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1.
J Vet Emerg Crit Care (San Antonio) ; 30(1): 34-40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31858721

RESUMO

OBJECTIVE: To test an equine-derived polyvalent viperid antivenom (EPVA) in the treatment of dogs with evidence of viper envenomation. DESIGN: Prospective, multicenter observational study. SETTING: Veterinary emergency and critical care hospitals. ANIMALS: A total of 82 client-owned dogs with progressive clinical signs after viperid snakebite were enrolled in the study. INTERVENTIONS: Equine-derived polyvalent viperid antivenom was administered at a dosage of 1 mL/kg body weight, either by IV infusion or SC injection. MEASUREMENTS AND MAIN RESULTS: A standardized snakebite severity score (SSS) was used to characterize the severity of envenomation and the clinical course after EPVA treatment. Most dogs had improved SSS both at 4 (65.8%) and 8 hours (81.7%) following EPVA administration. Five dogs died. At the 4-week assessment, 3 dogs had slightly abnormal hematological or coagulation parameters; all other surviving dogs showed no abnormalities. Antivenom-related acute or intermediate reactions occurred in 12 dogs (14.6%). CONCLUSIONS: In the first study on antivenom in dogs in Italy, the effects of progressive viper envenomation were stabilized or reversed in the large majority of dogs receiving EPVA, as confirmed by the SSS analyses.


Assuntos
Antivenenos/uso terapêutico , Venenos de Crotalídeos , Doenças do Cão/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mordeduras de Serpentes/veterinária , Animais , Cães , Emergências/veterinária , Feminino , Cavalos , Itália , Masculino , Estudos Prospectivos , Mordeduras de Serpentes/tratamento farmacológico , Resultado do Tratamento , Viperidae
2.
Wilderness Environ Med ; 30(4): 446-449, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31699647

RESUMO

Snake envenomation during pregnancy is an uncommon emergency with several potential complications associated with the poisoning and its treatment. This case discusses a 27-y-old gravida 3, para 1102 (3 total pregnancies, 1 term birth, 1 premature birth, 0 abortions, 2 living births, twins) at 36 wk gestation who was bitten by a presumed Agkistrodon contortrix (copperhead snake). She had worsening pain and swelling in the right lower limb. Crotalidae polyvalent immune Fab was administered. The patient felt significantly better with improvement in swelling. She had a reactive nonstress test and reassuring coagulation studies. She gave birth to a healthy female infant 12 d later. This case supports the use of Crotalidae polyvalent immune Fab for venomous snakebites in pregnant patients to prevent possible maternal and fetal morbidity and mortality.


Assuntos
Agkistrodon , Antivenenos/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mordeduras de Serpentes/terapia , Adulto , Animais , Antivenenos/administração & dosagem , Venenos de Crotalídeos/envenenamento , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Gravidez , Resultado da Gravidez
3.
Int Immunopharmacol ; 75: 105714, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352323

RESUMO

Feline calicivirus (FCV) causes upper respiratory tract infections in felines and threatens the health of wild and domestic felines. Clinically, specific drugs to treat FCV have not yet been developed. Here, IgG was extracted from inactivated FCV-immunized horse sera. Equine F(ab')2 fragments were obtained from pepsin-digested IgG and then purified by protein-G column chromatography. In our study, equine immunoglobulin F(ab')2 fragments showed efficient neutralizing activity in vitro against FCV and had therapeutic and prophylactic effects in FCV-infected cats. The anti-FCV-specific F(ab')2 fragment can significantly alleviate the clinical symptoms of FCV-infected cats and reduce the viral loads of the trachea, lung and spleen. These results indicate that the F(ab')2 fragment prepared from inactivated FCV-immunized horses may be used as a prophylactic and therapeutic agent for diseases caused by FCV.


Assuntos
Infecções por Caliciviridae/terapia , Doenças do Gato/terapia , Cavalos/imunologia , Imunização Passiva , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Animais , Anticorpos Antivirais/imunologia , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/virologia , Calicivirus Felino/imunologia , Doenças do Gato/virologia , Gatos , Feminino , Imunoglobulina G/imunologia , Pulmão/virologia , Baço/virologia , Traqueia/virologia , Vacinas Virais
6.
Ann Emerg Med ; 74(3): 439-449, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30926190

