Effect of xylazine on interovulatory interval and serum progesterone concentrations in the horse mare

The objective of this study was to determine the effect of the alpha(2)-adrenergic agonist, xylazine, on interovulatory interval and progesterone concentrations in the horse mare. Mares were assigned to one of four treatments: Group 1 (controls) received an intramuscular injection (i.m.) of 5 cc saline (n=6), Group 2 received 10 mg prostaglandin F(2alpha) (PGF(2alpha)) i.m. (n=5), Group 3 received 500 mg xylazine i.m. (n=6) and group 4 received an intravenous injection (i.v) of 350 mg xylazine (n=6). Treatment was administered on Day 10 of the estrous cycle (Day 0 = Day of detected ovulation). There was no difference in length of interovulatory interval between PGF(2alpha)-treated mares and control mares (mean +/- SEM; 18.8 +/- 1.0 versus 21.7 +/- 1.6 d). When compared with either xylazine-treated group, PGF(2alpha)-treated mares had a shorter interovulatory interval (18.3 +/- 1.0 d versus 22.2 +/- 0.6 and 22.8 +/- 1.3 d, respectively; P < 0.05). There was no difference in the length of interovulatory interval between control mares and either xylazine-treated group. At the time of treatment all mares had progesterone concentrations > 10 ng/ml, therefore the onset of luteolysis was defined as the day of the estrous cycle when progesterone concentrations decreased below 10 ng/ml. In PGF(2alpha)-treated mares, this event occurred earlier than in any other group (Day 11.2 +/- 0.2 of the estrous cycle versus 16.0 +/- 1.3 for control, Day 15.7 +/- 0.2 for Group 3 and Day 15.2 +/- 0.6 for Group 4; P < 0.002). It was concluded that a single treatment with xylazine, either by an intramuscular or intravenous route, had no significant effect on interovulatory interval or progesterone concentrations in horse mares.     

The suppressive effect of antilymphocyte globulin (ALG) on the formation of anti-ALG antibodies]

The quantitative follow-up of precipitin formation against IgG aids in investigating the question whether ALG when applied to the organism tends to suppress the immune reaction against ALG. Rabbits locally immunized with pig anti-rabbit ALG were repeatedly treated i.v. with the same ALG, and to control groups normal pig IgG and NaCl saline was administered. It was found that antilymphocytic antibodies greatly suppressed the precipitation formation against IgG molecules. In the later stages of application this effect became more pronounced, evidently due to the specific suppression induced by long-term administration of relatively high doses of antigen. A possible improvement in the prevention of precipitin formation in ALG treated patients, i.e. substitution of currently applied tolerogenic dose of normal IgG by a similar dose of ALG is suggested.     

Behavioral sensitization to delta 9-tetrahydrocannabinol and cross-sensitization with morphine: differential changes in accumbal shell and core dopamine transmission

Although cannabinoid-induced behavioral sensitization and cross-sensitization with opiates has been recently demonstrated, no information is available on the associated state and responsiveness of dopamine (DA) transmission in the nucleus accumbens (NAc) shell and core. In this study we investigate by means of dual probe microdialysis, the effect of exposure to a sensitizing regimen of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and morphine on the extracellular concentrations of DA under basal conditions and after challenge with Delta(9)-THC and morphine in the NAc shell and core. Different groups of male Sprague-Dawley rats were administered twice daily for 3 days with increasing doses of Delta(9)-THC (2, 4, and 8 mg/kg i.p.), morphine (10, 20, and 40 mg/kg s.c.), and vehicle. After 14-20 days from the last injection, the animals were implanted with two microdialysis probes, one aimed at the NAc shell and the other at the core. The following day animals pre-treated with Delta(9)-THC and vehicle controls were challenged with 150 microg/kg i.v. of Delta(9)-THC or 0.5 mg/kg i.v. of morphine. Animals pre-treated with morphine and their vehicle controls were administered with 150 microg/kg i.v. of Delta(9)-THC. Rats pre-exposed to Delta(9)-THC showed behavioral sensitization associated with a reduced stimulation of DA transmission in the NAc shell and an increased stimulation in the NAc core in response to Delta(9)-THC challenge. Pre-exposure to Delta(9)-THC induced behavioral sensitization to morphine also, but only a reduced stimulation of DA transmission in the NAc shell was observed. Animals pre-treated with morphine showed behavioral sensitization and differential changes of DA in the NAc shell and core in response to Delta(9)-THC challenge with a decreased response in the shell and an increased response in the core. The results show that Delta(9)-THC-induced behavioral sensitization is associated with changes in the responsiveness of DA transmission in the NAc subdivisions that are similar to those observed in the sensitization induced by other drugs of abuse.     

