中草药红背丝绸不同成分对内皮素-1效应拮抗作用的研究

本文用中草药红背丝绸醇提物、乙酸乙脂提取物和单体ＣＡ－１２０１ 三种不同成分对ＥＴ－１ 在动物整体及离体水平生物学效应的拮抗作用进行了研究。结果发现：这三种成分对ＥＴ－１ 致小鼠进行死亡有保护作用，使得小鼠的死亡率及死亡数下降；并可拮抗ＥＴ－１ 致胸主动脉的缩血管效应，醇提物和乙酸乙脂提取物（１０－ ７母液）拮抗ＥＴ 缩血管效应分别为５７．２７％ 和５８．６１％ ；ＣＡ－１２０１ １０－ ８和１０－ ９ Ｍ 亦能拮抗ＥＴ－１ 的缩血管效应；醇提物和乙酸乙脂提取物口服及ＣＡ－１２０１ 静脉注射后能拮抗ＥＴ－１ 的升压作用，拮抗ＥＴ－１ 作用均呈现明显的剂量依赖性。提示中草药红背丝绸不同成分可拮抗ＥＴ－１ 的生物学效应。     

Clinical profile,species-specific severity grading,and outcome determinants of snake envenomation: An Indian tertiary care hospital-based prospective study

Objective:

We undertook this study to assess the clinical profile and outcome determinants of different snake envenomation as well as to assign species-specific severity grade to different cases based on clinico – laboratory evidence scale.

Materials and Methods:

A prospective clinico – epidemiologic evaluation for outcome determinants of snakebite envenomation was carried out based on a clinico – laboratory severity grading scale, among 76 patients over a period of 2 years, in a tertiary care hospital in southern India.

Results:

Majority of patients were male agricultural workers (53.9%) followed by housewives (19.7%), and students (9.2%). Occurrence of viper snake envenomation with hemotoxic syndrome (73.68%) was highest followed by cobra and krait envenomation with neurotoxic (19.73%) and hemo – neurotoxic (5.3%) syndrome, respectively. On the contrary, maximum mortality and severity was seen in krait (60%) followed by cobra (13.33%) and viper (8.9%) envenomation. The average dose of anti-snake venom (ASV) administered varied from 9.83 (±7.22) to 20.25 (±4.92) vials throughout grade I to IV in all snake species envenomation. An increase in severity grade, ASV dose, and mortality were observed with the corresponding delay in ‘bite to needle time.’ Also, initial traditional treatments and krait species envenomation were significantly associated with higher grades of severity and mortality.

Conclusion:

There is an urgent need to spread awareness among the community for avoidance of traditional treatment and any delay in medical intervention in snakebite incidents.     

中草药拮抗内皮素—1生物效应的药理模型及对红背丝绸作用的评价

本研究建立了中草药拮抗内皮素 ( ET)生物效应的药理学模型 ,通过对 ET- 1引起动物的急性死亡、升压及缩血管作用的拮抗 ,达到评价中草药拮抗 ET生物效能的目的 ,并用红背丝绸醇提物在该模型上进行了验证。结果表明 ,红背丝绸醇提物能减少 ET- 1引起的小鼠死亡数并延长死亡时间、降低 ET- 1的升压效应 ,并在体外拮抗 ET- 1的缩血管作用。     

Prospective evaluation of pain,swelling, and disability from copperhead envenomation

Context: In light of the existing controversy regarding antivenin treatment for copperhead envenomation, a more detailed analysis of the disability from this species is needed. Objective: Our objective was to prospectively determine the duration of pain, swelling, and functional disability, i.e., residual venom effects, in patients with copperhead envenomation. Methods: Patients with venomous snakebite reported to the North Texas Poison Center between April 2009 and November 2011 were assessed. Patients with confirmed envenomations were contacted by a specialist in poison information. Day zero was the day of the bite and verbal phone consent for study enrollment was obtained at that time. The patient (or their guardian) was contacted by phone daily thereafter, and asked to rate their pain, edema/swelling, and disability using the modified DASH and LEFS scales. Patients were followed to resolution of all symptoms or return to baseline. Results: About 104 cases of venomous snakebite were followed; of which 17 were excluded due to being a dry bites (5) or for having insufficient data during follow-up (11) or due to coagulopathy (1). Overall, residual venom effects from copperhead bites for most patients last between 7 and 13 days. Median time to complete pain resolution was 7 days (mean?=?10.7 days). Median length of time to resolution of swelling was 10 days (mean?=?13 days) and median length of time to resolution of functional disability was 9 days (mean?=?12.2 days). Discussion: Residual venom effects from copperhead envenomation in this study had a slightly shorter duration than some other studies. Data are skewed due to outliers where residual venom effects lasted for up to 89 days. Initial reoccurrence of some symptoms may be seen. Antivenom (AV) is currently being used for a large percentage of patients with copperhead envenomation. Finally, no differences in duration of venom effects were seen based on age or location of bite. Conclusion: Our study suggests that residual venom effects from copperhead species persist for between 10 and 13 days but may persist for months. Future studies are necessary to identify risk factors for severe/prolonged injury and to define the benefit of AV in patients with copperhead envenomation.     

