Protein Quantity on the Air–Solid Interface Determines Degradation Rates of Human Growth Hormone in Lyophilized Samples

Recombinant human growth hormone (rhGH) was lyophilized with various glass-forming stabilizers, employing cycles that incorporated various freezing and annealing procedures to manipulate glass formation kinetics, associated relaxation processes, and glass-specific surface areas (SSAs). The secondary structure in the cake was monitored by infrared and in reconstituted samples by circular dichroism. The rhGH concentrations on the surface of lyophilized powders were determined from electron spectroscopy for chemical analysis. Glass transition temperature (T_g), SSAs, and water contents were determined immediately after lyophilization. Lyophilized samples were incubated at 323 K for 16 weeks, and the resulting extents of rhGH aggregation, oxidation, and deamidation were determined after rehydration. Water contents and T_g were independent of lyophilization process parameters. Compared with samples lyophilized after rapid freezing, rhGH in samples that had been annealed in frozen solids prior to drying, or annealed in glassy solids after secondary drying retained more native-like protein secondary structure, had a smaller fraction of the protein on the surface of the cake, and exhibited lower levels of degradation during incubation. A simple kinetic model suggested that the differences in the extent of rhGH degradation during storage in the dried state between different formulations and processing methods could largely be ascribed to the associated levels of rhGH at the solid–air interface after lyophilization. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.     

Evaluation of the toxicological safety of erinacine A-enriched Hericium erinaceus in a 28-day oral feeding study in Sprague–Dawley rats

Natural products have attained great importance as they are believed to be the new alternative medicines for conventional therapy. As numerous studies have proved the tremendous medicinal values of Hericium erinaceus, it is necessary to take into account its safety as well as its risk for the recipient. However, mushroom mycelium has an identity distinct from mushrooms, as two specific classes of compounds, hericenones and erinacines, can only be extracted from both the fruit body and the cultured mycelium, respectively. Therefore, this is the first report on the evaluation of the toxicity of H. erinaceus mycelium, enriched with 5 mg/g erinacine A, by a 28-day repeated oral administration study in Sprague–Dawley rats. Three doses of 1 (Low), 2 (Mid) and 3 (High) g/kg body weight/day were selected for the study while distilled water served as control. All animals survived to the end of the study. No abnormal changes were observed in clinical signs. No adverse or test article-related differences were found in urinalysis, haematology and serum biochemistry parameters, between the treatment and control groups. No gross pathological findings and histopathological differences were seen. Therefore, the no-observed-adverse-effect level of erinacine A-enriched H. erinaceus is greater than 3 g/kg body weight/day.     

Environmental and health impact of unrecovered API from pharmaceutical manufacturing wastes: A review of contemporary treatment,recycling and management strategies

Pharmaceutical industries are imminent for the survival of any contemporary society as their products are valuable for the populace's health and wellness. However, the wastes of these industries have become a nuisance with severe implications on human health and ecosystem, especially in many developing countries where they are discharged indiscriminately into the environment, either untreated or poorly treated. Pharmaceutical Manufacturing Waste (PMW) effluents have been reported to possess a high BOD and COD, as well as recoverable APIs of various classes of pharmaceuticals. Moreover, antibiotic residues in these effluents are implicated in the progression and spread of antibiotic resistance in the aquatic and agroecosystem. Globally, the diverse activities of various pharmaceutical industries, owing to their diverse products, have resulted in difficulty in developing universal management and treatment protocols. Consequently, regulatory bodies/institutions find it challenging to monitor waste disposal practices of these industries adequately, primarily owing to their non-disclosure policies of intellectual properties. Hence, to a large extent, the onus for a sustainable society regarding PMWs lies in the decision and policies of these industries. Therefore, this review aims to foster informed policy-making decisions regarding waste management practices of pharmaceutical industries.     

Genetic characterization of a densovirus isolated from great tit (Parus major) in China

During a study of ornithophilous viruses in China, a new densovirus (DNV) was isolated from the lung tissue of Parus major (PmDNV-JL). The complete genome of PmDNV-JL was cloned and sequenced. Five open reading frames (ORFs) were identified in the 5166 nt sequence, on the basis of deduced amino acids. It was further shown that this virus caused cytopathic effects (CPE) in Feline kidney cells. The NS1 gene sequence of PmDNV-JL shares 70–99% nucleotide sequence identity with isolates of the Blattella germanica densovirus (BgDNV) and BgDNV-like virus. Phylogenetic analysis indicated that the predicted amino acid sequences of capsid (VP) and non-structural domain (NS1) of PmDNV-JL clustered with the BgDNV and were similar to BgDNV-HB within the genus Densovirus.     

Succès du traitement par paclitaxel d’une rechute viscérale d’un sarcome de Kaposi après transplantation rénale

We report the observation of a patient who presented with post-transplant Kaposi's sarcoma after a delay of eight months with a dual cutaneous and palatal localisation. The reduction in immunosuppressive treatment and the introduction of Rapamune® allowed good clinical progress initially with regression of the skin lesions. He subsequently presented later a skin relapse with visceral localisation. Chemotherapy was conducted based on weekly paclitaxel infusions allowing partial remission and maintenance of renal graft function with good clinical tolerance.     

Antihepatitis B therapy: a review of current medications and novel small molecule inhibitors

There are approximately 350 million hepatitis B virus (HBV) carriers worldwide. Chronic HBV infection increases the risk of liver cirrhosis and hepatocellular carcinoma. To date, two classes of antiviral drugs have been approved by the Food and Drug Administration for the treatment of hepatitis B, immunomodulators (interferon [IFN]‐α and pegylated‐interferon [PEG‐IFN]‐α) and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF], and entecavir [ETV]). Of these, ETV, TDF, and PEG‐IFN‐α are the most effective and are currently recommended for anti‐HBV therapy. However, these therapies are less than optimal because of their low rate of viral DNA and surface antigen clearance; thus, there exists a significant unmet medical need for safe and efficacious new anti‐HBV drugs. Covering diverse chemical structures and mechanisms of action, non‐nucleos(t)ide compounds offer great promise in the search for new anti‐HBV drugs. This review summarizes the currently approved anti‐HBV drugs and highlights advances in the identification and characterization of novel small molecule HBV inhibitors. We discuss the sources, structures, anti‐HBV effects, mechanisms of action, and potential toxicities of these novel inhibitors.