Effects of glucocorticoids on weight change during the treatment of Wegener's granulomatosis

Objective Weight gain is a side effect of glucocorticoid (GC) use, but the natural history and health implications of changes in weight that occur during the treatment of inflammatory disease are not understood. Methods We evaluated data from the Wegener's Granulomatosis Etanercept Trial. Patients were categorized according to clinical outcome at 1 year: remission (no disease flares), single flare, or multiple flares. Risk factors for gaining ≥10 kg were examined in multivariate models. Results Weights at baseline and 1 year were available for 157 (93%) of the 168 patients analyzed. During year 1, the mean cumulative prednisone dosage in the multiple flares subgroup was 7.9 gm, compared with 6.0 gm and 3.9 gm in the single flare and remission subgroups, respectively ( P 10 kg in the first year of treatment. The quantity of weight gained by patients during treatment has potential future health implications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58632/1/23561_ftp.pd

Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality associated with cardiometabolic disorders including dyslipidaemia, insulin resistance, and cachectic obesity. Tumour necrosis factor inhibitors and interleukin 6 receptor blocker licensed for the treatment of RA decrease inflammation and could thus improve cardiovascular risk, but their effects on body composition and metabolic profile need to be clarified. We investigated the effects of tocilizumab (TCZ), a humanized anti‐interleukin 6 receptor antibody, on body composition and metabolic profile in patients treated for RA. Methods Twenty‐one active RA patients treated with TCZ were included in a 1 year open follow‐up study. Waist circumference, body mass index, blood pressure, lipid profile, fasting glucose, insulin, serum levels of adipokines and pancreatic/gastrointestinal hormones, and body composition (dual‐energy X‐ray absorptiometry) were measured at baseline and 6 and 12 months of treatment. At baseline, RA patients were compared with 21 non‐RA controls matched for age, sex, body mass index, and metabolic syndrome. Results Compared with controls, body composition was altered in RA with a decrease in total and appendicular lean mass, whereas fat composition was not modified. Among RA patients, 28.6% had a skeletal muscle mass index below the cut‐off point for sarcopaenia (4.8% of controls). After 1 year of treatment with TCZ, there was a significant weight gain without changes for fat mass. In contrast, an increase in lean mass was observed with a significant gain in appendicular lean mass and skeletal muscle mass index between 6 and 12 months. Distribution of the fat was modified with a decrease in trunk/peripheral fat ratio and an increase in subcutaneous adipose tissue. No changes for waist circumference, blood pressure, fasting glucose, and atherogenic index were observed. Conclusions Despite weight gain during treatment with TCZ, no increase in fat but a modification in fat distribution was observed. In contrast, muscle gain suggests that blocking IL‐6 might be efficient in treating sarcopaenia associated with RA

Locomotion and muscle mass measures in a murine model of collagen-induced arthritis

Background: Rheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and can in part be explained by a decreased physical activity. The murine collagen induced arthritis (CIA) model has been proven to be a useful model in RA research since it shares many immunological and pathological features with human RA. The present study explored the interactions between arthritis development, locomotion and muscle mass in the CIA model. Methods: CIA was induced in male DBA/1 mice. Locomotion was registered at different time points by a camera and evaluated by a computerized tracing system. Arthritis severity was detected by the traditionally used semi-quantitative clinical scores. The muscle mass of the hind-legs was detected at the end of the study by weighing. A methotrexate (MTX) intervention group was included to study the applicability of the locomotion and muscle mass for testing effectiveness of interventions in more detail. Results: There is a strong correlation between clinical arthritis and locomotion. The correlations between muscle mass and locomotion or clinical arthritis were less pronounced. MTX intervention resulted in an improvement of disease severity accompanied by an increase in locomotion and muscle mass. Conclusion: The present data demonstrate that registration of locomotion followed by a computerized evaluation of the movements is a simple non invasive quantitative method to define disease severity and evaluate effectiveness of therapeutic agents in the CIA model.

Weight reduction is not a major reason for improvement in rheumatoid arthritis from lacto-vegetarian, vegan or Mediterranean diets

OBJECTIVES: Several investigators have reported that clinical improvements of patients with rheumatoid arthritis (RA), from participating in therapeutic diet intervention studies, have been accompanied by loss of body weight. This has raised the question whether weight reduction per se can improve RA. In order to test this hypothesis, three previously conducted diet intervention studies, comprising 95 patients with RA, were pooled. Together with Age, Gender, and Disease Duration, change during the test period in body weight, characterised dichotomously as reduction or no reduction (dichoΔBody Weight), as well as Diet (dichotomously as ordinary diet or test diet), were the independent variables. Dependent variables were the difference (Δ) from baseline to conclusion of the study in five different disease outcome measures. ΔESR and ΔPain Score were both characterised numerically and dichotomously (improvement or no improvement). ΔAcute Phase Response, ΔPhysical Function, and ΔTender Joint Count were characterised dichotomously only. Multiple logistic regression was used to analyse associations between the independent and the disease outcome variables. RESULTS: Statistically significant correlations were found between Diet and three disease outcome variables i.e. ΔAcute-Phase Response, ΔPain Score, and ΔPhysical Function. Δ Body Weight was univariately only correlated to ΔAcute-Phase Response but not significant when diet was taken into account. CONCLUSION: Body weight reduction did not significantly contribute to the improvement in rheumatoid arthritis when eating lacto-vegetarian, vegan or Mediterranean diets

