Impact of obesity and nitric oxide synthase gene G894T polymorphism on essential hypertension.

Hypertension is a multifactorial disease caused by environmental, metabolic and genetic factors, but little is currently known on the complex interplay between these factors and blood pressure. The aim of the present study was to assess the potential impact of obesity, and angiotensin-converting enzyme (ACE) I/D polymorphism and endothelial nitric oxide synthase gene (NOS3) 4a/4b, G894T and -T786C variants on the essential hypertension. The study group consisted of 1,027 Caucasian adults of Polish nationality (45.5 ± 13.6 years old), of which 401 met the criteria for hypertension. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides were determined by standard procedures. The ACE I/D polymorphism and three polymorphisms in NOS3 gene (4a/4b, G894T, -T786C) were detected by the PCR method. Multivariable logistic regression demonstrated that age above 45 years, diabetes, dyslipidemia, smoking and male sex are important risk factors for hypertension and no significant influence of variants in ACE and NOS3 genes on this risk was recognized. Obese subjects had a 3.27-times higher risk (OR = 3.27, 95% CI: 2.37 - 4.52) of hypertension than non-obese, and in obese the NOS3 894T allele was associated with 1.37 fold higher risk of hypertension (P = 0.031). The distribution of NOS3 G894T genotypes supported the co-dominant (OR = 1.35, P = 0.034, Pfit = 0.435) or recessive (OR = 2.00, P = 0.046, Pfit = 0.286), but not dominant model of inheritance (P = 0.100). The study indicates that in obese NOS3 G894T polymorphism may enhance hypertension risk. However, in the presence of such strong risk factors as age, diabetes and smoking, the impact of this genetic variant seems to be attenuated. Further studies are needed to reveal the usefulness of G894T polymorphism in hypertension risk assessment in obese.

Effect of 1alpha-vitamin D3 and estrogen therapy on cortical bone mechanical properties in the ovariectomized rat model.

It is well documented that both bone mass and size of ovariectomized rats can be increased by 1alpha-vitamin D3 therapy. The repercussion of this therapy on bone mechanical competence is far less clear. Therefore, the objective of this study was to examine the mechanical properties of the shaft femur in ovariectomized rats (3 months old) receiving estrogen (0.25 mg/kg-week) and /or 1alpha-vitamin D3 (0.5 microgram/kg-day). The medication was given during 6 months starting immediately after ovariectomy or starting 3 months later. Torsional testing was performed from which the parameters strength, stiffness, maximum angular displacement, and energy-absorbing capacity (toughness) were derived. Multiple regression models were generated to estimate the relative importance of the therapies on bone mechanical properties. Bone stiffness increased with age. Ovariectomy improved bone mechanical parameters until 6 months postovariectomy, whereas estrogen treatment resulted in similar mechanical properties as those in intact age-matched controls. A significant improvement of all mechanical parameters was observed after 1alpha-vitamin D3 therapy. The combined therapy of 1alpha-vitamin D3 and estrogen was less effective than 1alpha-vitamin D3 alone, but better than estrogen therapy alone, suggesting interactive effects between both therapies. We conclude that 1alpha-vitamin D3 treatment of ovariectomized rats improves bone mechanical competence, which might be partially related to alterations in both bone mass and size.

Gastrointestinal and pancreatic complications after kidney transplantation.

In a retrospective study of 165 renal allograft recipients, the influence of the route of prednisolone administration on the frequency of early and late gastrointestinal complications was analysed. Late complications were more frequent in patients treated orally than in those treated intravenously (a statistically significant difference). Patients on intravenous therapy had more early complications, but this difference did not reach a statistically significant level.

[Arrhythmogenic right-ventricular dysplasia--a case report]. / Arytmogenna dysplazja prawej komory--opis przypadku.

A case of arrhythmogenic right ventricular dysplasia (ARVD) in a 28 year old man is reported. Diagnosis was based on ECG, echocardiographic and scintigraphic findings. Echocardiography and scintigraphy revealed an enlarged right ventricle and normal left ventricle. The abnormalities specific for ARVD were free wall motion abnormalities, particularly akinetic areas and microaneurysms . Ventricular tachycardia and premature ventricular contractions of left bundle branch block (LBBB) pattern were recorded. A titer against mycoplasma and concentrations of immunoglobulins were normal. Anti-++ smooth muscle antibodies were detected. The patient was treated with amiodarone . There were no clinical, echocardiographic and ECG features of ARVD in the patient's brother.

