Hormonal Dysfunction in Male Infertility -Diagnosis and Treatment !

Male Infertility:

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

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A Primeview on Sickle Cell Disease !

Primeview:

Sickle cell disease (SCD) is a group of inherited disorders caused by mutations in HBB, which encodes haemoglobin subunit β. Haemoglobin molecules that include mutant sickle β-globin subunits can polymerize; erythrocytes that contain mostly haemoglobin polymers assume a sickled form and are prone to haemolysis. Other pathophysiological mechanisms that contribute to the SCD phenotype are vaso-occlusion and activation of the immune system. SCD is characterized by a remarkable phenotypic complexity. Common acute complications are acute pain events, acute chest syndrome and stroke; chronic complications (including chronic kidney disease) can damage all organs. Hydroxycarbamide, blood transfusions and haematopoietic stem cell transplantation can reduce the severity of the disease. Early diagnosis is crucial to improve survival, and universal newborn screening programmes have been implemented in some countries but are challenging in low-income, high-burden settings.

Sickle cell disease (SCD) is an umbrella term that defines a group of inherited diseases (including sickle cell anaemia (SCA), HbSC and HbSβ-thalassaemia) characterized by mutations in the gene encoding the haemoglobin subunit β (HBB). Haemoglobin (Hb) is a tetrameric protein composed of different combinations of globin subunits; each globin subunit is associated with the cofactor haem, which can carry a molecule of oxygen. Hb is expressed by red blood cells, both reticulocytes (immature red blood cells) and erythrocytes (mature red blood cells). Several genes encode different types of globin proteins, and their various tetrameric combinations generate multiple types of Hb, which are normally expressed at different stages of life — embryonic, fetal and adult. Hb A (HbA), the most abundant (>90%) form of adult Hb, comprises two α-globin subunits (encoded by the duplicated HBA1 and HBA2 genes) and two β-globin subunits.

A single nucleotide substitution in HBB results in the sickle Hb (HbS) allele βS; the mutant protein generated from the βS allele is the sickle β-globin subunit and has an amino acid substitution. Under conditions of deoxygenation (that is, when the Hb is not bound to oxygen), Hb tetramers that include two of these mutant sickle β-globin subunits (that is, HbS) can polymerize and cause the erythrocytes to assume a crescent or sickled shape from which the disease takes its name. Hb tetramers with one sickle β-globin subunit can also polymerize, albeit not as efficiently as HbS. Sickle erythrocytes can lead to recurrent vaso-occlusive episodes that are the hallmark of SCD. SCD is inherited as an autosomal codominant trait; individuals who are heterozygous for the βS allele carry the sickle cell trait (HbAS) but do not have SCD, whereas individuals who are homozygous for the βS allele have SCA. SCA, the most common form of SCD, is a lifelong disease characterized by chronic haemolytic anaemia, unpredictable episodes of pain and widespread organ damage.

This primeview focuses on SCA and aims to balance such remarkable advances with the key major challenges remaining worldwide to improve the prevention and management of this chronic disease and ultimately to discover an affordable cure.

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Molecular Basis of Tolerance and Immunity to Antigens.

Molecular Immunology

The intestinal immune system has to discriminate between harmful and beneficial antigens. Although strong protective immunity is essential to prevent invasion by pathogens, equivalent responses against dietary proteins or commensal bacteria can lead to chronic disease. These responses are normally prevented by a complex interplay of regulatory mechanisms. This article reviews the unique aspects of the local microenvironment of the intestinal immune system and discuss how these promote the development of regulatory responses that ensure the maintenance of homeostasis in the gut.

The intestinal immune system is the largest and most complex part of the immune system. Not only does it encounter more antigen than any other part of the body, but it must also discriminate clearly between invasive organisms and harmless antigens, such as food proteins and commensal bacteria. Most human pathogens enter the body through a mucosal surface, such as the intestine, and strong immune responses are required to protect this physiologically essential tissue. In addition, it is important to prevent further dissemination of such infections. By contrast, active immunity against non-pathogenic materials would be wasteful, and hypersensitivity responses against dietary antigens or commensal bacteria can lead to inflammatory disorders such as Coeliac Disease and Crohn's Disease, respectively. As a result, the usual response to harmless gut antigens is the induction of local and systemic immunological tolerance, known as oral tolerance. In addition to its physiological importance, this phenomenon can be exploited for the immunotherapy of autoimmune and inflammatory diseases, but it is also an obstacle to the development of recombinant oral vaccines. For these reasons, there is great interest in the processes that determine the immunological consequences of oral administration of antigen. To some extent, this discrimination between harmful and harmless antigens also occurs in other parts of the immune system, as it partly results from inherent properties of the antigen and associated adjuvants. Nevertheless, it has been proposed that there are also specific features of mucosal tissues that favour the induction of tolerance, the production of immunoglobulin A antibodies and, to a lesser extent, T helper 2 (TH2)-cell responses. Several features of mucosal tissues might contribute to these effects, including a unique ontogeny and anatomical patterning, specialized cells and organs that are involved in the uptake of antigen, distinctive subsets of antigen-presenting cells (APCs) and several unusual populations of B and T cells. In addition, the migration of lymphocytes to the intestine is controlled by a series of unique adhesion molecules and chemokine receptors.

