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Biomedical subjects

J A Da Silva

Publications and source records attributed to J A Da Silva.

At least 19 recordsLinked to original sources
PubMed2000

Optimizing glucocorticoid therapy in rheumatoid arthritis.

Glucocorticoids have a profound effect on the immune system and also on the HPA axis. Present insights into these mechanisms are discussed. Glucocorticoid resistance and clinical efficacy in the treatment of RA are reviewed. There is growing evidence for a positive effect of low-dose glucocorticoids on the retardation of erosive joint damage. Side effects of glucocorticoids on bone are now better controlled. Some guidelines to optimize glucocorticoid therapy in RA are given regarding dosage, timing, managing of side effects, and (new) types of glucocorticoids.

Arthritis, Rheumatoid↗
PubMed2000

[Primary intracerebral hemorrhage. Retrospective study of 72 operated cases].

We analysed 72 cases of primary intracranial hemorrhage surgically treated from 1970 to 1999. The hemorrhages were diagnosed by computerized axial tomography in 52 patients. Most hematomas were situated in the cerebral hemispheres (30 percent in thalamus-basal ganglia region and 50 percent in the subcortical matter). There were 10 patients with cerebellar hemorrhage. Hypertension (based in blood pressure recordings in the hospital and history) was found in 24 patients (33 percent). The most frequent findings were coma, intracranial hypertension and hemimotor deficit. The death rate registered was 27.7 percent; however, it was found a significant difference in the mortality index when considering the 70-79 decade (62.7 percent) and the 90-99 decade (20.7 percent). A critical analysis was made about depth hematomas, consciousness state and intracranial hypertension with herniation related to surgical procedure.

Adult↗
PubMed2000

Psychophysical power functions for apparent area in perceptive, memory, and inference conditions for observers of different age groups.

The purpose of this research was to verify the effect of age on the exponent of the power function in Perceptive, Memory, and Inference experimental conditions. In the Memory condition the intervals of 2 min., 8, 24, and 48 hr. and 1 wk. were used between acquisition of information and remembering. For each experimental condition the ages of observers ranged between 17 and 35 years (Group I), 40-55 years (Group II), and 60-77 years (Group III), and education ranged from high school to graduate school. The observers estimated the areas of the Brazilian satires using the psychophysical method of magnitude estimation. No significant differences were obtained for Groups I, II, and III for each experimental condition, except in the Memory Condition with the 24-hr. interval. Analysis for experimental conditions and ages showed a significant difference between the Perceptive Condition and each of the others, but no difference between the Inference and Memory Conditions. These results indicated that in the remembering processes there is no loss of information as a function of age. From the small variability in the power function exponents for the three ages, we may assume that age could be related to amount of education of the observers, which suggests study is important.

Adult↗
PubMed1999

Sex hormones and glucocorticoids: interactions with the immune system.

Gender and sex hormones exert powerful effects in the susceptibility and progression of numerous human and experimental autoimmune diseases. This has been attributed to direct immunological effects of sex hormones that impact a clear gender dimorphism on the immune system. Globally, estrogens depress T cell-dependent immune function and diseases, but enhance antibody production and aggravate B cell-dependent diseases. Androgens suppress both T-cell and B-cell immune responses and virtually always result in the suppression of disease expression. Defects in the hypothalamic-pituitary-adrenal (HPA) axis have been proposed to play an important role in the pathogenesis of autoimmune diseases. Glucocorticoid response to stress, including immune challenge, is strongly inhibited by androgens and enhanced by estrogens. Complex three-way interactions between these systems appear to be involved in gender dimorphism of the immune system. This paper reviews the mechanisms involved in interactions between sex steroids and the HPA axis, addresses the possibility of similar interactions on immunocompetent cells, and explores an integrated perspective of the impact of these interplays on the immune system.

Animals↗
PubMed1999

Destruction of articular cartilage by alpha 2 macroglobulin elastase complexes: role in rheumatoid arthritis.

