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PubMed2002

Two derivative spectrophotometric determinations of indapamide in pharmaceutical dosage forms.

Simple, fast and reliable derivative spectrophotometric methods were developed for determination of indapamide in bulk and pharmaceutical dosage forms. The solutions of standard and the sample were prepared in methanol. The quantitative determination of the drug was carried out using the first-derivative values measured at 252.8 nm (N=6) and the second-derivative values measured at 260.4 nm (N=9). Calibration graphs constructed at their wavelengths of determination were linear in the concentration range of indapamide using peak to zero 1.00-30.00 microg ml(-1) for first-derivative and 1.00-35.00 microg ml(-1) for second-derivative spectrophotometric method. The developed methods were successfully applied for the assay of pharmaceutical dosage forms which do not require any preliminary separation or treatment of the samples. The details of the statistical treatment of analytical data are also presented. The results obtained from two derivative spectrophotometry were compared with a spectrophotometric method reported in literature and no significant difference was found statistically.

Dosage Forms↗
PubMed1999

Simultaneous determination of tinidazole, furazolidone and diloxanide furoate in a combined tablet preparation by second-derivative spectrophotometry.

A second-derivative spectrophotometric procedure has been developed for the simultaneous determination of tinidazole (TD), furazolidone (FD) and diloxanide furoate (DF) in a commercial preparation. The method consists of the utilization of second-derivative absorption spectra of tablet extract in distilled water and then determination of the analyte concentration in the mixture was carried out using zero-crossing (ZC) and ratio-compensation (RC) techniques. Calibration graphs constructed at their wavelengths of determination were linear in the concentration range of TD (5-20 microg ml(-1)), FD (2.5-10 microg ml(-1)) and DF (7.5-15 microg ml(-1)). The results were found to be accurate and free from interference. The details of the statistical treatment of analytical data are also presented.

Antiprotozoal Agents↗
PubMed1998

Alternative strategies for uncovering genes contributing to alcoholism risk: unpredictable findings in a genetic wonderland.

In spite of technological advances in genetic mapping, the field of alcoholism genetics has had few findings that could be confirmed. Possible sources for the largely negative results and suggested ways for improving the search for genes contributing to alcoholism risk are discussed. These include the choice of phenotype to be studied, whether narrow or broad, whether only mild or severe forms are included, and whether or not comorbidity should be excluded. The ascertainment schema for selecting families utilized in our laboratory which results in an especially high recurrence risk will be discussed with respect to finding candidate genes. The complexity of the alcoholism phenotype will be discussed with respect to the existence of phenocopies, genetic heterogeneity, and the difficulties associated with defining the disorder in a way that covers all ages and both genders adequately. Finally, the equivocal results found for the D2 dopamine receptor are discussed with respect to current data analytic techniques, which emphasize affected sib-pairs, techniques that may be especially problematic for a disorder such as alcoholism that has marked tendencies for phenocopies to arise.

Alcoholism↗
PubMed2003

Cerebral blood flow in depressed patients: a methodological comparison of statistical parametric mapping and region of interest analyses.

Functional brain imaging has assumed a leading role in neuropsychiatric research. However, findings reported for mental disorders often vary. Whether this reflects diversity in pathophysiology or heterogeneity of imaging techniques and data-analytic procedures is still unknown. This study compares region of interest (ROI) and statistical parametric mapping (SPM) analyses of a Tc99m-HMPAO single photon emission computed tomography (SPECT) imaging study of 23 depressed and 21 control subjects. Reduced regional cerebral blood flow (rCBF) was demonstrated by both methods in the right parietal and occipital lobes, but additional regions were identified only on ROI analysis (left temporal) and only on SPM analysis (left parietal). To investigate the contribution of SPM spatial normalization to these discrepancies, further ROI analyses were performed, applying the original ROI templates to normalized images, and applying regions identified by SPM to the original images. This study demonstrated considerable overlap in findings of SPM and ROI analyses. Differences between these methods may be mostly related to subjective placement of ROIs in ROI analysis, and standardized warping inherent in normalization in SPM. Given the advantages and drawbacks of each procedure, the choice of methodology should be determined in accordance with the study design, and complementary use of both methods may be considered.

Adult↗
PubMed2000

Differential diagnosis between community-acquired pneumonia and non-pneumonia diseases of the chest in the emergency ward.

