RESUMO
Previous evidence suggested that lymphocytic thyroiditis (LT) was a variant of Hashimoto's thyroiditis (HT), thus the aim of the current study is to quantify structural changes in histological specimens taken from HT and LT patients. A total of 600 images containing a single lymphocyte nucleus (300 nuclei per group) were obtained from 20 patients with HT and LT. In order to quantify changes in the nuclear architecture of investigated lymphocytes, the fractal dimension (FD) and some gray-level co-occurrence matrix texture parameters (angular second moment, inverse difference moment, contrast, entropy, and correlation) were calculated for each nucleus. A statistically significant difference in the FD of the "binary-outlined" nucleus and that of the corresponding "black-and-white" nucleus was detected between HT and LT lymphocyte nuclei. In addition, there was also a statistically significant difference in contrast and correlation between HT and LT lymphocyte nuclei. In conclusion, the results of this study suggested that there was a difference in structural complexity between investigated lymphocyte nuclei; additionally, LT lymphocytes possessed probably more complex texture and larger variations as well as more asymmetrical nuclei compared with HT lymphocytes. Accordingly, these findings indicate that LT is probably not a variant of HT; however, more complex studies are necessary to estimate differences between these types of thyroiditis.
Assuntos
Núcleo Celular/patologia , Cromatina/patologia , Fractais , Doença de Hashimoto/patologia , Linfócitos/citologia , Tireoidite Autoimune/patologia , Adulto , Idoso , Algoritmos , Gráficos por Computador , Feminino , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/terapia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Tireoidite Autoimune/diagnóstico por imagem , Tireoidite Autoimune/terapiaRESUMO
BACKGROUND/AIM: Osteoporotic fractures are a major cause of morbidity in the population. Therefore, fracture prevention strategies should be a major concern, and one of the priorities in the primary health care system. The aim of the study was to assess fracture and fall risk factors, and fracture risk level in patients with acute hip fracture, and to evaluate if there had been adequate osteoporosis treatment prior to fracture in this group of patients. METHODS: Fracture and fall risk factors were assessed in 342 patients, > or = 65 years old, hospitalized due to acute hip fracture at the Clinic for Orthopedic Surgery and Traumatology, Clinical Centre of Serbia in a 12-month period. Fall risk factors were assessed with the Fracture Risk Assessment (FRAX) algorithm, and patients were classified in respect to fracture risk level. RESULTS: Hip fracture occurred in the majority of the patients in the high risk group (74.2%), where no additional bone mineral density testing was needed. Less than 10% of the patients had a diagnosis of osteoporosis before injury, while less than 2% were treated. Cognitive impairment (95.3%), visual impairment (58.2%), lower index of daily activities (51.8%), and depression (47.1%) were the most frequently observed fall risk factors. CONCLUSION: The results of our investigation reveal insufficient identification of clinical fracture risk factors in the primary care setting, inadequate treatment of osteoporosis and, consequently, ineffective prevention of hip fractures in the geriatric population. The introduction of FRAX into clinical practice enables more effective acknowledgment of patients with elevated fracture risk, even if bone density measurement is not available. The results of this study have a special significance for everyday clinical practice, because they impose a need for reviewing the existing approaches to osteoporosis prevention, and precise definiment of hip prevention strategies.
