Determination of caffeine in dietary supplements by miniaturized portable liquid chromatography.

In this study three miniaturized liquid chromatography (LC) instruments have been evaluated and compared for the analysis of caffeine in dietary supplements, namely a benchtop capillary LC (capLC) system, a benchtop nano LC (nanoLC)system and a portable LC system. Commercial products derived from different sources of caffeine have been analyzed. Under optimized conditions, the methods based on benchtop systems were superior in terms of sensitivity. The limits of detection (LODs) found with the capLC and nanoLC systems were 0.01 and 0.003 µg mL-1, respectively, whereas the LOD obtained with the portable LC instrument was of 1 µg mL-1. The portable LC-based method was superior in terms of simplicity and throughput (total analysis time < 15 min). On the basis of the results obtained, a new method for the rapid measurement of caffeine in dietary supplements by portable miniaturized LC is presented. This method provided good linearity within the 1-20 µg mL-1 interval, and it allowed the quantification of caffeine even in products derived from decaffeinated green coffee extracts. The contents of caffeine found with the proposed portable LC method in the real samples analyzed ranged from 1.38 to 7 mg per gram of product, which were values statistically equivalent to those found with the benchtop capLC and nanoLC methods, being the precision, expressed as relative standard deviation (RDS), of 2 -14% (n = 3). The proposed portable LC based method can be used as a simple and rapid alternative to estimate the quality, effectiveness and safety of dietary supplements, regarding their caffeine content.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Effect of Silymarin in Pdx-1 expression and the proliferation of pancreatic ß-cells in a pancreatectomy model.

In type 1 Diabetes Mellitus (DM) there is a destruction of pancreatic ß-cells (80-90%) at the time of detection, in DM type 2 these cells are decreased significantly. The Pdx1 transcription factor plays a central role in pancreatic development and in insulin gene expression. Previously, we have demonstrated that Silymarin recovers the normal morphology and endocrine function of damaged pancreatic tissue in alloxan induced diabetic rats. The aim of this study was to analyze the effect of Silymarin in Pdx1 gene expression and its repercussion on insulin gene expression and ß-cell proliferation. 72 Wistar rats were partially pancreatectomized (60%) and divided into 12 groups. Six groups were treated daily with Silymarin (200mg/kg p.o.) for 3, 7, 14, 21, 42 and 63 day periods. Also, an unpancreatectomized control group was performed. At each time interval three animals from each group were administered BrdU 18 h before the sacrifice. Insulin and Pdx-1 gene expression were assessed by RT-PCR assay in total pancreatic RNA. ß-Cell proliferation was determined by immunoperoxidase assay. In contrast to the animals that were only pancreatectomized, the Silymarin treatment induced an increase in both Pdx1 and insulin gene expression as well as ß-cell proliferation in pancreatic tissue (control=2.6±0.28%; untreated=14.25±0.56%; treated=39.08±4.62%). Consequently, serum insulin levels rose (control=1.01±0.02 ng/ml; untreated=1.18±0.42 ng/ml; treated=4.58±0.58 ng/ml) and serum glucose levels decreased in these animals (control=6.2±0.01 mM; untreated=9.02±0.41 mM; treated=6.41±0.32 mM). These results suggest that Silymarin may induce the proliferation of insulin-producing cells.

Mortalidad infantil en un hospital de nivel terciario. Limitación de esfuerzo terapéutico, correspondencia clínico-patológica y precisión diagnóstica / Infant mortality in a third level paediatric hospital. therapeutic effort limitation, clinical-pathological agreement and diagnostic accuracy

