Effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment-naïve infected patients.

The aim of this study was to evaluate the effect of antiretroviral therapy on inflammatory markers of endothelial dysfunction in HIV treatment-naïve infected patients. This was a prospective cohort study in HIV treatment-naïve infected patients. The patients were assigned to a untreated group or a treatment group according to the therapeutic strategy received. Patients in the treatment group received efavirenz or lopinavir/ritonavir, each given with zidovudine and lamivudine. HIV RNA, CD4(+) cell count, and the levels of hsCRP, sCD40L, sICAM-1, sVCAM-1, and sE-selectin were measured before and 12 weeks after treatment. Fifty patients were enrolled: 13 in the untreated group and 37 in the treatment group; 48 (96%) completed the follow-up. The mean (± SD) age was 33 ± 9 years, and 38 (79%) were men. The median pretreatment CD4(+) cell counts were 263 cells/ml (IQR 118-341) in the treatment group and 658 cells/ml (IQR 475-887) in the untreated group. In the treatment group, the median serum sVCAM-1 and sICAM-1 levels decreased by a small but significant amount (1,400 and 228 ng/ml, respectively, P<0.05) from before to after the 12 weeks. These levels did not change in the untreated group. Antiretroviral therapy is associated with a decrease in sVCAM-1 and sICAM-1 levels after 12 weeks of treatment.

Familial Hypercholesterolemia: Update and Review.

Knowledge of epidemiology, genetic etiopathogenesis, diagnostic criteria, and management of familial hypercholesterolemia have increased in the last two decades. Several population studies have shown that familial hypercholesterolemia is more frequent than previously thought, making this entity the most common metabolic disease with monogenic inheritance in the world. Identification of causal heterozygous pathogenic variants in LDLR, APOB, and PCSK9 genes has increased diagnostic accuracy of classical criteria (extreme hypercholesterolemia, personal / family history of premature coronary artery disease or other cardiovascular diseases). Genetic screening has been recently introduced in many European countries to detect patients with familial hypercholesterolemia, mainly affected pediatric subjects, asymptomatic or those at the beggining of their disease, to increase surveillance and avoid complications such as cardiovascular diseases. Cholesterol- lowering drugs should be started as soon as the diagnosis is made. Various combinations between drugs can be used when the goal is not achieved. New therapies, including small interference ribonucleic acids (siRNA) are being tested in different clinical trials.

Acanthamoeba castellanii: morphological analysis of the interaction with human cornea.

The present study demonstrates that when Acanthamoeba castellanii trophozoites are co-cultivated with isolated human corneas, the amoeba can be invasive and cause damage to the intact corneal epithelium without the requirement of previous corneal abrasion. After adhesion, A. castellanii trophozoites migrate between cells forming bumps on the corneal cell layers and reaching Bowman s membrane in 3h, although no evidence of cell damage was observed until the phagocytic process was detected. Likewise, conditioned medium produced damage to the corneal cells that was proportional to the time of incubation, but this cytophatic effect involved only the most superficial layer of the human cornea and was not enough to explain amoebic invasion of Bowman s membrane. As a result of our observations, we suggest that the mechanical action of the trophozoites and phagocytosis of corneal cells during the process of corneal invasion are more important than previously suggested.

Characterization of langerhans cells in epidermal sheets along the body of Armadillo (Dasypus novemcinctus).

Armadillos are apparently important reservoirs of Mycobacterium leprae and an animal model for human leprosy, whose immune system has been poorly studied. We aimed at characterizing the armadillo's langerhans cells (LC) using epidermal sheets instead of tissue sections, since the latter restrict analysis only to cut-traversed cells. Epidermal sheets by providing an en face view, are particularly convenient to evaluate dendritic morphology (cells are complete), spatial distribution (regular vs. clustered), and frequency (cell number/tissue area). Lack of anti-armadillo antibodies was overcome using LC-restricted ATPase staining, allowing assessment of cell frequency, cell size, and dendrites extension. Average LC frequency in four animals was 528 LC/mm(2), showing a rather uniform non-clustered distribution, which increased towards the animal's head, while cell size increased towards the tail; without overt differences between sexes. The screening of antibodies to human DC (MHC-II, CD 1a, langerin, CD86) in armadillo epidermal sheets, revealed positive cells with prominent dendritic morphology only with MHC-II and CD86. This allowed us to test DC mobilization from epidermis into dermis under topical oxazolone stimulation, a finding that was corroborated using whole skin conventional sections. We hope that the characterization of armadillo's LC will incite studies of leprosy and immunity in this animal model.

Polymorphism rs2275913 of Interleukin-17A is related to more intensive therapy with disease-modifying anti rheumatic drugs in Mexican patients with Rheumatoid Arthritis.

AIM: The study has two aims: 1) to evaluate the association of IL-17 polymorphism rs2275913 with RA severity and 2) to evaluate if this particular SNP is associated with susceptibility for RA in Mexican patients. METHODS: Seventy-six RA patients and ninety-four healthy controls were included in the study. RA patients were evaluated according to DAS 28. Treatment with DMARD'S was prescribed and radiological damage was evaluated according to the Larsen method. A case-control study was used. Oral epithelial cells were obtained as source for genetic material. DNA was amplified using PCR. Subsequently, a RFLP was carried out. Finally, in order to confirm the IL-17 SNP rs2275913 presence, direct sequencing of the DNA was performed. RESULTS: A significant difference was observed between the RA patients and controls when the prevalence of IL-17 SNP rs2275913 was compared. There was a statistically significant disparity among the two groups with an OR of 5.6 (95%CI 1.5 - 20.9, P=<0.01). In this study was observed that the RA patients who were positive for the IL-17 polymorphism rs2275913 required 3 DMARDs to control the disease compared to 32% of the patients who were negative for the IL-17 polymorphism rs2275913, OR 6.6 (95%CI 1.6 - 27.0, P<0.01). CONCLUSION: This study draws two main conclusions: 1) The presence of IL-17 polymorphism rs2275913 is closely related to a more severe form of the disease and as a result, a higher number of DMARDs required to control it, 2) The presence of IL-17 polymorphism rs2275913 may confer a risk of developing RA in Mexican carriers.

Fasting Triglycerides and Glucose Index as a Diagnostic Test for Insulin Resistance in Young Adults.

BACKGROUND AND AIMS: Although the Glucose and Triglyceride levels (TyG) index is useful for identification of insulin resistance (IR) in different ethnic groups, it has not been evaluated in young adults. We undertook this study to evaluate the TyG index as a diagnostic test for IR in young adults. METHODS: A total of 5,538 healthy young adults, 3,795 (68.5%) non-pregnant women and 1,743 (31.5%) men, with an average age of 19.2 ± 1.4 years, were enrolled in a population-based cross-sectional study. To estimate diagnostic characteristics of the TyG index, a randomized subsample of the target population (n = 75) was under euglycemic-hyperinsulinemic clamp test. Using the cutoff values obtained in the clamp study, the diagnostic concordance between TyG index and HOMA-IR was evaluated in the overall population. The TyG index was calculated as the Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. RESULTS: Normal weight, overweight, and obesity were identified in 3,632 (65.6%), 1,355 (24.5%), and 551 (9.9%) participants. A total of 346 (9.1%) men and 278 (15.9%) women exhibited IR. The best cutoff value of TyG index for diagnosis of IR was 4.55 (sensitivity 0.687, negative predictive value (NPV) 0.844, and negative likelihood ratio (NLR) 0.47) for women and 4.68 (sensitivity 0.673, NPV 0.900, and NLR 0.45) for men. In normal-weight individuals the diagnostic concordance between TyG index and HOMA-IR was 0.934 and 0.915, in the overweight subjects was 0.908 and 0.895 and, in the obese participants 0.916 and 0.950, for men and women, respectively. CONCLUSIONS: TyG index may be useful for screening IR in young adults.

Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration.

When dengue virus (DENV)-infected mosquitoes use their proboscis to probe into human skin during blood feeding, both saliva and virus are released. During this process, cells from the epidermis and dermis layers of the skin, along with small blood vessels, may get exposed to or infected with DENV. In these microenvironments of the skin, the presence of DENV initiates a complex interplay among the DENV-infected and non-infected neighboring cells at the initial bite site. Previous studies suggested that DENV-infected human dermal fibroblasts (HDFs) participate in the immune response against DENV by secreting soluble mediators of innate immunity. In the present study, we investigated whether DENV-infected HDFs activate human dermal microvascular endothelial cells (HDMECs) in co-cultures. Our results suggest that co-cultures of DENV-infected HDFs and HDMECs elicit soluble mediators that are sufficient to reduce viral replication, activate HDMECs, and induce leukocyte migration through HDMEC monolayers. These effects were partly dependent on HDF donor and DENV serotype, which may provide novel insights into the natural variation in host susceptibility to DENV disease.

