Adenohypophyseal function in bitches treated with medroxyprogesterone acetate

The aim of this study was to investigate the effects of treatment with medroxyprogesterone acetate (MPA) on canine adenohypophyseal function. Five Beagle bitches were treated with MPA (10mg/kg, every 4 weeks) and their adenohypophyseal function was assessed in a combined adenohypophyseal function test. Four hypophysiotropic hormones (CRH, GHRH, GnRH, and TRH) were administered before and 2, 5, 8, and 11 months after the start of MPA treatment, and blood samples for determination of the plasma concentrations of ACTH, cortisol, GH, IGF-1, LH, FSH, prolactin, alpha-MSH, and TSH were collected at -15, 0, 5, 10, 20, 30, and 45 min after suprapituitary stimulation. MPA successfully prevented the occurrence of estrus, ovulation, and a subsequent luteal phase. MPA treatment did not affect basal and GnRH-induced plasma LH concentrations. The basal plasma FSH concentration was significantly higher at 2 months after the start of MPA treatment than before or at 5, 8, and 11 months after the start of treatment. The maximal FSH increment and the AUC for FSH after suprapituitary stimulation were significantly higher before treatment than at 5, 8, and 11 months of MPA treatment. Differences in mean basal plasma GH concentrations before and during treatment were not significant, but MPA treatment resulted in significantly elevated basal plasma IGF-1 concentrations at 8 and 11 months. MPA treatment did not affect basal and stimulated plasma ACTH concentrations, with the exception of a decreased AUC for ACTH at 11 months. In contrast, the maximal cortisol increment and the AUC for cortisol after suprapituitary stimulation were significantly lower during MPA treatment than prior to treatment. MPA treatment did not affect basal plasma concentrations of prolactin, TSH, and alpha-MSH, with the exception of slightly increased basal plasma TSH concentrations at 8 months of treatment. MPA treatment did not affect TRH-induced plasma concentrations of prolactin and TSH. In conclusion, the effects of chronic MPA treatment on adenohypophyseal function included increased FSH secretion, unaffected LH secretion, activation of the mammary GH-induced IGF-I secretion, slightly activated TSH secretion, suppression of the hypothalamic-pituitary-adrenocortical axis, and unaffected secretion of prolactin and alpha-MSH.     

The weakest link: medroxyprogesterone acetate in pig feed

Medroxyprogesterone acetate (MPA)-contaminated feed arrested the onset of farrowing, and induced post-lactational anoestrus in sows. Sixty percent of the sows developed cystic ovaries after weaning following exposure to pharmaceutical waste of MPA in glucose syrup. This waste ended up in acidified feed of by-products of a sow farm, and proved to be the cause of the disorders. Analysis by thin layer chromatography and Gas Chromatography/Mass Spectrometry of renal fat from 10 slaughter sows demonstrated residues of 2.5-8 ppb of MPA. Within the European Union use of MPA is illegal as growth promoter in production animals, and therefore MPA-exposed farms were placed under official control by the general inspection service. Clinical signs and diagnostic procedures of the initial case are presented and the role of the veterinary practitioner in detecting potential food safety hazards is discussed.     

Comparison of the histological changes in the dog after treatment with the progestins medroxyprogesterone acetate and proligestone

Abstract

Administration of progestins in the dog may result in overproduction of growth hormone, suppression of the hypothalamic‐pituitary‐adrenocortical axis, and insulin resistance. In this paper we present a comparison of the histological findings in control dogs and dogs treated with either medroxyprogesterone acetate (MPA) or proligestone (PROL).

Depot preparations of MPA or PROL were administered (SC) at 3‐week intervals in two groups of seven ovariohysterectomized beagle dogs, after which three dogs of each group were killed. After a 6‐month period without hormone treatment during which recovery was studied, the remaining dogs received five additional injections at the same interval and were subsequently killed. Tissue samples of four intact female beagle dogs served as controls.

Progestin treatment resulted in atrophy of the adrenal cortex. In both MPA‐ and PROL‐treated dogs, the thickness of the combined zona fasciculata and reticularis was significantly smaller than in control animals. In the mammary glands of progestin‐treated dogs there were well developed alveoli and normal ducts adjacent to foci of hyperplastic ductular epithelium. Five dogs in each treatment group had developed benign mammary tumours which varied from simple tubular and papillary adenomas to benign complex and mixed tumours, whereas no mammary tumours were observed in the control animals. In each treatment group, steroid‐induced hepatopathy was observed in the liver of three dogs. Vacuolation of the cells of the islets of Langerhans and the epithelium of the intercalated ducts was present in two dogs of each treatment group and was only observed after the second series of progestin administrations. Incidental findings included chronic pyelonephritis, aspecific dermatitis, and mucinous dysplasia of the gall bladder. No abnormalities were found in sections of spleen, lung, brain, or pituitary gland.

