Waliza Ansar

Scanning electron microscopic studies on antenna of Hemipyrellia ligurriens (Wiedemann, 1830) (Diptera: Calliphoridae)—A blow fly species of forensic importance

Blow flies (Diptera: Calliphoridae) are one of the foremost organisms amongst forensic insects to colonize corpses shortly after death, thus are of immense importance in the domain of forensic entomology. The blow fly Hemipyrellia ligurriens (Wiedemann, 1830) (Diptera: Calliphoridae) is considered as a forensically important fly species globally and is also known for its medical and veterinary importance. In the present study, we report for the first time scanning electron microscopic studies on the morphology of sensilla of antenna of adult male and female of H. ligurriens is with profound importance in better understanding of the insect morphology from forensic entomological perspective, and also could aid in proper identification of the species from other calliphorid flies. The structural peculiarities observed in the (i) antenna of H. ligurriens with three segments- scape, pedicel and flagellum with dorso-laterally placed arista (ii) densely covered microtrichia and most abundant trichoid sensilla identified on the antenna (iii) observation of only one type of sensilla, chaetic sensilla (ChI) on the scape (iv) two types of chaetic sensilla (ChI and ChII) and styloconic sensilla on the pedicel (v) the flagellum with three types of sensilla- trichoid, basiconic and coeloconic sensilla (vi) Basiconic sensilla with multiporous surfaces with characteristic olfactory function. Moderate sexual dimorphism in the width of the flagellum, the females with wider flagella than the males, bear significance to the fact that they bear more multi-porous sensilla than the males, thus suffice their need to detect oviposition sites. Significant difference was observed in the length and width of coeloconic sensilla between the two sexes, the females showed bigger coeloconic sensilla, suggesting their function in oviposition site detection and successful colonization in corpses.

Inflammation and Inflammatory Diseases, Markers, and Mediators: Role of CRP in Some Inflammatory Diseases

The knowledge of inflammation records dates back in first century AD. Initially discovered with features of rubor, tumor, calor, and dolor, scientific investigations have revealed chemical components, cells, and pathways involved in the process of inflammation. The body’s initial defense in response to infection, trauma, or inflammation is through the acute-phase response (APR). APR is a multifaceted set of systemic reactions seen shortly after the experience of a triggering event. One of the many aspects of an APR is the increased hepatic synthesis of positive acute-phase proteins (APPs) leading to increased serum concentration of these proteins. The serum level of these APPs returns to base concentration when the stimulating factor is not anymore present. Today a plethora of inflammatory diseases are causing concern to global health. All the key players and mediators of inflammation change its role with the change in setup of disease and patients. The biomarkers of inflammation and inflammatory mediators are also used as therapeutic targets in under-trial animal models. Even in clinical diagnosis of an inflammatory patient, some broad-spectrum markers were analyzed without individual dissection of each mediator or biomarker. This chapter also provides a review of the acute-phase protein C-reactive protein and its possible use as inflammatory biomarker in diseases. We have highlighted case studies of some patients from Kolkata, India, revealing inflammation from disease together with their clinical history. The question which we probe in here is that whether there is a correlation with the clinical history, C-reactive protein, and inflammation and whether CRP can act as a unique diagnostic and prognostic biomarker in some diseases. The future course of this chapter lies in identifying clinical markers for inflammation, the sequential flow of inflammatory responses for a wide spectrum of diseases and its diagnostic, and therapeutic application to screen out pro-inflammatory diseases vs. anti-inflammatory conditions.

