Biomedical Laboratory Science

Friday, July 31, 2020

Mechanism how SARS-CoV-2 causes COVID-19 progression !

"The viral receptor on human cells plays a critical role in disease progression !"
Viruses enter cells and initiate infection by binding to their cognate cell surface receptors. The expression and distribution of viral entry receptors therefore regulates their tropism, determining the tissues that are infected and thus disease pathogenesis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third human coronavirus known to co-opt the peptidase angiotensin-converting enzyme 2 (ACE2) for cell entry. The interaction between SARS-CoV-2 and ACE2 is critical to determining both tissue tropism and progression from early SARS-CoV-2 infection to severe coronavirus disease 2019 (COVID-19). Understanding the cellular basis of SARS-CoV-2 infection could reveal treatments that prevent the development of severe disease, and thus reduce mortality.
Key phases of disease progression
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2). Initial infection of cells in the upper respiratory tract may be asymptomatic, but these patients can still transmit the virus. For those who develop symptoms, up to 90% will have pneumonitis, caused by infection of cells in the lower respiratory tract. Some of these patients will progress to severe disease, with disruption of the epithelial-endothelial barrier, and multi-organ involvement.
As with all coronaviruses, SARS-CoV-2 cell entry is dependent on its 180-kDa spike (S) protein, which mediates two essential events: binding to ACE2 by the amino-terminal region, and fusion of viral and cellular membranes through the carboxyl-terminal region. Infection of lung cells requires host proteolytic activation of spike at a polybasic furin cleavage site. To date, this cleavage site is found in all spike proteins from clinical SARS-CoV-2 isolates, as well as some other highly pathogenic viruses (e.g., avian influenza A), but it is absent from SARS-CoV and is likely to have been acquired by recombination between coronaviruses in bats. Cleavage by the furin protease therefore expands SARS-CoV-2 cell tropism and may have facilitated transmission from bats to humans. Membrane fusion also requires cleavage by additional proteases, particularly transmembrane protease serine 2 (TMPRSS2), a host cell surface protease that cleaves spike shortly after binding ACE2. SARS-CoV-2 tropism is therefore dependent on expression of cellular proteases, as well as ACE2.




Wednesday, July 15, 2020

Coronavirus Disease (COVID-19) Outbreak Updates !

This is how Covid-19 is spreading pandemic across the globe ! And with community transmission, Nepal is into the third stage of this pandemic !!

Watching carefully the entire video presents a very interesting and important hidden information how rapidly the virus at first spreads in China, then subsequently to other countries, at the same time how some countries including China were able to control and maintain the rate of spread while others such as Italy not able to and USA making to top !

Wednesday, April 15, 2020

Laboratory Diagnosis of Coronavirus (COVID-19) - Rapid Diagnostic Test (RDT)!

Laboratory methods for diagnosing COVID-19 follow two pathways:

  1. Detection of the coronavirus itself, and
  2. Detection of the body's adaptive immune response to the virus.

The stage of COVID-19 disease progression determines which detection method is most effective. The rapid diagnostic (RDT) test complements nucleic acid methods such as RT-PCR to improve speed of diagnosis and monitor disease progression. As the disease primarily attacks the lungs, specimens taken from the upper respiratory tract may be poor in quality and could lead to false-negatives with PCR.

To understand the clinical significance of results obtained from the RDT, the following information must be considered:

  • The median incubation period is estimated to be 5.1 days.
  • Specific IgM antibodies to SARS-CoV-2 become detectable 3-5 days after onset of symptoms.

Therefore, the RDT should not be used until symptoms have been present for at least 3 days.

Monday, March 30, 2020

Watch the dynamic spread of the global pandemic COVID-19 !

This is how Covid-19 is spreading pandemic across the globe !

Watching carefully the entire video presents a very interesting and important hidden information how rapidly the virus at first spreads in China, then subsequently to other countries, at the same time how some countries including China were able to control and maintain the rate of spread while others such as Italy not able to and USA making to top !

Tuesday, December 3, 2019

What are proteins and how much do you need?

