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Covalently attaching polyethylene glycol (PEGylation) to therapeutic proteins is an increasingly important tool for improving stability, pharmacokinetic and pharmacodynamic properties. In this work, degradation of pegylated interferon alpha-2b (Mono-PEG-IFN) was induced using various physicochemical stress conditions (mechanical agitation, pH, temperature, and repeated freeze-thaw). Stability-indicating SE-HPLC assay was validated and employed for monitoring Mono-PEG-IFN in the presence of all degradation products. Results were expressed in terms of percentage decrease in Mono-PEG-IFN concentration (%Degradation) and peak area normalization method (%Purity). Separation was carried out using a mobile phase of phosphate buffer (100 mM, pH 6.8): 1-propanol (80:20 v/v) at 1.0 mL/min and 214 nm. Incubation at pH 4.0-10.0, 37°C for up to four weeks resulted in formation of aggregates, small molecular weight peptide fragments and mostly depegylated interferon. Similar degradation pattern but to lower extent was noted under short term storage conditions (24 h at 2-8°C and 37°C). No degradation was noted when the lyophilized powder was stored for 30 months at 2–8°C, under real-time stability conditions. It should be noted that expression of the results using %Purity, currently employed for batch release was not a reliable approach. Alternatively, the stability of Mono-PEG-IFN should be expressed as %Degradation that was shown to reveal minor changes in product stability. Results raised a concern about the efficacy and safety of reconstituted multi-dose vials of pegylated therapeutics that are stored refrigerated. The need for in-house validated testing protocols developed by local regulatory authorities to prevent access of substandard biotherapeutics to local markets is discussed.

The present study assessed the long-term daily administration of benzoic acid (BA), potassium sorbate (PS), chlorophyll (CPL), tartrazine (TAZ), and butylated hydroxyanisole (BHA) on hepato-renal changes and DNA damage in rats. Animals were orally administered with the 10 times of the acceptable daily intake (ADI) from each tested substance daily for 60 consecutive days. Blood, liver, and kidney samples were collected to evaluate hematological, biochemical, histopathological, and genotoxic alterations. The extent of liver and kidney damage was evaluated by comet assay and histopathologically. Significant reduction of leukocyte numbers and lymphocytes % in CPL- and TAZ-treated rats. However, significant increases in platelet count in all treated groups after 60 days were detected. The levels of serum transaminases enzymes (ALT, AST), alkaline phosphatase (ALP), and creatinine were significantly increased in all treatments except with BHA group, but no substantial differences were found in urea after 60 days. Aside from BHA, results of DNA damage revealed significant increases in tailed nuclei, tail moment, DNA% in the tail, and tail length in liver and kidney at different degrees. Moreover, the histopathological figures of liver and kidneys affirmed destructive and degenerative changes. The study indicates that most of the tested food additives may provoke genotoxicity and hepato-nephropathy, which could be serious for human health. Therefore, it is necessary to be informed about the hazardous effects of food additives and more attention should be focused towards using natural substitutes.

The present study assessed the long-term daily administration of benzoic acid (BA), potassium sorbate (PS), chlorophyll (CPL), tartrazine (TAZ), and butylated hydroxyanisole (BHA) on hepato-renal changes and DNA damage in rats. Animals were orally administered with the 10 times of the acceptable daily intake (ADI) from each tested substance daily for 60 consecutive days. Blood, liver, and kidney samples were collected to evaluate hematological, biochemical, histopathological, and genotoxic alterations. The extent of liver and kidney damage was evaluated by comet assay and histopathologically. Significant reduction of leukocyte numbers and lymphocytes % in CPL- and TAZ-treated rats. However, significant increases in platelet count in all treated groups after 60 days were detected. The levels of serum transaminases enzymes (ALT, AST), alkaline phosphatase (ALP), and creatinine were significantly increased in all treatments except with BHA group, but no substantial differences were found in urea after 60 days. Aside from BHA, results of DNA damage revealed significant increases in tailed nuclei, tail moment, DNA% in the tail, and tail length in liver and kidney at different degrees. Moreover, the histopathological figures of liver and kidneys affirmed destructive and degenerative changes. The study indicates that most of the tested food additives may provoke genotoxicity and hepato-nephropathy, which could be serious for human health. Therefore, it is necessary to be informed about the hazardous effects of food additives and more attention should be focused towards using natural substitutes.

This paper proposes an adaptive dynamic Mho distance relay based on a phase comparator scheme for protecting interconnected transmission networks compensated with a Thyristor Controlled Series Capacitor (TCSC). The proposed relay uses an impedance index factor to initiate the fault detection subroutine. The RMS of the positive sequence current of the faulted loop and the TCSC terminal current are compared for TCSC zone identification. A phase comparator for ground and phase distance elements is proposed, relying on the positive sequence voltage as a polarized memory quantity, while the operating and polarizing quantities are developed using estimated TCSC impedance to mitigate its negative impact. The proposed scheme is easy in implementation and independent on synchronized data transfer, as minimum communication requirements are needed. To evaluate the performance of the proposed scheme, extensive simulation studies were carried out on an IEEE9 bus system compensated with TCSC for different firing angles covering four modes of TCSC operations, different fault types, and fault locations. In addition, an IEEE-39 bus network, as a large interconnected system, is tested for validation purposes. The achieved results designate the precision of the proposed scheme. Moreover, the results indicate its effectiveness for fault resistance tolerance, close-in three phase faults, and stable power swing phenomenon compared with conventional relays.