Memory impairment induced by IL-1β is reversed by α-MSH through central melanocortin-4 receptors

Interleukin-1beta (IL-1β) significantly influences memory consolidation. Treatments that raise the level of IL-1β in the brain, given after training, impair contextual fear conditioning. The melanocortin α-MSH exerts potent anti-inflammatory actions by physiologically antagonizing the effect of pro-inflammatory cytokines. Five subtypes of melanocortin receptors (MC1R–MC5R) have been identified, with MC3R and MC4R predominating in the central nervous system. The present experiments show that injection of IL-1β (5 ng/0.25 μl) in dorsal hippocampus up to 15 min after training decreased freezing during the contextual fear test. The treatment with IL-1β (5 ng/0.25 μl) 12 h after conditioning cause amnesia when animals were tested 7 days post training. Thus, our results also demonstrated that IL-1β can influence persistence of long-term memory. We determined that animals previously injected with IL-1β can acquire a new contextual fear memory, demonstrating that the hippocampus was not damaged. Treatment with α-MSH (0.05 μg/0.25 μl) blocked the effect of IL-1β on contextual fear memory. Administration of the MC4 receptor antagonist HS014 (0.5 μg/0.25 μl) reversed the effect of α-MSH. However, treatment with γ-MSH (0.5 μg/0.25 μl), an MC3 agonist, did not affect IL-1β-induced impairment of memory consolidation. These results suggest that α-MSH, through central MC4R can inhibit the effect of IL-1β on memory consolidation.     

Diagnostic Interview for Genetic Studies (DIGS): inter-rater and test-retest reliability and validity in a Spanish population.

OBJECTIVE: To test the reliability and validity of the DIGS in Spanish population. METHODS: Inter-rater and test-retest reliability of the Spanish version of DIGS was tested in 95 inpatients and outpatients. The resultant diagnoses were compared with diagnoses obtained by the LEAD (Longitudinal Expert All Data) procedure as "gold standard". The kappa statistic was used to measure concordance between blind inter-raters and between the diagnoses obtained by LEAD procedure and through the DIGS. RESULTS: Overall kappa coefficient for inter-rater reliability was 0.956. The kappa value for individual diagnosis varied from major depression=0.877 to schizophrenia=1. Test-retest reliability was 0.926. Kappa for all individual target diagnoses ranged from 0.776 (major depression) to 1. Kappa between LEAD procedure and DIGS ranged from 0.704 (major depression) to 0.825 (bipolar I disorder). CONCLUSION: Most of the DSM-IV major psychiatric disorders can be assessed with acceptable to excellent reliability with the Spanish version of the DIGS interview. The Spanish version of DIGS showed an acceptable to excellent concurrent validity. Giving the good reliability and validity of Spanish version of DIGS it should be considered to identify psychiatric phenotypes for genetics studies.     

Evaluation of the Use of BioGlue® in the Treatment of High Anal Fistulas: Preliminary Results of a Pilot Study

Purpose Treatment of anal fistulas by use of adhesives is an attractive method because of its simplicity and it can be performed on an ambulatory basis. Furthermore, if the treatment is unsuccessful, adhesive use does not subsequently prevent the surgeon from utilizing alternative surgical techniques and/or products. BioGlue? Surgical Adhesive is a two-component surgical adhesive composed of bovine serum albumin and glutaraldehyde. We evaluated the usefulness of BioGlue? for the treatment of high transsphincter anal fistulas. Methods Patients diagnosed with high transsphincter anal fistulas of cryptoglandular origin, whether relapsed or not, were included in this study. A seton was placed before the injection of BioGlue? into the fistula track of high transsphincter anal fistulas in patients with secondary tracts and/or purulent collections. Clinical charts, operative reports, and endoanal echography results obtained for each patient were reviewed. Results Fourteen patients (13 males; mean age, 39.9 (range, 24–66) years) with high transsphincter anal fistulas of cryptoglandular origin were recruited into the study. The average time of symptom evolution was 35.6 (range, 2–96) months. Ten of 14 cases were for relapsed fistulas. Six patients required the placement of a seton 37 (range, 32–42) days before the BioGlue? injection. Patients were followed for a mean length of 13.92 (range, 3–21) months, and the fistula healed completely in only seven patients (50 percent). Conclusions These preliminary results demonstrate that BioGlue? may be useful for treating patients with high transsphincter anal fistulas. Further prospective long-term studies are needed.     

