Effects of glutamine on wound healing

Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 < 0·001). We conclude that in adults who eat healthy food, who do not have any factor that can affect wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing.     

The major histocompatibility complex region marked by HSP70-1 and HSP70- 2 variants is associated with clozapine-induced agranulocytosis in two different ethnic groups

Genes of the major histocompatibility complex (MHC) have been associated with susceptibility to drug-induced adverse reactions. We previously found that clozapine-induced agranulocytosis (CA) is associated with the HLA-DRB1*0402, DRB4*0101, DQB1*0302, DQA1*0301 haplotype in Ashkenazi Jewish patients and with the HLA-DRB1*1601, DRB5*02, DQB1*0502, DQA1*0102 haplotype in non-Jewish patients. In the present study, we tested the hypothesis that the variants of the heat- shock protein 70 (HSP-70) encoded by the HSP-70 loci located within the MHC region and known to be involved in apoptosis and regulation of cell proliferation could play an important role in molecular mechanisms of CA. First, we analyzed HSP70-2 polymorphism in risk-associated haplotypes from HLA homozygous cells and normal individuals and confirmed that the HSP70-2 9-kb variant was associated invariably with DR4 (HLA-DRB1*0402, DQB1*0302) and DR2 (HLA-DRB1*01601, DQB1*0502, DQA1*0102 and HLA-DRB1*1501, DQB1*0602) haplotypes, which were the haplotypes found increased in Jewish and non-Jewish patients with CA, respectively. The 9.0-kb variant was also found to be associated with HLA-B44, DRB1*0401 and HLA-B44, DRB1*07 haplotypes. Second, in patients with CA (12 Ashkenazi Jewish and 20 non-Jewish patients), HSP70-1 A and HSP70-2 9.0-kb variants were associated with the MHC haplotypes found by us to be markers of susceptibility to CA. The clozapine-treated control group had an excess number of HSP70-1 C and HSP70-2 8.5-kb variants, consistent with genetic resistance to CA associated with those variants. This finding supports our hypothesis that a dominant gene within the MHC region (marked by HSP70-1 and HSP70-2), but not necessarily HLA, is associated with CA in two different ethnic groups.     

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy—based on creatinine level, proteinuria and disease activity—was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.     

Serum leptin levels in gastric cancer patients and the relationship with insulin resistance

Introduction

Serum leptin levels have been examined in various cancers, with conflicting results. However, there is limited information regarding serum leptin levels and insulin resistance in gastric cancer patients. Therefore, we aimed to investigate serum leptin levels, performance status, insulin levels and insulin resistance in patients with gastric cancer. In addition, we examined the relationship between these measurements and leptin levels.

Material and methods

Thirty-nine patients with gastric cancer and 30 control subjects were enrolled in the study. Serum leptin, total protein, albumin, growth hormone, insulin and glucose levels were measured. The homeostasis model assessment (HOMA) was used to assess insulin resistance.

Results

Serum levels of insulin, glucose and growth hormone and insulin resistance were significantly lower in gastric cancer patients than controls (p < 0.05 for all). In the Pearson correlation analysis, insulin resistance was found to be significantly correlated with serum leptin levels in gastric cancer patients (r = 0.320, p = 0.047). We observed a significant negative correlation between performance status and insulin resistance in patients with cachexia (r = –0.512, p = 0.030), while no association was found in non-cachectic patients.

Conclusions

We concluded that serum leptin levels are significantly lower in gastric cancer patients. In addition, gastric cancer patients have decreases in insulin levels, insulin resistance and growth hormone levels. This study found a positive association between serum leptin levels and insulin resistance. Moreover, there is a negative association between serum leptin levels and growth hormone levels. Thus, low insulin and growth hormone levels may suppress the production of leptin in gastric cancer patients.     

