Novel CD3Z and CD3E Deficiency in Two Unrelated Females

Journal of Clinical Immunology -     

Flax lignan concentrate reverses alterations in blood pressure,left ventricular functions,lipid profile and antioxidant status in DOCA-salt induced renal hypertension in rats

Context Earlier we reported cardioprotective, antihyperlipidemic, and in vitro antioxidant activity of flax lignan concentrate (FLC) obtained from the seeds of Linum usitatissimum L. (Linaceae).

Objective To investigate the effect of FLC in deoxycorticosterone acetate (DOCA)-salt induced experimental renal hypertension in rats. Materials and methods Hypertension was induced in uninephrectomized (UNTZD) male Wistar rats (230–280?g) by injecting DOCA (25?mg/kg, subcutaneously, twice weekly) and supplementing 1% NaCl in drinking water for 5 weeks. The rats were divided in six groups. Captopril (30?mg/kg, p.o.) and FLC (200, 400 and 800?mg/kg, p.o.) were administered daily to the rats of groups III–VI, respectively, for 5 weeks. Various hemodynamic and biochemical parameters were investigated as well as histology of kidney and heart were carried out. Results In this study, the FLC (400 and 800?mg/kg) significantly (p?0.01, p?<?0.001) decreased the systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. It also significantly (p?0.01, p?<?0.001) decreased elevated end diastolic pressure (EDP), dP/dt max and dP/dt min, organs weights (kidney and heart) and activities of hepatic, renal and cardiac marker enzymes in the serum. Furthermore, FLC (400 and 800?mg/kg) significantly (p?p?0.001) restored altered antioxidant status, serum electrolyte level, lipid profile values, and histological abnormalities. Captopril (30?mg/kg) showed maximum antihypertensive effect but low dose of FLC (200?mg/kg) was not enough to show the antihypertensive activity. Conclusion FLC possessed antihypertensive effect via modulation of endogenous enzymes in DOCA-salt induced renal hypertension in rats.     

Slit design for efficient and accurate MTF measurement at megavoltage x-ray energies

Empirical determination of the modulation transfer function (MTF) for analog and digital mega-voltage x-ray imagers is a challenging task. The most common method used to determine MTF at megavoltage x-ray energies employs a long, narrow slit formed by two parallel, metal blocks in order to form a "slit beam." In this work, a detailed overview of some of the important considerations of slit design is presented. Based on these considerations, a novel, compact slit, using 19 cm thick tungsten blocks, was designed. The prototype slit was configured to attach to the accessory slot of the gantry of a linear accelerator, which greatly simplified the measurement process. Measurements were performed to determine the presampling MTF at 6 MV for an indirect detection active matrix flat panel imager prototype previously developed for megavoltage imaging applications. In addition, the effects of two important slit design parameters, material type and thickness, on the accuracy of MTF determination were investigated via a Monte Carlo-based theoretical study. Empirically determined MTFs obtained from the prototype slit closely match those from an earlier, less compact slit design based on 40 cm thick steel blocks. The results of the Monte Carlo-based theoretical studies indicate that the prototype slit achieves close-to-ideal performance in terms of accurately determining the MTF by virtue of practically 100% beam attenuation in regions other than the slit gap. Furthermore, the theoretical results suggest that it may be possible to achieve even further reductions in slit thickness without compromising measurement accuracy.     

Evaluation of genotoxicity testing of FDA approved large molecule therapeutics

Large molecule therapeutics (MW > 1000 daltons) are not expected to enter the cell and thus have reduced potential to interact directly with DNA or related physiological processes. Genotoxicity studies are therefore not relevant and typically not required for large molecule therapeutic candidates. Regulatory guidance supports this approach; however there are examples of marketed large molecule therapeutics where sponsors have conducted genotoxicity studies. A retrospective analysis was performed on genotoxicity studies of United States FDA approved large molecule therapeutics since 1998 identified through the Drugs@FDA website. This information was used to provide a data-driven rationale for genotoxicity evaluations of large molecule therapeutics. Fifty-three of the 99 therapeutics identified were tested for genotoxic potential. None of the therapeutics tested showed a positive outcome in any study except the peptide glucagon (GlucaGen®) showing equivocal in vitro results, as stated in the product labeling. Scientific rationale and data from this review indicate that testing of a majority of large molecule modalities do not add value to risk assessment and support current regulatory guidance. Similarly, the data do not support testing of peptides containing only natural amino acids. Peptides containing non-natural amino acids and small molecules in conjugated products may need to be tested.