Association of NAT2 polymorphisms with type 2 diabetes in a population from Bosnia and Herzegovina.

BACKGROUND AND AIMS: N-acetyltransferase 2 (NAT2) is a drug-metabolizing enzyme, which is genetically variable in human populations. Polymorphisms in the NAT2 gene have been associated with drug efficacy and toxicity as well as disease susceptibility. Recently, an association of NAT2 gene variation with risk of type 2 diabetes mellitus (T2DM) has been suggested. This is the first study performed in a population from Bosnia and Herzegovina (BH) in which the frequency of two common NAT2 polymorphisms, 341T>C (NAT2*5) and 590G>A (NAT2*6) was determined in diabetic patients. METHODS: The frequency of the NAT2*5 (341T>C) and NAT2*6 (590G>A) polymorphisms was analyzed by employing TaqMan SNP Genotyping Assays (Applied Biosystems) in a group of 63 patients with T2DM and 79 nondiabetic subjects. RESULTS: Our data demonstrated that the frequencies of NAT2*5 (341T>C) and NAT2*6 (590G>A) polymorphisms in BH population were in line with the Caucasians genotype data. The NAT2*5 and NAT2*6 alleles were in high linkage disequilibrium (D' = 0.969). Strinkingly, there was a significant difference in genotype frequencies for NAT2*5 (p <0.05) and NAT2*6 (p <0.001) polymorphisms between diabetic and nondiabetic subjects. NAT2*5 polymorphism was associated with 2.4-fold increased risk for developing T2DM (adjusted OR = 2.40, 95% CI = 1.10-5.25, p = 0.028). On the contrary, NAT2*6 variant significantly decreased by 5-fold susceptibility to the disease (adjusted OR = 0.20, 95% CI = 0.09-0.43, p <0.001). CONCLUSIONS: Our data demonstrated that NAT2 genetic variation appeared to be an important risk factor in development of T2DM.

[Introduction of insulin treatment on diabetes mellitus type 2]. / Pravovremeno uvodenje insulinske terapije kod Tip 2 secerne bolesti.

Diabetes mellitus is a chronic, incurable disorder, but can be successfully managed to improve patient's quality of life and extend lifetime. Late diabetic complications that affect various organs can be postponed with appropriate treatment. HbA(1C) value tells us about glucoregulation in last 3-4 month and it helps us in estimating the treatment efficiency. In last several years number of type 2 diabetics increased in the world and also in our country. Treatment approach must be aggressive to prevent late diabetic complications in type 2 diabetes. Type 2 diabetics can be treated with oral medications as monotherapy, or in various combinations as long as the following values can be maintained: HbA(1C) value under 7%, fasting blood glucose under 6.0 mmol/l and postprandial blood glucose under 8.9 mmol/l. Insulin treatment should be introduced when HbA(1C) value gets above 7%.

The statins in prevention of coronary heart diseases in type 2 diabetics.

UNLABELLED: We aimed to determine whether the administration of statins to type 2 diabetics without pre-existing CHD reduced the incidence of CHD and their effects on cholesterol and CRP levels. All the participants were carefully interviewed, clinically examined, and laboratory tested to exclude conditions likely to provoke an inflammatory response that was an exclusion criterion. EXCLUSION CRITERIA: Serious heart, liver or kidney problems, history of renal transplant, recent history of drug or alcohol abuse, HbA1c>10%, blood pressure >140/90 mmHg, BMI >35 kg/m2, triglycerides >3,0 mmol/dm3. 95 obese diabetics (mean age 60,9 years and BMI=31,59 kg/m2, diabetes duration more than 10 years) without pre-existing CHD, were included in the analysis and were randomized to simvastatin (25 female and 20 male used 40 mg simvastatin daily) or placebo (30 female and 20 male) group. After six months, simvastatin significantly lowered CRP levels by 19%, (p<0,01), cholesterol levels by 18%, TG levels by 8%, LDL levels by 20% and VLDL levels by 17%, whereas there was no change with placebo. After one year the difference sustained between groups. Coronary events were rarely in the simvastatin group (6,6%) than in the placebo group (14%). Coronary revascularizations were 4 in the placebo group and 1 in the simvastatin group. Rate of stroke was more often in the placebo group (18%) than in the simvastatin group (8,8%). So, reduction of acute CHD events is for 7,4% in the simvastatin group. Positive correlation was between CRP and CVD (r=0,29). Statin therapy reduced the risk of coronary heart disease in diabetics without CHD.

