Interrelationships Between Spinal Sympathetic Preganglionic Neurons, Autonomic Systems and Electrical Synapses Formed by Connexin36-containing Gap Junctions.

Spinal sympathetic preganglionic neurons (SPNs) are among the many neuronal populations in the mammalian central nervous system (CNS) where there is evidence for electrical coupling between cell pairs linked by gap junctions composed of connexin36 (Cx36). Understanding the organization of this coupling in relation to autonomic functions of spinal sympathetic systems requires knowledge of how these junctions are deployed among SPNs. Here, we document the distribution of immunofluorescence detection of Cx36 among SPNs identified by immunolabelling of their various markers, including choline acetyltransferase, nitric oxide and peripherin in adult and developing mouse and rat. In adult animals, labelling of Cx36 was exclusively punctate and dense concentrations of Cx36-puncta were distributed along the entire length of the spinal thoracic intermediolateral cell column (IML). These puncta were also seen in association with SPN dendritic processes in the lateral funiculus, the intercalated and central autonomic areas and those within and extending medially from the IML. All labelling for Cx36 was absent in spinal cords of Cx36 knockout mice. High densities of Cx36-puncta were already evident among clusters of SPNs in the IML of mouse and rat at postnatal days 10-12. In Cx36BAC::eGFP mice, eGFP reporter was absent in SPNs, thus representing false negative detection, but was localized to some glutamatergic and GABAergic synaptic terminals. Some eGFP+ terminals were found contacting SPN dendrites. These results indicate widespread Cx36 expression in SPNs, further supporting evidence of electrical coupling between these cells, and suggest that SPNs are innervated by neurons that themselves may be electrically coupled.

Improvement of Cognitive Indicators in Male Monkeys Exposed to Extremely Low-Frequency Electromagnetic Fields.

Today, the production of extremely low-frequency electromagnetic fields (ELF-EMFs) has significantly increased. This study aimed to investigate the effect of the ELF-EMFs on the structure and function of the brain in male rhesus monkeys in terms of visual learning (VL), visual memory (VM), and visual working memory (VWM). To conduct the study, four monkeys were selected, of whom two monkeys were irradiated by 12-Hz ELF-EMFs with a magnitude of 0.7 microtesla, and two monkeys were tested without irradiation (control group). A blood sample was taken in three stages, namely pre- and post-irradiated and the recovery phases. Changes in the plasma levels of sodium, potassium, and adrenocorticotropic hormone (ACTH) were evaluated. Moreover, gene expression of N-methyl-D-aspartate (NMDA) receptors was assessed. The anatomical change of the brain's prefrontal area was measured by magnetic resonance imaging and Digital Imaging and Communications in Medicine LiteBox file. The abilities of VL, VM, and VWM significantly improved after the irradiation. Furthermore, the expression of the NMDA receptors gene and the plasma levels of sodium, potassium, and ACTH significantly enhanced after the irradiation. However, the prefrontal area was not significantly affected by the irradiation. No significant differences were observed in any of the studied factors in the control group. Our findings suggested that ELF-EMFs irradiation at 12 Hz positively affected VL and VWM. Consequently, 12-Hz ELF-EMFs irradiations can be widely applied to improve cognitive abilities in monkeys.

Serological Investigation of H9N2 Avian Influenza Virus in Slaughtered Water Buffaloes (Bubalus bubalis) in Khuzestan, Iran.

The aim of the present was to evaluate the prevalence of H9N2-specific antibodies among water buffaloes (Bubalus bubalis). To this end, blood samples were obtained from 80 randomly selected water buffaloes, 40 cases of which were obtained in the winter months, and 40 cases were sampled in the spring months. The presence of H9N2-specific antibody was determined by hemagglutination inhibition method. The antibody was diagnosed in 14 buffaloes (i.e., 10 males and 4 females). There were no significant differences between the two genders and between different age groups in terms of antibody prevalence. The presence of the antibody had a seasonal pattern; in this regard, all positive cases were found in the winter months (P<0.01). Detection of antibody against H9N2 in water buffaloes suggests the presence of an avian-water buffalo cycle of H9N2 virus. Additional research is needed for the detection of the probable epidemiologic role of buffaloes in the interspecies transmission and pathogenesis of H9N2 avian influenza viruses.

