Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse.

Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with µ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway.

Ferric sulphate alterations on primary dentin and the adhesive interface.

PURPOSE: The purpose of this study was to test the hypothesis that the pulp medication ferric sulphate (FS) may remain on primary dentin, affecting its microchemical structure and the bond strength of adhesives to primary dentin. MATERIALS AND METHODS: The effects of FS and pre-bonding conditioning (37% phosphoric acid [PA] for 15 s or a self-etching primer, with or without the use of 2% chlorhexidine [CHX]) on FS-treated primary dentin were characterized using optical microscopy with Masson's and Perls' stains, variable-pressure SEM/energy-dispersive x-ray spectroscopy (VP-SEM/EDS), Fourier transform infrared spectroscopy (FT-IR), and x-ray diffraction. Ferric sulphate was applied for 30 s or 1 h for microchemical analysis. The adhesive interface and the bond strength were studied by VP-SEM/EDS and the µTBS test (1 mm2 bars, crosshead speed 0.5 mm/min), respectively. The study groups were: etch-and-rinse (E&R, Excite) adhesive (group 1); FS+E&R (group 2); FS+CHX+E&R (group 3); self-etching (SE, Adper Scotchbond) adhesive (group 4); FS+SE (group 5); FS+CHX+SE (group 6). RESULTS: Ferric sulphate application produced demineralization, gypsum formation, and adsorption of Fe on the dentin surface, and it modified the collagen structure of primary dentin. There were no effects of FS on bond strength of the tested etch-and-rinse adhesive system. FS slightly reduced the bond strength between the primary dentin and the SE adhesive, and the values were not restored by CHX (group 4 = 17.58 ± 5.52 MPa > group 5 = 14.26 ± 7.08 MPa = group 6 = 13.96 ± 4.87 MPa). CONCLUSIONS: Ferric sulphate alters the microchemical structure of primary dentin and can impair the adhesive strength of some self-etching adhesives.

Establishing cut-off values for apolipoprotein B and non-HDL-C according to LDL-C values in a South European population.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) remains the primary target of therapy in most strategies of dyslipidaemia management focused on cardiovascular disease prevention. Different guidelines have identified specific LDL-C cut-off points as targets for therapeutic intervention. Many clinical situations characterised by dyslipidaemia and elevated triglycerides are common in our environment and in overall industrialised countries. Thus, lipid goals based only on LDL-C could misclassify an important percentage of subjects. The objective of the present study was to establish cut-off point values for apoB and non-HDL-C in relation to the identified LDL-C cut-off points for cardiovascular risk in a South European population. METHODS: We performed a cross-sectional study including 1501 subjects (770 women and 731 men) between 18 and 80 years of age. Samples were collected after 12-14 h of fasting. Cholesterol, HDL-C, triglycerides and apoB levels were measured using direct methods. LDL-C was calculated by the Friedewald formula. Non-HDL-C was calculated as total cholesterol minus HDL-C. RESULTS: The Spearman's rank correlations between apoB and LDL-C (r 0.86, p < 0.0001), and between apoB and non-HDL-C (r 0.91, p < 0.0001) were both significant. The proposed cut-off points for apoB, according to LDL-C goals (70, 100, 130 and 160 mg/dl) in our population are 70, 80, 100 and 115 mg/dl respectively. The proposed cut-off values for non-HDL-C are 100, 120, 150 and 190 mg/dl respectively. CONCLUSION: The established LDL-C cut-off values could not be accurate to estimate cardiovascular risk in subjects with mild hypertriglyceridaemia, as frequently occurs in our Mediterranean population. To take into consideration the burden of atherogenic particles and better classify patients at risk we propose cut-off values for apoB or the equivalent for non-HDL-C. Prospective trials including cardiovascular variables are needed to validate our assumption.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

[Discussion groups as an approach to assess knowledge, attitudes and practices of hand hygiene among the adult intensive care unit professionals from a referral hospital]. / Grupos de discusión como abordaje para valorar conocimiento, actitudes y prácticas de higiene de manos en profesionales de la unidad de cuidados intensivos de adultos de un hospital de referencia.

