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1.
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
2.
J Sci Food Agric ; 100(2): 614-622, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31597198

RESUMO

BACKGROUND: Lonicera japonica Thunb is a common herb in East Asia. The flower buds are usually regarded as the traditional medicinal part, while leaves and stems are considered less valuable and receive little attention. This study compared the chemical constituents and anti-inflammatory effects of the different tissues in L. japonica Thunb for the first time. RESULTS: Thirty compounds were identified by ultra-performance liquid chromatography-photodiode detector-quadrupole / time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS/MS) analysis. Hydroxycinnamic acids, flavonoids, and iridoids were identified as the major components. The flower buds (FLJ), leaves (LLJ), and stems (SLJ) of L. japonica Thunb showed strong similarities in chemical components. The LLJ contained higher levels of hydroxycinnamic acids and flavonoids than the FLJ and SLJ. Furthermore, FLJ, LLJ, and SLJ exhibited potent anti-inflammatory activity in croton oil-induced ear edema and carrageenan-induced paw edema assays in mice. Moreover, FLJ, LLJ, and SLJ showed a cytoprotective effect on lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. Lipopolysaccharide-induced increases in nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were suppressed by treatments of FLJ, LLJ, and SLJ, respectively. The LLJ possessed a stronger anti-inflammatory effect than the FLJ. CONCLUSION: Leaves and stems of L. japonica Thunb have chemical components and anti-inflammatory properties similar to flower buds, and may become alternative or supplementary sources of flower buds. © 2019 Society of Chemical Industry.


Assuntos
Anti-Inflamatórios/química , Edema/tratamento farmacológico , Lonicera/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Animais , Anti-Inflamatórios/administração & dosagem , Carragenina/efeitos adversos , Cromatografia Líquida de Alta Pressão , Edema/induzido quimicamente , Edema/genética , Edema/imunologia , Flavonoides/administração & dosagem , Flavonoides/química , Flores/química , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Camundongos , Folhas de Planta/química , Caules de Planta/química , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
3.
Medicine (Baltimore) ; 98(45): e17933, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702679

RESUMO

Hemiplegic shoulder pain (HSP), which occurs in most patients with hemiplegia, causes considerable distress and worsens outcomes in rehabilitation. Although they have received the treatments such as anti-inflammatory drugs or physical therapy, many of the individuals remain suffering from shoulder pain 6 months after acute stroke event. In this retrospective study, we evaluated the effectiveness of ultrasound guided subacromial-subdeltoid (SASD) bursa injections with botulinum toxin type A (BoNT/A) compared to steroids for refractory HSP.The data were collected retrospectively by reviewing the patient's medical records and pain questionnaires in our rehabilitation center. In total, 38 patients who received ultrasound guided SASD bursa injection (BoNT/A group, n = 18; corticosteroid group, n = 20) were included. The pain visual analog scale (VAS) score at rest and during arm passive abduction, Fugl-Meyer score of upper limbs (F-M score) were evaluated before, 2, 4, 8, and 12 weeks after injection.Both 2 groups obtained a significant improvement of VAS score at rest or during arms passive abduction compared to baseline score (within group compare, P < .05). There were no significant differences of pain score improvement between two groups at week 2, 4, 8, and 12 after injection either at rest or during passive arm abduction (between 2 groups compare, P > .05). There were also no differences in results of the post treatment F-M score between 2 groups (between 2 groups compare, P > .05). Similarly, during the follow-up period no collateral effects were reported after BoNT/A injection.SASD bursa BoNT/A injection can substantially reduce the pain as corticosteroid in patients with HSP. BoNT/A injection could be a useful strategy for replacing steroids as a treatment for refractory HSP especially in the patients who cannot tolerate the steroids injection.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Fármacos Neuromusculares/administração & dosagem , Dor de Ombro/tratamento farmacológico , Idoso , Anti-Inflamatórios/administração & dosagem , Betametasona/administração & dosagem , Betametasona/análogos & derivados , Bolsa Sinovial/efeitos dos fármacos , Estudos de Casos e Controles , Feminino , Hemiplegia/complicações , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dor de Ombro/etiologia , Acidente Vascular Cerebral/complicações , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
4.
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
5.
JAMA ; 322(10): 936-945, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503307

