Envenomation by Trimeresurus stejnegeri stejnegeri: clinical manifestations, treatment and associated factors for wound necrosis.

BACKGROUND: Trimeresurus stejnegeri stejnegeri bite induces tissue swelling, pain, thrombocytopenia, rhabdomyolysis, and acute renal failure. However, the incidence of coagulopathy, factors associated with wound necrosis, and the appropriate management of this condition have not been well characterized yet. MATERIALS: This study included patients bitten by T. s. stejnegeri that were admitted to the study hospitals from 2001 to 2016. Patient characteristics, laboratory data, and management approaches were compared in victims with and without wound necrosis. RESULTS: A total of 185 patients were evaluated: three patients (1.6%) were asymptomatic; whereas tissue swelling and pain, local ecchymosis, wound necrosis, coagulopathy, thrombocytopenia, rhabdomyolysis, and renal impairment were present in 182, 53, 13, 15, 10, 1, and 3 patients, respectively. One patient died from coagulopathy and hemorrhagic shock. Antivenom was administered to all envenomed patients at a median time of 1.8 h after the bite. The median total dose of antivenom was five vials. Chi-square analysis showed that bitten fingers, using cold packs during first aid, presence of bullae or blisters, lymphangitis or lymphadenitis, local numbness and suspected infection to be significantly associated with wound necrosis. After adjustment using a multivariate logistic regression model, only cold packs as first aid, bulla or blister formation, and wound infection remained significant. CONCLUSIONS: The main effects of T. s. stejnegeri envenomation are tissue swelling, pain, and local ecchymosis. We do not recommend the use of cold packs during first aid to reduce wound pain, as this may be a risk factor for wound necrosis. In addition, patients with bulla or blister formation should be carefully examined for subsequent wound necrosis. Antiplatelet use may worsen systemic bleeding. No severe rhabdomyolysis or renal failure was observed in this large case series, we therefore considered that they were not prominent effects of T. s. stejnegeri bite.

Envenomation by Trimeresurus stejnegeri stejnegeri: clinical manifestations, treatment and associated factors for wound necrosis

Trimeresurus stejnegeri stejnegeri bite induces tissue swelling, pain, thrombocytopenia, rhabdomyolysis, and acute renal failure. However, the incidence of coagulopathy, factors associated with wound necrosis, and the appropriate management of this condition have not been well characterized yet. Materials: This study included patients bitten by T. s. stejnegeri that were admitted to the study hospitals from 2001 to 2016. Patient characteristics, laboratory data, and management approaches were compared in victims with and without wound necrosis. Results: A total of 185 patients were evaluated: three patients (1.6%) were asymptomatic; whereas tissue swelling and pain, local ecchymosis, wound necrosis, coagulopathy, thrombocytopenia, rhabdomyolysis, and renal impairment were present in 182, 53, 13, 15, 10, 1, and 3 patients, respectively. One patient died from coagulopathy and hemorrhagic shock. Antivenom was administered to all envenomed patients at a median time of 1.8 h after the bite. The median total dose of antivenom was five vials. Chi-square analysis showed that bitten fingers, using cold packs during first aid, presence of bullae or blisters, lymphangitis or lymphadenitis, local numbness and suspected infection to be significantly associated with wound necrosis. After adjustment using a multivariate logistic regression model, only cold packs as first aid, bulla or blister formation, and wound infection remained significant. Conclusions: The main effects of T. s. stejnegeri envenomation are tissue swelling, pain, and local ecchymosis. We do not recommend the use of cold packs during first aid to reduce wound pain, as this may be a risk factor for wound necrosis. In addition, patients with bulla or blister formation should be carefully examined for subsequent wound necrosis. Antiplatelet use may worsen systemic bleeding. No severe rhabdomyolysis or renal failure was observed in this large case series, we therefore considered that they were not prominent effects of T. s. stejnegeri bite.(AU)

Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection.