[Attempt at using chemoluminescence in modern diagnosis and monitoring of therapy in prostatic cancer]. / Próba wykorzystania chemiluminescencji we wspólczesnej diagnostyce i monitorowaniu terapii raka gruczolu krokowego.

The nature of chemoluminescence (Chl) is based on the measurement of plasma luminescence intensity, using a photoelectric system. In a group of 42 patients with prostatic cancer (PC), in 29 cases (69.0%) an increase of Chl was found while in 20 blood donors (control group) the Chl result was negative. Out of 29 patients with PC, Chl was studied in 20 cases for 12 months. These were patients after orchidectomy treated with flutamide. Chl demonstrated in them a decrease of luminescence intensity which correlated with a decrease of the level of prostatic markers (particularly PSA). These results may suggest that Chl may be a useful method in early diagnosis and probably may serve for trials of PC therapy monitoring. Further studies are necessary however, especially in order to explain the divergences in Chl measurements observed in individual cases, and to confirm the value of the method which is easy to perform at low expenses.

[Biochemical markers of bone remodelling and their usefulness in the diagnosis of osteoporosis]. / Biochemiczne markery przebudowy kosci i ich przydatnosc do diagnostyki osteoporozy.

In 65 subjects (42 women and 23 men) aged from 40 to 80 years, at risk for primary or secondary osteoporosis development without concomitant diseases affecting renal and hepatic function and vitamin D metabolism, alkaline phosphatase activity (F.A.s) and total calcium level (Cas) were determined in the blood serum, and also the excretion in the morning urine portion of hydroxyproline and calcium was measured in relation to creatinine excretion (FUHpr/kr; FUCa/kr). In each patient an X-ray was done of the thoracolumbar spine, and on its basis the X-ray vertebral index was calculated. The study has been undertaken in order to elucidate whether the above stated compounds regarded as biochemical markers of bone remodelling, and the X-ray vertebral index are useful in the diagnosis of osteoporosis. An increased F.A.s activity in the blood serum, and higher values of the X-ray vertebral index were found both in the group of patients with primary and secondary osteoporosis, in relation to normal values. It was found that FUHpr/kr and FUCa/kr were increased in patients with secondary osteoporosis in comparison to patients with primary osteoporosis. A statistically significant correlation was also noted between FUHpr/kr and FUCa/kr, and F.A.s in patients with primary and secondary osteoporosis. In both studied groups no relationship was found between the value of the X-ray vertebral index, and the levels of biochemical markers of bone remodelling.

[Effect of long term treatment with prednisone on remodeling of cancellous and cortical bone in dogs]. / Wplyw dlugotrwalego stosowania prednizonu na przebudowe tkanki kostnej gabczastej i zbitej psów.

The effect of 7 month prednisone administration on cancellous and compact bone remodeling in dogs was evaluated by means of histomorphometric and tetracycline labeling methods. It was found that treatment with prednisone resulted in decrease of bone mass which was caused by increased bone resorption as well as considerable diminution of bone formation. In the iliac bone those were manifested by increase in resorption of trabecular surface, decrease in osteoid surface, and reduction in the osteoid thickness, indicating, with a simultaneous decrease in mineralization rate, slowing down of the appositional rate of newly formed bone tissue. In the rib cortical bone treatment with prednisone resulted in increase of the resorption sites together with decrease of the formation sites and tetracycline-labeled osteons. Reduction in the osteoid thickness as well as in the mineralization rate was also observed. The changes of bone remodeling parameters due to prednisone, although proceeding in the same direction in both types of bone tissue, were more marked in the spongy bone than in the compact bone.

[The role of Helicobacter pylori in the development of chronic gastritis and gastroduodenal ulcers]. / Rola Helicobacter pylori w rozwoju przewleklego zapalenia blony sluzowej i choroby wrzodowej zoladka i dwunastnicy.

To determine the correlation between Helicobacter pylori colonization of the gastric mucosa and the incidence of chronic gastritis as well as gastric and duodenal ulcer, 52 patients (26 women and 26 men) aged 19-77 years (mean 46 years) with gastrointestinal symptoms were studied. Biopsy specimens for histological and bacteriological examinations were taken during upper gastrointestinal tract endoscopies. Helicobacter pylori was found in 21 (40%) patients: 14 women and 7 men (p less than 0.05). The organisms were present more often in cases with chronic gastritis and duodenal ulcer (p less than 0.05). They were not identified in any of 7 persons with normal histologic features (p less than 0.01). Helicobacter pylori was found on the gastric mucosa in 6 (75%) of 8 patients with duodenal ulcer but in none of 5 cases after partial gastrectomy with the methods of Billroth I or Billroth II (p less than 0.05).

