Distocia em tigre d'água-de-orelha-vermelha, Trachemys scripta elegans, wied (1839): relato de caso / Dystocia in red-eared slider, Trachemys scripta elegans, wied (1839): case report / Distocia en tortuga de orejas rojas, Trachemys scripta elegans, wied (1839): reporte de caso

Atualmente muitos répteis se tornaram animais de companhia e são mantidos como pet's exóticos. A espécie Trachemys scripta elegans, Wied (1839) é um animal exótico da América do Norte, sua identificação é realizada pelas marcas avermelhadas encontradas lateralmente a sua cabeça. Na rotina clínica as principais enfermidades que acometem os quelônios são as de origem reprodutiva, como a estase folicular e distocia. O objetivo deste trabalho foi relatar um caso recorrente de distocia em um tigre d'água fêmea, para isso, a anamnese, o histórico da paciente, e seus sinais clínicos, em conjunto com os exames complementares de imagem foram essenciais para se obter diagnóstico definitivo. O tratamento foi realizado com a indução medicamentosa utilizando borogluconato de cálcio, seguida da aplicação de ocitocina, esta trouxe resultados positivos para a eliminação dos ovos. Porém devido ao histórico do paciente, optou-se pela intervenção cirúrgica de ovariossalpingectomia, sendo está a maneira permanente de resolução da patologia. O protocolo terapêutico escolhido proporcionou um resultado satisfatório e bem estar ao animal.(AU)

Currently, many reptiles have become companion animals and are kept as exotic pets. The species Trachemys scripta elegans, Wied (1839) is an exotic animal from North America, and its identification is based on the reddish markings found laterally on its head. In routine clinical practice, the main diseases that affect chelonians are those of reproductive origin, such as follicular stasis and dystocia. The aim of this study was to report a recurrent case of dystocia in a female red-eared slider turtle. For this purpose, the patient's anamnesis, history, and clinical signs, along with complementary imaging exams, were essential to obtain a definitive diagnosis. The treatment involved medical induction using calcium borogluconate, followed by the administration of oxytocin, which yielded positive results in egg elimination. However, due to the patient's history, surgical intervention in the form of ovariosalpingectomy was chosen as the permanent solution to the pathology. The chosen therapeutic protocol provided a satisfactory outcome and improved the animal's well-being.(AU)

Actualmente muchos reptiles se han convertido en animales de compañía y se mantienen como mascotas exóticas. La especie Trachemys scripta elegans, Wied (1839) es un animal exótico de América del Norte, su identificación se realiza por las marcas rojizas que se encuentran lateralmente a su cabeza. En la rutina clínica, las principales enfermedades que afectan a los quelonios son las de origen reproductivo, como la estasis folicular y la distocia. El objetivo de este trabajo fue reportar un caso recurrente de distocia en una hembra de tigre de agua, para ello la anamnesis, la historia de la paciente y sus signos clínicos, junto con los exámenes imagenológicos complementarios fueron fundamentales para obtener un diagnóstico definitivo. El tratamiento se realizó con inducción farmacológica con borogluconato de calcio, seguido de la aplicación de oxitocina, que arrojó resultados positivos con la eliminación de huevos. Sin embargo, debido a los antecedentes de la paciente, se optó por la intervención quirúrgica de ovarialpingectomía, que es la forma definitiva de resolución de la patología. El protocolo terapéutico elegido proporcionó un resultado satisfactorio y bienestar al animal.(AU)

Tipos de partos y niveles de oxitocina, cortisol y hormonas tiroideas en plasma del cordón umbilical / Types of deliveries and levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma

Introducción: La placenta sintetiza y secreta varias hormonas que permiten la regulación del embarazo, el trabajo de parto y la adaptación metabólica materno-fetal. Su comportamiento asociado al tipo de parto puede dar información relevante sobre efectos epigenéticos. Objetivo: Describir el tipo de parto con los niveles de oxitocina, cortisol y hormonas tiroideas en plasma de cordón umbilical al nacer. Método: A 50 mujeres con embarazos principalmente normales se les cuantificaron los niveles neurohormonales en plasma de cordón umbilical, obtenido inmediatamente tras el periodo expulsivo. Los resultados se incorporaron a la base de datos clínicos de cada participante y se analizaron con Stata v.14.0. El protocolo fue aprobado por el comité de ética. Resultados: Hubo 33 partos vaginales (12 espontáneos, 13 acelerados y 8 inducidos) y 17 cesáreas (7 electivas y 10 de urgencia). Se observaron mayores niveles de cortisol en los partos vaginales acelerados; las cesáreas tuvieron menores niveles de cortisol y hormona estimulante de la tiroides. Las intervenciones clínicas, con altos o bajos niveles hormonales, están en directa relación con el tipo de parto. Conclusiones: El cortisol y la hormona estimulante de la tiroides medidos en plasma de cordón umbilical variaron según el tipo de parto. Esto es una primera cuantificación de hormonas en plasma de cordón umbilical y su posible regulación placentaria a propósito del tipo de parto.

