A new approach to define dynamics of the ion channel gates

Voltage-gated ion channels are of great importance in the generation and propagation of electrical signals in the excitable cell membranes. How these channels respond to changes in the potential across the membrane has been a challenging problem, and different approaches have been proposed to address the mechanism of voltage sensing and gating in these channels. In this study, we attempt a new approach by considering a simple two-state gate system and applying the path probability method to construct a nonequilibrium statistical mechanical model of the system. The model which is based on the principles of statistical physics provides a firm physical basis for ion channel gating.     

Activation kinetics of T-type calcium channel by a path probability approximation

We previously formulated dynamics of ion channel gates by the path probability method. In this study, we apply that theoretical approach to derive the activation rate kinetics of T-type calcium channel in thalamic relay neurons. We derive explicit expressions of the forward and backward rate constants and show that the proposed rate constants accurately capture form of the empirical time constant, and that they also provide its saturation to a constant value at depolarized membrane potentials. We also compare our derivations with linear and nonlinear thermodynamic models of rate kinetics obtained from the same calcium channel, and show that it is possible to capture saturation of the time constant for the depolarized membrane potentials by the only proposed rate constants.     

Conservative treatment of eminentia intercondylaris fractures of the tibia in children

Seventeen patients (16 children, 1 adolescent) were reviewed 31 months to 71 months after sustaining the common childhood fracture of the eminentia intercondylaris of the tibia. The aim was to assess long-term results and prognosis by clinical and radiological examination and to discover whether conservative treatment was adequate for type I and type II fractures according to Meyers and McKeever. Early improvement occurred in all patients after conservative treatment, but long-term results were not satisfactory in displaced fractures,which were treated with closed reduction and immobilization in extension. Therefore, anatomic reduction and rigid fixation should be obtained for displaced fractures of the eminentia intercondylaris of the tibia.     

Endocrine complications in patients with beta-thalassemia major

Thirty-seven patients with thalassemina major (TM) were studied to determine the extent and rate of endocrine complications. Mean haemoglobin and ferritin concentrations were 8.8 +/- 0.6 and 3,597 +/- 1,931, respectively. Provocation tests for growth hormone secretion were applied in patients with standing heights below the third centile and/or growth velocities below the 10th centile. Sexual maturation was assessed by using the criteria of Tanner. Glucose metabolism was assessed by fasting plasma glucose and glucose tolerance test. Basal thyroid function was measured and thyrotropin-releasing hormone tolerance test was carried out. Growth retardation was found in 40 per cent of patients and growth hormone deficiency was a prominent cause of growth retardation. Gonadal dysfunction was detected in 47 per cent of patients. Hypothyroidism was observed in 16 per cent and impaired glucose metabolism in 10.8 per cent patients. The high rate of endocrine disturbances indicates the importance of regular follow-up of thalassemia major patients with regard to endocrine complications of the disease.     

Intravenous magnesium sulfate prophylaxis for atrial fibrillation after coronary artery bypass surgery

OBJECTIVE: Atrial fibrillation is a rhythm disorder commonly seen early after coronary artery bypass grafting, and it increases morbidity. METHODS: To investigate the effectiveness of magnesium sulfate in the prophylaxis of atrial fibrillation, we conducted a prospective, randomized, placebo-controlled clinical study on 200 consecutive patients in whom we performed elective and initial coronary artery bypass grafting operations. In each group 50% of patients underwent beating-heart operations. In the treatment group 100 patients (76 men and 24 women; mean age, 57.63 +/- 9.68 years) received 24.34 mEq (3 g) of magnesium sulfate in 100 mL of saline solution that was administered over 2 hours (50 mL/h) preoperatively, perioperatively, and at postoperative days 0, 1, 2, and 3. In the control group 100 patients (74 men and 26 women; mean age, 59.96 +/- 9.29 years) received only 100 mL of saline solution according to the same administration schedule as the treatment group. RESULTS: Atrial fibrillation developed in 15 patients from the treatment group and in 16 patients from the control group. The arrhythmia developed after 37.87 +/- 12.76 and 45.26 +/- 15.27 hours in the treatment and control groups, respectively. Although a significant relationship was found between low magnesium sulfate levels and increased incidence of atrial fibrillation (P <.05), when the incidence of postoperative atrial fibrillation is concerned, no significant difference was found between the 2 groups (P >.05). Also, no significant difference was found between operations with cardiopulmonary bypass and beating-heart operations in terms of atrial fibrillation incidence (P >.05). However, atrial fibrillation extended the duration of hospital stay in both groups (P <.05). CONCLUSION: Our findings indicate that magnesium sulfate infusion alone is not sufficient for the prophylaxis of atrial fibrillation.     

