Roczniki Akademii Medycznej w Bialymstoku (1995)最新文献

Purpose: The purpose of the present study was to determine whether extracellular osmotic pressure modulates beta2-adrenergic stimulation of the contraction force and L-type Ca2+ current in human atrial myocytes.

Material and methods: Experiments were performed on human atrial trabeculae and myocytes isolated from the right atrium. The concentration dependent effect of salbutamol (SAL), a beta2-adrenoreceptor agonist, on peak tension (P) and L-type calcium current (ICaL) under isoosmolar (345 mOsm) and hyperosmolar (405 or 525 mOsm was achieved by adding of mannitol) conditions was studied.

Results: Salbutamol (10 nmol/L-10 micromol/L) added to the control solution increased P by 180.6 +/- 45.8% over control with a half-stimulation constant EC50 = 27 +/- 6 nmol/L. Under isoosmolar conditions SAL (0.1/10(3)nmol/L) increased ICaL by 182.3 +/- 19.8% over control with an EC50 2.9 +/- 0.9 nmol/L. In hyperosmolar solutions the same concentrations of SAL increased P and ICaL by 57.2 +/- 12.6% and 217.2 +/- 70.5% over control with EC50 = 640 +/- 260 nmol/L and 12 +/- 5 nmol/L respectively.

Conclusions: These results indicated that hyperosmolarity reduced the effect of beta2-adrenergic stimulation, i.e. the dose-response curve of salbutamol on L-type calcium current was shifted to the higher concentration range and maximal increase in contraction force was diminished in human atrial cells.

Purpose: The aim of the study was to estimate the anthropometric parameters and their relationship to serum levels of IGF-I, IGF-II, IGFBP-3, IGFBP-2 and leptin before and during intensive antineoplastic treatment for acute lymphoblastic leukaemia in children.

Material and methods: In 46 children in median age 6.6 years (range from 1.6 to 16) we evaluated at the time of diagnosis, after protocol I and after intensive treatment, height, body mass index (BMI) and IGF-I, IGF-II, IGFBP-3, IGFBP-2 and leptin.

Results: Height SDS lowered in successive points of analysis whereas BMI SDS rose after protocol II. IGF-I SDS was low and similar at each point, IGF-II SDS and IGFBP-3 SDS values augmented progressively and IGFBP-2 SDS was significantly elevated before treatment and lowered (but not normalized) during the therapy. Leptin SDS was elevated, especially after protocol I.

Conclusion: Leukaemia and its treatment affect directly growth factors, its binding proteins and leptin production leading to growth retardation and overweight.

Heart failure (HF) is a pathophysiological condition, when the heart can not provide adequate blood flow to the body organs. The main cause of HF is now ischemic heart disease (IHD), and the number of patients with HF in aging society is growing. HF is becoming the leading cause of death. Medical therapy does not provide satisfactory results in respect of symptoms and survival (5 year survival 28-40%). Therefore there is a trend towards early invasive methods of IHD treatment: percutaneous or surgical revascularisation and surgical reconstruction of myocardial damage. Most common surgical procedure in IHD is coronary artery bypass grafting (CABG). This treatment is safe and effective in patients with normal ventricular function (operative mortality 0.5%, 5 year survival >92%). Results in patients with impaired left ventricular (LV) function are better than conservative therapy, but still not satisfactory (operative mortality 8.4%, 5 year survival 65%). The modern surgical concept for improvement of ventricular function is left ventricular (LV) shape and volume restoration (SVR) accompanied by CABG. In cases of severe damage of myocardium resulting in left ventricular aneurysm or akinesia, SVR improves LV function and prevents further LV remodeling. At present it is under investigation whether SVR is of benefit for moderate-sized ventricles and NYHA class II symptoms. In case of ischemic mitral insufficiency mitral valve repair is a method of choice. The results of combined procedures in Heart Failure group (CABG + MV reconstruction or SVR) are better than CABG alone. Other surgical alternatives for HF treatment are: heart transplantation, ventricular assist devices (VAD), dynamic cardiomyoplasty, constrictive devices and cellular transplantation therapy. Heart transplantation is reserved for younger patients with less comorbidities. Shortage of donor organs and poor long-term results remains a main problem of such a treatment. VAD at present is still very expensive, and serves particularly as a "bridge to heart transplantation" or "bridge to recovery" rather than destination therapy. Despite of all achievements in medical or invasive HF treatment further basic and clinical works as well as new organization systems are necessary to find optimal strategies to reduce cost of care, improve quality of life and survival.

Purpose: To evaluate the effect of endurance exercise on the activity changes of selected lysosomal enzymes in particular types of rat muscle fibers, occurring by 0-4 days following the trial.

