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3.
AAPS PharmSciTech ; 20(7): 305, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506831

RESUMO

The aim of this study was to prepare a 20(S)-protopanaxadiol nanocrystalline suspension and enhance the bioavailability of 20(S)-protopanaxadiol by intramuscular injection. 20(S)-Protopanaxadiol nanocrystalline suspension was prepared using an anti-solvent combined with ultrasonic approach, in which meglumine and bovine serum albumin were screened as the optimized stabilizer and the coating agent during spray drying process, respectively. The optimal nanocrystallines were nearly spherical with a uniform particle size distribution, the mean particle size, polydispersity index, and drug loading of which were 151.20 ± 2.54 nm, 0.11 ± 0.01, and 47.15% (w/w), respectively. Sterile 20(S)-protopanaxadiol nanocrystalline suspension was obtained by passing through a 0.22-µm membrane, and the average filtration efficiency (FE%) was 99.96%. The cumulative release percentage of 20(S)-protopanaxadiol nanocrystalline suspension was 92.36% 20(S)-protopanaxadiol within 60 min in vitro, which was relatively rapid compared with that of the physical mixture for 12.51% and the 20(S)-protopanaxadiol bulk powder for 9.71% during the same time interval. The sterile 20(S)-protopanaxadiol nanocrystalline suspension caused minimal irritation responses by histological examination, indicating a good biocompatibility between the 20(S)-protopanaxadiol nanocrystalline suspension and muscle tissues. In pharmacokinetic study, the absolute bioavailability of 20(S)-protopanaxadiol nanocrystalline suspension for intramuscular injection and for oral gavage was 5.99 and 0.03, respectively. In summary, the 20(S)-protopanaxadiol nanocrystalline via intramuscular injection is an efficient drug delivery system to improve its bioavailability.


Assuntos
Sistemas de Liberação de Medicamentos , Sapogeninas/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Injeções Intramusculares , Masculino , Nanopartículas/química , Ratos , Ratos Sprague-Dawley , Sapogeninas/administração & dosagem , Sapogeninas/química , Soroalbumina Bovina/química , Suspensões
6.
Rev Assoc Med Bras (1992) ; 65(7): 982-987, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31389509

RESUMO

OBJECTIVE: A clinical, placebo-controlled, randomized, double-blind trial with two parallel groups. OBJECTIVE: to evaluate the efficacy of ropivacaine injection in each belly of the anterior and middle scalene muscles, guided by ultrasonography, in the treatment of Nonspecific Thoracic Outlet Syndrome (TOS) compared to cutaneous pressure. METHODS: 38 patients, 19 in the control group (skin pressure in each belly of the anterior and middle scalene muscles) and 19 in the intervention group (ropivacaine). Subjects with a diagnosis of Nonspecific Thoracic Outlet Syndrome, pain in upper limbs and/or neck, with no radiculopathy or neurological involvement of the limb affected due to compressive or encephalic root causes were included. The primary endpoint was functionality, evaluated by the Disabilities of the Arm, Shoulder, and Hand - DASH scale validated for use in Brasil. The time of the evaluations were T0 = before the intervention; T1 = immediately after; T2 = 1 week; T3 = 4 weeks; T4 = 12 weeks; for T1, the DASH scale was not applied. RESULTS: Concerning the DASH scale, it is possible to affirm with statistical significance (p> 0.05) that the intervention group presented an improvement of functionality at four weeks, which was maintained by the 12th week. CONCLUSION: In practical terms, we concluded that a 0.375% injection of ropivacaine at doses of 2.5 ml in each belly of the anterior and middle scalene muscles, guided by ultrasonography, in the treatment of Nonspecific Thoracic Outlet Syndrome helps to improve function.


Assuntos
Anestésicos Locais/administração & dosagem , Injeções Intramusculares/métodos , Músculos do Pescoço/efeitos dos fármacos , Ropivacaina/administração & dosagem , Síndrome do Desfiladeiro Torácico/tratamento farmacológico , Ultrassonografia de Intervenção/métodos , Método Duplo-Cego , Feminino , Humanos , Masculino , Fatores de Tempo , Resultado do Tratamento
7.
Minerva Med ; 110(5): 455-463, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368292

