Immunization of laboratory animal workers: occupational health and safety aspects.

Occupational immunization is an integral part of institutional occupational safety and health (OSH) programs. Laboratory animal workers (LAWs) are personnel working with various small and large vertebrate animals. LAWs are at the risk of contracting a myriad of zoonotic infections as they are occupationally exposed to animals and their biological products. Immunizing employees against such zoonotic pathogens is the best way to prevent disease transmission. This review provides information on various zoonotic diseases, vaccines available to protect against such infections, and vaccination schedules. Certain sections of institutional occupational immunization programs such as risk evaluation, immunizing special categories of personnel and exemption from immunization among others are also described. Additionally, the authors have discussed various probable modes of impact through which occupational immunization of laboratory animal workers fulfills different United Nations Sustainable Development Goals.

A Retrospective Comparison of Electrocardiographic Parameters in Ketamine and Tiletamine-Zolazepam Anesthetized Indian Rhesus Monkeys (Macaca mulatta).

Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies.

Comparison of different QT correction methods for nonclinical safety assessment in ketamine-anesthetized Indian rhesus monkeys (Macaca mulatta).

Rhesus monkeys are a non-rodent species employed in the preclinical safety evaluation of pharmaceuticals and biologics. These nonhuman primate species have been increasingly used in biomedical research because of the similarity in their ionic mechanisms of repolarization with humans. Heart rate and QT interval are two primary endpoints in determining the pro-arrhythmic risk of drugs. As heart rate and QT interval have an inverse relationship, any change in heart rate causes a subsequent change in QT interval. This warrants for calculation of a corrected QT interval. This study aimed to identify an appropriate formula that best corrected QT for change in heart rate. We employed seven formulas based on source-species type, clinical relevance, and requirements of various international regulatory guidelines. Data showed that corrected QT interval values varied drastically for different correction formulas. Equations were compared on their slope values based on QTc versus RR plots. The rank order of the slope for different formulas was (closest to farthest from zero) QTcNAK, QTcHAS, QTcBZT, QTcFRD, QTcVDW, QTcHDG, and QTcFRM. QTcNAK emerged to be the best correcting formula in this study. It showed the least correlation with the RR interval (r = -0.01) and displayed no significant difference amongst the sexes. As there is no universally recognized formula for preclinical use, the authors recommend developing a best-case scenario model for specific study designs and individual organizations. The data from this research will be helpful in deciding an appropriate QT correction formula for the safety assessment of new pharmaceuticals and biologics.

Non-clinical safety evaluation of a novel pharmaceutical salt, rosuvastatin ethanolamine, in Wistar rats.

Rosuvastatin, a second generation 3-Hydroxy-3-Methyl Glutaryl Coenzyme-A reductase inhibitor, is widely used for the management of hypercholesterolemia. Rosuvastatin ethanolamine, developed by Cadila Healthcare Ltd., is a novel, chemically stable, and pharmaceutically acceptable salt, having better physiochemical properties than commercially available Rosuvastatin salt. The objective of the present study is to evaluate safety, tolerability, and toxicokinetic profile of novel salt. Therefore, four weeks repeated dose oral (gavage) toxicity and toxicokinetic study of Rosuvastatin ethanolamine was carried out. The drugs were administered once daily at salt corrected dose of 15, 40, and 100 mg/kg for four weeks. No signs of toxicity were observed during repeated (four weeks) oral administrations of Rosuvastatin ethanolamine in rats up to 40 mg/kg. Single male mortality was observed at 100 mg/kg dose. Microscopy finding in liver was minimal to mild bile ductular proliferation, single cell necrosis, and hepatocellular vacuolation of cytoplasm with associated statistically significant serum elevation of transaminase enzymes; AST, ALT, ALP, and/or liver functional marker; total bilirubin with at ≥40 mg/kg. The systemic exposures (AUC0-24 and Cmax) were not markedly different between males and females, or between the administration periods (except high dose, where exposure on day 28 was approximately 2 to 3 fold higher than that of day 1. In conclusion, Rosuvastatin ethanolamine exhibited toxicities to liver as the target organ at ≥40 mg/kg in this study. These adverse effects with associated exposures should be taken into consideration for the future assessing of potential Rosuvastatin toxicities.

Refractive index change in bovine and human corneal stroma before and after lasik: a study of untreated and re-treated corneas implicating stromal hydration.

PURPOSE: To measure the refractive index (RI) of the mammalian corneal stroma in relation to hydration in vitro and human corneal stroma before and after LASIK. METHODS: RI at the anterior stromal surface of bovine corneal buttons was measured after the epithelium was scraped away. Samples were weighed and oven dried to calculate hydration. RI of the stromal bed surface was measured with a modified hand-held Abbé refractometer immediately before and after excimer laser photoablation. Thirty-one untreated persons (group 1: 44 corneas; age range, 19-65 years) and eight re-treated patients (group 2: 10 corneas) were examined. RESULTS: RI of bovine stromal surface was significantly associated with hydration (H) (RI = 1.4067 - 0.00599H, r = -0.9079, P < 0.001). Photoablation significantly increased the RI of the midstroma (group 1: 1.3721 +/- 0.0041 to 1.3839 +/- 0.0050; group 2: 1.3717 +/- 0.0038 to 1.3819 +/- 0.0039). Differences between groups were not significant. In group 1 (n = 31), change in RI (DeltaRI) was significantly related to preoperative RI (DeltaRI = 1.155 - 0.833RI, r = 0.595, P < 0.001) and RI was significantly related to age (x) (RI = 1.3634 + 0.00026x, r = 0.603, P < 0.001). CONCLUSIONS: Mammalian corneal stromal RI correlates with hydration. LASIK significantly increases the refractive index of the treated stromal bed, and this equates to an average change in hydration from 4.3 to 2.9. For individual cases, change in RI is associated with the pre-op RI. The lack of any difference between untreated and re-treated corneas suggests that with time hydration returns back to normal levels. The RI in the older corneal stroma is slightly higher relative to the RI in the younger corneal stroma.