Enhanced negative feedback sensitivity of the hypothalamus–pituitary–adrenal axis in chronic myogenous facial pain⋆

Dysregulations of the hypothalamus–pituitary–adrenal (HPA) axis, as a physiological substrate of stress, have been observed in patients with different stress‐related and chronic pain disorders. In this study, we investigated possible dysregulations of the HPA axis in patients with masticatory muscles pain. In 20 patients with myogenous facial pain and 20 healthy controls, awakening cortisol responses, i.e. cortisol rise in the first hour after awakening, as well as a short circadian free cortisol profile, i.e. four cortisol samples over 12h during the day, were assessed before and after administration of 0.5mg dexamethasone. Results: In comparison to controls, chronic myogenous facial pain patients showed enhanced and prolonged suppression of cortisol after the administration of 0.5mg dexamethasone. Unstimulated cortisol response (before dexamethasone‐intake) to awakening and cortisol levels during the day did not differ between the groups. Dysregulation in terms of enhanced negative feedback suppression exists in chronic myogenous facial pain. These results are in line with a multifactorial etiology of chronic facial pain, shifting the perspective away from a local towards a more central etiology with dysregulations in the stress and pain modulating system.     

Effector CD8+ T lymphocytes against liver stages of Plasmodium yoelii do not require gamma interferon for antiparasite activity

The protective immune response against liver stages of the malaria parasite critically requires CD8⁺ T cells. Although the nature of the effector mechanism utilized by these cells to repress parasite development remains unclear, a critical role for gamma interferon (IFN-γ) has been widely assumed based on circumstantial evidence. However, the requirement for CD8⁺ T-cell-mediated IFN-γ production in protective immunity to this pathogen has not been directly tested. In this report, we use an adoptive transfer strategy with circumsporozoite (CS) protein-specific transgenic T cells to examine the role of CD8⁺ T-cell-derived IFN-γ production in Plasmodium yoelii-infected mice. We show that despite a marginal reduction in the expansion of naive IFN-γ-deficient CS-specific transgenic T cells, their antiparasite activity remains intact. Further, adoptively transferred IFN-γ-deficient CD8⁺ T cells were as efficient as their wild-type counterparts in limiting parasite growth in naive mice. Taken together, these studies demonstrate that IFN-γ secretion by CS-specific CD8⁺ T cells is not essential to protect mice against live sporozoite challenge.     

Helminth infection impairs the immunogenicity of a Plasmodium falciparum DNA vaccine,but not irradiated sporozoites,in mice

Development of an effective vaccine against malaria remains a priority. However, a significant number of individuals living in tropical areas are also likely to be co-infected with helminths, which are known to adversely affect immune responses to a number of different existing vaccines. Here we compare the response to two prototype malaria vaccines: a transmission blocking DNA vaccine based on Pfs25, and a pre-erythrocytic malaria vaccine based on irradiated sporozoites in mice infected with the intestinal nematode Heligmosomoides polygyrus. Following primary immunization with Pfs25 DNA vaccine, levels of total IgG, as well as IgG1, IgG2a, IgG2b (all P = 0.0002), and IgG3 (P = 0.03) Pfs25 antibodies were significantly lower in H. polygyrus-infected mice versus worm-free controls. Similar results were observed even after two additional boosts, while clearance of worms with anthelmintic treatment 3 weeks prior to primary immunization significantly reversed the inhibitory effect of helminth infection. In contrast, helminth infection had no inhibitory effect on immunization with irradiated sporozoites. Mean anti-CSP antibody responses were similar between H. polygyrus-infected and worm-free control mice following immunization with a single dose (65,000 sporozoites) of live radiation attenuated (irradiated) Plasmodium yoelii sporozoites (17X, non-lethal strain), and protection upon sporozoite challenge was equivalent between groups. These results indicate that helminth infection may adversely affect certain anti-malarial vaccine strategies, and highlight the importance of these interactions for malaria vaccine development.     

Mortality and business cycles by level of development: evidence from Mexico

We investigate the relationship between mortality and business cycles within Mexico, where development varies significantly. We exploit this variation by separately analyzing the top ten and bottom ten developed states for the period 1993-2004. We find that while overall mortality is procyclical nationally and in the top ten states, it is countercyclical in the bottom ten. Further, we show that in the top ten states mortality due to non communicable conditions is procyclical, while in the bottom ten mortality due to non communicable conditions and infectious and parasitic diseases are countercyclical. Our results suggest that the relationship between mortality and business cycles may vary by level of development.     

