Conversion of spikers to bursters in pituitary cell networks: Is it better to disperse for maximum exposure or circle the wagons?

The endocrine cells of the pituitary gland are electrically active, and in vivo they form small networks where the bidirectional cell-cell coupling is through gap junctions. Numerous studies of dispersed pituitary cells have shown that typical behaviors are tonic spiking and bursting, the latter being more effective at evoking secretion. In this article, we use mathematical modeling to examine the dynamics of small networks of spiking and bursting pituitary cells. We demonstrate that intrinsic bursting cells are capable of converting intrinsic spikers into bursters, and perform a fast/slow analysis to show why this occurs. We then demonstrate the sensitivity of network dynamics to the placement of bursting cells within the network, and demonstrate strategies that are most effective at maximizing secretion from the population of cells. This study provides insights into the in vivo behavior of cells such as the stress-hormone-secreting pituitary corticotrophs that are switched from spiking to bursting by hypothalamic neurohormones. While much is known about the electrical properties of these cells when isolated from the pituitary, how they behave when part of an electrically coupled network has been largely unstudied.

Effect of heating on disposal point of main edible oils available in Iran market.

Deep frying is the most common method used for food preparation worldwide, which can lead to several chemical changes in used fat or oil in frying process including oxidation and polymerization. This study aimed to determine the effect of heating and different storage conditions on the disposal point of four types of the most common edible oils available in the Iranian market without and with the presence of food in terms of acid value (AV) and total polar compounds (TPC). AV and TPC of three types of marketed sunflower oil (especially for frying, cooking, solid vegetable) and ghee heated at 110, 150, 180, and 200°C with a portable oil meter DOM-24 (ATAGO, Japan) were determined. They were measured without the presence of food at four different temperatures and four different times in five storage conditions and with the presence of frying food (chicken and potatoes) at 110°C for 20 min in three replicates. The results showed that the AV and TPC contents in the case of ghee were above national and international standards without the presence of food. Also, in the process of frying chicken and potato, the reusability of all the studied oils was not possible for the second time and reached the disposal point. The increase in the rate of AV and TPC of oils was: ghee (Kermanshahi oil) > liquid cooking oil > frying oil ≥ solid vegetable oil.

Network Properties of Electrically Coupled Bursting Pituitary Cells.

The endocrine cells of the anterior pituitary gland are electrically active when stimulated or, in some cases, when not inhibited. The activity pattern thought to be most effective in releasing hormones is bursting, which consists of depolarization with small spikes that are much longer than single spikes. Although a majority of the research on cellular activity patterns has been performed on dispersed cells, the environment in situ is characterized by networks of coupled cells of the same type, at least in the case of somatotrophs and lactotrophs. This produces some degree of synchronization of their activity, which can be greatly increased by hormones and changes in the physiological state. In this computational study, we examine how electrical coupling among model cells influences synchronization of bursting oscillations among the population. We focus primarily on weak electrical coupling, since strong coupling leads to complete synchronization that is not characteristic of pituitary cell networks. We first look at small networks to point out several unexpected behaviors of the coupled system, and then consider a larger random scale-free network to determine what features of the structural network formed through gap junctional coupling among cells produce a high degree of functional coupling, i.e., clusters of synchronized cells. We employ several network centrality measures, and find that cells that are closely related in terms of their closeness centrality are most likely to be synchronized. We also find that structural hubs (cells with extensive coupling to other cells) are typically not functional hubs (cells synchronized with many other cells). Overall, in the case of weak electrical coupling, it is hard to predict the functional network that arises from a structural network, or to use a functional network as a means for determining the structural network that gives rise to it.

Chronic stress facilitates bursting electrical activity in pituitary corticotrophs.

