Nuclear Spin Relaxation in Viscous Liquids: Relaxation Stretching of Single-Particle Probes.

Spin-lattice relaxation rates R1(ω,T), probed via high-field and field-cycling nuclear magnetic resonance (NMR), are used to test the validity of frequency-temperature superposition (FTS) for the reorientation dynamics in viscous liquids. For several liquids, FTS is found to apply so that master curves can be generated. The susceptibility spectra are highly similar to those obtained from depolarized light scattering (DLS) and reveal an excess wing. Where FTS works, two approaches are suggested to access the susceptibility: (i) a plot of deuteron R1(T) vs the spin-spin relaxation rate R2(T) and (ii) a plot of R1(T) vs an independently measured reference time τref(T). Using single-frequency scans, (i) allows one to extract the relaxation stretching as well as the NMR coupling constant. Surveying 26 data sets, we find Kohlrausch functions with exponents 0.39 < ßK ≤ 0.67. Plots of the spin-spin relaxation rate R2─rescaled by the NMR coupling constant─as a function of temperature allow one to test how well site-specific NMR relaxations couple to a given reference process. Upon cooling of flexible molecule liquids, the site-specific dynamics is found to merge, suggesting that near Tg the molecules reorient essentially as a rigid entity. This presents a possible resolution for the much lower stretching parameters reported here at high temperatures that contrast with the ones that were reported to be universal in a recent DLS study close to Tg. Our analysis underlines that deuteron relaxation is a uniquely powerful tool to probe single-particle reorientation.

Nerve-Langerhans cell interactions in diabetes and aging.

Cutaneous infections are a leading cause of hospitalization of diabetic patients. Langerhans cells (LCs) are antigen-presenting cutaneous dendritic cells that protect against infections, and effects of diabetes and aging on these cells are unclear. We examined LCs in footpads of rats with streptozotocin-induced diabetes at 3 months of age following 4 weeks of diabetes, and at 6 months following 16 weeks of diabetes. Immunostaining of LCs using the selective marker protein langerin showed cutaneous LC composition increased between 3 and 6 months of age owing to increased LC numbers and size in control rats. In diabetic rats, LC numbers increased with age but, unlike 6 month old controls, cell size did not, suggesting that diabetes impairs the increase in cell size that is a hallmark of LC maturation. Diabetes reduced LC numbers after 4 weeks and numbers and sizes following 16 weeks. We examined the relation between LC and innervation and found that, while axon density decreased with aging, it was not affected by 16 weeks of diabetes. However, LCs expressing the neuronal marker PGP9.5 represented a source of error in axonal counts. These findings support the hypothesis that diabetes substantially impacts LC proliferation and maturation independent of effects on cutaneous innervation. Accordingly, the interactions of diabetes and aging on LCs may be important factors in predisposing diabetic patients to cutaneous ulcers and infections.

Evaluation of velvet bean meal as an alternative protein ingredient for poultry feed.

The effect of certain simple and cost-effective processing methods on the nutritional and anti-nutritional properties of seed materials of an under-utilized food legume, Mucuna pruriens (L.) DC. var. utilis (Wall. ex Wight) Baker ex Burck (velvet bean, VB), collected from Valanadu, Kerala, India was analyzed in experiment 1. The raw VB seeds were found to contain appreciable levels of crude protein (263.2 g/kg dry matter (DM)); ether extract (79.6 g/kg DM); crude fiber (95.8 g/kg DM) and ash content (38.4 g/kg DM). Among the different treatments used, soaking in sodium bicarbonate solution + autoclaving was more effective in reducing maximum levels of various anti-nutritional compounds of VB seeds. Furthermore, in experiment 2, the effect of inclusion of different levels of velvet bean meal (VBM; subjected to soaking in sodium bicarbonate solution + autoclaving) as an alternative protein source in poultry feed on the growth performance of commercial-type broiler birds was investigated. The results indicate that the inclusion of VBM up to the 40% level exhibited better growth performance of the broiler birds such as feed intake, body weight gain, feed conversion ratio and protein efficiency ratio in both the starter and finisher phases.

Preliminary Phytochemical Screening and Antimicrobial Studies of Lantana indica Roxb.