Ten-year trends in direct costs of asthma: a population-based study.

INTRODUCTION: There is little information on recent trends in the economic burden of asthma. Our objective was to estimate the excess costs of asthma and their trend in British Columbia, Canada, from 2002 to 2011. METHODS: A retrospective cohort of individuals aged 5-55 years was constructed from the provincial administrative health databases, consisting of patients with physician-diagnosed asthma and a propensity-score-matched comparison sample from the general population. Total direct medical costs were calculated as the sum of hospitalizations, outpatient visits and medication costs, adjusted to 2012 Canadian dollars ($). Excess costs were defined as the difference in costs between the asthma and comparison groups. RESULTS: A total of 341 457 individuals (mean age at entry 27.3, 54.1% female) were equally divided into the asthma and comparison groups. Excess costs in patients with asthma were $1028.0 (95% CI $982.7-$1073.4) per patient-year (PY). Medications contributed to the greatest share of excess costs ($471.7/PY), whereas hospitalization and outpatient costs were, respectively, $272.2/PY and $284.1/PY. Only $192.9/PY was attributable to asthma itself. There was a 2.9%/year increase in excess costs (P < 0.001), a combination of asthma-attributable costs declining by 0.8%/year while nonasthma excess costs increasing by 3.8%/year. The most dramatic trend was observed in asthma-related outpatient costs, which decreased by %6.6/year. CONCLUSIONS: A significant share of excess costs in asthma is not attributable to the disease itself. The pattern of costs changed significantly during the study period. The burden of comorbid conditions should be considered in developing evidence-based policies for management of patients with asthma.

Saving in medical costs by achieving guideline-based asthma symptom control: a population-based study.

BACKGROUND: Asthma control is increasingly used as an outcome measure in asthma trials. Economic evaluations of asthma interventions require converting the impact of interventions on control to impact on resource use. The purpose of this study was to estimate the savings in direct costs by achieving asthma symptom control as defined in the Global Initiative for Asthma (GINA) 2014 management strategy. METHODS: Adolescents and adults with asthma were recruited through random digit dialing. Asthma control per GINA and the use of healthcare resources were assessed at baseline and three-monthly visits up to 1 year. We used regression models to associate costs, measured in 2012 Canadian dollars ($), with symptom control, adjusting for potential confounding variables. RESULTS: The final sample included 517 individuals (average age 48.9, 65.8% female) with mostly mild-moderate asthma contributing 2033 follow-up visits. In 598 (29.4%), 809 (39.8%), and 626 (30.8%) of visits, asthma was symptomatically controlled, partially controlled, or uncontrolled, respectively. The average 3-month costs of asthma were $134.5. Of these, 20.5% were attributable to inpatient care, 47.8% to outpatient care, and 31.5% to medication. Compared to controlled asthma, partially controlled asthma was associated with a nonsignificant increase of $9.5 (95% CI -$13.6 - $32.6) in adjusted 3-month costs and uncontrolled asthma with a statistically significant increase of $81.7 (95% CI $48.5 - $114.9). CONCLUSION: A substantial fraction of this population-based sample of largely mild-moderate asthmatics was symptomatically uncontrolled. Achieving symptom control was associated with a reduction in direct costs. The adjusted values from this study can be used to inform cost-effectiveness analyses of asthma treatments.

Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population.