OBJECTIVE: Neutrophil elastase accounts for the ability of some fresh rheumatoid synovial fluids to degrade cartilage matrix in vitro. The aim of this study was to determine if enzyme activity could result from depletion of synovial fluid inhibitors or protection of the enzyme from inhibition. METHODS: The ability of synovial fluids to inhibit porcine pancreatic elastase was investigated together with chemical pretreatments capable of inactivating alpha 1 protease inhibitor (alpha 1PI) or preventing formation of alpha 2 macroglobulin (alpha 2M) elastase complexes. Subsequently, complexes of human neutrophil elastase with alpha 2M were prepared and applied to frozen sections of cartilage. Proteoglycan loss was quantified by alcian blue staining and scanning and integrating microdensitometry. Parallel studies were carried out using a low molecular weight chromogenic elastase substrate. The effects of alpha 1PI and SF on these systems were investigated. Finally, synovial fluids were subjected to gel filtration and the fractions assayed for elastase activity. High molecular weight fractions were pooled, concentrated, and tested for their ability to degrade cartilage sections. RESULTS: All synovial fluids reduced the activity of porcine pancreatic elastase, the inhibition mainly being attributable to alpha 1PI, whereas remaining activity resulted from complexes of elastase with alpha 2M. Complexes of human neutrophil elastase with alpha 2M were shown to cause proteoglycan degradation in frozen sections of human articular cartilage. Alpha 1PI prevented alpha 2M elastase complexes from degrading cartilage but not the chromogenic substrate. The data suggested that alpha 1PI does not inhibit elastase bound to alpha 2M but sterically hinders the complex. However, only one of five synovial fluids was able to completely block the actions of alpha 2M elastase complexes against cartilage. Gel filtration of rheumatoid synovial fluids showed elastase and cartilage degrading activity to be associated with fractions that contained alpha 2M, and not with fractions expected to contain free enzyme. CONCLUSIONS: The data suggest that synovial fluid alpha 2M elastase complexes can degrade cartilage matrix in rheumatoid arthritis.

Adult↗
PubMed1999

[Transitory cerebellar mutism: report of 2 cases].

We present two cases of mutism observed after resection of tumors of the cerebellum, in two children of the feminine sex, being in the first case of medulloblastoma and in the second of juvenile astrocytoma. In both patients there was pre-operative lesion of low cranial nerves. The pathophysiology of the mutism involves anatomical, vascular and emotional factors, being its essential characteristics discussed with base in revision of the literature.

Adolescent↗
PubMed1998

[Isolated fourth ventricle: report of 2 cases].

Two cases of isolated fourth ventricle are reported, the first due to cerebellar haemorrhage, and the second due to congenital hydrocephalus with multiple shunt revisions and Dandy-Walker cyst. In our opinion, there are two basic treatment for isolated forth ventricle. The direct approach to the fourth ventricle is indicated when there is presence of an intraventricular cyst. The fourth ventricular shunting, independent of the supratentorial shunt, is the best treatments for patients with an isolated fourth ventricle without the presence of a cyst.

Adolescent↗
PubMed1997

Visual perception of egocentric distance as assessed by triangulation.

Two triangulation methods for measuring perceived egocentric distance were examined. In the triangulation-by-pointing procedure, the observer views a target at some distance and, with eyes closed, attempts to point continuously at the target while traversing a path that passes by it. In the triangulation-by-walking procedure, the observer views a target and, with eyes closed, traverses a path that is oblique to the target; on command from the experimenter, the observer turns and walks toward the target. Two experiments using pointing and 3 using walking showed that perceived distance, averaged over observers, was accurate out to 15 m under full-cue conditions. For target distances between 15 and 25 m, the evidence indicates slight perceptual underestimation. Results also show that observers, on average, were accurate in imaginally updating the locations of previously viewed targets.

Adolescent↗
PubMed1996

Perturbations of hypothalamic-pituitary-gonadal (HPG) axis and adrenal androgen (AA) functions in rheumatoid arthritis.