Insulin sensitivity is mediated by the activation of the ACh/NO/cGMP pathway in rat liver

The hepatic parasympathetic nerves and hepatic nitric oxide synthase (NOS) are involved in the secretion of a hepatic insulin sensitizing substance (HISS), which mediates peripheral insulin sensitivity. We tested whether binding of ACh to hepatic muscarinic receptors is an upstream event to the synthesis of nitric oxide (NO), which, along with the activation of hepatic guanylate cyclase (GC), permits HISS release. Male Wistar rats (8-9 wk) were anesthetized with pentobarbital sodium (65 mg/kg). Insulin sensitivity was assessed using a euglycemic clamp [the rapid insulin sensitivity test (RIST)]. HISS inhibition was induced by antagonism of muscarinic receptors (atropine, 3 mg/kg i.v.) or by blockade of NOS [NG-nitro-L-arginine methyl ester (L-NAME), 1 mg/kg intraportally (i.p.v.)]. After the blockade, HISS action was tentatively restored using a NOdonor [3-morpholynosydnonimine (SIN-1), 5-10 mg/kg i.p.v.] or ACh (2.5-5 microg.kg(-1).min(-1) .i.p.v.). SIN-1 (10 mg/kg) reversed the inhibition caused by atropine (RIST postatropine 137.7 +/- 8.3 mg glucose/kg; reversed to 288.3 +/- 15.5 mg glucose/kg, n = 6) and by L-NAME (RIST post-L-NAME 152.2 +/- 21.3 mg glucose/kg; reversed to 321.7 +/- 44.7 mg glucose/kg, n = 5). ACh did not reverse HISS inhibition induced by L-NAME. The role of GC in HISS release was assessed using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 nmol/kg i.p.v.), a GC inhibitor that decreased HISS action (control RIST 237.6 +/- 18.6 mg glucose/kg; RIST post-ODQ 111.7 +/- 6.2 mg glucose/kg, n = 5). We propose that hepatic parasympathetic nerves release ACh, leading to hepatic NO synthesis, which activates GC, triggering HISS action.     

Effect of Cassia fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats

The hepatoprotective and antioxidant effect of Cassia fistula Linn. leaf extract on liver injury induced by diethylnitrosamine (DEN) was investigated. Wistar rats weighing 200+/-10g were administered a single dose of DEN (200mg/kg b.w., i.p.) and left for 30 days. For hepatoprotective studies, ethanolic leaf extract (ELE) of C. fistula Linn. (500mg/kg b.w., p.o.) was administered daily for 30 days. AST, ALT, ALP, LDH, gamma-GT and bilirubin were estimated in serum and liver tissue. Lipid peroxidation (LPO), SOD and CAT were also estimated in liver tissue as markers of oxidative stress. DEN induced hepatotoxicity in all the treated animals were evident by elevated serum ALT, AST, ALP and bilirubin levels and a simultaneous fall in their levels in the liver tissue after 30 days. Induction of oxidative stress in the liver was evidenced by increased LPO and fall in the activities of SOD and CAT. ELE administration for 30 days prevented the DEN induced hepatic injury and oxidative stress. In conclusion, it was observed that ELE of C. fistula Linn. protects the liver against DEN induced hepatic injury in rats.     

