A Metabolic Intravascular Platform to Study FDG Uptake in Vascular Injury.

PURPOSE: Metabolic alterations underlie many pathophysiological conditions, and their understanding is critical for the development of novel therapies. Although the assessment of metabolic changes in vivo has been historically challenging, recent developments in molecular imaging have allowed us to study novel metabolic research concepts directly in the living subject, bringing us closer to patients. However, in many instances, there is need for sensors that are in close proximity to the organ under investigation, for example to study vascular metabolism. METHODS: In this study, we developed and validated a metabolic detection platform directly in the living subject under an inflammatory condition. The signal collected by a scintillating fiber is amplified using a photomultiplier tube and decodified by an in-house tunable analysis platform. For in vivo testing, we based our experiments on the metabolic characteristics of macrophages, cells closely linked to inflammation and avid for glucose and its analog 18F-fluorodeoxyglucose (18F-FDG). The sensor was validated in New Zealand rabbits, in which inflammation was induced by either a) high cholesterol (HC) diet for 16 weeks or b) vascular balloon endothelial denudation followed by HC diet. RESULTS: There was no difference in weight, hemodynamics, blood pressure, or heart rate between the groups. Vascular inflammation was detected by the metabolic sensor (Inflammation: 0.60 ± 0.03 AU vs. control: 0.48 ± 0.03 AU, p = 0.01), even though no significant inflammation/atherosclerosis was detected by intravascular ultrasound, underscoring the high sensitivity of the system. These findings were confirmed by the presence of macrophages on ex vivo aortic tissue staining. CONCLUSION: In this study, we validated a tunable very sensitive metabolic sensor platform that can be used for the detection of vascular metabolism, such as inflammation. This sensor can be used not only for the detection of macrophage activity but, with alternative probes, it could allow the detection of other pathophysiological processes.

Interactions Between the Nematode Heterorhabditis amazonensis JPM4 and the Predator Macrolophus basicornis: Two Natural Enemies of Tuta absoluta Native to South America.

Entomopathogenic nematodes (EPNs) and predatory mirids are among the most effective natural enemies for the control of Tuta absoluta, a key pest of tomato worldwide. In the case of South America, the native EPN Heterorhabditis amazonensis and the predator Macrolophus basicornis (Stal) coexist in tomato. The intraguild interactions of two ENPs, H. amazonensis JPM4 and the widely used Steinernema carpocapsae, with the predator M. basicornis, were studied in laboratory setups with the objective of evaluating the potential interactions between them. We hypothesized that the two natural enemies do not interact negatively. The first nymphal stage of the predator was not affected when exposed to tomato leaves directly sprayed with both EPNs, which we attributed to the small size of its stylet. Individuals treated with H. amazonensis JPM4 had low mortality rates in all developmental stages with a maximum of 1.3%. Mortality was higher when the predator was exposed to S. carpocapsae (28% for adults) and correlated positively with increasing developmental stages. In prey choice tests between larvae infected with H. amazonensis and uninfected larvae, M. basicornis fed indistinctively showing no clear preference. When presented with choice larvae infected with S. carpocapsae, the consumption of healthy larvae was higher. In a no-choice prey acceptance experiment, M. basicornis preyed on both healthy and infected larvae with no difference in larvae consumed. Predators that had fed from infected larvae did not exhibit signs of nematode infection and survived. Our results indicate that the South American native H. amazonensis JPM4 and M. basicornis do not show a negative interaction and are promising candidates for combined use in T. absoluta biological control.

Update in Infectious Diseases 2019.

The IX Course of Antimicrobials and Infectious Diseases update included a review of the main issues in clinical microbiology, epidemiology and clinical aspects for a current approach of infectious pathology. The present introduction summarizes about the most important meetings related to infectious diseases during 2018 (ECCMID, IAS, ASM and ID Week). In addition, the course provides a practical information to focus on nosocomial infection models, with immunosuppressed patients or complex multidrug-resistant pathogens. The closing lecture of this year reviewed the infection during donation process.

Spatial and temporal variations in Spain in the standardised ratio of in-hospital mortality due to colorectal cancer, 2008-2014.

