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Clin Rehabil ; 33(9): 1479-1491, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31081365


OBJECTIVE: The aim of this study was to validate a novel pictorial-based Longshi Scale for evaluating a patient's disability by healthcare professionals and non-professionals. DESIGN: Prospective study. SETTING: Rehabilitation departments from a grade A, class 3 public hospital, a grade B, class 2 public hospital, and a private hospital and seven community rehabilitation centers. SUBJECTS: A total of 618 patients and 251 patients with functional disabilities were recruited in a two-phase study, respectively. MAIN MEASURES: Outcome measure: pictorial scale of activities of daily living (ADLs, Longshi Scale). Reference measure: Barthel Index. The Spearman correlation coefficient was used to analyze the validity of Longshi Scale against Barthel Index. RESULTS: In phase 1 study, from March 2016 to August 2016, the results demonstrated that the Longshi Scale was both reliable and valid (intraclass correlation coefficient based on two-way random effect (ICC2,1) = 0.877-0.974 for intra-rater reliability; ICC2,1 = 0.928-0.979; κ = 0.679-1.000 for inter-rater reliability; intraclass correlation coefficient based on one-way random effect (ICC1,1) = 0.921-0.984 for test-retest reliability and Spearman correlation coefficient = 0.836-0.899). In the second phase, in March 2018, results further demonstrated that the Longshi Scale had good inter-rater and intra-rater reliability among healthcare professionals and non-professionals including therapists, interns, and personal care aids (ICC1,1 = 0.822-0.882 on Day 1; ICC1,1 = 0.842-0.899 on Day 7 for inter-rater reliability). In addition, the Longshi Scale decreased assessment time significantly, compared with the Barthel Index assessment (P < 0.01). CONCLUSION: The Longshi Scale could potentially provide an efficient way for healthcare professionals and non-professionals who may have minimal training to assess the ADLs of functionally disabled patients.

Molecules ; 23(8)2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30065214


Snake venom is a complex cocktail of toxins which induces a series of clinical and pathophysiological manifestations in victims, including severe local tissue damage and systemic alterations. Deinagkistrodon acutus (D. acutus) ranks among the "big four" life-threatening venomous species in China, whose venom possesses strong myotoxicity and hematotoxicity that often lead to permanent disability or muscle atrophy. Varespladib, an inhibitor of mammalian phospholipase A2 (PLA2), has been recently reproposed as an effective antidote against snakebite envenomation. The present study aimed at evaluating the protective role of varespladib on muscle regeneration in envenomed mice. Mice were grouped and subjected to inoculation with D. acutus venom or a mixture of venom and varespladib or control vehicle in the gastrocnemius muscle. Local injuries including hemorrhage, myonecrosis, ulceration, and systemic damages including general dysfunction, visceral failure, and inflammatory responses were observed at 1, 3, 7, 14, and 21 days. The results indicated that most of the muscle myonecrosis and hemorrhage were alleviated by varespladib. Besides, the pretreated mice recovered rapidly with lesser atrophy and muscle fibrosis. In conclusion, the findings of the present study suggested that varespladib is an effective antidote that could neutralize D. acutus venom and allow for earlier and improved rehabilitation outcome.

Acetatos/farmacologia , Antídotos/farmacologia , Venenos de Crotalídeos/antagonistas & inibidores , Indóis/farmacologia , Necrose/tratamento farmacológico , Mordeduras de Serpentes/tratamento farmacológico , Úlcera/tratamento farmacológico , Angiopoietinas/genética , Angiopoietinas/metabolismo , Animais , Venenos de Crotalídeos/isolamento & purificação , Venenos de Crotalídeos/toxicidade , Crotalinae/fisiologia , Regulação da Expressão Gênica , Hemorragia/fisiopatologia , Hemorragia/prevenção & controle , Masculino , Camundongos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/lesões , Músculo Esquelético/inervação , Proteína MyoD/genética , Proteína MyoD/metabolismo , Miogenina/genética , Miogenina/metabolismo , Necrose/patologia , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Fosfolipases A2 Citosólicas/antagonistas & inibidores , Fosfolipases A2 Citosólicas/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Mordeduras de Serpentes/patologia , Úlcera/patologia
Molecules ; 23(2)2018 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-29439513


Phospholipase A2s (PLA2) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA2s, and was recently repurposed to a broad-spectrum inhibitor of PLA2 in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA2, which was estimated by IC50 in vitro and ED50 in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy.