Material and methods: The experiment was performed on 3 month old male Wistar rats with body mass 250 +/- 25 g, exposed to single physical exercise on moving track (speed 17 m x min(-1), decline 0 degree, duration 87.5 +/- 27.5 min). Biochemical analyses were performed on homogenized fast-twitch FTa and FTb (m. gastrocnemius) and slow-twitch ST (m. soleus) muscle fibers of animals sacrificed 2 h (group II), 6 h (III) or 96 h (IV) after exercise and control group. The measurements considered protein concentration and the activities of beta-glucuronidase (beta-GRS), N-acetyl-beta-D-glucosaminidase (NAG), and arylsulphatase A (ASA).

Results: In FTa fibers, ASA and beta-GRS activities were elevated in all the exercised groups, with the most evident changes in animals tested 96 h post trial (group IV), while the peak of NAG activity was demonstrated 2 h after exercise (group II). In contrast, in FTb and ST fibers the levels of all the enzymes studied peaked 96 h after exercise, following the transient decrease in activity.

Conclusions: The present study demonstrated that maximal running exercise, without the eccentric components, affects the activities of lysosomal enzymes in all types of rat muscular fibers. The lack of uniform activity profile for the lysosomal enzymes studied probably reflects the variety of their cellular functions.

The changes caused by Helicobacter pylori are a slow, progressing inflammatory process developing from several to dozen years. H. pylori infection leads to an inflammatory response in the gastric mucosa with granulocyte infiltrates in an acute form of the inflammation, and lymphocytes, plasmatic, macrophages and eosinophils in a chronic form inducing the development of gastric and duodenal ulcers and gastric cancer in some patients. The frequency and the type of morphological changes in the gastric mucosa were analyzed in children with positive IgG against H. pylori and the incidence of gastric and duodenal ulcers in family members of children examined was evaluated in our study. Gastritis was reported in 68.8% of children with positive IgG against H. pylori. Gastric ulcer was confirmed in 37.1% of families of children included in the study. Duodenal ulcers were found in 22.9% of families. The results obtained, indicate the usefulness of long-term observation and clinical follow-up of children with chronic gastritis of H. pylori ethiology taking into consideration bacterium eradication as prophylaxis of peptic ulceration.

Severe acute pancreatitis is characterized by a poor prognosis with local and systemic complications, high morbidity and mortality. From the morphological standpoint, almost all patients suffering from severe forms of acute pancreatitis present various degree of pancreatic necrosis. In these patients the occurrence of infection of pancreatic necrosis certainly represents a very important prognostic factor as it has worldwide accepted as the leading cause of death. In addition, the discovery of an infected necrosis represents a crucial point in the treatment of these patients as it is the only clear-cut shift from medical to surgical treatment in necrotizing pancreatitis. Over the last years, earlier and more precise identification of pancreatic necrosis together with availability of new classes of antibiotics with documented activity against the most commonly involved bacteria and able to reach in therapeutic concentration the pancreatic necrosis give us the opportunity to perform some important controlled clinical trials on antibiotic prophylaxis in necrotizing acute pancreatitis. The great majority of these studies showed the usefulness of a prophylactic regimen (using antibiotics such as fluoroquinolones and carbapenems) in terms of reduction of pancreatic and extrapancreatic infections in comparison with untreated controls. Nevertheless, some questions on this topic still present controversial aspects such as the antibiotic of choice, the duration of treatment, the possible opportunistic infections with fungi and/or resistant strains. Antibiotics may prove very useful in patients with documented infected necrosis and high anaesthesiological risk unfit for surgical debridement and drainage; some initial experiences show the possibility that antibiotic treatment may be curative without surgery in these selected cases.

Purpose: This study was undertaken to test the hypothesis that high concentrations of urea in gastric juice would have an influence on Helicobacter pylori infection in patients maintained on chronic hemodialysis (HD).

Material and methods: We investigated 30 patients (17 males, 13 females; mean age 50.8 +/- 2.9 years) with end-stage renal disease (ESRD) undergoing hemodialysis treatment (HD) for at least 6 months, who were compared to 31 patients (16 males, 15 females; mean age 61.3 +/- 2.2 years) with dyspeptic symptoms. Biopsies from the gastric antrum and body were taken for histological investigation. Urea and ammonia were measured in gastric juice, and the severity of gastritis was evaluated according to Sydney criteria.

Results: H. pylori infection was found in 19 (63%) HD patients and in 22 (71%) control subjects. Gastric juice urea concentration was significantly higher in HD patients than in controls and H. pylori infection caused a significant decrease in urea concentration in both groups. There was an inverse correlation between urea and ammonia concentration in gastric juice in both groups. Ammonia concentration in both groups was higher in H. pylori infected patients. In H. pylori negative subjects ammonia/urea ratio was lower in HD patients in comparison to controls. Ammonia/urea ratio was raised by H. pylori infection in both groups, and the difference between HD and control groups persisted. H. pylori infection was associated with polymorphonuclear infiltration of gastric mucosa. There was a significant correlation between gastric ammonia and mucosal polymorphonuclear leukocytes infiltration and gastritis score.

Conclusions: Higher urea levels in the gastric juice of chronically hemodialyzed patients do not seem to be a risk factor for infection with Helicobacter pylori.