[Effects of statins on postoperative treatment of patients after aortocoronary bypass grafting]. / Uticaj statina na postoperativni tretman pacijenata operiranih radi ugradnje aortokoronarnih premostenja.

AIM: There are no previous data about the anti-inflammatory effects of hypolipemic agents, statins, in patients after aortocoronary bypass grafting. The aim of this study was to demonstrate effects of simvastatine on postoperative treatment, laboratory findings and pericardial effusion during postoperative period, in patients after aortocoronary bypass grafting procedures. MATERIAL AND METHODS: The study included 80 patients with coronary arterial disease divided in two groups. The study group included 40 patients with coronary ischemic disease subjected to surgical implantation of aortocoronary bypass graft who received standard cardio-surgical postoperative treatment supplemented with 40 mg of simvastatine per day, starting at 8 hours after the patient's extubation until postoperative 14th day. The control group included 40 patients after aortocoronary bypass grafting procedures with standard intensive postoperative treatment. Evaluation included demographic data, surgical reports, postoperative laboratory parameters and echocardiography findings, taken during two days monitoring of postoperative pericardial effusion. Statistical data analysis was conducted using SPSS software. Parametric data were evaluated using Student T-test, while non-parametric data were processed using chi2 test and proportion analysis. Mann-Whitney U test was applied with CI of 95%, i.e., significance level p < 0.05. RESULTS: No significant differences were found between the observed groups with regards to demographic data, number of the implanted aortocoronary bypasses and postoperative laboratory parameters. However, the differences in echocardiographically determined dimensions of postoperative pericardial effusions measured during two days of postoperative observation (between the 3rd and the 14th day postoperative) were significant (p < 0.037, p < 0.01). CONCLUSION: In our study, statin therapy consisting of 40 mg/24 hrs was applied with no side effects and without interaction with the other postoperatively applied medications. Simvastatins, applied in the dosage of 40 mg/24 hrs, efficiently lead to significant reduction of postoperative pericardial effusions in postoperative period. In this limited group of patients, statins have exhibited good anti-inflammatory effects. Statins with standard therapy ought to be included in the early cardio-surgical postoperative period. Anti-inflammatory activities of statins should be further investigation on much larger patient sample. So far, there is no record of a large study of anti-inflammatory activities of hypolipemic agents that could waive the doubts into their effectiveness. It needs to be stressed that no large studies of anti-inflammatory activities of hypolipemic agents in cases of postoperative pericardial effusion were ever conducted.

[Perfusion myocardial scintigraphy - SPECT with TC-99m MIBI in detection coronary artery desease in diabetic patients]. / Perfuziona scintigrafija miokarda-SPECT sa TC-99m MIBI u detekciji koronarne bolesti kod pacijenata sa diabetes mellitus-om.

UNLABELLED: Diabetes mellitus is very frequent disease. The prevalence of coronary artery disease is higher in diabetic than in non-diabetic patients. Coronary artery disease (CAD) is the main cause of morbidity and mortalitiy in patients with Diabetes mellitus. The aim of this study was to evaluate usfulnes of myocardial perfusion scintigraphy in diabetic patients for detection of coronary artery disease. PATIENTS AND METHODS: this study included 15 patients with verified diabetes mellitus. All patients were treated with oral hypoglicemic or insulin. Parameters observed for every patients were level of lipemia (cholesterol, triglycerides), family hystory of CAD, hystory of chest pain. All patients underwent sress/rest Tc-99m MIBI study. We have performed one day protocol. Exercise tolerance test were performing in all patients according to the Bruce protocol. 260MBq was injected intravenously at peak exercise. 740MBg was injected for the rest. Myocardial perfusion scintigraphy was clasified as: 1. normal, 2. reversible defect or 3. irreversible defect. RESULTS: reversible perfusion defect we have found in 8 patients. The same patients had elevated glicemia, high level of lipemia; 1 patient had fixed defect, without any previous known history for myocardial infarction. In 6 patients we could not see any significant defect during stress/rest scintigraphy. CONCLUSION: The frequency of abnormal myocardial perfusion scintigraphy suggest that this procedure can be very useful in the detection of high-risk diabetic patients.