RESUMO

STUDY OBJECTIVE: The antivenom currently available for treatment of systemic black widow envenomation (latrodectism) is composed of equine whole immunoglobin. Although considered effective, it has been associated with anaphylaxis and 2 reported fatalities. We test the efficacy and safety of new equine antivenom composed of purified F(ab')2 antibody fragments. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at 16 sites across the United States. Subjects aged 10 years or older with moderate to severe pain because of black widow spider envenomation received F(ab')2 antivenom or placebo. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. Secondary measures of pain intensity differences and summed pain intensity difference were computed. Adverse events were recorded. RESULTS: Sixty patients were treated (29 antivenom and 31 placebo). The mean age was 39 years and 68% were male. There were 15 treatment failures in the antivenom group and 24 in the placebo group (P=.019). Differences in pain intensity difference between groups were lower at each postbaseline point, and the mean summed pain intensity difference was greater for the antivenom group (difference 2,133; 95% confidence interval 177 to 4,090). No deaths or serious drug-related adverse events were detected. CONCLUSION: The F(ab')2 antivenom met the predefined primary outcome of reduced treatment failures. Secondary outcomes of pain intensity difference and summed pain intensity difference also supported efficacy. The rate of symptom improvement in the placebo group was higher than expected, which may be related to enrollment criteria or placebo effect.


Assuntos
Antivenenos/uso terapêutico , Viúva Negra , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Picaduras de Aranhas/tratamento farmacológico , Adolescente , Adulto , Idoso , Animais , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Medição da Dor , Venenos de Aranha/envenenamento , Adulto Jovem
7.
Toxicon ; 163: 8-11, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30880187

RESUMO

Delayed or recurrent coagulopathy can occur up to 14 days after North American rattlesnake envenomation in patients that have been treated with Crotalidae Polyvalent Immune Fab (CroFab). There is little data in the literature characterizing the sequelae of North American rattlesnake envenomation in pregnancy and no previously published reports of recurrent coagulopathy in pregnancy. CASE REPORT: We present 2 cases of first trimester pregnant women requiring readmission and retreatment with Crotalidae Polyvalent Immune Fab (CroFab) after developing recurrent/late coagulopathy following North American Rattlesnake Envenomation. Both patients were initially admitted and treated with CroFab following snakebite and discharged home without coagulopathy. One patient developed significant hypofibrinogenemia and subsequent hemorrhage after spontaneous abortion secondary to recurrent venom induced hypofibrinogenemia. DISCUSSION: Pregnant women with recurrent or late coagulopathy may be at higher risk for hemorrhage and spontaneous abortion and require more frequent laboratory monitoring after initial hospitalization and treatment with antivenom. A lower threshold for re-treatment with CroFab may be warranted in patients with fibrinogen less than 100mg/dL even in the setting of a normal platelet count.


Assuntos
Antivenenos/uso terapêutico , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Venenos de Crotalídeos/antagonistas & inibidores , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mordeduras de Serpentes/terapia , Aborto Espontâneo/etiologia , Adulto , Animais , Crotalus , Feminino , Fibrinogênio/metabolismo , Hemorragia/complicações , Humanos , Gravidez , Primeiro Trimestre da Gravidez
8.
PLoS One ; 14(3): e0213077, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30835744

RESUMO

OBJECTIVE: Valid, reliable, and clinically relevant outcome measures are necessary in clinical studies of snake envenomation. The aim of this study was to evaluate the psychometric (validity and reliability) and clinimetric (minimal clinically important difference [MCID]) properties of the Patient-Specific Functional Scale (PSFS) in snakebite envenomation. METHODS: We performed a secondary analysis of two existing snakebite trials that measured clinical outcomes using the PSFS as well as other quality of life and functional assessments. Data were collected at 3, 7, 10, and 17 days. Reliability was determined using Cronbach's alpha for internal consistency and the intraclass correlation coefficient (ICC) for temporal stability at 10 and 17 days. Validity was assessed using concurrent validity correlating with the other assessments. The MCID was evaluated using the following criteria: (1) the distribution of stable patients according to both standard error of measurement (SEM) and responsiveness techniques, and (2) anchor-based methods to compare between individuals and to detect discriminant ability of a positive change with a receiver operator characteristic (ROC) curve and optimal cutoff point. RESULTS: A total of 86 patients were evaluated in this study. The average PSFS scores were 5.37 (SD 3.23), 7.95 (SD 2.22), and 9.12 (SD 1.37) at 3, 7, and 10 days, respectively. Negligible floor effect was observed (maximum of 8% at 3 days); however, a ceiling effect was observed at 17 days (25%). The PSFS showed good reliability with an internal consistency of 0.91 (Cronbach's alpha) (95% CI 0.88, 0.95) and a temporal stability of 0.83 (ICC) (95% CI 0.72, 0.89). The PSFS showed a strong positive correlation with quality of life and functional assessments. The MCID was approximately 1.0 for all methods. CONCLUSIONS: With an MCID of approximately 1 point, the PSFS is a valid and reliable tool to assess quality of life and functionality in patients with snake envenomation.