Coordination of an appropriate stress response is dependent upon anterior pituitary corticotroph excitability in response to hypothalamic secretagogues and glucocorticoid negative feedback. A key determinant of corticotroph excitability is large conductance calcium- and voltage-activated (BK) potassium channels that are critical for promoting corticotrophin-releasing hormone (CRH)-induced bursting that enhances adrenocorticotrophic hormone secretion. Previous studies revealed hypothalamic-pituitary-adrenal axis hyperexcitability following chronic stress (CS) is partly a function of increased corticotroph output. Thus, we hypothesise that chronic stress promotes corticotroph excitability through a BK-dependent mechanism. Corticotrophs from CS mice displayed significant increase in spontaneous bursting, which was suppressed by the BK blocker paxilline. Mathematical modelling reveals that the time constant of BK channel activation, plus properties and proportion of BK channels functionally coupled to L-type Ca2+ channels determines bursting activity. Surprisingly, CS corticotrophs (but not unstressed) display CRH-induced bursting even when the majority of BK channels are inhibited by paxilline, which modelling suggests is a consequence of the stochastic behaviour of a small number of BK channels coupled to L-type Ca2+ channels. Our data reveal that changes in the stochastic behaviour of a small number of BK channels can finely tune corticotroph excitability through stress-induced changes in BK channel properties. Importantly, regulation of BK channel function is highly context dependent allowing dynamic control of corticotroph excitability over a large range of time domains and physiological challenges in health and disease. This is likely to occur in other BK-expressing endocrine cells, with important implications for the physiological processes they regulate and the potential for therapy. KEY POINTS: Chronic stress (CS) is predicted to modify the electrical excitability of anterior pituitary corticotrophs. Electrophysiological recordings from isolated corticotrophs from CS male mice display spontaneous electrical bursting behaviour compared to the tonic spiking behaviour of unstressed corticotrophs. The increased spontaneous bursting from CS corticotrophs is BK-dependent and mathematical modelling reveals that the time constant of activation, properties and proportion of BK channels functionally coupled to L-type calcium channels determines the promotion of bursting activity. CS (but not unstressed) corticotrophs display corticotrophin-releasing hormone-induced bursting even when the majority of BK channels are pharmacologically inhibited, which can be explained by the stochastic behaviour of a small number of BK channels with distinct properties. Corticotroph excitability can be finely tuned by the stochastic behaviour of a small number of BK channels dependent on their properties and functional co-localisation with L-type calcium channels to control corticotroph excitability over diverse time domains and physiological challenges.

Fast-slow analysis of a stochastic mechanism for electrical bursting.

Electrical bursting oscillations in neurons and endocrine cells are activity patterns that facilitate the secretion of neurotransmitters and hormones and have been the focus of study for several decades. Mathematical modeling has been an extremely useful tool in this effort, and the use of fast-slow analysis has made it possible to understand bursting from a dynamic perspective and to make testable predictions about changes in system parameters or the cellular environment. It is typically the case that the electrical impulses that occur during the active phase of a burst are due to stable limit cycles in the fast subsystem of equations or, in the case of so-called "pseudo-plateau bursting," canards that are induced by a folded node singularity. In this article, we show an entirely different mechanism for bursting that relies on stochastic opening and closing of a key ion channel. We demonstrate, using fast-slow analysis, how the short-lived stochastic channel openings can yield a much longer response in which single action potentials are converted into bursts of action potentials. Without this stochastic element, the system is incapable of bursting. This mechanism can describe stochastic bursting in pituitary corticotrophs, which are small cells that exhibit a great deal of noise as well as other pituitary cells, such as lactotrophs and somatotrophs that exhibit noisy bursts of electrical activity.

Phantom bursting may underlie electrical bursting in single pancreatic ß-cells.