Colorectal cancer (CRC) is among the major causes of cancer-related morbidity, mortality, and human health problem worldwide. Single-nucleotide polymorphisms (SNPs) in different genes are reported to be effective in increased risk of CRC in different ethnic population. We conducted a case-control study in patients diagnosed with sporadic colorectal cancer (n = 115) and healthy controls based on colonoscopy evidences (n = 120).In this replicative study, we aimed to investigate the association of two previously reported polymorphisms, rs6983267 and rs4444903, with sporadic colorectal cancer in a subset of Iranian patients. Genotyping was performed via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A significant relation was found between rs6983267 variant in the 8q24 region and colorectal cancer. The distribution of G/G genotypes among sporadic CRC patients was more frequent than that in the control group (P value = 0.001). The frequency of the G allele in the colorectal cancer patient group was also higher than that in the control group (65% vs. 48%; P value = 0.001). Compared with GG genotype, individuals with G/T and T/T genotypes had lower risk to develop sporadic CRC (OR = 0.357, 95% CI = 0.201-0.635). For the rs4444903 SNP, no significant association (P value = 0.149) was found with colorectal cancer risk. In conclusion, our findings suggest that the 8q24 rs6983267 SNP may play a pivotal role in the development of sporadic CRC in Iranian population. Therefore, it may be included as a potential genetic susceptibility marker for sporadic CRC.

SU-E-I-51: Investigation of Absorbed Dose to the Skin, Eyes and Thyroid of Patients during CT Angiography and Comparison with Conventional Angiography.

PURPOSE: Imaging is one of the most important methods to diagnose cardiovascular and especially coronary artery diseases. The advent of multislice CT in recent years has made new capabilities for medical imaging. Coronary CT angiography as a new imaging method is performed with these devices. Despite of many advantages with it, patients absorbed dose is relatively high in coronary ct angiography, Then study on various aspects of absorbed dose to patients seems to be necessary. The aim of this study was to evaluate absorbed dose to patient's skin, thyroid and eye during coronary CT angiography and to compare it with the same organ doses in conventional angiography. METHODS: A number of 67 patients referring to Isfahan's Azzahra(s) and Sina hospitals for coronary CT angiography imaging were investigated to evaluate absorbed dose to their skin, thyroid and eyes. Organs absorbed dose was obtained via measurement by TLD. One pair GR-200 type TLDs were used for each organ dose measurement. TLDS were calibrated using Co 60 source before measuring. Absorbed dose to each organ considered to be as average of TLDs readout. Coronary CT angiography was performed either by 64 rows detectors CT lighspeed VCT in Azzahra(s) or Philips model in Sina hospitals. RESULTS: The average of absorbed dose to skin, thyroid and eye during coronary CT angiography was 8.32± 1.73, 2.06± 1.68 and 0.3± 0.16 cGy, respectively. Absorbed dose to the same organs during conventional coronary angiography was 6.64± 9.30, 0.15± 0.17 and 0.03± 0.03 cGy, respectively. There is a significant differences in adsorbed dose to these organs between coronary CT angiography and conventional angiography(p<0.001).absorbed dose to skin ranges between 5.15-12.22 cGy for CT angiography and between 0.07-39 cGy in conventional angiography. CONCLUSIONS: Absorbed dose to skin is higher than two other organs(thyroid and eye) due to direct irradiation. There is a significant variation in absorbed dose to skin for both CT and conventional angiography and it is greater for conventional angiography. Absorbed dose to organs is higher for CT angiography rather than conventional angiography. Radiation absorbed dose depends on various imaging selected parameters such as kVp and mAs, then, technicians play an important role on it. To decrease adsorbed dose to patients as low as possible they must be educated very well and implement what have learned in practice.

Predicción de eventos cardiacos futuros con SPECT de perfusión miocárdica: estudio de seguimiento a medio plazo / Prediction of future cardiac events using myocardial perfusion SPECT: a middle-term follow-up study