Objetivo: Analizar la mortalidad en un hospital infantil de tercer nivel y alta complejidad. Material y métodos: Se revisaron los fallecidos en el Hospital Infantil La Paz durante los años 2007, 2008 y 2009. Se analizaron datos epidemiológicos, diagnósticos clínicos y de autopsia y su correspondencia, y si se llegaba a un diagnóstico etiológico definitivo. La limitación del esfuerzo terapéutico y la previsibilidad del fallecimiento también fueron recogidas. Las variables fueron prospectivamente definidas al inicio. Resultados: Se estudiaron 253 fallecimientos (6,08 por mil ingresos). El 43,4% eran menores de 1 mes y el 63,9% menores de un año. La patología neonatal y la hemato-oncológica fueron las causas más frecuentes. Fallecieron en las tres unidades de cuidado intensivo el 87%. Se practicó autopsia a 53% de los fallecidos y se detectó un 7,8% de nuevos hallazgos significativos, aunque solo en un caso podría el tratamiento haber modificado el pronóstico. Limitación de esfuerzo terapéutico y cuidado paliativo se instauró en el 41,9%. El fallecimiento era esperado al inicio del proceso en 83,9%, En 92% se consideró que existía un diagnóstico definitivo y en 86,4% un diagnóstico etiológico de los procesos que condujeron al fallecimiento. Conclusiones: El análisis de la mortalidad hospitalaria permite evaluar la calidad de la asistencia pediátrica y detectar resultados adversos. La autopsia continúa proporcionando información relevante. La limitación de esfuerzo terapéutico y cuidado paliativo es una medida cada vez más frecuente en la edad pediátrica. El número de niños que muere sin diagnóstico etiológico sigue siendo alto(AU)

Objective: To study infant and child mortality in a third level children's hospital treating highly complex patients. Patients and methods: All children dying in the period 2007- 2009 at La Paz Children's Hospital were evaluated. Epidemiological data, autopsy rate, clinical and autopsy diagnoses and their correspondence and the number of, patients with precise final diagnoses were analysed. Therapeutic effort limitation and palliative care were also evaluated as well as if the final result was expected according to the initial disease or clinical condition of the patients. All the variables were prospectively defined at the start of the study period. Results: A total of 253 cases (6.08‰ admissions) were analysed. The two leading causes of death were disorders related to prematurity and low birth weight, and haematology oncology malignant diseases. Most patients (87%) died in an intensive care unit (neonatal or paediatric). During the study period 134 autopsies (53%) were performed, and new clinically significant findings were observed in 12 of these (7.8%) but in only one case the treatment could have possibly modified the prognosis (class I discrepancy). Therapeutic effort limitation and palliative care were implemented in 41.9%. Death was initially expected in 83.9% of cases. An accurate final diagnosis was defined in 92%, and the aetiology of the disease was considered to be identified in 86.4% of all deaths. Conclusions: Hospital mortality analysis is useful to evaluate the quality of the paediatric care and to detect adverse results that could be corrected. Paediatric autopsy continues to provide clinically significant data for paediatricians and families. Therapeutic effort limitation and palliative care is increasingly applied in paediatric end of life care. The number of infants and children dying without a final aetiological diagnosis is still considerably high(AU)

Effect of silymarin on kidneys of rats suffering from alloxan-induced diabetes mellitus.

Oxidative stress contributes to the pathogenesis of diabetes mellitus and its sequelae nephropathy. The kidneys are especially prone to damage by free radicals. We therefore tested the effect of the flavonoid mixture silymarin, a free radical scavenger, on the activity and gene expression of superoxide dismutase, glutathione peroxidase and catalase, as well as on renal tissue morphology in rats with alloxan-induced diabetes mellitus. Alloxan-intoxicated rats were treated with silymarin 20 days after alloxan administration for 9 weeks. Alloxan-induced tissue damage and decreased the activity of the three enzymes, SOD (U/mg prot.): 14.4±1.75 vs 112±6.45 control, p<0.05, n=6; GSHPx (µM NADPH/min/mg prot.): 0.02±0.002 vs 0.121±0.01 control, p<0.05, n=6; CAT (k/seg/mg prot.): 0.022±0.003 vs 0.044±0.002 control, p<0.05, n=6. Silymarin treatment prevented tissue damage and restored the activity (SOD: 110.7±12.9U/mg prot.; GSHPx: 0.329±0.031 µM NADPH/min/mg prot.; CAT: 0.054±0.002 k/seg/mg prot., n=6) and gene expression of the three antioxidant enzymes after 20 days of alloxan administration (SOD: 12.00±0.57 control, 9.00±0.1 diabetic p<0.05, 11.00±0.20 silymarin treated; GSHPx: 6.01±0.78 control, 9.03±0.3 diabetic p<0.05, 7.02±0.07 silymarin treated; CAT: 9.03±1.07 control, 12.02±0.60 diabetic p<0.05, 8.06±0.31 silymarin treated, n=6). It is suggested in this study that recuperative effect of silymarin on the renal tissue damage induced by alloxan may be related to an increase in the activity and recovery of gene expression of antioxidant enzymes which in addition to the glutathione system constitute some of the most important defense mechanisms against free radicals damage. As these results show, silymarin may be considered potentially in the treatment of diabetic nephropathy.

