Rocky Mountain spotted fever: ‘starry sky’ appearance with diffusion-weighted imaging in a child

We present a case of Rocky Mountain spotted fever encephalitis in a child imaged utilizing diffusion-weighted MRI. Although the imaging and clinical manifestations of this entity have been previously described, a review of the literature did not reveal any such cases reported in children utilizing diffusion-weighted imaging. The imaging findings and clinical history are presented as well as a brief review of this disease.     

In vitro and in vivo characterization of A-940894: a potent histamine H4 receptor antagonist with anti-inflammatory properties

Background and purpose:

The histamine H₄ receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H₄ receptor antagonist, A-940894 (4-piperazin-1-yl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-d]pyrimidin-2-ylamine).

Experimental approach:

We have analysed the pharmacological profile of A-940894 at mouse native, rat recombinant and human recombinant and native, histamine H₄ receptors by radioligand binding, calcium mobilization, mast cell shape change, eosinophil chemotaxis assays and in the mouse model of zymosan-induced peritonitis.

Key results:

A-940894 potently binds to both human and rat histamine H₄ receptors and exhibits considerably lower affinity for the human histamine H₁, H₂ or H₃ receptors. It potently blocked histamine-evoked calcium mobilization in the fluorometric imaging plate reader assays and inhibited histamine-induced shape change of mouse bone marrow-derived mast cells and chemotaxis of human eosinophils in vitro. In a mouse mast cell-dependent model of zymosan-induced peritonitis, A-940894 significantly blocked neutrophil influx and reduced intraperitoneal prostaglandin D₂ levels. Finally, A-940894 has good pharmacokinetic properties, including half-life and oral bioavailability in rats and mice.

Conclusions and Implications:

These data suggest that A-940894 is a potent and selective histamine H₄ receptor antagonist with pharmacokinetic properties suitable for long-term in vivo testing and could serve as a useful tool for the further characterization of histamine H₄ receptor pharmacology.     

The role of PKA and PKCε pathways in prostaglandin E2-mediated hypernociception

Background and purpose:

Protein kinase (PK) A and the ε isoform of PKC (PKCε) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKCε to the development of prostaglandin E₂ (PGE₂)-induced mechanical hypernociception.

Experimental approach:

Prostaglandin E₂-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKCε was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws.

Key results:

Hypernociception induced by PGE₂ (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKCε (PKCεI) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE₂ but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKCε, while the hypernociception induced by paw injection of PKCε agonist was not affected by an inhibitor of PKA (AKAPI).

Conclusions and implications:

Taken together, these findings are consistent with the suggestion that PKA activates PKCε, which is a novel mechanism of interaction between these kinases during the development of PGE₂-induced mechanical hypernociception.     

误诊为药源性肌病的抗合成酶综合征1例

1例42岁男性慢性乙型肝炎患者口服拉米夫定（100mg,1次／d）和阿德福韦酯（10mg,1次／d）治疗,约1个月后出现四肢肌肉酸痛、乏力,双下肢水肿。实验室检查：肌酸激酶9368U／L,肌红蛋白〉4317o,μg／L。肌电图示右侧三角肌肌源性损害。疑为横纹肌溶解症。停用拉米夫定及阿德福韦酯,肌酸激酶下降,肌无力症状好转。1年后,患者再次出现双下肢水肿并腹胀伴间断发热。肌酸激酶5546U／L,肌红蛋白〉1200μg／L,抗Jo-1抗体阳性。诊断：多发性肌炎,抗合成酶综合征。给予保肝、利尿、营养神经等治疗。2周后,加用恩替卡韦0．5mg、1次／d抗病毒治疗。2个月后,给予糖皮质激素治疗。1个月后,患者四肢肌肉酸痛、无力症状基本缓解,复查肌酸激酶正常。     

Ciliary dysfunction and obesity

Mok CA, Héon E, Zhen M. Ciliary dysfunction and obesity.
Obesity associates with increased health risks such as heart disease, stroke and diabetes. The steady rise in the obese population worldwide poses an increasing burden on health systems. Genetic factors contribute to the development of obesity, and the elucidation of their physiological functions helps to understand the cause, and improve the prevention, diagnosis and treatment for this disorder. Primary cilia are evolutionarily conserved organelles whose dysfunctions lead to human disorders now defined as ciliopathies. Human ciliopathies present pleiotropic and overlapping phenotypes that often include retinal degeneration, cystic renal anomalies and obesity. Increasing evidence implicates an intriguing involvement of cilia in lipid/energy homeostasis. Here we discuss recent studies in support of the key roles of ciliary genes in the development and pathology of obesity in various animal models. Genes affecting ciliary development and function may pose promising candidate underlying genetic factors that contribute to the development of common obesity.     

