Effects of dipyridamole, soluflazine and related molecules on adenosine uptake and metabolism by isolated human red blood cells

Summary— The suggestion that adenosine may have beneficial effects on post reperfusion survival following cardiac ischaemia has led to the search for agents which increase the concentration of this substance in the ischemic region as a possible therapeutic approach to the treatment of angina and myocardial infarction. In the present study, dipyridamole, soluflazine and lidoflazine, known inhibitors of the nucleotide exchange system, have been shown using an HPLC method to prevent the decrease in the concentration od added adenosine outside human red blood cells in vitro. However, the results suggest that this effect was due to inhibition of adenosine deaminase rather than inhibition of nucleotide exchange as had previously been suggested. The selective inhibitor of adenosine deaminase erythro-9-(2 hydroxy-3-nonyl adenosine) exhibited the same profile of activity in the human red blood cell assay. pIC₅₀ values for the four compounds named above were found to be 6.80 ± 0.09, 6.95 ± .03, 6.10 ± 0.14 and 7.39 ± 0.05 vs adenosine disapearance observed in the extracellular incubation medium respectively. Thus, as the disappearance of adenosine outside the cells was not due to its uptake but to its catabolism, this in vitro method does not appear to be predictive for the ability of compounds to act on adenosine uptake into cardiac myocytes. Any antiischemic action of these agents is more readily explained by an inhibition of the catabolism of adenosine and not by the inhibition of its transport across the membrane of cardiac myocytes.     

Cerebral microgyria, thalamic cell size and auditory temporal processing in male and female rats

Induction of microgyria by freezing injury to the developing somatosensory cortex of neonatal rats causes a defect in fast auditory processing in males, but not in females. It was speculated that early damage to the cortex has sexually dimorphic cascading effects on other brain regions mediating auditory processing, which can lead to the observed behavioral deficits. In the current series of experiments, bilateral microgyri were induced by placement of a freezing probe on the skulls of newborn male and female rats, and these animals were tested in adulthood for auditory temporal processing. Control animals received sham surgery. The brains from these animals were embedded in celloidin, cut in the coronal plane and the following morphometric measures assessed: microgyric volume, medial geniculate nucleus (MGN) volume, cell number, and cell size, and, as a control, dorsal lateral geniculate nucleus (dLGN) volume, cell number and cell size. There were no sex differences in the cortical pathology of lesioned animals. However, microgyric males had more small and fewer large neurons in the MGN than their sham-operated counterparts, whereas there was no difference between lesioned and sham-operated females. There was no effect on dLGN cell size distribution in either sex. Microgyric males were significantly impaired in fast auditory temporal processing when compared to control males, whereas lesioned females exhibited no behavioral deficits. These results suggest that early injury to the cerebral cortex may have different effects on specific thalamic nuclei in males and females, with corresponding differences in behavioral effects.      

Intravesical migration of intrauterine device resulting in pregnancy

Spontaneous migration of an intrauterine device into the bladder is very rare. A 29-year-old woman in whom an intrauterine device had been placed 6 years previously, presented complaining of chronic pelvic pain and recurrent irritative urinary tract symptoms. One year after insertion she had became pregnant and given birth without complications. Intravesical migration of the intrauterine device was confirmed by sonography and cystoscopy. The intrauterine device was removed by suprapubic cystostomy.     

Platelet glycine, glutamate and aspartate in primary headache

Platelet levels of glutamic and aspartic acid and glycine were measured in patients with migraine with aura, migraine without aura, tension headache and cluster headache. High levels of these amino acids were found in patients with migraine with aura compared to normal subjects and other headache groups. During headache, glutamate levels further increased in migraine with aura patients. These findings may have relevance to the neurological symptoms of migraine with aura.     

Comparison of the content and subpopulations of CD3 and CD34 positive cells in bone marrow harvests and G-CSF-mobilized peripheral blood leukapheresis products from healthy adult donors

Recombinant human granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem/progenitor cells (PBPC) have replaced bone marrow (BM) harvests for autologous transplantation after myeloablative therapy in cancer patients. G-CSF-mobilized PBPC from healthy donors contain one log excess of T lymphocytes representing a potential risk for graft-versus-host disease (GVHD). However, recent pilot clinical studies of G-CSF-mobilized allogeneic PBPC transplantation have shown rapid haematological recovery and no severe acute GVHD except in a very few cases. Therefore, the risk of inducing severe acute GVHD is not as high as was expected during the pioneering period of allogeneic PBPC transplantation.The present study was performed to address the possible reasons for the rapid haematological recovery and the absence of severe acute GVHD observed after allogeneic PBPC transplantation by comparing the contents and subsets of CD3⁺ and CD34⁺ G-CSF-mobilized PBPC (n = 31) with those of BM (n = 26) allografts from healthy adult donors. The present results revealed that the phenotypic profiles of CD3⁺ and CD34⁺ cells differ between PBPC and BM allografts. The single PBPC leukapheresis product contained 10 times more mononuclear cells, 1.5 times more CD34⁺ cells, 5.5 times more CD3⁺ T lymphocytes, 3 times more CD19⁺ B lymphocytes and 3.8 times more CD14⁺ monocytes than the single BM harvest. Both CD34⁺CD33⁺ myeloid progenitor cells and CD34⁺HLA-DR- long-term reconstituting haemopoietic stem cells were significantly increased in the CD34⁺ G-CSF-mobilized PBPC compared with the CD34⁺ BM cells; median 73.1% and 30.4% vs 60.6% and 5.0%, respectively, P < 0.01.The percentage of CD3⁺ cells coexpressing CD4 (T helper/inducer) was similar in both PBPC and BM allografts, 47.2% and 45.6%, respectively, whereas the percentage of CD3⁺ cells coexpressing CD8 (T suppressor/cytotoxic) was significantly decreased in PBPC compared with BM; 37.0% vs 55.9%, p < 0.01.     

Symptoms of classic migraine attacks: Modifications brought about by metoprolol

There is little information available concerning whether, and to what extent, migraine-prophylactic agents interfere with the symptoms of migraine attacks. The present study is a placebo-controlled, double-blind study concerning metoprolol in classic migraine. The data refer to the symptoms of single migraine attacks. During metoprolol treatment more attacks were characterized as mild (p = 0.002), and mean global rating (an integrated estimate of headache intensity and of other discomfort) was lower (4.2 versus 5.2, p = 0.003). The mean headache intensity per attack (1.97 versus 2.15) and the mean duration (5.5 versus 6.8 h) were not significantly different. Consumption of analgesics per attack was lower during metoprolol treatment (0.6 versus 1.1; p = 0.02). Attacks with associated symptoms accompanying the headache were fewer during metoprolol treatment (p = 0.014). Total visual and non-visual aura symptoms occurred with similar frequency, but scintillations and paraesthesia were more frequent during metoprolol treatment, whereas speech disturbances were less frequent. In spite of lower consumption of analgesics, the symptoms appeared milder during metoprolol than during placebo. The pattern of changes indicates that metoprolol exerts its action via the sympathetic nervous system; peripheral vasoconstriction is hardly the underlying mechanism of action.     

Compliance with antibiotic prophylaxis in urinary tract infection

Compliance with antibiotic prophylaxis after urinary tract infection was assessed in 32 children, using a parent questionnaire, and a urine test for antibacterial substances. In 31 (97%) cases, parents reported giving the antibiotics every day but only 22 (69%) of urine tests were positive. Failure to understand the reasons for prophylaxis and non-compliance were significantly associated.