Nanogoldpharmaceutics (i) The use of colloidal gold to treat experimentally-induced arthritis in rat models; (ii) Characterization of the gold in Swarna bhasma, a microparticulate used in traditional Indian medicine

Nanosized gold particles (27 +/− 3 nm) have been proven to be effective in ameliorating the symptoms of mycobacterial-, collagen- and pristane-induced arthritis in rat models. This contrasts with the drug sodium aurothiomalate that was only effective against mycobacterial-induced arthritis but not to the same extent as Au⁰. Gold in the traditional Indian Ayurvedic medicine,Swarna bhasma (gold ash), has been characterized as globular particles of gold with an average size of 56–57 nm.     

Integrated fertilizer requirements of groundnut-wheat cropping system

Investigations were carried out in a long term field experiment from 1976 to 1982, on a loamy sand soil to find out the fertilizer requirements of groundnut and wheat grown in fixed rotation. Application of 26 kgP/ha to wheat alone was found to be sufficient for both wheat and succeeding groundnut. Application of phosphorus to both wheat and groundnut did not result in extra beneficial effect over P application to wheat alone. However, application of 26 kg P/ha to groundnut alone was not sufficient for succeeding wheat. There was no response from K application (25 kg K/ha) in either of these two crops. Increasing the dose of N from 50–150 kg/ha to wheat significantly increased the grain yield of wheat but the pod yield of succeeding groundnut were markedly lowered. Response of wheat to 150 kg N/ha was more marked when P was also applied to wheat and response was less when P was applied to preceding groundnut alone. Zinc application at 6.25 kg/ha to wheat alone resulted in significant increase in grain yield of wheat and pod yield of succeeding groundnut.     

Incremental value of prognostic testing in patients with known or suspected ischemic heart disease: a basis for optimal utilization of exercise technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography

OBJECTIVES: This study assessed the incremental prognostic implications of normal and equivocal exercise technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) and sought to determine its incremental prognostic value, impact on patient management and cost implications. BACKGROUND: The prognostic implications of Tc-99m sestamibi SPECT are not well defined, and risk stratification using this test has not been explored. METHODS: We studied 1,702 patients referred for exercise Tc-99m sestamibi SPECT who were followed up for a mean (+/- SD) of 20 +/- 5 months. Patients with previous percutaneous transluminal coronary angioplasty or coronary artery bypass surgery were excluded. The SPECT studies were assessed using semiquantitative visual analysis. Cardiac death and myocardial infarction were considered "hard" events, and coronary angioplasty and bypass surgery > 60 days after testing were considered "soft" events. RESULTS: Of the 1,702 patients studied, 1,131 had normal or equivocal scan results. A total of 10 events occurred in this group (1 cardiac death and 1 myocardial infarction [0.2% hard events]; 4 coronary angioplasty and 4 bypass surgery procedures [0.7% soft events]). The rates of hard events and referral to catheterization after SPECT were similarly low in patients with a low (< 0.15), intermediate (0.15 to 0.85) and high (> 0.85) post-exercise treadmill test (ETT) likelihood of coronary artery disease. With respect to scan type, patients with normal, probably normal or equivocal scan results had similarly low hard event rates. In the 571 patients with abnormal scan results, there were 43 hard events (7.5%) and 42 soft events (7.4%) (p < 0.001 vs. 1,131 patients with normal scan results for both). When the complete spectrum of scan responses was considered, SPECT provided incremental prognostic value in all patient subgroups analyzed. However, the nuclear scan was cost-effective only in patients with interpretable exercise ECG responses and an intermediate to high post-ETT likelihood of coronary artery disease and in those with uninterpretable exercise ECG responses and an intermediate to high pre-ETT likelihood of coronary artery disease. CONCLUSIONS: Normal or equivocal exercise Tc-99m sestamibi study results are associated with a benign prognosis, even in patients with a high likelihood of coronary artery disease. Although incremental prognostic value is added by nuclear testing in all patient subgroups, a testing strategy incorporating nuclear testing proved to be cost-effective only in the groups with an intermediate to high likelihood of coronary artery disease before scanning.     

