Efficacy of Agmatine Treatment in Experimental Acute Pancreatitis Rat Model.

BACKGROUND/AIMS: Acute pancreatitis which is characterized by pancreatic inflammation can sometimes be difficult to treat because of limited therapeutic options. The purpose of the study was to assess the effects of agmatine in the acute pancreatitis experimental rat model. MATERIALS AND METHODS: An acute pancreatitis model was created with the administration of cerulein in 40 female Sprague-Dawley rats. Agmatine was administered as a protective agent at 5 mg/kg (low dose) and 10 mg/kg (high dose). The rats were divided into 5 groups, each with 8 rats: group 1 (acute pancreatitis); group 2 (acute pancreatitis+low-dose agmatine 5 mg/kg); group 3 (acute pancreatitis+high-dose agmatine 10 mg/kg); group 4 (placebo, acute pancreatitis+saline); and group 5 (sham and saline infusion). All rats were sacrificed 24 hours after the last injection, and the levels of superoxide dismutase, interleukin-1 beta, and tumor necrosis factor-alpha were assessed in blood samples collected via cardiac puncture. Histopathological examination was performed by a pathologist, who was blind to the groups, according to the Schoenberg's pancreatitis scoring index. RESULTS: The amylase (16.67 and 37.89 U/L), glutathione peroxidase (13.62 and 18.44 ng/mL), tumor necrosis factor-α (39.68 and 64 ng/mL), interleukin-1 (484.73 and 561.83 pg/mL), and transforming growth factor-ß (110.52 and 126.34 ng/L) levels were significantly lower and superoxide dismutase (1.29 and 0.98 ng/L) and malondialdehyde (0.99 and 0.96 nmol/mL) levels were significantly higher in group 3 compared to group 1 (P < .05). Moreover glutathione peroxidase, tumor necrosis factor-α, and transforming growth factor-ß levels were lower, and malondialdehyde levels were higher in the group 3 compared to group 2 (P < .05). Although the Schoenberg's pancreatitis scoring index was not significantly different between the high- and low-dose treatment groups, rats who received high-dose treatment had significantly lower scores compared to those with acute pancreatitis group. CONCLUSION: This is the first study that evaluated the efficacy of agmatine in an experimental model of acute pancreatitis. Agmatine, an anti-inflammatory and antioxidant agent, had a protective effect in an experimental rat model of acute pancreatitis.

Inhibition of TRAF6 improves hyperlipidemic acute pancreatitis by alleviating pyroptosis in vitro and in vivo rat models.

OBJECTIVE: Hypertriglyceridemia (HTG) is one of the common causes of acute pancreatitis (AP). Hyperlipidemic acute pancreatitis (HTG-AP) is associated with higher mortality owing to its tendency for greater severity and rapid progression. The purpose of this study was to explore the mechanism of involvement of tumor necrosis factor receptor-related factor 6 (TRAF6) in pyroptosis during HTG-AP. METHODS: The HTG environment was simulated with palmitic acid treatment in vitro and a high-fat diet in vivo. Cerulein was used to establish the HTG-AP model, followed by genetic and pharmacological inhibition of TRAF6. Pyroptosis activation, inflammatory reaction, and the interaction between TRAF6 and pyroptosis in HTG-AP were assessed. RESULTS: HTG was found to aggravate the development of pancreatitis, accompanied by increased pyroptosis and enhanced inflammatory response in HTG-AP models. Mechanistically, TRAF6 downregulation decreased the activation of pyroptosis in cerulein-induced HTG-AP. CONCLUSION: Collectively, inhibition of TRAF6 improved HTG-AP and the associated inflammation by alleviating pyroptosis.

Study on the Mechanism of Dachaihu Decoction in the Treatment of Acute Pancreatitis Based on Artificial Intelligence Combined with in vivo Experiments.

BACKGROUND AND AIM: To explore the possible mechanism of Dachaihu Decoction (DCHD) in the treatment of AP, and use in vivo experiments to verify. METHODS: The targets and active ingredients of DCHD in the treatment of AP were obtained through network pharmacology, and the preliminary verification was carried out by molecular docking. Caerulein was used to develop the AP rat model. H&E staining was performed to observe variations in pancreatic tissue. Western blot and RT-qPCR were conducted to evaluate the associated proteins and mRNA. RESULTS: The network pharmacology and molecular docking results showed that the key targets (EGFR, TNF, SRC, VEGFA and CTNNB1) and key active components (beta-sitosterol, stigmasterol, baicalein, quercetin, and kaempferol) of DCHD in the treatment of AP had good binding. H&E staining revealed that rat pancreatic tissues considerably damaged post caerulein intervention, and it has also been suggested that DCHD ameliorates damage to pancreatic tissue. Simultaneously, EGFR, TNF, SRC, VEGFA protein, and mRNA expression levels were increased in the model group compared to the blank group (P < 0.01), whereas CTNNB1 expression was found to be decreased in the model group (P < 0.01). Compared with the model group, the protein expression levels of EGFR, TNF, SRC, and VEGFA in the treatment group were down-regulated (P < 0.01), and CTNNB1 was up-regulated (P < 0.05). CONCLUSION: DCHD protects pancreatic tissues and improves symptoms in AP rats by upregulating CTNNB1 protein and mRNA while inhibiting EGFR, TNF, SRC, and VEGFA protein and mRNA expression.

Development and Characterization of Novel Chronic Eosinophilic Inflammation- Mediated Murine Model of Malignant Pancreatitis.

AIMS: Develop a novel murine models of malignant pancreatitis. BACKGROUND: Although patients with chronic pancreatitis are at a greater risk of developing pancreatic cancer, there is no definitive mouse model that currently develops chronic pancreatitis-induced pancreatic cancer. OBJECTIVE: Characterization of eosinophilic inflammation-mediated malignant pancreatitis in novel murine model. METHODS: We developed a murine model of chronic eosinophilic inflammation associated with pancreatitis that also shows characteristic features of pancreatic malignancy. The mouse received cerulein and azoxymethane via intraperitoneal administration developed pathological malignant phenotype, as well as concomitant lung inflammation. RESULTS: We discovered pathological alterations in the pancreas that were associated with chronic pancreatitis, including a buildup of eosinophilic inflammation. Eosinophil degranulation was reported nearby in the pancreas tissue sections that show acinar-to-ductal metaplasia and acinar cell atrophy, both of which are characteristic of pancreatic malignancies. Additionally, we also observed the formation of PanIN lesions after three initial doses of AOM and eight weeks of cerulein with the AOM treatment regimen. We discovered that persistent pancreatic eosinophilic inflammation linked with a pancreatic malignant phenotype contributes to pulmonary damage. The RNA seq analysis also confirmed the induction of fibro-inflammatory and oncogenic proteins in pancreas and lung tissues. Further, in the current manuscript, we now report the stepwise kinetically time-dependent cellular inflammation, genes and proteins involved in the development of pancreatitis malignancy and associated acute lung injury by analyzing the mice of 3 AOM with 3, 8, and 12 weeks of the cerulein challenged protocol regime. CONCLUSION: We first show that sustained long-term eosinophilic inflammation induces time-dependent proinflammatory, profibrotic and malignancy-associated genes that promote pancreatic malignancy and acute lung injury in mice.

Targeting Plk1 Sensitizes Pancreatic Cancer to Immune Checkpoint Therapy.

Polo-like kinase 1 (Plk1) plays an important role in cell-cycle regulation. Recent work has suggested that Plk1 could be a biomarker of gemcitabine response in pancreatic ductal adenocarcinoma (PDAC). Although targeting Plk1 to treat PDAC has been attempted in clinical trials, the results were not promising, and the mechanisms of resistance to Plk1 inhibition is poorly understood. In addition, the role of Plk1 in PDAC progression requires further elucidation. Here, we showed that Plk1 was associated with poor outcomes in patients with PDAC. In an inducible transgenic mouse line with specific expression of Plk1 in the pancreas, Plk1 overexpression significantly inhibited caerulein-induced acute pancreatitis and delayed development of acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Bioinformatics analyses identified the regulatory networks in which Plk1 is involved in PDAC disease progression, including multiple inflammation-related pathways. Unexpectedly, inhibition or depletion of Plk1 resulted in upregulation of PD-L1 via activation of the NF-κB pathway. Mechanistically, Plk1-mediated phosphorylation of RB at S758 inhibited the translocation of NF-κB to nucleus, inactivating the pathway. Inhibition of Plk1 sensitized PDAC to immune checkpoint blockade therapy through activation of an antitumor immune response. Together, Plk1 suppresses PDAC progression and inhibits NF-κB activity, and targeting Plk1 can potentiate the efficacy of immunotherapy in PDAC. SIGNIFICANCE: Inhibition of Plk1 induces upregulation of PD-L1 expression in pancreatic ductal adenocarcinoma, stimulating antitumor immunity and sensitizing tumors to immunotherapy.

Stem bark of Fraxinus rhynchophylla ameliorates the severity of pancreatic fibrosis by regulating the TGF-ß/Smad signaling pathway.

Chronic pancreatitis (CP) is a pathological fibroinflammatory syndrome of the pancreas. Currently, there are no therapeutic agents available for treating CP-associated pancreatic fibrosis. Fraxinus rhynchophylla (FR) reportedly exhibits anti-inflammatory, antioxidative and antitumor activities. Although FR possesses numerous properties associated with the regulation of diverse diseases, the effects of FR on CP remain unknown. Herein, we examined the effects of FR on CP. For CP induction, mice were intraperitoneally administered cerulein (50 µg/kg) 6 times a day, 4 days per week for 3 weeks. FR extract (100 or 400 mg/kg) or saline (control group) was intraperitoneally injected 1 hour before the first cerulein injection. After 3 weeks, the pancreas was harvested for histological analysis. In addition, pancreatic stellate cells (PSCs) were isolated to examine the antifibrogenic effects and regulatory mechanisms of FR. Administration of FR significantly inhibited histological damage in the pancreas, increased pancreatic acinar cell survival, decreased PSC activation and collagen deposition, and decreased pro-inflammatory cytokines. Moreover, FR treatment inhibited the expression of fibrotic mediators, such as α-smooth muscle actin (α-SMA), collagen, fibronectin 1, and decreased pro-inflammatory cytokines in isolated PSCs stimulated with transforming growth factor (TGF)-ß. Furthermore, FR treatment suppressed the phosphorylation of Smad 2/3 but not of Smad 1/5 in TGF-ß-stimulated PSCs. Collectively, these results suggest that FR ameliorates pancreatic fibrosis by inhibiting PSC activation during CP.

Breathing exercises: influence on breathing patterns and thoracoabdominal motion in healthy subjects / Exercícios respiratórios: influência sobre o padrão respiratório e o movimento toracoabdominal em indivíduos saudáveis

BACKGROUND: The mechanisms underlying breathing exercises have not been fully elucidated. OBJECTIVES: To evaluate the impact of four on breathing exercises (diaphragmatic breathing, inspiratory sighs, sustained maximal inspiration and intercostal exercise) the on breathing pattern and thoracoabdominal motion in healthy subjects. METHOD: Fifteen subjects of both sexes, aged 23±1.5 years old and with normal pulmonary function tests, participated in the study. The subjects were evaluated using the optoelectronic plethysmography system in a supine position with a trunk inclination of 45° during quiet breathing and the breathing exercises. The order of the breathing exercises was randomized. Statistical analysis was performed by the Friedman test and an ANOVA for repeated measures with one factor (breathing exercises), followed by preplanned contrasts and Bonferroni correction. A p<0.005 value was considered significant. RESULTS: All breathing exercises significantly increased the tidal volume of the chest wall (Vcw) and reduced the respiratory rate (RR) in comparison to quiet breathing. The diaphragmatic breathing exercise was responsible for the lowest Vcw, the lowest contribution of the rib cage, and the highest contribution of the abdomen. The sustained maximal inspiration exercise promoted greater reduction in RR compared to the diaphragmatic and intercostal exercises. Inspiratory sighs and intercostal exercises were responsible for the highest values of minute ventilation. Thoracoabdominal asynchrony variables increased significantly during diaphragmatic breathing. CONCLUSIONS: The results showed that the breathing exercises investigated in this study produced modifications in the breathing pattern (e.g., increase in tidal volume and decrease in RR) as well as in thoracoabdominal motion (e.g., increase in abdominal contribution during diaphragmatic breathing), among others. .

CONTEXTUALIZAÇÃO: Os mecanismos envolvidos na execução dos exercícios respiratórios não foram completamente elucidados. OBJETIVOS: Avaliar o impacto de quatro exercícios respiratórios(diafragmático, suspiros inspiratórios, inspiração máxima sustentada e intercostal) sobre o padrão respiratório e o movimento toracoabdominal em indivíduos saudáveis. MÉTODO: Participaram do estudo15 indivíduos de ambos os sexos (23±1,5 anos com prova de função pulmonar normal). Os indivíduos foram avaliados por meio da pletismografia optoeletrônica na posição supina com inclinação de tronco de 45° durante a respiração tranquila e durante a realização dos exercícios respiratórios. A ordem dos exercícios foi randomizada. Os dados foram analisados pelo teste de Friedman e ANOVA para medidas repetidas com um fator (exercícios respiratórios) seguidos de contrastes pré-planejados e correção de Bonferroni, sendo p<0,005 considerado significativo. RESULTADOS: Todos os exercícios respiratórios promoveram aumento significativo do volume corrente da parede torácica (VCpt) e redução da frequência respiratória (f) quando comparados à respiração tranquila. O exercício diafragmático foi responsável pelo menor VCpt, menor contribuição da caixa torácica e maior contribuição do abdômen. A inspiração máxima sustentada promoveu redução significativamente maior da f comparada aos exercícios diafragmático e intercostal. Os exercícios suspiros inspiratórios e intercostal foram responsáveis pelos maiores valores de ventilação minuto. Os índices de assincronia toracoabdominal aumentaram significativamente ...

Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice.

Capsaicin is a major biologically active ingredient of chili peppers. Extensive studies indicate that capsaicin is a cancer-suppressing agent via blocking the activities of several signal transduction pathways including nuclear factor-kappaB, activator protein-1 and signal transducer and activator of transcription 3. However, there is little study on the effect of capsaicin on pancreatic carcinogenesis. In the present study, the effect of capsaicin on pancreatitis and pancreatic intraepithelial neoplasia (PanIN) was determined in a mutant Kras-driven and caerulein-induced pancreatitis-associated carcinogenesis in LSL-Kras(G12D)/Pdx1-Cre mice. Forty-five LSL-Kras(G12D)/Pdx1-Cre mice and 10 wild-type mice were subjected to one dose of caerulein (250 µg/kg body wt, intraperitoneally) at age 4 weeks to induce and synchronize the development of chronic pancreatitis and PanIN lesions. One week after caerulein induction, animals were randomly distributed into three groups and fed with either AIN-76A diet, AIN-76A diet containing 10 p.p.m. capsaicin or 20 p.p.m. capsaicin for a total of 8 weeks. The results showed that capsaicin significantly reduced the severity of chronic pancreatitis, as determined by evaluating the loss of acini, inflammatory cell infiltration and stromal fibrosis. PanIN formation was frequently observed in the LSL-Kras(G12D)/Pdx1-Cre mice. The progression of PanIN-1 to high-grade PanIN-2 and -3 were significantly inhibited by capsaicin. Further immunochemical studies revealed that treatment with 10 and 20 p.p.m. capsaicin significantly reduced proliferating cell nuclear antigen-labeled cell proliferation and suppressed phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun as well blocked Hedgehog/GLI pathway activation. These results indicate that capsaicin could be a promising agent for the chemoprevention of pancreatic carcinogenesis, possibly via inhibiting pancreatitis and mutant Kras-led ERK activation.

Fatty acid synthase blockade protects steatotic livers from warm ischemia reperfusion injury and transplantation.

Cerulenin has been shown to reduce body weight and hepatic steatosis in murine models of obesity by inhibiting fatty acid synthase (FAS). We have shown that attenuating intrahepatocyte lipid content diminished the sensitivity of ob/ob mice to ischemia/reperfusion injury and improved survival after liver transplantation. The mechanism of action is by inhibition of fatty acid metabolism by downregulating PPARalpha, as well as mitochondrial uncoupling protein 2 (UCP2), with a concomitant increase in ATP. A short treatment course of cerulenin prior to I/R injury is ideal for protection of steatotic livers. Cerulenin opens the potential for expanding the use of steatotic livers in transplantation.

Pancreatitis experimental con ceruleína: evaluación del alcoholismo crónico / Cerulein in acute experimental pancreatitis: chronic alcoholism evaluation

Antecedentes: En EE.UU la pancreatitis aguda de origen alcohólico es del 65 por ciento, en nuestro país es la segunda causa después de la biliar. Objetivos: Analizar los cambios ocasionados por la ceruleína (simil sintético de la colecistokinina), en páncreas, pulmón, hígado y riñón en ratas Wistar, sometidas a intoxicación crónica con alcohol (vino blanco y tinto) durante cuatro meses. Lugar de aplicación: Clínica Privada. Diseño: Trabajo experimental. Material y métodos: Fueron tratadas 51 ratas hembras Wistar que se mantuvieron durante cuatro meses con alimentación para ratas y bebieron exclusivamente vino blanco 17, tinto 17 y agua como control 17. Al finalizar, se dividieron en dos grupos de 21 ratas: Grupo 1 (Control), 7 animales con agua; 7 animales con vino blanco y 7 con vino tinto. Grupo 2 + Ceruleína. 7 animales con agua + ceruleína; 7 animales con vino blanco + ceruleína y 7 animales con vino tinto + ceruleína. Se provocó pancreatitis aguda con 3 inyecciones de ceruleína con dosis de 7,5 mg por kg a las 0, 1 y 2 horas...

Efeito protetor da reduçäo do conteúdo enzimático do pâncreas na lesäo pulmonar da pancreatite aguda / Protective effect of reduction of pancreatic enzyme content on the pancreas in acute pulmonary pancreatitis

A lesao pulmonar surge em até 50-70 por cento dos pacientes com pancreatite aguda. A infusao de ceruleína em doses fisiológicas reduz o conteúdo enzimático do pâncreas com diminuiçao da taxa de mortalidade da pancreatite. Com objetivo de avaliar o efeito da reduçao do conteúdo enzimático do pâncreas sobre a lesao pulmonar da pancreatite aguda, foi induzida pancreatite em ratos Wistar através da infusao, dentro do ducto biliar, de soluçao de taurocolato de sódio a 5 por cento: grupo I, ratos com pancreatite; grupo II, ratos nos quais pancreatite foi induzida somente após reduçao do conteúdo enzimático do pâncreas, e grupo III, controle. A lesao pulmonar foi avaliada através da utilizaçao do corante azul de Evans, sendo menor no grupo II comparativamente ao I (P O,05). Especula-se que a reduçao do conteúdo enzimático do pâncreas diminui a lesao pulmonar da pancreatite aguda pela reduçao da quantidade de enzimas que atinge a circulaçao sistêmica.

Alleviation of gallbladder complications by treatment of hepatic arterial embolization with caerulein.

Transcatheter arterial embolization (TAE) with the concurrent use of caerulein was assessed for the purpose of preventing gallbladder complications often seen after TAE of hepatic carcinoma. Ninety-six cases with primary hepatic carcinoma, who had undergone TAE in the right hepatic arterial region over the past 4 years, were divided into three groups: 22 cases for which embolization was possible on a selective basis by passing the catheter to the peripheral side beyond the bifurcated region of the cystic artery; 40 cases who had undergone TAE in which caerulein was not administered, from the central side of the bifurcated region of the cystic artery; and 34 cases given 20 micrograms caerulein 15-30 min before TAE. A comparison was made using the abdominal pain, pyrexia, rate of leukocytosis and the US findings of the gallbladder as the indices of the gallbladder complications. As a result, it became evident that it was possible to prevent or alleviate gallbladder complications if caerulein were administered before TAE in cases where the embolizing substances were infused in the right hepatic artery from the central side of the bifurcated region of the cystic artery. It was conclusively shown that the gallbladder blood flow decreases if the organ is contracted by caerulein, which in turn causes a decrease in the inflow of the embolizing substances whereby complications are alleviated.

Effect of caerulein on abdominal pain following transcatheter hepatic arterial embolization in malignant liver cancer patients.

The severity of pain occurring in the right hypochondrium after transcatheter hepatic arterial embolization carried out in the treatment of malignant hepatic tumors was compared between a caerulein-treated group and a non-caerulein-treated group. The caerulein-treated group and the non-treated group each comprised nine patients Gelfoam powder was used as an occlusive agent. Even though there were no statistically significant differences between the two groups, the caerulein-treated group tended to demonstrate milder pain in the right hypochondricus, less incidence of tenderness and needed fewer administrations of analgesic than did the non-treated group. None of the three patients showing cystic artery contraction after the caerulein administration developed right hypochondricus pain or tenderness, or required the administration of analgesic. It was concluded that caerulein is useful in relieving right hypochondricus pain occurring after transcatheter hepatic arterial embolization.

Non-invasive treatment for retained common bile duct stones in patients with T tube in situ: saline washout after intravenous ceruletide.

The combination of ceruletide-induced relaxation of the sphincter of Oddi plus flushing with saline has recently been proposed as a novel procedure for the treatment of residual common bile duct (CBD) stones. In this study we have administered intravenous ceruletide (2 ng kg-1 body weight min-1 for 1 h) plus intraductal saline (800-3000 ml, infused at a rate that kept biliary pressure below 30 cmH2O) to a group of 14 patients. The treatment induced the passage of residual stones in 11 subjects (79 per cent) with complete clearance in 7 (50 per cent). The majority of the cleared concretions (11/15) had a diameter less than 10 mm. No severe side-effects were recorded during the treatment. Four of the seven subjects who exhibited incomplete CBD clearance underwent a short cycle of mono-octanoin administration in order to reduce the size of residual radiolucent stones. This course of treatment was followed by another attempt with intravenous ceruletide and saline washout which gave a successful response in an additional three cases. These data indicate that the combination of ceruletide and flushing is a safe and inexpensive method for treatment of residual stones. The procedure is feasible for both radiolucent and radio-opaque stones and is mainly eligible for small concretions of diameter less than 10 mm. Larger (greater than 10 mm) radiolucent stones may be partially dissolved with mono-octanoin and then eliminated by the washout technique.

Pharmacological manipulation of adynamic ileus: controlled randomized double-blind study of ceruletide on intestinal motor activity after elective abdominal surgery.

In a double-blind placebo-controlled trial of patients undergoing elective abdominal surgery (n = 91), a single intravenous infusion of ceruletide (2.5 ng kg-1 min-1 for 1 hour) resulted in audible bowel sounds in 42/47 patients as opposed to 30/44 receiving placebo (P less than 0.025). Excessive bowel sounds were noted in 16 patients in the ceruletide group and four receiving placebo (P less than 0.01). Significantly more patients (P less than 0.01) in the ceruletide group (22/45 versus 9/44) passed flatus per rectum between the second and third post-operative day. Ceruletide infusion was accompanied by a significant increase in the incidence of nausea and vomiting (P less than 0.005, P less than 0.0025) but these side effects were short-lived. These results indicate that ceruletide is likely to be a useful therapeutic agent for acute intestinal adynamic motility disorders.

[Usefulness of caerulein in suppressing post-TAE complications of the gallbladder].

While transcatheter hepatic arterial embolization (TAE) has been extensively performed as a form of treatment for nonresectable malignant hepatic tumors, complications, such as abdominal pain, fever or leukocytosis due to gallbladder infarction by embolic materials frequently occur and have not yet been overcome. We devised a new procedure for reducing the incidence of gallbladder infarction by administering caerulein prior to TAE. Between 1984 and 1986, 63 patients with hepatocellular carcinoma were treated by TAE with the use of Gelfoam. These patients were divided into 3 groups. Fourteen patients underwent TAE in which the tip of the catheter was placed in the right hepatic artery distal to the origin of the cystic artery (group A). In the other patients the tip of the catheter was placed proximal to the origin of the cystic artery; 40 patients were not treated by caerulein (group B); 9 patients were administered caerulein 20 micrograms intramuscularly 15 to 30 minutes prior to TAE. The incidence of complications after TAE, such as abdominal pain, fever over 38 degrees C, leukocytosis and ultrasonographical abnormalities of the gallbladder was compared in these 3 groups. The results showed that in group C (TAE after administration of caerulein), the incidence of complications was significantly decreased compared with group B(TAE without caerulein). The authors suggest that post-TAE infarction of the gallbladder is effectively diminished by contracting it with caerulein.

A neuroendocrinological study of responders and non-responders to ceruletide treatment in chronic neuroleptic-resistant schizophrenia.

To define the characteristics of chronic schizophrenic patients who had responded poorly to treatment with ceruletide, several neuroendocrinological tests were carried out in 5 responders and 5 non-responders. Both thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone stimulation were within normal ranges in all subjects. The luteinizing hormone response to luteinizing hormone-releasing hormone, was slightly weaker in non-responders. There were no differences in the insulin tolerance test between responders and non-responders. Unusually delayed or prolonged growth hormone response to arginine infusion was observed in non-responders. These findings suggest dysfunction of the hypothalamo-pituitary system, especially of the arcuate nucleus and its functionally related areas, in non-responders.

Estudio a doble ciego de la eficacia y tolerancia de ceruletida comparado con pentazocina en el dolor postoperatorio / Study doble blind of the efficacy and tolerance of ceruletide, comparing with pentazocine in postoperative pain

Se evoluó la eficacia y la tolerancia de la ceruletida en el dolor postoperatorio, en un estudo doble ciego, randomizado y comparado

Ceruletide vs. metoclopramide in postoperative intestinal paralysis. A double-blind clinical trial.

Sequential analysis of a double-blind clinical trial involving 26 patients demonstrated a statistically significant superiority of ceruletide over metroclopramide in restoring peristalsis in intestinal paralysis after abdominal surgery (P less than 0.05).