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Topic Review
Adenosine Deaminase
Adenosine deaminase (ADA, EC 3.5.4.4) - the enzyme engaged in purine metabolism that irreversibly converts adenosine or 2′deoxyadenosine to inosine or 2′deoxyinosine, respectively. In human tissues, it occurs as two isoenzymes: ADA1 and ADA2. ADA1 constitutes the majority of ADA activity and it is present in virtually all tissues, while ADA2 has been found with ADA1 only in monocytes/macrophages. Both ADA isoenzymes are present in cytosolic form, soluble fraction that can be located away from the originating cell, or as ecto-enzymes binding to the cell surface by dedicated proteins. Intracellularly, ADA plays a significant role counteracting high concentrations of 2'deoxyadenosine. When intracellular ADA activity is lowered, e.g. during severe combined immunodeficiency disease (SCID), 2′deoxyadenosine accumulates and is converted to 2′-deoxyadenosine-5′-triphosphate (dATP), which inhibits ribonucleotide reductase (RNR), a crucial enzyme in DNA synthesis that follows disrupted T-cell development. Intracellular concentration of adenosine, the second substrate for ADA, is maintained inside the cell on the low level by adenosine kinase with Km value ~ 1 µM. Under conditions of low energy charge, adenosine-5′-monophosphate (AMP) that originates from adenosine-5′-triphosphate (ATP) degradation, is rapidly transformed to adenosine, which is not immediately deaminated to inosine due to high Km of ADA (25–100 µM). This results in temporary accumulation of adenosine that is vigorously exported out the cell via equilibrative nucleoside transporters (ENTs). Therefore, transmembrane adenosine transport, together with the activities of ecto-ADA and soluble ADA are important regulators of extracellular adenosine concentration. Except enzymatic function, ecto-ADA plays a significant extra-enzymatic role in the interactions between cells that expressed ADA-anchoring proteins on their surfaces. This co-stimulatory and cell-to-cell connecting actions along with its activity regulate many cellular processes related to proliferation and differentiation, which affect pathological conditions associated with cardiovascular diseases such as endothelial activation and dysfunction, inflammation, myocardial ischemia-reperfusion injury, or coagulation disorders. Since these pathologies are associated with ADA overexpression, the inhibition of its activity as well as binding to the surface proteins exhibit an attractive therapeutic potential in cardiovascular diseases.
  • 1.8K
  • 30 Oct 2020
Topic Review
Extra Virgin Olive Oil
Extra virgin olive oil (EVOO) is responsible for a large part of many health benefits associated with Mediterranean diet as it is a fundamental ingredient of this diet. The peculiarities of this golden highly valued product are in part due to the requirements that must be met to achieve this title, namely, it has to be obtained using exclusively mechanical procedures, its free acidity cannot be greater than 0.8%, it must not show sensory defects and it has to possess a fruity taste. All these characteristics are key factors to EVOO quality, thus the chemical composition of these many health-promoting compounds, such as unsaturated fatty acids (which are also the major compounds, especially oleic acid), as well as minor components such as tocopherols or phenolic compounds (which behave as natural antioxidants) must be preserved. Due to the presence of all these compounds, the daily consumption of EVOO entails health benefits such as cardioprotective, antioxidant, anti-inflammatory, anti-tumor properties or acting as regulators of the intestinal microbiota, among others. Taking all together, conserving EVOO chemical composition is essential to preserve its properties, so it is worth to control certain factors during storage like exposure to light, temperature, oxygen presence or the chosen packaging material, to maintain its quality and extend its shelf-life until its consumption.