OBJECTIVE: Lipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the clinical manifestation and mechanistic relevance of plasma triglyceride (TG), cholesterol (Chol), lipoproteins and apolipoproteins (apos) after DAA treatment. DESIGN: Twenty-four patients with chronic genotype 1 (GT1) HCV treated with elbasvir/grazoprevir or ledipasvir/sofosbuvir for 12 weeks, and followed-up thereafter, were recruited. Their TG, Chol, apoAI and apoB levels were quantified in plasma samples and individually fractionated lipoprotein of various classes. Liver fibrosis was evaluated using the FIB-4 Score. The TG and Chol loading capacities were calculated with normalisation to apoB, which represents per very low density lipoprotein (VLDL) and LDL particle unit RESULTS: DAA treatment achieved a sustained virological response rate of 91.7% and reduced the FIB-4 Score. Relative to the baseline, the plasma TG level was reduced but the Chol level increased gradually. Plasma apoB levels and apoB/apoAI ratio were transiently downregulated as early as the first 4 weeks of treatment. The TG and Chol loading capacities in VLDL were elevated by ~20% during the period of DAA treatment and had steadily increased by 100% at follow-up. Furthermore, the TG-to-Chol ratio in VLDL was increased, while the ratio in LDL was reduced, indicating an efficient catabolism. CONCLUSION: The DAA treatment of patients with chronic hepatitis C might lead to efficient HCV eradication and hepatic improvement concomitantly evolving with favouring lipoprotein/apo metabolisms.

Lipoprotein lipase liberates free fatty acids to inhibit HCV infection and prevent hepatic lipid accumulation.

Lipoprotein lipase (LPL) has been identified as an anti-hepatitis C virus (HCV) host factor, but the cellular mechanism remains elusive. Here, we investigated the cellular mechanism of LPL involving in anti-HCV. The functional activation of peroxisome proliferator-activated receptor (PPAR) α signal by LPL transducing into hepatocytes was investigated in HCV-infected cells, primary human hepatocytes, and in HCV-core transgenic mice. The result showed that the levels of transcriptional transactivity and nuclear translocation of PPARα in Huh7 cells and primary human hepatocytes were elevated by physiologically ranged LPL treatment of either very-low density lipoprotein or HCV particles. The LPL-induced hepatic PPARα activation was weakened by blocking the LPL enzymatic activity, and by preventing the cellular uptake of free unsaturated fatty acids with either albumin chelator or silencing of CD36 translocase. The knockdowns of PPARα and CD36 reversed the LPL-mediated suppression of HCV infection. Furthermore, treatment with LPL, like the direct activation of PPARα, not only reduced the levels of apolipoproteins B, E, and J, which are involved in assembly and release of HCV virions, but also alleviated hepatic lipid accumulation induced by core protein. HCV-core transgenic mice exhibited more hepatic miR-27b, which negatively regulates PPARα expression, than did the wild-type controls. The induction of LPL activity by fasting in the core transgenic mice activated PPARα downstream target genes that are involved in fatty acid ß-oxidation. Taken together, our study reveals dual beneficial outcomes of LPL in anti-HCV and anti-steatosis and shed light on the control of chronic hepatitis C in relation to LPL modulators.

Lead, mercury, and arsenic poisoning due to topical use of traditional Chinese medicines.

