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Biomedical subjects

A Valentin

Publications and source records attributed to A Valentin.

At least 19 recordsLinked to original sources

In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid.

Extracts of leaves of Alchornea cordifolia were studied for their antiplasmodial activities. Chloroformic and ether extracts were found to be inactive while the ethanolic extract exhibited mild in vitro activity against Plasmodium falciparum. Fractionation of this extract led us to isolate ellagic acid as the active constituent of the extract with IC(50) in the range of 0.2-0.5 microM. Cytotoxicity of ethanolic fraction and ellagic acid was also estimated on human fibroblasts cells (IC(50) on Hela cells = 7.3 microM at 24 h for ellagic acid).

Animals↗

Diode laser emission linewidth determination: application to H2O line profile studies in the 5 and 1.4 microm regions.

In order to study absorption line profiles using the stabilized diode laser spectrometer of Laboratoire de Physique Moléculaire et Applications (LPMA), a reliable determination of the emission line shape of different diodes laser is needed. In the near infrared region (1.39 and 1.66 microm) we used Distributed Feed Back diode lasers which operate around room temperature and in the middle infrared (5 and 8 microm) we used lead salt diode lasers cooled in a helium closed cycle cryostat or in a liquid nitrogen dewar. Some results obtained in H2O line profile studies in the 1.39 and 5 microm regions are presented as examples demonstrating how absorption line profile measurements can lead to erroneous values of the spectroscopic parameters when the contribution of the diode laser emission line width is neglected.

Spectrophotometry↗

Pressure broadening study at low temperature: application to methane.

We studied the R(0) line profile in the CH4 v4 band from room temperature to 188 K with N2 as a perturber, to 100 K with O2 as perturber, and from room temperature to 15 K using He as a perturber. The N2 and O2 measurements were performed over a total pressure range of 15-110 mbar, and for the He measurements the maximum sample pressure at 15 K was 1.10 mbar. Broadening parameters were determined, taking into account the confinement narrowing (Dicke effect), and narrowing parameters, deduced from the soft or hard collision model, are compared with the dynamic friction coefficient calculated values. We also obtained preliminary values for the temperature dependence of the N2, O2 and He line broadening parameters for this transition.

Cold Temperature↗

[Flying fitness of patients with cardiovascular diseases].

Air travel of persons with coronary heart disease, heart failure and cyanotic congenital heart disease will be without complications and problems in the most cases. Prerequisite for an uneventful flight are stable cardiac conditions and an extensive cardiac examination including echocardiography and exercise testing before starting the journey. Careful travel planning and timing to reduce travel stress is mandatory. To determine fitness for air travel left heart catheterization is required in most patients with acute coronary syndrome. Patients with an acute coronary syndrome may repatriated with medical escort within the first 2 weeks after the acute event. Patients with a low risk profile can fly with reasonable safety 14 to 21 days after the acute event without medical escort. Fitness to travel may be given within a few days after successful percutaneous coronary intervention in individual cases. Patients with severe acute cardiovascular diseases and an appropriate medical indication may be transferred by air ambulance after acute local medical care and pretransfer stabilisation with ambulance jet under intensive care conditions. In these cases close cooperation between the doctor in charge, cardiologist and cardiologic department respectively and air ambulance is mandatory.

Aerospace Medicine↗

Antiplasmodial activity of aspidosperma indole alkaloids.

The antiplasmodial activity of twelve alkaloids with an aspidospermane skeleton was estimated in vitro on chloroquine-resistant and sensitive strains of Plasmodium falciparum. Seven tetracyclic alkaloids possessing a free ethyl chain such aspidospermine, showed IC50 after incubation for 72 h between 3.2 and 15.4 microM. Moreover, four pentacyclic alkaloids with ethyl chain included in a tetrahydrofuran, such haplocine, showed a reduced activity, with IC50, after 72 h, between 22.6 and 52.6 microM. According to these results, a chloroquine-potentiating experiment was also performed with two of the most active compounds. Isobolograms were obtained and demonstrated a synergic effect of N-formyl-aspidospermidine and aspidospermine when associated with chloroquine. The cytotoxicity and the selectivity index of some alkaloids were also estimated.