Risk factors for stress fracture among young female cross-country runners

PURPOSE: To identify risk factors for stress fracture among young female distance runners. METHODS: Participants were 127 competitive female distance runners, aged 18-26, who provided at least some follow-up data in a randomized trial among 150 runners of the effects of oral contraceptives on bone health. After completing a baseline questionnaire and undergoing bone densitometry, they were followed an average of 1.85 yr. RESULTS: Eighteen participants had at least one stress fracture during follow-up. Baseline characteristics associated (P<0.10) in multivariate analysis with stress fracture occurrence were one or more previous stress fractures (rate ratio [RR] [95% confidence interval]=6.42 (1.80-22.87), lower whole-body bone mineral content (RR=2.70 [1.26-5.88] per 1-SD [293.2 g] decrease), younger chronologic age (RR=1.42 [1.05-1.92] per 1-yr decrease), lower dietary calcium intake (RR=1.11 [0.98-1.25] per 100-mg decrease), and younger age at menarche (RR=1.92 [1.15-3.23] per 1-yr decrease). Although not statistically significant, a history of irregular menstrual periods was also associated with increased risk (RR=3.41 [0.69-16.91]). Training-related factors did not affect risk. CONCLUSION: The results of this and other studies indicate that risk factors for stress fracture among young female runners include previous stress fractures, lower bone mass, and, although not statistically significant in this study, menstrual irregularity. More study is needed of the associations between stress fracture and age, calcium intake, and age at menarche. Given the importance of stress fractures to runners, identifying preventive measures is of high priority.     

B Cells Are Essential for Moderating the Inflammatory Response and Controlling Bacterial Multiplication in a Mouse Model of Vaccination against Chlamydophila abortus Infection

The use of inactivated vaccines associated with suitable adjuvants has been demonstrated to confer a good level of protection against Chlamydophila abortus. However, the basis of the immune protective response induced by these vaccines has been poorly studied. B cells act as an immune regulatory population during primary infection by C. abortus. Thus, it was considered of interest to study the role of B cells in an infection after immunization with a killed vaccine. For this, C57BL/6 and B-cell-deficient mice were immunized with a killed vaccine against C. abortus using QS-21 as the adjuvant. After challenge, the course of infection was established by analysis of morbidity, C. abortus burden in the liver, and histopathological changes. The immune response induced was studied by real-time PCR techniques. Experiments involving transfer of immune serum from vaccinated or previously infected mice were also carried out. The lack of B cells reduced the protection conferred by the QS-21 adjuvant vaccine. Vaccinated B-cell-deficient mice showed a 1,000-fold-greater bacterial burden in the liver than their wild-type counterparts. Obvious differences existed in the liver, where a severe neutrophilic reaction and extended areas of necrosis were observed with vaccinated B-cell-deficient mice. An analysis of the immune response pointed to a significant increase in inflammatory cytokines and chemokines and the deficient production of transforming growth factor beta. The transfer of antibodies restored the level of protection. This study demonstrates that B cells play a crucial role in controlling C. abortus multiplication and prevent an exacerbated inflammatory response.Chlamydophila abortus is a gram-negative obligate intracellular bacterium responsible for enzootic abortion in small ruminants. The disease caused by the bacteria is the most commonly diagnosed cause of ovine abortion in a number of western countries, where it is responsible for severe economic loss. C. abortus can also induce abortion in pregnant women as a result of contact with aborting sheep and goats (27).Mouse models have been widely used in studies of the pathogenesis and immune response induced by members of the family Chlamydiaceae (6, 15, 19, 37). The use of these models in C. abortus infection has underlined the importance of innate immunity controlling the infection (23), the role of the cellular immune response in its clearance (20), and several aspects of the pathogenesis of C. abortus-induced abortion (4, 8). These experimental studies demonstrated that after systemic spreading of C. abortus, the establishment of an effective immune response can eliminate the infection in all organs except the placenta of pregnant animals, where multiplication of the bacteria induces abortion (12). The effective immune response observed for the spleen and liver involves neutrophils and NK cells that act as a first line of defense (9) and in the recruitment of other leukocyte subpopulations (35). Also, a strong type 1 specific immune response is rapidly induced, involving the production of proinflammatory cytokines, especially gamma interferon (IFN-γ) (33), and the activation of T cells, with CD8⁺ T cells playing an important role in the resolution of the infection (14). The role of the humoral immune response during the C. abortus infection has been less studied, but an immunomodulatory role suggested for B cells in the early events of the primary infection would protect mice against an exaggerated inflammatory response (7). Furthermore, it has been reported that C. abortus infection can induce the production of neutralizing antibodies that provide protection after a passive transfer (13, 21).Research into an effective vaccine against C. abortus has been carried out in several laboratories. A temperature-sensitive mutant strain of C. abortus (strain 1B) was developed as a live vaccine (44) providing a good level of protection. However, concerns still remain over the safety of using live attenuated vaccines, particularly as regards the possibility of colonization of the human placenta or of the attenuated strain reverting to virulence, with the consequent potential to cause disease and abortion in the vaccinated animal (28). Killed vaccines against C. abortus are safer and have been demonstrated to confer effective protection when they are used with a suitable adjuvant (16). The immune mechanisms involved in the protection conferred by the killed vaccines against C. abortus are poorly understood, and since B cells play a substantial role in the development of the response against the primary infection, it would be valuable to analyze the role of B cells in the immune response induced by a killed vaccine in order to develop more effective and safer vaccines.     

