Susan little, dvm, diplomate abvp (feline)


Susan Little, DVM Diplomate, American Board of Veterinary Practitioners, Certified in Feline Practice Infertility in the Queen
June 2006
Record KeepingŠ Health and breeding records are very important; breeders of pedigreed cats need a simple but complete system to record data for each breeding cat Š Individual record for each cat: a. Call name and registered name; registration number; microchip number b. Complete description and photo c. Birth date d. Sire and dam e. Vaccination and deworming record f. Record of major health problems and their treatment g. Record of elective procedures (i.e. dental cleanings, spay, neuter, etc.) Š Additional records for breeding cats should include at a minimum: a. Age at first heat b. Record of each heat and the breeding plans c. Record of any health problems during the pregnancy and of any medications administered d. Record of each breeding (name of tom, dates bred, number of breedings, whether breeding was witnessed, any problems) and its outcome (i.e. pregnancy or date of return to heat) e. Record of each pregnancy (projected due date, actual due date, number of kittens born live/dead, any congenital defects or other problems) f. Description of each delivery (length of time, interventions needed, etc.) g. Dates/results of any x-rays/ultrasounds done for reproductive reasons h. Birth weights of kittens, health problems in the neonatal period i. Health status of each kitten at 1 and 5 years of age, if known InfertilityŠ Infertility may mean one of the following in female cats: y Inability to be bred by a male y Inability to conceive after successful breeding y Inability to carry a pregnancy to term Š Cats that are difficult to breed may produce other cats who are difficult to
Š Investigation of infertility in the queen requires: 1. A complete physical exam and thorough medical history (including drugs or herbal products administered and vaccination history) 2. Blood chemistries, complete blood count, urinalysis, retrovirus testing 3. Vaginal cytology, serum progesterone to establish phase of estrous cycle 4. Evaluation of diet, housing, show/travel stresses Bytown Cat Hospital 422 McArthur Ave. Ottawa, Ontario, Canada K1K 1G6 Phone 613-741-2460 [email protected] Fax 613-741-8463 5. Evaluation of social interactions with other cats in cattery 6. Evaluation of breeding behaviour when with male 7. Evaluation of cattery environment: temperature, ventilation, available light, population density, cage design, etc. Resources for healthy indoor feline environments: Although this website is geared toward cats in research settings, there is valuable information for catteries: Failure to Cycle Š Immaturity: First estrus may occur any time between 4 and 21 months of age Š Senility: Queens over 8 years old may have absent or infrequent estrus cycles Š Previous ovariohysterectomy/ovariectomy: Serum luteinizing hormone (LH) will be over 1 ng/ml in OHE/ovariectomized females due to loss of negative feedback from ovaries Š True primary anestrus: Queens that fail show first estrus by 24 months of age (uncommon); evaluate karyotype for chromosomal abnormalities Š Secondary anestrus: failure to cycle, or infrequent cycles 1. Silent estrus: Normal hormonal events without behavioral estrus
• Queens that are timid, low on social scale in cattery; crowded conditions • Must differentiate from pseudopregnancy due to spontaneous ovulation • House queen with different cats (smaller group) or separately; expose to tom 2. Inadequate daylight: Indoor housing may not ensure enough hours daylight
• 14-16 hours artificial light necessary; equivalent to 100-watt light bulb per 13 x 13 foot space; if you can read a newspaper, it is enough light 3. Spontaneous ovulation/pseudopregnancy: Noncopulatory ovulation may be a
cause of long interestrus intervals (40-50 days) • Detect with vaginal cytology and elevated serum progesterone in the absence of confirmed pregnancy 4. Intercurrent diseases/stressors: Conditions causing debilitation or prolonged ill
health may affect estrous cycles; stressors such as frequent exhibition/travel, crowding, antagonistic interactions with other cats may also suppress cycles 5. Medications: Some medications may interfere with estrous cycles by suppressing
gonadotropin secretion, such as corticosteroids, progestins, anabolic steroids, androgens; some antifungals such as ketoconazole can lower testosterone levels, griseofulvin could inhibit spermatogenesis Galastop , Boehringer Ingelheim) may be useful in inducing estrus, not well studied in the queen Š FSH can be used to induce estrus in the queen, but prolonged usage has been associated with cystic ovaries: • Day 1: 2.0 mg, IM; Days 2 and 3: 1.0 mg, IM; Days 4 and 5: 0.5 mg, IM Bytown Cat Hospital 422 McArthur Ave. Ottawa, Ontario, Canada K1K 1G6 Phone 613-741-2460 [email protected] Fax 613-741-8463 Prolonged or Persistent Estrus
1. Normal phenomena:
• May be due to very short interestrus intervals or receptivity to mating during the nonfollicular phase of the estrous cycle • Investigate using vaginal cytology, serum estradiol levels every 2-3 days over a 3- • Breed queen to an experienced male, or induce ovulation with GnRH (25 µg intramuscularly) • Try to induce anestrus by maintaining queen in less than 8-10 hours of daylight 2. Ovarian cysts and tumours:
• Cats can have both functional and non-functional ovarian and parovarian cysts; tumours most common in older queens • Evaluate with ultrasonography, serum estradiol levels
Failure to Conceive with a Normal Cycle
1. Maternal abnormalities:
• Congenital defects: persistent hymen, vaginal strictures • Inbreeding depression: intensive inbreeding can cause subfertility, loss of vigor and reproductive capacity • Uterine disease: cystic endometrial hyperplasia (CEH)/pyometra a. Ultrasound uterus (uterine wall thickness, fluid accumulation) b. Laparoscopy or laparotomy to visualize reproductive tract, biopsy/culture uterus (for valuable queens) c. Queens with repeated pseudopregnancies may have CEH d. Ultrasound 18-21 days after breeding to differentiate failure to conceive from early fetal death 2. Male infertility: breed queen to a proven sire (sired kittens within previous 6
months); check male for presence of hair ring around base of penis that can prevent intromission 3. Breeding management issues:
• Review breeding management, videotape breedings if necessary • Fearful queen may not breed, fear impairs hormonal events; dominant queens may require sedation to allow male to breed (best medication to use not known) • Partner preferences and aversions are known to occur • If queen returns to estrus less than 21 days after breeding, she did not ovulate, probably due to inadequate breedings (incomplete breedings, too few breedings) • Check timing of breeding (too early, too late); best to breed days 2-4 • Check serum progesterone 1-2 weeks after breeding to see if ovulation occurred; ovulation is associated with serum progesterone > 2 ng/ml 4. Failure to ovulate: If breeding management issues have been ruled out as a cause,
ovulation can be induced with GnRH or hCG • Repeated treatments have been associated with immune-mediated decreases in Bytown Cat Hospital 422 McArthur Ave. Ottawa, Ontario, Canada K1K 1G6 Phone 613-741-2460 [email protected] Fax 613-741-8463 5. Fetal resorption/abortion: Queen returns to estrus 60+ days after breeding
Cystic Endometrial Hyperplasia (CEH)
Š Disorder of proliferative and degenerative changes in endometrium associated with
