The effects of seasonal variations and weather conditions on the occurrence of heart attacks in Hungary between 2000-2004

INTRODUCTION: The onset of acute myocardial infarct shows circadian and seasonal variations, that are influenced by sex, age and the changes of weather conditions as well. AIM: The purpose of our present study is to investigate whether a seasonal variation can be found in the onset of myocardial infarctions during the period under investigation, and whether certain meteorological factors (air temperature, atmospheric pressure, front movements) influence the incidence of myocardial infarction. METHODS: Retrospective analysis has been carried out on patients admitted because of acute myocardial infarct in Hungary between 2000 and 2004 ( n=81.956). Data have been taken from the database of the National Health Insurance Fund Administration based on the International Classification of Diseases (ICD). Weather related data were provided by the National Meteorology Service. RESULTS: Regarding seasonal distribution the peak incidence period of acute myocardial infarct was spring, whereas the lowest number of events was observed during the summer months. There was a marked difference in the number of events per season ( p<0.001). A medium level negative correlation was found between the monthly average temperature and the occurrence of heart attack ( r=-0.404) during the period examined. A positive correlation was shown between front movements and the of number of events per season ( r=0.053). CONCLUSION: Our findings show that certain meteorological factors may be related to the onset of acute myocardial infarct, however, a number of other factors may also play an important role.     

The collecting duct is the major source of prorenin in diabetes

In addition to the juxtaglomerular apparatus, renin is also synthesized in renal tubular epithelium, including the collecting duct (CD). Angiotensin (Ang) II differentially regulates the synthesis of juxtaglomerular (inhibition) and CD (stimulation) renin. Because diabetes mellitus, a disease with high intrarenal renin-Ang system and Ang II activity, is characterized by high prorenin levels, we hypothesized that the CD is the major source of prorenin in diabetes. Renin granular content was visualized using in vivo multiphoton microscopy of the kidney in diabetic Munich-Wistar rats. Diabetes caused a 3.5-fold increase in CD renin, in contrast to less pronounced juxtaglomerular changes. Ang II type 1 receptor blockade with Olmesartan reduced CD renin to control levels but significantly increased juxtaglomerular renin. Using a fluorogenic renin assay, the prorenin component of CD renin content was measured by assessing the difference in enzymatic activity of medullary homogenates before and after trypsin activation of prorenin. Trypsinization caused no change in control renin activity but a 5-fold increase in diabetes. Studies on a CD cell line (M1) showed a 22-fold increase in renin activity after trypsinization and a further 35-fold increase with Ang II treatment. Therefore, prorenin significantly contributes to baseline CD renin. Diabetes, possibly via Ang II, greatly stimulates CD prorenin and causes hyperplasia of renin-producing connecting segments. These novel findings suggest that, in a rat model of diabetes, prorenin content and release from the CD may be more important than the juxtaglomerular apparatus in contrast to the existing paradigm.     

The potential role of FDG PET-CT in the characterization of the activity of Crohn’s disease,staging follow-up and prognosis estimation: a pilot study

Objectives: FDG PET-CT is a global, noninvasive, sensitive method to determine the location and activity of inflammatory lesions. Segmental FDG uptake is proportional with immune cell infiltration of bowel. Our aim was to evaluate prospectively the role of PET in patients with active Crohn’s disease (CD) before and after one year’s biological therapy, and to compare simple endoscopic score for CD (SES-CD), CD activity index (CDAI) and global PET scores. We also analyzed the prognostic value of initial PET scores.

Patients: Twelve patients were selected: six male/six female, ages between 18 and 39, average: 24 years, with CDAI values >300.

Methods: We scored the FDG uptake in the small intestine and the four colon segments (on a scale 0–3 for each), and summed them thus forming a global PET score. The scoring was based on the maximal standardized uptake value of the intestinal segment, related to the SUVmax of the liver (as a reference for normal tissue activity). The SES-CD, CDAI and global PET scores before and after treatment were statistically compared.

Results: There were significant changes in CDAI and SES-CD after therapy, PET scores improved only in patients’ subgroup with high (>4) initial PET score, indicating good prognosis of biological treatment. In active disease, PET was more informative than endoscopy to access the extent of the inflammation, and small intestine involvement.

Conclusions: FDG PET-CT score is a promising, noninvasive complementary method in the staging, treatment planning and follow-up of CD. Limitation of the study is the small number of patients.     

Selective NR1/2B N-methyl-D-aspartate receptor antagonists among indole-2-carboxamides and benzimidazole-2-carboxamides

(4-Benzylpiperidine-1-yl)-(6-hydroxy-1H-indole-2-yl)-methanone (6a) derived from (E)-1-(4-benzylpiperidin-1-yl)-3-(4-hydroxy-phenyl)-propenone (5) was identified as a potent NR2B subunit-selective antagonist of the NMDA receptor. To establish the structure-activity relationship (SAR) and to attempt the improvement of the ADME properties of the lead, a series of compounds were prepared and tested. Several derivatives showed low nanomolar activity both in the binding and in the functional assay. In a formalin-induced hyperalgesia model in mice, 6a and (4-benzylpiperidine-1-yl)-[5(6)-hydroxy-1H-benzimidazol-2-yl]-methanone (60a) were as active as besonprodil (2) after oral administration. A CoMSIA model was developed based on binding data of a series of indole- and benzimidazole-2-carboxamides.     

Molecular epidemiology of VIM-4 metallo-beta-lactamase-producing Pseudomonas sp. isolates in Hungary

VIM metallo-beta-lactamase-producing serotype O11 or O12 Pseudomonas aeruginosa isolates infecting or colonizing 19 patients from seven hospitals in Hungary were characterized between October 2003 and November 2005. Macrorestriction analysis revealed the involvement of hospitals from three different towns in northwest Hungary in an outbreak caused by VIM-4-producing P. aeruginosa.     

Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney

Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein-coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products through renal hyperfiltration, and it could also link metabolic diseases, such as diabetes, or metabolic syndrome with RAS overactivation, systemic hypertension, and organ injury.     

Orlistat increases serum paraoxonase activity in obese patients

Background and aimPrevious studies have demonstrated that oxidative stress is increased in obese patients. The high-density lipoprotein (HDL) associated human paraoxonase 1 (PON1) can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. Our objective was to assess the effects of orlistat therapy combined with diet on body mass index (BMI), waist circumference, lipid parameters, blood pressure, serum glucose level and PON1 activity.Methods and resultsA longitudinal, multicenter, randomized study with and without orlistat treatment was performed. One hundred thirty nine otherwise healthy, obese subjects were divided in to two groups: 78 persons received orlistat (120 mg three times a day) combined with diet while 61 persons were kept on diet only. Anthropometrical parameters, serum lipid levels and PON1 activity were measured at baseline and after 6 months of treatment. BMI and waist circumference were reduced more pronouncedly in the orlistat group than in the control group. Patients receiving orlistat also had significantly greater improvements in fasting blood glucose levels and blood pressure. The orlistat-treated group showed a greater reduction in total cholesterol and triglyceride levels. In addition, the serum PON1 activity in these patients was significantly increased compared to the diet-only group.ConclusionsThe 6-month treatment with orlistat had a beneficial effect on the lipid profile and improved the antioxidant status by increasing serum PON1 activity. However, because of the limited therapeutic effectiveness, obese patients with hypercholesterolemia should receive additional lipid lowering medications.