The aim of the present study was to investigate the antimicrobial and preliminary phytochemical properties of Lantana indica Roxb. The aqueous and organic solvent (ethyl acetate and methanol) extracts from the leaves of Lantana indica (Verbenaceae) were tested against Staphylococcus aureus, Bacillus subtilis, Steptococcus pyrogens, Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Aspergillus niger and Candida albicans by agar well diffusion method. The results showed promising antibacterial activity against the tested bacteria. Among these, methanol and aqueous extracts were found to possess a more potent inhibitory effect when compared to the ethyl acetate extract. Preliminary phytochemical analysis of extracts revealed the presence of antimicrobial compounds such as carbohydrates, proteins, tannins and flavonoidal glycosides. The result of this study validates the use of methanol and aqueous extract of this species in ethnomedicine, favouring the isolation of antibacterial agents from the leaf extract of Lantana indica.

Clinical application of multidetector CT angiography and perfusion imaging in acute stroke.

This article illustrates clinical application of 64 Detector CT Angiography and Perfusion of the Brain in the triage of acute stroke in patients with a view to thrombolytic therapy. CTA and perfusion of the Brain is less expensive and relatively widely available compared to Magnetic Resonance Imaging. This technique is likely to be widely used in the triage of the acute stroke patient in the near future.

Preliminary phytochemical screening of some Indian Medicinal Plants.

Alkaloids, tannins, saponins, steroid, terpenoid, flavonoids, phenolic compounds and cardie glycoside distribution in five medicinal plants belonging to different families were assessed and compared. The medicinal plants investigated were Asteracantha longifolia (L.) Nees, Psassiflora edulis Sims, Berberis tinctoria Lesch, Sphaeranthus indicus Linn, and Solanum trilobatum Linn. All the plants were found to contain Phenols, Cardiac glycosides, Steroids, Saponins and Tannin except for the absence of flavonoids and Terpenoids in A. longifolia (L.)Nees and Alkaloids in, P edulis Sims, A.longifolia (L.)Nees, B. tinctoria Lesch and S. indicus Linn. respectively. The significance of the plants in traditional medicine and the importance of the distribution of these chemical constituents were discussed with respect to the role of these plants in ethnomedicine in India.

Antibacterial activity of Eupatorium glandulosum leaves.

Antibacterial screening of petroleum ether, chloroform, ethyl acetate, methanol and aqueous extracts of Eupatorium glandulosum leaves exhibited a broad spectrum of inhibitory activity against Gram (+) and Gram (-) pathogenic bacteria.

ANTIMICROBIAL POTENTIAL OF VITEX TRIFOLIA Linn.

Vitex trifolia (Local name - Nirnocchi, sirunocchi) is well known for its medicinal property. The present investigation encompasses evaluation of antibacterial potential of Vitex trifolia against certain pathogenic bacterial strains. Preliminary phytochemical studies were also made and results are given.

From strong to fragile glass formers: secondary relaxation in polyalcohols.

We have studied details of the molecular origin of slow secondary relaxation near T(g) in a series of neat polyalcohols by means of dielectric spectroscopy and (2)H NMR. From glycerol to threitol, xylitol, and sorbitol the appearance of the secondary relaxation changes gradually from a wing-type scenario to a pronounced beta peak. It is found that in sorbitol the dynamics of the whole molecule contributes equally to the beta process, while in glycerol the hydrogen bond forming OH groups remain rather rigid compared to the hydrogens bonded to the carbon skeleton.

Prognostic value of dobutamine stress technetium-99m-sestamibi single-photon emission computed tomography myocardial perfusion imaging: stratification of a high-risk population.

