RESUMEN
The mutagens produced through chemical reaction between chlorine and the insecticide fenitrothion were studied by using a quadrupole GC-MS. The mutagenicity and the mutagen formation potential (MFP) of the identified by-products were evaluated by the Ames assay (preincubation method) using Salmonella typhimurium TA100 without exogenous activation by S9 mix (TA100-S9). Before conducting GC/MS analyses, six compounds were presumed to be produced in chlorinated fenitrothion. These compounds were confirmed to be produced by the GC/MS analyses, but none of them were mutagenic. One of the chlorination by-products, 3-methyl-4-nitrophenol, has 19 times greater MFP than that of fenitrothion. This result suggests that a major mutagen in chlorinated fenitrothion will be produced via a chemical reaction between chlorine and 3-methyl-4-nitrophenol.
Asunto(s)
Fenitrotión/química , Halogenación , Insecticidas/química , Mutágenos/química , Cromatografía de Gases y Espectrometría de Masas , Pruebas de MutagenicidadRESUMEN
The effects of highly purified natural porcine cholecystokinin (CCK) and synthetic caerulein on the rate of flow of pancreatic juice, the rate of output of amylase, and the rate of release of immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) were simultaneously investigated in the isolated perfused rat pancreas. The maximal flow rate of pancreatic juice was obtained with concentrations of CCK ranging from 0.5 to 10 mU/ml, whereas amylase output was maximal at CCK concentrations from 1 to 10 mU/ml. Caerulein at concentrations of 0.05-1 ng/ml induced a similar maximal flow rate and amylase secretion. Supramaximal stimulatory concentrations of these peptides resulted in lower rates of release of fluid and amylase than with the maximally effective concentrations. Stimulation of IRI and IRG release was elicited only with concentrations of peptides supramaximal for effects on the exocrine responses. The demonstration of very similar discrepancies between the doses of caerulein required to elicit maximal exocrine responses and those required to elicit endocrine responses provide strong evidence that the pattern of the effect of the porcine CCK is accounted for by CCK itself. Although caerulein had no influence on IRI response when superimposed on 100 or 150 mg/100 ml glucose stimulation, preperfusion of caerulein led to a significant enhancement of IRI response to a subsequent glucose stimulation in both phases. The augmentation effect was completely separate from the direct IRI-stimulating effect of caerulein, because the CCK-like peptide requires no glucose for insulinotropic action. Because the concentrations of the peptides necessary for stimulation of endocrine responses were inhibitory in their effects on exocrine responses, it may be inferred that it is unlikely that the endocrine effect is physiologically important, though the results of caerulein for augmenting glucose-stimulated IRI release suggests a possible role for CCK in carbohydrate metabolism.
Asunto(s)
Ceruletida/farmacología , Colecistoquinina/farmacología , Islotes Pancreáticos/efectos de los fármacos , Páncreas/efectos de los fármacos , Amilasas/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Glucagón/metabolismo , Glucosa/farmacología , Técnicas In Vitro , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Masculino , Páncreas/metabolismo , Jugo Pancreático/metabolismo , RatasRESUMEN
Exocrine secretory function in response to 10 pM to 10 nM synthetic secretin was evaluated in perfused pancreas isolated from control, streptozocin-induced diabetic (STZ-D), alloxan-induced diabetic (ALX-D), and insulin-treated STZ-D rats. In STZ-D rats, the basal rate of pancreatic juice flow was significantly increased (10.3 +/- 1.0 microliters/20 min) compared with control rats (4.4 +/- 0.2 microliters/20 min). The basal rate of amylase output as well as pancreatic amylase content were significantly decreased to less than 5% of control values. The basal rates of protein and trypsinogen outputs were similar in both groups. In both control and diabetic rats, secretin caused a dose-dependent increase in exocrine secretion. Secretin (10 pM to 10 nM) induced 1.1- to 11.7-fold increases in exocrine secretion in STZ-D rats. These increases were significantly lower than the 2.1- to 20.8-fold increases in control rats. Furthermore, there was no significant increase in exocrine secretion from STZ-D rats in response to 10 pM secretin, although this concentration of secretin caused a significant increase in control rats. Secretin-induced exocrine secretion in ALX-D rats was similar to that in STZ-D rats. In insulin-treated STZ-D rats, the basal rates of pancreatic secretion were not significantly different from those of control rats. These results suggest that insulin resistance in this patient was due to a circulating factor of low molecular weight that uncoupled insulin stimulation of glucose transport from receptor binding and phosphorylation. The factor appears to increase the binding activity of the alpha-subunit of the insulin receptor without affecting the kinase activity of the beta-subunit.