RESUMO
In the wide field of nutraceuticals, the effects of mushrooms on immunity, cancer and including autoimmunity have been proposed for centuries but in recent years a growing interest has led scientists to elucidate which specific compounds have bioactive properties and through which mechanisms. Glucans and specific proteins are responsible for most of the biological effects of mushrooms, particularly in terms of immunomodulatory and anti-tumor results. Proteins with bioactive effects include lectins, fungal immunomodulatory proteins (FIPs), ribosome inactivating proteins (RIPs), ribonucleases, laccases, among others. At the present status of knowledge, numerous studies have been performed on cell lines and murine models while only a few clinical trials have been conducted. As in most cases of dietary components, the multitude of variables implicated in the final effect and an inadequate standardization are expected to affect the observed differences, thus making the available evidence insufficient to justify the treatment of human diseases with mushrooms extracts. We will herein provide a comprehensive review and critically discussion the biochemical changes induced by different mushroom compounds as observed in in vitro studies, particularly on macrophages, dendritic cells, T cells, and NK cells, compared to in vivo and human studies. Additional effects are represented by lipids which constitute a minor part of mushrooms but may have a role in reducing serum cholesterol levels or phenols acting as antioxidant and reducing agents. Human studies provide a minority of available data, as well illustrated by a placebo-controlled study of athletes treated with ß-glucan from Pleurotus ostreatus. Variables influencing study outcomes include different mushrooms strains, growing conditions, developmental stage, part of mushroom used, extraction method, and storage conditions. We foresee that future rigorous research will be needed to determine the potential of mushroom compounds for human health to reproduce the effects of some compounds such as lentinan which a metaanalysis demonstrated to increase the efficacy of chemotherapy in the treatment of lung cancer and in the improvement of the patients quality of life.
Assuntos
Agaricales , Produtos Biológicos , Imunidade , Agaricales/química , Agaricales/classificação , Agaricales/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Autoimunidade/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Proteínas Alimentares/metabolismo , Suplementos Nutricionais , Avaliação do Impacto na Saúde , Humanos , Imunidade/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Imunomodulação , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , beta-Glucanas/metabolismoRESUMO
The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory support and broad-spectrum antiviral drugs, empirically utilized, as a targeted therapy and vaccines have not been developed. Based upon our limited knowledge on the pathogenesis of CoViD-19, a potential role of some anti-rheumatic drugs may be hypothesized, acting as direct antivirals or targeting host immune response. Antimalarial drugs, commonly used in rheumatology, may alter the lysosomal proteases that mediates the viral entry into the cell and have demonstrated efficacy in improving the infection. Anti-IL-1 and anti-IL-6 may interfere with the cytokine storm in severe cases and use of tocilizumab has shown good outcomes in a small cohort. Baricitinib has both antiviral and anti-inflammatory properties. Checkpoints inhibitors such as anti-CD200 and anti-PD1 could have a role in the treatment of CoViD-19. Rheumatic disease patients taking immunosuppressive drugs should be recommended to maintain the chronic therapy, prevent infection by avoiding social contacts and pausing immunosuppressants in case of infection. National and international registries are being created to collect data on rheumatic patients with CoViD-19.
