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1.
Ann Otol Rhinol Laryngol ; 129(1): 87-90, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31416334

RESUMO

OBJECTIVES: To highlight a severe case of rhinotillexomania (compulsive nasal picking) and its potential to manifest as empty nose syndrome (ENS). METHODS: A single case report with the presentation and management of a patient with severe rhinotillexomania who presented with chronic obstructive symptoms. We review the current literature on rhinotillexomania and ENS. RESULTS: This patient's manifestations mimic the obstructive symptoms of ENS, despite widely patent nasal passages. CONCLUSION: This is the first report of rhinotillexomania manifesting with features of ENS.


Assuntos
Comportamento Compulsivo/complicações , Perfuração do Septo Nasal/etiologia , Idoso , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Endoscopia , Humanos , Umidificadores , Masculino , Mupirocina/uso terapêutico , Obstrução Nasal , Perfuração do Septo Nasal/diagnóstico , Perfuração do Septo Nasal/terapia , Doenças Nasais/diagnóstico , Doenças Nasais/etiologia , Doenças Nasais/terapia , Síndrome , Irrigação Terapêutica , Tomografia Computadorizada por Raios X
2.
Equine Vet J ; 52(1): 131-135, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31006122

RESUMO

BACKGROUND: Locally administered corticosteroids are commonly used to treat joint diseases in sport and racehorses. As they are also the most potent drugs for the treatment of equine asthma, we hypothesised that the intra-articular corticosteroids used to treat joint diseases also improve the lung function in horses with severe asthma, thus potentially delaying the diagnosis of this common lung condition. OBJECTIVES: To compare the effects of intra-articular (IA) and intramuscular (IM) triamcinolone acetonide (TA) on lung function in horses with severe asthma. STUDY DESIGN: Randomised and controlled experiment on asthma-prone research animals. METHODS: Horses with severe asthma in clinical exacerbation were given either 20 mg of TA in both tarsocrural joints (n = 5; 40 mg/horse) or 40 mg of TA intramuscularly (n = 5). Lung function and TA serum concentrations were measured weekly for 35 days. TA serum concentrations were also evaluated on day 3. RESULTS: The pulmonary resistance (RL ) and elastance (EL ) values decreased by day 7 in the IA group (P<0.0001 and P = 0.003, respectively) and by day 14 in the IM group (P = 0.002 and 0.03, respectively). Lung function was improved up to days 21 and 28 in the IA and IM groups, respectively, when compared with baseline. TA serum levels were below the quantification limit (100 pg/ml) for 4 and 3 of the 5 horses in the IA and IM groups, respectively, on day 7. The area under the curve for RL , EL and the serum concentrations of TA were similar in both groups. MAIN LIMITATIONS: The response of horses with severe asthma might differ from that of high-performance horses with mild/moderate asthma. CONCLUSIONS: Intra-articular administration of TA improves lung function in horses with severe asthma, an effect that persists when TA serum concentration is below the quantification level that is employed as a threshold by the International Association of Racing Commissioners.


Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/veterinária , Doenças dos Cavalos/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Feminino , Cavalos , Injeções Intra-Articulares , Injeções Intramusculares , Masculino , Triancinolona Acetonida/administração & dosagem
3.
J Photochem Photobiol B ; 200: 111635, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31671372

