Redução do uso de medição em praticantes de mediação transcendental / Reduced use of measurement in transcendental mediation practitioners

Ao proporcionar o relaxamento do corpo e da mente, a prática regular de Meditação Transcendental (MT) pode reduzir o uso de fármacos. O objetivo do trabalho foi avaliar a redução do uso de medicação em praticantes regulares de Meditação Transcendental Sidhi, na cidade de Maringá, noroeste do Paraná. No final de 2021, um questionário estruturado foi respondido por 46 meditantes Shida de um projeto de extensão universitária desenvolvido na Universidade Estadual de Maringá, campus sede. Observou-se que ao aprender a meditar, 23,9% dos entrevistados deixaram de utilizar fármacos, principalmente psicotrópicos; 21,7% diminuíram a dosagem de analgésicos e/ou anti-inflamatórios e 6,5% incitaram o tratamento farmacológico de doenças crônicas de base. Do total dos respondentes, 60,9% relataram terem se automedicado durante as suas vidas, e 17,4% das possíveis combinações farmacológicas apresentavam a possibilidade de interação medicamentosa, principalmente entre os psicotrópicos e/ou analgésicos com eles mesmos ou com outros fármacos. Fatores psíquicos, fisiológicos, sociais e ambientais podem influenciar o desenvolvimento e tratamento das patologias. Conclui-se que ao reduzir o uso de fármacos e possíveis interações medicamentosas, a MT é uma possível alternativa para complementar o tratamento de doenças relacionadas

Morbidity in older HIV-infected patients: impact of long-term antiretroviral use.

The introduction of HAART has represented a major advance in the care of people with HIV. By markedly increasing life expectancy, HAART has significantly changed the pattern of HIV infection in developed countries, the "graying" of the HIV-infected population being a powerful testament to its success. However, this has presented physicians with new challenges relating to the care of older patients with HIV, many of whom exhibit a "frailty syndrome" associated with increased comorbidity and chronic low-grade inflammation in a process which has recently been termed "inflammaging". This paper reviews the pattern of morbidity seen in older HIV-infected patients and examines the effects, both beneficial and deleterious, of antiretroviral therapy. The efficacy and tolerability of antiretroviral therapy is of particular importance in older patients, given the likelihood that increased frailty may magnify the consequences both of suboptimal viral suppression and of toxicity, and in view of the complications that may arise from the presence of comorbidities and resultant polypharmacy. The challenge is to maximize antiviral efficacy and minimize toxicity, while taking into account the often complex web of comorbidities that may be present in these patients. This challenge is being met through the refinement of existing antiretroviral therapy regimens, the development of new agents, and a growing focus on a more holistic approach to care, which acknowledges the importance of the overall "health picture" and of good communication and cooperation between treating physicians and patients.

ß-Lapachone ameliorization of experimental autoimmune encephalomyelitis.

ß-Lapachone is a naturally occurring quinine, originally isolated from the bark of the lapacho tree (Tabebuia avellanedae) which is currently being evaluated in clinical trials for the treatment of cancer. In addition, recent investigations suggest its potential application for treatment of inflammatory diseases. Multiple sclerosis (MS) is an autoimmune disorder characterized by CNS inflammation and demyelination. Reactive T cells including IL-17 and IFN-γ-secreting T cells are believed to initiate MS and the associated animal model system experimental autoimmune encephalomyelitis (EAE). IL-12 family cytokines secreted by peripheral dendritic cells (DCs) and CNS microglia are capable of modulating T-cell phenotypes. The present studies demonstrated that ß-lapachone selectively inhibited the expression of IL-12 family cytokines including IL-12 and IL-23 by DCs and microglia, and reduced IL-17 production by CD4(+) T-cells indirectly through suppressing IL-23 expression by microglia. Importantly, our studies also demonstrated that ß-lapachone ameliorated the development on EAE. ß-Lapachone suppression of EAE was associated with decreased expression of mRNAs encoding IL-12 family cytokines, IL-23R and IL-17RA, and molecules important in Toll-like receptor signaling. Collectively, these studies suggest mechanisms by which ß-lapachone suppresses EAE and suggest that ß-lapachone may be effective in the treatment of inflammatory diseases such as MS.

