The effects of hypothyroidism in rats on serum leptin concentrations and leptin mRNA levels in adipose tissue and relationship with body fat composition

Both thyroid hormones and leptin affect sympathetic nervous system activity, basal metabolic rate, body fat mass, food intake, and thermogenesis, and each one also affects the actions of the other. We examined the alterations in serum leptin concentrations and leptin mRNA expression in hypothyroid rats and investigated the relation between serum leptin and leptin mRNA levels with the total adipose tissue mass and total body weight. Twenty male Wistar rats were divided into 2 groups, euthyroid and hypothyroid. Their body compositions were examined by Dual Energy X-ray Absorptiometry at the beginning and end of the study. Serum leptin concentrations and levels of leptin mRNA in the retroperitoneal white adipose tissue were measured at the end of the study. Serum leptin concentrations did not show any difference between the two groups (1.9 +/- 0.2 ng/ml in the hypo and euthyroid group, P > 0.05), but the fat mass of the hypothyroid rats were lower than the euthyroid rats (21.1 +/- 2.5 g in the euthyroid group and 14.2 +/- 1.9 g in the hypothyroid group, P > 0.05 between groups at the end of the study) although the difference between the groups was statistically not significant. Leptin mRNA level was significantly higher in the hypothyroid group than in the euthyroid group (21.6 +/- 1.6 vs. 15.1 +/- 1.2 ng respectively, P = 0.002) although the dissected retroperitoneal fat weight was significantly lower in the hypothyroid group versus the euthyroid group (1.0 +/- 0.2 vs. 1.8 +/- 0.2 g respectively, P = 0.013). In conclusion, the change of leptin mRNA expression in white adipocytes was thought to be the direct result of hypothyroidism or a compensatory response to metabolic changes caused by hypothyroidism.     

Thrombocytosis in rheumatoid arthritis: JAK2V617F-positive essential thrombocythemia

Thrombocytosis is an important laboratory finding in rheumatoid arthritis (RA) and it has a correlation with disease activity. Janus kinase 2 valin 617 phenylalanine (JAK2V617F) mutation has gained importance in the diagnosis of myeloproliferative diseases recently. There is no published report in literature on the association between RA and JAK2V617F-positive essential thrombocythemia (ET). In this report, we present a JAK2V617F-positive ET case that had RA. A 57-year-old male patient was diagnosed with RA according to the criteria of American College of Rheumatology (ACR), whose complaint was of pain in the hands and morning stiffness lasting for about 2 h. The patient was evaluated for thrombocytosis because he was in remission and suffering persistent thrombocytosis under treatment. After excluding the causes of secondary thrombocytosis, bone marrow aspiration and biopsy was performed. On peripheral blood and bone marrow PCR examination, the patient was detected to be JAK2V617F positive heterozygously and diagnosed with ET. As a conclusion, mild–moderate thrombocytosis is frequent in RA; however, ET can be diagnosed by JAK2V617F evaluation in peripheral blood in thrombocytosis, especially when platelet count is more than 1 million/ml and when persisting thrombocytosis is detected in RA remission.     

Detection of metabolites of the new synthetic cannabinoid CUMYL‐4CN‐BINACA in authentic urine samples and human liver microsomes using high‐resolution mass spectrometry

