eChapters

1. Introduction

Plant metabolites are the major sources of pharmaceutical food additives, fragrances and pesticides. It is estimated that the market potential for herbal drugs in the western world alone could range from US $ 4.9 billion to 47 billion by the year 2000 if the AIDS epidemic continues unchecked (Biotechnology and Development, 1991). A similar situation exists for plant based food additives, fragrances and bio-pesticides. The natural resources for plant based chemicals are limited but the consumer preference for natural products is greater. Alternative avenues for plant products have gained prominence during the past few years. In recent years, plant Biotechnology has gained considerable importance for the production of phytochemicals (Heble, 1996).

During the past three decades, several phytochemicals with biological activities have been identified from higher plants for plant tissue culture industry (Verpoorte et al., 1991). Vincristine, vinblastine, artemisinin, taxol and podophyllotoxin are in the list of approved drugs. Some products under clinical trials are forskolin, castanospermine, ginkgolides and hyperin (Heble, 1996). In recent years, there has been renewed interest in screening higher plants for novel biologically active products particularly to combat such ailment that have defined synthetics and antibiotics. This has resulted in the development therapeutics used in the treatment of cancer, hypertension, AIDS, malaria and other diseases.

The pandemic in 2019-2022 spread swiftly and became global in no time, caused by SARS-CoV-2. Vaccines were rapidly developed against the virus to restore public health and save global economy. Vaccines for immunisation drives were developed in a year of the pandemic becoming global and approved for ‘emergency use’ following expeditious development protocols. Vaccine development employed numerous nucleic acid, adenovirus and protein-based state-of-art molecular platforms, alongside the conventional attenuated and inactivated virus approaches. The majority of the attempts were successful and approved for use. All the approved vaccines were found safe and effective as per Phase I through Phase III clinical trials’ results. Mass immunisation drives demonstrably led to reduced hospitalisation, low disease severity and less mortality. Yet, there were initial vaccination hesitation across the world due to associated safety concerns about its possible long-term negative consequences. A part of it was attributed to technical reasons (as clinical trials were not fully complete with sturdy and convincing outcomes), and a majority was due to the misinformation that floated on the social media and other digital communications. Vaccine deployment across the globe was far from being equitable. Thus, immunisation was rapid in higher income (developed) nations with access to innovative advanced vaccines while low immunisation rates were seen in the low- and medium-income countries accessing majorly the vaccines based on simple technology. Given the scale and spread of the pandemic, scaled-up vaccine production and equitable distribution to limit viral spread and improve global health and socioeconomy were critical. This chapter attempts to dissect these scenarios and lessons learnt from these to prepare better for any such pandemic in future.

Introduction
Defining GLP: Good Laboratory Practices (GLP) are a comprehensive set of quality system principles designed to ensure the reliability, reproducibility, and integrity of non-clinical health and environmental safety studies. These principles establish a framework for planning, performing, monitoring, recording, reporting, and archiving studies. Adherence to GLP is crucial for generating data that can be trusted and utilized for regulatory submissions and scientific advancements.
Purpose of GLP
• To ensure the quality and integrity of non-clinical and clinical laboratory studies.
• To provide assurance that data submitted to regulatory authorities is truly reliable.
• To standardize procedures and practices in non-clinical and clinical studies.
Scope of GLP
• Primarily applies to non-clinical health and environmental safety studies.
• These studies often support applications for research or marketing permits for regulated products (e.g., pharmaceuticals, pesticides, food additives).
Key Elements of GLP
• Organizational structure and personnel responsibilities.
• Standard operating procedures (SOPs).