Introduction: The placenta synthesizes and secretes several hormones allowing the regulation of pregnancy, labor and maternal-fetal metabolic adaptation. Their behavior associated with the type of delivery, may provide relevant information on epigenetic effects. Objective: To describe the type of delivery with the levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma at birth. Method: Neurohormonal levels from umbilical cord plasma obtained immediately post expulsion, were quantified in 50 women with mainly normal pregnancies. Results incorporated into the clinical database of each participant, statistically analyzed in Stata v.14.0. Protocol approved by ethics committee. Results: 33 were vaginal deliveries (12 spontaneous, 13 accelerated, 8 induced) and 17 cesarean sections (7 elective and 10 emergency). Higher cortisol levels were observed in accelerated vaginal deliveries, cesarean sections had lower cortisol and thyroid stimulating hormone levels. While clinical interventions, with high or low hormone levels, were related to the type of delivery. Conclusions: Cortisol and thyroid stimulating hormone measured in umbilical cord plasma varied according to the type of delivery. This is a first quantification of hormones in umbilical cord plasma and their possible placental regulation in relation to the type of delivery.

The Importance of Experimental Investigation of the Peripheral Oxytocin System.

Oxytocin and oxytocin receptors are synthesized in the periphery where paracrine/autocrine actions have been described alongside endocrine actions effected by central release of oxytocin from the posterior pituitary. In the female reproductive system, classical actions of uterine contraction and milk ejection from mammary glands are accompanied by actions in the ovaries where roles in steroidogenesis, follicle recruitment and ovulation have been described. Steroidogenesis, contractile activity, and gamete health are similarly affected by oxytocin in the male reproductive tract. In the cardiovascular system, a local oxytocinergic system appears to play an important cardio-protective role. This role is likely associated with emerging evidence that peripheral oxytocin is an important hormone in the endocrinology of glucose homeostasis due to its actions in adipose, the pancreas, and the largely ignored oxytocinergic systems of the adrenal glands and liver. Gene polymorphisms are shown to be associated with a number of reported traits, not least factors associated with metabolic syndrome.

Oxytocin receptor gene polymorphism and low serum oxytocin level are associated with hyperphagia and obesity in adolescents.

BACKGROUND/OBJECTIVES: In recent years, oxytocin (OXT) and polymorphisms in the oxytocin receptor (OXTR) gene have been reported to play roles in obesity pathogenesis. However, there was no study evaluating OXTR gene variants in childhood obesity. The aim of the study was to investigate the relation of OXTR gene polymorphisms and serum OXT levels with metabolic and anthropometric parameters in obese and healthy adolescents. SUBJECTS/METHODS: The study was a multi-centered case-control study, which was conducted on obese and healthy adolescents aged between 12 and 17 years. Serum OXT and leptin levels were measured, and OXTR gene variants were studied by qPCR (rs53576) and RFLP (rs2254298) methods. RESULTS: A total of 250 obese and 250 healthy adolescents were included in this study. In the obese group, serum OXT level was lower and leptin level was higher than the control group. In the obese group, frequencies of homozygous mutant (G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were higher than the control group. Homozygous mutant(G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were found to increase the risk of obesity compared to the wild type (A/A) genotype [OR = 6.05 and OR = 3.06; p < 0.001, respectively]. In patients with homozygous mutant (G/G) and heterozygous (A/G) genotype for rs53576 polymorphism, serum OXT levels were lower than the wild type (A/A) genotype. In the obese group, hyperphagia score was higher than the control group and correlated negatively with serum OXT level. CONCLUSIONS: This study revealed that low serum OXT level, which is associated with hyperphagia may be an underlying cause for obesity in adolescents. For rs53576 polymorphism of the OXTR gene, obesity risk is higher in patients with homozygous mutant(G/G) and heterozygous(A/G)genotypes.

