Effect of a high systemic background level of vitamin A on the teratogenicity of all-trans-retinoic acid given either acutely or subacutely

Groups of 12 Charles River CD virgin female rats were either supplemented with 25,000 IU/kg of vitamin A palmitate or not during the first 8 days of pregnancy and in the first experiment given a single dose of either 5 or 10 mg/kg of all-trans-retinoic acid (RA) on day 9 of pregnancy. In a second experiment, similar groups were given either 4 or 8 mg/kg RA daily from day 6 through day 15 so that each treatment with RA was given to vitamin A supplemented rats or nonsupplemented rats. The high systemic background of vitamin A increased the teratogenicity of the 10 mg/kg dose of RA given on day 9 by 50%, but reduced the teratogenicity of the 8 mg/kg dose given on days 6-15. The reasons for this paradox are discussed and related to the human propensity to self-medicate with megadoses of vitamins.     

The influence of supplemental vitamins A and E on ovine humoral immune response

These experiments determined if supplemental vitamins A and/or E would enhance ovine antibody responses. All-rac-alpha-tocopheryl acetate was fed to lambs approximately 6 months old (30 to 40 kg) at levels of 33 (controls), 121, 276, 396, and 476 mg/kg of feed (which are total vitamin E levels). Primary and secondary immunizations with 10 mg keyhole limpet hemocyanin (KLH) were given. A nonlinear dose response of serum antibody titers was observed and the 476 mg vitamin E/kg treatment significantly enhanced (P less than 0.05) the peak primary response over controls. Retinyl acetate fed at five levels ranging from 7000 (the control level) to 97,400 IU/kg feed failed to influence antibody production to 10 mg KLH of lambs about 6 months old (29 to 41 kg). There was no detectable response to an ovalbumin antigen (100 mg). Neonatal lambs were injected with retinyl palmitate or the carrier of the injected vitamin. These lambs failed to raise antibody titers to either of the antigens administered (10 mg KLH, 100 mg ovalbumin). This was apparently due to a neonatal period of immune paralysis to certain antigens. A preliminary study showed that no KLH-specific antibodies are detectable in lambs immunized earlier than 7 weeks of age. Lambs in this age range were utilized in the last trial in which four treatments were applied: 3000 mg oral vitamin E, 400,000 IU injected vitamin A, 4 ml of the injectable vitamin A carrier, or no treatment. Half of the animals in each of these groups were immunized with 15 mg KLH and 1 ml Brucella ovis bacterin and the other half served as nonimmunized controls. No significant differences in titers to KLH were observed. Lambs receiving 3000 mg vitamin E or the carrier produced secondary peak anti-B. ovis titers higher (P less than 0.05) than those of the untreated controls.     

Increased retinoic acid metabolism following 3,3',4,4',5,5'-hexabromobiphenyl injection

Young male Wistar rats received single i.p. injections of 3,3',4,4',5,5'-hexabromobiphenyl. In rats dosed with 40 mg/kg, food consumption and growth as well as liver retinol and retinyl palmitate concentrations decreased, while serum retinol and liver weight increased within 28 days following the injection. In rats receiving a 20-mg/kg dose, food consumption, growth, liver weight, and serum retinol were not affect, although liver retinol and retinyl palmitate concentrations declined to 23 and 21% of their respective control values. Vitamin A metabolism was studied in liver microsomes prepared from rats sacrificed 7 days after the 20-mg/kg injection. The rate of retinoic acid hydroxylation via the cytochrome P-450 system to 4-hydroxyretinoic acid plus the subsequent oxidation to 4-ketoretinoic acid was significantly elevated. Retinoic acid conjugation by UDP-glucuronyl transferase was also significantly increased. These changes corresponded with increased activities of cytochrome P-450-dependent aryl hydrocarbon hydroxylase and UDP-glucuronyltransferase conjugation of p-nitrophenol. These results provide a direct link between enzyme induction due to xenobiotics and specific steps in the vitamin A metabolic pathway.     