Assuntos
Antivenenos/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Avaliação de Resultados em Cuidados de Saúde , Psicometria , Qualidade de Vida , Curva ROC , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Resultado do Tratamento , Estados Unidos , Adulto Jovem
9.
Am J Emerg Med ; 37(4): 798.e3-798.e5, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30770242

RESUMO

Treatment of chronic digitalis intoxication includes suspension of drug intake, which may be sufficient in case of mild manifestations, and supportive measures. Severe bradycardia requires the administration of atropine or isoproterenol; placement of a temporary pacemaker may be required in case of absent response to pharmacological therapy. Severe and life-threatening manifestations should be treated with digoxin-specific fragment antigen binding antibodies (Fab). Therapeutic plasma exchange has been suggested, in addition to Fab therapy, to maximize the clearance of Fab-digoxin complexes in patients with renal failure. To date, few case reports have described the use of such a therapeutic approach; currently, extracorporeal methods are not recommended as part of the treatment of digitalis intoxication, and stronger evidence is required to establish their benefit.


Assuntos
Digoxina/envenenamento , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Troca Plasmática , Insuficiência Renal/terapia , Idoso , Bradicardia/induzido quimicamente , Bradicardia/terapia , Digoxina/sangue , Feminino , Humanos , Taxa de Depuração Metabólica , Envenenamento/terapia , Insuficiência Renal/sangue
10.
Expert Opin Biol Ther ; 19(4): 335-342, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30686077

RESUMO

INTRODUCTION: Dry age-related macular degeneration (AMD) and Stargardt Macular Dystrophy (STGD1) result in vision loss due to progressive atrophy of the macula and lack of effective treatments. Numerous studies have implicated complement-associated inflammation as a contributor to both diseases. AREAS COVERED: The complement factor D inhibitor, lampalizumab, failed to halt geographic atrophy (GA) progression in phase 3 studies. The complement factor 3 (C3) inhibitor, APL-2, has shown potential to reduce GA growth in a phase 2 trial, supporting advancement to phase 3 trials. The intravenous complement factor 5 (C5) inhibitor, eculizumab, failed to halt GA progression in a phase 2 study. Another C5 inhibitor, avacincaptad pegol, is delivered by intravitreal injection, and will be studied for safety and preliminary signs of efficacy for AMD and STGD1 patients in phase 2 trials. LFG316 (C5 inhibitor) and CLG561 (properdin inhibitor) failed to halt GA progression in phase 2 studies. A phase 1 trial is evaluating the effects of combining LFG316 and CL561. Complement inhibition by gene therapy will be explored in the phase 1 trial of HMR59 in AMD patients. EXPERT OPINION: While complement inhibition has not yet demonstrated the ability to halt GA progression in a phase 3 trial, further study is warranted.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Atrofia Geográfica/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Doença de Stargardt/tratamento farmacológico , Ensaios Clínicos como Assunto , Complemento C3/imunologia , Complemento C5/imunologia , Fator D do Complemento/imunologia , Terapia Genética , Atrofia Geográfica/patologia , Atrofia Geográfica/terapia , Humanos , Doença de Stargardt/patologia , Doença de Stargardt/terapia
11.
Nanomedicine ; 17: 13-25, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30654186

RESUMO

Immunoliposomes (ILs), obtained with monoclonal antibodies (mAbs) decorating the liposome surface, are used for cancer treatment. These mAbs provide the recognition of molecules upregulated in cancer cells, like Programmed Death-Ligand 1 (PD-L1), an immune-checkpoint involved in tumor resistance, forming a complex that blocks this molecule and thereby, induces antitumor immune response. This mechanism introduces a new concept for ILs. ILs coupled to anti-PD-L1 or its Fab' fragment have been developed and in vitro/in vivo characterized. Factors such as coupling methods, PEG density and ligand size were optimized. In vitro data showed that Fab'-ILs displayed the highest PD-L1 cell interaction, correlating with a higher in vivo tumor accumulation and an increase of effector cytotoxic CD8+ T cells, providing tumor shrinkage and total regression in 20% of mice. Therefore, a novel immune-nanoplatform able to modulate the immune system has been developed, allowing the encapsulation of several agents for combinatorial therapies.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Neoplasias/terapia , Receptor de Morte Celular Programada 1/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Feminino , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunoterapia , Lipossomos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/imunologia
13.
Rheumatology (Oxford) ; 58(3): 382-387, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29660084