Intranasal midazolam in piglets: pharmacodynamics (0.2 vs 0.4 mg/kg) and pharmacokinetics (0.4 mg/kg) with bioavailability determination

Intranasal midazolam was studied in two series of piglets: series 1, n = 20 (18 +/- 3 kg), a randomized double blind pharmacodynamic study to compare doses of 0.2 mg/kg and 0.4 mg/kg; series 2, n = 9 (42 +/- 8 kg), a pharmacokinetic study with a 0.4 mg/kg dose administered either intravenously (i.v.) or intranasally (i.n.) in a cross-over protocol with a one-week wash-out period between each. In series 1, midazolam caused significant anxiolysis and sedation within 3 to 4 min, without a significant difference between 0.2 and 0.4 mg/kg doses for any of the studied parameters. In series 2, after intranasal midazolam administration of 0.4 mg/kg, plasma concentrations attained a maximum (Cmax) of 0.13 +/- 0.04 mg/l at 5 min (median Tmax) and remained higher than 0.04 mg/l until 60 min. The bioavailability factor (F) in this study was F = 0.64 +/- 0.17 by the intranasal route. The terminal half-life (T1/2 lambda z) = 145 +/- 138 min was comparable with the i.v. administration half-life (158 +/- 127 min). In conclusion, optimal intranasal midazolam dose in piglets was 0.2 mg/kg, which procures rapid and reliable sedation, adapted to laboratory piglets.     

Suppression of anti-mouse immunoglobulin antibodies in subhuman primates receiving murine monoclonal antibodies against T cell antigens

Murine monoclonal antibodies stimulate the production of human anti-mouse immunoglobulin antibodies (AMIA) when administered to patients. This limits their long-term usefulness as therapeutic and diagnostic agents. We report the use of three maneuvers to suppress AMIA against T cell-specific monoclonal antibodies in cynomolgus monkeys. Twelve monkeys received daily i.v. infusions of 1 mg each of anti-Leu-2a, -3a, and -5 on days 1 through 10. One group (control) received no suppressive regimen. The second group received cyclosporine, 12.5 mg/kg daily on days -7 to +14. The third group (PI) were passively immunized with 0.4 ml of hyperimmune monkey AMIA serum on days -7, -1, 2, 4, 6, and 8. The fourth group (TLI) received 1700 rad fractionated total lymphoid irradiation ending on day -1. The animals treated with TLI were markedly delayed in the onset of AMIA, which was suppressed to less than 1% of the control group. The AMIA specific for the constant region of animals receiving PI was also suppressed to one-third of control. The majority of the AMIA in all the animals was anti-idiotypic and wholly anti-idiotypic in the TLI animals.     

Failure of naloxone to stimulate luteinizing hormone secretion during pregnancy and steroid treatment of ovariectomized beef cows

The response of serum luteinizing hormone (LH) to naloxone, an opiate antagonist, and gonadotropin-releasing hormone (GnRH) was measured in cows in late pregnancy to assess opioid inhibition of LH. Blood samples were collected at 15-min intervals for 7 h. In a Latin Square arrangement, each cow (n = 6) received naloxone (0, 0.5, and 1.0 mg/kg BW, i.v.; 2 cows each) at Hour 2 on 3 consecutive days (9 +/- 2 days prepartum). GnRH (7 ng/kg body weight, i.v.) was administered at Hour 5 to all cows on each day. Mean serum LH concentrations (x +/- SE) before naloxone injection were similar (0.4 +/- 0.1 ng/ml), with no serum LH pulses observed during the experiment. Mean serum LH concentrations post-naloxone were similar (0.4 +/- 0.1 ng/ml) to concentrations pre-naloxone. Mean serum LH concentrations increased (p less than 0.05) following GnRH administration (7 ng/kg) and did not differ among cows receiving different dosages of naloxone (0 mg/kg, 1.44 +/- 0.20; 0.5 mg/kg, 1.0 +/- 0.1; 1.0 mg/kg, 0.9 +/- 0.1 ng/ml). In Experiment 2, LH response to naloxone and GnRH was measured in 12 ovariectomized cows on Day 19 of estrogen and progesterone treatment (5 micrograms/kg BW estrogen: 0.2 mg/kg BW progesterone) and on Days 7 and 14 after steroid treatment. On Day 19, naloxone failed to increase serum LH concentrations (Pre: 0.4 +/- 0.1; Post: 0.4 +/- 0.1 ng/ml) after 0, 0.5, or 1.0 mg/kg BW.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous urea secretion into the sheep gastrointestinal tract.

