Increased Efficacy of Antivenom Combined with Hyperbaric Oxygen on Deinagkistrodon acutus Envenomation in Adult Rats.

BACKGROUND: Snakebites are a neglected threat to global human health with a high morbidity rate. The present study explored the efficacy of antivenom with hyperbaric oxygen (HBO) intervention on snakebites, which could provide the experimental basis for clinical adjuvant therapy. METHODS: Male Sprague-Dawley rats (n = 96) were randomized into four groups: the poison model was established by injecting Deinagkistrodon acutus (D. acutus) venom (0.8 LD50) via the caudal vein; the antivenom group was injected immediately with specific antivenom via the caudal vein after successful establishment of the envenomation model; and the antivenom + HBO group was exposed to HBO environment for 1 h once at predetermined periods of 0 h, 4 h, 12 h, and 23 h after antivenin administration. Each HBO time point had six rats; the control group was left untreated. The rats in the experimental group were euthanized at the corresponding time points after HBO therapy, and brain tissue and blood were harvested immediately. Hematoxylin and eosin (H&E) staining was used to investigate the pathological changes in the rat brain. Immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Western blotting were used to detect the expression of Nestin mRNA and protein in the subventricular zone (SVZ) of the brain. The levels of coagulation function (prothrombin time, activated partial thromboplastin time [APTT], and fibrinogen) and oxidation/antioxidation index (malondialdehyde [MDA] and superoxide dismutase [SOD]) were analyzed. Data were analyzed using one-way analysis of variance. RESULTS: The brain tissue from rats in the poison model was observed for pathological changes using H&E staining. Tissues showed edema, decreased cell number, and disordered arrangement in the SVZ in the snake venom group. The antivenom - HBO intervention significantly alleviated these observations and was more prominent in the antivenom + HBO group. The serum levels of SOD and MDA in the snake venom group were increased and the antivenom - HBO intervention further increased the SOD levels but significantly decreased the MDA levels; however, this was enhanced within 1 h after HBO administration (MDA: F = 5.540, P = 0.008, SOD: F = 7.361, P = 0.000). Activated partial thromboplastin time (APTT) was significantly abnormal after venom administration but improved after antivenom and was even more significant in the antivenom + HBO group 5 h after envenomation (F = 25.430, P = 0.000). Only a few nestin-positive cells were observed in the envenomation model. The expression levels were significant in the antivenom and antivenom + HBO groups within 1 and 5 h after envenomation and were more significant in the antivenom + HBO group as determined by IHC, real-time PCR, and Western blotting (P < 0.05). D. acutus envenomation has neurotoxic effects in the brain of rats. CONCLUSIONS: Antivenin and HBO, respectively, induced a neuroprotective effect after D. acutus envenomation by attenuating brain edema, upregulating nestin expression in SVZ, and improving coagulopathy and oxidative stress. The intervention efficacy of antivenom with HBO was maximum within 5 h after envenomation and was more efficacious than antivenom alone.

Hyperbaric Oxygenation Protects Against Ischemia-Reperfusion Injury in Transplanted Rat Kidneys by Triggering Autophagy and Inhibiting Inflammatory Response.

BACKGROUND Ischemia-reperfusion injury (IRI) is a clinically common pathologic process defined as the inability to improve neuronal function. This study aimed to investigate the pathological mechanism of IRI and to explore effects of hyperbaric oxygenation (HBO) on autophagy and inflammatory response in IRI. MATERIAL AND METHODS Ninety Sprague-Dawley (SD) rats were randomly divided into a Sham group, a kidney transplant group (Trans), and a kidney transplant plus HBO treatment group (Trans+HBO). The kidney was harvested from the donor and transplanted to recipient rats according to a previously reported study. Rats were anesthetized using pentobarbital-natrium, and the kidney was resected and fixed in 4% paraformaldehyde. Serum creatinine (Scr) was detected using an automatic biochemical analyzer. The interleukin-6 (IL-6) level was assessed using enzyme-linked immunosorbent assay (ELISA). LC-3 was examined using indirect immunofluorescence assay and immunochemistry assay. LC-3 mRNA levels were analyzed using real-time PCR (RT-PCR). RESULTS The kidney transplant IRI model was successfully established. Scr and IL-6 levels were significantly increased in the Trans group (P<0.05). HBO significantly enhanced Scr and IL-6 levels. Scr was positively correlated with IL-6 levels (r-0.607, P<0.05). HBO increased LC-3 protein and mRNA expression in kidney-transplanted rats compared to the Sham and Trans group (P<0.05). Moreover, immunofluorescence assay also showed that LC-3 protein mainly distributes along renal tubular epithelial cells in a linear manner. CONCLUSIONS Autophagy dysfunction and inflammatory response after renal transplantation play important roles in processes of IRI. HBO treatment protects against the renal injury of IRI in renal tissues at the early stage, which may be triggered by the IL-6 pathway.

Osseous metastasis of cutaneous squamous cell carcinoma treated successfully with oxaliplatin, tegafur and leucovorin combination chemotherapy: a case report.

Bone metastasis from cutaneous squamous cell carcinoma (SCC) is rare. We report a case of cutaneous SCC which was diagnosed by the presence of bone metastasis and treated with combination chemotherapy. A 53 year male had tissue contusion and persistent ulcer in the multiple regions of body for about 30 years and treat with Chinese Herbal Drugs in several hospitals, however, did not thorough cure. He was referred to our hospital for a dermatological examination in March 2009. Excisional biopsy and positron emission tomography-computed tomography (PET-CT) scan showed an invasive cutaneous SCC concomitant bone metastasis. Surgical treatment is limited, because of multiple cancerous ulcer and metastatic spreading. Therefore, we proceed to treat with oxaliplatin, tegafur and leucovorin (LV) combination chemotherapy and other adjuvant therapy. About 5 months following chemotherapy, the general situation of the patient was improved. Further cycle of chemotherapy resulted in complete disappearance of the tumor masses (confirmed by PET-CT). So far, there was no evidence of local recurrence or distant metastasis. This report indicates that the combination chemotherapy of oxaliplatin, tegafur and LV seems to have a considerable therapeutic effect for cutaneous SCC concomitant malignant bone metastasis.