RESUMO

Parkinson disease is one of the most common neurological movement disorders affecting geriatric population. Biosynthesized gold nanoparticles are the ideal alternatives spotlighted by many researchers to treat various diseases. In the present study we synthesized gold nanoparticles using the root extract of Paeonia mountan, woody trees which are used in traditional Chinese medicine to be prescribed for diverse diseases. The synthesis of gold nanoparticles was confirmed with UV-Vis spectroscopic analysis and characterized using FTIR, HR-TEM, EDAX and XRD analysis. The cytotoxicity property of synthesized gold nanoparticles was assessed using MTT assay in the murine microglial BV2 cells. The neuroprotective effect of synthesized gold nanoparticles in inflammatory agent lipopolysaccharides triggered murine microglial BV2 cells was evaluated using nitric oxide, prostaglandin E2 and inflammatory cytokines assays such as IL-6&IL-1ß. Further to confirm in vivo effect of synthesized nanoparticles, the nanoparticles were treated to Parkinson induced C57BL/6 mice. Behavioral, biochemical and molecular analysis were performed to estimate the potency of synthesized gold nanoparticles against the Parkinson induction in mice model. Our characterization results prove the gold nanoparticles synthesized using Paeonia mountan fulfills the requirement of ideal nanodrug and it potentially inhibited the inflammation in in vitro murine microglial BV2. The results of in vivo experiments authentically confirm gold nanoparticles synthesized using Paeonia mountan alleviates the neuroinflammation and improves the motor coordination in Parkinson induced mice.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Fármacos Neuroprotetores/química , Paeonia/química , Extratos Vegetais/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Química Verde , Lipopolissacarídeos/farmacologia , Masculino , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico/metabolismo , Paeonia/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doença de Parkinson/veterinária , Raízes de Plantas/química , Raízes de Plantas/metabolismo
4.
Anticancer Res ; 39(11): 6355-6358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704867

RESUMO

BACKGROUND/AIM: Pneumonitis is a serious complication after radiotherapy of breast cancer. This study aimed to identify its prevalence and potential risk factors. PATIENTS AND METHODS: A total of 606 patients irradiated following breast-conserving surgery or mastectomy were retrospectively analyzed. In patients developing pneumonitis, radiation and clinical parameters were investigated to identify potential risk factors. RESULTS: Eleven patients (1.8%) developed a pneumonitis grade ≥2. Mean doses to the ipsilateral lung were >7 Gy in 5 patients (45%). Of the other patients, 5 had a chronic inflammatory disease. Six patients (55%) had another malignancy (4 previous contralateral breast cancers, 1 previous ovarian and thyroid cancer, 1 synchronous carcinoma-in-situ (pTis) at the contralateral breast). Five patients (45%) received chemotherapy including taxanes and 4 patients (36%) received trastuzumab. CONCLUSION: The prevalence of pneumonitis was 1.8%. Potential risk factors included mean radiation dose to ipsilateral lung >7 Gy, systemic treatment with taxanes or trastuzumab, chronic inflammatory disease and history of another malignancy.


Assuntos
Neoplasias da Mama/radioterapia , Pneumonite por Radiação/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Carcinoma in Situ/radioterapia , Feminino , Humanos , Pulmão/efeitos da radiação , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas , Prednisolona/uso terapêutico , Prevalência , Pneumonite por Radiação/tratamento farmacológico , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
5.
Medicine (Baltimore) ; 98(38): e17208, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567972

RESUMO

Ulcerative colitis (UC) and Crohn disease (CD) are the most common forms of inflammatory bowel disease (IBD). Because these subtypes of IBD are characterized by periods of activity and remission, an understanding of the modulation of biochemical markers with the clinical features of IBD or its treatment, may be useful for determining the correct treatment protocol.This study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with IBD, correlation with clinical findings of disease, and modulation according to the pharmacologic therapy.A case-control study was carried out in Zacatecas, Mexico. The 27 protein profiles of serum from 53 participants (23 UC, 11 CD, and 19 controls) were evaluated using the Pro Human Cytokine 27-Plex immunoassay (Bio-Rad).Considering the controls as a reference, the group with IBD endoscopic activity showed higher serum levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1 receptor antagonist (IL-1Ra), and platelet-derived growth factor BB (PDGF-BB) (P < .05). Interferon-induced protein 10 (IP-10) was associated with extraintestinal symptoms of disease (P = .041). Both PDGF-BB and interleukin 6 (IL-6) showed the strongest correlations with clinical features of IBD. Levels of IL-6, IL-7, and monocyte chemoattractant protein 1 were higher with 5-aminosalicylic acid (5-ASA) + Azathioprine therapy than controls (P < .05). Combined therapy with 5-ASA + Adalimumab led to the strongest changes in marker modulation: IL-4, IL-5, IL-15, and PDGF-BB, were upregulated (P < .05).Elevated serum levels of G-CSF, IL-1Ra, and PDGF-BB were associated with IBD endoscopic activity, and of IP-10 with extraintestinal manifestations of IBD. Combined therapy of 5-ASA + Adalimumab produced significant upregulation of IL-4, IL-5, IL-15, and PDGF-BB. This information may be useful for deciding on the course of pharmacologic therapy for patients with IBD and for generating new therapy alternatives to improve the outcome of patients with IBD.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Doenças Inflamatórias Intestinais/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Adalimumab/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Becaplermina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CXCL10/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-6/sangue , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Receptores de Interleucina-1/sangue
6.
Z Gastroenterol ; 57(10): 1218-1225, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31610585