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Páncreas/metabolismo , Secretina/farmacología , Amilasas/metabolismo , Animales , Técnicas In Vitro , Masculino , Consumo de Oxígeno/efectos de los fármacos , Páncreas/efectos de los fármacos , Páncreas/fisiopatología , Jugo Pancreático/efectos de los fármacos , Jugo Pancreático/metabolismo , Perfusión , Ratas , Ratas Endogámicas , Valores de ReferenciaRESUMEN
We examined the effects of various stimuli on immunoreactive insulin (IRI) and glucagon (IRG) release from perfused pancreases isolated from control and streptozocin-induced diabetic (STZ-D) rats. Diabetes was induced by injecting 30 mg/kg STZ into rats fasted for 16-18 h 12-17 days before our experiments. Glucose (11.1 mM) caused a distinct biphasic pattern of IRI release from the control pancreas, whereas the first phase was marginal and the second phase was absent in the diabetic pancreas. Arginine (20 mM)-induced IRI release was similar in both groups, whereas IRG release was greater in the control rats than in the diabetic rats. Thus, this model of STZ-D simulates a certain class of non-insulin-dependent diabetes mellitus (NIDDM). In these diabetic animals, the cholecystokinin (CCK) analogue ceruletide (620 pM) caused a significantly greater increase in IRI release in the presence of 5.6 mM glucose than in the control rats, but ceruletide caused a similar IRG release in both groups. Because CCK and ceruletide stimulate phosphoinositide turnover in pancreatic islets, we examined the effects of carbachol and phorbol ester TPA on IRI release in the presence of 5.6 mM glucose. Carbachol (10 microM), which is thought to generate similar second messengers as ceruletide, induced greater IRI release in diabetic than in control rats. TPA (100 nM) caused a significantly greater increase in IRI release from the diabetic than the control pancreas. Our results demonstrate that the insulin-releasing mechanism involved in protein kinase C activation is enhanced in this model of NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Ceruletida/farmacología , Diabetes Mellitus Experimental/metabolismo , Islotes Pancreáticos/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Animales , Arginina/farmacología , Carbacol/farmacología , Diabetes Mellitus Experimental/fisiopatología , Glucagón/metabolismo , Glucosa/farmacología , Insulina/metabolismo , Islotes Pancreáticos/patología , Islotes Pancreáticos/fisiopatología , Masculino , Ratas , Ratas Endogámicas , EstreptozocinaRESUMEN
The ability of various C-terminal fragments of cholecystokinin (CCK) to increase pancreatic exocrine and endocrine secretion was examined in the isolated perfused rat pancreas. CCK octapeptide (CCK-8) induced biphasic dose-response curves for stimulation of pancreatic juice and amylase secretion. Maximal pancreatic juice and amylase output were obtained with 100 pM CCK-8. Concentrations of CCK-8 that caused pancreatic exocrine secretion also increased insulin release in the presence of 8.3 mM glucose. The tetrapeptide of CCK also simultaneously stimulated both exocrine and endocrine secretion, but was about 100,000 times less potent than CCK-8. By contrast both deca- and tetradecapeptide of CCK at a concentration of 100 pM stimulated secretion of pancreatic juice and amylase, and elicited insulin release comparably to CCK-8. The complete CCK-8 sequence was required as deamidated CCK-8 was without effects on exocrine and endocrine pancreatic secretion at a concentration of 100 pM. The present observations suggest that the structural requirements for CCK-induced insulin secretion are the same as those for CCK-induced exocrine secretions, and that the amino acids in position 5-8 and the amidated residue on the C-terminus are required for physiological activity of CCK on both the exocrine and endocrine pancreas. It is concluded that C-terminal fragments of CCK with eight or more amino acid residues are potent potentiators of insulin release as well as pancreatic exocrine stimulants.
