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In Peru, The National Health Authority (SUSALUD) is granted the responsibility to promote, protect and defend the health rights of every citizen. However, in the Peruvian Health System (PHS) there exists an insufficient culture of health rights, a low level of knowledge of health rights by the population, and a limited degree of cooperation between users, providers and funders. In light of this limited popular participation in the health rights of the citizenry, it has been necessary for SUSALUD to pursue various activities in order to promote the exercise of health rights by Peruvians. Among the strategies implemented are the development of Organized Boards of Users (OBU) and a Program of Integrated Actions for the Promotion of Health Rights (PIAPHI). The aim of both interventions is to increase the level of trust between citizens and government, which fosters and strengthens the capacity of citizens to pursue their health rights. In this article we begin with a brief presentation on the state of knowledge, attitudes and practices of users of the health system regarding their rights. Then we explain both programs, their goals and procedures, and a general description of their activities. Also, some indicators of process and some results are presented along with discussion and future prospects. We believe that the gradual implementation of the OBU and PIAPHI programs will enhance the participation of Peruvians in their health system, and will contribute positively to their empowerment and the pursuit of their health rights.

Objectives To estimate the prevalence of ineffective access to drugs (IAD) and associated factors in patients receiving a prescription in an outpatient clinic in Peru. Materials and Methods We performed a secondary data-analysis of the National Survey on User Satisfaction of Health Services (ENSUSALUD 2014), a two-stage population-based study carried out in health care centers of the Ministry of Health and Regional Governments (MOHRG), Social Security (EsSalud), Armed Forces and Police (AFP) and the private sector across all 25 regions of Peru. IAD was defined as incomplete or no dispensing of any prescribed medication in the health care center pharmacy. Generalized linear models with Poisson distribution for complex survey sampling were fit to estimate prevalence ratios (PR) and 95% confidence intervals (CI). Results Out of 13,360 participants, 80.9 % (95% CI: 79.9-81.8) had an active prescription, and of those, 90.8 % (95% CI: 90.1-91.6) sought their medications in a health care center pharmacy, where 30.6 % (95% CI 28.8-32.4) had IAD. In the multiple regression model, receiving medical attention in the MOHRG (PR 4.8; 95%CI: 3.5-6.54) or AFP (PR: 3.2; 95%CI: 2.3-4.5), being over 60 years old (PR: 1.17; 95%CI: 1.04-1.34) and being in the poorest income quintile (PR: 1.05; 95%CI: 1.05-1.41) increased IAD. Furthermore, in contrast to seeking care for pregnancy or other routine control, IAD was also more common for medical consultation for diseases diagnosed in the last 15 days (PR: 1.37; 95% CI: 1.05-1.79) or more than 15 days prior (PR: 1.51; 95% CI: 1.16-1.97). Conclusions In Peru, IAD is associated with the provider institution, older age, poverty and the reason for medical consultation. We suggest strategies to promote access to medicines, especially in the most disadvantaged segments of the Peruvian population.

Insulin signaling to the glomerular podocyte is important for normal kidney function and is implicated in the pathogenesis of diabetic nephropathy (DN). This study determined the role of the insulin receptor substrate 2 (IRS2) in this system. Conditionally immortalized murine podocytes were generated from wild-type (WT) and insulin receptor substrate 2-deficient mice (Irs2(-/-)). Insulin signaling, glucose transport, cellular motility and cytoskeleton rearrangement were then analyzed. Within the glomerulus IRS2 is enriched in the podocyte and is preferentially phosphorylated by insulin in comparison to IRS1. Irs2(-/-) podocytes are significantly insulin resistant in respect to AKT signaling, insulin-stimulated GLUT4-mediated glucose uptake, filamentous actin (F-actin) cytoskeleton remodeling and cell motility. Mechanistically, we discovered that Irs2 deficiency causes insulin resistance through up-regulation of the phosphatase and tensin homolog (PTEN). Importantly, suppressing PTEN in Irs2(-/-) podocytes rescued insulin sensitivity. In conclusion, this study has identified for the first time IRS2 as a critical molecule for sensitizing the podocyte to insulin actions through its ability to modulate PTEN expression. This finding reveals two potential molecular targets in the podocyte for modulating insulin sensitivity and treating DN., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: We can find in Spain several university studies concerning diet and lifestyle, showing them as an effective strategy to prevent chronic diseases., Objectives: To evaluate the energy and nutrient intake and adherence to the Mediterranean Diet (DM) in a group of college students with different academic profile and to compare the quality of the diet among students attending degrees in Health Science (HS) and those attending other degree courses (not HS)., Methods: 77 students (80.3% female) from the Campus of Soria, 37 HS students and 40 not HS (mean age 21.2 ± 2.1 years), completed a questionnaire on socio-biographical data, the test KIDMED of adhesion to Mediterranean diet and recorded food intake for seven days. The amount of energy and nutrients was estimated using the software Nutriber (version 1.1.1.3r). Student t test or U Mann-Whitney were used to compare means of independent samples and the criterion of significance was set at p <0,05., Results and Discussion: The respondent students, regardless of their academic profile, follow a low calorie diet with more protein and fat consumption than the recommended amount, and less carbohydrate and fiber, which is reflected in the insufficient intake of some vitamins and minerals. However, we observed a higher percentage of respondents with high adhesion to the parameters of the DM in the HS group (51.4%) than in the No HS group (30.8%)., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Jumbo squid is an important fishery resource in Mexico, and its muscle is lean and white and it has a very low price in the market. It is abundant, but with little or nothing added value, therefore is necessary to search alternatives of processing. Due to muscle characteristics, the aim of this study was to obtain protein concentrates using different methods. They were obtained by means of acidic (acid protein concentrates) and alkaline (alkaline protein concentrates) dissolution. Moreover, a protein concentrate was obtained by direct isoelectric precipitation and by the traditional method (neutral protein concentrates). The yield with better results was alkaline protein concentrates (63.58 ± 1.8%). The gel hardness was significantly different (p < 0.05), especially for the alkaline protein concentrates. The acid protein concentrates, isoelectric precipitation and alkaline protein concentrates were better with regard to the neutral protein concentrates, concerning the emulsifying and foaming properties. The protein concentrates by means of alkaline dissolution gave a better gelling property, but all the processes had the potential to obtain protein with emulsifying and foaming properties.