The effect of amisulpride, olanzapine, quetiapine, and aripiprazole single administration on c-Fos expression in vasopressinergic and oxytocinergic neurons of the rat hypothalamic paraventricular nucleus.

Antipsychotics, including amisulpride (AMI), quetiapine (QUE), aripiprazole (ARI), and olanzapine (OLA), are used to treat mental illnesses associated with psychotic symptoms. The effect of these drugs on c-Fos expression in vasopressinergic (AVP) and oxytocinergic (OXY) neurons was studied in the hypothalamic paraventricular nucleus (PVN) of rats. The presence of c-Fos in AVP and OXY perikarya was investigated in seven PVN cells segregations: the anterior (Ant), dorsal cup (Dc), wing-shaped (Wi), periventricular zone (Pe), circle-shaped core (Co) and shell of core (Sh), and the posterior (pPVN) after an acute treatment with AMI-20 mg/kg, QUE-15 mg/kg, ARI-10 mg/kg, and OLA-5 mg/kg/bw in rats. Ninety min after treatments, the animals were sacrificed by transcardial perfusion with fixative and the PVN area sliced into 35 µm thick coronal sections for immunohistochemistry. The c-Fos was processed by avidin-biotin-peroxidase complex intensified with nickel-enhanced 3,3'-diaminobenzidine tetrahydrochloride. Visualization of AVP- and OXY-synthesizing neurons was achieved by a fluorescent marker Alexa Flour 568. The c-Fos-AVP and c-Fos-OXY colocalizations were evaluated from c-Fos stained sections merged with AVP or OXY ones. AMI, QUE, ARI, and OLA, single administration distinctly increased the c-Fos expression in each of the PVN cells segregations. QUE induced the highest magnitude of activation of AVP and OXY neurons, while OLA and AMI had only moderate effects. Incontestable variabilities detected in c-Fos expression in PVN AVP and OXY neurons extend the knowledge of selected antipsychotics extra-striatal actions and may also be helpful in a presumption of their possible functional impact.

Structurally related peptide impurity identification and accurate quantification for synthetic oxytocin by liquid chromatography-high-resolution mass spectrometry.

Oxytocin (OXT) is an important peptide that is mainly used as a therapeutic drug to induce labor or strengthen uterine contractions, or to control bleeding after childbirth. OXT has also been reported as a biomarker linked to emotion, and as a potential biomarker for cancer diagnosis. The accurate purity characterization of OXT calibrators is critical for quality control of pharmaceuticals and the development of reference measurement systems for this analyte in laboratory medicine. OXT possesses the particular analytical measurement challenge of a disulfide bond. Accurate value assignment of the purity of oxytocin calibrators can be carried out by applying the mass balance approach or alternative approaches such as amino acid analysis, quantitative nuclear magnetic resonance spectrometry, and nitrogen determination. In order to avoid biases, all these approaches require a correction for structurally related peptide impurities. Structurally related peptide impurities present in a synthetic OXT material have been identified and quantified by a newly developed and in-house-validated liquid chromatography-high-resolution mass spectrometry (LC-hrMS) method. This method was adopted for the measurement of the study material used for an international comparison evaluating the competencies of laboratories to perform peptide characterization. Eighteen structurally related impurities were identified, confirmed, and accurately quantified in the OXT study material by using LC-hrMS. The study material contained a total mass fraction of 31.1 mg/g structurally related OXT impurities with an associated expanded uncertainty of 1.7 mg/g.

A selective comprehensive reversed-phase×reversed-phase 2D-liquid chromatography approach with multiple complementary detectors as advanced generic method for the quality control of synthetic and therapeutic peptides.

