Determination of the welfare status of freeroaming dogs in two urban centres in Chile. / Determinación del estado de bienestar en perros callejeros de dos centros urbanos de Chile.

Free-roaming dogs are not only a public health and ethical problem, they are also an environmental and economic one. Although the general belief is that freeroaming dogs are not in good condition, there have been insufficient studies in Chile to address and analyse the issue. The objective of this research was to assess the welfare of free-roaming dogs in the centre of the cities of Santiago and Valparaíso. The evaluation was carried out using an observational method and assessed a total of 554 dogs. The following variables were analysed: body condition, motor impairment, skin condition, respiratory disease, reaction to humans and other variables. In addition, spatial distribution was considered, and age, sex and social behaviour were estimated. When the results were analysed in terms of frequency, it was found that, in Valparaíso (n = 204), 37% of the dogs assessed had compromised welfare (poor or fair), while 63% had positive welfare (good or optimal). In contrast, in Santiago (n = 350), only 21.7% had compromised welfare, while 78.3% had positive welfare. With respect to social behaviour, 55% of the dogs assessed in Valparaíso and 68% of those assessed in Santiago led a solitary lifestyle. Although most of the individuals were in good condition, a high percentage were unable to meet the requirements for them to live in harmony with their environment.

Les chiens de rue ou errants posent des problèmes non seulement de santé publique et d'éthique, mais aussi environnementaux et économiques. La condition générale de ces chiens est intuitivement perçue comme n'étant pas bonne mais au Chili le sujet n'a guère fait l'objet d'analyses approfondies. Les auteurs présentent les résultats d'une étude visant à évaluer le bien-être animal des chiens errants du centre-ville de Santiago et de Valparaíso. Cette évaluation a reposé sur l'observation de 554 chiens au total et sur l'analyse d'un certain nombre de variables dont la condition physique, les difficultés motrices, l'état de la peau et du pelage, la présence de maladies respiratoires et les réactions face à l'être humain. La distribution spatiale des chiens examinés a été consignée, ainsi que l'âge estimé, le sexe et le comportement social de chaque animal. Les résultats ont été analysés en termes de fréquence. À Valparaíso, les observations ont fait état d'un niveau de bien-être compromis (allant de mauvais à médiocre) chez 37 % des chiens (n = 204) et d'un pourcentage de 63 % de chiens présentant un niveau de bien-être satisfaisant (bon à optimal). En revanche, à Santiago (n = 350), 21 % seulement des chiens observés présentaient un état de bien-être compromis tandis que 78,3 % présentaient un état de bien-être satisfaisant. En ce qui concerne le comportement social, 55 % des chiens observés à Valparaíso et 68 % de ceux observés à Santiago avaient un mode de vie solitaire. Si la majorité des chiens se trouvaient en bon état physique, un pourcentage élevé d'entre eux ne parvenaient pas à satisfaire les besoins leur permettant de vivre en équilibre avec leur environnement.

Los perros callejeros constituyen no solo un problema de salud pública y ético, sino también, medioambiental y económico. Si bien se cree que estos perros no se encuentran en buenas condiciones, en Chile los estudios que abordan y analizan este tema son insuficientes. El objetivo de esta investigación fue evaluar el bienestar en perros callejeros en el centro de las ciudades de Santiago y Valparaíso. La evaluación se realizó a través de un método observacional en un total de 554 perros, y se analizaron las siguientes variables: condición corporal, dificultad motora, estado de la piel, enfermedad respiratoria, reacción hacia el humano y otras variables. Además, se consideró la distribución espacial y se estimó la edad, el sexo y la conducta social. Los resultados fueron analizados en términos de frecuencia, y se observó que en Valparaíso (n = 204), el 37% de los perros presentaba un bienestar comprometido (malo - escaso) mientras que el 63% presentaba un bienestar favorable (bueno u óptimo). En cambio, en Santiago (n = 350), sólo un 21,7% presentaba un estado de bienestar comprometido mientras que el 78,3% presentaba un estado de bienestar favorable. Asimismo, respecto a la conducta social, un 55% de los perros evaluados en Valparaíso y un 68% de los evaluados en Santiago mostraron un estilo de vida solitario. Si bien los individuos en su mayoría se encontraban en buenas condiciones, un alto porcentaje no lograba satisfacer las necesidades para estar en equilibrio con su entorno.