BACKGROUND: Colorectal cancer (CRC) is the second cause of tumour mortality in Spain and Europe. To date, no studies have been conducted in Spain to evaluate the spatial and temporal distribution of the excess risk of death during hospitalisation for CRC. METHODS: A cohort was constructed of all episodes of hospitalisation in Spain due to CRC (codes 153 and 154 of the International Classification of Diseases, 9th edition, Clinical Modification) during the period 2008-2014, based on the minimum basic data set published by the Ministry of Health. Mortality ratios were calculated per region for each of the years analyzed (spatial or cross-sectional analysis) and during the overall study period, for each region independently (temporal or longitudinal analysis). In the first of these analyses, particular note was taken of the regions and years in which the limits of two and three standard deviations were exceeded. RESULTS: Two hundred and fifty eight thousand, nine hundred and twenty seven episodes of CRC were analysed. The patients were predominantly male (60.6%), with an average hospital stay of 13.16 days. Half underwent surgery during admission and on average presented more than six diagnoses at discharge. The spatial analysis revealed mortality ratios that deviated by at least three standard deviations in the following regions: Islas Canarias, Asturias, Valencia, Extremadura, País Vasco and Andalucía. The longitudinal analysis showed that most regions presented one or more years when CRC mortality was at least 15% higher than expected during the period; outstanding in this respect were Asturias, Navarra and La Rioja, where this excess risk was detected in at least 2 years. CONCLUSIONS: Geographic and temporal patterns of the distribution of the excess risk of mortality from CRC in Spain are described using SMRs. We conclude that during the study period, the geographic pattern of mortality in Spain did not coincide with the excess risk of mortality calculated using the SMR method described by Jarman and Foster. This method of risk estimation can be a useful tool for the study of mortality risk and its spatial variations.

Influencia de variables psicológicas en pacientes obesos mórbidos operados con cirugía bariátrica tras 24 meses de evolución / Influence of psychological variables in morbidly obese patients undergoing bariatric surgery after 24 months of evolution

Introducción: El tratamiento de la obesidad mórbida mediante la cirugía bariátrica es más efectivo que las opciones no quirúrgicas. Las tasas de fracaso o recaída oscilan entre el 20 y el 30%. El estudio pretende analizar la influencia de determinadas variables psicológicas (autoestima, apoyo social, estrategias de afrontamiento y personalidad) en el mantenimiento de la pérdida de peso de los pacientes después de la cirugía bariátrica. Métodos: Se realizó un estudio de cohorte compuesta por 64 pacientes intervenidos mediante cirugía bariátrica con 24 meses de seguimiento. Al final del periodo, los pacientes fueron divididos en 2subcohortes según fueran éxitos o fracasos. Se consideró éxito o evolución favorable cuando el valor del porcentaje de sobrepeso perdido era 50 o superior. Resultados: No se observaron diferencias estadísticamente significativas entre los 2 grupos en ninguna variable estudiada. Todos los pacientes tuvieron alta la autoestima (87,3 los que fracasan y 88,1 los que tienen éxito) y el apoyo social (90,2 frente a 90,9). Los pacientes que tuvieron éxito presentaron puntuaciones más altas para la reestructuración cognitiva (57,1) y eran más introvertidos (47,1); mientras que los que fracasaron anotaron más alto en pensamiento desiderativo (65,7) y eran más propensos a la agresión (50,7) y el neuroticismo (51,7). Conclusiones: Una alta autoestima y un alto apoyo social no garantizan el éxito del tratamiento. Los grupos difieren en la forma en que hicieron frente a la obesidad, pero los datos obtenidos no justifican la evolución del peso. En ausencia de psicopatología, la variación de los rasgos de personalidad entre los grupos de pacientes es insuficiente para predecir los resultados (AU)

Background: Bariatric surgery is considered a more effective means of achieving weight loss than non-surgical options in morbid obesity. Rates of failure or relapse range from 20 to 30%. The study aims to analyse the influence of psychological variables (self-esteem, social support, coping strategies and personality) in the maintenance of weight loss after bariatric surgery. Methods: A cohort study was conducted involving 64 patients undergoing bariatric surgery for 24 months. At the end of the follow-up period, patients were divided into 2 sub-cohorts classified as successes or failures. Success or favorable development was considered when the value of percent excess weight loss was 50 or higher. Results: No statistically significant differences were observed between the 2 groups in any variable studied. All patients had high self-esteem (87,3 those who failed and 88,1 those who are successful) and social support (90,2 and 90,9). Patients who succeed presented higher scores for cognitive restructuring (57,1) and were more introverted (47,1), while those who failed scored more highly in desiderative thinking (65,7) and were more prone to aggression (50,7) and neuroticism (51,7). Conclusions: High self-esteem and social support does not guarantee successful treatment. The groups differed in how they coped with obesity but the data obtained do not justify the weight evolution. In the absence of psychopathology, personality trait variability between patients is insufficient to predict the results (AU)

Influence of psychological variables in morbidly obese patients undergoing bariatric surgery after 24 months of evolution. / Influencia de variables psicológicas en pacientes obesos mórbidos operados con cirugía bariátrica tras 24 meses de evolución.

BACKGROUND: Bariatric surgery is considered a more effective means of achieving weight loss than non-surgical options in morbid obesity. Rates of failure or relapse range from 20 to 30%. The study aims to analyse the influence of psychological variables (self-esteem, social support, coping strategies and personality) in the maintenance of weight loss after bariatric surgery. METHODS: A cohort study was conducted involving 64 patients undergoing bariatric surgery for 24 months. At the end of the follow-up period, patients were divided into 2sub-cohorts classified as successes or failures. Success or favorable development was considered when the value of percent excess weight loss was 50 or higher. RESULTS: No statistically significant differences were observed between the 2groups in any variable studied. All patients had high self-esteem (87,3 those who failed and 88,1 those who are successful) and social support (90,2 and 90,9). Patients who succeed presented higher scores for cognitive restructuring (57,1) and were more introverted (47,1), while those who failed scored more highly in desiderative thinking (65,7) and were more prone to aggression (50,7) and neuroticism (51,7). CONCLUSIONS: High self-esteem and social support does not guarantee successful treatment. The groups differed in how they coped with obesity but the data obtained do not justify the weight evolution. In the absence of psychopathology, personality trait variability between patients is insufficient to predict the results.

Agricultural management systems affect the green lacewing community (Neuroptera: Chrysopidae) in olive orchards in southern Spain.

Green lacewings are generalist predators whose conservation is important for pest control in olive orchards (Olea europaea L.) Sustainable farming practices, as opposed to conventional management techniques, are believed to foster the presence of natural enemies. This study therefore aims to analyze the effect of 1) herbicidal weed cover removal and insecticide applications, and 2) the general management systems used in the olive orchards of southern Spain on chrysopid assemblages and abundance. Green lacewing adults and larvae were collected from olive orchards under conventional, integrated, and organic management systems. In addition, chemical analyses of residues were carried out to determine the presence of insecticidal and herbicidal residues. Eight adult species and three genera of larvae were identified. No rare species were captured from the most intensively farmed orchard, which therefore recorded the most limited chrysopid diversity with a very marked dominance of Chrysoperla carnea s.l.. No effect of dimethoate treatments on Chrysoperla larvae or C. carnea s.l. adults was observed. However, the presence of insecticide residues was associated with the depletion of Dichochrysa larvae. The absence of herbicide treatments favored C. carnea s.l. adult presence on olive trees while larval abundance decreased. Dichochrysa larvae were more abundant when weed cover received no treatment. In relation to the management systems studied, no difference in Chrysoperla larval abundance was observed between conventional and organic orchards. However, Dichochrysa larvae were more abundant in orchards under organic management.

Circulating humanin levels are associated with preserved coronary endothelial function.

Humanin is a small endogenous antiapoptotic peptide, originally identified as protective against Alzheimer's disease, but subsequently also found on human endothelium as well as carotid artery plaques. Endothelial dysfunction is a precursor to the development of atherosclerotic plaques, which are characterized by a highly proinflammatory, reactive oxygen species, and apoptotic milieu. Previous animal studies demonstrated that humanin administration may improve endothelial function. Thus the aim of this study was to test the hypothesis that patients with coronary endothelial dysfunction have reduced systemic levels of humanin. Forty patients undergoing coronary angiography and endothelial function testing were included and subsequently divided into two groups based on coronary blood flow (CBF) response to intracoronary acetylcholine (normal ≥ 50% increase from baseline, n = 20 each). Aortic plasma samples were obtained at the time of catheterization for the analysis of humanin levels and traditional biomarkers of atherosclerosis including C-reactive protein, Lp-Pla(2), and homocysteine. Baseline characteristics were similar in both groups. Patients with coronary endothelial dysfunction (change in CBF = -33 ± 25%) had significantly lower humanin levels (1.3 ± 1.1 vs. 2.2 ± 1.5 ng/ml, P = 0.03) compared with those with normal coronary endothelial function (change in CBF = 194 ± 157%). There was a significant and positive correlation between improved CBF and humanin levels (P = 0.0091) not seen with changes in coronary flow reserve (P = 0.76). C-reactive protein, Lp-Pla(2), and homocysteine were not associated with humanin levels. Thus we observed that preserved human coronary endothelial function is uniquely associated with higher systemic humanin levels, introducing a potential diagnostic and/or therapeutic target for patients with coronary endothelial function.