Assuntos
Terapia Biológica , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Doenças Reumáticas/complicações , Doenças Reumáticas/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antimaláricos/uso terapêutico , Antirreumáticos/uso terapêutico , Azetidinas/uso terapêutico , Betacoronavirus/efeitos dos fármacos , COVID-19 , Infecções por Coronavirus/prevenção & controle , Citocinas/imunologia , Humanos , Imunossupressores/uso terapêutico , Interleucina-1/antagonistas & inibidores , Interleucina-6/antagonistas & inibidores , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Purinas , Pirazóis , SARS-CoV-2 , Sulfonamidas/uso terapêutico , Internalização do Vírus/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
Systemic lupus is the prototypic human autoimmune disease. It is a kaleidoscope of autoreactivities, with clear indications of both a genetic and environmental basis. Indeed, it is a disease that can manifest in virtually every tissue and organ and can also be found spontaneously in a number of animal species, including dogs, cats and horses. Moreover, there are multiple murine models of lupus, the first of which, New Zealand Black (NZB) mice, were discovered in 1959. Despite an enormous effort from scientists in multiple disciplines, the etiology of lupus remains elusive and the introduction of new therapies has been disappointing. Fortunately, significant advances have occurred to help patients through the general principles of internal medicine, including antibiotics, dialysis, and of course use of steroids and immunosuppressive agents. However, the magic bullet has yet to be discovered. One of the major causes of morbidity in lupus remains lupus nephritis and there has been significant effort and encouragement in understanding the pathogenesis, renal histologic classification, and use of therapeutic protocols to induce and sustain remission of lupus nephritis. Indeed, the first use of evidence-based clinical trials in lupus was initiated by Dr. Alfred D. Steinberg at NIH in pioneering studies involving either oral or intravenous pulses of cyclophosphamide, azathioprine or corticosteroids alone and/or some combination. Cyclophosphamide intravenously proved to be superior and the use of cyclophosphamide in combination with methylprednisolone remained the standard protocol for the treatment of lupus nephritis for decades. Although alternative therapies have been introduced, including mycophenolate mofetil, the use of therapies first pioneered at NIH may still be considered standard of care in the appropriate indications. More targeted therapies are much desired. In this review we provide a comprehensive overview of lupus nephritis and the evolution of clinical treatments.
Assuntos
Nefrite Lúpica/terapia , Animais , Biópsia , Técnicas Histológicas/história , Técnicas Histológicas/métodos , História do Século XX , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/históriaRESUMO
The significant decrease in mortality rates worldwide, the increased proportion of patients achieving a durable remission, and the recent approval of a new drug after several decades are encouraging advances in the tangled history of systemic lupus erythematosus (SLE). However, when data are observed more closely, the research findings on disease pathogenesis and targeted treatments have been quite misleading, as illustrated by the central role of B cells but the missed endpoints in rituximab clinical trials which are burdened by the wide variability of SLE manifestations or the ethnic determinants of disease severity. Other biologic therapies, on the other hand, inhibit B cell stimulating factor BAFF but are proving to be short of revolutionary, not yet overcoming high-dose long-term glucocorticoids still largely used without an agreement on what clinical targets are to be sought in the proposed treat-to-target approach. The large amount of data from genome-wide association studies, the detailed reports on T cell epigenetics, or the numerous established and novel animal models have also proven insufficient to change our understanding of the human disease. Nonetheless, we have now tools for a better and earlier SLE diagnosis, thanks to reliable biomarkers, improved care of kidney involvement, better pregnancy outcomes, while the neuropsychiatric manifestations remain challenging. These advances are well mirrored by some proposed synthetic drugs, such as tacrolimus, or biologics, including IFNα inhibitors and other drugs capable to modulate the immune system. Ultimately, we may foresee that genetic and epigenetic data, along with the variable clinical manifestations represent the bases for SLE to become an ideal candidate for the introduction of truly personalized medicine.
Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/terapia , Medicina de Precisão , Animais , Autoimunidade , Linfócitos B/imunologia , Linfócitos B/metabolismo , Terapia Biológica/métodos , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Epigênese Genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Medicina de Precisão/métodos , Gravidez , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
In the United States, as in most of the world, there are large numbers of nutraceuticals that are sold and which people take to boost their immune response. There are, in addition, almost an equal number of products sold to reduce allergies. However, very few consumers, and indeed physicians, are aware of what a structure/function claim is. Structure/function claims are labeling claims that can be used to describe the potential effects of a dietary ingredient or similar substance on the structure or function of the human body. This category of claims was created by legislation contained in the Dietary Supplement Health and Education Act. The intent was to supply consumers with reasonably substantiated information that would allow them to make educated choices about their diet and health. They were not intended to have the same weight and substantiation as the claims made for conventional prescription pharmaceuticals. Rather, they were proposed to fill the gap between consumer desire for over-the-counter supplements and foods, and rigorous and generally more potent and potentially "toxic" prescription medications. The legally mandated disclaimer, stating that the U.S. Food and Drug Administration has not evaluated the structure/function claim, often leads to misinterpretation. While there should be a biologic premise underlying the claim, there is not an absolute requirement for a conventional rigorous placebo-controlled dose response trial. While this may not be the clinical standard that a typical scientific oriented society might desire, it reflects the attempts of the FDA to find common grounds and to allow consumers to use products that are generally considered as safe based on historical use and biologic comparisons. The logic of, indeed need for, structure/function claims is straightforward; however, of equal importance is that nutraceuticals should be properly labeled, have accuracy in their ingredients, be free of contamination, be safe, and have a reasonable body of data that supports their efficacy.
Assuntos
Suplementos Nutricionais , Legislação de Medicamentos , United States Food and Drug Administration , Informação de Saúde ao Consumidor , Suplementos Nutricionais/análise , Suplementos Nutricionais/história , Suplementos Nutricionais/normas , Rotulagem de Medicamentos , Alimentos , História do Século XX , Humanos , Aplicação da Lei , Estados UnidosRESUMO
PURPOSE OF REVIEW: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by immunomediated destruction of small and medium-sized intrahepatic bile ducts. In 1987, a cDNA for a 74âkDa mitochondrial autoantigen was cloned and identified as the E2 component of the mitochondrial pyruvate dehydrogenase complex, which improved the diagnosis and changed research directions in this field. In 1958, the first Chinese case of PBC was reported. But until 1990, a comprehensive description of the characteristics of Chinese PBC patients was published. In China we now know that PBC is not rare and usually does not progress to cirrhosis. RECENT FINDINGS: The number of Chinese patients with PBC has increased each and every year. This increase may be associated with the changes of liver disease spectrum, the application of convenient autoantibody detection kits, and the comprehensive understanding of the disease. It may also reflect, however, a westernization change in environmental features with China. There is now significant and important basic and clinical research on PBC in China, with major contributions in diagnostic criteria, treatment, and on basic biology. This has led to exciting proposals based on Chinese PBC cohorts. SUMMARY: Chinese hepatologists and scientists are now focusing their efforts on PBC. These efforts have led to new diagnostic biomarkers, novel therapeutic methods (stem cells and Chinese traditional medicine), and unique immunological mechanisms, including roles for T-follicular helper cells and monocyte subpopulations, both of which are involved in the breach of immune tolerance for PBC.
Assuntos
Cirrose Hepática Biliar , China/epidemiologia , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/epidemiologia , Cirrose Hepática Biliar/etiologia , Cirrose Hepática Biliar/terapiaRESUMO
There remain significant obstacles in developing biologics to treat primary biliary cholangitis (PBC). Although a number of agents have been studied both in murine models and human patients, the results have been relatively disappointing. IL-22 is a member of the IL-10 family and has multiple theoretical reasons for predicting successful usage in PBC. We have taken advantage of an IL-22 expressing adeno-associated virus (AAV-IL-22) to address the potential role of IL-22 in not only protecting mice from autoimmune cholangitis, but also in treating animals with established portal inflammation. Using our established mouse model of 2-OA-OVA immunization, including α-galactosylceramide (α-GalCer) stimulation, we treated mice both before and after the onset of clinical disease with AAV-IL-22. Firstly, AAV-IL-22 treatment given prior to 2-OA-OVA and α-GalCer exposure, i.e. before the onset of disease, significantly reduces the portal inflammatory response, production of Th1 cytokines and appearance of liver fibrosis. It also reduced the liver lymphotropic chemokines CCL5, CCL19, CXCL9, and CXCL10. Secondly, and more importantly, therapeutic use of AAV-IL-22, administered after the onset of disease, achieved a greater hurdle and significantly improved portal pathology. Further the improvements in inflammation were negatively correlated with levels of CCL5 and CXCL10 and positively correlated with levels of IL-22. In conclusion, we submit that the clinical use of IL-22 has a potential role in modulating the inflammatory portal process in patients with PBC.
