Effects of immune supplementation and immune challenge on oxidative status and physiology in a model bird:implications for ecologists

One route to gain insight into the causes and consequences of ecological differentiation is to understand the underlying physiological mechanisms. We explored the relationships between immunological and oxidative status and investigated how birds cope physiologically with the effects of immune-derived oxidative damage. We successively implemented two experimental manipulations to alter physiological status in a model bird species: the homing pigeon (Columba livia). The first manipulation, an immune supplementation, was achieved by oral administration of lysozyme, a naturally occurring and non-specific antimicrobial enzyme. The second manipulation, an immune challenge, took the form of an injection with lipopolysaccharide, a bacterial endotoxin. Between groups of lysozyme-treated and control birds, we compared lipopolysaccharide-induced changes in reactive oxygen metabolites, total antioxidant capacity, haptoglobin, oxygen consumption, body mass and cloacal temperature. Lysozyme supplementation intensified the lipopolysaccharide-induced inflammatory response and generated short-term oxidative and metabolic costs. We identified significant interactions between immune supplementation and immune challenge in terms of reactive oxygen metabolites, haptoglobin and oxygen consumption. Our study provides alternative interpretations of differences in oxidative and immunological indices and demonstrates that these indices can also fluctuate and interact across very short time scales, reflecting something akin to current ‘health status’ or ‘physiological condition’. These ephemeral effects highlight the need to broadly consider current physiological condition when drawing conclusions that relate physiology to ecology and evolution

Asymptomatic Oosteolysis of Ribs and Clavicles in Progressive Systemic Sclerosis

The association of severe osteolysis of clavicles and ribs in a patient with progressive systemic sclerosis is reported. The disappearance of the clavicles and upper ribs was not associated with any symptoms. The possible causes of this uncommon association are discussed

Does Colchicine really work? The results of the first controlled study in acute gout

We have performed the first controlled study of colchicine in acute gout, to determine its efficacy and toxicity, and to define the natural history of acute gout. Two-thirds of colchicine-treated patients improved after 48 hours, but only one-third of the patients receiving placebo demonstrated similar improvement. The colchicine-treated patients responded earlier; significant differences from placebo were shown after 18-30 hours. All patients given colchicine developed diarrhea after a median time of 24 hours (mean dose of colchicine 6.7 mg). This side effect occurred before relief of pain in most patients

Capillary Microscopy in Eosinophilic Fasciitis

Capillary microscopy was performed on 19 patients with eosinophilic fasciitis. These patients were compared with 13 individuals with progressive systemic sclerosis (scleroderma). Capillary patterns were normal in 16 of 19 (84%) eosinophilic fasciitis patients; 3 exhibited either borderline or nonspecific changes, and none showed a definite scleroderma pattern. In contrast, characteristic nailfold capillary changes, consisting of both dilatation and loss of capillaries, were present in 11 of 13 (85%) scleroderma patients; the remaining 2 showed scleroderma-type abnormalities of only 1 finger and were, therefore, classified as borderline. These results suggest that capillary microscopy may help to distinguish these 2 disorders.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37763/1/1780260507_ftp.pd

Male Systemic Sclerosis and Occupational Silica Exposure: A Population-Based Study

BACKGROUND: The continuing uncertainty about the silica-systemic sclerosis relationship led to the investigation of its role as a disease determinant in a large population-based study of systemic sclerosis. AIMS: To compare the frequency, socioeconomic and educational status, age-specific prevalence and duration of occupational silica exposure in males with and without systemic sclerosis. To assess the temporal relationship between exposure and disease onset. To estimate disease latency. To compare disease characteristics between silica-exposed and non-silica-exposed male cases. METHODS: The study was case-control in design. The exposure variable was occupational silica exposure as assessed by an occupational health officer blinded to case/control status and the outcome variable was systemic sclerosis. The employed instrument comprised either a standardised telephone questionnaire (interviewed cases and controls) or medical records (deceased or living-status-unknown cases). RESULTS: Sixty of 160 cases (37.5%) and 11 of 83 (13.3%) controls had occupational silica exposure (OR=3.93; 1.84-8.54). Comparison of data between 64 interviewed cases and all controls demonstrated initial occupational silica exposure occurring before age 40, comparable educational status but significantly different cumulative socioeconomic status with cases being over-represented in semi-skilled and unskilled occupations. Cross-sectional 'current' occupational data underestimated cumulative silica exposure by more than 50%. Silica exposure uniformly preceded onset of second disease symptoms and disease diagnosis. In most, it also preceded onset of first disease symptoms. Disease latency approximated two decades. No disease features distinguished silica-associated systemic sclerosis from idiopathic systemic sclerosis. The duration of silica exposure in the interviewed silica-exposed cases did not significantly exceed that of silica-exposed controls. CONCLUSIONS: Male systemic sclerosis displays socioeconomic dependence. Silica is a disease determinant in male systemic sclerosis, with disease features including a long latency and clinical characteristics indistinguishable from idiopathic disease. Cross-sectional 'current' occupational data underestimate cumulative occupational silica exposure

