Congenital esophageal stenosis: a rare malformation of the foregut.

Congenital esophageal stenosis (CES) is a type of esophageal stenosis, and three histological subtypes (tracheobronchial remnants, fibromuscular thickening or fibromuscular stenosis, and membranous webbing or esophageal membrane) are described. Symptoms of CES usually appears with the introduction of the semisolid alimentation. Dysphagia is the most common symptom, but esophageal food impaction, respiratory distress or failure to thrive can be clinical manifestations of CES. Wide spectrum of differential diagnoses leads to delayed definitive diagnosis and appropriate treatment. Depends on hystological subtype of CES, some treatment procedures (dilation or segmental esophageal resection) are recommended, but individually approach is still important in terms of frequency and type of dilation procedures or type of the surgical treatment. Dysphagia can persist after the treatment and a long follow-up period is recommended. In 33% of patients with CES, a different malformations in the digestive system, but also in the other systems, are described.

Comparison between the effects of selenomethionine and S-adenosylmethionine in preventing cholestasis-induced rat liver damage.

We aimed to evaluate whether two methionine-related compounds, S-adenosylmethionine (SAM), and selenomethionine (SM), could lessen liver damage induced by regurgitated bile in a model of rat bile duct ligation (BDL). Hepatoprotective potentials of S-adenosylmethionine and selenomethionine were estimated based on the changes of serum liver damage parameters (aminotransferases, alkaline phosphatase, gamma-glutamyltranspeptidase and lactate dehydrogenase activity, and bilirubin concentration), tissue oxidative [xanthine oxidase (XO) and catalase activity, thiobarbituric acid reactive substances (TBARS) levels] and inflammatory [tumor necrosis factor-alfa (TNF-α) concentration] parameters, and morphological liver tissue alterations that follow cholestasis. The treatment regimens proved themselves able to prevent significant liver damage induced by cholestasis. Both SAM and SM decreased XO activity and TBARS levels and increased catalase activity, while only SM significantly reduced TNF-α concentration. Morphological changes related to bile-induced liver damage were also found to be partially diminished by SAM and SM. In view of the mechanisms of action of the two tested methionine-derived compounds, one might say that SM predominantly acted as an antioxidant, while SAM exerted its activity by potentially modulating different gene expression and protein structures. It is also worth mentioning that this is the first study (to the best of our knowledge) that dealt with the effects of SM on BDL-induced liver injury in rats and of the findings that speak favorably of this powerful antioxidant.

Expression of prolactin receptors in the duodenum, kidneys and skeletal system during physiological and sulpiride-induced hyperprolactinaemia.

INTRODUCTION AND AIM: Hyperprolactinaemia in pregnancy leads to mild and reversible changes in the maternal skeletal system, and medicamentous hyperprolactinemia causes more detrimental effects. We conducted an experimental study to evaluate differences between Prlr gene expression in the duodenum, vertebrae and kidneys during physiological and medicamentous hyperprolactinaemia, which could influence calcium homeostasis. METHODS: Experimental animals (18 weeks old, Wistar female rats) were divided as follows: group P (nine rats that were 3 weeks pregnant), group M (ten rats that were intramuscularly administrated sulpiride (10 mg/kg) twice daily for 3 weeks), and the control group (C, ten age-matched nulliparous rats, 18-week-old). Laboratory investigations included measurements of serum ionized calcium, phosphorus, urinary calcium and phosphorus excretion, osteocalcin (OC), serum procollagen type 1 N-terminal propeptide (P1NP), vitamin D, parathyroid hormone (PTH) and prolactin (PRL). Relative quantification of gene expression for prolactin receptors in the duodenum, vertebrae and kidneys was determined using real-time PCR. RESULTS: Expression of the Prlr gene was significantly higher in the duodenum (p < 0.001) and lower in vertebrae (p < 0.001) and kidneys (p < 0.01) in rats with physiological hyperprolactinaemia (PHP) than in the control group. Significantly lower Prlr expression in the duodenum was verified (p < 0.001), along with increased Prlr gene expression in vertebrae (p < 0.001) and kidneys (p < 0.01), in rats with medicamentous hyperprolactinaemia (MHP) than in the C group. CONCLUSIONS: Downregulation of Prlr gene expression in the duodenum may explain the diminished intestinal calcium absorption in medicamentous hyperprolactinaemia. Prolactin takes calcium from the skeletal system following increased Prlr gene expression in the vertebrae to maintain calcium homeostasis, which increases the harmful effect on bone metabolism compared to that of physiological hyperprolactinaemia.

