Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model

Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5−/− mice, while MIP-1 α−/− mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.     

Anti-CCP in systemic lupus erythematosus patients: a cross sectional study in Brazilian patients

Recently, it has been found that some lupus patients may have anti-cyclic citrullinated peptide antibodies (anti-CCP), although the clinical significance of such finding is not well established. Systemic lupus erythematosus (SLE) patients may have joint complaints that are very similar to those observed in rheumatoid arthritis (RA). In early stages of disease, this form of arthritis can be difficult to differentiate from RA, so it is not rare that some SLE patients are initially misdiagnosed to have this disease. This study aims to investigate the prevalence of anti-CCP in SLE patients from Southern Brazil and its association with clinical and serological profiles. One hundred nine SLE patients were studied for anti-CCP and compared with data of 156 RA patients and 100 healthy volunteers. Comparison of clinical and autoantibody profile of anti-CCP-positive and anti-CCP-negative SLE patients was done. All SLE patients positive of anti-CCP were submitted to hand and feet X-rays. Anti-CCP was positive in 15 of 109 SLE patients, and one of them had confirmed the diagnosis of rhupus. This prevalence was significantly higher than in healthy controls (p?=?0.0004) and lower than in RA patients (p?<?0.0001). No relationship could be found with clinical profile, including joint complaints. SLE patients with anti-CCP had higher prevalence of anti-Ro (p?=?0.02) and anti-La (p?=?0.004) autoantibodies, in comparison with those negative to anti-CCP. We found that 13.7 % of Brazilian patients with SLE have positive anti-CCP. Patients with anti-CCP showed higher prevalence of anti-Ro and anti-La autoantibodies than those negative for anti-CCP. Only a careful and prolonged follow-up will reveal the real clinical value of these markers in each patient individually.     

USEFULNESS OF kDNA PCR IN THE DIAGNOSIS OF VISCERAL LEISHMANIASIS REACTIVATION IN CO-INFECTED PATIENTS

SUMMARY

It is important to develop new methods for diagnosing relapses in the co-infection of visceral leishmaniasis (VL) and HIV to enable earlier detection using less invasive methods. We report a case of a co-infected patient who had relapses after VL treatment, where the qualitative kDNA PCR showed a good performance. The kDNA PCR seems to be a useful tool for diagnosing VL and may be a good marker for predicting VL relapses after treatment of co-infected patients with clinical symptoms of the disease.     

Dry eyes in patients with diabetes mellitus

Dry eyes may be caused by impairment in the tear production or excessive tear evaporation and are associated with photophobia, red eyes, vision impairment, local pain and pruritus. It has been described that patients with Diabetes Mellitus (DM) may have a higher prevalence of dry eyes than normal population.This is a case control study of 120 patients with Diabetes Mellitus (DM) and 120 paired controls aiming to compare their prevalence of dry eyes (by the Schirmer test) and its severity (measured by OSDI or Ocular Surface Disease Index) as well as their association with diseases’ clinical variables.We found that 38.3% of DM patients had dry eyes, a prevalence that was higher than controls (p = 0.02). At univariate analysis, they were found to be more common in older individuals (p = 0.001) with type 2 diabetes (p = 0.001) and in those using metformin (p = 0.001). A multivariate linear regression showed that metformin use was the only independent variable associated with dry eyes. When patients with dry eyes with and without DM were compared, no differences in the symptom’s intensity were found.     

Systemic lupus erythematosus and Raynaud's phenomenon

BACKGROUND

Patients with systemic lupus erythematosus seem to belong to different serological and clinical subgroups of the disease. Genetic background can cause the appearance of these subgroups.

OBJECTIVE

To determine whether Brazilian patients who have systemic lupus erythematosus and Raynaud''s phenomenon differ from those who do not.

METHODS

Retrospective analysis of 373 medical records of systemic lupus erythematosus patients studied for demographic, clinical and serological data. A comparative analysis was performed of individuals with and without RP.

RESULTS

There was a positive association between Raynaud''s phenomenon and age at diagnosis (p=0.02), presence of anti-Sm (p=0.01) antibodies and anti-RNP (p<0.0001). Furthermore, a negative association was found between Raynaud''s phenomenon and hemolysis (p=0.01), serositis (p=0.01), glomerulonephritis (p=0.0004) and IgM aCL (p=0.004) antibodies.

CONCLUSION

Raynaud''s phenomenon patients appear to belong to a systemic lupus erythematosus subset with a spectrum of clinical manifestations located in a more benign pole of the disease.     

The chemopreventive agent oltipraz possesses potent antiangiogenic activity in vitro, ex vivo, and in vivo and inhibits tumor xenograft growth.

