Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up.

INTRODUCTION: Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child's neurodevelopment and behaviour development, overall health and mortality. METHODS AND ANALYSIS: This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed using the intention-to-treat approach. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (Dutch WMO-law) did not apply to our study (W21_386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results.

Arginine Vasotocin Directly Regulates Spermatogenesis in Adult Zebrafish (Danio rerio) Testes.

The neuropeptide vasopressin is known for its regulation of osmotic balance in mammals. Arginine vasotocin (AVT) is a non-mammalian homolog of this neuropeptide that is present in fish. Limited information suggested that vasopressin and its homologs may also influence reproductive function. In the present study, we investigated the direct effect of AVT on spermatogenesis, using zebrafish as a model organism. Results demonstrate that AVT and its receptors (avpr1aa, avpr2aa, avpr1ab, avpr2ab, and avpr2l) are expressed in the zebrafish brain and testes. The direct action of AVT on spermatogenesis was investigated using an ex vivo culture of mature zebrafish testes for 7 days. Using histological, morphometric, and biochemical approaches, we observed direct actions of AVT on zebrafish testicular function. AVT treatment directly increased the number of spermatozoa in an androgen-dependent manner, while reducing mitotic cells and the proliferation activity of type B spermatogonia. The observed stimulatory action of AVT on spermiogenesis was blocked by flutamide, an androgen receptor antagonist. The present results support the novel hypothesis that AVT stimulates short-term androgen-dependent spermiogenesis. However, its prolonged presence may lead to diminished spermatogenesis by reducing the proliferation of spermatogonia B, resulting in a diminished turnover of spermatogonia, spermatids, and spermatozoa. The overall findings offer an insight into the physiological significance of vasopressin and its homologs in vertebrates as a contributing factor in the multifactorial regulation of male reproduction.

Atosiban interacts with growth hormones as adjuvants in frozen-thawed embryo transfer cycles.

Objective: To investigate the interaction between atosiban and growth hormone (GH) as adjuvants in frozen-thawed embryo transfer (FET) cycles. Method: A total of 11627 patients who underwent FET at Xiamen University Affiliated Chenggong Hospital between January 2018 to December 2022 were retrospectively analyzed. Among them, 482 patients received atosiban and 275 patients received GH. The interactions were estimated by comparing the odds ratio (OR) for pregnancy comparing patients with or without atosiban adjuvant in cohorts stratified according to the presence of GH use in either the overall cohort or a propensity score (PS) matched cohort. An interaction term (atosiban × GH) was introduced to a multivariate model to calculate the ratio of OR (ORR) adjusted for confounders. Results: For all patients receiving atosiban administration, no obvious effect on pregnancy was observed in comparison with either matched or unmatched controls. However, when the patients were stratified according to GH administration, atosiban showed a significant association with clinical pregnancy in comparison with either matched or unmatched controls among patients with GH treatment with rate ratios (RR) of 1.32 (95%CI: 1.05,1.67) and 1.35 (95%CI: 1,1.82), respectively. On the other hand, however, the association was absent among patients without GH treatment. The adjusted ORRs in both matched and unmatched cohorts were 2.44 (95%CI: 1.07,5.84) and 1.95 (95%CI: 1.05, 3.49) respectively. Conclusion: The combination use of atosiban and GH in FET cycles is potentially beneficial to the pregnancy. However, indications for the use of atosiban and GH may need further assessment.

Intraperitoneal administration of arginine vasotocin (AVT) induces anorexigenic and anxiogenic actions via the brain V1a receptor-signaling pathway in the tiger puffer, Takifugu rubripes.

Arginine vasotocin (AVT) is produced mainly in the hypothalamus and as a neurohypophyseal hormone peripherally regulates water-mineral balance in sub-mammals. In addition, AVT-containing neurons innervate several areas of the brain, and AVT also acts centrally as both an anorexigenic and anxiogenic factor in goldfish. However, it is unclear whether these central effects operate in fish in general. In the present study, therefore, we investigated AVT-like immunoreactivity in the brain of the tiger puffer, a cultured fish with a high market value in Japan and also a representative marine teleost species, focusing particularly on whether AVT affects food intake and psychomotor activity. AVT-like immunoreactivity was distributed higher in the ventral region of the telencephalon, the hypothalamus and midbrain. Intraperitoneal (IP) administration of AVT at 100 pmol g-1 body weight (BW) increased the immunoreactivity of phosphorylated ribosomal proteinS6 (RPS6), a neuronal activation marker, in the telencephalon and diencephalon, decreased food consumption and enhanced thigmotaxis. AVT-induced anorexigenic and anxiogenic actions were blocked by IP co-injection of a V1a receptor (V1aR) antagonist, Manning compound (MC) at 300 pmol g-1 BW. These results suggest that AVT acts as an anorexigenic and anxiogenic factor via the V1aR-signaling pathway in the tiger puffer brain.