The available evidence reviewed does not allow definitive response to the question of a primary versus secondary role of sex hormone perturbations in RA. However, this conclusion should not be discouraging in view of the relatively recent focus upon this facet of the physiopathogenesis of RA and the enormous complexities of sex hormone biology and this disease. Specifically, data on the incidence of RA as well as life cycle changes in serum androgenic-anabolic (A-A) and sex hormone levels suggest important risk correlations. Furthermore, HLA-susceptibility markers for RA, gender, menopause and older age are all factors which significantly relate to the risk of developing RA and each has been shown to associate with sex hormone status. Whether or not HPG-AA hormonal status may modulate RA risk (or its course) primarily and independently or merely be predictive markers of other biological mechanisms was critically considered and requires further study. Sex hormone influences on cellular and humoral immunological reactivity and vascular pathogenetic mechanisms in RA were summarized. Androgens generally suppress immunoreactivity and cartilage responses to inflammation-mediated injury processes and may enhance synovial macrophage-like lining cell apoptosis. Oestrogens generally enhance immunoreactivity, offer some protection to inflammation-mediated cartilage damage (but less than androgens) and may inhibit apoptosis in certain in vitro cell models. Scant information is available on the balance of sex hormones (and glucocorticoids) in RA or its presumed pathogenetic mechanisms. Data were reviewed which support the concept of a spectrum of androgenicity in the normal population, particularly among women. A simplified schema of trophic and tropic steroidogenic mechanisms was proposed which could influence androgenic-anabolic (A-A) status and might relate to RA. Serum concentrations of DHAS (mumol/l), T (nmol/l) and O2 (pmol/l) span several orders of magnitude in normal physiology. The effects of alterations in the individual levels of these sex hormones and deviations from their normal physiological balance are not well understood. Critical attention to their biological functions is needed in RA as well as in health and disease generally. Such focused clinical and experimental investigations of HPG-AA functions promise to clarify the complex physiopathology of RA and contribute to its improved long-term management.

Adrenal Glands↗
PubMed1996

A randomized trial of testosterone therapy in males with rheumatoid arthritis.

Thirty-five male patients, aged 34-79 yr, with definite rheumatoid arthritis (RA) were recruited from out-patient clinics and randomized to receive monthly injections of testosterone enanthate 250 mg or placebo as an adjunct therapy for 9 months. Endpoints included disease activity parameters and bone mineral density (BMD). At baseline, there were negative correlations between the ESR and serum testosterone (r = -0.42, P < 0.01) and BMD (hip, r = -0.65, P < 0.01). A total of 29.6% of all patients had at least one vertebral fracture, most having multiple fractures. Back pain, however, was not more prevalent in fracture patients (55% vs 50%). Disease activity was significantly higher in the fracture group (joint score P < 0.05, rheumatoid factor P < 0.01). Thirty patients completed the trial, 15 receiving testosterone and 15 receiving placebo. There were significant rises in serum testosterone, dihydrotestosterone and oestradiol in the treatment group. There was no significant effect of treatment on disease activity overall, five patients receiving testosterone underwent a "flare'. Differences in mean BMD following testosterone or placebo were non-significant (spine: +1.2% vs -1.1%; femur: -0.3% vs +0.3%). There was no suggestion of a positive effect of testosterone on disease activity in men with RA.

Adult↗
PubMed1994

Direct degradation of articular cartilage by rheumatoid synovial fluid: contribution of proteolytic enzymes.

OBJECTIVE: To test the effects of synovial fluids (SF) on human cartilage in an in vitro model. METHODS: Freshly collected SF were incubated with cryostat sections of articular cartilage, and glycosaminoglycan (GAG) loss determined by microdensitometry after alcian blue staining. RESULTS: Of 20 rheumatoid SF, 11 induced significant GAG loss compared with only 3 out of 15 osteoarthritic SF. The effect of rheumatoid fluids appeared to be related to disease activity. GAG loss was partially prevented by a broad spectrum serine protease inhibitor and a specific elastase inhibitor. Cartilage degrading activity was lost on storage which may explain why it has not been widely reported before. CONCLUSION: Rheumatoid SF can directly degrade cartilage through the action of proteases. There is an involvement of serine proteases, elastase in particular.

Adult↗
PubMed1994

The influence of sex in arthritis: is cartilage an overlooked factor?

