Piperazinyl oxime ethers as NK-1 receptor antagonists.

The synthesis and structure-activity relations for a new class of centrally active NK-1 receptor antagonists are described. The new compounds are based on piperazine 2 and contain an oxime ether functionality. Several new compounds have high affinity for the NK-1 receptor and show good antagonistic activity in the gerbil foot-tapping assay.

Short-term oral toxicity of pentyl ether, 1,4-diethoxybutane, and 1,6-dimethoxyhexane in male rats.

Pentyl ether (PE) and two newly synthesized polyoxy ethers, 1,4-diethoxybutane (DEB) and 1,6-dimethoxyhexane (DMH), have been proposed as candidate diesel fuel additives. To characterize and compare their toxicity and to provide information for risk assessment, a 4-week oral study was conducted on these compounds. Male Sprague-Dawley rats (288 +/- 20 g) were divided into groups of seven animals each, and were administered by gavage low (2 mg/kg body weight), medium (20 mg/kg body weight), or high (200 mg/kg body weight) doses of PE, DEB, or DMH, respectively, 5 days/week for 4 weeks. Animals in the control group received the vehicle (corn oil, 1 ml/100 g body weight) only. At the end of the exposure period, relative testis and thymus weights were reduced by 30 and 46%, respectively, in animals treated with the high dose of DMH. Significant reductions in serum lactate dehydrogenase (LDH), serum uric acid, and blood platelet counts were also observed in the high dose of DMH. Serum corticosterone was significantly depressed in the high doses of PE and DEB and in the low dose of DMH. Serum thiobarbituric acid-reactive substances (TBARS) were decreased (p < 0.05) in all DMH treatment groups and in the medium and high dose PE and DEB groups, while liver TBARS were unaffected by treatment. In the liver, increased glutathione (GSH) level and glutathione-S-transferases activity were detected in the high dose DMH group. Urinary ascorbic acid levels were markedly increased in animals receiving the high doses of PE, DEB, and DMH. Urinary formic acid was increased by 13 times in the high dose PE and DEB groups. Testes of all animals receiving the high dose of DMH showed a moderate to marked degree of degeneration of the seminiferous tubules, including a mild degree of vacuolation. At the same time, the epididymis of these animals had substantially reduced sperm density with prominent presence of spermatid giant cells. Mild histological changes were seen in the liver at all dose levels for all three chemicals. Thyroid effects were also observed in the high dose PE and DEB groups and in the medium and high dose DMH groups. It was concluded that DMH is the most toxic of the three ethers tested, with testicular, epidiymal, and thymic effects being the most prominent at 200 mg/kg. Other significant changes included depressed platelet counts and serum biochemical changes. Increased production of formic acid, an ocular toxin, from PE and DEB treatments may also be of toxicological concern.

Dose-response of flurbiprofen on postoperative pain and emesis after paediatric strabismus surgery.

PURPOSE: Intravenous flurbiprofen, a non-steroidal antiinflammatory drug (NSAID), has been used recently for postoperative pain relief in adults. The drug is also likely to have antiemetic property. The present study was undertaken to investigate the effect of flurbiprofen on postoperative pain and emesis in children undergoing strabismus surgery, which is well known to produce postoperative nausea and vomiting. METHODS: In a prospective, randomised, controlled clinical trial, 90 children aged 2-11 yr received saline (control), flurbiprofen 0.5 mg.kg-1, or flurbiprofen 1 mg.kg-1. Saline and flurbiprofen were administered i.v. immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). No opioids or antiemetics were administered throughout the study. The incidence and frequency of vomiting were compared among groups. RESULTS: Flurbiprofen 1 mg.kg-1 provided lower OPS (highest) scores during the eight hours after surgery and a reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. The two doses of flurbiprofen failed to decrease the incidence and frequency of vomiting. CONCLUSION: These data suggest that preoperative flurbiprofen 1 mg.kg-1 iv is a simple and effective approach to postoperative pain relief but not to the prevention of emesis following paediatric strabismus surgery.

Endoscopic transpapillary catheterization of the gallbladder followed by external shock wave lithotripsy and solvent infusion for the treatment of gallstone disease.

Herein we describe the techniques and early results of attempted endoscopic transpapillary catheterization of the gallbladder (ETCG) in combination with external shock wave lithotripsy (ESWL) and solvent infusion in the treatment of 23 consecutive, symptomatic patients with gallstones. Despite anticipated difficulty in advancing wires and catheters through the cystic duct, impeded by tortuosity of its lumen, ETCG was successfully accomplished in 20 of the 23 patients (86.9%). Through an indwelling catheter, obstructed gallbladders were drained in 4 patients and combined treatment with ESWL and infused solvents was carried out in 18 patients. Combined treatment resulted in elimination of gallstones from the gallbladders of 14 of 18 patients (77.7%). Treatment was complicated by mild pancreatitis in only 1 of 20 successfully catheterized patients; there was no mortality.

