucose ("hyperglycemic" cells), 7) 20 mmol/l D-glucose plus 0.5 micromol/l celiprolol, 8) 20 mmol/l D-glucose plus 0.05 micromol/l metoprolol, and 9) 20 mmol/l D-glucose plus 0.5 micromol/l celiprolol plus 5 micromol/l propranolol. Using the Fura-2 technique, application of either 1 nmol/l bradykinin or 1 micromol/l ATP to the normoglycemic endothelial cells led to a significant increase in intracellular calcium, whereas the hyperglycemic cells showed significantly less reactivity to both agents. Exposure of endothelial cells to L-glucose did not show any difference to normoglycemic controls. Coadministration of 20 mmol/l glucose and celiprolol demonstrated that the alteration of the calcium signal induced by high D-glucose concentrations could be significantly antagonized with celiprolol. In contrast, coincubation with metoprolol failed to normalize the calcium signal. This effect of celiprolol was completely abolished in the presence of propranolol. In normoglycemic cells, none of the beta-blockers influenced the intracellular calcium response to bradykinin or ATP. These results indicate that chronic treatment with high D-glucose concentrations leads to an impairment of calcium signaling, which might be ameliorated by celiprolol.

Depletion of white adipocyte progenitors induces beige adipocyte differentiation and suppresses obesity development.

Overgrowth of white adipose tissue (WAT) in obesity occurs as a result of adipocyte hypertrophy and hyperplasia. Expansion and renewal of adipocytes relies on proliferation and differentiation of white adipocyte progenitors (WAP); however, the requirement of WAP for obesity development has not been proven. Here, we investigate whether depletion of WAP can be used to prevent WAT expansion. We test this approach by using a hunter-killer peptide designed to induce apoptosis selectively in WAP. We show that targeted WAP cytoablation results in a long-term WAT growth suppression despite increased caloric intake in a mouse diet-induced obesity model. Our data indicate that WAP depletion results in a compensatory population of adipose tissue with beige adipocytes. Consistent with reported thermogenic capacity of beige adipose tissue, WAP-depleted mice display increased energy expenditure. We conclude that targeting of white adipocyte progenitors could be developed as a strategy to sustained modulation of WAT metabolic activity.

The effect of the calcium-antagonist nitrendipine on intracellular calcium concentration in endothelial cells.

1. Nitrendipine induces NO-release from coronary vascular endothelium presumably by activating endothelial NO-synthase. We have investigated whether this effect may be mediated by an influence on the intracellular calcium in endothelial cells. 2. Bovine aortic endothelial cells (BAEC) were incubated with Fura-2/AM (1 microM) for 30 min and Fura-2 fluorescence was measured at 510 nm in response to chopped excitation with both 340 and 380 nm. The ratio 340/380 nm (known to reflect changes in intracellular calcium) was calculated from these data. 3. Nitrendipine (0.1 to 100 microM) led to a significant, concentration-dependent, monophasic increase in [Ca2+]i in suspended BAEC by 11 +/- 2 nM (0.1 microM), 23 +/- 3 nM (1 microM), 34 +/- 4 nM (10 microM) and by 47 +/- 5 nM (100 microM) from a control levels of 118 +/- 10 nM. 4. This elevation of intracellular calcium was prevented by pretreatment of BAECs with gadolinium (100 microM) or by incubation with calcium free saline solution. In contrast, the application of 0.3 microM thapsigargin did not abolish the nitrendipine-induced calcium signal. In additional experiments it was shown that the nitrendipine-induced NO-release (as measured with the oxy-haemoglobin-method could also be inhibited by gadolinium and was absent in calcium-free solution. 5. Thus, nitrendipine elevates intracellular calcium in suspended BAECs in a concentration-dependent manner. This elevation is mainly due to a gadolinium-sensitive calcium influx from the extracellular space rather than a calcium release from intracellular stores.

Dual mode of action of dihydropyridine calcium antagonists: a role for nitric oxide.

