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1.
Methods Mol Biol ; 2587: 467-478, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36401044

RESUMO

In vivo testing of glucocorticoid steroids in dystrophic mice offers important insights in benefits and risks of those drugs in the pathological context of muscular dystrophy. Frequency of dosing changes the spectrum of glucocorticoid effects on muscle and metabolic homeostasis. Here, we describe a combination of non-invasive and invasive methods to quantitatively discriminate the specific effects of intermittent (once-weekly) versus mainstay (once-daily) regimens on muscle fibrosis, muscle function, and metabolic homeostasis in murine models of Duchenne and limb-girdle muscular dystrophies.


Assuntos
Distrofia Muscular do Cíngulo dos Membros , Distrofia Muscular de Duchenne , Camundongos , Animais , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Modelos Animais de Doenças , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular do Cíngulo dos Membros/tratamento farmacológico , Distrofia Muscular do Cíngulo dos Membros/patologia
2.
Immunol Allergy Clin North Am ; 43(1): 159-168, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36411001

RESUMO

Mastocytosis is a rare neoplastic disorder of the mast cell lineage resulting in unregulated proliferation and activation of mast cells. Symptoms worsen in about one-third of pregnant patients. Treatment focuses on management of symptoms with antimediator therapy (H1 & H2 antihistamines, glucocorticoids, and epinephrine, if required). Medication selection requires care during labor and delivery. Although it is generally considered safe to use a medication patient tolerated before, some common medications may need to be avoided or used with caution (eg, codeine, morphine, nonsteroidal antiinflammatory drugs, vancomycin) if the patient does not have any history of exposure to them.


Assuntos
Mastocitose , Feminino , Gravidez , Humanos , Mastocitose/diagnóstico , Mastocitose/terapia , Mastócitos , Anti-Inflamatórios não Esteroides , Epinefrina , Glucocorticoides , Doenças Raras
3.
Gen Comp Endocrinol ; 330: 114150, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36349607

RESUMO

Among all the regulatory homeostatic networks in vertebrates, the activation of the hypothalamic-pituitaryadrenal axis during the stress response, has gained considerable attention, and the measurement of fecal glucocorticoids (FGC) has become an invaluable tool to assess adrenocortical activity related to stressful events in wild and captive animals. However, the use of FGC requires the validation of measurement techniques and the proper selection of the specific hormone according to the study species. The main objective of this study was to identify the dominant glucocorticoid (GC) hormone in the stress response of black-tailed prairie dogs (Cynomys ludovicianus) in an arid grassland of Chihuahua, Mexico. A capture stress challenge in the field was developed to determine if the levels of glucocorticoids (cortisol and corticosterone) both in serum and fecal samples could be attributed to stress in Cynomys ludovicianus. The samples were analysed with the technique of liquid phase radioimmunoassay , and this study showed that both cortisol and corticosterone are present at measurable levels in serum and fecal samples of black-tailed prairie dogs. We found that both GCs were present in similar concentrations in serum, however, corticosterone concentration in fecal samples was higher than cortisol. Likewise, biochemical validations performed in this study to test the assay reached acceptable levels of reliability. Therefore, we confirm that fecal analysis can be implemented as a method to measure stress responses in wild prairie dogs.


Assuntos
Corticosterona , Glucocorticoides , Animais , Hidrocortisona , México , Reprodutibilidade dos Testes , Sciuridae
4.
Gen Comp Endocrinol ; 330: 114141, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36272446

RESUMO

Living in variable and unpredictable environments, organisms face recurrent stressful situations. The endocrine stress response, which includes the secretion of glucocorticoids, helps organisms to cope with these perturbations. Although short-term elevations of glucocorticoid levels are often associated with immediate beneficial consequences for individuals, long-term glucocorticoid elevation can compromise key physiological functions such as immunity. While laboratory works highlighted the immunosuppressive effect of long-term elevated glucocorticoids, it remains largely unknown, especially in wild animals, whether this relationship is modulated by individual and environmental characteristics. In this study, we explored the co-variation between integrated cortisol levels, assessed non-invasively using faecal cortisol metabolites (FCMs), and 12 constitutive indices of innate, inflammatory, and adaptive immune functions, in wild roe deer living in three populations with previously known contrasting environmental conditions. Using longitudinal data on 564 individuals, we further investigated whether age and spatio-temporal variations in the quantity and quality of food resources modulate the relationship between FCMs and immunity. Negative covariation with glucocorticoids was evident only for innate and inflammatory markers of immunity, while adaptive immunity appeared to be positively or not linked to glucocorticoids. In addition, the negative covariations were generally stronger in individuals facing harsh environmental constraints and in old individuals. Therefore, our results highlight the importance of measuring multiple immune markers of immunity in individuals from contrasted environments to unravel the complex relationships between glucocorticoids and immunity in wild animals. Our results also help explain conflicting results found in the literature and could improve our understanding of the link between elevated glucocorticoid levels and disease spread, and its consequences on population dynamics.