Localised Langerhans cell histiocytosis of the hypothalamic-pituitary region: case report and literature review.

INTRODUCTION: Langerhans cell histiocytosis (LCH) localised in the hypothalamic-pituitary region (HPR) is very rare, especially in adults. Diabetes insipidus (DI) is considered to be a hallmark of HPR LCH, while anterior pituitary abnormalities are usually seen as consequences of surgery, radiotherapy or chemotherapy. CASE DESCRIPTION: We present a patient with localised HPR LCH with dominant anterior pituitary dysfunction and tumour mass effects but without DI. Seven years after surgery and local radiotherapy, she is stable. Control MRI shows no residual tumour growth and thorough physical examination is still without any signs of disease spread. CONCLUSIONS: Anterior pituitary deficiency can appear without DI and not only as a consequence of LCH treatment. All patients with LCH should be screened for this endocrine abnormality so that appropriate substitution therapy may be provided.

Relationship of adipokine to insulin sensitivity and glycemic regulation in obese women--the effect of body weight reduction by caloric restriction.

BACKGROUND/AIM: Visceral fat is highly active metabolic and endocrine tissue which secretes many adipokines that act both on local and systemic level. It is believed that adipokines and "low-grade inflammatory state" represent a potential link between obesity, metabolic syndrome, insulin resistance and cardiovascular disease. Leptin and adiponectin are considered to be the most important adipokines with the potential metabolic and cardiovascular effects. Body weight loss improves insulin sensitivity and decreases risk for most complications associated with obesity. The aim of this study was to determine the effects of moderate loss of body weight on the level of leptin and adiponectin, insulin sensitivity and abnormalities of glycoregulation in obese women, to determine whether and to what extent the secretory products of adipose tissue, leptin and adiponectin contribute to insulin sensitivity, as well as to assess their relationship and influence on glycemia and insulinemia during the period of losing body weight using a calorie restricted diet. METHODS: The study involved 90 obese female subjects (BMI > or = 30 kg/m2) of different age with weight loss no less than 5% during a six-month period by application of restricted dietary regime. The calorie range was between 1,100-1,350 kcal. Serum levels of leptin and adiponectin, fasting glucose, fasting insulinemia, and Homeostasis Model Assessment of Insulin Resistance (HOMA-R) index were determined in all the subjects initially and after weight reduction. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test--OGTT. RESULTS: Applying a 6-month restrictive dietary regime the subjects achieved an average weight loss of 8.73 +/- 1.98 kg and 8.64 +/- 1.96%, which led to the reduction of fasting glycemia, fasting insulinemia and HOMA-R index at the maximum level of statistical significance (p < 0.001). The achieved reduction led to a statistically significant decrease of leptin level and increase of adiponectin level (p < 0.001). The correction of the established pre-diabetic disorders of glycoregulation was not statistically significant. There was a statistically significant correlation between the anthropometric parameters, leptin, adiponectin, fasting glycemia, fasting insulinemia and HOMA-R index. There was a positive correlation between leptin, fasting insulinemia and HOMA-R, as well as a statistically significant negative correlation between adiponectin, fasting insulinemia and HOMA-R index (p < 0.01). CONCLUSION: Body weight increase and central fat accumulation lead to changes in serum levels of leptin and adiponectin, reduction of insulin sensitivity and development of glycemic dysregulation. Secretory products of adipose tissue, leptin and adiponectin contribute to the genesis of these disorders. The obtained results show that the effect of adiponectin on insulin sensitivity is more significant. The analysis of the effects of weight loss on the investigated parameters shows that moderate weight reduction by restrictive dietary regime lead to changes of investigated parameters at the maximum level of statistical significance. Such results emphasize the importance of weight reduction in obese persons, as well as the need for consistent implementation of restricted dietary regime in the process of treatment of obesity.

