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1.
Mali Med ; 36(2): 14-18, 2021.
Article in French | MEDLINE | ID: mdl-37973586

ABSTRACT

INTRODUCTION: The rapid diagnostic capacities of laboratories in Mali have been an essential element in the response to COVID-19. The University Clinical Research center (UCRC) diagnosed the first cases of Mali COVID-19. OBJECTIVE: The objective was to describe the contribution of the UCRC in the diagnosis of Covid-19 and to clinically and epidemiologically characterize the patients tested in the UCRC laboratory. MATERIALS AND METHODS: A cross-sectional study was conducted during eight months of intense activity. The samples were sent from the National Institute of Public Health (INSP) to the UCRC. RESULTS: The UCRC tested 12,406 contacts and suspected samples and confirmed the diagnosis in 1091 patients, or 9%. The most common symptoms were cough (48.78%), headache (34.14%), fatigue / weakness (34.14%), while (33.33%) of the patients were asymptomatic. The sample positivity rate among new cases decreased from May to September 2020, despite almost 230% of the number of samples tested. CONCLUSION: The laboratory played a major role in the response and there may be a low transmission of the virus in the Malian community.


INTRODUCTION: Les capacités de diagnostic rapide des laboratoires au Mali ont été un élément essentiel dans la riposte contre la COVID-19. Le Centre Universitaire de Recherche Clinique (UCRC)a diagnostiqué les premiers cas du Mali. OBJECTIF: Etait de décrire l'apport de l'UCRC dans le diagnostic de la Covid-19 et de caractériser cliniquement et épidémiologiquement les patients testés au laboratoire de l'UCRC. MATÉRIELS ET MÉTHODES: Une étude transversale a été conduite pendant huit mois d'activité intense. Les échantillons ont été envoyés de l'Institut National de Santé Publique (INSP) à l'UCRC. RÉSULTATS: L'UCRC a testé 12 406 échantillons contacts et suspects et a confirmé le diagnostic chez 1091 patients soit 9%. Les symptômes les plus rencontrés ont été la toux (48,78%), les maux de tête (34,14%), la fatigue/faiblesse (34,14%), tandis que (33,33%) des patients étaient asymptomatiques. Le taux de positivité des échantillons a diminué entre mai et août et avec une légère diminution en septembre 2020,avec près de 230% du nombre d'échantillons testés. CONCLUSION: Le laboratoire a joué un grand rôle dans la riposte et il y'aurait une faible transmission du virus dans la communauté Malienne.

2.
J Clin Tuberc Other Mycobact Dis ; 17: 100128, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31788570

ABSTRACT

INTRODUCTION: Diabetes Mellitus (DM) increases worldwide, mostly in low- and middle-income countries. In Mali, the prevalence in the adult population is estimated at 1.8%, but tuberculosis (TB) patients are not systematically screened. The goal of our study was to determine the prevalence of DM among newly diagnosed TB patients. METHODS: We conducted a cross sectional study and a pilot prospective cohort study in four health centers in Bamako. All patients underwent fasting capillary-blood glucose (FCBG) test at Day 0, and repeated after one-week of TB treatment. Venous FBG test was performed for discrepancies between the two FCBG results. Thereafter, FCBG was performed for pilot study at month-2 (M2) and M5 of TB treatment. RESULTS: Two hundred and one patients were enrolled in this study. Impaired fasting blood glucose was identified in 17 (8.5%), of whom 11 (5.5%) had DM (VFBG >7 mmol/L). Among patients with DM, seven (63.6%) had successful TB treatment outcome, versus 142 (74.7%) of those without DM (p = 0.64), and (OR: 1.69, 95%CI 0.47-6.02). CONCLUSION: The prevalence of DM among TB patients in Bamako exceeds that of the general population and screening at TB diagnosis suffices to identify those with DM. Systematic screening of both diseases will allow better treatment.

3.
J Org Chem ; 66(16): 5317-28, 2001 Aug 10.
Article in English | MEDLINE | ID: mdl-11485450

ABSTRACT

The synthesis of 16a'-homo-leurosidine was achieved through enantioselective generation of a ring D'-seco-precursor 33 (without requirement of a chiral auxiliary). Its cyclization provided the N(b')-quaternary salt 35 with a configuration corresponding to the atropisomeric form 8a rather than 8b of the target product. On debenzylation, the amine 8a was obtained and found not to isomerize thermally to the anticipated atropisomer 8b (in contrast to its lower homologue, with its formation of natural leurosidine). However, on protonation, a 1:1 mixture of atropisomers of 16a'-homo-leurosidine was obtained. A synthesis of 16a'-homo-vinblastine provided two atropisomers 5a and 5b for the free base at equilibrium (1:2.3 at room temperature in CDCl(3)), with a shift to the major conformer 5b with increasing solvent acidity or decreasing temperature. The synthesis was achieved through a stereoselective inversion of the tertiary hydroxyl function in the enantioselectively generated C-20' progenitor 39.


Subject(s)
Alkaloids/chemical synthesis , Antineoplastic Agents, Phytogenic/chemical synthesis , Vinblastine/chemical synthesis , Vinca Alkaloids , Alkaloids/chemistry , Alkaloids/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Mice , Molecular Conformation , Tumor Cells, Cultured , Vinblastine/analogs & derivatives , Vinblastine/chemistry , Vinblastine/pharmacology
4.
Bioorg Med Chem Lett ; 11(17): 2249-52, 2001 Sep 03.
Article in English | MEDLINE | ID: mdl-11527708

ABSTRACT

The preparation of two new fluorescent derivatives of paclitaxel in which the fluorophore is bonded to paclitaxel at the C-10 position is reported. Both analogues, 10-deacetyl-10-(m-aminobenzoyl)paclitaxel (1, BTax) and 10-deacetyl-10-[7-(diethylamino) coumarin-3-carbonyl]paclitaxel (2, CTax) retain good activity as promoters of in vitro tubulin assembly. Microtubule binding enhances the emission intensity of both probes.


Subject(s)
Fluorescent Dyes/chemistry , Microtubules/metabolism , Paclitaxel/chemistry , Taxoids , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/metabolism , Paclitaxel/analogs & derivatives , Paclitaxel/metabolism , Spectrometry, Fluorescence , Structure-Activity Relationship , Tubulin/metabolism
5.
Org Lett ; 3(16): 2461-4, 2001 Aug 09.
Article in English | MEDLINE | ID: mdl-11483035

ABSTRACT

[reaction: see text] This work describes the synthesis of two novel macrocyclic taxoid constructs by ring-closing olefin metathesis (RCM) and their biological evaluation. Computational studies examine conformational profiles of 1 and 2 for their fit to the beta-tubulin binding site determined by electron crystallography. The results support the hypothesis that paclitaxel binds to microtubules in a "T" conformation.


Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/pharmacology , Paclitaxel/chemical synthesis , Paclitaxel/pharmacology , Binding Sites , Crystallography, X-Ray , Cyclization , Humans , Indicators and Reagents , Models, Molecular , Molecular Conformation , Paclitaxel/analogs & derivatives , Tubulin/chemistry , Tumor Cells, Cultured
6.
Biochemistry ; 40(23): 6964-70, 2001 Jun 12.
Article in English | MEDLINE | ID: mdl-11389612

ABSTRACT

Baccatin III is widely considered to be an inactive derivative of Taxol. We have reexamined its effect on in vitro assembly of tubulin under a variety of conditions. We found baccatin III to be active in all circumstances in which Taxol is active: it assembled GTP-tubulin, GDP-tubulin, and microtubule protein into normal microtubules and stabilized these polymers against cold-induced disassembly. The effect of baccatin III on in vitro microtubule assembly was quantitatively assessed through determination of critical concentrations, which can be used to obtain the apparent equilibrium constants for the addition of tubulin subunits to growing microtubules. The apparent equilibrium constants for the growth reaction for baccatin III-induced GTP-tubulin and GDP-tubulin assembly measured at 37 degrees C were 4.2-4.6-fold less than those measured for Taxol-induced GTP-tubulin and GDP-tubulin assembly. These data indicate that the entire Taxol side chain contributes only about -1 kcal/mol to the apparent standard free energy of microtubule growth at 37 degrees C regardless of the nature of the E site nucleotide. These data also support the idea that the majority of the interactions between Taxol and tubulin that affect this equilibrium occur between the baccatin portion of the molecule and the binding site. We have also observed a structural difference in microtubules formed using baccatin III and Taxol. Baccatin III-induced microtubules were routinely much longer than those assembled by Taxol, even when very high concentrations of baccatin III were employed. One interpretation of these data is that baccatin III and Taxol differ in their abilities to nucleate GTP-tubulin. This difference in activity may have bearing on the large disparity in cytotoxicity of the two molecules.