Administration of Atosiban, an oxytocin receptor antagonist, ameliorates autistic-like behaviors in a female rat model of valproic acid-induced autism.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients. In the study, we specifically explored the role of the OXT signaling pathway in a VPA-induced female rat's model of autism. The data showed that there was an increase of either oxytocin or its receptor expressions in both the hippocampus and the prefrontal cortex of VPA-induced female offspring. To determine if the excess of OXT signaling contributed to autism symptoms in female rats, exogenous oxytocin and oxytocin receptor antagonists Atosiban were used in the experiment. It was found that exogenous oxytocin triggered autism-like behaviors in wild-type female rats by intranasal administration. More interestingly, several autism-like deficits including social interaction, anxiety, and repeat stereotypical sexual behavior in the VPA female offspring were significantly attenuated by oxytocin receptor antagonists Atosiban. Moreover, Atosiban also effectively improved the synaptic plasticity impairment induced by VPA in female offspring. Our results suggest that oxytocin receptor antagonists significantly improve autistic-like behaviors in a female rat model of valproic acid-induced autism.

Intracerebroventricular injection of kisspeptin in male rats activates hypothalamo-pituitary-gonadal axis, but not hypothalamo-pituitary-adrenal axis.

Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 µg), kisspeptin + astressin 2B (1 µg), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.

The oxytocin antagonist cligosiban reduces human prostate contractility: Implications for the treatment of benign prostatic hyperplasia.

BACKGROUND AND PURPOSE: With increasing life expectancy, benign prostatic hyperplasia (BPH) consequently affects more ageing men, illustrating the urgent need for advancements in BPH therapy. One emerging possibility may be the use of oxytocin antagonists to relax smooth muscle cells in the prostate, similar to the currently used (although often associated with side effects) α1-adrenoceptor blockers. EXPERIMENTAL APPROACH: For the first time we used live-imaging, combined with a novel image analysis method, to investigate the multidirectional contractions of the human prostate and determine their changes in response to oxytocin and the oxytocin antagonists atosiban and cligosiban. Human prostate samples were obtained and compared from patients undergoing prostatectomy due to prostate cancer as well as from patients with transurethral resection of prostate tissue due to severe BPH. KEY RESULTS: The two cohorts of tissue samples showed spontaneous multidirectional contractions, which significantly increased after the addition of oxytocin. Different to atosiban, which showed ambiguous effects of short duration, only long-acting cligosiban reliably prevented, as well as counteracted, any contractile oxytocin effect. Furthermore, cligosiban visibly reduced not only oxytocin-induced contractions, but also showed intrinsic activity to relax prostatic tissue. CONCLUSION AND IMPLICATIONS: Thus, the oxytocin antagonist cligosiban could be an interesting candidate in the search for novel BPH treatment options.

Bryophyllum pinnatum Inhibits Oxytocin and Vasopressin Signaling in Myometrial Cells.

The medicinal plant Bryophyllum pinnatum was previously shown to block oxytocin (OT)-induced signals in myometrial cells, consistent with its tocolytic effect observed in patients. OT activates not only OT receptors but also V1A receptors, two receptors with high receptor homology that are both expressed in the myometrium and play a crucial role in myometrial contraction signaling. We aimed to study the molecular pharmacology of B. pinnatum herbal preparations using specific receptor ligands, the human myometrial cell line hTERT-C3, and cell lines expressing recombinant human OT and V1A receptors.We found that press juice from B. pinnatum (BPJ) inhibits both OT- and vasopressin (AVP)-induced intracellular calcium increases in hTERT-C3 myometrial cells. In additional assays performed with cells expressing recombinant receptors, BPJ also inhibited OT and V1A receptor-mediated signals with a similar potency (IC50 about 0.5 mg/mL). We further studied endogenous OT- and AVP-sensitive receptors in hTERT-C3 cells and found that OT and AVP stimulated those receptors with similar potency (EC50 of ~ 1 nM), suggesting expression of both receptor subtypes. This interpretation was corroborated by the antagonist potencies of atosiban and relcovaptan that we found. However, using qPCR, we almost exclusively found expression of OT receptors suggesting a pharmacological difference between recombinant OT receptors and native receptors expressed in hTERT-C3 cells.In conclusion, we show that B. pinnatum inhibits both OT and AVP signaling, which may point beyond its tocolytic effects to other indications involving a disbalance in the vasopressinergic system.

