1.The role of bacterial toxin-antitoxin systems in phage abortive infections.
Yang HAI ; Xiaoyu WANG ; Jianping XIE
Chinese Journal of Biotechnology 2022;38(9):3291-3300
Bacteria are often infected by large numbers of phages, and host bacteria have evolved diverse molecular strategies in the race with phages, with abortive infection (Abi) being one of them. The toxin-antitoxin system (TA) is expressed in response to bacterial stress, mediating hypometabolism and even dormancy, as well as directly reducing the formation of offspring phages. In addition, some of the toxins' sequences and structures are highly homologous to Cas, and phages even encode antitoxin analogs to block the activity of the corresponding toxins. This suggests that the failure of phage infection due to bacterial death in abortive infections is highly compatible with TA function, whereas TA may be one of the main resistance and defense forces for phage infestation of the host. This review summarized the TA systems involved in phage abortive infections based on classification and function. Moreover, TA systems with abortive functions and future use in antibiotic development and disease treatment were predicted. This will facilitate the understanding of bacterial-phage interactions as well as phage therapy and related synthetic biology research.
Anti-Bacterial Agents
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Antitoxins/chemistry*
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Bacteria/genetics*
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Bacterial Proteins/chemistry*
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Bacterial Toxins/genetics*
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Bacteriophages/genetics*
;
Toxin-Antitoxin Systems/genetics*
2.Evaluation of Potency on Diphtheria and Tetanus Toxoid for Adult Vaccines by In Vivo Toxin Neutralization Assay Using National Reference Standards.
Chan Woong CHOI ; Jae Hoon MOON ; Jae Ok KIM ; Si Hyung YOO ; Hyeon Guk KIM ; Jung Hwan KIM ; Tae Jun PARK ; Sung Soon KIM
Osong Public Health and Research Perspectives 2018;9(5):278-282
OBJECTIVES: Vaccinations against diphtheria and tetanus are essential in providing immunity against these bacterial infections. The potency of diphtheria and tetanus toxoid vaccines can be measured using the in vivo toxin neutralization assay. The limit of potency of this assay was determined only for children. Therefore, we assessed the potency of adult vaccines using this assay to identify the feasibility of limit for adult vaccines. METHODS: Fifteen lots of tetanus-reduced diphtheria and tetanus-diphtheria-acellular pertussis vaccines were used. In vivo toxin neutralization and lethal challenge assays were conducted on each vaccine to calculate the potencies of the toxoids. National reference standards for toxins and antitoxins were used for in vivo toxin neutralization assay. RESULTS: All 15 lots satisfied the limits of potency for lethal challenge assay. The potency of diphtheria and tetanus toxoids exceeded 1 and 8 units/mL, respectively, for in vivo toxin neutralization assay. CONCLUSION: Although additional studies are required for new assays and limits, the current level of potency for adult vaccines as determined by in vivo toxin neutralization assay, was demonstrated in this study. Such efforts to improve assays are expected to promote the development of diphtheria and tetanus vaccines for adults and to contribute to vaccine self-sufficiency.
Adult*
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Antitoxins
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Bacterial Infections
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Child
;
Diphtheria Toxoid
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Diphtheria*
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Humans
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Tetanus Toxoid*
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Tetanus*
;
Toxoids
;
Vaccination
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Vaccines*
;
Whooping Cough
3.Antiendotoxin effect of Jinhuaqingre capsules.
Jiafu HOU ; Leilei WU ; Yuting CAI ; Changjiu GAO ; Jindan AN ; Zhongcheng YU
Journal of Zhejiang University. Medical sciences 2017;46(1):74-79
To investigate the anti-pyretic and anti-endotoxin effect of Chinese herb medicine Jinhuaqingre capsules.Thirty healthy male New Zealand rabbits with lipopolysaccharide-induced fever were divided into 5 groups (6 rabbits in each): animals in model group were given normal saline by gavage, animals in positive control group were given aspirin (0.2 g/kg), and animals in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0 or 1.5 g/kg, respectively. The changes in body temperature of rabbits were observed. Fifty healthy Kunming mice were divided into 5 groups (10 mice in each): mice in model group were given normal saline by gavage, mice in positive control group were given aspirin (0.2 g/kg), and those in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0, 1.5 g/kg, respectively. Matrix coloration method was used to detect the degradation rate of endotoxin in mice.The body temperature in rabbits of high and medium dose Jinhuaqingre capsule groups declined significantly 60 min after drug administration, and the temperature of high-dose group returned to the baseline after 300 min; while the body temperature of low-dose group started to decline at 180 min after drug administration. The endotoxin degradation rates in mice of high, medium and low dose groups was (56.73±3.12)%, (47.23±1.77)% and (21.08±2.30)% at 30 min after drug administration; those were (82.76±1.00)%, (64.75±1.77)% and (38.21±1.57)% at 60 min after drug administration, respectively.Chinese herb medicine Jinhuanigre capsules have anti-pyretic and anti-endotoxin effects, which may provide a new option for the treatment of heat-toxin syndrome.
