Evaluation of anti-nociceptive effects of neuronal nicotinic acetylcholine receptor (NAChR) ligands in the rat tail-flick assay

In the present investigation, anti-nociceptive effects of neuronal nicotinic acetylcholine receptor (NAChR) ligands, (+)- and (-)-nicotine, cytisine, methylcarbamylcholine (MCC), dimethylphenylpiperazinium iodide (DMPP), and (+/-)-epibatidine were evaluated in the rat tail-flick assay both after subcutaneous (s.c.) and intracerebroventricular (i.c.v.) administration. The pharmacology of the tail-flick response to NAChR ligands after s.c. and i.c.v. routes was similar. Epibatidine was the most potent ligand examined with a longer duration of action than any other agonist. (-)-Nicotine was more active than (+)-nicotine indicating stereospecificity. ICV administration studies indicated an apparent partial agonist activity for (+)-nicotine in the tail-flick response. Tail-flick responses to NAChR agonists are independent of opioid and muscarinic pathways and appear to be mediated both by central and peripheral NAChR recognition sites. Central administration of MCC activates both NAChR and muscarinic anti-nociceptive mechanisms. Studies employing the alpha-adrenergic receptor alkylating agent, phenoxybenzamine or the noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), suggested that the NAChR-noradrenergic and NAChR-serotoninergic interactions play an important role in the tail-flick response. Studies employing a selective alpha-bungarotoxin-sensitive NAChR receptor antagonist, methyllycaconitine (MLA), suggested a minimal role for these receptors in the tail-flick response. The biochemical studies also indicated that a sub-population of NAChR receptors are located pre-synaptically on noradrenergic and/or serotoninergic pathways in the hippocampus.     

A clinicopathologic study of mucinous gastric carcinoma including multivariate analysis

BACKGROUND: Mucinous gastric carcinoma (MGC) is a rare subtype of gastric adenocarcinoma, and its clinical and pathologic features are still controversial. To clarify the significance of this subtype of carcinoma, the authors conducted a case-control study to investigate the clinicopathologic characteristics of MGC and determine whether this mucin-producing histologic type is associated with a worse prognosis than other gastric carcinomas. METHODS: Twenty-two cases of MGC and 46 patients with nonmucinous gastric carcinoma (NGC) were included. Patients were evaluated on the basis of age, gender, tumor size, location, depth of tumor invasion, histologic differentiation, lymph node involvement, organ metastasis, stage at presentation, surgical curability, adjuvant chemotherapy and radiation therapy. To determine whether the MGC itself was an independent prognostic factor, a multivariate analysis was performed with the Cox proportional hazards model. RESULTS: The MGC patients were found to have larger tumors (P < 0.001), tumors more often located in the upper stomach (P < 0.05), more serosal invasion (P < 0.05), more lymph node involvement (P < 0.05), greater frequency of advanced stage disease (P < 0.01), and lower 5-year survival rates (P < 0.05) than NGC patients. There was no significant correlation between the subtypes of differentiation of MGC and other data, including the prognosis. Multivariate analysis showed that clinically important predictive factors were serosal invasion and disease stage at diagnosis. The mucinous histologic type itself was not an independent factor for poor prognosis. CONCLUSIONS: The overall survival rate for patients with MGC was worse than that for patients with NGC. The poor prognosis was correlated with more advanced stage at diagnosis and more frequent serosal invasion, not with the mucinous histologic type.     

Effects of albumin and/or furosemide therapy on pulmonary edema induced by hydrochloric acid aspiration in rabbits

Aspiration of hydrochloric acid in rabbits resulted in an increased P(A-a)O2 together with increases in both lung water volume and lung extravascular albumin. This finding suggests lung damage following acid aspiration is related to changes in capillary permeability, with pulmonary edema resulting from the movement of albumin and water into the interstitial space. Therapy with albumin and furosemide together reduced the lung water and albumin accumulation and decreased P(A-a)O2. Treatment with albumin or furosemide alone was ineffective. Caution should be exercised in administering albumin alone for therapy of pulmonary edema when plasma protein is not clearly decreased, or when increased pulmonary capillary permeability is suspected.     

Tremorogenic effects of intracaudate d-amphetamine and their suppression by dopamine

Pronounced tremors were produced in unanesthetized cats following intracaudate (I.C.) injections of either d-amphetamine (15 mug), dl-methamphetamine (20 mug), l-amphetamine (48 mug) or 3-methoxytyramine (68-120 mug). Yet, a series of other chemically and pharmacologically related phenylethylamines, including dopamine (90 mug), were not tremorogenic even at substantially higher doses. The d-amphetamine tremors developed rapidly, failed to exhibit tachyphylaxis to repeated challenging doses (15 mug) and were not influenced by pretreatment with alpha-methyl-p-tyrosine. They also developed independently of local acetylcholine activity as evidenced by the inability of cholinergic antagonists (scopolamine and hemicholinium) to interfere with the tremors. Significant qualitative differences were found between the I.C. effects of d-amphetamine (15 mug) and dopamine (15-90 mug): d-amphetamine further increased the intensity of ongoing tremors induced by physostigmine (111 mug I.C.), whereas, dopamine readily inhibited the latter. When superimposed, I.C. dopamine was equally effective in suppressing d-amphetamine tremor activity. The results emphasize the selective tremorogenic actions of d-amphetamine and call attention to the contrasting stabilizing role of dopamine. This would suggest that two types of adrenergic receptor sites are operative in the caudate in neuroregulation of involuntary movements.     

Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.     

Petroleum components and objectionable malodorous substances in fish flesh polluted by boiler fuel oil

Green fish (Girella punctata) and eel (Angulla rostrata) were reared in two types of artificially oil-polluted test dilutions for the purpose of measuring the petroleum substances infiltrating the flesh. One test dilution contained untreated mineral oil and the other test dilution contained residue mineral oil after chemical treatment. Vapours from fish flesh samples were analyzed by gas chromatography. Unsaturated aliphatic hydrocarbons and some aromatic hydrocarbons were revealed as sources of the repugnant odour.