[Comparison of the coronary angiography and operative findings in coronary diabetic and non-diabetic patients]. / Komparacija koronarografskih i operativnih nalaza na srcu u koronarnih bolesnika sa i bez secerne bolesti.

AIM: To evaluate whether diabetic patients differ from non-diabetic patients when referred for coronary angiography and coronary revascularization procedures regarding previous history, indications for and findings at coronary angiography as well as medications. PATIENTS AND METHODS: Data were prospectively collected on 100 patients referred for consideration of the coronary revascularization. All patients were divided into two groups: 50 diabetic patients with coronary angiography exams and second group of 50 non-diabetic patients also with coronary angiography exams. Data were evaluated statically with SPSS program. We used Leven's variance test with CI: 95% and significance level p < 0.05. RESULTS: Our data were shown no differences in age or sex in the two groups. In diabetic patients group the left ventricle volumes were greater, and more often presented myocardial walls segmental abnormalities, as well as depressed myocardial function (EF < 40%). Coronary angiography exams in diabetic group had shown greater changes in left main, proximal part of all coronary arteries. Three vessel diseases were more often present in diabetic groupe. CONCLUSIONS: Number of bypass grafts were significantlly greater in diabetic groupe, what is expected because of differences in results already presented in our paper. Diabetes mellitus stayed metabolic syndrom which accelerated inflamatory, coagulation and atherotrombotic proccess as one of the main risk factors of the atherosclerosis of all vessels esspecially coronary arteries.

Immunosuppressive therapy protocols in kidney transplantation in adults.

In practical terms, regardless of HLA compatibility level, whenever tissues are transplanted from one person to another it is essential to suppress the immune response of the recipient. A variety of methods are available however, the most frequently used ones have the disadvantage of being immunologicaly non specific. The consequence is a difficult balance between immunosuppression sufficient to prevent the tissue rejection and maintenance of immune system at the level of ability to adequately deal with an infection. The goal, not yet achieved, is to find a way of generating donor specific immunosuppression that leaves the immune machinery otherwise completely intact. The major approaches to immunosuppression are described below.

[Evaluation of the tumor of the pituitary gland (hypophysis) between 2000-2005. On the intensive care of The Endocrinology Clinic of the Clinical Center of the University of Sarajevo]. / Evaluacija tumora hipofize u periodu 2000-2005. g. u Intenzivnoj njezi endokrinoloske klinike KCUS.

INTRODUCTION: Tumors of the pituitary gland can be adenomas, and more often, cancers, representing 10-15% of intracranial neoplasm. We make a difference between them according to their size, expansion, hormone's activity and local and endocrinological manifestations. The goal of the research was to reveal the presence of tumors of the pituitary gland in the period 2000-2005 among patients hospitalized on the Intensive Care of the Endocrinology Clinic. PATIENTS AND METHODS: Data from anamnesis of all patients with verified tumor of the pituitary gland between 2000.-2005 were used in the research work. RESULTS: Total number of patients with the tumor of pituitary gland was 40, 29 women and 11 men, and 35 % of patients were aged between 45 and 60. Main symptoms: headache -16, eye trouble -17, sexual dysfunction -8, growth of acres -5, and others symptoms -8 patients. There were 23 (57,5%) cases of micro adenoma and 17 (42,5 %) macro adenomas. From the total number of patients 23 were operated, 8 micro adenomas and 15 macro adenomas. The number of secreting adenomas was 25 (62,5 %) and 15 (37,5 %) were non-secreting. Secreting adenomas were: prolactinomas--14, acromegalies -7, Cushing syndromes -2, TSH producing -2. Non-secreting adenomas were: craniopharyngeomas--11, meningiomas -2, and 2 non-secreting micro adenomas. Most of prolactinomas were treated with drugs, and 3 cases of prolactinoma were operated. 6 cases of acromegaly were operated and 1 micro adenoma is still under medical supervision, with the therapy of bromocriptine. 3 of those patients have the residuum, and 4 of them have high level of hGH. 11 craniopharyngeomas were operated and all patients, except one, are under substitution therapy. 2 meningiomas were operated and those patients are also under substitution therapy. 1 case of TSH producing tumor was operated, but residuum and hyperthyroidism are still presents, and the micro adenoma, for the hyperplasia reason, disappeared with adequate substitution therapy. The Cushing syndrome, confirmed with MRI diagnostics, wasn't operated; it remained under conservative therapy, and in the other case, where we didn't isolate a pathological substrate, the patient exited. CONCLUSION: Tumors of the pituitary gland we mainly treat applying surgery methods, together with post operational substitution therapy or additional therapy with drugs. Only prolactinomas are tumors which are successfully treated with drugs.

