Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease.

Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account.

In vitro and in vivo activities of 1,3,4-thiadiazole-2-arylhydrazone derivatives of megazol against Trypanosoma cruzi.

From a series of 1,3,4-thiadiazole-2-arylhydrazone derivatives of megazol screened in vitro against Trypanosoma cruzi, eight (S1 to S8) were selected for in vivo screening by single-dose oral administration (200 mg/kg of body weight) to infected mice at 5 days postinfection (dpi). Based on significant decreases in both parasitemia levels and mortality rates, S2 and S3 were selected for further assays. Despite having no in vivo effect, S1 was included since it was 2-fold more potent against trypomastigotes than megazol in vitro. Trypomastigotes treated with S1, S2, or S3 showed alterations of the flagellar structure and of the nuclear envelope. When assayed on intracellular amastigotes, the selectivity index (SI) for macrophages was in the range of >27 to >63 and for cardiac cells was >32 for S1 and >48 for megazol. In noninfected mice, S1 did not alter the levels of glutamic oxalacetic transaminase (GOT), glutamate pyruvate transaminase (GPT), or urea. S2 led to an increase in GOT, S3 to increases in GOT and GPT, and megazol to an increase in GOT. Infected mice were treated with each derivative at 50 and 100 mg/kg from dpi 6 to 15: S1 did not interfere with the course of infection or reduce the number of inflammatory foci in the cardiac tissue, S2 led to a significant decrease of parasitemia, and S3 decreased mortality. There was no direct correlation between the in vitro effect on trypomastigotes and amastigotes and the results of the treatment in experimental models, as S1 showed a high potency in vitro while, in two different schemes of in vivo treatment, no decrease of parasitemia or mortality was observed.

Reperfusion therapy in patients with acute ischaemic stroke caused by cervical artery dissection. / Tratamientos de reperfusión en el infarto cerebral agudo por disección de arterias cervicales.

INTRODUCTION: Cervical artery dissection (CAD) is responsible for up to 20% of all ischaemic strokes in patients younger than 45. The benefits of acute-phase reperfusion therapy in these patients have yet to be confirmed. METHODS: We conducted a retrospective review of patients with CAD admitted to a comprehensive stroke centre between 2010 and 2015. We recorded baseline clinical characteristics, treatments, functional outcomes, and mortality. RESULTS: We identified 35 cases of CAD (23 carotid/12 vertebral); mean age was 43.5 ± 9.5 years and 67.7% were men. Ten patients (32.3%) had a history of trauma. The most frequent risk factors were arterial hypertension (29%) and smoking (35.5%). The most common clinical presentation was ischaemic stroke (29 patients, 93.5%). The median baseline National Institute of Health Stroke Scale score was 6 (range, 0-41). The most frequently used diagnostic method was CT angiography (74.2%), followed by MRI (64.5%) and digital subtraction angiography (45.6%). Seven patients (22.6%) were treated with intravenous fibrinolysis and 11 (35.5%) with endovascular treatment plus intravenous fibrinolysis; at 3 months, functional independence (modified Rankin Scale scores 0-2) was achieved by 57.1% and 63.6% of these cases, respectively. One patient died (3.2%). CONCLUSIONS: In our sample, the most common form of presentation of CAD was ischaemic stroke. Reperfusion therapy seems to be a safe and effective option for these patients, and outcomes resemble those of other patients with ischaemic stroke. Larger comparative studies are necessary to better assess response to reperfusion therapy in acute ischaemic stroke.

Flavonoids and the gastrointestinal tract: Local and systemic effects.

The gastrointestinal (GI) tract plays a central role in the absorption, distribution, metabolism, and excretion of flavonoids, which ultimately define the health effects of these bioactives. These aspects are modulated by the interactions of flavonoids with other dietary components, environmental factors, the host, and the GI microbiota. Flavonoid can target molecules in the luminal content, the different GI tract cell types, and the microbiota. Importantly, flavonoid actions at the GI tract can have an impact systemically, e.g. on glucose homeostasis, lipid and energy metabolism, or cardiovascular risk factors. The beneficial actions of flavonoids at the GI include their capacity to: i) protect the intestinal epithelium against pharmacological insults and food toxins; ii) modulate the activity of enzymes involved in lipid and carbohydrate absorption; iii) maintain the intestinal barrier integrity; iv) modulate the secretion of gut hormones; v) modulate the GI tract immune system; vi) exert potential anti-colorectal cancer activity; and vii) shape microbiota composition and function. Further understanding of the mechanisms mediating the effects of flavonoids on the intestine (and its microbiota) is of critical importance given the relevance of the GI tract on sustaining overall health and of the widespread recommendations of increasing the intake of plant bioactives.