Purpose: Routine screening for evidence of DNA mismatch repair abnormalities can identify colorectal cancer patients with Lynch syndrome, but impact in usual care settings requires study. After implementing routine screening at our university and safety-net health systems as usual practice, our aims were to determine outcomes, including screening process quality., Methods: We conducted a retrospective cohort study from 1 May 2010 to 1 May 2011. Screening included reflexive immunohistochemistry to evaluate DNA mismatch repair protein expression for patients with colorectal cancer aged ≤70 years, with a cancer genetics team following up results. Screening outcomes, as well as challenges to a high-quality screening process were evaluated., Results: We included 129 patients (mean age 56 years, 36% female); 100 had immunohistochemistry screening completed. Twelve patients had abnormal immunohistochemistry: four with definite Lynch syndrome, four with probable Lynch syndrome, and three without Lynch syndrome; one patient had an incomplete work-up. Lynch syndrome was confirmed for 6/13 asymptomatic relatives tested. Screening process quality was optimal for 77.5% of patients. Barriers to optimal quality screening included ensuring reflexive immunohistochemistry completion, complete follow-up of abnormal immunohistochemistry, and timely incorporation of results into clinical decision making., Conclusion: Usual care implementation of routine screening for Lynch syndrome can result in significant rates of detection, even in a largely safety-net setting. To optimize implementation, challenges to high-quality Lynch syndrome screening, such as ensuring reflexive screening completion and clinically indicated genetic testing and follow-up for abnormal screens, must be identified and addressed., Competing Interests: The authors declare no conflict of interest.

Background: Parenteral nutrition (PN) is a costly technology used widely to provide nutrition to patients who have an inaccessible or non-functioning intestine. Two all-in-one systems currently being used are customized formulations and three-compartment bags., Objective: To provide a systematic cost comparison of the two all-in-one PN systems: individualized (made from nutrient solutions) versus commercialized (made from three-compartment bag), both prepared in hospital pharmacies., Setting: This study was conducted in three public Spanish hospitals., Method: We conducted a cost-minimization study to analyze prospectively the total cost of PN bags, accounting for all of the processes involved in preparing and delivering PN bags (cost of manpower, nutrition solutions, medical supplies and quality controls) in three different healthcare settings. To compare therapeutic alternatives of equivalent nutritional value, the study was performed for the most frequently employed formulation and similar to commercial preparations. A univariate sensitivity analysis was performed to evaluate the impact of different rates of use of three-compartment PN bag., Results: 157 routine acts of PN bag preparation (65 customized and 92 three-compartment) were observed and timed over 9 days. Total costs of the 157 PN bags were included in the study. Mean costs of customized bags were higher than three-compartment bags, 51.16 ± 5.63 € versus 39.69 ± 3.00 € respectively (p < 0.01). Manpower costs were responsible for the majority of the differences found (70%). The time to complete an adult bag for the hospital compounded system was a mean of 25.9 minutes longer than the three-compartment system. In scenarios using a three-compartment system for 30%, 70% and 90% of PN provision, a cost savings of 4.3%, 10.1% and 12.9% respectively could be achieved. Greatest rates of changing from customized bags (70% and 90%), in a hospital with 1,800 PN bags/year, might reduce the annual budget by 9306 € and 11,964.8 €, respectively. Meanwhile, in a large facility the savings for 8,000 TPN days would be 64,248 € and 82,605 €, respectively., Conclusions: Since seeking cost-reduction of effective treatments is needed, the use of three-compartment bags for standard adult PN could lead to cost savings. Our data should be helpful for health care providers to calculate their own cost of administer., (Copyright AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.)

Aim: Serum ICAM-1 (sICAM-1) is known to be a smoking-associated inflammatory marker, but data in chronic obstructive pulmonary disease (COPD) are lacking., Patients & Methods: A total of 142 COPD cases (48 active smokers) and 55 controls (41 active smokers) were consecutively enrolled in this cross-sectional study. The peripheral blood concentrations of sICAM-1, IL-8 (CXCL8), CRP and serum amyloid A (SAA) were determined by ELISA., Results: CRP and SAA (log-scale) were elevated in the patients with COPD compared with the control subjects (p = 0.005 for CRP and p = 0.024 for SAA). sICAM-1 was associated with active smoking when corrected for age, gender, the presence of COPD, inhaled corticosteroid use, BMI and forced expiratory volume in 1 s as covariates., Conclusion: The present study confirms an association between sICAM-1 levels and active smoking in a group of COPD and non-COPD active smokers.

