3’-当归酰氧基-4’-乙酰氧基-3’,4’-双氢邪蒿内酯对麻醉犬短时缺血后心肌功能不良的影响(英文)

静脉输入3’-当归酰氧基-4’-乙酰氧基-3’,4’-双氢邪蒿内酯(0.15mg·kg~(-1)·min~(-1))30min对15min闭塞犬左前降枝伴3h再灌注后心肌收缩功能的影响被研究。用超声微测距法测定心肌节段收缩(SS)长度表明:该药迅速改善心肌收缩功能不良,再灌后5min即使SS％恢复到用药前的41±51％(P<0.05,n=8),对血流动力学无明显影响。     

Thrombocytopenia associated with platelet-associated immunoglobulin G in alcoholic hepatitis

Abstract A 45 year old Japanese man with alcoholic hepatitis developed thrombocytopenia together with an increase in the level of platelet-associated immunoglobulin G (PAIgG). Bone marrow aspiration revealed a normal nucleated cell count and a slight increase of megakaryocytes. After abstinence from alcohol, laboratory and symptomatic improvement occurred in association with a prompt increase in the platelet count and a corresponding decrease of PAIgG. These findings suggest that PAIgG may have been involved in the development of thrombocytopenia in this patient.     

The Disposition of the Tolcapone 3-O-Methylated Metabolite is Affected by the Route of Administration in Rats

Abstract— Catechol-O-methyltransferase (COMT) catalyses the transfer of the methyl group from S-adenyl-l -methionine (SAM) to one of the hydroxy groups of a catechol, usually the hydroxy group in position 3. COMT is present mainly in a soluble form (S-COMT) in the cytosol, but a small fraction is bound to cell membranes (MB-COMT). MB-COMT has higher affinity for the catechol substrate than does S-COMT by a factor of > 10, and high MB-COMT activity is observed in the intestinal muscle layer. The present study investigates the effect of the administration route on the disposition of the tolcapone 3-O-methylated metabolite following intravenous and oral tolcapone administration in rats. Tolcapone is a substrate for COMT although the 3-O-methylated metabolite produced has no pharmacological actions. The 3-O-methylated metabolite was eliminated very slowly following oral administration of tolcapone, and its concentration approached a plateau level, which was in contrast to the situation following intravenous administration of tolcapone. It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low K_i). The fraction of the intravenous dose of tolcapone metabolized to the 3-O-methylated metabolite at 10 mg kg^?1 was 2·6%, whereas those of the oral doses, which were corrected by the bioavailability, were 5·4% for 20 mg kg^?1 and 2·7% for 40 mg kg^?1.     

Inhibitory Activity of Camptothecin Derivatives Against Acetylcholinesterase in Dogs and Their Binding Activity to Acetylcholine Receptors in Rats

Abstract— A camptothecin derivative, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), shows a potent antitumour activity in experimental tumour models and in clinical trials. However, CPT-11 induced early diarrhoea and vomiting at high dose levels in clinical studies and showed an acetylcholine-like action on the guinea-pig ileum and trachea. In the present study, we investigated the activities of camptothecin derivatives in inhibiting acetylcholinesterase (AChE) and in binding to muscarinic acetylcholine receptors (AChR). CPT-11 inhibited AChE and binding of the specific ligand to AChR with respective 50% inhibition concentrations of 0·2 and 5 μm . These inhibitions were induced by camptothecin derivatives having an amino group at the C-10 position (or the C-4 position of hexacyclic derivatives), but were not or were only slightly induced by the others. Early defecation and vomiting in dogs were observed after intravenous injection of DU-6596 and DU-6888, two hexacyclic derivatives having the aminomethyl group at the C-4 position, and of CPT-11. DU-6174, however, which has a hydroxy group at this position, induced no early defecation and little vomiting. Plasma concentrations of CPT-11, DU-6596 and DU-6888 after intravenous treatment at doses causing such early adverse effects were maintained for 1 h or longer at levels sufficient to inhibit AChE. These results suggest that the inhibition of AChE by camptothecin derivatives with an amino group at the C-10 position (or the C-4 position) relates to the early defecation or diarrhoea and vomiting.     

Inhibition of Rat Acute Inflammatory Paw Oedema by Dihemiphthalate of Glycyrrhetinic Acid Derivatives: Comparison with Glycyrrhetinic Acid

Abstract— The anti-inflammatory profile of dihemiphthalate compounds of glycyrrhetinic acid derivatives in acute rat paw oedema induced by various vasoactive agents was compared with the parent compound. Three dihemiphthalate compounds (the di-sodium salt of 18 β-olean-12-ene-3β,30-diol di-O-hemiphthalate, 18β-olean-9(11),12-dione-3β,30-diol di-O-hemiphthalate and olean-11,13(18)-diene-3β,30-diol di-O-hemiphthalate), significantly inhibited development of carrageenan-induced rat paw oedema during the first 3 h (ED50 70, 90, and 108 mg kg^?1 respectively, p.o.), while glycyrrhetinic acid (ED50, 200 mg kg^?1) showed a significant inhibition of paw oedema 3 h after carrageenan treatment. The dihemiphthalate compounds also suppressed mouse paw oedema induced by histamine, bradykinin, and PAF acether at doses of less than 100 mg kg^?1. However, these compounds failed to inhibit 5-HT-induced mouse paw oedema. Glycyrrhetinic acid had little effect on mouse paw inflammation induced by the above irritants. The three compounds at 10^?7-10^?4 m , inhibited histamine-induced contraction of guinea-pig isolated ileum. However, concentration-response curves to 5-HT and bradykinin were not affected by the same compounds. These results suggest that the dihemiphthalate compounds modulate vascular permeability caused by endogenous vasoactive agents as one of the anti-inflammatory mechanisms. This action is quite different from that of glycyrrhetinic acid.     

Erosion of a penile prosthesis due to an indwelling urethral catheter as a late complication

A case of erosion of a penile prosthesis caused by indwelling of a catheter in the urethra is reported. A 73-year-old man had maintained sexual intercourse with penile prostheses (Jonas prosthesis, 19 cm) for 11 years without any complications until he developed cerebral infarction. One month after starting an indwelling urethral catheter in a neurosurgery clinic, the left-side penile prosthesis eroded from the area of the fossa navicularis, and was immediately removed. This type of complication is not unusual in patients with a neurogenic bladder. However, it is not well recognized in patients who suddenly develop a neurogenic bladder following a long-term uneventful period after the implantation of penile prostheses. Therefore, urologists should inform patients who receive this type of treatment that erosion of the prosthesis may develop when they need an indwelling urethral catheter as a late complication.     

Two Cases of Malignancy-Associated Hypercalcemia Treated with Mithramycin

The hypocalcemic effect of mithramycin, an antitumor antibiotic,was studied in two consecutive hypercalcemic patients with malignancy.Case 1 was a 60-year-old woman with advanced breast cancer.Severe, generalized bone metastasis seemed to be the cause ofthe hypercalcemia. Serum calcium levels reached 14.6mg/dl (ionizedcalcium 3.84 mEq/I) despite continued therapy with saline (5liters/day) with frosemide (60mg/day, intravenously), high dosesof elcatonin (up to 440 MRC units/day) and prednisolone (30mg/day). Case 2 was a 49-year-old woman with recurrence of ovariancancer. Bone metastasis was not found on X-ray films. Hypercalcemiawas progressive in spite of extensive treatments with saline(2 liters/day) with frosemide (40 mg/day), indomethacin (150mg/day), elcatonin (160 MRC units/day) and prednisolone (30mg/day). Meantime, serum calcium rose to 14.6mg/dl (ionizedcalcium 3.57 mEq/I). In both cases, mithramycin (1.25 mg) wasthen administered intravenously. Serum calcium levels droppedto 9.6 and 9.4 mg/dl two days after the administration of mithramycinin case 1 and case 2, respectively. These observations indicate that mithramycin is more effectivethan any other drug tested for the treatment of hypercalcemiacaused by malignancy irrespective of the presence or absenceof bone metastasis. Therefore, it should be widely used forhypercalcemic emergency.     

Micro-determination of cyclic AMP levels in human epidermis, dermis and hair follicles

In order to study the biological and possible pathological roles of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the skin, it is mandatory to measure cyclic AMP in 50-100 mug of microdissected epidermis, dermis or appendages. In the present study, we offer a method of extracting cyclic AMP from less than 100 mug of tissue, removing contaminating nucleotides and scaling down Gilman's method to fit the analysis of small amounts of tissue. Cyclic AMP levels in the dermis, epidermis, and hair follicles (bulbs) were approximately 1, 2 and 3-5 pmols/mug dry weight tissue respectively. This procedure is applicable to the measurement of cyclic AMP levels in limited foci of healthy or diseased skin.     

A Case of Small Cell Carcinoma of the Lung Producing ADH, ACTH, MSH and Calcitonin: Successful Treatment of Severe Hyponatremia with Furosemide and Hypertonic Saline

A 48-year-old man with a small cell carcinoma of the lung presentedhyponatremia and was diagnosed as having the syndrome of inappropriateADH secretion. A plasma ADH bioassay confirmed this syndrome.During the clinical course, the patient developed a hyponatremiccrisis with a serum sodium of 108mEq/l. His hyponatremia wasrapidly corrected by infusing furosemide in conjunction withhypertonic saline. The postmortem studies demonstrated ADH bioactivityin the tumor tissues, as well as immunoreactive ACTH, ß-MSHand calcitonin. Tumor hypersecretion of ACTH appeared to bethe cause of the patient's hyperresponsiveness to exogenousACTH and of the bilateral adrenocortical hyperplasia observedat the time of autopsy. Therefore, this was a case of a multiple hormone-producing smallcell carcinoma of the lung, in which the severe clinical manifestationsof SIADH were successfully treated with furosemide and hypertonicsaline.