Management of Moderate to Severe Psoriasis in Routine Clinical Practice in Spanish Hospitals. / Manejo de la psoriasis moderada-grave en condiciones de práctica habitual en el ámbito hospitalario español.

BACKGROUND: There is currently little information available on the management of patients with psoriasis in the daily clinical practice of dermatologists in Spain. OBJECTIVE: The aim of this study was to survey a group of Spanish dermatologists with particular expertise in the management of psoriasis to determine their opinions on the protocols used in routine clinical practice. MATERIAL AND METHODS: A cross-sectional study based on an online survey about the management of psoriasis sent to 75 dermatologists. The survey, which was specifically designed for the study, included 12questions on different aspects of clinical practice in the treatment of moderate to severe psoriasis. RESULTS: The response rate was 96% (n=72). Biologics were the most widely used monotherapy option. In total, 64.3% of respondents reported that their patients used conventional systemic therapies for 1 to 2years before switching to a biologic drug and that the main reason for the switch was unstable control of disease activity. Overall, 85.7% assigned a "high" or "very high" importance to the use of a Psoriasis Area Severity Index score of <3 as a treatment goal. The drugs of choice among the respondents were etanercept for pediatric patients (78.6%), adalimumab and etanercept for patients with psoriatic arthritis (64.3%), and ustekinumab in patients frequently away from home (78.6%) and patients with a history of multiple sclerosis, demyelinating diseases (64.3%), or poor adherence to treatment (71.4%). CONCLUSION: This study provides a unique overview of the opinions of a representative sample of expert dermatologists on the current use of biologics for the treatment of psoriasis in Spain.

Use of e-mail for Parkinson's disease consultations: Are answers just a clic away? / El correo electrónico en la consulta de Parkinson: ¿soluciones a un clic?

INTRODUCTION: The clinical problems of patients with movement disorders (MD) are complex, and the duration and frequency of face-to-face consultations may be insufficient to meet their needs. We analysed the implementation of an e-mail-based query service for our MD unit's patients and their primary care physicians (PCPs). METHODS: We retrospectively reviewed all consecutive emails sent and received over a period of 4 months, one year after implementation of the e-mail inquiry system. All patients received the during consultations, and PCPs, during scheduled informative meetings. We recorded and later analysed the profile of the questioner, patients' demographic and clinical data, number of queries, reason for consultation, and actions taken. RESULTS: From 1 January 2015 to 30 April 2015, the service received 137 emails from 63 patients (43% male, mean age 71±10.5) diagnosed with Parkinson's disease (76%), atypical parkinsonism (10%), and others (14%); 116 responses were sent. Twenty (32%) emails were written by patients, 38 (60%) by their caregivers, and 5 (8%) by their PCPs. The reasons for consultation were clinical in 50 cases (80%): 16 (32%) described clinical deterioration, 14 (28%) onset of new symptoms, and 20 (40%) side effects or concerns about medications. In 13 cases (20%), the query was bureaucratic: 11 were related to appointments (85%) and 2 were requests for clinical reports (15%). In response, new appointments were scheduled in 9 cases (14%), while the rest of the questions were answered by email. Patients were satisfied overall and the additional care burden on specialists was not excessive. CONCLUSIONS: Implementing an e-mail-based consultation system is feasible in MD units. It facilitates both communication between neurologists and patients and continued care in the primary care setting.

Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis.

Cathepsin K, a lysosomal cysteine protease critical for bone remodeling by osteoclasts, was recently identified as the deficient enzyme causing pycnodysostosis, an autosomal recessive osteosclerotic skeletal dysplasia. To investigate the nature of molecular lesions causing this disease, mutations in the cathepsin K gene from eight families were determined, identifying seven novel mutations (K52X, G79E, Q190X, Y212C, A277E, A277V, and R312G). Expression of the first pro region missense mutation in a cysteine protease, G79E, in Pichia pastoris resulted in an unstable precursor protein, consistent with misfolding of the proenzyme. Expression of five mature region missense defects revealed that G146R, A277E, A277V, and R312G precursors were unstable, and no mature proteins or protease activity were detected. The Y212C precursor was activated to its mature form in a manner similar to that of the wild-type cathepsin K. The mature Y212C enzyme retained its dipeptide substrate specificity and gelatinolytic activity, but it had markedly decreased activity toward type I collagen and a cathepsin K-specific tripeptide substrate, indicating that it was unable to bind collagen triple helix. These studies demonstrated the molecular heterogeneity of mutations causing pycnodysostosis, indicated that pro region conformation directs proper folding of the proenzyme, and suggested that the cathepsin K active site contains a critical collagen-binding domain.