RESUMO

Importance: Methotrexate and mycophenolate mofetil are commonly used immunomodulatory therapies for achieving corticosteroid-sparing control of noninfectious uveitis, but there is uncertainty about which drug is more effective. Objective: To compare the effect of methotrexate and mycophenolate for achieving corticosteroid-sparing control of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design, Setting, and Participants: The First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial screened 265 adults with noninfectious uveitis requiring corticosteroid-sparing immunosuppressive therapy from 9 referral eye centers in India, the United States, Australia, Saudi Arabia, and Mexico between August 22, 2013, and August 16, 2017. Follow-up ended on August 20, 2018. Interventions: Patients were randomized to receive oral methotrexate, 25 mg weekly (n = 107), or oral mycophenolate mofetil, 3 g daily (n = 109). Main Outcomes and Measures: The primary outcome was treatment success at 6 months, which was defined as having control of inflammation in both eyes, no more than 7.5 mg prednisone daily and less than or equal to 2 drops of prednisolone acetate 1%, and no treatment failure due to safety or intolerability. Patients underwent follow-up to 12 months while receiving the same treatment or switched to the other antimetabolite, depending on their 6-month outcome. Results: Among 216 patients who were randomized (median age, 38 years; 135 (62.5%) women), 194 (89.8%) completed follow-up through 6 months. Treatment success occurred in 64 (66.7%) patients in the methotrexate group vs 56 (57.1%) in the mycophenolate group (difference, 9.5% [95% CI, -5.3% to 21.8%]; odds ratio [OR], 1.50 [95% CI, 0.81 to 2.81]; P = .20). Among patients with posterior uveitis or panuveitis, treatment success was achieved in 58 (74.4%) in the methotrexate group vs 42 (55.3%) in the mycophenolate group (difference, 19.1% [95% CI, 3.6% to 30.6%]; OR, 2.35 [95% CI, 1.16 to 4.90]; P = .02); whereas among patients with intermediate uveitis treatment success occurred in 6 (33.3%) in the methotrexate group vs 14 (63.6%) in the mycophenolate group (difference, -30.3% [95% CI, -51.6% to 1.1%]; OR, 0.29 [95% CI, 0.08 to 1.05]; P = .07; P for interaction = .004). Elevated liver enzymes were the most common nonserious laboratory adverse event, occurring in 14 patients (13.0%) in the methotrexate group and 8 patients (7.4%) in the mycophenolate group. Conclusions and Relevance: Among adults with noninfectious uveitis, the use of mycophenolate mofetil compared with methotrexate as first-line corticosteroid-sparing treatment did not result in superior control of inflammation. Further research is needed to determine if either drug is more effective based on the anatomical subtype of uveitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01829295.


Assuntos
Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Uveíte/tratamento farmacológico , Adulto , Anti-Inflamatórios/administração & dosagem , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Testes de Função Hepática , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Prednisolona/administração & dosagem
6.
J Drugs Dermatol ; 18(9): 924-927, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524349

RESUMO

Acne is primarily an inflammatory disease. Anti-inflammatory dose doxycycline (40mg: 30mg immediate release and 10mg delayed release beads) is approved for the treatment of rosacea but with demonstrated efficacy for acne. Fixed combination adapalene 0.3% and benzoyl peroxide 2.5% gel is a once-daily formulation approved for the topical management of acne vulgaris. It has both anti-inflammatory and anti-comedogenic properties. Options for management of severe acne are somewhat limited; many patients are not candidates for or refuse treatment with isotretinoin. Systemic antibiotics may be indicated; acne treatment guidelines emphasize antibiotic stewardship in light of increasing concerns about antibiotic resistance and call for the judicious use of conventional systemic antibiotics. This single-center, open label pilot study involving 20 subjects with severe acne assessed the effects of combination treatment using anti-inflammatory dose doxycycline plus adapalene 0.3% and benzoyl peroxide 2.5% gel on IGA scores as well as inflammatory lesion, non-inflammatory lesion, and nodule counts. By week 12, 95% of subjects had at least a 2-grade improvement in IGA scores. Reductions in inflammatory and non-inflammatory lesion counts were statistically significant beginning at week 4 and continuing through week 12. By week 4, the percentage of patients with 0 nodules was 70%, compared to baseline of 20%. Further improvements were seen through week 12. Treatment was well-tolerated with no serious treatment-related adverse events. Combination treatment with anti-inflammatory dose doxycycline plus combination adapalene 0.3% and benzoyl peroxide 2.5% gel is safe and effective for management of severe acne. J Drugs Dermatol. 2019;18(9):924-927.