RESUMO

INTRODUCTION: Response to anti-TNF therapy is crucial for life expectancy and life quality in patients with severe Crohn's disease. We investigated if a previously reported gene expression profile predictive for infliximab response could be also applied to adalimumab response in an independent cohort. METHODS: Forty-seven Slovene Crohn's disease patients indicated for adalimumab therapy were enrolled in the study. Inflamed and non-inflamed colon biopsy samples were obtained during routine colonoscopy prior to adalimumab treatment. Response to adalimumab was measured with IBDQ. Gene expression in inflamed and non-inflamed colon biopsy samples was measured with RT-qPCR. Genotypes were extracted from previously available genotype data. Statistical analysis was performed with SPSS software. The R package e1071 was used to train bootstrap aggregated support vector machines (SVM). RESULTS: SVM prediction model analysis was used to analyze pooled, non-inflamed, and inflamed colon tissue datasets using IBDQ response after 4, 12, 20 and 30 weeks of adalimumab treatment. The bagging approach was used in an endeavor to obtain 100 % accuracy using 10 × 100 or 100 × 100 iterations. Average adalimumab response prediction accuracy is 75.5 % for pooled samples, 90.5 % for inflamed samples, and 100 % for non-inflamed samples. Moreover, models trained on selected SNPs from analyzed genes had an average accuracy of 92.8 %, confirming the involvement of genetic regions mapping the reported genes. Finally, using combined gene expression and SNP data we observed 100 % adalimumab response prediction accuracy for pooled, inflamed, and non-inflamed datasets. DISCUSSION: Our study supports the reported genetic anti-TNF response profile and extends it for adalimumab prediction.


Assuntos
Adalimumab , Doença de Crohn , Marcadores Genéticos , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Eslovênia
7.
Wiad Lek ; 72(9 cz 1): 1671-1675, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31586981

RESUMO

Osteoarthritis is the disease connected with aging which is characterised by progressive degeneration of all elements building the joint but also influencing the muscles constituting motor unit with the affected joint. The effective and unified therapy has not been yet introduced despite the broad multi-site studies concentrating on metabolic pathways responsible for the development of the disease. The reason of which is probably its multifactorial aetiology. The treatment methods are based on decreasing of cartilage destruction activity, retardation of proinflammatory factors activity and fighting with pain. Physiotherapy, movement rehabilitation, painkillers, anti-inflammatory drugs, glucosamine sulphates and hyaluronic acids are used as therapeutic strategies. The methods recently introduced are platelet rich plasma concentrates and stem cells injected directly into the affected joint. The aim of this review article was the presentation of differential therapeutic options offered to patients in different stages of osteoarthritis.


Assuntos
Envelhecimento , Cartilagem/patologia , Osteoartrite/terapia , Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Glucosamina/uso terapêutico , Humanos , Ácido Hialurônico/uso terapêutico
8.
Orv Hetil ; 160(44): 1744-1750, 2019 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-31657252

RESUMO

We present herewith cases of non-infectious uveitis with biological treatment where the ocular complaints were the initial symptoms indicating a multi-organ autoimmune disease. The first case was a patient with panuveitis and Vogt-Koyanagi-Harada disease, the second case was also a panuveitic patient with sarcoidosis and the third case was a patient with intermediate uveitis and inflammatory bowel disease. In all cases, emerging new, biological therapy (adalimumab) was necessary to achieve permanent inactive period of uveitis and the autoimmune disease. Introducing systemic biological treatment (adalimumab) in ophthalmology is crucial in the therapy of immune-mediated, non-infectious uveitis in order to preserve visual acuity. Orv Hetil. 2019; 160(44): 1744-1750.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Oftalmologia , Pan-Uveíte/tratamento farmacológico , Uveíte/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Pan-Uveíte/diagnóstico , Sarcoidose/diagnóstico , Resultado do Tratamento , Uveíte/diagnóstico , Síndrome Uveomeningoencefálica/diagnóstico , Acuidade Visual
9.
Arq Bras Cir Dig ; 32(3): e1451, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31644671