  • 1.8K
  • 05 Nov 2020
Topic Review
Volumetric Muscle Loss
Volumetric muscle loss (VML) is the massive wasting of skeletal muscle tissue due to traumatic events or surgical ablation. This pathological condition exceeds the physiological healing process carried out by the muscle itself, which owns remarkable capacity to restore damages but only when limited in dimensions. Upon VML occurring, the affected area is severely compromised, heavily influencing the affected person’s quality of life. Overall, this condition is often associated with chronic disability, which makes the return to duty of highly specialized professional figures (e.g., military personnel or athletes) almost impossible. The actual treatment for VML is based on surgical conservative treatment followed by physical exercise; nevertheless, the results, in terms of either lost mass and/or functionality recovery, are still poor. On the other hand, the efforts of the scientific community are focusing on reconstructive therapy aiming at muscular tissue void volume replenishment by exploiting biomimetic matrix or artificial tissue implantation. Reconstructing strategies represent a valid option to build new muscular tissue not only to recover damaged muscles, but also to better socket prosthesis in terms of anchorage surfaces and reinnervation substrates for reconstructed mass. 
  • 1.8K
  • 26 May 2021
Topic Review
IBD
Inflammatory bowel disease (IBD) continue to cause substantial morbidity and massive productivity loss globally. IBD is more common among the productive generation (age group of <30yrs) and affects their quality of life. A single mechanism responsible for IBD is difficult to determine due to the complex interplay of multiple factors including host’s genetic predisposition and environmental factors. The relapsing nature of IBD demands repeated treatment implicating a substantial financial burden to individual patients and the concerned healthcare system, especially in developing nations. This review focuses on the causes of IBD,risk factors, current treatment options and challenges, the role played by the natural products in IBD health care; and situate these natural products within the current biodiscovery research agenda, including the applications of drug discovery techniques and the search for next generation drugs to treat IBD.
  • 1.8K
  • 29 Oct 2020
Topic Review
Dexibuprofen
S-(+) enantiomer of ibuprofen (IBU) dexibuprofen (DXI) is known to be more potent than its R-(−) form and exhibits many advantages over the racemic mixture of IBU such as lower toxicity, greater clinical efficacy, and lesser variability in therapeutic effects. Moreover, DXI potential has been recently advocated to reduce cancer development and prevent the development of neurodegenerative diseases in addition to its anti-inflammatory properties. 
  • 1.8K
  • 23 Jun 2021
Topic Review
Taylor Manifest Anxiety Scale
The Taylor Manifest Anxiety Scale, often shortened to TMAS, is a test of anxiety as a personality trait, and was created by Janet Taylor in 1953 to identify subjects who would be useful in the study of anxiety disorders. The TMAS originally consisted of 50 true or false questions a person answers by reflecting on themselves, in order to determine their anxiety level. Janet Taylor spent her career in the field of psychology studying anxiety and gender development. Her scale has often been used to separate normal participants from those who would be considered to have pathological anxiety levels. The TMAS has been shown to have high test-retest reliability. The test is for adults but in 1956 a children's form was developed. The test was very popular for many years after its development but is now used infrequently.
  • 1.8K
  • 05 Nov 2022
Topic Review
Cholinergic Receptors
Cholinergic receptors are activated by acetylcholine, a neurotransmitter that is released by the motor neurons for sensory and motor processing.
  • 1.8K
  • 30 Dec 2021
Topic Review
SARS-CoV-2 and COVID-19
Morbidity and mortality of coronavirus disease 2019 (COVID-19) are due in large part to severe cytokine storm and hypercoagulable state brought on by dysregulated host-inflammatory immune response, ultimately leading to multi-organ failure. Exacerbated oxidative stress caused by increased levels of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) along with decreased levels of interferon α and interferon β (IFN-α, IFN-β) are mainly believed to drive the disease process. Based on the evidence attesting to the ability of glutathione (GSH) to inhibit viral replication and decrease levels of IL-6 in human immunodeficiency virus (HIV) and tuberculosis (TB) patients, as well as beneficial effects of GSH on other pulmonary diseases processes, we believe the use of liposomal GSH could be beneficial in COVID-19 patients.