RESUMO

Peripheral neuropathies are frequently encountered in clinical practice and are associated with a major impairment in quality of life. However, their management remains poor, and current therapies are often burdened with major side effects and can present poor efficacy on pain and functionality. Therefore, it has been suggested that the combination of two or more different drugs may improve analgesic efficacy and reduce side effects. Tricortin® 1000 is formulated with 12 mg of Brain cortex phospholipid liposomes + 1000 µg of Cyanocobalamin injectable solution (PL+CNCbl) for intramuscular use and is indicated in the treatment of poly-algo-neuropathic syndromes. This combination exerts a marked neurotrophic action by promoting the synthesis of endogenous phospholipids; moreover, the peculiar formulation optimizes the delivery of CNCbl which has analgesic and neurotrophic action. This paper discusses the pharmacotherapy of peripheral neuropathies, including low-back pain, neck pain, postherpetic neuropathy (PHN) and focuses on the fixed dose combination PL+CNCbl clinical efficacy in association with other treatments or in monotherapy.


Assuntos
Analgésicos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Fosfolipídeos/uso terapêutico , Vitamina B 12/uso terapêutico , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Córtex Cerebral/química , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Humanos , Injeções Intramusculares , Lipossomos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/efeitos adversos , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Fosfolipídeos/administração & dosagem , Fosfolipídeos/efeitos adversos , Vitamina B 12/administração & dosagem , Vitamina B 12/efeitos adversos
8.
Medicine (Baltimore) ; 98(35): e16895, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464920

RESUMO

RATIONALE: Methotrexate (MTX) is an antimetabolite of folic acid, which is used for management of ectopic pregnancy. MTX-related toxicity may include cutaneous mucosal damage, bone marrow suppression, gastrointestinal disorders (gastritis, diarrhea, hematitis), liver and kidney function damage, pulmonary toxicity, cardiac toxicity, and nerve toxicity. However, it is not usual for vulvar edema induced by low-dose methotrexate. PATIENT CONCERNS: In this case report, we described a patient with severe vulvar edema and oral cavity ulceration and scalp ulceration induced by low-dose MTX treatment for ectopic pregnancy. Her presenting complaints were pain in the vulva, oral cavity, and scalp. DIAGNOSES: The patient was diagnosed based on clinical findings for MTX toxic reactions. INTERVENTIONS: Vulva was disinfectioned with iodide and Kangfuxin solution, her mouth was rinsed with mouthwash. Three compound glycyrrhizin tablets were orally administered (3 times/day). After 10 days, the broken skin and mucous membrane healed. OUTCOMES: The vulvar edema and oral cavity ulceration and scalp ulceration healed. LESSONS: Our study demonstrated that even low-dose MTX can be induced skin and mucosal injury, patients and doctors should timely detection of drug toxicity reactions, immediately rescue, prompt discontinuation of medication, and symptomatic treatment to avoid accidental occurrence.


Assuntos
Metotrexato/administração & dosagem , Metronidazol/administração & dosagem , Gravidez Ectópica/tratamento farmacológico , Vaginite por Trichomonas/tratamento farmacológico , Doenças da Vulva/induzido quimicamente , Dor Abdominal/etiologia , Administração Oral , Adulto , China , Feminino , Ácido Glicirrízico/administração & dosagem , Ácido Glicirrízico/uso terapêutico , Humanos , Injeções Intramusculares , Materia Medica/administração & dosagem , Materia Medica/uso terapêutico , Metotrexato/efeitos adversos , Metronidazol/uso terapêutico , Gravidez , Gravidez Ectópica/diagnóstico , Resultado do Tratamento , Hemorragia Uterina/etiologia , Doenças da Vulva/tratamento farmacológico
9.
Fish Shellfish Immunol ; 92: 649-654, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31265911

RESUMO

Singapore grouper iridovirus (SGIV) is the main grouper-infecting virus in southern China that causes serious economic losses. However, there is no effective way to control this viral disease. In this study, SGIV ORF19R (SGIV-19R) encoding a viral membrane protein was constructed into pcDNA3.1-HA and then was used to evaluate the immune protective effects in grouper Epinephelus coioides. Subcellular localization showed that SGIV-19R distributed in the cytoplasm and co-localization analysis indicated the protein partially co-localized with the endoplasmic reticulum (ER). RT-PCR and Western blot analyses confirmed the expression of the vaccine plasmids in grouper muscle tissues. Moreover, the transcription levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), myxovirus resistance 1 (Mx1) and immunoglobulin M (IgM) genes were significantly up-regulated in the spleen, liver and kidney of vaccinated groupers. SGIV challenge experiments showed the relative percent survival (RPS) was significantly enhanced in fish with 49.9% at the DNA dose of 45 µg pcDNA3.1-19R, while 75.0% RPS when using 90 µg pcDNA3.1-19R. Meanwhile, vaccination with pcDNA3.1-19R significantly reduced the virus replication, evidenced by a low viral load in the spleen of survivals groupers after SGIV challenge. These results imply that pcDNA3.1-19R could induce protective immunity in grouper, and might be a potential vaccine candidate for controlling SGIV disease.