Assuntos
Cervos , Animais , Cervos/metabolismo , Animais Selvagens/metabolismo , Glucocorticoides/metabolismo , Hidrocortisona/metabolismo , Imunidade Adaptativa
5.
Gen Comp Endocrinol ; 330: 114147, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36272448

RESUMO

African penguins (Spheniscus demersus) are an endangered species, with approximately 70,000 mature adults remaining in the wild. Population loss is linked to a combination of environmental and anthropogenic stressors. The aim of the study was to validate a commercially available enzyme immunoassay (EIA) to assess adrenal activity and measure the response to stressors in the feces of African penguins. Fecal samples (n = 609) were collected from 12 African penguins housed at Mystic Aquarium throughout their natural lifecycle, including breeding and molt, where measurable changes in fecal glucocorticoid metabolite (FGM) levels are predicted to occur. Fecal samples collected post-veterinary exam were used for biological validation. Longitudinal analysis shows a significant difference (p = <0.0001) between the average FGM levels during baseline and breeding season, 33.97 ± 1.30 ng/g and 50.21 ± 3.18 ng/g, respectively. Females displayed significantly higher FGM levels than males during both baseline (p = 0.0386; females = 38.80 ± 2.19 ng/g; males = 29.34 ± 1.37 ng/g) and breeding periods (p = 0.0175; females = 57.53 ± 4.84 ng/g; males = 42.69 ± 3.95 ng/g). Average FGM levels decreased significantly over the three-week molting period, from 85.40 ± 20.35 ng/g at week one to 20.23 ± 5.30 ng/g at week three. A seasonal difference in FGM levels was observed in both male and female fecal samples, with Fall having the highest average FGM levels, 54.38 ± 3.64 ng/g, and Summer the lowest, 30.87 ± 2.21 ng/g. General linear mixed model analysis determined that lifecycle (females) and visitor presence (males) were the two factors which best explained the variation in FGM levels observed, however neither factor was found to be significant. These results show FGM analysis can detect physiologically meaningful changes in endocrine activity in African penguins and can be used to monitor health for penguins in aquaria and in the wild, thus contributing to conservation efforts for the survival of the species.


Assuntos
Spheniscidae , Animais , Masculino , Feminino , Spheniscidae/metabolismo , Glucocorticoides/metabolismo , Técnicas Imunoenzimáticas , Fezes/química , Espécies em Perigo de Extinção
6.
Gen Comp Endocrinol ; 330: 114126, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36122793

RESUMO

Alzheimer's disease (AD) is a progressive, dementing, whole-body disorder that presents with decline in cognitive, behavioral, and emotional functions, as well as endocrine dysregulation. The etiology of AD is not fully understood but stress- and anxiety-related hormones may play a role in its development and trajectory. The glucocorticoid cascade hypothesis posits that levels of glucocorticoids increase with age, leading to dysregulated negative feedback, further elevated glucocorticoids, and resulting neuropathology. We examined the impact of age (from 2 to 10 months) and stressor exposure (predator odor) on hormone levels (corticosterone and ghrelin), anxiety-like behavior (open field and light dark tests), and memory-related behavior (novel object recognition; NOR), and whether these various measures correlated with neuropathology (hippocampus and cortex amyloid beta, Aß) in male and female APPswe/PS1dE9 transgenic and non-transgenic mice. Additionally, we performed exploratory analyses to probe if the open field and light dark test as commonly used tasks to assess anxiety levels were correlated. Consistent with the glucocorticoid cascade hypothesis, baseline corticosterone increased with age. Predator odor exposure elevated corticosterone at each age, but in contrast to the glucocorticoid cascade hypothesis, the magnitude of stressor-induced elevations in corticosterone levels did not increase with age. Overall, transgenic mice had higher post-stressor, but not baseline, corticosterone than non-transgenic mice, and across both genotypes, females consistently had higher (baseline and post-stressor) corticosterone than males. Behavior in the open field test primarily showed decreased locomotion with age, and this was pronounced in transgenic females. Anxiety-like behaviors in the light dark test were exacerbated following predator odor, and female transgenic mice were the most impacted. Compared to transgenic males, transgenic females had higher Aß concentrations and showed more anxiety-like behavior. Performance on the NOR did not differ significantly between genotypes. Lastly, we did not find robust, statistically significant correlations among corticosterone, ghrelin, recognition memory, anxiety-like behaviors, or Aß, suggesting outcomes are not strongly related on the individual level. Our data suggest that despite Aß accumulation in the hippocampus and cortex, male and female APPswePS1dE9 transgenic mice do not differ robustly from their non-transgenic littermates in physiological, endocrine, and behavioral measures at the range of ages studied here.


