FPL 62064, a topically active 5-lipoxygenase/cyclooxygenase inhibitor

FLP 62064 [N-(4-methoxyphenyl)-1-phenyl-1H-pyrazole-3-amine] is a dual inhibitor of prostaglandin synthetase and 5-lipoxygenase. The compound had anti-inflammatory activity in vivo in a number of models. It inhibited peritoneal inflammation induced by immune-complex when given locally. When applied to the skin, FPL 62064 inhibited UV irradiation-induced erythema and PGE2 formation in the guinea pig and also oedema formation and eicosanoid production in the mouse ear produced by arachidonic acid. Co-injected with arachidonic acid in rabbit skin, FPL 62064 inhibited oedema and eicosanoid formation.     

Nitrobid therapy in sudden sensorineural hearing loss

The efficacy of local application of Nitrobid oinment in the treatment of idiopathic sudden sensorineural hearing loss has been presented Overall good to fair recovery occured in 40% of the patients, important prognostic indicators were found to be severity of initial hearing loss, time from onset to initial visit, age of the patient and hearing status of the opposite ear.     

Physical and physiological profiles of Malaysian dragon boat rowers.

Maximal oxygen consumption (VO2max) and maximal workload attained (WLmax) were determined in 28 Malaysian dragon boat rowers who were exercised to exhaustion on an arm ergometer. Mean VO2max was 2.75 l min-1 at a mean WLmax of 195.5 W. Anaerobic endurance power of the arms, determined by cranking at 100 RPM at a workload of 400 W and the time taken to maintain the cadence until it fell to 75 RPM, was 34.9(+/- 2.3) s. Leg performance, as determined by standing long jump and vertical jump, was 140.0(+/- 4.5) kg m and 100.3(+/- 3.1) kg m s-1 respectively. Right hand grip strength was significantly (p < 0.001) greater than the left hand. Percentage body fat of the rowers was 11.8(+/- 0.6)%. These values represent the first measurements of their kind performed on dragon boat rowers in Malaysia.     

The pharmacological properties of the imidazobenzodiazepine, FG 8205, a novel partial agonist at the benzodiazepine receptor

1. The pharmacological properties of the benzodiazepine receptor ligand, FG 8205 (7-chloro-5,6-dihydro-5-methyl-6-oxo-3-(5-isopropyl-1,2,4-oxadiazol++ +-3-yl)-4H- imidazol[1,5a][1,4]benzodiazepine) have been examined. 2. FG 8205 potently displaced [3H]-flumazenil binding in rat cortical membranes with a Ki of 3.3 nM, but was inactive at 13 neurotransmitter recognition sites. 3. Consistent with a partial agonist profile, the affinity of FG 8205 for the benzodiazepine recognition site was increased in the presence of gamma-aminobutyric acid (GABA, 300 microM) by a degree (-log [IC50 in the presence of GABA/IC50 alone] = 0.34) significantly less than found for diazepam (0.46). FG 8205 also potentiated the inhibitory potency of the GABAA-receptor agonist, isoguvacine, on the hippocampal CA1 population spike and, again, the maximum shift (-log dose-ratio = 0.2) was significantly less than that seen with diazepam (0.4). 4. In anticonvulsant studies, the ED50 doses of FG 8205 and diazepam needed to antagonize seizures induced by pentylenetetrazol (PTZ) or by sound in audiogenic seizure prone mice were similar with values of 0.2-0.3 mg kg-1, i.p. However, even high doses of FG 8205 (50 mg kg-1) did not protect against seizures induced by electroshock. 5. FG 8205 released responding suppressed by footshock in a rat operant conditioned emotional response task over the dose range 0.5-50 mg kg-1 (i.p.). Similar doses of FG 8205 had a marked taming effect in cynomolgus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for the presence of a non-catecholamine, clonidine-displacing substance in crude, methanolic extracts of bovine brain and lung