Asunto(s)
Gastrinas/farmacología , Islotes Pancreáticos/metabolismo , Páncreas/metabolismo , Tetragastrina/farmacología , Amilasas/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Insulina/metabolismo , Secreción de Insulina , Masculino , Páncreas/efectos de los fármacos , Jugo Pancreático/metabolismo , Ratas , Ratas Endogámicas , Sincalida/farmacologíaRESUMEN
(Bu)2cGMP is known to act as a specific competitive inhibitor for gastrin and cholecystokinin (CCK) peptides. We have examined the effects of (Bu)2cGMP on CCK octapeptide (CCK-8) stimulation of insulin release in the isolated perfused pancreas and compared them with those on protein output. Addition of (Bu)2cGMP after a 20-min perfusion with 100 pM CCK-8 resulted in two distinctly different phases of insulin suppression. There was a sharp initial decline in insulin release for 3 min, followed by transient recovery toward the control level for 5 min, and then a small decline until termination of (Bu)2cGMP infusion. (Bu)2cGMP produced a concentration-dependent inhibition of both phases of insulin decrement. (Bu)2cGMP also produced a concentration-dependent inhibition of protein output. Addition of 1 mM (Bu)2cGMP rapidly and completely abolished CCK-8-stimulated protein output. Since CCK is released by meal intake and exogenous CCK stimulates insulin release and augments glucose-induced insulin release, it is possible that endogenous CCK plays an important role in the enteroinsular axis. The present findings of blockade of CCK-8-induced insulin release by selective antagonist of the action of CCK provide evidence for CCK as a mediator in the enteroinsular axis.
Asunto(s)
GMP Cíclico/análogos & derivados , GMP Dibutiril Cíclico/farmacología , Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Sincalida/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Masculino , Perfusión , Ratas , Ratas Endogámicas , Tasa de Secreción/efectos de los fármacos , Sincalida/farmacologíaRESUMEN
The effect of pure natural porcine cholecystokinin (CCK) and synthetic caerulein on endocrine and exocrine pancreatic secretion was investigated in the isolated perfused rat pancreas in the presence of physiological concentrations of glucose. CCK (0.25 mU/ml) or caerulein (0.01 ng/ml) potentiated the insulin secretion induced by 5.6 mM glucose; a significant increase in pancreatic exocrine secretion was also observed at these doses of CCK or caerulein. Further increases in the concentration of CCK (0.25 to 1 mU/ml) or caerulein (0.01 to 1 ng/ml) resulted in dose-dependent increases in both insulin and pancreatic exocrine secretion. The effectiveness of CCK and caerulein as insulinotropic agents depended on the glucose concentration; they were more effective at higher concentrations of glucose. Thus, CCK or caerulein significantly and coincidentally stimulated both insulin secretion and pancreatic exocrine function if 5.6 mM or more glucose is present, whereas in previous studies using 2.8 mM glucose, stimulation of insulin secretion was elicited only with concentrations of the peptides supramaximal for an effect on pancreatic exocrine secretion. CCK may contribute to the entero-insular axis.