Assuntos
Doença de Alzheimer , Glucocorticoides , Camundongos , Masculino , Feminino , Animais , Corticosterona , Grelina , Peptídeos beta-Amiloides/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Ansiedade , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Camundongos Transgênicos , Envelhecimento/fisiologia , Estresse Psicológico
7.
Domest Anim Endocrinol ; 82: 106767, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36244193

RESUMO

Health and welfare are inextricably linked within efficient and sustainable dairy production, and several potential risk factors may affect the well-being of dairy cows, including chronic stress. Although auditory stimuli could be used as a tool to decrease the potential stress that cows might experience, it is seldom applied to livestock production systems due to the perception that enrichment is an unnecessary expense. This study aimed to explore the effect of auditory stimuli as a form of enrichment in a Holstein herd by monitoring fecal glucocorticoid metabolite (fGCM) concentrations (a non-invasive, stress-associated biomarker). Cow activity level and milk yield were also measured. Nine cows in their second and third lactation were divided into 3 groups, using a Latin Square experimental design, exposing each cow group to each of the 3 treatments, namely constant exposure (CE), limited exposure (LE), and no exposure (NE) to classical music. FGCMs were quantified using a group-specific enzyme immunoassay detecting 11,17-dioxoandrostanes. Compared to LE and NE animals, cows exposed to constant music had significantly lower fGCM concentrations (P = 0.012), as well as higher milk yields (P < 0.0001) and lowered activity levels during the morning (P = 0.005) and the evening activity period (P = 0.048). These findings indicate that auditory stimuli in the form of classical music may have a positive effect on the welfare of cows as well as milk yield, which hold economic benefits for the producer and potentially reduces the number of cows needed for profitable production.


Assuntos
Glucocorticoides , Leite , Feminino , Bovinos , Animais , Glucocorticoides/metabolismo , Lactação , Fezes , Dieta/veterinária
8.
Comput Math Methods Med ; 2022: 2935992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35341003

RESUMO

Background: To evaluate the clinical effects and safety of glucocorticoids for patients with nonarteritic anterior ischemic optic neuropathy (NAION). Methods: The databases MEDLINE, Embase, PubMed, Cochrane Database, and Web of Science were used to search for the relevant studies, and full-text articles that reported on the evaluation of glucocorticoids vs. no-treatment or placebo for patients with NAION. Review Manager 5.4 was used to estimate the pooled effects of the results among selected studies. Forest plots, funnel plots, and Begg's rank correlation were also performed on the included articles. Results: A total of 983 patients were contained in the 9 studies that satisfied the eligibility criteria. The meta-analysis showed that, compared with the control group, the glucocorticoid group had significantly improved the VA (MD: -0.25, 95% CI [-0.45, -0.05], P = 0.02), VF (MD: -0.50, 95% CI [-0.94, -0.07], P = 0.02), and RNFL (MD: -14.10, 95% CI [-26.41, -1.79], P = 0.02) in NAION patients and had a high improvement rate of VA (RR 1.31, 95% CI [1.12, 1.52], P = 0.0005). No significant publication bias was observed in our study. Discussion. Our research preliminarily confirmed the effectiveness of glucocorticoids for NAION treatment, but more high-quality RCTs focusing on the hormone adverse reactions should be performed to verify our conclusions.


Assuntos
Glucocorticoides , Neuropatia Óptica Isquêmica , Glucocorticoides/uso terapêutico , Humanos , Neuropatia Óptica Isquêmica/tratamento farmacológico
9.
Mol Cell Endocrinol ; 544: 111541, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973370