BACKGROUND: Metal poisonings through a mucocutaneous route are reported rarely in the literature. METHODS: We report 2 cases of heavy metal intoxication from inappropriate use of Chinese mineral medicines confirmed by toxicologic investigations. RESULTS: A 51-year-old man developed perianal gangrene and a high fever after a 2-week anal use of hong-dan herbal mixtures for anal fistula. He presented gastrointestinal and constitutional symptoms, followed by skin rash, anemia, hair loss, peripheral neuropathy, and muscle atrophy. Elevated urine arsenic and mercury confirmed the heavy metal poisonings. The hong-dan mixture contained lead tetraoxide, arsenic, and mercury. He was treated with 2,3-dimercapto-1-propanesulfonic acid, with partial improvement, but peripheral neuropathy persists 4 years later. A 75-year-old man developed anorexia, weight loss, headache, dizziness, nausea, vomiting, constipation, weakness, and anemia after a 3-month use of an herbal patch for chronic leg ulcer. His blood lead concentration was 226 µg/dL, and the lead content of the herbal patch was 517 mg/g. Chelation with ethylene diamine tetraacetic acid and dimercaptosuccinic acid was followed by clinical recovery. CONCLUSION: These cases documented serious systemic poisoning after the short-term use of traditional Chinese medicines containing heavy metals in damaged or infected tissue.

Acute human glufosinate-containing herbicide poisoning.

BACKGROUND: Glufosinate-containing herbicides are commonly used worldwide. Data on acute human glufosinate poisoning however remain scarce. METHODS: We retrospectively reviewed the medical records of all glufosinate poisoned cases reported to the Taiwan National Poison Control Center and two medical centers in Taiwan from August 1993 through February 2010. Their demographic and clinical data were then analyzed to identify potential predictors of severe effects following acute glufosinate poisoning. RESULTS: One hundred and thirty-one patients, including 115 oral and 16 non-oral exposures, were eligible for final analysis. Among patients with oral exposure, 25 were asymptomatic, while the others developed gastrointestinal, neurological, cardiovascular, and/or respiratory manifestations. Seven patients (6.1%) died following deliberate glufosinate ingestion. The median dose of glufosinate ingestion was 30.4 grams (interquartile range 18.5-45.6 grams) in the severe/fatal group compared to 6.8 grams (interquartile range 3.7-16.2 grams) in the non-severe group (p <0.001). Older age (≥ 61 years; adjusted OR 4.9, 95% CI 1.3-17.9) and larger amount of glufosinate ingestion (≥ 13.9 grams; adjusted OR 25.2, 95% CI 4.8-132.5) were positively associated with the development of severe toxicity, whereas ethanol consumption (adjusted OR 0.1, 95% CI <0.1-0.5) was inversely associated with the risk of severe toxicity. CONCLUSION: Although glufosinate is generally thought to be of low toxicity to humans, severe effects can occur and may be associated with older age, larger amount of ingestion and absence of concomitant ethanol consumption.

Acute hemolysis following iodine tincture ingestion.

Iodine tincture poisoning is uncommon regardless of its widespread use as an antiseptic in daily practice. Previously reported effects of iodine-containing antiseptic poisoning included topical irritation, corrosive effects, allergic response, and hepatic or renal injury, which mainly resulted from complications of topical use during surgical procedures. We herein reported an unusual case of severe hemolysis and acute renal failure following intentional ingestion of iodine tincture containing 60 mg/ml iodine and 40 mg/ml potassium iodide in 70% v/v ethanol. The patient completely recovered 8 weeks later after receiving supportive treatment, plasma exchange, and temporary hemodialysis.

Acute severe chromium poisoning after dermal exposure to hexavalent chromium.

Severe acute chromium poisoning related to dermal involvement has rarely been reported in the literature. We report a case of acute severe chromium poisoning through skin exposure as a result of a chemical burn of 15% of the body surface area and multiple organ failure after short-term exposure. Medical interventions, including mechanical ventilation, continuous venovenous hemofiltration, and plasmapheresis were performed. In addition, a chelating agent, dimercaptopropane sulfonic acid, was infused intravenously, combined with intravenous N-acetylcysteine and ascorbic acid as adjuvant therapy. The patient was discharged on day 33 without long-term sequelae. The consequence of transdermal exposure of hexavalent chromium should not be overlooked.

Human Melia azedarach poisoning.