There is a huge, still increasing market for synthetic and therapeutic peptides. Their quality control is commonly based on a generic reversed-phase liquid chromatography (RPLC) method with C18 stationary phase and acetonitrile gradient with 0.1% trifluoroacetic acid in the mobile phase. It performs exceptionally well for a wide variety of impurities, yet structurally closely related impurities with similar sequences, not resolved in preparative RPLC, may easily coelute in the corresponding QC run as well. To address this problem an advanced generic 2D-LC impurity profiling method was developed in this work. It employs a selective comprehensive (high resolution sampling) RP×RP 2D-LC separation using a 100×2.1 mm ID column with the common acidic generic gradient in the first dimension, while RPLC under basic pH on a short 30×3 mm ID column is used in the second dimension. Recording data with a UV detector at 215 nm after 1D separation provides the common generic 1D chromatogram. However, after the 2D separation a flow splitter enabled recording of the signals of complementary detectors comprising a diode array detector (DAD) in-line with a charged aerosol detector (CAD) and a quadrupole-time-of-flight (QTOF) mass spectrometer (MS) with an electrospray ionization (ESI) source. Generic conditions of this 2D-LC method have been established through optimization of 2D stationary and mobile phase considering different pH values and buffer concentrations. The orthogonal separation principle has been documented by a number of therapeutic peptides including Exenatide, Octreotide, Cyclosporine A and Oxytocin as well as some other proprietary synthetic peptides. The information density can be further enhanced by using the QTOF-MS detector by data independent acquisition with SWATH. Through this sequential window acquisition of all theoretical fragment ion mass spectra it became possible to collect MS/MS data comprehensively in the high-resolution sampling window, thus enabling the extraction of 2D-EICs from fragment ions and the generation of 2D-contour plots of all product ions. Using Oxytocin as an example for an important therapeutic peptide, the ability of this advanced generic sRP-UV×RP-DAD-CAD-ESI-QTOF-MS/MS method with SWATH for peptide quality control is discussed.

The Impact of a 20-Minute Animal-Assisted Activity Session on the Physiological and Emotional States in Patients With Fibromyalgia.

OBJECTIVE: To study the direct physiological and emotional impact of an animal-assisted activity (AAA) session (a form of complementary and integrative medicine) in patients with fibromyalgia (FM). PATIENTS AND METHODS: The study population consisted of 221 participants with FM who were attending Mayo Clinic's Fibromyalgia Treatment Program between August 5, 2017, and September 1, 2018. This was a randomized controlled trial. Participants were randomly assigned to either the treatment group (a 20-minute session with a certified therapy dog and handler) or the control group (a 20-minute session with a handler only). To gain a better understanding of the direct physiological and emotional effects of AAA in patients with FM, we used multiple noninvasive physiologic-emotional biomarkers, including salivary cortisol and oxytocin concentrations, tympanic membrane temperatures, and various cardiac parameters, in addition to standardized pain and mood-based questionnaires. RESULTS: Results show a decrease in heart rate, an increase in heart rate variability, an increase in well-being survey scores, an increase in salivary oxytocin, and subsequent tympanic membrane temperature changes, suggesting that participants in the treatment group were in a more positive emotional-physiologic state as a result of the AAA session compared with the control group. CONCLUSION: Our results suggest that a 20-minute therapy dog visit in an outpatient setting can significantly and positively impact the physical and mental health of patients with FM.

Oxytocin release deficit and social cognition in craniopharyngioma patients.

Oxytocin is a neuropeptide known to affect social behaviour and cognition. Craniopharyngioma patients are considered to have an oxytocin-release-deficit caused by a rare tumour affecting the pituitary and/or the hypothalamus relevant for oxytocin production and release. To assess social behaviour and socio-cognitive abilities in this patient group, we tested 13 patients and 23 healthy controls on self-report questionnaires and an eye-tracking paradigm including fast facial emotion recognition. Additionally, saliva oxytocin levels acquired before and after a physical stress induction were available from a previous study, representing the reactivity of the oxytocin system. The data revealed three major results. First, patients with an oxytocin-release-deficit scored higher on self-reported autistic traits and reduced levels of hedonia for social encounters, although they showed no impairments in attributing mental states. Second, patients showed more difficulties in the fast emotion recognition task. Third, although automatic gaze behaviour during emotion recognition did not differ between groups, gaze behaviour was related to the reactivity of the oxytocin system across all participants. Taken together, these findings demonstrate the importance of investigating the reactivity of the oxytocin system and its relationship with social cognition. Our findings suggest that reduced emotional processing abilities may represent a pathological feature in a group of craniopharyngioma patients, indicating that this patient group might benefit from specific treatments within the social domain.

The Effects of Essential Oil on Salivary Oxytocin Concentration in Postmenopausal Women.