The use of meperidine hydrochloride for chemical restraint in certain cetaceans and pinnipeds

Meperidine HCl was administered intramuscularly by hand-syringe to a number of individuals representing several species of cetaceans (n = 95) and pinnipeds (n = 36). Dosage administered was 0.11 mg/kg, 0.23 mg/kg or 0.45 mg/kg, with the majority of animals receiving the middle dosage. Meperidine HCl provided moderate restraint in cetaceans without obvious deleterious effects. Restraint was achieved rapidly, with maximum effect occurring 20 min after intramuscular injection and lasting for 2 to 3 hr. Analgesia appeared to last as long as 4 hr and was sometimes accompanied by a restoration of appetite in animals suffering from physical discomfort. Higher doses produced increased sedation and analgesia without noticeably depressing respiration. Meperidine HCl provided moderate restraint for phocids and walrus (Odobenus rosmarus) without apparent detriment. California sea lions (Zalophus californianus) showed little restraint, but demonstrated profound respiratory depression.     

High dietary vitamin A interferes with tissue α-tocopherol concentrations in fattening pigs: a study that examines administration and withdrawal times

This study aimed to assess the interaction between different dietary vitamin A (dVitA) levels and the same concentration of vitamin E (100 IU all-rac-α-tocopheryl acetate/kg feed) in growing-finishing pigs. In the first experiment, two fat sources × two dVitA levels (0 v. 100 000 IU) were used. The supplementation of 100 000 IU dVitA induced a range of 5.13 to 30.03 μg retinol/g liver, 62.78 to 426.88 μg retinol palmitate/g liver, and 0.60 to 1.96 μg retinol/g fat. Dietary fat did not affect retinol or retinyl palmitate deposition in pigs. The high concentration of dVitA produced lower fat and liver α-tocopherol concentrations, and increased susceptibility of muscle tissue to oxidation. A second experiment was carried out to study the retinol and α-tocopherol retention at different withdrawal times prior to slaughter (two dVitA levels; 0 v. 100 000 IU). A high dose of 100 000 IU vitamin A during a short 2-week period was enough to induce α-tocopherol depletion in liver and fat to a similar extent as when 100 000 IU were administered during the whole fattening. Muscle, fat and liver α-tocopherol concentrations were not affected by dVitA in the 1300-13 000 IU/kg range, but liver α-tocopherol concentration was higher when vitamin A was removed from the vitamin mix 5 weeks prior to slaughter (experiment 3).     

MIF-1 fails to modify agonist-induced oral activity in neonatal 6-OHDA-treated rats

-Prolyl- -leucyl-glycinamide (MIF-1) is known to attenuate apomorphine-induced stereotypies in adult rats that are lesioned as neonates with 6-hydroxydopamine (6-OHDA). To test whether MIF-1 would affect dopamine (DA) agonist-induced and serotonin (5-HT) agonist-induced oral activity, both intact and neonatal 6-OHDA-treated rats were studied. Rats at 3 days from birth were injected with desipramine (20 mg/kg, IP), 1 h before 6-OHDA HBr (100 μg, salt form, in each lateral ventricle) or its vehicle, saline-ascorbic acid (0.1%). At approximately 6 months rats were treated with MIF-1 (0.1, 1.0, or 10.0 mg/kg, IP), 10 min before SKF 39393 HCl (1.0 mg/kg, IP) or m-chlorophenylpiperazine 2HCl (m-CPP 2HCl; 0.5 mg/kg, IP), DA D₁ and 5-HT_1C,2 receptor agonists, respectively. Although both agonists increased oral activity in control and neonatal 6-OHDA-treated rats, MIF-1 did not modify the response. In rats that received either of the three doses of MIF-1 for 21 consecutive days, there was still no observed effect of MIF-1 on the oral response of control and 6-OHDA-lesioned rats to SKF 38393 and m-CPP. These findings indicate that MIF-1 does not modify the oral activity response of supersensitized D₁ and 5-HT_1C receptors in adult rats that are lesioned neonatally with 6-OHDA.     