Comparison of terbutaline and atosiban as tocolytic agents in intrauterine repair of myelomeningocele: a retrospective cohort study.

BACKGROUND: Myelomeningocele (MMC) is a neural tube defect disease. Antenatal repair of fetal MMC is an alternative to postnatal repair. Many agents can be used as tocolytics during the in utero fetal repair such as ß2-agonists and oxytocin receptor antagonists, with possible maternal and fetal repercussions. This study aims to compare maternal arterial blood gas analysis between terbutaline or atosiban, as tocolytic agents, during intrauterine MMC repair. METHODS: Retrospective cohort study. Patients were divided into two groups depending on the main tocolytic agent used during intrauterine MMC repair: atosiban (16) or terbutaline (9). Maternal arterial blood gas samples were analyzed on three moments: post induction (baseline, before the start of tocolysis), before extubation, and two hours after the end of the surgery. RESULTS: Twenty-five patients were included and assessed. Before extubation, the terbutaline group showed lower arterial pH (7.347 ± 0.05 vs. 7.396 ± 0.02 for atosiban, p = 0.006) and higher arterial lactate (28.33 ± 12.76 mg.dL-1 vs. 13.06 ± 6.35 mg.dL-1, for atosiban, p = 0.001) levels. CONCLUSIONS: Patients who received terbutaline had more acidosis and higher levels of lactate, compared to those who received atosiban, during intrauterine fetal MMC repair.

Early starvation in European seabass (Dicentrarchus labrax) larvae has no drastic effect on hepatic intermediary metabolism in juveniles.

The present study aims to investigate nutritional programming through early starvation in the European seabass (Dicentrarchus labrax). European seabass larvae were fasted at three different developmental periods for three durations from 60 to 65 dph (F1), 81 to 87 dph (F2), and 123 to 133 dph (F3). Immediate effects were investigated by studying gene expression of npy (neuropeptide Y) and avt (Arginine vasotocin) in the head, while potential long-term effects (i.e., programming) were evaluated on intermediary metabolism later in life (in juveniles). Our findings indicate a direct effect regarding gene expression in the head only for F1, with higher avt mRNA level in fasted larved compared to controls. The early starvation periods had no long-term effect on growth performance (body weight and body length). Regarding intermediary metabolism, we analyzed related key plasma metabolites which reflect the intermediary metabolism: no differences for glucose, triglycerides, and free fatty acids in the plasma were observed in juveniles irrespective of the three early starvation stimuli. As programming is mainly linked to molecular mechanisms, we then studied hepatic mRNA levels for 23 key actors of glucose, lipid, amino acid, and energy metabolism. For many of the metabolic genes, there was no impact of early starvation in juveniles, except for three genes involved in glucose metabolism (glut2-glucose transporter and pk-pyruvate kinase) and lipid metabolism (acly-ATP citrate lyase) which were higher in F2 compared to control. Together, these results highlight that starvation between 81 to 87 dph may have more long-term impact, suggesting the existence of a developmental window for programming by starvation. In conclusion, European seabass appeared to be resilient to early starvation during larvae stages without drastic impacts on intermediary metabolism later in life.

Effects of atosiban on clinical outcome in frozen-thawed embryo transfer: a propensity score matching study.