Assuntos
Fraturas do Quadril/prevenção & controle , Fraturas por Osteoporose/prevenção & controle , Acidentes por Quedas , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/etiologia , Humanos , Masculino , Medição de Risco , Fatores de RiscoRESUMO
Pregnancy-associated spinal osteoporosis (PPSO) is a rare condition characterized by severe back pain occurring near the end of the first pregnancy or shortly afterward. The aim of this report is to present a 12-year follow-up of a patient with PPSO. Also, the outcomes of patient's two pregnancies and her infants after long-term treatment with bisphosphonates are assessed. A young woman was referred to our tertiary care hospital aged 30 years, due to intense pain in thoracic and lumbar region that started during the last month of her first pregnancy and got worse after delivery. Bone mineral density (BMD) measurement, clinical, and biochemical parameters were performed. Extremely low lumbar spine BMD, L2-L4: 0.627 g/cm(2), T-score -4.8, Z-score -4.3, 52% young adult indicated severe osteoporosis. Cyclical treatment with etidronate and then pamidronate was started, and a substantial increase in the BMD and the reduction in back pain intensity were observed. An increase in BMD of 44.8% over baseline was observed after 12 years of follow-up. Her two pregnancies were uneventful, and no neonatal adverse effects were observed. Control DXA scan in her girl child aged 6.8 years revealed low BMD at the lumbar spine. As PPSO seems to be an underdiagnosed severe disease, caution is recommended if back pain occurs in the last trimester or early post-partum period. Although pre-pregnancy use of bisphosponates does not pose a substantial fetal risk, their use in women of childbearing age might best be done only when strong clinical indications exist.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Ácido Etidrônico/uso terapêutico , Osteoporose/patologia , Complicações na Gravidez , Adulto , Dor nas Costas/tratamento farmacológico , Dor nas Costas/etiologia , Dor nas Costas/patologia , Densidade Óssea/efeitos dos fármacos , Criança , Feminino , Humanos , Recém-Nascido , Nascido Vivo , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Vértebras Lombares/patologia , Masculino , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Pamidronato , Gravidez , RadiografiaRESUMO
Natural autoantibodies (NAbs) are continually produced throughout life and have an ability to recognize self and altered self, as well as foreign antigens, by recognizing cellular pattern recognition receptors. Sometimes NAb specificity demonstrates overlap between human and pathologic proteomes. This information can be useful in selecting target sequences for screening purposes. In this study we undertook a multi-step bioinformatics search to predict a virus-derived peptide that can be recognized by NAbs in sera of uninfected individuals. We selected protein hepatitis C virus (HCV) NS5A as a target sequence, motivated by the fact that the HCV proteome is characterized by extensive sequence similarities to the human proteome, and because screening for anti-HCV antibodies, including anti-NS5A, is important clinically, particularly in screening of potential blood donors. The virus-specific peptide P1, and the homologous human peptide derived from enzyme-inducible nitric oxide synthase (iNOS), P2, exhibiting not only simple homology, but also complementarities of physicochemical patterns, were synthesized and 80 HCV-negative and 50 HCV-positive blood donor sera were tested by ELISA. These peptides reacted similarly (p<0.001) with HCV-negative sera, and in several cases the measured reactivity was significantly above the cut-off value of commercial anti-HCV screening assays. In HCV-positive sera, the titers of antibodies reactive with analyzed HCV NS5A peptide were not significantly increased (p<0.001) compared to host peptide, the implications of which are unclear, but may be consistent with these antibodies being "naturally produced." Finally, we extended our bioinformatics analyses to the dataset of human self-binding sequences, and propose a general approach for the selection of specific diagnostic and screening antigens for use in immunoassays.
Assuntos
Autoanticorpos/sangue , Doadores de Sangue , Biologia Computacional/métodos , Hepatite C/diagnóstico , Proteínas não Estruturais Virais/imunologia , Ensaio de Imunoadsorção Enzimática , Antígenos da Hepatite C/imunologia , Humanos , Peptídeos/síntese química , Peptídeos/imunologia , Soro/imunologiaRESUMO
The aim of this study was to establish microbial and heavy metal pollution of the Sava River at three locations close to industry and urban areas (Sabac, Obrenovac, Beograd) in Serbia. Heavy metal analysis included Cu, Zn, Pb, and Cd in the river water and sediment samples. Using the microbiological analysis we tried to establish the effectiveness of total coliforms, faecal coliforms and Escherichia coli in detecting pollution of surface waters. We found that E. coli levels steadily increased downstream from Sabac (location 1; 2100 MPN per 100 mL) to Belgrade (location 3; 10000 MPN per 100 mL). To prevent bacterial contamination, it is necessary to reduce the discharge of wastewater with faecal matters near highly populated towns. Heavy metal levels in sediments correlated with those in the river water. Fluctuations attributed mainly to anthropogenic sources were not high. These results point to acceptable anthropogenic contribution to heavy metal content in the Sava River and to low environmental risk.
