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1.
Biochem Pharmacol ; 178: 114050, 2020 08.
Article in English | MEDLINE | ID: mdl-32446887

ABSTRACT

Efavirenz (EFV) is used for antiretroviral treatment of HIV infection, and successfully inhibits viral replication and mother-to-child transmission of HIV during pregnancy and childbirth. Unfortunately, the drug induces neuropsychiatric symptoms such as anxiety and depressed mood and potentially affects cognitive performance. EFV acts on, among others, the serotonin transporter and serotonin receptors that are expressed in the developing brain. Yet, how perinatal EFV exposure affects brain cytoarchitecture remains unclear. Here, we exposed pregnant and lactating rats to EFV, and examined in the medial prefrontal cortex (mPFC) of their adult offspring the effects of the maternal EFV exposure on cortical architecture. We observed a significant decrease in the number of cells, mainly mature neurons, in the infra/prelimbic and cingulate cortices of adult offspring. Next, we found an altered cortical cytoarchitecture characterized by a significant reduction in deep- and superficial-layer cells. This was accompanied by a sharp increase in programmed cell death, as we identified a significantly higher number of cleaved Caspase-3-positive cells. Finally, the serotonergic and dopaminergic innervation of the mPFC subdomains was increased. Thus, the perinatal exposure to EFV provoked in the mPFC of adult offspring cell death, significant changes in cytoarchitecture, and disturbances in serotonergic and dopaminergic innervation. Our results are important in the light of EFV treatment of HIV-positive pregnant women, and its effect on brain development and cognitive behavior.


Subject(s)
Alkynes/toxicity , Benzoxazines/toxicity , Cyclopropanes/toxicity , Prefrontal Cortex/drug effects , Prefrontal Cortex/pathology , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/pathology , Reverse Transcriptase Inhibitors/toxicity , Animals , Animals, Newborn , Anti-HIV Agents/toxicity , Female , Male , Prefrontal Cortex/growth & development , Pregnancy , Rats , Rats, Wistar
2.
Lupus ; 28(13): 1549-1557, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31619143

ABSTRACT

OBJECTIVE: This study aimed to analyze the expression of the high mobility group box-1 (HMGB1) protein in neutrophil extracellular traps (NETs) of patients with lupus nephritis (LN) and its association with clinical and histopathological features of the disease. METHODS: Twenty-three patients with biopsy-confirmed LN and 14 systemic lupus erythematosus (SLE) patients with active disease (SLE Disease Activity Index (SLEDAI) score ≥ 6) and no evidence of LN were included. Clinical and laboratory features were recorded. NETs and the expression of HMGB1 were assessed by confocal microscopy, and serum HMGB1 levels were measured by ELISA. RESULTS: In comparison to patients without kidney disease, patients with LN had a higher expression of HMGB1 in spontaneous (57 vs. 30.4; p = 0.027) and lipopolysaccharide (LPS)-induced (55.8 vs. 24.9; p = 0.005) NETs. We found a positive correlation between serum HMGB1 and the expression of HMGB1 in LPS-induced NETs (r = 0.447, p = 0.017). The expression of HMGB1 in spontaneous NETs correlated with SLEDAI score (r = 0.514, p = 0.001), anti-dsDNA antibodies (r = 0.467, p = 0.004), the rate of glomerular filtration descent (r = 0.543, p = 0.001), and diverse histopathological components of active nephritis in the kidney biopsy, such as the activity index (r = 0.581, p = 0.004), fibrinoid necrosis (r = 0.603, p = 0.002), and cellular crescents (r = 0.486, p = 0.019). CONCLUSIONS: In patients with SLE, NETs are a source of extracellular HMGB1. The expression of HMGB1 in NETs is higher among patients with LN, which correlates with clinical and histopathological features of active nephritis and suggest a possible role of this alarmin in the pathophysiology of kidney damage in SLE.


Subject(s)
Extracellular Traps/metabolism , HMGB1 Protein/metabolism , Lupus Erythematosus, Systemic/physiopathology , Lupus Nephritis/physiopathology , Adult , Case-Control Studies , Female , HMGB1 Protein/blood , Humans , Lupus Nephritis/blood , Male , Severity of Illness Index , Young Adult
3.
Cell Tissue Bank ; 16(2): 287-94, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25098349

ABSTRACT

The neuropathological examination of postmortem human brain tissue is an essential resource for the definitive diagnosis and research on neurodegenerative diseases. Due to the growing need of donated brains to supply the Brain Banks, the understanding of the factors associated with the consent for the donation in our context is an important aspect of the process of brain donation. The verbal answers and the donation consent rate were evaluated in three groups: 30 relatives of patients who underwent verification of the cause of death, 14 patients assisted at a neurology ambulatory outpatient clinic, and 18 patients' relatives. The donation consent rates were of 46.6, 92.8 and 88.8 %, respectively. The main reasons for refusal were the disagreement with the autopsy, philosophical and religious issues, objections from other family members, and the consideration of the wishes of the deceased. The consent was specially motivated by the interest in the advances of scientific knowledge, altruistic reasons and the personal experiences with the disease. Factors as the emotional fragility at the moment of death, the beliefs, family matters, and the lack of knowledge are key elements in the donation process. Future goals include the establishment of a brain donor program with the support of academic institutions, hospitals, scientists, community, patient's associations and autopsy assistants. Approaching patients and relatives in specialized ambulatories clinic during assistance is probably the most efficient mean of obtaining brains for research.


Subject(s)
Brain/surgery , Family/ethnology , Tissue Donors , Tissue and Organ Procurement , Autopsy/methods , Brain/pathology , Brazil , Decision Making/physiology , Family/psychology , Health Knowledge, Attitudes, Practice , Humans , Tissue Donors/psychology
4.
Rev Cubana Med Trop ; 53(2): 111-7, 2001.
Article in Spanish | MEDLINE | ID: mdl-15844299

ABSTRACT

Toxoplasmposis is one of the zoonotic diseases which is widely spread all over the world. It is caused by Toxoplasma gondii. In this paper we made a chronological synthesis of some of the numerous investigations that have been made in the world and in Cuba.


Subject(s)
Biomedical Research/history , Toxoplasmosis/history , Animals , History, 20th Century , Humans
5.
J Clin Microbiol ; 27(12): 2684-6, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2687317

ABSTRACT

One hundred fifty-five biopsy specimens from the gastric mucosa of 81 patients undergoing routine endoscopy procedures were tested for the presence of Campylobacter pylori by three methods: Gram stain, culture, and modified Minitek, a rapid urea disk test (BBL Microbiology Systems, Cockeysville, Md.). Twenty-nine patients were infected with C. pylori. Sensitivities and specificities of detection were 100 and 94% with the Minitek test and 93 and 100% with Gram stain, respectively. Rapid testing by the urea disk is a simple, cost-effective, and accurate method for detecting the presence of C. pylori in gastric biopsy specimens.


Subject(s)
Campylobacter/isolation & purification , Gastric Mucosa/microbiology , Urea/metabolism , Urease/analysis , Bacteriological Techniques , Biopsy , Campylobacter/enzymology , Gastritis/microbiology , Gastroscopy , Humans , Predictive Value of Tests
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