Anti-Müllerian hormone in queens: Serum concentrations and total ovarian follicle population.

The objectives of this study were: a) To report anti-Müllerian hormone (AMH) serum concentrations in neonatal, pre and postpubertal female cats. b) To establish the relationship between serum AMH with either age and estrous cycle c) To correlate the total number of different ovarian follicle types with AMH in adult queens. A single blood sample was collected from 10 neonates (including 5 male), 15 prepubertal and 48 postpubertal female cats to measure AMH. Eight, 10, and 18 of this latter group were in follicular (FP), luteal phase (LP), and anestrus (AN), respectively. The total number of each follicle type was histologically counted using the Gougeon and Chainy (1987) formula in a subgroup of 10 adult queens. Overall AMH mean of these the female cats was 6.31 ± 0.54 ng/mL. The neonatal females had lower AMH serum concentrations than their male littermates (2.56 ± 0.49 vs. >23 ng/mL; P < 0.01). Concentrations were also higher in prepubertal than in neonatal and postpubertal cats (11.79 ± 1.36 vs. 2.56 ± 0.49 vs. 4.87 ± 0.38 ng/mL; P < 0.01). Queens below 12 mo of age had the highest AMH levels (10.41 ± 1.16; P < 0.01). Age was inversely correlated with AMH (r = -0.5; P < 0.01). Animals in FP had lower AMH concentrations than AN females (2.51 ± 0.33 vs. 5.46 ± 0.76 ng/mL; P < 0.05). No difference in the total number of each follicle type were found between either ovary (P > 0.05). A high correlation was only found between small antral follicles and AMH concentrations (r = 0.85; P < 0.01). It was concluded, that AMH can provide an indirect, reliable marker for the assessment of ovarian follicle size and functionality. Age as well as pubertal state should be considered when evaluating AMH concentrations in this species.

Physical, histological, endocrinological and steroidogenical evaluation of male cats postnatally exposed to sexual steroids.

To test the hypothesis that postnatal sexual steroids induce an impairment of domestic male cat reproductive function, this study describes the physical, endocrine, steroidogenical and histological effects of a single, high dose of a postnatal sexual steroid in this species. Twenty male kittens were randomly assigned within the first 24 h of birth to: Testosterone enanthate 12.5 mg sc (TE; n = 8), medroxyprogesterone acetate 10 mg sc (MA; n = 6), or Placebo sc (PL; n = 6). The cats were followed until puberty when they were castrated. Kittens achieved puberty without age differences among groups (P > 0.05). Two MA cats presented abnormal testicular descent. Histological evaluation of the MA (P < 0.01), but not of TE testes revealed decreased diameter (P < 0.01) and epithelial height (P < 0.01) of the seminiferous tubules. Leydig cell nuclear area was also reduced in this group. Conversely, tubular/intertubular ratio was increased in TE animals (P < 0.01). Quantitative real-time PCR analysis of mRNA expression of testicular tissue revealed no significant differences among groups for StAR, CYP17A1 and androgen receptors. TE animals showed decreased CYP19A1 mRNA expression (P < 0.05). In the first 4 postnatal weeks, fecal testosterone (T) values were high, basal and intermediate in TE, MA and PL (P < 0.05), respectively. These differences progressively diminished and the three groups presented basal T concentrations from the 7th week on (P > 0.05). It was concluded that the postnatal progestagen initially suppressed the gonadal axis and caused an impairment of spermatogenesis and testicular descent at puberty. Androgen treatment caused downregulation of the final steroidogenic cascade.

Postponement of canine puberty by neonatal administration of a long term release GnRH superagonist.

The objective of this study was to assess the efficiency and clinical safety of postnatal administration of a GnRH agonist on canine puberty postponement. Sexual steroids and histological gonadal changes were also described. Twenty-four littermate puppies were randomly assigned to: Deslorelin acetate 18.8 mg sc (DESLO; n = 12) or Placebo: sc (PLACE; n = 12) postnatally. The dogs were clinically and endocrinologically followed up until puberty when they were gonadectomized and their gonads histomorphometrically studied. Deslorelin postponed the age of puberty (72.7 ±â€¯4.8 vs. 35.8 ±â€¯1.9 weeks; P < 0.01) in these dogs. At the time of this submission, 3 DESLO dogs (108 weeks old) remain non-pubertal. All dogs concluded growing at a similar age (29.75 ±â€¯2.44 vs. 29.25 ±â€¯0.90 weeks; P > 0.1) independently of their group and pubertal status. None of the females had side effects while the 2 non pubertal DESLO males presented bilateral cryptorchydism. All the bitches ovulated at puberty (P > 0.1) and the 2 DESLO that were mated became pregnant. Deslorelin postponed basal serum sexual steroids up to puberty in both genders (P < 0.01). The histomorphometrical study of the testes revealed that the tubular diameter (P < 0.05), germinal epithelium height and composition (P < 0.01) were decreased in DESLO group. Ovarian structures did not differ between treatments (P > 0.05). It was concluded that postnatal deslorelin decreased sexual steroids reversibly postponing puberty in both genders without side effects in bitches and causing 2/6 of cryptorchydism and impairment of testicular histomorphometry in male dogs.

