Euphol prevents experimental autoimmune encephalomyelitis in mice: evidence for the underlying mechanisms

Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological properties and is considered to have anti-inflammatory action. However there are no reports about the effects and mechanisms of euphol in experimental autoimmune encephalomyelitis (EAE), an established model of MS. Here we report the effects and the underlying mechanisms of action of euphol in EAE. Euphol (1-10mg/kg) was administered orally at different time-points of EAE. Immunological and inflammatory responses were evaluated by real-time PCR, Western blot and flow cytometry assays. We provide evidence that euphol significantly attenuates neurological signs of EAE. These beneficial effects of euphol seem to be associated with the down-regulation of mRNA and protein expression of some pro-inflammatory mediators such as TNF-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the CNS. Furthermore, in vitro, euphol consistently inhibited the T cell-mediated immune response including the production of T(H)1 and T(H)17 cytokines in spleen cells of untreated EAE animals. Likewise, oral euphol treatment inhibited the infiltration of T(H)17 myelin-specific cells into the CNS through the adhesion molecule, lymphocyte function-associated antigen 1 (LFA-1). Our findings reveal that oral administration of euphol consistently reduces and limits the severity and development of EAE. Therefore, euphol might represent a potential molecule of interest for the treatment of MS and other T(H)17 cell-mediated inflammatory diseases.     

螺内酯对阵发性心房颤动发作的影响

目的观察螺内酯对阵发性心房颤动(AF)的抑制作用及对心房结构和功能重构的影响。方法选择因Ⅲ度房室传导阻滞植入双腔起搏器的阵发性AF患者96例,分为两组,治疗组(48例)给予螺内酯20 mg/d,对照组(48例)不予螺内酯治疗。随访12个月,观察研究前后血浆醛固酮(Ald)浓度、AF发作情况、左房结构和功能变化。结果治疗组应用螺内酯12个月后Ald水平较前明显降低(5.30 ng/dl vs 7.70 ng/dl,P<0.01),AF发作次数及AF负荷明显减少,左房内径、左房最大容积、左房最小容积及左房收缩期前容积均减小,左房射血分数增高(P均<0.01)。与对照组相比,上述指标亦有显著差异(P均<0.05)。结论醛固酮受体拮抗剂——螺内酯能够抑制阵发性AF患者心房结构和功能的改变,减少AF发生率及持续时间。     

Update on nonsurgical, ultraconservative approaches to treat effectively non-cavitated caries lesions in permanent teeth

Dental caries on tooth surfaces is still a problem in many industrialized countries. For many years, dentistry was influenced by a mechanical approach characterized by the use of high-speed rotary cutting instruments, and dentists predominantly used surgical methods to address caries. This included radical removal of diseased portions of the tooth, along with material-driven geometric extensions to areas that were assumed to be caries-resistant. This concept of extension for prevention was introduced by G. V. Black and influenced dentists for more than 120 years. Recently, a new paradigm of operative conservatism, sometimes referred to as "minimally invasive dentistry," has gained popularity. This paradigm is designed to promote maximum preservation of healthy dental structures over a lifetime. The aim of this review is to discuss the efficacy of current nonsurgical treatments for non-cavitated caries lesions in permanent teeth. Based on results obtained from clinical trials, this review evaluates treatments such as consumption of CPP-ACP added gums, resin infiltration and fissure sealing. Although in a few cases an invasive approach is needed to arrest caries progression, the non-surgical approach generally provides potential benefits that include conserving structure by delaying intervention or minimizing the operative procedure. All current non-invasive methods are effective in treating non-cavitated caries lesions. The adoption of non-invasive approaches in the management of these lesions can preserve dental tissues, thus increasing tooth longevity.     

Microchimerism in labial salivary glands of hematopoietic stem cell transplanted patients

Oral Diseases (2011) 17 , 484–488 Objective: Microchimerism has been extensively investigated in autoimmune diseases, which display similarities with graft‐vs‐host disease. This study was conducted to investigate the presence of microchimerism in minor salivary glands of hematopoietic stem cell transplanted patients, one of the targets of graft‐vs‐host disease. Methods: Labial salivary glands biopsy specimens from 11 stem cell transplanted patients were analysed. The samples were grouped in control (five specimens from a female‐to‐female transplantation) and study group (five glands from male‐to‐female transplantation). One male transplanted patient was used as a positive control. Fluorescence in situ hybridization with Y‐chromosome probe and immunofluorescence with anticytokeratin AE1/AE3 and CD45 were used to identify Y‐chromosome positive glandular epithelial cells from allogeneic hematopoietic stem cell transplanted patients. Results: In the study group, all samples were positive to Y‐chromosome and cytokeratin AE1/AE3, in agreement with the pattern exhibited by male labial salivary gland. None of the samples from control group were positive to Y‐chromosome despite being positive to cytokeratin AE1/AE3. Positivity to CD45 was not relevant. Conclusion: Microchimerism in the labial salivary glands of sex‐mismatched stem cell transplanted patients is a real phenomenon. Further studies are necessary to elucidate the impact of this phenomenon on the clinical status of stem cell transplanted patients.     

The scientific nursing production about the clinic: an integrativa review

The objective of this study was to learn about the production of nursing knowledge in Brazil associated with the clinic theme. This is a qualitative study performed by means of an integrative review. Data collection was performed on the SciELO database using the keywords nursing and clinic, present in the abstracts of articles. It was found that the clinic is seen as an instrument used to establish connections between research and nursing care, having a constant movement of constructing and deconstructing knowledge and practices. The study results may contribute with the production of research and knowledge in nursing, providing elements to subsidize improvements in nursing care, in which there is an interaction between practice and biological and non-biological knowledge.     

Progression of periodontitis in a sample of regular and irregular compliers under maintenance therapy: a 3-year follow-up study

Background: To our knowledge, prospective studies (matched for sex, smoking, and diabetes) that investigated the influence of compliance in the progression of periodontitis and tooth loss in periodontal maintenance therapy (PMT) programs were not previously reported. Methods: A total of 58 regular complier (RC) and 58 erratic complier (EC) individuals were recruited from a prospective cohort with 238 patients under PMT and matched by sex, diabetes, and smoking habits. A full‐mouth periodontal examination that included bleeding on probing (BOP), probing depths (PDs), clinical attachment levels, and number of teeth were determined at all PMT visits during a 3‐year interval. The influence of variables of interest was tested through multivariate logistic regression. Results: The progression of periodontitis and tooth loss was significantly lower among RC compared to EC patients. A higher progression of periodontitis was observed among EC patients who smoked. The final logistic model for the progression of periodontitis in the RC group included smoking (odds ratio [OR]: 4.2) and >30% of sites with BOP (OR: 2.8), and the final logistic model for the progression of periodontitis in the EC group included smoking (OR: 7.3), >30% of sites with BOP (OR: 3.2), PDs of 4 to 6 mm in 10% of sites (OR: 3.5), diabetes (OR: 1.9), and number of lost teeth (OR: 3.1). Conclusions: RC patients presented a lower progression of periodontitis and tooth loss compared to EC patients. This result highlighted the influence of the pattern of compliance in maintaining a good periodontal status. Moreover, important risk variables such as smoking and diabetes influenced the periodontal status and should be considered when determining the risk profile and interval time for PMT visits.     

Captopril increases the intensity of monocyte infection by Trypanosoma cruzi and induces human T helper type 17 cells

The anti-hypertensive drug captopril is used commonly to reduce blood pressure of patients with severe forms of Chagas disease, a cardiomyopathy caused by chronic infection with the intracellular protozoan Trypanosoma cruzi. Captopril acts by inhibiting angiotensin-converting enzyme (ACE), the vasopressor metallopeptidase that generates angiotensin II and promotes the degradation of bradykinin (BK). Recent studies in mice models of Chagas disease indicated that captopril can potentiate the T helper type 1 (Th1)-directing natural adjuvant property of BK. Equipped with kinin-releasing cysteine proteases, T. cruzi trypomastigotes were shown previously to invade non-professional phagocytic cells, such as human endothelial cells and murine cardiomyocytes, through the signalling of G protein-coupled bradykinin receptors (B(2) KR). Monocytes are also parasitized by T. cruzi and these cells are known to be important for the host immune response during infection. Here we showed that captopril increases the intensity of T. cruzi infection of human monocytes in vitro. The increased parasitism was accompanied by up-regulated expression of ACE in human monocytes. While T. cruzi infection increased the expression of interleukin (IL)-10 by monocytes significantly, compared to uninfected cells, T. cruzi infection in association with captopril down-modulated IL-10 expression by the monocytes. Surprisingly, studies with peripheral blood mononuclear cells revealed that addition of the ACE inhibitor in association with T. cruzi increased expression of IL-17 by CD4(+) T cells in a B(2) KR-dependent manner. Collectively, our results suggest that captopril might interfere with host-parasite equilibrium by enhancing infection of monocytes, decreasing the expression of the modulatory cytokine IL-10, while guiding development of the proinflammatory Th17 subset.     

Oral myiasis: a case report

Oral Myiasis is a rare pathology in humans and is associated with poor oral hygiene, alcoholism, senility, suppurating lesions, severe halitosis and others conditions. The treatment is a mechanical removal of the maggots one by one but a systemic treatment with Ivermectin, a semi-synthetic macrolide antibiotic, have been used for treatment for oral myiasis. We present a case report of a 32-year-old man indigent, alcohol-dependent with an extensive necrotic area and acute swelling in upper lip and fetid odor. The patient's management included topic use of gentian violet, oral therapy with ivermectin (6 mg orally), surgical exploration to remove the larvae and necrotic tissue. After the complete larvae removal the swelling and the wounds were healing normally, the patients was referred to plastic surgery to repair tissue damage. The prevention of human myiasis is by education, but unfortunately in the developing countries some people live in low social condition, predisposing the occurrence of the infestation.     

Characterization of ecto-phosphatase activities of Trypanosoma cruzi: a comparative study between Colombiana and Y strains

The etiological agent of Chagas disease, Trypanosoma cruzi, is consisted of two phylogenetic lineages. Using live epimastigotes, in this study we have characterized ecto-phosphatase activities of two strains of T. cruzi, one (Y strain) is a member of group T. cruzi I and the other (Colombiana) is a member of group T. cruzi II. About one-third of the total ecto-phosphatase activity from the Y strain was Mg(2+)-dependent, but no such activity was observed with Colombiana. The level of Mg(2+)-independent activity was dramatically different in the two strains, with Colombiana showing more than 15-fold higher activity. Experiments using classical inhibitors of acid phosphatases, as well as inhibitors of phosphotyrosine phosphatase, showed a decrease in these phosphatase activities, with different patterns of inhibition. The Mg(2+)-independent activities of the Colombiana and Y strains decreased inversely with pH, varying from 6.5 to 8.0. On the other hand, the Mg(2+)-dependent activity of the Y strain increased concomitantly with the increase in pH in the same range.     

Transcranial Doppler assessment of cerebral blood flow: effect of cardiac transplantation

The authors prospectively studied transcranial Doppler changes in patients with refractory congestive heart failure before and after cardiac transplantation. They evaluated 22 patients preoperatively and 14 patients after transplantation. Mean postoperative flow velocity increased by 53.3% (p < 0.0001). Preoperative waveform changes became normal after transplantation.