[Vaccine for prevention of type 1 diabetes mellitus]. / Vakcina za prevenciju diabetesa tipa 1.

Diabetes mellitus type 1, known as insulin dependent diabetes mellitus (IDDM), results from a chronic autoimmune destruction of the insulin secreting pancreatic beta cells. This autoimmune process is marked by circulating auto antibodies to beta cell antigens. GAD 65 (Glutamic Acid Decarboxylase) auto antibodies are present in 70-80% of newly diagnosed patients with type 1 diabetes, and it can be detected many years before clinical onset of the disease. New knowledge in the imunopathogenesis have given expectation that imunotherapy will become routine manner for cure of diabetes mellitus type 1.

Effects of hyperglycemia and iron deficiency on kidney and heart function in type 2 diabetes disease.

Untreated anemia can caused significant cardiac and kidney damage. The aim of this study was to investigate the efficiency of anemia and hyperglycemia treatment in type 2 diabetes and their impact on kidney and heart impairment. The study is clinical retrospective and prospective and it was conducted in Clinic of Endocrinology, Diabetes Mellitus and Metabolic Diseases, University Clinical Center of Sarajevo. Prior to the study all patients were taking oral hypoglycemic drugs included sulfonylureas and biguanides. These subjects were put on 2 times daily fix mix insulin and biguanides after lunch. Each day, subjects received Iron tab 1 x 100 mg/ day, and C vitamin 1 x 100 mg/day. The results of our study are showing that effective treatment of glycaemia and anemia in patients with diabetes, reduces blood pressure, urine albumin secretion and pulse rate, diminishing cardiovascular damage and improving kidney function.

[LEAP (Lantus Early Access Programme) in Sarajevo]. / LEAP (Lantus Early Access Programme)--program za ranu dostupnost Lantusa u Sarajevu.

LEAP is multicentric study in phase IV. The first aim was to affirm Lantus efficacy and safety in every day practice, in local conditions. The second aims were to verify therapy successful by measuring fast blood glucose (FBG) and HbA1c and to estimate patients' pleasure. Duration of study was 2 months. Lantus was administrated subcutaneously daily. Doses were individual. HbA1c was measured at the begining of therapy and at the last control. Blood glucose was measured every day. The study included patients who did not reach the control of glycemy, or patients with frequent hypoglycemic crysis, older then 6 year. LEAP study in Sarajevo included 114 patients. Fifty four patients (47%) were men, and 60 (53%) were women. 46% diabetics have type 1 of diabetes mellitus and 54% have type 2 diabetes mellitus. The results of study demonstrated statistically significant decreasing of FBG and HbA1c in both groups (I group--patients younger than 18 years and II group--patients older than 18 years), p<0.05. FBG in I group on the start of Lantus therapy was 9.9+/-3.9 mmol/l but on ending control was 8.7+/-4.4 mmol/l (p<0.05). HbA1c on start of therapy was 9.4+/-1.9%, but on end control was 8.0+/-1.8% (p<0.05). FBG in II group on start was 13.6+/-4.7 mmol/l but on finish was 7.3+/-2.9 mmol/l (p<0.01). HbA1c on start was 9.3+/-1.8% and on end was 7.2+/-1.2% (p<0.01). These results showed that the Lantus is very efficacious for good glycoregulation. Just for two months, HbA1c decreased for 2%. Undesirable effects were not registered. We concluded that Lantus is very safe. Most patients (89%) were satisfied with therapy.

The effects of valsartan on lipid profile in normotensive type 2 diabetic patients.