PURPOSE: To evaluate the effects of atosiban on clinical outcomes in patients undergoing frozen-thawed embryo transfer. METHODS: The clinical data of 1093 infertile patients who underwent frozen-thawed embryo transfer in our center from January 2019 to December 2020 were retrospectively analyzed (control, 418; atosiban, 675). Propensity score matching (PSM) analysis identified 400 matched pairs of patients. The implantation rate, clinical pregnancy rate, live birth rate, biochemical pregnancy rate, abortion rate, multiple pregnancy rate, and ectopic pregnancy rate between the two groups were compared. RESULTS: Before PSM, patients differed by infertility factors, number of transferred embryos, and endometrial preparation protocol (P < 0.05). After PSM, characteristics were similar in corresponding patients of the atosiban and control groups. After propensity score matching, we found that there was no significant difference in the implantation rate, clinical pregnancy rate, live birth rate, biochemical pregnancy rate, abortion rate, multiple pregnancy rate, and ectopic pregnancy rate in atosiban and control group (P > 0.05). CONCLUSION: Atosiban did not improve the clinical outcomes of infertile patients with frozen-thawed embryo transfer.

Distribution of vasotocin- and vasoactive intestinal peptide- like immunoreactivity in the brain of penduline tit

Penduline tits are songbirds, used as model animals in numerous studies of sexual conflict. Nevertheless, the distribution of neuropeptides in the brain of this avian species remains largely unknown. Here we present some of the first results on distribution of vasotocin (AVT) and vasoactive intestinal peptide (VIP) in the brain of this songbird species, using immunohistochemical mapping. The bulk of AVT-like cells are found in the hypothalamic supraoptic, paraventricular and suprachiasmatic nuclei, medial bed nucleus of the stria terminalis, and along the lateral forebrain bundle. Most AVT-like fibres course toward the median eminence, but also in the medial bed nucleus of the stria terminalis, preoptic area and lateral septum. Further terminal fields occur in the dorsal thalamus, ventral tegmental area and pretectal area. Most VIP-like cells are in the lateral septal organ and arcuate nucleus. VIP-like fibres are distributed extensively in the hypothalamus, preoptic area, lateral septum, nucleus of the diagonal band. They are also found in the medial bed nucleus of the stria terminalis, amygdaloid nucleus of taenia, robust nucleus of the arcopallium, caudo-ventral hyperpallium, nucleus accumbens and the brainstem. The results indicate a high degree of conservatism in both AVT and VIP neuropeptidergic systems across avian species, as well as the different vertebrate taxa. The anatomical distribution of AVT and VIP in the penduline tit supports an involvement of these peptides in reproductive behaviours and social decision making, widely studied in this wild bird species

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Oxitocina-vasopresina: el futuro en tratamientos / Oxytocin-Vasopressin: the Future of Treatments

Las acciones de la oxitocina contemplan aspectos que incluyen la modulación de conductas destinadas al cuidado y crecimiento saludable de la descendencia. la oxitocina está relacionada con patrones sexuales y conducta maternal, actúa como neurotransmisor en el cerebro ejerciendo un papel esencial regulando el comportamiento social y afectivo. Investigaciones recientes demostraron que la oxitocina aumenta la empatía, facilita la conducta social, la confieanza hacia otros, y modifica la forma de procesamiento de las señales sociales, su codificación e interpretación, para así lograr una adecuada relación con pares. Estudios que apoyan el posible uso terapéutico de estas neurohormonas revelan datos alentadores al demostrar que mejoran la ansiedad social, que la oxitocina reduciría los síntomas psicóticos y disminuye déficit de la cognición social que no mejoran con tratamientos actuales. Por razones farmacocinéticas la vía de administración terpéutica es intranasal, lo cual aporta comodidad en su aplicación. Los trastornos psiquiátricos que se están investigando para evaluar el potencial beneficio del uso de estos neuropéptidos son esquizofrenia, trastornos del espectro autista, trastornos de ansiedad y estrés, y trastorno bordeline de la personalidad. El objetivo de esta revisión es actualizar avances en la investigación que sustentan la tuilización de estos neuropéptidos como propuesta terapéutica en psiquiatría

Oxytocin effects encompass aspects which include the modulation of behaviors intended for the care and healthy gowth of the offspring. Oxytocin is related to sexual patterns and maternal behavior and acts as a neurotransmitter in the brain, playing a key role in social and affective behavior. Recent studies have demonstrated that oxytocin increases empathy, facilitates social behavior, trust towards others, and also changes the way in which social signals are processed, as well as their coding and interpretation, thus leading to a suitable relationship with peers. Studies supporting the potential therapeutic use of these neurohormones reveal encouraging data by demonstrating that these imporve social anxiety, that oxyctocin might reduce psychotic symptoms and social cognitive deficit that do not imporve with the treatments aviable. For pharmacokinetics reasons, the route of administration of oxytocin is intranasal, which makes its application more comfortable. The psychiatric disorders which disorders that are currently being investigated to assess the potential benefit of oxytocin are schizophrenia, autistic spectrum disorders, anxiety disorders and stress, and bordeline personality disorder. The purpose of this review is to provide an updante on the investigations that justify the use of these neuropeptide as therapeutic treatment