Assuntos
Escherichia coli/isolamento & purificação , Metais Pesados/análise , Rios/química , Rios/microbiologia , Microbiologia da Água , Poluentes Químicos da Água/análise , Poluição da Água , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiologia , SérviaRESUMO
INTRODUCTION: Osteoporosis is a serious problem, since about 50% of women over the age of 50 suffer at least one osteoporotic fracture. OBJECTIVE: The aim of this study was to evaluate compliance as well as the efficiency and safety of ibandronate treatment over a 6-month period in reducing the risk of subsequent fracture in women with postmenopausal osteoporosis. METHODS: A multicenter, prospective, observational study was conducted during one year in thirteen medical centres in Serbia. In the first part of the study the participants received ibandronate tablets (150 mg) once a month for six months. In the second part, the patients were under clinical follow-up. RESULTS: The mean age of the 184 menopausal women included in the study was 66.2 +/- 9.4 years. In 40.2% of the subjects the disease had been clinically manifest during the five preceding years. The mean T-score value at the onset of our investigation was -3.1 +/- 0.84 in 160 (87%) patients who were diagnosed osteoporosis. Compression vertebral fractures alone were noted in 24% of the women, spontaneous nonvertebral fractures in 49.4% and both in 4.9%. A history of osteoporotic fractures was much more common in patients with three or four risk factors (p = 0.001). Out of 39 adverse events during therapy with once monthly bisphosphonates only 2 (3.3%) were classified as severe. During the treatment, spontaneous fractures occurred in 13 (7.1%) patients. CONCLUSION: Ibadronate treatment once a month for 6 months was shown to be very safe, tolerated well and without more serious side effects.
Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Feminino , Fraturas por Compressão/prevenção & controle , Humanos , Ácido Ibandrônico , Pessoa de Meia-IdadeRESUMO
In the recent years, iodine was associated to the development of apoptosis in thyroid diseases. The aim of the present study is to determine the expression of pro-apoptotic and anti-apoptotic proteins, Bax and Bcl-2, in a Wistar rat experimental model of thyroiditis induced by administration of different doses of potassium iodide. Immunohistochemical staining was done with chromogen diaminobenzidine on avidin-biotin peroxidase using the Animal Research Kit (ARK), stained with antibodies to Bcl-2 and Bax proteins. The intensity and distribution of positive staining were evaluated by light microscopy on a scale of 0 to 4. Bax protein was expressed in the area of regenerating follicular cells in high percent in potassium iodide treated rats, but was not expressed in thyrocytes from control rats. Bcl-2 expression was constantly observed in thyrocytes of the control group and in the mantle-zone of lymphoid follicular infiltrates. Our results show that Bax expression is significantly higher in the Wistar rat experimental model of thyroiditis than in the control group. These data suggest that the increased expression of Bax may contribute to the role of apoptosis in the pathogenesis of experimental thyroiditis.
Assuntos
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Glândula Tireoide/metabolismo , Tireoidite/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Masculino , Iodeto de Potássio/administração & dosagem , Iodeto de Potássio/toxicidade , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Ratos Wistar , Soroalbumina Bovina/toxicidade , Glândula Tireoide/efeitos dos fármacos , Tireoidite/induzido quimicamente , Tireoidite/genética , Proteína X Associada a bcl-2/genéticaRESUMO
INTRODUCTION: Potassium iodine (KI) is used as a drug therapy for treating numerous diseases such as small-vessel vasculitis, erythema nodosum, vasculitis nodularis, Sweet's syndrome, tuberculosis and granulomatosis, and for iodized salt. At the same time, KI can be harmful. Iodine intake may increase the frequency of thyroiditis in humans, and may induce the occurrence of experimental thyroiditis (ET) in animals. Investigations on an experimental model for the examination of thyroiditis in Wistar rats have clearly showed morphological changes in the rat thyroid evoked by KI administration. OBJECTIVE: The purpose of this study was to compare the effects of low and high doses of KI on the thyroid gland of Wistar rats and determine the effect on hormone status (T4, T3 and TSH) in this rat strain. METHODS: Two groups of rats from the Wistar strain were treated with a low iodine dose (225 microg/g BW) and with a high iodine dose (675 microg/g BW) of KI solutions. Untreated nonimmunized animals served as controls. The solution was administrated daily intraperitoneally during the period of 26 consecutive days. RESULTS: Monitoring hormone status (TSH, T3 and T4) and morphological changes it was found that therapeutic doses of KI applied in treatment induced the occurrence of experimental thyroiditis (chronic destructive Hashimoto's thyroiditis in humans) and cell necrosis in animals not carrying a genetic susceptibility. Significant inflammatory changes were observed in rats treated with a high iodine dose. CONCLUSION: The early iodine induced cell necrosis and inflammation in the nonimmunized animals without genetic susceptibility is a new experimental model of thyroiditis.