Valsartan as angiotensin-II receptor antagonist in normotensive diabetic may provide kidney and heart protection. It also increases insulin receptor sensitivity. The aim of this study was to investigate the effect of valsartan on lipid profile in normotensive type 2 diabetic patients. Fifteen normotensive patients with type 2 diabetes mellitus, mean age 58.6+/-5.6 years, with mean BMI 28.6+/-2.5 kg/m2, were treated with valsartan in doses 20-80 mg per day. After a year of treatment with valsartan we witnessed significant decrease in total cholesterol level (6.8+/-1.4 to 5.4+/-0.9 mmol/l, p<0.05) and low density lipoprotein (LDL) from 4.5 to 2.7 mmol/l. Triglycerides were not affected significantly. Albumin excretion in urine significantly decreased. Level of basal insulin (from 256 to 78 pmol/l) has, also, decreased. In type 2 diabetes mellitus, the use of angiotensin-II receptor antagonists reduces the progression from micro to macro albuminuria. These results suggest that the angiotensin-II receptor antagonist decreases lipid serum levels in normotensive diabetes mellitus type 2 patients.

Gene analysis of steroid 5 alpha-reductase 1 in hyperandrogenic women.

AIM: To examine the gene encoding for 5alpha-reductase type 1 in hyperandrogenic women, and assess the association of its eventual mutations or polymorphisms with the development of the hyperandrogenic female pattern. METHODS: Sixteen hyperandrogenic women were included in the study. Single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing were performed after polymerase chain reaction amplification of each of the 5 exons of the SRD5A1 gene in both hyperandrogenic and control group (16 participants). RESULTS: Sequence analysis identified the existence of many polymorphisms; in codon 24 of exon 1, GGC (Gly) into GAC (Asp); in codon 30 of exon 1, CGG (Arg) into CGC (Arg); in exon 3 codon 169, ACA to ACG (both encoding for threonine); in exon 5, AGA to AGG (both encoding for arginine, codon 260); and T/C polymorphism in intron 2. Polymorphisms were found in both groups. CONCLUSION: Polymorphisms of SRD5A1 gene were the same in both hyperandrogenic and healthy women, indicating no significant associations of genetic polymorphisms/variations of SRD5A1 gene with clinical manifestations of hyperandrogenic disorders in women.

[Contemporary methods of prevention and treatment diabetic kidney disease]. / Savremene metode prevencije i tretmana dijabeticne bubrezne bolesti.

The number of people with diabetes is increasing worldwide. Diabetes is the leading cause of end-stage renal disease. Diabetic kidney disease has been reported to occur in 25-40% of people with type 1 or type 2 diabetes. Recent studies have demonstrated that the onset and course of diabetic nephropathy can be significantly improved by intervention in early stage of the development of this complication. In this article we will review the current recommendations regarding the prevention and treatment of diabetic nephropathy.

A simple method of DNA extraction in solving difficult criminal cases.

AIM: We examined combined use in house method and DNA IQ system (Promega) procedure for the extraction DNA from biological trace in order to help the solving some crime cases. METHOD: Simple and efficient method for extraction of the DNA from biological trace samples included the well washed trousers and the knife without any visual biological trails (from some one hard criminal case). In this method there were used: centrifuge, microwave oven, shaker, chelex, proteinase K, DNA IQ System (Promega). RESULTS: The extraction of DNA could be done within 2.5 hours or over the night. The DNA prepared on this way was good quality and could be used for STR analysis. CONCLUSIONS: This combined, simple, and safe method could be used for extraction DNA from samples containing a minute amount of the biological trace.

[Detection of antibodies against cytomegalovirus in donors and recipients of kidney transplants]. / Ispitivanje antitijela protiv citomegalovirusa kod donatora i primaoca bubreznog transplantata.

UNLABELLED: The paper analyzed the values and titer of IgM and IgG antibodies on CMV in donors and recipients of kidney transplntats. The objective was to investigate the presence of CMV in donors and recipients. SUBJECT AND METHODS: Test enzignost anti CMV/IgM was used. Detection of antibodies in 15 donors before transplantation and in 22 patients-recipients before and after the transplantation was done. RESULTS: From total of 15 donors, the values of IgM ranged from 0,002 I.U. do 0,080 I.U. One case was positive. Four patients were seropositive and treated by Gancyclovirom 10 mg/kg/b.w (body weight) in period of 3 month. IgM values ranged from 0.88399 to 25978. The control finding 3 patients was negative, in 1 patient positive (IgM 0.569). In 18 patients the finding was negative. Refererent value for IgM is < 0.10 the result is negative. For IgG four times greater value comparing to the basic value was found. CONCLUSION: The most significant factor for reactivation of CMV infection is iatrogenic Immunosuppressive therapy. Exclusion of CMV infection in donors and negative finding in recipient decrease.