Dihydropyridine calcium antagonists have been used for many years in the treatment of angina pectoris and hypertension. According to the common view, their mechanism of action is based on an inhibition of the smooth muscle L-type calcium current, thus decreasing intracellular calcium concentration and inducing smooth muscular relaxation. However, in recent years evidence has accumulated that besides the smooth muscle effects of these agents, their effect on the endothelium must also to be taken into account. It was shown that dihydropyridines can induce the release of nitric oxide (NO) from the vascular endothelium of various vessels and in different species. This was first shown by Günther and colleagues by assaying the methaemoglobin formation in the presence of intact endothelium (in porcine coronary arteries) with and without treatment with nitrendipine. These findings were later confirmed by direct measurement of NO or of nitrite production. In addition, in several preparations, including micro- and macrovasculature, the sensitivity of the vasorelaxing effect of the dihydropyridines to inhibitors of NO-synthase, such as L-N(G)-nitroarginine (LNNA) or L-N-nitro-arginine-methyl-ester (L-NAME), has been shown. With these studies it became evident that the NO-releasing effect was not unique to nitrendipine but was a group phenomenon shared by the dihydropyridines and several nondihydropyridine calcium antagonists. In addition to their action on vascular endothelium, NO release by nifedipine has also been detected in platelets. There are also studies showing long term effects of calcium antagonists involving NO release. Regarding the underlying mechanism of NO release, nitrendipine was shown, not to decrease but to increase intracellular Ca2+ in cultured endothelial cells. This increase was sensitive to both Ca2+-free extracellular superfusion and to gadolinium, a lanthanide known to inhibit shear-stress activated cation channels. This increase in intracellular calcium can activate endothelial NO-synthase, thus inducing the release of NO. These findings on a dual mode of action, i.e. the direct relaxing effect by inhibition of the smooth muscle L-type calcium current and indirect relaxing effect by release of NO from vascular endothelium may help to understand the beneficial antihypertensive effects of the dihydropyridine calcium antagonists and the preferential effect of certain drugs in certain vascular regions (resistance versus conductive vessels). In addition, NO release from both vascular endothelium and platelets may contribute to the antiatherosclerotic and antithrombotic effects described for certain dihydropyridines.

Acetylsalicylic acid enhances arrhythmogeneity in a model of local ischemia of isolated rabbit hearts.

Acetylsalicylic acid often is used in the treatment and prophylaxis of regional myocardial ischemia and infarction. However, only little is known about its electrophysiological effects and on possible proarrhythmic effects of the drug. Thus, the aim of this study was to evaluate the electrophysiological effects of acetylsalicylic acid in normal isolated saline perfused rabbit hearts and in hearts submitted to regional ischemia. Isolated saline perfused rabbit hearts were treated with increasing concentrations of acetylsalicylic acid (0.05, 0.1, 0.5 and 1 microM). The epicardial activation and repolarisation process were analysed using an epicardial mapping (256 unipolar leads). Activation and repolarisation time were determined for each electrode from which data the 'breakthrough-points' of epicardial activation were determined. At each electrode an activation vector was calculated giving the direction and velocity of the local excitation wave. The similarity of selected heart beats compared to the control was evaluated by determination of the percentage of identical breakthrough-points and of similar vectors (deviation < or = 5 degrees). At each electrode the local epicardial action potential duration was assessed as the activation recovery interval and the standard deviation of the epicardial action potential duration (of 256 leads, = dispersion) was determined. In a second series of experiments 30 min regional ischemia was induced by occlusion of the left descendent coronary artery followed by 30 min reperfusion in the absence or presence of 0.5 microM acetylsalicylic acid or 1 micro/M indomethacin. The degree of ischemia was assessed by the reduction in coronary flow, by the degree of ST-elevation and by the area in which ST-elevation was registered. Under non-ischemic conditions acetylsalicylic acid led to an increase in the epicardial action potential duration (7%), a decrease in the breakthrough-point similarity (by 10%) and vectorfield similarity (by 15%). In control hearts submitted to regional ischemia the similarity of the vectorfields and of the breakthrough-points, as well as the duration of the epicardial action potentials were markedly reduced while the dispersion was greatly increased. In the ischemic region there was a significant ST-deviation from the isoelectrical line. These changes of ST-segments were significantly enhanced by 0.5 microM acetylsalicylic acid, so that in all (7/7) acetylsalicylic acid treated hearts sustained ventricular fibrillation occurred after 20 min ischemia, whereas in the absence of acetylsalicylic acid fibrillation was found in only 2/7 hearts during reperfusion and not during ischemia. 1 microM indomethacin did not cause these changes. In all ischemia/reperfusion series of experiments the reduction in coronary flow and left ventricular pressure by ischemia was of the same degree and we did not observe significant differences in the size of ischemic area. Using 14C-acetylsalicylic acid, an accumulation of acetylsalicylic acid in the ischemic region could be observed. From these results we conclude, that acetylsalicylic acid can induce ventricular fibrillation. Thus, in acute myocardial ischemia, acetylsalicylic acid may have (besides the well known and desired antiaggregatory effects) electrophysiologic side effects which seem to be proarrhythmic in regional ischemia at least in this model.