Assuntos
Imunidade Adaptativa , Bass/imunologia , Doenças dos Peixes/prevenção & controle , Imunidade Inata , Ranavirus/imunologia , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Animais , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/prevenção & controle , Infecções por Vírus de DNA/veterinária , Doenças dos Peixes/imunologia , Injeções Intramusculares/veterinária , Iridovirus/fisiologia , Distribuição Aleatória , Proteínas da Matriz Viral/imunologia
10.
JAMA ; 322(2): 123-133, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287523

RESUMO

Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases. Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points. Conclusions and Relevance: Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months. Trial Registration: ClinicalTrials.gov Identifier: NCT01610414.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vacina contra Herpes Zoster , Herpes Zoster/prevenção & controle , Hospedeiro Imunocomprometido , Adjuvantes Imunológicos , Adulto , Feminino , Seguimentos , Herpes Zoster/epidemiologia , Vacina contra Herpes Zoster/administração & dosagem , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/prevenção & controle , Modelos de Riscos Proporcionais , Método Simples-Cego , Transplante Autólogo , Vacinas Sintéticas/administração & dosagem
11.
J Zoo Wildl Med ; 50(2): 457-460, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260214

RESUMO

Two anesthetic protocols in adult giraffe were compared by retrospective study. Thirteen anesthesia records for medetomidine-ketamine (MK) and seven for medetomidine-ketamine with a potent opioid (MKO) were evaluated for differences in demographic, behavioral, drug, and respiratory parameters. Giraffe stood significantly more quickly with MKO vs MK though MK animals were physically restrained to preclude premature standing as part of normal recovery practices (5.5 min vs 21.4 min, P = 0.01). Regurgitation was recorded in 5/13 and resedation in 4/13 MK animals. The range of values for blood lactate was higher in MKO (5.18-11.25 mM/L) than in MK giraffe (0.78-6.08 mM/L). Despite limitations of a retrospective study, both MK and MKO giraffe anesthesia protocols exhibit benefits and side effects. Awareness and management of these factors will improve outcomes until standardized, prospective studies of giraffe immobilization offer more comprehensive guidance on protocol selection.


Assuntos
Analgésicos Opioides/farmacologia , Anestesia/veterinária , Girafas , Ketamina/farmacologia , Medetomidina/farmacologia , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anestésicos Dissociativos/administração & dosagem , Anestésicos Dissociativos/efeitos adversos , Anestésicos Dissociativos/farmacologia , Animais , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Injeções Intramusculares , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Medetomidina/administração & dosagem , Medetomidina/efeitos adversos , Estudos Retrospectivos
12.
J Zoo Wildl Med ; 50(2): 466-469, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260216

RESUMO

Pharmacokinetics study of ceftiofur crystalline free acid (CCFA) was conducted in 14 adult captive smooth dogfish (Mustelus canis). A single dose of CCFA at 6.6 mg/kg was administered intramuscularly. Blood samples were collected prior to treatment and at 1, 2, 6, 12, 24, 32, 48, 72, 96, 120, 144, and 168 hr posttreatment. Naïve pooling of data from four sharks was used to generate the average plasma drug concentration at each time point. After concluding the study, additional blood samples were opportunistically collected from five randomly selected sharks at 1,920 hr. Plasma ceftiofur and desfuroylceftiofur metabolite concentrations were determined using reversed-phase high performance liquid chromatography (HPLC). Pharmacokinetic analysis was performed using a noncompartmental technique. Peak plasma concentration (Cmax) was 3.75 µg/ml with a time to Cmax (Tmax) of 96 hr. Ceftiofur plasma concentrations were maintained above 2 µg/ml for at least 168 hr and were still quantifiable at 1,920 hr.


Assuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Tubarões/sangue , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Área Sob a Curva , Cefalosporinas/administração & dosagem , Cefalosporinas/sangue , Injeções Intramusculares
13.
Neuron ; 103(4): 627-641.e7, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31255487

RESUMO

Analysis of human pathology led Braak to postulate that α-synuclein (α-syn) pathology could spread from the gut to brain via the vagus nerve. Here, we test this postulate by assessing α-synucleinopathy in the brain in a novel gut-to-brain α-syn transmission mouse model, where pathological α-syn preformed fibrils were injected into the duodenal and pyloric muscularis layer. Spread of pathologic α-syn in brain, as assessed by phosphorylation of serine 129 of α-syn, was observed first in the dorsal motor nucleus, then in caudal portions of the hindbrain, including the locus coeruleus, and much later in basolateral amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta. Moreover, loss of dopaminergic neurons and motor and non-motor symptoms were observed in a similar temporal manner. Truncal vagotomy and α-syn deficiency prevented the gut-to-brain spread of α-synucleinopathy and associated neurodegeneration and behavioral deficits. This study supports the Braak hypothesis in the etiology of idiopathic Parkinson's disease (PD).


Assuntos
Transporte Axonal , Transtornos Parkinsonianos/etiologia , Agregados Proteicos , Nervo Vago/metabolismo , alfa-Sinucleína/farmacocinética , Animais , Química Encefálica , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Duodeno/inervação , Duodeno/metabolismo , Humanos , Injeções Intramusculares , Corpos de Lewy/metabolismo , Aprendizagem em Labirinto , Transtornos da Memória/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Neurológicos , Músculo Liso/inervação , Músculo Liso/metabolismo , Comportamento de Nidação/fisiologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/prevenção & controle , Transtornos Parkinsonianos/psicologia , Fosforilação , Processamento de Proteína Pós-Traducional , Piloro/inervação , Piloro/metabolismo , Teste de Desempenho do Rota-Rod , Vagotomia , alfa-Sinucleína/administração & dosagem , alfa-Sinucleína/deficiência , alfa-Sinucleína/toxicidade
14.
Cancer Radiother ; 23(4): 312-315, 2019 Jul.
Artigo em Francês | MEDLINE | ID: mdl-31147172

RESUMO

PURPOSE: To report the results of Botulinum Toxin A (BTA) for radiation-induced head and neck pain. MATERIALS AND METHODS: This single-center retrospective study included all the patients treated at our institution with botulinum toxin A injections for radiation-induced head and neck pain between 2006 and 2017. Pain was evaluated by each patient on a visual analogue scale (VAS) (between 0 and 10) before, and 1 month after the injection. RESULTS: Sixteen patients were included in this series. The mean value of the pain was 8.5 before and 8 after the first injection. The difference was statistically significant (p<0.01). Major response occurred in 15 patients (VAS≤3 after BTA) and complete response in 11 patients (VAS=0 after BTA). CONCLUSION: Botulinum toxin is an effective treatment for radiation-induced head and neck pain.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Cervicalgia/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Radioterapia/efeitos adversos , Adulto , Idoso , Eletromiografia , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Cervicalgia/etiologia , Estudos Retrospectivos , Escala Visual Analógica
15.
Clin Drug Investig ; 39(8): 713-735, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152368

RESUMO

BACKGROUND: Several second-generation antipsychotics (SGAs) are available in long-acting injectable (LAI) formulations. OBJECTIVE: To systematically review the effects of the two formulations, Monohydrate and Lauroxil, of Aripiprazole LAI in patients with schizophrenia and bipolar disorder during an acute episode or during maintenance treatment. METHODS: On September 18, 2018, we adopted the following search strategy: (aripiprazole OR OPC-14597 OR Abilify) AND (long-acting OR depot OR LAI OR once monthly OR prolonged release OR monohydrate OR lauroxil) on PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials. Furthermore, we searched the ClinicalTrials.gov site for possible additional studies. RESULTS: We included 28 papers dealing with randomised assignment of aripiprazole LAI formulations in schizophrenia and bipolar disorder in survival studies after stabilisation, in acute studies, and in head-to-head comparisons. Both monohydrate and lauroxil formulations reduced relapses/recurrences with respect to comparators (placebo or 50 mg once-monthly monohydrate) and improved symptomatology in acute schizophrenia. LIMITATIONS: Only a small number of studies were included in our review, with widely overlapping samples. While a high proportion of studies were wholly or partly industry-sponsored, their outcomes do not appear to have been affected. CONCLUSION: Aripiprazole LAI may to be efficacious in reducing relapse of schizophrenia and bipolar disorder in the long term in stabilised patients and in improving symptoms of schizophrenia during its acute phase, with both monohydrate and lauroxil formulations showing efficacy.