Assuntos
Acne Vulgar/tratamento farmacológico , Combinação Adapaleno e Peróxido de Benzoil/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Doxiciclina/administração & dosagem , Combinação Adapaleno e Peróxido de Benzoil/efeitos adversos , Administração Cutânea , Administração Oral , Adolescente , Adulto , Criança , Fármacos Dermatológicos/efeitos adversos , Relação Dose-Resposta a Droga , Doxiciclina/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Géis , Humanos , Masculino , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
7.
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
9.
Medicine (Baltimore) ; 98(34): e15852, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441836

RESUMO

BACKGROUND: The purpose of this study was to investigate the benefits and harm of combined administration of tranexamic acid (TXA) and dexamethasone (Dexa) in total knee arthroplasty (TKA). METHODS: A total of 88 consecutive patients undergoing TKA for knee osteoarthritis were stratified in 2 groups. All surgeries were performed under general anesthesia. Brief, patients in the TXA + Dexa group (n = 45) received 10 mg Dexa just after the anesthesia, and repeated at 24 hours after the surgery; and patients in the TXA group (n = 43) received 2 ml of normal saline solution at the same time. The measured outcomes were the C-reactive protein (CRP) and interleukin-6 (IL-6) from preoperatively to postoperatively, and postoperative nausea and vomiting (PONV), fatigue, range of motion (ROM), length of stay (LOS), and the analgesic and antiemetic rescue consumption RESULTS:: The level of CRP and IL-6 in the TXA + Dexa group were lower than that in the TXA group at 24 hours (P < .001, P < .001), 48 hours (P < .001, P < .001), and 72 hours (P < .001, P < .001) after the surgery. The pain scores in the TXA + Dexa group were lower during walking at 24 hours (P < .001), 48 hours (P < .001), and 72 hours (P < .001) and at rest at 24 hours (P = .022) after the surgery. Patients in the TXA + Dexa group had a lower nausea score, the incidence of PONV, fatigue, and the analgesic and antiemetic rescue consumption, and had a greater ROM than that in the TXA group. No significant differences were found in LOS and complications. CONCLUSION: The combined administration of TXA + Dexa significantly reduced the level of postoperative CRP and IL-6, relieve postoperative pain, ameliorate the incidence of POVN, provide additional analgesic and antiemetic effects, reduce postoperative fatigue, and improve ROM, without increasing the risk of complications in primary TKA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/métodos , Dexametasona/uso terapêutico , Ácido Tranexâmico/uso terapêutico , Idoso , Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antieméticos/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Proteína C-Reativa/efeitos dos fármacos , Dexametasona/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/biossíntese , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle , Amplitude de Movimento Articular , Ácido Tranexâmico/administração & dosagem
10.
Medicine (Baltimore) ; 98(33): e16714, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415364

RESUMO

To investigate the efficiency and clinical safety of intra-articular triamcinolone acetonide (TA) injection under the guide of ultrasonography combined with standard treatment for treating refractory small joints arthritis in rheumatoid arthritis (RA) patients.TA was injected upon confirmation of the needle inserting into the articular cavity. The dose was 40 mg for the wrist, 20 mg for the metacarpophalangeal (MCP) joint and 20 mg for the proximal interphalangeal (PIP) joint, respectively. Visual analogue scale (VAS) for joint pain, swelling, tenderness, synovial hyperplasia and power Doppler signal scores were evaluated at pretreatment, and post-treatment 24 hours, 1 week, 4 weeks as well as 12 weeks.The VAS for pain and tenderness scores showed gradual improvement at 24 hours, 1 week, 4 weeks and 12 weeks after treatment compared with the baseline levels (P' < .005). The swelling showed no changes at 24 hours after treatment compared with the baseline, and showed gradual improvement at 1 week, 4 weeks and 12 weeks after treatment (P' < .005). Significant decrease was noticed in the synovial hyperplasia score at 4 weeks and 12 weeks compared with the baseline level. Power Doppler signal score showed significant decrease at post-treatment 24 hours, which showed further decrease at 1 week and 4 weeks.Ultrasound-guided intra-articular TA injection is effective for treating RA patients with refractory small joints arthritis without changing the original treatment plan.


Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Reumatoide/complicações , Sinovite/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Ultrassonografia de Intervenção/métodos , Adolescente , Adulto , Idoso , Feminino , Articulações dos Dedos/efeitos dos fármacos , Humanos , Injeções Intra-Articulares , Masculino , Articulação Metacarpofalângica/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Sinovite/etiologia , Sinovite/patologia , Resultado do Tratamento , Articulação do Punho/efeitos dos fármacos , Adulto Jovem
11.
Am J Vet Res ; 80(8): 743-755, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31339769

RESUMO

OBJECTIVE: To evaluate the clinicopathologic, hemodynamic, and echocardiographic effects of short-term administration of anti-inflammatory dosages of prednisolone to systemically normal cats. ANIMALS: 10 cats with allergic dermatitis and 10 healthy control cats. PROCEDURES: Cats with allergic dermatitis were randomly allocated to 2 groups and received 2 dosages of prednisolone (1 and 2 mg/kg/d, PO, for 7 days) in a crossover design followed by 9-day tapering and 14-day washout periods. Each prednisolone-treated cat was matched to a healthy control cat on the basis of sex, neuter status, age (± 1 year), and body weight (± 10%). Control cats received no treatment during the 35-day observation period. Clinicopathologic, echocardiographic, and hemodynamic variables were measured at baseline (day 0) and predetermined times during and after prednisolone administration and compared within and between the 2 treatment groups. RESULTS: Prednisolone-treated cats had expected clinicopathologic alterations (mild increases in neutrophil and monocyte counts and serum concentrations of albumin, cholesterol, and triglycerides) but systolic arterial blood pressure; blood glucose, serum potassium, and cardiac biomarker concentrations; urinary sodium excretion; and echocardiographic variables did not differ significantly from baseline at any time. Statistically significant, albeit clinically irrelevant, increases in blood glucose and N-terminal pro-B-type natriuretic peptide concentrations were observed between baseline and the prednisolone pharmacokinetic steady state (7 days after initiation) only when the 2-mg/kg dosage was administered. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated short-term oral administration of anti-inflammatory dosages of prednisolone did not cause relevant hemodynamic, echocardiographic, or diabetogenic effects in systemically normal cats with allergic dermatitis.


Assuntos
Anti-Inflamatórios/farmacologia , Gatos , Glucocorticoides/farmacologia , Prednisolona/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Doenças do Gato/tratamento farmacológico , Dermatite/tratamento farmacológico , Dermatite/veterinária , Ecocardiografia/efeitos dos fármacos , Ecocardiografia/veterinária , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Distribuição Aleatória
12.
Rom J Ophthalmol ; 63(2): 161-165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334395

RESUMO

Objective: To establish the magnitude of endothelial cells alterations in acute anterior uveitis (AAU) and the clinical impact of local anti-inflammatory treatment. Methods: 27 patients at first episode of unilateral AAU were included. According to the moment of presentation in our departments, two different groups were created, early treatment uveitis group (ETUG) and delayed treatment uveitis group (DTUG). Each patient underwent a corneal endothelial specular microscopy, in both eyes, two weeks after we begun the topical treatment. Results: A statistically significant endothelial cells loss in the uveitis eye was identified in both groups, more important in DTUG. Also, in this group, the pleomorfism, polimegathism and central corneal thickness (CCT) were statistically significant increased. Conclusions: The patients with unilateral AAU and delayed presentation showed more important alterations, first structural and then functional, due to a prolonged inflammatory response. This, in association with other favorable ocular conditions can progress to a permanent corneal endothelial decompensation. The sooner the anti-inflammatory treatment was initiated, the more limited were the destructive processes. Abbreviations: AAU = Acute Anterior Uveitis, ETUG = Early Treatment Uveitis Group, DTUG = Delayed Treatment Uveitis Group, CCT = Central Corneal Thickness, CV = Coefficient of Variation, ECD = Endothelial Cells Density, HEX = Percentage of Hexagonal Cells.