The hypertriglyceridemic waist phenotype and metabolic syndrome by differing criteria in type 2 diabetic patients and their relation to lipids and blood glucose control.

BACKGROUND: Metabolic syndrome (MetS) describes clustering of obesity, dyslipidemia, hyperglycemia and hypertension and increases risk for cardiovascular disease and type 2 diabetes. The 'hypertriglyceridemic waist' phenotype (HTGW) represents a simple approach to identifying individuals with increased risk. The aim of the study was to determine the prevalence of HTGW and MetS in type 2 diabetic patients, and to examine their relation to lipids and blood glucose control. MATERIAL AND METHODS: 300 type 2 diabetic patients were analysed, and their history of diabetes, anthropometric measures, measurements of blood pressure (BP), lipids and glycemic control parameters were taken. RESULTS: In type 2 diabetic patients, the prevalence of MetS was 71.0% by the AHA/NHLBI definition and 75.33% by the IDF definition. The prevalence was 62.58% and 66.45% in men, and 80% and 84.83% in women by the same definitions, respectively. There were 41.33% of patients with HTGW (42.76% among women and 40% among men). There were statistically significant differences of age, fasting plasma glucose (FPG) and postprandial glucose (PPG) in women with and without MetS according to both definitions, and of total and LDL cholesterol with and without MetS according to AHA/NHLBI (but not IDF). In men, there were statistically significant differences of total cholesterol and of HbA(1c) with and without MetS according to AHA/NHLBI (but not IDF). Women with HTGW had higher levels of total and LDL cholesterol, systolic and diastolic BP. Men with HTGW had higher levels of total cholesterol, diastolic BP, HbA(1c), FPG and PPG. CONCLUSIONS: Determining MetS or HTGW helps identify those with increased cardiovascular risk.

[Exercise as a therapeutic option in cardiometabolic risk reduction].

Regular physical activity is meant to be one of the most important nonpharmacological tools in reducing overall cardiometabolic risk since it significantly regulates body weight, blood pressure, blood glucose and lipid levels, and it also improves strength flexibility and quality of life and reduces stress. However, it should be individually prescribed, according to the patient's previous health status, individual desires and goals. Previous examinations (exercise stress testing, searching for vascular and neurological complications) are highly recommended in order to avoid potential risks (cardiovascular, microvascular, macrovascular, musculosceletal) ones. It should be strictly defined according to the type (aerobic vs. anaerobic activities), frequency (at least 3-5 times a week), duration (at least 20 to 60 minutes per session), intensity (55-90% of maximal heart rate) and energy expenditure (700-2000 kcal per week). It is highly recommended to be performed under supervision, at least at the beginning of the programme. Regular physical activity should become a part of everybody's lifestyle, especially in people at a high cardiovascular risk, in order to prevent the disease, as well as in those with already diagnosed cardiovascular disease, to prevent its complications.

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

BACKGROUND/AIM: Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. METHODS: A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. RESULTS: Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). CONCLUSION: Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Thyroid blood flow and uptake of technetium-99m pertechnetate in Graves' disease.

