eChapters

ABSTRACT

Purine Nucleoside Phosphorylase (PNP) is an enzyme that functions in the purine salvage pathway by catalyzing the phosphorolysis of purine nucleoside thereby releasing the purine bases and phosphorylated sugar. Interest in PNP as a drug target arises from its role in T-cell proliferation and T-cell mediated autoimmune diseases. Recently, we have isolated the compound, coixol, from the plant Scoparia dulcis L. and its three-dimensional structure has been elucidated. As the structure of the coixol mimics the structure of PNP inhibitors, we have undertaken the molecular modeling studies of this compound with Human PNP, as a screening test for further in vivo studies. Generally PNP inhibitors have been synthesized with a ribose sugar moiety attached to them. As the plant Scoparia dulcis L. contains glucose and rhamnose (six membered ring), these sugar moieties are also included along with ribose in the presen study. In order to understand the binding mode and interactions of the isolated compound attached with different sugar groups, we have carried out the docking studies with Human PNP. The interactions between the ligand molecules and active site residues of Human PNP are similar to those of solved complexes and the energy values are also comparable, which clearly indicate that these ligands may act as inhibitors.

Antimicrobial resistance (AMR) is a mounting global health emergency that threatens the effectiveness of modern medicine and veterinary care. In India, the challenge is compounded by high antibiotic consumption, unregulated access to antimicrobials, and widespread use in agriculture and animal husbandry. The World Health Organization has identified the Eskape pathogens— Enterococcus faecium, Staphylococcus aureus, Klebsiellapneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp, as priority organisms due to their ability to “escape” the effects of antibiotics and cause life-threatening infections. Simultaneously, zoonotic transmission of resistant bacteria from animals to humans is emerging as a critical concern, particularly in regions with close human-animal interfaces like Jammu & Kashmir. The importance of Eskape pathogens to the establishment and promotion of antimicrobial resistance in hospitalized patients was first recognized in a 2008 by Rice. The morbidity and mortality associated with Gram-negative Eskape pathogens is particularly concerning, as new antimicrobial agentsthose with activity against multidrug-resistant and pan-resistant Gram-negative strainshave not emerged as quickly as needed. Consequently, nosocomial infections continue to pose a serious threat to patient health, especially among critically ill inpatients and those undergoing invasive procedures or requiring the placement of medical devices. Eskape pathogens are well known for their intricate resistance mechanisms, often leaving clinicians with limited therapeutic options. Due to their significant role in driving antimicrobial resistance within hospital settings, consistent and systematic monitoring of their resistance profiles is crucial for guiding effective infection control and therapeutic strategies.This also serves as a critical indicator of regional resistance trends among hospitalized populations. In animal sector, the wastewater of livestock slaughterhouses, animal products (raw or processed) have been considered a source of multidrugresistant bacteria with clinical implications as well as their dissemination into the environment and entry into human food chain.Bacteria from the livestock can act as opportunistic pathogens and carry resistance genes that are important for both veterinary and human health. Since many antibiotics are used in both human and animal health fields, the resistant bacteria enter the environmentespecially through wastewater treatment plants affected by slaughterhouse wasteposing risks to public health. Among the various sources, the water used during poultry slaughtering often contains multidrug-resistant bacteria and can expose slaughterhouse workers to infection. To reduce these risks, it’s important to develop strategies that limit bacterial release into the water systems and prevent their spread to people and the environment. The development of AMR has been attributed to several factors comprising of microbial mutations rendering the antibiotics ineffective, human interference such as over use and over-prescription of antimicrobials, agricultural and commercial application of antimicrobials in the animal sector, and human behavioural factors (Vijayalaxmi et al., 2021). An expected annual rise of antimicrobial resistance (AMR) by 5–10 % annually has been predicted by the Indian Council of Medical Research (ICMR) Annual Report 2021 due to wide spread abusive use of broad-spectrum antibiotics (ICMR Annual Report 2021). Twelve families of priority drug-resistant bacteria (critical, high and medium) posing great threat to human health in terms of resistance to selected antimicrobials have been identified in priority pathogen list (PPL) of Global Action Plan, World Health Organisation (WHO) to stimulate the research towards the development of new antimicrobials against a particular drug-resistance (WHO,2017). From the Indian perspective, AMR is a grave concern as the Indian population is the highest consumer of antibiotics in the world (10.7 units per person). The poor public health systems, hospital infections, high rate of infectious diseases, easy availability of inexpensive

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.

