Excretion of three alkaloids from Simiao Pills in urine, feces, and bile between normal and type 2 diabetic rats / 中国中药杂志

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P<0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t_(1/2) and K_e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.

Advances in research of traditional Chinese medicine for promoting bile secretion and excretion / 中国中药杂志

Cholagogic traditional Chinese medicines refer to those that can promote bile secretion and excretion, strengthen gallbladder contraction and promote gallbladder emptying. They are mainly used to treat cholecystitis, gallstones, cholestasis, biliary tract infection, jaundice hepatitis and other diseases in clinical application. As a traditional medicine in our country, Chinese herbal medicines have many advantages, such as extensive resources, low cost, little or no toxic and side effects, and in addition, it is not easy for animals to produce drug resistance. With the progress of science and technology and the rapid development of traditional Chinese medicine, many achievements have been made in the research of cholagogic traditional Chinese medicines. Traditional Chinese medicine plays a cholagogic role mainly by promoting bile secretion, regulating SCP2 mRNA, FXR, BSEP and efflux transporter protein, dissolving cholesterol, promoting the relaxation of Oddi's sphincter and changing the composition of bile, etc. Traditional Chinese medicine decoction, traditional Chinese medicine preparation, Chinese medicine combined with acupuncture, ear acupoint pressing, soaking bath, western medicine and alike are often used to treat biliary system diseases in clinical practice. The effective rate of combination of traditional Chinese medicine and other methods was significantly higher than that of compound prescription, western medicine, acupuncture and soaking bath alone. General attack therapy and new therapies are also used in clinical treatment. The clinical effect of traditional Chinese medicine is remarkable. By means of literature review, the pharmacological effects, mechanism and clinical application of Chinese herbal medicines and compound prescriptions with gallbladder-promoting effect in the past 15 years were summarized in this paper. At the same time, some existing problems were found and prospects were expected.

Bacteriocinogenic Lactococcus lactis subsp: lactis DF04Mi isolated from goat milk: Evaluation of the probiotic potential

Lactic acid bacteria capable of producing bacteriocins and presenting probiotic potential open innovative technological applications in the dairy industry. In this study, a bacteriocinogenic strain (Lactococcus lactis subsp. lactis DF4Mi) was isolated from goat milk, and studied for its probiotic potential. Lc. lactis DF4Mi was resistant to acidic pH and oxbile, presented co-aggregation with Listeria monocytogenes, and was not affected by several drugs from different generic groups, being sensitive to most tested antibiotics. These properties indicate that this Lc. lactis strain can be used for enhancement of dairy foods safety and quality, in combination with potential probiotic properties.

Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction / Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction.

The present tests were undertaken in order to analyze in male Wistar rats the changes in the exocrine and endocrine pancreas and on the interactions that normally evolve in the insulo-pancreon-axis. To evaluate this by a single i.p. Boots secretin injection, glycemia (G), amylasemia (A) and lipasemia (L) were determined. In bile-pancreatic secretion, we analyzed, pre and post-secretin, the following parameters: volume (V), bicarbonate output (BO), amylase output (AO) and lipase output (LO). Three groups of tests were done: a) control (C); b) streptozotocin-treated non-diabetic-rats (St-ND) and c) streptozotocin-treated diabetic animals (St-D) which showed morning glycemia values higher than 16.0 mmol/l. Four months later, under Tiopental i.p anesthesia, a bile-pancreatic fistula was done. Following a 30 min basal period, Boots secretin (20 CU/kg) was i.p injected. Bile-pancreatic secretion put in evidence a significant fall of BO in both St-ND and St-D series. In controls, AO revealed a post-secretin increase of 160

, while in the St-D rats showed a depression of 41

. The behavior of L was different, being augmented (+27

) in the C, while in the St-D rats the response was significantly higher (+95

). In bile-pancreatic-secretion, the fall of BO and AO in the St-ND and St-D series in respect to the C, are probably consequence of the diminishing potentiating effects exerted normally by insulin on the secretin-induced water and bicarbonate secretion of the pancreon units. In contrast, the rising of LO in the St-D, an expression of an enhancing pancreocyte’s synthesis and secretion of lipase. The blood changes of A (depression) and of L (increase) in respect to the C values, although without reaching significant level, mirror those observed in bile-pancreatic secretion.