Different basic as well as advanced laboratory equipment need to be used in a laboratory while conducting experiments. Many of them like pH meter, laminar air-flow hood, viscometer, thermometer, magnetic stirrer, microwave ovens, incubators, sand-bath, water-bath, oil-bath, etc. are the basic and simple equipment which require to be used routinely while conducting experiments in a laboratory. However, basic knowledge of their operation, handling procedure, when to be used, how to be used, and more importantly what not to be done with it, etc. are essential for keeping them in serviceable condition as well as for the accuracy/precision in their operation. In this chapter, we will discuss about some of the routinely used laboratory equipment along, while some other sophisticated equipment will be discussed in other chapters.

pH Meter

A pH meter measures exactly the H+ concentration of a solution; thus indicates acidity or alkalinity of a solution with greater precision. Actually, it measures the difference in electrical potential between a pH electrode and a reference electrode, and display the results converted into the corresponding pH value. Electrode is the key part (rod-like structure, usually made of glass) of a pH meter, having a bulb at the bottom containing a sensor. The pH meters range from simple and inexpensive pen-like devices (portable/pocket pH meter) to complex and expensive laboratory instruments with computer interface (Figure 5.1).

Frequent calibration of a pH meter using the solutions of known pH (standard solution of pH 4.01, 7.00, 10.01, Figure 5.2), generally before each use, ensures the accuracy of the instrument. For very precise work the pH meter should be calibrated before each measurement. For normal use calibration should be performed at the beginning of each day. This is necessary because the glass electrode does not give a reproducible measurement over a longer period of time.

Introduction

The antibiotics are low molecular weight natural, semi-synthetic, or synthetic substance that kills or slows the growth of germs while causing little or no harm to the host is considered an antimicrobial (Walsh, 2000). Antibiotics are the type of medicine produced by some microorganisms that kill or slow the growth of other microorganisms. It includes any of a large group of chemical substances, as penicillin or streptomycin, produced by various microorganisms and fungi, having the capacity in dilute solutions to inhibit the growth of or to destroy bacteria and other microorganisms, used chiefly in the treatment of infectious diseases (De Vetten et al., 2003). However today, a large number of bacteria are resistant to various antibiotics. Antibiotic resistance occurs when a bacterium becomes able to survive and multiply despite the presence of an antibiotic that would normally control or kill it. In other words, the bacteria become “resistant” and continue to grow even at therapeutic levels of the antibiotic. While antibiotic resistance is a natural phenomenon, it is accelerated by the selective pressure exerted when an antibiotic is used. Bacteria that are naturally resistant to the antibiotic have a better chance of survival compared to those that are susceptible. As the susceptible bacteria are killed or inhibited, resistant strains are favored and continue to thrive (Holme et al., 2006). Some resistance arises without human influence, as bacteria can naturally produce antibiotics against other microorganisms, resulting in a low-level, natural selection for antibiotic resistance. However, the current surge in antibiotic resistant bacteria is largely attributed to the overuse and misuse of antibiotics. One of the main issues facing public health is antimicrobial resistance, particularly in developing nations where access to and use of medications are easier than in developed nations, leading to a disproportionately higher rate of inappropriate antibiotic use and higher resistance levels (Ganguly et al., 2011). Antimicrobial resistance will make it more difficult to control infections in the community and make health care services less effective (Bhatia et al., 2010). It is well known that India has one of the highest rates of infectious disease burdens in the world, and that the country’s high rates of malnutrition and inadequate sanitation make these circumstances worse (http://www. resistancestrategies.org/wpcontent/uploads/2011/03/Indiareport).

Introduction

Antimicrobials, viz. antibiotics, antivirals, antifungals and anthelmintics are substances widely used to prevent and treat infections in humans, fish & prawn, livestock animals, and crops. In a situation where microorganisms such as bacteria, viruses, parasites or fungi become resistant to antimicrobial treatments to which they were previously susceptible, it is apprehended that antimicrobial resistance in the microbes has evolved. In fact, antibiotic resistant bacteria evade the effects of antibiotics and multiply in their own way leading to severe health consequences in human and animals. The menace is such that antimicrobial resistance (AMR) hinders treatment modalities targeted for infectious diseases. The hazards of antimicrobial resistance is frequently observed in various pathogenic and non-pathogenic organisms, viz. Salmonella spp., Campylobacter spp., Yersinia sp., E. coli serotype O157:H7, enterococci, Pasteurella sp., Actinobacillus sp. with varying severity (McEwen and Fedorka-Cray, 2002). Microorganisms that develop resistance to commonly used antimicrobials are referred to as superbugs. Globally it is a matter of great concern that it spreads rapidly and threatening the ability to treat common infectious diseases, resulting in prolonged illness, disability and death. Without any effective antimicrobial agent, treatment of infectious diseases, many medical procedures like cancer therapy, diabetes management, organ transplantation, and major surgery will not be possible. The microbes showing resistance to multiple antimicrobials are commonly known as multidrug resistance (MDR) organisms (Magiorakos et al., 2012).

