Oestrogen receptor evaluation in Pomeranian dogs with hair cycle arrest (alopecia X) on melatonin supplementation

The role of oestrogen receptors in dogs with hair cycle arrest (alopecia X) was investigated by immunohistochemistry. The purpose of this study was to determine if hair regrowth in dogs with hair cycle arrest treated with melatonin was associated with a decrease in follicular oestrogen receptors. Fifteen Pomeranians (excluding intact females) with hair cycle arrest were enrolled. Two biopsies were obtained from alopecic areas of the trunk before and after 3 months on melatonin. Haematoxylin and eosin-stained tissues were examined and oestrogen receptor-alpha was demonstrated immunohistochemically. Common histopathological findings included hyperkeratosis, follicular keratosis, excessive tricholemmal keratinization (flame follicles), thin epidermis, few small anagen bulbs, epidermal pigmentation and melanin aggregates within follicular keratin. Melanin aggregates within basal cells and hair were an occasional finding. After 3 months, 40% (six) dogs had mild to moderate hair regrowth. Biopsies from six dogs showed histological evidence of an increase in anagen hairs and eight dogs had a decrease in epidermal pigmentation. Moderate to marked staining intensity of oestrogen receptor-alpha was noted in all sebaceous gland basal cells, all small hair bulbs and follicular epithelium of telogen hairs. There was no oestrogen receptor-alpha staining of nuclei within the epidermis, apocrine glands or dermal fibroblasts. Large anagen hair bulbs had minimal to no oestrogen receptor staining. Hair regrowth was not associated with a change in oestrogen receptor-alpha staining.     

Adrenal steroid hormone concentrations in dogs with hair cycle arrest (Alopecia X) before and during treatment with melatonin and mitotane

The purpose of the study was to evaluate intermediate adrenal steroid hormones (ISH) in neutered dogs with hair cycle arrest (Alopecia X) during treatment with melatonin, and to see if hair re-growth is associated with sex hormone concentrations within the normal ranges. Twenty-nine neutered, euthyroid, and normo-cortisolemic dogs were enrolled in the study (23 Pomeranians, three keeshonds, two miniature poodles, and one Siberian husky). Coat assessment and an ACTH stimulation test were performed pre-treatment and approximately every 4 months for a year post treatment. Melatonin was administered initially at 3-6 mg, every 12 h. Based on clinical progression, each dog was continued on the current dose of melatonin, given an increased dose of melatonin or changed to mitotane. Partial to complete hair re-growth occurred in 14/23 Pomeranians, and partial re-growth in 3/3 keeshond and 1/2 poodle dogs. A Siberian husky dog failed to re-grow hair. Fifteen dogs had partial hair re-growth at the first re-evaluation. Melatonin dosage was increased in eight dogs but only one had improved hair re-growth. On mitotane treatment, partial to complete hair re-growth was seen in 4/6 dogs and no re-growth in 2/6 dogs. No significant decrease in sex hormone concentrations were seen during melatonin or mitotane treatment. Concentrations of ISH in dogs with hair re-growth did not differ significantly from pre-treatment values. At the completion of the study, androstenedione, progesterone and 17-hydroxyprogesterone were still above reference ranges in 21, 64 and 36%, respectively, of dogs with partial to complete hair re-growth. In conclusion, 62% of dogs had partial to complete hair re-growth. However, not all dogs with hair re-growth had concentrations of ISH within the normal range.     

Histology of the hair cycle in male beagle dogs

A detailed histologic study of the hair follicles of male Beagle dogs was made to determine changes in microscopic structure associated with the three stages in the hair cycle. Observed changes are that the bulbs of hair follicles in anagen are more closely associated with adipose tissue than they are in telogen. This is due to the deeper penetration of the follicles into the subcutaneous tissue during anagen. The hair germ cells of telogen were presumed to arise from the stratum basale of the matrix cells rather than from the outer root sheath cells. During telogen, the dermal papilla is separated from the club hair, but remains in close proximity to it. There is no connecting stalk as is reported for other animals.     

