Zinc status in chronic pancreatitis and its relationship with exocrine and endocrine insufficiency.

CONTEXT: A major role of the pancreas in zinc homeostasis has been suggested. OBJECTIVE: To assess erythrocyte zinc status in chronic pancreatitis and to correlate it with pancreatic exocrine and endocrine insufficiency. PATIENTS: One hundred and one patients with chronic pancreatitis (34 alcoholic chronic pancreatitis, 67 tropical chronic pancreatitis) were prospectively studied. MAIN OUTCOME MEASURE: Disease characteristics and imaging features were recorded. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. Exocrine insufficiency was assessed using polyclonal antibody ELISA for pancreatic stool elastase1. Endocrine insufficiency was assessed by serum glucose levels and insulin requirement. RESULTS: Erythrocyte zinc was significantly lower in chronic pancreatitis patients than in the controls (26.5+/-9.5 microg/g Hb vs. 38.0+/-6.6 microg/g Hb; P<0.001), and in tropical chronic pancreatitis than in alcoholic chronic pancreatitis (25.0+/-10.4 microg/g Hb vs. 29.6+/-6.5 microg/g Hb, P=0.001). In chronic pancreatitis patients who had exocrine insufficiency, erythrocyte zinc positively correlated with stool elastase1 (r=0.587, P<0.001). Erythrocyte zinc levels were significantly lower in diabetic patients as compared to non-diabetics (P=0.036). CONCLUSIONS: This study demonstrates zinc deficiency in chronic pancreatitis patients, and that zinc deficiency correlates with exocrine and endocrine insufficiency. Further studies may clarify the possible benefits of zinc supplementation in chronic pancreatitis.

Protective effect of Hachimi-jio-gan against the development of pancreatic fibrosis and oxidative damage in Otsuka Long-Evans Tokushima Fatty rats.

In our previous study, the polyherbal drug Hachimi-jio-gan was reported to possess a protective effect against the progression of diabetic nephropathy by attenuating glucose toxicity and renal damage with a type 2 diabetic model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Based on these findings, this study was undertaken to reveal the effect of Hachimi-jio-gan on pancreatic damage focusing on fibrosis and oxidative stress in type 2 diabetes. OLETF rats were orally administered Hachimi-jio-gan for 32 weeks, and we assessed the changes in the serum glucose level every 8 weeks, as well as those of body weight, and food and water consumption every 4 weeks. In addition, pancreatic wet weight, insulin content, and Western blot analyses of transforming growth factor-beta(1), fibronectin, and nuclear factor-kappaB-related inflammatory enzymes, such as inducible nitric oxide synthesis and cyclooxygenase-2, were also performed in the pancreas. As a consequence, long-term treatment with Hachimi-jio-gan had a hypoglycemic effect, reducing pancreatic atrophy and fibrosis, and ameliorating the oxidative status. Therefore, this may provide evidence that Hachimi-jio-gan is a therapeutic target for preventing the development of pancreatic damage concomitant with hyperglycemia in type 2 diabetes.

Effect of parenteral and enteral nutrition combined with octreotide on pancreatic exocrine secretion of patients with pancreatic fistula.

AIM: To evaluate the effect of parenteral and enteral nutrition combined with octreotide on pancreatic exocrine secretion of the patients with pancreatic fistula. METHODS: Pancreatic juice, drained directly from the pancreatic fistula, was collected, and the volume, protein, amylase, HCO(3)(-), K(+), Na(+) and Cl(-) were determined on d 1, 4 and 7 before and after 7-d treatment with octreotide, respectively. RESULTS: No differences in exocrine pancreatic secretion were observed during the enteral and parenteral nutrition period (t = 2.03, P > 0.05); there were significant decreases in pancreatic juice secretion volume, protein, amylase, HCO(3)(-), K(+), Na(+) and Cl(-) after parenteral and enteral nutrition combined with octreotide compared with octreotide pretreatment (t = 4.14, P < 0.05). CONCLUSION: There is no stimulatory effect on the pancreatic secretion by intrajejunal nutrition and parenteral nutrition. Octreotide is effective on the reduction of pancreatic fistula output.

Treatment of Shwachman syndrome by Japanese herbal medicine (Juzen-taiho-to): stimulatory effects of its fatty acids on hemopoiesis in patients.

Juzen-taiho-to (a Japanese herbal medicine) has been traditionally administered to patients with anemia, neutropenia, or wasting syndrome. We previously attempted to isolate and purify the hemopoiesis-stimulatory components in Juzen-taiho-to extracts using an in vitro hemopoietic stem cell (HSC) assay method in which mouse HSCs can proliferate on a stromal cell line (MS-5). We have found that fatty acids (particularly oleic acid and linolenic acid) actively promote the proliferation of HSCs, and that the effect is mediated by stromal cells, rather than by any direct action on the HSCs. In the present study, we show, using human normal bone marrow cells (BMCs) and umbilical cord blood cells, that similar stimulatory effects are due to the presence of oleic acid and linolenic acid, which stimulate the proliferation of HSCs in stroma-based culture systems. Furthermore, a marked stimulatory effect was noted on BMCs from patients with Shwachman syndrome, which shows pancreatic and bone marrow dysfunctions. We also show the data on hemopoietic recovery after the administration of Juzen-taiho-to to a patient with Shwachman syndrome. These findings suggest that decreased fatty acid levels in the blood, caused by exocrine pancreatic insufficiency, induce bone marrow dysfunction in Shwachman syndrome.

[Correction of the gastric and duodenal motility by laser puncture in pancreatobiliary diseases]. / Korrektsiia motoriki zheludka i dvenadtsatiperstnoi kishki pri zabolevaniiakh organov pankreatobiliarnoi zony metodom lazeropunktury.

96.7 percent of patients with affections of organs of the pancreatobiliary zone displayed motor function disorders of upper portions of the alimentary canal (AC). A characteristic sign of the pathological process in pancreatobiliary organs is decreased frequency of recordable biopotentials and qualitative changes in electrogastrogrames. Changes in qualitative characteristics of the electrogastrogram are clearly related to increase in the intraduodenal pressure recordable with the aid of the "open catheter" technique. Laseropuncture is an effective supplementary method for correction of motility disorders in the upper portions of AC in those patients presenting with affections of the pancreatobiliary organs.

The effect of sennosides on bacterial translocation and survival in a model of acute hemorrhagic pancreatitis.

Bacterial translocation leading to subsequent infectious complications is a significant determinant of outcome in acute hemorrhagic pancreatitis (AHP). The colonic ileus and impaired intestinal barrier function that often accompany AHP may predispose to translocation. Sennoside is a naturally occurring cathartic and choleretic agent that stimulates intestinal mucous secretion and has potent promotility effects. The impact of sennoside-induced intestinal motility and secretory function on bacterial translocation and survival was studied in a rat model of AHP. Severe acute pancreatitis was induced in rats by the intraductal infusion of 2% sodium deoxycholate (DCA, 0.4 ml/kg). A group of sham-operated rats (group A) received intraductal saline, whereas experimental animals were subsequently administered distilled water (group B) or sennoside solution (group C) by gavage every 8 h. After 48 h, intestinal transit of fluorescein isothiocyanate-labeled dextran, serum endotoxin, and amylase levels, and bacterial translocation to mesenteric lymph nodes (MLNs) and pancreatic tissue were determined. The pancreas and intestine were sampled for histologic study. All group A animals survived and did not develop pancreatitis or endotoxemia, whereas groups B and C all demonstrated severe hemorrhagic pancreatitis with evidence of necrosis. Mortality at 48 h was 55% in group B versus 12.5% in group C. Inhibition of intestinal motility was noted in 40% versus 20%, and endotoxin levels were 61.36+/-28.26 pg/L versus 5.41+/-3.58 pg/L in group B versus group C rats, respectively (p<0.001). Pancreatic tissue and MLN cultures were positive in 100% of group B survivors versus 14% of group C survivors (p<0.05). Histologic examination of the intestine in group C animals showed increased mucous secretion, proliferation of goblet cells, and evidence of rapid turnover/renewal of enterocytes. Treatment with the cathartic agent, sennoside, reduced translocation of endotoxin and bacteria, restored intestinal motility, increased mucous secretion, and reduced mortality in a model of acute hemorrhagic pancreatitis in the rat. Other cathartics may have similar properties and may be useful in preventing infectious complications in acute pancreatitis.

Iron overload in the rat pancreas following portacaval shunting and dietary iron supplementation.

Reproduction of pancreatic iron overload in an animal model has been difficult to achieve primarily because of the first-pass extraction of iron by the liver. We hypothesized that portacaval shunting would avoid this hepatic phenomenon and increase pancreatic iron deposition. An end-to-side portacaval shunt was surgically created in male Sprague-Dawley rats, and they were subsequently fed a carbonyl iron-supplemented diet for 17 weeks. This resulted in marked iron accumulation in the pancreas (1621 +/- 188 micrograms/g) compared to minimal deposition in sham-operated rats fed the same diet (138 +/- 53 micrograms/g). Iron deposition in the acinar and centroacinar cells was confirmed histologically by Gomori staining, as well as by ultrastructural examination. Iron overloading was associated with enhanced oxidative stress evidenced by a twofold increase in the levels of glutathione disulfide and thiobarbituric acid-reactive substances. Also, adducts of proteins with malondialdehyde and 4-hydroxynonenal were demonstrated in acinar and ductal cells. Other apparent consequences of iron overload were a 50% reduction in pancreatic amylase content and a decrease in pancreatic protein concentration. These hypotrophic changes were associated with a reduced mass of zymogen granules in the acinar cells noted histologically. Our results show that a combination of portacaval shunting and carbonyl iron feeding achieve pancreatic iron overload and support the role of oxidative stress in the pathogenesis of iron-induced damage in the pancreas.

Ionic control of beta cell function in nesidioblastosis. A possible therapeutic role for calcium channel blockade.

A preterm female infant presented with intractable hypoglycaemia within 10 minutes of delivery. Normoglycaemia could be maintained only by the intravenous infusion of glucose at a rate of 20-22 mg/kg/min. Persistent hyperinsulinaemic hypoglycaemia of infancy was diagnosed from an inappropriately raised plasma insulin concentration (33 mU/l) at the time of hypoglycaemia (blood glucose < 0.5 mmol/l). Medical treatment with glucagon, somatostatin, and diazoxide led to only a modest reduction in the intravenous glucose requirement; a 95% pancreatectomy was performed and histological 'nesidioblastosis' confirmed. In vitro electrophysiological studies using patch clamp techniques on isolated pancreatic beta cells characterised the ionic basis for insulin secretion in nesidioblastosis. The beta cells were depolarised in low ambient glucose concentrations with persistently firing action potentials; these were blocked reversibly by the calcium channel blocking agent verapamil. Persistent postoperative hyperinsulinaemic hypoglycaemia was treated with oral nifedipine. This increased median blood glucose concentrations from 3.5 to 4.8 mmol/l and increased in duration the child's tolerance to fasting from 3 to 10.5 hours. These data allude to an abnormality in the ionic control of insulin release in nesidioblastosis and offer a new logical approach to treatment which requires further evaluation.

Simposio: enfermedades del páncreas. Apoyo nutricio en pancreatitis aguda grave ¿es útil? / Symposium Diseases of pancreas: nutritional support in severe acute pancreatitis, is it usefull?

Objetivo: Analizar los resultados del apoyo nutricio en pancreatitis aguda grave. Sede: Clínica de hiperalimentación y cirugía, Guadalajara, Jalisco, México. Diseño: Estudio retrospectivo, observacional, sin análisis estadístico ni grupo control. Pacientes y métodos: Se estudiaron 17 pacientes portadores de pancreatitis aguda grave (PAG) que recibieron apoyo nutricio durante un período comprendido entre enero de 1991 a enero de 1995. Los criterios de inclusión fueron los siguientes: cuadro clínico y datos de laboratorio de la enfermedad en estudio, evidencia de necrosis pancreática en la tomografía axial computarizada (TAC), con o sin masa abdominal palpable, con 3 o más criterios de Ranson y que hubieran sido seguidos en su evolución y resultado final por los investigadores. Se analizaron las siguientes variables edad, sexo, etiología de la pancreatitis aguda, días de evoluación y ayuno al momento de la interconsulta, albúmina inicial y final, peso inicial y final, tipo de apoyo nutricio y requerimientos aportados, número de días con apoyo nutricio, días de estancia en cuidados intensivos y en el hospital, apoyo nutricio en el hogar durante la convalecencia; tipo de tratamiento médico o quirúrgico, número de intervencione spractidadas, estratificación por criterios de Ranson, métodos de acceso para el apoyo nutricio y morbilidad hospitalaria. Resultados: Doce pacientes fueron hombres y 5 mujees su promedio de edad fue de 36 años, mínima de 13 y máxima de 60 años. La etiología de la pancreatitis aguda fue por el alcoholismo en 6 pacientes, biliar en 5, postraumática en 3, secundaria a medicamentos en 2 y por hiperlipidemia en uno. Promedio de días de evolución y ayuno al momento de la interconsulta para apoyo nutricio 9; todos presentaron entre 3 y 7 criterios de Ranson, promedio 4. Albúmina inicial promedio de 2.7 g/dl, final de 3.4 g/dl. Quince pacientes requirieron 2 cirugías en promedio y 2 fueron tratados conservadoramente. Doce recibieron nutrición parenteral a través de un catéter venoso central de múltiples vías y 5 recibieron nutrición mixta. El promedio de proteínas administradas fue de 2g/kg/día. Diez pacientes permanecieron, en promedio, 10 días en terapia intensiva y el apoyo nutricio se dio por espacio de 25 días en promedio, con extremos de 10 días mínimo y 45 máximo. Todos los pacientes perdieron, en promedio, 15 por ciento de su peso. La morbilidad fue del 70.5 por ciento, la estancia hospitalaria promedio fue de 25 días con mínimo de 10 a 45 días. Dos pacientes fallecieron por falla orgánica múltiple (FOM) (12 por ciento): Conclusión: La aplicación temprana de nutrición artificial disminuye la morbimortalidad

Role of apoptosis in copper deficiency-induced pancreatic involution in the rat.

Rats maintained on a copper-deficient diet supplemented with a copper-chelating agent, triethylenetetramine tetrahydrochloride, for 8 to 10 weeks show marked involution of pancreatic acinar tissue. The present study deals with the possible mechanism of pancreatic acinar cell involution during copper deficiency. Sequential light and electron microscopic observations during the copper-depletion regimen, suggest that apoptosis is the main cause of progressive loss of acinar cells. At 4 weeks of copper deficiency, the apoptotic index was 2 +/- 0.6/1,000 cells. By 6 weeks, the apoptotic index reached a maximum of 95 +/- 25/1,000. By 8 weeks, there was almost total loss of acinar cells. The earliest change of apoptosis was characterized by condensation and margination of chromatin against nuclear membrane. Subsequently, several apoptotic bodies displayed pyknotic nucleus and eosinophilic cytoplasmic condensation. Apoptotic bodies were extruded into the interstitium or phagocytosed by unaffected acinar cells. No associated pancreatic inflammation was present. These results indicate that apoptosis is the process involved in pancreatic involution caused by copper deficiency. The molecular mechanism(s) by which copper deficiency causes apoptosis remain unclear.

[Effect of the antioxidant dibunol on the course of a neurodystrophic process in the rat pancreas]. / Vliianie antioksidanta dibunola na techenie neirodistroficheskogo protsessa v podzheludochnoi zheleze krys.

In experiments on rats using histochemical methods it was postulated that injection of dibunol (ionol) in conditions of subdiaphragmatic vagotomy has a correlative effect on neurodystrophic process in pancreas during the time of observation (7, 14, 30 days postoperation).

Prilocaine-induced methemoglobinemia in a child with Shwachman syndrome.

A case of methemoglobinemia after injection of prilocaine in a patient who had Shwachman syndrome (Shwachman-Diamond syndrome) is presented. The report reinforces the need to be cognizant of dose/weight/mass relationships in patients receiving medications capable of oxidizing hemoglobin.

Clinical chemistry of vitamin B12.

PIP: This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.^ieng

Parotid salivary gland function in patients with exocrine pancreatic insufficiency.

Parotid function tests were performed on 12 patients with pancreatic insufficiency due to chronic pancreatitis. The concentrations of sodium and bicarbonate in stimulated parotid juice were reduced compared to controls (p less than 0.001). The secretion of 75Se-selenomethionine by the parotid salivary gland and exocrine pancreas following a Lundh test meal was measured in 12 patients with normal pancreatic function and 16 patients with exocrine pancreatic insufficiency. Eight of these patients had chronic pancreatitis both parotid and pancreatic secretion of the isotope were impaired. In pancreatic carcinoma the pancreatic excretion was impaired with no significant impairment of parotid secretion. The combined pancreatic/parotid radio-selenium test may be useful in differentiating between chronic pancreatitis and pancreatic carcinoma as the cause of pancreatic insufficiency.