Differential effects of human recombinant interleukin-1 beta on cytochrome P-450-dependent activities in cultured fetal rat hepatocytes.

The immunomodulator interleukin-1 beta (IL-1) is one of the major inflammatory mediators. In vivo, it has been reported to depress some rat liver cytochromes P-450 (cytochrome P-450). Our aim was to study those effects in vitro, using cultured fetal rat hepatocytes as a model. Testosterone 6 beta-hydroxylase (cytochrome P-450 IIIA family activity) was not depressed by IL-1 treatments, but its induction by dexamethasone was prevented. The effect was time- and dose-dependent. Ethoxyresorufine-O-deethylase (cytochrome P-450 IA1 activity) decreased after IL-1 treatment, and dexamethasone partially prevented this inhibition. Acute phase effects of IL-1 were assayed by albumin and transferrin secretions. The cell's sensitivity to glucocorticoids was determined by tyrosine-aminotransferase activity. Our data demonstrate that IL-1 was able to prevent the glucocorticoid induction of cytochrome P-450 IIIA involving at least two different mechanisms. This is in agreement with the theory suggesting that the induction of CYPIIIA family by glucocorticoids requires the presence of the glucocorticoid receptor and some other regulatory elements. Other cytochrome P-450-dependent activities (IIA1, IIB1/2, and IIC11) were inhibited by IL-1 treatments, depending on dose and time, but some were also protected by dexamethasone.     

Differences in the activation of m. biceps brachii in the control of slow isotonic movements and isometric contractions

Summary We have compared muscle activation in the control of slow isotonic movements and isometric contractions. Specific attention has been given to the contribution of the two force-grading mechanisms, the recruitment of motor units and the modulation of firing frequency in motor units that have already been recruited. The recruitment order of the m. biceps motor units under study was the same during isometric contractions and slow isotonic movements. However, the recruitment thresholds of the m. biceps units were considerably lower for both isotonic flexion and extension movements, even at velocities as low as 2 deg/s, than for isometric contractions. Furthermore, firing frequency at recruitment was found to depend on the motor task: at recruitment the motoneurone starts firing with a higher firing frequency during isotonic flexion movements and a lower firing frequency during isotonic extension movements than during isometric contractions. Two main conclusions can be drawn from these results. First of all, the concept of one single activation parameter (total synaptic drive?) cannot account for the motor-unit behaviour observed during our experiments: the relative contribution of the two forcegrading mechanisms is different for different tasks. Secondly, the distribution of activity among flexor motoneurone pools is different for isometric contractions and isotonic movements.     

HIV/AIDS and intimate partner violence: intersecting women's health issues in the United States

This article reviews 35 U.S. studies on the intersection of HIV and adult intimate partner violence (IPV). Most studies describe rates of IPV among women at risk or living with HIV/AIDS and identify correlates, using multiple types of convenience samples (e.g., women in methadone treatment, women in shelters or clinics), cross-sectional designs, and self-reported risk behaviors. HIV-positive women appear to experience any IPV at rates comparable to HIV-negative women from the same underlying populations; however, their abuse seems to be more frequent and more severe. The authors found only four relevant interventions and none addressed sexually transmitted HIV and partner violence risk reduction simultaneously. There is a critical need for research on (a) causal pathways and cumulative effects of the syndemic issues of violence, HIV, and substance abuse and (b) interventions that target IPV victims at risk for HIV, as well as HIV-positive women who may be experiencing IPV.     

Cigarette smoke-induced differential gene expression in blood cells from monozygotic twin pairs

Chemical carcinogenesis induced by lifestyle factors like cigarette smoking is a major research area in molecular epidemiology. Gene expression analysis of large numbers of genes simultaneously using microarrays holds the opportunity to study the effects of such an exposure at the genome level yielding more mechanism-based information. Therefore, the aim of our study was to investigate multiple gene expressions in blood, indicative for the effects caused by cigarette smoke. Smoking-discordant monozygotic twin pairs (n=9) were studied to diminish influences of genetic background. Using a dedicated microarray containing 600 toxicologically relevant genes, we investigated which genes are differentially expressed in smokers compared to non-smokers. We also looked for genes of which the expression changes correlated with DNA adducts, a biomarker of effective dose for exposure to cigarette smoke carcinogens. The mean DNA adduct level in smokers differed significantly from that in non-smokers (mean +/- standard error 1.96 +/- 0.24 versus 1.17 +/- 0.16 adducts per 10(8) nucleotides, respectively; P=0.04). The genes of which the expression differed most significantly between smokers and non-smokers are ATF4, MAPK14, SOD2, CYP1B1 and SERPINB2. CYP1B1 and SOD2 can directly be linked to cigarette smoke exposure, whereas the other genes are associated with stress or environmentally induced response. Main functions of the genes influenced by cigarette smoking comprise carcinogen metabolism, oxidative stress response and anti-apoptosis.     