Chronic regulation of the expression of the gap junction protein connexin 43 in transfected HeLa cells.

Gap junction channels are essential for intercellular communication. Among the most abundant gap junction channel proteins is connexin 43 (Cx43). The goal of our study was to find out, whether Cx43 content may be regulated via adenylyl cyclase (AC)/cAMP/protein kinase A (PKA), protein kinase C (PKC) pathways or by a tyrosine kinase coupled pathway, i.e. TNF alpha-receptor dependent pathway. Therefore, we used HeLa cells transfected with Cx43 and exposed these cells for 24 h to either db-cAMP (10(-4)M), forskolin (10(-5)M), the phorbolester phorbol-12,13-didecanoate PDD (10(-7)M) (or its inactive form 4 alpha-PDD), TNF alpha (10 U/ml) with or without additional treatment with the MAP kinase inhibitors SB203580 (10(-5) M, p38 MAP-kinase inhibitor) or the MEK1-inhibitor PD98059 (10(-5)M). Cx43 content was analysed using Western blot analysis. All results were confirmed by a second series of identical experiments using Cx43 immunohistochemistry. We found significantly enhanced Cx43 content in cells treated with db-cAMP, forskolin, PDD or TNF alpha (p<0.05), while 4 alpha-PDD or the solvent DMSO exerted no effect. These increases in Cx43 content could be completely suppressed by SB203580 (p<0.05) but not by PD98059. In absence of a stimulating drug, these inhibitors (SB203580 or PD98059) did not affect Cx43 content. Additional PCR experiments revealed increases in Cx43-mRNA under the influence of db-cAMP, forskolin, PDD or TNFalpha (p<0.05), which all could be completely suppressed by SB203580. From these results we conclude that 1.Cx43 content can be regulated via AC/cAMP/PKA, PKC and TNF alpha-receptor-dependent pathways 2. Activation of p38 MAP kinase is a common pathway for regulation of Cx43 content in HeLa cells

Propranolol unmasks class III like electrophysiological properties of norepinephrine.