L-arginine supplementation normalizes bone turnover and preserves bone mass in streptozotocin-induced diabetic rats.

Osteopenia, an important complication of diabetes mellitus, is responsible of an increase in bone fracture and of a delay in fracture healing. The pathogenesis of this complication is unclear, however decreased availability and synthesis of nitric oxide (NO) may be regarded as a possible cause of disregulation of bone turnover. The aim of our study was to evaluate the effect of streptozotocin (STZ)-induced diabetes in the rat on bone mineral density (BMD) and bone turnover. We also examined whether supplementation of L-arginine (which acts as a NO substrate) could be beneficial for bone. After 6 weeks of STZ treatment, diabetic rats showed a significant decrease of BMD in the whole body, at the spine, at the pelvis, and at the femur. Bone turnover evaluation revealed a significant decrease in the serum levels of osteocalcin (a marker of bone formation), and an increase of the serum levels of the C-terminal telopeptide of type I collagen (RatLaps; a marker of bone resorption). L-arginine supplementation prevented the diabetes-induced reduction of BMD and osteocalcin, and the increase of RatLaps. These pharmacological actions of L-arginine produce a new suggestion that increase of NO synthesis and availability is potentially useful for effective prevention and treatment of osteopenia associated with diabetes.

Effects of calcitonin on the brain of aged rats.

We have recently demonstrated that calcitonin, a putative neuromodulator, may influence extrapyramidal motor system by decreasing nigro-striatal dopaminergic function. Since calcitonin is extensively used in aged patients, we have investigated whether calcitonin might influence extrapyramidal motor behavior (haloperidol-induced catalepsy and apomorphine-induced hyperactivity) in rats of different ages. Intracerebroventricular injection of salmon calcitonin (1 micrograms/kg) prevented apomorphine-induced hyperactivity in 2, 7, 18 or 21 month old rats, but potentiated haloperidol-induced catalepsy only in 2 or 7 month old rats. In addition, in all the animals salmon calcitonin significantly decreased the secretion of prolactin, an anterior pituitary hormone that may act at central level enhancing nigro-striatal dopaminergic activity.

Behavioral effects of amylin injected intracerebroventricularly in the rat.

Amylin is a peptide of pancreatic origin that has been reported to possess high-affinity binding sites in the brain and to affect central dopaminergic and serotonergic neurotransmission. Administered ICV the peptide induced a dose-dependent decrease of locomotor activity without affecting grooming and sniffing. At a dose of 5 micrograms/ rat, it antagonized the hypermotility and stereotypies induced by s.c. injection of amphetamine (2 mg/kg) or of the dopamine receptor agonist, apomorphine (250 mg/kg). Amylin did not change significantly the effect of haloperidol (0.5 mg/kg, s.c.) on locomotor activity, grooming, and sniffing. Moreover, the peptide did not modify the locomotor behavior of animals injected with the 5-HT2 antagonist, ritanserin (2 mg/kg, s.c.). These results suggest that amylin may exert motor effects, probably by interfering with central dopaminergic neurotransmission.

Effects of centrally injected amylin on sexually behavior of male rats.