Assuntos
Iodeto de Potássio/administração & dosagem , Hormônios Tireóideos/sangue , Tireotropina/sangue , Animais , Masculino , Iodeto de Potássio/farmacologia , Ratos , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologiaRESUMO
INTRODUCTION: Apoptosis is a highly regulated mechanism of cell death that differs from necrosis and plays an important role in normal tissue development, homeostasis and immune regulation. DISEASES AND APOPTOSIS: Apoptosis is involved in many diseases. Defective apoptosis can cause systemic autoimmunity by allowing the survival of autoreactive lymphocytes. It may also be involved in the pathogenesis of organ-specific autoimmune diseases such as Hashimoto's thyroiditis and in the pathogenesis of tumors. MECHANISM PROGRAMMED DEATH CELL: Apoptosis is regulated at multiple levels, including death receptor and ligand expression, adapter protein, cascades of caspases, mitochondria and the expression of anti apoptotic and pro apoptotic proteins. Apoptotic cell death can occur by two different pathways. Type I is initiated by the activation of death receptors (Fas, TNF-receptor-family) on the plasma membrane followed by activation of caspase 8. Type II involves changes in mitochondrial integrity initiated by various effectors, leading to the release of cytochrome c and activation of caspase 9. MECHANISM OF APOPTOSIS IN HASHIMOTO THYROIDITIS: The thyroid cell destruction characteristic of autoimmune thyroiditis can be seen as the consequence of inappropriate expression of Fas or TRAIL death pathway molecules and down-regulation of the apoptosis controlling protein Bcl-2, which may be induced by cytokines released locally by infiltrating lymphocytes. Thyroid cell destruction in autoimmune hypothyroidism is dependent on T cell-mediated cytotoxicity with the likely additional effect of death receptor-mediated apoptosis. Modulation of apoptosis-related proteins by T helper 1 and T helper 2 cytokines controls thyrocyte survival in thyroid autoimmunity.
Assuntos
Apoptose/fisiologia , Doença de Hashimoto/fisiopatologia , HumanosRESUMO
Insulin-like growth factor-1 (IGF-1) is a hormone and growth factor closely related to insulin. The autocrine/paracrine actions of IGF-1 involve activation of inducible nitric oxide synthase (iNOS) and the Na(+), K(+)-ATPase sodium pump in cardiovascular tissues. Data from literature indicate that iNOS is expressed in vascular smooth muscle cells (VSMC) and that IGF-1-induced release of NO is both rapid and delayed. We hypothesize that impaired IGF-1-induced sodium pump activity/expression in rats with type 1 diabetes is related to activation of phosphatidylinositol 3 kinase (PI3K)/cytosolic phospholipase 2 (cPLA(2))/protein kinase B (Akt) signaling, and that IGF-1 prevents acute and chronic dysfunction of iNOS and sodium pump activity in a chemically induced model of type 1 diabetes, the streptozotocin-treated rat heart (STZ). Understanding how iNOS and sodium pump activity are regulated by IGF-1 activation of the PI3K/cPLA(2)/Akt cascade should provide novel and fundamental knowledge regarding the regulatory actions of IGF-1 in promoting vasodilation. Since insulin resistance is currently a major focus of research, the use of IGF-1 to improve insulin resistance and glucose metabolism has opened a new arena for treatment of comorbid conditions. Future investigations should now focus on mechanisms of action of IGF-1 and its clinical applicability.