Hair cycle in dogs with different hair types in a tropical region of Brazil

Hair cycle activity has been extensively studied in humans, sheep and laboratory animals, but there is a lack of information in dogs. Besides varying according to species, breed, sex and general health, hair growth is mainly affected by climatic variations. The aim of the study was to evaluate the follicle activity in three breeds of dogs with different hair types, in the city of Viçosa, Minas Gerais (latitude 20°45′S), Brazil. Twenty‐one male dogs of boxer, labrador and schnauzer breeds were trichographically analysed monthly over 12 consecutive months. Hair percentage of telogen and anagen hairs at the different stages of the hair cycle in boxers and labradors was not significantly different, but both differed from the schnauzers. A significant correlation between hair follicle cycle and environmental temperature and photoperiod was noted in the boxers and labradors. In these breeds, a larger number of telogen hairs were observed during the hottest months of the year, and an increase in anagen hairs during the coldest months. The mean percentage of telogen hairs was 93, 90 and 55.3% for boxer, labrador and schnauzer, respectively.     

Alkaline phosphatase reaction in hair follicles of male beagle dogs during hair cycle stages.

The literature reviewed has revealed differences of opinion concerning the location of alkaline phosphates and its relationship to the hair cycle stages. This project was undertaken to determine alkaline phosphatase activity in the hair follicle stages: anagen, catagen, and telogen. Skin biopsy samples were collected over a period of 1 year from 9 purebred male Beagle dogs. At the beginning of the experiment 3 dogs were 2 weeks of age, 3 dogs were 12 months of age and 3 dogs were 21 months of age. The skin biopsies were taken monthly from alternate sides of each animal near the thoracolumbar region. Samples were fixed in 80% chilled alcohol and the alkaline phosphatase activity was determined by Gomori's calcium cobalt method. A total of 250 slides with seven sections per slide was examined. Each slide contained between 14–60 hair follicles. During anagen stage, the reaction of the dermal papilla for the presence of alkaline phosphatase was variable. A weak or negative reaction was observed in this study which was an unexpected finding. The reaction of the dermal papilla to alkaline phosphatase was positive in catagen stage. The cells of the dermal papillae in telogen stage were strongly alkaline phosphatase positive. The reaction was not confined to the blood vessels but occurred in all parts of the dermal papilla in both early and late stages.     

The impact of body site, topical melatonin and brushing on hair regrowth after clipping normal Siberian Husky dogs

The aims of this study were to determine the impact of body site, vigorous brushing and topical melatonin treatment on hair regrowth after clipping normal dogs. Siberian Husky dogs were randomly assigned to three groups of eight dogs each. All dogs had the lumbosacral region and both lateral thighs clipped. The left thigh and lumbosacral area received no treatment and were compared in all 24 dogs. Eight dogs had the right thigh treated with 0.1% melatonin twice daily for 2 months, and hair regrowth was compared with the left thigh. Eight dogs had the right thigh brushed twice daily for 2 months, and hair regrowth was compared with the left thigh. Eight dogs had neither thigh treated. Hairs were plucked before and 2 months postclipping, and the proportion of hair growth from the original length was calculated and compared as described above. Biopsy samples were collected before and after treatment to determine if brushing induced dermal inflammation and melatonin increased the proportion of anagen follicles. Proportionally, left thigh hairs were significantly longer compared to lumbosacral hairs 2 months postclipping. No significant differences in hair regrowth were noted between the nontreated thigh and the thigh treated with melatonin or brushed. No significant difference in dermal inflammation was noted before and after brushing. No significant differences were observed in the proportion of anagen follicles before and after topical melatonin treatment. Our results showed that the hairs in the lumbosacral region were proportionally shorter than lateral thigh hairs 2 months postclipping. Moreover, topical melatonin and brushing had no impact on hair regrowth after clipping normal dogs.     