Background: Heat shock protein 27 (HSP27) is a small HSP up-regulated in response to stress in the kidney. The relationship between HSP27 and intrarenal oxygenation in patients with native and transplant kidney disease is unknown., Methods: We compared HSP27 levels, intrarenal oxygenation measured by blood oxygen-level dependent (BOLD) imaging using R(2)* values, and perfusion determined by arterial spin labeling (ASL) magnetic resonance imaging (MRI), between patients with native and transplant kidney disease (n=28)., Results: There were no statistical differences in mean age (53.9 vs. 47.1 years), kidney function (63.6 vs. 50.7 ml/min per 1.73 m(2)), mean arterial blood pressure (91.6 vs. 91.1 mm Hg), hematocrit (40.6% vs. 39.3%), diuretic or angiotensin-converting enzyme inhibitor use, serum or urine levels of hydrogen peroxide, nitric oxide, F(2) isoprostanes and HSP27 between native and transplant kidneys. BOLD-MRI studies demonstrated comparable patterns in intrarenal oxygen bioavailability (medullary R(2)* 18.1 vs. 18.3/s and cortical R(2)* 12 vs. 11.7/s, respectively). However, medullary perfusion was significantly lower in transplant kidneys (36.4 vs. 78.7 ml/100 g per minute, p=0.0002). There was a linear relationship between serum HSP27 concentrations and medullary perfusion in kidney allografts (HSP27 concentration [ng/mL] = 0.78 + 0.09 medullary perfusion, R(2)=0.43, p=0.01)., Conclusions: Our study demonstrates that medullary perfusion is significantly lower in kidney allografts compared with native kidneys with comparable renal function. We further noted a direct association between serum HSP27 levels and medullary perfusion after transplantation. Additional studies are needed to examine the role of HSP27 as a biomarker of kidney disease progression.

Inadequate organ donation limits transplantation for many in need of a life-saving organ. Race of donor families and requesting coordinators may impact the authorization rate for organ donation. We evaluated authorization rates for organ donation within the New York Organ Donor Network by race during 2009 and 2010. The donation authorization rate varied considerably according to the race of the donor. The authorization rate was 57% for Hispanic, 53% for Caucasian, 48% for African-American, and 23% for Asian donor families. Fifty-five percent of donor families agreed to donation when there was racial concordance between coordinator and donor. Donation authorization was 49% when a racial mis-match existed. When adjusted for coordinator training and experience, racial discordance had a lesser impact on authorization rates. Our findings suggest the need for education and communication strategies to overcome racial-associated perception during the organ donation process.

"Off-label" prescribing is the use of a drug in a fashion other than one approved by the Food and Drug Administration (FDA). Some courts assume that the PDR is comprehensive enough to apply its guidelines to establish the standard of care. This assumption undermines the physician's judgment in deciding how, when and for what ailment a drug should be used. It substitutes the judgment of the PDR and FDA for the physician in assessing illness and applied pharmacology. We report the results of a survey presented to leaders in the United States medical community and review medical literature and legal cases addressing off-label prescribing. Unlike some US courts, the medical community does not consider the PDR as representative of all applications of drug use, nor does it consider the PDR as the standard of medical care.

Objectives: To describe the severity of the 2009 influenza A/H1N1v illness among pregnant women admitted to Spanish intensive care units., Design and Patients: Prospective, observational, multicenter study conducted in 148 Spanish intensive care units. We reviewed demographic and clinical data from the Spanish Society of Intensive Care Medicine database reported from April 23, 2009, to February 15, 2010. We included women of reproductive age (15-44 yrs) with confirmed A/H1N1v infection admitted to intensive care units., Main Results: Two hundred thirty-four women of reproductive age were admitted to intensive care units, 50 (21.4%) of them pregnant. Seven deaths were recorded in pregnant and 22 in nonpregnant women. Among intensive care unit admissions, there were no statistically significant differences between pregnant women and nonpregnant in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment scores, chest x-rays, inotrope requirement, or need for mechanical ventilation or steroid therapy. Mortality risk was significantly associated with Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and obesity. Viral pneumonia was more frequent in pregnant women than in nonpregnant women, with an odds ratio (adjusted for asthma, time from onset influenza symptoms to hospital admission and obesity) of 4.9 (95% confidence interval: 1.4-17.2). The development of primary viral pneumonia in women of reproductive age appeared to be related to the time of commencement of antiviral treatment, the lowest rates being reported with initiation of antiviral therapy within 48 hrs of symptom onset (63.6% vs. 82.6%, p = .03). However, antiviral therapy was started within this time span in only 14% of pregnant women., Conclusions: More than 20% of women of reproductive age admitted to intensive care unit for pH1N1 infection were pregnant. Pregnancy was significantly associated with primary viral pneumonia. Pregnant women should receive prompt treatment with oseltamivir within 48 hrs of the onset of influenza symptoms.