Proteins are large molecules that our cells need to function properly. They consist of amino acids. The structure and function of our bodies depend on proteins. The regulation of the body's cells, tissues, and organs cannot happen without them.

Muscles, skin, bones, and other parts of the human body contain significant amounts of protein, including enzymes, hormones, and antibodies.

Proteins also work as neurotransmitters. Hemoglobin, a carrier of oxygen in the blood, is a protein.

What are proteins?

Proteins are long chains of amino acids that form the basis of all life. They are like machines that make all living things, whether viruses, bacteria, butterflies, jellyfish, plants, or human function.



Monday, November 25, 2019

Hormonal Dysfunction in Male Infertility -Diagnosis and Treatment !

Treatment of infertility-related hormonal dysfunction in men requires an understanding of the hormonal basis of spermatogenesis. The best method for accurately determining male androgenization status remains elusive. Treatment of hormonal dysfunction can fall into two categories — empirical and targeted. Empirical therapy refers to experience-based treatment approaches in the absence of an identifiable etiology. Targeted therapy refers to the correction of a specific underlying hormonal abnormality.

Since the first case reports in 1910 of testicular atrophy after canine hypophysectomy, the hormonal basis of human reproduction has been an area of evolving investigation. An array of treatment modalities are available for hormonal dysfunction in the setting of male infertility, but the diagnosis of such dysfunction and its treatment is often empirical, or guided by the clinician's judgement, and can be open to interpretation. Our ability to understand the intra testicular hormonal environment and its effect on spermatogenesis is limited by current methods of routine clinical investigation.

Investigations into female infertility benefit from reliance on objective, verifiable outcomes such as ovulation, biochemical pregnancy, and clinical pregnancy. Meanwhile, the male counterpart has been hampered by the necessary dependence on bulk seminal parameters, which are notoriously poor predictors of fertility potential. Perhaps the only truly reliable semen analysis is one indicating azoospermia and that is where the most exciting clinical outcomes research has focused.

This review article describes and discusses the pathophysiology, diagnosis, and treatment of fertility-associated male hormonal dysfunction.
  • Oestradiol is the principal mediator of negative feedback on the hypothalamic–pituitary axis, which illustrates the influence of selective oestrogen receptor modulators and aromatase inhibitors on male hormonal parameters
  • Serum hormonal assays are unreliable indicators of intratesticular androgen levels, and the best approach for determining male androgen status remains elusive
  • Follicle-stimulating hormone and inhibin B are markers of spermatogenesis and their relative values in the setting of an intact hypothalamic–pituitary–gonadal axis provide important information about testicular function
  • Targeted hormonal therapy corrects specific hormonal dysfunctions, empirical hormonal therapy is employed when no underlying cause is identified and the evidence for empirical therapy is dependent on the type of medication used
  • A return of sperm to the ejaculate or successful surgical sperm retrieval among men with azoospermia owing to spermatogenic dysfunction are the most objective indicators of outcomes of hormonal therapy






Saturday, November 23, 2019

How to Increase Laboratory Accuracy with Direct HbA1c Testing !

Diabetes is a global epidemic affecting in the region of 425 million people according to the International Diabetes Federation. Worryingly, this figure is on the rise with forecasts suggesting diabetes will affect up to 629 million people globally by 2045. Such a dramatic increase highlights the fundamental need for better disease management. When we look at the worldwide prevalence of diabetes, the United States is one of the most prominent countries affected.

HbA1c - an important biomarker for diabetes management and control !

HbA1c, also known as hemoglobin A1c or glycated hemoglobin, is an important blood test used to determine how well diabetes is being controlled. It develops when hemoglobin, a protein within the red blood cells that carries oxygen throughout the body, joins with glucose in the blood, becoming “glycated.” The concentration of HbA1c in the blood of diabetic patients increases with rising blood glucose levels and is representative of the mean blood glucose level over the preceding six to eight weeks. HbA1c can therefore be described as a long-term indicator of diabetic control, unlike blood glucose which is only a short-term indicator of diabetic control. It is recommended that HbA1c levels are monitored every three to four months.


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