There were no significant differences in the frequencies of the various abnormalities between MPA‐ and PROL‐treated dogs. Our findings correspond with the clinical and biochemical results after treatment of dogs with MPA and PROL. The high incidence of mammary tumours might be associated with our recent finding that in the dog progestins induce ectopic production of growth hormone in the mammary gland. The dog might be a good model for further studies on hormonally induced breast cancers.     

Long-term prevention of estrus in the bitch and queen using chlormadinone acetate

Estrus was prevented with weekly oral administration of 2 mg chlormadinone acetate for 2.0 to 9.8 y in bitches and queens. Abnormalities, including mammary or uterine disorders, or both, were noted in 7 out of 14 bitches and 9 out of 24 queens during this long-term treatment.     

Prevention of estrus in the queen with chlormadinone acetate administered orally.

The possibility of estrus prevention in the queen by the oral administration of chlormadinone acetate was examined. The animals used were 29 mature and 15 immature queens. For 16 mature females, 4-12.5 mg was given daily by mouth for 7 days every 3 months. Ten of the 16 queens given this treatment came into estrus within 4 months of the first treatment. For 28 females including the immature, 2-12.5 mg was given once a week throughout the experiment. This treatment prevented estrous activity for at least 1 year. In the queens in this study, the side effects were not observed excepting an increase in body weight during treatment. Our results showed that oral administration of this drug weekly is safe and reliable for long-range prevention of estrus in queens.     

Concentration of estrone, estradiol and estriol in the blood of pregnant sheep after induction of estrus with chlormadinone acetate and medroxyprogesterone acetate]

The radioisotopic method of 131J-labelled albumin was employed to determine the distribution of acidic proteinase activity in some organs and tissues of chickens. The highest enzymatic activities were found in intestine wall, in pancreas, and in liver. Considerably lower activities were ascertained in kidneys, brain, lungs, and heart. The different proportions of these enzymes in homogenates and supernatant fractions (106 000 g) testify to a lack of uniformity in the solubility of cathepsins in the organs tested. The tested organs, with the exception of pancreas, did not show any enzymatic activity of neutral proteinases.     

醋酸甲孕酮单克隆抗体的制备与鉴定

用人工合成的醋酸甲孕酮-牛血清白蛋白(MPA-BSA)作为抗原免疫BALB/c小鼠,利用杂交瘤技术筛选得到1株稳定分泌醋酸甲孕酮单克隆抗体的杂交瘤细胞株4C11A3B6,该细胞株经体外传代和冻存复苏后抗体分泌稳定。间接ELISA测定培养上清效价为1∶640,诱生腹水效价为1∶2.56×106。经鉴定:杂交瘤细胞分泌的抗体亚型为IgG2а。竞争抑制ELISA(ciELISA)检测显示其IC50为22 ng/mL,与常见抗生素及结构类似物的交叉反应小,表明该单抗具有较好的敏感性和特异性。     

Incompatibility between lasalocid and chloramphenicol in broiler chicks after a long-term simultaneous administration

Two growth experiments were conducted to evaluate in broiler chicks the compatibility between lasalocid medication in the feed (at 90 or 125 ppm) and a long-term administration of chloramphenicol either via the feed (500 ppm) or via the drinking water (500 mg/liter).The simultaneous administration of lasalocid and chloramphenicol generally caused severe growth depression, decreased feed intake and impaired feed conversion. Several chicks showed evident symptoms of intoxication, such as ataxia, leg weakness and paralysis. The development and frequency of these symptoms were dependent on the dosage of lasalocid and on the duration of the simultaneous administration.Biochemical examinations (Experiment 2) revealed in the affected chicks significant changes in several parameters, in particular a markedly increased activity of creatine kinase and GOT in the plasma. It confirmed that the observed leg weakness and paralysis were caused by myodegeneration.     

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t_1/2α) and elimination half-life (t_1/2β) were 0.36 ± 0.07 h and 7.42 ± 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vd_ss) was 4.66 ± 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (C_max) was 0.43 ± 0.06 µg/ml at 1.36 ± 0.39 h (T_max). The mean absorption (t_1/2ka) and elimination half-life (t_1/2β) of NFLXGA were 0.78 ± 0.27 h and 7.13 ± 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 ± 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.     

Parenteral use of medroxyprogesterone acetate as an antifertility agent in the bitch

10 kg unbred Beagle and mongrel bitches were used in each of 4 experiments (exp). 6 alpha-methyl-17 alpha-acetoxyprogesterone (MAP or medroxyprogesterone acetate) was prepared as a sterile aqueous suspension (50 mg/ml) and was used in exps 1, 2 and 3. Tritiated MAP was used in exp 4. In exp 1, 7 bitches were given 500 mg and 7 were given 50 mg subcutaneously (sc). 6 controls were used. In exp 2, 50, 100 or 250 mg were given sc, intramuscular (im) or intraperitoneal (ip) to 4 dogs at each dose level and route of administration. In exp 3, 12.5 or 25 mg was given either sc or im in 4 groups of 8 bitches each. In exp 4, a single 50 mg mixture of MAP and tritiated MAP was given to each of 3 dogs: 1 sc, 1 im, and 1 ip. Results of exp 1 showed those on 500 mg had first posttreatment estrus an average of 504 days (range of 247-730) after injection. Those on 50 mg averaged 329 days (range of 205-429). Breeding resulted in 6 live pups/litter for the controls 5.2 for those on 50 mg, and 4 for those on 500 mg. In exp 2, results showed prolonged cycling in those injected sc (295 days to estrus), while those injected im reached estrous in 225 days and those injected ip in 148 days. In exp 3, 3 on 25 mg sc had a 6 month estrous delay while 4 did when injected im. 3 of 16 given 12.5 mg sc and im had a 6 month delay in cycling. Exp 4 showed ip treated dogs had estrus 148 days after treatment, 225 days for im, and 295 days for sc. Ip treated dogs whelped 5 pups; im 7 pups; and sc, 5 pups. 7 months lapsed before nearly all of the 50 mg sc administered dose was excreted. An additional 2.5 months lapsed before estrus occurred in this dog.     

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and intramuscular administration to horses

The pharmacokinetic properties of norfloxacin-glycine acetate (NFLXGA) were determined in six horses following a single intravenous (i.v.) and intramuscular (i.m.) dose of 4 mgkg(-1) body weight. Following i.v. and i.m. administration, the plasma drug concentrations were best fitted by an open two-compartment model with a rapid distribution phase. After i.v. NFLXGA administration, the distribution (t(1/2alpha)) and elimination half-life (t(1/2beta)) were 0.42 (0.05) and 5.44 (1.36)h. The volume of distribution of NFLXGA at steady state (Vd(ss)) was 2.19 (0.53) Lkg(-1). After NFLXGA i.m. administration, the maximal absorption concentration (C(max)) was 0.44 (0.04) microgml(-1) at 0.86 (0.15)h (T(max)). The mean absorption (t(1/2ka)) and elimination half-life (t(1/2beta)) of NFLXGA were 0.27 (0.07) and 9.47 (2.24)h, respectively. The mean systemic bioavailability (F) following i.m. administration was 55 (12)%. The optimal dosage for each administration route was calculated from the pharmacokinetic data on the basis of the area under the inhibitory plasma concentration-time curve (AUIC) every 24h and was found to be 13.36 and 7.35 mgkg(-1) for i.m. and i.v. administration, respectively.     

Modulation of anthracycline activity in canine mammary tumour cells in vitro by medroxyprogesterone acetate

Failure of chemotherapy with anthracyclines as a result of drug resistance and toxicity is a major problem in the clinical management of neoplasia. The aim of the present study was to evaluate the activity of medroxyprogesterone acetate (MPA) as a chemosensitiser on anthracycline cytotoxicity. The study investigated whether such an effect could be related to an increase in lipid peroxidation, nitric oxide production, membrane fluidity and intracellular anthracycline concentration. The results showed that anthracyclines decreased nitric oxide production but increased membrane viscosity (polarisation constant) and lipid hydroperoxide formation in canine mammary tumour cells. Moreover, it was found that both drug-induced cytotoxicity and membrane viscosity increased in the presence of MPA. Conversely, lipid hydroperoxides decreased in MPA-supplemented cells. Medroxyprogesterone acetate did not show any effect on nitric oxide production. The two anthracyclines used (doxorubicin and idarubicin) showed differential intranuclear accumulation in canine mammary tumour cells, and MPA significantly modified intracellular concentration of anthracyclines.     