Assuntos
Doenças Autoimunes/terapia , Terapia Biológica/métodos , Colangite/terapia , Interleucinas/imunologia , Fígado/imunologia , Sistema Porta/imunologia , Animais , Quimiocina CCL19/imunologia , Quimiocina CCL19/metabolismo , Quimiocina CCL5/imunologia , Quimiocina CCL5/metabolismo , Quimiocina CXCL10/imunologia , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/imunologia , Quimiocina CXCL9/metabolismo , Dependovirus , Modelos Animais de Doenças , Feminino , Galactosilceramidas/imunologia , Galactosilceramidas/farmacologia , Vetores Genéticos , Interleucinas/genética , Fígado/irrigação sanguínea , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/terapia , Camundongos , Camundongos Endogâmicos C57BL , Sistema Porta/patologia , Interleucina 22RESUMO
The metabolic syndrome is a major worldwide health care issue and a dominant risk factor for cardiovascular disease. The liver manifestations of this syndrome include nonalcoholic fatty liver disease (NAFLD) and its progressive variant nonalcoholic steatohepatitis (NASH). Although significant research has been performed, the basic pathogenesis of NAFLD/NASH remains controversial and effective treatments are still unavailable. We have previously reported on a murine model of NASH induced by the neonatal injection of monosodium glutamate (MSG), which includes the clinical manifestations of central obesity, diabetes, hyperlipidemia, and ultimately liver inflammation, fibrosis, and cancer. Although MSG is considered a safe food additive, its administration to pregnant rats increases the voracity and growth hormone levels in the offspring. To further understand the biology of this model, we have investigated the influence of the calorie intake on these clinical manifestations by feeding animals a restrictive diet. MSG-treated animals fed a restrictive diet continue to manifest obesity and early stage NASH but have improvements in serum lipid profiles. At 12 months of age, mice had manifestations of obesity, whether animals were fed a restricted or control diet, but animals fed a restrictive diet had a reduction in the progression of NASH. In conclusion, MSG appears to be a critical factor in the initiation of obesity, whereas calorie intake may modulate the progression of disease.
Assuntos
Obesidade/dietoterapia , Glutamato de Sódio/efeitos adversos , Animais , Dieta Redutora , Progressão da Doença , Fígado Gorduroso/dietoterapia , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Humanos , Masculino , Camundongos Endogâmicos ICR , Hepatopatia Gordurosa não Alcoólica , Obesidade/complicações , Obesidade/metabolismo , Glutamato de Sódio/metabolismoRESUMO
Historically, vitamin D has been associated with the regulation of bone metabolism. However, increasing evidence demonstrates a strong association between vitamin D signaling and many biological processes that regulate immune responses. The discovery of the vitamin D receptor in multiple immune cell lineages, such as monocytes, dendritic cells, and activated T cells credits vitamin D with a novel role in modulating immunological functions and its subsequent role in the development or prevention of autoimmune diseases. In this review we, discuss five major areas in vitamin D biology of high immunological significance: (1) the metabolism of vitamin D; (2) the significance of vitamin D receptor polymorphisms in autoimmune diseases, such as multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; (3) vitamin D receptor transcriptional regulation of immune cell lineages, including Th1, Th17, Th2, regulatory T, and natural killer T cells; (4) the prevalence of vitamin D insufficiency/deficiency in patients with multiple sclerosis, type 1 diabetes mellitus, and systemic lupus erythematosus; and finally, (5) the therapeutic effects of vitamin D supplementation on disease severity and progression.
Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Receptores de Calcitriol/genética , Subpopulações de Linfócitos T/imunologia , Células Th1/imunologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/metabolismo , Animais , Doenças Autoimunes/terapia , Diferenciação Celular , Linhagem da Célula , Dietoterapia , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Polimorfismo Genético , Deficiência de Vitamina D/terapiaRESUMO
Integrative medicine is a relatively new discipline which attempts to combine allopathic medicine with alternative or complementary medicine, to reap the benefits of both forms of medicine in optimizing the care of patients. Integrative medicine concentrates on treating the patient as a whole, both in body and mind. While the scientific method and "evidence-based" clinical research drives the management and treatment of diseases in conventional Western medicine, alternative or complementary medicine is based on unproven yet potentially beneficial techniques that have been developed throughout history, dating back to the ancient cultures in the Middle East, Africa, and China. In spite of the lack of evidence of most alternative medicine techniques, these methodologies have been practiced for centuries with great acceptance in many countries. It is in the Western world, where "modern" medicine is dictated by the scientific method, that the most controversy in the use of these alternative modes of therapy exists. Since the science behind alternative medicine is incomplete or non-existent, it is difficult for those trained in Western medicine to accept or adopt this approach. But perhaps it is the failure of Western medicine to adequately guarantee our well being and good health that have led to the ongoing debate between the medical profession and the general public as to the benefits of these alternative treatments. In one sense, integrative medicine may be a futile attempt to coin a new term in the hope of legitimizing alternative medicine. On the other hand, there is a wealth of historical experience in the use of the techniques. Studies to evaluate the scientific basis behind ancient medical techniques are ongoing, and it is to be expected that the results will neither be uniformly positive nor negative. Of particular interest is the effect of traditional medicine, herbal formulations, and manipulative techniques on the immune system, and its application in the treatment of autoimmune and allergic diseases. Studies are being designed or conducted to investigate immune effects of herbal formulations or their components. Herbal plants or medicines may lead to skewing of the Th1/Th2 balance in either direction, thus may offer potential application in the treatment of allergic or autoimmune diseases.
Assuntos
Doenças Autoimunes/terapia , Hipersensibilidade/terapia , Medicina Integrativa , China , Terapias Complementares , Humanos , Terapia Nutricional , Estados UnidosRESUMO
Anemia and immunological dysfunction (i.e. immunosenescence) are commonly found in older subjects and nutritional approaches are sought to counteract these phenomena. Spirulina is a filamentous and multicellular bule-green alga capable of reducing inflammation and also manifesting antioxidant effects. We hypothesized that Spirulina may ameliorate anemia and immunosenescence in senior citizens with a history of anemia. We enrolled 40 volunteers of both sexes with an age of 50 years or older who had no history of major chronic diseases. Participants took a Spirulina supplementation for 12 weeks and were administered comprehensive dietary questionnaires to determine their nutritional regimen during the study. Complete cell count (CCC) and indoleamine 2,3-dioxygenase (IDO) enzyme activity, as a sign of immune function, were determined at baseline and weeks 6 and 12 of supplementation. Thirty study participants completed the entire study and the data obtained were analyzed. Over the 12-week study period, there was a steady increase in average values of mean corpuscular hemoglobin in subjects of both sexes. In addition, mean corpuscular volume and mean corpuscular hemoglobin concentration also increased in male participants. Older women appeared to benefit more rapidly from Spirulina supplements. Similarly, the majority of subjects manifested increased IDO activity and white blood cell count at 6 and 12 weeks of Spirulina supplementation. Spirulina may ameliorate anemia and immunosenescence in older subjects. We encourage large human studies to determine whether this safe supplement could prove beneficial in randomized clinical trials.