Animals
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Antitoxins
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pharmacology
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Aspirin
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therapeutic use
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Dose-Response Relationship, Drug
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Drugs, Chinese Herbal
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Fever
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chemically induced
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drug therapy
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Lipopolysaccharides
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antagonists & inhibitors
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Male
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Medicine, Chinese Traditional
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Mice
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Rabbits
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Sodium Chloride
;
therapeutic use
4.Does the Traditional Snakebite Severity Score Correctly Classify the Envenomated Patients with Snake?.
Seungoh KANG ; Jeongmi MOON ; Byeongjo CHUN
Journal of the Korean Society of Emergency Medicine 2016;27(3):272-279
PURPOSE: The aim of this study was to help set the domestic guidelines for administration of antivenom to envenomated patients with snake. METHODS: This retrospective observation case series comprised 128 patients with a snake envenomation. The patients were divided into two groups according to the need for additional antivenom after the initial treatment strategy based on the traditional snakebite severity grading scale; one group recovered successfully with the initial treatment decision and did not require an additional antivenom (N=85) and the other group required an additional administration of antivenom later (N=43). RESULTS: The group requiring additional administration of antivenom showed a higher local effect score and traditional snakebite severity grading at presentation, a shorter prothrombin and activated partial prothrombin time, a higher frequency of rhabdomyolysis and disseminated intravascular coagulopathy, and longer hospitalization than the group that did not require an antivenom later. The most common cause of additional administration was the progression of local symptoms. The independent factor associated with the need for additional antivenom administration was a local effect scoring of pain score (odds ratio, 2.477; 95% confidence interval, 1.309 to 4.689). The optimal cut off value of local effect scoring of pain was 1.5 with 62.8% sensitivity and 71.8% specificity. CONCLUSION: The local effect scoring of pain should be considered when treating patients who are envenomated with a snake using the traditional snakebite severity scale. If the local effect scoring of pain is more than 2, an increase of antivenom should be considered and the patients should be assessed frequently.
Antivenins
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Hospitalization
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Humans
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Prothrombin
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Prothrombin Time
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Retrospective Studies
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Rhabdomyolysis
;
Sensitivity and Specificity
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Snake Bites*
;
Snakes*
;
Venoms
5.Does the traditional snakebite severity score correctly classify envenomated patients?.
Seungho KANG ; Jeongmi MOON ; Byeongjo CHUN
Clinical and Experimental Emergency Medicine 2016;3(1):34-40
OBJECTIVE: This study aims to help set domestic guidelines for administration of antivenom to envenomated patients after snakebites. METHODS: This retrospective observational case series comprised 128 patients with snake envenomation. The patients were divided into two groups according to the need for additional antivenom after the initial treatment based on the traditional snakebite severity grading scale. One group successfully recovered after the initial treatment and did not need any additional antivenom (n=85) and the other needed an additional administration of antivenom (n=43). RESULTS: The group requiring additional administration of antivenom showed a higher local effect score and a traditional snakebite severity grade at presentation, a shorter prothrombin and activated partial prothrombin time, a higher frequency of rhabdomyolysis and disseminated intravascular coagulopathy, and longer hospitalization than the group that did not need additional antivenom. The most common cause for additional administration was the progression of local symptoms. The independent factor that was associated with the need for additional antivenom was the local effect pain score (odds ratio, 2.477; 95% confidence interval, 1.309 to 4.689). The optimal cut-off value of the local effect pain score was 1.5 with 62.8% sensitivity and 71.8% specificity. CONCLUSION: When treating patients who are envenomated by a snake, and when using the traditional snakebite severity scale, the local effect pain score should be taken into account. If the score is more than 2, additional antivenom should be considered and the patient should be frequently assessed.
Antivenins
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Hospitalization
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Humans
;
Prothrombin
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Prothrombin Time
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Retrospective Studies
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Rhabdomyolysis
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Sensitivity and Specificity
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Snake Bites*
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Snakes
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Venoms
6.Ocular Manifestations of Venomous Snake Bite over a One-year Period in a Tertiary Care Hospital.