OBJECTIVES: This work was undertaken to define the intrinsic cardiac risk of the patient population referred for dobutamine stress perfusion imaging and to determine whether dobutamine technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography (SPECT) imaging is capable of risk stratification in this population. BACKGROUND: In animal models, dobutamine attenuates the myocardial uptake of (99m)Tc-sestamibi resulting in underestimation of coronary stenoses. Therefore, we hypothesized that the prognostic value of dobutamine stress (99m)Tc-sestamibi SPECT myocardial perfusion imaging might be impaired, owing to reduced detection of coronary stenoses. METHODS: We reviewed the clinical outcome of 308 patients (166 women, 142 men) who underwent dobutamine stress SPECT (99m)Tc-sestamibi imaging at our institution from September 1992 through December 1996. RESULTS: During an average follow-up of 1.9 +/- 1.1 years, there were 33 hard cardiac events (18 myocardial infarctions [MI] and 15 cardiac deaths) corresponding to an annual cardiac event rate of 5.8%/year, which is significantly higher than the event rate for patients referred for exercise SPECT imaging at our institution (2.2%/year). Event rates were higher after an abnormal dobutamine (99m)Tc-sestamibi SPECT study (10.0%/year) than after a normal study (2.3%/year) (p < 0.01), even after adjusting for clinical variables. In the subgroup (n = 29) with dobutamine-induced ST-segment depression and abnormal SPECT imaging, the prognosis was poor, with annual cardiac death and nonfatal MI rates of 7.9% and 13.2%, respectively. CONCLUSIONS: Patients referred for dobutamine perfusion imaging are a high-risk population, and dobutamine stress (99m)Tc-sestamibi SPECT imaging is capable of risk stratification in these patients.

Overexpression of stably transfected human glutathione S-transferase P1-1 protects against DNA damage by benzo[a]pyrene diol-epoxide in human T47D cells.

The (+)-anti enantiomer of benzo[a]pyrene-7,8-dihydrodiol-9, 10-epoxide (BPDE) is a potent mutagenic and carcinogenic metabolite of benzo[a]pyrene (BP), and a major fraction is conjugated with glutathione in vivo. The chemopreventive role of glutathione S-transferases (GSTs) in protecting against covalent modification of DNA and other cellular macromolecules by BPDE was modeled in human T47D and MCF-7 cell lines previously stably transfected with human GSTpi1 (hGSTP1). Cells were exposed to [3H]BPDE (30-600 nM). Dose-response experiments indicated that the high level of expression of hGSTP1-1 in the T47Dpi cell line (4411 +/- 183 milliunits/mg of cytosolic protein, using 1-Cl-2,4-dinitrobenzene as substrate), resulted in 70-90% reduction in the covalent 3H-adduct formation in DNA or RNA isolated from the GSTP1-transfected T47Dpi cell line. The lower level of hGSTP1-1 expression in the transfected MCF-7 cell line (91 milliunits/mg) provided only marginal protection against [3H]BPDE adduct formation and did not affect sensitivity to BPDE-induced cytotoxicity. Protection against BPDE-induced cytotoxicity was observed only in the T47Dpi cell line, which had an IC50 value 5.8-fold greater than that of the T47Dneo control cell line. Measurement of glutathione conjugates of BPDE indicated that the total conjugation was 5-fold higher in the GSTpi-transfected T47D line, most of which was exported into the culture medium over the 20-min exposure period. These results indicate that hGSTP1-1 protects effectively against DNA and RNA modification by BPDE, but moderate to high level expression may be required for strong protection against BPDE-induced genotoxicity and cytotoxicity.

Chemoprotective functions of glutathione S-transferases in cell lines induced to express specific isozymes by stable transfection.

The authors have shown that expression of mGSTM1-1 or hGSTP1-1 in MCF-7 cells protects against DNA alkylation by 4-nitroquinoline-1-oxide (NQO) in an isozyme-specific manner and is commensurate with relative specific activity. Expression of GSTs also conferred protection against both DNA strand breaks and sister-chromatid exchange induced by NQO. Interestingly, GST expression did not protect against NQO cytotoxicity in transfected MCF-7 cell lines, although resistance to NQO cytotoxicity was observed in a T47D pi transfectant line, expressing much higher specific activity of the transfected hGSTP1-1. However, high level expression of hGSTP1-1 or mGSTM1-1 in V79 transfectants did not confer resistance to cytotoxicity, indicating that expression of GST alone is not sufficient. The authors have also shown protection against AFB1 in cell lines expressing transfected rat CYP2B1 (V79MZr2B1) and transfected mGST-Yc (mGSTA3-3). Protection was observed against both alkylation of DNA (3-fold) by [3H]AFB1 and against AFB1 cytotoxicity (7-fold). Similarly, V79MZr1A1 cells that express CYP1A1 and either transfected human or murine GSTP1-1 (< 5000 mIU/mg, CDNB) exhibited > 70% decrease in covalent labeling of total nucleic acids by [3H]BPDE. However, no protection against the cytotoxicity of BPDE was conferred by expression of hGSTP1-1. Overall, these results indicate that in some (NQO or BPDE), but not all (AFB1) cases, protection by GST expression against DNA damage is more effective than protection against cytotoxicity. In addition, there is evidence to indicate that additional factor(s) other than high GST isozyme expression level and good substrate efficacy affect the degree of protection against cytotoxicity of reactive electrophiles. This includes the differential protection against NQO cytotoxicity in T47D pi, but not V79 Xh pi-33 cells and also the recent studies which showed that expression of the MRP GS-X conjugate efflux transporter confers synergistic protection against NQO cytotoxicity when co-expressed with transfected human GSTP1-1 in MCF-7 cells. Thus, protective efficacy conferred by GST expression can vary with different cellular targets and/or experimental end-points, as well as with variations in relative specific activity or in different cellular phenotypic contexts.