OBJECTIVES: The adherence to hand hygiene practices among the adult Intensive Care Unit (ICU) professionals in this hospital has not improved substantially in the last years, regardless of the theoretical training sessions conducted. A study was made of the knowledge, attitudes, and practices of the ICU personnel in this field. METHODS: Several small discussion groups with ICU staff organised by preventive medicine professionals were scheduled in March 2018. Semi-structured questions on hand hygiene and use of gloves were included. The points discussed were listed into strengths and weaknesses. Knowledge was then assessed using an anonymous questionnaire, after the sessions. RESULTS: Thirteen 60-minute sessions were carried out with 157 participants from all professional categories (82% from ICU, median=11 participants / session). The majority perceived hand hygiene as a priority issue of personal responsibility for patient safety. They identified factors that limit their ability to improve their adherence. Certain habits have more to do with personal preferences than with theoretical knowledge or technical indications. CONCLUSIONS: The discussion groups have helped to make a diagnosis of the situation that will be useful to strengthen those areas of improvement that have been identified. If we aim for a cultural change, and eliminate incorrect habits, it seems more useful to carry out adequate continuing education as part of the daily routine of professionals.

Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia.

We have examined the apo AI - 75 (G/A) and apo AI + 83(MspI +/-) polymorphisms at the APOA1 gene locus for associations with plasma lipid levels and response to an NCEP-I diet in 69 (44 women, 25 men) heterozygotes for familial hypercholesterolemia (FH). Subjects were studied at baseline (after consuming for one month a diet with 35%, fat, 10% saturated, and 300 mg/day cholesterol) and after 3 months of an NCEP-I diet. No gender-related differences for any of the lipid variables examined were found and the data were analyzed for men and women combined. For the apo AI - 75 (G/A) polymorphism, there were 51 G/G and 18 G/A subjects. At baseline, G/A subjects showed significantly lower total cholesterol (p = 0.0036), and LDL-C (p = 0.0023), and apo B (p = 0.0209), than G/G individuals, but no differences were found for HDL-C, triglycerides and VLDL-C values. Following the NCEP-I diet these genotype-related differences remained significant for total and LDL-C. The MspI (-) allele at the apo AI + 83 polymorphism was detected in the heterozygous state in five subjects and its presence was not associated with altered baseline lipids nor with dietary response to the NCEP-I diet. Our results suggest that FH subjects carrying the A allele at the apoAI - 75 (G/A) polymorphism have significantly lower total and LDL-C and apo B baseline levels but respond to a low-fat diet with similar reductions in total and LDL-C when compared with homozygotes for the G allele at this polymorphic site.

Can alprostadil improve liver failure in HIV-infected patients with severe acute viral hepatitis?

Liver failure with hepatic encephalopathy during an acute viral hepatitis carries a very high mortality. Liver transplantation is the usual treatment, but for poor candidates for transplantation only supportive therapy is available. Two patients with HIV infection developed an acute B hepatitis with liver insufficiency and hepatic encephalopathy. After an alprostadil infusion was begun they improved quickly and made a full recovery. This drug merits further investigation.

Hyperuricemia-hyperlipemia association in the absence of obesity and alcohol abuse.

We carried out a study of 43 male asymptomatic subjects with high levels of uric acid but showing no signs of arterial hypertension, obesity or alcohol abuse. Initially, we investigated cholesterol levels, triglycerides in blood serum and the very low density lipoprotein fraction. The results showed asymptomatic hyperuricemia, frequently associated with mixed hyperlipidemia or hypertriglyceridemia. In our cases, however, the association was not connected to exogenous factors such as obesity or alcohol consumption. We also found the very low density lipoprotein fraction to be anomalous compared to the control group, which suggests that the metabolism of this lipoprotein is altered by the aforesaid association.

Renal excretion of urate by hyperuricaemic-hyperlipidemic patients.