This review article discusses the anatomical factors which determine the special nature of small intestinal immune responses, and the unique processes and cells involved in the uptake and presentation of antigen to T cells in the gut. In particular, it focuses on the local factors that determine the behaviour of APCs and T cells in the gut and discuss recent evidence that challenges the conventional dogma that Peyer’s patches are the only site for the initiation of mucosal immunity and tolerance.

It also focuses on the small intestine, as this tissue has been studied in most detail and it contains the largest proportion of immune cells in the gut. However, the reader should be aware that each compartment of the intestine, from the oropharynx to the stomach and to the rectum, has its own specializations, which might have individual effects on immune regulation in response to local antigens.

• The intestinal immune system is an anatomically and functionally distinct compartment, in which a careful distinction must be made between harmful antigens, such as invasive pathogens, and harmless antigens, such as dietary proteins or commensal bacteria.

• The default response to harmless antigens is the induction of tolerance. A breakdown in this physiological process can lead to disease.

• Immune responses and tolerance in the gut are initiated in organized lymphoid organs, such as the Peyer's patches and mesenteric lymph nodes (MLNs). The mucosa contains effector or regulatory cells that migrate there selectively, from the MLNs, in the lymph and bloodstream under the control of α4β7 integrins and the chemokine receptor CCR9.

• Pathogens might enter the intestinal immune system through M cells in the follicle-associated epithelium of the Peyer's patches, whereas soluble antigens might gain access predominantly through the normal epithelium that covers the villus mucosa.

• Peyer's patches, lamina propria and MLNs contain unusual populations of dendritic cells (DCs), some of which are characterized by the production of interleukin-10 (IL-10) and which polarize T cells to an IL-4-, IL-10- and transforming growth factor-β (TGF-β)-producing 'regulatory' phenotype.

• Genetically determined factors, together with luminal bacteria, might act on epithelial and stromal components of the intestinal mucosa to produce a local microenvironment that is dominated by the constitutive production of prostaglandin E2 (PGE2), TGF-β and IL-10. Under physiological conditions, this favours the differentiation of regulatory DCs and T cells, which leads to systemic tolerance and/or immunoglobulin-A production.

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I Want to be a Medical Lab Technologist. What will my Salary be?

The job: Medical laboratory technologist

The role: From throat swabs to cancer screens, blood tests to DNA tests, Canadians generate over 440 million medical test results a year, which are conducted by medical laboratory technologists (MLTs).

“We would have been there the day you were born to test you for certain disorders as a baby, and you would have never known,” says Christine Nielsen, the chief executive officer of the Canadian Society for Medical Laboratory Science in Hamilton . “As a healthy adult, when your doctor sends you off for lab tests and just wants to see what your glucose [level] is, your specimen goes through our people.”

Read more: I Want to be a Medical Lab Technologist. What will my Salary be?

National Microbiology Lab technician, Lillian Mendoza, processes patient samples for the measles

virus and genotyping in Winnipeg Manitoba, February 19, 2015.

Source: theglobeandmail

ERBA Mannheim Clinical Chemistry Analyzer XL-1000

Automated high throughput random access analyzer, it offers continuous sample loading facility using racks. Contrary to other automatic analyzers, the sample loading is automatic instead of manual thereby enhancing precision.

• Throughput of upto 1040 tests/hour with ISE- 800 photometric tests/ hr and 240 tests/ hr with ISE
• Permanent hard glass cuvettes – requiring no replacement for upto 4-5 years
• Direct ISE measurement for Na/K/Cl/Li (optional)
• Auto re-run, auto dilution, reflex testing
• Probes with clot detection & Vertical Obstruction Detection feature
• Low reagent/test consumption -requires reagent volume of just 150 µL, thereby proving to be cost effective for laboratories
• Extensive Quality Control menu (L-J chart, twin plot, QC rules)

Read more: ERBA Mannheim Clinical Chemistry Analyzer XL-1000

Source: ERBA Mannheim

Building a career in the biomedical laboratory sciences.

Passion is the key to success, says Jim Smith in his keynote speech at the London NatureJobs Career Expo.

Jim Smith is a successful scientist by anyone’s measure. The UK scientist helped discover key growth factors required for the early development of embryos, and has received numerous awards for his scientific contributions. Smith now juggles three high-level roles at the UK Medical Research Council (MRC), National Institute of Medical Research and the soon-to-be-opened Francis Crick Institute in London with the running of his own lab at the MRC.

Like many people who have excelled in their field, Smith’s career has the illusion of being planned from the start. However he says this was not the case. He didn’t study biology until he was persuaded to take a cell biology class at the University of Cambridge while studying for a degree in natural sciences.

He fell so in love with the subject that he progressed to a PhD studentship with the famous development biologist Lewis Wolport. “You should allow yourself to fall in love with your subject, become engrossed by it,” Smith says. This passion is a key to success he stresses, because it drives you to put the necessary effort in. “There are times in your career when you know that working twice as hard will produce double the results, at these times you should work 3 or 4 times as hard,” Smith says.

Finding the ‘niche’ in science that you are most passionate about can be challenging.

Read more: Building a career in the biomedical laboratory sciences.

Source: naturejobs