Fístula colovesical de origen diverticular / Results of surgical treatment of colovesical fistulas of diverticular origin

Background: The main causes of colovesical fistulas are diverticular disease of the colon and colon carcinoma. Aim: To analyze the results of the surgical treatment of colovesical fistulas of diverticular origin. Material and Methods: Retrospective analysis of all patients operated for a colovesical fistula of diverticular origin. Results: From 141 patients subjected to a colon excision for diverticular disease, 18 had a colovesical fistula. The latter, compared to patients without fistulas were male in a higher proportion, were younger and had more concomitant diseases. Pneumaturia was reported in 83 percent and urine fecal soiling in 56 percent. In two thirds of patients, the fistula appeared in the absence of a diverticular crisis. Abdominal CAT sean demonstrated the fistula in 80 percent of cases. It was complemented with barium enema and cystoscopy. Excision with immediate anastomosis was the surgical procedure used in 94 percent of patients, without sequelae or relapse, after a mean follow up of 74 months. No patient died during the procedure or required a new intervention. Conclusions: Colovesical fistulas are most common in young men with associated diseases and their treatment of choice, with good long-term results, is primary excision.

Antecedentes: El objetivo de este estudio es analizar los resultados del tratamiento quirúrgico de la Fístula Coló Vesical (FCV) de origen diverticular, los que se comparan con la enfermedad diverticular no fistulizada. Pacientes y Método: Análisis retrospectivo de todos los pacientes intervenidos por una FCV de origen diverticular en forma consecutiva. Resultados: De un total de 141 pacientes resecados por una enfermedad diverticular del colon sigmoides, la indicación quirúrgica en 27 (19,3 por ciento) fue la presencia de una fístula, de las cuales 18 corresponden a una FCV. El grupo con FCV tiene predominio de hombres (p = 0,0001), más joven (p = 0,027) y con mayor incidencia de enfermedades asociadas (p = 0,0001). La neumaturia se presentó en el 83 por ciento y la fecaluria en el 56 por ciento. En dos tercios de los casos la FCV se estableció en ausencia de una crisis diverticular previa. El estudio más relevante para demostrar la presencia de una FCV fue la tomografía computada (80 por ciento), que se complementa con el enema balitado y la cistoscopia. La resección con anastomosis inmediata, más simple sutura de la vejiga fue el procedimiento empleado en el 94 por ciento de los pacientes, sin secuelas ni casos de recidiva, con un seguimiento global promedio de 74,2 meses (extremos 12-158). No hubo reoperaciones ni mortalidad operatoria. Conclusiones: la FCV de origen diverticular es una condición patológica poco frecuente que afecta a pacientes varones en la séptima década de la vida, con múltiples enfermedades asociadas y que frecuentemente se instala en forma silenciosa. La resección primaria es el tratamiento de elección con buenos resultados a largo plazo.

Ag-doped manganite nanoparticles: new materials for temperature-controlled medical hyperthermia.

The purpose of this study was to introduce newly synthesized nanomaterials as an alternative to superparamagnetic ironoxide based particles (SPIO) and thus to launch a new platform for highly controllable hyperthermia cancer therapy and imaging. The new material that forms the basis for this article is lanthanum manganite particles with silver ions inserted into the perovskite lattice: La(1-x)Ag(x)MnO(3+delta). Adjusting the silver doping level, it is possible to control the Curie temperature (T(c)) in the hyperthermia range of interest (41-44 degrees C). A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) is suggested. New nanoparticles are stable, and their properties were not affected by the typical ambient conditions in the living tissue. It is possible to monitor the particle uptake and retention by MRI. When these particles are placed into an alternating magnetic field, their temperature increases to the definite value near T(c) and then remains constant if the magnetic field is maintained. During the hyperthermia procedure, the temperature can be restricted, thereby preventing the necrosis of normal tissue. A new class of nanoparticles based on silver-doped manganites La(1-x)Ag(x)MnO(3+delta) was suggested. Ag-doped perovskite manganites particles clearly demonstrated the effect of adjustable Curie temperature necessary for highly controllable cellular hyperthermia. The magnetic relaxation properties of the particles are comparable with that of SPIO, and so we were able to monitor the particle movement and retention by MRI. Thus, the new material combines the MRI contrast enhancement capability with targeted hyperthermia treatment.