Oxitocina-vasopresina: el futuro en tratamientos / Oxytocin-Vasopressin: the Future of Treatments

Las acciones de la oxitocina contemplan aspectos que incluyen la modulación de conductas destinadas al cuidado y crecimiento saludable de la descendencia. la oxitocina está relacionada con patrones sexuales y conducta maternal, actúa como neurotransmisor en el cerebro ejerciendo un papel esencial regulando el comportamiento social y afectivo. Investigaciones recientes demostraron que la oxitocina aumenta la empatía, facilita la conducta social, la confieanza hacia otros, y modifica la forma de procesamiento de las señales sociales, su codificación e interpretación, para así lograr una adecuada relación con pares. Estudios que apoyan el posible uso terapéutico de estas neurohormonas revelan datos alentadores al demostrar que mejoran la ansiedad social, que la oxitocina reduciría los síntomas psicóticos y disminuye déficit de la cognición social que no mejoran con tratamientos actuales. Por razones farmacocinéticas la vía de administración terpéutica es intranasal, lo cual aporta comodidad en su aplicación. Los trastornos psiquiátricos que se están investigando para evaluar el potencial beneficio del uso de estos neuropéptidos son esquizofrenia, trastornos del espectro autista, trastornos de ansiedad y estrés, y trastorno bordeline de la personalidad. El objetivo de esta revisión es actualizar avances en la investigación que sustentan la tuilización de estos neuropéptidos como propuesta terapéutica en psiquiatría (AU)

Oxytocin effects encompass aspects which include the modulation of behaviors intended for the care and healthy gowth of the offspring. Oxytocin is related to sexual patterns and maternal behavior and acts as a neurotransmitter in the brain, playing a key role in social and affective behavior. Recent studies have demonstrated that oxytocin increases empathy, facilitates social behavior, trust towards others, and also changes the way in which social signals are processed, as well as their coding and interpretation, thus leading to a suitable relationship with peers. Studies supporting the potential therapeutic use of these neurohormones reveal encouraging data by demonstrating that these imporve social anxiety, that oxyctocin might reduce psychotic symptoms and social cognitive deficit that do not imporve with the treatments aviable. For pharmacokinetics reasons, the route of administration of oxytocin is intranasal, which makes its application more comfortable. The psychiatric disorders which disorders that are currently being investigated to assess the potential benefit of oxytocin are schizophrenia, autistic spectrum disorders, anxiety disorders and stress, and bordeline personality disorder. The purpose of this review is to provide an updante on the investigations that justify the use of these neuropeptide as therapeutic treatment (AU)

Effects of Abdominal Breathing on State Anxiety, Stress, and Tocolytic Dosage for Pregnant Women in Preterm Labor

PURPOSE: The purpose of this study was to identify the effects of abdominal breathing on state anxiety, stress and tocolytic dosage for pregnant women in preterm labor. METHODS: The participants were 60 pregnant women in preterm labor who were hospitalized from April to July, 2009. Thirty participants were assigned to the experimental group and 30 to the control group. None of them had any other complications except preterm labor. The modified Mason's breathing technique was used with the experimental group 3 times a day for 3 days. Data were collected using a self-report questionnaire and chart review, and analyzed with the SPSS 13.0 WIN program. RESULTS: "State anxiety of the experimental group will be lower than that of the control group" was supported. "Stress of the experimental group will be lower than that of the control group" was supported. "The Ritodrine dosage for the experimental group will be lower than that of the control group" was supported. "The Atosiban dosage for the experimental group will be lower than that of the control group" was supported. CONCLUSION: These results indicate that abdominal breathing is an effective nursing intervention for pregnant women in preterm labor.