Alkaloids↗

CCAAT-enhancer-binding protein beta (C/EBP beta) activates CCR5 promoter: increased C/EBP beta and CCR5 in T lymphocytes from HIV-1-infected individuals.

C/EBPbeta is a member of a family of leucine zipper transcription factors that are involved in regulating the expression of several cytokines, including IL-1, IL-6, IL-8, TNF, and macrophage-inflammatory protein-1alpha. We identified multiple C/EBPbeta binding sites within the gene for CCR5, suggesting that C/EBPbeta may be involved in its regulation. Transient transfection experiments in both myeloid and lymphoid cells showed an increase in CCR5 promoter-driven green fluorescent protein production in the presence of C/EBPbeta. Deletion analysis identified two C/EBPbeta-responsive regions in the CCR5 gene, one in the promoter region and one at the 3' part of the intron. We provide evidence that, in myeloid cells (U937), C/EBPbeta independently activates CCR5 expression through sites located either in the promoter region or in the intron of the CCR5 gene. In contrast, in lymphoid cells (Jurkat) the presence of the intronic cis-regulatory regions is required for C/EBPbeta-mediated activation. In agreement with the functional data, EMSA demonstrated that in both myeloid and lymphoid cells C/EBPbeta binds specifically to sites present in the intron, whereas interaction with the sites located in the promoter was cell type specific and was detected only in myeloid cells. Analysis of C/EBPbeta in primary PBMCs obtained from HIV-1-infected individuals revealed a significant increase in C/EBPbeta expression. The enhanced C/EBPbeta activity correlated with a higher frequency of circulating CCR5(+) lymphocytes in AIDS patients and with a decline in CD4 lymphocyte numbers. Taken together, these results suggest that C/EBPbeta is an important regulator of CCR5 expression and may play a relevant role in the pathogenesis of HIV disease.

Binding Sites↗

Evaluation of the logistic organ dysfunction system for the assessment of organ dysfunction and mortality in critically ill patients.

OBJECTIVES: To evaluate the performance of the logistic organ dysfunction (LOD) system for the assessment of morbidity and mortality in multiple organ dysfunction/failure (MOD/F) in an independent database and to evaluate the use of sequential LOD measurements for the prediction of outcome. DESIGN AND SETTING: Prospective, multicentric cohort study in 13 adult medical, surgical, and mixed intensive care units (ICUs) in Austria. PATIENTS: A total of 2,893 consecutive admissions to the ICUs. MEASUREMENTS AND MAIN RESULTS: Patient vital status at ICU and hospital discharge was recorded. Univariate analysis showed that the LOD was able to distinguish between survivors and nonsurvivors (2 vs. 6 median score). Within organ systems, higher levels of the severity of organ dysfunction were consistently associated with higher mortality. For the prediction of hospital mortality, the original prognostic LOD model did not perform well in our patients, as indicated by the goodness-of-fit C statistic. Using multiple logistic regression we developed a prognostic model with a satisfactory fit in our patients. The integration of further measurements during the ICU stay increased discrimination but not calibration. CONCLUSIONS: The LOD system is well correlated well with the numbers and levels of organ dysfunctions and discriminates well between survivors and nonsurvivors. It can thus be used to quantify the baseline severity of organ dysfunction. Moreover, after customization of the predictive equation the LOD predicted hospital mortality in our patients with high precision. It thus provides a combined measure of morbidity and mortality for critically ill patients with MOD/F.

Aged↗

Assessment of functional knee bracing: an in vivo three-dimensional kinematic analysis of the anterior cruciate deficient knee.

