The effect of long-term administration of low oral doses of chlormadinone acetate on heat cycles and ovarian functions in beef heifers

Chlormadinone acetate (CAP) was given orally for 42 days to four groups of 15 regularly cycling Hereford heifers in Central Mexico (19°N, altitude 2200 m). The CAP doses (0.625; 1.25 and 2.5 mg/day per animal) represent 1/16th, 1/8th and 1/4th, respectively, of the cycle synchronizing dose of 10 mg. Heat was observed for 1 hour at 06.00, 12.00 and 18.00 h and animals in heat were rectally palpated at 6 h intervals until ovulation had occurred. Observations continued for the duration of the treatment period and 26 days thereafter. CAP treatment had significant effects. With 2.5 mg, occurrence of the next heat was delayed in 8 and inhibited in 6 animals; nine animals had synchronized heat after CAP withdrawal; five animals did not ovulate but developed luteinized follicles; animals not cycling had prolonged periods of vulvar swelling. With 1.25 mg CAP, most animals continued cycling, but estrous intervals were prolonged and 3 animals developed luteinized follicles. With 0.625 mg CAP, only a slight prolongation in estrous intervals and of the heat periods was observed.Individual differences in response to CAP were marked in all treatment groups. CAP at the higher doses interfered with mechanisms of ovulation and was partially effective in preventing heat and follicular development.In cycling animals the length of the cycle, the duration of heat and the daily variations of the onset of heat were within reported limits. The interval between disappearance of heat symptoms and ovulations (21.23 h) was about twice that reported in the literature. Ovulations followed a daily rhythm with a major peak between 24.00 and 0.600 h and a minor elevation between 12.00 and 18.00 h.     

Comparative studies on the superovulatory effect of PMSG and FSH in water buffalo (Bubalus bubalis )

A total of thirty-eight lactating water buffalo cows were treated in four experiments simultaneously either with FSH (first group) or PMSG(second group). To the first group (half of the animals), a total dose of 40 mg FSH-P at 12-hr intervals was given i.m. within a 4-day period. The second group was treated i.m. with 3000 IU PMSG (Gestyl). Forty-eight hours after initiation of the superovulatory treatment all buffaloes were given 500 ug Cloprostenol. Fi seen buffaloes from the FSH-treated group (78.9%) and 17 from the second group (89.5%) came into heat at average PGF 2 alpha/standing heat intervals of 42.8+/-1.48 and 44.8+/-2.31, respectively. Superovulatory treatment resulted in meath number of 4.3+/-0.87 and 1.9+/-0.50 CL and 0.5+/-0.24 and 2.2+/-0.82 follicles for the first and second group. Twenty-five eggs were recovered after non-surgical flushing from 8 of 13 flushes in the first group and all except one were fertilized and classified as good embryos. Twelve eggs were recovered from 4 of 11 flushes in the second group and 11 of the eggs were fertilized and 10 of them classified as good ones.     

Acute Toxicity of Ochratoxins A and B in Chicks

Ochratoxins A and B were given to 1-day-old Babcock B-300 cockerels to evaluate acute toxic effects. Two trials with ochratoxin A gave 7-day oral median lethal dose estimates of 116 mug (3.3 mg/kg) and 135 mug (3.9 mg/kg) per chick. Chicks given daily oral doses of 100 mug of ochratoxin A died on the second day. Single subcutaneous doses of 400 mug of ochratoxin A were also lethal. The 7-day oral median lethal dose of B was estimated at 1,890 mug (54 mg/kg) per chick. Chicks given oral doses of 100 mug of ochratoxin B daily for 10 days survived. Sublethal doses of both ochratoxins A and B resulted in growth suppression which was proportional to the amount of ochratoxin given. Visceral gout was the principal gross finding. Microscopic examinations revealed acute nephrosis, hepatic degeneration or focal necrosis, and enteritis. Suppression of hematopoiesis in the bone marrow and depletion of lymphoid elements from the spleen and bursa of Fabricius were frequently seen. Both ochratoxins appeared to have similar pathological effects. This is the first report on the toxicity of ochratoxin B.     

Ovarian follicular response to different hormonal stimulation treatments in Canindé goats

The objective of the present study was to evaluate the effect of different hormonal stimulation treatments on the antral follicular population of naturalized Canindé goats. Adult goats (n=17) having estrous cycles at regular intervals were treated with intra-vaginal sponges containing 60 mg medroxyprogesterone acetate for 11 days, combined with an application of 50 μg d-cloprostenol on the Day 8 of treatment. For ovarian stimulation, goats were distributed into the following experimental groups: (a) multiple doses (MD), with a total of 120 mg NIH-FSH P1 in five intramuscular injections (30/30; 20/20 and 20 mg) at 12-h intervals; (b) three doses (TD), with a total of 120 mg NIH-FSH P1 in three intramuscular injections (60; 40 and 20 mg) at 24 h intervals; (c) one dose (OD), which consisted of the use of 70 mg NIH-FSH P1 combined with 200 IU eCG administered intramuscularly 36 h before sponge removal. In the MD and TD groups, FSH injections were begun on the Day 8 of progestagen treatment. The ovaries of all animals were observed by transrectal real time ultrasonography (TRU) during the follicular stimulation protocols. All follicles ≥2 mm were counted, measured and classified according to greatest diameter. The ultrasonographic assessment of the ovaries provided for well-defined ovarian structures. At the time of insertion of the sponges (Day 0), significant differences were observed (P<0.05) for the mean number of large follicles between the treated groups. Meanwhile, on Day 11, the three treatments did not differ (P<0.05), regardless of the follicular category. The diameter of small follicles was similar in MD, TD and OD during the whole period of the study. In the TD group, diameter of the large follicles was less (P<0.05) on Day 10 when compared to MD and OD. However, these differences were not observed on Day 11. In conclusion, the three treatments produced comparable distribution of the follicular populations. However, the single dose treatment can be preferred because of its simplicity and efficacious follicular response.     

Nicotine is not clastogenic at doses of 1 or 2 mg/kg body weight given orally to male mice

Nicotne has been tested in the conventional mouse bone marrow assay. Single doses of 1 mg/kg bw or 2 mg/kg bw were given by oral intubations and bone marrow was sampled at 24 h (1 mg/kg) or at 6, 12 and 18 h after treatment (2 mg/kg). Nicotine treatment did not increase the micronucleus frequencies in polychromatic erythrocytes while the positive control compound mitomycin C yielded the expected result. These data contradict the only published in vivo study of nicotine in which 1.1 mg/kg bw was called positive for the induction of chromosomal aberrations in mouse bone marrow cells at all sampling intervals, even as early as 6 h after treatment. It is discussed that aberration scoring is a matter of subjectivity and depends on strict discrimination criteria between gaps and true DNA discontinuities, i.e. breaks. International collaboration has shown that micronucleus scoring is less subjective, hence more reliable. Therefore it is concluded that nocotine is not clastogenic at the doses and time intervals tested in the present experiments.     

Nicotine is not clastogenic at doses of 1 or 2 mg/kg body weight given orally to male mice

Nicotine has been tested in the conventional mouse bone marrow assay. Single doses of 1mg/kg bw or 2mg/kg bw were given by oral intubations and bone marrow was sampled at 24h (1mg/kg) or at 6, 12 and 18 h after treatment (2mg/kg). Nicotine treatment did not increase the micronucleus frequencies in polychromatic erythrocytes while the positive control compound mitomycin C yielded the expected result. These data contradict the only published in vivo study of nicotine in which 1.1mg/kg bw was called positive for the induction of chromosomal aberrations in mouse bone marrow cells at all sampling intervals, even as early as 6h after treatment. It is discussed that aberration scoring is a matter of subjectivity and depends on strict discrimination criteria between gaps and true DNA discontinuities, i.e. breaks. International collaboration has shown that micronucleus scoring is less subjective, hence more reliable. Therefore it is concluded that nicotine is not clastogenic at the doses and time intervals tested in the present experiments.     

Effects of follicle-stimulating hormone with and without luteinizing hormone on serum hormone concentrations, follicle growth, and intrafollicular estradiol and aromatase activity in gonadotropin-releasing hormone-immunized heifers