Assuntos
Antipsicóticos/administração & dosagem , Aripiprazol/administração & dosagem , Transtorno Bipolar/tratamento farmacológico , Preparações de Ação Retardada , Esquizofrenia/tratamento farmacológico , Adulto , Humanos , Injeções Intramusculares , Masculino , Recidiva
16.
J Vet Emerg Crit Care (San Antonio) ; 29(4): 360-365, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31240797

RESUMO

OBJECTIVE: To compare the efficacy of hydromorphone and dexmedetomidine at inducing emesis in cats. DESIGN: Prospective, blinded, randomized crossover study. SETTING: Veterinary university teaching hospital. ANIMALS: 12 healthy purpose-bred cats. INTERVENTIONS: Cats were randomly assigned to receive hydromorphone (0.1 mg/kg, subcutaneously) or dexmedetomidine (7 µg/kg, IM). Following administration, the incidences of emesis, number of emetic events, signs of nausea (hypersalivation, lip licking), temperature, heart rate, respiratory rate, and sedation score were recorded for 6 hours. MEASUREMENTS AND MAIN RESULTS: Emesis was successful in 9 of 12 (75%) cats when treated with hydromorphone and in 7 of 12 (58%) cats when treated with dexmedetomidine (P = 0.67). Dexmedetomidine was more likely to cause sedation than hydromorphone (P < 0.001). Heart rate in cats was significantly decreased at 1 and 2 hours post-hydromorphone (P = 0.003, 0.014, respectively) and at 1, 2, 3, 5, 6 hours post-dexmedetomidine (P = 0.001, 0.003, 0.038, 0.013, 0.001, respectively). Cats were more likely to develop an increase in body temperature with hydromorphone administration although this was not clinically significant. CONCLUSIONS: Results of the present study indicate that hydromorphone is an effective alternative to dexmedetomidine for the induction of emesis in cats. Hydromorphone appears to cause less sedation and less decrease in heart rate. Further investigation into the most adequate dose of hydromorphone for optimizing emesis is warranted.


Assuntos
Gatos/fisiologia , Dexmedetomidina/farmacologia , Eméticos/uso terapêutico , Hidromorfona/farmacologia , Vômito/veterinária , Animais , Estudos Cross-Over , Dexmedetomidina/administração & dosagem , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hidromorfona/administração & dosagem , Injeções Intramusculares/veterinária , Masculino , Estudos Prospectivos , Distribuição Aleatória , Vômito/induzido quimicamente
17.
Cancer Immunol Immunother ; 68(8): 1273-1286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31243491

RESUMO

Therapeutic cancer vaccines have met limited clinical success. In the setting of cancer, the immune system is either tolerized and/or has a limited tumor-specific T cell repertoire. In this study, we explore whether intratumoral (IT) vaccination with an HPV vaccine can elicit quantitative and qualitative differences in immune response as compared to intramuscular (IM) vaccination to overcome immune resistance in established tumors. We report that IT administration of an HPV-16 E7 peptide vaccine formulated with polyinosinic-polycytidylic acid [poly(I:C)] generated an enhanced antitumor effect relative to IM delivery. The elicited anti-tumor effect with IT vaccination was consistent among the vaccinated groups and across various C57BL/6 substrains. IT vaccination resulted in an increased frequency of PD-1hi TILs, which represented both vaccine-targeted and non-vaccine-targeted tumor-specific CD8+ T cells. Overall, the CD8+/Treg ratio was increased within the tumor microenvironment using IT vaccination. We also assessed transcriptional changes in several immune-related genes in the tumor microenvironment of the various treated groups, and our data suggest that IT vaccination leads to upregulation of a broad complement of immunomodulatory genes, including upregulation of interferon gamma (IFNγ) and antigen presentation and processing machine (APM) components. IT vaccine delivery is superior to traditional IM vaccination routes with the potential to improve tumor immunogenicity, which has potential clinical application in the setting of accessible lesions such as head and neck squamous cell carcinomas (HNSCCs).


Assuntos
Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Experimentais/imunologia , Proteínas E7 de Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Linfócitos T Reguladores/imunologia , Animais , Apresentação do Antígeno/genética , Vacinas Anticâncer/imunologia , Carcinoma de Células Escamosas/imunologia , Células Cultivadas , Citotoxicidade Imunológica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Imunidade Celular/genética , Injeções Intramusculares , Interferon gama/genética , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Poli I-C/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Vacinação
18.
Dtsch Med Wochenschr ; 144(11): 759-763, 2019 06.
Artigo em Alemão | MEDLINE | ID: mdl-31163477