Insulin is secreted by pancreatic ß-cellsthat are electrically coupled into micro-organs called islets of Langerhans. The secretion is due to the influx of Ca2+ions that accompany electrical impulses, which are clustered into bursts. So-called "medium bursting" occurs in many ß-cellsin intact islets, while in other islets the ß-cellsexhibit "slow bursting", with a much longer period. Each burst brings in Ca2+ that, through exocytosis, results in insulin secretion. When isolated from an islet, ß-cellsbehave very differently. The electrical activity is much noisier, and consists primarily of trains of irregularly-timed spikes, or fast or slow bursting. Medium bursting, so often seen in intact islets, is rarely if ever observed. In this study, we examine what the isolated cell behavior can tell us about the mechanism for bursting in intact islets. A previous mathematical study concluded that the slow bursting observed in isolated ß-cells, and therefore most likely in islets, must be due to intrinsic glycolytic oscillations, since this mechanism for bursting is robust to noise. It was demonstrated that an alternate mechanism, phantom bursting, was very sensitive to noise, and therefore could not account for the slow bursting in single cells. We re-examine these conclusions, motivated by recent experimental and mathematical modeling evidence that slow bursting in intact islets is, at least in many cases, driven by the phantom bursting mechanism and not endogenous glycolytic oscillations. We employ two phantom bursting models, one minimal and the other more biophysical, to determine the sensitivity of medium and slow bursting to electrical current noise. In the minimal model, both forms of bursting are highly sensitive to noise. In the biophysical model, while medium bursting is sensitive to noise, slow bursting is much less sensitive. This suggests that the slow bursting seen in isolated ß-cellsmay be due to a phantom bursting mechanism, and by extension, slow bursting in intact islets may also be driven by this mechanism.

Dataset for adsorptive removal of tetracycline (TC) from aqueous solution via natural light weight expanded clay aggregate (LECA) and LECA coated with manganese oxide nanoparticles in the presence of H2O2.

In this data article, natural (NL) and manganese oxide-modified LECA (MML) adsorbents were applied for adsorptive removal of Tetracycline (TC) from aqueous solution. The used adsorbents was characterized using fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray fluorescence spectroscopy (XRF). The chemical analysis of XRF data revealed increased chemical composition of Mn as MnO to 8.96 wt%. The SEM patterns were illustrated the extent of surface and enhanced porosity in MML with Mn. In optimum operational conditions, maximum removal percentage of TC was achieved at 51.5 and 99.4% using NL and MML, respectively. The maximum adsorption capacities obtained from Langmuir modeling were 6.89 and 9.24 for NL and MML, respectively. The modeling of the adsorption kinetics revealed that TC adsorption by both NL and MML adsorbents was best-fitted with a pseudo-first-order model (R 2 = 0.978). The isotherm studies of TC adsorption by MML showed that the Freundlich isotherm was the most appropriate model, with a higher coefficient of determination. The obtained data was illustrated that high competitive capacity of chloride and hardness ions compared with other ions against TC adsorption.

Administration of Intravenous Zoledronic Acid Every 3 Months vs. Annually in ß-thalassemia Patients with Low Bone Mineral Density: a Retrospective Comparison of Efficacy.

INTRODUCTION: The benefit of annual administration of zoledronic acid in the management of thalassemia-associated osteoporosis is unknown. AIM: The aims of this study were to evaluate the efficacy of treatment with two different dosing regimens of IV zoledronic acid (annually versus every 3 months) for increasing low bone mineral density (BMD) in patients with osteoporosis associated with ß-thalassemia as annually and 3-monthly on bone density in patients. MATERIALS AND METHODS: This retrospective, single-center study analyzed patients' clinical records and bone density measurements. Those enrolled in the study were 14 to 53 years of age, had documented ß-thalassemia, and were treated with IV zoledronic acid on either an annual or every 3 months dosing regimen. Dual-energy X-ray absorptiometry was used to obtain the z-score for BMD in the lumbar spine and femoral neck. RESULTS: Thirty-four patients were enrolled in the study; 15 (44.1%) had been treated annually, and 19 (55.9%) had been treated every month. In patients receiving treatment with the once-yearly dose of zoledronic acid, significant increases were observed in the lumbar spine BMD z-score, from -2.45 ± 0.69 to -1.97 ± 0.82 (P=0.02). When comparing BMD across the two treatment regimens, the mean lumbar spine BMD was 0.82 greater (95% CI 0.31, 1.33, P=0.003) and the mean femoral neck BMD 0.37 greater (95% CI -0.15, 0.87, P=0.1) in the group receiving annual zoledronic acid treatment. CONCLUSIONS: In patients with thalassemia-associated osteopenia, annual treatment with zoledronic acid increases lumbar spine bone density while being more effective, less expensive, and associated with fewer adverse events than dosing every 3 months.

The Short Term Effects of Shock-Wave Therapy for Tennis Elbow: a Clinical Trial Study.

BACKGROUND: Tennis elbow is one of the most often diagnosed pathology of the upper extremity and different treatments have been suggested for this disease, so this study was to investigate the effects of extracorporeal shock wave therapy in Tennis elbow treatment. MATERIALS AND METHODS: We design a before and after clinical trial study (registry number: IRCT2012072610405N1) and investigated 40 patients with tennis elbow disease. All patients received 2000 pulses extracorporeal shock wave by piezoelectric device (WOLF Company) daily for one-week. The severity of pain was the primary outcome and measured with visual analogue scale (VAS). Secondary outcome was the ability to perform daily activities using questionnaire's quick DASH (Disabilities of the Arm, Shoulder and Hand). Primary and secondary outcomes at baseline, 30 and 60 days after intervention were measured. RESULTS: The mean age of patients was 43.80±8.97 years and 28 patients (70%) were female. The mean duration of disease was 6.5 ± 7.9 month. The mean score of VAS pain score reduced from 7.25±1.54cm (median=7cm) before treatment to 2.76±2.08cm (median=2cm) at 60 days after the end of treatment (P<0.001). The Quick Dash score reduced significantly from 25.20±5.31 (median=25) before treatment to 8.69±8.32 (median=6) at 60 days after the treatment (P<0.001). CONCLUSION: For newly diagnosed patients with tennis elbow, extracorporeal shock wave therapy can reduce the severity of pain and improve daily activity.

Pilonidal Sinus Operations Performed Under Local Anesthesia versus the General Anesthesia: Clinical Trial Study.

BACKGROUNDS: Various methods were defined to prepare patients for the pilonidal sinus surgery including local, spinal, and general anesthesia. But there is no powerful evidence to differ these procedures. Therefore, in the current study, we compared local and general anesthesia in the pilonidal sinus surgery. METHODS & MATERIAL: in this clinical trial (IRCT201312031786N5) study 60 patients with the pilonidal sinus disease divided to two groups of local anesthesia versus general anesthesia. For local anesthesia we used 6ml of 2% lidocaine with an epinephrine (1:200,000), 6ml of 0.5% bupivacaine, 1ml fentanyl (50µg/ml), 1ml clonidine (75µg/ml) and for general anesthesia fentanyl 1.5 µg.kg-1, thiopental 3-5 mg.kg-1, followed by the trachea intubation facilitated by atracurim 0.5 mg.kg-1 with maintenance of isoflurane 1-3% in nitrous oxygen 70% and oxygen 30%. The student t-test and Chi-square test were applied to evaluate the differences. RESULTS: there were 30 patients with the mean age of 27.43±8.42 years in local anesthesia group and 30 cases with the mean age of 27.5±8.44 years underwent general anesthesia. The recovery time was significantly lower in the local anesthesia group (P=0.000). The oxygen saturation of the general anesthesia group was significantly higher at 1 and 20 minutes after the operation. The average of pain score was significantly higher in general anesthesia group at 3h and 6h after surgery (P<0.001). There were no significant differences in post-operative complications and hospital length of stay. CONCLUSION: this investigation revealed that local anesthesia has decreased pain during 48 hours after the surgery, shorter recovery time, and the less consumption of painkillers. So, we concluded that we can consider local anesthesia as a good alternative for the general anesthesia in the pilonidal sinus surgery.

Evaluation the Relationship Between Thyroid Nodule Size with Malignancy and Accuracy of Fine Needle Aspiration Biopsy (FNAB).

INTRODUCTION: Some studies have shown largest thyroid nodule size, especially ≥4cm that can predict malignancy and reduce fine needle aspiration biopsy (FNAB) accuracy. Therefore, this study is designed to evaluate relationship between thyroid nodule sizes with malignancy and its effect on FNBA accuracy. MATERIALS AND METHODS: a retrospective analytical study design aims to investigate all patients with thyroid nodules who referred to surgery department of Imam-Khomeini Hospital of Mazandaran University of Medical Sciences in Sari from 20 March 2008 to 22 March 2014. We collected patient's demographic data, nodules size, FNAB reports and final pathology (after surgery) reports from their medical records. All data were analyses performed by SPSS18. RESULTS: 167 patients (153 women) with mean age of 41.56±13.24 years old were enrolled for this study. In final pathology; 38 patients (22.8%) had malignant nodules. The mean age of patients with or without malignant nodules were 34.93±11.86 and 42.37±12.26 years old, respectively (P=0.002). The mean size of benign and malignant nodules were 2.91±1.29 cm and 3.38±1.86 cm, respectively (P=0.15). 25.2% of <4 cm nodules and 17.9% of ≥4 cm nodules were diagnosed as a malignant (P=0.29). FNAB was done on 95 patients that reported benign in 60 patients (63.2%), malignant in 18 patients (18.9%) and suspicious in 17 patients (17.9%). Positive and negative results of FNAB in all nodules were 3.5% and 6.3%, in <4cm nodules were 5.8% and 6.2% and in ≥4cm nodules were zero and 6.7%, respectively. The sensitivity, specificity, Positive predict value (PPV), negative predict value (NPV) and overall accuracy (OA) of FNAB in all nodules were 76.19%, 96.49%, 88.88%, 91.66% and 91.02%, and in <4cm nodules were 78.57%, 94.11%, 84.61%, 91.42% and 89.58%, and in ≥4cm nodules were 71.4%, 100%, 100%, 92% and 93.33%, respectively. CONCLUSION: the results of this study revealed that the size of the thyroid nodules is not reliable at predicting malignancy and should not be applied in medical decision making. FNAB showed good specificity but the sensitivity was low in our study. In ≥4cm nodules; FNAB sensitivity was decreased and accompanied by higher false-negative results. Furthermore, FNABs with suspicious results were associated with high probability of malignancy.

A Survey of Severity and Distribution of Musculoskeletal Pain in Multiple Sclerosis Patients; a Cross-Sectional Study.

BACKGROUND: Pain, a common phenomenon in multiple sclerosis (MS) patients, is associated with many symptoms and problems. AIM: To investigation severity and distribution of musculoskeletal pain in MS patients. METHODS: In this cross-sectional study, 115 members of the Mazandaran MS Association with confirmed MS were randomly selected to participate in the study. The patients were asked to fill out Numerical Rating Score and Nodric questionnaires, respectively. The data was analyzed by SPSS ver. 16 software. RESULTS: The mean age of the participants was 30.43±5.86 years and 88 cases (76.5%) were female. The mean disease duration was 26.34±24.32 months and 87.8% of the cases were experiencing pain at the time of study. The mean pain severity was 3.75±2.25 and worst pain experienced was 5.73±2.12. The most common pain sites were: the knees (55.7%), wrist (43.5%), and neck (41.7%). Women experience higher prevalence of shoulder, upper back, and ankle pain (P<0.05). In 62 cases (53.91%) MS interfered with daily functioning at least for a time. The prevalence of upper back and neck pain was higher in cases with a shorter disease duration (P<0.05). CONCLUSIONS: Pain was very common in patients with MS and not relevant to sex or age. In the majority of the cases more than 1 limb was involved and the prevalence of pain in the lower limbs was higher, especially in the knees. In females, the prevalence of pain in the shoulders, upper back, and ankle was higher compared to males. Also, neck and upper-back pain were found in the early stages of the disease.

Highly cadmium tolerant fungi: their tolerance and removal potential.

BACKGROUND: Soil and effluent of lead and zinc industries contain high concentration of cadmium. The present study was conducted to isolate tolerant fungal strains from cadmium -polluted sites in Zanjan province, Iran. METHODS: Cadmium tolerance and bioremediation capacity of seven isolates including Aspergilus versicolor, Aspergillus fumigatus, Paecilomyces sp.9, Paecilomyces sp.G, Terichoderma sp, Microsporum sp,Cladosporium sp were determined. RESULTS: Minimum inhibitory concentration values among 1,000-4,000 mg l-(1)proved great ability of isolated strains to survive in cadmium polluted environments. The most tolerant fungi, Aspergilus versicolor, showed tolerance index of 0.8 in 100 mg l-(1) cadmium agar media. Fungal resistance against cadmium is depended directly on strain's biological function. A. versicolor was found to bioaccumulate over7 mg of cadmium per 1 g of mycelium, followed by 5.878, 5.243, and 5.075, 4.557 by Paecilomyces sp, Aspergilus fumigatus, Microsporum sp and Terichoderma sp, respectively. CONCLUSION: It can be noted that tolerance of the strains appears to be independent from bioaccumulation capacity. Finally, the results indicated that A. versicolor could be a prospective candidate for bioremediation processes.

Evaluations of erectile dysfunction before and after on-pump coronary artery bypass graft surgery.

BACKGROUND: Erectile dysfunction (ED) is common in cardiovascular disease (CVD) and indicates a complication of coronary artery bypass graft surgery (CABG). This study was designed to evaluate the status of erectile dysfunction in patients with CAD before and after CABG surgery. METHODS: We designed a prospective cohort study on male patients candidates for elective on-pump CABG between June 2006 to October 2012 in 3 hospitals in Sari, Iran (Fatemeh Zahra, Shafa and Nime-Shaban Hospitals). Patient's primary data were collected based on the International Index of Erectile Function questionnaire (IIEF-5) at baseline 6 months after surgery. The severity of dysfunction was categorized as, normal, mild to moderate and moderate to severe based on IIEF score. RESULTS: Four hundred twenty-six male patients with mean age of 58.69±12.49 years participated in this study. 166 patients had DM (38.96%) 230 patients had hypertension (54%). 307 patients had three-vessel impairment (72.07%) and 119 patients with one or two vessel impairment (27.93%). The 15.02%, 18.07%, 23%, 31.92% and 11.97%, at baseline changed to 16.90%, 19.95%, 23.71%, 32.22% and 8.21%, at endpoint (P=0.01). Also, the mean±SD of IIEF-5 score before and after surgery was 13.95±5.44 and 14.20±5.69, respectively (P=0.001). CONCLUSION: The result of our study shows that on-pump CABG surgery has a positive effect on the improvement of erectile dysfunction 6 months after surgery.

Efficiency of non-ionic surfactants - EDTA for treating TPH and heavy metals from contaminated soil.

Introduction of fuel hydrocarbons and inorganic compounds (heavy metals) into the soil, resulting in a change of the soil quality, which is likely to affect use of the soil or endangering public health and ground water. This study aimed to determine a series of parameters to remediation of TPH and heavy metals contaminated soil by non-ionic surfactants- chelating agents washing process. In this experimental study, the effects of soil washing time, agitation speed, concentration of surfactant, chelating agent and pH on the removal efficiency were studied. The results showed that TPH removal by nonionic surfactants (Tween 80, Brij 35) in optimal condition were 70-80% and 60-65%, respectively. Addition of chelating agent (EDTA) significantly increases Cd and Pb removal. The washing of soil by non- ionic surfactants and EDTA was effective in remediation of TPH and heavy metals from contaminated soil, thus it can be recommended for remediation of contaminated soil.

Clinical management and outcomes of papillary, follicular and medullary thyroid cancer surgery.

The clinical characteristics, pathological subtypes and patients' survival in 40 patients with thyroid carcinoma between March 2007 and March 2012 were evaluated. This study included 33 (82.5 %) females and seven (17.5%) males (female to male ratio of 4.7:1). The median age of patients was 47.5 (range; 24-64). Papillary carcinoma was the commonest pathological subtype (23 patients, 57.5%), followed by follicular carcinoma (14 patients, 35%) and medullary carcinoma (3 cases, 7.5%). Total thryoidectomy was performed in 30 (75%), lobectomy in six (15%), subtotal and multifocal thryoidectomy in two (5%) patients. The median time of follow up was 3 years with range of 1-5 years. After ive years 34 (85%) patients were alive and six (15%) were dead. The overall 5-year actuarial survival was 85%, for papillary carcinoma 91.3%, for follicular carcinoma 85.7% and for medullary carcinoma it was 33.3%. The results suggest that total thryoidectomy had better outcome in comparison with other surgeries.