Urea turnover and the proportion of endogenous urea secreted and excreted in the saliva, the bile, the pancreatic juice and the urine and directly across the wall of the digestive tract was studied in 6 experiments, after a single i.v. dose of labelled 15N, in two adult sheep weighing 49 and 50 kg, with permanent biliary and pancreatic fistulus and with an exteriorized right parotid duct. It was found that, of the total amount of endogenous urea secreted into the animals' digestive tract (0.2694+/-0.0138 mg/min/kg b.w.), 10.27+/-0.94% reached the contents in the saliva, 2.12+/-0.28% in the bile and 0.66+/-0.08% in the pancreatic juice, and that 86.95+/-2.1% was secreted into the gastrointestinal tract, across its wall, from the blood capillaries. Exogenous turnover amounted to 0.3228+/-0.192 mg/min/kg. Of the total amount of 476.6 mg i.v. injected 15N urea, 274.1+/-8.86 mg was excreted in the urine 5.1+/-0.9 mg in the bile, 3.19+/-0.06 mg in the pancreatic juice, 4.96+/-0.76 mg via the right parotid gland and 9.34+/-1.09 mg in the faeces. The results show that the quantitatively most important part of the recirculation of endogenous urea is its passage from the blood across the wall of the gastrointestinal tract into its contents.     

Somatostatin treatment affects testicular function in stallions

This study investigated the regulation of growth hormone (GH) release in stallions and tested the hypothesis that the somatotrophic axis influences testicular function. Basal plasma GH concentrations, effects of an experimental decrease of GH release on testicular function and an opioidergic regulation of GH release were investigated in Shetland stallions (n=6). No seasonal variations in plasma GH concentrations were found over a 12-month period. Treatment with the somatostatin analogue octreotid (100mg twice daily over 10 days) caused a decrease in semen motility from 38.7+/-8.4% progressively motile spermatozoa before treatment to 18.3+/-5.4% on day 3 after end of treatment (P<0.05). Values returned to 35.0+/-8.5% on day 5 after treatment. On the last day of octreotid treatment, a hCG stimulation test was performed (3000IU hCG i.v.). The hCG-induced testosterone release was significantly higher in saline treated than in octreotid pretreated animals (P<0.05). Neither plasma GH concentrations nor volume and density of ejaculates, total sperm count, or semen morphology were different between saline and octreotid treatments. Injection of the opioid antagonist naloxone (0.5mg/kg) significantly increased GH release in June (from 1.1+/-0.3ng/ml before to 3.7+/-2.2), while a minor and not significant increase occurred in January. In conclusion, our results indicate a non-seasonal basal GH release with a fine-modulation by season-dependent opioidergic mechanisms in the male horse. A transient decrease in semen motility and hCG-induced testosterone release following ocreotid treatment indicate a role of GH in the regulation of testicular function in stallions.     

A comparison of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits.

We evaluated and compared the effects of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits. Fourteen New Zealand White rabbits were randomly assigned to receive either medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-propofol (4 mg/kg, i.v.) (n = 7) or medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-midazolam (0.5 mg/kg, i.m.)-propofol (2 mg/kg, i.v.) (n = 7). Five minutes after medetomidine-atropine or medetomidine-atropine-midazolam i.m. injection, propofol was administered i.v. Both medetomidine and medetomidine-midazolam rapidly (within 5 minutes) immobilized all rabbits and greatly eased the i.v. administration of propofol. Endotracheal intubation was accomplished easily after propofol injection in both groups. There was no significant difference between medetomidine-propofol and medetomidine-midazolam-propofol-treated rabbits in heart rate, respiratory rate, mean arterial pressure, or end-tidal CO2. The addition of midazolam to the medetomidine-propofol regimen significantly (P < 0.05) prolonged the duration of ear-pinch analgesia (25.0 +/- 7.1 vs. 36.7 +/- 8.9 minutes), the time from extubation to sternal recumbency (0.0 vs. 26.7 +/- 8.1 minutes), and the time from extubation to standing (0.0 vs. 39.5 +/- 11.3 minutes) without inducing significant changes in arterial blood pressure and end-tidal alveolar CO2. We consider both medetomidine-propofol and medetomidine-midazolam-propofol combinations to be safe and effective regimens for induction and short-term anesthesia in rabbits.     

