3^rd Year Medical Student Diponegoro University School of Medicine Semarang – Indonesia

correspondence and discussion: fadelmuhammadg@student.undip.ac.id

Dengue fever is a quite highly occurs infectious disease particularly in tropical countries where the Aedes aegypti mosquitos breeding and exist. Another species known as Aedes albopictus also recognized as the vector of the dengue fever infection. As in 2010, The Ministry of Health Indonesia reported that more than 150,000 people across Indonesia were infected, and more than 1,400 people, mostly children, died of the disease. By comparison, in Thailand last year there were 57,000 infections and 70 fatalities. DENV-3 is the most common serotype circulating, although all four serotypes are present in Indonesia.

Biology of Dengue Virus

Dengue virus (DENV) belongs to the flaviviridae family, single-stranded positive polarity RNA virus. It causes human infectious disease that clinically manifested from the mild dengue fever (DF), dengue hemorrhagic fever (DHF) up to the severe and life-threatening dengue shock syndrome (DSS). The virus structurally consists of three structural proteins, capsid protein C, membrane protein M, envelope protein E and seven nonstructural proteins, NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5.

Transmission and Infection Mechanism

The viruses multiply within the female Mosquito gut, and residence at salivary glands, where during the blood feeding the viruses are transmitted directly into human bloodstream. Reticuloendothelial cells become the place where the viruses replicates and viremia appears after 5 up to 7 days of infection.

At the fifth day of first week, the neutralizing homotypic antibodies will be released and these antibodies are specified enough to attack the viruses. During this period, the primary infection healed. But these homotypic neutralizing-antibodies are not providing protection towards other serotypes.

Immunopathogenesis Theory: Antibody Dependent Enchancement

Another antibodies also secreted, known as the non-neutralizing antibodies that against the other three serotypes. During the secondary (other serotype infection) these antibodies bind to the viruses, and also bind to the Fc receptors at the reticuloendothelial cells surface. These mechanisms continue with the complex-penetration into these cells, and viral replications happen inside these cells.

During secondary infections, these enhancing antibodies will not neutralize the other DENV serotypes. As the consequences, the intracellular infections increase and the viremia also increases. Infection of increased numbers of monocytes results in an increased release of cytokines into the circulation and this leads to vascular damage, shock and hemorrhage, especially into the gastrointestinal tract and skin.

References

1. Brooks, F. Geo et al. (2008). Dengue virus in Jawetz, Melnick and Adelberg Medical Microbiology 23^rd Edition. McGraw Hill Medical Textbooks.
2. Goering, Richard et al. (2007). Dengue Virus in Mims Medical Microbiology 3^rd Edition. Mosby Medical Textbooks.

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Pathogenesis of Dengue Virus Infection and Antibody Dependent Enhancement – Fadel Muhammad Garishah Rev of Med Sci

A new breakthrough in biomedical sciences born out. This breakthrough will give relief to many idiopathic-infertile males, azoospermic and helpless infertile male. As we know, azoospermic condition caused by many aspects, including Infertility of known (possible) cause 42.6%, Idiopathic infertility 30.0%, Hypogonadism 10.1%, General/systemic disease 2.2%, Cryopreservation due to malignant disease 7.8%, Disturbance of erection/ejaculation 2.4%, Obstruction 2.2%, Gynecomastia 1.5%, Y-chromosomal deletion 0.3%, Other chromosomal aberrations 0.2%, and other 0.7%.

Idiopathic infertility, Cryopreservation due to malignant, Y-chromosome deletion, and Sertoli cells only phenomenon make more impossible for infertile couples to achive even Intracytoplasmic sperm injection (ICSI). The absence of spermatozoa, is the main role key that blocks the possibilities.

Sperm Made from Bone Marrow Stem Cells

Stem cells are undifferentiated and naive cells that may turn into every single cell that consist our body. They used to be known as embryonic stem cells during our embriological development. During our adult stage, certainly we have adult stem cells, primarily located within our bone marrow, where they constitutes all of our cellular component of blood. Those naive stem cells may induced and directed to differentiate into the specified human body cell. Previous researches and studies indicated that it may build up some organ such as liver, heart, and pancreas.

Designed by Professor Karim Nayernia, a professor of Cell Biology, Stem Cells from Newcastle Unversity Institute of Human Genetics, Newcastle, England, those stem cells are induced and directed to change into spermatogonia cells that may help male with Sertoly-cells-only syndrome.This research is mice-based research, and to be continued into human based research as soon as possible.

Mechanism

1) Stem cells isolated from bone marrow of male volunteers. 2) In laboratory, stem cells cultured and identified. Some induced to become spermatological cells – which normally become sperm cells. 3) Transplantation of cells into testicle – so far performed in mice

Discussion
Prof Nayernia and his team took bone marrow from male volunteers and isolated the mesenchymal stem cells. These cells have previously been found to grow into other body tissues such as muscle. But the researchers induced a small number of them to develop into what appeared to be spermatagonial cells – cells found in the testes which would normally develop into mature sperm cells.”Our next goal is to see if we can get the spermatagonial stem cells to progress to mature sperm in the laboratory and this should take around three to five years of experiments,” Professor Nayernia said.

The researchers say that they have already created spermatogonial cells from bone marrow tissue taken from men, which may make it possible for scientists one day soon to restore fertility for men who are unable to produce sperm naturally. Having succeeded in the procedure using male bone marrow, the researchers are seeking ethical permission to attempt to create synthetic sperm cells from a woman’s bone marrow tissue.

“Theoretically it is possible,” said Nayernia. “The problem is whether the sperm cells are functional or not. I don’t think there is an ethical barrier, so long as it’s safe. We are in the process of applying for ethical approval. We are preparing now to apply to use the existing bone marrow stem cell bank here in Newcastle. We need permission from the patient who supplied the bone marrow, the ethics committee and the hospital itself.”

Conclusion

If this method works, and the sperms not only able to be created but also effective and able to behave like the spermatozoa themselves, it’s totally a relief for azoospermic males. Although certainly need more confirmation from ethical aspects and also genetics if then later find some abnormalities related this sperm.

References:

• BBC News Human Sperm Made form Bone Marrow, Friday, 13 April 2007, cited July 9th 2011, 18.30
• Percentage distribution of diagnoses of 12,945 patients attending the Institute of Reproductive Medicine of the University of Münster, Cited from Andrology Male Reproductive Health and Dysfunction 3rd Edition, Susan Nieschlag, © Springer-Verlag Berlin Heidelberg 2010

Male reproductive system regulates male sexual structural changes, male masculinity, and the hormonal changes that undergo with the same pathway of male puberty is very important for the male fertility and spermatogenesis.  Under Luitenizing Hormon (LH) and  Interstitial Cells Stimulating Hormone (male FSH) from Hypophysis, the Leydig’s cells produce testosterone. While Sertoli cells actively foster the spermatogonia, and provide proteins and growth factor for them to go through spermatogenesis, and  matured  into spermatozoa. Testosterone is not only important for the spermatogenesis, but also sexual libido stimulation and manhood sexual functions.

Testosterone belongs to steroid hormones, and its receptors located both in the nucleus of cells, also cellular cytoplasm. In the blood circulation, testosterone binds to globulins, SHGB 30% and albumin 70%. Free testosterone in the blood circulation is around 0.5-3%.

Secretion mechanism is regulated by GnRH of hypothalamus, induces the releasing of LH and FSH from hypophysis, through blood circulation delivered to the Seminiferous tubules, activating Leydig cells to synthesize and secrete testosterone. 95% of circulated testosterone is secreted by testes, while 5% comes from Adrenal Gland Cortex, Reticularis Zone. Dihydrotestosterone (DHT) acts in the external genital organ development, prostate gland development, acnes, male hair (chest hair, armpit, pubic hair, hand and leg hair all body hair) also development of baldness. Testosterone is a body-building hormone, gives effects towards muscle mass, and bone growth. Spermatogenesis and Wolfii duct development also initiated by testosterone.

Androgen synthesis begins when LH binds to its seven transmembrane, G protein-coupled receptor that activate the cyclic AMP pathway. Stimulation of the LH receptor induces Steroid Acute Regulatory (StAR) protein that works along with several steroidogenic enzymes involved in androgen synthesis.

In the reticular zone of adrenal gland, and in the interstitial cells of Leydig, androgens biosynthesis generated. The process initiated by conversion of cholesterol into pregnenolone. Pregnenolone then converts into androstenedione and or dehydroepiandrosterone (DHEA converts into androstenedione). Androstenedione transforms into testosterone. Testosterone can transform into Dihydrotestosterone catalyzed by 5-alpha-reductase enzyme. Testosterone secretion rates is around 4-9 mg/day in normal adult male.

Androgen influenced men’s malehood and maleness. More muscle mass, less fat mass, supports men’s activities, that related to outdoor activities that need more musculoskeletal and physical acts. Male skin composition thicker and rich of sebaceous and sudoriferous glands, help them to adapt the sunrays and Ultraviolet rays. Oily skin helps to trap pathogens, and sweat includes in the physiological thermoregulatory mechanism. Reproductively, androgen causes masculine and virilize male, that attracts female. Women tend to attracted with muscular male, and looked much more masculine.

References:

Prof, Jameson, J. Larry, MD, PhD. Harrison’s Endocrinology 2nd Edition. 2010. McGraw Hill Medicine. China

William F Ganong MD, .Review of Med. Physiol. 22nd Edition. 2008. EGC. Jakarta