To evaluate the roles of FSH and LH in follicular growth, GnRH-immunized anestrous heifers (n = 17) were randomly assigned (Day 0) to one of three groups (n = 5 or 6). Group 1 received i.m. injections of 1.5 mg porcine FSH (pFSH) 4 times/day for 2 days; group 2 received i.v. injections of 150 microg pLH 6 times/day for 6 days; group 3 received both pFSH and pLH as described for groups 1 and 2. After slaughter on Day 6, measurements were made of follicle number and size, and follicular fluid concentrations of progesterone (P(4)), estradiol (E(2)), and aromatase activity. Injection of pFSH increased (P: < 0.01) the serum concentrations of FSH between 12 and 54 h. Infusion of pLH increased (P: < 0.05) mean and basal concentrations of LH and LH pulse frequency. Serum E(2) concentrations were higher (P: < 0.05) for heifers given pFSH + pLH than those given either pFSH or pLH alone. There was no difference (P: > or = 0.24) between treatments in the number of small follicles (<5 mm). Heifers given pFSH or pFSH + pLH had more (P: < or = 0.02) medium follicles (5.0-9.5 mm) than those that were given pLH alone (none present). Heifers given pFSH + pLH had more (P: = 0.04) large follicles (> or =10 mm) than those given either pLH or pFSH alone (none present). Overall, only 1 of 35 small follicles and 2 of 96 medium follicles were E(2)-active (i.e., E(2):P(4) >1.0), whereas 18 of 21 large follicles (all in the pFSH + pLH treatment) were E(2)-active; of these, 8 of 18 had aromatase activity. Concentrations of E(2) and E(2) activity in follicular fluid were correlated (r > or = 0.57; P: < 0.0001) with aromatase activity in heifers given pLH + pFSH. In conclusion, pLH failed to stimulate follicle growth greater than 5 mm; pFSH stimulated growth of medium follicles that were E(2)-inactive at slaughter and failed to increase serum E(2) concentrations; whereas pFSH + pLH stimulated growth of medium follicles and E(2)-active large follicles, and a 10- to 14-fold increase in serum E(2) concentrations.     

Clinical and cell kinetic data on the combination of cytosine arabinoside with daunorubicin, isosfamide, thioguanine, and vincristine for remission induction and maintenance in patients with acute myelocytic leukaemia (author's transl)]

31 adult patients (study A) with acute myelocytic leukaemia were treated for remission induction with cytosine arabinoside (ARA-C, 100 mg/m2/day) by a 7 (5) day continuous infusion. 3 (2) doses of daunorubicin (DNR, 45 mg/m2 i.v.) were added at daily intervals. For maintenance 5 day ARA-C was given monthly in sequential combination with DNR, thioguanine (TG), or ifosfamide (IFOS). 16 (52%) patients achieved complete remission (C.R.) after 1.8 (1-3) courses and 6.7 (3-10) weeks from treatment start. The median survival for responders and non-responders was 11.5 months, early death rate within 6 weeks was 3 (10%). Median remission duration was 13.5 months. Among 11 patients surving for 7-22 months 7 patients are in first remission for 5.5-20.5 months. DNR, IFOS and TG were given before the 3rd day of ARA-C infusion. In a previous group of 34 leukaemic patients and in 44 therapy courses DNA histograms of bone marrow cells using pulse cytophotometry showed marked accumulation in S-phase for 75% of courses. Also (G2 + M)-cells in the DNA distribution and thymidine pulse labelling indices were markedly increased in most cases, whereas thymidine uptake by scintillation counter was diminished and mitotic indices had not changed significantly. In now 15 patients (study B) the induction regimen was intensified by adding vincristine (VCR, 2 mg i.v.) and 3 doses of IFOS (600 mg/m2 i.v.). Preliminary results are 50% C.R. after 1,7 (1-2) courses and 6.8 (5-10) weeks from initiation of therapy. 2 patients died in the first 6 weeks.     

Translocation yield from the mouse spermatogonial stem cell following fractionated X-ray treatments: influence of unequal fraction size and of increasing fractionation interval