Development and validation of a LC-MS/MS method with electrospray ionization for determination of LASSBio-579 in rat plasma.

A simple and sensitive LC-MS/MS analytical method was developed and validated for the determination of LASSBio-579 in plasma rat, using fluconazole as internal standard. Analyses were performed on a Shimadzu HPLC system using a Shimadzu C18 column and isocratic elution with acetonitrile-water (80:20, v/v), containing 0.4mM ammonium hydroxide and 0.2 mM acetic acid at a flow rate of 1.0 ml/min (split ratio 1:5). A Micromass triple quadrupole mass spectrometer, equipped with an electrospray ionization interface, operated in the positive mode. Plasma samples were deproteinized with acetonitrile (1:2) and 50 microl of the supernatant were injected into the system. The retention times of LASSBio-579 and IS were approximately 4.7 and 2.4 min, respectively. Calibration curves in spiked plasma were linear over the concentration range of 30-2000 ng/ml with determination coefficient >0.98. The lower limit of quantification was 30 ng/ml. The accuracy of method was within 15%. Intra- and inter-day relative standard deviations were less or equal to 13.5% and 6.4%, respectively. The applicability of the LC-MS/MS method for pharmacokinetic studies was tested using plasma samples obtained after intraperitoneal administration of LASSBio-579 to male Wistar rats. No interference from endogenous substances was observed, showing the specificity of the method developed. The reported method can provide the necessary sensitivity, linearity, precision, accuracy, and specificity to allow the determination of LASSBio-579 in pre-clinical pharmacokinetic studies.

Tratamiento del embarazo ectópico en cicatriz de cesárea: revisión de la literatura a propósito de 3 casos / Treatment of ectopic pregnancy in a cesarean scar: review of the literature regarding 3 cases

INTRODUCCIÓN Y OBJETIVOS: El embarazo en cicatriz de cesárea previa (ECC) es una entidad poco frecuente que puede tener graves consecuencias. Hasta la fecha no existen esquemas estandarizados de tratamiento y su manejo óptimo sigue siendo controvertido. Nuestro objetivo es realizar una revisión de la literatura publicada sobre el manejo del ECC y proponer un algoritmo. También exponemos tres casos de ECC resueltos con diferentes tratamientos en el Hospital Universitario Infanta Elena MÉTODOS: Búsqueda de la literatura en bases de datos utilizando las palabras clave: "embarazo en cicatriz cesárea"," gestación ectópica en cicatriz cesárea", "tratamiento", "manejo". RESULTADOS: Las opciones terapéuticas pueden ser médicas, quirúrgicas o una combinación de ambas. Los tratamientos quirúrgicos tienen altas tasas de éxito, sin embargo, son más invasivos y no están exentos de riesgo. La combinación de tratamientos parece aumentar la tasa de éxito, no obstante, podría implicar un mayor riesgo de efectos secundarios y costes. CONCLUSIONES: El manejo de los ECC debe de ser individualizado, basado en la evidencia científica, en los medios disponibles y la experiencia de los profesionales en los distintos procedimientos, guiándonos por el tipo de ECC y su grado de vascularización e invasión, grosor del miometrio, niveles de beta-hCG, presencia de actividad cardiaca, clínica y estabilidad hemodinámica de la paciente. Deben tenerse en cuenta las circunstancias y patología intercurrente de la mujer, así como su deseo genésico o de preservación del útero.

INTRODUCTION AND OBJECTIVES: Cesarean scar pregnancy (CSP) is a rare entity that can cause serious consequences. Up to now, there are no standardized treatment schemes, and its optimal management remains controversial. Our objetive is to review the literature regarding CSP management and propose an algorithm. We also present three cases of CSP resolved with different treatments at Hospital Universitario Infanta Elena. METHODS: Literature search in databases using the following keywords: pregnancy with cesarean section, ectopic pregnancy with cesarean section, treatment, management. RESULTS: The therapeutic options can be medical, surgical or a combination of both. Surgical treatments have high success rates; however, they are more invasive and are not without risk. The combination of treatments seems to increase the success rate; however, it could imply a higher risk of side effects and costs. CONCLUSIONS: The management of CSP must be individualized; based on scientific evidence, on the means available, and on the experience of the professionals in the different procedures; guided by the type of CSP and its degree of vascularization and invasion, by the thickness of the myometrium, beta-hCG levels, presence of cardiac activity, and by clinical and hemodynamic stability of the patient. The circumstances and intercurrent pathology of the patient must be considered, as well as her desire for future pregnancy or preservation of the uterus.