Background: Cryptogenic organizing pneumonia (COP) is a rare disease, and its diagnosis requires histological confirmation. The objective of our study was to describe the findings of the thoracic high-resolution computed tomography (HR-CT) and bronchoalveolar lavage (BAL) in patients with confirmed COP and evaluate the complementary diagnostic use of BAL and thoracic HR-CT., Methods: Patients recorded in the registry of interstitial pulmonary diseases between 1991 and 2008 were located and the COP patients selected., Results: We identified 21 patients with histological confirmation of COP. The median age was 58.0 ± 15.9 years, and 61.9% of patients were female. The most frequent thoracic HR-CT profile was patchy infiltrate (71.4%), followed by parenchymatous consolidation (42.9%). The most frequent BAL profile was mixed alveolitis (62%) with lymphocyte predominance, a CD4/CD8 index of 0.4 and foamy macrophages. The effectiveness of transbronchial biopsy was 66.6%. The diagnostic utility of Poletti's BAL criteria gives us a specificity of 88.8%, although the sensitivity obtained was low. The specificity of certain HR-CT profiles is 99%. In addition, we observed a complementary use of the HR-CT and the BAL., Conclusions: The imaging findings and BAL could be useful for patients with appropriate clinical presentation and for those whose transbronchial biopsy is negative or for whom a confirmatory biopsy cannot be performed., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Medication nonadherence is common and results in preventable disease complications. This study assessed the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events., Methods and Results: In this multicenter, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥ 50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients' pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end point of all-cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62, 95% confidence interval 0.50 to 0.78) and were more likely to be adherent (odds ratio 1.91, 95% confidence interval 1.19 to 3.05) than control group patients at 6 months. After 5 years, 16% of the patients in the intervention group and 19% in the control group met the composite end point (hazard ratio 0.97, 95% confidence interval 0.67 to 1.39)., Conclusions: A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events.

Collagen-based biomaterials have been widely used due to its binding capabilities. However the properties and potential use of new collagen sources are still under investigation. Fish by-products are an excellent source of collagen. Thus, acid-soluble collagen (ASC) was extracted, and biochemical and physicochemically characterized from one under-utilized specie, jumbo squid (Dosidicus gigas). In addition, commercial chitosan (95-50%)-ASC (5-50%) blend films were successfully prepared by casting, and characterized by infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The molecular masses of the ASC subunits were about 190kDa, 110kDa, and 97kDa, the content of proline and hydroxyproline was 10.9% and 2.8%, respectively. The FT-IR and nuclear magnetic resonance spectra ((1)H NMR) confirmed collagen peptidic crosslinks, and one endothermic peak was found at 119 degrees C. The FT-IR spectrum showed that chitosan and ASC remain linked into the films mainly due to hydrogen bonding. The 85:15 (chitosan:ASC) ratio was selected for its thermal and mechanical analyses. The thermograms of this film indicated the presence of two peaks, one at 87-98 degrees C and the other at 142-182 degrees C. The chitosan:ASC blend produced a transparent and brittle film, with high percentage of elongation at break, and low tensile strength in comparison to chitosan films. D. gigas mantle might be useful as a new source of plasticizer agent in the preparation of biofilms in composites with chitosan., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Aim: It has been recently shown that the original BODE index has a high degree of correlation with two modified BODE indexes using maximal oxygen uptake expressed either as mL/min/kg (mBODE) or as the percentage predicted (mBODE%). In this study we investigated the agreement between the two modified BODE indexes (mBODE and mBODE%) in patients with stable chronic obstructive pulmonary disease (COPD)., Methods: A total of 169 patients with stable COPD were enrolled in this cross-sectional study. Differences between the two mBODE indexes were assessed using kappa coefficients and Bland-Altman plots. One out of every three patients underwent the six-minute walking test to investigate the agreement with the original BODE index., Results: Correlations between the two mBODE indexes with each other (r = 0.96, P < 0.001) and with the original BODE index (mBODE r = 0.88, P < 0.001; mBODE% r = 0.93, P < 0.001) were excellent. However, the two mBODE indexes were significantly different from each other (mBODE 5.27 +/- 2.3 versus mBODE% 4.31 +/- 2.5; P < 0.001). The kappa coefficients were significantly lower (entire study group k = 0.5, P < 0.001) for every GOLD stage. The mean difference between the two mBODE indexes was 0.8 +/- 0.6 units. Differences with the original BODE were higher for the mBODE (1.8 +/- 0.9) than for the mBODE% (0.6 +/- 0.8)., Conclusions: The new mBODE indexes are highly correlated but significantly different from each other. The differences between the novel indexes deserve further scrutiny.