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:

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.).

? Secondary metabolites of toxigenic fungi on animal food and food ingredients which causes adverse effects when consumed.

? 1942-44: Mycotoxicosis in man and animals was recognized in Russia. Fatal outbreaks of “toxic alimentary aleukia”. 

? 1955: “Hepatitis X” in dog and in cattle and swine in 1957.

? 1960: “Turkey- X disease” and 100,000 turkeys died in England due to Aspergillus flavus infested ground nut meal.

? 1962: Aflatoxin was first isolated.

? Favorable conditions for growth of fungi: Min. 15% moisture (10-13%), relative humidity: 90-95% (> 70%), ambient temp. of 24-25ºC (4-35ºC).

? Moulds infested feed along with nutritionally poor and inadequate diet makes animal more susceptible to mycotoxins induced harmful effects.

? More than 100 toxigenic fungi and mycotoxins have been identified during the last three decades.

Introduction
Antimicrobial resistance (AMR) is a mounting global crisis that threatens public health, food security, and development. The rapid spread of resistant pathogens has rendered many conventional antibiotics ineffective, leading to longer illnesses, increased mortality, and escalating healthcare costs(1)(2). The World Health Organization characterizes AMR as a top-ten global health threat, driven by overuse, misuse, and inadequate dosing of antibiotics. It already kills 700,000 people a year and is expected to kill 10 million people a year by 2050 if nothing is done about it(3). After penicillin was introduced to the market in 1941, the first signs of resistance appeared in staphylococci, streptococci, and gonococci. By 1942, Staphylococcus aureus, which was penicillin-resistant, emerged(4). Drug resistance must be effectively addressed for a few reasons, including public health, economic considerations, and the long-term viability of medicine. Maintaining the effectiveness of existing treatments for infectious diseases is an important objective(5). NDDS technologies have emerged as powerful tools to enhance the delivery, bioavailability, and targeting of antimicrobial agents, potentially reviving older antibiotics, and maximizing the efficacy of novel compounds(6). Parallelly, AI has found impactful applications in biomedical data analysis, drug discovery, and the rational design of therapies by processing complex datasets, predicting resistance patterns, and guiding the creation of new molecules. The integration of AI with NDDS marks a paradigm shift to optimizes delivery systems, guides individualized treatment plans, and advances the field towards precision medicine for infectious diseases (7). This chapter surveys the convergence of these technologies, exploring how AIenhanced NDDS platforms are reshaping the response to AMR. Additionally, it examines diverse AI models and algorithms employed in the prediction, optimisation, and management of drug resistance, enhanced by real-time case studies for thorough comprehension(fig1.).

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.

Introduction
Antimicrobial resistance (AMR) is increasingly recognised as a “silent pandemic,” threatening global health and development. In 2019 alone, bacterial AMR was directly responsible for 1.27 million deaths and contributed to nearly 5 million more worldwide. Projections warn that by 2050, unchecked AMR could result in 10 million annual deaths and impose a staggering economic burden of USD 100 trillion. A major driver of this crisis is the indiscriminate and often prophylactic use of antibiotics in livestock production systems, which account for a majority of global antimicrobial consumption. The One Health framework—emphasising the interconnectedness of animal, human, and environmental health—offers a strategic pathway for mitigating AMR. It requires dismantling sectoral silos and fostering collaboration among veterinarians, physicians, public health authorities, food safety regulators, and environmental scientists. Against this backdrop, NDDB has positioned itself as a frontrunner in India by embedding One Health principles into large-scale field programmes. Since 2014, NDDB has progressively promoted alternative medicine for bovine mastitis control under its Mastitis Conrol Project (MCP), subsequently expanding in 2017–18 into a broader Disease Control through Alternate Methods (DCAM) project with Ethnoveterinary Medicine (EVM) as the central pillar.
Building Up: From DCAM to DISHA as One Health Strategy
Building on the successes of MCP, DCAM, and BCP, NDDB launched the Dairy Integrated Safety and Health Action (DISHA) project for 2025–2030, DISHA consolidates NDDB’s One Health strategy by combining animal health management, zoonotic disease surveillance, and food safety monitoring. Its objectives include: managing bovine cases with EVM, organising farmer awareness programmes, training veterinarians and health workers, screening cattle as well as their owner for brucellosis, and testing bulk milk samples for aflatoxins and antibiotic residues. Importantly, DISHA also addresses emerging food system contaminants such as microplastics, per- and polyfluoroalkyl substances (PFAs), Bisphenol-A (BPA) and heavy metals, thereby broadening the scope of One Health beyond infectious diseases.

