RESUMO
BACKGROUND: Focal pancreatitis (FP) is a confined inflammation that mimics a pancreatic mass. Its imaging diagnosis is important to avoid unnecessary procedures. PURPOSE: To describe the spectrum of magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) and diffusion-weighted MRI (DWI) findings of focal pancreatitis mimicking pancreatic masses. MATERIAL AND METHODS: Findings of MRI/MRCP including DWI with a b value of 0 and 600 s/mm(2) in 14 patients with pancreatic masses on MRI were retrospectively reviewed and compared to normal pancreas in 14 patients as a control group. RESULTS: FP revealed hypointense signal intensity (SI) (3/14), hypo- to isointense SI (7/14), or isointense SI (4/14) on T1-weighted images, and hypointense SI (1/14), isointense SI (5/14), iso- to hyperintense SI (7/14), or hyperintense SI (1/14) on T2-weighted images compared to remaining pancreas (RP). MRCP images revealed dilatation of the common bile duct (CBD) and main pancreatic duct (MPD) (5/14), dilatation of the MPD only (3/14), dilatation of the CBD only (3/14), and normal MPD and CBD (3/14). Both FP and RP revealed three types of time-signal intensity curves: 1) rapid rise to a peak, with a rapid decline (FP=2, RP=4), 2) slow rise to a peak, followed by a slow decline (FP=5, RP=4), and 3) slower rise to a peak, with a slow decline or plateau (FP=7, RP=6). Mean apparent diffusion coefficient (ADC) values for FP and RP were 2.09+/-0.18 and 2.03+/-0.2 x 10(-3) mm(2)/s, respectively. ADC values of FP and RP revealed no significant difference. CONCLUSION: The spectrum of imaging findings of focal pancreatitis on MRI/MRCP including DWI was described. Findings of FP were not distinctive as compared to the remaining pancreas.
Assuntos
Colangiopancreatografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Pancreatite/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste/administração & dosagem , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Gadolínio DTPA , Humanos , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
The mechanism of regulation of negative feedback inhibition of the exocrine pancreas and its possible role in decreasing the exocrine secretion of the grafted human pancreas is unknown. To evaluate this we studied the effect of oral pancreatic enzymes on the stimulated transplanted pancreatic exocrine secretion in eight patients with allograft pancreaticocystostomies. After an 8-hr fast, all graft exocrine secretions via graft stent, fistula, and urinary anastomosis were collected for a 1-hr basal period. A standard 300-ml Lundh test meal was then ingested, and all exocrine secretions were collected in 30-min intervals for 3 hr. This test was repeated with 6 capsules of pancrelipase (24,000 units of lipase, 120,000 units of amylase, and 150,000 units of protease) given with the Lundh test meal. Stent, urine and fistula volume, amylase, and pH were measured for each collection period. The total 3-hr amylase secreted after the test meal and the test meal plus pancrelipase were compared. The period of peak amylase secretion after the test meal alone was compared with the same period after the test meal plus pancrelipase and the premeal basal period. The total amylase decreased 34% from 5550 +/- 1000 to 3680 +/- 740 IU/3 hr (P < .03) with pancrelipase. The peak amylase secretion decreased 63% from 1520 +/- 271 to 567 +/- 185 IU/30 min (P < .02) with the addition of pancrelipase to the test meal. Pancrelipase eliminated all meal-stimulated amylase secretion with the mean secretion 16% below the basal secretion of 674 +/- 117 IU/30 min. We conclude that pancreatic negative feedback inhibition significantly decreases meal-stimulated and basal exocrine secretion in the transplanted human pancreas.