Background: The differential diagnosis of community-acquired pneumonia and some non-pneumonia diseases involving the chest may sometimes be cumbersome. Adding some objective variables to the diagnostic strategy may be helpful.We evaluated the main objective variables that are usually available in the emergency ward and that may be valuable in this differential diagnosis. Methods: We recorded epidemiological, clinical, and analytical data, as well as that obtained from physical examination, from 284 consecutive patients diagnosed in the emergency ward as having community-acquired pneumonia. The diagnosis was reviewed by the investigators applying pre-set diagnostic criteria. Statistical analysis was then performed comparing data from patients with a definitive diagnosis of community-acquired pneumonia with those with a final diagnosis of non-pneumonia disease excluding acute exacerbations of chronic bronchitis. Results: In the univariate analysis, C-reactive protein (difference of means 93 mg/l; 95% C.I. 47, 140), erythrocyte sedimentation rate (d.m. 19 mm/h; 95% C.I. 3, 35), leukocyte count (d.m. 3.5x10(9)/l; 95% C.I. 0.5, 6.4), and temperature (d.m. 0.5 degrees C; 95% C.I. 0.1, 0.9) discriminated between community-acquired pneumonia and non-pneumonia diseases. In the multivariate analysis, only C-reactive protein remained in the equation. Conclusions: C-reactive protein, erythrocyte sedimentation rate, leukocyte count, and temperature were measurable variables that proved to be useful in the differential diagnosis between community-acquired pneumonia and non-pneumonia diseases. C-reactive protein appears to be the most suitable for this purpose.

Journal Article↗
PubMed1994

Fermentation monitoring and process control.

During the past year, several papers describing the potential of new sensor devices for application in real bioprocesses have been published. Biosensors, optical sensors, and immunosensors are all gaining in importance. At present, the development of correct/adequate interfacing of biosensors to bioprocesses is the major limitation on progress. On the basis of new analytical data, a more precise modeling and control of fermentations can now be performed. Recent research efforts attest to the increasing importance of this area in biotechnology.

Biosensing Techniques↗
PubMed2000

Genetic variations of the apolipoprotein E gene determine the plasma triglyceride levels after heart transplantation.

OBJECTIVES: To study whether the presence of the polymorphism in the apolipoprotein E (apo E) gene influences the lipid profile in heart-transplant recipients. METHODS: A cohort of 103 recipients of heart transplant (93 men and 10 women, with a mean age of 47 +/- 13 years) under triple immunosuppressive therapy were submitted to a genetic study of the apo E gene region. Anthropometric and analytical data, including lipid profile and arterial blood pressure were collected prior to transplantation and 3, 6, 12, and 24 months after it. RESULTS: 65 subjects present the genotype E3E3, 27 the genotype E3E4, 6 the genotype E2E3, and 5 the genotype E2E4. Carriers of the E2 allele (that is, genotypes E3E2 and E4E2) had higher total plasma triglyceride (TG) levels after 3 months (3.47 +/- 1.88 mmol/liter p < 0.001) and after 1 year of transplantation (3.13 +/- 1.77 mmol/liter p < 0.05) than the other genotypes. There were no differences in the plasma levels of total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C). Multiple regression analysis revealed that the apoprotein E gene polymorphism determines 5% (p = 0.0425) and age 8.7% (p < 0.009) of the variants in TG levels. CONCLUSIONS: The presence of the E2 allele in heart-transplant recipients produces a greater rise in total TG plasma levels than the other genotypes.

Apolipoprotein A-I↗
PubMed2001

The redfish species Sebastes viviparus, Sebastes marinus and Sebastes mentella have different composition of their tissue fatty acids.

The fatty acid profile in the tissue of heart, gill, skull- and otolith-oil of the three redfish species, Sebastes viviparus, S. marinus and S. mentella was determined by a chemometric method, consisting of methanolysis of samples of the tissues and of the oils and gas chromatography of the resulting fatty acid methyl esters. The analytical data were treated by multivariate statistics comprising principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA). Although the differences in fatty acid composition among the two tissues and two oils were the dominating features of the data, the three species had significantly different fatty acid profiles within each tissue. Variation among the individuals was considerable. The fatty acid profiles appeared to be species specific. The mutual relationship between S. marinus and S. mentella is closer than the relationship between either of them and S. viviparus. A comparison with a corresponding investigation on the same three species from another location indicates that the observed differences do not seem to be affected by biotic or abiotic factors.

Animals↗
PubMed2000

Anti-mutagenic structural modification by fluorine-substitution in highly mutagenic 4-methylquinoline derivatives.