Combining vitamin A and vaccines: convenience or conflict?

The present thesis is based on 11 papers from 1995-2010. The studies have mainly taken place at the Bandim Health Project in Guinea-Bissau, West Africa, but a reanalysis of a randomised trial from Ghana is also included. My research has explored the consequences of combining high-dose vitamin A supplementation and childhood vaccines. Vitamin A deficiency is associated with increased mortality. To protect against the consequences of vitamin A deficiency the World Health Organization recommends that high-dose vitamin A supplements be given together with routine vaccines to children between 6 months and 5 years of age in more than 100 low-income countries. The recommendation is based on logistical considerations. The consequences of combining vitamin A and vaccines were not investigated in randomised trials prior to the implementation of this policy - it was assumed that the interventions were independent. My first project aimed to study the effect on the immune response to measles of providing vitamin A together with measles vaccine. We found that the two interventions were not independent. Vitamin A enhanced the antibody response to measles vaccine given at 9 months of age significantly, especially in boys. The effects were sustained over time; the children who had received vitamin A with their measles vaccine were more protected against measles at 6-8 years of age. Though vitamin A supplementation had a beneficial effect on the immune response to measles vaccine, it intrigued me that the effect of vitamin A supplementation on overall mortality was not always beneficial. While vitamin A was beneficial when given after 6 months of age, and two studies had shown a beneficial effect when given at birth, all studies testing the effect between 1-5 months of age had found no effect. These time windows are dominated by three different childhood vaccines: BCG vaccine given at birth, diphtheria-tetanus-pertussis (DTP) vaccine given between 1-5 months of age, and measles vaccine given at 9 months of age. These vaccines have been shown to have strong effects on mortality from infectious diseases in general, so-called non-specific effects. The live BCG and measles vaccine protects against more mortality than can be ascribed to the prevention of tuberculosis and measles, respectively. The inactivated DTP vaccine worryingly has been associated with increased mortality from other infectious diseases. Both positive and negative effects are strongest for girls. I proposed the hypothesis that vitamin A amplifies not only the specific vaccine effects, as we saw for measles vaccine, but also the non-specific effects of vaccines on mortality from other infectious diseases. According to my hypothesis, vitamin A would enhance the non-specific beneficial effects on mortality of BCG and measles vaccine, but also the negative effects of DTP vaccine. Hence, the hypothesis offered an explanation for the mortality-age pattern after vitamin A supplementation. Since it was formulated, I have aimed to test this hypothesis. Since it is associated with ethical problems to randomise children above 6 months of age to vitamin A supplementation, and to randomise children in general to recommended vaccines, we have had to be pragmatic when designing the trials. Hence, our studies have taken many different forms. We conducted an observational study during a vitamin A campaign in which missing vaccines were also provided, and a randomised trial testing the effect of two different doses of vitamin A during another campaign; we tested the effect of providing vitamin A with BCG at birth in two randomised trials, and we reanalysed data from one of the original randomised trials of vitamin A supplementation from the perspective of vaccination status. In all studies the main outcome was mortality. The results document that vitamin A supplements do more than protect against vitamin A deficiency. They support the hypothesis that vitamin A supplements interact with vaccines with important consequences for mortality. First, a smaller dose of vitamin A was more beneficial than a larger dose for girls. Second, the effect of vitamin A given with DTP vaccine was significantly different from the effect of vitamin A given with measles vaccine, and children, who received vitamin A with DTP vaccine, had higher mortality than children, who had received vitamin A alone, or who did not receive anything. Third, vitamin A given with BCG at birth interacted negatively with subsequent DTP vaccines in girls. Fourth, the effect of vitamin A to older children in Ghana depended on vaccination status, being beneficial in boys, but harmful in girls who received DTP vaccine during follow-up. The results also show that boys and girls respond differently to vitamin A and vaccines. It is a common assumption within public health in low-income countries that interventions can be combined without producing unexpected consequences. The work presented in this thesis confronts this assumption; the results show that vitamin A and vaccines should be seen not only as specific interventions with specific and independent effects, but as immuno-modulators, which can interact with important consequences for overall mortality. Combining interventions can be convenient and lead to synergistic health benefits, but we documented several examples, where it also leads to unexpectedly increased mortality. Thus, to optimise the child health intervention policy in low-income countries a shift in paradigm is needed. Health interventions should no longer be seen as merely specific and independent, and the policy should probably not be the same for boys and girls. Though more complex, it is necessary to evaluate all health interventions in terms of their effect on overall mortality - and their potential interactions with other health interventions and potential sex-differential effects should always be investigated. Only in this way can we assure that the children in the poorest countries get the best possible treatment and avoid using large amounts of money and resources on interventions which may, in worst case, kill them.