Application of ultrasonography has become a routine practice in canine and feline medicine to detect pregnancy, to ascertain foetal wellbeing, to ascertain live/dead status of the foetus, ovarian dynamics, and to diagnose reproductive ailments (uterine, ovarian,) in females. Sonography is also being preferred in males for the diagnosis of diseases of prostate gland, cryptorchid, and testicular diseases.

This chapter attempts to travel the timeline and dissect historical perspectives of vaccination. Vaccine that protects and shields from numerous dangerous diseases (vaccine-preventable diseases; VPD) is an important area of research and development. Considering that vaccine has been very useful in successfully combating numerous infectious diseases in the past 200 years, they are considered as a historical turning point in the field of public health and medicines. Critical illnesses like the smallpox and wild polio (virus types 2 and 3) have mostly been eradicated as a result of mass immunisation programmes worldwide. Research, collaboration and widespread vaccination campaigns were necessary in vaccination efforts to control and ultimately eradicate infectious diseases. Biotechnological research has progressed to a level where producing recombinant vaccines is feasible. Research and development efforts on therapeutic vaccines are ongoing. Vaccine research in recombinant DNA/RNA technologies and therapeutic vaccinations for specific illnesses seem to be the future. This article offers a comprehensive history of vaccination since inception to its present forms, with future projections. Beginning with the variolation techniques in the early 17th century, it discusses the important turn of events from its discovery to the continued advancements and inventions till the covid-19 vaccine. Alongside the detailed core aspect, the chapter also describes the benefits of the one health approach with the zoonotic diseases in focus.

Messenger RNA (mRNA) vaccine was the first authorised vaccine developed using mRNA vaccine production technology, against SARS-CoV-2. Well accepted by the population, it proved to be a major life saving intervention during the COVID-19 pandemic. This article discusses the mRNA vaccine technology and its major advantages, and provides an update on the various ongoing and completed clinical trials on the leading mRNA vaccines against various viral diseases. It also delves into the prospects and the technical challenges associated with the manufacturing of mRNA vaccine and the issues with its deployment in the low- and middle-income countries around the world. Despite the already available classical vaccine candidates, the persistent interest and continuous research in mRNA vaccine technology and the related storage, immunogenicity and lipid nanoparticles delivery aspects have helped in expanding and upgrading the vaccinology arsenals to counter diseases. The technology holds promises in opening new vistas to protect against infectious diseases and the associated complications, where safe and effective immunisations are currently lacking. Furthermore, as mRNA vaccines evolve, they offer new hope against neglected and reemerging diseases like rabies, Zika, and Nipah viruses. The flexibility and rapid adaptability of this platform underscore its potential to address unmet medical needs, laying the groundwork for universal and multi-pathogen vaccines, vital in averting future pandemics. Enhanced by advancements in nanotechnology and innovative delivery systems, mRNA vaccines are poised to revolutionise infectious disease prevention, cancer treatment, and genetic disorders, marking a new era in vaccinology and offering hope for global health challenges through continued investment in research and infrastructure.

The R&D thrust in the pharmaceutical sector is focused on development of new drugs, innovative/indigenous processes for known drugs and development of plant based drugs through investigation of leads from the traditional systems of medicine. In addition, many nutraceuticals are being consumed from unregulated markets for their perceived benefits in health care and improvement of quality of life.

Natural pharmaceuticals, nutraceuticals and cosmeceuticals are of great importance as a reservoir of chemical diversity aimed at new drug discovery and can be explored as potential antimicrobial, cardiovascular, immunosuppressive, and anticancer drugs. Around 80% of all such products are of plant origin; their sales exceeded $ 65 billion in 2003. Examples of plant products and derivatives used by the pharmaceutical industry include Paclitaxel, Vincristine, Vinblastine, Artemisinin, Camptothecin, Podophyllotoxin and such.