We have previously shown that fluorine-substitution at position 3 of quinoline deprived this molecule of mutagenicity, possibly due to interference with the yield of its metabolically activated form, the 1,4-hydrated 2,3-epoxide (enamine epoxide), which is directly responsible for the mutagenic modification of DNA. To further explore the possibility of a method for anti-mutagenic modification of mutagens by fluorine-substitution, 4-methylquinoline (4-MeQ), the most mutagenic form of all the quinoline derivatives examined so far, was used as a target in the present study. Five mono- and di-fluorinated derivatives of 4-MeQ, 2-fluoro-4-methylquinoline (2-F-4-MeQ), 6-F-4-MeQ, 7-F-4-MeQ, 2,6-difluoro-4-methylquinoline (2, 6-diF-4-MeQ), and 2,7-diF-4-MeQ, were subjected to analysis of their structure-mutagenicity relationships. The 2-fluorinated derivatives (2-F-4-MeQ, 2,6-diF-4-MeQ, and 2,7-diF-4-MeQ) were all non-mutagenic in the Ames test. 7-F-4-MeQ was as highly mutagenic as, and 6-F-4-MeQ was less mutagenic than non-fluorinated 4-MeQ. Metabolic studies were also conducted with 4-MeQ, 2-F-4-MeQ, 6-F-4-MeQ, and 7-F-4-MeQ, using a liver microsomal enzyme fraction prepared from the 3-methylcholanthrene-treated rat. The HPLC analytical data showed that, although the metabolic patterns (hydroxylation at 4-methyl group as a main metabolic pathway and 3-hydroxylation as a minor pathway) of these four F-MeQs were similar to one another, only the 3-hydroxy metabolite of 2-F-4-MeQ was not produced under the present experimental conditions employed. These results suggest that fluorine-substitution at position 2 of 4-MeQ inhibited the formation of the enamine epoxide in the pyridine moiety and deprived this molecule of mutagenicity as in the case of quinoline.

Animals↗
PubMed2003

Vibrational study of new Pt(II) and Pd(II) complexes with functionalized nitrogen-containing tertiary phosphine oxides. Ab initio study of ortho-, meta- and para-dimethylphosphinylmethyleneoxyaniline.

Vibrational study of new Pt(II) and Pd(II) complexes of functionalized nitrogen-containing tertiary phosphine oxides, namely ortho-, meta- and para-dimethylphosphinylmethyleneoxyaniline (o-, m- and p-dpmoa), (CH3)2P(O)CH2OC6H4NH2, have been presented. Geometry optimization of the ligands was performed at HF/6-31G* and B3LYP/6-31G* levels of the theory. Harmonic frequencies were calculated at HF/6-31G* optimized geometries. Relative gas-phase and solution-phase (H2O and CH3CN) basicities of o-, m- and p-dpmoa ligands have been determined by ab initio calculations at STO-3G level with the Onsager reaction field model. On the basis of the vibrational study, physical and analytical data it was suggested that the ligands in the complexes studied coordinate through the amino group and form square-planar platinum and palladium complexes of the general formula ML2Cl2 (M = Pt, Pd, L = o-, m- and p-dpmoa).

Ligands↗
PubMed2003

Spectral, electrochemical and molecular orbital studies on solvatochromic mixed ligand copper(II) complexes of malonate and diamine derivatives.

Solvatochromic mixed ligand complexes of copper(II) with malonate and diamine derivatives, Cu(n)(RMal)(diam)(n)X(m) (where n=1 or 2, m=1-4, RMal, malonic acid (H(2)Mal), diethylmalonate (HDEtMal) or diethylethoxyethylenemalonate (DEtEMal), and diam, ethylenediamine (en), 1,3-propylenediamine (1,3-pn), N,N,N'-trimethylethylenediamine (Me(3)en), N,N,N'-triethylethylenediamine (Et(3)en), N,N,N',N'-tetramethylethylenediamine (Me(4)en), N,N,N',N'-tetramethylpropylenediamine (Me(4)pn), or N-methyl-1,4-diazacycloheptane (medach); and X=ClO(4)(-) or Cl(-)), has been synthesized and characterized by spectroscopic, magnetic, molar conductance and electrochemical measurements. The mass spectra along with the analytical data of the complexes show peaks with m/e corresponding to a bridged binuclear structure for the chloride complexes, while perchlorate complexes showed either mononuclear structure for DEtMal and DEtEMal or bridged binuclear structure for Mal complexes. These results correspond to IR spectral data, which indicated that the modes of ester and carboxylato coordination sites are mono- and/or bidentate. The d-d absorption bands in weak donor solvents suggest square-planar and distorted square pyramidal-trigonal bipyramid geometries for the perchlorate and chloride complexes; respectively. On the other hand, an octahedral structure is identified for complexes in strong donor solvents. Perchlorate complexes show a drastic color change from violet to green as the donation ability of solvent increases, whereas chloride complexes are highly affected by the acceptor properties of the solvent. Cyclic voltammetric measurements on the complexes, proposed a quasi-reversible or irreversible and mainly diffusion controlled reduction process. Such behavior has been explained according to the ECE mechanism. A linear correlation has been found between the Cu(II) reduction potential and the spectral data. Molecular orbital calculations were performed for the ligands on the bases of PM3 level and the results corresponded to the experimental data. The data are discussed in terms of chromotropic concept and its applications as a Lewis acid-base color indicator.