Assuntos
Anti-Inflamatórios/administração & dosagem , Epitélio Posterior/patologia , Inflamação/tratamento farmacológico , Uveíte Anterior/tratamento farmacológico , Doença Aguda , Administração Tópica , Adulto , Contagem de Células , Epitélio Posterior/efeitos dos fármacos , Feminino , Humanos , Inflamação/patologia , Masculino , Soluções Oftálmicas , Uveíte Anterior/diagnóstico
13.
Gastroenterology ; 157(4): 1019-1031.e7, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31279870

RESUMO

BACKGROUND & AIMS: Although ustekinumab is an effective therapy for moderate to severe Crohn's disease (CD), its effects on the microscopic manifestations of CD are unknown. METHODS: We evaluated the effects of ustekinumab on histologic CD activity in an analysis of data from 251 participants in phase 3 induction and maintenance studies. Two endoscopic biopsy samples were collected at weeks 0, 8, and 44 from the ileum, splenic flexure, and rectum (18 biopsy samples from each patient). Histologic activity was assessed based on global histology activity scores (GHASs). RESULTS: At week 8, the mean GHAS was significantly reduced after ustekinumab induction treatment (from 10.4 ± 7.0 to 7.1 ± 5.9; P < .001) but not in patients who received placebo (from 9.2 ± 6.4 to 7.8 ± 6.2). At week 44 in the randomized maintenance therapy population, the mean GHAS remained reduced from week 8 in patients who received subcutaneous ustekinumab (90 mg every 8 weeks; from 7.4 ± 7.7 to 6.1 ± 4.7) but not every 12 weeks (from 5.3 ± 3.9 to 8.7 ± 4.1) or placebo (from 9.2 ± 3.8 to 10.9 ± 7.1). In the pooled (randomized and nonrandomized) maintenance therapy population, histologic improvement continued in patients given ustekinumab every 8 weeks (from 7.1 ± 6.2 to 5.2 ± 4.2; P < .0001) but not in those given ustekinumab every 12 weeks (from 6.1 ± 5.7 to 7.2 ± 5.1) or placebo (from 8.2 ± 4.2 to 8.9 ± 6.8). A significantly greater proportion of patients achieved histologic response (≥50% decrease in GHAS from baseline) at week 44 if they received ustekinumab every 8 weeks (50% in the randomized maintenance population and 54% in the pooled maintenance population) compared with every 12 weeks (17% and 39% in the randomized and pooled populations, respectively) or placebo (0% and 22% in the randomized and pooled populations, respectively) (P = .0137 for every 8 weeks vs placebo and P = .3529 for every 12 weeks vs placebo in the randomized population; P = .0168 for every 8 weeks vs placebo and P = .3069 for every 12 weeks vs placebo in the pooled population). Regional and overall mean GHASs correlated with the simple endoscopic score for CD (r = .6255, P < .0001). Multivariate analysis found an association between histologic improvement and endoscopic or histologic burden at baseline. CONCLUSIONS: In an analysis of data from participants in phase 3 induction and maintenance trials, we found histologic improvement in a greater proportion of patients given ustekinumab vs placebo. The largest improvements occurred in patients who received ustekinumab maintenance therapy every 8 weeks. ClinicalTrials.gov nos. NCT01369329, NCT01369342, and NCT01369355.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Ustekinumab/administração & dosagem , Cicatrização/efeitos dos fármacos , Adulto , Anti-Inflamatórios/efeitos adversos , Biópsia , Doença de Crohn/patologia , Esquema de Medicação , Endoscopia Gastrointestinal , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Quimioterapia de Indução , Mucosa Intestinal/patologia , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Ustekinumab/efeitos adversos
14.
Int J Mol Sci ; 20(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261895