Spermatogonial stem cells identified by molecular expression of PLZF,integrin β1 and reactivity to Dolichos biflorus agglutinin in alpaca adult testes

The identification system of spermatogonial stem cell (SSC) was established in alpaca using the molecular expression as well as the reactivity pattern to Dolichos biflorus agglutinin (DBA) by flow cytometry. Twenty‐four testicles with their epididymis were recovered from adult alpacas at the slaughterhouse of Huancavelica—Perú. Samples were transported to the Laboratory of Reproductive Physiology at Universidad Nacional Mayor de San Marcos. Testes were selected for our study when the progressive motility of epididymal spermatozoa (ESPM) was above 30%. Isolation of SSC was performed with two enzymatic digestions. Finally, sperm viability was evaluated by means of the trypan blue vital stain in spermatogonial round cells. Samples with more than 80% viability were selected. Isolated cells cultured for 2 days were used for identifying the presence of SSCs by the expression of integrin β1 (116 bp) and PLZF (206 bp) genes. Spermatogonia were classified according to the DBA reactivity. Spermatogonia with a strong positive to DBA (sDBA⁺) were classified as SSC (Mean ± SEM=4.44 ± 0.68%). Spermatogonia in early differentiation stages stained weakly positive with DBA (wDBA⁺) (Mean ± SEM=37.44 ± 3.07%) and differentiated round cells as DBA negative (Mean ± SEM=54.12 ± 3.18%). With the use of molecular and DBA markers, it is possible to identify easily the spermatogonial stem cells in alpaca.     

The prevalence,clinical status and genotype of cystic fibrosis patients living in Cuba using national registry data

BackgroundWe aimed to establish a national cystic fibrosis (CF) registry for Cuba, a developing country.MethodsRegional centres that deliver care for all CF patients provided information for a national database.FindingsThe prevalence of CF in Cuba is 26.3 cases per 1,000,000 population. The median age at diagnosis is 2 years, and the median age of the total population was 15 years. Of those aged 16 years or older, the prevalence of Pseudomonas aeruginosa infection was 46%, the prevalence of Staphylococcus aureus infection was 36%, and 80% of individuals were receiving oral azithromycin. The commonest gene mutation was F508del which was observed in 50% of patients.InterpretationThese data demonstrate that it is possible to establish a national CF registry in a developing country such as Cuba. This provides baseline data to permit evaluation of health care delivery enable the spread of good clinical practice nationally.     

A survey of emergency medical services in mountain areas of Europe and North America: official recommendations of the International Commission for Mountain Emergency Medicine (ICAR Medcom)

Survey of on-site treatment of patients in mountain areas of 14 countries in Europe and North America (nonresponder rate 33%) to compare emergency medical services. Around 37,535 ground rescuers and 747 helicopters are ready for evacuation of casualties and patients in mountain areas. And 1316 physicians and 50,967 paramedics take part in ground and air mountain rescue operations. In Europe, 63.2% of helicopters have a physician on board, 17.8% are staffed with a paramedic, and 19% have no medically trained personnel on board. In North America, 31.6% (p < 0.001) of helicopters are staffed with a doctor, 59.3% (p < 0.001) with a paramedic, and 9.1% (p < 0.001) have no medical personnel. The percentage of on-site treatment according to the recommendations of the International Liaison Committee on Resuscitation (ILCOR) or International Commission for Alpine Rescue (ICAR) varies among all countries (p < 0.001) and is positively related to the percentage of physician-staffed helicopters (r = 0.76, p < 0.001). Paramedics in 90.9% countries are obliged to be medically trained, but physicians only need to have a standardized training in emergency medicine in 50% (p < 0.042). On-site treatment according to ILCOR or ICAR recommendations is performed more often in countries where physicians are regularly involved in mountain rescue operations. However, no conclusions can be drawn from the data as to the efficiency of treatment. The data show a lack of medical education in specific, mountain rescue-related problems. Physicians involved should undergo suitable training.     

Th1/Th2 cytokine profiles in saliva of HIV-positive smokers with oropharyngeal candidiasis

Oropharyngeal candidiasis (OPC) is a common opportunistic infection among HIV-positive individuals and often correlates with a CD4 cell number < 200 cells/microl. This study further examined the association of smoking and OPC in HIV-positive persons. A strong association between smoking and OPC was seen in HIV-positive individuals with > or =200 CD4 cells/microl. In HIV-positive persons with > or =200 CD4 cells/microl, OPC+ smokers had lower gamma-interferon (IFN-gamma) concentrations and a trend toward higher interleukin (IL)-4 concentrations in whole saliva compared to OPC- persons with > or =200 CD4 cells/microl, a cytokine profile consistent with that observed in HIV+OPC+ persons with < 200 CD4 cells/microl. These results suggest that premature OPC in HIV-positive smokers is associated with altered oral host defence mechanisms that cannot be overcome by levels of systemic CD4 cells that are otherwise sufficient to protect against OPC.