RESUMO

Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) accounts for a big portion of non-traumatic ONFH; nevertheless, the pathogenesis has not yet been fully understood. GC-induced endothelial dysfunction might be a major contributor to ONFH progression. The Gene Expression Omnibus (GEO) dataset was analyzed to identify deregulated miRNAs in ONFH; among deregulated miRNAs, the physiological functions of miR-122-5p on ONFH and endothelial dysfunction remain unclear. In the present study, miR-122-5p showed to be under-expressed within GC-induced ONFH femoral head tissues and GC-stimulated bone microvascular endothelial cells (BMECs). In human umbilical vein endothelial cells (HUVECs) and BMECs, GC stimulation significantly repressed cell viability, promoted cell apoptosis and increased the mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IFN-γ. After overexpressing miR-122-5p, GC-induced endothelial injuries were attenuated, as manifested by rescued cell viability, cell migration, and tube formation capacity. Regarding the BMP signaling, GC decreased the protein levels of BMP-2/6/7 and SMAD-1/5/8, whereas miR-122-5p overexpression significantly attenuated the inhibitory effects of GC on these proteins. Online tool and experimental analyses revealed the direct binding between miR-122-5p and GREM2, a specific antagonist of BMP-2. In contrast to miR-122-5p overexpression, GREM2 overexpression aggravated GC-induced endothelial injury; GREM2 silencing partially eliminated the effects of miR-122-5p inhibition on GC-stimulated HUVECs and BMECs. Finally, GREM2 silencing reversed the suppressive effects of GC on BMP-2/6/7 and SMAD-1/5/8, and attenuated the effects of miR-122-5p inhibition on these proteins upon GC stimulation. Conclusively, the present study demonstrates a miR-122-5p/GREM2 axis modulating the GC-induced endothelial damage via the BMP/SMAD signaling. Considering the critical role of endothelial function in ONFH pathogenesis, the in vivo role and clinical application of the miR-122-5p/GREM2 axis is worthy of further investigation.


Assuntos
Glucocorticoides , MicroRNAs , Apoptose , Citocinas/metabolismo , Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/patologia , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais
10.
Ophthalmic Surg Lasers Imaging Retina ; 53(11): 612-618, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36378615

RESUMO

BACKGROUND AND OBJECTIVES: To explore the incidence of adverse events after bilateral same-day intravitreal 0.7-mg dexamethasone implant (SDIDI) injections. MATERIALS AND METHODS: We performed an IRB approved, single-center, retrospective review of patients receiving bilateral SDIDI injections from January 1, 2016 to October 31, 2021 and reviewed adverse events that occurred within 3 months of injection. RESULTS: A total of 206 bilateral (412 eyes) SDIDI injections were performed in 59 patients. Ocular hypertension or the addition of intraocular pressure (IOP) lowering drops occurred in 121 (29.4%) eyes after IDI. Two (0.5%) eyes required glaucoma drainage surgeries. Of the 117 phakic eyes, 32 (27.4%) had progression of cataract or cataract extraction. There were two (0.5%) episodes of vitreous hemorrhage and one (0.2%) retinal tear with retinal detachment. There were no cases of endophthalmitis. CONCLUSION: Serious complication rates after bilateral same-day IDI injections appears low. Increased IOP that requires intervention can occur. [Ophthalmic Surg Lasers Imaging Retina 2022;53:612-618.].


Assuntos
Glaucoma , Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Dexametasona/efeitos adversos , Injeções Intravítreas , Glucocorticoides/efeitos adversos , Implantes de Medicamento/efeitos adversos , Acuidade Visual , Pressão Intraocular , Glaucoma/etiologia , Estudos Retrospectivos
11.
BMC Ophthalmol ; 22(1): 445, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36401233

RESUMO

BACKGROUND: We would assess the efficacy of intravitreal injection of triamcinolone acetonide IVTA combined with standard phacoemulsification on the central subfield macular thickness (CSMT), the progression of diabetic retinopathy (DR), and the corrected distant visual acuity (CDVA) in type 2 diabetic patients. METHODS: In this prospective single-blinded randomized clinical trial we recruited patients with type 2 diabetes who were eligible for cataract surgery. The patients were randomly assigned to two groups. The case group received an intravitreal IVTA at the end of phacoemulsification, and the control group had routine surgery. CSMT, progression of DR, CDVA, IOP, and adverse events including endophthalmitis were compared between the groups preoperatively and at 1, 3, and 6 months postoperatively. RESULTS: Among a total of 66 patients that were treated within the study period, 50 patients were included in the final analysis. The case group comprised 21 eyes, and the control group included 29 eyes. Regression models and corrected ANOVA test for repeated measures showed a significant reduction in CSMT at 3 and 6 months postoperatively, which was most significant when the preoperative CSMT was ≥300 µm, with a cut-off value of 347.3 µm in the case group (p < 0.000). DR progression was halted in the case group at 6 months with 52.38% of patients having their DR classified as moderate (P = 0.012). CDVA was significantly improved from baseline 6/60 (logMAR 1.0) pre-op to 6/6 (logMAR 0.00) at 6 months post-op in the case group, and from baseline 6/120 (logMAR 1.3) pre-op to 6/12 (logMAR 0.3) at 6 months post-op in the control group. The gain in visual acuity was significantly higher in the case group at all study points (p < 0.001). No significant rise in IOP was observed at any study point in both groups (p = 0.23 > 0.05). No endophthalmitis was recorded. CONCLUSIONS: Diabetic patients benefit significantly from cataract surgery. This study supports IVTA injection at the end of phacoemulsification in diabetic patients. Triamcinolone is an affordable (which is of particular importance in low-income countries as per our setting), and relatively safe "phaco-enhancer". TRIAL REGISTRATION: NCT05413330. Initial release 10/06/2022. Unique Protocol ID: UDMS-Opthal-01-2022.