Asunto(s)
Ceruletida/farmacología , Colecistoquinina/farmacología , Glucosa/farmacología , Insulina/metabolismo , Páncreas/efectos de los fármacos , Amilasas/metabolismo , Animales , Polipéptido Inhibidor Gástrico/farmacología , Técnicas In Vitro , Secreción de Insulina , Masculino , Páncreas/metabolismo , Ratas , Ratas EndogámicasRESUMEN
The kinetics of insulin secretion in response to glucose were studied in the in vitro perfused rat pancreas before and after removal of islet cell tumors induced by streptozotocin and nicotinamide. In addition, insulin secretion before and after tumor removal was compared with that from normal pancreata before and after sham operations, respectively. Thus, the two pancreas preparations were subjected to repeated perfusions with glucose. Perfusion of pancreata containing tumors with 8.4 mM glucose resulted in biphasic release in a pattern similar to that of normal pancreas. However, both basal and stimulated insulin secretion of tumor-bearing pancreata were greater than either those of pancreata from which tumors had been excluded by ligature or those of normal pancreata before sham operation. A second increase in the concentration of glucose from 2.8 to 8.4 mM also produced a biphasic release of insulin from extratumoral pancreata as well as from sham-operated normal pancreata. However, the insulin secretory response to glucose of extratumoral pancreatic tissue was less than that of control pancreatic tissue. Our findings indicate that pancreatic islet cell tumors induced by streptozotocin and nicotinamide respond to glucose with typical biphasic insulin release. Thus, chemically induced rat insulinomata may provide a readily available and valuable model of insulin-secreting tissue, analogous to normal islets. Furthermore, our study suggests that the B cell function of pancreata containing tumors is inhibited by the preexisting tumor-induced hyperinsulinism or by its metabolic consequences.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/metabolismo , Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Neoplasias Pancreáticas/metabolismo , Adenoma de Células de los Islotes Pancreáticos/inducido químicamente , Animales , Glucosa/farmacología , Técnicas In Vitro , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Cinética , Masculino , Neoplasias Experimentales/metabolismo , Neoplasias Pancreáticas/inducido químicamente , Perfusión , Ratas , EstreptozocinaRESUMEN
The effects of nine novel 2-benzylamino-1,3,5-triazines on photosynthetic reactions were measured in thylakoids isolated from wild-type and atrazine-resistant plants of Chenopodium album. The resistant plants have a mutation of serine for glycine at position 264 of the D1 protein. The measurement of oxygen evolution and chlorophyll a fluorescence induction indicated a 2-4-fold stronger inhibition by the 6-trifluoromethyl analogues of Photosystem II-dependent electron flow than atrazine. Analogues having a 6-methyl-, 6-monofluoromethyl or 6-difluoromethyl substitution were weak inhibitors, indicating that the 6-trifluoro group is very important for strong inhibition. All the nine novel 2-benzylamino-1,3,5-triazines were almost as active in wild-type as in atrazine-resistant thylakoids, indicating that the benzylamino substitution may be important for the lack of resistance in the atrazine-resistant plants.
RESUMEN
Pancreatic exocrine and endocrine secretory dynamics were studied in the isolated perfused pancreata of rats fed a normal diet or a diet supplemented with the alpha-glucosidase inhibitor, acarbose (150 mg/100 g food). After 10 days, the body weight of acarbose-treated rats was slightly lower than that of the control rats despite a larger food intake. Pancreatic amylase levels were significantly decreased, trypsinogen levels were significantly increased, and lipase levels were unaltered in the treated group compared with the controls. Basal and caerulein-stimulated flow rates of pancreatic juice as well as basal amylase output were similar in both groups, whereas caerulein-stimulated amylase output was significantly lower in the acarbose-treated group. Secretory responsiveness of amylase in the treated group was, however, about twice as high as that in the control group when related to pancreatic amylase content. Insulin release in response to either glucose or cerulein was similar in both groups. These findings indicate that treatment with acarbose may alter pancreatic enzyme content without changing the secretory responsiveness of either the exocrine or endocrine pancreas.
Asunto(s)
Glucosidasas/antagonistas & inhibidores , Inhibidores de Glicósido Hidrolasas , Islotes Pancreáticos/efectos de los fármacos , Oligosacáridos/farmacología , Páncreas/efectos de los fármacos , Trisacáridos/farmacología , Acarbosa , Amilasas/metabolismo , Animales , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/fisiología , Masculino , Páncreas/enzimología , Páncreas/fisiología , Ratas , Ratas EndogámicasRESUMEN
A giant coronary aneurysm arising from the sinus node artery is reported. Diagnosis of this lesion by computed tomography and angiography is illustrated. The operative management is described. "Off-pump" aneurysmectomy was successfully performed. The role of occlusion test of the aneurysm inflow tract is emphasized.