Ultrasonography in organs transplantation.

With steady improvement in grafts survival due to improved efficacy of immunosuppressant protocols, refinement in surgical technique and the establishment of national system for coordination of organ distribution (United Network for Organ Sharing), organ transplantation is increasingly the preferred treatment option for patients with end-stage-renal-liver-pancreas diseases. Organ availability remains a major rate limiting factor. As the number of grafts lost due to rejection, infection and poor surgical technique has decreased, the relative clinical importance of graft loss due to vascular complications has been increasing. Real time ultrasound with power, color and duplex Doppler provides accurate, high resolution images of vascular morphology and (likely) function in organ grafts. In addition, serial exams can be performed without the risks associated with repeated use of intravenous contrast or exposure to ionizing radiation.

[Unilateral pheochromocytoma and adrenal gland hyperplasia]. / Unilateralni feohromocitom i hiperplazija nadbubrega.

Woman, forty two years old, has been hospitalized because of frequent headache, palpitation and tremor of lips with paroxysmal increase of blood pressure. The adrenals have examined. The status of the hormones has checked many times but showed increased values of VMA and 17-OH steroids only once. There is no possibility to measure the catcholamines. Analysis of other hormones has showed normal values except of paradoxal hGH increase during suppressive hGH test and hypoglycemia in OGTT test. The changes of the left adrenal, which size was 25x18 and 30x25 mm, have diagnosed by MRI of adrenals. It has been suspected microadenoma by MRI of pituitary gland. The left adrenalectomy has been done. During the surgery hypertension and tachyarrhythmia has occurred and treated by fentolamin and propranolol. No complications have been noticed after the surgery. The status of the adrenals hormones are in the normal range. Patohystological analysis has proved phcochromocytoma and hyperplasy.

[Amylin--a partner hormone to insulin]. / Amylin partner hormon inzulinu.

This article will provide an overview of some of the known functions of a recently discovered hormone, amylin, a partner hormone to insulin. Studies indicate that amylin has a role in the postmeal glucose regulation through effects on glucagon secretion, nutrient delivery and food intake. Three hormones--amylin, glucagon and insulin--are a critical part of postmeal glucose regulation. The interaction of these hormones and their role in the regulation of postmeal glucose concentrations is the subject of this article.

[Role of C-reactive protein in systemic lupus erythematosus]. / Uloga C-reaktivnog proteina (CRP) kod sistemnog lupus eritematodesa (SLE).

We prospectively estimated the CRP and erythrocyte sedimentation rate (ESR) level in the blood of patients with systemic lupus erythematosus (SLE), with aim to find the difference between relapse and infection, especially because the high fever is the same clinical sign for both. After following this problem, considering the relation between SLE and infection, we have found that: When SLE is active disease, the infection is common complication, Immunosuppressive therapy, particularly with steroids, prepares the conditions for infection, Infection and SLE are going together, and here is believe that infection is making the worsening of basic disease, A lot of SLE syndromes are differentiated with difficulties from syndromes caused from infection (pneumonia, arthritis, serositis). During 2 (two) years follow up of 10 patients suffering from SLE and fulfilled ARA criteria, we found 5 relapses and 3 infections, and all of them were followed and analyzed. We used the additional criteria for the estimation of the disease activity every patient separately. The CRP blood level was measured every month. According to a lot of clinicians, normal values of CRP are 0-0.5 mg/dl (0-5 mg/L) and ESR between 12-20 mm. Levels over 15 mg/L (1.5 mg/dl) are found with 4 SLE patients (5 SLE relapses), and 2 patients with infections (3 cases of infection). The median value of CRP in the course of infection was more than 60 mg/L, in comparison with SLE relapse (16.5 mg/L). All patients with SLE relapse had increased ESR level, but CRP wasn't, while with infection ESR and CRP were regularly increased in all cases. Measuring CRP in SLE is helpful in differentiating between infection and relapse, only under one condition: that serositis previously wasn't present.