Immune variations in bipolar disorder: phasic differences

OBJECTIVES: To characterize the immunological variations of patients with a bipolar disorder (BD) diagnosis in manic (BDm) and depressive (BDd) phases, by the quantification of the serum levels of interleukin (IL)-1beta, -2, -4, -6 and tumor necrosis factor alpha (TNF-alpha). METHODS: Twenty physically healthy patients with a BD type I diagnosis and 33 matched controls were studied, after giving informed consent. The inclusion criteria included at least three weeks without any kind of psychopharmacological treatment, Young Mania Rating Scale score > or =20 for BDm (n = 10) and Hamilton Depression Rating Scale score > or =21 for BDd patients (n = 10). Exclusion criteria included any infectious diseases, allergies or any other kind of medical illness that required treatment with immunosuppressors, as well as any other diagnosis in Axis I. Physical and laboratory examinations were performed to rule out any clinical illness. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum cytokines concentration. RESULTS: BD patients, when compared to controls, showed significant differences (p < or = 0.05) in the serum levels of the measured cytokines. The sub-group of BDd patients showed an increase in IL-6 and TNF-alpha, as well as a decrease in IL-2 concentration. The BDm sub-group, on the other hand, showed an increase in TNF-alpha and IL-4 values, with a low concentration of IL-1 and IL-2. The comparison between both sub-groups suggests that there is a distinctive cytokine pattern for the specific phases of the disorder: for mania, we found a high IL-4 and low IL-1beta and IL-6 concentration, while in the depressive phase, the inverse pattern was found. CONCLUSIONS: Our results show the existence of phasic differences in the serum levels of cytokines in BD.     

High density of weak replication origins in a 75-kb region of chromosome 2 of fission yeast

Using a two-dimensional gel electrophoresis origin mapping technique and cell synchronization, we have studied replication timing and mapped origins in a 75-kb region of chromosome 2 of Schizosaccharomyces pombe . Three of the five mapped origins are moderately active and the other two are very weak. DNA fragments containing the three moderately active origins and one weak origin are ARS-positive whereas that containing the other weak origin is ARS-negative. Three ARS elements reported earlier from this region appear to be inactive as chromosomal origins. The centromere-proximal 45 kb of this region replicates earlier than the telomere-proximal 30 kb. A transition from early to late replication occurs within 10 kb of the chromosomally inactive ars727 , suggesting a possible role of the previously reported late-replication-enforcing region in determining chromosomal replication timing of the region. These results in conjunction with those from some other studies suggest that, in S. pombe , the actual number of potential origins may be significantly higher than previously detected in many genome-wide studies, and the relationship between ARS activity and chromosomal origin activity is not as simple as in Saccharomyces cerevisiae .     

Mifepristone-induced vaginal bleeding is associated with increased immunostaining for cyclooxygenase-2 and decrease in prostaglandin dehydrogenase in luteal phase endometrium

The mechanism of mifepristone-induced vaginal bleeding and endometrial shedding was investigated in 13 women who took 200 mg mifepristone in the midluteal phase on d 8 after the onset of the urinary LH surge (LH+8). Endometrial biopsies were collected, 6-24 h after mifepristone (group 1, n = 7) or 36-48 h after mifepristone (group 2, n = 6), and compared with those from a control group in the midluteal phase (n = 7). All women reported vaginal bleeding commencing 36-48 h after taking mifepristone. Treatment with mifepristone significantly reduced serum progesterone levels in all women, when compared with the controls (13.2 nM vs. 34.8 nM, P = 0.001). After mifepristone, a significant increase in cyclooxygenase-2 immunoreactivity was apparent at 36-48 h (P = 0.0018), whereas prostaglandin 15 dehydrogenase enzyme-positive immunostaining declined, to be virtually absent by 36-48 h in both glands and in stroma (P < 0.05). There was no change in intensity or distribution of staining for steroid receptors after mifepristone. The changes in immunostaining for cyclooxygenase-2 and prostaglandin 15 dehydrogenase strongly support the hypothesis that an increase in the local concentration of prostaglandins in the endometrium is involved in the mechanism of bleeding induced by mifepristone in the luteal phase.     