RESUMO

Preventive approaches for age-related memory decline and dementia have become a high priority in the aging society because of the lack of therapeutic approaches. Recent epidemiological studies have reported that fermented dairy products can help prevent dementia. Previously, we identified tryptophan-tyrosine (WY) and tryptophan-methionine (WM) peptides as the suppressants of activation of the primary microglia and showed that WY peptide consumption suppresses inflammation in the brains of Alzheimer's disease model mice. However, the effects of the WM peptide on inflammation in the brain and Alzheimer's pathology have not been investigated. Here, we evaluated the effect of WM peptide consumption on Alzheimer's disease model (5×FAD) mice. In 5×FAD mice, intake of WM peptide suppressed the production of inflammatory cytokines, activation of microglia, and infiltration of activated microglia around ß amyloid (Aß) depositions. WM peptide intake reduced Aß deposition in the cortex and hippocampus and then improved the object recognition memory. Taken together with previous reports, the current findings indicate that ingestion of tryptophan-related peptides or food material rich in tryptophan-related peptides, thereby regulating microglial activity, represents a potential preventive approach for cognitive decline and dementia related to inflammation.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Dipeptídeos/farmacologia , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Suplementos Nutricionais , Dipeptídeos/administração & dosagem , Dipeptídeos/química , Dipeptídeos/uso terapêutico , Feminino , Metionina/química , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteínas do Leite/química , Triptofano/química
15.
Chin J Nat Med ; 17(6): 461-468, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262458

RESUMO

In the present study, we investigated anti-inflammatory effect of Cardamine komarovii flower (CKF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). We determined the effect of CKF methanolic extracts on LPS-induced pro-inflammatory mediators NO and prostaglandin E2 (PGE2), production of pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6), and related protein expression levels of MyD88/TRIF signaling pathways in peritoneal macrophages (PMs). Nuclear translocation of NF-κB-p65 was analyzed by immunofluorescence. For the in vivo experiments, an ALI model was established to detect the number of inflammatory cells and inflammatory factors (IL-1ß, TNF-α, and IL-6) in bronchoalveolar lavage fluid (BALF) of mice. The pathological damage in lung tissues was evaluated through H&E staining. Our results showed that CKF can decrease the production of inflammatory mediators, such as NO and PGE2, by inhibiting their synthesis-related enzymes iNOS and COX-2 in LPS-induced PMs. In addition, CKF can downregulate the mRNA levels of IL-1ß, TNF-α, and IL-6 to inhibit the production of inflammatory factors. Mechanism studies indicated that CKF possesses a fine anti-inflammatory effect by regulating MyD88/TRIF dependent signaling pathways. Immunocytochemistry staining showed that the CKF extract attenuates the LPS-induced translocation of NF-kB p65 subunit in the nucleus from the cytoplasm. In vivo experiments revealed that the number of inflammatory cells and IL-1ß in BALF of mice decrease after CKF treatment. Histopathological observation of lung tissues showed that CKF can remarkably improve alveolar clearance and infiltration of interstitial and alveolar cells after LPS stimulation. In conclusion, our results suggest that CKF inhibits LPS-induced inflammatory response by inhibiting the MyD88/TRIF signaling pathways, thereby protecting mice from LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Cardamine/química , Fator 88 de Diferenciação Mieloide/metabolismo , Extratos Vegetais/administração & dosagem , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Flores/química , Humanos , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
J Agric Food Chem ; 67(28): 7855-7868, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31274310

RESUMO

Bee pollen (BP) collected from different floras possesses various potential bioactivities, but the mechanism-related research on anti-inflammatory effects is limited. Here, three types of BP originating from Camellia sinensis L. (BP-Cs), Nelumbo nucifera Gaertn. (BP-Nn), and Brassica campestris L. (BP-Bc) were assessed using molecular and metabolomics methods to determine their anti-inflammatory effects. The differences in polyphenolic abundance of three types of BP extracts were determined by HPLC-DAD/Q-TOF-MS. In vitro anti-inflammatory effects of three BP extracts were evaluated in a lipopolysaccharide (LPS)-induced RAW 264.7 cells model. BP-Cs extract with the most abundant polyphenols was found to be the most effective in reducing inflammation by downregulating inflammatory-related genes expression and blocking the activation of MAPK and NF-κB signaling pathways. Polyphenol-rich BP-Cs was further evaluated for their in vivo anti-inflammatory effect in a LPS-induced acute lung injury mouse model. An UPLC-Q-TOF/MS-based metabolomics approach was applied to analyze metabolite changes in mouse serum. Weshowed that the pretreated BP-Cs extract alleviated inflammation and regulated glycerophospholipid metabolism significantly. Our findings provide a foundation for developing and justifying BP as a potential anti-inflammatory ingredient in functional foods or nutraceutical formulations.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Extratos Vegetais/administração & dosagem , Pólen/química , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/imunologia , Animais , Anti-Inflamatórios/química , Abelhas , Brassica/química , Camellia sinensis/química , Cromatografia Líquida de Alta Pressão , Humanos , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Nelumbo/química , Extratos Vegetais/química , Polifenóis/administração & dosagem , Polifenóis/química , Células RAW 264.7
17.
J Agric Food Chem ; 67(32): 8810-8818, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31318199