Psychophysiological analysis of the influence of vasopressin on speech in patients with post-stroke aphasias

Speech is an attribute of the human species. Central speech disorders following stroke are unique models for the investigation of the organization of speech. Achievements in neurobiology suggest that there are possible neuroendocrine mechanisms involved in the organization of speech. It is known that the neuropeptide vasotocin, analogous of vasopressin in mammals, modulates various components of vocalization in animals. Furthermore, the positive influence of vasopressin on memory, which plays an important role in the formation of speech, has been described. In this study, speech organization processes and their recovery with the administration of vasopressin (1-desamino-8-D-arginin-vasopressin) to 26 patients with chronic aphasias after stroke were investigated. Results showed that sub-endocrine doses of the neuropeptide with intranasal administration had positive influence primarily on simple forms of speech and secondarily on composite forms. There were no statistically significant differences between the sensory and integrative components of the organization of speech processes with vasopressin. In all cases, the positive effect of the neuropeptide was demonstrated. As a result of the effects, speech regulated by both brain hemispheres improved. It is suggested that the neuropeptide optimizes the activity both in the left and right hemispheres, with primary influence on the right hemisphere. The persistence of the acquired effects is explained by an induction of compensatory processes resulting in the reorganization of the intra-central connections by vasopressin (AU)

El habla es un atributo de la especie humana. Los trastornos centrales del habla después de una trombosis cerebral son modelos únicos para la investigación de la organización del habla. Los logros en la neurobiología sugieren que posiblemente haya mecanismos neuroendocrinos implicados en la organización del habla. Se sabe que el neuropéptido vasotocina, análogo de la vasopresina en los mamíferos, modula varios componentes de la vocalización en los animales. Además, se ha descrito la influencia positiva dela vasopresina en la memoria, que juega un papel importante en la formación del habla. En este estudio, se investigaron los procesos de la organización del habla y su recuperación con la administración de la vasopresina (1-desamino-8-D-arginin-vasopressin) a 26 pacientes con afasias crónicas después de una trombosis cerebral. Los resultados mostraron que las dosis sub-endocrinas del neuropéptido con administración intranasal tuvo influencia positiva primariamente en las formas simples del habla y, de manera secundaria, en las formas compuestas. No hubo diferencias estadísticamente significativas entre los componentes sensoriales e integrativos de la organización de los procesos del habla con vasopresina. En todos los casos, se demostró el efecto positivo del neuropéptido. Como resultado de los efectos, mejoró el habla regulado por ambos hemisferios. Se sugiere que el neuropéptido optimiza la actividad tanto en el hemisferio izquierdo como en el derecho, con influencia primaria sobre el hemisferio derecho.La persistencia de los efectos adquiridos se explica por la inducción de procesos compensatorios como resultado de la reorganización de las conexiones intra-centrales por la vasopresina (AU)

The distribution of vasotocin and mesotocin immunoreactivity in the brain of the snake, Bothrops jararaca

Polyclonal antibodies against vasotocin (AVT) and mesotocin (MST) were used to explore the distribution of these peptides in thebrain of the snake Bothrops jararaca . Magnocellular AVT- and MST-immunoreactive (ir) perikarya were observed in the supraopticnucleus (SON), being AVT-ir neurons more numerous. A portion of the SON, in the lateroventral margin of the diencephalonventrally to optic tract, showed only AVT-ir perikarya and fibers. However, the caudal most portion displayed only mesotocinergicperikarya. Parvocellular and magnocellular AVT- and MST-ir perikarya were present in the paraventricular nucleus (PVN) beingAVT-ir fibers more abundant than MST-ir. Vasotocinergic perikarya were also found in a dorsolateral aggregation (DLA) far fromthe PVN. Mesotocinergic perikarya were also present in the recessus infundibular nucleus and ependyma near to paraventricularorgan. Nerve fibers emerging from supraoptic and paraventricular nuclei run along the diencephalic floor, internal zone of themedian eminence (ME) to end in the neural lobe. Also a dense network of AVT- and MST-ir fibers was present in the external zoneof the ME, close to the vessels of the hypophysial portal system. As a rule, all regions having vasotocinergic and mesotocinergicperikarya also showed immunoreactive fibers. Vasotocinergic and mesotocinergic fibers but not perikarya were found in the laminaterminalis (LT). Moreover AVT-ir fibers were present in the nucleus accumbens and MST-ir fibers in the septum. In mesencephalonand rhombencephalon MST-ir fibers were more numerous than AVT-ir fibers. Vasotocinergic and mesotocinergic fibers inextrahypothalamic areas suggest that these peptides could function as neurotransmitters and/or neuromodulators in the snake B.jararaca.