(1) The genetic response of the mouse spermatogonial stem cell to a high dose of X-rays given in two unequal fractions 24 h apart can be dependent upon the order in which the two fractions are given. When 1000 R was administered as 100 R followed by 900 R the recovered translocation yield (22%) was similar to that which can be obtained by extrapolation from lower doses and also to that of a 500 + 500 R 24 h fractionation. By contrast, when the 900 R preceded the 100 R the response was much lower (7.4%), yet still greater than that produced by a single 1000 R treatment (4.5%). The same order of effectiveness was observed for length of sterile period. (2) The sub-additive translocation yields previously obtained with 800 R treatments given in fractions of 500 R and 300 R at intervals of 3-12 days were found to be maintained with intervals up to at least 15 days but additivity was regained by the end of the third week. Sterile period data indicated that with these intervals the germinal epithelium had recovered sufficiently from the first fraction for spermatogenesis to restart before the second fraction was given. (3) It is concluded from the two experiments that (a) 24 h after a radiation exposure the surviving stem cells are more sensitive than formerly both to killing and genetic damage, (b) at this time they are no longer heterogeneous in their radiosensitivities, so that increasing yields of genetic damage may be obtained with increasing dose i.e. there is no fall in yield at higher doses, (c) the change in sensitivity could be a consequence of a synchronization to a sensitive stage in a cell cycle, or to a transitional phase preparatory to entering a different cell cycle. (d) to achieve rapid repopulation of the germinal epithelium the surviving stem cells are stimulated to enter a shorter cell cycle and this is the cause of the sub-additive translocation yields with fractionation intervals of 3-15 days, (e) the recommencement of spermatogenesis is associated with the reestablishment of the heterogeneity in radiosensitivity among the stem cells. At this time additive translocation yields can again be recovered.     

Age-related decline of lymphoid-tissue components in the oral mucosa of the lip,cheek and soft palate of Macaca fascicularis

Summary In three mature monkeys (Macaca fascicularis; 3.5±0.3 kg in weight), the labial, buccal and soft-palate mucosae were examined morphologically and stereologically. Using fixation by perfusion, standardized methods of tissue preparation and morphometric analysis at the light-microscopic level, the gross dimensions (i.e., epithelial thickness, width of combined lamina propria/submucosa) and the volumetric composition of the oral mucosae were estimated and compared with those of young animals examined previously. The data show (1) an age-related decline in the volume and prevalence of organized lymphoid tissue (i.e., lymphoid follicles associated with secretory ducts), (2) a stable plasma-cell density in the interglandular connective tissue, and (3) an increase of glandular tissue in mature versus young animals. It is suggested that the lymphoid follicles associated with secretory ducts, providing for plasma-cell generation, mirror the tonsillar lymphoid tissue declining after puberty.     

Effects of repeated anaesthesia with ketamine/medetomidine and of pre-anaesthetic administration of buprenorphine in rats

Two groups of rats were anaesthetized at weekly intervals for 6 weeks with either ketamine/medetomidine alone (60 mg/0.4 mg/kg i.p.) or ketamine/medetomidine (45 mg/0.3 mg/kg i.p.) one hour following buprenorphine (0.05 mg/kg s.c.). Animals that received buprenorphine had longer periods of surgical anaesthesia (P = 0.04) and a greater depression of both mean pedal withdrawal score (P < 0.01) and mean respiratory rate (P = 0.014). Mean total duration of anaesthesia was also greater in the buprenorphine group on day 1. Sleep times reduced with successive doses of anaesthetic in the buprenorphine group (P = 0.024). Two animals in the buprenorphine group died. Repeated anaesthesia with ketamine/medetomidine alone was not associated with anaesthetic mortality. These results indicate that although buprenorphine has a clear anaesthetic-sparing effect, its use with ketamine/medetomidine may be associated with an increased risk of anaesthetic-related mortality.     

On the mutagenicity of methadone hydrochloride. Induced dominant lethal mutation and spermatocyte chromosomal aberrations in treated males

The mutagenicity of methadone hydrochloride was tested in male mice using the dominant lethal mutation technique and the spermatocyte test of treated mice. Male mice of C3H inbred strain received one of the following doses, 1, 2, 4 or 6 mg/kg body weight once a day for 3 consecutive days. Another group of mice served as control and received saline instead. Treated males were then mated to virgin females at 3-day intervals for a period of 45 days. Pregnant females were dissected at mid-term and the corpora lutea and intrauterine contents were recorded. The spermatocytes of treated males were examined 45-50 d after treatments with methadone and abnormal pairing configurations were scored. The methadone treatment was found to increase the rate of preimplantation deaths consistently in all post-meiotic stages with all doses used. In addition, the higher doses, 4 and 6 mg, affected spermatogonia stages. Quantitatively, the dose-response relationship cannot be demonstrated though the spectrum of effect increased with higher doses as more spermatogenesis stages became more sensitive to the treatment. In many cases the frequency of live implants showed a positive correlation with preimplantation deaths in contrast with the frequency of early deaths which showed only sporadic variation. The mutation indices based on total embryonic death indicate that methadone hydrochloride affected several stages of germ-cell maturation namely, spermatozoa (M.I. 14-35), late spermatids (M.I. 15-48), early spermatids (M.I. 14-50), late spermatocytes (M.I. 15-43) and spermatogonial stages (M.I. 12-63). Chromosome analysis at diakinesis-metaphase 1 revealed significant increase in the frequency of sex chromosome and autosome univalents with different doses of methadone. The smallest dose applied was quite effective and the data represent direct dose-response relationship. Of the multivalent configuration, the most frequent type was chain quadrivalents. The frequencies of total translocations per cell were estimated as 0.1, 0.16 and 0.2 for the 4 applied doses illustrating a dose-response relationship for the doses: 1, 2 and 4 mg, whereas with the higher dose, 6 mg, an abrupt decrease was apparent (0.05). This study calls for concern regarding the possible genetic hazards this drug may impose upon human populations.     