OBJECTIVE: To describe three-dimensional tibial and femoral movements in vivo and examine the effect of a brace on knee kinematics during moderate to intense activity. DESIGN: Skeletal kinematics of anterior cruciate ligament deficient knees was measured with and without braces during moderate to intense activity. BACKGROUND: Invasive markers implanted into the tibia and femur are the most accurate means to directly measure skeletal motion and may provide a more sensitive measure of the differences between brace conditions. METHODS: Steinmann traction pins were implanted into the femur and tibia of four subjects having a partial or complete anterior cruciate ligament rupture. Non-braced and braced conditions were randomly assigned and subjects jumped for maximal horizontal distance to sufficiently stress the anterior cruciate ligament. RESULTS: Intra-subject peak vertical force and posterior shear force were generally consistent between conditions. Intra-subject kinematics was repeatable but linear displacements between brace conditions were small. Differences in angular and linear skeletal motion were observed across subjects. Bracing the anterior cruciate ligament deficient knee resulted in only minor kinematic changes in tibiofemoral joint motion. CONCLUSION: In this study, no consistent reductions in anterior tibial translations were observed as a function of the knee brace tested. Relevance. Investigations have reported that knee braces fail when high loads are encountered or when load is applied in an unpredictable manner. Questions remain regarding tibiofemoral joint motion, in particular linear displacements. The pin technique is a means for direct skeletal measurement and may provide a more sensitive measure of the differences between brace conditions.

Adult↗

Bioactive acridone alkaloids from Swinglea glutinosa.

A new prenylated acridone alkaloid, 1,3,5-trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone (1), was isolated from the stembark of Swinglea glutinosa, along with three known acridone alkaloids, 5-hydroxynoracronycine (2), 1,3,5-trihydroxy-4-methoxy-2-(3-methylbut-2-enyl)-10-methyl-9-acridone (3), and 1,3,5-trihydroxy-4-methoxy-10-methylacridone (4). The isolated alkaloids were assessed in vitro against chloroquine-sensitive and -resistant Plasmodium falciparum strains and for cytotoxicity using HeLa cells.

Acridines↗

Fulminant septic melioidosis after a vacation in Thailand.

Severe infection with Burkholderia pseudomallei (formerly Pseudomonas pseudomallei), the bacterium causing melioidosis, is a common cause of acquired septicaemia in south-east Asia and northern Australia. A few cases of infected travellers returning to European countries have been reported. Melioidosis is a tropical disease, the clinical presentation ranging from asymptomatic infection to fulminant sepsis. Predisposing conditions such as impaired cellular immunity, preexisting renal failure or diabetes mellitus seem to enhance the severity of the disease. For a definite diagnosis the bacterium has to be isolated. The antimicrobial treatment of choice is ceftazidime in combination with co-trimoxazole or doxycycline. Even with correct antibiotic treatment the mortality rate is high in cases of fulminant sepsis. We report a 29-year old man with Type I diabetes who acquired melioidosis during a vacation in Thailand. After returning to Austria he was admitted to the intensive care unit with multiple organ failure. Despite intensive care treatment the patient's infection proved lethal. Burkholderia pseudomallei was isolated from the blood and bronchoalveolar lavage.

Adult↗

CXCR4 mediates entry and productive infection of syncytia-inducing (X4) HIV-1 strains in primary macrophages.

CCR5 and CXCR4 are the main coreceptors for non-syncytia-inducing (NSI) and syncytia-inducing (SI) HIV-1 strains, respectively. NSI HIV-1 isolates do not infect either human lymphoid or monocytoid cell lines, and this inability correlates with the absence of CCR5 expression in these cell types. The ability of SI HIV-1 isolates to infect human primary macrophages has been disputed. Here, we report that CXCR4 is expressed in primary blood-derived human mononuclear phagocytes at all stages of differentiation, although the maturation process correlates with downregulation of CXCR4 mRNA. Infection experiments with the SI molecular clone NL4-3 tagged with a mutant of the green fluorescent protein established that both monocytes and attached macrophages are susceptible to infection with CXCR4-restricted HIV-1 strains. NL4-3 entry into primary macrophages could be blocked by SDF-1alpha in a dose-dependent manner, or by the anti-CXCR4 monoclonal antibody 12G5. HIV-1 entry led to productive infection. No evidence of postentry defects or nuclear import delay for CXCR4-restricted HIV-1 strains was detected using a quantitative real-time PCR assay measuring HIV-1 DNA entry into the nucleus. Macrophages infected by HIV-1 and expressing virus were maintained in culture for long periods of time (up to 5 months). These results demonstrate that CXCR4 is the main HIV-1 SI coreceptor in human primary macrophages and underline the importance of the macrophage as a long-living viral reservoir for HIV-1.