Amylin (AMY) is a peptide of pancreatic origin principally involved in the carbohydrate metabolism, but that may interfere with central and peripheral dopamine (DA) pathways. The peptide, injected intracerebroventricularly (ICV) at the dose of 2.5 microg/rat, induced a decrease of copulatory activity in good copulators (GCO) and sluggish (SLU) male rats. The dose of 0.1 microg/rat did not affect significantly the sexual behavior of GCO rats, whereas AMY 0.5 microg/rat increased only the latency and reduced the frequency of ejaculation. At the dose of 2.5 microg/rat AMY antagonized the activation of sexual behavior induced by the DA receptor agonist, apomorphine administered subcutaneously (SC) at the dose of 100 microg/kg. Moreover, this inhibitory effect was blocked by the calcitonin gene-related peptide and AMY receptor antagonist, CGRP (8-37) fragment (injected ICV at the dose of 1 microg/rat). These data suggest that AMY may exert inhibitory effects on male sexual behavior in rats, probably interfering with central DA neurotransmission and with CGRP receptors.

Repeated calcitonin treatment reduces the stimulation of inositol phospholipid by norepinephrine and serotonin in rat hippocampus and cerebral cortex.

Stimulation of inositol phospholipid hydrolysis by norepinephrine or 5-hydroxytryptamine was reduced in hippocampal or cortical slices from rats repeatedly injected with (Asu1.7)eel-calcitonin (2.5 IU/kg i.p.). This effect was specific, as the basal or carbamylcholine-stimulated inositol phospholipid hydrolysis was unchanged in slices from calcitonin-injected animals. The reduced responsiveness to norepinephrine did not reflect a decreased number or affinity of alpha 1-adrenergic recognition sites, suggesting that calcitonin treatment leads to a reduced coupling between alpha 1-adrenoceptors and phospholipase C.

Hyperalgesic activity of parathyroid hormone and its fragments in male rats.

Results presented in this paper indicate that intracerebroventricular injection of parathyroid hormone reduces pain threshold in male rats. This effect is induced by whole molecule (84 amino acids) or by fragments 1-34 and 44-68 of PTH. The fragment 65-84 of PTH does not induce any change in pain threshold.

Effects of calcitonin on rat extrapyramidal motor system: behavioral and biochemical data.

The effects of i.v.c. injection of human and salmon calcitonin on biochemical and behavioral parameters related to the extrapyramidal motor system, were investigated in male rats. Calcitonin injection resulted in a potentiation of haloperidol-induced catalepsy and a partial prevention of apomorphine-induced hyperactivity. Moreover calcitonin induced a significant decrease in nigral GAD activity but no change in striatal DA and DOPAC concentration or GAD activity. The results are discussed in view of a primary action of calcitonin on the striatonigral GABAergic pathway mediating the DA-related behavioral messages of striatal origin.

Role of serotonin in the analgesic activity of calcitonin.

The acute effects of peripherally administered methysergide or phentolamine on the analgesic activity of salmon calcitonin (sCT) injected into the lateral ventricle were investigated in male rats. Methysergide, but not phentolamine, significantly (P less than 0.05) antagonized the analgesic activity of sCT at 60 and 120 min after the administration of the peptide. The results obtained suggest that the analgesic activity of sCT may involve central serotonergic system(s), while the central noradrenergic system does not seem to be needed for this activity.

Bimodal action of [Asu1,7]eel-calcitonin on phosphoinositide hydrolysis in cultured anterior pituitary cells.

[Asu1,7]Eel-calcitonin, a semisynthetic analog of eel-calcitonin displaying high stability and full biological activity, was used to study the effect of calcitonin on phosphoinositide turnover in cultured anterior pituitary cells. Incubation of cells with [Asu1,7]eel-calcitonin produced a slight, concentration-dependent increase in [3H]inositol monophosphate accumulation, without modifying thyrotropin-releasing hormone (TRH)-stimulated phosphoinositide hydrolysis. This effect was correlated with a stimulatory action on prolactin secretion. Conversely, a long-term preincubation with [Asu1,7]eel-calcitonin reduced basal as well as TRH-induced [3H]inositol monophosphate formation. This effect was concentration-dependent, was not due to an increase of cyclic AMP intracellular levels, and was attenuated in the presence of maximally effective concentrations of TRH. Such a long incubation in the presence of [Asu1,7]eel-calcitonin resulted in a marked inhibition of prolactin secretion. The present data confirm and extend previous findings showing an interference of calcitonin with the intracellular cascade consequent to membrane phospholipase C activation and further support a role for calcitonin in the modulation of hormone secretion at the pituitary.