Oxidative Stress Affects [alpha]- Tocopherol Content in Soybean Embryonic Axes upon Imbibition and following Germination.

The content of [alpha]-tocopherol ([alpha]T) in isolated soybean (Glycine max, var Hood) embryonic axes was measured upon germination. Dry, high-vigor axes contained 1.2 [plus or minus] 0.1, nmol/axis and after an increase during the initial 6 h of imbibition, there was a decline to 1.0 [plus or minus] 0.1 nmol/axis at 24 h of incubation. Incubation in the presence of the redox-cycling agent paraquat (4 mM) for 24 h increased the [alpha]T content to 1.9 [plus or minus] 0.2 nmol/axis. When the incubation medium was supplemented with 500 [mu]M Fe-EDTA over 24 h, the content of [alpha]T increased to 1.8 [plus or minus] 0.1 nmol/axis. Isolated axes from soybean seeds stored for 56 months contained 6.5 [plus or minus] 0.3 nmol of [alpha]T/axis after 24 h of imbibition as compared to 1.0 [plus or minus] 0.1 nmol of [alpha]T/axis in axes from soybean seeds stored for 8 months. In all of these experimental situations, oxidant production as assessed in vivo by a fluorometric assay was increased by 4 mM paraquat (8-fold), 500 [mu]M iron (2-fold), and 56 months of storage (4-fold) after 24 h of imbibition. The data presented here suggest that the cellular content of [alpha]T is physiologically adjusted as a response to conditions of oxidative stress.

Angiotensin II blockade improves mitochondrial function in spontaneously hypertensive rats.

Angiotensin II can induce oxidant stress by stimulating vascular superoxide production. Hypertension promotes mitochondrial function decline in brain, liver and heart. The aim of this study was to investigate whether a) hypertension is associated to kidney mitochondrial dysfunction, and b) angiotensin II blockade can reverse potential mitochondrial changes in hypertension. Four-month-old male spontaneously hypertensive rats (SHR) received drinking water containing candesartan (7.5 mg/kg/day, SHR+Cand), or no additions (SHR) for 4-months. Eight-month-old Wistar-Kyoto rats (WKY), that received water with no additions, were used as control. Systolic blood pressure, proteinuria, cortical glomerular area, and glomerular and tubulointerstitial alpha-smooth muscle actin labeling, were significantly higher, and creatinine clearance was significantly lower, in SHR relative to WKY and SHR+Cand. In SHR, kidney mitochondria membrane potential, and nitric oxide synthase and cytochrome oxidase activities were significantly lower than in WKY and SHR+Cand. In SHR, mitochondrial hydrogen peroxide production was significantly higher than in WKY and SHR+Cand. The results suggest that, in hypertension, increased mitochondrial oxidant production may mediate kidney mitochondria dysfunction. Candesartan preserved mitochondrial function, probably favoring the maintenance of adequate cellular and tissue function in the kidney. The known renal protective effects of candesartan in hypertension may be related to the improvement of mitochondrial function. This may be an additional or alternative explanation for some of the beneficial effects of AT1 receptor antagonists.

A propósito de un caso: útero miomatoso gigante torsionado / Torsion of a giant miomatous uterus: report of a clinical case autores

OBJETIVO: Reportar el caso de una torsión de útero, trompas y ambos ovarios a nivel de cuello uterino. Describir la patogenia, sintomatología y tratamiento, como un caso infrecuente y potencialmente grave, en la práctica clínica diaria. MATERIAL Y MÉTODOS: Analizar el curso de esta extremadamente rara patología, en una mujer postmenopáusica de 59 años. Se trata de un caso raro de torsión uterina en un útero no gestante, reportando los hallazgos en los exámenes previos a la cirugía y los hallazgos intraoperatorios e histopatológicos postcirugía. La resonancia magnética fue fundamental en el diagnóstico de la paciente y la laparotomía realizada demostró una torsión de cuerpo uterino de 360 ° a nivel de cérvix, y un gran mioma pediculado con signos de necrosis. Hemos revisado los últimos artículos de esta rara patología RESULTADOS Y DISCUSIÓN: La paciente fue operada. Se realizó una histerectomía total mediante una laparotomía media supra e infraumbilical. Los ovarios no tenían signos de necrosis. CONCLUSIONES: Debemos tener en cuenta esta posibilidad diagnóstica, en pacientes con aumento de tamaño uterino y clínica de dolor abdominal, ya que aunque es muy infrecuente, su diagnóstico es importante, ya que puede ser peligroso para la vida de la paciente.

