Low-Level But Not High-Level Baroreceptor Stimulation Inhibits Atrial Fibrillation in a Pig Model of Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) increases susceptibility to atrial fibrillation (AF) by a combined sympatho-vagal hyperactivation. The purpose of this study was to investigate the effect of autonomic nervous system modulation by low-level baroreceptor stimulation (LL-BRS) compared to high-level BRS (HL-BRS) on atrial arrhythmogenic changes in a pig model of OSA. METHODS AND RESULTS: Sixteen pigs received tracheotomy under general urethane/chloralose anesthesia. Group 1 pigs (n = 8) received LL-BRS (at 80% of that slowing sinus rate) for 3 hours and group 2 pigs (n = 8) received HL-BRS (slowing sinus rate). Changes in atrial effective refractory period (AERP) and AF-inducibility were determined during applied negative thoracic pressure (NTP) for 2 minutes before and at the end of the 3-hour stimulation protocol. Group 1: LL-BRS prolonged AERP from 150 ± 5 to 172 ± 19 milliseconds (P < 0.001). After 3 hours of LL-BRS, NTP-induced AERP-shortening was diminished from -51 ± 10 milliseconds (-34%) to -22 ± 4 milliseconds (-13%) (P < 0.01). AF-inducibility during NTP maneuvers decreased from 90% at baseline to 15% (P < 0.01). Group 2: HL-BRS shortened AERP from 150 ± 17 to 132 ± 8 milliseconds (P = 0.024). After 3 hours of HL-BRS, NTP-induced AERP-shortening was increased from -55 ± 7 milliseconds (-36%) to -72 ± 11 milliseconds (-54%) (P < 0.05) and AF-inducibility was not affected. NTP-induced changes in blood gases and blood pressure were not different between the groups. CONCLUSION: LL-BRS suppressed NTP-induced AERP-shortening and AF-inducibility. By contrast HL-BRS further perpetuated NTP-induced AERP-shortening and increased AF-inducibility. These findings support only the use of LL-BRS as a novel therapeutic modality to treat AF in OSA.

Multiple Sclerosis Epidemiology in Middle East and North Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple sclerosis (MS) is one of the most common neurological disorders and a leading cause of nontraumatic disability in young adults in many countries. Recent reports from the Middle East and North Africa have suggested a moderate to high risk of MS in these countries. METHODS: A literature search was performed in August 2014 in MEDLINE, EMBASE, and IMEMR to retrieve original population-based studies on MS epidemiology in the Middle East and North African countries published between 1st January 1985 and 1st August 2014. We designed search strategies using the key words: MS, prevalence, incidence, and epidemiology. According to the inclusion criteria, 52 studies were included in this systematic review. RESULTS: McDonald's criteria were the most widely used diagnostic criteria in the studies. Most studies were conducted in single hospital-based centers with a defined catchment area. The female/male ratio ranged from 0.8 in Oman to 4.3 in Saudi Arabia. MS prevalence ranged from 14.77/100,000 population in Kuwait (2000) to 101.4/100,000 in Turkey (2006). The overall MS prevalence in the region was 51.52/100,000. The mean age at disease onset ranged from 25.2 years in Kuwait to 32.5 years in Northeastern Iran, with an overall estimate of 28.54 years. CONCLUSIONS: Recent advances in MS registries will allow nation-wide studies and temporal comparisons between countries, provided that age- and sex-standardized estimates are available.

Potential impact of air pollution on multiple sclerosis in Tehran, Iran.

BACKGROUND: Multiple sclerosis (MS) incidence has dramatically increased in Tehran, Iran. The health impact of air pollution in Tehran underscores the attention to a possible association to this environmental risk factor. In this study, the authors aimed to analyze the spatial distribution of prevalent MS cases and their association with the spatial patterns of air pollution. METHODS: Patient records meeting McDonald's criteria for definite MS diagnosis with disease onset during 2003-2013 were obtained. Next, the location of 2,188 patients was successfully geo-referenced within Tehran metropolis by geographic information system (GIS) bureau of Iran's post office based on their phone numbers. A cluster analysis was performed using the average nearest neighbor index (ANNI) and quadrat analysis. The long-term exposures of MS patients to particulate matter (PM10), sulfur dioxide (SO2), nitrogen oxide (NO), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated using the previously developed land use regression models. RESULTS: Prevalent MS cases had a clustered pattern in Tehran. A significant difference in exposure to PM10, SO2, NO2, and NOx (p < 0.001) was observed in MS cases compared with controls. CONCLUSION: This study revealed the potential role of long-term exposure to air pollutants as an environmental risk factor in MS.