Protein content of antivenoms and relationship with their immunochemical reactivity and neutralization assays

Context. Therapy for snakebites relies on the application of antivenoms, which may be produced with different immunogenic mixtures of venom and possess different pharmaceutical characteristics. For these reasons, immunological cross-reactivity and heterologous neutralization were analyzed relative to the protein content of three antivenoms used in the Americas. Methods. The antivenoms studied were composed of equine F(ab’)₂ fragments from animals immunized with Crotalinae venoms. The antivenoms were tested against venoms of seven pit viper species from Argentina, seven from Mexico, one from Costa Rica, and one from Colombia. Results. Immunoblotting showed high cross-reactivity of all major protein bands with all the antivenoms tested. ELISA results also showed high cross-reactivity among the different venoms and antivenoms, and a high heterologous neutralization was observed. The results can be interpreted in different ways depending on whether the reactivity is considered in terms of the volume of antivenom used or by the amount of protein contained in this volume of antivenom. The antivenoms with high immunochemical reactivity and neutralizing capacity were those with higher protein content per vial; but when doses were adjusted by protein content, antivenoms of apparently lower neutralizing capacity and immunochemical reactivity showed at least similar potency and reactivity although volumetrically at higher doses. Conclusion. Protein content relative to neutralization potency of different products must be taken into account when antivenoms are compared, in addition to the volume required for therapeutic effect. These results show the importance of obtaining high-affinity and high-avidity antibodies to achieve good neutralization using low protein concentration and low-volume antivenoms.     

Effect of externally applied Jidesheng anti-venom on skin and soft-tissue necrosis after Chinese cobra bite： a retrospective study

OBJECTIVE： To evaluate the effects of Jidesheng anti-venom used externally for skin and soft-tissue necrosis from Chinese cobra bite. METHODS： A retrospective review was performed according to the clinical data recorded from Janu- ary 2002 to December 2012. A total of 126 patients （116 females and 10 males） with skin and soft-tis- sue necrosis due to Chinese cobra bite were divided into two groups. The control group was treated externally with 40% glyceride magnesium sulfate （n=52）, and the treatment group was given Jidesheng anti-venom externally （n=74）. The data collected included maximum local necrotic area of skin and soft tissues, de-tumescence time, healing time, and skin-grafting rate. RESULTS： There were no significant differences in gender, age, and disease condition between the control and treatment groups （P〉0.05）. No statistically significant difference was found in de-tumes- cence time between the two groups （P〉0.05）. The maximum local necrotic area of skin and soft tissues was （19.9 ± 7.3） cm2 in the treatment group, while it was （23.3 ±6.4） cm2 in the control group. The healing time of the treatment group was shorter than that of the control group [（32.1 ± 3.7） vs （34.4±4.5） days）] The skin-grafting rate in the treatment group was lower than that of the control group （10.81% vs 25.00%）. There were statistically significant differences in maximum local necrotic area of skin and soft tissues, healing time, and skin-grafting rate between the control and treatment groups （all P〈0.05）. CONCLUSION： External application of Jidesheng anti-venom may help to promote wound healing and reduce the skin-grafting rate in cases of skin and soft-tissue necrosis due to Chinese cobra bite.     

Effect of externally applied Jidesheng anti-venom on skin and soft-tissue necrosis after Chinese cobra bite: a retrospective study

Objective

To evaluate the effects of Jidesheng anti-venom used externally for skin and soft-tissue necrosis from Chinese cobra bite.

Methods

A retrospective review was performed according to the clinical data recorded from January 2002 to December 2012. A total of 126 patients (116 females and 10 males) with skin and soft-tissue necrosis due to Chinese cobra bite were divided into two groups. The control group was treated externally with 40% glyceride magnesium sulfate (n=52), and the treatment group was given Jidesheng anti-venom externally (n=74). The data collected included maximum local necrotic area of skin and soft tissues, de-tumescence time, healing time, and skin-grafting rate.