CUMYL‐4CN‐BINACA(1‐(4‐cyanobutyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H–indazole‐3‐carboxamide) is a recently introduced indazole‐3‐carboxamide‐type synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine, Istanbul Narcotics Department, in May 2016 in Turkey. Recently introduced SCs are not detected in routine toxicological analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL‐4CN‐BINACA by investigating its metabolism in human liver microsomes and to confirm the results in authentic urine samples (n = 80). In this study, 5 μM CUMYL‐4CN‐BINACA was incubated with human liver microsomes (HLMs) for up to 3 hours, and metabolites were identified using liquid chromatography–high‐resolution mass spectrometry (LC–HRMS). Less than 21% of the CUMYL‐4CN‐BINACA parent compound remained after 3 hours of incubation. We identified 18 metabolites that were formed via monohydroxylation, dealkylation, oxidative decyanation to aldehyde, alcohol, and carboxylic acid formation, glucuronidation or reaction combinations. CUMYL‐4CN‐BINACA N‐butanoic acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL‐4CN‐BINACA was not detected; CUMYL‐4CN‐BINACA N‐butanoic acid (M16) was major metabolite after β‐glucuronidase hydrolysis. Based on these findings, we recommend using M16 (CUMYL‐4CN‐BINACA N‐butanoic acid), M8 and M11 (hydroxylcumyl CUMYL‐4CN‐BINACA) as urinary marker metabolites to confirm CUMYL‐4CN‐BINACA intake.     

The effect of graft nephrectomy on long-term graft function and survival in kidney retransplantation

We retrospectively evaluated the long-term results of 53 (3.5%) recipients who received second allograft among 1486 kidney transplants between November 3, 1975 and June 30, 2004. Two study groups were patients in Group 1 (n = 21) who underwent allograft nephrectomy and those in Group 2 (n = 32) who did not. We assessed demographic features, rejection rates throughout the follow-up period, and serum creatinine levels at 12 months as well as graft and patient survival rates, postoperative complications, time interval between transplantations, and HLA matches. Forty-three patients who underwent retransplantation received kidneys from living-related donors and the remaining 10 from cadaveric donors. Mean serum creatinine levels of Group 1 versus Group 2 were 1.8 mg/dL (range, 0.8 to 6.6 mg/dL) versus 2.1 +/- 1.1 mg/dL (range, 1.1 to 7.1 mg/dL). HLA-AB and HLA-DR mismatches were 1.9 +/- 1.1 versus 1 +/- 0.6, respectively (P = .01). Acute rejection rates were not significantly different between Groups 1 (9/21, 43%) and 2 (12/32, 38%) (P < .05). The average intervals between the first and the second transplantations were 62 +/- 26 months in Group 1 (P = .02) and 32 +/- 11 months in Group 2. One-, 3-, and 5-year graft survival rates in Group 1 versus Group 2 were 83% versus 89% (P > .05); 64% versus 79% (P > .05), and 45% versus 68% (P = .04), respectively. In conclusion, we did not observe any advantage of graft nephrectomy before retransplantation. The length of the interval between the first and the second transplantations may have a negative correlation with second graft survival.     

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma gene in first-degree relatives of subjects with polycystic ovary syndrome.

AIM: This study was designed to examine the relationship between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and insulin resistance (IR) in first-degree relatives of subjects with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: One hundred and twenty family members of 55 patients with PCOS and 80 unrelated healthy control subjects without a family history of diabetes or PCOS were studied. IR was assessed by homeostatic model assessment (HOMA-IR) and area under the curve (AUC) for insulin during an oral glucose tolerance test in subjects with normal glucose tolerance and controls. Genetic analysis of the PPAR-gamma gene Pro12Ala polymorphism was performed by restriction fragment length polymorphism. RESULTS: Fasting insulin, HOMA-IR and AUC insulin were significantly higher in first-degree relatives of PCOS subjects than in controls. A significantly different allele distribution of the Pro12Ala polymorphism of PPAR-gamma was observed between the two groups, with the frequency of the variant Ala isoform being significantly reduced in the first-degree relatives of PCOS subjects (10.8%, 13 subjects) compared with the control group (22.5%, 18 subjects). All Pro12Ala polymorphisms of the PPAR-gamma gene were heterozygous. Compared with first-degree relatives of PCOS subjects with the Pro12Pro polymorphism of PPAR-gamma, first-degree relatives of PCOS subjects with the Pro12Ala polymorphism had low fasting insulin, HOMA-IR and AUC insulin levels. The combined prevalence rate for impaired glucose tolerance, impaired fasting glucose and diabetes was 40% (16 subjects) in mothers and 52% (20 subjects) in fathers of PCOS women. CONCLUSION: Our findings suggest that Pro12Ala PPAR-gamma gene polymorphism may be protective against IR and might prevent the development of diabetes mellitus in the first-degree relatives of subjects with PCOS.     