Asunto(s)
Aneurisma Coronario/cirugía , Nodo Sinoatrial/cirugía , Anciano , Aneurisma Coronario/diagnóstico por imagen , Aneurisma Coronario/patología , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Nodo Sinoatrial/patología , Tomografía Computarizada por Rayos XRESUMEN
Pancreatic exocrine function in rats given synthetic protease inhibitor camostate (200 mg/kg body weight) perorally once daily for 10 days was investigated. Pancreatic wet weight was significantly increased in the camostate-treated rats. The increase in pancreatic weight was associated with pronounced hypertrophy and moderate hyperplasia. Total amylase, trypsin, and lipase contents in the pancreas were also increased in the camostate-treated group compared with the control rats. Secretory patterns of pancreatic juice and amylase in response to caerulein were similar in both groups, whereas the dose-response curve for pancreatic juice secretion in the camostate-treated rats was shifted tenfold toward higher concentrations of caerulein. Basal and caerulein-stimulated flow rates of pancreatic juice were significantly greater in the camostate-treated rats than the control rats, although both groups showed a threefold increase over basal secretion in response to maximal stimulation. Amylase outputs in basal state and in response to submaximal doses of caerulein were significantly lower, whereas those to maximal and supramaximal doses were significantly greater in the camostate-treated animals than that in the control rats. These results indicate that treatment with camostate induces pancreatic hypertrophy and hyperplasia, and that the secretory function of the hypertrophied pancreas is quantitatively but not qualitatively altered.
Asunto(s)
Gabexato/análogos & derivados , Guanidinas/farmacología , Páncreas/efectos de los fármacos , Jugo Pancreático/metabolismo , Inhibidores de Proteasas/farmacología , Animales , Ésteres , Masculino , Jugo Pancreático/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
The acute and chronic effects of hydrocortisone on insulin secretion were examined in the isolated perfused rat pancreas. In the first part of this study, the chronic effects of hydrocortisone on insulin release were examined using isolated perfused pancreas prepared from rats that had been given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, 5.0, and 10.0 mg/kg body weight once daily for 7 days. Hydrocortisone treatment led to a dose-dependent increase in insulin secretion in response to 8.3 mM glucose. The insulin response to 100 pM cholecystokinin (CCK-8) was also significantly higher in the hydrocortisone-treated rats than in the control group. However, the increment of insulin level over the value before CCK-8 addition in rats treated with hydrocortisone was not significantly different from that in the control rats. In the second part, the acute effects of hydrocortisone on insulin release were studied. Hydrocortisone (17-hydroxycorticosterone) at a concentration of 100 microM caused significant inhibition of the stimulatory effect of CCK-8 on insulin secretion. The inhibition started within 1 min of the beginning of hydrocortisone administration and ceased immediately after the termination of its infusion. We have demonstrated in this study a dual effect of hydrocortisone on insulin release: first, the potentiation of the insulin secretion stimulated by glucose but not by CCK-8 and, second, the inhibition of CCK-8-stimulated insulin secretion.
Asunto(s)
Hidrocortisona/farmacología , Insulina/metabolismo , Páncreas/efectos de los fármacos , Animales , Glucemia/análisis , Colecistoquinina/farmacología , Glucosa/farmacología , Técnicas In Vitro , Secreción de Insulina , Masculino , Páncreas/metabolismo , Perfusión , Ratas , Ratas EndogámicasRESUMEN
CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC.
Asunto(s)
Antígenos de Neoplasias/sangre , Neoplasias de los Conductos Biliares/sangre , Conductos Biliares Intrahepáticos , Biomarcadores de Tumor/sangre , Biomarcadores , Carcinoma Hepatocelular/sangre , Colangiocarcinoma/sangre , Neoplasias Hepáticas/sangre , Neoplasias de los Conductos Biliares/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Colangiocarcinoma/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Queratina-19 , Queratinas , Neoplasias Hepáticas/diagnóstico , Masculino , Persona de Mediana Edad , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , Tomografía Computarizada por Rayos X , alfa-Fetoproteínas/metabolismoRESUMEN
The mode of inhibition of a new complex oligosaccharide that inhibits the alpha-glucoside hydrolase activity of pancreatic and salivary alpha-amylase was studied. Kinetic analysis revealed a non-competitive type of inhibition with a Ki of 1.47 +/- 0.03 micrograms when tested against human pancreatic alpha-amylase and 3.89 +/- 0.08 micrograms against human salivary alpha-amylase. The inhibitory action of alpha-glucoside hydrolase inhibitor (alpha-GHI) on pancreatic amylase was observed over a wide range of pH (6.0--7.9), whereas the inhibition of salivary amylase was optimal at pH 6.5. Column chromatographic investigations suggested the possible formation of an enzyme-inhibitor complex because the mixture of alpha-GHI and pancreatic alpha-amylase was eluted as a single component through a Sephadex G200 column. However, this enzyme-inhibitor complex was easily separated into each component and the enzyme activity was fully recovered after electrophoresis.
