Functional inactivation of orexin 1 receptors in CA1 region impairs acquisition, consolidation and retrieval in Morris water maze task

Orexin containing neurons in the lateral hypothalamic area (LHA) produce orexin-A (hypocretin-1) and orexin-B (hypocretin-2) and send their axons to the hippocampus, which predominantly expresses orexin 1 receptors (OX1Rs) showing a higher affinity to orexin-A. Recent studies have shown that central administration of orexin-A has an effect on learning and memory but literature concerning the role of orexinergic system in cognition remains controversial. Therefore, we examined the effect of pre-training, post-training and pre-probe trial intrahippocampal CA1 administration of a selective OX1R the orexin 1 receptor antagonist SB-334867-A (1.5, 3, 6 microg/0.5 microl) on acquisition, consolidation and retrieval in a single-day testing version of Morris water maze (MWM) task. Our results show that, SB-334867-A impaired acquisition, consolidation and retrieval of MWM task as compared with the control group. This drug had no effect on escape latency of a non-spatial visual discrimination task. Therefore, it seems that endogenous orexins, especially orexin-A, play an important role in spatial learning and memory in the rat.     

Mental health problems of Iranian female adolescents and its association with pubertal development: a nationwide study

Mental health problems including emotional and behavioral problems during puberty may be under influence of different risk factors including cultures, living in urban or rural areas and ethnic factors which may vary between different countries. The main aim of this study is to investigate the profile of emotional and behavioral problems and the role of factors such as age, stage of puberty, ethnicity, rurality and living in urban area, as risk factors in Iranian girls. As a part of a large national study we evaluated the emotional and behavioral problems in different stages of puberty in a community sample of Iranian adolescent girls from public schools that were selected by clustered random sampling method. In all subjects, demographic characteristics, and pubertal stages were measured. Emotional and behavioral problems were evaluated using Strength and Difficulties Questionnaire (SDQ). The associations of age, pubertal development indices, socioeconomic and demographic factors with the behavioral problems were assessed. A total number of 4576 students enrolled the study and responded to the questions. The mean age of participants was 13.83 ± 2.19 years. The mean total score of difficulties in participants was 14.34 ± 5.81. According to these results 813 (17.8%) adolescents had total problem scores higher than Goodman's cutoff points and the most frequent problem domain was conduct problems (20.5%). According to the results the most related variable with the total difficulty score of SDQ were ethnicity, residency in urban areas and development of menstrual cycle respectively. The results of this study showed that the most correlated factors with mental health problems in Iranian girls during puberty are ethnicity, urbanity and development of menstrual cycle.     

VIP-loaded PLGA as an anti-asthma nanodrug candidate

Poly lactic-co-glycolic acid (PLGA), a biodegradable polymer, can effectively protect encapsulated peptides from enzymatic degradation. PLGA was approved by FDA as a safe drug delivery system suitable for inhalation administration. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, displays anti-inflammatory and anti-spasmodic effects, which can be considered as a new therapeutic option to control and treat asthma. Because of in vivo enzymatic degradation of VIP including in the lung, there is a need for an applicable delivery system. In light of this, the purpose of this study was to prepare VIP-loaded PLGA microspheres as a drug delivery system, assuming that the newly-introduced model has the ability to persist for a longer time in respiratory tracts. The PLGA microsphere was produced, and loaded with VIP as an applicable nanodrug system. A series of physiochemical properties were determined, including the morphological characteristics, average size of nanoparticles, electric charge distribution, FTIR spectroscopy absorption, and loading and releasing percentage of the nanodrug. VIP-loaded PLGA exhibited an average size of approximately 550?±?50 nm. Additionally, the produced microsphere showed 78 % VIP release after 10 h at the pH value corresponding to bronchioalveolar microenvironment (approximately 6.5). In the present study, PLGA was formulated and used as a delivery system for VIP. Taken together, the newly-introduced nanodrug seems to be helpful for the clinical treatment of allergic asthma. PLGA nanoparticles can be considered as a potential efficient delivery system for VIP in the respiratory system.     

Biliary brush cytology in the assessment of biliary strictures at a tertiary center in Iran

Background: Confirmation of cholangiocarcinoma and other malignant bile duct stenosis is challenging. The aim of the current study was to assess the accuracy of brush cytology for diagnosis of malignant biliary strictures. Methods: 105 patients with hepatic biliary strictures undergoing ERCP were included in this study. Prospectively collected data included symptoms, results of biochemical testing and imaging procedures, as well as details of ERCP. Exclusion criteria were: 1) strictures that would not permit passage of guidewire and brush accession; and 2) post-operative strictures. Brushings of the bile duct strictures were performed. All patients were followed for at least 6 months. The final diagnosis was confirmed following surgery, histopathological diagnosis of the lesion, radiological infiltration of adjacent organs or metastases, or after at least a 6-month follow-up. Results: 88 brush samples from 88 patients were of appropriate quality. The overall diagnostic sensitivity and specificity for malignant nature of biliary strictures were 40.7% and 100%, respectively. The sensitivity was 66.6 % for ampullary carcinomas, 36.3% for pancreatic cancer and 32.5% for cholangiocarcinomas. Conclusions: Despite the low sensitivity, due to the relative ease and safety, brush cytology should remain the first choice for diagnosis of causes of biliary strictures.     

Melatonin,an inhibitory agent in breast cancer

Background

The heterogeneous nature of breast cancer makes it one of the most challenging cancers to treat. Due to the stimulatory effect of estrogen in mammary cancer progression, anti-estrogenic agents like melatonin have found their way into breast cancer treatment. Further studies confirmed a reverse correlation between nocturnal melatonin levels and the development of mammary cancer. In this study we reviewed the molecular inhibitory effects of melatonin in breast cancer therapy.

Methods

To open access the articles, Google scholar and science direct were used as a motor search. We used from valid external and internal databases. To reach the search formula, we determined mean key words like breast cancer, melatonin, cell proliferation and death. To retrieval the related articles, we continuously search the articles from 1984 to 2015. The relevance and the quality of the 480 articles were screened; at least we selected 80 eligible articles about melatonin molecular mechanism in breast cancer.

Result

The results showed that melatonin not only inhibits breast cancer cell growth, but also is capable of inhibiting angiogenesis, cancer cell invasion, and telomerase activity. Interestingly this hormone is able to induce apoptosis through the suppression or induction of a wide range of signaling pathways. Moreover, it seems that the concomitant administration of melatonin with other conventional chemotherapy agents had beneficial effects for patients with breast cancer, by alleviating unfavorable effects of those agents and enhancing their efficacy.

Conclusion

The broad inhibitory effects of melatonin in breast cancer make it a promising agent and may add it to the list of potential drugs in treatment of this cancer.