The precipitation and cross-linking of lens crystallins by ascorbic acid

Bovine lens beta-crystallin was incubated with increasing concentrations of sugars and sugar derivatives for a period of 2 weeks in the dark at 37 degrees C. Marked protein precipitation and a browning reaction was observed with both ascorbic acid (ASA) and dehydroascorbic acid (DHA), but little or no reaction was seen with several other sugars and sugar analogs. Similar incubations were carried out with 20 mM ASA, 20 mM DHA and 20 mM glucose, but with increasing amounts of the individual crystallins. Glucose was capable of precipitating gamma-crystallin in the presence of air, but this reaction was decreased if dithiothreitol and a chelating agent were added prior to incubation. ASA and DHA produced precipitation and browning with gamma- and beta-crystallin, but not with alpha-crystallin or lens soluble proteins. Similar reactivities were observed both in air and under reducing conditions. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of these reaction mixtures showed little or no cross-linking with any of the lens proteins by glucose. ASA and DHA caused detectable dimer formation with gamma-crystallin, but produced the formation of dimers as well as highly polymerized proteins at the top of the gel with all the other crystallins and with lens soluble proteins. A time-course experiment with alpha-crystallin in the presence of air showed no cross-linking with 100 mM glucose over a 6-week period; however, 10 mM ASA caused definite cross-linking at 2 weeks, and at 6 weeks a dark smear of protein was visible throughout the gel. ASA was still capable of inducing cross-linking under low oxygen conditions but the protein smearing was markedly diminished. Further, the cross-linking pattern was similar to that seen in the water-insoluble fraction from older human lenses and cataracts. This reaction may be significant in vivo because cross-linking was observed under low-oxygen conditions with as little as 2 mM ASA, which is the level of ASA normally present in human lenses.     

Effect of a Single Nighttime Dose of Oxazepam on Seizure Duration in Electroconvulsive Therapy

In a double-blind crossover study, 12 depressed inpatients receiving bilateral electroconvulsive therapy (ECT) were given 22.5 mg oxazepam or placebo (identical tablets, randomized order) the night before treatment. Seizure duration was measured using the cuff method and a total of 20 pairs of measurements were made. Mean duration after oxazepam administration was 0.9 s longer than after placebo; this difference was not statistically significant. The relevant lower one-sided 95% confidence limit was -4.1 s. Single administration of oxazepam, 22.5 mg, has little average effect on seizure duration in ECT.     

Blockade of Ca2+‐activated K+ channels in T cells: an option for the treatment of multiple sclerosis?

Voltage- and Ca(2+)-dependent K(+) channels in the membrane of both T and B lymphocytes are important for the cellular immune response. In the current issue of the European Journal of Immunology, Reich et al. demonstrate that selective blockade of the intermediate-conductance Ca(2+)-activated K(+) channel (the IK channel encoded by the KCNN4 gene) prevents cytokine production in the spinal chord and ameliorates the development of EAE caused by injection of myelin oligodendrocyte glycoprotein (MOG)(35-55) in mice. These data renew the focus on the IK channel as a potential target for the development of new immune-suppressant drugs for the treatment of autoimmune diseases.     

The longitudinal validity of proxy-reported CHU9D

Quality of Life Research - The Child Health Utility 9D (CHU9D) currently represents the only preference-based health-related quality-of-life instrument designed exclusively from its inception for...     

Effect of chronic lithium treatment with or without haloperidol on number and sizes of neurons in rat neocortex

The present study used stereological methods to determine whether long-term administration of lithium, with or without haloperidol, affects the number and average volume of neocortical neurons. Twenty-five rats were divided into three groups and given no treatment, lithium, or lithium combined with haloperidol. Serum lithium levels ranged from 0.5 to 0.8 mmol/l. Haloperidol was injected intraperitoneally at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the brains were prepared. Neocortical volume, density of neurons, total number of neurons and mean volume of neurons were estimated. As no differences were found between the groups, the present study provides no evidence for quantitative morphological changes in the cerebral cortex due to long-term therapeutic levels of lithium, with or without haloperidol.     

Long-term prognosis of acute low back pain in patients seen in general practice: a 1-year prospective follow-up study.

OBJECTIVES: We aimed to examine the prognosis of acute low back pain (LBP) in patients in general practice and to identify prognostic factors associated with the long-term prognosis based on information immediately available to the GP. METHOD: We conducted a prospective cohort study in general practice in Denmark. The patients were those aged 18-60 years consulting their GP due to an episode of LBP lasting less than 2 weeks. The GPs collected data regarding 34 exposure variables, including their global assessment of the likelihood of chronic LBP. Outcome variables were collected from the patients after 1, 6 and 12 months. The outcome measures were days on sick leave, and functional or complete recovery from LBP. RESULTS: In total, 503 (96%) patients were followed during the whole study period. Fifty per cent of the patients on sick leave returned to work within 8 days; after 1 year, only 2% remained on sick leave. At the 1-year follow-up, 45% of the patients continued to complain of LBP. Logistic regression analyses showed that the factors most significantly associated with poor long-term LBP outcome were (i) severity of LBP at inclusion, (ii) assessments by the GP of susceptibility to develop chronic LBP and (iii) a history of LBP having caused previous sick leave. CONCLUSIONS: LBP in general practice has a good prognosis with regard to sick leave, but a high proportion of patients continue to complain of LBP. We were not able to identify objective measures that strongly predict the prognosis of the individual LBP patient. The overall assessment by the GPs seems to be the most important predictor associated with the long-term outcome.