Tag Archive | Neutrophil granulocyte

How Plerixa Fights Neutropenia

English: Reference ranges for white blood cell...

Ariana-Leilani suffer from Severe Chronic Neutroepnai.   Neutropenia is a condition characterized by the lack of a type of white blood cells, also known as neutrophils, in one’s blood circulation. Patients with neutropenia who receive plerixafor become prone to oral, skin, genital infections and in worst cases, a fatal whole-body infection.

Previously, it was known that Plerixafor increases the concentration of these white blood cells in the blood by inhibiting a protein called CXCR4. This inhibition prevents neutrophils in the blood stream from returning to the bone marrow, which is the primary compartment where the white blood cells are stored and released. It is therefore commonly accepted that the efficacy of the drug arises only from the release of these white blood cells from the bone marrow.

However, scientists at SIgN found that the inhibition of CXCR4 by the drug actually plays a dual role – it increases the neutrophil count in the blood through their release from the lungs, while simultaneously promoting their retention in the blood stream. Results of the study were published in the Journal of Experimental Medicine (JEM).

Discovery of this additional mode of action not only provides a deeper understanding on the drug’s mechanism; it also contributes to a more effective use of the drug, which may help to reduce the risk of bacterial infections in neutropenic patients.

“We have identified the precise mechanisms of plerixafor treatment, which has important implications on its usage. We can understand through this study the effectiveness or limitations of the drug on certain patients and thereafter craft new clinical approaches to better treat them. Our study forms a conceptual framework to establish improved therapeutic strategies for neutropenia,” said team leader Dr. Ng Lai Guan from SIgN.

The article can be found at: Devi S et al. (2013) Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow.

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Tips On Care For a Patient with Neutropenia

Ariana-Leilani is not getting needed medicine for her neutropenia, please sign her petition:

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Study Looks At Genetic Basis of Neutropenia

A new paper by S Gautam, S Kirschnek, I E Gentle, C Kopiniok, P Henneke, H Häcker, L Malleret, A Belaaouaj and G Häcker:

Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3−/− mice. 

Read More: Cell Death and Differentiation

What constitutes a reasonable workup for neutropenia in an otherwise healthy young person?

English: Promyelocyte, bone marrow smear.

English: Promyelocyte, bone marrow smear. (Photo credit: Wikipedia)

Neutropenia is defined as a deficiency of circulating neutrophils or an absolute neutrophil count <1,500 µL. This condition can be attributable to a reduction in bone-marrow production or increased loss of bone marrow from the circulation. A thorough history is the best place to start in your evaluation of a healthy child with a low neutrophil count.

A viral infection is the most common cause in children (not infants). The neutropenia develops during the illness and persists for up to one week after resolution. Measles, mumps and rubella vaccine as well as varicella vaccine can also trigger transient neutropenia. Another possible cause is bacterial infection.

Nutritional deficits in folic acid, vitamin B12 or copper can also lead to a drop in neutrophils. Lastly, look carefully at any drugs the patient is currently taking or may have recently finished taking. Herbal therapies and supplements also deserve evaluation. — Julee B. Waldrop, DNP (175-1)

Ariana-Leilani has severe chronic neutropenia, absolute neutrophil count <500 µL.    As noted, drugs can cause neutropenia.  However, her medical providers at Medstar Georgetown University Hospital have refused to give her a toxicology test.   That is why she need GCSF medicine (to boost her ANC) and an independent medical examination as soon as possible.    Sign her petition today so she can live.

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Study Finds In Neutropenia the immune system is balanced on a knife-edge

Developed by Weizmann Institute mathematicians working with physicians at the Meir Medical Center in Israel, and Roche’s research center in Basel, Switzerland, a model demonstrates how the immune system functions under conditions of neutropenia resulting from chemotherapy or bone marrow transplant.

Corroborated by evaluation of healthy individuals, the model indicates that the ability of white blood cells, primarily neutrophils, to tackle bacterial infections doesn’t just depend on absolute cell number, or the bacteria-to-cell ratio, but is affected by factors including neutrophil function and the permeability of tissues to bacteria, which can increase as a result of chemotherapy. Effectively, in neutropenia the immune system is balanced on a knife-edge—described mathematically as bistability—which can go either way as a result of even minor disturbances to the equilibrium.

In healthy people, the fact that the effectiveness of neutrophils varies from one person to another usually has no significant consequences. In contrast, in patients with neutropenia, this individual variability can make a difference between life and death. 

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Read More: Mathematical Model of Neutropenia 

Ariana-Leilani King Pfeiffer

Ariana-Leilani King Pfeiffer

New Research on recombinant granulocyte colony stimulating factor (rG-CSF) in Cyclic Neutropenia (Yanay, Dale and Osborn)

Abstract:

Cyclic neutropenia occurs in humans and grey collie dogs, is characterized by recurrent neutropenia and is treated by repeated injections of recombinant granulocyte colony stimulating factor (rG-CSF). As dose escalation of lentivirus may be clinically necessary we monitored the outcome of four sequential intramuscular injections of G-CSF-lentivirus of 3×107 infectious units per Kg of body weight to a normal dog and a grey collie. In the normal dog absolute neutrophil counts were significantly increased after each dose of virus with mean levels of 27.75±3.00; 31.50±1.40; 35.05±1.68, 43.88±2.94 x103 cells/µl respectfully (p<0.001) and elevated neutrophil counts of 31.18±7.81 x103 cells/µl were maintained for over 6 years with no adverse effects. A grey collie dog with a mean count of 1.94±1.48 x103 cells/µl received G-CSF-lentivirus and we observed sustained elevations in neutrophil levels for over 5 months with a mean of 26.00±11.00×103 cells/µl, significantly increased over pretreatment level (p<0.001). Following the second and third virus administration mean neutrophil counts of 15.80±6.14 and 11.52±4.90×103 cells/µl were significantly reduced over cell counts following the first virus administration (p<0.001). However, following the 4th virus administration mean neutrophil counts of 15.21±4.50×103 cells/µl were significantly increased over the previous virus (p<0.05). Throughout the nearly 3 years of virus administrations the dog gained weight, was healthy and showed neutrophil counts significantly higher than pretreatment levels (p<0.001). These studies suggest that patients with cyclic and other neutropenias may be treated by escalating doses of G-CSF-lentivirus to obtain a desired therapeutic neutrophil count.

Read More:

Repeated Lentivirus-mediated G-CSF Administration to Treat Canine Cyclic Neutropenia

Dr. Ofer Yanay, Dr. David Dale, and Prof. William R Osborne. Human Gene Therapy

 

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