Elemental analysis using radioisotope excited X-ray fluorescence

The measurement of energies and intensities of fluorescent X-rays emitted from a given material when atoms are bombarded with suitable projectiles like electrons, protons, α-particles or protons has been successfully used for non-destructive elemental analysis. Use of radioisotopes as a source of exciting radiation in combination with high resolution semiconductor detectors in X-ray fluorescence has found wide applications in elemental analysis. Energy dispersive X-ray fluorescence is useful in multi-elemental analysis, and thus finds a wide variety of applications. A radioisotope excited X-ray fluorescence spectrometer consisting of a 30 mm² × 3 mm Si(Li) detector having a resolution of 200 eV at 5.9 keV coupled to a System 100 Canberra multichannel analyser has been used. A side source geometry using 20 mCi ¹⁰⁹Cd source together with PC AXIL software have been used for the study of environmental and geological samples in Botswana.     

Effect of tryptophan on hepatic polyribosomal disaggregation due to hypertonic sodium chloride.

The effect of tryptophan on the disaggregation of hepatic polyribosomes and on the inhibition of hepatic protein synthesis in rats due to the administration of hypertonic NaCl solutions was studied. Overnight-fasted rats were given by stomach tube or intraperitoneally hypertonic (6.2 to 10.7 per cent) NaCl alone or with 30 mg. of L-tryptophan and were killed 30 minutes later. The hypertonic NaCl treated rats revealed marked hepatic polyribosomal disaggregation and inhibition of hepatic protein synthesis (in vitro incorporation of 14C-leucine into proteins). Rats that received tryptophan alone or in a complete amino acid mixture in addition to hypertonic NaCl revealed a marked improvement in the patterns of hepatic polyribosomes and an increase in in vitro hepatic protein synthesis over that in hypertonic NaCl treated rats. The incorporation of 14C-orotate in hepatic messenger RNA (peak appearing between the 4 S and 18 S RNA fractions) associated with hepatic polyribosomes was studied. Administration of hypertonic NaCl alone caused a decrease in incorporation into hepatic messenger RNA whereas administration of hypertonic NaCl plus tryptophan caused an increase in incorporation into hepatic messenger RNA. Thus, tryptophan appears to cause an increase in hepatic messenger RNA as well as to prevent to a great extent the hepatic polyribosomal disaggregation and the inhibition of hepatic protein synthesis due to hypertonic NaCl.     

Effect of tryptophan on hepatoma and host liver of rats: Influence after treatment with hypertonic sodium chloride and carbon tetrachloride

Female inbred Buffalo rats bearing intrahepatically transplanted hepatoma 5123 were subjected intraperitoneally to the acute administration of hypertonic NaCl or CCl₄ followed by a tube-feeding of l-tryptophan. The responses in terms of changes in polyribosomal aggregation and protein synthesis (in vitro) of host liver and hepatoma were evaluated. While treatment with hypertonic NaCl or CCl₄ caused disaggregation of polyribosomes and inhibition of protein synthesis in both host liver and hepatoma, the subsequent administration of tryptophan caused some improvement in both parameters in host liver but not in hepatoma. Administration of hypertonic NaCl alone caused a decrease in [¹⁴C]orotate incorporation into poly(A)-mRNA of host liver and hepatoma, whereas administration of tryptophan after hypertonic NaCl caused a significant improvement in host liver alone. Following the tryptophan administration, the activities of nuclear DNA-dependent RNA polymerases I and II, and of nuclear-envelope nucleoside triphosphatase, as well as labeled nuclear RNA release in vitro were slightly elevated in host liver but not in hepatoma. Tryptophan-related compounds, 5-hydroxy-dl-tryptophan, 5-fluorotryptophan, indole, and 3-hydroxyanthranilic acid, when administered in place of l-tryptophan, did not appreciably affect polyribosomal aggregation or protein synthesis in vitro in host liver or hepatoma.     