Hematologic abnormalities associated with chronic acetaminophen administration in a dog

Large numbers of eccentrocytes (erythrocytes with hemoglobin contracted to one side of the cell) were seen on a stained blood smear from a Dachshund with compensated hemolytic anemia. The 7-kg dog had been given 325 mg of acetaminophen orally once daily for 6 weeks by the client, because the dog exhibited signs attributed to abdominal pain. More than half of the erythrocytes contained small Heinz bodies visualized after methyl violet staining. The methemoglobin content was 6.4% (normal less than 2%) when measured 16 hours after the last acetaminophen tablet was given. High serum alanin transaminase and alkaline phosphatase activities and hyperbilirubinuria were measured. All abnormal laboratory findings were attributable to acetaminophen-induced oxidative damage to erythrocytes and hepatocytes.     

Concentration of methylprednisolone in the centrodistal joint after administration of methylprednisolone acetate in the tarsometatarsal joint

REASONS FOR PERFORMING STUDY: The centrodistal (CD) and tarsometatarsal (TMT) joints are often injected individually with a corticosteroid to resolve lameness caused by osteoarthritis (OA). There are no data available regarding diffusion of methylprednisolone (MP) from the TMT joint to the CD joint. HYPOTHESIS: A therapeutic concentration of MP diffuses into the CD joint after methylprednisolone acetate (MPA) is administered into the TMT joint. OBJECTIVE: To measure the concentration of MP in the CD joint after MPA was administered into the TMT joint. METHODS: MPA was administered into a TMT joint of 16 horses. At different times, the ipsilateral CD joint of these horses was injected with a small amount of saline and recovered saline was measured for concentration of MP using high performance liquid chromatography. RESULTS: Six hours after administration of MPA into the TMT joint, a therapeutic concentration of MP was found in all 10 CD joints sampled at this time. CONCLUSIONS: Horses with pain arising from the distal 2 joints of the hock can be treated by administering MPA into the TMT joint alone. POTENTIAL RELEVANCE: Administering MPA into the TMT joint only, to treat OA of the distal 2 hock joints, reduces the difficulties and risks associated with centesis of the CD joint.     

Challenging diagnosis--icterus associated with a single perforating duodenal ulcer after long-term nonsteroidal antiinflammatory drug administration in a dog

A dog developed icterus, vomiting, and anorexia 2 wk after orthopedic surgery and treatment with meloxicam for approximately 1 y. Exploratory laparotomy revealed a single perforated duodenal ulcer. The most likely cause of the hyperbilirubinemia was intrahepatic cholestasis resulting from peritonitis associated with the perforation.     

Hemodynamic effects of methylprednisolone acetate administration in cats

OBJECTIVE: To investigate the mechanisms by which corticosteroid administration may predispose cats to congestive heart failure (CHF). ANIMALS: 12 cats receiving methylprednisolone acetate (MPA) for the treatment of dermatologic disorders. PROCEDURE: The study was conducted as a repeated-measures design. Various baseline variables were measured, after which MPA (5 mg/kg, IM) was administered. The same variables were then measured at 3 to 6 days and at 16 to 24 days after MPA administration. Evaluations included physical examination, systolic blood pressure measurement, hematologic analysis, serum biochemical analysis, thoracic radiography, echocardiography, and total body water and plasma volume determination. RESULTS: MPA resulted in a substantial increase in serum glucose concentration at 3 to 6 days after administration. Concurrently, RBC count, Hct, and hemoglobin concentration as well as serum concentrations of the major extracellular electrolytes, sodium and chloride, decreased. Plasma volume increased by 13.4% (> 40% in 3 cats), whereas total body water and body weight slightly decreased. All variables returned to baseline by 16 to 24 days after MPA administration. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that MPA administration in cats causes plasma volume expansion as a result of an intra to extracellular fluid shift secondary to glucocorticoid-mediated extracellular hyperglycemia. This mechanism is analogous to the plasma volume expansion that accompanies uncontrolled diabetes mellitus in humans. Any cardiovascular disorders that impair the normal compensatory mechanisms for increased plasma volume may predispose cats to CHF following MPA administration.