The use of epostane, a 3(beta)-hydroxysteroid dehydrogenase delta 4-5 isomerase enzyme inhibitor, in oil suspension as a mismating agent in the dog

Administration of epostane as a single subcutaneous injection in sesame oil prevented or terminated pregnancy in bred beagle bitches (P = 0.002). Doses of 15 and 20 mg/kg prevented or terminated pregnancy in all of 14 bred beagle bitches studied but demonstrated a high rate of serious abscess formation at the injection site. A dose of 10 mg/kg was partially effective in 3 of 12 subjects whelping live pups, and a dose of 2.5 mg/kg was completely ineffective in 12 of 12 subjects whelping live pups. Plasma progesterone levels were lowered in dose-related fashion with respect to both depth of depression (P < 0.01) and length of time (P < 0.05). Subjects in which pregnancy was maintained had significant differences (P < 0.01) in progesterone patterns compared with nonpregnant subjects, as measured by area under the curve. No clinically significant differences were seen between treated and control females with respect to return to estrus, subsequent fertility, or in a battery of serum electrolytes, blood parameters and serum enzymes.     

Induction of chromosome aberrations, micronucleus formation and sperm abnormalities in mouse following carbofuran exposure

Carbofuran was tested to study in vivo cytogenetic effects in mouse bone marrow cells and morphological alterations in sperms. The acute oral and intraperitoneal (i.p.) LD(50) of carbofuran was determined to be 9.5 or 2.0 mg/kg b.w. in mice, respectively. The animals were orally administered 1.9, 3.8 or 5.7 mg/kg b.w. (20, 40 and 60% of LD(50)) of carbofuran for 24 h or 1.9 mg/kg b.w. for 4 consecutive days (cumulative 7.6 mg/kg or 80% of LD(50)) to analyse chromosome aberrations (CAs). For micronucleus test (MT) animals were orally exposed to 5.7 mg/kg b.w. for 24 and 48 h or 1.9 mg/kg b.w. for 4 consecutive days. For reference mice were exposed to peanut oil (negative control) and cyclophosphamide (20 mg/kg) or ethyl methanesulfonate (EMS: 100 mg/kg) positive control for CAs and MT respectively. To analyse the effect on sperm morphology mice were exposed to single i.p. dose of 1 and 2 mg/kg b.w. of carbofuran and repeatedly to 0.5 mg/kg for 5 consecutive days. Cytogenetic analysis revealed that all the test doses induced mitotic inhibition, CAs, micronucleus (MN) formation and sperm abnormalities in a dose dependent manner. Present observations concurrent with earlier reports substantiate the genotoxic potential of carbofuran and possible risk to human beings.     

Prolonged and multiple immobilizations of the southern elephant seal using ketamine hydrochloride-xylazine hydrochloride or ketamine hydrochloride-diazepam combinations

Thirty seven southern elephant seals (Mirounga leonina) were singularly or repeatedly immobilized with combinations of ketamine hydrochloride (HCl) and xylazine HCl or ketamine HCl and diazepam. Atropine sulphate was included in the drug combinations. To permit experimental procedures the seals were immobilized for periods of 30-330 min. The mean induction dose of ketamine HCl was 8.71 +/- 0.25 mg/kg (mean +/- SE). The mean induction time was 16.02 +/- 2.62 min. For the elephant seals immobilized for periods in excess of 180 min, the mean dose of ketamine HCl used per hr was 3.31 +/- 0.13 mg/kg/hr and the mean dose of ketamine HCl used per hr postinduction was 1.31 +/- 0.15 mg/kg/hr. The mean dose of diazepam used was 0.09 +/- 0.01 mg/kg and the mean dose of xylazine HCl was 0.41 +/- 0.01 mg/kg. Elephant seals were weighed on 20 occasions (weight range: 897-1,932 kg) and the relationship between standard length and weight was found to be: Weight = 9.98 length - 2,317.63 (r2 = 0.724). Adverse reactions to seals immobilized only once or twice were not observed. Two seals immobilized on three occasions developed abscesses at the site of injection.     

