Melanocortins applied intravitreally delay retinal dystrophy in Royal College of Surgeons rats

Background -Melanocyte-stimulating hormone (MSH) is a neurotrophic agent. In Royal College of Surgeons (RCS) rats, the effects of an MSH analog (MA) were investigated on: (1) the preservation of photoreceptors in vivo following MA intravitreal injection; (2) whether MA is a mitogenic factor.Methods The study comprised five RCS rat groups, two injected with different doses of MA, one injected with PBS , and two non-injected groups. A single injection of MA or PBS was applied intravitreally to RCS rats on postnatal day 20 (20p). Photoreceptor preservation on 40p was studied using light microscopy. Considering the mitogenic effect of MA, it was studied whether cell proliferation was induced by MA in cultured retinal pigment epithelium (RPE) using the thymidine uptake technique.Results In degenerating untreated RCS retinae the number of photoreceptor rows on 40p was 60–70% lower than on 20p. Retinae treated with higher doses of MA revealed on 40p a localized significant photoreceptor rescue in the retinal hemisphere which had been injected. However, only a small area of photoreceptor preservation was noted in the injected hemisphere in retinae treated with the lower MA dose. MA showed no mitogenic effect in endothelial or RPE cell culture in vitro.Conclusions This study is the first to demonstrate that: (1) intravitreally injected MA promotes a dose-related localized rescue of photoreceptors in RCS retinae which may be related to the hormones neurotrophic activity; (2) MA has no mitogenic or angiogenic properties; (3) MA, as a neuroprotective agent, might be considered for future treatment of retinal dystrophy.     

Effects of polarizing solution on glucose uptake of rat oxygenated or hypoxic ventricular myocytes

1. Although adult cardiac metabolism depends on fatty acids rather than on carbohydrates, hypoxic hearts consume glucose and infusion with a glucose-insulin-potassium solution (GIK) helps in the recovery of the pressure register, the heart rate and electrocardiogram of rat hypoxic whole hearts. 2. Rat myocytes obtained by enzymatic disaggregation captured significant amounts of glucose in Tyrode's solution (9.8 +/- 2.05% during oxygenation and 16.26 +/- 2.76% during hypoxia) after 60 min incubation. Cells incubated with GIK showed a significantly increased glucose uptake (to 30.04 +/- 1.99% during oxygenation and to 37.06 +/- 1.97% during hypoxia). 3. Glucose was the component of the Tyrode's solution that most enhanced its own entry, increasing glucose entry to 45.42 +/- 2.64% with oxygen and 41.42 +/- 2.69% under hypoxia. 4. Antibodies against glucose transporters 1 and 4 (GLUT-1 and -4, respectively) decreased glucose transport during GIK treatment under hypoxia. 5. We conclude that GIK has beneficial effects mediated by GLUT-1 and -4 during hypoxia, inducing recovery of the damaged tissue.     

Determination of the minimal clinically significant difference on a patient visual analog sleep quality scale

The amount of change in quality of sleep (QOS), as measured by a 100-mm visual analog scale (VAS), that constitutes a minimum clinically significant difference was determined. A total of 428 patients with insomnia aged 55 years and older received placebo (2 weeks), prolonged release melatonin 2 mg (3 weeks) and then placebo (2 weeks). Sleep quality was assessed by the end of each period using the Leeds Sleep Evaluation Questionnaire (LSEQ) QOS variable and a five-point severity-rating scale. The mean difference between current and preceding VAS scores in patients improving or worsening by 1 point was 13 mm (95% CI 11-16). Correlation analysis indicated that a change of 1 point was associated with a mean change of 10.3 mm on the VAS. In conclusion, a change of 10 mm change in the 100-mm VAS QOS variable of the LSEQ, signifies an important change in patients' sleep quality.     

Plasminogen activator is enriched in the synaptosomal plasma membranes

The intracellular localization of the serine protease plasminogen activator was analyzed in homogenates of bovine brain cortex using differential fractionation procedures. The distribution of the enzyme was clearly different from that of cytosol and mitochondrial markers, and was similar to that of plasma membrane proteins and of the muscarinic acetylcholine receptor, which is a specific marker for the synaptic membrane. The specific activity of plasminogen activator was increased in fractions enriched in intact synaptosomes. Most of the enzyme in intact synaptosomes was found to be firmly associated with the synaptosomal membrane, and could be solubilized by high concentrations of salt or by non-ionic detergent. Purified synaptic vesicles, however, did not contain large amounts of plasminogen activator. Bovine brain synaptosomes were shown to contain two species of the enzyme, having apparent molecular weights of 80,000 and 55,000. The presence of plasminogen activator in the synaptosomal membrane may indicate its possible involvement in the functioning of nerve terminals.     

Small-size ribosomal RNA species in Trypanosoma cruzi

Trypanosoma cruzi ribosomal RNA was analyzed electrophoresis. On agarose gels, where both large- and small-size species are grossly fractionable, it revealed two bands in the small-size region. These were similar in size to the mammalian 5.8 S and 5 S species. Increased resolution, however, showed these two bands to be composite. The pseudo 5.8 S band contained three, and the pseudo 5 S two, discretely sized molecules. The ribosomal binding of four of these five novel species is apparently dependent on large ribosomal subunit proteins. One species is hydrogen bonded to the beta species of 24 S ribosomal RNA. The five species were estimated to be 261, 217, 197, 141 and 110 nucleotides long.     

Study of the antiaggregating activity of new phenacyl-piperazine derivatives

The antiplatelet activity of twelve new derivatives of phenacyl-piperazine was studied. Eight of them proved to be inactive by Born's method. The other four compound partially inhibited the aggregating effects induced by adrenaline and ADP, but did not prevent the effects produced by collagen. Although it was not possible to establish any relationship between chemical structure and antiplatelet activity, it looks as if there is a certain relationship between the analgesic and the antiplatelet effect. The compounds tested did not usually modify bleeding time.