Results

There were no significant differences in gender, age, and disease condition between the control and treatment groups (P>0.05). No statistically significant difference was found in de-tumescence time between the two groups (P>0.05). The maximum local necrotic area of skin and soft tissues was (19.9 ± 7.3) cm² in the treatment group, while it was (23.3 ± 6.4) cm² in the control group. The healing time of the treatment group was shorter than that of the control group [(32.1 ± 3.7) vs (34.4±4.5) days)] The skin-grafting rate in the treatment group was lower than that of the control group (10.81% vs 25.00%). There were statistically significant differences in maximum local necrotic area of skin and soft tissues, healing time, and skin-grafting rate between the control and treatment groups (all P<0.05).

Conclusion

External application of Jidesheng anti-venom may help to promote wound healing and reduce the skin-grafting rate in cases of skin and soft-tissue necrosis due to Chinese cobra bite.     

Recurrent,persistent, or late,new-onset hematologic abnormalities in Crotaline snakebite

Background.?Hematologic effects from rattlesnake envenomation exhibit a phenomenon of recurrent, persistent or late, new onset (late) abnormalities in some Fab antivenom‐treated patients 4 or more days post‐envenomation. Indicators that reliably identify or exclude those patients at risk of late hematologic effects have not been developed.

Methods.?This was a retrospective, observational case series of rattlesnake bite records at two US poison centers. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for D‐dimer, fibrinogen, platelets, platelet count trend, INR and PTT associated with late hematologic abnormalities, were determined.

Results.?Three hundred seventy six cases were reviewed. Sixty cases met inclusion criteria. Overall, 17 of 60 patients (28%) had a hematologic abnormality as a result of envenomation. Eleven of 60 patients (65% of those with a hematologic abnormality; 18% overall) developed late hematologic abnormalities 4 or more days post‐envenomation. Four patients had late, new onset hypofibrinogenemia and/or thrombocytopenia. All were associated with early D‐dimer elevation and/or platelet rise in response to FabAV treatment, respectively. Normal hematologic parameters in the first 48 h post‐envenomation and the lack of a greater than 20% rise in platelets within 4 h post‐antivenom administration had a 100% NPV for late hematologic effects.

Conclusions.?Patients with early onset hypofibrinogenemia, a positive D‐dimer, thrombocytopenia, or a 20% increase in platelet count within 4 h post‐treatment had a significant likelihood of late hematologic effects. Patients in whom fibrinogen, D‐dimer, INR, PTT, and platelet counts remained normal throughout the first 48 h post‐envenomation, and who did not exhibit a >20% increase in platelet count within 4 h post‐antivenom administration, did not develop late hematologic effects.     

Cerebellar Dysfunction in Chronic Toluene Abuse: Beneficial Response to Amantadine Hydrochloride

Case Report: A 21-year-old man who had sniffed toluene since the age of 13 presented with a 4-year history of progressive cerebellar dysfunction and visual deterioration. The patient's condition did not improve despite 5 months of abstinence. Magnetic resonance imaging revealed cerebral atrophy and hypointensity signals in the white matter and bilaterally in the globus pallidus, thalamus, red nucleus, and substantia nigra. Amantadine hydrochloride therapy (100 mg/d, then 200 mg/d) resulted in dramatic improvement of his cerebellar and visual symptoms.     

Exotic snake bites in the Czech Republic—Epidemiological and clinical aspects during 15-year period (1999–2013)

Only one natural venomous snake—the adder viper—lives in the central European region and its bite is usually associated only with mild course of envenoming. Cases of envenoming caused by exotic snakes among their breeders are clinically more important. Objective. The aim of this study was to analyze the epidemiological and clinical aspects of registered venomous bites caused by exotic snakes in the Czech Republic over a period of 15 years (1999–2013). Materials and methods. This is an observational case series. Data have been collected retrospectively from a database and medical charts of the Toxinology Center belonging to the General University Hospital in Prague. Results. In total, 87 cases of exotic snakebites caused by 34 venomous snake species were registered during the study period, coming from 18 genera of Elapinae, Viperinae, and Crotalinae subfamilies. In the cohort, 29 patients (33.3%) developed systemic envenoming and 17 (19.5%) were treated with antivenom. Ten cases of envenoming (11.5%) were considered as potentially life threatening. No patient died due to envenoming caused by exotic snake bites during the study period. Four illustrative cases of envenoming (Echis pyramidum, Dendroaspis polylepis, Protobothrops mangshanensis, and Proatheris superciliaris) are described in detail. Conclusion. Bites caused by exotic snakes resulted in serious and life-threatening envenomings in some patients. Early transfer to the Center, antivenom administration, and support of failing organ functions contributed to favorable outcome of victims.