Cells, Cultured↗

Multivariate analysis-based prediction rule for pulmonary embolism.

The diagnosis of pulmonary embolism (PE) is still an unresolved problem. The aim of this prospective observational study was to derive and validate a prediction rule (PEscore) by which PE can be diagnosed by easily obtainable and rapidly available investigations. Included were consecutive patients with a clinical suspicion of PE admitted to a community hospital. Risk factors and clinical and instrumental investigations were registered. PE was diagnosed by angiography, scintigraphy, or autopsy. In 168 patients, PE was either diagnosed (angiography, n = 28; autopsy, n = 18) or excluded (angiography, n = 12; scintigraphy, n = 99; autopsy, n = 11). Based on the results of clinical and instrumental findings, a PEscore was derived by a multiple regression analysis, calculated as: [0.29 x proven leg vein thrombosis (0 = no, 1 = yes)] + [0.25 x ECG right heart strain (0 = no, 1 = yes)] + [0.22 x neck vein distension (0 = no, 1 = yes)] + [0.20 x dyspnoea (0 = no, 1 = yes)] + [0.13 x suspicious chest X-ray (0 = no, 1 = yes)] - [0.17 (constant)]. The PEscore was tested further in 139 subsequent cases. In these patients, the PEscore was 0.65+/-0.17 (diagnosed PE, n = 47) and 0.18+/-0.17 (excluded PE, n = 92), respectively (p = 0.0001). Depending on a given PE-score, the level of probability of PE can be assessed. Calculation of the PEscore can be helpful in clinical decisions when PE is suspected.

Adult↗

Outcome in patients with intracerebral hemorrhage: predictors of survival.

BACKGROUND AND PURPOSE: The aim of this retrospective study was to determine in-hospital mortality and morbidity secondary to intracerebral hemorrhage and to analyse variables considered to be significantly associated with survival in these patients. PATIENTS AND METHODS: The study cohort consisted of 135 consecutive patients with intracerebral hemorrhage, admitted to a large community hospital in the urban area of Vienna. The diagnosis of intracerebral hemorrhage was established in all cases with axial computed tomography. The following variables were analysed: age, sex, Glasgow coma score on admission, location of hematomas, intraventricular hemorrhage, neurosurgical interventions and medical complications. RESULTS: Sixty-seven (49.6%) of the 135 patients died, 50 (37%) of them during the first 4 days after the acute event, 13 within the 1st week and 4 within one month. In a multivariate analysis the risk of death was significantly increased by the presence of intraventricular hemorrhage (p < 0.01), a Glasgow coma score of 6 or less (p < 0.0001) and age greater than 60 years (p < 0.001). Gender, medical complications and surgical removal of hemorrhage with or without additional ventriculostomy did not correlate significantly with outcome while an infratentorial location of hematoma showed a trend (p < 0.15) towards a higher mortality. CONCLUSION: A Glasgow coma score of 6 or less on admission, age greater than 60 years and the presence of intraventricular hemorrhage appear to be predictors of mortality in patients with intracerebral hemorrhage.

Adult↗

The nu(1) and nu(3) Bands of the (17)O(16)O(17)O Isotopomer of Ozone.