RESUMO

BACKGROUND: Hypovolemic shock is a common disease in polytrauma patients and may develop ischemia in various organs, increasing morbidity and mortality. The bowel is usually most affected by this condition. AIM: To evaluate the effects of copaiba oil on the intestinal mucosa's injury of rats submitted to hypovolemic shock. METHOD: Fifteen rats were divided into three groups: sham - simulated surgery; ischemia - animals submitted to hypovolemic shock; and copaiba - animals submitted to hypovolemic shock previously treated with copaiba oil. Mean blood pressure, arterial blood gas after shock induction, degree of intestinal lesion and villus length were evaluated. RESULTS: The sham presented the lowest values of lactate and PaCO2 and the highest values of mean arterial pressure, pH and bicarbonate in relation to the other groups. The degree of mesenteric lesion was zero in the sham group; 3.00±1.00 in the ischemia group; and 3.00±0.71 in the copaiba group. The villus length was 173.60±8.42 in the sham, 142.77±8.33 in the ischemia and 143.01±9.57 in the copaiba group. There was a significant difference between the sham and the other groups (p<0.05); however, there not significant difference between groups Ischemia and copaiba. CONCLUSION: Administration of copaiba oil did not reduce the intestinal mucosa lesion of rats after hypovolemic shock.


Assuntos
Anti-Inflamatórios/farmacologia , Fabaceae/química , Mucosa Intestinal/efeitos dos fármacos , Óleos Vegetais/farmacologia , Choque , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Íleo/patologia , Mucosa Intestinal/patologia , Isquemia/tratamento farmacológico , Masculino , Óleos Vegetais/química , Óleos Vegetais/uso terapêutico , Distribuição Aleatória , Ratos Wistar , Choque/tratamento farmacológico
11.
N Engl J Med ; 381(13): 1201-1214, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553833

RESUMO

BACKGROUND: The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown. METHODS: We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). RESULTS: The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo. CONCLUSIONS: Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Quimioterapia de Indução , Infusões Intravenosas , Injeções Subcutâneas , Quimioterapia de Manutenção , Masculino , Gravidade do Paciente , Indução de Remissão/métodos , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos
12.
N Engl J Med ; 381(13): 1215-1226, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553834

RESUMO

BACKGROUND: Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking. METHODS: In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52. RESULTS: A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years. CONCLUSIONS: In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.).


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Adalimumab/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Indução de Remissão/métodos
13.
Cochrane Database Syst Rev ; 9: CD001869, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486071