La ciclosporina a inhibe la respuesta de la permeabilidad osmótica al agua a la hormona antidiurética en la vejiga del sapo y a la angiotensina ii y hormona antidiurética en piel de sapo / Ciclosporine A inhibits the osmotic water flow response of isolated toad bladder to arginine-vasotocin and to angiotensin ii and arginine-vasotocin in isolated toad skin

El objeto del presente trabajo fue evaluar los efectos de la ciclosporina A (CyA) en la respuesta del flujo osmótico de agua de la vejiga aislada de sapo a la arginina-vasotocina (AVT) y a la angiotensina II (Ang II) y AVT en piel aislada de sapo. La CyA añadida al lado dérmico de la piel aislada de sapo o al lado seroso de la vejiga en concentraciones de 0,42. 10-6M a 0,42. 10-7M no tuvo efecto en la permeabilidad osmótica basal (Posm) pero inhibió la respuesta hormonal a la AVT en ambas membranas (AVT 10-10M en vejiga de sapo y 10-8 a 10-9M en piel de sapo). La CyA también inhibió la respuesta de la Posm a la Ang II (10-7M) en piel de sapo en concentraciones de 0,42. 10-6M y 0,42. 10-7M. En vejiga de sapo pudo demostrarse que el efecto inhibitorio fue reversible. La CyA en concentraciones de 0,42. 10-6M inhibió la respuesta de la Posm en piel de sapo a la teofilina (3,2. 10-3M) y al dibutiril AMP cíclico (6,2. 10-3M) sugiriendo un efecto distal a la generación de AMP cíclico. Estas respuestas apoyarían la posibilidad de un efecto diurético en el nefrón de los mamíferos. (AU)

Angiotensin-(1-7) increases osmotic water permeability in isolated toad skin

Angiotensin-(1-7) (Ang-(1-7)) increased osmotic water permeability in the isolated toad skin, a tissue with functional properties similar to those of the distal mammalian nephron. Concentrations of 0.1 to 10 ÁM were effective, with a peak at 20 min. This effect was similar in magnitude to that of frog skin angiotensin II (Ang II) and oxytocin but lower than that of human Ang II and arginine-vasotocin. The AT2 angiotensin receptor antagonist PD 123319 (1.0 ÁM) fully inhibited the response to 0.1 ÁM Ang-(1-7) but had no effect on the response to Ang II at the same concentration. The specific receptor antagonist of Ang-(1-7), A-779, was ineffective in blocking the response to Ang-(1-7) and to frog skin Ang II. The AT1 receptor subtype antagonist losartan, which blocked the response to frog skin Ang II, was ineffective in blocking the response to Ang-(1-7). The present results support the view of an antidiuretic action of Ang-(1-7) in the mammalian nephron

Effect of Arginine Vasotocin on the Rabbit Renal Function / 대한신장학회잡지

Arginine vasotocin has long been known as an antidiuretic hormone in non-mammalian vertebrates. The peptide has also been found in mammalian tissues. The physiological significance of the peptide, however, has not yet been clarified in mammals. To define the effect of arginine vasotocin on the water and electrolyte balance in mammalian vertebrates, experiments have been done. Intrarenal arterial infusion of arginine vasotocin, 0.01-10ng/kg/min resulted in dose-dependent decreases in urine volume and free water clearance and an increase in urinary osmolarity. Arginine vasotocin, in a dose of 0.03ng/kg/min, induced an increase in water reabsorption without changes in glomerular filtration rate. Intrarenal infusion of arginine vasotocin in doses ranging from 0.1 to 3.0 or 10.0ng/kg/min resulted in decreases in glomerular filtration rate and renal plasma flow. However, no dose dependence were observed. Intrarenal infusion of arginine vasotocin from 0.3 to 10 ng/kg/min induced dose-dependent natriuretic and kaliuretic effects with concomitant suppression of renin secretion. The renal effects of arginine vasotocin were blocked by arginine vasopressin V2-receptor antagonist [d(CH2)5, D-Phe2, Ile4, Ala9-NH2]-vasopressin but were not blocked by[d(CH2)5, D-Ile2, Ile4, Arg8]- vaso pression. These data suggest that the effect of arginine vasotocin on the renal function are similar to that of vasopressin in mammalian vertebrates. The data also suggest that the renal effects of arginine vasotocin may be coupled to the receptor system which is similar, if not identical, to that of arginine vasopressin.