Sex emerges as a predominant risk and prognostic factor from epidemiological studies in a variety of rheumatic diseases. Investigations into the underlying mechanisms stress sex related differences in immune and inflammatory responses. Cartilage destruction is an essential feature of most arthropathies and plays an essential role in the symptomatology and progression of arthritis. Based on published evidence and recent experimental observations, we explore the possibility that sex differences in articular cartilage may be an important, though unrecognized, factor in the effects of sex and related hormones in the progression of articular disease.

Animals↗
PubMed1994

Sex differences in inflammation induced cartilage damage in rodents. The influence of sex steroids.

OBJECTIVE: To investigate sex differences in granulomatous inflammation and its effects upon articular cartilage and to assess the potential role of sex steroids in the process. METHODS: The cotton-pellet cartilage implant model was used with male and female mice in the presence and absence of gonadectomy and hormone replacement. The effects of granulomatous tissue upon articular cartilage was assessed and tissue content of interleukin 1 (IL-1) was determined. The expression of sex hormone receptors in inflammatory tissue was investigated by immunocytochemistry. RESULTS: Female mice showed a higher ability than males to degrade cartilage irrespective of the sex of the cartilage implanted. Gonadectomy resulted in a significant acceleration of cartilage damage in both sexes, which was reverted by estrogen replacement in females and androgen replacement in males. Female granulomata had significantly higher IL-1 content than those from males. Gonadectomy was associated with an increased IL-1 content in males but not in females, the effects being abolished by androgen replacement in males. Estrogen and androgen receptors were identified in inflammatory cells from the granulomatous tissue. CONCLUSION: Our data demonstrate that sex hormones affect inflammation induced cartilage degradation in male and female mice probably through the modulation of cytokine production and release in the granulomatous tissue. Further investigation on the effects of sex steroids in inflammation induced cartilage degradation may help elucidate their pathogenic role and therapeutic potential in human disease.

Animals↗
PubMed1993

Protective effect of androgens against inflammation induced cartilage degradation in male rodents.

OBJECTIVES: Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents. METHODS: An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals. RESULTS: Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage. CONCLUSIONS: Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability.

Androgens↗
PubMed1993

Sex steroids affect glucocorticoid response to chronic inflammation and to interleukin-1.

The influence of gender and sex hormones upon both the hypothalamic-pituitary-adrenal (HPA) axis and the immune and inflammatory responses is well recognized, but it is not clear to what extent the two effects are interdependent. We have investigated this interaction using a chronic inflammation model. Corticosterone levels were measured in mature BALB/c male and female mice, which were intact, sham-operated or gonadectomized. No significant differences were found between groups in baseline corticosterone, but systemic inflammation (cotton-induced granulomas) resulted in stimulation of the HPA axis in a reproducible pattern. Corticosterone levels were higher in sham-operated females than in males, but gonadectomy had opposing effects in the two genders, resulting in reduced levels in females but significantly increased levels in males. A similar pattern emerged after stimulation by ether exposure or injection of interleukin-1 beta. In the chronic inflammatory model, replacement of ovariectomized females with physiological levels of progesterone restored a response similar to that of intact females. Physiological levels of 5 alpha-dihydrotestosterone prevented the increase in corticosterone levels caused by castration in males and also resulted in reduced corticosterone levels in sham-operated females. Oestradiol treatment did not affect corticosterone levels. Release of interleukin-1 by peritoneal macrophages from intact and gonadectomized mice with chronic inflammation followed a similar pattern, females releasing more than males. These data suggest a complex inter-relationship between sex steroids, inflammatory stimuli and the HPA axis, such that females have a greater tendency than males to generate activating signals and in addition have a greater sensitivity to such factors.

Animals↗
PubMed1992

The role of pregnancy in the course and aetiology of rheumatoid arthritis.

The aetiology of rheumatoid arthritis (RA) is unknown, although being female is generally recognized as the most important independent risk factor, the disease being 2 to 3 times more frequent in females than in males. The dramatic effect of pregnancy in rheumatoid arthritis has been documented for over 50 years. This review examines the evidence and possible mechanisms by which pregnancy modifies the disease process and may alter predisposition to the development of RA in later life.

Arthritis, Rheumatoid↗