Isolated perfused spontaneously beating rabbit hearts were treated with increasing concentrations of norepinephrine (0.01, 0.1, 0.5 mumol/l) either alone or in presence of propranolol (0.1 mumol/l). For analysis of the epicardial activation and repolarization process and epicardial mapping (256 unipolar leads) was performed. For each electrode the activation and repolarization time was determined. From these data the "breakthrough-points" (BTP) of epicardial activation were determined. At each electrode an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heart beats (under NE) compared to control was evaluated by determination of the percentage of identical BTP and of similar VEC (deviation < or = 5 degrees). Moreover at each electrode the local activation recovery interval (ARI) and its standard deviation (of 256 leads, dispersion, DISP) were determined. Norepinephrine alone (0.01, 0.1, 0.5 mumol/l) led to an increase in left ventricular pressure, heart rate and DISP with concomitant frequency dependent reduction in ARI, and to changes in the epicardial activation pattern (reduction in BTP, VEC). We found that in the presence of propranolol (0.1 mumol/l) norepinephrine prolonged ARI and reduced ARI-dispersion. This effect was not due to changes in heart rate. The disturbing effects on the activation pattern were diminished. These effects could be prevented by pretreatment with 1 mumol/l prazosin. From these results we conclude, that norepinephrine prolongs the relative action potential duration via stimulation of alpha 1-adrenoceptor and enhances cellular coupling.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxyphil cell carcinoma of the parathyroid: a rare cause of hyperparathyroidism.

Oxyphil carcinoma of the parathyroid is an extremely rare tumour, only two previous patients having been reported. We report a 55-year-old woman with this condition, who presented with a picture of hyperparathyroidism, including hypercalcaemia, hypercalciuria, hypophosphataemia, increased alkaline phosphatase, and bony lesions. Biopsy of a bone lesion was consistent with brown tumour. Fine needle aspiration cytology and subsequent operative histology of the parathyroid lesion showed an oxyphil cell tumour with malignant characteristics. Following excision, the patient made a good recovery, complicated only by postoperative hypocalcaemia.

Comparative nephrotoxic effects of cis-platinum (II), cis-palladium (II), and cis-rhodium (III) metal coordination compounds in rat kidneys.

A Sprague-Dawley rat kidney perfusion technique was used in situ to study the effects of cis-dichloro-diamine platinum, PdCl2 (2,6-diaminopyridine), and RhCl3 (2,6-diaminopyridine) on sodium and calcium retention in the whole kidney. The technique involves perfusion of both kidneys via the abdominal aorta and then through the right and left renal arteries and dorsal aorta. Compared to controls, kidneys perfused independently with the three coordination compounds showed approximately equal to 45% decrease and approximately equal to 117% increase in Na+ and Ca2+ retention, respectively. Perfusates containing the coordination compounds in addition to 15 mM ouabain showed approximately equal to 76% decrease in Na+ and insignificant increase in renal Ca2+ retention. Hence, one can rule out the presence of voltage-gated Ca(2+)-channels at the basolateral side due to membrane depolarization. These results suggest that the three metal coordination compounds showed identical nephrotoxic effects on the handling of Na+ and Ca2+ ions by inhibiting both the Na(+)-Ca(2+)-anti-porter and the Na(+)-H(+)-exchanger with laxing effects on nonvoltage-gated Ca(2+)-channels at the basolateral side. However, their effects on the Na(+)-K(+)-ATPase and the Na(+)-Ca2+ symporter was insignificant.

[Thrombotic thrombocytopenic purpura (Moschkowitz-syndrome) caused by ticlopidine]. / Thrombotisch-thrombozytopenische Purpura (Moschcowitz-Syndrom), verursacht durch Ticlopidin.

BACKGROUND: Only in a few case reports the thrombotic thrombocytopenic purpura was related to ticlopidine with a controversial discussion about this association. CASE REPORT: In a 57-year-old female patient, who was admitted with fluctuating central neurological abnormalities and generalized purpura, was made the diagnosis of a thrombotic thrombocytopenic purpura (TTP, Moschcowitz' syndrome). On admission there were a distinct anemia and thrombocytopenia. Corresponding to the hemolysis the laboratory findings showed raised reticulocytes and elevated LDH with > 900 U/l. The peripheral blood smear showed an enrichment of fragmented red cells (15%) and the bone marrow indicated a hyperplastic erythrocytopoesis and a left shift in megakaryocytopoesis. An increase of eosinophilic granulocytes and the tissue basophilic cells directed to a possible allergic phenomenon of the underlying disease. Until 3 weeks before admission she had been on ticlopidine after a left heart catheter with stenting the left coronary artery 6 weeks earlier. Beside taking of acetylsalicylacid and thyroid hormone there was no other regular medication. An early treatment with fresh frozen plasma and plasmapheresis with plasma exchange with fresh frozen plasma led directly to an elevation of thrombocytes and a normalization of hemolytic parameters. CONCLUSION: This case demonstrates the possible relationship between thrombotic thrombocytopenic purpura and the administration of ticlopidine.