RESUMO

BACKGROUND: Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. This review was first published in 2001 and most recently updated in 2015. Since a significant benefit of corticosteroids for the early management of Bell's palsy has been demonstrated, the main focus of this update, as in the previous version, was to determine the effect of adding antivirals to corticosteroid treatment. We undertook this update to integrate additional evidence and to better assess the robustness of findings, taking risk of bias fully into account. OBJECTIVES: To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. SEARCH METHODS: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS in July 2019. We reviewed the bibliographies of the identified trials and contacted trial authors to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) or quasi-RCTs of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that followed-up participants for less than three months. DATA COLLECTION AND ANALYSIS: We independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. We performed sensitivity analyses excluding trials at high or unclear risk of bias in at least five domains, and reported these data as the primary analyses. MAIN RESULTS: Fourteen trials, including 2488 participants, met the inclusion criteria. Most were small, and most were at high or unclear risk of bias in multiple domains. We included four new studies at this update.Incomplete recoveryA combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in people with Bell's palsy compared to corticosteroids alone (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.38 to 1.74; 3 trials, N = 766; random-effects; low-certainty evidence). We excluded 10 trials that were at high or unclear risk of bias in several domains from this analysis and limited all analyses to studies at lower risk of bias. Recovery rates were better in participants receiving corticosteroids alone than antivirals alone (RR 2.69, 95% CI 0.73 to 10.01; 2 trials, N = 667; random-effects), but the result was imprecise and allowed for the possibility of no effect. The rate of incomplete recovery was lower with antivirals plus corticosteroids than with placebo or no treatment (RR 0.56, 95% CI 0.42 to 0.76; 2 trials, N = 658; random-effects). Antivirals alone had no clear effect on incomplete recovery rates compared with placebo, but the result was imprecise (RR 1.10, 95% CI 0.87 to 1.40; 2 trials, N = 658; fixed-effect). For people with severe Bell's palsy (House-Brackmann score of 5 and 6, or equivalent on other scales), we found that the combination of antivirals and corticosteroids had no clear effect on incomplete recovery at month six compared to corticosteroids alone, although the result was again imprecise (RR 0.82, 95% CI 0.57 to 1.17; 2 trials, N = 98; random-effects).Motor synkinesis or crocodile tearsAntivirals plus corticosteroids reduced the proportion of participants who experienced these long-term sequelae from Bell's palsy compared to placebo plus corticosteroids (RR 0.56, 95% CI 0.36 to 0.87; 2 trials, N = 469; fixed-effect; moderate-certainty evidence). Antivirals plus corticosteroids reduced long-term sequelae compared to placebo but there was no clear difference in this outcome with antivirals alone compared to placebo.Adverse events Adverse event data were available in four studies providing data on 1592 participants. None of the four comparisons showed clear differences in adverse events between treatment and comparison arms (very low-certainty evidence); for the comparison of antivirals plus corticosteroids and corticosteroids alone in studies at lower risk of bias, the RR was 1.17 (95% CI 0.81 to 1.69; 2 trials, N = 656; fixed-effect; very low-certainty evidence). AUTHORS' CONCLUSIONS: The combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in comparison to corticosteroids alone in Bell's palsy of various degrees of severity, or in people with severe Bell's palsy, but the results were very imprecise. Corticosteroids alone were probably more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no clear benefit from antivirals alone over placebo.The combination of antivirals and corticosteroids probably reduced the late sequelae of Bell's palsy compared with corticosteroids alone. Studies also showed fewer episodes of long-term sequelae in corticosteroid-treated participants than antiviral-treated participants.We found no clear difference in adverse events from the use of antivirals compared with either placebo or corticosteroids, but the evidence is too uncertain for us to draw conclusions.An adequately powered RCT in people with Bell's palsy that compares different antiviral agents may be indicated.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Paralisia de Bell/tratamento farmacológico , Paralisia de Bell/virologia , Quimioterapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Autoimmun Rev ; 18(11): 102390, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520803

RESUMO

Cytokines play a central role in the pathophysiology of autoimmune and inflammatory diseases. Several cytokines signal through the JAK-STAT pathway, which is now recognized as a major target to inhibit the effect of a wide array of cytokines. JAK inhibitors are increasingly used in the setting of inflammatory and autoimmune diseases. While the currently approved drugs are panJAK inhibitors, more selective small molecules are being developed and tested in various rheumatic disorders. In this extensive review, we present evidence- or hypothesis-based perspectives for these drugs in various rheumatologic conditions, such as rheumatoid arthritis, systemic lupus erythematosus, giant cell arteritis, and autoinflammatory diseases.


Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Animais , Humanos
15.
Nihon Shokakibyo Gakkai Zasshi ; 116(9): 732-738, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31511459