Neural mechanisms in cardiac arrhythmias associated with epileptogenic activity: the effect of phenobarbital in the cat

Sudden unexplained death accounts for 5-17% of mortality in epileptic persons; autonomic dysfunction is thought to be a contributing factor. This paper describes the effect of phenobarbital (PB) pretreatment (20 mg/kg, i.v.) one hour prior to pentylenetetrazol (PTZ) 10, 20, 50, 100, 200, and 2000 mg/kg, i.v. given at ten minute intervals on autonomic parameters in the cat. PB depressed heart rate, blood pressure, and postganglionic cardiac sympathetic neural discharge, but did not significantly alter vagal discharge. PB shifted the peak duration of interictal activity from a lower to a higher dose of PTZ without affecting the average duration across doses. PB also significantly diminished the increases in heart rate and blood pressure induced by PTZ but altered neither the occurrence of arrhythmias nor the changes in cardiac autonomic neural discharge. Thus, PB appears to prevent only some forms of autonomic dysfunction associated with epileptogenic activity in this model.     

A method for maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women.

The effectiveness of combining the subcutaneous administration of short- and intermediate-acting insulin with the intravenous infusion of glucose in maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women was tested. Fifty women were given intermediate-acting insulin twice daily in doses that were fractions of their usual dose, based on the projected duration of labour. In addition, they were given regular (i.e., short-acting) insulin every 6 hours, the dose being 1% of their total daily insulin dose for every increase of 10 mg/dl above 100 mg/dl (5.6 mmol/l) in the plasma glucose level 1 hour previously; the levels were measured every 3 hours. All the patients were fasting and received a basal intravenous infusion of 6 g/h of glucose; the rate of infusion was increased by 1 g/h for every decrease of 10 mg/dl in the plasma glucose level below 100 mg/dl. The mean plasma glucose levels (+/- standard deviation) were 90 +/- 46 mg/dl after 3 hours of labour, 92 +/- 35 mg/dl after 6 hours, 97 +/- 49 mg/dl after 9 hours and 107 +/- 65 mg/dl after 12 hours. With only one exception, in a premature infant, the 5-minute Apgar scores were identical to those of the infants of nondiabetic women.     

Effect of intravenously-administered putative and potential antagonists of ethanol on sleep time in ethanol-narcotized mice

Groups of male CD-1 mice (n = 12/group) were injected intraperitoneally (IP) with 5 g ethanol/kg of body weight. After loss of righting reflex, they were given vehicle or one of 2-3 doses of reputed or potential antagonists of ethanol intravenously (IV). Sleep time was measured from loss to return of righting reflex. Mean sleep time (MST) was increased significantly (P less than 0.05) by a large dose of dl-amphetamine (24 mg/kg) and by 4-aminopyridine (1, 5 mg/kg). Significant (P less than 0.01) increases were also produced by small and large doses of aminophylline (25, 100 mg/kg) and by yohimbine (1, 5 mg/kg). MST was not altered significantly by small and medium doses of dl-amphetamine (6, 12 mg/kg), a medium dose of aminophylline (50 mg/kg), or by any doses of naloxone, thyrotropin-releasing hormone, propranolol, physostigmine, doxapram, or Ro 15-4513. When Ro 15-4513 was given IP 15 minutes before ethanol (n = 6/group), onset and duration of narcosis were not altered. None of the compounds tested was an effective IV antidote for deep ethanol narcosis because of drug side effects, toxicity, prolongation of MST, or insufficient shortening of MST.     