Brainstem encephalitis and acute disseminated encephalomyelitis following mumps

A previously healthy female, aged 4 years 3 months, developed brainstem encephalitis with clinical manifestations of fever, decreased level of consciousness, and left facial and abducens paralysis 1 week after bilateral parotitis. Twenty days after remission of encephalitis, she manifested new symptoms of ataxia, dysarthria, and fever. Magnetic resonance imaging revealed multiple hyperintense lesions which were increased in size when compared with the first magnetic resonance imaging. She was treated with glucocorticoids and intravenous immunoglobulin. Forty-eight days after therapy, she was able to walk with support and recovered completely on follow-up. Brainstem encephalitis and acute disseminating encephalomyelitis are discussed as rare complications of mumps.     

A case of mitral papillary muscle rupture due to blunt chest trauma

Mitral regurgitation due to papillary muscle rupture after blunt chest trauma is uncommon. Sudden onset severe mitral regurgitation may lead to death due to heart failure if surgical repair is delayed. A previously healthy 12-year-old girl underwent splenectomy and chest tube insertion for pneumothorax after a traffic accident in a vehicle 15 days before. She was discharged from the hospital after a nine-day follow-up. She was presented to our hospital due to respiratory distress. On physical examination, an apical holosystolic murmur radiating to the axillary region was recognized. Transthoracic echocardiogram showed severe mitral regurgitation with freely moving posterior mitral chordae and prolapse of the posterior mitral valve leaflet. She received reimplantation of the complete ruptured posteromedial papillary muscle of the mitral valve. Her medical condition improved after the operation. On the postoperative echocardiogram, the left ventricular systolic function was normal with no mitral regurgitation.     

Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism

OBJECTIVE: Adiponectin, an adipose tissue-derived hormone, has been reported to have anti-inflammatory and anti-atherogenic effects. The physiological effect of adiponectin on the metabolic changes and its relation with cardiovascular risk factors in thyroid dysfunction states is still not clear. The aim of the study was to evaluate plasma adiponectin level and its relation to cardiovascular risk factors in patients with thyroid dysfunction. PATIENTS AND MEASUREMENTS: Sixty-seven patients with hypothyroidism, 56 patients with hyperthyroidism and 52 age- and sex-matched euthyroid subjects were enrolled in the study. Adiponectin, C-reactive protein (CRP), homocysteine (Hcy), lipid parameters, Lipoprotein(a) [Lp (a)], Apolipoprotein (Apo) A, Apo B and fibrinogen levels were measured in all subjects. Insulin sensitivity was determined using the Homeostasis Model Assessment (HOMA-IR). RESULTS: Circulating adiponectin levels were not different between the groups (16.2 +/- 5.0, 15.1 +/- 3.7, 15.9 +/- 4.8 ng/ml; hypothyroid, hyperthyroid, euthyroid group, respectively). Plasma adiponectin levels correlated negatively with body mass index (BMI) and HOMA-IR index and positively with high-density lipoprotein cholesterol (HDL-C) in all groups. There was a significant correlation between adiponectin and CRP levels in both hypothyroid and hyperthyroid groups. In all groups, adiponectin levels did not correlate with age, systolic blood pressure, diastolic blood pressure and thyroid hormones. Multiple regression analysis revealed BMI and HDL-C levels to be the most important predictors of circulating adiponectin levels. CONCLUSIONS: Plasma adiponectin levels are associated with BMI and HDL-C levels in patients with hypothyroidism and hyperthyroidism. But there is not a direct relation of adiponectin with thyroid hormones in these patients.