aging; chronic subclinical condition; common in queens over 5 years and maiden queens over 3 years, but can be seen at any age Š Progesterone induces hyperplasia of the surface or glandular epithelium and cystic dilatation of the uterine glands; fluid in the cystic structures is usually uncontaminated, but if free in the uterus, it will support bacterial growth; progesterone also inhibits the local immune response and decreases myometrial contractility Š Repeated pseudopregnancies may predispose some queens to CEH; progestins used to control estrus also a risk factor Š Diagnosis: queen is not ill but fails to conceive or has small litters; ultrasound may detect thickening of uterus; definitive diagnosis only with uterine biopsy Š No treatment for uncomplicated CEH; endometritis (CEH plus bacterial infection) may respond to prolonged antibiotic treatment but can progress to pyometra Pyometra Š Severe endometrial infection with accumulation of pus in uterus Š Typically occurs following an estrus, when bacteria from vagina invade uterus through open cervix; usually associated with CEH Š Vagina normally has bacteria present; vaginal cultures therefore hard to interpret; most common bacteria are E. coli and Streptococcus, Staphylococcus, etc. Š Clinical signs: Vulvar discharge (if cervix open), depression, dehydration, anorexia, fever, weight loss, distended abdomen Š Diagnosis: Increased white blood cell count, enlarged uterus on x-rays or ultrasound Š Treatment: IV fluids may be needed, antibiotics (fluoroquinolones, amoxicillin- clavulanate) plus ovariohysterectomy (OHE) or prostaglandin therapy for valuable breeding queens Š Antibiotics alone, vaginal douches not very effective Š Prostaglandin therapy: best for open-cervix; complication rate is low! • Candidate queens are under 6 years, in good health (no asthma), no retained fetal material or live fetuses, no complications (i.e. uterine torsion) Prostaglandin F2α, dinoprost (Lutalyse , Pharmacia & Upjohn) treatment: queen may or may not be hospitalized; different dosing options: ƒ High dose: 0.1 to 0.25 mg/kg SC twice daily for 5 to 7 days ƒ Low dose: 0.02 to 0.05 mg/kg SC 4-6 times daily for 5 to 10 days • Treatment may cause cervix to open, uterus to contract, may cause lysis of CL • Monitor for: rising fever, abdominal pain, systemic illness, uterine rupture • Assess success of treatment by monitoring white blood cell counts, ultrasound • Side effects common at higher doses, especially first day: restlessness, vocalizing, panting, vomiting, diarrhea, salivation, intense grooming of flanks and vulva; lasts 15-20 min; side effects uncommon at low doses (often only a bit of salivation) • Re-examine cat 1 and 2 weeks post-treatment: clear vulvar discharge by day 7, normal by 14 days; if bloody or purulent discharge persists, treat again Bytown Cat Hospital 422 McArthur Ave. Ottawa, Ontario, Canada K1K 1G6 Phone 613-741-2460 [email protected] Fax 613-741-8463 • Breed at next heat! Fertility rates after treatment are good (80% or better) • Adjunctive therapy: ƒ Prolonged oral antibiotic therapy (4-6 weeks) ƒ Cabergoline ( Galastop , Boehringer Ingelheim): 5 µg/kg, PO, 5 days; prolactin inhibitor, luteolytic, no side effects ƒ Aglepristone ( Alizine , Virbac): progesterone receptor antagonist, 10-15 mg/kg, SC, 2 days in a row
References
Davidson, A.P. et al.: Treatment of pyometra in cats, using prostaglandin F2 alpha: 21
cases (1982-1990). J Amer Vet Med Assoc 200(6):825-828;1992. Davidson, A.P.: Medical management of pyometra with prostaglandin F2 alpha in the dog and cat. Kirk's Current Veterinary Therapy XII Small Animal Practice (J.D. Bonagura, ed.). W.B. Saunders, Philadelphia, P.A., 1995; pp 1081-1083. Johnston, S.D. et al.: Clinical approach to the complaint of infertility in the queen. Canine and Feline Theriogenology. W.B. Saunders, Philadelphia, P.A., 2001; pp 486-495. Lawler, D.F. et al.: Histopathologic features, environmental factors, and serum estrogen, progesterone, and prolactin values associated with ovarian phase and inflammatory uterine disease in cats. Amer J Vet Res 52(10):1747-1753; 1991. Little, S. Uncovering the cause of infertility in queens. Vet Med 96(7): 557-568, 2001. Potter, K. et al.: Clinical and pathologic features of endometrial hyperplasia, pyometra, and endometritis in cats: 79 cases (1980-1985). J Amer Vet Med Assoc 198(8):1427-1431; 1991. Stabenfeldt, G.H.; Pedersen, N.C.: Reproduction and reproductive disorders. Feline Husbandry: Diseases and Management in the Multiple Cat Environment (P.W. Pratt, ed.). American Veterinary Publications, Goleta, A.A., 1991; pp 129-162. Wolf, A.M.: Infertility in the queen. Current Veterinary Therapy XI Small Animal Practice (R.W. Kirk; J.D. Bonagura, eds.). W.B. Saunders, Philadelphia, P.A., 1992; pp 947-954. Wright, P.J.; Watts, J.R.: The infertile female. Manual of Small Animal Reproduction and Neonatology (G. Simpson; G. England; M. Harvey, eds.). British Small Animal Veterinary Association, Cheltenham, U.K., 1998; pp 17-33. Bytown Cat Hospital 422 McArthur Ave. Ottawa, Ontario, Canada K1K 1G6 Phone 613-741-2460 [email protected] Fax 613-741-8463 DRUG FORMULARY for Feline Reproduction 10-15 mg/kg, SQ, 2 days Alizine® 0.25 mg/cat, PO, 5 to 7 days Parlodel® Mammary hyperplasia, 5 µg/kg, PO, SID, 5 to 7 days Galastop® pyometra, abortion (after (combine with cloprostenol for Dostinex® Abortion (after 25 days, 5 µg/kg, SC, every 48 hours Estrumate® with cabergoline) 2 mg/cat, IM, SID first day, then reduce dose to 1.0 or 0.5 mg SID for 4 more days (max. of 5 days) GnRH (gonadorelin): Induce ovulation when in 25 µg/cat, IM, once Cystorelin® Induce ovulation when in 250 µg/cat, IM, daily on first 3 Chorulon® Postpone estrus (start in 2.5 mg/cat, PO, weekly; Provera®, 2.0 mg/kg, IM, every 5 months Depo-Provera® Megestrol acetate: Postpone estrus (start in 2.5 mg/cat, PO, weekly Ayerst Stimulate milk 0.2-0.4 mg/kg, PO, TID Reglan® and generics Oxytocin Various 2.5-5.0 units/cat, IM every 20-30 minutes, max 3 doses Postpone estrus (start in 100 mg/cat, SC, every 5 months Delvosteron® Prostaglandin F2α Pyometra, induce 0.1-0.25 mg/kg, SQ, BID to TID Lutalyse® abortion after 35 days Stop premature labor 0.03-0.08 mg/kg, BID to TID Bricanyl®, Brethine® Note: Many of these drugs are not licensed for use in the cat in all countries, or may not be
licensed for these indications. Not all medications are available in all countries or may not be
available in veterinary formulations. Drugs may be available under different brand names from
different manufacturers. Always consult your veterinarian about any medication for your cat.
Bytown Cat Hospital 422 McArthur Ave. Ottawa, Ontario, Canada K1K 1G6 Phone 613-741-2460 [email protected] Fax 613-741-8463

Source: http://www.rexringen.nu/jubileum/notes/Infertility_Queen_2006.pdf

cris.cumulus.vub.ac.be

Vrije Universiteit Brussel Regulation of beta2-Adrenergic Receptor Function by Conformationally SelectiveSingle-Domain IntrabodiesStaus, Dean P.; Wingler, Laura M.; Strachan, Ryan T.; Rasmussen, Soren G. F.; Pardon, Els;Ahn, Seungkirl; Steyaert, Jan; Kobilka, Brian K; Lefkowitz, Robert J. Published in:Molecular Pharmacology

Cannabinoid cb1 receptor in the modulation of stress coping behavior in mice: the role of serotonin and different forebrain neuronal subpopulations

Contents lists available at Cannabinoid CB1 receptor in the modulation of stress coping behavior in mice:The role of serotonin and different forebrain neuronal subpopulations M. Häring , M. Grieb , K. Monory , B. Lutz F.A. Moreira a Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128 Mainz, Germanyb Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, MG 31270-901, Brazil