Assuntos
Catarata , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Edema Macular , Facoemulsificação , Humanos , Injeções Intravítreas , Edema Macular/etiologia , Edema Macular/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Estudos Prospectivos , Glucocorticoides , Tomografia de Coerência Óptica , Triancinolona Acetonida/uso terapêutico , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Catarata/induzido quimicamente
12.
Front Endocrinol (Lausanne) ; 13: 1037177, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407312

RESUMO

Steroid hormone receptors (SHRs) belong to a large family of ligand-activated nuclear receptors that share certain characteristics and possess others that make them unique. It was thought for many years that the specificity of hormone response lay in the ligand. Although this may be true for pure agonists, the natural ligands as progesterone, corticosterone and cortisol present a broader effect by simultaneous activation of several SHRs. Moreover, SHRs share structural and functional characteristics that range from similarities between ligand-binding pockets to recognition of specific DNA sequences. These properties are clearly evident in progesterone (PR) and glucocorticoid receptors (GR); however, the biological responses triggered by each receptor in the presence of its ligand are different, and in some cases, even opposite. Thus, what confers the specificity of response to a given receptor is a long-standing topic of discussion that has not yet been unveiled. The levels of expression of each receptor, the differential interaction with coregulators, the chromatin accessibility as well as the DNA sequence of the target regions in the genome, are reliable sources of variability in hormone action that could explain the results obtained so far. Yet, to add further complexity to this scenario, it has been described that receptors can form heterocomplexes which can either compromise or potentiate the respective hormone-activated pathways with its possible impact on the pathological condition. In the present review, we summarized the state of the art of the functional cross-talk between PR and GR in breast cancer cells and we also discussed new paradigms of specificity in hormone action.


Assuntos
Neoplasias , Receptores de Progesterona , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Glucocorticoides/farmacologia , Ligantes , Progesterona/farmacologia , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo
13.
Drug Des Devel Ther ; 16: 3929-3946, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36411860

RESUMO

Purpose: Long-term glucocorticoid- usage can lead to glucocorticoid-induced osteoporosis (GIOP). The study focused on the preventative effects of a novel active vitamin D3 analog, eldecalcitol (ED-71), against GIOP and explored the underlying molecular mechanisms. Methods: Intraperitoneal injection of methylprednisolone (MPED) or dexamethasone (DEX) induced the GIOP model within C57BL/6 mice in vivo. Simultaneously, ED-71 was orally supplemented. Bone histological alterations, microstructure parameters, novel bone formation rates, and osteogenic factor changes were evaluated by hematoxylin-eosin (HE) staining, micro-computed tomography, calcein/tetracycline labeling, and immunohistochemical (IHC) staining. The osteogenic differentiation level and mineralization in pre-osteoblast MC3T3-E1 cells were evaluated in vitro using alkaline phosphatase (ALP) staining, alizarin red (AR) staining, quantitative polymerase chain reaction (qPCR), Western blotting, and immunofluorescence staining. Results: ED-71 partially prevented bone mass reduction and microstructure parameter alterations among GIOP-induced mice. Moreover, ED-71 also promoted new bone formation and osteoblast activity while inhibiting osteoclasts. In vitro, ED-71 promoted osteogenic differentiation and mineralization in DEX-treated MC3T3-E1 cells and boosted the levels of osteogenic-related factors. Additionally, GSK3-ß and ß-catenin expression levels were elevated after ED-71 was added to cells and were accompanied by reduced Notch expression. The Wnt signaling inhibitor XAV939 and Notch overexpression reversed the ED-71 promotional effects toward osteogenic differentiation and mineralization. Conclusion: ED-71 prevented GIOP by enhancing osteogenic differentiation through Notch and Wnt/GSK-3ß/ß-catenin signaling. The results provide a novel translational direction for the clinical application of ED-71 against GIOP.


