Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

Synthesis of antimicrobial agents. 1. Syntheses and antibacterial activities of 7-(azole substituted)quinolones

A series of 6-fluoro- and 6,8-difluoro-7-(azole substituted)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared. Structure-activity relationship studies indicated that the antibacterial potency was better when the 6,8-substituents were fluorine atoms and the 7-substituent was either 1-imidazolyl, 20, or 4-methyl-1-imidazolyl, 25. From the results of studies on pharmacokinetic profile and toxicity, 20 and 25 were found to possess excellent antibacterial activities and to show high blood levels after oral administration to mice with low toxicity.     

A method for evaluating antianginal drugs in experimental animals: assessment of myocardial ischemia by myocardial pH

This paper describes a method by which antianginal drugs can be evaluated in the dog heart in situ. Myocardial pH was measured continuously by a micro glass pH electrode inserted in the left ventricular endocardial layers of the dog anesthetized with pentobarbital. Occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH, and release of the LAD restored the pH. The myocardial acidosis induced by ischemia was metabolic in nature and accompanied by a decrease in the levels of adenosine triphosphate and creatine phosphate and an increase in the levels of lactate in the myocardium. Drugs were injected intravenously 30 min after incomplete (partial) occlusion ot the LAD, lasting until 60 min after drug injection. Propranolol, atenolol, and sotalol markedly attenuated the myocardial pH that had been decreased by LAD occlusion. Nitroglycerin, diltiazem, and nicorandil also attenuated the pH, but these drugs were less active in attenuating myocardial acidosis. Dipyridamole, nifedipine, and beta-2 adrenoceptor antagonists were least active in this regard. It is concluded that myocardial pH can be used as an indicator of myocardial regional ischemia and utilized for evaluation of antianginal drugs.     

Lenticulostriate vasculopathy in twin-to-twin transfusion syndrome.

Intracranial pathology is a common and important complication in extremely low birth weight babies. Lenticulostriate vasculopathy (LSV) is an abnormal finding on cranial ultrasounds of sick babies and has been associated with congenital infection, chromosomal aberration and twin-to-twin transfusion. We describe a previously unreported situation of LSV being detected in both donor and recipient twin. This pair of monochorionic, diamniotic twins was admitted to the Neonatal Intensive Care Unit at 28 weeks of gestation. The mother underwent an emergency caesarean section because ultrasound and Doppler studies showed stage III twin-to-twin transfusion syndrome. The first twin weighed 998 g and second twin weighed 600 g. The first twin had an uneventful stay, whereas the second twin needed prolonged continuous positive airway pressure and indomethacin for patent ductus arteriosus. Both of them developed LSV. The clinical significance of this condition on the neuro-developmental outcome of a neonate has not yet been fully determined.     

Skin test results and self-reported symptom severity in allergic rhinitis: the role of psychological factors

BACKGROUND: In allergic conditions, the degree of skin test reactivity does not always correlate with the severity of clinical symptoms. Additional factors may contribute to the reported symptom severity. OBJECTIVES: To investigate the association between the magnitude of the skin prick test (SPT) response and the reported symptom severity in patients with allergic rhinitis and the possible modifying role of psychological factors. METHODS: One hundred four patients with allergic rhinitis and 23 with non-allergic rhinitis, classified according to their SPT response to 19 aeroallergens, were asked to rate the severity of five symptoms and to indicate whether their symptoms intensified on exposure to five common aeroallergens. They also completed a psychological questionnaire. Results Reported symptom severity of allergic rhinitis did not correlate with weal size for any of the aeroallergens tested or with the number of positive responses on SPT. It was not related to patient age, sex, or education. The reported symptoms severity correlated positively (0.29, P < 0.01) with reported symptom intensification on exposure to allergens. Moreover, both outcomes were positively associated with the psychological factors of hypochondriasis (0.20, P < 0.05 and 0.18, P < 0.05, respectively), and somatic awareness (0.24, P < 0.05 and 0.33, P < 0.01, respectively), but not with neuroticism. CONCLUSIONS: The severity of symptoms experienced by patients with allergic rhinitis is apparently not related to the magnitude of SPT response, but rather to psychological factors of hypochondriasis and somatic awareness. Physicians should be aware of the contribution of psychological factors to patient perceptions of the intensity of symptoms and of the intensification of symptoms on their exposure to allergens.     

Functional innervation of the striatum by ventral mesencephalic grafts in mice with inherited nigrostriatal dopamine deficiency

Weaver mutant mice are characterized by a decrease in striatal dopamine (DA), which is associated with a progressive loss of DA neurones in the substantia nigra. This mutant thus provides the opportunity to examine the functional effects of DA neurones grafted to the striatum in a genetic model of parkinsonism. Ventral mesencephalic tissue from normal foetuses was placed on the surface of the right dorsal striatum of adult weaver mutants. After grafting, animals were tested for methamphetamine-induced circling behaviour. Mutants with DA containing grafts displayed a significant circling bias toward the left, non-grafted side. Mutants without grafts did not display any rotational bias to either side. These results demonstrate that grafted DA containing neurones establish a functional innervation of the weaver striatum and suggest that grafting of neural tissue is a viable approach in restoring function in genetic degenerative disorders of the nigrostriatal system.