Fístula sigmoidoapendicular de origen diverticular / Sigmoidoappendiceal fistula of diverticular origin: report of one case

Se presenta un caso de fístula sigmoidoapendicular de origen diverticular diagnosticado por enema baritado en el estudio electivo de una paciente anciana, luego de un episodio de diverticulitis tratado en forma médica. El enema baritado es el examen de elección para demostrar este tipo de fístula. El estudio histopatológico permite certificar el origen diverticular de esta condición. Habitualmente la sigmoidectomía más apendicectomía es el tratamiento de elección con resultados satisfactorios. En el caso que se presenta fue necesario realizar una ileotiflectomía por la concomitancia con un cáncer avanzado de ciego. La fístula coloentérica de origen diverticular representa el 1 a 4 por ciento de las indicaciones de cirugía electiva por una enfermedad diverticular del colon sigmoides. Dentro de ellas, la fístula sigmoideo-apendicular de origen diverticular es excepcional y sólo hemos encontrado tres casos documentados de esta rara forma de fístula coloentérica.

Winery solid residue revalorization into oil and antioxidant with nutraceutical properties by an enzyme assisted process.

Revalorization of the winery industry residue, grape seed is studied for the production of an oil and defatted meal with nutraceutical properties. Conventional grape seed oil extraction process is carried out by pressing at high temperature affecting the product quality. Oil extraction by cold pressing improves product quality, but it gives a low oil yield. Oil extracted is increased at the pressing stage, when an enzymatic pre-treatment is incorporated in to the conventional process. The yield is determined by determining the residual oil in the pressed cake. Using an enzymatic treatment during 9 hours at 45 degrees C and 50% of moisture, with a mixture of two commercial enzymes grape seed oil extraction yield by cold pressing is raised up to 72%, being a 59.4% increment in comparison to the yield obtained by the control, without enzymes. The defatted meal by enzimatic assisted process improves its phenolic compounds between 2 and 4 times, depending on the conditions of phenolics extraction in comparison to the control samples.

Silymarin induces recovery of pancreatic function after alloxan damage in rats.

Alloxan has been widely used to produce experimental diabetes mellitus syndrome. This compound causes necrosis of pancreatic beta-cells and, as is well known, induces oxidant free radicals which play a relevant role in the etiology and pathogenesis of both experimental and human diabetes mellitus. Previously we have reported hypoglycemic and antilipoperoxidative actions of silymarin in serum and pancreatic tissue respectively. The aim of this study was to test whether silymarin could reduce the hyperglycemia and revert the pancreatic damage in alloxan treated rats, tested with silymarin in two protocols: using both compounds simultaneously for four or eight doses, or using the compound 20 days after alloxan administration for 9 weeks. Serum glucose and insulin were determined, and pancreatic fragments were used for histology and insulin immunohistochemistry. Pancreatic islets were isolated to assess insulin and Pdx1 mRNA expression by RT-PCR. Our results showed that 72 hours after alloxan administration, serum glucose increased and serum insulin decreased significantly, whereas pancreatic tissue presented morphological abnormalities such as islet shrinkage, necrotic areas, loss of cell organization, widespread lipoid deposits throughout the exocrine tissue, and loss of beta cells, but insulin and glucagon immunoreactivity was scattered if any. In contrast the pancreatic tissue and both insulin and glucose serum levels of rats treated with silymarin were similar to those of control animals. In addition, insulin and glucagon immunoreactive cells patterns in Langerhans islets were also normal, and normal insulin and Pdx1 mRNA expression patterns were detected during pancreatic recovery in Langerhans islets. The overall results suggest that silymarin induces pancreatic function recovery demonstrated by insulin and glucagon expression protein and normoglycemia after alloxan pancreatic damage in rats.

Beta-sheet breaker peptide prevents Abeta-induced spatial memory impairments with partial reduction of amyloid deposits.

