Investigating the Cocaine-induced Reduction of Potassium Current on the Generation of Action Potentials Using a Computational Model.

Introduction: Drugs of abuse, such as cocaine, affect different brain regions and lead to pathological memories. These abnormal memories may occur due to changes in synaptic transmissions or variations in synaptic properties of neurons. It has been shown that cocaine inhibits delayed rectifying potassium currents in affected brain regions and can create pathological memories.This study investigates how the change in the conductance of delayed rectifying potassium channels can affect the produced action potentials using a computational model. Methods: We present a computational model with different channels and receptors, including sodium, potassium, calcium, NMDARs, and AMPARs, which can produce burst-type action potentials. In the simulations, by changing the delayed rectifying potassium conductance bifurcation diagram is calculated. Results: By decreasing the potassium current for a fixed stimulatory signal, burst-type action potentials can be generated. In the following and with a further reduction of potassium conductance, produced action potentials exhibit non-linear and even chaotic behaviors. Conclusion: Results show that for a specific range of potassium conductance, a chaotic regime emerges in produced action potentials. These chaotic oscillations may play a role in inducing abnormal memories. Highlights: Cocaine consumption reduces the potassium current in affected cells.Decreasing the potassium currents elicits burst action potentials.Produced bursts might have chaotic behaviors.Chaotic oscillations might be related to the toxic effects of cocaine. Plain Language Summary: Drugs of abuse such as cocaine can manipulate brain circuits and may form some pathological memories. These memories can lead to long-term addiction. Furthermore, these drugs also can have toxic effects on the cells. Researchers are looking for the mechanisms that can lead to abnormal memories and toxic effects of drugs. It seems that an efficient mechanism that can be used by drugs of abuse is the manipulation of potassium currents in the affected cells. Here, in a computational model, we have shown that changes in the conductance of delayed rectifying potassium channels can lead to nonlinear and even chaotic behaviors in the produced action potentials. These behaviors might have a role in drug toxic effects.

Role of blood glucose and fat profile in lung function pattern of Indian type 2 diabetic subjects.

BACKGROUND AND OBJECTIVES: It has been hypothesized that changes in lung function can occur in patients with diabetes. Nevertheless, it is unclear how much of this correlation links with biomarkers of metabolism disorder. We have investigated the association between hypoglycaemic and fat profile with lung function in Indian diabetic subjects. DESIGN: Prospective observational study. SETTING: Diabetes care unit of King Edward Memorial (KEM) hospital. PATIENTS: Out of 465 patients who agreed to participate in this study, valid lung function data were available from 347 Type 2 diabetic subjects. MEASUREMENTS: Pulmonary function test including predicted forced vital capacity (% FVC), predicted forced expiratory volume in 1 second (% FEV1) and FEV1/FVC ratio were assessed. We also examined fat profile, glucose, HbA1c, hemoglobin and other hematological parameters. RESULTS: Four hundred sixty-five subjects aged 55 ± 11 participated in the study. Predicted forced vital capacity, % FEV1 and FEV1/FVC ratio was 85.88 ± 13.53, 85.87 ± 14.06 and 82.03 ± 6.83, respectively. Also, approximately 8 to 17% of the participant reported having at least one chronic respiratory symptom or lung disease. We found that high glycaemic measures (i.e. fasting and post-meal plasma glucose) are linked with dyspnea. In addition, HDL (high-density lipoprotein) concentration was directly associated with % FVC. CONCLUSIONS: It is difficult to draw a clear conclusion about the cause-effect relationship or clinical impact based on this study alone. However, identification of clinically meaningful elements for developing a screening program is critical.

Systemic inflammation (C-reactive protein) in type 2 diabetic patients is associated with ambient air pollution in Pune City, India.

OBJECTIVE: To study the association between ambient air pollutants and serum C-reactive protein (CRP) concentration in 1,392 type 2 diabetic patients in Pune, India. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted that linked daily time series of ambient air pollution data (obtained from central monitoring sites) and plasma CRP concentration in type 2 diabetic patients from the Wellcome Trust Genetic (WellGen) Study, recruited between March 2005 and May 2007. Air pollution effects on CRP concentration were investigated with delays (lags) of 0-7 days and multiday averaging spans of 7, 14, and 30 days before blood collection adjusted for age, sex, BMI, hemoglobin, fasting plasma glucose, treatment with agents with anti-inflammatory action, season, air temperature, and relative humidity. RESULTS: Median CRP concentration was 3.49 mg/L. For 1 SD increase in SO(2) and oxides of nitrogen (NO(x)) concentrations in ambient air, a day before blood collection (lag(1)), we observed a significant increase in CRP (9.34 and 7.77%, respectively). The effect was higher with lag(2) (12.42% for SO(2) and 11.60% for NO(x)) and wore off progressively thereafter. We also found a significant association with multiday averaging times of up to 30 and 7 days for SO(2) and NO(x), respectively. No significant associations were found between particulate matter with an aerodynamic profile ≤10 µm (PM(10)) and CRP concentration except in summer. The association was significantly higher among patients with a shorter duration of diabetes, and in those not on statin and thiazolidinedione treatment. CONCLUSIONS: We demonstrate, for the first time, a possible contribution of ambient air pollution to systemic inflammation in Indian type 2 diabetic patients. This may have implications for vascular complications of diabetes.

Quantitative T2* magnetic resonance imaging for evaluation of iron deposition in the brain of ß-thalassemia patients.

BACKGROUND: Iron overload is a common clinical problem in patients with ß-thalassemia major. The purpose of this study was to assess the presence of excess iron in certain areas of the brain (thalamus, midbrain, adenohypophysis and basal ganglia) in patients with ß-thalassemia major and evaluate the association with serum ferritin and liver iron content. MATERIALS AND METHODS: A cross-sectional study on 53 patients with ß-thalassemia major and 40 healthy controls was carried out. All patients and healthy controls underwent magnetic resonance imaging (MRI) examinations of the brain and liver. Multiecho fast gradient echo sequence was used and T2* values were calculated based on the Brompton protocol. Correlations between T2* values in the brain with T2* values in the liver as well as serum ferritin levels were investigated. RESULTS: There were no significant differences between patients and healthy controls with respect to age and sex. Patients had significantly lower T2* values in basal ganglia (striatum), thalamus and adenohypophysis compared to controls while there were no differences in the midbrain (red nucleus). There were no significant correlations between liver T2* values or serum ferritin with T2* values of basal ganglia (striatum), thalamus and adenohypophysis in patients or healthy controls. There were no significant correlations between T2* values of adenohypophysis and thalamus or basal ganglia (striatum) while these variables were significantly correlated in healthy controls. CONCLUSIONS: Serum ferritin and liver iron content may not be good indicators of brain iron deposition in patients with ß thalassemia major. Nevertheless, the quantitative T2* MRI technique is useful for evaluation of brain iron overload in ß thalassemia major patients.

Prevalence of fungal infection among Iranian patients with chronic sinusitis.

Chronic sinusitis is a major cause of morbidity today. Regional variations in the incidence of this disease have been reported. The aim of this study was to evaluate the incidence of fungal infection as the causative agent of chronic sinusitis among Iranian patients. A cross sectional hospital based study was designed; the patients underwent paranasal sinus washing and maxillary sinus biopsy. All specimens were studied by light microscopy. Fungal culturing was employed to confirm diagnosis. The patients underwent Computed Tomography for sinus evaluation. Of 162 participants, 12 samples from patients showed fungal elements, 2 of them Aspergillus fulvous (1.2%), 9 of them Alternaria species (5.56%) and 1 of them Psilomysis (0.6%). All patients presented radiologic evidence of sinusitis, ranging from mucosal thickening to total opacity. In conclusion, results obtained showed a low prevalence of fungal sinusitis among Iranian patients with chronic sinusitis. Findings also showed that Alternaria is the most causative agent.

The role of Helicobacter pylori infection in gastro-oesophageal reflux in Iranian children.

BACKGROUND: The relationship between Helicobacter pylori and gastro-oesophageal reflux disease (GORD) in children is controversial. AIM: To determine the role of H. pylori infection and GORD in children living in a region which is endemic for H. pylori infection. METHODS: A cross-sectional study was undertaken in 263 children aged 3-18 years, all of whom had symptoms of GORD and underwent upper gastro-intestinal endoscopy. H. pylori status was determined by conventional rapid urease test and Giemsa staining of antral and cardiac biopsies. Biopsies of the oesophagus and gastric mucosa were obtained from the lower oesophagus, the antrum and cardia according to standard protocol. RESULTS: Of the 263 patients, 81 (31·5%) had GORD and 162 (61·5%) had gastritis. There were 59 H. pylori-infected patients (22·4%) and 204 were uninfected. H. pylori infection was detected in 52 (88·1%) of the antral and 10 (1·9%) of the cardiac biopsies. Three (5·1%) of the biopsies revealed infection of both antrum and cardia and in seven (11·8%) only the cardia was infected. The prevalence of H. pylori infection among patients with GORD (13/83, 15%) was significantly lower than in those without GORD (46/180, 26%) (OR 0·54, CI 0·27-0·93, p<0·05). The prevalence of H. pylori infection among those with gastritis (48/162, 30%) was significantly higher than in those without gastritis (11/101, 10·8%) (OR 3·44, CI 1·69-7·015, p<0·001). CONCLUSION: H. pylori infection might protect against GORD.