Irs2 Inactivation Suppresses Tumor Progression in Pten+/− Mice

Mutations in the phosphatase and tensin homologue (PTEN)/phosphatidylinositol-3 kinase-α (PI3K) signaling pathway are frequently found in human cancer. In addition, Pten^+/− mice develop tumors in multiple organs because of the activation of the PI3K signaling cascade. Because activation of PI3K signaling leads to feedback inhibition of insulin receptor substrate-2 (IRS2) expression, an upstream activator of PI3K, we therefore anticipated that IRS2 expression would be low in tumors that lack PTEN. Surprisingly, however, an elevation of IRS2 was often detected in tumor samples in which PTEN levels were compromised. To determine the potential contribution of Irs2 to tumor progression, Pten^+/− mice were crossed with Irs2^+/− mice. Deletion of Irs2 did not affect the initiation of neoplasia found in Pten^+/− mice but suppressed cancer cell growth, proliferation, and invasion through the basement membrane. Deletion of Irs2 also attenuated the expression of Myc in prostatic intraepithelial neoplasia in Pten^+/− mice. In addition, the expression levels of IRS2 and MYC were highly correlated in human prostate cancer, and IRS2 could stimulate MYC expression in cultured cells. Our findings provide evidence that the PI3K-activating adaptor Irs2 contributes to tumor progression in Pten^+/− mice by stimulating both Myc and DNA synthesis.     

Ethanol-Induced Stimulation of Hepatic Ornithine Decarboxylase Activity in the Rat

The effect of a single feeding of ethanol on hepatic ornithine decarboxylase (ODC) activity in rats was investigated. Ethanol (7.5 g/kg body weight) was tube-fed to overnight-fasted rats as a 50% (v/v) solution in water 1, 2, 3, 4, 8, 12, or 24 hr before sacrifice. The levels of ODC activity in the livers were assayed in vitro by measuring the release of ¹⁴C0₂ from 0L-1-¹⁴C-ornithine. Hepatic ODC activities were significantly stimulated by ethanol (7.5 g/kg body weight) beginning at 1 hr and reaching a peak at 4 hr (more than a 16-fold increase over zero time controls). Single feedings of varying doses of ethanol (2.5, 5.0, or 7.5 g/kg body weight) to overnight-fasted rats 3 hr before sacrifice also exhibited significant increases (3 to 13-fold) in the hepatic ODC activities. In vitro ¹⁴C-leucir>e incorporation into protein using hepatic microsomes of ethanol-treated rats was decreased in comparison with that of controls. The ethanoMnduced stimulation of hepatic ODC activity was not abolished by pretreatment with pyrazoie, an inhibitor of ethanol metabolism. However, the stimulation of hepatic ODC activity by ethanol was suppressed by actinomycin D or cycloheximide, indicating that the enhancement is attributable to the synthesis of new enzyme protein. Furthermore, abolition of the stimulation of hepatic ODC activity due to ethanol by prior adrenalectomy suggests that the induced increase is probably mediated through stimulation of adrenal hormones. These studies demonstrate that a single dose of ethanol per os can significantly enhance in the rat the activity of hepatic ODC, a key enzyyme in the biosynthesis of polyamines, and that the effect is indirect, via adrenal hormones.     

Synthesis and antimicrobial screening of some novel chalcones and flavanones substituted with higher alkyl chains

As a part of our program to generate some novel flavonoid frameworks substituted with higher alkyl groups as possible antimicrobial agents, we have in total synthesized twelve novel chalcones (11–16) and their corresponding flavanones (17–22) substituted with either nonyl or dodecyl chains in ring B in very good to excellent yields. The synthesized compounds have been screened for their antimicrobial potential against six bacterial and four fungal strains. The tested compounds, in general, showed significant antibacterial and comparable antifungal activities. While the chalcone (16) with a dodecyl chain showed highly promising antibacterial activity against almost all the organisms tested, the chalcone (13) with nonyl chain showed promising antifungal activity against Candida rugosa and Aspergillus niger strains.     

Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States

The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection.