Cancer is a malignant neoplasm defined as an abnormal growth and division of cells. Molecular mechanisms of cancer predicted that there are two broad categories of genes such as proto-oncogenes and tumor suppressor genes control mitotic cell division. Tumor suppressor genes inhibit cell division, survival, or other properties of cancer cells. Oncogenes are the mutations of normal host genes which are proto-oncogene. Proto-oncogenes are good genes that normally control the essential cell functions such as cell proliferation and differentiation through signal transduction.
Abnormal signal transduction can lead to cancer which engulfs the brain, blood, lymph nodes, lungs, bone, and every other bodily organ, part, or system. But why is heart rarely affected by the cancer? This answer is much more silent yet and literature on heart cancer is quite limited. So it is very crucial topic for the genomic scientist and pharmacologist to explore the reason behind this. Primary cardiac tumor was scarce whereas malignant heart tumors also known as angiosarcoma or cardiac sarcoma are extremely rare. A sarcoma is a type of tumor that originates in the soft tissues of the body. A type of rhabdomyosarcoma occurs in the cardiac muscle tissues
At
the root of many of society’s major health concerns plaguing millions of
Americans each year is the concept of inflammation. Encompassingcardiovascular, oncologic, dermatologic, pain management, and neurologic
diseases, the peripheral and systemic manifestations of inflammation has been
increasingly shown to be a major culprit in disease spread.Broad examples of
this can be seen in various neurologic disease states.
Demyelinating diseases such as
Multiple Sclerosis and degenerative changes associated with dementia have many
factors with inflammation being one of those. The inflammatory cascade with itsincorporation of pro inflammatory cytokines and transcriptional factors has
been shown to be suggestive in the pathophysiology of these diseases .
Similarly, glial cells, acting as neural supports, have been shown to play a
role in the production of these same pro inflammatory cells (IL-1B, IL-6, IL-8,
TNF-alpha). The overproduction of these mediators is suggestive of
neurodegenerative progression in both acute (ischemic injury) and chronic
degenerative neural disorders.
Transient Receptor Potential (TRP) channels are an evolutionarily ancient and diverse superfamily of cation channels. Many TRP channels are involved in the transduction of stimuli of different sensory modalities: photo-, thermoreception, chemosensory reception and perhaps, mechanoreception and the activity of several TRP channels appear to be directly mediated by osmolarity and/or humidity. Like many other species across different phyla, mammals use TRP channels to detect a variety of physical and chemical stimuli including compounds derived from food plants and spices.
An interesting feature of some TRP channel family members is their ability to detect and integrate qualitatively different stimuli. For example, the temperature sensitive mammalian TRPV1 (sensitive to high temperature) and TRPM8 (sensitive to low temperature) channels were also demonstrated to interact with chemical compounds associated with high or low temperature perception, such as chili pepper derived capsaicinoids and menthol from peppermint respectively.
Protein binding is of great importance in pharmacokinetics and drug dosing due to the fact that protein bound drug is therapeutically unavailable for its intended action. It is only the unbound portion of the drug that is pharmacologically active. Thus, medications that are highly protein bound have a lower free fraction; the inverse relationship exists for minimally protein bound drugs.
Hepcidin is a small peptide hormone produced by the liver, which ensures for a tight balance of systemic and cellular iron levels in the body. Although its function appeared to be related to drosophila’s antimicrobial peptides like defensins, hepcidin is nowadays established as the key systemic regulator of iron homeostasis. Hepcidin orchestrates systemic iron fluxes by blocking iron absorption form the duodenum and iron release from macrophages. It does so by binding to ferroportin, the sole iron-exporter predominantly expressed on macrophages and enterocytes, causing its internalization, degradation and subsequent iron retention within the macrophages . The principal function of hepcidin in the regulation of systemic iron levels has been revealed using genetically engineered mouse models with overexpression or loss-off hepcidin function. Lack of hepcidin expression or mutations affecting regulators of hepcidin expression (e.g. Hfe) cause hemochromatosis, a common genetic iron overload disorder.
Methotrexate is a folic acid
antagonist, widely used as a chemotherapeutic agent in the treatment of various
cancerous stages (leukaemia, lymphoma, osteosarcoma, head and neck tumours,
lung cancer, breast cancer, etc.) and in the treatment of various inflammatory
diseases. It is also used for the treatment of multiple sclerosis,dermatomyositis, sarcoidosis, psoriasis, and rheumatoid arthritis, disorders
causing inflammation. Its side effects include hypersensitivity pneumonia,
central and peripheral nervous system toxicity, liver and gastrointestinal
system dysfunctions and hematologic failure.