Expression of telomerase & its significance in the diagnosis of pancreatic cancer.

Pancreatic cancer has one of the worst prognoses among all types of cancers. The survival rate is less than 5 per cent; this is due to difficulty in diagnosing at an early stage. Despite the improvements in diagnostic imaging techniques such as computed tomography, magnetic resonance imaging, etc., the early diagnosis of pancreatic cancer is still difficult. Alternative methods of diagnosing pancreatic cancer at an early stage are presently been explored. The detection of telomerase activity has been proposed to be a useful tool in the diagnosis of pancreatic cancer. Telomerase is made up of three major parts namely, human telomerase reverse transcriptase, human telomerase and telomerase -associated protein. Several researchers have shown telomerase activity in tissues and fluids of patients with pancreatic and other types of cancers. About 95 per cent telomerase activity has been detected in pancreatic adenocarcinoma. Since telomerase activity is present in a vast majority of human cancers, it might have a role in the diagnosis and treatment of cancer.

Inhibition of acyl-coenzyme A:cholesterol acyltransferase stimulates cholesterol efflux from macrophages and stimulates farnesoid X receptor in hepatocytes

We investigated the mechanism of spontaneous cholesterol efflux induced by acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibition, and how an alteration of cholesterol metabolism in macrophages impacts on that in HepG2 cells. Oleic acid anilide (OAA), a known ACAT inhibitor reduced lipid storage substantially by promotion of cholesterol catabolism and repression of cholesteryl ester accumulation without further increase of cytotoxicity in acetylated low-density lipoprotein-loaded THP-1 macrophages. Analysis of expressed mRNA and protein revealed that cholesterol 7alpha-hydroxylase (CYP7A1), oxysterol 7alpha- hydroxylase (CYP7B1), and cholesterol 27-hydroxylase (CYP27) were highly induced by ACAT inhibition. The presence of a functional cytochrome P450 pathway was confirmed by quantification of the biliary cholesterol mass in cell monolayers and extracelluar medium. Notably, massively secreted biliary cholesterol from macrophages suppressed the expression of CYP7 proteins in a farnesoid X receptor (FXR)-dependent manner in HepG2 cells. The findings reported here provide new insight into mechanisms of spontaneous cholesterol efflux, and suggest that ACAT inhibition may stimulate cholesterol-catabolic (cytochrome P450) pathway in lesion-macrophages, in contrast, suppress it in hepatocyte via FXR induced by biliary cholesterol (BC).

Discrete analysis of bile acid in serum and bile with 3 alpha-hydroxysteroid dehydrogenase and diaphorase immobilized onto alkylamine glass beads.

3alpha-Hydroxysteroid dehydrogenase (3alpha-HSD) from Pseudomonas testosteronei and diaphorase (lipoyl dehydrogenase) from Clostridium spp were immobilized individually onto alkylamine glass beads through glutaraldehyde coupling. A cost-effective enzymic colorimetric method for determination of bile acid in the serum and bile was developed employing mixture of the immobilized enzymes. The method was based upon measurement of NADH generated from NAD+ during oxidation of bile acid by immobilized 3alpha-HSD with a color reagent consisting of nitrobluetetrazolium (NBT) chloride salt and immobilized diaphorase in 0.065 M sodium phosphate buffer (pH 7.0). The minimum detection limit of the method was 4.8 pmol/L in the serum and 19.5 micromol/L in bile. The per cent recovery of added bile acid in the serum and bile was 89.1 and 95.0, respectively. Within and between batch coefficients of variation (CV) for bile acid determination were <1.0% and <0.2% in the serum and <0.2% and <0.6% in bile, respectively. A good correlation for bile acid in the serum (r1= 0.95) and in bile (r2 = 0.93) was obtained by a standard chemical method (a commonly used method in India) and the present method. The mixture of immobilized 3alpha-HSD and diaphorase lost 30% of its initial activity after 4 months of regular use. The cost of bile acid determination for 100 the serum and bile samples by the present method was found to be lower than by a commercially available method (Sigma kit 450-A).