RESUMO

Citrus grandis (L.) Osbeck is a popular fruit cultivated around the world, and its peels are sometimes used for the treatment of cough, abdominal pain, and indigestion in China. However, the peel is discarded after fruit consumption in most cases, and its chemical constituents and biological activities have not been validated before. The present study focused on evaluation of the chemical and pharmacological profile of coumarins from peels of C. grandis against inflammation. The extracts and phytochemicals from peels of C. grandis were prepared, and anti-inflammatory activities were carried out in vivo and in vitro, including inhibiting xylene-induced ear edema and carrageenan-induced paw edema in mice and the production of inflammatory cytokines (interleukin 1ß, prostaglandin 2, and tumor-necrosis factor α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results indicated that methanolic extract, ethyl acetate fraction, and four major coumarins (compounds 7, 8, 13, and 16) inhibited swelling induced by xylene and carrageenan, separately, in vivo. Furthermore, 18 coumarins inhibited inflammatory factor secretion in macrophages primed by LPS, in which compounds 4, 6, 7, 10, 17 showed the most pronounced change, which were comparable to dexamethasone. In summary, peel of C. grandis showed an anti-inflammatory effect and coumarin compounds were responsible for regulating inflammatory mediators and cytokines, which might provide a novel nutritional strategy for inflammatory diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Citrus/química , Cumarínicos/administração & dosagem , Edema/tratamento farmacológico , Frutas/química , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Cumarínicos/química , Cumarínicos/isolamento & purificação , Dinoprostona/imunologia , Edema/genética , Edema/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Resíduos/análise
18.
J Dermatol ; 46(9): 802-807, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271451

RESUMO

Perifolliculitis capitis abscedens et suffodiens (PCAS) or dissecting cellulitis is a rare condition presenting deep follicular occlusions, follicular ruptures and follicular infections in the scalp area with unknown etiology, which consequently cause primary neutrophilic cicatricial alopecia by the repeated follicular inflammation. PCAS is categorized as one of the "follicular occlusion tetrad" along with hidradenitis suppurativa, acne conglobata and pilonidal cyst. In the pathogenesis of the follicular occlusion tetrad, the involvement of neutrophils and its activator tumor necrosis factor (TNF) have been discussed. Here, we report a case of PCAS that was successfully treated with adalimumab, a human anti-TNF monoclonal antibody. This is the first Asian case of PCAS that was improved by a TNF inhibitor.


Assuntos
Adalimumab/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Celulite (Flegmão)/tratamento farmacológico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Dermatopatias Genéticas/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Celulite (Flegmão)/imunologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Injeções Subcutâneas , Masculino , Dermatoses do Couro Cabeludo/imunologia , Dermatopatias Genéticas/imunologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
19.
Cochrane Database Syst Rev ; 7: CD001915, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31271656