The rates of gas-phase elimination of trimethyl orthovalerate and trimethyl orthochloroacetate have been determined in a static system, and the reaction Pyrex vessels have been deactivated with the product of decomposition of allyl bromide. The reactions are unimolecular and follow a first-order rate law. The working temperature and pressure ranges were 313-410 degrees C and 40-140 Torr, respectively. The rate coefficients for the homogeneous reaction are given by the following Arrhenius expressions: for trimethyl orthovalerate: log k (s(-1)) = [(14.00 +/- 0.28) - (196.3 +/- 1.7) (kJ/mol)] (2.303RT)(-1), (r = 0.9999); and for trimethyl orthochloroacetate: log k (s(-1)) = [(13.54 +/- 0.21) - (209.3 +/- 1.9)(kJ/mol)](2.303RT)(-1), (r = 0.9998). The theoretical calculations of the kinetic and thermodynamic parameters were carried out by using B3LYP, B3PW91, MPW1PW91, and PBEPBE methods. The theoretical results show reasonably good agreement with the experimental energy and enthalpy of activation values when using the B3PW91/6-31++G** method for trimethyl orthovalerate and PBEPBE /6-31++G** for trimethyl orthochloroacetate. These calculations suggest a molecular concerted nonsynchronous mechanism where C-OCH(3) bond polarization, in the sense C(delta+)...(delta-)OCH(3), is the rate-determining step. The increase in electron density of the oxygen atom at OCH(3) eases the abstraction of the hydrogen of the adjacent C-H bond in a four-membered cyclic structure to give methanol and the corresponding unsaturated ketal. The electron-donor substituent enhances decomposition rates by stabilizing the positive charge developing in the transition state at the carbon bearing the three methoxy groups, whereas the electron-withdrawing substituent destabilizes this charge, thus retarding the reaction.

Introduction: Patients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain., Methods: We used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay., Results: Illness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 +/- 3.3)., Conclusions: Over a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons.

Adenosine monophosphate (AMP) deaminase was purified from jumbo squid mantle muscle by chromatography in cellulose phosphate, Q-Fast and 5'-AMP sepharose. Specific activity of 2.5U/mg protein, 4.5% recovery and 133.68 purification fold were obtained at the end of the experiment. SDS-PAGE showed a single band with 87kDa molecular mass, native PAGE proved a band of 178kDa, whereas gel filtration detected a 180kDa protein, suggesting the homodimeric nature of this enzyme, in which subunits are not linked by covalent forces. Isoelectric focusing of this enzyme showed a pI of 5.76, which agrees with pI values of AMP deaminase from other invertebrate organisms. AMP deaminase presented a kinetic sigmoidal plot with Vmax of 1.16μM/min/mg, Km of 13mM, Kcat of 3.48μM.s(-1) and a Kcat/Km of 267 (mol/L)(-1).s(-1). The apparent relative low catalytic activity of jumbo squid muscle AMP deaminase in the absence of positive effectors is similar to that reported for homologous enzymes in other invertebrate organisms., (Copyright © 2008 Elsevier Ltd. All rights reserved.)

Background: Twenty-four-hour ambulatory blood pressure monitoring (ABPM) provides the most accurate efficacy assessment of an antihypertensive agent throughout a 24-hour dosing interval. The objective of this prospective, randomised, double-blind, parallel-group, multicentre study was to compare the antihypertensive efficacy of imidapril versus candesartan cilexetil using ABPM., Methods: After screening and a single-blind, placebo run-in phase, ambulatory adult patients with mild to moderate hypertension (defined as a mean office sitting diastolic BP [DBP] and systolic BP [SBP], respectively, of 90-109 mm Hg and 140-179 mm Hg, and a mean ABPM DBP and SBP, respectively, of >or=80 mm Hg and >or=125 mm Hg) were randomised to once-daily treatment with imidapril or candesartan cilexetil for 12 weeks. ABPM was performed at baseline and at the end of the 12-week treatment period in 112 patients (imidapril group, n=55; candesartan cilexetil group, n=57). To achieve the target BP of

We compared fasting lipids and other metabolic parameters in 211 normoglycemic patients meeting the DSM-IV diagnosis of schizophrenia or schizoaffective disorder undergoing continuous treatment with olanzapine, risperidone, or typical antipsychotics for at least 1 year. Blood samples were obtained after an 11-hour (+/-1 h) observed fast. Olanzapine-treated patients had significantly higher mean fasting triglyceride levels (2.3 +/- 1.8 mmol/L) than risperidone- (1.7 +/- 0.9 mmol/L, P = 0.022), but not typical antipsychotic-treated patients (1.8 +/- 1 mmol/L). There were no significant differences in total low-density (LDL-C) or high-density lipoprotein cholesterol levels. Apolipoprotein-B and very low density lipoprotein cholesterol levels were significantly higher in the olanzapine- versus risperidone-treated patients, but there were no significant differences between olanzapine- and typical antipsychotic-treated patients. Treatment groups did not differ significantly in LDL particle size, the prevalence of an "atherogenic" lipid profile, or estimated insulin sensitivity. Although interpretation of this study is limited by the cross-sectional study design, it provides additional insight concerning the relationship between antipsychotic use and plasma lipid parameters in this population.