Effects of intra-abdominal pressure on adrenal gland function and morphology in rats

Intra-abdominal hypertension and abdominal compartment syndrome (IAH/ACS) are life-threatening conditions and caused by several clinical status. Although there is insufficient data regarding its effects on adrenal glands. This study aimed to identify whether elevated intra-abdominal pressure (IAP) caused any alteration on the morphology and function of adrenal glands in a rat model. Twenty four Sprague-Dawley male rats were included in the study. Animals were allocated into 4 groups. IAP was elevated to 15 mmHg for one hour and four hours in group 2 and 4. Group 1 and 3 were sham groups. Blood samples were taken for the assessment of plasma adrenaline, noradrenaline, and corticosterone levels and adrenalectomies were performed to evaluate apoptosis. Blood adrenaline, noradrenaline and corticosterone levels were significantly higher in the study groups compared with the sham groups. However, there were no significant changes in apoptotic index scores in the study groups as compared to sham groups. These results support that increased IAH leads to discharge of catecholamine and corticosterone from the adrenal glands. Failure to demonstrate similar changes in apoptotic index score may be concluded as apoptosis is not a leading pathway for impairment of adrenal glands during IAH period.     

Evaluation of increased arterial stiffness in pediatric patients with cystic fibrosis by augmentation index and pulse wave velocity analysis

With the increase in life expectancy, cardiovascular complications of cystic fibrosis (CF) have come to the forefront. Increased arterial stiffness is a marker of increased cardiovascular risk. The aim of this study was to compare both pulse wave velocity (PWV) and augmentation index (Aix) measurements in children with CF and to compare them with healthy controls. We hypothesized that children with CF had increased arterial stiffness, although traditional risk factors for CVD were not observed. Forty‐four patients and age and sex‐matched 30 healthy controls were included in the study. Hemodynamic measurements were compared in both groups, together with traditional risk factors. Peripheral blood pressure parameters of CF and control groups were similar (P > .05). Bodyweight and BMI were significantly lower in the CF group (P < .001). Serum cholesterol, HDL, and LDL levels were significantly lower in the CF group, whereas fasting blood glucose and triglyceride levels were significantly higher than the control group (P < .05). Mean ± SD Aix was significantly higher in the CF group (33.22 ± 13.87%) compared with the control group (24.93 ± 10.58%), respectively (P < .05), while PWV was similar. No significant correlation between PWV and Aix and fasting blood glucose and lipid profile in both groups (P > .05). Children with CF have been shown to have increased arterial stiffness compared to healthy children. Although there are not many traditional risk factors, increased arterial stiffness have been demonstrated in children with CF. The effects of this process starting from childhood on the development of CVD in adulthood are not known. Therefore, further studies are needed.     

Prepubertal Unilateral Gynecomastia: Report of 2 Cases

Prepubertal unilateral gynecomastia is an extremely rare condition. At present, its etiology and management strategy are not well known. Two unrelated prepubertal boys of ages 8 and 9 who presented with complaints of unilateral enlargement of breast tissue are reported. Physical examination, biochemical, hormonal and oncologic work-up findings were normal. Both patients were treated with peripheral liposuction successfully. Histopathological and immunohistochemical examinations showed benign fibroglandular gynecomastia and intensive (3+) estrogen receptor expression in 100% of periductal epithelial cells. Although an extremely rare and generally benign condition, patients with prepubertal unilateral gynecomastia should have a full endocrine and oncologic work-up.     

Novel Growth Hormone-Releasing Hormone Receptor Gene Mutations in Turkish Children with Isolated Growth Hormone Deficiency

Objective: Isolated growth hormone deficiency (IGHD) is defined as a medical condition associated with growth failure due to insufficient production of GH or lack of GH action. Mutations in the gene encoding for GH-releasing hormone receptor (GHRHR) have been detected in patients with IGHD type IB. However, genetic defects on GHRHR causing IGHD in the Turkish population have not yet been reported. To identify mutations on GHRHR gene in a population of Turkish children with IGHD.Methods: Ninety-six Turkish children with IGHD were included in this study. Exon1-13 and exon/intron boundaries of GHRHR were amplified by suitable primers. The polymerase chain reaction products for GHRHR gene were sequenced with primers.Results: We analyzed the GHRHR gene for mutations in ninety-six patients with IGHD based on sequence results. We identified novel p.K264E, p.S317T, p.S330L, p.G369V, p.T257A and C base insertion on position 380 (c.380inserC) mutations. In 5 of the patients, the mutation was homozygote and in 1-heterozygote (p.S317T).Conclusion: Six new missense mutations and one first case of insertion mutations for the GHRHR gene are reported.