人参总皂苷和远志总苷配伍对小鼠抗抑郁作用

目的确定人参总皂苷（GTS）和远志总苷（PTG）抗抑郁配伍剂量比例,形成参远苷（SGY）制剂,为研制开发抗抑郁新药提供实验数据。方法采用析因设计方法,GTS和PTG均选取25、50、100 mg/kg三个剂量,按照完全随机的两因素3×3实验设计,得到参远苷的9个不同配比组。C57BL/6J小鼠（用于悬尾实验）和ICR小鼠（用于强迫游泳实验）随机分为对照组、阳性药组（10 mg/kg,帕罗西汀用于悬尾实验;阿米替林用于强迫游泳实验）及参远苷的9个不同配比组,共11组。灌胃给药7 d,观察各组对悬尾或强迫游泳实验小鼠不动时间的影响,并通过空场实验观察参远苷各配比对小鼠自主活动的影响。参远苷与单味GTS、PTG的抗抑郁作用比较实验中,C57BL/6J小鼠（用于悬尾实验）和ICR小鼠（用于强迫游泳实验）随机分为对照组、阳性药组（10 mg/kg,帕罗西汀用于悬尾实验;阿米替林用于强迫游泳实验）、参远苷低中高剂量组（37.5、75、150 mg/kg）、GTS和PTG各四个剂量组（均为18.75、37.5、75、150 mg/kg）,共13组。灌胃给药7 d,观察各组对悬尾或强迫游泳实验小鼠不动时间的影响。结果析因设计结果表明,GTS和PTG之间无交互效应。参远苷配比组75 mg/kg（GTS∶PTG为50∶25）及150mg.kg-1（GTS∶PTG为100∶50）显著并稳定缩短悬尾或强迫游泳不动时间（P〈0.05）,得出GTS和PTG的剂量配伍比例为2：1。空场实验结果显示,参远苷各配比对小鼠运动总路程无影响。参远苷与单味GTS、PTG抗抑郁作用比较实验结果显示,GTS 75、150 mg/kg缩短悬尾实验小鼠不动时间（P〈0.01,P〈0.05）,对强迫游泳实验小鼠不动时间无影响。PTG 18.75、37.5 mg/kg缩短强迫游泳实验小鼠不动时间（P〈0.01,P〈0.05）,对悬尾实验小鼠不动时间无影响。参远苷75、150 mg/kg缩短悬尾实验小鼠不动时间（P〈0.05）。同时,参远苷37.5、75 mg/kg缩短强迫游泳实验小鼠不动时间（P〈0.01,P〈0.05）。结论 GTS和PTG以2：1的比例形成的参远苷（SYG）制剂,质量容易控制,作用机制多样,符合抑郁症复杂多样的发病机制,优于单味GTS和PTG,进一步研究之后,有可能成为新型的抗抑郁药物。     

Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice

The possible analgesic effect of melatonin was investigated in young male ICR mice. The formalin test which elicits typically 2 phases of pain response, the acute (first) phase and tonic (second) phase, was used. The test was performed in the late light period when the mice have been reported to be more sensitive to pain. Compared to control mice, no significant difference in nociceptive response was observed when melatonin was injected intraperitoneally at doses of 0.1, 5, and 20, mg/kg body weight. The combined effects of melatonin with diazepam and/or morphine, were also investigated. Melatonin, injected at 20 mg/kg 15 min before formalin test, significantly increased the antinociceptive response of diazepam (1 mg/kg) or morphine (5 mg/kg) in the second phase. In addition, when melatonin was given at 20 mg/kg together with diazepam and morphine, antinociceptive responses in both the first and second phase were increased. These data indicate the synergistic analgesia effect of melatonin with morphine and diazepam and suggest the possible involvement of melatonin as an adjunct medicine for pain patients.     