Assuntos
Osteogênese , Osteoporose , Camundongos , Animais , beta Catenina/metabolismo , Via de Sinalização Wnt , Glucocorticoides/uso terapêutico , Glicogênio Sintase Quinase 3 beta/metabolismo , Microtomografia por Raio-X , Quinase 3 da Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/farmacologia , Quinase 3 da Glicogênio Sintase/uso terapêutico , Camundongos Endogâmicos C57BL , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Osteoblastos
14.
Proc Biol Sci ; 289(1986): 20221235, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36350212

RESUMO

Fluctuations in environmental temperature affect energy metabolism and stimulate the expression of reversible phenotypic plasticity in vertebrate behavioural and physiological traits. Changes in circulating concentrations of glucocorticoid hormones often underpin environmentally induced phenotypic plasticity. Ongoing climate change is predicted to increase fluctuations in environmental temperature globally, making it imperative to determine the standing phenotypic variation in glucocorticoid responses of free-living populations to evaluate their potential for coping via plastic or evolutionary changes. Using a reaction norm approach, we repeatedly sampled wild great tit (Parus major) individuals for circulating glucocorticoid concentrations during reproduction across five years to quantify individual variation in glucocorticoid plasticity along an environmental temperature gradient. As expected, baseline and stress-induced glucocorticoid concentrations increased with lower environmental temperatures at the population and within-individual level. Moreover, we provide unique evidence that individuals differ significantly in their plastic responses to the temperature gradient for both glucocorticoid traits, with some displaying greater plasticity than others. Average concentrations and degree of plasticity covaried for baseline glucocorticoids, indicating that these two reaction norm components are linked. Hence, individual variation in glucocorticoid plasticity in response to a key environmental factor exists in a wild vertebrate population, representing a crucial step to assess their potential to endure temperature fluctuations.


Assuntos
Glucocorticoides , Passeriformes , Humanos , Animais , Temperatura , Passeriformes/fisiologia , Estações do Ano , Reprodução , Vertebrados
15.
Medicine (Baltimore) ; 101(46): e31395, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401422

RESUMO

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease. The clinical effectiveness of ursodeoxycholic acid (UDCA) plus glucocorticoids and/or immunosuppressants remains controversial in PBC patients. The study aimed to compare the efficacy of monotherapy and combination therapy in patients with PBC and to assess the factors affecting the efficacy. In this retrospective study, 266 patients diagnosed with PBC were divided into monotherapy group (UDCA), double therapy group (UDCA plus glucocorticoids or immunosuppressants), and triple therapy group (UDCA plus glucocorticoids and immunosuppressants) according to different treatments. Demographic characteristics, immune parameters, biochemistry profiles, and other indicators were evaluated at baseline, 6 months, and 1 year following treatment. The prognosis was evaluated using the Paris II standard. The liver transplant-free survival at 3, 5, 10, and 15 years was predicted by GLOBE score. All statistical analyses were conducted using SPSS (version 24) software (SPSS Inc, Chicago, IL). The long-term survival rate of the triple therapy group was significantly improved compared with the monotherapy group (P = .005). In addition, multivariate analysis showed that abnormal platelet count, alkaline phosphatase, and albumin levels were risk factors for poor response. When IgG levels were elevated but below twice the upper limit of normal, the clinical benefit was not significant compared with monotherapy (P > .05). Compared with monotherapy and double therapy, triple therapy may improve the long-term survival rate of PBC patients. Abnormal platelet count, alkaline phosphatase, and albumin levels were associated with a poor prognosis.


Assuntos
Cirrose Hepática Biliar , Ácido Ursodesoxicólico , Humanos , Ácido Ursodesoxicólico/uso terapêutico , Glucocorticoides/uso terapêutico , Colagogos e Coleréticos/uso terapêutico , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/complicações , Imunossupressores/uso terapêutico , Fosfatase Alcalina/uso terapêutico , Estudos Retrospectivos , Taxa de Sobrevida , Albuminas/uso terapêutico
16.
BMC Gastroenterol ; 22(1): 474, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402945