Current evidence supports the notion that beta-amyloid deposits or Abeta intermediates may be responsible for the pathogenesis in Alzheimer's disease (AD) patients. In the present work, we have assessed the neuroprotective effect of the chronic intraperitoneal administration of a five-amino-acid beta-sheet breaker peptide (iAbeta5p) on the rat behavioral deficit induced by the intrahippocampal Abeta-fibrils injection. At 1 month after the injection, animals showed a partial reduction of the amyloid deposits formed and a decreased astrocytic response around the injection site. More importantly, we report that following the iAbeta5p treatment, hippocampal-dependent spatial learning paradigms, including the standard Morris water maze and a working memory analysis, showed a significant prevention from impairments induced by Abeta deposits in the dorsal hippocampus. Thus, it is possible that a noninvasive treatment such as the one presented here with beta-sheet breaker peptides may be used as a potential therapy for AD patients.

Resultados del tratamiento quirúrgico de la endometriosis colorrectal: Análisis de 10 pacientes consecutivas / Results of surgical treatment of the colorectal endometriosis: Analysis of 10 consecutive patients

Se revisa en forma retrospectiva los resultados del estudio y tratamiento de 10 pacientes sometidas a una resección radical por una endometriosis colorrectal (EMCR) profunda en un período de 12 años. El promedio de edad fue de 36,6 años (extremos 29-45), 7 pacientes consultaron por dolor pélvico invalidante en el contexto de una esterilidad primaria y 8 habían sido sometidas entre 1 y 4 exploraciones quirúrgicas. El enema baritado de doble contraste complementado con la tomografía computada sugirieron el diagnóstico de EMCR en 6 pacientes. El diagnóstico preoperatorio de EMCR fue correcto en 7 casos basado en los antecedentes y el estudio por imágenes. El rectosigmoides fue el segmento afectado en 9 pacientes, la región ileocecal en 3 y multifocal en 2. La intervención inicial fue una resección anterior en 8 casos (3 bajas) y la colectomía derecha en 3, requiriendo dos pacientes una histerectomía adicional. El seguimiento fluctúa entre 3 meses y 12 años, durante el cual una paciente logra un parto de término, con un control satisfactorio de los síntomas en todas las pacientes evaluadas. No se pudo establecer una correlación clara entre la sintomatología y la profundidad del compromiso endometrial. El rol de la cirugía radical está claramente establecido en el manejo de la EMCR invasiva sintomática, la que se puede efectuar en forma tradicional o por vía laparoscópica.

Sigmoidocele / Sigmoidocele

Se presenta el caso clínico de una paciente de 67 años portadora de una constipación crónica pertinaz que consulta por disquecia intensa caracterizada por evacuación incompleta, pujo excesivo, distensión y dolor abdominal que la obliga a pasar horas en el baño. El enema barítado descartó patología orgánica relevante y el tiempo de tránsito colónico mostró una retención de los marcadores a nivel del colon sigmoides y descendente. Con el diagnóstico de una obstrucción de salida se efectuó una defecografía que reveló un sigmoidocele 3º, apreciándose que el asa sigmoidea se interpone entre el recto y la vagina alcanzando el plano de apoyo del periné en el WC. En la exploración quirúrgica destacó la profundidad del fondo de saco de Douglas y la elongación del sigmoides, siendo sometida a una sigmoidectomía con una evolución postoperatoria satisfactoria. A los 15 meses se efectúa una defecografía de control que revela un descenso patológico del piso pelviano y un enterocele. A los 23 meses de observación la paciente evalúa satisfactoriamente la intervención, refiere tener tres evacuaciones semanales con disquecia leve y el uso ocasional de laxantes. El principal problema diagnóstico de esta anomalía es la coexistencia de otras alteraciones del piso pélvico que pueden afectar los resultados funcionales de la corrección del sigmoidocele