Role of CRP in Malaria

The worldwide situation of malaria is alarming. Increasing new cases of transmission of malarial infections in areas where it had not occurred before and the tendency to reinfect the areas from where it had been eradicated earlier remain the major concern with malaria. The mechanism of resistance to antimalarial drugs has increased; there are cases of mixed and single infections, emergence of malarial infections in non-endemic areas, and complication of infections in endemic areas. The vector resistance to insecticides has also become widespread. Nearly 220 million new infections annually are reported to occur globally. It is mostly endemic in continents of Africa, Asia, and Central and South America. Malaria turned out to be a major threat to public health today in more than 90 countries. C-reactive protein (CRP) is an acute-phase reactant and also a biomarker for inflammation. CRP can bind to different immune cells and also can activate various immune cells in various downstream signaling pathways. It plays various immunomodulatory roles and acts as a key molecule in the immune system. It can bind to a few kinds of Fcγ receptors present on the cell surface of various immune cells. The plasma concentration of CRP increases in different diseases during the inflammatory conditions. Its concentration also varies in acute versus chronic conditions. The role of CRP as an inflammatory biomarker and as an index/biomarker in a disease state,or its binding to different cells subsequently modulates the function of those cells. The various immunomodulatory roles of CRP in malaria are detailed in this chapter.

Acute-Phase Proteins and Responses and Their Application in Clinical Chemistry

The host innate responses to immunological stress initiate with a nonspecific response followed by specific responses. Host homeostasis is affected due to injury, infection, surgery, trauma, neoplastic growth, or immunological disorders and is combated by a prominent systemic reaction of the organism known as acute-phase response (APR). At the tissue injury sites and sites of invasion of microbes, a series of tissue responses are itself initiated. The activation of vascular system and inflammatory cells and release of pro-inflammatory cytokines are the key steps of these responses. These responses are then amplified by the overproduction of cytokines and different inflammatory mediators released in blood circulation. The acute-phase response is also characterized by hepatic secretion of some proteins termed as acute-phase proteins (APP). APR characterized by alteration in blood plasma composition is beneficial to the host in preventing microbial propagation and thus helps in restoring homeostasis. Multifunctional APPs can opsonize the invading microbes and activate the complement system and remove dead cells and free radicals. In this chapter, the changes induced by acute-phase response disruption of host body homeostasis are discussed. In addition, the diagnostic, prognostic, and therapeutic use of APPs in assessing health in animals as well as human patients is also described.

CRP and Diabetes: Sugar Is Not So Sweet

The complications and burden of the metabolic syndrome of diabetes is increasing worldwide. This metabolic disease is represented with inappropriate hyperglycemia either due to deficiency of insulin secretion or reduction in the biologic effectiveness of insulin. The pathogenesis of the multifactorial diabetes is very complicated. To control this pandemic disease, the pathophysiology of the disease and stipulated drug targeting covering definite areas are needed. During the progression of a prediabetic patient to diabetic, inflammation plays a key role, including insulin resistance and decreased beta cell secretory capacity. Insulin resistance plays a prominent role in the pathophysiology of various macrovascular complications. Drugs targeting through different inflammatory pathways represent a newer approach in the therapeutics of diabetes and its related complications.

CRP: Historical Perspective, Structure, Evolution, Synthesis, Clinical and Biological Functions

The C-reactive protein (CRP) is a plasma protein belonging to pentraxin family and has hepatic origin. It is the chief component of any inflammatory reaction. A key mediator of the innate immune system, an inflammatory biomarker whose concentration rapidly increases to nearly or more than 1000-folds above the normal values during tissue injury or infection. CRP functions through interaction of components of both humoral and cellular effector mechanisms of inflammation. Although considered as an acute-phase protein in tissue injury, infection and inflammation has now attained a distinct status of inflammatory disease marker not only in cardiovascular diseases but has well-known clinical and pathological relevance. The present study encompassing a number of diseases and associated conditions has highly illuminated the research field with the therapeutic role of CRP in health and disease. The future prospect of this chapter lies in the monitoring and understanding the applicability of CRP in the biology of various diseases.

Microheterogeneity of Proteins: Role in Diseases

Protein posttranslational modifications largely influence their biological functions. The functions included effect on receptor binding, metabolism of the protein, tissue uptake, degradation, excretion, and protein–protein interactions. Modifications of proteins at and after translation also called as posttranslational modifications or PTM occur at a normal physiological concentration of the protein. However, in some diseases, modifications highly specific to the disease also are known to occur. Thus, disease-specific posttranslational modifications find importance as diagnostic markers in clinical medicine. Different approaches, most of which are analytical to study the posttranslational modifications in protein together their interactions, and their complex structure and function are illustrated by various researchers in immunology, biochemistry, biophysics, and clinical medicine and in proteomics. Immuno assay based affinity purification of protein by HPLC and chromatographic methods, and characterization of proteins by lectin binding assays, biophysical methods like MS or mass spectrometry, and surface-enhanced laser desorption/ionization method find importance as diagnostic techniques in clinical proteomic studies, in the detection of the disease-specific protein modification.