K V PRAVEEN KUMAR ; S PRAVEEN KUMAR ; Nirupama KASTURI ; Shashi AHUJA
Korean Journal of Ophthalmology 2015;29(4):256-262
PURPOSE: Ocular manifestations in snake-bite injuries are quite rare. However, the unusual presentations, diagnosis and their management can pose challenges when they present to the ophthalmologist. Early detection of these treatable conditions can prevent visual loss in these patients who are systemically unstable and are unaware of their ocular condition. To address this, a study was conducted with the aim of identifying the various ocular manifestations of snake bite in a tertiary care center. METHODS: This is a one-year institute-based prospective study report of 12 snake bite victims admitted to a tertiary hospital with ocular manifestations between June 2013 to June 2014, which provides data about the demographic characteristics, clinical profiles, ocular manifestations, and their outcomes. RESULTS: Twelve cases of snake bite with ocular manifestations were included of which six were viper bites, three were cobra bites and three were unknown bites. Six patients presented with bilateral acute angle closure glaucoma (50%), two patients had anterior uveitis (16.6%) of which one patient had concomitant optic neuritis. One patient had exudative retinal detachment (8.3%), one patient had thrombocytopenia with subconjunctival hemorrhage (8.3%) and two patients had external ophthalmoplegia (16.6%). CONCLUSIONS: Bilateral angle closure glaucoma was the most common ocular manifestation followed by anterior uveitis and external ophthalmoplegia. Snake bite can result in significant ocular morbidity in a majority of patients but spontaneous recovery with anti-snake venom, steroids and conservative management results in good visual prognosis.
Acute Disease
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Adolescent
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Adult
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Animals
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Antivenins/therapeutic use
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*Elapidae
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Female
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Follow-Up Studies
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Glaucoma, Angle-Closure/diagnosis/*etiology/therapy
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Humans
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Male
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Middle Aged
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Ophthalmoplegia/diagnosis/*etiology/therapy
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Prospective Studies
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Snake Bites/*complications/diagnosis/therapy
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Snake Venoms/*poisoning
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Tertiary Healthcare
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Time Factors
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Uveitis, Anterior/diagnosis/*etiology/therapy
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*Viperidae
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Young Adult
7.Snakebite in Korea: A Guideline to Primary Surgical Management.
Jung Ho RHA ; Sung Min KWON ; Jin Rok OH ; Byung Keun HAN ; Kang Hyung LEE ; Jae Hyun KIM
Yonsei Medical Journal 2015;56(5):1443-1448
PURPOSE: Snakebite is an emergency which causes local symptoms such as pain and edema around the bite. Systemic symptoms may also develop, such as dizziness or renal failure, and may even cause death. The purpose of this research was to assess the validity and safety of snakebite protocol for surgery when treating snakebite patients. MATERIALS AND METHODS: Retrospective research was performed on patients who were admitted after being treated at the emergency center from January 2008 to December 2012. When necessary, debridement was also performed, and 46 of 111 patients (41.4%) underwent debridement. Those who had received debridement without antivenom administration due to a positive skin reaction test were classified as group A, and group B received antivenom and delayed debridement. We reviewed the emergency and admission charts of the patients in each group and recorded and compared their age, sex, bite site, severity of local and general symptoms, time to receive antivenin, and complications. RESULTS: Of the ten patients (21.7%) in group A, two (66.6%) developed cellulites, and one of them experienced skin necrosis, resulting in a skin graft. In group B, there were 36 patients (78.2%), 19 (52.7%) of whom developed cellulitis. Skin necrosis occurred in two patients, and one of these patients received a skin graft. Compartment syndrome was found in one patient, and fasciotomy and a skin graft were performed. CONCLUSION: The treatment protocol implemented to treat snakebite patients admitted to the emergency center during this research was safely and properly followed during surgical treatment.
Adult
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Aged
;
Antivenins/administration & dosage
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Combined Modality Therapy
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Compartment Syndromes
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Debridement/*methods
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Disease Management
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Edema/etiology
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Female
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Humans
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Male
;
Middle Aged
;
Necrosis
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*Practice Guidelines as Topic
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Republic of Korea
;
Retrospective Studies
;
Severity of Illness Index
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Skin/pathology
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Skin Transplantation/*methods
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Snake Bites/complications/*diagnosis/pathology/*surgery
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Snake Venoms/adverse effects
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Soft Tissue Injuries/etiology/*pathology/surgery
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Treatment Outcome
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Wound Healing/physiology
8.The current situation and strategies of snake antivenomimmunoglobulins research and development.
Jing TIAN ; Quan-shui FAN ; Ying ZHENG
Acta Pharmaceutica Sinica 2015;50(12):1573-1580
Snake antivenomimmunoglobulins are considered to be the most efficient drugs in snake envenomings. Most snake antivenomimmunoglobulins all over the world are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum till now. In this review, we retrospect the history of snake antivenomimmunoglobulins, analysis the present situation and pay the close attention on the key technological links in the process of research and manufacturing, such as properties of IgG and its fragments, selection and preparation of immunogen, optimization of immunization schedule and protein isolation and purification, which can be available for the reference in the research and development of snake antivenom.