Resolução laparoscópica da coledocolitíase / Laparoscopic resolution of the choledocholithiasis

A via transcística, para alguns cirurgiões, tornou-se abordagem preferencial, na exploração laparoscópica das vias biliares. Objetivo - analisar dificuldades, limitações, indicações, resoluções e vantagens da exploração laparoscópica das vias biliares, relacionadas às vias de acesso e à drenagem interna. Casuística e métodos - estudo retrospectivo de 52 pacientes submetidos ao tratamento da coledocolitíase por laparoscopia utilizando-se da colangiografia dinâmica / The transcystic approach, for some surgeons, became preferential for the laparoscopic common bile duct exploration. Aim - To analyze difficulties, limitations, indications, resolutions and advantagens of the laporoscopic exploration, related to the ways of access and the internal drainage. Patients and methods - retrospective study of 52 patients sumitted to the treatment of choledocholithiasis by laparoscopic surgery using dynamic cholangiography, choledochoscopy or laparoscopic ultrasound, according to the acces...

Digestive stimulant action of spices: a myth or reality?

Spices have long been recognized for their digestive stimulant action. Several spices are also employed in medicinal preparations against digestive disorders in traditional and Indian systems of medicine. Earlier reports on the digestive stimulant action of spices are largely empirical; only in recent years, this beneficial attribute of spices has been authenticated in exhaustive animal studies. Animal studies have shown that many spices induce higher secretion of bile acids which play a vital role in fat digestion and absorption. When consumed through the diet also spices produce significant stimulation of the activities of pancreatic lipase, amylase and proteases. A few of them also have been shown to have beneficial effect on the terminal digestive enzymes of small intestinal mucosa. Concomitant with such a stimulation of either bile secretion or activity of digestive enzymes by these spices, leading to an accelerated digestion, a reduction in the food transit time in the gastrointestinal tract has also been shown. Thus, the digestive stimulant action of spices seems to be mediated through two possible modes: (i) by stimulating the liver to secrete bile rich in bile acids, components that are vital for fat digestion and absorption, and (ii) by a stimulation of enzyme activities that are responsible for digestion. This review highlights the available information on the influence of spices on the digestive secretions and enzymes.

Hepatobiliary clearance of labelled mebrofenin in normal and D-galactosamine HCl-induced hepatitis rats and the protective effect of turmeric extract.

This study was carried out to see the hepatobiliary clearance of 99m Tc-Mebrofenin radiopharmaceutical in D-galactosamine induced hepatic rats. Furthermore, protective effect of turmeric extract has been studied in these hepatitis rats. Hepatitis was induced with intraperitoneal injection of D-galactosamine (400 mg/kg b. wt) in these rats. 1% turmeric extract was given along with their normal diet for 15 days. Turmeric extract treatment significantly increased the hepatic uptake of radioactivity and accelerated the excretion of 99m Tc-Mebrofenin as compared to control rats. (P < 0.001). In D-galactosamine administered rats, a significant delay was observed in 99m Tc-Mebrofenin excretion as compared to controls. However, D-galactosamine administered rats, pretreated with turmeric extract or concurrently treated with turmeric extract showed a near normal pattern of 99m Tc-Mebrofenin excretion. Hence, it can be suggested that turmeric extract may improve the liver function by detoxification.

Evaluación de cultivos de bilis en pacientes con litiasis coledociana y su modificación posterior a la y colocación del tubo de Kehr / Evaluation of cultivation of bilis in patients with diagnosis of choledocholithiasis and modificated posterior place of Kehr tube

Se seleccionaron quince pacientes con diagnóstico de litiasis coledociana no residual, en quienes se realizó coledocotomia con colocación de tubo de Kehr. La edad promedio de los pacientes fue de 38.8 años; 14 (93.3 por ciento) de los pacientes pertenecieron al sexo femenino y 1 (6,66 por ciento) al sexo masculino. Se tomó cultivo de bilis durante la colecodocotomia, al cuarto día de postoperatorio y al retirar el tubo de Kehr. Se observó la presencia de gérmenes al momento de la intervención en ocho pacientes con un total de 10 germenes aislados, siendo el predominio E.coli (40 por ciento). Al cuarto día del postoperatorio, fueron aislados 16 gérmenes en catorce pacientes (93.33 por ciento siendo los más frecuentes E.coli (29.41 por ciento) y Enterobacter (23.52 por ciento). Al retirar el tubo de Kehr entre el séptimo y octavo día del postoperatorio, se aislaron 31 gérmenes en los quince pacientes, aparecieron con mayor E.coli (16.12 por ciento), Enterobacter (12.90 por ciento) y Klebsiella (12.90 por ciento). Se encontró la existencia de una relación entre el número de gérmenes aislados y el tiempo de permanencia del tubo de Kehr (p:0.000140)