RESUMO

BACKGROUND: Although various treatments help reduce abdominal pain, real-world pain medication utilization among patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving advanced therapies is poorly understood. The aim is to understand the utilization of pain medication 12 months before and after the initiation of advanced therapies among patients with newly diagnosed CD or UC. METHODS: This retrospective, observational cohort study used administrative medical and pharmacy claims data of patients with CD or UC from HealthCore Integrated Research Database (HIRD®). The data from patients with use of pain medication over 12 months follow-up (after the initiation date of advanced therapies) were collected and analyzed. Differences in the use of pain medication 12 months before and after the initiation of advanced therapies were assessed using McNemar's and Wilcoxon signed-rank test. RESULTS: Prior to initiating advanced therapies, 23.1% of patients with CD (N = 540) received nonsteroidal anti-inflammatory drugs (NSAIDs), 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators; similarly, 20.9% of patients with UC (N = 373) received NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators. After receiving advanced therapies for 12 months, patients reported a reduction in the use of steroids (78.1% vs. 58.9%, P < 0.001 in CD; 91.4% vs. 74.3%, P < 0.001 in UC), opioids (49.4% vs. 41.5%, P = 0.004 in CD; 40.8% vs. 36.5%, P = 0.194 in UC), and NSAIDs (23.1% vs. 15.0%, P < 0.001 in CD; 20.9% vs. 15.8%, P = 0.035 in UC), while the use of neuromodulators significantly increased (29.3% vs. 33.7%, P = 0.007 in CD; 29.5% vs. 35.7%; P = 0.006 in UC). CONCLUSIONS: The use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators was common among patients with CD or UC. These results highlight that patients with CD or UC continued to receive pain medications even after initiating advanced therapies.


Assuntos
Colite Ulcerativa , Doença de Crohn , Humanos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Estudos Retrospectivos , Glucocorticoides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor
17.
Front Immunol ; 13: 971366, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405743

RESUMO

Background: To investigate the therapeutic effects and safety of low-dose and standard-dose rituximab (RTX) in the treatment of antiphospholipid syndrome (APS). Methods: In this real-world study, we included 22 consecutive patients with APS who received RTX. Standard dose (SD) was defined as an overall dosage of RTX ≥ 1000mg in the induction period, and low dose (LD) was defined as an overall dosage of RTX <1000mg. Results: Of included patients, 1 patients died, 2 patients withdrew and 19 patients completed 6-month follow-up. Nine patients received SD-RTX and 13 patients received LD-RTX, and elder patients [LD-RTX vs. SD-RTX: (49.1 ± 15.5) vs. (35.8 ± 12.3) years, p = 0.044] and patients with later-onset [LD-RTX vs. SD-RTX: (46.8 ± 16.3) vs. (31.3 ± 13.6) years, p = 0.029] were more frequently included in LD-RTX than SD-RTX. Following 6 month RTX treatment, 8 patients (42.1%) achieved complete remission, 8 patients (42.1%) achieved partial remission and 3 patients (15.8%) showed no remission. The titers of anticardiolipin antibodies [baseline vs. 6 months: 30.8 (10.7, 90) vs. 19.5 (2.45, 69.10) U/L, p = 0.023] and the levels of erythrocyte sedimentation rate [baseline vs. 6 months: 29 (6, 63) vs. '6 (3, 14) mm/h, p = 0.021] exhibited a significantly decrease in all APS patients. Remission rate and titers of anti-ß2-glycoprotein I and lupus anticoagulant did not differ significantly between two groups. Conclusion: RTX might be a safe and effective option for patients with APS, and low dose confers equal efficacy as standard dose. Further cohort studies are needed to confirm our findings.


Assuntos
Síndrome Antifosfolipídica , Humanos , Idoso , Rituximab/efeitos adversos , Projetos Piloto , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Indução de Remissão , Glucocorticoides/uso terapêutico
18.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364901

RESUMO

Identifying characteristics associated with fast or slow growth during early life in a pig model will help in the design of nutritional strategies or recommendations during infancy. The aim of this study was to identify if a differential growth during lactation and/or the nursery period may be associated with fecal microbiota composition and fermentation capacity, as well as to leave a print of glucocorticoid biomarkers in the hair. Seventy-five commercial male and female pigs showing extreme growth in the lactation and nursery periods were selected, creating four groups (First, lactation growth, d0-d21; second, nursery growth, d21-d62): Slow_Slow, Slow_Fast, Fast_Slow, and Fast_Fast. At d63 of life, hair and fecal samples were collected. Fast-growing pigs during nursery had higher cortisone concentrations in the hair (p < 0.05) and a tendency to have a lower cortisol-to-cortisone ratio (p = 0.061). Both lactation and nursery growth conditioned the fecal microbiota structure (p < 0.05). Additionally, fast-growing pigs during nursery had higher evenness (p < 0.05). Lactation growth influenced the relative abundance of eight bacterial genera, while nursery growth affected only two bacterial genera (p < 0.05). The fecal butyrate concentration was higher with fast growth in lactation and/or nursery (p < 0.05), suggesting it has an important role in growth, while total SCFA and acetate were related to lactation growth (p < 0.05). In conclusion, piglets' growth during nursery and, especially, the lactation period was associated with changes in their microbiota composition and fermentation capacity, evidencing the critical role of early colonization on the establishment of the adult microbiota. Additionally, cortisol conversion to cortisone was increased in animals with fast growth, but further research is necessary to determine its implications.