Epidural bupivacaine, sufentanil or the combination for post-thoracotomy pain

Analgesia with epidural bupivacaine, sufentanil or the combination was studied in 50 patients who had undergone thoracotomy. During operation all patients received an initial dose of bupivacaine 0.5% with adrenaline 5 micrograms.ml-1 (5-10 ml) by thoracic epidural catheter. One hour later the patients were divided into three groups: the bupivacaine group (bupivacaine 0.125%), the sufentanil group (50 micrograms sufentanil in 60 ml normal saline) and the combination group (50 micrograms sufentanil in 60 ml bupivacaine 0.125%). Analgesia in the three groups was provided by a continuous epidural infusion (5-10 ml.h-1) for 3 days. The mean dose of bupivacaine was significantly higher (P less than 0.05) in the bupivacaine group (12.07 mg.h-1 (s.e.mean 0.97 mg.h-1)), compared with the combination group (9.82 mg.h-1 (s.e.mean 0.43 mg.h-1)). The mean dose of sufentanil in the sufentanil group was similar to the combination group (6.37 micrograms.h-1 (s.e.mean 0.23 micrograms.h-1) and 6.52 micrograms.h-1 (s.e.mean 0.28 micrograms.h-1), respectively. The pain scores on the inverse visual analogue scale of most patients in the bupivacaine group were unacceptably low. The sufentanil group had much better pain scores, but on exercise these patients experienced more pain than the combination group. The combination group had, overall, better pain scores. In the combination group, there were better respiratory results.     

Comparison of the effects and disposition kinetics of articaine and lidocaine in 20 patients undergoing intravenous regional anaesthesia during day case surgery.

The aim of this investigation was to assess the effects and dispostion kinetics of the local anaesthetic drugs (±)articaine and lidocaine during intravenous regional anaesthesia (IVRA). The mean onset time of surgical analgesia of articaine was 2.5±1.1 min and that of lidocaine 11.2 ± 5.1 min (p = 0.0006). None of the patients exhibited objective symptoms of toxicity, either local or systemic, during injection of articaine or lidocaine, nor were there any subjective complaints. No changes in blood pressure, heart rate or oxygen saturation were observed with these local anesthetics at any time during the procedure, nor after deflation of the tourniquet. After releasing the tourniquet, articaine appears in the blood and is rapidly eliminated with a t1/2a of 5±3 min and a t1/2 of 59±39 min due to hydrolysis. Lidocaine is rapidly and biexponentially eliminated with similar halflives of t1/2a of 4±2 min and a t1/2 of 79±31 min. Total body clearance of articaine (8.9±3.5 L/min) is ten times greater than that of lidocaine (0.9±0.4 L/min; p = 0.0005). We concluded that both (±)articaine and lidocaine are suitable and safe agents for IVRA with rapid onset of good surgical anaesthesia. Articaine is a racemic mixture, which is nowadays considered as less favourable. After releasing the tourniquet, articaine is eliminated with a t1/2 of 60 min and lidocaine with a t1/2 of 80 min. Quicker onset and shorter elimination time favours (±)articaine over lidocaine for IVRA in day case settings so that patients treated with articaine will be drug free more quickly than those who receive lidocaine. Faster elimination and more rapid onset are important advantages for articaine in IVRA for daycase procedures.     

Churg-Strauss syndrome in a patient with asthma treated with montelukast

A 75-year-old woman with a history of asthma, rhinitis and nasal polyps was admitted due to petechial lesions on the lower left leg and weakness of the right foot. Six weeks prior to admission, she had started treatment with montelukast 10 mg daily. Based on the asthma, eosinophilia, mononeuritis of the right leg and a skin biopsy showing small vessel vasculitis with eosinophilic granulocytes, the patient was diagnosed with Churg-Strauss syndrome (CSS). After consulting with the pulmonologist, montelukast therapy was discontinued and replaced with a combined preparation of a parasympatholytic and a P2-sympathomimetic. The patient was also given prednisone 60 mg daily, which resulted in prompt clinical improvement and resolution of the eosinophilia. Development of CSS has been associated with the use of montelukast and should be considered in patients with asthma who develop new symptoms, such as neuritis, vasculitis of the skin or pulmonary infiltrates with an increase in eosinophilia during montelukast therapy. In these patients, treatment with montelukast should be discontinued, although whether a causal relationship exists between montelukast and CSS continues to be debated in the literature.     

A double blind comparison of lidocaine 2% with or without glucose for spinal anesthesia

The aim of the study was to compare lidocaine 2% plain to lidocaine 2% with glucose 8% for spinal anesthesia. Forty male patients scheduled for urologic surgery participated. The patients were randomly divided into two groups: the plain (P) group received 4 ml of glucose-free lidocaine 2%, the heavy (H) group received 4 ml of lidocaine 2% containing 8% glucose. After the injection, the patients remained in the sitting position for three minutes before they were placed supine.
The onset and maximum level of sensory blockade were similar with both preparations (T7-T8). In both groups there were respectively 3 (P) and 4 (H) patients who did not acquire a sensory level above T10. There was a tendency towards a longer duration of sensory blockade in the P group. The patients in both groups developed an almost complete motor blockade within approximately 10 minutes. Duration of complete motorblockade of the lower extremities was significantly shorter for the H group: 59.1 ±6.5 minutes (mean±SEM) than the P group: 89.5±6.4 minutes.
We consider lidocaine 2% with or without glucose a suitable agent for subarachnoid anesthesia for short procedures. As hyperbaric lidocaine results in a more rapid recovery of motor blockade, it may have advantages for patients in day-case settings.