Cardiac fibroblasts inhibit ß-adrenoceptor-dependent connexin43 expression in neonatal rat cardiomyocytes.

Cardiac fibroblasts play an important role in adverse cardiac remodelling. As in many cardiac diseases connexin43 (Cx43) is altered, we wanted to elucidate whether fibroblasts may influence cardiac Cx43 expression. We used four different cell culture systems of neonatal rat cardiomyocytes (CM) and fibroblasts (FB): type 1, pure CM culture; type 2, co-culture of CM/FB; type 3, pure FB culture; type 4, Transwell® system: CM/FB co-cultured but separated by a microporous membrane. Stimulation of types 1-3 cell culture models with isoprenaline significantly enhanced Cx43-protein and Cx43-mRNA expression as well as phosphorylation of ERK and translocation of AP1 and CREB only in the CM cultures; whereas, the CM/FB co-cultures and the FB cultures did not respond to isoprenaline. Similarly, if CM and FB were separated by a microporous membrane (Transwell® system) the isoprenaline-induced increase in CM Cx43 was completely suppressed, suggesting the existence of a soluble factor responsible for the suppressant effect of FB. Angiotensin II determination in types 1 and 2 cell culture supernatants revealed that the CM/FB co-cultures exhibited a significant higher angiotensin II release than the CM cultures. Furthermore, we aimed to inhibit angiotensin II signal transduction pathway: blockade of AT1 receptors or PKC inhibition restored the responsiveness of CM/FB co-cultures to isoprenaline. Moreover, external addition of angiotensin II to CM cultures also resulted in suppression of isoprenaline-stimulated Cx43 expression in an AT1-receptor- and PKC-dependent manner. Thus, our study indicates that cardiac fibroblasts inhibit ß-adrenoceptor-dependent Cx43 signalling in CM involving angiotensin II.

[Update on endocrine hypertension]. / Données récentes sur l'hypertension endocrine.

Endocrine hypertension is the most common cause of secondary hypertension affecting ~3 % of the population, with primary hyperaldosteronism and pheochromocytoma being the principal conditions. Both diseases share an increased cardiovascular risk in comparison with essential hypertension patients (at the same blood pressure level). This augmented cardiovascular risk as well as the availability of specific treatment emphasize the importance of timely and correct diagnosis. Primary hyperaldosteronism, representing one tenth of hypertensive patients, is an under-diagnosed disease partly because of difficult diagnostic steps and absence of standard criteria. Recently, the description of somatic mutations in KCNJ5 gene in Conn adenomas had precipitated a resurgence of research activity to understand the pathophysiology of this common disease. Research had confirmed the role of these mutations in aldosterone hypersecretion; however, its role in adenoma formation is still to be elucidated. Elsewhere, much remains to be done in order to understand the pathogenesis of bilateral idiopathic hyperaldosteronism, the other common subtype of primary hyperaldosteronism. In pheochromocytoma, the revolution of genetics has led to major advances in the characterization of this rare disease. It is now clear that up to 50 % of patients with pheochromocytoma have a genetic abnormality and that different pheochromocytomas segregate into two clusters with distinct genotypes, signal transduction pathways and expression of biomarkers (phenotype). This continuing progress has huge effects on patient's management and follow-up. In this article we will shed light on the recent developments in both diseases with emphasis on their role in patient care.