Suplementación de DL-Ó-tocoferol acetato oral en niños con colestasis crónica y déficit de vitamina E / Supplement of Oral DL-Ó-Tocopherol Acetate in children with chronic cholestasis and vitamin E deficit

Objetivo. Determinar la dosis oral suplementaria de dl-Ó-tocoferol acetato para mantener niveles séricos de Ó-tocoferol normales en niños con colestasis crónicas y déficit de vitamina E. Antecedentes. La malabsorción y deficiencia de vitamina E en niños con colestasis crónica se presenta en un 60-70 por ciento, causando un síndrome de degeneración neurológica progresiva entre 18 y 24 meses si no se corrige. La pronta suplementación con vitamina E determina la prevención e irreversibilidad de dicho déficit. Método. Realizamos un estudio prospectivo, longitudinal y comparativo de 60 niños divididos en tres grupos, con déficit de vitamina E y colestasis crónica. Luego de una evaluación inicial y por 15 días, cada grupo recibió suplementación oral con 100 UI, 200 UI y 400 UI diarias de dl-Ó-tocoferol acetato, respectivamente. Fueron monitorizados los niveles séricos de Ó-tocoferol, la función neurológica y los parámetros bioquímicos durante la suplementación. Resultados. Ninguna de las dosis suplementarias orales de dl-Ó-tocoferol acetato administradas por 15 días normalizaron los niveles séricos de Ó-tocoferol (p>0.06). La función neurológica, que no encontraba alterada al inicio del estudio en ninguno de los pacientes, permaneció estable luego de los 15 días, a dosis de 100 UI, 200 UI y 400 UI, a pesar de ser seguro, no mantuvo los niveles séricos normales de Ó-tocoferol en niños con colestasis crónica y déficit de vitamina E

Metabolismo hepático / Hepatic metabolism

As autoras revisam aspectos básicos do metabolismo hepático, com a discussäo do metabolismo da bilirrubina, das proteínas, dos glicídios e lipídios.

Effect of orally administered betel leaf (Piper betle Linn.) on digestive enzymes of pancreas and intestinal mucosa and on bile production in rats.

The influence of two varieties of betel leaf (Piper betle Linn.) namely, the pungent Mysore and non-pungent Ambadi, was examined on digestive enzymes of pancreas and intestinal mucosa and on bile secretion in experimental rats. The betel leaves were administered orally at two doses which were either comparable to human consumption level or 5 times this. The results indicated that while these betel leaves do not influence bile secretion and composition, they have a significant stimulatory influence on pancreatic lipase activity. Besides, the Ambadi variety of betel leaf has a positive stimulatory influence on intestinal digestive enzymes, especially lipase, amylase and disaccharidases. A slight lowering in the activity of these intestinal enzymes was seen when Mysore variety of betel leaf was administered, and this variety also had a negative effect on pancreatic amylase. Further, both the betel leaf varieties have shown decreasing influence on pancreatic trypsin and chymotrypsin activities.

Bilirragia atípica postgastrectomía / Atipic postgastrectomy bile leakage

Se presenta la experiencia acumulada entre los años 1983 y 1993 con una complicación poco frecuente y de la cual no hemos encontrado publicaciones. La complicación consiste en la salida de bilis por los drenajes en forma precoz, que normalmente hace pensar en algún defecto anastomótico. En este período, hemos practicado sobre 800 gastrectomías, presentándose esta complicación en 9 casos (4 hombres y 5 mujeres, con un promedio de edad de 59 años). En 5 casos la causa fue la filtración de bilis por pequeños conductillos del lecho hepático, abiertos durante la operación y en los restantes 4 pacientes, la filtración de bilis se presentó en conductillos biliares del ligamento triangular izquierdo del hígado. En los 5 casos objetivados por operación, se observó que la bilirragia estaba controlada completamente por los drenajes. Con esta experiencia los 4 casos restantes se manejaron en forma conservadora, observándose que la bilirragia cesó espontáneamente entre los 5 y 25 días. No hubo mortalidad directa relacionada con esta complicación

Biliary proteins from hepatic bile of rats fed curcumin or capsaicin inhibit cholesterol crystal nucleation in supersaturated model bile.