Influenza vaccination and vitamin K antagonist treatment: a placebo-controlled, randomized, double-blind crossover study.

BACKGROUND: Among millions of persons vaccinated against influenza virus each year, many are older patients treated with several drugs, including vitamin K antagonists (VKAs), among which warfarin is the most commonly used. Due to high interpatient and intrapatient variability, the therapeutic dose of VKA has to be individualized by monitoring of international normalized ratio (INR) values. The objectives of this study were to evaluate variation in the INR and warfarin weekly dose variation after influenza vaccination administration and to follow up patients for related hemorrhagic and thrombotic events to evaluate the safety of the influenza vaccine and to assess the immunogenicity of the influenza vaccination in patients receiving VKAs. METHODS: One hundred four patients on a stable VKA regimen and with an indication for influenza vaccination were randomized to receive influenza vaccination and subsequent placebo administration, or vice versa. All patients were tested for coagulation variables, clinical events, and antibody response against vaccine components. RESULTS: Similar mean prothrombin times, expressed as the INR and VKA weekly dose, were found in patients after receiving vaccine or placebo. The absence of any vaccination effect on VKA treatment was confirmed using a linear mixed-effects model. The percentages of time that patients were in therapeutic range were 70.7% after receiving vaccine and 72.4% after receiving placebo (P = .57). There were no fatal or major bleeding events and 11 minor mucocutaneous hemorrhagic events. After vaccination, the percentage of seroprotected patients ranged from 92.0% to 100.0% depending on the vaccine antigen examined. CONCLUSIONS: Influenza vaccination had no significant effect on INR values or warfarin sodium weekly doses. Close monitoring of INR values is not required after influenza vaccination in patients on stable long-term VKA regimens. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00222638.

Bullous pemphigoid in an infant using complementary medicine.

Bullous pemphigoid (BP) is an acquired immunobullous disorder rarely seen in childhood. We report the case of an infant with BP successfully treated with oral corticosteroids. The onset of BP was associated with use of complementary medications and we speculate that these may have been triggering factors.

Brain-derived neurotrophic factor selectively enhances allergen-specific IgE production.

We studied the effect of brain-derived neurotrophic factor (BDNF) on in vitro Japanese cedar pollen (JCP)-specific IgE production by mononuclear cells from atopic keratoconjunctivitis patients with JCP allergy. BDNF enhanced JCP-specific IgE production in a dose-dependent fashion in cultures of mononuclear cells stimulated with JCP, and maximal enhancement was achieved at 10 ng/ml. In contrast, BDNF had no effect on JCP-specific IgA or IgG4 production. On the other hand, other neurotrophins, NGF, NT-3, or NGF failed to enhance JCP-specific IgE production. Moreover, anti-BDNF mAb specifically blocked BDNF-induced enhancement of JCP-specific IgE production. Study for cytokine production revealed that BDNF decreased production of Th1 cytokines, IFN-gamma and IL-12, while it had no effect on production of TH2 cytokines, IL-4, IL-10 and IL-13, in cultures of mononuclear cells stimulated with JCP. These results indicate that BDNF relatively skews cytokine pattern toward Th2 type. Collectively, BDNF may increase allergen-specific IgE production, which may in turn aggravate allergic symptoms.