Responses of Corpuscles of Stannius to intra-peritoneal vitamin-D3 administration in teleost Labeo rohita (Hamilton, 1822) reared in water with two different levels of calcium concentration

This study assessed the responses of vitamin-D₃ intraperitoneally injected to Rohu, Labeo rohita @ of 0 IU/kg bw (only solvent), 100 IU/kg bw and 500 IU/kg bw reared in 20 and 40 ppm of calcium (Ca) enriched water. The cellular changes in Corpuscles of Stannius (CS) gland, serum Ca, and inorganic phosphate (P_i) level were analysed up to the 60th day. Rohu administered with 100 IU/kg bw D₃ and exposed to 40 ppm Ca-rich water exhibited notable hyperplasia of CS compared with their control groups. Notable changes with high serum Ca level (13.87 ± 0.3 mg/dl) was detected on the 5th day in fish exposed to 40 ppm Ca-rich water, while related values attained (13.74 ± 0.1 mg/dl) only after 7 days in 20 ppm Ca-rich water of 500 IU/kg bw vitamin D₃ injection. Similarly, high serum P_i level (7.66 ± 0.2 mg/dl) in 40 ppm Ca injected with D₃ at 500 IU/kg bw. The results demonstrated that the Ca homeostasis of Labeo rohita is influenced by intra-peritoneal vitamin D₃. Progressive studies should be conducted by increasing the dose of vitamin D₃ to investigate optimum dose/supplement in feed for commercially important aquaculture teleost Labeo rohita for maximum and sustainable absorption of Ca from the variable water Calcium levels to maintain Ca²⁺ homeostasis.     

Effect of beta-carotene administration on reproductive function of horse and pony mares

The objective of this study was to determine whether supplemental beta-carotene would influence reproductive function in mares maintained on spring and summer pastures and to characterize plasma carotene concentrations during the estrous cycle. Carotene concentrations in plasma did not vary with day of estrous cycle (P = 0.7455). Mares receiving every other day injections of beta-carotene (400 mg; n = 4) or saline (10 ml; n = 4) during proestrus/estrus did not differ in plasma estradiol (E(2)) concentrations (P = 0.6313), follicle development (P = 0.8068), or plasma progesterone (P(4)) concentrations during the following diestrus (P = 0.4954). Moreover, no differences in plasma P(4) concentrations (P = 0.9047) were detected between mares receiving every other day injections of beta-carotene (400 mg; n = 4) or saline (10 ml; n = 4) during diestrus. However, administration of beta-carotene raised plasma carotene concentrations relative to controls when injected during proestrus/estrus (P = 0.0096) and diestrus (P = 0.0099). Pregnancy rates (P = 0.4900) and number of cycles required for pregnancy (P = 0.2880) were similar for mares administered injections of saline (10 ml; n = 37), beta-carotene (400 mg; n = 37), vitamin A (160,000 IU; n = 38), or vitamin A + beta-carotene (160,000 IU + 400 mg; n = 43), on the first or second day of estrus and on the day of breeding. Therefore, these results collectively suggest that supplemental beta-carotene does not affect the reproductive function of mares fed adequate dietary carotene. Whether supplemental beta-carotene would enhance reproductive function in mares on low carotene diets warrants further investigation.     

