Echoes of Medieval and Pre-Modern Animal Trials in the Interlude Declamatio sub forma iudicii (1735)

Declamatio sub forma judicii can be found in the Graudenz Codex (1731–1740). It is an interlude that jokingly reports an animal trial. The interlude is a humorous treatment of the historical trials on animals that continued from the Middle Ages to the eighteenth century. Onthe one hand, such eighteenth-century discussions of animal trials continued the medieval tradition. This would confirm the diagnosis about the existence of the “long Middle Ages”, especially in Central and Eastern Europe, where the cultural trends could be somehow belated in comparison to those in the West. On the other hand, perhaps writing about animal trials in the eighteenth century was already a form of medievalism. High culture propagated anthropocentrism in its thinking about animals, while folk culture entailed anthropomorphism. In animal trials animals are treated as subjects to the same regulations as humans, which means that they were seen as very much similar to humans. The eighteenth-century interlude recreates this tradition, but it is a source of satirical laughter.

MEDICINAL PLANTS AND PHYTOCHEMICALS IN PREVENTION AND MANAGEMENT OF LIFE STYLE DISORDERS: PHARMACOLOGICAL STUDIES AND CHALLENGES

The prevalence of lifestyle disorders such as hypertension, diabetes mellitus (DM), dyslipidemia, and overweight/obesity is rising rapidly. Recently the popularity of herbal supplements among patients with lifestyle disorders has been increasing. Consumption of a plant-based diet consisted of appropriate phytochemicals has been accepted as a reliable means for the prevention and management of several disorders. Phytochemicals play a crucial role in disease prevention, especially when lifestyle changes alone are not found effective. Various human and animal trials have established the pharmacological action of phytonutrients present in herbal plants. Several bioactive compounds such as polyphenols, flavonoids, alkaloids, and stilbenes. are present in plants such as garlic, Aloe vera, turmeric, tulsi, and drumstick. that have shown a significant beneficial effect on DM, metabolic syndrome, lipid disorders, etc. This review focuses on the therapeutic effect of some of the high potential herbal plants and their phytochemicals in the management of lifestyle disorders and the challenges with the use of herbal medicines.

FumDSB Can Reduce the Toxic Effects of Fumonisin B1 by Regulating Several Brain-Gut Peptides in Both the Hypothalamus and Jejunum of Growing Pigs

Fumonisin B1 (FB1) is the most common food-borne mycotoxin produced by the Fusarium species, posing a potential threat to human and animal health. Pigs are more sensitive to FB1 ingested from feed compared to other farmed livestock. Enzymatic degradation is an ideal detoxification method that has attracted much attention. This study aimed to explore the functional characteristics of the carboxylesterase FumDSB in growing pigs from the perspective of brain–gut regulation. A total of 24 growing pigs were divided into three groups. The control group was fed a basal diet, the FB1 group was supplemented with FB1 at 5 mg/kg feed, and the FumDSB group received added FumDSB based on the diet of the FB1 group. After 35 days of animal trials, samples from the hypothalamus and jejunum were analyzed through HE staining, qRT-PCR and immunohistochemistry. The results demonstrated that the ingestion of FB1 can reduce the feed intake and weight gain of growing pigs, indicating that several appetite-related brain-gut peptides (including NPY, PYY, ghrelin and obestatin, etc.) play important roles in the anorexia response induced by FB1. After adding FumDSB as detoxifying enzymes, however, the anorexia effects of FB1 were alleviated, and the expression and distribution of the corresponding brain-gut peptides exhibited a certain degree of regulation. In conclusion, the addition of FumDSB can reduce the anorexia effects of FB1 by regulating several brain-gut peptides in both the hypothalamus and the jejunum of growing pigs.

Structural Biology of Nanobodies against the Spike Protein of SARS-CoV-2

Nanobodies are 130 amino acid single‑domain antibodies (VHH) derived from the unique heavy-chain-only subclass of Camelid immunogloblins. Their small molecular size, facile expression, high affinity and stability have combined to make them unique targeting reagents with numerous applications in the biomedical sciences. The first nanobody agent has now entered the clinic as a treatment against a blood disorder. The spread of the SARS-CoV-2 virus has seen the global scientific endeavour work to accelerate the development of technologies to try to defeat a pandemic that has now killed over four million people. In a remarkably short period of time, multiple studies have reported nanobodies directed against the viral Spike protein. Several agents have been tested in culture and demonstrate potent neutralisation of the virus or pseudovirus. A few agents have completed animal trials with very encouraging results showing their potential for treating infection. Here, we discuss the structural features that guide the nanobody recognition of the receptor binding domain of the Spike protein of SARS-CoV-2.