We studied the renal urate excretory function in two groups of hyperuricaemic male patients composed of individuals with associated hyperlipidemia and hyperuricaemic-normolipidemic individuals, respectively. Both the hyperlipidemia and the hyperuricaemia were primary inasmuch as none of the patients studied was obese or had an above-normal alcohol intake or blood hypertension. The results obtained show that hyperuricaemic-hyperlipidemic patients have higher serum levels of uric acid and poorer urate excretion as reflected in smaller clearance and fractioned excretion of the metabolite than hyperuricaemic-normolipidemic patients. This, in turn, suggests the occurrence of differences in the extent of the urate handling anomalies between the two groups of patients.

[Familial hypercholesterolemia and plasma Lp(a) levels: 2 cardiovascular risk factors]. / Hipercolesterolemia familiar y niveles plasmáticos de Lp(a): dos factores de riesgo cardiovascular.

OBJECTIVE: Lipoprotein (a) (Lp(a)) is a modified LDL particle in human plasma. Elevated Lp(a) plasma concentration has been associated with increase risk of premature heart disease in most cross-sectional studies. Familial hypercholesterolemia (FH) is a genetic disorder characterized by an elevation of LDL cholesterol (LDL-C) caused by molecular defects in the LDL receptor gene. The aim of our study is to analyze Lp(a) values in a genetic diagnosed FH group without coronary heart disease (CHD) and explain the considerable variation in clinical severity of FH patients. METHOD: We have study plasma lipids and lipoprotein levels in 60 subjects with familial hypercholesterolemia without CHD and in 74 normolipidemic controls without personal history of CHD and dyslipidemia of the Valencia area in Spain. RESULTS: We found differences in total and LDL cholesterol levels and apo B values as expected and also in plasma Lp(a) levels and log transformed values between FH subjects and normolipidemic controls (22.3 mg/dl +/- 19.4 vs 12.5 mg/dl +/- 12.6 p = 0.001 and 1.12 +/- 0.53 vs. 0.84 +/- 0.58 p = 0.008). The percentage of FH subjects with a cut point Lp(a) value > 20 mg/dl is significantly elevated in this group (47% vs 21% p = 0.002). Because of family relationships within the entire study population we also have compared 23 FH probands with the normolipidemic controls. Again the same results have been obtained (Lp(a) levels of 23.21 mg/dl +/- 19.2 vs 12.54 mg/dl +/- 12.63 p = 0.019 and log Lp(a) values of 1.19 +/- 0.42 vs 0.84 +/- 0.58 p = 0.01). CONCLUSION: Our results indicate that FH subjects will have a more cardiovascular risk due to the potentiation of hypercholesterolemia and elevated Lp(a) values, indicating the addition effects of two different locus implicated in premature coronary heart disease and could explain the considerable variation in clinical severity of FH.

[Plasma lipoprotein (a) values in familial defective ligand apo B 100 in a South European population]. / Estudio de los valores plasmáticos de Lp(a) en el defecto familiar de unión de la apo B 100 en una población mediterránea del sur de Europa.

AIMS: 1) to study lipoprotein (a) (Lp(a)) plasma values in subjects with familial ligand-defective apo B 100 (FDB). METHODS: We studied 19 heterozygous FDB subjects (8 males) from 12 families, carriers of R3500Q mutation on apo B gene and 90 controls (34 males). The genetic diagnosis was established with PCR-SSCP analysis and automatic sequencing. In all subjects plasma lipids, apolipoprotein B and Lp(a) levels were determined with standard procedures. RESULTS: Subjects carriers of R3500Q mutation on apo B gene have significantly higher plasma Lp(a) and log transformed Lp(a) values and prevalence of Lp(a) > 30 cut point for coronary heart disease than controls. CONCLUSIONS: Subjects with FDB showed higher Lp(a) plasma values than controls, although the mechanism and the clinical consequences of these result are not known.

[Computerized graph at the ICU]. / Una gráfica informatizada en U.C.I.

The authors describe the installation and application of a computerized management system for clinical information in an intensive care-resuscitation unit. The authors analyze the installation of the hardware and software as well as the professional preparation provided to personnel. They review the different sections which comprise this program, describing the use(s) of each. They conclude by analyzing the advantages and disadvantages detected over the two years during which they have employed this program, highlighting the qualities derived from its daily use which make it a tool that facilitates daily nursing tasks. This report was presented at "Inforenf 2000", "Inforenf 2001" and "Seeiuc 2000".