RESUMO

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is widely accepted as the operation of choice for refractory ulcerative colitis (UC), UC with dysplasia or cancer, or familial adenomatous polyposis. Pouchitis is the most frequent complication after IPAA for UC. Although the pathogenesis of pouchitis remains unclear, current evidence suggests that dysbiosis and mucosal immune response are important mechanisms. Antibiotics are the first-line treatment for the condition, but some patients develop chronic refractory pouchitis. Such cases can be treated with regimens such as longer courses of antibiotic combinations, mesalazine, corticosteroids, probiotics, or biologics. But if pouch inflammation is not ameliorated, a permanent ileostomy may be required. A 40-year-old man had undergone IPAA for UC and was diagnosed with pouchitis according to the Pouchitis Disease Activity Index. Antibiotics, mesalazine, and corticosteroids were given, but the inflammation was difficult to control. He developed chronic refractory pouchitis associated with perianal abscesses and anal fistulae. Following a seton procedure for fistulae, adalimumab (ADA) was administered. After 42 weeks, the ulcers in the pouch became scarred, and the anal fistulae were closed endoscopically. After remission was induced, it has been maintained. ADA is a fully human anti-tumor necrosis factor-α (TNF-α) monoclonal antibody that has been successfully used to treat refractory Crohn disease of the ileoanal pouch. Although some studies report that infliximab, a chimeric anti-TNF-α monoclonal antibody, is efficacious in patients with refractory pouchitis, clinical evidence for the use of ADA is limited. This case illustrates achievement of induction and maintenance of remission of refractory pouchitis with ADA. It is possible that patients with this condition can avoid a permanent ileostomy with anti-TNF-α therapy. In the near future, further study of long-term clinical outcomes of anti-TNF-α therapy is expected.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/cirurgia , Pouchite/diagnóstico , Proctocolectomia Restauradora , Adulto , Humanos , Masculino , Fator de Necrose Tumoral alfa
16.
APMIS ; 127(12): 789-796, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512766

RESUMO

The aim was to examine anti-tumor necrosis factor α (anti-TNFα) therapy influence changes on Th17 and Th22 cells in patients with spondyloarthritis (SpA), and its correlation with changes in clinical and magnetic resonance imaging (MRI) activity and chronicity scores. The Th17 and Th22 cells were assessed at baseline, after 12 and 52 weeks of anti-TNFα therapy by flow cytometry (ClinicalTrials.gov NCT4682724). The percentages of both Th17 and Th22 cells were increased by 70% at baseline compared with healthy controls (both p < 0.01). During treatment, these two subsets increased further to be 170% (Th17) and 123% (Th22) above levels in healthy controls (both p < 0.01). The same subsets decrease their expression of IL-23R significantly during the observation period (p < 0.05). High levels of Th17 and Th22 cells at baseline were associated with the degree of chronic changes in the sacroiliac joints on MRI and a good clinical response to anti-TNFα treatment after one year. Plasma levels were not associated with clinical changes. Th17 cells, and Th22 subsets, increased during one year of anti-TNF-α therapy in SpA, regardless of their clinical improvement. This supports that both the Th17 and Th22 subsets could be involved in the progression in SpA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Espondilartrite/tratamento farmacológico , Linfócitos T Auxiliares-Indutores/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/farmacologia , Feminino , Citometria de Fluxo , Humanos , Interleucina-17/metabolismo , Interleucinas/metabolismo , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina/metabolismo , Espondilartrite/diagnóstico por imagem , Espondilartrite/imunologia , Espondilartrite/patologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Resultado do Tratamento
17.
J Ayub Med Coll Abbottabad ; 31(3): 422-426, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31535520

RESUMO

BACKGROUND: Endotracheal intubation is one of the basic prerequisites of general anaesthesia. Recovery of patients is delayed due to the development of post-operative nausea, vomiting, sore throat and shivering. This study was conducted to determine role of dexamethasone for improved recovery of patients. METHODS: This randomized controlled trial was performed in the Department of Anaesthesia, Ayub Teaching Hospital, Abbottabad from June to November 2018. One hundred and twenty-two consenting patients of both genders, aged between 18-60 years, American Society of Anaesthesiologists (ASA) I and II, scheduled for general surgeries of 60-180 minutes duration under general anaesthesia were included. Patients with long duration surgeries, anticipated difficult airways, nasogastric tube in situ, upper respiratory tract infections, on steroid therapy and critically ill and emergency surgeries were excluded. They were randomly allocated into two groups by lottery method as dexamethasone (group A, n=61) or Placebo (group B, n=61). Postoperative nausea, vomiting, sore throat was observed at 2, 12 and 24 hours, shivering was observed at 2 hours only and patient satisfaction at 24 hours post-operatively. RESULTS: Group A patients had statistically proven better outcomes at 2, 12 and 24 hours for post-operative sore throat, nausea and vomiting, shivering was controlled in 24.5% p-value (0.006). Patient satisfaction was found in 83.6% of group A patients.. CONCLUSIONS: Thus, dexamethasone is effective drug for prevention of postoperative nausea, vomiting, sore throat and shivering in general surgical procedures thus improving patient satisfaction and their early discharge.


Assuntos
Anestesia Geral/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Complicações Pós-Operatórias , Adolescente , Adulto , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Adulto Jovem
18.
Eur J Endocrinol ; 181(5): 519-524, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31536966

RESUMO

Objectives: Amiodarone-induced thyrotoxicosis (AIT) affects up to 3% of treated patients. Type 2 AIT (AIT2) is a destructive thyroiditis and is usually treated with medium-high oral doses of prednisone. As AIT may worsen the underlying heart disease, a rapid control of thyroid function is desirable. We aimed to determine whether a combined intravenous methylprednisolone (IVMP) pulses therapy associated to prednisone in the interpulse period can represent an efficient and safe alternative to urgent total thyroidectomy in patients with AIT2 not responsive to prednisone alone. Design and methods: Patients presenting with a severe AIT2 studied in a tertiary referral Center from August 2018 to April 2019. We included four patients requiring a rapid improvement of thyroid function for their underlying cardiac disorders. The baseline doses of oral prednisone (range: 5-12.5 mg/day) and IVMP (range: 250-500 twice a week) were determined according to the severity of the thyrotoxicosis and were titrated based on clinical response. Results: Combined treatment was effective in all patients in the prompt restoration of euthyroidism and no major adverse events were reported during the follow-up. In all cases, FT4 and FT3 levels normalized at 3-5 weeks of treatment. A permanent hypothyroidism was observed in one patient, 3 months after the discontinuation of treatment. Conclusions: We report for the first time that the combined intravenous and oral steroid therapy is effective in patients with AIT2. The treatment is well tolerated and leads to a rapid improvement of thyroid function, avoiding urgent total thyroidectomy and favoring a quick functional recovery and rehabilitation of cardiac patients.


Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Tireotoxicose/induzido quimicamente , Tireotoxicose/tratamento farmacológico , Administração Intravenosa , Idoso , Humanos , Iodo/urina , Masculino , Pessoa de Meia-Idade , Tireoglobulina/sangue , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
19.
Expert Opin Investig Drugs ; 28(10): 827-833, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31474120

RESUMO

Introduction: A compound that simultaneously inhibits PDE3 and PDE4 should increase airway caliber by relaxing the smooth muscle and, simultaneously, suppress airway inflammatory responses. Ensifentrine (RPL554) is considered a PDE3/4 inhibitor, although its affinity for PDE3 is 3,440 times higher than that for PDE4, that is under clinical development for the treatment of asthma and COPD and, potentially, cystic fibrosis. Areas covered: We analyze the development of this molecule from its basic pharmacology to the present clinical Phase II studies. Expert opinion: Ensifentrine is an interesting drug but there is a lack of solid studies that still does not allow us to correctly allocate this molecule in the current COPD and even asthma therapeutic armamentarium. Furthermore, apparently ensifentrine has not yet entered Phase III clinical development and, in any case, there is no reliable evidence of its ability to elicit an anti-inflammatory activity in patients with COPD or asthma. Therefore, the real anti-inflammatory profile of ensifentrine must be clarified with new studies of basic pharmacology and adequate clinical studies specifically designed. However, at present the most intriguing perspective is linked to its possible use in the treatment of cystic fibrosis, also considering the lack of valid therapeutic options for this disease.


Assuntos
Asma/tratamento farmacológico , Isoquinolinas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pirimidinonas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Asma/fisiopatologia , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Desenvolvimento de Medicamentos/métodos , Humanos , Isoquinolinas/farmacologia , Inibidores da Fosfodiesterase 3/farmacologia , Inibidores da Fosfodiesterase 3/uso terapêutico , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Pirimidinonas/farmacologia
20.
Chem Biol Interact ; 311: 108790, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31400342

RESUMO

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1-50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time-course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2'-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , Interferon gama/metabolismo , Nociceptividade/efeitos dos fármacos , Receptores Opioides/metabolismo , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/genética , Edema/tratamento farmacológico , Edema/patologia , Comportamento Exploratório/efeitos dos fármacos , Pé/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Interferon gama/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Dor/tratamento farmacológico , Dor/patologia , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores Opioides/genética , Testes de Toxicidade Aguda , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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