Copper↗
PubMed2003

Spectroscopic studies on chromotropic mixed-ligand copper(II) complexes containing o-hydroxy benzoyl derivatives and dinitrogen bases.

Synthesis of chromotropic copper(II) mixed ligand complexes of o-hydroxy benzoyl derivatives (L1) and dinitrogen bases (L2), general formula Cun(L1)(L2)nXn; where n=1 or 2, L1=4,6-diacetyl-resorcinol (H2DACR), o-hydroxy benzaldhyde (HOHBZ) or o-hydroxy acetophenone (HOHAP), L2=N,N,N',N'-tetramethylethylenediamine (Me4en), 1,10-phenanthroline (phen) or bipyridine (bipy) and X=ClO4-, NO3- or Br- have been reported. Spectral, magnetic and molar conductance measurements as well as analytical data of these complexes show either mononuclear structure for OHBZ and OHAP or binuclear structure for DACR complexes. The IR stretching vibration frequencies of Cu-N and Cu-O are linearly correlated with the d-d absorption frequencies. The d-d absorption bands of Me4en-complexes in weak donor solvents suggest square-planar, distorted octahedral and distorted trigonal bipyramid geometries for the perchlorate, nitrate and bromide complexes, respectively. However, an octahedral structure is identified for the complexes in strong donor solvents. Perchlorate complexes show a remarkable color change from violet to green as the donor ability of the axial ligand increases, whereas bromide complexes are mainly affected by the Lewis acidity of the axial ligand. Specific and non-specific interactions of solvent molecules with the complexes are investigated using the unified solvation model. Calculations of the electronic transition probability (f) of the d-d band along with molecular orbital calculations of ligands have been carried out and correlated with the experimental data.

Chromogenic Compounds↗
PubMed2000

Implementation of a rapid microbial screening procedure for biotransformation activities.

A rapid and efficient microbial screening procedure was developed utilizing a 24-well plate format in conjunction with an automated liquid handling system and an HPLC. For the evaluation of this miniaturized and automated screening system, we selected the bioreduction of 6-bromo-beta-tetralone to 6-bromo-beta-tetralol. This procedure employed both yeast and rhodococci libraries, representing a culture collection comprised of several hundred strains, from which to screen for desirable bioconversion activity. Most of these strains had demonstrated bioreducing activity during previous screens to insure a "hit rate" as high as possible. The cultivation of microbes in the plate format was facile, time saving, and efficient compared to the standard method of screening utilizing larger volumes, such as test tubes or shake flasks. This improved method of screening for bioconversion activity, employing pre-selected microbial libraries based on microtiter plates and a fully roboticized analytical system, proved to rapidly yield valuable leads which compared advantageously with a more classical approach. A total of 192 yeast strains and 48 rhodococci strains were screened using this procedure. Analytical data revealed that 78% of the strains tested bioconverted the tetralone to the desired alcohol.

Journal Article↗
PubMed2001

Power of regression and maximum likelihood methods to map QTL from sib-pair and DZ twin data.

A common study design to map quantitative trait loci (QTL) is to compare the phenotypes and marker genotypes of two or more siblings in a sample of unrelated sib groups, and to test for linkage between chromosome location and quantitative trait values. The simplest case is sib pairs only, in particular dizygotic twin pairs, and a simple and elegant regression method was proposed by Haseman & Elston in 1972 to test for linkage. Since then, several other methods have been proposed to test for linkage. In this study, we derived the statistical power of linear regression and maximum likelihood methods to map QTL from sib pair data analytically, and determined which methods are superior under which set of population parameters. In particular, we considered four regression-based and three maximum likelihood-based approaches, and derived asymptotic approximations of the mean test statistic and statistical power for each method. It was found, both analytically and by computer simulation, that the revisited or new Haseman-Elston method (based upon the mean-corrected crossproduct of the observations on sib-pairs) is less powerful than a full maximum likelihood approach and is also inferior to the Haseman-Elston method under a realistic range of values for the population parameters. We found that a simple regression method, based upon both the squared difference and the mean-corrected squared sum of the observations on sib-pairs, is as powerful as a full maximum likelihood approach. Our derivations of statistical power for regression and maximum likelihood methods provide a simple way to compare alternative methods and obviate the need to perform elaborate computer simulations. DZ twin pairs are likely to be more powerful for linkage analysis than ordinary siblings because they may share more common environmental effects, thereby increasing the proportion of within-family variance that is explained by a QTL.