Following our earlier observations that curcumin and capsaicin are antilithogenic in mice and hamsters, attempts were now made to understand the manner in which these spice principles were acting. For this purpose, the hepatic biles of rats fed a control, lithogenic, and lithogenic diet supplemented with curcumin or capsaicin were subjected to gel filtration chromatography (sepharose-4B-Cl) and the LMW protein fractions were tested for their ability to influence cholesterol crystal growth in model bile. The LMW protein fraction from the lithogenic group bile shortened the nucleation time and increased the crystal growth rate and final crystal concentration. But with the LMW protein fractions from the biles of rats on the lithogenic group supplemented with curcumin or capsaicin, the nucleation times were prolonged and the crystal growth rates and final crystal concentrations were decreased. The LMW fractions were further purified into three different sugar specific proteins by affinity chromatography. A higher proportion of LMW proteins from the lithogenic group bile was bound to Con-A whereas higher proportions of LMW proteins from the groups fed with curcumin and capsaicin were respectively bound to wheat germ agglutinin and Helix pomatia lectin. The Con-A bound fraction obtained from the lithogenic group showed a pro-nucleating effect. In contrast, the WGA-bound fraction obtained from curcumin group or the Helix pomatia lectin bound fraction obtained from capsaicin group showed a potent antinucleating activity.

Mecanismos de defesa da bile / Defense mechanisms of the bile

Nesta revisao sao explicados cada um dos quatro mecanismos de defesa da bile contra a infecçao por microorganismos patógenos, bem como suas açoes integradas. Nesse contexto, incluem-se as barreiras anatômicas (complexos unitivos e esfíncter de Oddid), os mecanismos físicos (fluxo biliar e muco), os fatores químicos (sais biliares) e os mecanismos imunológicos (células de Kupffer e imunoglobulina A secretada). A quebra do funcionamento harmônico desses mecanismos pode levar a sérias infecçoes. Nesse sentido, o aumento da pressao intra-biliar (causada por obstruçao parcial ou completa do fluxo biliar) e doenças do parênquima hepático desempenham papel fundamental. Dessa forma, confirma-se a importância da preservaçao desses mecanismos de defesa no indivíduo saudável.

Papillary hyperplasia and cholesterolosis of the gallbladder

La hiperplasia papilar de la vesícula biliar es una modificación peculiar de la mucosa, que se caracteriza por un aumento del número y altura de sus pliegues y la presencia de ramificaciónes y anastomosis (Fig. 3), además de cambios en el epitelio: núcleos ovalados o redondos, más grandes y leptocromáticos, desplezados hacia la porción central de los citoplasmas (Fig 4). La colesterolosis vesicular es una patología bien conocida: macrófago espumosos con colesterol en el corion, por debajo del epitelio (Fig 5). En el servicio de Anatomía Patológica de los Policlínicos PAMI I y PAMI II de Rosario, Argentina, se diagnosticaron en un período de cinco años (enero 1984 a diciembre de 1989), 376 (28,4 por ciento hiperplasias papilares y 206 (15,6 por ciento colesterolosis en 1323 vesículas biliares vesículas biliares extirpadas por diferentes diagnósticos clínico-quirúrgicos (Tabla 1). Se observó un aumento significativo del número, altura, ramificaçöes y anastomosis de los pliegues de la mucosa en 50 vesículas con hiperplasia papilar muestreadas al azar, comparadas con 9 vesículas sin alteraciones patológicas evidentes (inflamación, fibrosis, hiperplasias o metaplasias) que se utilizaron como controles (Tabla 2). Se encontró una asociación estadísticamente significativa (p < 0,001) entre la hiperplasia papilar y la colesterolosis (Tabla 3). Estos resultados sugieren que la hiperplasia papilar podría ser la expresión morfológica de una adaptación funcional de la mucosa de la vesícula biliar destinada a facilitar la reabsorción de colesterol de la bilis vesicular hacia los capilares del corion. El aumento de la presión en los conductos biliares extrahepáticos y/o la concentración de colesterol en la bilis podrían ser los factores desencadeantes de la hiperplasia papilar. La colesterolosis seria consecuencia de un exceso de colesterol reabsorbido que al saturar el intersticio es fagocitado por los macrófagos