Association of SARC-F Score and Rockwood Clinical Frailty Scale with CT-Derived Muscle Mass in Patients with Aortic Aneurysms.

OBJECTIVES: Patients with aortic aneurysms (AA) are often co-morbid and susceptible to frailty. Low core muscle mass has been used as a surrogate marker of sarcopenia and indicator of frailty. This study aimed to assess association between core muscle mass with sarcopenia screening tool SARC-F and Clinical Frailty Scale (CFS) in patients with AA. METHODS: Prospective audit of patients in pre-operative aortic clinic between 01/07/2019-31/01/2020 including frailty assessment using Rockwood CFS and sarcopenia screening using SARC-F questionnaire. Psoas and sartorius muscle area were measured on pre-operative CT scans and adjusted for height. Association was assessed using Spearman's rank correlation coefficient. RESULTS: Of 84 patients assessed, median age was 75 years [72,82], 84.5% were men, 65.5% were multimorbid and 63.1% had polypharmacy. Nineteen percent were identified as frail (CFS score >3) and 6.1% positively screened for sarcopenia (SARC-F score 4 or more). Median psoas area (PMA) at L3 was 5.6cm2/m2 [4.8,6.6] and L4 was 7.4cm2/m2 [6.3,8.6]. Median sartorius area (SMA) was 1.8 cm2/m2 [1.5,2.2]. CFS demonstrated weak but statistically significant negative correlation with height-adjusted PMA at L3 (r=-0.25, p=0.034) but not at L4 (r=-0.23, p=0.051) or with SMA (r=-0.22, p=0.065). No association was observed between SARC-F score and PMA or SMA (L3 PMA r=-0.015, p=0.9; L4 PMA r=-0.0014, p= 0.99; SMA r=-0.051, p=0.67). CONCLUSION: CFS showed higher association with CT-derived muscle mass than SARC-F. Comprehensive pre-operative risk-stratification tools which incorporate frailty assessment and body composition analysis may assist in decision making for surgery and allow opportunity for pre-habilitation.

The inhibitory effect of combination treatment with leptin and cannabinoid CB1 receptor agonist on food intake and body weight gain is mediated by serotonin 1B and 2C receptors.

Previous studies reported that the co-injection of leptin and cannabinoid CB1 receptor antagonists reduces food intake and body weight in rats, and this effect is more profound than that induced by these compounds individually. Additionally, serotonin mediates the effects of numerous anorectic drugs. To investigate whether serotonin interacts with leptin and endocannabinoids to affect food intake and body weight, we administered 5-hydroxytryptamine(HT)1B and 5-hydroxytryptamine(HT)2C serotonin receptor antagonists (3 mg/kg GR 127935 and 0.5 mg/kg SB 242084, respectively) to male Wistar rats treated simultaneously with leptin (100 µg/kg) and the CB1 receptor inverse agonist AM 251 (1 mg/kg) for 3 days. In accordance with previous findings, the co-injection of leptin and AM 251, but not the individual injection of each drug, resulted in a significant decrease in food intake and body weight gain. Blockade of the 5-HT1B and 5-HT2C receptors completely abolished the leptin- and AM 251-induced anorectic and body-weight-reducing effects. These results suggest that serotonin mediates the leptin- and AM 251-dependent regulation of feeding behavior in rats via the 5-HT1B and 5-HT2C receptors.

Impact of an autologous oxygenating matrix culture system on rat islet transplantation outcome.

Disruption of the pancreatic islet environment combined with the decrease in oxygen supply that occurs during isolation leads to poor islet survival. The aim of this study was to validate the benefit of using a plasma-based scaffold supplemented with perfluorodecalin to improve islet transplantation outcome. Rat islets were cultured in three conditions: i) control group, ii) plasma based-matrix (P-matrix), and iii) P-matrix supplemented with emulsified perfluorodecalin. After 24 h culture, matrix/cell contacts (Integrinß1, p-FAK/FAK, p-Akt/Akt), survival (caspase 3, TUNEL, FDA/PI), function, and HIF-1α translocation were assessed. Afterwards, P-matrices were dissolved and the islets were intraportally transplanted. Graft function was monitored for 31 days with glycaemia and C-peptide follow up. Inflammation was assessed by histology (macrophage and granulocyte staining) and thrombin/anti-thrombin complex measurement. Islet survival correlated with an increase in integrin, FAK, and Akt activation in P-matrices and function was maintained. Perfluorodecalin supplementation decreased translocation of HIF-1α in the nucleus and post-transplantation islet structure was better preserved in P-matrices, but a quicker activation of IBMIR resulted in early loss of graft function. "Oxygenating" P-matrices provided a real benefit to islet survival and resistance in vivo. However, intraportal transplantation is not suitable for this kind of culture due to IBMIR; thus, alternative sites must be explored.

The influence od melatonin receptors antagonists, luzindole and 4-phenyl-2-propionamidotetralin (4-P-PDOT), on melatonin-dependent vasopressin and adrenocorticotropic hormone (ACTH) release from the rat hypothalamo-hypophysial system. In vitro and in vivo studies.

Melatonin exerts its biological role acting via G protein-coupled membrane receptors - MT1 and MT2, as well as through cytoplasmic and/or nuclear receptors. Melatonin has previously been shown to change vasopressin (AVP) and adrenocorticotropic hormone (ACTH) secretion dependently on its concentration. To determine whether the response of vasopressinergic neurones to different concentrations of melatonin is mediated through the membrane MT1 and/or MT2 receptors, the influence of luzindole - an antagonist of both MT1 and MT2 receptors, and 4-phenyl-2-propionamidotetralin (4-P-PDOT) - a selective MT2 receptor antagonist, on melatonin-dependent AVP release from the rat hypothalamo-neurohypophysial (H-NH) system was studied in vitro (melatonin at the concentrations of 10(-9), 10(-7) and 10(-3) M) and in vivo (melatonin at the concentrations of 10(-9) and 10(-7) M). Moreover, the second goal of this study was to find out whether melatonin receptors MT1 and/or MT2 are involved in the regulation of ACTH and corticosterone secretion into the blood. We have demonstrated that melatonin, at the concentrations of 10(-9) and 10(-7) M, significantly inhibited AVP secretion from isolated rat H-NH explants when antagonists solvent (i.e. 0.1% DMSO) was present in the medium. Neither luzindole, nor 4-P-PDOT, applied without melatonin, did influence AVP release in vitro. Luzindole applied together with melatonin (10(-7) M and 10(-9) M) significantly suppressed melatonin-dependent effect, while 4-PPDOT did not eliminate the inhibitory influence of 10(-7) M and 10(-9) M melatonin on AVP secretion from isolated rat H-NH explants. Melatonin at a concentration of 10(-3) M significantly increased AVP release when the H-NH explants were incubated in the medium containing luzindole or 4-P-PDOT. Under present experimental in vivo conditions, infused intracerebroventricularly (i.c.v.) melatonin, at a concentration close to its physiological level in the blood, significantly diminished AVP secretion into the blood, however, at higher concentration (10(-7) M) it remained inactive in this process. Moreover, melatonin at both concentrations of 10(-9) M and 10(-7) M, was able to inhibit AVP secretion into the blood (and increase its neurohypophysial content) when animals were previously i.c.v. injected with 4-P-PDOT, but not with luzindole. Blood plasma concentration of ACTH was diminished significantly by 10(-7) M melatonin in DMSO-infused, but not in luzindole- or 4-P-PDOT-injected rats, however, it remained inactive in modifying the corticosterone blood plasma concentrations in any of the studied subgroups. The present study demonstrates that subtype MT1 membrane receptor may contribute to the inhibitory effect of physiological concentration of melatonin on functional regulation of vasopressinergic neurones in the rat. However, for the stimulatory effect of pharmacological dose of the hormone on AVP secretion in vitro, mechanisms different from membrane MT1/MT2 receptors are involved. The present experiment do not determines whether MT1 and/or MT2 receptors affect the function of the rat pituitary-adrenal cortex axis.

2-Amino-1,3,4-thiadiazole derivative (FABT) inhibits the extracellular signal-regulated kinase pathway and induces cell cycle arrest in human non-small lung carcinoma cells.

The anticancer potential of 2-amino-1,3,4-thiadiazole compounds has been documented by in vitro and in vivo studies. In our previous research, we described the synthesis as well as the antiproliferative and neuroprotective activities of 2-(4-fluorophenyloamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole (FABT). The aim of the present study was to investigate the molecular mechanisms involved in FABT-induced growth inhibition in A549 lung carcinoma cells. Western blotting analysis revealed that FABT inhibited the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, and Real-time PCR analysis showed no changes in the expression of P44ERK1 and CREB1 genes. Furthermore, FABT induced cell cycle arrest in the GO/G1 phase and enhanced p27/Kip1 expression. Our results suggest that FABT acts by inhibiting ERK1/2 pathway and cell cycle progression through G1 into S phase in A549 cells. Further studies are needed to completely explain the molecular mechanisms of anticancer action of this 2-aminothiadiazole derivative.

Perfluorocarbon emulsions prevent hypoxia of pancreatic ß-cells.

As oxygen carriers, perfluorocarbon emulsions might be useful to decrease hypoxia of pancreatic islets before transplantation. However, their hydrophobicity prevents their homogenisation in culture medium. To increase the surface of contact between islets and Perfluorooctyl bromide (PFOB), and consequently oxygen delivery, we tested effect of a PFOB emulsion in culture medium on ß-cell lines and rat pancreatic islets. RINm5F ß-cell line or pancreatic rat islets were incubated for 3 days in the presence of PFOB emulsion in media (3.5% w/v). Preoxygenation of the medium was performed before culture. Cell viability was assessed by apoptotic markers (Bax and Bcl-2) and by staining (fluoresceine diacetate and propidium iodide). ß-Cell functionality was determined by insulin release during a glucose stimulation test and. Hypoxia markers, HIF-1α and VEGF, were studied at days 1 and 3 using RT-PCR, Western blotting, and ELISA. PFOB emulsions preserved viability and functionality of RINm5F cells with a decrease of HIF-1α and VEGF expression. Islets viability was preserved during 3 days of culture. Secretion of VEGF was higher in untreated control (0.09 ± 0.041 µg VEGF/mg total protein) than in PFOB emulsion incubated islets (0.02 ± 0.19 µg VEGF/mg total protein, n = 4, p < 0.05) at day 1. At day 3, VEGF secretion was increased as compared to day 1 in control (0.23 ± 0.04 µg VEGF/mg total protein) but it was imbalance by the presence of PFOB emulsion (0.09 ± 0.03 µg VEGF/mg total protein, n = 5, p < 0.05). While insulin secretion was maintained in response to a glucose stimulation test until day 3 when islets were incubated in the presence of PFOB emulsion preoxygenated (0.81 ± 0.16 at day 1 vs. 0.75 ± 0.24 at day 3), the ability to secrete insulin in the presence of high glucose concentration was lost in islets controls (0.51 ± 0.18 at day 1 vs. 0.21 ± 0.13 at day 3). Atmospheric oxygen delivery by PFOB emulsion might be sufficient to decrease islets hypoxia. However, to improve islets functionality, overoxygenation is needed. Finally, maintenance of islet viability and functionality for several days after isolation could improve the outcome of islets transplantation.

Use of perfluorodecalin for pancreatic islet culture prior to transplantation: a liquid-liquid interface culture system--preliminary report.

Although the issue remains controversial, short-term culture is probably beneficial for islet graft quality. However, significant islet loss is invariably observed. This is related to reduced survival of large islets, which is compromised by hypoxia under standard culture conditions. We aimed to develop a method of culture, which would avoid exposure to relative hypoxia and hence maintain the quality of islets. Isolated rat islets cultured for 48 h in a liquid-liquid interface culture system (LICS) with a perfluorocarbon were compared to islets cultured under standard (C1) and suboptimal conditions (C2). Islets were tested for viability and response to a glucose challenge, and a marginal mass was transplanted into syngeneic diabetic recipients. The viability of islets after 24-h culture in LICS was higher than in C1 and C2 groups (89.0% vs. 77.5% and 64.6%, respectively) and decreased with time to reach 79.0%, 62.9%, and 53.4% after 72-h culture. The stimulation index in LICS-cultured islets was also significantly higher than in C1 and C2 groups (12.3 ± 0.4 vs. 5.8 ± 0.5 and 4.1 ± 0.2, respectively). Following transplantation of LICS-cultured islets 50% of recipients were rendered normoglycemic compared with 14.3% and 31.3% for C2 and fresh islets, respectively. Our liquid-liquid interface culture system using perfluorodecalin provides optimized culture conditions, which preserve both islet viability and their ability to engraft successfully after intraportal transplantation and could be used for islet transportation.

Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of gonadotrophin-releasing hormone (GnRH), its analogues and melatonin.

The influence of gonadotrophin-releasing hormone (GnRH) and its analogues (i.e., agonist and antagonist) on vasopressin (VP) release from the rat hypothalamo-neurohypophysial (H-N) system was studied both in vitro and in vivo. Additionally, it was determined whether the possible response of vasopressinergic neurones to these peptides could be modified by melatonin through a cAMP-dependent mechanism. In this study we demonstrate, for the first time, that the highly selective GnRH agonist (i.e., [Des-Gly(10),D-His(Bzl)(6),Pro-NHEt(9)]-LHRH; histrelin) stimulates the release of VP from the rat H-N system, while native GnRH and its antagonist remain inactive in modifying this process in vitro. Melatonin significantly inhibited basal and histrelin-induced release of VP in vitro, but displayed no significant influence on VP secretion when GnRH or its antagonist were present in a medium. Melatonin fully suppressed forskolin-stimulated VP release from the rat H-N system. On the other hand, addition of forskolin to a medium containing both histrelin and melatonin did not further alter the inhibitory influence of melatonin on the histrelin-dependent release of VP in vitro. After intracerebroventricular (i.c.v.) infusion of native GnRH or its agonist, blood plasma VP concentration was significantly higher than in control animals, which was accompanied by decreased content of the hormone in the neurohypophysis. Intravenous (i.v.) injection of melatonin did not change, in any subgroup, blood plasma VP concentration, when compared to the vehicle-injected rats. However, the neurohypophysial levels of the hormone were significantly higher after melatonin injection in control, GnRH- and histrelin-infused animals. Our present results suggest that activation of the GnRH receptor in the hypothalamus is involved in stimulation of VP secretion from the rat H-N system. We have also shown that melatonin, at a concentration close to its physiological level in the blood, significantly reduces the in vitro response of vasopressinergic neurones to a GnRH agonist - histrelin; this effect of melatonin could be mediated through intracellular processes that involve, among others, the cAMP-dependent mechanism.

Oxytocin release from the rat neurohypophysis into the blood: effects of tachykinin NK-1 and NK-2 receptors agonists and antagonists.

The aim of the present study was to investigate the effect of peptide NK-1 and NK-2 receptors agonists and antagonists (and their natural ligands, i.e., substance P and neurokinin A) on the oxytocin (OT) secretion from the rat neurohypophysis into the blood. Intracerebroventricular (icv) injection of substance P (SP) or highly selective NK-1 receptor agonist--[(Sar(9),Met(O2)(11))-Substance P]-- significantly stimulated the OT secretion from the rat neurohypophysis into the general circulation. After icv injection of the NK-1 receptor antagonist--[(Tyr(6),D-Phe(7),D-His(9))-Substance P (6-11)]--the blood plasma OT concentration was significantly lower, when compared to vehicle-injected animals. On the other hand, the icv administered neurokinin A (NKA) and the NK-2 receptor agonist--[(beta-Ala(8))-Neurokinin A (4-10)]--were essentially inactive in modifying OT secretion. However, such injection of the NK-2 receptor antagonist--[(Tyr(5),D-Trp(6,8,9),Lys-NH2(10))-Neurokinin A (4-10)]--was found to diminish the blood plasma hormone concentration, when compared to vehicle-injected animals. The neurohypophysial content of OT was decreased in NKA-treated rats, but neither the NK-2 receptor agonist nor antagonist were able to affect the OT output from the rat posterior pituitary. The hypothalamic levels of OT were not modified by any of the studied peptides. The present data strongly indicate a major role for the tachykinin NK-1 receptor in SP- and/or NKA-dependent regulation of OT secretion from the rat neurohypophysis into the blood.

Effect of melatonin on the vasopressin secretion as influenced by tachykinin NK-1 receptor agonist and antagonist: in vivo and in vitro studies.

The aim of the present study was to investigate the influence of melatonin on vasopressin (AVP) release from the rat hypothalamo-neurohypophysial (H-NH) system, both in vivo and in vitro, possibly modified by the peptide NK-1 and/or NK-2 receptor agonists and antagonists. Highly selective NK-1 receptor agonist, i.e., [Sar(9),Met(O(2))(11)]-Substance P, has been shown to enhance the AVP release from isolated rat H-NH system in vitro, while the NK-1 receptor antagonist--(Tyr(6),DPhe(7),D-His(9))-Substance P (6-11) as well as the NK-2 receptor selective agonist--(beta-Ala(8))-Neurokinin A (4-10) and antagonist--(Tyr(5),D-Trp(6,8,9),Lys-NH(2)(10))-Neurokinin A (4-10) were essentially inactive in modifying AVP secretion. Melatonin inhibited basal release of AVP but was not able to reduce significantly the in vitro response of vasopressinergic neurones to NK-1 receptor agonist. After intracerebroventricular (icv) administration, substance P (SP), neurokinin A (NKA) and the NK-1 receptor agonist (all at the concentration of 10(-7) M/L) significantly enhanced plasma AVP concentration. Such stimulatory effect of the latter peptide on AVP output from the eurohypophysis was reduced by an intravenous (iv) injection of melatonin, which itself (at a concentration of 5 ng/ml) caused a significant decrease in AVP release 10 min after injection. The inhibitory influence of melatonin on the AVP secretion was absent in rats injected icv with both tachykinin receptors antagonists, the NK-2 receptor agonist or NKA. The present data indicate a distinct role for NK-1 receptor in NKA/SP-mediated regulation of AVP release from the rat H-NH system. They have also shown that, under present experimental conditions, the stimulatory effect of NK-1 receptor activation on AVP secretion into the blood is sensitive to inhibitory influence of melatonin.

An improved method of fluorescent dual insulin and endothelial staining allows visualisation of the revascularisation of intraportally transplanted islets.

BACKGROUND: Intraportally transplanted islets are avascular at the time of transplantation and take up to 14 days to fully revascularize, during which time up to 60% of islet mass may be lost. To investigate and improve islet revascularization, a robust method for the visualization and quantification of this process is required. METHODS: Islets isolated from Lewis rats were transplanted intraportally into the liver of diabetic syngeneic Lewis recipients. The animals were humanely killed either on the day of transplant or at 3, 5, 7, or 14 days posttransplant. The harvested livers were sectioned and stained with Bandeiraea simplicifolia lectin (for endothelial cells) and anti-insulin antibody and counterstained with DAPI. The slides were visualized with a fluorescent microscope. RESULTS: Islets were visualized over the whole time course. Insulin and endothelial staining was clearly visualized on the day of transplantation, but by day 3 endothelial staining was scarce within the islet. By day 5, early vessel formation could be seen within the islet, but insulin staining was patchy and associated with apoptotic nuclei. By day 7, vessels could be seen throughout the islet and insulin staining had returned. Day 14 sections showed a fully revascularized islet. CONCLUSIONS: The staining provided good delineation of islet endothelium and beta-cell location, with clear observation of the revascularization process. This technique also suggests that days 3 through 5 may be a critical period for islet survival and provides a good model for studying the effects of manipulating the revascularization process.

Role of tachykinin receptors and melatonin in oxitocin secretion from isolated rat hypothalmo-neurohypophysial system.

Present investigations were undertaken to study the influence of peptide NK-1 and NK-2 receptor agonists and antagonists as well as substance P and neurokinin A (the natural ligands for these tachykinin receptors) on oxytocin (OT) release from isolated rat hypothalamo-neurohypophysial (H-N) system as well as to determine whether the tachykinin NK-1 and/or NK-2 receptors contribute to the response of oxytocinergic neurons to melatonin. The results show, for the first time, that highly selective NK-1 receptor agonist, i.e., [Sar(9),Met(O(2))(11)]-Substance P, enhances while the NK-1 receptor antagonist (Tyr(6),D-Phe(7),D-His(9))-Substance P (6-11) - sendide - diminishes significantly OT secretion; the latter peptide was also found to antagonize the substance P-induced hormone release from isolated rat H-N system, when used at the concentration of 10(-7) M/L. Melatonin significantly inhibited basal and substance P-stimulated OT secretion. Neurokinin A and the NK-2 receptor selective agonist (beta-Ala(8))-Neurokinin A (4-10) as well as the NK-2 receptor antagonist (Tyr(5),D-Trp(6,8,9),Lys-NH(2)(10))-Neurokinin A (4-10) were essentially inactive in modifying OT release from the rat H-N system in vitro. The present data indicate a distinct role for tachykinin NK-1 (rather than NK-2) receptor in tachykinin-mediated regulation of OT secretion from the rat H-N system. Under present experimental conditions, however, a role of respective tachykinin receptors in the response of oxytocinergic neurons to melatonin has not been found.

Pancreatic islets isolation using different protocols with in situ flushing and intraductal collagenase injection.

Human islet transplantation seems to be a very promising clinical procedure for patients with type I diabetes mellitus. The aim of our study was to investigate the influence of in situ intravascular flushing with University of Wisconsin (UW) solution and intraductal collagenase injection at the time of pancreas procurement on the isolated islets and exocrine tissue injury. Our experiments indicated that in situ perfusion with the UW solution has a beneficial effect on pancreatic islets and intraductal distention results in an increase in the concentration of pancreatic enzymes released into the cold preservation solution during ischemic conditions. Cold ischemia reduced islet yield, but pancreas perfusion with the UW solution showed better ischemic tolerance of isolated islets during glucose static incubation. We conclude that intravascular pancreas flushing has a crucial effect on recovery and yield of pancreatic islets and protects against exocrine tissue injury.

Effect of donor treatment with heparinoids on graft function after intraportal transplantation of a marginal islet mass: an experimental study.

Heparinoids interact with factors that are involved in ischemia-reperfusion injury and thus may prevent organ injury. We therefore studied the effects on subsequent intraportal islet transplantation of systemic administration of unfractionated and N-desulphated heparin to donors prior to pancreatectomy. Donor rats were given an intravenous injection of either heparin (1.3 mg/kg or 13.3 mg/kg; 200 U/kg or 2000 U/kg, respectively) or N-desulphated heparin (50 mg/kg; approximately 5 U/kg) at 5 to 10 minutes prior to pancreas procurement. Five hundred freshly isolated islets were injected intraportally into syngeneic male Lewis recipients that had developed streptozotocin-induced diabetes. Blood glucose and body weight were monitored for 5 weeks thereafter. Rats transplanted with islets from donors given high dose heparin showed a fall in blood glucose from 25.1 +/- 1.4 to 11.0 +/- 2.7 mmol/L (P <.01) with 60% of animals euglycemic within the first week. In contrast, the controls, did not show a fall in glucose levels at 1 week and none had become euglycaemic. Normalization of glycemia was slower in recipients of islets from animals treated with the lower dose of heparin. Results were intermediate with islets from donors given N-desulphated heparin. Nevertheless, all heparinoids used in this study caused more than a doubling of the number of animals achieving normoglycemia by 3 to 4 weeks. We hypothesize that pretreatment of the donor with heparin protects islet integrity during procurement and isolation and hence accelerates islet engraftment and remodelling. Since the effect was seen with N-desulphated heparin, which has negligible anticoagulant properties, we believe the mechanism to be independent of the anticoagulant activity.

Neurokinin A and the neurohypophysial response to melatonin: in vitro studies.

The aim of this study was to investigate a possible role of neurokinin A (a member of a family of peptides known as tachykinins) in the pineal-neurohypophysial interrelationship. The effect of neurokinin A (NKA) alone or in the presence of pineal hormone - melatonin on basal and K(+)-stimulated vasopressin and oxytocin secretion from the hypothalamo-neurohypophysial system was studied in vitro. The present results show that NKA stimulated basal vasopressin and oxytocin release from the isolated hypothalamo-neurohypophysial system, when used at the concentration of 10(-7) M/L. Melatonin diminished basal release of the neurohypophysial hormones; it also significantly inhibited the NKA-stimulated secretion of vasopressin and oxytocin. Lower concentrations of NKA did not affect the neurohypophysial hormones basal release, however, when melatonin was added to the medium enriched with NKA at the concentration of 10(-9) M/L, the vasopressin secretion from the hypothalamo-neurohypophysial explants was decreased significantly. The K(+)-evoked release of neurohypophysial hormones was not further modified by either NKA or melatonin. The present results confirm previous reports as to the inhibitory effect of melatonin on both vasopressin and oxytocin secretion from the hypothalamo-neurohypophysial complex in vitro. However, under present experimental conditions, the contribution of NKA in the mechanisms of pineal-neurohypophysial interrelationships has not been demonstrated.

The hypothalamo-neurohypophysial response to melatonin.

The present paper reviews the findings accumulated on the role of pineal gland and its hormone - melatonin - in regulation of the hypothalamo-neurohypophysial system activity. Effects of modified photoperiod, pinealectomy or treatment with melatonin on the vasopressin and oxytocin biosynthesis and/or secretion have been described. Taken together, the in vivo and in vitro data suggest that the effect of melatonin on the vasopressin and oxytocin secretion depends on this pineal hormone concentration and experimental conditions.