Enfermedad de Hirschsprung en adultos / Hirschsprung's disease in adults

Se presenta la experiencia en el diagnóstico y tratamiento de 9 pacientes portadores de una enfermedad de Hirschsprung (EH) diagnosticados en la edad adulta en un período de 10 años, en el contexto de un estudio prospectivo de la constipación crónica pertinaz. Se trata de 6 mujeres y 3 hombres con una edad promedio de 24 años (extremos 15-46), con una historia de constipación desde la infancia en 5 y desde la adolescencia en 4, complicados con un fecaloma en forma iterativa en 6 casos. El enema baritado demostró un segmento contraído en embudo en 4 pacientes, megarrecto en 2 y dolicosigmoides en 3. La manometría anorrectal mostró ausencia del reflujo recto anal inhibitorio (RRAI) en los 5 pacientes en que el examen se realizó. La esfinteromiectomía anorrectal (EM) se efectuó con fines diagnósticos en 8 pacientes, fue exitosa en una paciente con EH de segmento ultracorto que completa 156 m de seguimiento. En el resto la respuesta fue nula o transitoria, motivo por el cual 6 pacientes se intervienen con la técnica de Duhamel-Haddad, una paciente rechaza la cirugía y otro se interviene en otro centro. El control alejado es de 76 meses como promedio (extremos 36-156), de los cuales 7 casos superan los 6 años. En el seguimiento a largo plazo fallece una paciente a los 3 años por obstrucción intestinal reiterada y complicaciones sépticas, confirmándose en ella una aganglionosis intestinal total. El resto de los pacientes sometidos a cirugía resectiva han corregido su hábito defecatorio con continencia plena. La EH debe sospecharse en todo paciente adulto que sufre de una constipación crónica pertinaz. Aunque el enema baritado y la manometría anorrectal pueden sugerir esta condición, sólo la biopsia de grosor total permite establecer el diagnóstico definitivo y puede ser terapéutica en casos seleccionados

Prevention of alloxan-induced diabetes mellitus in the rat by silymarin.

Silymarin is a free-radical scavenger and a membrane stabilizer which prevents lipoperoxidation and its associated cell damage in some experimental models. It has been proposed that lipid peroxidation caused by free radicals may be involved in alloxan-induced diabetes mellitus. Alloxan elicits pancreatic lipid peroxidation which precedes the appearance of hyperglycemia in mice. We studied the effects of silymarin on rat pancreas, the effect of this flavonoid on pancreatic, hepatic and blood glutathione (GSH) together with the pancreatic malondialdehyde concentrations in response to alloxan. On its own, silymarin increases pancreatic and blood GSH without changes in either hepatic GSH or in blood glucose. Silymarin prevents the increase in lipid peroxidation produced by alloxan. It also blunts the sustained increment in plasma glucose induced by alloxan. We suggest that silymarin has a protective effect on the pancreatic damage in experimental diabetes mellitus. This may be related to its antioxidative properties and to the increase in concentrations of plasma and pancreatic glutathione.

Effect of portal vein ligation and silymarin treatment on aspirin metabolism and disposition in rats.

The influence of portal hypertension on the metabolism and pharmacokinetics of aspirin was evaluated after the administration of a single oral dose of acetylsalicylic acid (20 mgkg(-1)) in portal-vein-ligated (PVL) rats. Experiments were also performed in control (sham-operated rats) and in rats that received an oral daily dose (150 mgkg(-1)) of silymarin from the tenth day after surgery for 7 d. Plasma concentration profiles of all groups exhibited monoexponential decay but with important changes in pharmacokinetic parameters. The aspirin elimination constant (k) for PVL rats was lower than for control rats, whereas the plasma half-life and area under the curve were greater than those in the control group. However, Cmax was comparable with that of the control rats. Urinary excretion of the metabolites (salicylic acid and glucuronides) was significantly altered in PVL rats: the urinary glucuronides were reduced and urinary salicylic acid was increased. The activities of plasma and liver esterases were increased significantly in PVL rats, while the activity of p-nitroanisole-O-demethylase was not affected. Depletion of cytochrome P 450 was also noted in the same group of rats. Silymarin markedly reversed the alterations found in the PVL group.

Is erythrocyte alkaline phosphatase activity a marker of zinc status in humans?

The identification of an enzyme activity that responds to changes in Zn intake may serve as a useful biomarker for Zn status. Alkaline phosphatase (ALP) is a dimeric protein with each subunit containing two Zn atoms. The activity of ALP in erythrocytes (E) decreases as a result of a low Zn diet, which suggests that this enzyme may be a marker of Zn status. To investigate this further, we determined the response of E-ALP in six healthy subjects following supplementation with 50 mg Zn (4.2 x RDI) daily for 4 wk. A small but significant increase in plasma Zn was observed with supplementation (p < 0.05), whereas there was no significant change in E-Zn over the same period. Plasma and E-Cu showed no change. Conversely, the activity of E-ALP increased in all subjects from 1.7 +/- 0.5 to 5.9 +/- 0.7 U/g protein (mean +/- SE) (p < 0.0001). The small change observed in plasma Zn is not biologically significant in view of the many documented factors that influence its concentration. Our data support the hypothesis that E-ALP is a marker of Zn status in humans.