Acetatos/farmacologia , Antivenenos/farmacologia , Venenos de Crotalídeos/toxicidade , Indóis/farmacologia , Inibidores de Fosfolipase A2/farmacologia , Fosfolipases A2/metabolismo , Mordeduras de Serpentes/tratamento farmacológico , Alanina Transaminase/antagonistas & inibidores , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/antagonistas & inibidores , Aspartato Aminotransferases/sangue , Creatina Quinase/sangue , Crotalinae/fisiologia , Equimose/prevenção & controle , Edema/prevenção & controle , Feminino , Isoenzimas/antagonistas & inibidores , Isoenzimas/sangue , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/sangue , Camundongos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Mordeduras de Serpentes/metabolismo , Mordeduras de Serpentes/fisiopatologia
Toxicon ; 137: 83-91, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28746861


SaPLIγ is a novel gamma phospholipase A2 inhibitor (PLI) recently isolated from Sinonatrix annularis, a Chinese endemic non-venomous snake. To explore the neutralization effects of saPLIγ in snakebite envenomation, a dose equivalent to LD50 of Deinagkistrodon acutus, Agkistrodon halys and Naja atra venom with/without saPLIγ was inoculated into the gastrocnemius muscle of female Kunming mice. The ability of saPLIγ to inhibit myonecrosis and systemic toxicity were evaluated through investigations of muscle histopathology, and determination of the serum levels of creatine kinase (CK), lactate dehydrogenase isoenzyme1 (LDH1) and aspartate transferase (AST). Edema of the gastrocnemius muscle was evaluated by calculating the width difference between the inoculated limb and the contralateral leg. Desmin loss in the gastrocnemius muscle was determined by Western blot analysis. Co-immunoprecipitation and shotgun LC-MS/MS analyses were performed to identify venom proteins that interact with saPLIγ. All the envenomed mice had significantly elevated serum CK, LDH1 and AST levels, whereas the levels were decreased significantly in the presence of saPLIγ. Histopathological evaluation of gastrocnemius muscle sections showed severe snake venom-induced damage, characterized by leukocyte infiltration and erythrocyte leakage, leading to local edema. Myonecrosis, hemorrhage and desmin loss were significantly attenuated by saPLIγ. SaPLIγ interacted with a wide range of venom proteins, including PLA2s, metalloproteinases and C type lectins, which may contribute to broad anti-venom effects.

Biomed Res Int ; 2017: 6592820, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29318152


Snakebite envenomation is a neglected global health problem, causing substantial mortality, disability, and psychological morbidity, especially in rural tropical and subtropical zones. Antivenin is currently the only specific medicine for envenomation. However, it is restricted by cold storage, snakebite diagnosis, and high price. Snake venom phospholipase A2s (svPLA2s) are found in all kinds of venomous snake families (e.g., Viperidae, Elapidae, and Colubridae). Along with their catalytic activity, svPLA2s elicit a wide variety of pharmacological effects that play a pivotal role in envenomation damage. Hence, neutralization of the svPLA2s could weaken or inhibit toxic damage. Here we overviewed the latest knowledge on the distribution, pathophysiological effects, and inhibitors of svPLA2s to elucidate the potential for a novel, wide spectrum antivenom drug targeting svPLA2s.

Antivenenos , Inibidores de Fosfolipase A2/uso terapêutico , Fosfolipases A2/imunologia , Venenos de Serpentes/imunologia , Animais , Antivenenos/imunologia , Antivenenos/uso terapêutico , Estabilidade de Medicamentos , Humanos