Inhaled corticosteroid use in HIV‐positive individuals taking protease inhibitors: a review of pharmacokinetics,case reports and clinical management

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug?drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug?drug interaction in order to suggest options for the clinical management of HIV‐positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.     

复发性皮肤坏死性嗜酸性血管炎1例并文献复习

报道1例复发性皮肤坏死性嗜酸性血管炎并对相关文献进行复习。患者，女，64岁，因双下肢痛性皮疹12天就诊。偶有干咳，无哮喘病史。皮肤科查体：双下肢散在紫红色斑片、斑块，胫前数个结节、血疱样损害；右前臂有少量类似损害。外周血嗜酸性粒细胞计数增多。胸部X线提示双肺渗出性改变。皮损组织病理符合皮肤坏死性嗜酸性血管炎。口服强的松45mg/天治疗1周后临床症状明显好转，激素减量过程中曾有复发。     

A final common pathway for depression: implications for therapy

Depression in humans and animal models has been found to be accompanied by a hypoactivity of brain regions involved in positively motivated behavior together with a hyperactivity in regions involved in stress responses. Both sets of changes are reversed by diverse antidepressant treatments. It has been proposed that this neural pattern underlies the symptoms common to most forms of depression, which are the loss of positively motivated behavior and the increase in stress. The present paper discusses how this framework can organize diverse findings on the multiple factors associated with this disorder. The hypothesis suggests new therapeutic strategies involving treatment with low-dose corticosteroids to suppress the stress network or with antagonists of α_1A- and agonists of α_1B-adrenoceptors to disinhibit or activate the positive motivational network, respectively.     

Sex-specific endothelial dysfunction induced by high-cholesterol diet in rats: The role of protein tyrosine kinase and nitric oxide

Background and aimsAtherosclerosis is a chronic process playing a crucial role in the pathogenesis of cardiovascular disease. Sex-specific differences in the incidence of atherosclerosis indicate that estrogen has a protective effect on the cardiovascular disease. However, the role of sex on endothelium responses in animal models of high cholesterol (HC) diet-induced atherosclerosis has not been fully investigated. This study was aimed to investigate vascular responses in HC-fed rats.Methods and resultsMale and female Sprague rats (12-week-old) were treated with either a standard diet (n = 12 of each sex) or an HC enriched diet (n = 12 of each sex) containing 2% cholesterol for 24 weeks. HC treated animals (both sexes) showed increased levels of total cholesterol, LDL-cholesterol, triglyceride and blood pressure (BP) compared to control rats. While the BP of control rats (both sexes) was increased following aminoguanidine administration (AG, 100 mg/kg i.p.), it was not changed in HC animals (both sexes). The hypotensive effect of acetylcholine was significantly impaired in male HC-treated rats. In vitro experiments demonstrated that aortic rings from HC group (both sexes) had an increased contractile response to phenylephrine and a decreased vasodilatory response to acetylcholine. The vasorelaxant effect of acetylcholine in HC rats (only male) was improved by applying 10^?5 M genistein (tyrosine kinase inhibitor) or AG.ConclusionHC diet alters endothelium function through Nitric oxide (NO) and tyrosine kinase pathways in male rats.     

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??Inhaled corticosteroids??ICS?? are the most effective medicine for chronic airway inflammation nowdays. Atomization inhalation has been widely applied in clinics because of its efficacy??fewer side-effects and convenience. Here??we focused on some points which should be paid attention to??including how to choose appropriate patients??how to ensure the effectiveness of inhaled steroids and how to reduce possible side-effects.     

Molecular characterization of genome segment 2 encoding RNA dependent RNA polymerase of Antheraea mylitta cytoplasmic polyhedrosis virus

Genome segment 2 (S2) from Antheraea mylitta cypovirus (AmCPV) was converted into cDNA, cloned and sequenced. S2 consisted of 3798 nucleotides with a long ORF encoding a 1116 amino acid long protein (123 kDa). BLAST and phylogenetic analysis showed 29% sequence identity and close relatedness of AmCPV S2 with RNA dependent RNA polymerase (RdRp) of other insect cypoviruses, suggesting a common origin of all insect cypoviruses. The ORF of S2 was expressed as 123 kDa soluble His-tagged fusion protein in insect cells via baculovirus recombinants which exhibited RdRp activity in an in vitro RNA polymerase assay without any intrinsic terminal transferase activity. Maximum activity was observed at 37 °C at pH 6.0 in the presence of 3 mM MgCl_2. Site directed mutagenesis confirmed the importance of the conserved GDD motif. This is the first report of functional characterization of a cypoviral RdRp which may lead to the development of anti-viral agents.     

Adolescent brain maturation,the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia

Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose–time–effect relationship should be central.