OBJECTIVE: To report a case of torsion of the uterus, fallopian tubes and both ovaries around the uterine collum and the symptomatology, pathogenesis and treatment of this uncommon pathology. MATERIAL AND METHODS: The article analyses the course of this extremely rare pathology in a postmenopausical woman of 59 years. It is a rare case like a non gravid uterine torsion in a postmenopausical woman. We have the exams previous to the surgery, the finds intraoperative and the histolopathological reports postsurgery. RMN was the most important in diagnosis and the laparotomy showed a 360° an uterus increased on size and a big pedunculated myoma with signs of necrosis We have reviewed the latest articles on this strange pathology RESULTS AND DISCUSSION: The patient was operated. A infra-supra medium laparotomy was practiced and a total hysterectomy was made. Ovarians had not signs of necrosis. CONCLUSIONS: We must take into account, in patients with pathologies that increase uterine size and abdominal pain, the possibility of uterine torsion. Although it is a very infrequent pathology, its diagnosis is important, since it can be dangerous for the life of the patient

(+)-Catechin prevents human plasma oxidation.

Based on the recognized capacity of (+)-catechin (CTCH) to prevent free radical-mediated damage in different biological systems, its role in the protection of human plasma from oxidation was investigated. Samples of human blood plasma were incubated with 50 mM AAPH [2,2'-azobis-(2-amidinopropane) clorhidrate] or AMVN [2,2'-azobis(2,4-valeronitrile)], in the absence or the presence of CTCH (0.01 to 1 mM). Lipid oxidation was evaluated measuring the formation of 2-thiobarbituric acid reactive substances (TBARS). Alpha-tocopherol (AT), beta-carotene (BC), and CTCH were measured by reverse phase HPLC with electrochemical detection. TBARS formation was dependent on incubation time and on the nature of the azocompound, yielding 4.8 +/- 0.9, and 14.9 +/- 3.4 microM MDA, after 4 h, in AAPH and AMVN-exposed plasma, respectively. Plasma AT and BC were extensively depleted under these oxidant conditions. The addition of CTCH prevented or delayed the formation of TBARS, and the depletion of AT and BC in a dose dependent manner. This antioxidant effect was dependent on the concentration of CTCH and on the physical characteristics of the radical initiator. CTCH supplementation modified not only the lag time for the antioxidants depletion, but also the consumption rate. These results indicate that CTCH was an effective antioxidant in human blood plasma, delaying the consumption of endogenous lipid soluble antioxidants (AT and BC) and inhibiting lipid oxidation.

Tissue damage in acute myocardial infarction: selective protection by vitamin E.

A growing amount of scientific evidence supports the participation of oxygen radicals in heart disease and, consequently, a protective effect of vitamin E (VE), beta-carotene (BC), and other antioxidants. The aim of this study was to correlate plasma VE and BC concentration with the clinical course of the acute myocardial infarction (AMI). We evaluated 120 patients that were admitted at the coronary units within 12 h after the development of AMI symptoms. The AMI was diagnosed by clinical and biochemical criteria and by electrocardiography and echocardiography. Plasma VE and BC concentration was determined by high performance liquid chromatography. The patients were separated according to the plasma concentration of VE (group H, VE > 17.5 microM; group L, VE < 17.5 microM). Clinical history of patients, age, sex, associated cardiovascular risk factors, AMI localization, hemodynamic class, and the treatment received were similar between different groups. The blood levels of creatine phosphokinase (CK) evaluated either 24- or 48-h after admittance, were higher in group L than in group H (24 h: H = 436 +/- 31 U/ml vs. L = 642 +/- 84 U/ml; p < .005; 48 h: H = 242 +/- 21 U/ml; L = 423 +/- 82 U/ml, p < 0.005). The number of deflexions in the electrocardiogram at admittance (ECG-D) was significantly higher in group L than in group H (4.7 +/- 0.3 vs. 3.7 +/- 0.2; p < .005). The number of new Q waves in the ECG of release (ECG-Q) was higher in group L than in group H (2.9 +/- 0.3 vs. 2.2 +/- 0.2; p < .05). The number of segments affected in the echocardiograms (EC-S) was: L = 5.3 +/- 0.6 vs. H = 4.4 +/- 0.2; p = 0.11. No significant differences in CK levels, ECG-D, ECG-Q, and EC-S were observed when the patients were separated according their plasma BC levels. These results indicate that a high concentration of plasma VE, but not BC, was associated with a diminution in the creatine phosphokinase release and with the AMI extension.