RESUMO

BACKGROUND: The reduction of lung inflammation is one of the goals of cystic fibrosis therapy. Inhaled corticosteroids are often used in this respect to treat children and adults with cystic fibrosis. The rationale for this is their potential to reduce lung damage arising from inflammation, as well as their effect on symptomatic wheezing. It is important to establish the current level of evidence for the risks and benefits of inhaled corticosteroids, especially in the light of their known adverse effects on growth. This is an update of a previously published review; however, due to the lack of research in this area, we do not envisage undertaking any further updates. OBJECTIVES: To assess the effectiveness of taking regular inhaled corticosteroids compared to not taking them in children and adults with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We requested information from pharmaceutical companies manufacturing inhaled corticosteroids and authors of identified trials.Date of most recent search of the Group's Trials Register: 19 November 2018. SELECTION CRITERIA: Randomised or quasi-randomised trials, published and unpublished, comparing inhaled corticosteroids to placebo or standard treatment in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two independent authors assessed methodological quality and risk of bias in trials using established criteria and extracted data using standard pro formas. The quality of the evidence was assessed using the GRADE criteria. MAIN RESULTS: The searches identified 35 citations, of which 27 (representing 13 trials) were eligible for inclusion. These 13 trials reported the use of inhaled corticosteroids in 525 people with cystic fibrosis aged between 6 and 55 years. One was a withdrawal trial in 171 individuals who were already taking inhaled corticosteroids. Methodological quality and risk of bias were difficult to assess from published information.Objective measures of airway function were reported in most trials but were often incomplete and reported at different time points. We found no difference in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) % predicted in any of the trials, although the quality of the evidence was low due to risks of bias within the included trials and low participant numbers. We are uncertain whether inhaled corticosteroids result in an improvement in exercise tolerance, bronchial hyperreactivity or exacerbations as the quality of the evidence was very low. Data from one trial suggested that inhaled corticosteroids may make little or no difference to quality of life (low-quality evidence).Three trials reported adverse effects, but the quality of the evidence is low and so we are uncertain whether inhaled corticosteroids increase the risk of adverse effects. However, one study did show that growth was adversely affected by high doses of inhaled corticosteroids. AUTHORS' CONCLUSIONS: Evidence from these trials is of low to very low quality and insufficient to establish whether inhaled corticosteroids are beneficial in cystic fibrosis, but withdrawal in those already taking them has been shown to be safe. There is some evidence they may cause harm in terms of growth. It has not been established whether long-term use is beneficial in reducing lung inflammation, which should improve survival, but it is unlikely this will be proven conclusively in a randomised controlled trial.


Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Fibrose Cística/tratamento farmacológico , Administração por Inalação , Adolescente , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Criança , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Capacidade Vital , Adulto Jovem
20.
Acta Vet Scand ; 61(1): 28, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221173

RESUMO

BACKGROUND: Dexamethasone is used for the intra-articular route of administration in management of aseptic arthritis in horses. Despite its widespread use there is very little quantitative data of the disposition and response to dexamethasone. The aim of this study was to investigate and describe the synovial fluid and plasma dexamethasone concentration over time and to explore the relation between synovial fluid concentration and response using clinical endpoints as response biomarkers after IA injection of dexamethasone disodium salt solution in an equine model of synovitis. RESULTS: Inflammation was induced in the radiocarpal joint of six horses by injection of 2 ng lipopolysaccharide (LPS). Two hours later either saline or dexamethasone was injected in the same joint in a two treatment cross over design. Each horse was treated once with one of the six doses dexamethasone used (0.01, 0.03, 0.1, 0.3, 1 or 3 mg) and once with saline. Dexamethasone was quantified by means of UHPLC-MS/MS. Dexamethasone disposition was characterised by means of a non-linear mixed effects model. Lameness was evaluated both objectively with an inertial sensor based system and subjectively scored using a numerical scale (0-5). Joint circumference, skin temperature over the joint and rectal temperature were also recorded. The LPS-challenge induced lameness in all horses with high inter-individual variability. Dexamethasone significantly decreased lameness compared with saline. Other variables were not statistically significant different between treatments. Objective lameness scoring was the most sensitive method used in this study to evaluate the lameness response. A pharmacokinetic/pharmacodynamic model was successfully fitted to experimental dexamethasone and lameness data. The model allowed characterization of the dexamethasone synovial fluid concentration-time course, the systemic exposure to dexamethasone after intra-articular administration and the concentration-response relation in an experimental model of synovitis. CONCLUSIONS: The quantitative data improve the understanding of the pharmacology of dexamethasone and might serve as input for future experiments and possibly contribute to maintain integrity of equine sports.


Assuntos
Dexametasona/administração & dosagem , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/tratamento farmacológico , Lipopolissacarídeos , Sinovite/veterinária , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Dexametasona/farmacocinética , Cavalos , Injeções Intra-Articulares/veterinária , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico
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