Poison induced pica in rats.

Two experiments investigating the effects of poisoning on the consumption of non-nutritive substances are reported. In the first experiment, rats were poisoned with lithium chloride or Red Squill and offered a choice between food and soil. In the second experiment, rats were poisoned with cyclophosphamide and offered a choice between food and kaolin. Following treatment, poisoned rats in both experiments increased their consumption of the non-nutritive substances. Additionally, rats poisoned with logarithmic doses consumed amounts of the non-nutritive substances proportionate to the amount of poison administered. It was suggested that increased pica is an illness-response behavior of the rat, analogous to vomiting in other species, which can be used as an easily quantifiable behavioral assay of noxious drug effects.     

Analysis of Hymenoptera stings reported to the Illinois Poison Center

Although there is some detailed research on anaphylactic reactions to Hymenoptera venom, there continues to be little epidemiological data about the distribution, trend, and factors associated with the occurrence of Hymenoptera envenomations in humans. We describe characteristics of persons suffering Hymenoptera stings from bees, wasps, and hornets as reported to the Illinois Poison Center, and assess seasonal, climatologic, and time trends of calls for envenomations between 2002 and 2007. Mean daily temperature and mean daily atmospheric pressure were positively associated with envenomations, whereas wind speed was negatively associated with envenomations. We also observed a significant increase in calls for envenomations on summer holidays (P < 0.001). In addition, our findings showed that the number of calls for envenomations declined by nearly half after 2005 (P < 0.001) compared with previous years. Our findings indicate that the decline in bees, wasps, and hornets may be widespread, affecting both wild and commercial populations, and that the decline appears to have been rapid and sustained in recent years. Poison center data are a valuable resource for the surveillance of poisoning in humans, but our findings show that the data can be used to monitor changes in nonhuman species.     

Single Dose Parenteral Hyposensitization to Poison Ivy Urushiol in Guinea Pigs

Abstract

Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of lmg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of penta-decyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significandy different from the single dose group. These findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyposensitization can be reasonably accomplished in a single dose treatment regimen.     

Poison exon annotations improve the yield of clinically relevant variants in genomic diagnostic testing

PurposeNeurodevelopmental disorders (NDDs) often result from rare genetic variation, but genomic testing yield for NDDs remains below 50%, suggesting that clinically relevant variants may be missed by standard analyses. Here, we analyze “poison exons” (PEs), which are evolutionarily conserved alternative exons often absent from standard gene annotations. Variants that alter PE inclusion can lead to loss of function and may be highly penetrant contributors to disease.MethodsWe curated published RNA sequencing data from developing mouse cortex to define 1937 conserved PE regions potentially relevant to NDDs, and we analyzed variants found by genome sequencing in multiple NDD cohorts.ResultsAcross 2999 probands, we found 6 novel clinically relevant variants in PE regions. Five of these variants are in genes that are part of the sodium voltage-gated channel alpha subunit family (SCN1A, SCN2A, and SCN8A), which is associated with epilepsies. One variant is in SNRPB, associated with cerebrocostomandibular syndrome. These variants have moderate to high computational impact assessments, are absent from population variant databases, and in genes with gene-phenotype associations consistent with each probands reported features.ConclusionWith a very minimal increase in variant analysis burden (average of 0.77 variants per proband), annotation of PEs can improve diagnostic yield for NDDs and likely other congenital conditions.     

Poison Domains Block Transit of Translocated Substrates via the Legionella pneumophila Icm/Dot System

Legionella pneumophila uses the Icm/Dot type 4B secretion system (T4BSS) to deliver translocated protein substrates to the host cell, promoting replication vacuole formation. The conformational state of the translocated substrates within the bacterial cell is unknown, so we sought to determine if folded substrates could be translocated via this system. Fusions of L. pneumophila Icm/Dot-translocated substrates (IDTS) to dihydrofolate reductase (DHFR) or ubiquitin (Ub), small proteins known to fold rapidly, resulted in proteins with low translocation efficiencies. The folded moieties did not cause increased aggregation of the IDTS and did not impede interaction with the adaptor protein complex IcmS/IcmW, which is thought to form a soluble complex that promotes translocation. The translocation defect was alleviated with a Ub moiety harboring mutations known to destabilize its structure, indicating that unfolded proteins are preferred substrates. Real-time analysis of translocation, following movement during the first 30 min after bacterial contact with host cells, revealed that the folded moiety caused a kinetic defect in IDTS translocation. Expression of an IDTS fused to a folded moiety interfered with the translocation of other IDTS, consistent with it causing a blockage of the translocation channel. Furthermore, the folded protein fusions also interfered with intracellular growth, consistent with inefficient or impaired translocation of proteins critical for L. pneumophila intracellular growth. These studies indicate that substrates of the Icm/Dot T4SS are translocated to the host cytosol in an unfolded conformation and that folded proteins are stalled within the translocation channel, impairing the function of the secretion system.     

Immune control

The immune system's job is protection from illness. Following a long period of HIV infection, the immune system often fails. Opportunistic infections may ensue during this slow process of disease progression. Some HIV-positive people, however, do not experience immune system damage, do not develop opportunistic infections, and have undetectable levels of HIV. These long-term nonprogressors are being studied by Dr. Bruce Walker from Harvard University. Background information on how the immune system normally controls HIV and the importance of HIV-specific memory T4 cells is presented. Dr. Walker and other researchers hope to learn how to keep the immune system working against HIV. Preliminary results that demonstrate restoration of immune functions are presented.     

蜂毒清1号对轻中度毒蜂蜇伤患者心肝肾功能影响的临床研究

目的 探讨自拟中药（蜂毒清颗粒1号）对轻中度毒蜂蛰伤患者的临床疗效。方法 选择2016年5月~2018年5月我院急诊科收治的轻中度蜂蛰伤患者420例,随机分为治疗组与对照组,各210例。对照组患者给予常规治疗方案,治疗组在对照组基础上经中医辨证给予蜂毒清1号颗粒口服。比较两组临床疗效、肝肾功能恢复情况,心肌酶水平及住院时间。结果 治疗组总有效率为98.09%,高于对照组的93.81%,差异有统计学意义（P＜0.05）;治疗组的心肌酶、肝功能指标均较对照组下降,差异有统计学意义（P＜0.05）;两组患者肾功能指标比较,差异无统计学意义（P＞0.05）;治疗组患者住院时间少于对照组[（4.15±1.50）d vs （6.25±2.05）d],差异有统计学意义（P＜0.05）。结论 常规西医治疗联合蜂毒清颗粒1号能够改善轻中度蜂蜇伤患者病情,提高临床疗效,缩短病程时间。另外,对于轻中度蜂蛰伤患者,早期应重视其心肌酶、肝功能变化情况。