Assuntos
Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 1/terapia , Óxido Nítrico Sintase Tipo II/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Óxido Nítrico Sintase Tipo II/fisiologia , Ratos , ATPase Trocadora de Sódio-Potássio/fisiologiaRESUMO
INTRODUCTION: The principal indication for surgical intervention in chronic pancreatitis is intractable pain. Depending upon the presence of dilated pancreatic ductal system, pancreatic duct drainage procedures and different kinds of pancreatic resections are applied. OBJECTIVE: The objective of the study was to show the most appropriate procedure to gain the most possible benefits in dependence of type of pathohistological process in chronic pancreatitis. METHOD: Our study included 58 patients with intractable pain caused by chronic pancreatitis of alcoholic genesis. The first group consisted of 30 patients with dilated pancreatic ductal system more than 10 mm. The second group involved 28 patients without dilated pancreatic ductal system. Pain relief, weight gain and glucose tolerance were monitored. RESULTS: All patients of Group I (30) underwent latero-lateral pancreaticojejunal--Puestow operation. 80% of patients had no pain after 6 month, 13.6% had rare pain and 2 patients, i.e. 6.4%, who continued to consume alcohol, had strong pain. Group II consisting of 28 patients was without dilated pancreatic ductal system. This group was subjected to various types of pancreatic resections. Whipple procedure (W) was done in 6 patients, pylorus preserving Whipple (PPW) in 7 cases, and duodenum preserving cephalic pancreatectomy (DPCP) was performed in 15 patients. Generally, 89.2% of patients had no pain 6 month after the operation. An average weight gain was 1.9 kg in W group, 2.8 kg in PPW group and 4.1 kg in DPCP group. Insulin-dependent diabetes was recorded in 66.6% in W group, 57.1% in PPW group and 0% in DPCP group. CONCLUSION: According to our opinion, DPCP may be considered the procedure of choice for surgical treatment of pain in chronic pancreatitis in patients without dilatation of pancreas ductal system because of no serious postoperative metabolic consequences.
Assuntos
Dor Intratável/etiologia , Pancreatite Crônica/cirurgia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia/métodos , Pancreaticoduodenectomia/métodos , Pancreatite Alcoólica/complicações , Pancreatite Alcoólica/cirurgia , Pancreatite Crônica/complicaçõesRESUMO
INTRODUCTION: Hepatitis C is a post-transfusion hepatitis which causes serious problems in blood transfusion. Blood testing requires highly sensitive and specific assays with high predictive value. GENOMIC CHARACTERISTICS OF HEPATITIS C VIRUS: According to recommendations of International Association for the study of Liver Diseases etiological diagnosis of hepatitis is based on highly sensitive third generation assays: epitopes in the NS5 region comprising noncoding sequence UTR with 324-341 well conserved pair of homologous basis in 92% HCV genomes, therefore appropriate for virus RNA detection. DEVELOPMENT OF ASSAYS FOR HEPATITIS VIRUS: The first generation of immunoenzyme tests (IET) were based on detection of antibodies on antigen c 100-3, which is a part of the NS4 region of HCV genome. The second generation of tests with two recombinant proteins--c22-3 and c200, achieved higher sensitivity of assays. The third generation included epitopes from NS5 region, and removed the antigen c100-3. DEVELOPMENT OF AUTOIMMUNITY: Autoimmunity is a pathophysiological mechanism that's leads to chronic inflammatory diseases. Autoimunity is characterized by loss of tolerance towards self-antigens. Viral hepatitis C is associated with development of autoimmune phenomena. MOLECULAR MIMICRY: Molecular mimicry, as a mechanism of autoimmunity, was investigated to establish cross-Reactive immune reactions between HCV antigen and human nitrogen-oxide synthase, Tyrosine kinase Lck and hepatic growth factor activator. CROSS REACTIVITY BETWEEN HCV PROTEINS AND HUMAN PROTEINS: HCV capsid proteins initiate the autoimmune process in the liver because of cross reaction of antibodies with human Gor protein 19-27, which causes autoimmune chronic hepatitis. However, analysis of human protein from protein basis Swiss-prot shows homology between NS5 region and 3 human protein nitrogen oxide synthases, tyrosine kinase-Lck, proto-oncogene and hepatic growth factor activator. According to protein data analysis and competitive in vitro experiments, it was concluded that presence of auto-antibodies is probably the consequence of cross reactive immune response. CONCLUSION: Homology of amino acid sequences in the NS5 region of the HCV genome with nitrogen-oxide synthase, tyrosine kinase-Lck, and hepatic growth factor activator, causes auto-immune phenomena in HC, and can be a model for researching autoimmunity and human virus-induced autoimmune diseases.