Halogenated compounds as inducers of lipid peroxidation in tissue slices.

Twenty-seven halogenated compounds were screened as potential inducers of lipid peroxidation in rat liver, kidney, spleen, and testes slices. In addition to the known lipid peroxidation inducers--carbon tetrachloride and bromotrichloromethane--the novel compounds carbon tetrabromide, p-bromobenzyl bromide, and benzyl bromide increased lipid peroxidation in each of the tissues studied. Lipid peroxidation was measured by release of thiobarbituric acid-reactive substances (TBARS) from the tissue slices. The amount of TBARS released from liver slices incubated with bromotrichloromethane, carbon tetrabromide, dichloromethane, bromobenzene, chloroform, bromoform, benzyl chloride, bromochloromethane, and carbon tetrabromide correlated with the lethality of these compounds as evaluated by their oral LD50 in rats. The lethality of a number of the compounds tested did not correlate with their capacity to induce lipid peroxidation.

Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes.

Liver slices were used to measure lipid peroxidation induced by bromotrichloromethane, tert-butyl hydroperoxide (t-BOOH), or ferrous iron. The responses of liver homogenates and microsomes to oxidative conditions were compared with the response of tissue slices. Lipid peroxidation was evaluated by the production of thiobarbituric acid-reactive substances (TBARS). As was observed in homogenates and microsomes, TBARS production by liver slices depended upon the amount of tissue, the incubation time, inducer, the amount of inducer, and the presence of antioxidant. Control liver slices incubated at 37 degrees C for 2 h produced 19 nmol of TBARS per g of liver. When slices were incubated in the presence of 1 mM BrCCl3, 1 mM t-BOOH, or 50 microM ferrous iron, TBARS production increased 4.6-, 8.2-, or 6.7-fold over the control value, respectively. Comparable induction of TBARS by liver homogenates and microsomes was observed when these preparations were incubated with the same inducers. Addition of 5 microM butylated hydroxytoluene (BHT) prevented the induction of TBARS by 50 microM ferrous iron by liver slices. The results indicate the usefulness of tissue slices to measure lipid peroxidation. The usefulness of tissue slices is emphasized when a number of compounds or tissues are studied and tissue integrity is desired as in toxicological, pharmacological, and nutritional studies where reduced numbers of experimental animals is a relevant issue.

Application of simulation modeling to lipid peroxidation processes.

A quantitative simulation model was developed that utilized present knowledge of lipid peroxidation in biological systems. The simulation model incorporated the following features: peroxidizability of polyunsaturated lipids, activation of inducers and their initiation of lipid peroxidation, concurrent autoxidation, inhibition of lipid peroxidation by vitamin E, reduction of some of the hydroperoxides by glutathione peroxidase, and formation of thiobarbituric acid-reactive substances. Simulation calculations were done using a computer spreadsheet program. When the simulation program was applied to tissue slice and microsomal peroxidizing systems, the results of the stimulation were in agreement with the experimental data.

Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver.

We have characterized the effect of angiotensin converting enzyme (ACE) inhibitors on the activity of CuZn-superoxide dismutase (CuZn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and selenium-dependent glutathione peroxidase (Se-GPx). CF1 mice (4-month-old females) were administered water containing enalapril (20 mg/l) or captopril (50 mg/l), during 4 to 11 weeks. After 11 weeks, enalapril treatment caused an increase in the activity of CuZn-SOD, Mn-SOD and Se-GPx, from 19 +/- 4 to 46 +/- 7, 2.1 +/- 0.2 to 3.8 +/- 0.2 units/mg protein and 27 +/- 3 to 54 +/- 3 milliunits/mg protein, respectively. After 11 weeks, captopril treatment increased the activities (P < 0.05) of CuZn-SOD, MnSOD and Se-GPx to 35 +/- 4, 2.9 +/- 0.2 units/mg protein, and 38 +/- 2 milliunits/mg protein, respectively. Catalase activity was not affected by the treatments. These results suggest that ACE inhibitors may protect cell components from oxidative damage by increasing the enzymatic antioxidant defenses.