Objectives: The aim of this study was to find essential oils that have increased the oxytocin concentration in postmenopausal women. Methods: Fifteen postmenopausal women participated in this study and the effects of 10 different essential oils were investigated. The essential oils included rose otto, sweet orange, lavender, neroli, frankincense, jasmine absolute, ylang ylang, roman chamomile, clary sage, and Indian sandalwood. The subjects were exposed to the control first for 20 min, followed by exposure to an essential oil for 20 min. Each subject received exposure to only a single kind of essential oil per day. Saliva was collected four times for each patient: immediately before and immediately after control exposure, and immediately before and immediately after essential oil exposure. The oxytocin concentration in the saliva was measured using a competitive ELISA kit. Results: The results showed that salivary oxytocin concentrations increased significantly more after exposure to lavender, neroli, jasmine absolute, roman chamomile, clary sage, and Indian sandalwood than after exposure to the control odor. Conclusions: The aroma of certain essential oils may elicit increased secretion of oxytocin in postmenopausal women. This study suggests that olfactory stimulation with any of a number of essential oils increases salivary oxytocin concentrations, which may inhibit aging-induced reduction in muscle mass and function in women.

Ocitocina na produção e composição do leite / Oxytocin application in production and milk composition

Objetivou-se analisar a aplicação da ocitocina influenciando na eficiência da ejeção do leite; ao ponto de ocorrer um aumento da produção e mudanças na composição. Foram utilizados 45 animais, durante 105 dias, divididos em três tratamentos, no tratamento 1 (T1) os animais receberam 0,5ml de soro fisiológico, logo após realizava-se a ordenha destes animais, sendo considerado o tratamento controle, no T2 os animais receberam ocitocina antes do início da ordenha, e logo após ordenhava-se estes animais; no T3 os animais receberam ocitocina ao final da ordenha e reordenhava-se estes animais. Para aferir a produção das vacas foram usados medidores de leite, com pesagens de produção realizadas quinzenalmente. Após aferido a produção de todos os animais, as amostras de leite foram coletadas e encaminhadas para as análises posterior. As variáveis físico-químicas do leite analisadas foram: porcentagem de gordura, lactose e proteína. Os resultados foram submetidos à análise de variância e posteriormente, ao teste de comparação de médias, com diferença estatística significativa de 5%. De acordo com os resultados obtidos a ocitocina influenciou na produção leiteira com um aumento na produtividade diária por animal, mas não se observou diferenças significativas nas médias de porcentagem de gordura, lactose e proteína do leite.

This study aimed to analyze the application of oxytocin influence in the milk ejection efficiency; as to occur an increase in production and changes in milk composition. 45 animals were used for 105 days, divided into three treatments, the treatment one received 0.5ml of physiological saline, in the treatment two were given oxytocin to the animals before the milking; and in treatment theree the animals received oxytocin at the end of milking. To measure the cow's milk production, milk meters were used, and were performed fortnightly. After measured the production of all animals, samples were collected and sent for analysis. The physico-chemical variables analyzed were: percentage of fat, lactose and protein. The results were submitted to ANOVA and subsequently the mean comparison test, with statistical significance of 5%. According to obtained results oxytocin influence the milk production with a significant increase in daily productivity per animal, but there was no significant difference in percentage of fat, lactose and milk protein.

Ocitocina na produção e composição do leite / Oxytocin application in production and milk composition

Objetivou-se analisar a aplicação da ocitocina influenciando na eficiência da ejeção do leite; ao ponto de ocorrer um aumento da produção e mudanças na composição. Foram utilizados 45 animais, durante 105 dias, divididos em três tratamentos, no tratamento 1 (T1) os animais receberam 0,5ml de soro fisiológico, logo após realizava-se a ordenha destes animais, sendo considerado o tratamento controle, no T2 os animais receberam ocitocina antes do início da ordenha, e logo após ordenhava-se estes animais; no T3 os animais receberam ocitocina ao final da ordenha e reordenhava-se estes animais. Para aferir a produção das vacas foram usados medidores de leite, com pesagens de produção realizadas quinzenalmente. Após aferido a produção de todos os animais, as amostras de leite foram coletadas e encaminhadas para as análises posteriores. As variáveis físico-químicas do leite analisadas foram: porcentagem de gordura, lactose e proteína. Os resultados foram submetidos à análise de variância e posteriormente, ao teste de comparação de médias, com diferença estatística significativa de 5%. De acordo com os resultados obtidos a ocitocina influenciou na produção leiteira com um aumento na produtividade diária por animal, mas não se observou diferenças significativas nas médias de porcentagem de gordura, lactose e proteína do leite.