Inadequate prenatal care and maternal country of birth: a retrospective study of southeast Spain.

OBJECTIVE: To quantify the association between the maternal country of birth and inadequacy in the use of prenatal care, and to identify factors that might explain this association. STUDY DESIGN: A retrospective case series was carried out in a public hospital in southern Spain, including 6873 women who delivered between 2005 and 2007. The maternal country of birth was categorised into four regional groups: Spain, Maghreb (north-west Africa), Eastern Europe and Others (non-Spain), while the use of prenatal care was quantified according to a modified Kotelchuck index: APNCU-1M and APNCU 2M. The effect of country of birth on inadequate prenatal care was analysed using a multiple logistic regression model designed to accommodate factors such as age, parity, previous miscarriages, and pre-gestational and gestational risks. Likelihood ratio tests were performed to assess any interactions. RESULTS: A significant association was found between maternal country of birth and inadequate prenatal care regardless of the index used. Under APNCU 1-M the strength of association was strongest for Eastern European origin (odds ratio (OR) 6.17, 95% confidence interval (CI) 5.2-7.32), followed by the Maghreb (OR: 5.58, 95% CI: 4.69-6.64). These associations remained virtually unchanged after adjusting for potential confounders. Interactions were observed between age and parity, with the highest risk of inadequacy seen among the Eastern European childbearing women over 34 years of age having 1-2 previous children (OR: 7.63, 95% CI: 3.65-15.92). CONCLUSION: Prenatal health care initiatives would benefit from the study of a larger number of variables to address the differences between different groups of women. We recommend the widespread use of standardised indices for the study of prenatal care utilisation.

Role of oxidative stress in hypoxia preconditioning of cells transplanted to the myocardium: a molecular imaging study.

AIM: Cell-based therapies are a potential therapeutic alternative for the treatment of coronary artery disease (CAD). However, transplanted cells undergo significant death in the living subject. Hypoxic preconditioning (HPC) is a potential intervention to increase transplanted cell survival. However, the biological mechanisms of this benefit remain unclear. We hypothesize that the beneficial effect of HPC on stem cell survival is in part due to preservation of oxidant status, an effect that will be monitored using state-of-the-art molecular imaging. METHODS: H9c2 rat cardiomyoblasts expressing the construct CMV-firefly luciferase (h9c2-fluc), with and without HPC, were exposed to hypoxia, and oxidative stress and cell survival were measured. Subsequently, H9c2-fluc cells, with and without HPC, were injected into the myocardium of rats and cell survival was monitored daily with Bioluminescence (BLI) using a CCD camera. RESULTS: Compared to controls, cells exposed to hypoxia had increased amount of reactive oxygen species (ROS, control: 14.1±0.9 vs. hypoxia: 19.5 ± 2.0 RFU/µg protein, P=0.02) and decreased cell survival (control: 0.29 ± 0.005 vs. hypoxia: 0.24 ± 0.005 OD, P<0.001). HPC treatment decreased the amount of hypoxia-induced ROS (HPC: 11.5 ± 0.7RFU/µg protein, P=0.002 vs. hypoxia and P=0.11 vs. control), associated with improved survival (HPC: 0.27 ± 0.004OD/µg protein, P=0.002 vs. hypoxia and P=0.005 vs. control). Most importantly, compared to un-conditioned cells, HPC-cells had increased cell survival after transplantation to the myocardium (C: 34.7 ± 6.7% vs. HPC: 83.4 ± 17.5% at day 5 compared to day 1, P=0.01). CONCLUSION: The beneficial effect of HPC is in part due to preservation of oxidant status. Molecular imaging can assess changes in cell survival in the living subject and has the potential to be applied clinically.

[Evaluation of bone mineral density, bone turnover markers, the OPG/RANKL system and sTNF-RI in Crohn's disease]. / Valoración de la densidad mineral ósea, marcadores de remodelado óseo, el sistema OPG/RANKL y el sTNF-RI en la enfermedad de Crohn.

INTRODUCTION: Patients with Crohn's disease are at risk of developing osteoporosis, a disease in which the inflammatory process seems to be gaining importance. We performed a cross-sectional study to evaluate bone metabolism, osteoclastogenic factors [receptor activator of NF-kB ligand (RANK-L) and osteoprotegerin (OPG)] and soluble tumor necrosis factor-α receptor I (sTNF-RI) in patients with Crohn's disease and to correlate the findings with the degree of disease activity. METHOD: Sixty-four patients with Crohn's disease from the province of Granada (Spain) were included in this study. Bone mineral density (BMD) was studied through dual X-ray absorptiometry. Immunoassay was used to assess markers of bone formation [bone alkaline phosphatase (bALP) and osteocalcin (OC)] and bone resorption [tartrate resistant acid phosphatase (TRAP) and carboxyterminal telopeptide of type I procollagen (CTX)] as well as RANKL, OPG and sTNF-RI. RESULTS: The percentage of patients with a Z-score ≤-2 in the femoral neck or lumbar spine was 20.3% and was higher in patients with active disease, although this difference was not significant. This percentage was only higher in patients receiving corticosteroids (11.1 vs. 9.1%; P=.001). Patients with the highest disease activity had higher TRAP levels. No significant differences were found in BMD but significant differences were found in TRAP levels with respect to C-reactive protein concentrations. No association was found between levels of OPG, RANKL and sTNF-RI and BMD or disease activity. CONCLUSIONS: A substantial proportion of our patients had low BMD. Levels of bone turnover markers suggested higher bone resorption, possibly in relation to disease activity, without a compensatory increase in bone formation.

Valoración de la densidad mineral ósea, marcadores de remodelado óseo, el sistema OPG/RANKL y el sTNF-RI en la enfermedad de Crohn / Evaluation of bone mineral density, BONE TURNOVER MARKERS, the OPG/RANKL system and sTNF-RI in Crohn's disease

IntroducciónLos enfermos de Crohn se encuentran en riesgo de desarrollar osteoporosis, en la que el proceso inflamatorio parece tener una importancia creciente. Presentamos un estudio transversal con el fin de valorar la situación del metabolismo óseo y los factores de osteoclastogénesis (ligando del receptor activador del NFκB -RANKL- y la osteoprotegerina -OPG-), además del receptor soluble del TNF-α tipo I (sTNF-RI) en enfermos de Crohn, comparando según el grado de actividad de la enfermedad.MétodoSe determinó en 64 enfermos de Crohn de la provincia de Granada la densidad mineral ósea (DMO) mediante absorciometría dual por rayos X, y los marcadores de formación (fosfatasa alcalina ósea –bALP- y osteocalcina –OC-) y resorción ósea (fosfatasa ácida tartrato resistente –TRAP- y telopéptido carboxiterminal del procolágeno tipo I –CTX-), así como el RANKL, la OPG y el sTNF-RI, mediante inmunoensayo.ResultadosEl porcentaje de pacientes con Z-score ≤-2 en CF o CL fue del 20,3%, siendo mayor en aquellos con enfermedad activa, aunque no de forma significativa. Este porcentaje fue solamente mayor en aquellos pacientes que tomaban corticoides (11,1 vs. 9,1%; p=0,001). Los enfermos más activos presentaron niveles de TRAP más elevados, sin encontrar diferencias significativas en cuanto a la DMO. Sí las hubo con relación a los niveles de TRAP con respecto a los niveles de proteína C reactiva. No se encontró relación entre los niveles de OPG, RANKL y sTNF-RI, y la DMO o la actividad de la enfermedad.ConclusionesLa prevalencia de una DMO entre nuestros pacientes fue alta. Los resultados con respecto a los marcadores de recambio óseo sugieren que resorción ósea estaría incrementada, posiblemente en relación con la actividad de la enfermedad, sin un aumento compensatorio de la formación ósea (AU)

IntroductionPatients with Crohn's disease are at risk of developing osteoporosis, a disease in which the inflammatory process seems to be gaining importance. We performed a cross-sectional study to evaluate bone metabolism, osteoclastogenic factors [receptor activator of NF-kB ligand (RANK-L) and osteoprotegerin (OPG)] and soluble tumor necrosis factor-α receptor I (sTNF-RI) in patients with Crohn's disease and to correlate the findings with the degree of disease activity.MethodSixty-four patients with Crohn's disease from the province of Granada (Spain) were included in this study. Bone mineral density (BMD) was studied through dual X-ray absorptiometry. Immunoassay was used to assess markers of bone formation [bone alkaline phosphatase (bALP) and osteocalcin (OC)] and bone resorption [tartrate resistant acid phosphatase (TRAP) and carboxyterminal telopeptide of type I procollagen (CTX)] as well as RANKL, OPG and sTNF-RI.ResultsThe percentage of patients with a Z-score ≤-2 in the femoral neck or lumbar spine was 20.3% and was higher in patients with active disease, although this difference was not significant. This percentage was only higher in patients receiving corticosteroids (11.1 vs. 9.1%; P=.001). Patients with the highest disease activity had higher TRAP levels. No significant differences were found in BMD but significant differences were found in TRAP levels with respect to C-reactive protein concentrations. No association was found between levels of OPG, RANKL and sTNF-RI and BMD or disease activity.ConclusionsA substantial proportion of our patients had low BMD. Levels of bone turnover markers suggested higher bone resorption, possibly in relation to disease activity, without a compensatory increase in bone formation (AU)

Indirect imaging of cardiac-specific transgene expression using a bidirectional two-step transcriptional amplification strategy.

Transcriptional targeting for cardiac gene therapy is limited by the relatively weak activity of most cardiac-specific promoters. We have developed a bidirectional plasmid vector, which uses a two-step transcriptional amplification (TSTA) strategy to enhance the expression of two optical reporter genes, firefly luciferase (fluc) and Renilla luciferase (hrluc), driven by the cardiac troponin T (cTnT) promoter. The vector was characterized in vitro and in living mice using luminometry and bioluminescence imaging to assess its ability to mediate strong, correlated reporter gene expression in a cardiac cell line and the myocardium, while minimizing expression in non-cardiac cell lines and the liver. In vitro, the TSTA system significantly enhanced cTnT-mediated reporter gene expression with moderate preservation of cardiac specificity. After intramyocardial and hydrodynamic tail vein delivery of an hrluc-enhanced variant of the vector, long-term fluc expression was observed in the heart, but not in the liver. In both the cardiac cell line and the myocardium, fluc expression correlated well with hrluc expression. These results show the vector's ability to effectively amplify and couple transgene expression in a cardiac-specific manner. Further replacement of either reporter gene with a therapeutic gene should allow non-invasive imaging of targeted gene therapy in living subjects.

Medicinal plants in the Mediterranean area: synthesis of the results of the project Rubia.

AIM OF STUDY: Within the scope of the European project RUBIA (ICA3-2002-10023), research has been performed on the traditional use and handling of plant species in several Mediterranean countries, Albania, Algeria, Cyprus, Egypt, Italy, Morocco, and Spain. This paper synthesises the chief results related to the medicinal utilization of those plants. MATERIAL AND METHODS: The information has been gathered by means of semi-structured interviews (1256) and techniques of participant observation with 803 informants. In each of the participating countries the study areas were selected by means of uniform criteria defined at the beginning of the study. RESULTS AND CONCLUSIONS: A total of 985 species have been catalogued, of which 406 have medicinal use. This work constitutes the first comparative study performed with ethnobotanical data gathered by a coordinated methodology in the Mediterranean area. An exhaustive list is provided for the species catalogued, indicating the regions where each plant was mentioned. ETHNOPHARMACOLOGICAL RELEVANCE: This information underlines the ethnobotanical richness of the region and the need to broaden this study to other areas of the Mediterranean. Furthermore, this constitutes a base for future phytochemical and pharmacological studies which could lead to new therapeutic products.

Spontaneous bilateral femoral neck fracture due to osteomalacia.

An 85-year-old woman presented with spontaneous and simultaneous displaced bilateral fracture of the femoral neck. She suffered from nutritional osteomalacia and had had poor exposure to sunlight. Both hips were replaced at the same time by partial hip arthroplasty. (Hip International 2004; 14: 55-7).

Renal blood flow in hypercholesterolemic pigs is increased by chronic antioxidant treatment.

Oxygen radical species can influence vascular tone, and antioxidants may have hemodynamic and vascular effects. To date, the vascular effects of chronic intervention with a combination of antioxidant vitamins E and C on renal blood flow (RBF) in hypercholesterolemia (which increases oxidative stress) have not been fully defined. The aim of this intervention study was to explore the involvement of increased oxidative stress in pig RBF disturbance by using chronic dietary antioxidant vitamin intervention. Responses of RBF to the acetylcholine (Ach) were measured in vivo using electron beam computed tomography (EBCT). Acetylcholine significantly increased RBF in normal and hypercholesterolemic + vitamins (P < 0.05 for both), but not in hypercholesterolemic pigs (P=0.1). In normocholesterolemic + vitamins pigs, Ach infusion did not induce any further increase in RBF, but RBF was similar to that observed in normal and hypercholesterolemic + vitamins under the same conditions, and tended to be higher than in hypercholesterolemic pigs (P=0.06). Thus, antioxidants improve RBF in hypercholesterolemic pigs and this effect may help to prevent renal diseases and hypertension in animals.

Kinetic-spectrophotometric determination of theophylline, dyphylline, and proxyphylline by use of partial least-squares regression.

A kinetic-spectrophotometric method for the determination of theophylline, dyphylline and proxyphylline, based on their azo coupling reaction with the diazonium ion of sulfanilic acid after a treatment with alkali, is proposed. The absorbance is recorded from 340 to 600 nm every second during reaction for 90 s, and calibration is performed by partial least-squares regression, using first derivative spectra values. Mixtures containing 2.5-13 micro g mL(-1) dyphylline and proxyphylline, and 2-9 micro g mL(-1) theophylline were successfully resolved with root mean squared errors of prediction (RMSEP) of 0.4, 0.3, and 0.2 for dyphylline, proxyphylline, and theophylline, respectively. The proposed method was satisfactorily applied to the determination of the three compounds in a commercially available pharmaceutical preparation and provided results similar to those obtained by HPLC.

Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia.

OBJECTIVE: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. METHODS: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. RESULTS: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93+/-6%) and Group 2 (89+/-7%) but impaired in Group 3 (71+/-11%; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88+/-2.45 per-mm(2)) and Group 3 (4.50+/-1.37 per-mm(2)) compared to Group 1 (2.97+/-1.37 per-mm(2); P<0.05 vs. Group 2 and 3). CONCLUSION: This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.

Functional assessment of the circulation of the single kidney.

Functional alterations in the renal circulation that can contribute to abnormal renal perfusion have been demonstrated in various models of renal injury. To detect impairments in renal vascular function, renal flow reserve can be determined by repeated measurements of renal blood flow (RBF) during pharmacological challenge with short-acting vasodilators that should increase RBF in kidneys that are not severely damaged structurally. Among the invasive techniques for such measurements, the most readily available is probably the intravascular Doppler, which can be employed during renal angiography for rapid evaluation of changes in RBF during intrarenal injections of vasoactive substances. High-resolution tomographic imaging techniques, like electron-beam x-ray computed tomography, further offer the potential for noninvasive measurements of renal parenchymal perfusion and function, in association with either intrarenal or systemic injections of vasoactive substances. Acetylcholine is a potent short-acting renal vasodilator that can be useful to assess the response of the renal microcirculation, define renal flow reserve, and examine the endothelium-dependent responses of RBF. Such assessments of the function of the renal circulation can assist in evaluation of patients with systemic or renal disease for early detection and monitoring of renovascular injury.

Multi-component kinetic-spectrophotometric analysis. Selection of wavelength and time ranges.

An empirical method for the selection of the best wavelength and time ranges which can be used in the quantification of binary mixtures, in a kinetic-spectrophotometric system, is proposed. It is based on finding those ranges which provide the least correlation between the kinetic profiles and the spectra of the products of reaction. The method was applied to the analysis of binary mixtures using simulated data with different rate constant ratios and in the presence of an interference that shows spectral overlap with the analytes. Subsequently, the proposed method was applied to the resolution of dyphylline and proxyphylline mixtures. The system studied was characterized by an elevated similarity in the kinetic behavior of the analytes under pseudo-first-order conditions and an elevated degree of spectral overlap of the products of reaction. In spite of this, satisfactory results were obtained in the quantification of the two analytes. The standard error of prediction (SEP) and the standard deviation between replicates (SDBR) did not show significant differences, being of the order of 4 and of 3% for dyphylline and proxyphylline, respectively.