Adrenomedullin and ocular inflammation in the rabbit.

Adrenomedullin administered peripherally in the rabbit (at doses of 1.25, 2.5 and 5 microg/kg ) caused a dose-dependent conjunctival hyperemia accompanied by an increase of inflammatory cell number and prostaglandin E(2) concentration in the aqueous humor, and of uveal vascular response and myeloperoxidase activity. The inflammatory effect of the peptide, injected at the dose of 5 microg/kg, was abolished by pretreatment with the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methylester (50 mg/kg, i.v.). Moreover, the i.v. pretreatment with the calcitonin gene-related peptide 8-37 fragment (calcitonin gene-related peptide, CGRP-(8-37), 2.5 microg/kg), receptor antagonist of CGRP, did not inhibit the conjunctival hyperemia. In contrast, the i.v. pretreatment with the adrenomedullin receptor antagonist, adrenomedullin-(22-52) fragment (2.5 microg/kg), abolished adrenomedullin-induced ocular inflammation. These results suggest that adrenomedullin causes conjunctival hyperemia, and this effect involves the nitric oxide system acting through specific adrenomedullin receptors.

L-arginine prevents bone loss and bone collagen breakdown in cyclosporin A-treated rats.

Cyclosporin A is implicated in the pathogenesis of post-transplantation bone disease. Because of recent evidence that cyclosporin A may cause renal and cardiovascular toxicity by inhibiting nitric oxide (NO) activity, and that NO slows bone remodeling and bone loss in animal and human studies, we investigated a possible link between NO production and beneficial effects on bone health in cyclosporin A-treated rats. Thirty-six 10-week-old male rats were assigned to six groups of six animals each, and treated for 4 weeks with: vehicle; cyclosporin A; L-arginine; N(G)-nitro-L-arginine methylester (L-NAME, a general inhibitor of NO synthase activity); a combination of cyclosporin A+L-arginine; and a combination of cyclosporin A+L-NAME. Whole body and regional (spine and pelvis) bone mineral content of rats were measured under basal conditions and at the end of the treatment period by dual-energy X-ray absorptiometry (DXA) scanning. Femur weights and serum concentrations of pyridinoline, a reliable marker of bone resorption, were measured at the end of the study period. Cyclosporin A-, L-NAME-, and cyclosporin A+L-NAME-treated rats had significantly lower bone mineral content and femur weights, and significantly higher pyridinoline levels than did control animals. The administration of L-arginine appeared to prevent bone loss caused by cyclosporin A, suggesting that this amino acid, which can be converted to produce NO, might prove useful in preventing disturbed bone modeling and inhibition of bone growth associated with cyclosporin A therapy.

A role for nitric oxide in the anti-ulcer activity of calcitonin gene-related peptide.

The anti-ulcer activity of calcitonin gene-related peptide (CGRP) was inhibited, in a dose-dependent manner, by pretreatment with NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Our results suggest that endogenous nitric oxide is involved in the anti-ulcer activity of CGRP.

Parathyroid hormone fragment 1-34 inhibits drug-induced inflammation in various experimental models.

We investigated the effect of the administration of rat parathyroid hormone-(1-34) on acute or chronic inflammatory processes in different experimental animal models. Fragment 1-34 of parathyroid hormone had an inhibitory effect in all inflammatory acute tests. The dose-response experiments showed that the maximal anti-inflammatory and anti-exudative effects appeared at the dose of 3.30 and 0.33 micrograms/kg, respectively. The anti-inflammatory effect was observed in the first phase of the inflammatory process. In the carrageenin-induced edema test the anti-inflammatory activity began to decline after 180 min. In contrast, this peptide was inactive in the inflammatory chronic test we used.