Assuntos
Anemia/dietoterapia , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Suplementos Nutricionais , Spirulina , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/diagnóstico , Anemia/imunologia , Hemoglobinas/genética , Hemoglobinas/metabolismo , Humanos , Imunidade/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Pessoa de Meia-Idade , Spirulina/imunologiaRESUMO
Osteonecrosis is a serious condition involving bone destruction that frequently requires surgical treatment to rebuild the joint. While there is an abundance of literature documenting corticosteroid related osteonecrosis, there is no consensus as to the relative risk of osteonecrosis after administration of steroids via parenteral, oral, topical, inhaled and other routes. This risk is an important prognostic indicator because identification and conservative intervention can potentially reduce morbidity associated with aggressive surgical treatment of osteonecrosis. This paper provides insight into establishing guidelines related to the risk of developing osteonecrosis as a result of corticosteroid use. Case studies, retrospective studies and prospective studies in humans on different corticosteroids and varied dosages were assessed. Most cases of osteonecrosis are secondary to systemically administered corticosteroids and/or high dose daily therapy, particularly in patients with underlying comorbidities including connective tissue diseases, hyperlipidemia, or previous trauma. Previous case reports of osteonecrosis related to inhaled or topical use of steroids are complicated by the fact that in the great majority of cases, the patients are also treated with systemic steroids prior to the development of osteonecrosis. Based on the literature, a set of recommendations regarding the risk of osteonecrosis in patients on steroids was formulated.
Assuntos
Corticosteroides/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Osteonecrose/induzido quimicamente , Esteroides/efeitos adversos , Administração Oral , Corticosteroides/administração & dosagem , Animais , Osso e Ossos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Infusões Parenterais , Esteroides/administração & dosagemRESUMO
Approximately 6 in 10 Americans report regularly using some type of dietary supplement, and approximately 1 in 6 Americans reports using herbal remedies on a regular basis. The diversity of manufacturers, manufacturing processes, and quality control issues are enormous. As with all plant products, herbal products are complex mixtures of a variety of chemical constituents with considerable variation in the growth, harvesting, and storage conditions, including different extraction procedures. Furthermore, not only is there variation in batches, but also the potential for contamination. In addition, herbal products have the potential to interact with pharmaceuticals. These problems have led to consumer and physician confusion about the use of herbal products and have not been satisfactorily resolved, because the Food and Drug Administration has only very recently started to fulfill its mission of consumer protection in the realm of dietary supplements. More importantly, we provide a working plan for addressing this important issue.
Assuntos
Suplementos Nutricionais/normas , Suplementos Nutricionais/efeitos adversos , Interações Ervas-Drogas , Medicina Herbária/normas , Humanos , Estados Unidos , United States Food and Drug Administration/normasRESUMO
The Kampo formula keishibukuryogan (KBG, Guizhifulingwan) is frequently used in traditional Japanese and Chinese medicine to treat several symptoms and manifests anti-inflammatory and scavenging effects. Nonalcoholic fatty liver disease (NAFLD) is a common manifestation of the metabolic syndrome and has the potential to evolve to liver cirrhosis through chronic inflammation and steatohepatisis (NASH). We have recently reported the KBG significant effectiveness on liver injury in a NASH animal model that prompted us to prescribe to KBG (TJ-25). We performed a retrospective study and reviewed the charts of outpatients who were prescribed KBG for 8-12 weeks due to non-liver-related symptoms (n= 11) over the past year to evaluate the clinical outcome. In six of these cases, biochemical and ultrasound signs of NAFLD were observed. KBG led to a significant reduction in liver injury tests and blood cholesterol but had no effects on body weight in all NAFLD cases. Further, liver tests and lipid profiles returned to baseline values when KBG treatment was stopped. On the basis of data on a small number of subjects, we suggest that the use of KBG is a safe complementary treatment in patients with NAFLD. While it is unlikely that Kampo formulas may substitute the current nutritional approaches to the metabolic syndrome, future studies should address the possibility of an additive effect, possibly through anti-inflammatory mechanisms.