Using 0.002 cm(-1) resolution Fourier transform absorption spectra of an (17)O-enriched ozone sample, an extensive analysis of the nu(3) band together with a partial identification of the nu(1) band of the (17)O(16)O(17)O isotopomer of ozone has been performed for the first time. As for other C(2v)-type ozone isotopomers [J.-M. Flaud and R. Bacis, Spectrochim. Acta, Part A 54, 3-16 (1998)], the (001) rotational levels are involved in a Coriolis-type resonance with the levels of the (100) vibrational state. The experimental rotational levels of the (001) and (100) vibrational states have been satisfactorily reproduced using a Hamiltonian matrix which takes into account the observed rovibrational resonances. In this way precise vibrational energies and rotational and coupling constants were deduced and the following band centers nu(0)(nu(3)) = 1030.0946 cm(-1) and nu(0)(nu(1)) = 1086.7490 cm(-1) were obtained for the nu(3) and nu(1) bands, respectively. Copyright 2000 Academic Press.

Journal Article↗

Ratios of observed to expected mortality are affected by differences in case mix and quality of care.

OBJECTIVES: To validate SAPS II-AM, a recently customized version of the Simplified Acute Physiology Score II (SAPS II) in a larger cohort of Austrian intensive care patients and to evaluate the effect of the customization process on the ratio of observed to expected mortality. DESIGN: Prospective, multicentric cohort study. PATIENTS AND SETTING: A total of 2,901 patients consecutively admitted to 13 adult medical, surgical, and mixed intensive care units (ICUs) in Austria. MEASUREMENTS AND RESULTS: After the database was divided randomly into a development sample (n = 1,450) and a validation sample (n = 1,451), logistic regression was used to develop a new model (SAPS II-AM2). The original SAPS II, the SAPS IIAM, and the newly developed SAPS II-AM2 were then compared by means of calibration, discrimination and O/E ratios. Differences in O/E ratios before and after customization (deltaO/E) were calculated. The Hosmer-Lemeshow goodness-of-fit H and C statistics revealed poor calibration of the original SAPS II on the database. The new model, SAPS II-AM2, performed better than the SAPS II-AM and excellent in the validation data set. However, mean O/E ratios varied widely among diagnostic categories (range 0.55-1.05 for the SAPS II). Moreover, the deltaO/E of the 13 ICUs ranged from -3.6 % to +25 %. CONCLUSIONS: Today's severity scoring systems, such as the SAPS II, are limited by not measuring (and adjusting for) a profound part of what constitutes case mix. Changes in the distribution of patient characteristics (known and unknown) therefore affect prognostic accuracy. First-level customization was not able to solve all these problems. Using O/E ratios for quality of care comparisons one must therefore be critical when using these data and should search for possible confounding factors. In the case of unsatisfactory calibration, customized severity of illness models may be useful as an adjunct for quality control.

APACHE↗

Antiplasmodial activity of plant extracts used in west African traditional medicine.

Five plants originating from Ivory Coast were selected after an ethnobotanical survey, Alchornea cordifolia, Mitragyna inermis, Nauclea diderrichii, Pterocarpus santalinoides, and Terminalia glaucescens. Traditional healers for the treatment of malaria commonly used these plants. Extracts of these plants were tested on three strains of Plasmodium falciparum, FcB1-Colombia and FcM29-Cameroon (chloroquine-resistant strains) and a Nigerian chloroquine-sensitive strain. Extracts were obtained by preparing decoction in water of the powdered plant, the technique used by most of the traditional healers. A radioactive micromethod allowed the evaluation of the in vitro activity of the extracts on P. falciparum. Concentrations inhibiting 50% of the parasite growth (IC(50)) ranged from 2.34 to more than 500 microg/ml according to the plant. For the most active plants (A. cordifolia and T. glaucescens) ethanol and pentane extracts were made and tested. The IC(50) values obtained for these extracts ranged from 0.35 to 43.40 microg/ml. The stage specificity of the ethanol extracts of A. cordifolia and T. glaucescens and pentane extract of T. glaucescens on the parasite erythrocytic cycle were determined. The ethanol extract of T. glaucescens showed its highest activity at the transition from the trophozoite to the schizont stages. Cytotoxicity was estimated on human fibroblasts (HeLa) cells and a cytotoxicity/antiplasmodial index was calculated, it ranged between 5 and 21, and the best antiplasmodial extract (T. glaucescens ethanol extract) had the higher index (>20).

Animals↗