Asunto(s)
Amilasas/antagonistas & inhibidores , Glucosidasas/antagonistas & inhibidores , Inhibidores de Glicósido Hidrolasas , Páncreas/enzimología , Saliva/enzimología , alfa-Amilasas/antagonistas & inhibidores , Cromatografía en Gel , Humanos , Concentración de Iones de Hidrógeno , CinéticaRESUMEN
The clinical usefulness of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases was evaluated. The mean serum PSTI level of 41 healthy normal persons was 9.4 ng/ml (ranging from 5.2 to 16.7 ng/ml). Serum PSTI levels were abnormally raised in all patients with acute pancreatitis ranging from 35.0 to 4500 ng/ml, but were almost within normal range in patients with chronic pancreatitis, pancreatic cyst, acute abdominal emergencies such as perforated ulcer and intestinal obstruction, and macroamylasemia. There was no correlation between serum PSTI levels and total or pancreatic-type isoamylase activity. Patients with acute pancreatitis in whom the elevation of serum PSTI was transient and occurred after that of serum amylase activity had relatively mild symptoms and recovered along with normalization of serum PSTI levels. On the other hand, patients whose serum PSTI values became increased coincidentally with serum amylase activity and remained elevated, had severe clinical symptoms and unfavorable clinical outcome. Of 2 patients who underwent partial pancreatectomy, the serum PSTI level increased markedly in one who developed postoperative pancreatitis but not in the other without pancreatitis. In contrast to patients with acute pancreatitis, the serum response to the secretin stimulation in patients with chronic pancreatitis, was only small and transient, reaching the maximum at 10 min after administration of secretin. These results suggest that measurement of serum PSTI concentration may be useful in the diagnosis of acute pancreatitis and that the degree of rise and the duration of the elevated levels of serum PSTI are closely related to the severity of acute pancreatitis.
Asunto(s)
Enfermedades Pancreáticas/sangre , Inhibidor de Tripsina Pancreática de Kazal/sangre , Inhibidores de Tripsina/sangre , Enfermedad Aguda , Adulto , Amilasas/sangre , Enfermedad Crónica , Humanos , Isoenzimas/sangre , Cinética , Persona de Mediana Edad , Quiste Pancreático/sangre , Pancreatitis/sangreRESUMEN
Prevalence of vascular complications in newly diagnosed untreated diabetic patients with obesity was studied over a period of 18 years. A total of 742 patients including 241 subjects with obesity (BMI greater than 25) were analyzed. Obese patients showed higher serum cholesterol and triglyceride and lower HDL-cholesterol levels than non-obese patients. Average prevalence of obesity is shown to be 32.5% with higher prevalence in women (37.8%) than in men (28.3%, P less than 0.01). No definite change is found in yearly prevalence throughout the observation period. Ischemic ECG findings and hypertension were observed more frequently in obese (35.8% and 34.9%, respectively) than in non-obese (25.2%, P less than 0.02; 24.5%, P less than 0.01, respectively) subjects, while diabetic retinopathy was less in obese patients (P less than 0.05). The prevalence of proteinuria was almost the same in obese and non-obese groups. These results coincide with the general concept that obesity may be responsible for the development of macroangiopathy in diabetes mellitus.
Asunto(s)
Complicaciones de la Diabetes , Angiopatías Diabéticas/epidemiología , Obesidad , Adulto , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Angiopatías Diabéticas/etiología , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedades Vasculares/complicacionesRESUMEN
The relationship between the severity of diabetes mellitus and pancreatic exocrine function was investigated in rats made diabetic by injecting 3 different doses of streptozotocin (30, 45 or 60 mg/kg body weight). The expected correlation was obtained between the dose of streptozotocin and degree of elevation of blood glucose and decrease in pancreatic insulin content. Pancreatic amylase content of the diabetic rats was less than that of control rats and was in parallel with less values in pancreatic insulin content. On the other hand, trypsinogen content of diabetic rats was greater than that of control. Basal and caerulein-stimulated flow rates of pancreatic juice and protein output were similar in the control and in all 3 groups of diabetic rats. In contrast, there was a graded response of amylase and trypsinogen, depending upon the content of each enzyme in the pancreas. Both basal and caerulein-stimulated amylase outputs from diabetic rat pancreas were significantly reduced in parallel with the severity of diabetic state, but were similar to those from the control rats when related to the total pancreatic content. The present findings indicate that pancreatic exocrine dysfunction in diabetes mellitus is closely related to the severity of the disease, but the secretory dynamics in the perfused pancreas are not altered.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Páncreas/fisiopatología , Amilasas/análisis , Animales , Glucemia/análisis , Ceruletida , Glucagón/análisis , Glucagón/sangre , Insulina/análisis , Insulina/sangre , Masculino , Páncreas/análisis , Páncreas/enzimología , Pruebas de Función Pancreática , Jugo Pancreático/análisis , Jugo Pancreático/fisiología , Proteínas/análisis , Ratas , Ratas Endogámicas , Estreptozocina , Tripsinógeno/análisisRESUMEN
The effect of the alpha-glucosidase inhibitor acarbose on pancreatic exocrine and endocrine function was studied using the isolated perfused pancreata prepared from rats fed a normal (control diet) or an acarbose-containing sucrose- (ACS diet) or glucose-supplemented diet (ACG diet) for 10 days. Pancreatic amylase and insulin contents in rats fed the ACS diet were significantly decreased compared with those in rats with the control diet. Rats fed the ACG diet, however, had normal enzyme and hormone contents. Basal and cerulein-stimulated flow rates of pancreatic juice in rats with the ACS or ACG diet were similar to those in rats fed the control diet, suggesting that the pancreata from rats treated with acarbose have normal sensitivity and responsiveness to cerulein. On the other hand, cerulein-stimulated amylase output was significantly decreased in rats with the ACS diet, but was normal in rats with the ACG diet. Insulin secretion to both glucose and cerulein stimulation in rats fed the ACS diet was reduced by approximately 55% compared with the control rats. On the other hand, rats fed the ACG diet showed normal insulin secretion to glucose stimulation, although the insulin response to cerulein stimulation was reduced by 30%. These results suggest that the addition of acarbose to the sucrose-rich diet decreases the secretory responsiveness of amylase to cerulein stimulation and that of insulin to both glucose and cerulein stimulation. All these alterations, except the sensitivity of B cells to cerulein, can be normalized by replacing sucrose with glucose.
Asunto(s)
Carbohidratos de la Dieta/farmacología , Glucosa/farmacología , Inhibidores de Glicósido Hidrolasas , Islotes Pancreáticos/efectos de los fármacos , Páncreas/efectos de los fármacos , Sacarosa/farmacología , Trisacáridos/farmacología , Acarbosa , Amilasas/metabolismo , Animales , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Lipasa/metabolismo , Masculino , Páncreas/enzimología , Jugo Pancreático/efectos de los fármacos , Jugo Pancreático/metabolismo , Ratas , Ratas Endogámicas , Valores de Referencia , Tripsina/metabolismoRESUMEN
Novel 2-(benzylamino)-4-methyl-6-(trifluoromethyl)-1,3,5-triazines have the same 1,3,5-triazine skeleton as atrazine, although some of them, for example, 2-(3-chlorobenzylamino)-4-methyl-6-(trifluoromethyl)-1,3,5-tria zin e [pI(50)(spinach) = 7.21], show a >3 times stronger photosynthetic electron transport inhibitory activity than atrazine [pI(50)(spinach) = 6.72]. The new triazines have only one amino group at the triazine ring, and their molecular shapes are different from atrazine. The replacement of the bound [(14)C]atrazine by 1,3,5-triazines was tested to determine whether the novel 1,3,5-triazine analogues exhibit the same binding pattern at the D1-protein as atrazine. It was found that [(14)C]atrazine bound to the D1-protein was replaced by the triazine tested by a clearly competitive interaction. Obviously, the novel 1,3,5-triazines are attached to the same binding niche as atrazine.