Phase II study of vinorelbine by oral route (in a hard gelatine capsule) for metastatic breast cancer patients. A trial of the phase I/II study group of the Association for Medical Oncology of the German Cancer Society.

17 patients with advanced low-risk breast carcinoma not previously pretreated by cytostatic agents were treated by Vinorelbine (VIN), 5'-Nor-anhydro-vinblastine, a new semisynthetic compound of the vinca alkaloid series. A dose of 130 mg per week was administered in a hard gelatine formulation for at least eight weeks. Out of 15 evaluable patients, no complete or partial remission was observed. However, there were 9 patients (60%) achieving no change and tumor stabilization, respectively, lasting for a median of 3.0 months. Main toxicities were leukopenia (17.7%, WHO grade 3-4), nausea and vomiting (17.7%, WHO grade 3-4), and acute diarrhea (70.6%, WHO grade 1-4). Thus, further trials with the oral medication used for this study are not recommended.

Permeability of abnormal rat skin.

We have measured the permeability (to water in vivo and in vitro) and examined the histology of rat skin after mild, superficial epidermal alterations: scalpel blade (Cat I) and sandpaper abrasion (Cat II), adhesive tape stripping (Cat III), and suction blister top removal (Cat IV). After each alteration the permeability was increased (Cat IV greater than Cat III greater than Cat II greater than Cat I) and the epidermis regenerated in a distinct, biphasic manner, as indicated by the permeability and histology data. The rapid first phase corresponded with a decrease in permeability and the development of a scab (the greater the increased permeability, the slower the rate of regeneration). The second phase was more gradual (with a similar rate of regeneration after each alteration) and corresponded with a return to normal permeability and gradual thickening of the stratum corneum (return to normal corresponded with degree of initial stratum corneum removal). A similar, though slower biphasic regeneration has been reported to occur in human skin following similar types of alterations. It is concluded that abnormal rat skin is suitable for quantifying absorption through abnormal epidermis.

Intrabronchial instillation of paraquat in rats: lung morphology and retention study.

Various amounts of paraquat (10(-5) to 10(-12) g) in 0.1 ml saline were instilled directly into the left bronchus of male adult rats. Gravimetric, macroscopic, and microscopic studies on the left lobe of the lung showed that 10(-5) g of paraquat produced lung oedema and macroscopic lesions two and 14 days after doing. The pathology of the lung was similar to that seen after systemic poisoning. When 10(-6) g of paraquat was instilled, some animals developed lung oedema and macroscopic lesions. Microscopic examination showed subtle changes in the parenchyma of the lung. With amounts of paraquat equal to or less than 10(-7) g (doses as little as 10(-12) g were used), no changes in the lung were seen. This is contrary to published accounts in which amounts as low as 10(-12) g (1 Pg) were reported to cause acute damage to the rabbit lung. When 3H paraquat was instilled into the left lobe (doses of 10(-5) to 10(-10) g were used), the loss of paraquat from the lung was biphasic. The initial half-life was less than one hour. The secondary phase obeyed first-order kinetics, and the half-life was dependent on the dose of paraquat instilled. This half-life was as short as 11 hours when 10(-5) g paraquat was instilled and was 76 hours after the instillation of 10(-10) g paraquat. The decrease in the half-life of the secondary phase with increasing doses of paraquat is possibly associated with the production of oedema or lung cell damage, or both. After the instillation of 10(-8) g 3H paraquat, the initial half-life was less than 15 minutes, and paraquat was detected in the urine and plasma at that time. This suggests that 50% of the instilled paraquat was rapidly absorbed from the lung into the plasma.