Community mental health: Training program in a School of Public Health

The new look implied by the label community mental health is understood by many to mean the adoption of a public health approach to mental health. In this paper, a psychologist outlines the salient elements in such an approach as embodied in a community mental health training program located for a decade at the Harvard School of Public Health. To make the role transition from traditional mental health clinician to community mental health worker, it may be mandatory to become familiar with the theoretical models, principles of practice, and specific research tools of the public health profession. Since only a few can arrange to undertake formal training at schools of public health, it is hoped that each mental health discipline will increasingly include exposure to key public health concepts in its own professional training program.This paper was presented at the annual convention of the American Psychological Association, September 4, 1964, Los Angeles, California. Since this paper was written, N.I.M.H. has sponsored the Boston Conference on the Training of Psychologists in Community Mental Health, May 4–8, 1965, Swampscott, Massachusetts. Proceedings of this conference are expected to be published and available by the fall of 1965.     

Twelve new microsatellite loci for the sulphur molly (Poecilia sulphuraria) and the related Atlantic molly (P. mexicana)

The recent discovery of a population of highly sulphide-adapted mollies in the sulphide springs of Ojos del Azufre ??La Gloria??, in Chiapas, Mexico has prompted various questions concerning their potential evolutionary uniqueness. Because of their phenotypic similarity they have been linked to the endemic and highly endangered sulphur molly (Poecilia sulphuraria) from the Ba?os del Azufre, another sulphur-spring complex in the same river system. We developed twelve new microsatellite markers from 299 sequences that contained putative microsatellite motifs from a ??next generation?? sequencing run and applied them to P. sulphuraria from ??La Gloria?? and the Ba?os del Azufre and two clear-water populations of the closely related P. mexicana.     

Sand Fly Fauna (Diptera,Pcychodidae, Phlebotominae) in Different Leishmaniasis-Endemic Areas of Ecuador,Surveyed Using a Newly Named Mini-Shannon Trap

To study the sand fly fauna, surveys were performed at four different leishmaniasis-endemic sites in Ecuador from February 2013 to April 2014. A modified and simplified version of the conventional Shannon trap was named “mini-Shannon trap” and put to multiple uses at the different study sites in limited, forested and narrow spaces. The mini-Shannon, CDC light trap and protected human landing method were employed for sand fly collection. The species identification of sand flies was performed mainly based on the morphology of spermathecae and cibarium, after dissection of fresh samples. In this study, therefore, only female samples were used for analysis. A total of 1,480 female sand flies belonging to 25 Lutzomyia species were collected. The number of female sand flies collected was 417 (28.2%) using the mini-Shannon trap, 259 (17.5%) using the CDC light trap and 804 (54.3%) by human landing. The total number of sand flies per trap collected by the different methods was markedly affected by the study site, probably because of the various composition of species at each locality. Furthermore, as an additional study, the attraction of sand flies to mini-Shannon traps powered with LED white-light and LED black-light was investigated preliminarily, together with the CDC light trap and human landing. As a result, a total of 426 sand flies of nine Lutzomyia species, including seven man-biting and two non-biting species, were collected during three capture trials in May and June 2014 in an area endemic for leishmaniasis (La Ventura). The black-light proved relatively superior to the white-light with regard to capture numbers, but no significant statistical difference was observed between the two traps.     

Genotyping of sand fly species in Peruvian Andes where leishmaniasis is endemic

Genotyping of sand fly species circulating in Peru was established on the basis of PCR-restriction fragment length polymorphisms (RFLPs) of the 18S ribosomal RNA (rRNA) gene. The sequences of 18S rRNA gene fragments from 12 Lutzomyia and 1 Warileya species were determined and their RFLP-patterns were analyzed. Consequently, RFLP analysis with the restriction enzyme AfaI and then HapII or KpnI, followed by XspI successfully differentiated them. Intraspecific genetic diversity affecting RFLP-patterns was not detected in the specimens collected from 24 areas of 8 departments. The genotyping was applied to the surveillance of sand flies collected from Andean areas where leishmaniasis is endemic, and its usability was verified. The present method promises to be a powerful tool for the classification and surveillance of sand flies circulating in Peru.     

Molecular dynamic simulations of the catalytic subunit of calpains 1, 2, 5, and 10: Structural analysis with an aim toward drug design

Calpains are cysteine proteases involved in the development of several human chronic illnesses such as neurodegenerative diseases, cardiovascular ailments, diabetes, and obesity which constitutes them into possible therapeutic targets. Here, using molecular dynamic simulations and docking, we studied the binding of known inhibitors to representative members of classical and nonclassical calpains. Our aim is to gain better understanding on the inhibition mechanism of calpains and to develop better and more specific inhibitors. Our atomistic models confirmed the importance of calcium ions for the structure of calpains and, as a consequence, their functionality. With these models and their subsequent use in molecular docking, essential structural requirements were identified for the binding of ligands to the calpain catalytic site that provide useful information for the design of new selective calpain inhibitors.