Assuntos
Transplante de Pâncreas/fisiologia , Pâncreas/enzimologia , Pâncreas/metabolismo , Amilases/metabolismo , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas/cirurgia , Retroalimentação/fisiologia , Feminino , Humanos , Masculino , Extratos Pancreáticos/fisiologia , Fatores de TempoRESUMO
Octreotide acetate (Sandostatin), a long-acting somatostatin analogue, has been demonstrated to have an inhibitory effect on exocrine secretion in the neurally intact pancreas. This study was designed to evaluate the effect of this agent on exocrine secretion in the denervated canine pancreas, utilizing animals with pancreatic autografts and functioning pancreaticocystostomies. The rates of secretion of urinary (autograft) amylase (units/min) and bicarbonate (mM/min), over a five-hr interval, were determined in the basal state (group A, n = 10), after a bolus injection of 400 micrograms of Sandostatin (group B, n = 5), after a standard meal (group C, n = 5), or a meal preceded by 400 micrograms of Sandostatin (group D, n = 5). Basal secretion of amylase was decreased for 4 hr following Sandostatin, although this decrease was not significant. Conversely, basal bicarbonate secretion was not inhibited by Sandostatin. When compared with group C (22.4 +/- 3.2), a significant inhibition of meal-stimulated amylase release was demonstrated in group D (5.4 +/- 0.21, P = 0.0006) during the first hour after Sandostatin was given. This inhibition remained significant at 2 hr (group C = 38.5 +/- 5.2 versus group D = 9.4 +/- 0.8; P = 0.0006) and 3 hr (group C = 38.6 +/- 6.3 versus group D = 17.5 +/- 0.9; P = 0.0108) after Sandostatin was given. In addition, meal-stimulated bicarbonate secretion was significantly inhibited for 2 hr following Sandostatin (group C = 0.19 +/- 0.03 versus group D = 0.07 +/- 0.02, P = 0.0096; and group C = 0.23 +/- 0.03 versus group D = 0.10 +/- 0.01, P = 0.0018, respectively). These studies demonstrate that Sandostatin has a profound inhibitory effect on meal-stimulated enzyme and bicarbonate release in a denervated canine autograft model. Although the site of action of this agent remains to be defined, Sandostatin may have therapeutic potential in clinical pancreas transplantation.
Assuntos
Octreotida/farmacologia , Transplante de Pâncreas , Pâncreas/efeitos dos fármacos , Amilases/metabolismo , Animais , Bicarbonatos/metabolismo , Colecistocinina/metabolismo , Cães , Feminino , Alimentos , Pâncreas/metabolismo , Transplante AutólogoRESUMO
We have seen that UGI bleeding is a serious and apparently growing problem for seniors. Of special concern in the older patient are the frequency with which serious peptic disease presents silently, the limitation frequently imposed on adequate pain relief from NSAIDs, and the higher complication rates from most of the causes of UGI bleeding. Care of the elderly would be enhanced by research focused on defining those older patients most at risk of experiencing NSAID-induced peptic complications, improved methods for preventing or treating NSAID-induced ulceration that are well tolerated and cost-effective, and better regimens for preventing the recurrence of ulcers and UGI bleeding in these patients. In regard to the last, future investigation of the role of H. pylori, methods for successfully eliminating the organism, and the effect of eradication on patients' subsequent course may be particularly helpful.
Assuntos
Úlcera Péptica/epidemiologia , Fatores Etários , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/uso terapêutico , Protocolos Clínicos/normas , Comorbidade , Árvores de Decisões , Endoscopia , Humanos , Incidência , Masculino , Úlcera Péptica/mortalidade , Úlcera Péptica/terapia , Recidiva , Fatores de RiscoRESUMO
We report a case in an infant of horse bot fly myiasis that was unusual because the maggot had developed to the second instar (of three potential instars). This represents the first report of such late development in a human. The case occurred in a rural area of the Pacific northwest (Washington) in late summer.
Assuntos
Dípteros/crescimento & desenvolvimento , Miíase , Animais , Anti-Infecciosos Locais/uso terapêutico , Cefalexina/uso terapêutico , Cefalosporinas/uso terapêutico , Dípteros/parasitologia , Humanos , Lactente , Larva/crescimento & desenvolvimento , Larva/parasitologia , Masculino , Miíase/cirurgia , Povidona-Iodo/uso terapêutico , População Rural , WashingtonRESUMO
This study was designed to investigate a possible mechanism of action by which octreotide acetate causes insulin suppression in the denervated pancreas. Canine tissue slices were placed in a pH-adjusted medium with varying concentrations of glucose and octreotide acetate: Experiment 1, 30 min in basal medium with 0.6 mg/ml glucose; Experiment 2, addition of 6.0 mg/ml glucose; Experiment 3, addition of 4 microg octreotide acetate/70 ml (comparable to 100 microg/25 kg body weight); Experiment 4, addition of 16 microg octreotide acetate/70 ml; Experiment 5, incubation with 6.0 mg glucose/ml and 4 microg octreotide acetate/70 ml; Experiment 6, incubation with 6.0 mg glucose/ml and 16 microg octreotide acetate/70 ml; Experiment 7, preincubation with 4 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml; and Experiment 8, preincubation with 16 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml. Medium levels of insulin, glucagon, and amylase were collected at intervals during the incubation periods. There was an appropriate increase in the rate of insulin release to glucose stimulation in the high-glucose (6.0 mg/ml) group. There was no significant inhibition of basal or glucose-stimulated insulin release with either simultaneous or pretreatment of the canine pancreatic tissue slices with either concentration of octreotide acetate. These studies support an indirect mechanism by which octreotide acetate exerts its inhibitory effect on endocrine and exocrine function in the canine pancreas transplant model.