The nutraceutical marketplace in Europe is estimated to be $ 9 billion, while the US marketplace, estimated to be $10-12 billion in 2003, is expanding at a compounded rate of more than 20% per year. US Congress has fueled the rapid growth of nutraceuticals with the passage of the Dietary Supplement Health and Education Act (DSHEA) in 1994. Globally, there have been efforts to monitor quality and regulate the growing business of herbal drugs and traditional medicine.

Nitrate - Nitrite Poisoning
Sources
Accidental ingestion/grazing of Plants which are Nitrate accumulators 

1 Introduction

The purpose of these Guidelines on Audit Quality is to assist Supreme Audit Institutions assure the high quality of their work and the resulting products. This Section describes the background of the document, provides key definitions applicable to these guidelines, discusses the types of SAIs and audits to which the guidelines apply, lays out the form in which the guidelines are presented and identifies some other sources of useful guidance for assuring quality. Section 2 then deals with quality control as the “hot review” ofthe audit process. Subsections 2.1 — 2.6 set forth some basic premises for establishing effective quality controls, discuss the nature of the controls required to assure quality in the areas of selection and timing of audits, planning specific audits, executing audits, reporting the results of audits, and following up on audits, respectively. Section 3 describes the procedures necessary to assure that needed quality controls are in place and operating effectively, that is it presents the characteristics of post-audit quality assurance. Finally, Section 4 focuses on institutional measures to enhance quality, especially management of human resources (recruitment, training, staff development and ethical standards), institutional risks and external relations. The Annexes provide other information that was considered potentially useful, including reference material, checklists and excerpts regarding quality controls from other guidance documents. The list of reference documents is contained in Annex A.

Audit quality is obtained by a process of identifying and administering the activities needed to achieve the quality objectives of an SAI. All types of SAI need to understand the benefits that can be realised once audit quality is made a priority. Improving audit quality requires a systematic SAI- wide approach. Piecemeal efforts by individuals and individual audit teams are not enough and will not work. There are no quick fixes to be obtained where audit quality is concerned. SAIs needs to proceed methodically in an organised way to fix each quality issue and problem in turn. As new problems will always emerge, this should be a continuous process for the SAI. It is also evident that most audit quality related problems are mainly the result ofpoor management of the audit process or the SAI itself.

This guidance explains when a botanical drug may be marketed under an over-the-counter (OTC) drug monograph and when FDA approval of a new drug application (NDA) is needed. In addition, this document provides guidance to sponsors on submitting investigational new drug applications (INDs) for botanical drug products, including those botanical products (or botanicals) currently lawfully marketed as foods and dietary supplements in the United States. This guidance also discusses several areas in which, because of the unique nature of botanicals, FDA finds it appropriate to apply regulatory policies that differ from those applied to synthetic, semisynthetic, or otherwise highly purified or chemically modified drugs (including antibiotics). In particular, the guidance states that applicants may submit reduced documentation of preclinical safety and of chemistry, manufacturing, and controls (CMC) to support an IND for initial clinical studies of botanicals that have been legally marketed in the United States as dietary supplements or cosmetics without any known safety concerns.

The process of vaccine development involves numerous stages from research, discovery, innovation, formulation, testing, mass production, logistics, deployment and administering the vaccine to the target population. The COVID-19 pandemic expedited the endeavour to develop vaccine worldwide that is unparalleled in history. In addition to the steps that were similar during the usual vaccine development process, it called for stronger collaborative teamwork with stricter deadlines during the pandemic due to the emergency situation that built up everywhere (in its spread as well as severity). Research was expedited, potential candidate vaccines were discovered and the proofs of concept were designed that paved the way for pre-clinical efficacy testing. Multiple-step clinical trials to ascertain that the vaccines were effective and safe at least for ‘emergency use’ in human subjects were carried out swiftly. The emergency usage regulatory approval and recommending the usage pattern involved accelerated review procedures. It immediately followed rapid scaling-up for increased production in order to meet the need to save as many human lives as possible across the globe. The approved vaccines were simultaneously evaluated for safety through dedicated pharmacovigilance systems. The future of vaccine development shall also focus on improving the worldwide access to vaccines, managing the virus variants and streamlining mass vaccination campaigns. Comprehending the research, development and administration phases to create and implement life saving vaccinations within the regulatory framework amid international health emergencies as encountered during the COVID-19 pandemic and the enormous collective endeavours are highlighted in this chapter.