Assuntos
Hepacivirus/genética , Antígenos de Hepatite/genética , Hepatite C/transmissão , Homologia de Sequência de Aminoácidos , Reação Transfusional , Autoimunidade , Reações Cruzadas , Hepatite C/imunologia , Fator de Crescimento de Hepatócito/genética , Humanos , Óxido Nítrico Sintase/genética , Proteínas Tirosina Quinases/genética , Proto-Oncogene Mas , Serina Endopeptidases/genéticaRESUMO
Fungal bone infections constitute about 0.1-0.2% of all osteomyelitis cases. The disease, mycetoma pedis, most often affects the feet and is also known as madura foot. Mycetoma, extremely rare in this geographic area, is endemic in tropical and subtropical regions. We present a case of mycetoma pedis (madura foot). The patient was a 50-year-old woman. The clinical signs included pain, indurations, and local redness. The anamnesis was very long, about 10 years. The operative material was routinely stained with haematoxylin-eosine [HE]. Granulomatous inflammation of the bone was confirmed pathologically. All pathological characteristics pointed to a fungal infection in the form of mycetoma pedis. Special staining for fungi was performed: PAS, Grocott's hexamine-silver, and Giemsa, confirming the diagnosis of mycetoma. A definitive microbiological analysis was carried out through tissue inoculation on the Sabouraud dextrose agar laboratory media for fungal cultivation. Pseudoallescheria boydii, the sexual stage of Monosporium apiospermum, was isolated. After microbiological verification of fungal infection, surgical therapy was carried out. Seven months after the first operation, the patient had the same clinical signs. The diagnostic procedure was repeated and mycetoma was confirmed once again. Surgery was again the therapy of choice, because Pseudoallescheria boydii is resistant to treatment with antimycotic drugs.
Assuntos
Micetoma/microbiologia , Osteomielite/microbiologia , Pseudallescheria , Scedosporium , Feminino , Granuloma/diagnóstico , Granuloma/microbiologia , Granuloma/cirurgia , Humanos , Pessoa de Meia-Idade , Micetoma/diagnóstico , Micetoma/cirurgia , Osteomielite/diagnóstico , Osteomielite/cirurgia , RecidivaRESUMO
Perfectly projected and impeccably created, the endocrine system precisely regulates the most delicate immune processes. The immune and neuroendocrine systems are two essential physiological components of mammalian organisms important for protection from the infection and disease on one hand, and on the other, for regulation of metabolism and other physiological activities; namely, the evidence has been found indicating that there is active and dynamic collaboration of these systems in the execution of their designated functions. These interactions occur at many stages of embryonic and neonatal development, and they are a continual part of normal homeostatic balance necessary to preserve health. There is communication between neuroendocrine and immune system via cytokines, neurotransmitters and peptide hormones which act, in both systems,, through the same receptor molecules (Scheme 1). Many investigators have reported the increased thymic weight in experimental animals due to both castration and adrenalectomy. The discovery from 1898 revealing that thymus was enlarged in castrated rabbits has been considered the embryo of hybrid medical discipline, i.e. the immunoendocrinology. In the actual literature, at least in that available to us, it has not been noted that the appearance of the eunuchs, i.e. the castrates, stimulated the analytical approach to this phenomenon. Endocrine influences appear to be a part of bidirectional circuitry, namely, thymic hormones also regulate the release of hormones from the pituitary gland. Physiologically, thymus is under neuroendocrine control. It is apparent that the circulating levels of distinct peptide hormones are necessary to maintain a series of biological functions related both to microenvironmental and lymphoid cells of the organ. The neuroendocrine control of the thymus appears to be extremely complex, with apparent presence of complete Intrathymic biological circuitry involving the production of pituitary hormones, as well as the expression of their respective receptors by thymic cell. The influence of gonadectomy on the humoral immunity has been controversial. All investigations agree that women have higher titres of all classes of circulating antibodies than men. The application of estrogens stimulated the formation of antibodies in the circulation. Then, if there were no sex glands, the immune response of the individual would be enhanced. Both the cellular and the humoral immune response is more powerful in the adult normal women than in men of the same age. The immune response is different in different sexes meaning that there is a sexual dimorphism. This difference has not been noted before the puberty. It has been noticed that the substitution therapy has alleviated the late skin hypersensitivity. The estrogens have also curtailed the rejection time of the transplant and all reactions in which T-effector lymphocytes have been involved. NK-cells and T-lymphocytes activities have been decreased by the action of estrogens, as well as the release of thymus hormones. Cortical RE cells express a surface antigen, gp200-MR6, which plays a significant role in thymocyte differentiation. Irrespectively of which pathway may be triggered by neuroendocrine factors, the effects are pleiotropic and result in modulation of the expression of several genes in different cell types. Thymic neuroendocrine polypeptides are the source of self-antigens presented by MHC molecules enabling the differentiation of haematopoietic stem cells. Thymic nurse cells also produce thymosins beta 3 and beta 4 and display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+ and presence of common leukocyte antigen (CLA+). GH enhances thymocyte release from TNCs, as well as the reconstitution of these lymphoepithelial complexes. Similarto its role as a regulator of bone metabolism through regulating osteoprotegerin (OPG) production, the estrogen is involved in the processes of thymocyte development although aromatase mRNA has not been detectable in the thymus. While the increase of TNC number during lactation may be linked to the process of reconstruction of the thymic lymphoid population, the increased activity of lymphoepithelial interactions on GD14 may be associated with thymic engagement in pregnancy-induced immune processes The major antigens in the experimental autoimmune hypophysitis in rats are growth hormone, thyrotropin, and luteinizing hormone. The intrathymic T-lymphocyte selection is a complex, multistep process, influenced by several functionally specialised RE cells and under immuno-neuroendocrine regulation control reflecting the dynamic changes of the mammalian organism. In HIV-1-infected adults treated with growth hormone, thymic mass and circulating naive CD4 T cells are increased. The treatment would be easier for the diseased, as well as to us, the physicians, if we were aware of two millennia old wisdom--that the disease is a visit of God.
Assuntos
Hormônios/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Neuroimunomodulação , Timo/fisiologia , Animais , Humanos , Sistemas Neurossecretores/fisiologiaRESUMO
Most school doctors, who lived in the period of Early Christianity from 1st to 4th century A.D. and who were canonized saints, have been known, up to these days, among people and in scientific and medical circles as Holy Healers. It is understood that only exclusively educated medical experts, trained to heal professionally and prepare medicines are considered Holy Healers. Out of all Holy Healers, St. Kosma and Damian, St. Panteleimon, St. Luke, etc., are highly respected by our people. St. Luke (1st century A.D.) is specially honored by Serbian nation. His relics were taken to Smederevo in 1453 and then the town became "the place of many cures and new healing spot". Out of these relics, only the foot of St. Luke was preserved in a very good condition and it remained in the possession of the Serbian Orthodox Church. In old documents written in old Greek and clerical-slavic language, St. Luke is glorified as "reliable doctor both for soul and body..." St. Luke is respected as a protector of medicine and pharmacy, doctors and pharmacists, and patients, as well as many families (family patron of the Serbs), even of the whole regions. Many chemist's shops and hospitals are named by this Saint, what is the confirmation that his cult and recognition of his personality and his work are still present in our milieu.