Effect of epidural and intravenous use of the neurokinin-1 (NK-1) receptor antagonist maropitant on the sevoflurane minimum alveolar concentration (MAC) in dogs

ObjectiveTo determine the effect of maropitant, an NK-1 receptor antagonist on the minimum alveolar concentration (MAC) of sevoflurane after intravenous and epidural administration to dogs.Study designProspective experimental study.AnimalsSeven, adult, spayed-female dogs (24.8 ± 1.9 kg).MethodsEach dog was anesthetized twice with sevoflurane in oxygen, with at least 10 days separating the anesthetic events. The minimum alveolar concentration (MAC) of sevoflurane was determined using the tail-clamp technique. During the first anesthetic event, the MAC of sevoflurane was determined initially and again after intravenous administration of maropitant (5 mg kg^?1) and an infusion (150 μg kg^?1 hour^?1). During the second anesthetic event, an epidural catheter was advanced to the 4th lumbar vertebra and MAC was determined after administration of saline and maropitant (1 mg kg^?1) epidurally. All MAC determinations were done in duplicate. The MAC values were adjusted to sea level and compared using student's t-test.ResultsThe baseline MAC for sevoflurane was 2.08 ± 0.25%. Intravenous maropitant decreased (p < 0.05) MAC by 16% (1.74 ± 0.17%). In contrast, epidural administration of either saline or maropitant did not change (p > 0.05) the MAC (2.17 ± 0.34% and 1.92 ± 0.12%, respectively).Conclusion and clinical relevanceMaropitant decreased the MAC of sevoflurane when administered intravenously to dogs but not after epidural administration.     

Retrospective evaluation of sex hormones and steroid hormone intermediates in dogs with alopecia

The purpose of this study was to determine if there are specific steroid hormone aberrations associated with suspect endocrine alopecias in dogs in whom hypothyroidism and hyperadrenocorticism have been excluded. Steroid hormone panels submitted to the UTCVM endocrinology laboratory over a 7.5-year period (783 samples) from dogs with alopecia were reviewed. During this period, 276 dogs met the criteria for inclusion and were comprised of 54 different breeds. Approximately 73% of dogs had at least one baseline or post-ACTH stimulation steroid hormone intermediate greater than the normal range. The most frequent hormone elevation noted was for progesterone (57.6% of samples). When compared with normal dogs, oestradiol was significantly greater in Keeshond dogs and progesterone was significantly greater in Pomeranian and Siberian Husky dogs. Not all individual dogs had hormone abnormalities. Chow Chow, Samoyed and Malamute dogs had the greatest percentage of normal steroid hormone intermediates of the dogs in this study. Baseline cortisol concentrations were significantly correlated with progesterone, 17-hydroxyprogesterone (17-OHP) and androstenedione. Results of this study suggest that the pathomechanism of the alopecia, at least for some breeds, may not relate to steroid hormone intermediates and emphasizes the need for breed specific normals.     

Kinetic gait and subjective analysis of the effects of a tachykinin receptor antagonist in dogs with sodium urate-induced synovitis

OBJECTIVE: To examine the ability of preemptive administration of a proprietary neurokinin-1 (NK(1)) receptor antagonist to attenuate limb dysfunction associated with monosodium urate-induced synovitis in the stifle joints of dogs. ANIMALS: 16 clinically normal adult mixed-breed dogs (8 males and 8 females). PROCEDURES: A crossover study was conducted in 2 phases. Dogs were assigned to 2 groups (8 dogs/group) and orally administered an NK(1) receptor antagonist (3 mg/kg) or a control substance once daily for 4 days. Synovitis was then induced in the left stifle joint by intra-articular injection of monosodium urate. Investigators were not aware of treatment group assignments. Dogs were evaluated by use of subjective lameness scores during standing, walking, and trotting and by use of ground reaction force data 3, 6, 9, 12, and 24 hours after urate injection. After a 21-day washout period, the experiment was repeated with each dog administered the other treatment and injected with monosodium urate in the contralateral stifle joint. RESULTS: No significant differences were detected between the NK(1) receptor antagonist and control treatments with regard to peak vertical force, vertical impulse area, or subjective evaluations of lameness during standing, walking, or trotting, except during walking 24 hours after monosodium urate injection. CONCLUSIONS AND CLINICAL RELEVANCE: Preemptive administration of an NK(1) receptor antagonist failed to significantly improve subjective or objective outcome measures in dogs with monosodium urate-induced synovitis.     