  • 1.8K
  • 25 Dec 2020
Topic Review
Adenosine and COVID-19
Coronavirus disease 2019 (COVID-19) patients can develop interstitial pneumonia, which, in turn, can evolve into acute respiratory distress syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has proteins capable of promoting the cytokine storm, especially in patients with comorbidities, including obesity. Since currently no resolutive therapy for ARDS has been found and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Through its receptors, adenosine is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier, and reduce the damage due to an overactivation of the immune system, such as that occurring in cytokine storms. These features are known in ischemia/reperfusion models and could also be exploited in acute lung injury with hypoxia. Considering these hypotheses, a COVID-19 patient with unresponsive respiratory failure was treated with adenosine for compassionate use. The results showed a rapid improvement of clinical conditions, with negativity of SARS-CoV2 detection.
  • 1.8K
  • 23 May 2022
Topic Review
Tuskegee Syphilis Experiment
The Tuskegee Study of Untreated Syphilis in the African American Male was a clinical study conducted between 1932 and 1972 by the United States Public Health Service. The purpose of this study was to observe the natural history of untreated syphilis; the African-American men in the study were only told they were receiving free health care from the Federal government of the United States. The Public Health Service started the study in 1932 in collaboration with Tuskegee University (then the Tuskegee Institute), a historically black college in Alabama. Investigators enrolled in the study a total of 600 impoverished, African-American sharecroppers from Macon County, Alabama. Of these men, 399 had latent syphilis, with a control group of 201 men who were not infected. As an incentive for participation in the study, the men were promised free medical care, but were deceived by the PHS, who disguised placebos, ineffective methods, and diagnostic procedures as treatment. The men who had syphilis were never informed of their diagnosis, despite the risk of infecting others, and the fact that the disease could lead to blindness, deafness, mental illness, heart disease, bone deterioration, collapse of the central nervous system, and death.. According to the Centers for Disease Control and Prevention, the men were told that they were being treated for "bad blood,” a colloquialism that described various conditions such as syphilis, anemia and fatigue. "Bad blood"—specifically the collection of illnesses the term included—was a leading cause of death within the southern African-American community. The men were initially told that the study was only going to last six months, but it was extended to 40 years. After funding for treatment was lost, the study was continued without informing the men that they would never be treated. None of the infected men were treated with penicillin despite the fact that by 1947, the antibiotic had become the standard treatment for syphilis. Study clinicians could have chosen to treat all syphilitic subjects and close the study, or split off a control group for testing with penicillin. Instead, they continued the study without treating any participants; they withheld treatment and information about it from the subjects. In addition, scientists prevented participants from accessing syphilis treatment programs available to other residents in the area. The study continued, under numerous Public Health Service supervisors, until 1972, when a leak to the press resulted in its termination on November 16 of that year. The victims of the study, all African-American, included numerous men who died of syphilis, 40 wives who contracted the disease and 19 children born with congenital syphilis. The 40-year Tuskegee Study of Untreated Syphilis in the African American Male study was a major violation of ethical standards. Researchers knowingly failed to treat participants appropriately after penicillin was proven to be an effective treatment for syphilis and became widely available. Moreover, participants remained ignorant of the study clinicians’ true purpose, which was to observe the natural course of untreated syphilis. The revelation in 1972 of study failures by a whistleblower, Peter Buxtun, led to major changes in U.S. law and regulation concerning the protection of participants in clinical studies. Now studies require informed consent, communication of diagnosis and accurate reporting of test results. The Tuskegee Syphilis Study, cited as "arguably the most infamous biomedical research study in U.S. history," led to the 1979 Belmont Report and to the establishment of the Office for Human Research Protections (OHRP). It also led to federal laws and regulations requiring institutional review boards for the protection of human subjects in studies involving them. The OHRP manages this responsibility within the United States Department of Health and Human Services (HHS). On May 16, 1997, President Bill Clinton formally apologized on behalf of the United States to victims of the study.
  • 1.8K
  • 07 Nov 2022
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