[Effect of gender and obesity on postprandial lipemia in non-diabetic normolipidemic subjects and subjects with familial combined hyperlipidemia]. / Efecto del género y de la obesidad en la lipemia posprandial en sujetos sanos normolipidémicos no diabéticos y sujetos con hiperlipemia familiar combinada.

INTRODUCTION: A new method based on self-measurement of diurnal capillary triglycerides (TG) facilitates the study of postprandial lipemia (PL). The objectives of our study are: to evaluate the effect of gender and obesity on PL measured by self-determination of diurnal capillary TG with Accutrend GCT in normolipidemic non-diabetic subjects and subjects with familial combined hyperlipidemia (FCH). MATERIAL AND METHODS: We studied 23 FCH subjects (10 males) and 45 normolipidemic non-diabetic subjects (29 males). All subjects self-determine 3 diurnal capillary TG profiles during a week. RESULTS: In normolipidemic non diabetic subjects significantly higher diurnal TG profiles and area under the curve of TG (AUCTGc) (25.25 +/-9.09 vs 19.71 +/- 6.16 mmolh/l) were found in males compared to females. In FCH subjects these differences were not found and the AUCTGc correlated with BMI (r = 0.510, p < 0.05) and waist circumference (r = 0.453, p < 0.05). Obese subjects (BMI >or= 27 kg/m2) showed diurnal TG profiles and AUCTGc significantly higher than the non-obese. DISCUSSION: Normolipidemic non diabetic females showed a lower PL compared to males, probably due to the effect of estrogens in PL metabolism. Obesity negatively influences PL in normolipidemic non diabetic subjects and subjects with FCH.

International conference on the healthy effect of virgin olive oil.

1. Ageing represents a great concern in developed countries because the number of people involved and the pathologies related with it, like atherosclerosis, morbus Parkinson, Alzheimer's disease, vascular dementia, cognitive decline, diabetes and cancer. 2. Epidemiological studies suggest that a Mediterranean diet (which is rich in virgin olive oil) decreases the risk of cardiovascular disease. 3. The Mediterranean diet, rich in virgin olive oil, improves the major risk factors for cardiovascular disease, such as the lipoprotein profile, blood pressure, glucose metabolism and antithrombotic profile. Endothelial function, inflammation and oxidative stress are also positively modulated. Some of these effects are attributed to minor components of virgin olive oil. Therefore, the definition of the Mediterranean diet should include virgin olive oil. 4. Different observational studies conducted in humans have shown that the intake of monounsaturated fat may be protective against age-related cognitive decline and Alzheimer's disease. 5. Microconstituents from virgin olive oil are bioavailable in humans and have shown antioxidant properties and capacity to improve endothelial function. Furthermore they are also able to modify the haemostasis, showing antithrombotic properties. 6. In countries where the populations fulfilled a typical Mediterranean diet, such as Spain, Greece and Italy, where virgin olive oil is the principal source of fat, cancer incidence rates are lower than in northern European countries. 7. The protective effect of virgin olive oil can be most important in the first decades of life, which suggests that the dietetic benefit of virgin olive oil intake should be initiated before puberty, and maintained through life. 8. The more recent studies consistently support that the Mediterranean diet, based in virgin olive oil, is compatible with a healthier ageing and increased longevity. However, despite the significant advances of the recent years, the final proof about the specific mechanisms and contributing role of the different components of virgin olive oil to its beneficial effects requires further investigations.

[Visceral leishmaniasis: a comparative study of patients with and without human immunodeficiency virus infection]. / Leishmaniasis visceral: estudio comparativo de pacientes con y sin infección por el virus de la inmunodeficiencia humana.