Unusual presentation of eosinophilic fasciitis: two case reports and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Eosinophilic fasciitis is an uncommon disorder with unknown etiology and a poorly understood pathogenesis. We present the cases of two patients with eosinophilic fasciitis with unusual presentation, and describe the clinical characteristics and laboratory findings related to them.</p> <p>Case presentation</p> <p>The first case involves a 29-year-old Turkish man admitted with pain, edema and induration of his right-upper and left-lower limbs. Unilateral edema and stiffness with prominent pretibial edema was noted upon physical examination. A high eosinophil count was found on the peripheral smear. The second case involves a 63-year-old Turkish man who had pain, edema, erythema, and itching on his upper and lower extremities, which developed after strenuous physical activity. He had cervical lymphadenopathy and polyarthritis upon physical examination, and rheumatoid factor and antinuclear antibody upon laboratory examination.</p> <p>Conclusion</p> <p>Eosinophilic fasciitis can present with various symptoms. When patients exhibit eosinophilia, arthralgia and myalgia, eosinophilic fasciitis should be considered as a possible diagnosis.</p

Connective tissue activation

Four normal (NF) and 4 scleroderma skin fibro-blast (SF) strains were compared with respect to 1) basal 14 C-glucosamine and 35 SO 4 -labeled glycosaminoglycan (GAG) synthesis, 2) responsiveness to autacoid mediators, and 3) performance following maximal stimulation. Under basal conditions, SF synthesized and secreted 2–3 times more radioactive hyaluronic acid than the NF ( P < 0.001); molecular volume by gel chromatography was similar and suggested a high molecular weight product. SF were essentially as responsive to normal lymphoid and platelet factors as were NF. No consistent qualitative or quantitative differences in sulfated GAG synthesis were noted between the 2 groups of cells. Incubation of NF and SF with a false “core protein” such as p-nitrophenyl-Β-D-xyloside suggested that synthesis of the core protein was rate limiting; SF and NF were equally facile in SO 4 -GAG chain synthesis in the presence of a Β-xyloside. SF appear to retain in vitro a partially activated state for many generations, at least with respect to hyaluronic acid synthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37761/1/1780261109_ftp.pd

Pathogenesis of Scleroderma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65784/1/j.1365-4362.1984.tb05678.x.pd

Familial Risk Estimation in Systemic Sclerosis

BACKGROUND: Familial systemic sclerosis has been rarely reported. Assumptions have therefore been made implying no familial disease aggregation. This study critically challenges the assumption using a methodical population-based epidemiological approach to quantify the prevalence and characteristics of familial systemic sclerosis. METHODS: In this retrospective cohort study the systemic sclerosis prevalence in first degree family members was compared between 715 systemic sclerosis patients (710 families) and 371 randomly ascertained age and gender group-matched general practice controls (371 families). These data, obtained by telephone questionnaire (living patients) or medical records review (deceased patients and untraceable patients of unknown living status), were validated, where necessary, and expressed in terms of relative risk, absolute risk and population point prevalence. RESULTS: Systemic sclerosis affecting first degree members was validated in ten of 710 families. Reporting of systemic disease in another four more distant family members, and the co-occurrence of systemic and localised disease in three families was also documented. Observed and expected disease subtype concordance was 80% (44-97%) and 68% respectively and the female predominance among familial cases was similar to that for non-familial disease. The risk of disease in a subsequent first degree relative was compared to the risk in an initial first degree family member. Its estimated magnitude was wide (11-158). However, use of population prevalence data to determine the expected number of systemic sclerosis patients in the negative cohorts' families suggests the higher estimate is more realistic. Despite the high magnitude, the absolute disease risk in first degree family members remained low--approximating 1%. The population prevalence of familial systemic sclerosis approximated 1.4/million. CONCLUSIONS: This study substantially increases the otherwise small list of documented instances of familial systemic sclerosis. More importantly, it quantifies the risk for the first time, ranking it as the disease's most powerful determinant identified to date

Particles for Local Delivery of Proteins Using Intra-Articular Route

Designing a vehicle for local delivery of proteins using intra-articular route is an attractive option to minimize the adverse effects associated with systemic exposure and to maximize the efficacy. Slowly dissolving silylated microparticles are designed with specific size and shape that are capable of extending the retention time of a model protein (bovine serum albumin) in the murine knee joint. No cytotoxicity is observed for the reconstituted formulation when tested against synovial fibroblasts and RAW 264.7 macrophages