RESUMO

SLE has a complex pathogenesis, and multiple therapeutic targets have been discovered in recent years. In spite of belimumab being approved by the US Food and Drug Administration and the widespread use of rituximab, there have been many failed attempts to treat SLE successfully using biologic agents. In this review, we consider newer biologic approaches that might offer the hope of improving the outcome of SLE patients. These include the fully humanized anti-CD20 mAbs, PEGylated anti-CD40L, IFNα inhibitors, rigerimod and immune complexes blockade.


Assuntos
Produtos Biológicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Rituximab/uso terapêutico , Resultado do Tratamento
14.
J Hand Surg Am ; 44(2): 137-142, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30057221

RESUMO

Encounters with venomous snakes can lead to substantial morbidity or mortality if managed inappropriately. Medical management is the mainstay of treatment, but surgery may be necessary in rare cases. The hand surgeon should be well versed in the types of venomous snakes, the mechanism of action of venom, and the management of these injuries, given the frequency of hand envenomation. The indications for surgery are not well established and rely on clinical judgment and practitioner's experience. An understanding of previously reported outcomes and an algorithmic approach to treatment will help improve patient care and avoid complications.


Assuntos
Antivenenos/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mordeduras de Serpentes/terapia , Extremidade Superior/lesões , Analgésicos Opioides/uso terapêutico , Animais , Criança , Síndromes Compartimentais/etiologia , Síndromes Compartimentais/cirurgia , Desbridamento , Fasciotomia , Humanos , Masculino , Necrose/cirurgia , Venenos de Serpentes/imunologia , Toxoide Tetânico , Extremidade Superior/cirurgia
15.
Clin Toxicol (Phila) ; 57(1): 25-30, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30175628

RESUMO

BACKGROUND: No previous research has studied whether early snake antivenom administration leads to better clinical outcomes than late antivenom administration in North American pit viper envenomation. METHODS: A secondary analysis of data from a clinical trial of Fab antivenom (FabAV) versus placebo for copperhead snake envenomation was conducted. Patients treated before the median time to FabAV administration were classified as receiving early treatment and those treated after the median time were defined as the late treatment group. A Cox proportional hazards model was used to compare time to full recovery on the Patient-Specific Functional Scale (PSFS) instrument between groups. Secondary analyses compared estimated mean PSFS scores using a generalized linear model and the estimated proportion of patients with full recovery at each time point using logistic regression. To evaluate for confounding, the main analysis was repeated using data from placebo-treated subjects. RESULTS: Forty-five subjects were treated with FabAV at a median of 5.47 h after envenomation. Patients in the early treatment group had a significantly shorter time to full recovery than those treated late (median time: 17 versus 28 days, p = .025). Model-estimated PSFS scores were numerically higher at each time point in the early group. No difference was found between patients treated early versus late with placebo. CONCLUSIONS: In this secondary analysis of trial data, recovery of limb function was faster when Fab antivenom was administered soon after envenomation, as opposed to late administration.


Assuntos
Agkistrodon , Antivenenos/administração & dosagem , Venenos de Crotalídeos/antagonistas & inibidores , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Extremidade Inferior/lesões , Mordeduras de Serpentes/tratamento farmacológico , Extremidade Superior/lesões , Adulto , Animais , Antivenenos/uso terapêutico , Intervenção Médica Precoce , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Extremidade Inferior/fisiopatologia , Masculino , Modelos de Riscos Proporcionais , Recuperação de Função Fisiológica , Mordeduras de Serpentes/fisiopatologia , Fatores de Tempo , Extremidade Superior/fisiopatologia
16.
Clin Toxicol (Phila) ; 57(3): 164-167, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30260274