Effect of combined histamine H1 and H3 receptor blockade on cutaneous microvascular permeability elicited by compound 48/80

The pharmacological consequences of combining a histamine H1 receptor antagonist with a H3 antagonist on cutaneous microvascular permeability due to intradermal (i.d.) injections of compound 48/80, a mast cell liberator of histamine, was studied in the anesthetized guinea pig. Compound 48/80 (0.0003, 0.001, 0.003 and 0.01%) induced permeability responses were attenuated, as determined by Evans blue extravasation, in animals pretreated with the H1 antagonist, chlorpheniramine (CTM; 1.0 mg/kg, i.v.) by 17 +/- 4, 31 +/- 4, 32 +/- 4 and 37 +/- 4%, respectively. Combination treatment with an H1 and H3 antagonist displayed greater inhibitory efficacy against the effects elicited by compound 48/80. Specifically, combined treatment with CTM (1.0 mg/kg, i.v.) and the H3 antagonist, thioperamide (THIO 1.0 mg/kg,i.v.) inhibited the skin responses of i.d. compound 48/80 (0.0003, 0.001, 0.003 and 0.01%) by 36 +/- 4, 45 +/- 4, 49 +/- 4 and 54 +/- 4%. A second H3 antagonist, clobenpropit (CLOB; 0.3 mg/kg, i.v.) plus CTM (1.0 mg/kg, i.v.) also inhibited Evans blue extravasation. Treatment with THIO (1.0 mg/kg, i.v.) and CLOB (0.3 mg/kg, i.v.) administered alone had no effect on compound 48/80-induced skin responses. We conclude that combination administration of a H1 and a H3 histamine receptor antagonist produces greater inhibitory effect on cutaneous microvascular permeability produced by released mast cell-derived histamine than either a H1 or H3 antagonist administered separately. In addition, the antiallergy activity of combining a H3 antihistamine with a H3 antagonist activity might provide a novel approach for the treatment of allergic skin diseases such as urticaria.     

Nicotine-induced sensitization to ambulatory stimulant effect produced by daily administration into the ventral tegmental area and the nucleus accumbens in rats.

Bilateral injections of nicotine (30 micrograms/side) into the ventral tegmental area (VTA) and the nucleus accumbens (NACC) increased the ambulatory activity in rats. Moreover, daily injections of nicotine (10, 20 and 30 micrograms/side) into the VTA and the NACC for 6 successive days produced sensitization to the ambulatory stimulant effect of nicotine. Sensitization produced by daily injections of nicotine (20 micrograms/side) into both the sites was maintained for withdrawal periods of 10 days. Mecamylamine (2 mg/kg, i.p.), SCH23390 (0.05 mg/kg, i.p.) and spiperone (0.1 mg/kg, i.p.) antagonized nicotine-induced sensitization to the ambulatory stimulant nicotine-induced sensitization to the ambulatory stimulant effect produced by daily injections into the VTA. These results suggest that nicotine-induced sensitization to the ambulatory stimulant effect involves the stimulation of the mesolimbic dopaminergic pathway through the nicotinic acetylcholine receptor (nAChR) in the VTA and the NACC.     

Suppression of ethanol and lipopolysaccharide-induced liver injury by extracts of Hydrangeae Dulcis Folium in rats

In female SD rats that were injected with 4 g/kg BW ethanol p.o. followed by a 5 mg/kg BW lipopolysaccharide (LPS) i.v. injection, serum glutamic pyruvic transaminases (GPT) activity increased to about eight times that of normal rats. In this model, rats that had been fed a diet containing 1% Hydrangeae Dulcis Folium (HDF) extracts for fifteen days showed significantly lower serum GPT activity (380.0+/-58.2 IU/l) than the control group (3527.0+/-774.1 IU/l). HDF's efficacy was far superior to milk thistle in this model (2950.0+/-915.9 IU/l). When mouse macrophages were treated with HDF extracts at 50 microg/ml, TNF-alpha production induced by LPS was suppressed to about 10% of the control. Rat serum TNF-alpha levels induced by LPS was decreased to 58.7% of the control by administering 1000 mg/kg BW HDF extract p.o. These results indicate that HDF prevents alcohol-induced liver injury through the inhibition of TNF-alpha production.     