Immediate percutaneous intramedullary fixation and functional bracing for the treatment of pediatric femoral shaft fracture

Fifty-three consecutive children ages 6 to 14 with femur fractures treated with early percutaneous intramedullary fixation were evaluated retrospectively. The operation was performed within 24 hours in 50 patients and in the remainder after 48 hours. All patients were mobilized and allowed full weight-bearing in a functional brace in the early postoperative period. The average hospital stay was 4 days. The average follow-up was 24 months. There were no significant intra- or postoperative complications. An average overgrowth of 1.8 mm was measured using scanogram 24 months after surgery. In the authors' experience, this technique is highly effective for the treatment of children 6 to 14 years old with femur fractures. The main advantages of this method are early weight-bearing, immediate mobilization, short hospitalization, and fewer complications.     

An overview: Human polyomavirus JC virus and its associated disorders

JC virus (JCV) is a polyomavirus infecting greater than 80% of the human population early in life. Replication of this virus in oligodendrocytes and astrocytes results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals, most notably acquired immunodeficiency syndrome (AIDS) patients. Moreover, recent studies have pointed to the association of JCV with a variety of brain tumors, including medulloblastoma. The JCV genome encodes for viral early protein, including large and small T antigens and the newly discovered isoform T', at the early phase of infection and the structural proteins VP1, VP2, and VP3 at the late stage of the lytic cycle. In addition, the late gene is responsible for the production of a small nonstructural protein, agnoprotein, whose function is not fully understood. Here, we have summarized some aspects of the JCV genome structure and function, and its associated diseases, including PML and brain tumors.     

Biological considerations in locally advanced breast cancer treated with anthracycline-based neoadjuvant chemotherapy: thymidine labelling index is an independent indicator of clinical outcome

The present retrospective study aims to determine the clinical value of thymidine labelling index (TLI) together with other established clinical and biological factors in 116 locally advanced breast cancer (LABC) patients treated with anthracycline-based neoadjuvant chemotherapy, surgery, adjuvant chemotherapy and radiotherapy. TLI was determined in 71 LABC patients with a median of 2.62% (0–23.64%) and a mean of 4.71%±5.54. As a result of neoadjuvant chemotherapy, 85 patients (73%) responded to chemotherapy (CT), whereas 31 patients were unresponsive (27%). No relationship has been found between the pretreatment biological variables including TLI, estrogen receptor (ER), progesteron receptor (PgR) status and clinical parameters such as the chemotherapy response rates and axillary lymph node involvement following chemotherapy. Median follow-up was 35 months (18–97 months) and the 3-year overall survival (OS) and disease free survival (DFS) rates were 71.6% and 52.2%, respectively. In univariate analysis, patients with inflammatory breast cancer, high TLI-index (2.62%), lymph node (LN) positivity or >3 positive lymph nodes following neoadjuvant chemotherapy and without any response to neoadjuvant chemotherapy were found to have worse DFS and OS-rates and high local and systemic recurrence rates. In multivariate analysis, TLI was estimated as the most powerful independent factor affecting the OS in LABC patients among the other established clinical and biological parameters (p=0.02). These results suggest that TLI is an important independent indicator of clinical outcome in patients with LABC and these patients with high TLI levels require more effective treatment modalities.     

Traditional and “new” cardiovascular risk markers and factors in pediatric dialysis patients

Cardiovascular disease (CVD) is the principal cause of mortality in patients with end-stage renal disease (ESRD). The aim of this study was to analyze carotid intima-media thickness (cIMT), endothelium-dependent dilatation (EDD), and left ventricular mass index (LVMI) as the cardiovascular risk markers and to investigate the independent risk factors of these markers in pediatric dialysis patients. This study included 39 children and adolescents undergoing dialysis (15 hemodialysis and 24 peritoneal dialysis) and 15 age- and gender-matched healthy subjects. The cIMT and EDD were assessed by high-resolution ultrasound, and LVMI was calculated from standard echocardiographic measurements. Compared with control subjects, cIMT standard deviation scores (SDS), LVMI, total homocysteine (tHcy), and high-sensitivity C-reactive protein (hs-CRP) values were significantly higher in patients, but EDD values did not differ. The mean hs-CRP level was significantly higher in hemodialysis (HD) patients than in peritoneal dialysis (PD) patients. The cIMT-SDS and LVMI were associated with several variables in univariate analysis. Stepwise linear regression analysis, indexed SBP (p = 0.017), and hemoglobin (p = 0.001) turned out to be independent variables for predicting LVMI, and a significant predictor of cIMT was indexed diastolic blood pressure (DBP) (p = 0.035). The causes of atherosclerosis and left ventricular hypertrophy are multifactorial in children and adolescents with ESRD. Better management of hypertension and anemia may be priorities for preventing or improving CVD in these patients.