Background: Several studies have shown
that human immunodeficiency virus (HIV) maintains residual replication in the
lymph nodes of patients with undetectable viral load in peripheral blood
despite highly active antiretroviral therapy (HAART). In other words, while the
virus is eliminated in the peripheral blood by antiretroviral drugs, it
continues to infect and replicate in new cells in the lymphoid tissue. This
shows that the treatments used today against HIV do not achieve the total
elimination of the virus in the body.
Other studies demonstrated that the
concentrations of antiretrovirals at the lymph node level were lower compared
to the concentrations in peripheral blood, not reaching optimal levels to stop
viral replication. Additional investigations in intestinal mucosa showed that
HIV RNA can be detected in the intestine of patients with successful HAART,
suggesting that the intestinal mucosa is a cellular reservoir where HAART
inhibits viral replication but does not eradicate the virus, therefore that it
is necessary to carry out more in-depth studies in order to improve the
understanding of the pathogenesis of HIV at the level of the intestinal mucosa.
The above-captioned issues motivated the present investigation in search of
micro- and nanoscale findings with a possible therapeutic approach.
Objective: The present study aimed to
determine the ultrastructural findings on Rectal Mucosa (RM) of patients with
HIV/AIDS and anorectal pathologies (ARP), at micrometric and nanometric scales.
Materials and Methods: 5 patients were
evaluated, 18 - 55 years old, with ARP (HIV co-infection with HPV, n = 4, and
HIV-negative patient with HPV infection) (control n = 1), who were referred to
the Coloproctology Unit of the HUC, and subjected to rectoscopy and biopsy. RM
samples were identified, placed in a sterile plastic bottle with 1 mL of 2%
glutaraldehyde, and immediately transported for routine processing of fine cut
(60 - 90 nm) to be evaluated via Transmission Electron Microscopy (TEM). They
were fixed with Karnovsky solution with Millonig phosphate buffer (pH 7.4 and
320 mOsm) and post-fixed with OsO4 under the same conditions of pH and
osmolarity.
Results: Ultrastructural findings, at
10-6 scale: 1) Intestinal mucosa: vacuoles of mucus of different sizes that
seem to be fused. 2) Smooth muscle cells: loss of definition of contractile
myofilaments mass. 3) Unmyelinated axons and terminals of Schwann cells (SC):
Edema and loss of their plasma membranes in some areas of association with axon
terminals as well as abundant collagen fibers associated with SC. Ultrastructural
findings, at 10-9 scale: 1) Smooth muscle cells: folded wrapper cores and edema
of mitochondria and rough endoplasmic reticulum cisterns (RER). 2) Myelinated
axon terminals: Loss of synaptic vesicles. 3) Fibroblasts: One observes
mitochondria and cisterns of RER with alterations. All these alterations can
generate intestinal and anorectal dysfunction in these patients. The use of
nanotechnology can be very useful for the therapeutic approach to HIV, offering
unique advantages, such as improving the bioavailability, water solubility,
stability, and targeting capacity of antiretroviral drugs, especially in those
difficult sites for an effective therapeutic approach.
Conclusions: HIV causes changes in
rectal and muscular mucosa despite HAART treatment with undetectable viral
load. Nano-drugs could play an important role in drug delivery in sites where
conventional ART has limited access, so as to achieve sufficient concentrations
to execute optimal therapeutic responses and virus eradication in anatomical
and intracellular sites.
Author (s) Details
Maria Antonieta Annunziato
Department of Internal Medicine, Medical
Attention Center, General Checkups, Medical Exams and Consultations, Wheelchair
Center, (BANDESIR), Caracas, Venezuela and Latin American Association of
Clinical Nanomedicine (LATNAMCLI), Caracas, Venezuela.
Carlos Sardiñas
Coloproctology Unit, Caracas University
Hospital (HUC), Caracas, Venezuela.
Hector J. Finol
Center for Electron Microscopy, Sciences
Faculty, Central University of Venezuela, Caracas, Venezuela.
Ana Carvajal
Department of Infectious Diseases,
University Hospital of Caracas (HUC), Caracas, Venezuela.
Antonio Roschman-González
Center for Electron Microscopy, Sciences
Faculty, Central University of Venezuela, Caracas, Venezuela and School of
Biology, Faculty of Sciences, Central University of Venezuela, Caracas,
Venezuela.
Yetsenia De Gouveia
School of Biology, Faculty of Sciences,
Central University of Venezuela, Caracas, Venezuela.
Estefanie García
School of Biology, Faculty of Sciences,
Central University of Venezuela, Caracas, Venezuela.
Liseth Garibaldi
Department of Electronic Microscopy,
Venezuelan Institute of Scientific Research (IVIC), Miranda State, Venezuela.
Please see the book here:- https://doi.org/10.9734/bpi/mmrnp/v5/1606
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