RESUMO

CONTEXT: The administration of Crotalidae polyvalent immune Fab (FabAV) currently requires close observation, so patients can be monitored for hypersensitivity reactions. The objective of this study was to evaluate the occurrence of hypersensitivity reactions to FabAV. METHOD: This was a retrospective cohort study utilizing data from a statewide poison center database in the United States. Records of all patients envenomated by a rattlesnake and treated with FabAV between January 2002 and December 2014 were evaluated. Patients with acute hypersensitivity reactions were identified, and reactions were evaluated descriptively. RESULTS: A total of 1340 adult and pediatric patients received FabAV during the study period. Of these, 19 (1.4%) patients had a potential reaction to FabAV, with 10 requiring a reduction in infusion rate, but none requiring discontinuation of the antivenom. Reactions occurred during the loading dose (n = 10), maintenance doses (n = 4), or were delayed reactions (n = 6). Symptoms recorded included pruritus (n = 8), hives (n = 8), rash (n = 7), vomiting (n = 7), nausea (n = 6), dyspnea or wheezing (n = 4), diaphoresis (n = 3), throat irritation (n = 2), and mild hypotension (n = 2). One patient was given a concomitant administration of low dose epinephrine infusion until completion of the antivenom course. However, none of the reactions were considered to be life-threatening. CONCLUSION: FabAV appears to be associated with a low incidence of acute hypersensitivity reactions. Patients may not require placement in a location capable of detecting and rapidly responding to hemodynamic and/or airway issues for FabAV monitoring alone.


Assuntos
Antivenenos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fatores Imunológicos/efeitos adversos , Adulto , Idoso , Antivenenos/uso terapêutico , Estudos de Coortes , Venenos de Crotalídeos/imunologia , Bases de Dados Factuais , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Centros de Controle de Intoxicações , Estudos Retrospectivos , Mordeduras de Serpentes/tratamento farmacológico , Resultado do Tratamento , Estados Unidos/epidemiologia
17.
Mol Pharm ; 16(1): 86-95, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30444371

RESUMO

The collection of aqueous humor (phase 1 b/2 Mahalo study) from patients dosed intravitreally with anti-factor D (AFD; FCFD4514S, lampalizumab), a humanized antibody fragment previously under investigation to treat geographic atrophy (GA) secondary to age-related macular degeneration, presented a unique opportunity to examine AFD properties in clinical samples. We investigated AFD stability and target-binding characteristics to set up strategies for engineering and evaluating optimized molecules that enable less frequent dosing. Two variants, AFD.v8 and AFD.v14, were evaluated as alternatives to AFD for longer-acting treatments. Mass spectrometry, surface plasmon resonance, and immunoassay were used to assess AFD stability and binding activity in aqueous humor samples from Mahalo patients. In vitro stability and binding activity of AFD, AFD.v8, and AFD.v14 were assessed in human vitreous humor versus buffer at 37 °C over 16 weeks and in vivo in rabbits over 28 days along with pharmacokinetic determinations. In human aqueous humor, AFD specific binding was >85% through 30 days, and deamidation was <3% through 60 days, consistent with the AFD stability and binding activity in vitreous humor from humans in vitro and rabbits in vivo. Target binding, stability, and rabbit pharmacokinetic parameters of AFD.v8 and AFD.v14 were similar to those of AFD. Physiological stability and activity of AFD translated across in vitro and in vivo studies in humans and rabbits. The two variants AFD.v8 and AFD.v14 demonstrated comparable potency and pharmacokinetics. These findings, along with previously demonstrated improved solubility of AFD.v8 and AFD.v14, provide proof-of-concept for developing other similar long-acting therapeutic variants.


Assuntos
Humor Aquoso/metabolismo , Fator D do Complemento/antagonistas & inibidores , Fragmentos Fab das Imunoglobulinas/metabolismo , Animais , Atrofia Geográfica/metabolismo , Humanos , Imunoensaio , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Degeneração Macular/metabolismo , Masculino , Espectrometria de Massas , Coelhos , Ressonância de Plasmônio de Superfície , Corpo Vítreo/metabolismo
18.
Med Sci (Paris) ; 35(12): 1098-1105, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31903923

RESUMO

The hinge region is a short sequence of the heavy chains (H) of antibodies linking the Fab (Fragment antigen binding) region to the Fc (Fragment crystallisable) region. The functional properties of the four IgG subclasses partly result from the sequence differences of their hinge regions as some amino acids of the lower hinge region are located within or in the close vicinity of the C1q and FcγR binding sites on the IgG H chains. In addition, the hinge is susceptible to proteolytic cleavage by many proteases present in tumor and/or inflammatory microenvironment capable of affecting functional responses. Thus, an optimal format of the hinge region remains a major challenge for the development of new therapeutic antibodies.


