Advertisement

Topics

Ontogenesis of the P-Glycoprotein in Human Lymphocytes Influence of HIV and Antiretroviral Therapeutics

2014-08-27 03:29:43 | BioPortfolio

Summary

The P-glycoprotein (P-gp) is a membranous transporter that modulates the intracellular concentrations of many drugs and plays thus a major role in the efficacy of the therapeutics that act within the lymphocytes, such as antiretroviral drugs. We aim at studying the evolution of this transporter's expression and activity on lymphocytes in relation with the human development from newborns to adults. We also aim at studying the influence of HIV and antiretroviral treatments on this transporter, especially anti-protease drugs, within the children population.

Description

Several groups of drugs involved in the treatment of major pathologies act within the lymphocyte, such as anticancer, immunosuppressive and antiretroviral drugs. These molecules depend on membranous transporters to get inside the lymphocyte and be effective. Among those transporters, the P-glycoprotein (P-gp) plays a major role, especially because of the variety of its substrates among therapeutic molecules. Its expression and activity are well known within the adult population, as well as its modulations mediated by certain groups of drugs, such as protease inhibitors in the treatment of HIV. Yet, there is very little data on children, even though they are exposed to the same therapeutic molecules as the adults. Therefore, we aim at studying the evolution of this transporter's expression and activity on the different lymphocyte populations, in relation to the human development from newborns to adults. We also aim at studying the influence of HIV and antiretroviral treatments on this transporter, especially anti-protease drugs, within the children population. P-gp activity is quantified by flow cytometry, through the efflux of a fluorescent substrate, in the presence or absence of a P-gp inhibitor. P-gp expression is measured on isolated motonucleus cells with the quantification of mRNA encoded for the transporter by RT-PCR (Reverse Transcription - Polymerase Chain Reaction). Patients of every age, from newborns to adults, are recruited within eight different age groups and three HIV status groups (HIV non infected, HIV infected untreated, HIV infected treated). The objective is to recruit ten patients in each age group for each HIV status. Blood samples are obtained from hospitalized children and adults with their consent. The patients will be recruited for one year. Our objective is to determine whether the P-gp expression and/or activity are influenced by age, HIV status and antiretroviral treatments, in order to prevent, depending on developmental stages, ineffectiveness or toxicity due to inadequate intracellular concentrations.

After the first evaluations, principal investigators decided to add one year more for three groups on eight.

For two groups of these three, genetic polymorphism of Mdr1 will be done.

Study Design

Time Perspective: Cross-Sectional

Conditions

HIV Infections

Location

Hopital Necker Enfants Malades
Paris
France
75015

Status

Completed

Source

Assistance Publique - Hôpitaux de Paris

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:29:43-0400

Clinical Trials [171 Associated Clinical Trials listed on BioPortfolio]

Japanese Study Evaluating Safety, Efficacy and Acceptability of Telithromycin in Children With Infections

The primary objective is to assess the safety of telithromycin (HMR 3647) (20% fine granules) 1g filling sachet in children with infections (Respiratory tract infections, Dermatological in...

An Investigational Agent for the Treatment of Complicated Intra-Abdominal Infections or Acute Pelvic Infections

The purpose of this study is to determine the effect of an approved medication for adults for an investigational use in pediatric patients 3 months to 17 years for the treatment of complic...

Caspofungin Study for Fungal Infections in Adults in Critical Care Settings

Adults admitted to intensive care units are at risk for a variety of complications. One of the most frequent complications is the development of new infections. Infections due to a fungus...

Surgical Wound Infections After Vascular Surgery: Prospective Multicenter Trial

The purpose of this multicentre prospective trial is to determine the incidence and risk factors for surgical wound infections. Also the investigators will evaluate consequences of wound i...

Study Evaluating the Pharmacokinetics (PK), Safety, and Tolerability of Tigecycline in Patients 8 to 11 Years of Age

To determine the pharmacokinetic profile and to evaluate the safety and tolerability of ascending multiple doses of tigecycline in patients aged 8 to 11 years with selected serious infecti...

PubMed Articles [3222 Associated PubMed Articles listed on BioPortfolio]

Fungal Infections Increase the Mortality Rate Three-Fold in Necrotizing Soft-Tissue Infections.

Necrotizing soft-tissue infections (NSTIs) result in significant morbidity and mortality rates, with as many as 76% of patients dying during their index admission. Published data suggest NSTIs rarely ...

Dengue Chikungunya co-infection: A live-in relationship??

Dengue and Chikungunya are viral infections that are a major public health hazard in recent times. Both these infections are caused by RNA viruses termed arboviruses owing to their requirement of an a...

Congenital Cytomegalovirus Infection in the Absence of Maternal Cytomegalovirus-IgM Antibodies.

Congenital cytomegalovirus (cCMV) infections are the most prevalent intrauterine infections worldwide and are the result of maternal primary or non-primary infections. Early maternal primary infection...

Role of Honey in Topical and Systemic Bacterial Infections.

The development of bacterial resistance to antibiotics has made it more difficult and expensive to treat infections. Honey is getting worldwide attention as a topical therapeutic agent for wound infec...

A syndemic approach to assess the effect of substance use and social disparities on the evolution of HIV/HCV infections in British Columbia.

Co-occurrence of social conditions and infections may affect HIV/HCV disease risk and progression. We examined the changes in relationship of these social conditions and infections on HIV and hepatiti...

Medical and Biotech [MESH] Definitions

Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of TOGAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; BUNYAVIRIDAE INFECTIONS; PICORNAVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RETROVIRIDAE INFECTIONS; and ARENAVIRIDAE INFECTIONS.

Viral infections of the leptomeninges and subarachnoid space. TOGAVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; RUBELLA; BUNYAVIRIDAE INFECTIONS; ORBIVIRUS infections; PICORNAVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RHABDOVIRIDAE INFECTIONS; ARENAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; JC VIRUS infections; and RETROVIRIDAE INFECTIONS may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, PHOTOPHOBIA, and signs of meningeal irritation. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)

Infections with viruses of the family PARAMYXOVIRIDAE. This includes MORBILLIVIRUS INFECTIONS; RESPIROVIRUS INFECTIONS; PNEUMOVIRUS INFECTIONS; HENIPAVIRUS INFECTIONS; AVULAVIRUS INFECTIONS; and RUBULAVIRUS INFECTIONS.

Pathogenic infections of the brain, spinal cord, and meninges. DNA VIRUS INFECTIONS; RNA VIRUS INFECTIONS; BACTERIAL INFECTIONS; MYCOPLASMA INFECTIONS; SPIROCHAETALES INFECTIONS; fungal infections; PROTOZOAN INFECTIONS; HELMINTHIASIS; and PRION DISEASES may involve the central nervous system as a primary or secondary process.

Infections with viruses of the order MONONEGAVIRALES. The concept includes FILOVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; and RHABDOVIRIDAE INFECTIONS.

More From BioPortfolio on "Ontogenesis of the P-Glycoprotein in Human Lymphocytes Influence of HIV and Antiretroviral Therapeutics"

Quick Search
Advertisement
 

Relevant Topics

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

AIDS and HIV
AIDS; Acquired Immune Deficiency Syndrome. HIV; Human Immunodeficiency Virus HIV infection causes AIDS. HIV infection also causes the production of anti-HIV antibodies, which forms the test for HIV in patients. People who have the HIV antibodies are ...


Searches Linking to this Trial