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fígado Gorduroso/tratamento farmacológico , Inflamação/tratamento farmacológico , Adulto , Fígado Gorduroso/imunologia , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Flavanols and procyanidins isolated from cocoa have been reported to possess multiple activities potentially relevant to oxidant defenses, vascular function, and immune function. In a combination of in vivo and in vitro studies, we and others have observed that cocoa can be an anti-inflammatory modulator and that compounds in cocoa are capable of modulating eicosanoid production, platelet aggregation, and the pool size of nitric oxide. The present study extends these findings by examining the in vitro effects of cocoa procyanidins on polymorphonuclear cells (PMNs). PMNs, part of the innate arm of the immune system, represent 50-60% of the total peripheral white blood cells and are the first cells to be recruited to the sites of inflammation or injury secondary to bacterial infections. Herein, we demonstrate that certain flavanols and procyanidins isolated from cocoa can moderate a subset of signaling pathways derived from lipopolysaccharide (LPS) stimulation of PMNs, mainly, PMN oxidative bursts and activation markers, and they can influence select apoptosis mechanisms. We hypothesize that flavanols and procyanidins can decrease the impact of LPS on the N-formyl-Met-Leu-Phe-primed PMN ability to generate reactive oxygen species by partially interfering in activation of the mitogen-activated protein kinase pathway.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cacau , Flavonóis/farmacologia , Neutrófilos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Adulto , Moléculas de Adesão Celular/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Masculino , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Explosão Respiratória/efeitos dos fármacos , Adulto JovemRESUMO
Systemic sclerosis (SSc) is a chronic autoimmune disease with clinical manifestations resulting from immune activation, fibrosis development, and damage of small blood vessels. Our aim was to critically illustrate the available data on the new treatments proposed for SSc to provide a clinically oriented overview of the current evidence. PubMed was used for literature search using "scleroderma" and "therapy" to identify all articles published on indexed journals between 1972 and 2008. The search was limited to publications in English and produced a total of 3,441 references, which included 735 review articles. These citations were then screened for articles dealing with the most recent therapy options for SSc, and 214 articles were selected for evaluation and discussion. Methotrexate, cyclophosphamide, calcium channel blockers, angiotensin converting enzyme inhibitors, prostacyclin analogues, D-penicillamine, and extracorporeal photopheresis are the most widely studied treatments for SSc and were considered as practiced treatments. Other therapeutic approaches have been developed more recently and include endothelin receptor antagonists and phosphodiesterase-5 inhibitors for pulmonary arterial hypertension and peripheral vascular disease. High-dose immunosuppression and stem cell transplantation constitute a promising treatment and data from randomized controlled trials are awaited. Intravenous gamma globulins, mycophenolate mophetil, collagen tolerance induction, rituximab, fluoxetine, pirfenidone, relaxin, halofuginone, anti-TGF-beta antibodies, and tyrosine kinase inhibitors awaits more solid data. The clinical management of patients with SSc remains a challenge and currently involves practiced and newly proposed therapeutic approaches. The disease pleiomorphism poses numerous difficulties to determine ideal outcomes to be used in clinical trials.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Escleroderma Sistêmico/terapia , Transdução de Sinais/efeitos dos fármacos , Animais , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diferenciação Celular/imunologia , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Fibroblastos/imunologia , Fibrose/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/fisiopatologia , Transdução de Sinais/imunologia , Vasodilatadores/uso terapêutico , Remodelação Ventricular/efeitos dos fármacosRESUMO
Data on the efficacy of herbal compounds are often burdened by the lack of appropriate controls or a limited statistical power. Treatments to prevent the progression of non alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain unsatisfactory. A total of 56 rabbits were arrayed into 7 groups fed with standard rabbit chow (SRC), SRC with 1% cholesterol, or each of the five experimental treatments (Kampo formulas 1% keishibukuryogan [KBG], 1% orengedokuto [OGT], and 1% shosaikoto [SST]; vitamin E [VE]; or pioglitazone [PG]) in a 1% cholesterol SRC. We analyzed changes after 12 weeks in plasma and liver lipid profiles, glucose metabolism, adipocytokines, oxidative stress, and liver fibrosis. Data demonstrated that all five treatments were associated with significant amelioration of lipid profiles, oxidative stress, and liver fibrosis compared to no supplementation. KBG was superior to VE and PG in the reduction of liver total cholesterol (P < 0.01) and lipid peroxidase levels (P < 0.05), urinary 8-hydroxy-2'-deoxyguanosine (P < 0.05), hepatic alpha-smooth muscle actin positive areas (P < 0.01) and activated stellate cells (P < 0.01). In conclusion, there was a statistically significant benefit of Kampo formulas (KBG in particular) on a dietary model of NAFLD/NASH. Future studies need to be directed at the mechanisms in the treatment of NASH.