Nerium oleander

? (Oleander, kaner, rose laurel)

? An ornamental plant and grown in lawns and gardens.

? Other species are Nerium indicum (kaner) & Thevetia peruviana (yellow oleander).

Sources

? Almost all animal species are poisoned.

? Ingestion of branches, stem or leaves during drought or periods of food scarcity or consumption of contaminated water by ruminants or horses.

? Chewing of leaves may be responsible for toxicity in dogs.

? Ingestion of 30-60 gram fresh leaves of oleander is fatal for horses, cattle and sheep.

? All parts of plant are toxic, the leaves and flowers may be less toxic than the seeds.

INTRODUCTION

? Nitrate poisoning is generally caused when animals eat too much forage that is high in nitrates not changed to protein in the plant.

? Poisoning can also happen when animals eat too much urea or nitrogen fertilizer spilled in the field or left where the animals can find it.

? Nitrate fertilizer is palatable, especially to cattle.

? Nitrates are relatively non-toxic.

? Reduction of nitrates depends on the supply of fermentable energy as carbohydrates supply hydrogen ions for reduction of nitrates and production of nitrite in rumen.

Nitrate – Nitrite Poisoning
Sources

Accidental ingestion/grazing of
Plants which are Nitrate accumulators

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

As the heart diseases in companion animals is becoming common as in humans, the research in canine cardiac diseases is one of the most extensive studies in the present scenario. As per the available literature, the overall occurrence of various cardiac abnormalities ranges from 0.37 percent to 1.67 percent in various parts of the country. Whereas, in western parts of the globe, nearly 8 million dogs suffer from heart disease accounting 10% of all dogs in the United States. Heart diseases are common among older dogs; up to 75% of senior dogs have some type of heart condition, and unfortunately, most go undiagnosed due to varied reasons. The recognition of canine cardiac diseases has been delayed, and ignored on account of lack of awareness and knowledge by the owner and inadequate diagnostic facility in our country. Physical examination, radiography, electrocardiography and echocardiography are most useful diagnostic procedures employed in diagnosing the cardiac diseases in dogs. However, majority of the acquired cardiac diseases are being managed medically with one or a combination of drugs. Improved diet management and health care of companion animals have led to increased life expectancy, as a result, cardiac diseases have become pivotal causes of death for both dogs and cats. For such reason, a major objective has become to increase the quality of life by reducing the expansion of cardiac diseases via early detection of diseases and provision of effective treatment.

A new buzz-word is rapidly spreading through the manufacturing and analytical environment. Discussions on the application of Non Invasive Research namely the Near Infrared (NIR) Spectroscopy are often found on the agenda of production, project, and technical and even board meetings. Engineers and chemists are confronted more frequently with the challenge to decide whether a NIR instrument will be the solution to their production quality control and other analytical problems. Are there really amazing machines that can determine protein, fat, moisture, fibre, starch, nicotine, alcohol, sugar, amino acids and whatever analyses you require on any product from foodstuff to fertilizer and animal feeds in less than a minute and so simple to operate that even the unskilled labourer can handle it? In this article we will endeavor to answer the questions that often crop up in the evaluation of NIR as an analytical technique towards Natural Products.

