Inhibition of autoimmune deterioration in MRL/lpr mice by vitamin E.

The potential of the antioxidant vitamin E to modulate the progress of the SLE-like (systemic lupus erythematosus) autoimmune disease in MRL/MP-lpr/lpr (MRL/lpr) mice is described. Mice were orally supplemented with 0.4 mg vitamin E per day 5 times per week from week 8 of age onwards and compared with mice on a commercial or a vitamin E-deficient diet. Supplementation with vitamin E extended the mean survival time from 157 to 196 days; the massive spleen and lymph node enlargements were reduced; mitogenic responses of B and T cells were normalized; the abnormal differentiation patterns of thymic and splenic cell sub-populations were changed; titers of anti-double stranded DNA antibodies, concentrations of serum amyloid P component (SAP, an acute phase protein), and proteinuria were reduced. The results indicate that vitamin E beneficially affects the development of the SLE-like disease in MRL/lpr mice suggesting a possible measure to reduce human SLE and probably various other autoimmune diseases in humans as well.     

Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension

BACKGROUND: Phosphodiesterase type 5 (PDE5) hydrolyzes cyclic guanosine monophosphate in the lung, thereby modulating nitric oxide (NO)/cyclic guanosine monophosphate-mediated pulmonary vasodilation. Inhibitors of PDE5 have been proposed for the treatment of pulmonary hypertension. In this study, we examined the pulmonary and systemic vasodilator properties of sildenafil, a novel selective PDE5 inhibitor, which has been approved for the treatment of erectile dysfunction. METHODS: In an awake lamb model of acute pulmonary hypertension induced by an intravenous infusion of the thromboxane analog U46619, we measured the effects of 12.5, 25, and 50 mg sildenafil administered via a nasogastric tube on pulmonary and systemic hemodynamics (n = 5). We also compared the effects of sildenafil (n = 7) and zaprinast (n = 5), a second PDE5 inhibitor, on the pulmonary vasodilator effects of 2.5, 10, and 40 parts per million inhaled NO. Finally, we examined the effect of infusing intravenous l-NAME (an inhibitor of endogenous NO production) on pulmonary vasodilation induced by 50 mg sildenafil (n = 6). RESULTS: Cumulative doses of sildenafil (12.5, 25, and 50 mg) decreased the pulmonary artery pressure 21%, 28%, and 42%, respectively, and the pulmonary vascular resistance 19%, 23%, and 45%, respectively. Systemic arterial pressure decreased 12% only after the maximum cumulative sildenafil dose. Neither sildenafil nor zaprinast augmented the ability of inhaled NO to dilate the pulmonary vasculature. Zaprinast, but not sildenafil, markedly prolonged the duration of pulmonary vasodilation after NO inhalation was discontinued. Infusion of l-NAME abolished sildenafil-induced pulmonary vasodilation. CONCLUSIONS: Sildenafil is a selective pulmonary vasodilator in an ovine model of acute pulmonary hypertension. Sildenafil induces pulmonary vasodilation via a NO-dependent mechanism. In contrast to zaprinast, sildenafil did not prolong the pulmonary vasodilator action of inhaled NO.     

Oestrogen treatment of constitutional tall stature: a risk-benefit ratio

Oestrogens are given in high doses for the treatment of tall stature in girls. The aim of this study was to obtain data considering efficiency, side effects, and acceptance of the treatment of 50 constitutionally tall girls treated with conjugated oestrogens (7.5-11.25 mg/day). The mean (SD) adult height predictions were 188.3 (4.4) cm and the achieved height was 5.2 (3.3) cm less than the predicted height. A greater reduction from final predicted height occurred when treatment was started at an early bone age (< 13.0 years) and with a remaining growth potential of greater than 10 cm. Even postmenarcheal girls, however, had a mean reduction of 4.8 (3.2) cm. The main side effects were considerable weight gain (> 10 kg), an increase in triglyceride concentrations (37.5% of the patients), and increased platelet aggregation (60% of the patients). Altogether 84.6% of the patients were satisfied with the treatment and 15.4% regretted having had it.     

Initial fixation strength of a hybrid technique for femoral ACL graft fixation

Aperture fixation with interference screws matching the diameter of the tunnel is associated with the risk of graft laceration and graft rotation. A hybrid fixation technique (extracortical and aperture fixation) with undersized interference screws provides a higher fixation strength when compared to an aperture fixation using only a screw matching the size of the tunnel and also reduces the risk of graft laceration. This research is an experimental laboratory study. We evaluated the initial fixation strength at time-zero of an extracortical-, a hybrid- and an aperture fixation in ACL reconstruction using extracortical buttons and different sized interference screws in porcine knees. The tests were performed using a single cycle and cyclic loading protocol. Analysis of yield load, maximum load and stiffness in the single cycle loading test showed no statistically significant differences for hybrid fixation with a 1 mm undersized screw and aperture fixation with a screw matching the size of the tunnel. Cyclic loading tests showed a statistically significant difference between hybrid and aperture fixation. The use of an undersized screw alone in aperture fixation resulted in insufficient fixation strength. The initial fixation strength of the hybrid technique with undersized screws is higher compared to an interference screw fixation alone. The hybrid fixation technique is an alternative for ACL graft fixation.     

Identification and quantification of isoguanosine in humans and mice

Isoguanine (2-hydroxyadenine), considered to be a non-natural nucleobase has, however, been shown to occur in the croton bean, butterfly wings and a mollusk. For the first time, to the best of our knowledge, we report the identification of isoguanosine (2-hydroxyadenosine), the ribonucleoside, in humans and mouse. Isoguanosine is identified and quantified in RNA from mouse liver samples and in human urine and cerebrospinal fluid. Isoguanine could not be detected as the 2′-deoxyribonucleoside in mouse liver DNA. It could be speculated that the source of isoguanosine was formation from adenosine during oxidative stress in the body. However, the urinary concentrations of isoguanosine and the levels in the liver found here by using isotope dilution liquid chromatography–tandem mass spectrometry are identical to or exceed those of 8-oxo-7,8-dihydro-2′-deoxyguanosine and 8-oxo-7,8-dihydro-guanosine. Guanine is the nucleobase that is oxidized the easiest, so it appears spectacular that the levels of isoguanosine are higher than the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine and 8-oxo-7,8-dihydro-guanosine. It also appears intriguing that it was only possible to detect the ribonucleoside isoguanosine and not the 2′-deoxyribonucleoside. These observations could indicate that the isoguanosine found is not formed by oxidative stress and could have biological functions.     

Prävention und Nachsorge der Sepsis

The 1st revision of the S2k guideline on the prevention and follow-up care of sepsis, provided by the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information on the effective and appropriate medical care of critically ill patients with severe sepsis or septic shock. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.