This study aimed to analyze the application of oxytocin influence in the milk ejection efficiency; as to occur an increase in production and changes in milk composition. 45 animals were used for 105 days, divided into three treatments, the treatment one received 0.5ml of physiological saline, in the treatment two were given oxytocin to the animals before the milking; and in treatment there the animals received oxytocin at the end of milking. To measure the cow’s milk production, milk meters were used, and were performed fortnightly. After measured the production of all animals, samples were collected and sent for analysis. The physicochemical variables analyzed were: percentage of fat, lactose and protein. The results were submitted to ANOVA and subsequently the mean comparison test, with statistical significance of 5%. According to obtained results oxytocin influence the milk production with a significant increase in daily productivity per animal, but there was no significant difference in percentage of fat, lactose and milk protein.

Demographic, sampling- and assay-related confounders of endogenous oxytocin concentrations: A systematic review and meta-analysis.

Studies on endogenous oxytocin concentrations are often criticized for the debatable comparability between specimens and the variation in reported values. We performed meta-regressions on k = 229 studies (n = 12 741 participants), testing whether specimen, extraction, sex, age, time of day, or fasting instructions influenced oxytocin measurements. Predicted oxytocin concentrations differed depending on specimen and extraction: Measurements were extremely high in unextracted blood, compared to extracted blood and other specimens. Measurements were higher in samples with more female participants and higher age. Instructions not to smoke before sampling were correlated with higher oxytocin in unextracted samples. There was no impact of instructions to refrain from eating, drinking, consume caffeine, alcohol or exercising. Oxytocin concentrations increased from morning to afternoon. Our results showed that oxytocin is differentially reflected in blood, saliva, urine and cerebrospinal fluid. Extraction impacts oxytocin measurements, particularly in blood. Considering relevant confounders might increase comparability between studies.

Effects of Lactobacillus reuteri-containing lozenges on healing after surgical removal of mandibular third molars: a randomised controlled trial.

We investigated the effect of probiotic supplements on oral wound healing, swelling, pain and discomfort after surgical removal of mandibular third molars. A second aim was to evaluate if the intervention could influence the concentrations of oxytocin in saliva. Sixty-four consecutive volunteers (18-34 years) were enrolled to a double-blind randomised placebo-controlled trial with two parallel arms. Following surgery, the patients were asked to take three lozenges per day containing two strains of Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo for two weeks. The clinical healing and extra-oral swelling were scored two weeks post-operatively. Samples of wound exudate were cultivated for the presence of Staphylococcus aureus and ß-haemolytic streptococci. Salivary oxytocin concentrations were analysed from pre- and post-surgery samples using ELISA technique. Compliance and the subjective perception of swelling, pain and discomfort were reported daily through visual analogue scales in a logbook. All patients except three completed the protocol and the postoperative course was uneventful in most cases. Minor extra-oral swellings were noted in five patients, but none required antibiotic treatment. At the 2-week follow-up, there were no significant differences in clinical wound healing index, extra-oral swelling, bacterial growth or salivary oxytocin levels between the groups. The self-reported data unveiled, however, a significantly reduced sense of swelling, in particular during the second week after surgery in the probiotic test group (P<0.05). Likewise, significantly fewer nights with disturbed sleep and fewer days with sick-leave from work were reported among the participants in the test group (P<0.05). No differences were found in the post-operative use of analgesics. In conclusion, we found no significant influence of probiotic supplements on objective wound healing after surgical extraction of impacted mandibular third molars. However, since the patients' perceived significant post-operative ameliorations, further studies are needed to explore the patient's value of the intervention.

Neuropathic Pain Up-Regulates Hypothalamo-Neurohypophysial and Hypothalamo-Spinal Oxytocinergic Pathways in Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rat.