Determination of acteoside in Cistanche deserticola and Boschniakia rossica and its pharmacokinetics in freely-moving rats using LC-MS/MS

A sensitive LC-MS/MS method with a simple solid-phase extraction for the determination of acteoside in rat plasma and tissue homogenates was established for the investigation of bioavailability and brain distribution in freely-moving rats. Acteoside in Cistanche deserticola and Boschniakia rossica was also determined. Acteoside and internal standard were separated on a RP-select B column (125mmx4.6mm i.d., particle size 5microm). The mobile phase consisted of 35% methanol and 65% acetic acid-water (1:100, v/v) at a flow-rate of 1mL/min. Acteoside and the internal standard were monitored using the multiple-reaction monitoring (MRM) mode at m/z transitions of 623-->161 and 609-->301, respectively. The acteoside content was 38.4+/-2.4mg/kg (n=3) for B. rossica, which is obviously lower than 21134.2+/-805.5mg/kg (n=3) of C. deserticola. The protein binding in rat plasma was 75.5+/-1.8%. The brain distribution result indicated that acteoside was evenly distributed in brain tissues (brain stem, cerebellum, the rest of the brain, cortex, hippocampus and striatum) which was about 0.45-0.68% of that in plasma (4.5+/-0.5microg/mL) after 15min of acteoside administration (10mg/kg, i.v.). After acteoside was given (3mg/kg, i.v.; 100mg/kg, p.o.), the oral bioavailability (AUC(p.o.)/dose(p.o.))/(AUC(i.v.)/dose(i.v.)) was only 0.12%.     

Suppressive effect of coenzyme Q10 on phospholipase A2 activation in cardiac cells after prolonged swimming.

Phospholipase A2 (PLA2) activity is elevated in cardiac microsomal fractions and phospholipids (PL) are much reduced in both the cardiac mitochondria and microsomal fractions from rats subjected to prolonged swimming. Preadministration of coenzyme Q10 (CoQ10 i.v. 30 mg/kg) significantly suppressed these changes. Two groups of 8-week-old male Wistar rats were trained to swim, receiving 30 min of training for 4 days. On the fifth day they were given an intravenous injection of either 30 mg/kg CoQ10 in saline or 1 ml saline. Thirty minutes later they began to swim for 3 hours carrying a weight representing 3% of body weight. On completion of the swim they were sacrified by instantaneous decapitation, and cardiac mitochondria were isolated. Mitochondria were also prepared from saline injected, unexercised control rats. Phosphatidylethanolamine (PE) and phosphatidylcholine (PC) concentrations were measured with HPLC and PLA2 activity was assayed fluorometrically. The mitochondrial concentrations (means +/- SEM, n = 6) of PE and PC were respectively 126 +/- 22 and 140 +/- 22 nmol/mg protein in the exercise-CoQ10 group against 66 +/- 4 and 50 +/- 10 nmol/mg protein in the exercise-saline group. The specific PLA2 activities (expressed as nmol degraded dipyrene phosphorylethanolamine substrate/hr/mg protein) in the microsomes was 0.20 +/- 0.02 in the exercise-CoQ10 group against 0.30 +/- 0.02 in the exercise-saline group. These results suggest CoQ10 has a protective effect against an excessive reduction in mitochondrial membrane phospholipids during prolonged exercise.     

Inhibition of luteinizing hormone secretion by delta9-tetrahydrocannabinol in the ovariectomized rat: effect of pretreatment with neurotransmitter or neuropeptide receptor antagonists.