Developmental toxicity evaluation of Bendectin in CD rats

Bendectin, composed of doxylamine succinate and pyridoxine HCl (1:1), is an antinauseant previously prescribed for nausea and vomiting during pregnancy. The present study examined the maternal and developmental effects of Bendectin (0, 200, 500, or 800 mg/kg/day, po) administered to timed-pregnant CD rats (36-41/group) during organogenesis (gestational days [gd] 6-15). At death (gd 20), all live fetuses were examined for external, visceral, and skeletal abnormalities. At 500 and 800 mg/kg/day, maternal toxicity included reduced food consumption during treatment and for the gestation period, increased water consumption in the posttreatment period, reduced weight gain during treatment, and sedation; water consumption was reduced during treatment and for the gestation period, and maternal mortality (17.1%) was observed only at the high dose. Developmental toxicity included reduced prenatal viability (800 mg/kg/day) and reduced fetal body weight/litter (500 and 800 mg/kg/day). In addition, reduced ossification of metacarpals (800 mg/kg/day), phalanges of the forelimbs (500 and 800 mg/kg/day), and of caudal vertebral centra (all doses) was observed. No increase in percent malformed live fetuses/litter was observed. The proportion of litters with one or more malformed fetuses was higher than vehicle controls only at 800 mg/kg/day, with short 13th rib (to which the test species is predisposed) as the predominant observation. By contrast, a positive control agent (nitrofen, 50 mg/kg/day, po, 14 dams) produced 85% malformed fetuses/litter with the predominant malformation being diaphragmatic hernia. In conclusion, the incidence of litters with one or more malformed fetuses was increased only at a dose of Bendectin which produced maternal mortality (17.1%) and other indices of maternal and developmental toxicity (see Discussion).     

D1, but not D2, dopamine receptor regulates steroid levels during the final stages of pikeperch gametogenesis

In pikeperch, Sander lucioperca, aquaculture hormonal treatment is usually applied to synchronize ovulation. However, the effect of dopamine (DA) receptor antagonists, in particular those blocking the D1 DA receptors, remains unknown. Thus, the aim of the present study was to investigate and compare the effects of D1 and D2 DA receptor antagonists on the sex-steroid production and reproductive performance of the species. Two experiments were performed during which mature pikeperch females were injected with different molecules: NaCl 0.9% (negative control) or human chorionic gonadotropin 500 IU/kg (positive control) in both experiments, metoclopramide (a D2 receptor antagonist; 4 mg/kg or 20 mg/kg) or SCH23390 (a D1 receptor antagonist; 0.8 mg/kg or 4 mg/kg) alone (experiment 1) or in combination with a salmon gonadotropin-releasing hormone analogue (sGnRHa at 25 µg/kg; experiment 2). In experiment 2, fish were also injected with sGnRHa (25 µg/kg) as positive control. Samplings of oocytes and blood were performed on the day of injection and after 24 h (both experiments), after 48 h (experiment 2) and at the time of ovulation (both experiments). In non-ovulating fish, samplings were performed 7 days (experiment 1) or 14 days (experiment 2) after injection. In experiment 2, various zootechnical parameters of fertilized eggs were recorded (survival, hatching and malformation rates). The two antagonists alone were ineffective in inducing the final stages and regulating sex-steroid (testosterone, 11 ketotestosterone, 17β estradiol and 17,20β-dihydroxy-4-pregnen-3-one) production. When administered with sGnRHa, both SCH23390 and metoclopramide induced the final stages. However, only SCH23390 stimulated testosterone (4 mg/kg) and 17β estradiol (0.8 mg/kg) production compared with sGnRHa alone. None of the treatments affected the survival, hatching or malformation rates. This is the first report suggesting that in pikeperch the D1, but not the D2, DA receptor antagonist would be involved in the testosterone and 17β estradiol production as a potentiator of the sGnRHa effect.     

Suspected secondary thiafentanil intoxication in a captive mountain lion (Puma concolor)

Inadvertent ingestion of thiafentanil oxalate by a captive adult female mountain lion (Puma concolor) caused a prolonged clinical syndrome that included sedation and depression, muscle tension, and myopathy that was incompletely antagonized by naltrexone HCl. A serum chemistry profile revealed markedly elevated creatinine phosphokinase (CK; 490,450 IU/l), alanine aminotransferase (ALT; 1,896 IU/l), and aspartate aminotransferase (AST; 4,321 IU/l) 2 days after onset. The affected animal's condition gradually improved over the next 15 days in response to supportive therapy that included diazepam (5 mg as needed), Normasol R (3 l/day), dexamethasone (tapering dose starting at 1 mg/kg), and ketoprofen (1 mg/kg). She eventually recovered completely. Based on these observations, carcasses of animals immobilized with thiafentanil should be marked and disposed of properly to preclude opportunities for secondary exposure and potential intoxication in scavenging species. In addition, caution is advised when using thiafentanil in animals that could be preyed upon before full metabolism of the drug.     