Cell proliferation kinetics in the hair root matrix of dogs with healthy skin and dogs with idiopathic seborrhea

Cell proliferation kinetic values were established for the hair root matrix of primary anagen follicles of 14 Beagles and 4 Cocker Spaniels with healthy skin and 9 Cocker Spaniels with primary idiopathic seborrhea. Indices were established by intradermal pulse labeling with tritiated thymidine, followed by cutaneous biopsy and autoradiography. The hair root matrix cell labeling index was 23.4 +/- 3.5% for Beagles, 24.4 +/- 4.0% for healthy Cocker Spaniels, and 24.9 +/- 4.3% for seborrheic Cocker Spaniels. These values indicate a rapidly proliferating cell population. Differences among these cell kinetic data for the 3 groups of dogs were not statistically significant. Although significant cell kinetic differences have been reported for other epidermal structures (interfollicular epithelium, upper hair follicle external root sheath, sebaceous glands) in seborrheic Cocker Spaniels, proliferation of hair root matrix cells apparently remains unaffected.     

Spermatogenic arrest associated with focal degenerative orchitis in related dogs

Four dogs with a history of infertility were found on examination to be azoospermic. Three of the dogs were related (a sire and two male offspring) and investigation revealed that some of their male ancestors had been of reduced fertility. There were degenerative changes in 20–40 per cent of the seminiferous tubules, a proportion of which were associated with a focal peritubular orchitis. There was a complete absence of spermatozoa in the rete testis, the vasa efferentia and the epididymis. The possibility that the condition is of an autoimmune nature is discussed. The unrelated dog had a non-inflammatory degeneration of tubules with complete absence of spermatogenesis.     

The pharmacokinetics of maropitant, a novel neurokinin type-1 receptor antagonist, in dogs

Maropitant is the first NK1 receptor antagonist developed to treat and prevent emesis in dogs; it is administered by subcutaneous (s.c.) injection at 1 mg/kg, or orally (p.o.), in tablet form, at either 2 or 8 mg/kg depending on indication. The absolute bioavailability of maropitant was markedly higher (90.7%) following s.c. injection than after oral administration (23.7% at the 2 mg/kg dose and 37.0% at the 8 mg/kg dose). First-pass metabolism contributes to the low bioavailability of maropitant following oral administration. The difference in bioavailability between the two oral doses reflects the nonlinear kinetics characterizing the disposition of maropitant within the 2-8 mg/kg dose range. Systemic clearance of maropitant following intravenous (i.v.) administration was 970, 995 and 533 mL/h.kg at doses of 1, 2 and 8 mg/kg, respectively. Nonproportional kinetics were observed for p.o. administered maropitant at doses ranging from 2 to 16 mg/kg but dose proportionality was demonstrated at higher doses (20-50 mg/kg). Linearity was also demonstrated following s.c. administration at 0.5, 1 and 2 mg/kg. Maximum plasma drug concentration (Cmax) occurred 0.75 h (tmax) after s.c. administration at 1 mg/kg, and at 1.7 and 1.9 h after oral administration of 8 and 2 mg/kg doses, respectively. The apparent terminal half-life of maropitant was 7.75, 4.03 and 5.46 h after dosing at 1 mg/kg (s.c.), 2 mg/kg (p.o.) and 8 mg/kg (p.o.), respectively. Feeding status had no effect on oral bioavailability. Limited accumulation occurred following once-daily administration of maropitant for five consecutive days at 1 mg/kg (s.c.) or 2 mg/kg (p.o.). At the dose of 8 mg/kg (p.o.) once daily for two consecutive days, the mean AUC(0-24h) (second dose) was 218% that of the first dose value. Urinary recovery of maropitant and its main metabolite was minimal (<1%), thus supporting the evidence that maropitant clearance is primarily hepatic.     

Impaired local deiodination of thyroxine to triiodothyronine in dogs with symmetrical truncal alopecia

Thyroid dysfunction causes certain dermatological alterations in dogs. Insufficient delivery of thyroid hormone to the skin may originate not only from inadequate thyroid function but also from impaired local activation of thyroxine in the target organ. Thyroid parameters and deiodination were investigated in healthy dogs (group C) and in dogs with cutaneous lesions associated with hypothyroidism (group H) or with a low-T₃ syndrome (group LT). The ability of the skin to convert T₄ to T₃ was impaired in both groups H and LT but not in the controls. It is concluded that impaired local deiodination may contribute to skin problems in dogs.Abbreviations bwt body weight - DTT dithiothreitol - PBS phosphate-buffered saline (pH 7.5, 0.05 mol/L) - PTU propylthiouracyl - RIA radioimmunoassay - TRH thyrotropin-releasing hormone - TSH thyroid-stimulating hormone     

Oestrogen receptor genotypes and litter size in Hungarian Large White pigs

A total of 869 litter records of 226 Hungarian Large White sows have been analysed to investigate the possible use of the oestrogen receptor gene (ESR) as marker to improve litter size. First, second and later parities have been evaluated separately. Frequencies of A = 0.55 and B =0.45 have been calculated for the two ESR alleles and the observed/expected number of the three genotypes were as follows: AA: 71/69.1, AB: 108/111.8 and BB: 47/45.1. BB type first and later parity sows were superior to AB and AA sows for number born alive (NBA), total number of born (TNB) and the corrected number of weaned piglets (CNW), respectively.     

Cardiorespiratory effects of a 5HT2 antagonist (R51703) in awake and anesthetized dogs.

To investigate cardiorespiratory effects of an experimental 5-hydroxytryptamine receptor antagonist (R51703) with sedative properties, intramuscular doses of the drug were studied in 6 awake dogs of mixed breed, and in 6 anesthetized beagles. Two doses (0.2 and 0.4 mg/kg) of R51703 and a saline control were studied in the awake dogs using a randomized crossover trial. Subsequently, the higher dose of R51703 was included as a component of halothane anesthesia to determine whether the halothane sparing effect of R51703 produced a beneficial alteration of hemodynamic function. Data were obtained at equipotent halothane/R51703 (H/R) and halothane/saline (H/S) doses equivalent to 1.0, 1.5 and 2.0 MAC. In awake dogs, heart rates tended to be lower in dogs sedated with R51703, significantly so at 30 min for both doses, and at 90 and 120 min for the 0.2 and 0.4 mg/kg doses, respectively (P < 0.05). The cardiac index (CI) was lower at 60 min with both doses compared to the saline control group. Both doses of R51703 reduced mean blood pressure at 30, 90 and 120 min, and diastolic pressure at 30 and 90 min after administration; however, systolic blood pressure (SBP) was not altered. Overall, the cardiovascular alterations were minimal in conscious dogs and there was no evidence of respiratory depression. In the anesthetized dogs, at equipotent MAC, CI tended to be lower with H/R than with H/S, though the difference was not significant. Heart rate and stroke volume index also tended to be lower in the dogs treated with R51703, while systemic vascular resistance tended to be higher: these changes were not significant. Mean and SBP were higher at each MAC multiple in the H/R group. It was concluded that the halothane sparing effect of R51703 did not substantially improve hemodynamic function compared to the use of halothane alone at equipotent doses.