Comparison of the effect of sodium fluoride and calcidiol on the rib cortical-endosteal surface remodeling in dogs receiving prednisone.

The effects of sodium fluoride and calcidiol on the remodeling of the rib cortical-endosteal surface were compared in dogs treated with prednisone over long-term periods. In the study histomorphometric and tetracycline-labeling methods were used. It was found that administration of sodium fluoride in combination with calcidiol and calcium carbonate limited the development of prednisone-induced osteoporosis to a higher degree than treatment with calcidiol and calcium. This included less enhancement of the bone resorption surface, an increase in both the bone formation surface and osteoid seam thickness in conjunction with a lower reduction in the mineralization rate. The changes induced by sodium fluoride had a favorable effect on the ratio of the resorption to the formation processes at the basal multicellular units of bone turnover.

[Comparison of the effects of sodium fluoride and calcidiol on the remodeling of the endosteal surface of the rib cortex in dogs after administration of prednisone]. / Porównanie wplywu fluorku sodu i kalcidiolu na przebudowe powierzchni sródkostnej kory zeber psów otrzymujacych prednizon.

The effects were compared of sodium fluoride and calcidiol on the remodeling of the rib cortical-endosteal surface of dogs treated with prednisone for long time periods. The study used a histomorphometric and tetracycline labeling methods. It was found that administration of sodium fluoride with calcidiol and calcium carbonate limited in a higher degree than the treatment with calcidiol and calcium carbonate the development of the osteoporotic changes induced by glucocorticoids. This included reduced enhancement of the bone resorption surface, increased bone formation surface and osteoid thickness connected with acceleration of mineralization rate. The changes induced by sodium fluoride had a favorable effect on the ratio of the resorption to the formation process at the sites of bone remodeling.

An analgesic effect of synthetic human calcitonin in patients with primary osteoporosis.

Examinations were performed in 20 adult male and female patients (pts) suffering from acute back pain due to vertebral compression fracture secondary to osteoporosis proved by lateral X-rays of the dorso-lumbar spine (Th3-L5), and bone mineral density with the method of dual energy X-ray absorptiometry. The synthetic human calcitonin (SUC) (0.5 mg) was injected I.M. every day during 28 days. Analgesic effect was evaluated on 0, 3, 7, 14, 21 and 28th day by patient's assessment of functional capacity, and physician's assessment of pain and mobility. On the same days biochemical variables of Ca-P homeostasis were determined. Treatment with calcitonin resulted in a positive analgesic effect. The functional capacity and mobility of pts increased with diminution of pain. No significant alterations of Ca-P homeostasis was observed. Mild and transient side effects as nausea and tachycardia were negligible. SHC appears to have a significant analgesic effect in treatment of primary osteoporosis.

Long-term consequences of surgical treatment of peptic ulcer.

Surgical treatment of peptic ulcer may lead to several late postoperative morphological and metabolic abnormalities. Forty two patients (16 females and 26 males) at mean age of 47 years after surgery for peptic ulcer (mean postoperative period of 9 years) were recruited in this study. Following methods have been used for evaluation of those patients: clinical and serum biochemical assessment, UGI tract endoscopy, histology of gastric or duodenal mucosa biopsies, test for H-pylori presence, Ca-P-Mg homeostasis and BMD using DXA-absorptiometry. No clinical and biochemical abnormalities were found. In 60% of examined pts gastritis or duodenitis with various degrees of the reflux were found endoscopicaly. In 64% of pts histology showed signs of mucosal inflammation. Recurrent ulcer was found in 3 pts. H-pylori was present in 16 pts (40%). The significant reduction of BMD, especially of the lumbar spine, in the pts after the PG resection in comparison to the pts with the vagotomy was found. Within several years after gastric operation the patient must be carefully evaluated and adequate supplementation of Ca and vitamin D is strongly recommended.

Effect of 1 alpha-vitamin D3 on bone strength and composition in growing rats with and without corticosteroid treatment.