Cardiac ultrasound is also known as echocardiography and it has a very important place in the diagnosis of cardiac diseases of the humans as well as animals. Echocardiography is an imaging of the heart using ultrasound. The diagnosis of congenital heart diseases, shunts, complex malformations, valvular heart diseases, different cardiomyopathies, endocarditis, pericardial effusion, cor pulmonale and cardiac tumours has been possible by cardiac ultra ultrasound that was otherwise difficult.

For the sake of convenience ruminants are broadly divided into two categories as large ruminants and small ruminants. Large ruminants consist of cattle and buffaloes and small ruminants consist of goats and sheep. Sonography is becoming an important part of diagnostic modalities in ruminants also. Its major use in ruminants is in reproduction and lameness.

3.1. Introduction

Various procedures performed on reptiles often necessitate chemical restraint or general anesthesia. Even routine tasks like physical examination and transportation can pose challenges, particularly with large or uncooperative reptilian patients. For safety reasons, venomous species are typically evaluated under chemical restraint. The respiratory anatomy and physiology of reptiles differ significantly from those of more familiar mammals, influencing their response to commonly used anesthetic agents. Historically, anesthetics recommended for reptiles had notable metabolic effects, but inhalant anesthesia has become more popular in recent times. Nonetheless, in species capable of anaerobic metabolism, induction with these agents may not be feasible (Girling 2013).

ABSTRACT

Advances in biotechnology, particularly methods for culturing plant cells and tissues can provide new means for the commercial processing of even rare plants and th chemicals they produce. These new technologies will extend and enhance the usefulness of plants as renewable resources of valuable chemicals. Aristolochic acid is mainly found in the genus Aristolochia. Aristolochic acid has been shown to hav anti-tumour activity and has been recommended for its activity against various effect of snakebite and its capacity to inhibit phospholipase A2 or other enzymes Considering the importance of medicinal use of A. bracteolata and A. indica, in th present study, they were selected for in vitro development and rapid multiplication o plant through tissue culture. The study was undertaken to enhance the in vitr production of Aristolochic acid in different tissue cultures. Cell suspension culture was established from friable calli of both the species in M liquid medium. Bergmann plating technique was carried out for cell line selection fo more production of Aristolochic acid. Primary transformation was carried out by Agrobacterium tumefaciens strain LBA4404 / pTOK233 with Gus and hpt genes to confirm the transgenic potential of A. bracteolata and A. indica. In order to enhance the productio of aristolochic acid in in vitro culture condition, the physical, chemical and biologica conditions were altered. Aristolochic acid was isolated, identified and purified from naturally growing plants as well as from tissue culture plants and all other cultur stages.

Nitrate – Nitrite Poisoning
Sources

Accidental ingestion/grazing of
Plants which are Nitrate accumulators

Introduction

The word mycotoxin is derived from myco, meaning mold and toxin, a poison. A great number of mold metabolites have been identified as mycotoxins. Thus mycotoxins are secondary fungal metabolites (i.e., metabolites not essential to the normal growth and reproduction of the fungus) which cause pathologic, physiologic, and/or biochemical lesions in other species (may include animals, plants, other microbes, etc.).

Mycotoxicosis - Poisoning of a biological system by a mycotoxin.

Mycotoxins  are  defined as toxic metabolites released by moulds under certain conditions conducive for their growth. Acute or chronic toxicoses can result from exposure to feed or bedding contaminated with toxins that may be produced during growth of various saprophytic or phytopathogenic fungi or molds on cereals, hay, straw, pastures, or any other fodder. A few principles characterize mycotoxic diseases: