Acute toxicity of tri-n-butyltin chloride (TBTC) in the Syrian golden hamster.

The effects of tri-n-butyltin chloride (TBTC) on Syrian golden hamsters were studied. TBTC in single doses of 0, 29.6, 44.4, 66.7, 100 or 150 mg/kg were given to 10 male hamsters in each group and the mortality rates were determined two weeks thereafter. They were 0% (0/10), 0% (0/10), 10% (1/10), 10% (1/10), 30% (3/10) and 70% (7/10) for 0, 29.6, 44.4, 66.7, 100 and 150 mg/kg groups, respectively. In the case of females, seven groups consisting of 10 animals each were given TBTC at doses of 0, 29.6, 44.4, 66.7, 100, 150, or 225 mg/kg. The mortality rates determined two weeks after the TBTC treatment were 0% (0/10), 10% (1/10), 10% (1/10), 0% (0/10), 40% (4/10), 30% (3/10) and 90% (9/10) for 0, 29.6, 44.4, 66.7, 100, and 225 mg/kg groups, respectively. Based on these mortality data, the LD50s via oral administration were determined as 146.9 mg/kg (95% C.I. 111.8-193.3 mg/kg) for the male and 172 mg/kg (95% C.I. 127.2-233.4 mg/kg) for the female. Regarding pathological changes, animals experienced lesions in the bile duct, such as the dilatation of the common bile duct and cholestasis, and/or adhesion of the bile duct to the liver, gallbladder, pancreas and duodenum. In a separate experiment, a single dose of 44.4 mg/kg TBTC was administered orally to 12 male hamsters, then the concentrations of TBTC and its metabolite, di-n-butyltin chloride (DBTC), in the liver were analyzed by means of gas chromatography for 14 days after the treatment. The maximum concentrations of TBTC and DBTC appeared one day after the administration, and decreased rapidly thereafter. The concentration of DBTC was found to be higher than that of TBTC throughout the experimental period.     

Diurnal sleep apnea in myotonic dystrophy]

We investigated diurnal sleep apnea in myotonic dystrophy with respiratory inductive plethysmography. Five of eight patients met criteria for sleep apnea syndrome and had central apnea mainly. In a case showing periodic breathing with apnea like Cheyne-Stokes type breathing, the duration of apnea and breath was even and the tidal volume went waxing and waning regularly. In the other four cases, central apneas were observed in sequence, but the duration of apnea and the tidal volume changed variously. Large breaths between apneas elevated arterial oxygen saturation rather than stable breaths without apnea. We suspected that hypoxemia, which exacerbated by involvement of respiratory muscles, supine position and sleep, initiated the hyperventilation between apneas. And then the saturation of oxygen raised by hyperventilation would cause central sleep apnea.     

Postprandial hypotension: microneurographic analysis and treatment with vasopressin

To clarify the mechanism of postprandial hypotension (PPH), we made microneurographic analyses of patients with PPH and 10 healthy controls by recording multi-unit vasoconstrictive impulses of muscle sympathetic nerve activity (MSNA) directly from the tibial nerve fascicles during a glucose tolerance test. Oral intake of 75 grams glucose in 225 ml of water produced significant and prolonged hypotension in all patients and an increase in MSNA in all healthy subjects. Insulin and glucose responses were not significantly correlated with arterial blood pressure reduction. PPH was prevented by an infusion of vasopressin (0.3 U/min) given before glucose intake. These results suggest that PPH is caused by the lack of sympathetic compensation for the systemic hypotensive stress of splanchnic blood pooling that occurs after food ingestion, and that prior treatment with vasopressin reduces the portal venous flow by constricting the splanchnic vessels in patients with PPH.     

Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activities in Shy-Drager syndrome

We observed changes in postganglionic efferent discharges of muscle sympathetic nerve (muscle sympathetic activity, MSA) microneurographically before and after the oral administration of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a precursor of norepinephrine, in a patient with Shy-Drager syndrome and irregular fluctuations of blood pressure. Before drug administration, MSA was only rarely observed with the patient in the supine position. There was a slight increase in MSA during head-up tilting to 40 degrees, and orthostatic hypotension (OH) occurred just after the body was tilted head upward to 40 degrees. MSA became prominent 30 minutes after the oral administration of 200 mg of L-threo-DOPS while the patient was in a 40 degree head-up position, and the OH was improved. The MSA discharge rate decreased and OH reappeared 3 hours after oral administration, when the plasma concentration of norepinephrine was at its highest level. We suggest that the OH improved mainly because of the increase in MSA due to L-threo-DOPS, and that the drug may activate sympathetic outflow at a site proximal to the sympathetic ganglion.     

Plasma thrombin-antithrombin III complexes in the diagnosis of primary hepatocellular carcinoma complicating liver cirrhosis.

Detection of hypercoagulable state might be helpful in the diagnosis of primary hepatocellular carcinoma (HCC) complicating liver cirrhosis (LC). Plasma levels of thrombin-antithrombin III complex (TAT) were determined in 50 patients of LC with or without HCC. The levels were above 2 ng/ml in 80% of 25 HCC patients, but only in 12% of 25 non-HCC patients (P less than 0.01). The levels over 2 ng/ml occurred even in five of six HCC patients whose serum alpha-fetoprotein levels were below 20 ng/ml as well as in two of three patients with HCC less than 2 cm in diameter. Those levels in HCC patients were significantly decreased within 8 days after treatment with transcatheter arterial embolization or infusion of antitumor agents, without affecting plasma antithrombin III levels. These results suggest that plasma TAT levels may be useful in the diagnosis of HCC complicating LC.     

A novel protein-tyrosine kinase, tec, is preferentially expressed in liver

To identify protein-tyrosine kinases which play an important role in the process of hepatocarcinogenesis, we have screened a murine liver cDNA library with v-fps kinase domain as a probe. Using low stringency screening, we could isolate cDNAs of a putative protein-tyrosine kinase, tec (tyrosine kinase expressed in hepatocellular carcinoma). Nucleotide sequences of the cDNAs show that the C-terminal domain of its predicted protein has significant homology with that of the members of the src family. The tec gene is expressed mainly in liver and faintly in heart, kidney and ovary. Northern analysis further shows that in 2 out of 4 cell lines of human hepatocellular carcinoma (HCC) the tec gene is highly expressed compared to normal human liver. This is the first report showing a protein-tyrosine kinase which may be specifically involved in the cell growth of hepatocytes or in the step of hepatocarcinogenesis.     

Allergenicity of Chironomidae in asthmatic patients

In order to clarify the relation between asthma and Chironomidae, we examined the cross-reactivity between Chironomidae and other common allergens. We noted significant correlations between positive skin tests with Chironomidae and with other allergens. The radioallergosorbent inhibition test, however, suggested that there may be no cross-reactivity or, if any, only very low cross-reactivity between midge allergens and mite, house dust (HD), silk, shrimp, or mosquito allergens.