Purpose: Thiazolidinedione derivatives (TZDs) are known to be ligands of peroxisome proliferator-activated receptor gamma (PPARgamma). In this study, we investigated the effect of a TZD, troglitazone, on inflammation and fibrogenesis in the pancreas of an experimental model of chronic pancreatitis.

Material and methods: Male WBN/Kob rats with spontaneous chronic pancreatitis were fed rat chow containing 0.2% troglitazone from 1 to 4 months of age. Immunohistochemical studies of rat pancreas were carried out with monoclonal mouse antibody against human alpha-smooth muscle actin (alpha-SMA) or rabbit polyclonal antibody against collagen type I, collagen type III, or fibronectin. Cytokine production was measured by enzyme-linked immunosorbent assay. The inhibitory action of troglitazone on nuclear factor-kappaB (NF-kappaB) binding activity in activated macrophages was also investigated.

Results: Long-term administration of troglitazone reduced inflammatory cell infiltration and fibrosis in the pancreas of WBN/Kob rats, and expression of alpha-SMA, procollagen I, III, and fibronectin was significantly reduced by troglitazone. The increase in TNF-alpha production by activated macrophages was significantly decreased by troglitazone. Peritoneal macrophages isolated from WBN/Kob rats produced a large amount of TNF-alpha, whereas those from troglitazone-treated WBN/Kob rats produced only a marginal amount of TNF-alpha. Lipopolysaccharide-induced NF-kappaB binding activity in peritoneal macrophages was also significantly reduced by troglitazone.

Conclusions: Troglitazone prevented the progression of chronic pancreatitis via inhibition of ECM synthesis and proinflammatory cytokine production mediated by the inhibition of NF-kappaB activity.

Purpose: Adiponectin (APM1)--a newly discovered adipocytokine secreted by fat tissue--was recently suggested to play a role in the genetic predisposition to type 2 diabetes, obesity and insulin resistance. Adiponectin gene is localized on chromosome 3q27 within the region which was identified as susceptibility locus for type 2 diabetes and metabolic syndrome. Till now genetic associations of two SNP in exon 2 (+45T/G) and intron 2 (+276G/T) of adiponectin gene with type 2 diabetes and adiponectin level were reported in Japanese population and with insulin resistance in some Caucasian populations (Italy, Germany). Moreover, in the proximal promoter region of the APM1 gene: SNP-11426A/G and -11391A/-11377G haplotype predicted the associations with fasting plasma glucose, type 2 diabetes and adiponectin levels. On the other hand the role of mutations in exon 3 of the adiponectin gene is not so well studied.

Material and methods: The aim of our study was the screening for rare mutation in exon 3 of adiponectin gene in the Polish subjects with type 2 diabetes as there is no data available about the frequency and role of these mutations in our population. The study was performed in the group of 187 Polish origin patients with type 2 diabetes (32 female and 155 male, mean age 54.1 +/- 8.6 yrs) and 102 age and sex matched healthy controls.

Results: The frequency of adiponectin gene mutations in exon 3 was 3.9%, while in the control group 0.98% and this difference was not statistically significant. We also observed that adiponectin level is significantly lower in patients with c.331 T-->C mutation (Y111H) in comparison to subjects without this mutation (5.0 ug/ml vs 14.4 ug/ml, p=0.0148).

Conclusions: To our knowledge the present study is the first which shows that in Polish populations.

Purpose: Thrombin activatable fibrinolysis inhibitor (TAFI) seems to be a potential haemostatic risk factor of coronary artery disease (CAD). Taking into account interactions between TAFI and haemostasis, especially during cardiopulmonary bypass, we decided to determine concentration of TAFI and activated TAFI (TAFIa) and other haemostasis markers in CABG patients.

Material and methods: 45 CAD patients (11 women, 34 men) undergoing elective CABG were included in the study. Blood samples were taken before the operation, on the 3rd, 7th day and 3 months after CABG. A value of p<0.05 was considered statistically significant.

Results: We found a significant decrease in TAFIa concentration on 3rd postoperative day: 6 microg/ml (0.3-43.2) vs 8.9 microg/ml (0.5-37) before CABG (p<0.05), a significant increase in TAFI concentration on the 7th postoperative day: 127.7% +/- 36.8 vs 112.18% +/- 30.34 of standard plasma concentration before CABG (p<0.05), significant increase in plasmin-antyplasmin (PAP) complexes concentration on 3rd and 7th day, respectively: 645 microg/l (323-1237) vs 406 microg/l (197-1840) before CABG (p<0.001); and 1030 microg/l (640-2149) vs 406 microg/l (197-1840) before CABG (p<0.0001). Before operation we found a significant negative correlation between PAP complexes concentration before CABG and EuroSCORE risk scale value (p<0.01).

Conclusions: In CABG patients, there is a significant increase in fibrinolytic activity due to decrease in TAFIa concentration, with simultaneous increase in PAP complexes. A significant negative correlation between PAP complexes concentration before CABG and EuroSCORE risk scale value stressed a potentially higher operation risk in patients with lower fibrinolytic activity.