Assuntos
Modelos Animais de Doenças , Medicina Baseada em Evidências , Fígado Gorduroso/tratamento farmacológico , Medicina Kampo , Adipocinas/sangue , Álcoois , Animais , Biomarcadores , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Química Farmacêutica , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Ácido Hialurônico/sangue , Lipídeos/sangue , Cirrose Hepática/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo , Coelhos , Fator de Crescimento Transformador beta1/sangueRESUMO
There has been a remarkable history in the treatment of patients with autoimmune disease in the last century. Prior to the development of newer NSAIDs and corticosteroids, the care of patients with autoimmune disease was limited to aspirin and generally homeopathic therapies such as paraffin. In the last 30 years, the introduction and acceptance of cytotoxic drugs such as methotrexate and cyclophosphamide have greatly advanced the treatment of patients with severe autoimmune diseases. However, the use and dose escalation of cytotoxic agents in severely ill patients is limited by toxicity and the potential for secondary malignancies that correlate with cumulative lifetime dosing. As hematopoietic stem cell transplant grew to become an established procedure for certain malignancies, reports of remission of coexistent autoimmune diseases began to emerge. Animal data subsequently supported a role for hematopoietic stem cell transplants for the primary indication of autoimmune diseases. On the basis of these reports, clinical trials of hematopoietic stem cell transplants for the primary indication of autoimmune disease were initiated in the late 1990s. We review the data from a decade of experience that has now accumulated for this novel approach to the management of autoimmunity.
Assuntos
Doenças Autoimunes/terapia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/imunologia , Animais , Doenças Autoimunes/imunologia , Ensaios Clínicos como Assunto , Doença Enxerto-Hospedeiro/imunologia , Humanos , Condicionamento Pré-Transplante , Imunologia de TransplantesRESUMO
Eczema is a chronic inflammatory skin disease that has reached nearly epidemic proportions in childhood. Moreover, it is a difficult disease to control and, with its onset in childhood, is often the first manifestation of atopy. The clinical features of eczema include itchy red skin accompanied by dryness and lichenification. In the past, treatment options consisted primarily of avoidance of soap and water. These options have considerably improved with both nonpharmacologic and pharmacologic approaches. However, eczema is still a treatment challenge. Part of the problem in developing new treatment options has been the relative failure in translating basic science information into clinical application. It is hoped that the newer biologics will help bridge this gap and lead to greater success rates.
Assuntos
Alérgenos , Eczema , Hipersensibilidade Alimentar , Fatores Imunológicos/uso terapêutico , Imunoterapia , Sabões/uso terapêutico , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aleitamento Materno , Criança , Pré-Escolar , Terapias Complementares/tendências , Diagnóstico Diferencial , Eczema/diagnóstico , Eczema/etiologia , Eczema/fisiopatologia , Eczema/terapia , Feminino , Hipersensibilidade Alimentar/complicações , Previsões , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Fatores Imunológicos/efeitos adversos , Lactente , Pessoa de Meia-Idade , Fototerapia , Fitoterapia , Fatores de RiscoRESUMO
The epidemic of non-alcoholic fatty liver disease (NAFLD) in the United States is staggering, and there is an enormous void in our understanding of the clinical epidemiology other than the common themes of obesity and insulin resistance. There is also a public health need to better define effective treatments of NAFLD, including dietary interventions and appropriate nutritional supplements. There is, however, a wealth of basic science that helps to set the stage for defining the mechanisms leading to liver pathology. In this article we will attempt to put these concepts in perspective to highlight the need for future research including the use of medicinal food.