Electroconvulsive seizures increase the expression of MAP kinase phosphatases in limbic regions of rat brain.

The mitogen-activated protein (MAP) kinase cascades regulate a variety of cellular activities, including cell growth, proliferation, and apoptosis, and are reported to play a role in the actions of antidepressant treatment. There are a number of different classes of protein phosphatases that could influence the MAP kinase cascade. One of these, the MAP kinase phosphatase (MKP) family, is known to play a key role in dephosphorylation of activated MAP kinase. In the present study, we analyzed the expression of the MKP1, MKP2, and MKP3 isoforms in rat brain after electroconvulsive seizure (ECS), considered the most effective treatment for depression. In situ hybridization analysis demonstrates that ECS differentially regulates the expression of the MKP isoforms. Expression of MKP1 mRNA is robustly increased by acute ECS in the major cell layers of the hippocampus, including the dentate gyrus granule cell layer and the CA1 and CA3 pyramidal cell layers. In contrast, MKP2 is induced mainly in the dentate gyrus and MKP3 is preferentially increased in the CA1 and CA3 cell layers. In the prefrontal cortex, all three MKP isoforms are upregulated by acute ECS administration. Chronic ECS resulted in a similar pattern of induction for each of the MKP subtypes, demonstrating that there is little or no desensitization of the response to repeated ECS. The induction of MKP expression serves as negative feedback control for the MAP kinase cascades. Upregulation of MKP expression could dampen the actions of ECS, indicating that blockade of the MKPs could enhance the actions of antidepressant treatment.     

Predictors of malignancy in patients with solitary pulmonary nodules undergoing pulmonary resection

BackgroundThe management of a solitary pulmonary nodule is a challenging issue in pulmonary disease. Although many factors have been defined as predictors for malignancy in solitary pulmonary nodules, the accurate diagnosis can only be established with the permanent histological diagnosis.ObjectiveWe tried to clarify the possible predictors of malignancy in solitary pulmonary nodules in patients who had definitive histological diagnosis.MethodsWe made a retrospective study to collect the data of patients with solitary pulmonary nodules who had histological diagnosis either before or after surgery. We made a statistical analysis of both the clinic and radiological features of these nodules with respect to malignancy both in contingency tables and with logistic regression analysis.ResultsWe had a total of 223 patients with a radiological diagnosis of solitary pulmonary nodule. Age, smoking status and pack years of smoking, maximum standardized uptake value (SUVmax), and radiological features such as solid component, spiculation, pleural tag, lobulation, calcification, and higher density were significant predictors of malignancy in contingency tables. Age, smoking status and smoking (pack/year), SUVmax, and radiological features including spiculation, pleural tag, lobulation, calcification, and higher density were the significant predictors in univariate analysis. However, multivariate analysis revealed only SUVmax greater than 2.5 (p < 0.0001), spiculation (p = 0.009), and age older than 61 years (p = 0.015) as the significant predictors for malignancy.ConclusionAge, SUVmax, and spiculation are the independent predictors of malignancy in patients with solitary pulmonary nodules.     

Insulin detemir improves glycemic control and reduces hypoglycemia in children with type 1 diabetes: findings from the Turkish cohort of the PREDICTIVE™ observational study

Background: Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts. Methods: The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE? (a large, multinational, observational) study. The children investigated were using basal–bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians. Results: Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7–8.9%, p < 0.001) and mean fasting glucose [185–162 mg/dL (10.3–9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged. Conclusions: Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.     

Extension of GnRH agonist through the luteal phase to improve the outcome of intracytoplasmic sperm injection

OBJECTIVE: To investigate the effect of continuous administration of gonadotropin-releasing hormone agonist (GnRHa) during the luteal phase in an intracytoplasmic sperm injection program. STUDY DESIGN: One hundred eighty-one women underwent a down-regulation protocol of GnRHa administered from the 21st day of the preceding cycle. Patients were randomized at initiation of stimulation by a computer-generated list. Group 1 patients (n = 90) were continuously administered GnRHa for 12 days after embryo transfer, while in group 2 patients GnRHa was stopped on the day of human chorionic gonadotropin administration. RESULTS: Demographic parameters, infertility etiologies, number of gonadotropin ampules used, number of mature oocytes recovered, rates of testicular sperm usage, number of embryos transferred, and cycle and transfer cancellation rates were similar in both groups. Clinical pregnancy rates, implantation rates and live birth rates did not show a significant difference. CONCLUSION: Extending GnRHa treatment through the luteal phase appeared not to have a significant impact on pregnancy or implantation rates in intracytoplasmic sperm injection cycles.     