RESUMO

HISTORY AND ADMISSION FINDINGS: In this case series, we describe 4 patients who presented to a rheumatologic clinic with very different complains however were ultimately diagnosed with the same underlying disease. The wide spectrum of symptoms included generalized maculopapular exanthema, arthralgia, myalgia and vision problems. One patient received anti-TNF therapy for ankylosing spondylitis and recurrent uveitis. On exam, joint swelling and skin changes were found. INVESTIGATION: All patients were found to have an elevated Treponema pallidum antibody titer and a positive of the rapid plasma reagin test. DIAGNOSIS: Patients were diagnosed with syphilis. TREATMENT AND COURSE: The first three patients received an intramuscular injection of 2.4 million benzabine penicillin G. The fourth patient was treated with penicillin 6 million IV 4 times a day for more than 14 days, due to immunosuppression CONCLUSION: In the presence of non-specific and often rather diffuse symptoms, with which patients in rheumatology often present, a non-primary rheumatological, e. g. infectious genesis, also needs to be considered. Due to the increasing incidence of syphilis in Germany in recent years special attention needs to be paid to this disease in rheumatological care.


Assuntos
Artralgia/microbiologia , Exantema , Infecções Oculares Bacterianas , Sífilis , Treponema pallidum , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Exantema/complicações , Exantema/diagnóstico , Exantema/tratamento farmacológico , Exantema/microbiologia , Infecções Oculares Bacterianas/complicações , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologia , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Penicilina G/administração & dosagem , Penicilina G/uso terapêutico , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sífilis/microbiologia , Sorodiagnóstico da Sífilis , Adulto Jovem
19.
Tokai J Exp Clin Med ; 44(2): 34-39, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31250424

RESUMO

OBJECTIVE: Post-stroke hemiplegic patients with a spastic clenched fist deformity that was caused by upper motor neuron syndrome often have problems with hygiene and nursing. Botulinum toxin-A (BTX-A) had been given for treatment of such patients to relieve spasticity by targeting finger joint muscles, such as the flexor digitorum superficialis and flexor digitorum profundus. However, some of these patients do not have satisfactory outcomes. Therefore, we aimed to examine the clinical efficacy and outcome of BTX-A treatment that targeted the upper lumbrical muscles (ULM) in patients with spastic clenched fist deformity caused by stoke. METHODS: Chronic stroke patients with spastic clenched fist deformity who received BTX-A treatment were evaluated retrospectively. We obtained data from medical records before and at 4 weeks after BTX-A injection to the ULM. The clinical data and outcome measures analyzed included range of motion, the Modified Ashworth Scale, the numeric graphic rating scale for pain, and 2 items from the disability assessment scale (ease of cleaning palm and trimming nail). RESULTS: Wilcoxon signed rank test showed that BTX-A treatment significantly improved all measures. CONCLUSION: BTX-A therapy to the ULM provided satisfactory outcomes in improving spastic clenched fist.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Articulações dos Dedos , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Músculo Esquelético , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/etiologia , Espasticidade Muscular/fisiopatologia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento
20.
Indian J Ophthalmol ; 67(7): 1133-1136, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31238428

RESUMO

Purpose: Our study aims at evaluating the efficacy and safety of botulinum toxin A in the early treatment of sixth nerve palsy in type 2 diabetic patients. Methods: This study is a prospective and interventional clinical case series of patients presenting with acute onset of sixth cranial nerve palsy, who received injection botulinum toxin A. Results: Thirty-one cases were included in the study. 58% of the study subjects had incomplete palsy at presentation (abduction deficit -1 to -3) and 42% had complete palsy (-4 and -5). The median dosage of injection was 5 U (range 3--6 U). The median follow-up period is 2 months. The P value shows that there is statistically significant improvement in head turn, ocular deviation in primary position, and improvement in abduction between baseline and 1 week (P-value <0.001), 1 month (P-value <0.001) and 2 month (P-value <0.001) postinjection follow-up visits. 90.3% of patients had full resolution of symptoms in the last follow-up visit. 83.9% of patients were successfully treated. Conclusion: Early injection of botulinum toxin A in select patients with acquired sixth nerve palsy due to diabetes is a safe and efficient treatment option in alleviating symptoms, restoring function and quality of life and reducing need for surgical interventions in future.


Assuntos
Doenças do Nervo Abducente/tratamento farmacológico , Toxinas Botulínicas Tipo A/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Doenças do Nervo Abducente/etiologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Movimentos Oculares/efeitos dos fármacos , Movimentos Oculares/fisiologia , Feminino , Seguimentos , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares/administração & dosagem , Músculos Oculomotores , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
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