Immunoreactivity of the serotonin-like and FMRF-amide-like nervous systems of four gnesiotrochan rotifers

Reorganization of the nervous system during metamorphosis is a common phenomenon across taxa (species through phyla). In phylum Rotifera, sessile species belonging to the superorder Gnesiotrocha metamorphose from free-swimming larvae into sessile adults. Once mature, gnesiotrochan rotifers display an intricate corona or infundibulum associated with lifestyle modalities and feeding behaviors. Here, I examine serotonin-like immunoreactivity (SLIR) and FMRF-amide-like immunoreactivity (FLIR) of the gnesiotrochans Lacinularia flosculosa, Collotheca ferox, and Acyclus inquietus with a focus on life stage and sex. Based on previous research, I hypothesize that 1) innervation of the larval nervous system will vary according to the lifestyle constraints observed in each species, and 2) innervation of the nervous system in male rotifers will vary from the adult female and will be similar to the female larvae. Neural features were observed using immunohistochemistry and confocal laser scanning microscopy to provide renditions of SLIR and FMRF-amide-like structures. The SLIR and FLIR nervous systems of L. flosculosa larvae showed a reduction of brain perikarya as larvae mature into adults. The nervous system of adult A. inquietus showed an absence of two SLIR varicosities, and the absence of two FLIR longitudinal neurites extending posteriorly into the larval foot. Contrastingly, the number FLIR brain perikarya increased in the nervous system of adult C. ferox. This may result from species-specific lifestyle adaptations (i.e., coloniality (L. flosculosa) versus feeding behaviors exhibited by predatory rotifers (C. ferox)), or lifestyle constraints associated with sessility. To further understand if the variation of SLIR/FLIR nervous system elements occurred because of metamorphosis, the direct developing gnesiotrochan rotifer Filinia longiseta was observed (neonate/adult and male/female). As expected, the reorganization of nervous system elements was not observed. However, similarities between the nervous system of males and females were observed. Similar to results of previous studies, SLIR structures comprising the nervous system are species-specific. The nervous system of male L. flosculosa, C. ferox, and A. inquietus was comparable to the larval stage, while the nervous system of male F. longiseta was comparable to the female. This may correlate with their morphologies or behaviors associated with motility. This phenomenon aligns with the concept of progenesis and suggests that the lifestyle constraints associated with the male life history may influence the development and evolution of their nervous system. This study represents the first examination of the relationships between sexual dimorphism and the nervous system in gnesiotrochan rotifers. The knowledge collected here enhances our comprehension of specific nervous system characteristics that may be essential to the diverse lifestyle demands associated with adulthood and sexes within Gnesiotrocha

Immunoreactivity of the Serotonin-Like and FMRF-Amide-Like Nervous Systems of Four Gnesiotrochan Rotifers

Reorganization of the nervous system during metamorphosis is a common phenomenon across taxa (species through phyla). In phylum Rotifera, sessile species belonging to the superorder Gnesiotrocha metamorphose from free-swimming larvae into sessile adults. Once mature, gnesiotrochan rotifers display an intricate corona or infundibulum associated with lifestyle modalities and feeding behaviors. Here, I examine serotonin-like immunoreactivity (SLIR) and FMRF-amide-like immunoreactivity (FLIR) of the gnesiotrochans Lacinularia flosculosa, Collotheca ferox, and Acyclus inquietus with a focus on life stage and sex. Based on previous research, I hypothesize that 1) innervation of the larval nervous system will vary according to the lifestyle constraints observed in each species, and 2) innervation of the nervous system in male rotifers will vary from the adult female and will be similar to the female larvae. Neural features were observed using immunohistochemistry and confocal laser scanning microscopy to provide renditions of SLIR and FMRF-amide-like structures. The SLIR and FLIR nervous systems of L. flosculosa larvae showed a reduction of brain perikarya as larvae mature into adults. The nervous system of adult A. inquietus showed an absence of two SLIR varicosities, and the absence of two FLIR longitudinal neurites extending posteriorly into the larval foot. Contrastingly, the number FLIR brain perikarya increased in the nervous system of adult C. ferox. This may result from species-specific lifestyle adaptations (i.e., coloniality (L. flosculosa) versus feeding behaviors exhibited by predatory rotifers (C. ferox)), or lifestyle constraints associated with sessility. To further understand if the variation of SLIR/FLIR nervous system elements occurred because of metamorphosis, the direct developing gnesiotrochan rotifer Filinia longiseta was observed (neonate/adult and male/female). As expected, the reorganization of nervous system elements was not observed. However, similarities between the nervous system of males and females were observed. Similar to results of previous studies, SLIR structures comprising the nervous system are species-specific. The nervous system of male L. flosculosa, C. ferox, and A. inquietus was comparable to the larval stage, while the nervous system of male F. longiseta was comparable to the female. This may correlate with their morphologies or behaviors associated with motility. This phenomenon aligns with the concept of progenesis and suggests that the lifestyle constraints associated with the male life history may influence the development and evolution of their nervous system. This study represents the first examination of the relationships between sexual dimorphism and the nervous system in gnesiotrochan rotifers. The knowledge collected here enhances our comprehension of specific nervous system characteristics that may be essential to the diverse lifestyle demands associated with adulthood and sexes within Gnesiotrocha