Despite the high incidence of neuropathic pain, its mechanism remains unclear. Oxytocin (OXT) is an established endogenous polypeptide produced in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. OXT, which is synthesized by OXT neurons in the SON and the magnocellular part of the PVN (mPVN), is delivered into the posterior pituitary (PP), then released into the systemic blood circulation. Meanwhile, OXT-containing neurosecretory cells in the parvocellular part of the PVN (pPVN) are directly projected to the spinal cord and are associated with sensory modulation. In this study, the OXT system in the hypothalamo-neurohypophysial and hypothalamo-spinal pathway was surveyed using a rat neuropathic pain model induced by partial sciatic nerve ligation (PSL). In the present study, we used transgenic rats expressing an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene. In a neuropathic pain model, mechanical allodynia was observed, and glial cell activation was also confirmed via immunohistochemistry. In this neuropathic pain model, a significant increase in the OXT-mRFP1 expression was observed in the PP, the SON, mPVN, and pPVN. Furthermore, OXT-mRFP1 granules with positive fluorescent reaction were remarkably increased in laminae I and II of the ipsilateral dorsal horn. Although the plasma concentrations of OXT did not significantly change, a significant increase of the mRNA levels of OXT and mRFP1 in the SON, mPVN, and pPVN were observed. These results suggest that neuropathic pain induced by PSL upregulates hypothalamic OXT synthesis and transportation to the OXTergic axon terminals in the PP and spinal cord.

Detection of oxytocin, atrial natriuretic peptide, and brain natriuretic peptide using novel imprinted polymers produced with amphiphilic monomers.

The cystine-bridged cyclic peptide hormones (CBCPHs) represent signature structural feature as well as unique biological activity. In this study, three CBCPHs have been identified and characterized, namely, oxytocin, atrial natriuretic peptides (ANPs), and brain natriuretic peptides (BNPs). Because research has shown that ANPs and BNPs are powerful diagnostic biomarkers for heart disease, a highly laudable endeavor would be to develop a novel sensor for detecting ANP or BNP levels. Therefore, an amphiphilic monomer Acr-His-NHNH-Fmoc was synthesized to form molecularly imprinted polymers (MIPs) for targeted CBCPH detection. First, oxytocin, a cardiovascular hormone and a CBCPH, was used as a template to fabricate MIPs on quartz crystal microbalance (QCM) chips. On the other hand, fabricated selected ANP segment or BNP segment as an epitope is able to construct epitope-mediated MIPs (EMIPs) for ANP or BNP. The developed oxytocin or ANP sensor reached a detection limitation of 0.1nM with the dissociation constants being 30pM for oxytocin and 20pM for ANP. Moreover, BNP sensor achieved a detection limitation of 2.89pM with an even lower Kd value as 2pM. Compared with the performance of EMIPs, the imprinted films showed high affinity and selectivity in special binding to CBCPHs. The developed MIPs-QCM biosensors thus provide an improved sensing platform using an amphiphilic monomer and may be useful for applications toward cyclotides, cystine knot motifs, or insulin-like peptides.

Validating the use of a commercial enzyme immunoassay to measure oxytocin in unextracted urine and saliva of the western lowland gorilla (Gorilla gorilla gorilla).

The neuroendocrine hormone oxytocin, which is an important physiological driver of social behavior and bonding, is increasingly being measured in conjunction with behavior to better understand primate sociality. To date no data are available on oxytocin concentrations within the genus Gorilla; however, as a result of their close genetic relatedness to humans, and tolerance-based social system, Gorilla represents an important group of study. The purpose of this study was to validate the measurement of urinary and salivary oxytocin in western lowland gorillas (Gorilla gorilla gorilla) to help facilitate future study of the interaction between oxytocin and behavior within the subspecies. The primary validation procedure was an intranasal challenge. Elevated oxytocin concentrations were observed in saliva samples taken 15-120 min post challenge. Urine levels remained within baseline range approximately 30 and 90 min following the challenge; however, elevated levels were observed 24 h post challenge. No diurnal variation was found in salivary samples taken at regular intervals throughout the day; however, morning urine samples had higher concentrations than afternoon samples. In addition, samples were collected opportunistically following three social events: play, breeding, and the death of a conspecific. Following the play bouts, salivary oxytocin was almost three times greater than baseline. Salivary oxytocin was also significantly higher 15 min post breeding compared to match-control samples. Following the death of a conspecific, the group mate's urinary oxytocin concentrations decreased by half compared to a baseline period when the group was intact. This study provides a biological validation of the measurement of urinary and salivary oxytocin in western lowland gorillas. These results suggest that urinary oxytocin measurements are suitable for establishing baseline levels, as they represent the build up of the previous day's concentrations, and salivary oxytocin measurements are suitable for assessing changes following specific events.