P.191 Development and Testing of a Novel Hydrogel Embolization Treatment for Neurovascular Diseases: Preliminary Animal Results

Background: Embolization represents a minimally invasive treatment modality for arteriovenous malformations (AVMs), tumors, aneurysms, and vessel sacrifice, but can be limited by currently available embolization agents. Discovery of new and improved agents could lead to better treatment outcomes. The goal of this project was to develop and test a novel embolization agent using hydrogels, a class of materials which may be bioengineered to suit a variety of indications. Methods: We devised a method of liquid hydrogel embolization with photo-modulated crosslinking for intravascular solidification, using a custom microcatheter set-up. We tested this in swine blood vessels (n=3), the swine renal arterial trees as a vascular tumor model (n=5), and the swine arterial-arterial networks of the rete mirabile as an AVM model (n=3). Hydrogel embolization was assessed for treatment efficacy and safety. Follow-up angiography was performed at 2-4 week intervals. Results: Hydrogel embolization was technically successful in all animals, with full occlusion of the vascular target immediately following embolization and at follow-up. There were no instances of clinical or angiographic complications. Conclusions: We demonstrated a novel method of dynamic photomodulation and delivery of bioengineered hydrogels to address current limitations of endovascular embolization therapies. This promising technology will be investigated further with longer-term comparative animal trials.

Abstract 1122‐000236: Intravascular Delivery and Crosslinking of Photosensitive Hydrogels for Embolizing Animal Models of AVMs and Tumors

Introduction : Embolization represents a minimally invasive treatment modality for arteriovenous malformations (AVMs), tumors, and other indications, but can be limited by currently available embolic agents, in terms of safety and efficacy. Discovery of new and improved agents could lead to better treatment outcomes. The goal of this project was to test a novel embolization methodology for the treatment of AVMs and tumors. Methods : We formulated low‐viscosity, shear‐thinning hydrogel formulations which were mixed with a photo‐initator agent and non‐ionic contrast medium. We then developed a method of intravascular hydrogel delivery with photo crosslinking at the tip of the catheter, using an integrated optical fibre. This allowed for rapid transition from a low viscosity liquid to a crosslinked solid‐state hydrogel to block blood flow to the vascular target. In addition, the UV intensity can be dynamically modulated, in real‐time, to modify the degree of crosslinking and thus the viscosity of the embolic agent. We utilized the swine rete mirabile as an animal model for AVMs, and the swine renal arterial tree (inferior segmental artery) as a model for hypervascular tumors. 5 animals were utilized without prior preparation. Embolization was graded based on degree of complete obliteration of the rete nidus or the renal arterial tree. Any non‐target embolization or other complications were recorded. Follow‐up angiography was performed at the 4‐week interval. Results : With a combination of shear‐thinning properties and dynamic modulation of photo crosslinking, we show that we are able to deliver an embolic agent with a viscosity range of up to 10^4 Pa*s through a single low viscosity precursor that is injectable through microcatheters (Figure 1). Using this methodology, hydrogel embolization was technically successful in all animals. Following embolization, 4/5 rete mirabile and 5/5 inferior renal arterial trees were completely obliterated. Representative angiographic images are shown in Figures 2 and 3. There were no instances of clinical or angiographic complications. Conclusions : We demonstrated a novel method of intravascular delivery of low viscosity photosensitive hydrogels, with photo crosslinking at the tip of the catheter, to successfully embolize animal models for AVMs and tumors. This promising technology will be investigated further with longer‐term comparative animal trials.

Relative Efficacy of Dry-Off Antimicrobial Treatments in Dairy Cattle to Cure Existing Intramammary Infections: A Systematic Review and Network Meta-Analysis