Assuntos
Anticorpos Monoclonais/química , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Fragmentos Fc das Imunoglobulinas/química , Sequência de Aminoácidos , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/uso terapêutico , Sítios de Ligação , Desenvolvimento de Medicamentos/métodos , Desenvolvimento de Medicamentos/tendências , Humanos , Fragmentos Fab das Imunoglobulinas/metabolismo , Fragmentos Fc das Imunoglobulinas/metabolismo , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Imunoglobulina G/química , Imunoglobulina G/metabolismo , Imunoglobulina G/uso terapêutico , Peptídeo Hidrolases/metabolismo , Engenharia de Proteínas/métodos , Engenharia de Proteínas/tendências , Proteólise
19.
South Med J ; 111(12): 716-720, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30512122

RESUMO

OBJECTIVE: To compare the incidence of hypersensitivity reactions following copperhead envenomation treated with Fab antivenom (FabAV) or placebo. METHODS: Patients with copperhead snakebites received treatment and follow-up in a prospective, randomized, double-blind, placebo-controlled trial of FabAV or placebo. The treatment allocation ratio was 2:1 (FabAV:placebo). All of the included patients received at least one dose of study treatment. We reviewed all treatment-emergent adverse events (AEs) using a previously published scale to classify likely hypersensitivity reactions as mild, moderate, or severe. RESULTS: We enrolled 74 patients at 13 sites. Forty-five patients received FabAV, and 29 patients received placebo. Five FabAV patients and 4 placebo patients had moderate envenomations; the rest were mild. Twenty-five FabAV patients and 8 placebo patients had at least 1 AE. Mild skin reactions occurred in 11 (24%) FabAV patients (pruritis, urticaria, rash, ecchymosis, erythema) and 1 (3%) placebo patient (pruritis). Moderate gastrointestinal AEs occurred in 7 (16%) FabAV patients (nausea, vomiting, constipation, diarrhea, oral paresthesia) and in 2 (7%) placebo patients (nausea). Respiratory AEs occurred in 3 (7%) FabAV patients (dyspnea, pulmonary embolism, nasal congestion, sneezing) and no placebo patients. Hypotension occurred in 1 patient in each group. CONCLUSIONS: In a randomized controlled trial of FabAV for copperhead bites, the incidence of hypersensitivity reactions was low. Most reactions were mild skin reactions.


Assuntos
Agkistrodon , Antivenenos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Mordeduras de Serpentes/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antivenenos/uso terapêutico , Criança , Método Duplo-Cego , Hipersensibilidade a Drogas/epidemiologia , Feminino , Seguimentos , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
20.
Invest Ophthalmol Vis Sci ; 59(4): AMD195-AMD201, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30383205

RESUMO

Purpose: Geographic atrophy (GA) is an advanced form of age-related macular degeneration. GA often initially spares the center of the fovea, leading to a functional disconnect between reading speed and distance visual acuity. This study was designed to determine the correlation between baseline GA lesion size, change in lesion size, and maximum reading speed (MRS) over 18 months. Methods: Post hoc analysis included US patients from the phase 2 Mahalo study of intravitreal lampalizumab with Minnesota low-vision reading (MNREAD) assessments at baseline and 6, 12, and 18 months. Binocular MRS was assessed using MNREAD Acuity Charts and GA lesion size by fundus autofluorescence. Correlations were estimated using Spearman's rank correlation coefficient. Results: Seventy-seven patients were included in the analysis. Baseline MRS correlated with baseline GA lesion size (correlation coefficient, -0.47; 95% confidence interval, -0.63 to -0.28; P < 0.0001). In patients with lesions ≥10 mm2 (four disc areas), the proportion reading below a nonfluent level (MRS, <40 words/min) at baseline (26.5%) increased to 64.7% by 18 months, versus patients with lesions <10 mm2 (baseline, 9.3%; 18 months, 7.0%). MRS declined by a median of 40.9% (interquartile range [IQR], -70.2 to -6.9) in patients with ≥2.5 mm2 lesion growth versus 8.2% (IQR, -34.6 to 11.0) in patients with <2.5 mm2 lesion growth from baseline to 18 months. Conclusions: These findings suggest that baseline GA lesion size and magnitude of lesion growth are associated with a decline in MRS over time and support the use of MRS as an evaluation of functional vision in patients with GA.


Assuntos
Atrofia Geográfica/fisiopatologia , Degeneração Macular/complicações , Leitura , Baixa Visão/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Atrofia Geográfica/tratamento farmacológico , Atrofia Geográfica/etiologia , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Injeções Intravítreas , Masculino , Método Simples-Cego , Visão Binocular/fisiologia , Acuidade Visual/fisiologia
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