Subject(s)
Alkaloids/pharmacology , Microtubules/metabolism , Taxoids , Tubulin/metabolism , Animals , Cattle , Dose-Response Relationship, Drug , Guanosine Triphosphate/metabolism , Inhibitory Concentration 50 , Microscopy, Electron , Microtubules/drug effects , Microtubules/ultrastructure , Paclitaxel/pharmacology , Polymers/metabolism , Tubulin/ultrastructure
7.
Biochemistry ; 39(3): 616-23, 2000 Jan 25.
Article in English | MEDLINE | ID: mdl-10642187

ABSTRACT

A fluorescent derivative of paclitaxel, 3'-N-m-aminobenzamido-3'-N-debenzamidopaclitaxel (N-AB-PT), has been prepared in order to probe paclitaxel-microtubule interactions. Fluorescence spectroscopy was used to quantitatively assess the association of N-AB-PT with microtubules. N-AB-PT was found equipotent with paclitaxel in promoting microtubule polymerization. Paclitaxel and N-AB-PT underwent rapid exchange with each other on microtubules assembled from GTP-, GDP-, and GMPCPP-tubulin. The equilibrium binding parameters for N-AB-PT to microtubules assembled from GTP-tubulin were derived through fluorescence titration. N-AB-PT bound to two types of sites on microtubules (K(d1) = 61 +/- 7.0 nM and K(d2) = 3.3 +/- 0.54 microM). The stoichiometry of each site was less than one ligand per tubulin dimer in the microtubule (n(1) = 0.81 +/- 0.03 and n(2) = 0.44 +/- 0.02). The binding experiments were repeated after exchanging the GTP for GDP or for GMPCPP. It was found that N-AB-PT bound to a single site on microtubules assembled from GDP-tubulin with a dissociation constant of 2.5 +/- 0.29 microM, and that N-AB-PT bound to a single site on microtubules assembled from GMPCPP-tubulin with a dissociation constant of 15 +/- 4.0 nM. It therefore appears that microtubules contain two types of binding sites for paclitaxel and that the binding site affinity for paclitaxel depends on the nucleotide content of tubulin. It has been established that paclitaxel binding does not inhibit GTP hydrolysis and microtubules assembled from GTP-tubulin in the presence of paclitaxel contain almost exclusively GDP at the E-site. We propose that although all the subunits of the microtubule at steady state are the same "GDP-tubulin-paclitaxel", they are formed through two paths: paclitaxel binding to a tubulin subunit before its E-site GTP hydrolysis is of high affinity, and paclitaxel binding to a tubulin subunit containing hydrolyzed GDP at its E-site is of low affinity.


Subject(s)
Guanine Nucleotides/metabolism , Microtubules/metabolism , Paclitaxel/analogs & derivatives , Paclitaxel/pharmacokinetics , Taxoids , Tubulin/metabolism , Animals , Brain/metabolism , Cattle , Fluorescent Dyes , Guanosine Diphosphate/metabolism , Guanosine Triphosphate/analogs & derivatives , Guanosine Triphosphate/metabolism , Kinetics , Paclitaxel/chemistry
8.
Biochemistry ; 39(2): 281-91, 2000 Jan 18.
Article in English | MEDLINE | ID: mdl-10630987

ABSTRACT

The conformation of microtubule-bound paclitaxel has been examined by fluorescence and solid-state NMR spectroscopy. A fluorescent derivative of paclitaxel, 3'-N-debenzoyl-3'-N-(m-aminobenzoyl)paclitaxel (N-AB-PT), was prepared by semisynthesis. No differences in the microtubule-promoting activity between N-AB-PT and paclitaxel were observed, demonstrating that addition of the amino group did not adversely affect the ligand-receptor association. The distance between the fluorophore N-AB-PT and the colchicine binding site on tubulin polymers was determined through time-resolved measurements of fluorescence resonance energy transfer to be 29 +/- 2 A. The absorption and emission spectra of N-AB-PT bound to microtubules and in various solvents were measured. A plot of the Stokes shift as a function of solvent polarity was highly unusual. The Stokes shift increased linearly with solvent polarity in protic solvents, which is expected due to the nature of the fluorophore. In aprotic solvents, however, the Stokes shift was invariant with solvent polarity, indicating that the fluorophore was somehow shielded from the effects of the solvent. These data are best explained by considering the solution-state conformational properties of paclitaxel. It is known that paclitaxel adopts different conformations depending on the nature of the solvent, and these fluorescence data are consistent with the molecule adopting a "hydrophobic collapsed" conformation in protic solvents and an "extended" conformation in aprotic solvents. The Stokes shift of microtubule-bound N-AB-PT was within the protic solvent region, demonstrating that microtubule-bound paclitaxel is in a hydrophobic collapsed conformation. Microtubule-bound paclitaxel was also investigated by solid-state NMR. Paclitaxel was labeled with (19)F at the para position of the C-2 benzoyl substituent and with (13)C and (15)N in the side chain. Distances between the fluorine and carbon nuclei were determined by REDOR. The distance between the fluorine and the 3'-amide carbonyl carbon was 9.8 +/- 0.5 A, and the distance between the fluorine atom and the 3'-methine carbon was 10. 3 +/- 0.5 A. These spectroscopic data were used in conjunction with molecular modeling to refine the microtubule-bound conformation of paclitaxel and to suggest an alternative orientation of the ligand within the paclitaxel binding site.


Subject(s)
Microtubules/chemistry , Paclitaxel/chemistry , Tubulin/chemistry , Animals , Binding Sites , Cattle , Colchicine/chemistry , Magnetic Resonance Spectroscopy/methods , Models, Molecular , Molecular Conformation , Molecular Structure , Paclitaxel/analogs & derivatives , Paclitaxel/chemical synthesis , Spectrometry, Fluorescence , Tubulin/isolation & purification
9.
Cancer Lett ; 130(1-2): 161-7, 1998 Aug 14.
Article in English | MEDLINE | ID: mdl-9751269

ABSTRACT

The ability of field bean protease inhibitor (FBPI) to inhibit ethylnitrosourea (ENU)-induced tumours of the nervous system of Sprague-Dawley rats was investigated. Groups of 1-day-old rats were injected intraperitoneally (i.p.) with neurocarcinogenic amounts of ENU and a few hours later, one group was treated i.p. with 80 mg of FBPI per kg body weight. This treatment was carried out three times a week for the first month and five times a week for the next month. Animals were killed when they were neurologically ill and their neural tissues were assessed for lesions. Those FBPI-treated rats which showed no illness were also killed to terminate the experiment about 8 weeks after the last rat of the control group was affected with paralysis. The neural tumours induced in all groups were predominantly large tumours found in the cerebrum of the rats. ENU-treated rats showed a 100% incidence of nervous system tumours with a mean time of manifestation of neurological symptoms of 282 days, which was significantly shorter in comparison to that noted in the FBPI-treated group. The latter group showed an incidence of 58.3%, i.e. a significant reduction of 41% in the incidence of neural tumours, as well as a lower mean value for the number of tumours per rat. All these aspects indicated that FBPI is a potential neurooncopreventive agent. A neural tumour incidence of 100% in the rats treated with heat-inactivated FBPI confirmed that the tumour suppressive activity of FBPI is related to its protease inhibitory activity.


Subject(s)
Central Nervous System Neoplasms/prevention & control , Enzyme Inhibitors/pharmacology , Fabaceae/chemistry , Plant Proteins/pharmacology , Plants, Medicinal , Animals , Carcinogens , Central Nervous System Neoplasms/chemically induced , Drug Screening Assays, Antitumor , Ethylnitrosourea , Female , Male , Peripheral Nervous System Neoplasms/chemically induced , Peripheral Nervous System Neoplasms/prevention & control , Rats , Rats, Sprague-Dawley
10.
Cancer Lett ; 129(1): 15-20, 1998 Jul 03.
Article in English | MEDLINE | ID: mdl-9714330

ABSTRACT

Metastasis is a characteristic and fatal feature of human malignancies. Its regulation is therefore of the utmost significance to clinicians. The present study was undertaken to determine whether a legume-derived protease inhibitor (PI) of trypsin/chymotrypsin, the field bean PI (FBPI), also has plasmin inhibitory activity and can inhibit pulmonary metastasis of B16F10 melanoma cells systemically injected into BDF1 mice. Two approaches to the problem were made. In the first, the melanoma cells were exposed to two different concentrations of the FBPI prior to their inoculation into animals. In the second, the mice were treated intraperitoneally with FBPI at a dose of 100 mg/kg body weight once daily for 10 days, the treatment being started soon after the systemic injection of the tumour cells. The study revealed that both modes of FBPI treatment could effectively block lung cell metastasis by the melanoma cells and that FBPI has plasmin blocking activity. Since urokinase type plasminogen activator and plasmin are known to play significant roles in tumour cell metastasis, the dose-dependent inhibitory effect of FBPI with antiplasmin activity on tumour cell metastasis suggests that its antimetastatogenic action is probably mediated through its plasmin inhibitory action.


Subject(s)
Lung Neoplasms/secondary , Melanoma, Experimental/pathology , Trypsin Inhibitors/pharmacology , Animals , Female , Lung Neoplasms/prevention & control , Mice , Mice, Inbred C57BL , Mice, Inbred DBA
11.
Biochemistry ; 37(19): 6636-44, 1998 May 12.
Article in English | MEDLINE | ID: mdl-9578547

ABSTRACT

Distances between the paclitaxel, colchicine, and exchangeable GTP binding sites on tubulin polymers have been probed using fluorescence spectroscopy. Techniques for measuring fluorescence resonance energy transfer (FRET) between fluorescent or chromophoric ligands for each binding site were employed. 2-Debenzoyl-2-(m-aminobenzoyl)paclitaxel (2-AB-PT) was the fluorophore ligand for the paclitaxel binding site; thiocolchicine, allocolchicine, and MDL 27048 were probes for the colchicine site, and 2'(or 3')-O-(trinitrophenyl)guanosine 5'-triphosphate (TNP-GTP) was the fluorophore ligand for the exchangeable GTP site. The distance between the colchicine and paclitaxel binding sites was determined with two different acceptor ligands in the colchicine site. An average distance distribution of 17 A was found in both cases. Energy transfer between 2-AB-PT bound to the paclitaxel site and TNP-GTP (acceptor) bound to the exchangeable GTP site was observed in the polymer. The average distance distribution between the fluorophores was 16.0 A, but the half-width of the distribution was large (17.9 A), which indicates that energy transfer between more than one donor-acceptor pair occurred in the system. One interpretation of this result is that 2-AB-PT serves as an energy transfer donor for two GTP sites, one contained on the same subunit and one on an adjacent protofilament. No FRET was observed between ligands bound to the colchicine and exchangeable GTP sites, indicating that the result of colchicine binding on the GTP region of beta-tubulin is a long range, allosteric effect. The results from these experiments are interpreted in terms of known structural features of microtubules.


Subject(s)
Colchicine/chemistry , Guanosine Triphosphate/chemistry , Paclitaxel/chemistry , Tubulin/chemistry , Animals , Binding Sites/drug effects , Cattle , Colchicine/metabolism , Energy Transfer/drug effects , Guanosine Triphosphate/metabolism , Guanosine Triphosphate/pharmacology , Ligands , Models, Molecular , Paclitaxel/metabolism , Spectrometry, Fluorescence , Trinitrobenzenes/chemistry , Trinitrobenzenes/pharmacology , Tubulin/metabolism
12.
Ear Nose Throat J ; 77(1): 40-3, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9473831

ABSTRACT

The objective of this study was to measure the effect of a single, preoperative 10 mg dose of dexamethasone on postoperative edema associated with rhinoplasty. This was a randomized, double-blind prospective study conducted in a military academic tertiary referral center. Twenty men, aged 18 to 45 years, were enrolled in the study over 28 months. All 20 men underwent rhinoplasty with osteotomy. Preoperative magnetic resonance imaging scans were obtained on the morning of surgery and postoperative scans were obtained within 48 hours. Postoperative edema was quantified as the difference in soft tissue thickness (mm) between the pre- and postoperative scans. Contrary to our expectations, the rhinoplasty patients who received dexamethasone had increased postoperative edema (p < 0.02) when compared to patients not receiving dexamethasone. This is the first objective, double-blind study that shows an increase in postoperative edema after rhinoplasty with a single preoperative dose of dexamethasone.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Dexamethasone/adverse effects , Edema/etiology , Nose Diseases/etiology , Rhinoplasty/adverse effects , Adolescent , Adult , Analysis of Variance , Anti-Inflammatory Agents/administration & dosage , Dexamethasone/administration & dosage , Double-Blind Method , Edema/diagnosis , Edema/prevention & control , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nose Diseases/diagnosis , Nose Diseases/prevention & control , Preoperative Care , Prospective Studies
13.
Eur J Biochem ; 249(1): 265-9, 1997 Oct 01.
Article in English | MEDLINE | ID: mdl-9363778

ABSTRACT

2-Methoxy-5-(2',3',4'-trimethoxy)-2,4,6-cycloheptatrien-1-one (MTC) is a colchicine analogue that lacks the B ring. 2-Methoxy-5-(2',4'-dimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MD) is an A-ring analogue of MTC, in which one methoxy group is replaced by a hydrogen atom. This paper describes the kinetic features of MDC binding to tubulin, and compares its behaviour with MTC to analyse the effect of the A-ring modification on the recognition process by tubulin. Binding is accompanied by a strong enhancement of MDC fluorescence and quenching of protein fluorescence. The kinetic and thermodynamic parameters were obtained from fluorescence stopped-flow measurements. The kinetics are described by a single exponential, indicating that this drug does not discriminate between the different tubulin isotypes. The observed pseudo-first-order rate constant of the fluorescence increase upon binding increases in a non-linear way, indicating that this ligand binds with a similar overall mechanism as colchicine and MTC, consisting of a fast initial binding of low affinity followed by a slower isomerisation step leading to full affinity. The K1 and k2 values for MDC at 25 degrees C were 540 +/- 65 M(-1) and 70 +/- 6 s(-1) respectively. From the temperature dependence, a reaction enthalpy change (deltaH(o)1) of the initial binding of 49 +/- 11 kJ/mol(-1) and an activation energy for the second step of 28 +/- 9 kJ/mol(-1) were calculated. Displacement experiments of bound MDC by MTC allowed the determination of a rate constant of reverse isomerisation of 0.60 +/- 0.07 s(-1) at 25 degrees C and the activation energy of 81 +/- 6 kJ/mol(-1). The overall binding constant was (6.3 +/- 0.2) x 10(4) M(-1) at 25 degrees C. Combination of these results with the kinetic parameters for association gives a full characterisation of the enthalpy pathway for the binding of MDC. The pathway of MDC is shown to differ considerably from that of MTC binding. Since its structural difference is located in ring A, this result indicates the use of ring A in the first step. The kinetics of the binding of MDC in the presence of some A-ring colchicine analogues (podophyllotoxin, 3',4',5'-trimethoxyacetophenone and N-acetylmescaline) and a C-ring analogue (tropolone methyl ether) suggest that the A and C rings are involved in the binding of MDC.


Subject(s)
Anisoles/chemistry , Anisoles/metabolism , Colchicine/analogs & derivatives , Cycloheptanes/chemistry , Cycloheptanes/metabolism , Tubulin/metabolism , Animals , Binding Sites , Binding, Competitive , Colchicine/chemistry , Colchicine/metabolism , In Vitro Techniques , Kinetics , Ligands , Molecular Structure , Protein Binding , Swine , Thermodynamics , Tropolone/analogs & derivatives , Tropolone/chemistry , Tropolone/metabolism , Tubulin/chemistry
14.
J Behav Med ; 20(1): 67-83, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9058180

ABSTRACT

In the context of sedentary middle-aged adults, the present study examined the relationships among domain-specific and global levels of self-esteem over the course of a 20-week exercise program. Additionally, the roles played by physical fitness, body composition, self-efficacy, and exercise participation as possible contributors to changes in physical self-worth were examined. Significant improvements in self-esteem at all levels were discovered with global esteem, physical self-worth, and perceptions of physical condition and attractive body increasing. Tests of the hierarchical structure of self-esteem showed greater improvements in physical condition and physical self-worth than global esteem and the relationships between global esteem and subdomain levels were shown to be mediated by physical self-worth. Hierarchical regression analyses showed changes in ratings of importance to have little impact on changes in physical self-worth. Both changes in efficacy and aerobic capacity were demonstrated to account for modest but significant variation in physical self-esteem. Results are discussed in terms of contemporary models of self-esteem, potential mediators of exercise effects on esteem, and the need to measure the constructs of interest appropriately.


Subject(s)
Exercise/psychology , Physical Fitness/psychology , Self Concept , Body Image , Female , Humans , Male , Middle Aged , Multivariate Analysis , Psychological Theory , Regression Analysis
15.
J Case Manag ; 6(4): 158-61, 1997.
Article in English | MEDLINE | ID: mdl-9644406

ABSTRACT

Older adults are underrepresented as recipients of mental health services, despite evidence that preventive interventions are effective and complement physical health interventions. Barriers to using these services include the stigma associated with mental health problems, lack of trained professionals and general barriers of availability and accessibility in rural service delivery. Case managers can play an important role in breaking down some of these barriers and assisting older adults to access t-ese services. Several outreach and educational models have been developed that are replicable and available to case managers.


Subject(s)
Aging , Case Management/organization & administration , Community Mental Health Services/organization & administration , Health Services Accessibility/organization & administration , Health Services for the Aged/organization & administration , Rural Health Services/organization & administration , Aged , Humans
16.
Biochem J ; 327 ( Pt 3): 685-8, 1997 Nov 01.
Article in English | MEDLINE | ID: mdl-9581543

ABSTRACT

Colchicide (IDE) is a colchicine (COL) analogue in which the C-10 methoxy group is replaced by a hydrogen atom. Its binding to tubulin is accompanied by a quenching of the protein fluorescence. The fluorescence decrease shows a monoexponential time dependence. The observed rate constant increases in a non-linear way with the total concentration of IDE, allowing the determination of a binding constant for an initial binding site (K1=5300+/-300 M-1) and the rate constant for the subsequent isomerization (k2=0.071+/-0.002 s-1) at 25 degrees C. The rate constant, k-2, for the reversed isomerization can be determined by displacement experiments. Despite the minor alteration of the C-ring substituent, the kinetic and thermodynamic parameters of binding are substantially different from those of COL itself, for both steps. In isocolchicine (ISO) the carbonyl oxygen atom and the methoxy groups of the C-ring have been interchanged. Its binding to tubulin only results in small fluorescence and absorbance changes. Therefore competition experiments with MTC [2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4, 6-cycloheptatrien-1-one] were performed. ISO competes rapidly and with low affinity with MTC. Fluorimetric titrations of tubulin with MDL (MDL 27048 or trans-1-(2,5 dimethoxyphenyl)-3-[4-(dimethylamino)phenyl]-2-methyl-2-propen-1 -one) in the presence and absence of ISO give evidence for the existence of a second, slow-reacting low-affinity site for ISO that is not accessible to MTC or MDL. The relevance of these results for the recognition of COL is analysed.


Subject(s)
Colchicine/analogs & derivatives , Colchicine/metabolism , Tubulin/metabolism , Animals , Isomerism , Kinetics , Ligands , Protein Binding , Spectrometry, Fluorescence , Swine , Thermodynamics
17.
Biochemistry ; 35(45): 14173-83, 1996 Nov 12.
Article in English | MEDLINE | ID: mdl-8916903

ABSTRACT

A fluorescent derivative of paclitaxel, 2-debenzoyl-2-(m-aminobenzoyl)paclitaxel (2-AB-PT), has been prepared. 2-AB-PT induces microtubule assembly in vitro, but is about 3-fold less potent than paclitaxel itself. The absorption and emission characteristics of 2-AB-PT were analyzed as a function of solvent. It was found that both spectra were perturbed by specific solvent effects when the solvent contained a hydrogen bond donor. The absorption and fluorescence spectra of 2-AB-PT bound to microtubules could not be mimicked by a single solvent, but the absorption and emission maxima of the tubulin-bound species could be duplicated by a solvent mixture of DMSO and water. These results indicate that the fluorophore binding site on the microtubule is in an environment of intermediate polarity that is accessible to a hydrogen bond donor in the vicinity of the m-amino group. In addition, tubulin fluorescence is quenched in the 2-AB-PT/microtubule complex, and energy transfer from tubulin to 2-AB-PT is apparent. These results indicate that substituents on the C-2 position of paclitaxel associate with tubulin when bound to the microtubule. 2-AB-PT binding to microtubules was quantitatively analyzed by fluorescence titrations. Two classes of binding sites for 2-AB-PT on microtubules were found. The high affinity site has an apparent association constant (K1app) of 2.0 (+/- 0.9) x 10(7) M-1 and an apparent binding stoichiometry (n1app) of 0.8 (+/- 0.1) sites/tubulin dimer in the microtubule. The apparent association constant for the lower affinity site is about 100-fold less than that of the higher affinity site (K2app = 2.1 (+/- 0.7) x 10(5) M-1), and the stoichiometry of the lower affinity site or class of sites (n2app) was found to be 1.3 +/- 0.1. Paclitaxel blocked 2-AB-PT binding to the high affinity site. No binding of 2-AB-PT to unassembled tubulin was observed, but the emission spectrum of 2-AB-PT in the presence of the tubulin-colchicine complex resembled the emission spectrum of the ligand bound to microtubules. It was previously shown that paclitaxel can induce GTPase activity in the tubulin-colchicine complex, indicating that paclitaxel can bind to unassembled tubulin in its complex with colchicine [Carlier, M.-F., & Pantaloni, D. (1983) Biochemistry 22, 4814-4822]. Rigorous characterization of the aggregation state of the protein under these conditions demonstrates that 2-AB-PT is also capable of binding to the tubulin-colchicine complex.