Background: Prescription monitoring in the United States suggests that oral olanzapine is prescribed in doses that exceed the approved range of 5 to 20 mg/d., Objective: In this double-blind, randomized study, the pharmacokinetics and tolerability of higher-dose (30 or 40 mg/d) olanzapine were examined relative to the highest approved dose (20 mg/d) among non-treatment-resistant patients with psychiatric illnesses., Methods: After a 10-day period in which all patients were stabilized on 20 mg/d olanzapine, 37 patients with schizophrenia, schizoaffective disorder, or bipolar I disorder were randomized to receive treatment with olanzapine 20 mg/d for 20 days (group A, n=12), 30 mg/d for 10 days followed by 40 mg/d for 10 days (group B, n=11), or 40 mg/d for 20 days (group C, n=14). On days 10, 20, and 30, blood samples were collected before dosing and at 1, 2, 5, 6, 10, 14, 18, and 24 hours after dosing. Plasma olanzapine concentrations were assayed using high-performance liquid chromatography with electrochemical detection. Tolerability was assessed by spontaneously reported treatment-emergent adverse events; changes from baseline in vital signs, electrocardiograms, and standard laboratory test values; incidences of categorically defined treatment-emergent akathisia and parkinsonism; and 2-hour standard oral glucose tolerance tests., Results: Of the 53 subjects who entered the study, 16 were excluded (7 because entry criteria were not met, 6 because of subject's decision, and 3 for other reasons). Subjects were primarily men (group A, 75%; group B, 55%; group C, 79%), approximately 40 years old (mean [SD] age: group A, 40.6 [8.6]; group B, 37.9 [8.6]; group C, 39.4 [9.2] years), and black (group A, 83%; group B, 55%; group C, 64% [the remainder were white]). Mean (SD) baseline weight was 84.0 (17.5) kg for group A, 82.1 (12.0) kg for group B, and 100.9 (23.3) kg for group C. By day 20, dose-proportional increases were observed in plasma olanzapine Cmax,ss and AUC. Geometric mean (percent coefficient of variation) values for groups A, B, and C at day 20 were as follows: Cmax,ss 57.8 (40.2), 75.6 (86.7), and 94.1 (50.2) ng/mL, respectively; and AUC: 997 (38.5), 1220 (88.0), and 1630 (53.9) ng . h/mL, respectively. The most frequently reported adverse events were weight gain (group A, 2/12 [17%]; group B, 3/11 [27%]; group C, 2/14 [14%]) and sedation (group A, 3/12 [25%]; group B, 2/11 [18%]; group C, 2/14 [14%]). Mean (SD) weight gain from baseline to end point was 3.5 (2.81) kg for group A, 3.0 (3.15) kg for group B, and 3.1 (2.22) kg for group C. Changes in glucose tolerance, vital signs, or laboratory parameters did not appear to be dose dependent. During double-blind therapy, 7 subjects experienced akathisia (spontaneously reported, n=3 [group C]; categorically defined, n=3 [group B]; both, n=1 [group C]). Of the subjects with categorically defined akathisia, 2 had a history of akathisia and the other had a score of 1 (questionable) on the Barnes Akathisia Scale at baseline. No cases of parkinsonism were observed at any time., Conclusions: Among these subjects with psychiatric illnesses, olanzapine at doses of 30 and 40 mg/d displayed a pharmacokinetic profile consistent with that of 20 mg/d. Higher-dose olanzapine exhibited a tolerance profile similar to that of 20 mg/d; however, akathisia may be more likely to occur at higher doses, particularly in subjects with a history of akathisia.

The aim of this study was to evaluate the effects of melatonin on the inflammatory response and hydroxyproline production in an experimental acute and chronic model of trinitrobenzene sulfonic (TNBS) acid-induced colitis in Wistar rats. In the acute model, melatonin (0.5, 1, and 2 mg/kg, i.p.) was applied 48, 24, and 1 hr prior to the induction of colitis and 24 and 48 hr after; the severity of colitis was less evident in melatonin-treated animals with significant response in the group treated with 2 mg/kg. All doses investigated significantly reduced the myeloperoxidase activity (MPO). In the chronic studies, melatonin (1 and 2 mg/kg, i.p.) was administered daily 24 hr before hapten instillation and for 7 or 21 days after TNBS; melatonin (2 mg/kg) worsened colitis evolution in the 21-day study with a significant increase in MPO activity and tumor necrosis factor-alpha production with respect to TNBS group. Histological slides were in concordance with macroscopic data where areas of extensive necrosis and edema, fibrosis, and absence of regenerated epithelium were observed. Moreover, the hydroxyproline determination, used as indicator of collagen production and fibrosis, also showed a marker increase. The results obtained in this experimental model showed that short-term administration is protective while in the long term it negatively influences evolution of inflammatory colitis; therefore, the immunostimulatory effect of melatonin in some situations when given chronically, such as during inflammatory bowel disease, might lead to negative consequences.

Thirty-six subjects aged 16 years or older judged at risk for a first episode of psychosis within a North American multi-site study of the schizophrenia prodrome [McGlashan et al., Schizophr. Res. (2003); Miller et al., Schizophr. Res. (2003)] performed at levels intermediate to population norms and data reported for schizophrenia samples on a comprehensive neuropsychological exam. In the context of normal intelligence, this intermediate status suggests that, as a group, these subjects are not fully normal in neuropsychological functioning. Conversely, the finding that they do not show the levels of impairment commonly observed in schizophrenia, including within the first episode, suggests that prodromal interventions might conceivably prevent, delay, or lessen the severity of declines associated with first psychotic episodes.