心血管危险因素对高血压患者心血管危险分层的影响

目的评估心血管危险因素对高血压患者心血管危险分层的影响。方法据中国高血压防治指南（基层板）对于高血压患者,按血压水平和总心血管危险因素进行危险分层,观察总心血管危险因素对高血压患者危险分层的影响。结果如果忽视危险因素的影响,中低危患者占52．5％,高危占29．7％。加上对危险因素的评估,低危及中危的患者明显减少,而高危（包括极高危）患者明显增加,比较差异有极显著性（户〈0．01）。影响心血管危险分层的危险因素中,比例最大的为血脂异常,在高危险组中占到40％,其次为早发心血管病家族史及吸烟史,分别占到24％和22％,然后是血糖异常和腹型肥胖,占18％和16％。结论心血管危险因素对高血压患者总心血管危险分层有着决定性的影响,治疗策略应根据初始危险分层进行。     

阴茎折断4例报告并文献复习

目的：报告4例阴茎折断,并对其诊断、治疗和预后进行文献复习,以提高对阴茎折断的认识水平。方法：回顾性分析4例阴茎折断患者的临床资料,结合国内、外文献对其病理、临床表现、诊断、治疗和预后进行探讨。其中3例通过临床表现确诊,1例通过超声波检查确诊。4例均急诊行阴茎血肿清除加白膜修补术。结果：术后随访2—120月,平均81个月,阴茎外观正常,性生活满意,无阴茎弯曲、痛性勃起、尿道狭窄等并发症。结论：阴茎折断临床罕见,粗暴性交为其主要病因,多伴有典型病史,急诊手术效果佳,并发症低,为阴茎折断的最佳治疗方法。     

Musicogenic seizures can arise from multiple temporal lobe foci: intracranial EEG analyses of three patients

PURPOSE: To determine the ictal-onset zone of musicogenic seizures by using intracranial EEG monitoring. METHODS: Musicogenic seizures in three patients with medically intractable musicogenic epilepsy were first localized by using noninvasive methods including, in one patient, ictal magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS). The ictal-onset zones in these patients were then further localized using by intracranial EEG monitoring, and the outcomes of the two patients who underwent epilepsy surgery were determined. RESULTS: Patient 1's musicogenic seizures localized to the right lateral temporal lobe, patient 2's originated in the right mesial temporal lobe, and patient 3's arose independently from both mesial temporal lobes. Patients 1 and 2 underwent resective epilepsy surgery and are seizure free (Engel class I). CONCLUSIONS: Musicogenic epilepsy is a heterogeneous syndrome with seizures that can arise from multiple temporal lobe foci. Patients with medically intractable musicogenic epilepsy and with unilateral ictal onset zones may be considered candidates for resective epilepsy surgery.     

PARP inhibition in atherosclerosis and its effects on dendritic cells,T cells and auto-antibody levels

Objective

Atherosclerosis is a chronic inflammatory process. Poly(ADP-ribose) polymerase-1 (PARP), a nuclear enzyme linked to DNA repair, has been shown to be involved in atherogenesis; however, the effects on dendritic cells, T cells and serum auto-antibody levels are not fully understood.

Methods

Male Apoe^-/- mice on a western diet were treated with the PARP inhibitor 1NO-1001 (n = 15), while the control group (n = 15) received 5% glucose solution for 10 weeks.

Results

Inhibition of PARP markedly reduced atherosclerotic lesion development (p = 0.001). Immunohistochemistry and mRNA analysis revealed a reduced inflammatory compound inside the lesion. Focusing on dendritic cells, INO-1001 reduced number of cells (p = 0.04), grade of activation, represented by I/12 (p = 0.04) and Cd83 (p = 0.03), and grade of attraction, represented by Mip3α (p = 0.02) in the plaque. Furthermore, INO-1001 decreased number of T lymphocyte (p = 0.003) in the lesion and grade of activation after stimulation with oxLDL in vitro. Moreover, serum IgM antibody levels to oxLDL were significantly lower in INO-1001 treated mice (p = 0.03).

Conclusions

Functional blockade of PARP by INO-1001 reduces atherosclerotic lesion development. The anti-atherogenic effect is beside already known mechanisms also moderated due to modulation of DC and T cell invasion and activation, DC attraction as well as IgM antibody levels to oxLDL.