Subject(s)
Colchicine/chemistry , Microtubules/chemistry , Paclitaxel/analogs & derivatives , Paclitaxel/chemistry , Taxoids , Tubulin/chemistry , Animals , Binding, Competitive , Cattle , Cell-Free System , Fluorescent Dyes , Hydrogen Bonding , Solvents , Spectrometry, Fluorescence , Structure-Activity Relationship , Ultracentrifugation
18.
J Gerontol B Psychol Sci Soc Sci ; 50(5): P229-35, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7656072

ABSTRACT

The present study examined the relationships among body composition, exercise participation, and physique anxiety in a sample of middle-aged, formerly sedentary males and females. Study variables were assessed prior to and following participation in a 20-week aerobic exercise program. Subjects reduced their weight, body fat, and body circumferences over the course of the program, as well as physique anxiety. Multivariate and hierarchical regression analyses revealed females and those subjects between 45 and 54 years to be significantly more physique-anxious than their older counterparts. Being female and failing to reduce hip circumference were significantly related to postprogram physique anxiety. Although those who exercised more frequently tended to be less physique-anxious in correlational analyses, exercise frequency was a nonsignificant predictor when controlling for body composition. Thus, it appears that body image is a concern across the female age spectrum rather than the sole province of undergraduate females.


Subject(s)
Anxiety , Body Image , Exercise , Middle Aged/psychology , Anthropometry , Body Composition , Female , Humans , Male , Weight Loss
19.
Prev Med ; 24(4): 319-28, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7479620

ABSTRACT

BACKGROUND: Whereas self-efficacy expectations have been identified as important determinants of exercise participation patterns, little empirical work that examines efficacy expectations as outcomes of exercise participation or their theoretical relationship to other psychological outcomes associated with exercise has been conducted. In the context of middle-aged males and females, the present study attempted to integrate social cognitive and impression management perspectives with respect to anxiety associated with exercise. METHODS: Formerly sedentary subjects participated in a 5-month exercise program with assessments of physique anxiety, efficacy, outcome expectations, and anthropometric variables prior to and following the program. RESULTS: Both acute bouts and long-term participation in exercise resulted in significant increases in self-efficacy. In turn, these changes in efficacy and initial positive outcome expectations were significant predictors of reductions in physique anxiety, even when controlling for the influence of gender and reductions in body fat, weight, and circumferences. CONCLUSIONS: The findings are discussed in terms of the implications for structure and content of exercise environments and the utility of the proposed theoretical integration. Strategies for enhancing beliefs regarding health and fitness outcomes associated with exercise rather than appearance outcomes may be required to maximize reductions in negative body image.


Subject(s)
Exercise/psychology , Self Concept , Anthropometry , Anxiety/psychology , Bicycling , Body Image , Exercise Test , Female , Health Behavior , Humans , Jogging , Male , Middle Aged , Motivation , Multivariate Analysis , Physical Fitness , Regression Analysis , Sex Factors , Walking
20.
J Gerontol Nurs ; 21(6): 39-45, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7782577

ABSTRACT

1. Nurses working with confused older adults in clinical settings need improved communication techniques. 2. Reality orientation is commonly used in nursing homes with disoriented persons; experienced nurses, however, often find it meets with withdrawal, vegetation or increasing hostility. 3. Validation strategies are communication techniques which are specifically matched to a particular stage of confusion. 4. When validation techniques are appropriately matched to confusional stage the effectiveness of the intervention can be significantly improved.


Subject(s)
Cognition Disorders/nursing , Communication , Geriatric Nursing/methods , Aged , Aged, 80 and over , Cognition Disorders/psychology , Humans
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