Background: The prodromal phase of schizophrenic disorders has been described prospectively. The present study aimed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo., Methods: This was a double-blind, randomized, parallel-groups, placebo-controlled trial with fixed-flexible dosing conducted at four sites. Sixty patients met prodromal diagnostic criteria, including attenuated psychotic symptoms, as determined by structured interviews. Olanzapine 5-15 mg daily or placebo was prescribed for 8 weeks., Results: In the mixed-effects, repeated-measures analysis, the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant, and post hoc analyses revealed that the olanzapine-placebo difference reached p<.10 by week 6 and p<.05 at week 8. Ratings of extrapyramidal symptoms remained low in each group and were not significantly different. Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients (p<.001)., Conclusions: This short-term analysis suggests olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients. Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo. Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment.

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.

Objectives: To compare endoscopic sclerotherapy, propranolol and distal splenorenal shunt in the prevention of rebleeding esophageal varices and mortality in alcoholic cirrhotics., Methods: Forty-three alcoholic cirrhotics that had bled from esophageal varices were randomized to sclerotherapy (13), shunt (15) or propranolol(15). Outcomes measured were rebleeding from varices and death., Results: There was no significant difference between the three treatment groups in relation to rebleeding rate or death. Continued alcohol consumption did not influence outcome., Conclusions: All three therapies were equally effective in preventing rebleeding from varices.

Muscarinic receptor subtypes in human and rat colon smooth muscle homogenates were characterized with [3H]N-methylscopolamine ([3H]NMS) by ligand binding studies. [3H]NMS saturation experiments show the existence of a homogeneous population of non-interacting binding sites with similar affinity (KD values of 1.38 +/- 0.20 nM in human colon smooth muscle and 1.48 +/- 0.47 nM in rat colon smooth muscle) and with Hill slopes close to unity in both samples of tissue. However, a significant (P less than 0.01) increase in muscarinic receptor density (Bmax) is found in human colon (29.9 +/- 2.9 fmol/mg protein) compared with rat colon (17.2 +/- 1.5 fmol/mg protein). Inhibition of [3H]NMS binding by non-labelled compounds shows the following order in human colon: atropine greater than AF-DX 116 greater than pirenzepine. Whereas in rat colon the rank order obtained is atropine greater than pirenzepine greater than AF-DX 116. Atropine and pirenzepine bind to a homogeneous population of binding sites, although pirenzepine shows higher affinity to bind to the sites present in rat colon (Ki = 1.08 +/- 0.08 microM) than those in human colon (Ki = 1.74 +/- 0.02 microM) (P less than 0.05). Similarly, IC50 values obtained in AF-DX 116 competition experiments were significantly different (P less than 0.01) in human colon (IC50 = 1.69 +/- 0.37 microM) than in rat colon (IC50 = 3.78 +/- 0.75 microM). Unlike atropine and pirenzepine, the inhibition of [3H]NMS binding by AF-DX 116 did not yield a simple mass-action binding curve (nH less than 1, P less than 0.01) suggesting the presence of more than one subtype of muscarinic receptor in both species. Computer analysis of these curves with a two binding site model suggests the presence of two populations of receptor. The apparent Ki1 value for the high affinity binding site is 0.49 +/- 0.07 microM for human colon smooth muscle and 0.33 +/- 0.05 microM for rat colon smooth muscle. The apparent Ki2 for the low affinity binding site is 8.01 +/- 1.0 microM for human samples and 6.07 +/- 1.1 microM for rat samples. These values are close enough to suggest that the first subtype of muscarinic receptor may be considered cardiac (M2) and the second subtype glandular (M3). The relative densities of the receptor subtypes are significantly different for both species. Human colon samples show the major densities of subtype M2, 22.62 +/- 1.11 fmol/mg protein, this represents 75.66 +/- 3.73% of the total receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

At least three pharmacologically different muscarinic receptor subtypes (M1, M2 and M3) have been identified in rat brain. While M1 and M2 subtypes can be directly labelled by selective ligands (3H-pirenzepine and 3H-AF-DX 116, respectively), there are no truly selective ligands for the M3 subtype. In the present study, we have investigated a possible method of studying the pharmacological M3 subtype in rat forebrain using the non-selective labelled antagonist 3H-N-methyl-scopolamine (3H-NMS) in the presence of unlabelled pirenzepine to protect the M1 subtype. The results obtained in kinetic experiments using 3H-NMS in presence of 30.10(-9) M unlabelled pirenzepine (Kon 1.2.10(-8) M-1 m-1, Koff 4.7.10(-2) m-1 and Kd 0.4.10(-9) M) are compatible with the studies carried out in rat pancreatic islets and submaxillary gland which contain predominantly the M3 subtype. We have also performed inhibition experiments with the selective antagonist AF-DX 116. Due to the small proportion of M2 receptors present in rat forebrain, this drug is able to discriminate between M1 and non M1 non M2 receptor subtypes in competition experiments with 3H-NMS versus AF-DX 116 (Ki values 0.28.10(-6) M and 4.3.10(-6) M, respectively). When the competition experiments were performed using 3H-NMS in presence of 30.10(-9) M unlabelled pirenzepine, the Ki value obtained was 3.8.10(-6) M, very close to the value obtained for the non M1 non M2 receptor in competition experiments with 3H-NMS versus AF-DX 116 and in excellent agreement with the affinity of this drug for the glandular M3 subtype. All these data suggest that the approach using the non-selective antagonist 3H-N-methyl-scopolamine in presence of unlabelled pirenzepine allows the study of the pharmacological M3 subtype in rat forebrain.

The binding of different ligands to muscarinic receptors in the central nervous system is regulated by several factors. Among these are the administration of drugs, disease, ontogeny or aging. Studies carried out in rat brains have demonstrated changes in the density of the muscarinic receptors at different times of the day. These changes might be related to variations in the circadian rhythms. In this work we have studied the binding of the [3H]-N-methyl-escopolamine, the agonist carbachol and the antagonist pirenzepine to muscarinic receptors in rat forebrains at 10.00, 14.00, 18.00, 22.00, 02.00 and 06.00 hr. We have observed changes in the density of muscarinic receptors but not changes in affinity to the radioligand. The Bmax values obtained by saturation studies were maximum at 14.00 hr and minimum at 02.00 hr (P less than 0.05 Mann-Whitney's test). Inhibition studies in the presence of the non-selective agonist carbachol and the selective antagonist pirenzepine, at the same time-points, did not show statistically significant changes in the Bmax values. These data indicate that changes in the Bmax values are only observed in the total population of muscarinic receptors and are not due to modifications in the subtypes of muscarinic receptors nor to the different affinity states of agonist binding.

Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescent-antibody assay (IFA), and Western immunoblot were used to test serum samples from 128 dogs for the presence of antibody to Borrelia burgdorferi. Sera included 72 samples from dogs suspected of having Lyme disease, 32 samples from dogs residing in areas in which Lyme disease was not considered endemic, and 24 samples from dogs with clinical and serologic evidence of immune-mediated disease (n = 10), Rocky Mountain spotted fever (n = 5), or leptospirosis (n = 9). Results of Western immunoblotting were used as the standard against which performances of ELISA and IFA were measured. ELISA was significantly more sensitive than IFA (84.8 versus 66.7%), although both tests were equally specific (93.5%). Eight samples that were positive by Western immunoblot were simultaneously negative by ELISA and IFA. Of these eight, four were from dogs suspected of having immune-mediated disease, two were from dogs suspected of having leptospirosis, and two were from dogs suspected of having Lyme disease. These results may indicate that sera from dogs with immune-mediated disease, and to a lesser extent sera from those with leptospirosis, cross-react with B. burgdorferi antigens. Alternatively, Western immunoblot results may not truly reflect Lyme disease status, particularly in the case of dogs with immune-mediated diseases. At present, however, the use of Western immunoblotting as a diagnostic standard for dogs offers the best alternative to a clinical definition of disease.

Thirty-six infants who developed grade III and IV intraventricular hemorrhages during the neonatal period were followed up to determine their developmental quotient. All of these infants had ventriculomegaly and 15 of them required a ventriculoperitoneal (VP) shunt during the neonatal period prior to discharge from Intensive Care Nursery. The mean developmental quotient for the infants with the VP shunt was 67.93. The mean developmental quotient for the infants with ventriculomegaly but no VP shunt was 88.71 (P less than 0.02). Among the nonshunted group of infants, 13 (61.9%) had developmental quotients greater than 85, and among the shunted group 5 infants (33.3%) had developmental quotients greater than 85. Fifty percent of the total group of infants had normal developmental quotients at a mean chronological age of 16.25 +/- 7.5 months (and corrected age 14 months). Infants developing posthemorrhagic hydrocephalus and requiring VP shunts had a poorer developmental outcome compared to those who did not require shunts.

We studied 20 unselected patients admitted to our Intensive Care Unit (ICU) suffering from acute respiratory failure (ARF), who needed mechanical ventilatory support. In all of them we followed a prospective protocol to investigate the value of mouth occlusion pressure (P0.1) as an indicator for weaning. Fifty-two tests were classified into three groups: a need to be reconnected to mechanical ventilation (MV), stable on intermittent mandatory ventilation (IMV), or spontaneous breathing on a T-tube (TT). The results showed that at increased values of P0.1 there were more difficulties in weaning patients from MV. Seventy-eight percent (78%) of the occasions where weaning was successful, values of P0.1 were less than or equal to 4.2 cm H2O, in chronic or non-chronic patients. Eighty-nine percent (89%) of the times when P0.1 values were higher than 4.2 cm H2O the same patients required ventilatory support, total (MV) or partial (IMV). These differences were statistically significant (p less than 0.01). We conclude that the P0.1 is an easily obtained non-invasive parameter, that can contribute along with other more conventional measurements to a superior indication for weaning.

Streptococcus faecalis 31H-1 is a proteolytic transconjugant of strain 31B, that harbors the 38.5 Mdal plasmid which codes for hemolysin in strain X14. It fails to express the hemolytic character in broth due to its proteolytic character. Hemolytic activity can be demonstrated when the proteolytic activity is inhibited by 10(-4) M EDTA. The effect of erythromycin (on the donor cells) and of proteinase K during conjugation suggests that the conjugation system involving the 38.5 Mdal plasmid of S. faecalis strain X14 is sex-pherormone mediated.