In India, Ayurveda, Siddha and Unani (ASU) systems of medicine are considered to be the oldest system of medicines. They prescribe drugs of herbal, mineral, metallic and animal origin for the treatment of many diseases. Being time tested systems of medicine and majority of the drugs used by them are of herbal origin these systems are considered to be safe. The use of ASU medicines continues to expand rapidly across the world. The interest and demand for ASU system of medicine is day-by-day increasing both within India and abroad.
Personal care industries are aggressively competing and crowding the market with wide variety of sun screeners and SPF products to offer sun protection benefit to the customers.Photosensitivity is the major precursor of skin cancer. The global warming and increase in the solar coverage of earth has made different parts of our planet vulnerable to UV radiation. Further several occupational reasons have increased the solar exposure of people thus making them ‘risk group’ to sun.
Protein binding is of great importance in pharmacokinetics and drug dosing due to the fact that protein bound drug is therapeutically unavailable for its intended action. It is only the unbound portion of the drug that is pharmacologically active. Thus, medications that are highly protein bound have a lower free fraction; the inverse relationship exists for minimally protein bound drugs.
Our understanding of how to use DNA methyltransferase (DNMT) inhibitors to target DNA methylation in cancer therapy have come a long way since the nucleotide analogs 5-Azacytidine (5-Aza-CR, Vidaza) and 5-Aza-2’-deoxycytidine (5-Aza-2-CdR, Decitabine) were approved by the FDA over a decade ago for the treatment of myeloid dysplastic syndrome. First developed as chemotherapeutic agents, these compounds (hereon referred collectively as AZA) were found to reduce DNA methylation level in tumor cells, thus acting as demethylating agents. DNA methylation is a covalent addition of a methyl group at the fifth carbon of cytosines that are present in the context of CpG dinucleotides. DNA methylation is a component of epigenetic machineries, which in normal cells, is critical for silencing of retrotransposons, and during genomic silencing and X-inactivation. Although the levels may vary, global changes in DNA methylation have been shown to be a key feature of cancer cells. Furthermore, DNA methylation is dynamic and pharmacologically reversible and thus, an attractive target for cancer therapy.
According to virtually all published Pharmacoeconomics guidelines, the base case analyses (understood as the main result) must be deterministic. That is, the main result of an economic model (the incremental cost-effectiveness ratio, ICER) is a fixed result and is not subject to any uncertainty analysis. For example, with deterministic base case analysis we can obtain an ICER of 10,000 € per QALY gained with a new drug versus the former, but we do not know what confidence can we accept this result and what is the likelihood that the drug is cost-effective for a certain willingness to pay. The one-way sensitivity analysis, usually presented as tornado diagram is a deterministic analysis very useful to determine which variables of the study drivers of the result are obtained in the base case.
According to the NICE guidelines "wherever possible the results of the economic comparisons should be subjected to sensitivity analysis testing. For example, when data are drawn exclusively from clinical trials, 95% confidence intervals can be calculated for cost-effectiveness ratios. When data are drawn from a variety of sources and used in a modelling framework, probabilistic sensitivity analysis is recommended in order to take account of the uncertainty around data values". According to the ISPOR guidelines "for model-based economic evaluations, parameter uncertainty may be represented for individual parameters in a deterministic sensitivity analysis or across all parameters simultaneously with probabilistic analysis".
Flavonoids
are a group of natural compounds having a benzo-pyrone ring, and over 4,000
flavonoid compounds have been characterized and classified according to
chemical structure. Available reports tend to show that secondary metabolitesof phenolic nature, including flavonoids are responsible for the variety ofpharmacological activities . Their activities are structure dependent. The
chemical nature of flavonoids depends on their structural class, degree of
hydroxylation, reduction, other substitutions, conjugations, and degree of
polymerization. Flavonoids are widely present in the plant kingdom exhibiting a
broad range of biological activities, including antibacterial, antifungal,
antiviral, anti-allergic, anti-inflammatory, and anti-proliferative and
antioxidant activities.
It has been reported that the intensity of the
antimicrobial activity of a flavonoid strongly depends on its chemical
structure, which is particularly influenced by the number and position of
various functional groups such as, hydroxyl, methoxy, halogens, nitro, methyl,
cyano groups attached to the two aromatic rings (A and B). The third ring C islinked through a three carbon chain, mostly organized as an oxygenatedheterocyclic ring. A very few reports are available to the substitution pattern
in ring C at 3-position. However 3-hydroxy flavones and 3-methyl flavones have
been synthesized by many researchers, but their further reductions at
2,3-position in ring C are rare and yet to be explored. Substitution pattern at
3-position of ring C mainly regulates bioavailability and metabolism. Whereas
substitution at ring A and B influence biological activity. Flavonoids are well
known as antibacterial agents against a wide range of pathogenic microorganism.