BACKGROUND: The changes that HIV coinfection can induce in clinical symptoms, response to treatment and prognosis of visceral Leishmaniasis (VL) are not well known. METHOD: We retrospectively describe the characteristics of VL in patients with and without HIV infection, between 1988-1998. RESULTS: Fifty episodes of VL were diagnosed in 40 patients. Nineteen (47.5%) were HIV coinfected, 57.8% of them have had an aids defining illness, and the median of CD4+ lymphocytes was 50/mm3. Clinical and laboratory data were similar to patients non HIV infected, except for lower levels of LDH (437 vs 578 U/ml; p = 0.02) and total lymphocytes (665 vs 1.500/mm3; p = 0.004) and higher levels of hemoglobin (9.8 vs 8.7 gr/dl; p = 0.01) and ESR (85 vs 44 mm; p = 0.01). The first episode of VL was diagnosed in 87.5% patients through bone marrow aspirate, and the other cases were diagnosed by biopsies of gum (2), lymph node (1) or liver (1). One patient was diagnosed clinically: he had a positive serology and a good response to antileishmanial therapy. Treatment failed in nine patients (22.5%), 7 HIV-coinfected. Eight patients died (20%), 6 HIV-coinfected. Five deaths were directly attributed to VL. Six coinfected patients (31.5%) relapsed and only one (4.7%) in the other group. CONCLUSIONS: We did not find major differences in clinical manifestations or laboratory data between the two groups. Biopsies of several tissues can be particularly helpful for diagnosis in immunocompromised patients with negative bone marrow aspirates. Failures, mortality and relapses are more common in HIV infected patients. VL coinfection usually affects HIV infected patients when they develop severe immunodepression.

[Outbreak of meningitis caused by echovirus type 30]. / Brote epidémico de meningitis por echovirus tipo 30.

OBJECTIVES: In the cold months of 1994-1995, we detected in our hospital an epidemic outbreak of acute enteroviral meningitis caused by echovirus type 30 (Echo 30). Until now, these outbreaks of viral epidemics had not been detected in Spain. PATIENTS AND METHODS: We reviewed retrospectively 46 clinical histories of patients who were admitted to our hospital between September 1994 and January 1995 with the diagnosis of acute lymphocytic meningitis, analyzing the clinical outbreak, epidemiological and laboratory characteristics, and how the outbreak spread. RESULTS: Regarding the patients, there was a prevalence in males, with an average age of 6 years and a range of 2 to 13 years of age. The most constant symptom was severe frontal headache, with signs of meningitis in only 50% of the cases. In the CSF, we found a predominance of PMN in the differential cell count in 63% of the cases, with the time of evolution before spinal puncture less than 24 hours in the majority of the patients. Viral cultures were performed on CSF, stool and throat scrapings in 16 patients with Echo 30 being isolated in 15 cases, which suggests 32.6% of the total cases. CONCLUSIONS: We detected in our environment an epidemic outbreak of viral meningitis caused by an agent not found previously in Spain, which presented epidemiological, clinical and laboratory characteristics similar to those reported in the literature. Its appearance during the cold months contrasts to what normally occurs.

Plasma Lp(a) values in familial hypercholesterolemia and its relation to coronary heart disease.

BACKGROUND AND AIM: To analyze plasma Lp(a) levels and examine different risk factors and coronary heart disease (CHD) in a sample of genetically diagnosed familial hypercholesterolemia (FH) patients. METHODS AND RESULTS: Ninety heterozygous FH patients and 41 non-FH relatives were enrolled in a study to evaluate their plasma and lipoprotein cholesterol, as well as their triglyceride and Lp(a) levels. We found no differences in plasma Lp(a) levels and log transformed values between 90 FH subjects and their 41 unaffected relatives (22.3 mg/dl +/- 19.4 vs 17.7 mg/dl +/- 21.3 and 1.12 +/- 0.5 vs 0.96 +/- 0.54) nor between null allele and defective allele FH subjects (log Lp (a) levels 2.013 +/- 0.282 vs 1.959 +/- 0.151). FH CHD+ were significantly older, and had higher mean systolic and diastolic blood pressure and higher mean plasma triglyceride levels than FH CHD-. No differences in mean and log transformed Lp(a) plasma concentrations were found. CONCLUSIONS: Plasma Lp(a) levels are not related to LDL receptor status and class mutations, nor to the presence of CHD in FH patients.