Associations between traumatic stress symptoms, pain and bio-active components in burn wounds.

OBJECTIVE: Pain and traumatic stress symptoms often co-occur. Evidence suggests that the neuropeptide oxytocine and pro-inflammatory cytokines are associated with both stress and pain. The aim of this pilot study was to explore relations between self-reported pain and traumatic stress, oxytocin and three cytokines in burn wounds. METHODS: An observational study in three burn centres was performed. Patients were invited to participate in the study when deep dermal injury was suspected. Patients completed the Impact of Event Scale (IES), a self-report questionnaire assessing traumatic stress symptoms, and they rated their pain the day prior to surgery. During surgery, eschar (i.e., burned tissue) was collected and stored at -80 ° C until analysis. When the data collection was complete, oxytocin and cytokine levels were analysed. RESULTS: Eschar from 53 patients was collected. Pain and stress scores were available from 42 and 36 patients respectively. Spearman correlational analyses showed an association between lower oxytocin levels at wound site and a higher total IES score (r = -0.37) and pain (r = -0.32). Mann-Whitney U tests comparing groups scoring high or low on pain or stress confirmed these associations. CONCLUSION: These analyses lend support to a hormonal pathway that may explain how psychological distress affects pain at skin level in patients with traumatic stress symptoms.

De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function.

Despite the high prevalence of panhypopituitarism and diabetes insipidus in patients with craniopharyngioma (CP), little is known about the functioning of the neuropeptide oxytocin in these patients. This is of special interest as tumor-associated lesions often impair sites critical for oxytocin production and release, and affective dysfunction in CP links with elsewhere reported prosocial, antidepressant and anxiolytic oxytocin effects. Using a prospective study-design, we tested whether oxytocin is reduced in CP-patients, and whether altered oxytocin levels account for affective and emotional dysfunction. 26 adult CP-patients and 26 healthy controls matched in sex and age underwent physical exercise, a stimulus previously shown to induce oxytocin release. Baseline and stimulated salivary oxytocin levels, as well as empathy, depression and anxiety scores were measured. Results showed that patients overall did not present with lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but baseline oxytocin levels were indeed reduced in patients with hypothalamic damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response to exercise-induced stimulation, all CP-patients showed a blunted oxytocin-release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with oxytocin levels. Regarding affective function, unexpectedly, higher baseline oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020, CI[.478; 5.292]); the positive link with higher depression failed to reach statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=-2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin measures. In conclusion, we observed reduced baseline oxytocin levels only in CP-patients with hypothalamic damage. Exercise-induced stimulation de-masked an oxytocin-deficiency in all CP-patients. Baseline oxytocin levels and stimulated OT-responses might have different effects on affective function, which should be considered in future substitution paradigms.

Changes in salivary oxytocin after inhalation of clary sage essential oil scent in term-pregnant women: a feasibility pilot study.

OBJECTIVES: This pilot study using a quasi-experimental design was conducted to evaluate the feasibility (i.e., limited efficacy, practicality, and acceptability) of our intervention protocol involving inhalation of the scent of clary sage essential oil by pregnant women and measurement of their preinhalation and postinhalation oxytocin levels. RESULTS: Participants were women of singleton pregnancies between 38 and 40 gestation weeks (N = 11). The experiment group (n = 5) inhaled the scent of clary sage essential oil diluted 50-fold with 10 mL of odorless propylene glycol for 20 min. Regarding limited efficacy, the oxytocin level 15 min postinhalation increased in 3 women and was unmeasurable in 2. The control group (n = 6) inhaled similarly without the 50-fold dilution of clary sage essential oil. Their oxytocin level increased in 2 women, decreased in 2, and was unmeasurable in 2. Uterine contraction was not observed in both groups. Regarding practicality, 3 of the 11 women could not collect sufficient saliva. The cortisol level decreased in both groups postinhalation. The protocol had no negative effects. Regarding acceptability, burden of the protocol was not observed. Trial registration The Clinical Trials Registry of University Hospital Medical Information Network in Japan-UMIN000017830. Registered:  June 8, 2015.