Animals
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Antivenins
;
pharmacology
;
Humans
;
Immunoglobulin G
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pharmacology
;
Snake Bites
;
drug therapy
;
Snakes
9.Bilateral Acute Anterior Uveitis and Optic Disc Edema Following a Snake Bite.
Praveen K KUMAR ; Shashi AHUJA ; Praveen S KUMAR
Korean Journal of Ophthalmology 2014;28(2):186-188
The authors wish to report a case of bilateral acute anterior uveitis and optic disc edema following a hemotoxic snake bite, in order to highlight the concomitant occurrence of these conditions and the potential adverse effects of anti-snake venom (ASV). A 35-year-old male was bitten by a viper at seventeen thirty hours, and was started on ASV. Two days following treatment he experienced sudden onset redness and painful diminution of vision in both eyes (OU). On examination, the patient's visual acuity (VA) in OU was 20/200. Examination revealed fresh keratic precipitates, cells, and flare in the anterior chamber (AC), posterior synechiae, sluggish and ill-sustained pupillary reaction, and hyperemic, edematous disc with blurred margins in OU. He was started on topical steroids, cycloplegics and intravenous methylprednisolone. Following treatment, the patient showed improvement and was continued on topical medications and oral prednisolone tapered over 3 weeks, after which VA OU improved, the AC showed no cells and flare and disc edema resolved. Uveitis and optic disc edema in snake bite can either be due to the direct toxic effects of the venom or the effect of ASV. Steroids have a beneficial role in the management of these symptoms.
Acute Disease
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Adult
;
Antivenins/*adverse effects
;
Glucocorticoids/administration & dosage
;
Humans
;
Hyperemia/drug therapy/etiology/pathology
;
Male
;
Methylprednisolone/administration & dosage
;
Papilledema/drug therapy/*etiology/pathology
;
Snake Bites/*complications/*therapy
;
Uveitis, Anterior/drug therapy/*etiology/pathology
10.Study on clinical efficacy of combination of traditional Chinese medicine and western medicine in treatment of pit viper bites and peripheral blood inflammatory factors.
Zhi-Mei FANG ; Guo-Hua HU ; Bao-Xiang HE ; Yi-Qing YIN ; Ling-Ling WU ; Guo-Chan HE
China Journal of Chinese Materia Medica 2013;38(7):1087-1090
OBJECTIVETo observe the clinical efficacy of combination of traditional Chinese medicine and western medicine in the treatment of patient bitten by agkistrodon halys pallas, and the changes in peripheral blood inflammatory factors (hs-PCR, IL-6, TNF-alpha).
METHODNinty-eight patients were divided into three groups according to their hospitalization dates: the western medicine group, in which 32 patients were treated with antivenom serum (6 000 U) for five days, once every day; the traditional Chinese medicine group, in which 32 patients were treated with anti pit viper No. 2 concentrated decoction (300 mL), twice to three times every day, for five days; and the combined traditional Chinese medicine and western medicine group, in which 35 patients were treated with the combination of Chinese and Western medicine treatment described above. Then blood samples of all of patients were obtained, and serum factors (hs-PCR, IL-6, TNF-alpha) in peripheral blood were measured by Elisa assay. Another 30 health volunteers were chosen as the normal control group.
RESULTThe serum inflammatory factors were significantly higher in all patients of the three groups than that in healthy control before treatment (P < 0.01), and decreased significantly after treatment. In particular, the more remarkable reduction was found in the combined traditional Chinese medicine and western medicine group compared with the western medicine group and the traditional medicine group (P < 0.01). Symptom elimination in the three groups was superior to the western medicine group and the traditional medicine group at the first day and the third day of treatment (P < 0.05, P < 0.01). Total clinical effective rate was 100% in the combined traditional Chinese medicine and western medicine group, 84. 37% in the traditional medicine group and 65.62% in the western medicine group, the clinical effective rate of the combined traditional Chinese medicine and western medicine group was notably superior to that of the western medicine group and the traditional medicine group (P < 0.01).
CONCLUSIONThe serum inflammatory factors increased significantly in patients bitten by agkistrodon halys pallas. Treatment with the combined traditional Chinese medicine and western medicine can significantly decrease the serum inflammatory factors, and increase clinical effect, with more obvious clinical efficacy compared with the western medicine group and the traditional medicine group.
Adolescent ; Adult ; Aged ; Antivenins ; administration & dosage ; Child ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Interleukin-6 ; blood ; immunology ; Male ; Middle Aged ; Snake Bites ; blood ; drug therapy ; immunology ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood ; immunology ; Young Adult

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