Adrenal suppression due to an interaction between ritonavir and injected triamcinolone: a case report

Two HIV-1 infected patients developed signs and symptoms consistent with adrenal suppression after being exposed to intra-articular triamcinolone acetate while also receiving ritonavir as part of their highly active antiretroviral therapy. Laboratory evaluation confirmed secondary adrenal suppression in both cases. Both patients recovered without the need for chronic replacement steroids. Adrenal suppression has been described as an adverse outcome in patients treated with fluticasone and concomitant ritonavir. In the reported cases, the adrenal suppression likely developed as a result of increased systemic concentrations of triamcinolone due to an inhibition of cytochrome p450 3A4 metabolism. Practitioners of HIV medicine should be aware of the potential negative interaction of injected triamcinolone and ritonavir.     

Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.     

The impact of cytokines on the expression of drug transporters,cytochrome P450 enzymes and chemokine receptors in human PBMC

Background and purpose:

The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC.

Experimental approach:

Human PBMC were incubated with cytokines for 48 h. ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes.

Key results:

We show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact on ABCB1 mRNA (% control 4745 ± 11961) and protein (% control 200 ± 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL-2 and interferon-γ (IFNγ) respectively] and saquinavir (decrease of 28% and 30% for IL-2 and IFNγ respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r² = 0.545).

Conclusions and implications:

These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells.     

Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose corticosteroid treatment

Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress. In experimental animals, short-term strategies that maintain partial diaphragm muscle neuromechanical activation mitigate diaphragmatic force loss. In animal models, studies on the influence of combined controlled mechanical ventilation and short-term high-dose methylprednisolone have given inconsistent results in regard to the effects on diaphragm muscle function. In the critically ill patient, further research is needed to establish the prevalence and mechanisms of ventilator-induced diaphragm muscle dysfunction, and the possible interaction between mechanical ventilation and the administration of high-dose corticosteroid. Until then, in caring for these patients, it is imperative to allow partial activation of the diaphragm, and to administer the lowest dose of corticosteroid for the shortest duration possible.     

Non‐ablative 1550‐nm erbium‐glass and ablative 10 600‐nm carbon dioxide fractional lasers for acne scars: a randomized split‐face study with blinded response evaluation

Background Non‐ablative 1550‐nm erbium‐doped fractional photothermolysis systems (FPS) and 10 600‐nm carbon dioxide fractional laser systems (CO₂ FS) have been effectively used to treat scars. Objective We compared the efficacy and safety of single‐session treatments of FPS and CO₂ FS for acne scars through a randomized, split‐face, evaluator‐blinded study. Methods Eight patients with acne scars were enrolled in this study. Half of each subject’s face was treated with FPS and the other half was treated with CO₂ FS. We used a quartile grading scale for evaluations. Results At 3 months after the treatment, the mean grade of improvement based on clinical assessment was 2.0 ± 0.5 for FPS and 2.5 ± 0.8 for CO₂ FS. On each side treated by FPS and CO₂ FS, the mean duration of post‐therapy crusting and scaling was 2.3 and 7.4 days respectively and that of post‐therapy erythema was 7.5 and 11.5 days respectively. The mean VAS pain score was 3.9 ± 2.0 with the FPS and 7.0 ± 2.0 with the CO₂ FS. Conclusion We demonstrated the efficacy and safety of single‐session acne scar treatment using FPS and CO₂ FS in East Asian patients. We believe that our study could be used as an essential reference when choosing laser modalities for scar treatment.     

美托洛尔治疗右室流出道室性早搏的效果观察

目的：观察美托洛尔对起源于右室流出道室性早搏的疗效。方法：选择起源于右室流出道的室性早搏患25例，给予美托洛尔治疗，剂量从6．25mg开始，无不良反应后，逐渐加量，最大剂量每天100－150mg，疗程3个月，用药前后查12导联体表心电图、24小时动态心电图及结合临床症状进行评定。结果：①临床症状评定：胸闷心悸25例，治疗后减轻20例，有效率为80％；焦虑20例，治疗后症状均消失，有效率为100％；头晕14例，治疗后减轻12例，有效率为85．7％。②室性早搏评定：25例中达到室性早搏抑制率70％有11例，有效率为44％；平均室性早搏抑制率为45．6％，6例成对室性早搏抑制率为80％，3例短阵室速消失，平均心率降低12．6／min。③生化指标：血糖、胆固醇、甘油、三酯治疗前后无明显改变。④2例因血压低未加药量。结论：美托洛尔治疗起源于右室流出道室性早搏疗效肯定，尤其对运动后早搏增多疗效较好，临床太改善较显，观察中未发现明显不良反应，无致心律失常现象。     

Body Surface Mapping and Nontraditional ECG Leads in Patients with Wolff-Parkinson-White Syndrome

A method of ECG mapping from 90 points on the chest surface is described in 41 male and 17 female patients, aged 6 to 59 years. All also underwent invasive electrophysiological investigation and intraoperative epicardial mapping. Fifty-two patients had one, three patients two, and one patient had three anomalous accessory pathways. Two patients had nodoventricular tracts (Mahaim fibers). We distinguished seven zones along the atrioventricular groove (AVG) to compare the data derived from epicardial, endocardial, and body surface mapping. A microcomputer was used for the analysis of all ECGs to construct and analyze the isopotential maps. The criterion for localization of the anomalous accessory pathways was determined after analysis of the data from all 58 patients. The localization criterion was the appearance of a minimal deflection (-0.09 +/- 0.03 mV) on the surface isopotential maps within the first 0.28 msec of the QRS complex. This criterion for localization of anomalous accessory pathways from the chest surface was proposed on the basis of comparison of data from selective coronary angiography, the ventriculogram, and the chest X ray i.e., radiographic-topographic-anatomical data. In 20 patients, 10-20 nontraditional ECG leads were recorded from the chest to reflect the atrioventricular groove. The number of nontraditional ECG leads depended on patient age, weight, and height. Localization of the accessory pathway in one of the seven zones was established by the earliest delta wave and its maximum deviation. It was possible to localize the anomalous accessory pathway and to suspect multiple pathways in 95% of cases using nontraditional ECG leads and the listed criteria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery

The influence of pregnancy on the dilator effects of acetylcholine in the isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1 microM) produced concentration- and endothelium-dependent relaxation of norepinephrine (3 microM)-induced contraction. The relaxation was greater in arteries from pregnant patients (P arteries) than from non-pregnant patients (NP arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/-2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation was increased in the presence of superoxide dismutase and greatly reduced in the presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L-NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide synthase inhibitors was reversed by L- arginine. We conclude that pregnancy enhances acetylcholine-induced nitric oxide synthesis and release in the human uterine artery.