Protective effects of calcitonin gene-related peptide in different experimental models of gastric ulcers.

Intravenous administration of calcitonin gene-related peptide (CGRP) prevented in a dose-dependent manner reserpine-induced gastric mucosal damage, but failed to affect the lesions produced by ethanol administration. In pylorus-ligated rats, CGRP significantly reduced gastric volume, total acid and peptic activity output as well as ulcer formation. These protective effects of CGRP were not present when rats were pretreated with cysteamine. Our data suggest that CGRP exerts its antisecretory and antiulcer activity, at least in part, by interfering with somatostatin transmission.

Effects of calcitonin on morphine tolerance and withdrawal syndrome in morphine physically dependent rats.

We investigated the effect of acute or chronic peripheral administration of [Asu1.7]eel-calcitonin on the development of tolerance to the analgesic effect of morphine and on the naloxone-precipitated withdrawal syndrome in morphine-dependent rats. Neither the analgesic effect of acute morphine nor the development of tolerance to the antinociceptive effect of this drug was modified by calcitonin. However, the chronic but not the acute administration of calcitonin attenuated some signs and symptoms of morphine withdrawal.

Effect of amylin in various experimental models of gastric ulcer.

Subcutaneous administration of amylin (20-40 micrograms/kg) prevented, in a dose-dependent manner, reserpine- and serotonin-induced gastric damage, but the anti-ulcer effect was not present when lesions were induced by pylorus ligation. The protective effect of amylin was inhibited by pretreatment with capsicin as well as CGRP-(8-37), a calcitonin gene-related peptide (CGRP) and amylin receptor antagonist, and was significantly reduced by domperidone, a dopamine D2 receptor antagonist, or neostigmine, an inhibitor of acetylcholinesterase. Our data suggest that the gastroprotective activity of amylin in some experimental models of gastric ulcers involves capsaicin-sensitive fibers and CGRP receptors. Moreover, the peptide interferes, at least in part, with the dopaminergic and parasympathetic systems.

Effect of parathyroid hormone, centrally or peripherally injected, on gastric activity in male rats.

Parathyroid hormone (PTH) injected peripherally did not interfere with the development of experimental ulcers. Conversely, when PTH was administered i.c.v. the development of ulcers was significantly inhibited. The gastric secretory volume and acid output were also reduced. The possibility is discussed that this antisecretory activity of PTH may be due to a direct effect at the CNS level.

Effects of centrally of peripherally injected adrenomedullin on reserpine-induced gastric lesions.

Adrenomedullin intracerebroventricularly administered (0.1 to 20 ng/rat i.c.v.), showed significant gastroprotective activity in a dose-dependent manner. When the peptide was intravenously administered (1 to 1000 ng/kg i.v.) it did not show significant gastroprotective activity in the same test. The gastroprotective effect of the peptide (10 ng/rat) was abolished by bilateral adrenalectomy, by pretreatment with the beta-adrenoceptor antagonist, propranolol (1 mg/kg i.p.), or by a calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37) fragment (1 or 10 ng/rat i.c.v.). This study showed that adrenomedullin is protective against reserpine-induced gastric lesions, that the action involves sympathetic nerve activity, and moreover interferes with CGRP receptors.

Possible role of prolactin in the modification of medial basal hypothalamic glutamic acid decarboxylase activity.

The effects of acute and chronic injections of haloperidol, sulpiride and apomorphine on serum prolactin (PRL) levels and medial basal hypothalamus (MBH) glutamic acid decarboxylase (GAD) activity were investigated in male rats. Parallel changes in PRL and GAD activity were observed in acutely treated animals. Conversely, a return to normal of the GAD activity associated with high plasma PRL levels was induced by chronic haloperidol and sulpiride treatment. Results are discussed in the light of the possible existence of a hypothetical PRL-gamma-aminobutyric acid (GABA) subsidiary feedback loop.