In the present study we have prepared crude, methanolic extracts of bovine lung and bovine brain and, using radioligand binding assays in conjunction with a number of simple chromatographic techniques, provided evidence for the presence of a non-catecholamine ’clonidine-displacing substance‘ (CDS). The level of CDS in lung extracts (9?units/g wet weight n=11) is approximately 3 times that in the brain extracts. Furthermore, the effect of the crude, methanolic extracts are selective for non-adrenoceptor, imidazoline (labelled by [ ³H]-idazoxan) and a ₂-adrenoceptor binding sites (labelled by [ ³H]-clonidine); both extracts are 5–10-fold more potent displacers of ligand binding to a ₂-adrenoceptors compared with binding to opiate receptors (labelled by [ ³H]-etorphine) and practically inactive against a ₁-adrenoceptor and muscarinic binding sites (labelled by [ ³H]- prazosin and [ ³H]-quinuclidinyl benzilate, respectively). With the exception of the non-adrenoceptor, imidazoline binding assay, which used rat kidney membranes labelled by [ ³H]-idazoxan in the presence of the a ₂-adrenoceptor antagonist RS-15385-197, all radioreceptor assays involved bovine cerebral cortex membranes. Although the extracts contain catecholamines (brain only), histamine (lung only) and monovalent cations (both), which have the potential to interfere with the radioligand binding assays, their concentrations were too low to account for the effects observed. Preliminary attempts at purification of the extracts revealed that CDS activities from the two tissues are similar, i.e., practically insoluble in organic solvents at room temperature, not affected by either Sep-Pak C ₁₈ column or anion exchange resins but retained (along with the monovalent cations) by cation exchange resin. However, following chromatographic separation on a Biogel P2 column, the CDS-containing eluates are cation-free and exhibit qualitatively similar elution profiles. Future experiments will involve further purification of ’clonidine-displacing substance‘ to characterize its interaction with a ₂-adrenoceptor binding sites in greater detail and establish whether it has biological activity consistent with the properties implied by its effects in radioligand binding assays.     

Presence of pulmonary intravascular macrophages in the equine lung: some structuro-functional properties.

The pulmonary intravascular macrophages (PIMs) have been described in several species of animals. This study demonstrates for the first time that the equine lung has PIMs as resident phagocytes in its microvasculature. Their salient features such as globular surface coat, structures of the endocytic pathway, and related cell organelles closely resemble those of the calf, goat, and sheep. The exquisite organization of the coat globules in the form of a linear chain was structurally similar to the lipolytic lipase and the heparin-sensitive globular coat from PIMs of calf, goat, and sheep. Monastral blue (MB) when employed as a tracer to assess the phagocytic properties of equine PIMs induced similar modification of the globules of the coat into lipid droplets, reminiscent of neutral lipids. Lipids droplets (modified coat globules) were delivered into acid phosphatase-positive endosomes and lysosomes. Concurrently, the unaltered globules of the coat, probably internalized via fluid-phase constitutive pinocytoses, followed a different endocytic pathway. Large-scale platelet uptake by the PIMs was observed with thrombocytopenia in MB-treated ponies. The possible significance of hypothetical LDL-coat and the endocytic organelles as equivalents of synthetic apparatus of vasoactive lipids in the PIMs of horse needs to be assessed in future studies.     

Predictive value of some biochemical indices in stone formers

Search is under way to develop reliable tests for the prediction of stone risk. Several indices and ratios on the basis of urinary excretions have been suggested. In the present study the applicability of some risk indices and ratios in slum dwellers of Dharavi area of Bombay was examined. No significant difference was observed in IAP (ionic activity product) and CORI (calcium oxalate risk index) between stone formers (SF) and normal subjects (NS). We have suggested two more adjuncts, PIR (promoter/inhibitor ratio) and COQ (calcium oxalate quotient), and found them to be quite useful in the detection of risk. Pre-existence of risk factor(s) in the majority of the normal population suggests that triggering of stone formation should be a transient phenomenon in this population. No consistent pattern of relationship between various urinary parameters was observed.     

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) collected interview and medical information relating to the child's past medical experiences from parents of 555 children diagnosed with cancer and parents of 1110 unaffected matched controls. No significant associations emerged overall for ante-natal care, place and mode of delivery, length of gestation, birth weight, condition at birth, special care, neonatal procedures or breast-feeding. Few risk factors relating to previous illnesses and medication were found, although increasing numbers of illnesses appeared to be associated with an increased risk of childhood cancer, particularly acute lymphoblastic leukaemia. A highly significant excess of case children had not been immunised (p = 0.005). In general, these results indicate that past medical experiences have little influence on the development of cancer in children.