Estradiol reduces depressive-like behavior through inhibiting nitric oxide/cyclic GMP pathway in ovariectomized mice.

Estradiol decline has been associated with depressive-like behavior in female mice and NO has been suggested to play a major role in the pathogenesis of major depression. This study was conducted to investigate the antidepressant-like effects of acute estradiol administration in female ovariectomized (OVX) mice and the possible role of nitric oxide (NO)/cyclic GMP (cGMP) pathway. To this end, bilateral ovariectomy was performed in female mice and different doses of estradiol were injected alone or in combination with non-specific NO synthase (NOS) inhibitor (L-NAME), selective neural NOS (nNOS) inhibitor (7-NI), an NO precursor (L-arginine) or selective phosphodiesterase type 5 inhibitor (sildenafil). The duration of immobility was recorded in the forced swimming test (FST) to assess the depressive behavior. Moreover, hippocampal levels of NO were determined in select groups. 10 days following the procedure, OVX mice showed significantly prolonged immobility time in comparison with the sham group. Estradiol (3, 10, and 30 µg/kg, s.c.), when injected 1 h prior to FST, exerted antidepressant-like effects in OVX mice. Both L-NAME (30 mg/kg, i.p.), and 7-NI (50 mg/kg, i.p.) significantly reduced the immobility times of OVX mice. Administration of a sub-effective dose of L-NAME (10mg/kg), 15 min after a sub-effective dose of estradiol (1 µg/kg, s.c.) had a robust antidepressant-like effect in OVX mice. Also a sub-effective dose of 7-NI (25 mg/kg), 30 min after a sub-effective dose of estradiol (1 µg/kg, s.c.) showed antidepressant-like effect in OVX mice. Both the NO precursor L-arginine (750 mg/kg, i.p.) and the cGMP-specific phosphodiesterase type 5 inhibitor sildenafil (5 mg/kg, i.p.), 30 min before estradiol treatment, prevented the antidepressant-like effect of a potent dose of estradiol (10 µg/kg, s.c.) in OVX mice. The present findings suggest that suppression of the NO synthase/NO/cGMP pathway may be involved in the antidepressant-like effects of estradiol in OVX mice.

The association between different features of sleep-disordered breathing and blood pressure: A cross-sectional study.

Sleep disordered breathing (SDB) is highly prevalent in patients with high blood pressure (BP). Severity of SDB can be evaluated by the number of apneas and hypopneas per hour (AHI) or by measures of hypoxia. The objective of this study was to assess the association between different measures of SDB and BP. In 134 consecutive patients, polygraphy was performed to determine the AHI. Pulse oximetry was used to determine hypoxemic burden (time below 90% oxygen saturation [T90] and hypoxia load [HL], representing the integrated area above the curve of desaturation). AHI did not correlate with systolic and diastolic BP or pulse pressure. In contrast, HL correlated with pulse pressure during the day (P = .01) and night (P = .0034) before and after adjustment for body mass index. The correlation between systolic BP and HL at night disappeared following adjustment for body mass index. This study generates the hypothesis that nocturnal hypoxemic burden may represent a suitable marker of BP pattern and a potential treatment target in hypertensive patients.

Behavioral despair associated with a mouse model of Crohn's disease: Role of nitric oxide pathway.

Crohn's disease (CD) is associated with increased psychiatric co-morbidities. Nitric oxide (NO) is implicated in inflammation and tissue injury in CD, and it may also play a central role in pathogenesis of the accompanying behavioral despair. This study investigated the role of the NO pathway in behavioral despair associated with a mouse model of CD. Colitis was induced by intrarectal (i.r.) injection of 2,4,6-trinitrobenzenesulfonic acid (10mg TNBS in 50% ethanol). Forced swimming test (FST), pharmacological studies and tissues collection were performed 72 h following TNBS administration. To address a possible inflammatory origin for the behavioral despair following colitis induction, tumor necrosis factor-alpha (TNF-α) level was measured in both the hippocampal and colonic tissue samples. In parallel, hippocampal inducible nitric oxide synthase (iNOS) and nitrite level were evaluated. Pharmacological studies targeting the NO pathway were performed 30-60 min before behavioral test. Colitis was confirmed by increased colonic TNF-α level and microscopic score. Colitic mice demonstrated a significantly higher immobility time in the FST associated to a significant increase of hippocampal TNF-α, iNOS expression and nitrite content. Acute NOS inhibition using either Nω-nitro-l-arginine methyl ester (a non-specific NOS inhibitor) or aminoguanidine hydrochloride (a specific iNOS inhibitor) decreased the immobility time in colitic groups. Moreover, acute treatment with both NOS inhibitors decreased the TNF-α level and nitrite content in the hippocampal samples. This study suggests that the NO pathway may be involved in the behavioral effects in the mouse TNBS model of CD. These findings endow new insights into the gut-brain communication during the development of colonic inflammation, which may ultimately lead to improved therapeutic strategies to combat behavior changes associated with gastrointestinal disorders.

HAV Immunity in Iranian Medical Students.

BACKGROUND: Hepatitis A, a fecal-oral transmitted disease, which has been considered endemic in developing countries, seems to change its pattern in developing countries because of their improved socioeconomic status. OBJECTIVES: In the present study, we aimed to determine the need of vaccination in 270 students at AJA University of Medical Sciences. MATERIALS AND METHODS: The serum level of anti-HAV antibody was checked in 270 students of AJA University of medical students, and effect of different factors, including age, gender, pre-university entrance exam region, familial education, familial income, clean water availability, and previous history of jaundice were tested. RESULTS: Of total 270 students, 30 were female. Their age ranged between 18 and 30 years old with the mean age of 20.58 years and just 34% of students had positive level of anti-HAV antibody. Age and sex had no role in positive serum level of anti-HAV antibody. According to analyzed data, lack of clean water availability, pre-university entrance exam region, lower family education, and poor health status estimation increased statistically the risk of HAV infection. CONCLUSIONS: Because 66% of students were anti-HAV antibody negative and they will work as health care workers in future, our study suggest vaccinating all students accepted at AJA University of Medical Sciences.

Risk factors for postoperative recurrence of Crohn's disease.

BACKGROUND: Postoperative relapse is a common feature of Crohn's disease (CD) in Western countries but its frequency and risk factors have not been studied in the Middle East where there is a rapid upsurge in the incidence of CD. This study aims to research the frequency and risk factors of its recurrence after surgery among 566 Iranian patients with CD in Tehran, Iran. METHODS: All 566 patients diagnosed with Crohn's disease that enrolled in Digestive Diseases Research Center (DDRC) Inflammatory Bowel Disease (IBD) from April 1991 until November 2011 were included in our study. We reviewed clinical data that included time of surgery, possible risk factors and follow up after surgery. Multivariate regression analysis was performed to seek possible risk factors for early postoperative recurrence. RESULTS: The mean age of patients was 30.85 (range: 12-88) years at the onset of enrollment. During a mean follow up of 55 months, 139 (24.5%) out of 566 Crohn's disease patients underwent at least one surgery while 32 (23%) required additional surgery during the period after their first surgical intervention. Cigarette smoking was a risk factor for both initial (p=0.001) and additional surgery (p<0.0001). The penetrating behavior of Crohn's disease, in addition to its effect on surgery (p<0.001), showed a significant influence on disease recurrence (p<0.0007) along with perianal involvement which was significantly associated with relapse (p=0.001). Although disease duration of more than ten years was a significant risk factor for surgery (p=0.043) its effect on recurrence was insignificant (p=0.059). CONCLUSION: The rate of initial and additional surgery is much lower in this region of the world, which is partially due to the relatively new occurrence of Crohn's disease in the Middle East. Cigarette smoking, disease duration over ten years, penetrating behavior of CD, and perianal disease were the main risk factors for surgery.