Assuntos
Fármacos Gastrointestinais/farmacologia , Insulina/metabolismo , Octreotida/farmacologia , Pâncreas/metabolismo , Amilases/metabolismo , Animais , Cães , Feminino , Glucagon/metabolismo , Glucose/farmacologia , Técnicas In Vitro , Secreção de Insulina , Pâncreas/efeitos dos fármacos , SincalidaRESUMO
Somatostatin and its analogue, octreotide acetate (Sandostatin), have been demonstrated to suppress exocrine secretion in a denervated canine pancreatic autograft model. To help define this inhibitory mechanism, the effect of these agents on cholecystokinin (CCK)-stimulated acinar cell secretion was evaluated. In vitro assessment evaluated the effect of somatostatin on octapeptide (OP)-CCK-stimulated amylase release of pancreatic tissue slices. In vivo assessment employed animals with pancreatic autografts and pancreaticocystostomies, evaluating the effect of a bolus intravenous injection of 100 micrograms of octreotide acetate on the basal and OP-CCK-stimulated (125 ng/kg/h) secretion of urinary (autograft) amylase and bicarbonate. Incubation of tissue slices with 0.16, 0.24, or 0.32 microgram/ml somatostatin had no significant effect on in vitro OP-CCK-simulated amylase release. Intravenous octreotide acetate resulted in a significant decrease in the basal rate of amylase secretion but had no significant effect on OP-CCK-stimulated autograft amylase or bicarbonate release. These studies demonstrate that octreotide acetate has an in vivo inhibitory effect on basal amylase release of pancreatic autografts but cannot counteract maximal stimulation with exogenous OP-CCK. Also, somatostatin does not inhibit OP-CCK-stimulated acinar cell secretion of pancreatic tissue slices. These results indicate that the exocrine inhibition produced by somatostatin analogues in the grafted pancreas occurs via an indirect mechanism.
Assuntos
Denervação , Octreotida/farmacologia , Pâncreas/inervação , Pâncreas/metabolismo , Sincalida/farmacologia , Somatostatina/farmacologia , Amilases/metabolismo , Animais , Bicarbonatos/metabolismo , Cães , FemininoRESUMO
Stenting of the biliary tract is performed for a variety of benign and malignant disorders. Although uncommon, proximal and distal migration of these stents is known to occur. We report a case of jejunal perforation from a distally migrated biliary stent.
Assuntos
Endoscopia Gastrointestinal/métodos , Migração de Corpo Estranho/complicações , Perfuração Intestinal/etiologia , Jejuno/lesões , Stents/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Falha de Equipamento , Migração de Corpo Estranho/cirurgia , Humanos , Perfuração Intestinal/cirurgia , Jejuno/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
Monitoring of urinary enzymuria has been utilized to detect allograft dysfunction after pancreas transplantation with pancreaticocystostomy. In addition, pharmacologic exocrine suppression has been advocated to minimize bicarbonate and protein wasting. Ensuring the validity of these approaches requires controlling both for immunologic alterations in transplant function and for the renal excretion of amylase, bicarbonate, and protein. Toward this end, adult mongrel dogs were divided into two groups. Group A animals underwent distal pancreatectomy alone, and group B animals underwent distal pancreatectomy with autotransplantation and pancreaticocystostomy. In each group, amylase, bicarbonate, and protein output were determined over a 5-hour period in the basal state, during a continuous infusion of octapeptide-cholecystokinin (OP-CCK) at 125 ng/kg/hour, and during a continuous infusion of OP-CCK (125 ng/kg/hour) plus a bolus injection of one clinical unit of secretion per kilogram. Bicarbonate output was not significantly different in the groups with and without autografts. Compared to nonautograft experiments, a statistically significant increase in amylase output was demonstrated in the autograft animals. An increase in protein output was also demonstrated in the autograft experiments, and this increase was statistically significant in the OP-CCK group and the OP-CCK and secretin group. In addition, compared to basal autograft secretion, OP-CCK and OP-CCK plus secretin stimulation resulted in a sustained and significant increase in urinary amylase and protein secretion, indicating preserved sensitivity of the denervated pancreas to exogenous hormones. These results indicate that the canine segmental pancreatic autograft model with pancreaticocystostomy is a suitable model to identify agents associated with exocrine inhibition after transplantation.