Assuntos
Cortisona , Microbiota , Suínos , Animais , Feminino , Masculino , Ração Animal/análise , Glucocorticoides , Hidrocortisona , Dieta , Cabelo
19.
Int J Mol Med ; 50(6)2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36367164

RESUMO

The synthesis and release of glucocorticoids in living organisms are related to their response to unfavorable stressful conditions in order to maintain homeostatic functions and survive. One such hormone in humans is cortisol, which is produced by the hypothalamic­pituitary­adrenal cortex axis and binds with the glucocorticoid receptor (GR) following its secretion. GR controls a number of distinct gene networks. Non­coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non­coding RNAs (lncRNAs), regulate the expression and function of GR, having a considerable impact on various biological processes and treatment approaches for numerous disorders. In the present review, the GR pathways and signaling as part of the stress response system are discussed. A detailed report on the role of miRNAs and lncRNAs in glucocorticoid signaling is also presented.


Assuntos
Fenômenos Biológicos , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Glucocorticoides , Redes Reguladoras de Genes , Receptores de Glucocorticoides/genética
20.
JAMA Netw Open ; 5(11): e2241622, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36367723

RESUMO

Importance: Minimal data are available regarding the postdischarge treatment of multisystem inflammatory syndrome in children (MIS-C). Objectives: To evaluate clinical characteristics associated with duration of postdischarge glucocorticoid use and assess postdischarge clinical course, laboratory test result trajectories, and adverse events in a multicenter cohort with MIS-C. Design, Setting, and Participants: This retrospective cohort study included patients with MIS-C hospitalized with severe illness and followed up for 3 months in an ambulatory setting. Patients younger than 21 years who were admitted between May 15, 2020, and May 31, 2021, at 13 US hospitals were included. Inclusion criteria were inpatient treatment comprising intravenous immunoglobulin, diagnosis of cardiovascular dysfunction (vasopressor requirement or left ventricular ejection fraction ≤55%), and availability of complete outpatient data for 3 months. Exposures: Glucocorticoid treatment. Main Outcomes and Measures: Main outcomes were patient characteristics associated with postdischarge glucocorticoid treatment, laboratory test result trajectories, and adverse events. Multivariable regression was used to evaluate factors associated with postdischarge weight gain (≥2 kg in 3 months) and hyperglycemia during illness. Results: Among 186 patients, the median age was 10.4 years (IQR, 6.7-14.2 years); most were male (107 [57.5%]), Black non-Hispanic (60 [32.3%]), and Hispanic or Latino (59 [31.7%]). Most children were critically ill (intensive care unit admission, 163 [87.6%]; vasopressor receipt, 134 [72.0%]) and received inpatient glucocorticoid treatment (178 [95.7%]). Most were discharged with continued glucocorticoid treatment (173 [93.0%]); median discharge dose was 42 mg/d (IQR, 30-60 mg/d) or 1.1 mg/kg/d (IQR, 0.7-1.7 mg/kg/d). Inpatient severity of illness was not associated with duration of postdischarge glucocorticoid treatment. Outpatient treatment duration varied (median, 23 days; IQR, 15-32 days). Time to normalization of C-reactive protein and ferritin levels was similar for glucocorticoid duration of less than 3 weeks vs 3 or more weeks. Readmission occurred in 7 patients (3.8%); none was for cardiovascular dysfunction. Hyperglycemia developed in 14 patients (8.1%). Seventy-five patients (43%) gained 2 kg or more after discharge (median 4.1 kg; IQR, 3.0-6.0 kg). Inpatient high-dose intravenous and oral glucocorticoid therapy was associated with postdischarge weight gain (adjusted odds ratio, 6.91; 95% CI, 1.92-24.91). Conclusions and Relevance: In this multicenter cohort of patients with MIS-C and cardiovascular dysfunction, postdischarge glucocorticoid treatment was often prolonged, but clinical outcomes were similar in patients prescribed shorter courses. Outpatient weight gain was common. Readmission was infrequent, with none for cardiovascular dysfunction. These findings suggest that strategies are needed to optimize postdischarge glucocorticoid courses for patients with MIS-C.


Assuntos
Hiperglicemia , Pneumonia Viral , Criança , Humanos , Masculino , Feminino , Pneumonia Viral/epidemiologia , Pandemias , Alta do Paciente , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Volume Sistólico , Assistência ao Convalescente , Função Ventricular Esquerda , Aumento de Peso
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