The aim of this study was to assess the relation of early thyroid blood flow (EBF) and technetium-99m pertechnetate ((99m)TcO(-)(4)) uptake, as an early diagnostic index in patients with Graves' disease (GD) by dynamic thyroid scintigraphy (40 frames, 3 sec/frame). Thirty patients with GD with mean age 50.0 +/- 9.0 y, range: 35.0-69.0 y, were studied. The results obtained were compared with those of 30 euthyroid individuals (EI) of mean age 46.9 +/- 12.5 y, range: 22.0-68.0 y. The parameters of (99m)TcO(-)(4) EBF and early uptake studied, derived from the background subtracted time activity curves, were as follows: a) The duration of the EBF in sec; b) The perfusion index (PI) - the ratio of counts at the beginning and at the end of the EBF; c) The uptake index 1 (UI1)- the counts ratio between the counts at the end of the EBF and at the 2nd min d) The uptake index 2 (UI2) - the counts ratio between the 1st min and the 2nd min of the uptake curve and e) Delayed (99m)TcO(-)(4) thyroid uptake (TcTU) at 20 min was also calculated as a percentage of net counts activity accumulated in the thyroid gland at 20 min. Results were as follows: a) The mean values of the duration of the EBF were shorter in GD patients (9.90 +/- 2.94 sec) than in EI (15.70 +/- 4.01 sec; P<0.0001); b) PI did not differ significantly (P>0.05); c) The mean UI1 and UI2 values of thyroid uptake of 99m TcO4- were significantly lower in GD (UI1=0.621, UI2=0.772) as compared to EI (UI1=1.106, UI2=0.947; P<0.0001 for both) and d) TcTU values were significantly higher in GD (13.6%) than in the group of EI (1.29%; P<0.0001). A good correlation was found in patients with GD between early (UI1 and UI2) and delayed TcTU (r = -0.562; P=0.010 and r = -0.459; P=0.042 respectively). Also, in patients with GD the EBF correlated poorly with UI1, UI2 and TcTU (P>0.05 for all these parameters). In conclusion, the results of this study indicate that the duration of EBF did not relate significantly to the height of TcTU values in patients with GD. On the contrary, the early uptake, indices UI1 and especially UI2 were shown to be faster in the majority of GD patients and correlated well with the TcTU. These parameters may be used as diagnostic indices for GD. Further investigation is required to support the above findings.

[Clinical and echocardiographic characteristics of patients with diabetic cardiomyopathy]. / Klinicke i ehokardiografske karakteristike bolesnika sa dijabetesnom kardiomiopatijom.

The aim of this study was to evaluate clinical and echocardiographic characteristics of patients with diabetic cardiomyopathy. The study included 72 patients, divided into two groups. The experimental group consisted of 32 diabetics, while 40 gender and age-matched healthy subjects were in the control group. In the experimental group there were 17 patients with insulin-dependent diabetes mellitus, and 15 patients with non-insulin-dependent diabetes mellitus. The average duration of diabetes mellitus was 9.53 years. All the patients underwent the following diagnostic procedures: standard laboratory tests, 12-lead ECG, chest X-ray, 24-h Holter ECG, and complete echocardiographic examination. More frequent appearance of ventricular rhythm disturbances (65.6% vs. 47.5%), increased heart rate (78.3 +/- 8.2 vs. 72.1 +/- 4.6 beats per minute), and alteration of diastolic (56.25% vs. 12.5%) and systolic function (43.8% vs. 0%) was registered in patients with diabetes, compared to the control group. Experimental group was divided, according to their left ventricular dimensions, into two subgroups: the subgroup with normal left ventricular dimensions, and the subgroup with the increased left ventricular dimensions. Patients with the increased left ventricular dimensions not only had significantly lower ejection fraction (37.4 +/- 7.0 vs. 61.3 +/- 4.2%), but also had significantly longer duration of diabetes (12.6 +/- 5.8 vs. 8.01 +/- 3.01 years), worse quality of glycoregulation (13.1 +/- 2.5 vs. 10.4 +/- 2.1%), and higher Shapiro's microvascular complications index (2.7 +/- 1.26 vs. 0.68 +/- 0.56). High degree of correlation was also found between the duration of diabetes, left ventricular ejection fraction (-0.86), and left ventricular mass (0.86). The similar level of correlation was shown with Shapiro's index (-0.77 and 0.88), as well as with morning glycaemia (-0.57 and 0.41). According to the obtained results it could be concluded that the changing rate of diabetic cardiomyopathy was in direct correlation with the quality of diabetes control, the duration of diabetes, and the presence of complications in other organs.