Angiogenesis plays a pivotal role in tumor growth and represents a key target for chemopreventive intervention. On the basis of the structural features and lack of target organ specificity of the synthetic dithiolethione oltipraz, inhibition of angiogenesis was assessed as a potential mechanism for its broad-based chemopreventive activity. The effects of oltipraz on the development and maturation of a vascular network was determined in vitro using two-dimensional capillary tube formation assays with human umbilical vein endothelial cells plated on Matrigel and ex vivo using primary rat aortic ring explant cultures in three-dimensional collagen gels, respectively. The antiangiogenic and antitumor efficacy of oltipraz administration in vivo in nude mice was evaluated by determining its effects on neovascularization in s.c. Matrigel implants seeded with vascular endothelial growth factor and basic fibroblast growth factor-stimulated porcine aortic endothelial cells and on tumor growth and angiogenesis in SVR murine angiosarcoma xenografts implanted s.c. A dose-dependent reduction (0.4-100 microM) in microvessel formation was observed in both human and rodent bioassays after oltipraz exposure, with inhibition approaching 100% in the rat aortic ring assay at the highest concentration (P < 0.01). Similarly, oltipraz (40 microM) inhibited complete capillary tube formation by human umbilical vein endothelial cells by 62% (P < 0.05) relative to control cultures. p.o. administration of oltipraz (250 mg/kg/day for 6 days) to nude mice implanted with porcine aortic endothelial cell-Matrigel plugs resulted in a 42% reduction in neovascularization (P < 0.05) relative to vehicle-treated control mice. Administration of the same dose of oltipraz to athymic mice bearing established s.c. SVR angiosarcoma xenografts for 10 days resulted in a significant inhibition of tumor growth as early as day 4 of dosing (P < 0.005), with a maximum inhibition of tumor growth (81%, P < 0.001) relative vehicle-treated mice by day 10. The observed efficacy of oltipraz in this model is comparable with that of SU 5416 and TNP-470, known antiangiogenic agents currently under clinical development. Plasma levels of oltipraz at the termination of in vivo efficacy studies were 66.4 +/- 7 microM as determined by reversed phase high-performance liquid chromatography, a concentration range associated with significant antiangiogenic activity of oltipraz in vitro and ex vivo. These data suggest that the chemopreventive agent oltipraz may be effective in the treatment of advanced stage cancers and metastases, in part, because of its antiangiogenic activity in vivo.     

A Model of Consequences of Need-Driven, Dementia-Compromised Behavior

PURPOSE: To extend the original need-driven, dementia-compromised behavior (NDB) model by explaining the consequences of behavioral symptoms for the person with dementia. ORGANIZING CONSTRUCT AND METHODS: Literature is reviewed and the consequences of expressing needs through need-driven, dementia-compromised behaviors are posited. The consequences of need-driven, dementia-compromised behavior (C-NDB) theory is proposed as a framework to improve understanding of the person with dementia and the consequences of behavioral symptoms and unmet needs. FINDINGS: Instead of normative verbal communication, people with significant dementia commonly communicate need via non-normative behaviors, making it difficult for caregivers to know that the person has a need and the extent of such need. Not meeting needs of people with dementia affects the person with dementia, care factors, and contextual factors. Cascading effects occur in which not meeting the original need results in new needs and behavioral symptoms. CONCLUSIONS: This framework indicates the consequences of expressing need behaviorally rather than verbally and shows that caregiver actions might moderate the events that lead to many needs being unresolved. Suggestions are made regarding future research questions deduced from the model.     

Patients with protracted pain: A survey conducted at The London Hospital

Physical pain has always been part of human experience, and throughout history it is recorded that doctors and wise men and women have sought to ease pain. The attitudes of those suffering pain, however, have varied from stoical acceptance to sullen endurance. Today, most people consciously seek to avoid pain or to have their pain eased, although they do not always expect what in fact appears to be possible. This study of 13 patients with protracted pain was carried out at The London Hospital by a professional group to see how patients regarded their own pain and the efforts of doctors and nurses to relieve it. The attitudes of the doctors and nurses were also studied, and the results, despite the limitations of the survey, suggest that: [List: see text]     

Whole-body and exchangeable potassium measurements in normal elderly subjects

A comparison of total body potassium status of eighteen healthy subjects with normal renal function, in the age group 65–85 years, measured by whole body counting and by total exchangeable potassium on plasma and urine samples taken at 24 h, shows that there is no delay in exchange in radioactive potassium in the elderly, and that the exchangeable method gives a reliable value of total body potassium. The results suggest that the normal range for potassium per kilogramme body weight is lower for old persons than for younger age groups.     

Medical politics: Decline in the hegemony of the Australian Medical Association?

The last 15 years have seen the emergence of medical associations challenging the long-standing hegemony of the Australian Medical Association (A.M.A.) in medical politics. The article focuses on the two major groups. The General Practitioner's Society in Australia and the Doctors Reform Society. Each represents the right and the left of an ideological spectrum within medical politics. Each has institutionalised longer term division within the profession which were contained within the A.M.A. so long as the basic principles and structure of Australia's voluntaristic health insurance schemes remained intact. Taken together, they represent a wider critique of the entrenched status and political power of the A.M.A.The article examines briefly the ideology, strategy and impact of each group. It concludes that their major significance lies, not in their effectiveness as pressure groups, but as they have affected the public image of the A.M.A. and of the profession as a whole. The future of each depends on secular changes affecting medicine and the profession, on the oversupply of doctors on economic stringencies, and importantly, on the reaction of the A.M.A. to critiques of its representative function.