Introducción. Los estudios de perfusión miocárdica (MPI) aportan una importante información para la estratificación del riesgo y para determinar el óptimo manejo clínico del paciente. El objetivo del presente estudio es valorar el factor pronóstico de los estudios SPECT de perfusión miocárdica para predecir futuros eventos cardiacos en la población asiática. Método. Se realizó un seguimiento prospectivo a 510 pacientes a los que se les realizó un estudio SPECT de perfusión miocárdica entre los años 2005-2006. Los datos de los pacientes se obtuvieron de los informes. El seguimiento se realizó mediante entrevista telefónica por un médico que desconocía los resultados del estudio MPI y los informes del hospital. Se completó el seguimiento en 482 pacientes (índice de seguimiento del 94,5%). Resultados. Con un periodo de seguimiento medio de 434±62 días, 14 de los 482 pacientes (2,9%) fallecieron por eventos cardiacos. En 61 paciente (12,7%) las condiciones clínicas requirieron de intervencionismo cardiaco (vasodilatación percutánea o bypass coronario). Aquellos pacientes sin eventos cardiacos en el seguimiento (incluyendo muerte cardiaca o infarto) eran más jóvenes y con alteraciones menos severas en MPI. Se encontraron alteraciones severas en los MOI (Summed Stress Score > 13) en el 42,9% de los pacientes con muerte cardiaca y en el 17,2% de los pacientes con infarto de miocardio. El índice de muerte cardiaca tuvo una relación directa con la severidad de las alteraciones en la gammagrafía, sin embargo, no se encontró esta relación con el índice de infartos. Conclusión. Los estudios de MPI tienen un valor clave en la estratificación del riesgo y en la predicción de eventos cardiaco fatales en el futuro en la población asiática. El riesgo de muerte cardiaca y la evolución a medio plazo de la enfermedad coronaria aumentan de forma significativa con la severidad de las alteraciones de MPI(AU)

Background. Myocardial perfusion imaging (MPI) provides highly valuable information for risk stratification and determination of optimal clinical management. The goal of the present study was to assess the prognostic value of myocardial perfusion SPECT for the prediction of future cardiac events in Asian population. Methods. Five hundred and ten consecutive patients, who had undergone myocardial perfusion SPECT between 2005 and 2006, were prospectively followed-up. Patients’ data were collected from recorded files. Follow-ups were performed by scripted telephone interviews by a physician blinded to the patients’ MPI results and also from the hospital records. The total completed follow-ups consisted of 482 patients (follow-up rate, 94.5%). Results. Over the mean follow-up period of 434±62 days, 14 out of 482 patients (2.9%) died from cardiac events. Also in 61 patients (12.7%), the clinical condition led to a cardiac intervention (Percutaneous coronary intervention or coronary artery bypass grafting). Those patients without cardiac events on follow-up (including cardiac death or myocardial infarction) were younger and with less severity of MPI abnormalities. Severe MPI abnormalities (Summed Stress Score > 13) were found in 42.9% of those with cardiac death, while in 17.2% of those with myocardial infarction. The rate of cardiac death had a direct relationship with the severity of scan abnormalities, however, the same association was not found between the severity of MPI abnormality and the rate of myocardial infarction. Conclusion. MPI is a valuable tool for risk stratification and prediction of future fatal cardiac events in Asian population. The risk of cardiac death as a mid-term outcome of coronary artery disease increases significantly with severity of MPI abnormalities(AU)

Prediction of future cardiac events using myocardial perfusion SPECT: a middle-term follow-up study.

BACKGROUND: Myocardial perfusion imaging (MPI) provides highly valuable information for risk stratification and determination of optimal clinical management. The goal of the present study was to assess the prognostic value of myocardial perfusion SPECT for the prediction of future cardiac events in Asian population. METHODS: Five hundred and ten consecutive patients, who had undergone myocardial perfusion SPECT between 2005 and 2006, were prospectively followed-up. Patients' data were collected from recorded files. Follow-ups were performed by scripted telephone interviews by a physician blinded to the patients' MPI results and also from the hospital records. The total completed follow-ups consisted of 482 patients (follow-up rate, 94.5%). RESULTS: Over the mean follow-up period of 434 ± 62 days, 14 out of 482 patients (2.9%) died from cardiac events. Also in 61 patients (12.7%), the clinical condition led to a cardiac intervention (Percutaneous coronary intervention or coronary artery bypass grafting). Those patients without cardiac events on follow-up (including cardiac death or myocardial infarction) were younger and with less severity of MPI abnormalities. Severe MPI abnormalities (Summed Stress Score > 13) were found in 42.9% of those with cardiac death, while in 17.2% of those with myocardial infarction. The rate of cardiac death had a direct relationship with the severity of scan abnormalities, however, the same association was not found between the severity of MPI abnormality and the rate of myocardial infarction. CONCLUSION: MPI is a valuable tool for risk stratification and prediction of future fatal cardiac events in Asian population. The risk of cardiac death as a mid-term outcome of coronary artery disease increases significantly with severity of MPI abnormalities.