Acute treatment with delta9-tetrahydrocannabinol [delta9-THC; 0.5 or 1.0 mg/kg b.w. intravenously (i.v.)], the major psychoactive constituent of marijuana, produces a dose-related suppression of pulsatile luteinizing hormone (LH) secretion in ovariectomized rats. To determine whether delta9-THC produces this response by altering neurotransmitter and/or neuropeptide systems involved in the regulation of LH secretion, ovariectomized rats were pretreated with antagonists for dopamine, norepinephrine, serotonin, or opioid receptors, and the effect of delta9-THC on LH release was determined. Pretreatment with the D2 receptor antagonists butaclamol (1.0 mg/kg b.w., intraperitoneally) or pimozide [0.63 mg/kg, subcutaneously (s.c.)], the opioid receptor antagonists naloxone (1-4 mg/kg, i.v.) or naltrexone (2 mg/kg, i.v.), the noradrenergic alpha2-receptor antagonist idazoxan (10 microg/kg, i.v.), or the serotonin 5-HT(1C/2) receptor antagonist ritanserin (1 or 5 mg/kg b.w., i.p.), did not alter delta9-THC-induced inhibition of pulsatile LH secretion. Pretreatment with a relatively high dose of the beta-adrenergic receptor blocker propranolol (6 mg/kg, i.v.) attenuated the ability of the low THC dose to inhibit LH release; however, lower doses of propranolol were without effect. Furthermore, the ability of a relatively nonspecific serotonin 5-HT(1A/1B) receptor antagonist pindolol (4 mg/kg, s.c.) or the specific 5-HT1A receptor antagonist WAY-100635 (1 mg/kg, s.c.) to significantly attenuate THC-induced LH suppression indicates that activation of serotonergic 5-HT1A receptors may be an important mode by which THC causes inhibition of LH release in the ovariectomized rat.     

Recombinant human interleukin-1 beta: new possibilities for the prophylaxis and correction of toxic myelodepression in patients with malignant tumors. I. Phase I-II clinical trials of recombinant human interleukin-1 beta as a leukopoiesis stimulator in cancer patients receiving combination chemotherapy.

Human recombinant interleukin-1 beta (IL-1beta), administered by intravenous drop infusion, at doses of 10-20 ng/kg daily over 5 days, to a group of 67 patients suffering from malignant tumors and with grade II-IV toxic leukopenia, caused an increase in the leukocyte count to the normal value, within, on average, 8 +/- 1 days. The leukostimulatory effect of IL-1beta, administered subcutaneously at an average dose of 4.6 +/- 0.3 ng/kg (n = 16), appeared to be almost equal to that found for intravenous drop infusion at a dose of 10-20 ng/kg (n = 67). In patients receiving subcutaneous IL-1beta injections, the peripheral blood total leukocyte and granulocyte counts achieved normal values within 9 days. The side effects of IL-1beta at a dose of 0.1-20.0 ng/kg were well tolerated.     

内源性硫化氢在脂多糖引起的肺动脉高压中的作用

为观察硫化氢(hydrogen sulfide,H2s)在脂多糖(1ipopolysaccharide,LPS)引起的肺动脉高压中的作用,应用离体血管环张力测定方法测定肺动脉反应性,采用生物化学方法测定肺动脉组织中H2S产出率和胱硫醚-γ-裂解酶(cystathionine γ-lyase,CSE)活性,定量PCR方法测定肺动脉组织中CSE表达水平.结果如下:(1)与对照组相比,LPS可显著升高肺动脉平均压(mean pulmonary arterial pressure,mPAP)[(1.82±0.29)kPa vs(1.43±0.26)kPa,P<0.01],降低肺动脉组织中H2S产出率[(26.33±7.84)vs(42.92±8.73)pmoFg wet tissue per minute,P<0.01]和ACh诱导的肺动脉内皮依赖性舒张反应[(75.72±7.22)%vs(86.40±4.40)%,P<0.01];(2)NariS可部分逆转上述变化,而PPG加剧上述变化;(3)CSE活性和CSE mRNA表达的变化与H2S产出率的变化相同.结果提示,LPS对内皮依赖性舒张反应的抑制导致肺动脉高压的发生,此作用可能与H2S有关.     

Induction of cytochrome P-450 forms by prolonged administration of nifedipine

In experiments on male Wistar rats it has been found that nifedipine applied in a dose of 10 mg/kg body weight i.p. daily for 20 days did not significantly increase the total amount of cytochrome P-450 but markedly increased the 7 alpha-, 16 beta- and 6 beta-hydroxylation of androstenedione in liver microsomes, suggesting the induction of cytochromes P-450a, P-450b and P-450p respectively. The induction of cytochrome P-450b was also confirmed immunochemically with polyclonal antibodies against cytochrome P-450b/e.