Two cases of macrocephaly and immune deficiency

Macrocephaly describes a head circumference greater than two standard deviations above the mean and is a feature of a number of genetic syndromes. Here we report on two patients with microcephaly, immune deficiency and anemia. In addition, one case had periventricular leukomalacia and the other case had myelinisation delay in periventricular white matter development. These cases may represent a distinct new syndrome.     

The role of extracellular matrix and activin-A in in vitro growth and survival of murine preantral follicles

Extracellular matrix plays a key role in cell growth, survival, and differentiation in a wide array of tissue types through integrin-mediated signaling pathways and its interaction with growth factors. This study investigates the role of extracellular matrix and its interaction with activin-A on in vitro growth and survival of mouse preantral follicles. Preantral follicles isolated from 14-day-old immature mouse ovaries were cultured either 3 dimensionally using basement membrane matrix (growth factor - reduced matrigel) or 2 dimensionally on cover slips coated with a single component of extracellular matrix (fibronectin, collagen, or laminin), on polylysine (negative control), or in standard culture plates in a serum-free culture medium with or without activin-A for 7 days. Follicles cultured in matrigel maintained well their 3-dimensional structure compared to those cultured conventionally. This observation was confirmed by analyzing 3-dimensional images of follicles cultured in matrigel and standard culture plate using confocal microscopy. Furthermore, follicles displayed higher growth and survival rates and exhibited antral space formation as early as day 5 of culture when activin-A was added to matrigel; in contrast, the addition of activin-A had no effect on the growth and survival of follicles cultured on individual extracellular matrix components after 7 days of culture. These data may suggest that 3-dimensional culture with extracellular matrix and activin-A provides a better milieu for in vitro growth and survival of preantral follicles in immature mice.     

Thyroid disorders in hemodialysis patients in an iodine-deficient community

There are various changes in the thyroid gland and its function in chronic renal failure (CRF). These changes include lower levels of circulating thyroid hormone, altered peripheral hormone metabolism, decreased binding to carrier proteins, possible reduction in tissue hormone content, and increased iodine storage in the thyroid gland. The decrease of excretion of urinary iodine in CRF increases serum inorganic iodine level and iodine content of the thyroid, which consequently enlarges the gland. This study is designed to investigate the prevalence of goiter and thyroid dysfunction in patients with end-stage renal disease (ESRD) on hemodialysis (HD) in an iodine-deficient community. Eighty-seven (40 females and 47 males) HD patients and 169 (79 females and 90 males) healthy individuals as controls are included. Sex ratios for the patient and control groups are 0.85 and 0.88, respectively. Mean ages for the patient and control groups are 42.94 +/- 11.88 and 40.20 +/- 10.72 years, respectively. Examination of the thyroid gland using ultrasonography along with simultaneous measurement of blood levels of free-T4 (FT4), free-T3 (FT3), and thyrotropin (TSH) are made for every individual. The presence of goiter demonstrable by ultrasonography is found in 32.2% of the uremic patients and in 23.5% of the controls and its prevalence increases with age (P = 0.01). In 32 (36.8%) of the patients and 29 (17.1%) of the controls at least one thyroid nodule is found in ultrasonography. Between patients with or without a nodular goiter the authors could not observe any difference for duration of dialysis and serum levels of TSH, FT4, FT3, calcium, and albumin. In ESRD patients the prevalence of nodular goiter is higher for females (47.5% vs. 27.7%, P = 0.045) and increases with age (P = 0.04). Though incidence of hyperthyroidism is found to be similar for the two groups (1.14% in ESRD patients vs. 1.10% in controls), hypothyroidism is observed in 3.4% of ESRD patients but only 0.6% of controls. This high incidence of hypothyroidism and nodular goiter in ESRD patients shows that screening for thyroid dysfunction and goiter, using appropriate laboratory tests and ultrasonography, should be considered in evaluation of every ESRD patient.