Effects of pH on rhodopsin photointermediates from lumirhodopsin to metarhodopsin II

Time-resolved absorption difference spectra of membrane suspensions of bovine rhodopsin at pH 5, 6, 7, 8, 9, and 10 were collected in the time range from 1 micro s to 200 ms after laser photolysis with 7-ns pulses of 477-nm light. The data were analyzed using singular value decomposition (SVD) and global exponential fitting. At pH 7 the data agree well with previously obtained data (Thorgeirsson et al. (1993) Biochemistry 32, 13861-13872) with fits improved at all pH's by inclusion of a small component due to an absorbance change caused by rotational diffusion which is detectable even at magic angle polarization. A "square scheme" suggested to best explain the previous data, which involves two branches following decay of the lumi intermediate with pathways (1) lumi --> MI480 right harpoon over left harpoon MII and (2) lumi right harpoon over left harpoon MI380 --> MII, could be confirmed throughout the entire pH range. However, to account for the increased rate of the MII --> MI480 reaction in path 1 for rising pH values, we propose that the MII in the square scheme consists of deprotonated MII and protonated MIIH+ forms in rapid equilibrium with each other, resulting in an extended square scheme and increasing the number of 380-nm products from two to three. In addition to the kinetic processes described by the extended square scheme, above pH 8 fast ( approximately 10 micro s) and slow ( approximately 50 ms) components were found. The fast component was assigned to the decay of a blue-shifted lumi intermediate, and the slow component, resolvable only at pH 10, was assigned to formation of a 450 nm absorbing photoproduct.     

Epidemiology of infection with Epstein-Barr virus types 1 and 2: lessons from the study of a T-cell-immunocompromised hemophilic cohort

In apparent contrast to earlier work on Epstein-Barr virus (EBV) carriage in the general Caucasian population, in vitro virus isolations from human immunodeficiency virus (HIV)-positive male homosexual cohorts have shown frequent examples of multiple EBV infection and an overall prevalence of type 2 EBV strains exceeding 30%. Here we ask to what extent these findings might hold true in another T-cell-immunocompromised cohort, HIV-positive hemophilic patients. Resident EBV strains were rescued within lymphoblastoid cell lines derived from the blood and throat washings of 39 such individuals, using the same in vitro protocols of virus isolation as for the homosexual cohort. A mean of 19 independent cell lines was made per patient, and in each case the resident virus was characterized by PCR-based viral genomic analysis and by immunoblotting to reveal the viral "EBNAprint." By these criteria a significant proportion (14 of 39) of the hemophilic cohort carried more than one EBV strain, suggesting that T-cell impairment does indeed sensitize virus carriers to reinfection with new strains of exogenously transmitted virus. However, the overall incidence of type 2 EBV infection was 10%, which is close to that observed in the earlier work with healthy carriers and substantially lower than that seen in HIV-positive homosexuals. We infer that type 2 EBV is relatively rare in the general Caucasian population but has become endemic in the homosexual community.     

Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography

BACKGROUND: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding. METHODS: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons. RESULTS: Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48). CONCLUSIONS: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.     

Conformations and folding of lysozyme ions in vacuo

Proton transfer reactivity of isolated charge states of the protein hen egg-white lysozyme shows that multiple distinct conformations of this protein are stable in the gas phase. The reactivities of the 9+ and 10+ charge state ions, formed by electrospray ionization of "native" (disulfide-intact) and "denatured" (disulfide-reduced) solutions, are consistent with values calculated for ions in their crystal structure and fully denatured conformations, respectively. Charge states below 8+ of both forms, formed by proton stripping, have similar or indistinguishable reactivities, indicating that the disulfide-reduced ions fold in the gas phase to a more compact conformation.     

Tests for comparing images based on randomization and permutation methods

Tests comparing image sets can play a critical role in PET research, providing a yes-no answer to the question "Are two image sets different?" The statistical goal is to determine how often observed differences would occur by chance alone. We examined randomization methods to provide several omnibus test for PET images and compared these tests with two currently used methods. In the first series of analyses, normally distributed image data were simulated fulfilling the requirements of standard statistical tests. These analyses generated power estimates and compared the various test statistics under optimal conditions. Varying whether the standard deviations were local or pooled estimates provided an assessment of a distinguishing feature between the SPM and Montreal methods. In a second series of analyses, we more closely simulated current PET acquisition and analysis techniques. Finally, PET images from normal subjects were used as an example of randomization. Randomization proved to be a highly flexible and powerful statistical procedure. Furthermore, the randomization test does not require extensive and unrealistic statistical assumptions made by standard procedures currently in use.