Chromosome Mapping↗
PubMed1979

Comparative aspects of milk proteins.

The current status of knowledge of the major proteins of milks of various species is evaluated. Most of the non-bovine milk proteins are homologous with the recognized families of those of Bos taurus, alpha S1-caseins, alpha S2-caseins, beta-caseins, kappa-caseins, beta-lactoglobulins, and alpha-lactalbumins, each family representing a separate genetic locus specific to the mammary gland. No prominent milk protein not homologous to one of these families has yet been discovered in milk of any species. Genetic polymorphism resulting from substitutions in the polypeptide chains and various degrees of post-translational phosphorylation, glycosylation, and proteolysis have been identified in milk proteins of several species. Total protein production ranges among species from about 0.5 to 10 g/d per kg0.75 maternal weight. Proportions of the several proteins vary greatly among species, but few accurate analytical data are available except for total casein and total whey protein contents.

Amino Acids↗
PubMed2006

A taxometric investigation of unipolar depression in a large community sample.

BACKGROUND: The question of whether unipolar clinical depression differs categorically from limited depressive complaints has important implications for the disorder's assessment, treatment and research. This crucial issue has proven difficult to resolve, in part because many studies to date have relied on self-report measures or on clinically homogeneous samples. We therefore applied Meehl's taxometric method to a large, clinically heterogeneous sample, and examined the latent structure of depressive episodes using both self-report and structured clinical interview data. METHOD: Data were derived from the Oregon Adolescent Depression Project, a large longitudinal community study. All analyses involved more than 1400 participants. MAXEIG (MAXimum EIGenvalue) and base rate estimation were performed separately for Beck Depression Inventory (BDI) items and for DSM-IV-based major depressive episode (MDE) symptoms. RESULTS: MAXEIG analyses of the BDI and MDE indicator sets appeared to converge on a taxonic structure for unipolar depression. Base rate estimates overall implied a latent depressive episode class that occurs more frequently than diagnosable MDEs but less frequently than persistent depressed or anhedonic mood. CONCLUSIONS: These findings provide tentative support for a categorical conceptualization and make it very clear that the continuity controversy regarding unipolar depression has not yet been decided in favor of dimensionality. To reconcile the conflicting reports to date, several data analytic and sampling issues need to be explored systematically.

Adolescent↗
PubMed2003

Early experiences and psychological development: conceptual questions, empirical illustrations, and implications for intervention.

This paper reviews alternative conceptual and descriptive models of how early exposure to risk may predict later development. Particular attention is paid to the methodological and data analytic strategies for differentiating among the models. Example empirical illustrations of human studies are then provided that highlight the potential significance of early experiences for behavioral/emotional development. Finally, implications of these models of early experiences for intervention and prevention are examined and identified as an important methodological tool for further research.

Age Factors↗
PubMed1997

The Hubble hypothesis and the developmentalist's dilemma.

Developmental psychopathology stands poised at the close of the 20th century on the horns of a major scientific dilemma. The essence of this dilemma lies in the contrast between its heuristically rich open system concepts on the one hand, and the closed system paradigm it adopted from mainstream psychology for investigating those models on the other. Many of the research methods, assessment strategies, and data analytic models of psychology's paradigm are predicated on closed system assumptions and explanatory models. Thus, they are fundamentally inadequate for studying humans, who are unparalleled among open systems in their wide ranging capacities for equifinal and multifinal functioning. Developmental psychopathology faces two challenges in successfully negotiating the developmentalist's dilemma. The first lies in recognizing how the current paradigm encourages research practices that are antithetical to developmental principles, yet continue to flourish. I argue that the developmentalist's dilemma is sustained by long standing, mutually enabling weaknesses in the paradigm's discovery methods and scientific standards. These interdependent weaknesses function like a distorted lens on the research process by variously sustaining the illusion of theoretical progress, obscuring the need for fundamental reforms, and both constraining and misguiding reform efforts. An understanding of how these influences arise and take their toll provides a foundation and rationale for engaging the second challenge. The essence of this challenge will be finding ways to resolve the developmentalist's dilemma outside the constraints of the existing paradigm by developing indigenous research strategies, methods, and standards with fidelity to the complexity of developmental phenomena.

Bias↗