Assuntos
Transplante de Pâncreas/fisiologia , Pâncreas/metabolismo , Amilases/metabolismo , Animais , Bicarbonatos/metabolismo , Cães , Feminino , Proteínas/metabolismo , Sincalida/farmacologia , Transplante AutólogoRESUMO
Recurrence of pain after cholecystectomy is common. This postcholecystectomy syndrome, defined as pain that is unexplained by upper abdominal radiologic and/or endoscopic studies, including endoscopic retrograde cholangiopancreatography, often results from sphincter of Oddi dysfunction. Endoscopic demonstration of elevated sphincter of Oddi pressures is required for diagnosis. The treatment of choice is usually endoscopic sphincterotomy, which yields long-term relief in most patients. Surgical sphincteroplasty or use of calcium channel blockers or long-acting nitrates may be effective if endoscopic sphincterotomy is not suitable.
Assuntos
Colecistectomia , Dor/etiologia , Complicações Pós-Operatórias , Esfíncter da Ampola Hepatopancreática/fisiopatologia , Humanos , Manometria , Dor Pós-Operatória , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , SíndromeRESUMO
The development of nonoperative methods of biliary drainage has altered traditional concepts regarding management of medical and surgical jaundice. Patients with newly diagnosed obstructive jaundice typically are elderly and have an unresectable neoplasm. Because surgical cure is often impossible and operation is usually risky in such patients, decompression of the biliary tree by endoscopic retrograde cholangiopancreatography and endoscopically inserted biliary stents has become an increasingly popular means of palliation. Percutaneous transhepatic cholangiography and surgical bilidigestive bypass remain important alternatives. Selection of optimal management for the individual patient requires an in-depth evaluation by a skilled team consisting of the primary care physician, endoscopist, interventional radiologist, and surgeon.
Assuntos
Colestase/terapia , Idoso , Bilirrubina/sangue , Colangiopancreatografia Retrógrada Endoscópica , Colestase/diagnóstico , Colestase/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Testes de Função Hepática , Cuidados Paliativos , StentsRESUMO
Common bile duct stones are frequently discovered after cholecystectomy or are the first sign of biliary tract disease. Because detection usually requires cholangiography and reoperation is technically difficult, risky, and thus undesirable, nonsurgical methods of identifying and removing the stones have evolved. Among these, endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic retrograde sphincterotomy and stone extraction is the method of choice after cholecystectomy. As newer methods of dealing with biliary disease evolve and alter the spectrum of complications, ERCP will remain an essential diagnostic and management tool.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Cálculos Biliares/diagnóstico , Cálculos Biliares/terapia , Esfinterotomia Endoscópica , Colecistectomia , HumanosAssuntos
Lipase/uso terapêutico , Transplante de Pâncreas , Extratos Pancreáticos/uso terapêutico , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Administração Oral , Adulto , Retroalimentação , Humanos , Masculino , Pâncreas/metabolismo , Pancreatite/tratamento farmacológico , PancrelipaseRESUMO
BACKGROUND AND STUDY AIMS: Midazolam HCl (Versed) is often used for intravenous conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and is increasingly used in endoscopic sphincter of Oddi (SO) manometry. The effect of medications on SO motility should be fully characterized if they are to be used during SO manometry. There has been controversy as to whether midazolam influences SO motility. The aim of this study was to determine the effect of midazolam on the normal SO. PATIENTS AND METHODS: The study population consisted of 60 patients presenting with recurrent abdominal pain who were found to have SO basal pressure of less than 40 mmHg on SO manometry. ERCP was performed in the standard fashion using a pneumohydraulic capillary perfused triple-lumen catheter system in a stationary pull-through method from the pancreatic and common bile ducts. In the test group 30 patients received 2 mg midazolam intravenously while the 30 patients in the control group received intravenous saline. SO manometry was performed, with recording of the basal pressure, phasic pressure, phasic amplitude, phasic frequency and ductal pressure before and 3 min after the intravenous infusion. The changes in basal, phasic and duct pressure as well as phasic frequency before and after the administration of saline and midazolam were compared. RESULTS: Midazolam causes a small but statistically significant reduction in basal and peak SO pressure (4 and 19 mmHg respectively), compared with saline. Diagnostic concordance (normal vs. abnormal) between the basal sphincter pressure before and after midazolam was seen in 100 % of patients. Midazolam does not significantly affect phasic amplitude, phasic frequency or duct pressure. CONCLUSIONS: Midazolam does not have a clinically significant influence on the accuracy of SO manometry in identifying normal sphincteric motility.
Assuntos
Hipnóticos e Sedativos/farmacologia , Manometria , Midazolam/farmacologia , Esfíncter da Ampola Hepatopancreática/efeitos dos fármacos , Dor Abdominal/diagnóstico , Dor Abdominal/cirurgia , Adulto , Estudos de Casos e Controles , Colangiopancreatografia Retrógrada Endoscópica , Sedação Consciente , Diazepam/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esfíncter da Ampola Hepatopancreática/fisiopatologiaRESUMO
This study was designed to determine the effect of a potent cholecystokinin antagonist, L-364,718, on canine pancreatic endocrine function following partial pancreatectomy. Plasma glucose, insulin, and glucagon were determined over a 2-hr interval following an intravenous bolus of 0.5 g/kg glucose in a 50% solution. The following groups were established: normal animals (group A, n = 5), normal animals pretreated with 20 nmole/kg L-364,178 (group B, n = 5), partially pancreatectomized animals (group C, n = 5), and partially pancreatectomized animals pretreated with 20 nmole/kg L-364,178 (group D, n = 5). In contrast to animals with an intact pancreas, pretreatment with L-364,718 following partial pancreatectomy resulted in a significant decrease in peak insulin (group C = 132.8 +/- 13.0 microU/ml vs Group D = 90.4 +/- 16.1 microU/ml, P < 0.05) and the basal-to-peak insulin difference (group C = 111.9 +/- 11.5 microU/ml vs group D = 77.5 +/- 16.6 microU/ml, P < 0.05). Despite this, the rate of glucose utilization (K value) was significantly increased in the partially pancreatectomized animals given the antagonist (group C = -1.22 +/- 0.22%/min vs group D = -2.79 +/- 0.427%/min) and there were no significant differences in basal or peak glucose when comparing the groups given L-364,718 with the groups given placebo (group A vs B and group C vs D). Thus, the CCK antagonist L-364,718 significantly decreases peak insulin in partially pancreatectomized animals but not in nonoperative control animals. There is a paradoxical increase in the rate of glucose utilization but no effect on glucose homeostasis. The effect of this antagonist in other models of reduced islet cell reserve (i.e., pancreas transplantation) remains to be determined.
Assuntos
Benzodiazepinonas/farmacologia , Antagonistas de Hormônios/farmacologia , Pâncreas/efeitos dos fármacos , Pancreatectomia , Animais , Glicemia/efeitos dos fármacos , Contagem de Células , Devazepida , Cães , Feminino , Glucagon/sangue , Glucose/metabolismo , Insulina/sangue , Ilhotas Pancreáticas/citologia , Pâncreas/citologia , Pâncreas/cirurgia , Receptor de Colecistocinina A , Receptores da Colecistocinina/antagonistas & inibidoresRESUMO
Although the efficacy of upper gastrointestinal endoscopy in the diagnosis of a graft-enteric fistula is defined, the clinical utility of colonoscopy in this problem is not well described. We report a case of a 65-yr-old white male with gastrointestinal bleeding and a suspected graft-enteric fistula which was diagnosed by an immediate preoperative colonoscopic examination. The colonoscopy performed under general anesthesia in the operating room not only documented the presence and location of the graft colonic fistula but also illustrated the necessity for a more radical surgical resection before any planned revascularization. The current literature on the various methods of diagnosis and management of graft-enteric fistula was reviewed.
Assuntos
Prótese Vascular , Fístula/diagnóstico , Artéria Ilíaca , Fístula Intestinal/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Doenças do Colo Sigmoide/diagnóstico , Idoso , Colonoscopia , Fístula/cirurgia , Humanos , Fístula Intestinal/cirurgia , Perna (Membro)/irrigação sanguínea , Masculino , Polietilenotereftalatos , Complicações Pós-Operatórias/cirurgia , Reoperação , Doenças do Colo Sigmoide/cirurgiaRESUMO
Animal studies suggest that aging is associated with anorexia and disordered gastrointestinal transit. To determine whether there is a relationship between the effects of aging on appetite and gastrointestinal transit in humans, 19 young (age 23-50 yr) and 14 elderly (age 70-84 yr) normal volunteers underwent measurements of 1) desire to eat, hunger, and fullness (visual analog scales); 2) gastric emptying (scintigraphy); 3) orocecal transit (breath hydrogen); 4) total gut transit (radiopaque markers); and 5) autonomic nerve function (cardiovascular reflexes). We found that, postprandially, elderly subjects had less desire to eat (P < 0.05) and less hunger (P < 0.05), but not a significantly greater fullness than younger subjects. Gastric emptying (50% emptying time) for solid (182 +/- 26 vs. 127 +/- 13 min, P < 0.05) and liquid (47 +/- 4 vs. 35 +/- 3 min, P < 0.05) meal components was slower in elderly subjects. Postprandial hunger was inversely related (r = -0.39, P < 0.05) to solid gastric emptying. There were no significant differences in orocecal and total gut transit times between the two groups. Autonomic nerve function was abnormal in 11 elderly but none of the young subjects (P < 0.01). We conclude that aging is associated with 1) diminished desire to eat and hunger, 2) slowing of solid and liquid gastric emptying, 3 no change in orocecal and total gut transit, and 4) autonomic nerve dysfunction. The slowing of gastric emptying may contribute to anorexia in aging subjects.
Assuntos
Envelhecimento/fisiologia , Anorexia/etiologia , Trânsito Gastrointestinal , Fome , Adulto , Idoso , Idoso de 80 Anos ou mais , Apetite , Feminino , Esvaziamento Gástrico , Humanos , Masculino , Pessoa de Meia-Idade , Resposta de Saciedade , Fatores de TempoRESUMO
This study evaluated the effect of the cholecystokinin antagonist L-364,718 on exocrine secretion in canine pancreatic autografts with pancreaticocystostomies. Urinary (autograft) amylase (U/min) and bicarbonate (mmole/min) secretion, over a 6 hr interval, were determined in the basal state (Group A), after a bolus injection of 20 nmoles/kg of L-364,718 (Group B), during a continuous cholecystokinin octapeptide (OP-CCK) infusion at 125 ng/kg/hr either alone (Group C), with a bolus injection of 20 nmoles/kg (Group D), or 30 nmoles/kg (Group E), of L-364,718 1 hr before initiating OP-CCK, or 20 nmoles/kg of L-364,718 1 hr after initiating OP-CCK (Group F). L-364,718 had no effect on basal or OP-CCK-stimulated secretion of bicarbonate. Basal amylase secretion was decreased 1 hr after L-364,718 and remained significantly lower than controls throughout the study interval. When compared to Group C (280.3 +/- 48.6), OP-CCK-stimulated amylase secretion was significantly lower for the first hour after L-364,718 in both Group D (157 +/- 46.7) and Group E (31.9 +/- 11.6). In Group E, 2, 3, and 4 hr post-L-364,718 amylase releases were 60.2 +/- 19.7, 77.7 +/- 25.1, and 87.2 +/- 28.3 compared to 335.5 +/- 85.9, 291.0 +/- 21.8, and 289.9 +/- 45.7 in Group C indicating a sustained significant inhibition of stimulated autograft amylase secretion with the higher L-364,718 dosage. In Group F, no significant change in amylase secretion was demonstrated, indicating that L-364,718 must be administered prior to CCK stimulation to be effective. These studies demonstrate that L-364,718 has a dose dependent, inhibitory effect on basal, and OP-CCK-stimulated amylase secretion in a denervated autograft model. The therapeutic potential of L-364,718 and other CCK receptor antagonists in pancreatic transplantation warrants further study.
Assuntos
Benzodiazepinonas/farmacologia , Colecistocinina/antagonistas & inibidores , Antagonistas de Hormônios/farmacologia , Transplante de Pâncreas , Pâncreas/efeitos dos fármacos , Amilases/metabolismo , Amilases/urina , Animais , Bicarbonatos/metabolismo , Devazepida , Cães , Feminino , Pâncreas/metabolismo , Sincalida/farmacologia , Fatores de TempoRESUMO
The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 microg/kg/hr x 6 hr, for 10 weeks. Procollagen alpha1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.