INTRODUCTION: In traditional Chinese medicine, Melia azedarach (Ku-lian) is used orally and topically as an antiparasitic and antifungal agent. Although toxicity of this plant has been widely described in veterinary literature, human poisoning is rarely reported. We describe five patients with M. azedarach poisoning who recovered with supportive care. CASE SERIES: Five patients were identified retrospectively from the database of the Taiwan National Poison Center at the Taipei Veterans General Hospital. Three cases were on-site patients, and two were telephone consultations from outside hospitals. Neurological symptoms were the major manifestation in four cases: weakness, myalgia, numbness, and ptosis. Treatment was symptomatic and supportive; all patients recovered without sequelae. DISCUSSION: It is not known which limonoids are responsible for human toxicity. In the Chinese medical literature, human M. azedarach poisoning is said to occur if six to nine fruits, 30 to 40 seeds, or 400 g of the bark is consumed. Onset of symptoms typically occurs within 4-6 h, but as short as 0.5 h had been documented. In our patients, the onset of M. azedarach poisoning was variable, ranging from a few hours to up to 3 weeks after consumption of the herb. CONCLUSIONS: M. azedarach poisoning may result in gastrointestinal, cardiovascular, respiratory, or neurological effects, and death in severe cases.

Acute hepatic injury and renal failure after ingestion of snake gallbladder.

Ingestion of snake gallbladder has been practiced in ancient Chinese civilizations to improve vision and relieve arthritic pain. Although little is known about the composition of snake gallbladder, ingestion is still practiced in some Chinese cultures. Adverse effects of ingesting snake gallbladder have not yet been reported. Here, we present a case of acute hepatic injury and delayed-onset renal failure after ingestion of snake gallbladders. The patient subsequently recovered after supportive care, combined with plasma exchange and hemodialysis. He was the only survivor of the four victims suffering from intoxication of snake gallbladder in the last three years in our hospital.

Divergent role of calcium on Abeta- and MPTP-induced cell death in SK-N-SH neuroblastoma.

We attempted to clarify the role of Ca2+ in cell death caused by beta-amyloid protein (Abeta) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in SK-N-SH neuroblastoma, respectively. Two insults both reduced cell viability in a concentration-dependent manner and induced equal cytotoxicity in the presence of 20 microM Abeta and 0.4 mM MPTP for 72 h, respectively (68+/-7 vs. 64+/-6% viability). Time-related study showed that Abeta evoked cell death occurred quickly at 24 h. Relatively, MPTP exhibited a delayed cell death significantly after 72 h of culture. Pretreating the cells with nimodipine and chelating of Ca2+ by EGTA plus 1,2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) successfully rescued Abeta-induced cell death but failed to prevent MPTP toxicity. ELISA determination of mono/oligonucleosomes accumulation showed the mode of cell death evoked by MPTP was presumably apoptosis while by Abeta was necrosis. SK-N-SH cells constitutively expressed the alpha(1C) subunit of L-type Ca2+ channel and exposure to Abeta or MPTP for 96 h did not further modify its expression. By contrast, alpha(1D) subunit was undetectable or low level expressed in basal condition, but was induced to express after Abeta and MPTP stimulation in a time-dependent manner. Functional assay revealed that KCl-evoked [Ca2+]i rise was significantly greater in Abeta-, but not in MPTP-treated cells when compared with control. Taken together, these results showed that Abeta and MPTP elicited different mode of cell death in SK-N-SH. Nevertheless, Ca2+ overload seems to solely display a crucial role in Abeta-induced cytotoxicity and over-expressed alpha(1D) may contribute to the disruption of cellular Ca2+ homeostasis.

Chlordiazepoxide-induced Stevens-Johnson syndrome.

The causes of Stevens-Johnson syndrome (SJS) can be categorized as iatrogenic, infectious or idiopathic. Drug-induced SJS is associated with various antibiotics, anticonvulsants, and other drugs. However, no previous reports have mentioned an association between chlordiazepoxide, a benzodiazepine sedative, and SJS. Here, we present a case of SJS induced by chlordiazepoxide overdose. This case reminds us that SJS may be an adverse effect of chlordiazepoxide. Further, overdosage with benzodiazepine sedatives should be added to the list of potential causes of SJS.

Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents.

A series of amides of caffeic acid were synthesized and evaluated for their anti-platelet and anti-oxidative activities. N-(2-Bromo-phenyl)-3-(3,4-dihydroxy-phenyl)-acrylamide (12) and N-(3-Bromo-phenyl)-3-(3,4-dihydroxy-phenyl)-acrylamide (13) exhibited potent inhibitory activity (IC(50)=5.8 and 6.7 microM, respectively) against arachidonic acid-induced (AA) platelet aggregation, comparable with invalid caffeic acid. Most of the synthesized caffeic acid anilides exhibited the promising anti-platelet aggregation in AA-induced assay and anti-oxidative activities. This study also exhibited that caffeic anilides displayed more potent anti-oxidative activity in the radical scavenging activity assay than trolox and vitamin E.

Clinical experience of acute ferric chloride poisoning.

Ferric chloride is both a corrosive acid and iron compound; reports of poisoning in humans are rare. A retrospective study was conducted to evaluate patients with ferric chloride exposure reported to Poison Control Center-Taipei Veterans General Hospital during 1990-2001. After exclusion of incomplete records, 16 patients with ferric chloride exposure were analyzed (9 male, 7 female aged 12 to 70 y). The exposures were occupational inhalation (18.7%), suicidal ingestion (56.3%), and accidental ingestion (25.0%). Major symptoms and signs were nausea/vomiting (68.8%), sore throat (68.8%), abdominal pain (37.5%), oral ulcers (37.5%), metabolic acidosis (25.0%), aspiration pneumonia (18.8%), respiratory failure (12.5%), diarrhea (12.5%), and hypotension (12.5%). The severity of poisonings were fatal 6.3%, severe 18.8%, moderate 31.2%, mild 37.5%, and asymptomatic 6.3%. Deferoxamine therapy was given in 9 hospitalized patients with good recovery; however the fatal case did not receive deferoxamine due to rapid deterioration and a late diagnosis. The serum iron level known in 7 cases ranged from 40 to 2440 microg/dL. Ingestion of ferric chloride may result in serious morbidity and mortality. Inappropriate labeling and storage lead to accidental swallowing or misdiagnosis. Early diagnosis is important, especially in seriously poisoned patients.

Identification of the antigenic determinants of the American cockroach allergen Per a 1 by error-prone PCR.

The group I allergen of cockroach is found in both American and German cockroaches, designated as Per a 1 and Bla g 1, respectively. Members of these allergens so far identified are composed of tandem repeats that may cause the high allergenicity of Per a 1 allergen. In this study, we used monoclonal antibodies HW-8 and HW-19, which can inhibit the binding of patient IgE to Per a 1 allergen, to define the structure of the antigenic determinants in Per a 1.0103 (designated C3), an isoallergen of Per a 1 allergen. Two recognition sites are present, one in the N-terminus (aa 1-208) and the other in the C-terminus (aa 208-395). The N-terminal epitope is not accessible to antibody molecules on the pET-expressed C3 protein. The C-terminal epitope was further localized to the aa 267-354 region (C3E) by colony immunoscreening of the cDNA epitope library. By negative screening of the mutated C3E expression library generated by error-prone PCR (ER-PCR), an approach which has rarely been applied in epitope mapping, the functional epitope was identified to lie in aa 318-337 with aa 323-331 being the core motif. The minimal region of the functional epitope was further delineated, by sequence alignment, to be D-x-[I, L]-A-[I, L]-L-P-V-D-E-[L, I]-x-A-[L, I], where x represents any amino acids. This motif is found in all Per a 1 allergens and may serve as a basis for designing a peptide vaccine for allergen-specific immunotherapy. To our knowledge, this is the first report for (1) detailed mapping of the cockroach allergens and (2) use of error-prone PCR random mutagenesis and negative selection in molecular allergology.