Studies on the Action of Nalidixic Acid in the Yeast Saccharomyces cerevisiae

The effect of the antibiotic nalidixic acid on macromolecular metabolism in the yeast Saccharomyces cerevisiae has been studied. It was found that, upon the addition of nalidixic acid to a logarithmically growing culture, there is a transient inhibition of total cell ribonucleic acid, deoxyribonucleic acid, and protein synthesis, after which the cells show an almost complete recovery. In addition, there is no preferential inhibition of yeast mitochondrial deoxyribonucleic acid synthesis.     

Cervical vertigo--cervical pain: an alternative and efficient treatment

OBJECTIVES: Cervical vertigo (CV) is commonly attributed to a disturbed cervical proprioception and is associated with cervical pain (CP). It is assumed to respond to a treatment that improves CP. In a prospective observational study, we examined whether a treatment originally devised for patients with CP could improve CV also in cases without CP. DESIGN: During a period of 3 years, a total of 238 consecutive patients, 41 patients with CV only, 43 patients with CV and CP, 154 patients with CP only, received the same treatment, which consisted of local anaesthetics applied on average in 8 sessions to a fixed set of epidermal, epithelial, and periosteal locations. Outcome was relief of symptoms measured by a verbal-analogue scale at the end of therapy and on average a year later. RESULTS: At the end of therapy, 58% of patients with CV responded with complete remissions compared to 41% of patients with CP. At follow-up a year later, there were complete remissions in more than 50% in CV as well as in CP. CONCLUSIONS: The applied therapy led to complete remissions of long duration in a high percentage of patients with CV even when symptoms of CP were missing. This therapy produced good effects for CP as well. Its neurophysiological basis is discussed and may offer a new approach not only to the treatment of CV and CP but in a general sense also to that of acute, chronic, and neuropathic pain. It needs to be emphasized, however, that this study was not a randomized controlled trial and its encouraging results have to be proved by further research.     

Empfehlungen der Deutschen Gesellschaft für Rheumatologie zum Einsatz von Tocilizumab bei der rheumatoiden Arthritis (Februar 2010)

The humanized anti-IL-6 receptor monoclonal antibody tocilizumab (TCZ) represents a new therapy approach for moderately severe to severe cases of rheumatoid arthritis (RA). The IL-6 concentration in the synovial fluid and peripheral circulation of patients with RA is elevated. TCZ recognises the IL-6 binding site of human IL-6R and blocks the IL-6 signaling pathway. TCZ is capable of correcting a multitude of pathological processes in RA, as has been shown in a number of studies. TCZ treatment should be combined with methotrexate. If the latter cannot be administered, TCZ can also be used as a monotherapy. The recommended dose is 8 mg/kg once every 4 weeks; the minimum dose per infusion is 480 mg. Close monitoring, in particular for infectious complications, is necessary. Clinical effects of TCZ are usually seen several weeks following initiation of therapy. If no significant clinical response is seen within 6 months, TCZ therapy should be ceased.     

Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of human steroids

Steroids such as dehydroepiandrosterone (DHEA) and epiandrosterone (EA) exert multiple effects in mammals including the inhibition of glucose-6-phosphate dehydrogenase (G6PDH). Initially, the inhibition was considered specific for the mammalian enzyme. The beneficial effect of these steroids on infections by protists and nematodes was attributed to stimulation of the immune system. However, we showed previously that DHEA and EA also inhibit Trypanosoma brucei and T. cruzi G6PDH, with low micromolar K(i)' values, but not the enzyme from Leishmania species, and kill in vitro cultured trypanosomes. We report here that, contrary to wild-type trypanosomes, mutant bloodstream-form T. brucei cells expressing L. mexicana G6PDH are not susceptible to the steroids, proving that G6PDH is the in situ target. Moreover, bromo-derivatives of the steroids show 50-100 fold lower K(i)' values for the enzyme and display an increased potency to kill the parasites. Therefore, the compounds offer promise for use in development of parasite-selective drugs.     

Rapid detection of myocardial infarction with a sensitive troponin test

Rapid identification and treatment of patients with a myocardial infarction (MI) is mandatory. We studied the diagnostic capacities of a sensitive troponin assay for detection of MI in emergency department patients within 2 hours after arrival. The study included 157 patients suspected of having non-ST-elevation acute coronary syndrome. Blood was drawn on arrival (T0) and 2 (T2), 6, and 12 hours later. At T2, a troponin concentration above the MI cutoff is 87% sensitive and 100% specific for MI detection (positive predictive value [PPV], 100%; negative predictive value [NPV], 96%). If a difference of more than 30% between the troponin measurements at T0 and T2 in the absence of an absolute troponin increase above the 99th percentile of a reference population is also considered indicative of MI, the sensitivity increases to 100% and specificity decreases to 87% (PPV, 70%; NPV, 100%). Sensitivity and specificity of creatine kinase-MB and myoglobin are lower than those of troponin. By using a sensitive troponin assay and simple algorithms, the diagnosis of MI can be determined within 2 hours after arrival at the emergency department. Measurement of myoglobin and creatine kinase-MB has no added value.