Pravastatin transport across the hepatocyte canalicular membrane requires both ATP and a transmembrane pH gradient

Hepatic excretion of non-bile acid organic anions is reported to be ATP-dependent and a defect of this transport has been reported in congenitally jaundiced rats, animal models of human Dubin-Johnson syndrome. To investigate the effect of the transmembrane pH gradient on hepatocyte canalicular membrane transport of ATP-dependent organic anions, uptake of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase-inhibiting organic anion, by hepatocyte canalicular membrane vesicles was observed in the presence or absence of transmembrane pH gradients. Uptake was assessed by a rapid filtration technique. ATP-dependent pravastatin uptake was stimulated in the presence of a transmembrane pH gradient (in > out) in Sprague-Dawley (SD) rats. Uptake was dependent on both pravastatin and ATP concentrations and showed saturation kinetics. After intravenous injection of [¹⁴C]-pravastatin (0.3 μmol), 81% of the dose was excreted in the bile within 35 min in SD rats, whereas only 20% was excreted in the bile in Eisai hyperbilirubinuria rats. ATP and the pH gradient also co-stimulated the uptake of pravastatin in Eisai hyperbilirubinuria rats, although the K_m was much higher and V_max was much lower than corresponding values in SD rats. This coincided well with the marked reduction in in vivo biliary excretion of pravastatin in jaundiced rats.     

Percutaneous Balloon Mitral Commissurotomy by the Inoue Balloon Resulting in Fatal Cardiac Tamponade: Stitching Phenomenon

This article presents the first case of fatal pericardial tamponade following immediately after- successful percutaneous balloon mitral commissurotonry by the Inoue balloon. The patient had a large right atrium associated with severe tricuspid regurgitation and this led to incorrect atrial puncture (so culled stitching phenomenon) under the Inoue method fir determining the site of fossa ovalis. (J lnterven Cardiol 1994; 7:33–37)     

3’-当归酰氧基-4’-乙酰氧基-3’,4’-双氢邪蒿内酯对麻醉犬心脏血流动力学的影响(英文)

本文研究了3’-当归酰氧基-4’-乙酰氧基-3’,4’-双氢邪蒿内酯(Pd-Ia)和地尔硫(艹卓)(Dil)对麻醉犬心脏血流动力学的影响。Pd-Ia剂量依赖性增加冠流量,减少主动脉压(MAP), dp/dt_(max),率压积(RPP)及全身血管阻力,并加快HR。Dil与Pd-Ia作用相似,但明显减慢HR。Pd-Ia对MAP及RPP的作用约为Dil的1/10。结果再次表明:Pd-Ia是一Ca~(2 )通道阻滞剂。     

Effects of Hypophysectomy on Patients With Advanced Breast Cancer in Relation to Pituitary Hormone Reserve Before and After the Operation

In four patients with advanced breast cancer, the TSH, prolactin,LH and FSH reserve was measured, before and after hypophysectomy,by stimulation with TRH and LH-RH. Two out of the four patientswere objectively improved following the operation. It was foundthat the clinical effects of hypophysectomy did not correlatewith changes in secretion of any of these pituitary hormones.In addition, the complete absence of pituitary hormones afteroperation did not necessarily mean that treatment had been effective. ^*This study was supported by Grants for Cancer Research andfor Specific Diseases from the Ministry of Health and Welfareand by a Grant-in-Aid for Cancer Research from the Ministryof Education, Science and Culture, Japan     

On the Transportation of Spermatozoa in the Vas Deferens

In this report the intraluminal pressure of the vas deferens was measured in vivo in male cross-bred dogs. The measurement of the pressure elucidated that the vas deferens repeated autonomic contraction. This contraction was not the so-called peristalsis but the entire portion of the vas deferens contracted simultaneously. Stimulation of the hypogastric nerves resulted in a prominent elevation of the pressure in the proximal portion of the vas deferens, i.e., the portion approximate to the epididymis, followed 5-10 seconds later by a rise in the distal portion, i.e., the portion approximate to the prostate. These results suggest that the spermatozoa present near the proximal end of the vas deferens are transported littly by little by the autonomic movements of the vas deferens and that on ejaculation the spermatozoa are pressed forward from the proximal end of the vas deferens to its peripheral end by the stimuli through the hypogastric nerves.     

STUDIES ON PEPTIDES

The octacosapeptide amide corresponding to the entire amino acid sequence of chicken VIP was synthesized in a conventional manner, using a new arginine derivative, N^G -mesitylene-2-sulfonylarginine, Arg(Mts). Treatment of a fragment, Z(OMe)-Thr-Asp-Asn-Tvr-NHNH₂ with methanesulfonic acid or HBr was found to give a product with a low recovery of Asp, after aminopeptidase digestion. Ring closure of the Asp-Asn unit seemed to be responsible for this phenomenon. Deprotection with HF or TFA exhibited definitely less such a tendency. In the final step of the synthesis, all protecting groups, including the Mts group, were removed by HF in the presence of m-cresol and the deprotected peptide was purified by ion-exchange chromatography on CM-cellulose followed by isoelectric focusing in Ampholine pH 9–11. Synthetic peptide exhibited the identical Rf value with that of natural chicken VIP and was active as the natural peptide.     

Cyclic AMP in skin: effects of acute ischaemia

The cyclic adenosine 3',5'-monophosphate (cyclic AMP) content of pig skin was measured several seconds to minutes after removal of the skin from the body. It increased very rapidly, reached a maximum by 2 min after removal (4 times higher than the initial level), then decreased very slowly. Propranolol injected into the animal before or added after the removal of the skin did not suppress this phenomenon. The practical significance of this finding (increase of cyclic AMP level in skin after ischaemia) is obvious-in order to measure cyclic AMP level in vivo, the sample must be frozen immediately to avoid an 'artificial' increase in cyclic AMP.     

Effects of short chain alcohols and hydrocarbon compounds on the adenylate cyclase of the skin

The cyclic AMP content of epidermal slices is increased by incubation with ethanol, the effect of which is dose-dependent from I to 5% concentration in the incubation media. n-Propanol and acetone are also effective at a concentration equimolar to 5% ethanol. Experimental results suggest that this effect of ethanol is due to activation of adenylate cyclase, rather than to the inactivation of cyclic AMP-phosphodiesterase.