Effect of exposure of pregnant rats to cadmium on prenatal and postnatal development of the young

Cadmium chloride in doses of 2, 12 and 40 mg Cd/kg was administered per os to pregnant rats from the 7th to 16th day of pregnancy. In another experiment female rats were exposed to cadmium oxide at a concentration of 0.02 mg Cd/m3 or 0.16 mg Cd/m3 for 5 hours a day and 5 days weekly for a period of 5 months or 1 mg Cd/m3 for 4 months. The exposure was then continued during mating and from the 1st to 20th day of pregnancy. A decrease in fertility was only observed in females exposed by inhalation to cadmium oxide at a concentration of 1 mg Cd/m3, at which concentration cadmium exhibits a considerable toxic effect on the whole organism. The young of females orally treated with CdCl2 in a dose of 40 mg Cd/kg displayed congenital defects in the form of sirenomelia or amelia, as well as raised cadmium levels in tissues. A retardation of intrauterine development manifested by lower body weight and slowed down osteogenesis was observed in the other groups. A cadmium concentration increase was not found in the tissues of the young in these groups. Inhalation exposure to 0.16 mg Cd/m3 of females prior to and during pregnancy induced in their young a decrease in viability, lower body weight gain, prolongation of latency in the negative-geotaxis test, lower locomotor activity and deteriorated development of the conditioned-reflex response. The offspring of females exposed to 0.02 mg Cd/m3 displayed lowered locomotor activity and worsened consolidation of the conditioned-reflex response.     

Inhibition By Vitamin A of Cyst Formation In Nyctotheroides Puytoraci Induced By Injecting Its Host Bufo Regularis With 20-Methylcholanthrene

SYNOPSIS. 20-Methylcholanthrene induced cyst formation in Nyctotheroides puytoraci when injected into its host Bufo regularis. Presumably this hydrocarbon or its metabolites reaches the parasites in the recta of treated host animals and induces encystment. However, injection of B. regularis with 0.5 mg of 20-methylcholanthrene + vitamin A palmitate (5,000 IU) inhibited the hydrocarbon-induced encystment of the parasites.     

"Paradoxical" analgesia and aggravated morphine dependence induced by opioid antagonists

Chronic treatment with naloxone (Nx) or naltrexone (Ntx) induces paradoxical analgesia. In the present study, the effects of chronic treatment with opioid receptor antagonists, such as nor-binaltorphimine (nor-BNI) for kappa and naltrindole (NTI) for delta receptors, on analgesic response using the hot plate test and on morphine physical dependence in rats were examined. The hot plate latency was significantly increased by pretreatment with Nx (5 mg/kg, s.c.), nor-BNI (20 mg/kg, i.p.) or NTI (20 mg/kg, i.p.) for 5 days. After chronic pretreatment with these antagonists, the rats were treated with morphine-admixed food (0.5 mg/g of food) for 3 days. Chronic pretreatment with Nx and NTI significantly increased Nx precipitated body weight loss in morphine dependent rats, while chronic pretreatment with nor-BNI produced small increase. These results indicate that chronic treatment with nor-BNI or NTI as well as with Nx induces obviously paradoxical analgesia, and that chronic blockade of mu or delta may enhance the development of physical dependence on morphine.     

Inhibition by vitamin A of cyst formation in Nyctotheroides puytoraci induced by injecting its host Bufo regularis with 20-methylcholanthrene

20-Methylcholanthrene induced cyst formation in Nyctotheroides puytoraci when injected into its host Bufo regularis. Presumably this hydrocarbon or its metabolites reaches the parasites in the recta of treated host animals and induces encystment. However, injection B. regularis with 0.5 mg of 20-methylcholanthrene + vitamin A palmitate (5,000 IU) inhibited the hydrocarbon-induced encystment of the parasites.