Effect of circadian rhythm disturbance on morphine preference and addiction in male rats: Involvement of period genes and dopamine D1 receptor.

It is claimed that a correlation exists between disturbance of circadian rhythms by factors such as alteration of normal light-dark cycle and the development of addiction. However, the exact mechanisms involved in this relationship are not much understood. Here we have studied the effect of constant light on morphine voluntary consumption and withdrawal symptoms and also investigated the involvement of Per1, Per2 and dopamine D1 receptor in these processes. Male wistar rats were kept under standard (LD) or constant light (LL) conditions for one month. The plasma concentration of melatonin was evaluated by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was used to determine the mRNA expression of Per1, Per2 and dopamine D1 receptor in the striatum and prefrontal cortex. Morphine preference (50mg/L) was evaluated in a two-bottle-choice paradigm for 10 weeks and withdrawal symptoms were recorded after administration of naloxone (3mg/kg). One month exposure to constant light resulted in a significant decrease of melatonin concentration in the LL group. In addition, mRNA levels of Per2 and dopamine D1 receptor were up-regulated in both the striatum and prefrontal cortex of the LL group. However, expression of Per1 gene was only up-regulated in the striatum of LL rats in comparison to LD animals. Furthermore, after one month exposure to constant light, morphine consumption and preference ratio and also severity of naloxone-induced withdrawal syndrome were significantly greater in LL animals. It is concluded that exposure to constant light by up-regulation of Per2 and dopamine D1 receptor in the striatum and prefrontal cortex and up-regulation of Per1 in the striatum and the possible involvement of melatonin makes animals vulnerable to morphine preference and addiction.

Golestan cohort study of oesophageal cancer: feasibility and first results.

To investigate the incidence of oesophageal cancer (EC) in the Golestan province of North-East Iran, we invited 1349 rural and urban inhabitants of Golestan province aged 35-80 to undergo extensive lifestyle interviews and to provide biological samples. The interview was repeated on a subset of 130 participants to assess reliability of questionnaire and medical information. Temperature at which tea was consumed was measured on two occasions by 110 subjects. Samples of rice, wheat and sorghum were tested for fumonisin contamination. An active follow-up was carried out after 6 and 12 months. A total of 1057 subjects (610 women and 447 men) participated in this feasibility study (78.4% participation rate). Cigarette smoking, opium and alcohol use were reported by 163 (13.8%), 93 (8.8%) and 39 (3.7%) subjects, respectively. Tobacco smoking was correlated with urinary cotinine (kappa = 0.74). Most questionnaire data had kappa > 0.7 in repeat measurements; tea temperature measurement was reliable (kappa = 0.71). No fumonisins were detected in the samples analysed. During the follow-up six subjects were lost (0.6%), two subjects developed EC (one dead, one alive); in all, 13 subjects died (with cause of death known for 11, 84.6%). Conducting a cohort study in Golestan is feasible with reliable information obtained for suspected risk factors; participants can be followed up for EC incidence and mortality.

Prevalence of gastric precancerous lesions in Ardabil, a high incidence province for gastric adenocarcinoma in the northwest of Iran.

BACKGROUND/AIMS: Ardabil Province, in northwestern Iran, has the highest rate of gastric (predominantly cardia) adenocarcinoma in Iran. This study aimed to investigate the feasibility of endoscopic screening and to look for associated Helicobacter pylori infection and gastric precancerous lesions. METHODS: One thousand one hundred and five adult volunteers, residents of Ardabil and Meshkinshahr, districts, 40 years old and above were selected and invited by a simple random household canvass in rural and urban locations. Informed consents were obtained and upper gastrointestinal video endoscopy was performed to biopsy all visible lesions and standard sites in the antrum, corpus, and cardia. RESULTS: One thousand and eleven of the invited individuals agreed to participate, including 494 men and 517 women, with a mean (SD) age of 53.32 (10.39) years. Endoscopy was well tolerated by all subjects; 96.7% of antral and 80.7% of cardia mucosal biopsies were satisfactory. The urease test or histology for H pylori was positive in at least 89.2% of subjects. Histological evidence of mucosal atrophy was seen in 39.3% of antral and 21.9% of cardia samples. Chronic gastritis with or without activity, reactive atypia of glandular epithelium, intestinal metaplasia, dysplasia, and cancer were found in 95.1%, 38.0%, 8.7%, 0.2%, and 0.3% of antral and 85.3%, 22.9%, 3.8%, 0.3%, and 0.1% of cardiac biopsies, respectively. CONCLUSION: Endoscopic screening for upper gastrointestinal diseases was feasible and well tolerated in Ardabil, Iran. Most subjects showed H pylori infection. Atrophic gastritis, reactive atypia, and intestinal metaplasia were common in antrum, corpus, and cardia subsites.

Endoscopic esophageal cancer survey in the western part of the Caspian Littoral.

After a hiatus of 30 years an attempt is now being made to re-assess the previously reported very high esophageal cancer incidence rates in the Caspian Littoral. The extraordinarily high incidence rates found in the eastern side of the Littoral, were re-confirmed five years ago for the Turkoman region, using esophageal balloon cytology supplemented by esophagoscopy of suspected cases. The focus this time was on the Ardabil province in the western side of the Caspian Littoral, where the rates reported 30 years ago were moderately high. A pilot chromoendoscopic screening program was scheduled for 650 asymptomatic adults from a randomly selected part of the city of Ardabil and adjoining villages, to evaluate the overall patterns of esophageal disease and to establish the utility of endoscopy as an esophageal cancer screening tool. 504 healthy volunteers, giving a compliance rate of 77.5%, submitted to esophagogastroscopy without any mishaps. Contrary to expectation, no dysplasia or esophageal cancer was found in 914 satisfactory biopsy specimens. Total absence of esophageal cancer or precursor dysplastic changes in the surveyed population in the western part of the Caspian Littoral was at variance with the cancer registry findings of three decades ago for the western part of the Littoral. A plausible explanation could be the improved socio-economic conditions and life style changes which have taken place in the recent past all along the Caspian Littoral, except in the Turkoman Plain.