The effects of 1 alpha-vitamin D3 were studied for 6 months in 2-month-old male and female rats on a moderately low calcium diet with or without low-dose prednisolone treatment. Both cortical bone mechanical and biochemical properties were examined. Femoral bone specimens were subjected to torsional loading tests. With age, bone strength and stiffness increased in both sexes, accompanied by an increased degree of mineralization (bone ash and calcium concentrations). During growth, strength and stiffness increased more in male than in female rats. When 1 alpha-vitamin D3 (0.5 micrograms/kg/day) was given alone, bone mechanical competence improved significantly whereas insulin-like growth factor-I (IGF-I) and calcium concentrations in the bone matrix were significantly reduced. Treatment with low-dose prednisolone (0.5 mg/kg/day) alone did not influence bone mechanical properties compared with intact control rats (without prednisolone) although a significant reduction in calcium concentration and an increased phosphorus concentration were measured. A combined therapy with prednisolone and 1 alpha-vitamin D3 significantly increased bone strength, toughness, and stiffness compared with control bones. Both mineralization degree (ash and calcium concentration) and IGF-I concentration were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium/phosphate/vitamin D homeostasis and bone mass in patients after gastrectomy, vagotomy, and cholecystectomy.

Sixty-two outpatients were assessed and divided into the following groups: 20 patients who had had partial gastrectomy (PG group), 22 patients who had had truncal vagotomy and pyloroplasty (TV group) or high selective vagotomy (HSV group), and 20 patients who had had cholecystectomy (CH group). The patients' age ranged from 35 to 64 years (mean 45 years), and the average postoperative period was 9 years. None of the patients evidenced clinical or biochemical symptoms of malnutrition or malabsorption or of diseases affecting vitamin D metabolism. The function of the kidneys and the liver was normal. An age-matched group of volunteers served as a control group. The calcium dietary intake was determined using a standardized questionnaire; and the levels of serum calcium (Cas), phosphate (Ps), alkaline phosphatase (AP), and 25-hydroxyvitamin D [25(OH)D] and the excretion of Ca in a sample of fasting urine corrected for concurrent creatine excretion (FuCa/cr) were assessed by means of standard laboratory techniques. The bone mineral density (BMD) of the lumbar spine (L2-4) and femoral neck (neck-L) was determined by means of dual energy x-ray absorptiometry (DXA). The daily Ca dietary intake was lower than recommended (RDA) in 80% of the patients, with most of them ingesting less than 300 mg daily. The mean values of Cas, Ps, AP, and FuCa/cr did not differ from those in the controls. Significantly reduced 25(OH)D levels were observed in the PG group (7.0 ng/ml) (p < 0.001) and CH group (12.5 ng/ml) (p < 0.01) compared with the values in the control group (20.0 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

[Combined therapy with calcitonin and high doses of active vitamin D3 metabolites in uremic hyperparathyroidism]. / Skojarzone leczenie kalcytonina i duzymi dawkami aktywnych metabolitów witaminy D3 we wtórnej do mocznicy nadczynnosci przytarczyc.

Active vitamin D3 pulse therapy effectively suppresses parathormone (PTH) synthesis in uremic hyperparathyroidism but high serum levels of calcitriol achieved can induce direct osteoclastic resorption and block bone formation. Therefore we found it interesting to examine whether an addition of the osteoclast inhibitor, calcitonin (CT), could reduce those unwanted effects. 75 hemodialysis patients with at least 5-fold 1-84 PTH serum level elevation were divided into 4 treatment groups: I (n = 19)-CT and 1 alpha-OH-D3; II (n = 20)-CT; III (n = 19)-1 alpha-OH-D3 (n = 10) or 1.25 (OH)2D3 (n = 9) alone; IV (n = 17)-none of these drugs. CT (200 IU) and 1 alpha-OH-D3/1.25(OH)2D3 (up to 5 micrograms) were given 3 times a week. Dialysate Ca was 1.40-1.45 (Group I, III) or 1.95-2.00 mmol/l (Group II, IV). Within 8 months serum 1-84 PTH fell by 75% (p < 0.001) in Group I and by 77% (p < 0.001) in Group II, serum Ca increased by 0.22 +/- 0.05 mmol/l in Group I (p < 0.005) and by 0.25 +/- 0.05 mmol/l in Group III (p < 0.005), alkaline phosphatase activity decreased by 35% in Group I (p < 0.01) and 31% in Group III (p < 0.005) whereas in Groups II and IV no significant changes were noted. In Group III no differences between patients taking 1 alpha-OH-D3 or 1.25 (OH)2D3 were observed. The significant reduction of serum hydroxyproline (37%; p < 0.001) was seen only in Group 1. The increase in bone mineral density (BMD) measured by dual-energy X-ray absorptiometry was greater in Group I than in Group III (p < 0.05). In Group II the effect was mostly insignificant, whereas in Group IV a substantial decrease (p < 0.001) in BMD was observed. These data suggest that combined therapy with CT and oral 1 alpha-OH-D3 pulses is more effective than pulses alone in inhibiting bone resorption and in increasing BMD in hemodialysis patients with uremic hyperparathyroid bone disease.