Función familiar y salud mental del cuidador de familiares con dependencia

ObjectiveTo analyse the influence of family function on the caregiver's perceived mental health.DesignCross-sectional study.SettingTwo primary care urban health centres.Participants153 caregivers of dependent people.MeasurementSociodemographic variables of caregiver and dependent relative and psychoactive drugs prescribed to caregiver. Caregiver questionnaires: mental health evaluated with General Health Questionnaire (GHQ-12), family function with adaptation, partnership, growth, affection and resolve (APGAR), and Duke University-University of North Carolina functional social support questionnaire. Care-recipient questionnaires: cognitive disorders with Pfeiffer and functional dependence level with Barthel.ResultsCaregiver's mean age was 63.8 years; 72.5% (n=111) were female; 57.5% have only primary school studies; and 37.1% take psychoactive drugs. More than 40% of the care-receivers have cognitive disorders and 49.7% have total functional impairment. According to the GHQ-12, 27% of the caregivers had mental health disorders; 31.3% of the families were dysfunctional and 32.7% had poor social support. The variables that significantly contributed to the explanation of caregiver's mental health have been: psychoactive drug intake, family function, social support and educational level.ConclusionFamily function is an important predictor of caregiver's mental health.     

Oestrogen receptors and their relation to neural receptive tissue of the labia minora

Associate Editor Michael G. Wyllie Editorial Board Ian Eardley, UK Jean Fourcroy, USA Sidney Glina, Brazil Julia Heiman, USA Chris McMahon, Australia Bob Millar, UK Alvaro Morales, Canada Michael Perelman, USA Marcel Waldinger, Netherlands

OBJECTIVE

To assess the cellular distributions of oestrogen receptors α and β (ERα and ERβ) and neuronal nitric oxide synthase (nNOS) in the labia minora, as knowledge about ER type and function may clarify the role of oestrogens in vaginal scar formation and improve outcomes in female genital surgery.

SUBJECTS AND METHODS

Labial samples were taken from 10 girls (aged 2–9 years) who underwent surgery for labial fusion. The waste tissue strips obtained were used for immunohistochemical identification of ERα and ERβ, and nNOS in the labia minora.

RESULTS

There was ERα nuclear staining in the stroma of the labia minora close to the clitoris, and basal and suprabasal in the epidermal cells membrane restricted to superficial sections of the labia minora. ERβ was found in the stroma of the labia minora closer to the clitoris and in superficial sections, in the basal epidermal cells membrane and apocrine glandular epithelial cells membrane. There was also ERβ cell membrane staining in the basal and suprabasal epithelial cells and fibroblasts in the lamina propria.

CONCLUSIONS

Established ER presence allows the consideration of the introitus of the vagina as a target for oestrogen therapy in various clinical and surgical situations. Continuing elucidation of the immunohistochemistry of this external genital tissue might assist in the development of molecular tools to treat genital abnormalities. Details of this immunohistochemistry may also advance the understanding of the effects of sexual differentiation on the brain and other organ systems.     

Lack of cross-species transmission of porcine endogenous retrovirus (PERV) to transplant recipients and abattoir workers in contact with pigs

This study investigated the potential transmission of porcine endogenous retrovirus (PERV) to solid-organ transplant recipients and abattoir workers in contact with pigs. Blood samples were obtained from volunteer healthy blood donors (Group A; n=33); pig-breeding farmers who had undergone a liver transplant (Group B; n=14); and pig abattoir workers (Group C; n=49). A second blood sample was obtained 1 year after the first sample from 10 of the abattoir workers (Group D). Tests included investigation for PERV-DNA, PERV-RNA, pig-specific mitochondrial DNA, a quantitative detection of PERV nucleic acids, and antibodies to PERV by two different Western Blots. All polymerase chain reaction and Western Blots assays were negative for PERV or antibodies to PERV. Therefore, the risks of cross-species transmission of PERV appear to be negligible for immunocompetent individuals and allotransplant recipients, even if they are in close and repeated contact with live pigs or pig tissues.