Follicular dynamics, repeatability and predictability of follicular recruitment in cows undergoing repeated follicular puncture

The aim of our study was to characterize follicular recruitment and growth in response to the repeated removal of follicles. All tertiary follicles (> 2 mm of diameter) in the ovaries of 10 non-lactating Holstein Friesian cows were punctured at midcycle (Day 0) by means of an ultrasound-guided needle. Puncture sessions were scheduled twice weekly at 3- or 4-d intervals over 3 mo. In the middle of the experiment, i.e., Week 7, the effects of 2- and 5-d intervals between follicular punctures were tested and compared with the previous 3- and 4-d intervals. After this period, 6 animals were slaughtered to study the effect of puncturing on gross ovarian morphology. The protocol of puncturing follicles with 3- to 4-d intervals was continued for an additional 3 mo in the remaining 4 animals. Twice-weekly puncturing of all tertiary follicles abolished estrous cycles and lead to an increase in follicular wave frequency without apparent negative effects on either the reproductive tract or ovaries. After puncture the new follicular wave attained full numerical development within 3 d. Two-day intervals resulted in a lower number of follicles than the 3-d interval (11.0 -/+ 3.8 vs 15.4 -/+ 6.1; P < 0.05). In contrast 4- and 5-d intervals between puncture resulted in an increase in follicle size when compared with that of the 3-d interval. The mean+SD number of recruited follicles varied between animals ranging between 78 +/- 2.5 to 19.2 -/+ 6.0. The mean number of follicles recruited increased from the first month (March) to the third month (May) of sampling (11.8 +/- 4.7 vs 16.4 +/- 6.5; P < 0.01), and then decreased between the third (May) and the sixth (August) month of sampling (21.5 +/- 4.7 vs 16.8 +/- 5.0; P < 0.01). During the experiment, the number of recruited follicles varied cyclically, with waves having a length of 6 puncture session (PS) or 3 wk (i.e., the mean length the bovine estrous cycle). Follicular recruitment after repeated ovum pick-up showed a high repeatability (r = 0.576) A model was also developed showing good predictability of the potential of animals to recruit follicles on the basis of the first 4 to 6 PS. Our results showed that despite large variation in follicular recruitment between animals, the high repeatability and good predictability of follicle recruitment demonstrates the possibility of characterizing animals on their potential for follicle growth.     

Reversible inhibitory effect of the non-steroidal antiandrogen flutamide (SCH 13521) on spermatogenesis in mice

The effects of a prolonged subcutaneous administration of SCH 13521 dissolved in 0.3% hydroxypropyl cellulose (2-8 weeks in daily doses of 0.2 or 1.0 mg amounting to an estimated equivalent of experimental and curative doses used by others in laboratory animals and men) were studied in males of the mouse inbred strain C57BL/6. Following the treatment, the activity of spermatogenesis (expressed as the mean number of seminiferous tubules containing mature sperm and epididymal sperm count) was inhibited while the testis weight was not reduced, obviously due to an absolute increase of the interstitial tissue which was a marked histological feature of the testes, particularly following the higher doses of SCH 13521. Lower doses and shorter-lasting administration of the compound seem to inhibit the activity more effectively because after a prolonged administration reparatory processes tend to be triggered via a stimulatory effect on the synthesis of testosterone in Leydig cells. The solvent alone, hydroxypropyl cellulose, had some inhibitory effect on spermatogenesis. The lymphoid system remained both morphologically and functionally unaffected by SCH 13521 unlike the steroidal antiandrogen cyproterone actetate.     

Ultrasonographic determination of ovarian follicular. Development in superovulated heifers pretreated with FSH-P at the beginning of the estrous cycle