Immune System: Freedom from the Burden of Diseases

In the daily life of a healthy individual, microorganisms are encountered at random, causing diseases only occasionally. The defense mechanisms mostly detect these microbes and destroyed them within minutes or hours through mechanisms of innate immunity. Adaptive immunity acts through antigen-specific lymphocytes to culminate pathogens. Both the innate and adaptive immune systems, to recognize pathogens, distinguish between self and nonself particles. The innate immunity discriminates very successfully between host cells and pathogens, providing earlier defenses and also induces adaptive immune responses. Defects in the components of innate immunity, in very rare cases, can lead to amplified susceptibility to infection, even in the presence of an intact adaptive immunity.

Role of CRP in Leishmaniasis

Different types of leishmaniasis are differentiated by range and complexity of clinical expressions ranging from asymptomatic infection to life-terrorizing illness. Visceral leishmaniasis (VL) is caused by an obligate intercellular parasite of the mononuclear phagocyte, Leishmania donovani, which causes a life-threatening disease. Leishmania during its stay in the human host have adapted to survive and proliferate in the host’s macrophages. The survival and proliferation of L. donovani in macrophages are largely due to the protection conferred by some family of glycosylinositol phospholipids or phosphoglycans on the cell surface or some secreted/expressed molecules of the host. C-reactive protein (CRP) is a prominent acute-phase protein of man. The serum concentration of CRP increases dramatically to nearly 10–1000-fold during inflammation following activation of hepatocytes by inflammatory cytokines. However, the function of CRP in inflammatory conditions and resistance to different infections is still less understood. CRP, a pattern recognition molecule, is present in host circulation. CRP binds to phosphorylcholine (PC) and some phosphorylated carbohydrates found on the surface of a number of microbes during their first entry into the mammalian host. Previously it was reported that CRP binds to the surface of L. donovani through their lipophosphoglycan (LPG) component and it increases the uptake of the parasite into host macrophages. Leishmania uses CRP to increase its infection without inducing any detrimental macrophage activation. The pathophysiology of different kinds of leishmaniasis was also abridged. CRP, being a phylogenetically conserved innate immune system recognition molecule, recognizes microbial determinants and components of damaged cells as an opsonin. CRP plays its effector function by activating the complement cascade and phagocytosis. A complete definition of the varied ligands used by CRP in recognizing the parasite is essential to understand its role in homeostasis and host defense. The main endeavor of this chapter is to unwind the functional significance of CRP in Leishmania infection, perpetuation, and survival in response to diverse host immune responses in the pathophysiology of its homeostatic mechanisms.

CRP and Cancer

C-reactive protein (CRP) as an acute-phase protein is a marker in inflammation, tissue injury and infection. The role of inflammation and CRP in different cancers is a recent matter of research. Increased CRP level is positively correlated with extent of disease and recurrence in advanced cancer. Its role as an interpreter of survival has been elucidated in melanoma, multiple myeloma, lymphoma, ovarian, renal, pancreatic and gastrointestinal tumors. The testing for CRP levels at the time of diagnosis could help clinicians determine severity of the disease with any adjacent inflammation, the tumor’s state of aggressiveness, or other conditions in the body and help guide therapeutics to improve overall survival. The poor prognosis in patients with different types of solid cancers is correlated with elevated plasma CRP levels. The circulating CRP concentrations has stronger correlation with the severity, extent and progression of many different tumor pathologies and the prognostic significance of these associations are consistent with CRP level. Thus CRP is not just being a marker of disease or an inflammatory biomarker but also it contributes to the pathogenesis of cancer also.