A survey of traditional Iranian food products for contamination with toxigenic Clostridium botulinum.

This study aimed to determine the rate of Clostridium botulinum contamination in some traditional Iranian food products (cheese, kashk and salted fish) and evaluate the efficacy of the mouse bioassay method in detection of C. botulinum toxins in these foods. A total of 131 samples (57 cheese, 11 kashk and 63 salted fish) were collected and examined to determine the rate of contamination by C. botulinum. Standard monovalent anti-toxins were used to determine the types of toxin. C. botulinum bacteria were detected in 4.58% of the examined samples (1.52% of cheese and 3.06% of salted fish samples). While no contamination was detected in the kashk samples, C. botulinum types A and E were found to be dominant in cheese and salted fish samples, respectively. These results indicate-some traditional Iranian foods may be contaminated with different types of C. botulinum, and the consumption of these products, either raw or cooked, may contribute to food-borne intoxications.

Morphine analgesia in patients with acute appendicitis: a randomised double-blind clinical trial.

BACKGROUND: The administration of analgesics to patients with acute abdominal pain due to acute appendicitis is controversial. A study was undertaken to assess the analgesic effect of morphine in patients with acute appendicitis. METHODS: A randomised double-blind clinical trial was conducted in Sina hospital, a general teaching hospital, from January 2004 to March 2005. Patients scheduled for appendectomy were randomised to receive 0.1 mg/kg morphine sulfate or saline (0.9%) to a maximum dose of 10 mg over a 5 min period. Patients were examined by surgeons not involved in their care before and after drug administration and their pain intensity and signs were recorded at each visit. The physicians were also asked to indicate their own treatment plan. The main outcome measures were pain intensity using a visual analogue scale (VAS) and signs of acute appendicitis. A favourable reduction in VAS score was defined as a change of >13 mm. RESULTS: Of the 71 patients enrolled in the study, 35 were allocated to receive morphine and 36 to receive placebo. One patient left the hospital before receiving morphine. No significant differences were seen between the two groups with regard to age, sex and initial VAS score. A more favourable change in VAS score was reported in the morphine group with a significantly greater reduction in the median VAS score than in the placebo group. Morphine administration did not cause significant changes in patients' signs or in the physicians' plans or diagnoses. No adverse events were seen in either group. CONCLUSION: Morphine can reduce pain in patients with acute appendicitis without affecting diagnostic accuracy. TRIAL REGISTRATION NUMBER: NCT00477061.

Effects of paraoxon and ethylparathion on choline oxidase from Alcaligenes species: inhibition and denaturation.

The kinetics and thermodynamics of the effects of paraoxon (POX) and ethylparathion (EPA) on choline oxidase (ChOx) were studied. Lineweaver-Burk plots of initial velocity data showed a parallel pattern indicating uncompetitive inhibition versus choline. The inhibition constant (K(I)) obtained from the secondary plots for POX and EPA were 0.14+/-0.01 and 0.48+/-0.05 mM, respectively, suggesting that POX is a more potent inhibitor of ChOx than EPA. UV absorption was used to monitor the denaturation of ChOx by POX and EPA. A decrease in FAD fluorescence associated with the interaction of POX and EPA with ChOx suggested a tertiary structural change. Interaction of the enzyme molecule with POX or EPA resulted in inhibition and subsequently denaturation of the enzyme. The results indicate that inhibition and denaturation of the enzyme by POX and EPA are linked, but not parallel events, with inhibition occurring at lower concentrations with respect to denaturation. This suggests that the loss of initial velocity of the enzyme is an active site specific effect and not due to global conformational changes induced by the inhibitors.

Mitochondrial function in shock.

Studies utilizing animal models of circulatory shock have revealed mitochondrial structural and functional damage in the liver, kidney, and brain. Adenosine triphosphate (ATP) synthesis and calcium transport rates of these mitochondria decline significantly during circulatory shock. The specific enzyme functions affected deleteriously by low flow states are the ATP synthetase, adenine nucleotide translocase, and carrier-mediated calcium transport. Other cellular alterations that possibly are responsible for, or are related to, the shock-induced mitochondrial deterioration are discussed. Differences in the mitochondrial responses to endotoxemia and hyperdynamic sepsis are described. Data are presented on the beneficial effects of early glucocorticoid treatment in prevention of mitochondrial functional deterioration during endotoxemia.

Alterations of mitochondrial metabolism and protein concentrations in subacute septicemia.

Male Sprague-Dawley rats were made septic by cecal ligation for a period of 6 days. Sham-operated rats were used as control animals. Septic rats developed gram-negative bacteremia within 18 to 24 h. Blood cultures were positive for Escherichia coli, Proteus spp., and Klebsiella spp. in all cases. Significant loss of body weight was observed in septic rats during the 6-day period, whereas control rats exhibited a steady gain in body weight after the second postoperative day. Liver and muscle mitochondria were isolated and analyzed 6 days after the operation in control and septic rats. Liver mitochondrial cytochrome a(a3), b, and c concentrations were normal in septic rats. Oxygen utilization rates in state 3 (during ATP synthesis) were also within the normal range. State 4 respiratory rates, however, were increased with glutamate and pyruvate as substrates, resulting in low respiratory control ratios in septic rats. Muscle mitochondria from septic rats exhibited several abnormalities: the yield of cytochromes b, c, and a(a3) per gram of tissue was 34% below normal in septic rats. ATP synthesis rates declined significantly with pyruvate as substrate. Respiratory control ratios were below normal with all substrates studied except glutamate. These data are in agreement with previous reports on loss of muscle proteins and abnormalities in energy fuel utilization in septic patients.

In vitro and in vivo association and subcellular distribution of toxic and experimentally modified endotoxin.

Cell association and organ distribution of toxic and experimentally modified endotoxin were compared in whole animals and hepatoma tissue culture (HTC) cells. For both toxic and poly-l-alpha-ornithine mixed endotoxin in vivo, most of the endotoxin becomes associated with the reticuloendothelial system (RES) rich organs. Organ distribution does not change from 1 to 5 h. Significantly less detoxified endotoxin becomes associated with RES-rich organs. Association and nuclear transfer of toxic endotoxin in HTC cells are gradual and time-dependent processes. Plasma treatment increased association of endotoxin with HTC cells. Poly-l-alpha-ornithine (4 micrograms/mL) also significantly increases HTC cell association of endotoxin, and nuclear transfer of endotoxin was similar in principle to the toxic material. Association of detoxified endotoxin with HTC cells is significantly higher than toxic endotoxin and increases with time. In contrast with toxic and poly-l-alpha-ornithine mixed endotoxin, nuclear association of alkaline-treated detoxified endotoxin did not increase significantly during 5 h incubation. Cumulatively, these observations indicate that while tissue culture cells could provide a more controllable experimental system by which to study the fate and pathogenic mechanism of endotoxin at the cellular and subcellular level, HTC cells under the conditions employed herein do not yield binding data which compare favorably with in vivo results. Caution must be exercised when extrapolating in vitro data to the actual in vivo action of endotoxin.

Transfer of drug resistance factor in Shigella sonnei isolated in Iran.

The pattern of drug resistance and incidence of R-factors were studied in Shigella sonnei strains isolated in Iran. Eighty-nine out of 172 strains (51.7%) were resistant to one or more drugs and multiple drug resistance was more common than single drug resistance. The most predominant pattern of resistance observed was (Tc, Cm, Sm, Su). By mixed cultivation, 85.7% of Shigella sonnei resistant strains isolated on the Central Plateau and 100% of the strains from the caspian littoral transferred at least a part of their resistance pattern to sensitive E. coli K12 F- (gamma). In this experiment, 67.1% of our resistant and 17% of our sensitive strains had colicinogenic properties. No such difference could be observed between R+ and sensitive strains isolated in the Caspian littoral.