This systematic review and network meta-analysis aimed to estimate the relative efficacy of dry cow antimicrobial therapies, registered in Canada and/or the United States, to cure existing intramammary infections (IMI) in dairy cattle. The controlled trials examining all-cause cures of existing IMI present at dry-off were eligible. Five databases and four conference proceeding platforms were searched. The risk of bias at the level of the outcome was assessed using the Cochrane 2.0 risk of bias instrument (Cochrane, Denmark), and the overall confidence in the findings from the network meta-analysis was assessed using the Confidence in Network Meta-Analysis (CINeMA) platform. Of 3,743 articles screened for eligibility by the two independent reviewers, 58 trials were included in the Bayesian network meta-analysis for the all-cause cure of existing IMI from dry-off to calving. No antimicrobial treatment (non-active control) was associated with a decreased risk of a cure compared with all other currently labeled antimicrobials in Canada and the United States; however, lack of replication trials for some antimicrobial products created large credibility intervals and, therefore, we were unable to identify meaningful comparisons between the products. Poor reporting of trial features, heterogeneity in outcome measurements, and high risk of bias in some domains further contributed to this inability to compare antimicrobials. Continued improvement in the reporting of animal trials is required to make recommendations for antimicrobial products on the basis of efficacy.Systematic Review Registration:https://atrium.lib.uoguelph.ca/xmlui/bitstream/handle/10214/16236/Protocol_NMA_efficacy_dryoff_antibiotics_cure_IMI.pdf?sequence=3&isAllowed=y.

SUATU STUDI LITERATUR: AKTIVITAS ANTIDIABETIC DARI KULIT JERUK (Citrus sp.)

Diabetes mellitus is a chronic metabolic disease, which is not able to secrete insulin in sufficient quantities or the body is unable to use insulin effectively so there is an excess glucose level and immediately suffer from some complications against the organs. Diabetes mellitus can be cured by herb utility which are thought to have compounds that has an antidiabetic effect. Therefore, this literature study discusses the antidiabetic activity of orange peel (Citrus sp.). The literature search was carried out on the Google Scholar search engine which used some keyword included antidiabetic, extract, orange peel, Citrus. In this literature study, there are inclusion and exclusion criteria for selecting journals as literature sources. The results of 12 literatures review that orange peel had antidiabetic activity by decrease blood glucose levels in some animal trials that had received an effective dose of orange peel extract in each of the reviewed studies. Hence, it can be concluded that various type of Citrus peels has antidiabetic effect.

Telomerase Gene Therapy: A Remission Towards Cancer

Telomerase is an enzyme which is culpable for the aliment and stability of telomeres. It also maintains the genomic integrity and chromosomal stability. The progressive shortening of telomeres may cause chromosomal instability and alternation in the telomerase. It may cause telomere attrition which can lead to oncogenic incidence in human. Cancer is a disease which is induced by genetic alternations in genes. The genetic mutation within the hTERT is a common type of scenario which is generally found above 90 percent of cancer. In cancer, the length of telomere and the activity of telomerase are very important for cancer cells to proliferate and also for the survival of tumors. Cancer cells regulate through several pathways to increase telomerase activity. There have been several advancements developed to inhibit the telomerase activity in cancer cell but the repercussion of those has demonstrated many adverse effects. Research on AAVs mediated telomerase gene therapy has demonstrated prominent outcomes in animal trials. Thus, it has the potential to bring significance shine in the telomerase cancer therapeutics. Here, in this review article we have analyzed studies related to telomerase gene therapeutics to cure cancer. We also have summarized the telomerase function and mechanism of action to cause cancer. Moreover, other current development in the clinical advances of telomerase inhibition in cancer is described.

122 Bioactive Peptides for Enhancing Intestine Health

Intestinal disorders and colitis affect both animals and humans. The pathogenesis behind the inflammation is complex and not entirely understood. Furthermore, the significant rise in antibiotic-resistant bacteria has emphasized an urgent need for alternative anti-infective therapies. Antimicrobial peptides (AMPs) is one of the appealing alternative to antibiotics due to their antimicrobial activity, mode of actions, and potential role in tissue repair. Epidermal growth factor (EGF) plays an important role in intestinal proliferation and differentiation and thus promotes intestinal development. Using food grade microorganisms such as Lactococcus lactis and yeast as hosts, our laboratory has produced recombinant porcine protegrin-1 (PG-1), a pig originated antimicrobial peptide and EGF via fermentation. Oral administration of PG-1 reduced Citrobacter rodentium induced intestinal infection in mice. This was evidenced by reduced histopathological changes in the colon, prevention of body weight loss, milder clinical signs of disease, and ultimately more effective clearance of bacterial infection. On the other hand, animal trials using the recombinant EGF demonstrated that it enhances intestinal development and growth of early weaned pig fed with antibiotic-free diet. Moreover, piglets challenged with enterotoxigenic Escherchia coli (E. coli) K88 showed similar beneficial responses to EGF as those fed diets with antibiotic in terms of improving gain to feed ratio and lowering oxidative stress. Taken together, our findings suggest the potential for cost-effective production and application of recombinant bioactive proteins as alternatives to antibiotics in animal health and production.