Effects of lysocellin and calcium level on mineral metabolism, performance and ruminal and plasma characteristics of beef steers.

Metabolism and growth experiments were conducted to determine the effects of lysocellin and calcium level on mineral metabolism and performance of beef steers. Lysocellin at 0 or 22 mg/kg and Ca at .3 or .6% of the diet were fed in a 2 x 2 factorial arrangement of treatments. Two steers averaging 287 kg BW were fed each diet consisting of 80% corn silage and 20% supplement (DM basis) in each of two metabolism trials. Steers were fed the diets for a 21-d preliminary period, followed by 7 d of total feces and urine collection. A lysocellin x Ca interaction was observed for nitrogen retention (P less than .01). Steers fed lysocellin and .6% Ca retained the most N (15.6 g/d), whereas steers receiving lysocellin and .3% Ca retained the least N (8.8 g/d). Lysocellin increased (P less than .05) apparent absorption of Mg. In one of the two metabolism trials, lysocellin increased (P less than .05) apparent absorption and retention of Ca. Apparent absorption and retention of Ca were higher (P less than .05) in steers fed .6% Ca when expressed as grams per day, but absorption and retention were lower (P less than .01) when expressed as a percentage of intake. In the other metabolism trial, the .6% Ca level decreased (P less than .05) urinary P excretion and increased (P less than .05) P retention as a percentage of absorbed P. In a growth experiment, 64 steers were fed similar levels of lysocellin and Ca for 119 d. Diets consisted of 90% corn silage and 10% supplement. Although no treatment effects on ADG, DMI or feed:gain were detected, lysocellin did affect concentration of several minerals in ruminal fluid and blood plasma.

[Percutaneous transhepatic lysis of gallstones]. / Zur perkutan-transhepatischen Lyse von Konkrementen der Gallenblase.

The present study reports on morphological findings obtained from 15 patients who were submitted to percutaneous transhepatic contact dissolution of gallbladder concrements with methyl-tert.-butyl ether (MTBE) and--in case of slightly calcified gallstones (n = 10)--with ethylene diamine tetraacetic acid (EDTA). At a maximum intracystic catheter placement time of four days complete lysis was obtained in 12 patients. As could be depicted by CT, the solvents induced significant regional or disseminated chemical cholecystitis in the majority of all cases. However, these changes proved to be completely reversible within about five weeks. It is concluded that with certain types of gallstones contact dissolution can be an effective alternative therapeutic technique which, however, requires meticulous morphological controlling in view of the time-consuming treatment of calcified concrements.

The effects of lysocellin and varying calcium levels on performance and ruminal and plasma characteristics of growing beef steers fed corn silage.

Twenty-four steers initially averaging 221 kg BW were used to evaluate the effects of lysocellin and calcium (Ca) level on performance and ruminal and plasma characteristics. Lysocellin at 0 or 22 mg/kg of diet and Ca at .3 or .6% were fed in a 2 X 2 factorial arrangement of treatments. Steers in individual pens had ad libitum access to a diet consisting of 80% corn silage and 20% (DM basis) of a protein, mineral and vitamin supplement. Ruminal fluid and blood samples were collected on d 42 and 85 of the 113-d trial. Steers fed the .6% Ca diet gained faster and required less feed/unit of gain than those fed the .3% Ca diet (P less than .05). There was a tendency for a lysocellin X Ca interaction for gain and feed efficiency (P less than .10). Lysocellin tended to depress performance when fed with .3% Ca, but it tended to improve gain and feed efficiency when fed with .6% Ca. Molar proportions of propionate were higher and those of acetate were lower (P less than .01) for steers fed lysocellin. Ruminal-soluble Zn, Fe and Cu levels were higher (P less than .01) in steers fed lysocellin. Ruminal-soluble Ca (P less than .01) was higher and ruminal-soluble P and Na were lower (P less than .01) in steers fed .6% Ca. Plasma K was higher (P less than .05) in steers fed .6% Ca but it was lower (P less than .05) in steers fed lysocellin. Results of this study indicate that dietary Ca affects certain metabolic responses to lysocellin in growing cattle.

[Clinical pharmacology of Opino-gel--the demonstration of its effectiveness (author's transl)]. / Zur klinischen Pharmakologie von Opino-Gel--ein Wirkungsnachweis

The effectiveness of topically-applied buphenin (in a gel basis) was demonstrated by rheography in a double-blind study. This finding was additionally corroborated by experimental local vascular (venous) rheography. The flow volume of the tested vessels showed an improvement.