1. Introduction

Buckwheat is one of the most important life supporting nutritious crops, which has come as a secondary crop in many countries and has now attained its position in the agriculture of many countries where cereals form the stable food for the people. Though the crop is not a cereal, the seeds themselves can bring the name ‘pseudocereal’ due to their similar usage as cereal grains. There are many species of buckwheat in the world, of which mainly nine species have agricultural value (Krkoskova and Mrazova, 2005). Generally, the genus Fagopyrum in the family Polygonaceae includes two buckwheat species used for food around the world: common buckwheat (F. esculentum Moench), which is almost grown on all continents, and tartary buckwheat (F. tataricum (L.) Gaertn), which originated in eastern Tibet or northwestern Yunnan in China and is grown only in Asia, Europe, and North America (Bonafaccia et al., 2003; Tsuji and Ohnishi, 2001).

Buckwheat is grown throughout a large area as a crop that fits the farming system on marginal and fairly unproductive land. It is used as a subsistence crop in many of the more mountainous areas where it is often grown with barley at the higher altitudes. Tartary buckwheat, because of its frost tolerance, is generally grown at the higher altitudes whereas common buckwheat is grown at the lower altitudes. In many areas the trend is for replacement of common buckwheat, which has lower yielding ability and lacks frost tolerance, with finger millet or other crops.

Introduction

The immense use of chemicals and pharmacological entities has put the public health at brisk of potential health hazards. These substances in modern days are presented in the form of common constituents of food, medicines, beverages and junk foods etc. However, long term consumption of these substances might be responsible for chronic toxicity, but the accidental ingestion of large quantities of these substances may result into adverse acute toxic reactions. Hence an experimenter should have the acumen to develop and perform the acute toxic tests in order to find out the lethal dose 50 i.e. LD50 of the substances.

Acute Toxicity Studies

Acute toxicity studies helps to establish the dose dependent adverse effect including mortalities. The LD50 has been used as a major parameter in screening of pharmacological agents for acute toxic potential. Apart from mortality, other biological effects and the time of onset, duration and degree of recovery on survived animals, are also important in evaluation of acute toxicity. Hence, acute toxicity study solely gives information about LD50, therapeutic index and the degree of safety of a pharmacological agent.

Acute toxicity is defined as adverse effects occur following oral or dermal administration of a single dose of a substance, or multiple doses given within 24 hours, or an inhalation exposure of 4 hours. Oral administration is the most common form of acute systemic toxicity testing.

The world turned into a grossly inhabitable during the infamous COVID-19 pandemic, with community health issues everywhere. Each one felt unsafe if other earthly inhabitants were, be it humans or other living beings. Onset of SARS CoV-2 set a ‘new normal’ world order. The ever-evolving and mutating SARS CoV-2 variants extended the pandemic wave after wave thereby complicating the situation, pushing the global healthcare system to its limits and exposing its underbelly. The continually evolving variants were more aggressively transmissive and infective. As the world still reels under tremendous healthcare pressure, other infectious diseases are emerging as are identified by the World Health Organisation (WHO), creating international health emergency situations. The situation becomes alarming with the increasing zoonotic (spillover) and reverse zoonotic (spillback) factors being more proactive in the disease spread. There is a greater need to vaccinate not only humans but also animals, especially the domesticated ones and known reservoirs/carriers. Vaccines must be developed on priority and equitably distributed as the first step to counter a pandemic or potential pandemic. Vaccination is self-limiting due to increasing reported breakthrough infection cases. A strong link of the environmental health to the overall global health needs to be acknowledged, and due diligent measures taken. Hence, there is a strong need of the One Health approach as a 360° solution, and follow it up at global-scale both in letter and spirit. This chapter discusses spillover and spillback of diseases like SARS-CoV-2 and Mpox as case examples, the mitigation strategies and the need for workable One Health models, and challenges and measures to counter future outbreaks. It stresses on foolproof vaccination strategies across to catalyse individual and herd immunities for universal wellbeing.