Failure of a single dose of medroxyprogesterone acetate to induce uterine infertility in postnatally treated domestic cats.

In mice and sheep, neonatal administration of progesterone or progestins inhibited development of uterine glands. The aims of the present study were (1) to describe uterine gland development on postnatal Days 6 to 8 and (2) to evaluate the effects of a single postnatal administration of a progestin on reproduction and adult uterine glands morphology and function in domestic cats. Necropsy was performed on three 1-week-old female cats which had died unrelated to this study. Ten female kittens were randomly assigned within the first 24 hours of birth to: medroxyprogesterone acetate 10 mg/animal subcutaneously (MPA; n = 6) or placebo (PLC; n = 4) and followed up until puberty when they were mated. Twenty-four days after the end of estrus, ovulation and pregnancy were diagnosed by serum progesterone measurement and ultrasonography, respectively. Then, all the cats were ovariohysterectomized. After necropsy or surgery, the excised organs were histologically evaluated. Seven queens ovulated (4 of 6 MPA and 3 of 4 PLC; P > 0.1) and were pregnant (P > 0.1). Four MPA cats presented endometrial hyperplasia and one of them developed a pyometra. The 1-week-old females presented uterine glands in the stage of budding and incipient penetration of the glandular epithelium into the underlying stroma. The MPA-treated queens revealed that the area occupied by uterine glands per square-micrometer (0.55 ± 0.2 vs. 0.49 ± 0.2; P > 0.1) and the height of the glandular epithelium (µm; 24.5 ± 6.7 vs. 24.4 ± 7.2; P > 0.1) did not differ from those of the PLC group. Neither significant gross nor microscopical differences were also found for ovaries (P > 0.1). It is concluded that 1-week-old kittens had an incipient stage of uterine gland development and that a single postnatal supraphysiological dose of MPA did not alter uterine adenogenesis in this species. Furthermore, this treatment seemed to predispose to uterine disease without prevention of fertility.

Histologic effect of a postnatal slow-release GnRH agonist on feline gonads.

In postnatal domestic cats, GnRH agonists suppressed fecal concentrations of sexual steroids and delayed puberty. The aim of this study was to describe the gross and microscopic morphometric effects of a single administration of the GnRH agonist, deslorelin acetate, on the gonads of postnatally treated cats. Twenty-seven postnatal male (n = 14) and female (n = 13) kittens were randomly assigned to one of the following treatment groups within the first 24 hours of birth: deslorelin acetate (1.6 mg, subcutaneous; DA, n = 16) or control that remained untreated (CO, n = 11) and spayed or castrated immediately after the onset of puberty. After surgical removal, the gonads were gross and histologically assessed. Sertoli cells also were examined immunohistochemically. Comparisons between the treatments were carried out by the Student t test. Gross gonadal wet weight and volume as well as gonadosomatic index were significantly lower in the DA than those in the CO males; these same parameters were not different in females. Primordial (461.4 + 3.0 vs. 1074.3 + 117.5; P < 0.01), primary (59.1 + 13.5 vs. 165.4 + 24.6; P < 0.01), and secondary (17.5 + 2.6 vs. 31.17 + 8.1; P < 0.05) follicles per mm(2) were decreased in DA than in CO gonads. Epididymal sperm motility and morphology were normal in all but two DA cats that had too few sperm to be evaluated. Germinal epithelial height (µm; 39.68 + 0.92 vs. 72.7 + 1.2; P < 0.01) and most of their cellular components as well as the Sertoli (cm(3); 0.1 + 0.02 vs. 0.24 + 0.05; P < 0.01) cells were diminished in the DA cats. Gonadotropin-releasing hormone agonist endocrine disruption during the neonatal critical reproductive time window may have a potential as a contraceptive agent in domestic felids.

Targeting apoptosis pathways in cancer and perspectives with natural compounds from mother nature.

Although the incidences are increasing day after day, scientists and researchers taken individually or by research group are trying to fight against cancer by several ways and also by different approaches and techniques. Sesquiterpenes, flavonoids, alkaloids, diterpenoids, and polyphenolic represent a large and diverse group of naturally occurring compounds found in a variety of fruits, vegetables, and medicinal plants with various anticancer properties. In this review, our aim is to give our perspective on the current status of the natural compounds belonging to these groups and discuss their natural sources, their anticancer activity, their molecular targets, and their mechanism of actions with specific emphasis on apoptosis pathways, which may help the further design and conduct of preclinical and clinical trials. Unlike pharmaceutical drugs, the selected natural compounds induce apoptosis by targeting multiple cellular signaling pathways including transcription factors, growth factors, tumor cell survival factors, inflammatory cytokines, protein kinases, and angiogenesis that are frequently deregulated in cancers and suggest that their simultaneous targeting by these compounds could result in efficacious and selective killing of cancer cells. This review suggests that they provide a novel opportunity for treatment of cancer, but clinical trials are still required to further validate them in cancer chemotherapy.

Effect of GnRH analogs in postnatal domestic cats.

The aim of this study was to reproductively assess the clinical and hormonal effects of a GnRH agonist (AG) and an antagonist (AN) administered during the postnatal period in domestic cats. Forty-eight male and female postnatal kittens were randomly assigned to deslorelin acetate 1.6 mg subcutaneous (AG; n = 16), acyline 33 µg/100 g subcutaneous weekly for 3 months (AN; n = 16), or control (CO; n = 16) which remained untreated. The cats were followed up (behavioral observation, physical examination, fecal sexual steroid determinations, mating test, and pregnancy diagnosis) up to puberty. Puberty was delayed (weeks) in the AG animals (62.9 ± 3.5; P < 0.01) but not in the AN (15.5 ± 1.7; P > 0.05) when they were compared with CO kittens (13.4 ± 0.4). Fifteen (15/16) of the AN and CO animals, and only 11 of 16 cats of the AG group were fertile (P > 0.1). No differences were found in body weight (P > 0.1) and measurements (P > 0.1), libido (P > 0.1) and in the appearance of side effects (P > 0.1; except a pyometra in an AG female) among groups. In both AG- and AN-treated males (testosterone; P < 0.01) and females (estradiol-17ß; P < 0.01) fecal hormone concentrations were lower than in CO group during the first five postnatal weeks but not later. It is concluded that the neonatal administration of these AG and AN decreased fecal sexual steroids during the first postnatal weeks causing, the agonists but not the antagonist, a significant, reversible delay in puberty appearance.

Fecal estradiol-17ß and testosterone in prepubertal domestic cats.

The aim of this article was to describe the time course of prepubertal sexual steroids in domestic cats. Fourteen newborn kittens were followed up until puberty (physical, behavioral, and hormonal changes). Fecal testosterone [T; males] and E estradiol 17-ß [E2; females] concentrations were analyzed by repeated measures ANOVA and two consecutive time windows (TWs) were used to compare changes in both male (postnatal weeks 1-4 vs. 5-14) and females (postnatal weeks 1-5 vs. 6-13). Puberty was achieved 14.3 ± 0.3 and 13.3 ± 0.4 weeks after birth in male and female cats, respectively. In both genders, during TW-1 fecal steroids concentrations were similar (males) or even higher (females) to that previously described for mature cats. Fecal T (P < 0.01) and E2 (P < 0.01) varied throughout the weeks. Differences were found when hormonal concentrations of TW-1 were compared with those of TW-2 both for male (61.4 ± 7.9 vs. 16.9 ± 2.2 ng/g; P < 0.01) and female (78.2 ± 12.5 vs. 11.2 ± 4.0 ng/g; P < 0.01) cats. It is concluded that in domestic cats there is a sexual steroid surge during the first 4 and 5 postnatal weeks in male and female animals, respectively.

Domestic queens under natural temperate photoperiod do not manifest seasonal anestrus.

Domestic cat seasonality between the tropics and the arctic zones is scarcely described and results are inconsistent. The aim of this study was to describe domestic feline seasonal patterns under a natural temperate photoperiod. A total of 372 estrous cycles were studied in 34 post pubertal cats during 900 days. The queens were housed in a cat colony (31°25' South Latitude, 64°11' West Longitude), acclimated under natural photoperiod and daily observed for reproductive behavior. Vaginal cytology was conducted three times a week. For each cat the number of estrous cycles and days in estrus per month for each year were recorded. The months of the year were grouped in four periods of 3 months each according to day length and photoperiod. Comparisons of estrous days among periods were performed by ANOVA for repeated measures. All the cats had estrous cycles throughout the year without intervals of anestrus. Mean number of estrous days differed among the periods (P<0.01), those of long day length and ascending photoperiod being greater (12.5±0.6) to those of descending photoperiod either with long (8.9±0.7) or short (9.3±0.7) days. When the two periods with ascending day lengths were merged and compared to the two periods with descending day lengths merged, the number of estrous days were greater when day length ascended (P<0.01). Nearly 60% of the estrous cycles occurred during the periods of ascending day length. It is concluded, that domestic cats under natural temperate photoperiod have estrous cycles throughout the year showing peak activity the months with increasing photoperiod.

Percutaneous endoscopic suturing is an alternative treatment for persistent gastrocutaneous post-PEG fistula.

Persistent gastrocutaneous fistula after the removal of a gastrostomy tube is an unusual complication associated with percutaneous endoscopic gastrostomy (PEG). Surgical closure has been usually the treatment of choice. Several endoscopic methods have been previously attempted to close the fistula, usually with poor results. We report a successful case of percutaneous endoscopic suturing of a persistent gastrocutaneous post-PEG fistula, using a monofilament absorbable suture. A biopsy forceps was used to deepithelialize both ends of the fistulous tract to promote granulation tissue formation. The gastrocutaneous fistula closed completely after the procedure and there were no complications during the follow-up.

Long-term melatonin treatment prolongs interestrus, but does not delay puberty, in domestic cats.

The objective was to assess the efficacy and safety of long-term administration of melatonin (either as an implant or given orally) on interestrus intervals in domestic cats. Additionally, the effect of melatonin implants on puberty postponement was studied. For these purposes, two randomized controlled trials were conducted. In the first, 68 interestrus intervals (in 28 postpubertal queens) were studied, and in the second, 32 prepubertal female cats were used. During anovulatory interestrus intervals (27 ovulatory interestrus intervals were excluded), postpubertal cats were assigned to the following three treatments: melatonin implant 18 mg/cat SC (n = 17; MEI); melatonin tablets, 4 mg/cat/d orally until the onset of estrus (n = 12; MEO); or control (n = 12; CTL). Prepubertal females were randomly assigned to the following three treatments: melatonin 18 mg/cat sc implants at either 1.9 ± 0.3 kg (MEI-A; n = 12) or 1.5 ± 0.3 kg (MEI-B; n = 10) body weight; or control (CTL; n = 10). Interestrus intervals in postpubertal MEI, MEO, and CTL groups were 63.8 ± 5.4, 63.0 ± 5.3 and 19.2 ± 1.4 d (P < 0.05), respectively. In these groups, intervals between onset of treatment and the first estrus cycle were 51.0 ± 4.7, 50.0 ± 6.1, and 12.6 ± 1.1 d (P < 0.05). In the second experiment, neither age (MEI-A: 232.4 ± 10.5, MEI-B: 208.6 ± 13.0 and CTL: 192.4 ± 20.1 d; P > 0.1) nor body weight (P > 0.1) at puberty differed among groups. None of the cats in either study had clinically apparent side effects. We concluded that long-term melatonin treatment of domestic cats slightly prolonged interestrus intervals, but did not postpone puberty.

Clips for the prevention and treatment of postpolypectomy bleeding (hemoclips in polypectomy).

INTRODUCTION: The most accurate method for the prevention and treatment of complications after polypectomy has not been well defined. The prophylactic use of hemoclips may reduce the risk of bleeding, mainly in pedunculated big polyps. OBJECTIVE: To evaluate the accuracy of hemoclips in the prophylaxis and treatment of bleeding after endoscopic polypectomy. MATERIAL AND METHODS: Retrospective study of 223 consecutive endoscopic polypectomies performed in our Endoscopy Unit between january and october 2001. Hemoclips were routinely used only for large polyps (15 to 40 mm); all of them were located in the colon except one, a gastric polyp. RESULTS: From a total of 223 polypectomies (215 patients), hemoclips were used for 34 (15.2%), in 30 of them just before and in 4 just after polypectomy. When used prophylactically no complication was observed, except one mild bleeding episode (3.3%) that stopped with the placing of a second hemoclip. The therapeutic clipping (4 polypectomies) induced immediate haemostasis in all cases. CONCLUSIONS: The prophylactic use of hemoclips is associated with a very low risk of bleeding after endoscopic resection of big polyps. Therapeutic clipping is an effective measure for polypectomy-related bleeding.