On Day 3 of the estrous cycle (estrus = Day 0), dairy heifers were given either 10 mg i.m. FSH-P (FSH-P primed; n = 9) or a saline vehicle (saline primed; n = 9). On Day 10, all heifers were superovulated with FSH-P (total = 27.7 mg i.m.) in declining doses over 5 d. Heifers were inseminated artificially at estrus. From Day 2 until estrus, the number and size of follicles >2 mm were monitored daily by ultrasonography. The mean (+/- SEM) number of corpora lutea (CL) (6.2 +/- 1.5 vs 10.7 +/- 0.9; P<0.05) and the mean number of recovered embryos and unfertilized ova (3.6 +/- 1.7 vs 8.4 +/- 2.2; P<0.05) were lower in FSH-P-primed than in saline-primed heifers. Prior to initiation of superovulation, follicles >10 mm appeared on Days 6 to 7 in saline-primed heifers but only on Days 8 to 10 in FSH-P-primed heifers (P<0.05). Also, until Day 10, the mean number of follicles 4 to 6 mm and 7 to 10 mm was higher (P<0.05) in FSH-P-primed than in saline-primed heifers. After initiation of the superovulatory treatment (Day 10 to estrus), saline-primed heifers had a greater and faster increase in the mean number of follicles >10 mm (P<0.02) than FSH-P-primed heifers did. Depletion in the number of follicles 2 to 3 mm (P<0.001) between Day 10 and estrus and in the number of follicles 4 to 6 mm (P<0.05) between Day 12 and estrus occurred in both groups of heifers. Decreased superovulatory response and embryo recovery in FSH-P-primed heifers may have been due to the presence of large follicles (>10 mm) prior to the initiation of the superovulatory treatment which reduced the ability of small follicles to grow into larger size classes during superovulatory treatment.     

Effects of a new injectable short-term release deslorelin in foal-heat mares

Mares treated with subcutaneous deslorelin implants on the first postpartum estrus early in the breeding season had significant reductions in the number of large follicles at early pregnancy examinations and delayed return to estrus (in mares that failed to become pregnant); these adverse effects were attributed to a prolonged release of the drug from the implant. In 2003, an injectable short-term release (<24 h) deslorelin product became available. The objective of this study was to determine if this product would hasten ovulation in early foaling first postpartum estrus mares without reducing the number of large follicles at early pregnancy examination (14-15 days postovulation). Beginning 5-6 days postpartum, first postpartum estrus (foal-heat) mares were teased daily and examined thrice weekly (Tuesday, Thursday and Saturday) by transrectal ultrasonography. Mares in estrus with a follicle > or = 34 mm diameter on Tuesdays or Thursdays were alternately assigned to: Treatment 1, n = 17; 1.5 mg injectable short-term release deslorelin, or Treatment 2, n = 16; Control (no treatment). The schedule allowed accurate determination of the number of mares ovulating within 2 days of treatment (i.e., ovulations detected on Thursday or Saturday). Mares were mated on the day of treatment and at 2-day intervals until either ovulation was confirmed or until behavioral estrus ceased. Transrectal ultrasonography was done 14-15 days after ovulation to assess ovarian follicles and pregnancy status. Fewer covers were required and more mares ovulated within 2 days of treatment in deslorelin-treated versus Control mares (P < 0.01). Pregnancy rates were normal (69%) in deslorelin-treated mares. The number of large follicles 14-15 days after ovulation did not differ between deslorelin-treated and Control mares (P > 0.10), suggesting follicular suppression did not occur with this formulation of deslorelin.     

Pharmacological actions of Y-24180: I. A potent and specific antagonist of platelet-activating factor

The ability of Y-24180, 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a] [1,4]diazepine to inhibit platelet-activating factor (PAF)-induced reactions was investigated. Y-24180 (0.0003–0.003 mg/kg, i.v.) dose-dependently inhibited PAF-induced bronchoconstriction in guinea pigs, but even at a high dose of 10 mg/kg, i.v., it was either inactive or weakly active against the bronchoconstriction induced by histamine, serotonin, acetylcholine, arachidonic acid, bradykinin, or leukotriene D₄. Oral doses (0.003–0.1 mg/kg) of Y-24180 also prevented hemoconcentration due to PAF in a dosedependent manner and produced a parallel shift of the PAF dose-response curve. Y-24180 (0.0003–0.1 mg/kg, i.v.) and WEB 2086 (0.03–1 mg/kg, i.v.) dose-dependently reversed PAF-induced hypotension in anesthetized rats. In mice, PAF-induced lethality was inhibited by Y-24180 and WEB 2086 with ED₅₀ values of 0.022 and 1.42 mg/kg, p.o., and 0.023 and 0.12 mg/kg, i.v., respectively. This protective effect of Y-24180 given p.o. persisted for at least 6 hr. In actively sensitized mice lethal anaphylactic shock was prevented by oral doses of Y-24180 and WEB 2086 with ED₅₀ values of 0.095 and 0.69 mg/kg, respectively. These results suggested that Y-24180 is an extremely potent and specific PAF antagonist with a good duration of action.