Diagnosis and management of histoplasmosis

Histoplasmosis occurs sporadically or during outbreaks in endemic areas. The risk for severe forms of histoplasmosis is substantially higher among the growing population of immunocompromised patients. Recent research efforts have focused on analyzing epidemics, identifying risk factors for the disease, developing improved noninvasive diagnostic assays, and assessing the roles of newer antifungal drugs. Guidelines have been published for the prevention of occupationally acquired histoplasmosis and for reducing the risk of disease in patients with HIV infection. A third-generation Histoplasma antigen assay has been developed, which has superior performance characteristics compared to other noninvasive diagnostic tests. Treatment guidelines for the various clinical forms of histoplasmosis have been formulated and updated. Two newer azoles with activity against Histoplasma capsulatum, voriconazole and posaconazole, have been released; in vitro susceptibility data and animal model results have been reported, and treatment experience with these drugs has accumulated.     

Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5

A variety of stress signals stimulate cardiac myocytes to undergo hypertrophy. Persistent cardiac hypertrophy is associated with elevated risk for the development of heart failure. Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy and that stress signals neutralize this repressive function by triggering phosphorylation- and CRM1-dependent nuclear export of these chromatin-modifying enzymes. However, the identities of cardiac HDAC kinases have remained unclear. Here, we demonstrate that signaling by protein kinase C (PKC) is sufficient and, in some cases, necessary to drive nuclear export of class II HDAC5 in cardiomyocytes. Inhibition of PKC prevents nucleocytoplasmic shuttling of HDAC5 in response to a subset of hypertrophic agonists. Moreover, a nonphosphorylatable HDAC5 mutant is refractory to PKC signaling and blocks cardiomyocyte hypertrophy mediated by pharmacological activators of PKC. We also demonstrate that protein kinase D (PKD), a downstream effector of PKC, directly phosphorylates HDAC5 and stimulates its nuclear export. These findings reveal a novel function for the PKC/PKD axis in coupling extracellular cues to chromatin modifications that control cellular growth, and they suggest potential utility for small-molecule inhibitors of this pathway in the treatment of pathological cardiac gene expression.     

铅锌镉联合染毒及营养干预对大鼠血液系统的影响研究

目的：了解铅锌镉联合染毒对大鼠血液系统的影响及营养干预对其损伤的修复作用。方法：选择SPF级初断乳Wistar大鼠72只,随机分为对照组、染毒组和干预组,分别采用生理盐水、铅锌镉联合染毒液及染毒后以营养干预液灌胃28天和56天之后,检测其血液系统中五元素和血细胞的指标。结果：染毒组较对照组大鼠血铜、血锌含量高,血钙含量低于对照组,差异均有统计学意义（P〈0．05）;染毒组血铜含量高于干预组,血钙含量低于干预组,差异均有统计学意义（P〈0．05）;干预组红细胞（RBC）计数、血红蛋白（Hb）、血细胞比容（HCT）均高于染毒组,差异均有统计学意义（P〈0．05）;对照组白细胞（WBC）计数高于染毒组、干预组,差异均有统计学意义（P〈0．05）。结论：铅镉对大鼠血铜、血钙、血锌水平有影响;综合营养干预对重金属元素造成的血液系统损伤有明显的拮抗作用,对血液系统有一定的保护及修复作用。     

Amblyomma sculptum: genetic diversity and rickettsias in the Brazilian Cerrado biome

Amblyomma sculptum (Ixodida: Ixodidae) Berlese, 1888 is the most important tick vector in Brazil, transmitting the bioagent of the most severe form of spotted fever (SF) in part of the Cerrado (in the states of Minas Gerais and São Paulo). In another part of the Cerrado (Central‐West region of Brazil), a milder form of SF has been recorded. However, neither the rickettsia nor the vector involved have been characterized. The aim of the current study was to analyse genetic variation and the presence of rickettsia in A. sculptum in Cerrado, from silent areas and with the milder form of SF. Samples were subjected to DNA extraction, amplification and sequencing of 12S rDNA, cytochrome oxidase subunit II and D‐loop mitochondrial genes (for tick population analyses), and gltA, htrA, ompA and gene D (sca4) genes for rickettsia researches. Exclusive haplotypes with low frequencies, high haplotype diversity and low nucleotide diversity, star‐shaped networks and significant results in neutrality tests indicate A. sculptum population expansions in some areas. Rickettsia amblyommatis, Candidatus Rickettsia andeanae and Rickettsia felis were detected. The A. sculptum diversity is not geographically, or biome delimited, pointing to a different potential in vector capacity, possibly associated with differing tick genetic profiles.     

Herpetomonas megaseliae, Crithidia fasciculata, and Leptomonas collosoma (Kinetoplastida, Trypanosomatidae) in Feces of Lizards Fed Culture Forms of the Flagellates

ABSTRACT. Herpetomonas megaseliae, Crithidia fasciculata , and Leptomonas collosoma from culture survived gut passage in Anolis carolinensis following their ingestion by this lizard. Maximum persistence of H. megaseliae in lizards, as detected by fecal culture, was seven days. No invasion of tissues by H. megaseliae could be detected by means of sectioned material, stained impression slides, or cultures inoculated with material from organs. Crithidia fasciculata was evident in cloacal fluid for up to three days in wet mount preparations. Leptomonas collosoma was observed in feces 24 h after the organisms were fed to lizards. Both C. fasciculata and L. collosoma were cultured from feces of lizards fed the parasites 24 h earlier. Herpetomonas megaseliae was differentiated in lizard feces, with greater than 40% of the forms observed being paramastigotes or opisthomastigotes. Truncate, semispherical forms resembling choanomastigotes were seen, but the kinetoplast was posterior to the nucleus in some of these. Many forms showed extensive coiling of the axoneme within the body of the flagellate. Choanomastigotes and spheromastigotes of C. fasciculata and promastigotes, sphero-mastigotes and amastigotes of L. collosoma were also observed in the feces.