A subpopulation of large granular von Willebrand Ag negative and CD105 positive endothelial cells, isolated from abdominal aortic aneurysms, overexpress ICAM-1 and Fas antigen.

The aim of this work was to determine whether there is a pre-established basal condition of the endothelial cells isolated from aortic abdominal aneurysm that might augment immune effector mechanisms and thus provide us an insight into the possible causes of aneurysm rupture. Endothelial cells isolated from saccular aortic aneurysm fragments were analyzed by cytofluorometry for the expression of different immune response-related molecules. Our results showed that there is a subpopulation of granule-rich, CD105 positive and von Willebrand antigen negative endothelial cells that have an enhanced basal expression of ICAM-1, and Fas antigen, but, interestingly, no apoptotic bodies were detected. Control endothelial cells derived from healthy areas of the same abdominal aortas did not show such enhanced expression. We conclude that in the endothelium that lines abdominal aorta aneurysms there is, at least, one endothelial cell subpopulation with an apparent inhibition of programmed cell death and in a proinflammatory activation status.

Increased concentrations of soluble CD40 ligand platelet in patients with primary antiphospholipidic syndrome.

OBJECTIVE: To determine the concentrations of sCD40L in patients with PAPS, and establish its association with the number of thrombosis. PATIENTS AND METHODS: We included patients with PAPS and healthy controls of the same age and sex. For analysis, patients with PAPS were divided into 2 groups: 1) patients with 1 thrombosis, and 2) patients with >1 thrombosis. Soluble CD40L concentrations were determined by ELISA method. RESULTS: sCD40L concentrations were significantly higher in patients with PAPS compared with the controls (9.72 ng ± 11.23 ng/ml vs. 4.69 ± 4.04 ng/ml) (P=.04) There was no association between serum levels of sCD40L and the number of thrombosis (1 thrombosis: 9.81 ± 9.87 ng/ml vs 9.63 ± 12.75 ng/ml in ≥ 1thrombosis (P=.13). In women with pregnancy and abortions, (13 patients) concentrations of sCD40L were higher than in those patients without a history of abortion (26 patients) but without statically significant difference (12.11 ± 16.46 ng/ml vs. 8.80 ± 8.61 ng/ml) (P=.33). There was no correlation between levels of sCD40L and the total number of thrombosis. CONCLUSIONS: Patients with PAPS have higher concentrations of sCD40L compared with healthy subjects, although this is not associated with a greater number of thrombosis. Among patients with PAPS, there is a tendency to higher concentrations of sCD40L in women with pregnancy and history of abortion. Since the platelet is the main cellular source of sCD40L, is possible that this pathway plays a pathogenic role in patients with PAPS.

High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract.

Dendritic cells (DC) are often arranged in planar layers in tissues with high antigenic exposure, such as skin and mucosae. Providing an en face view, this arrangement optimizes in situ analysis regarding morphology (even of individual dendrites), topographic distribution (regular/clustered) and quantification. The few reports on human genital DC usually utilize single markers and conventional sections, restricting immunolabelling only to cell parts sectioned by the cut. To better assess DC in situ, we labelled epithelial sheets, prepared from fresh cervix biopsies, with antibodies to major histocompatibility complex (MHC)-CII, CD1a and Langerin, revealing (with each of these markers) a dense DC network in a planar-like, regular distribution. Using the hybrid capture system to detect the high-risk mucotropic human papilloma virus (HPV) group, 16 positive and five negative women were studied and the results were compared between these groups. DC frequency per area was substantially reduced (to approximately 50% for the three markers) in samples from all HPV-infected patients compared with samples from controls. Unlike HPV(-) samples, Langerin(+) DC in HPV(+) cervix exhibited a highly accentuated dendritic appearance. We believe this to be the first study using these three DC-restricted markers (Langerin, CD1a and MHC-CII) in cervical epithelial sheets from high-risk HPV(+) donors and also the first study to demonstrate the morphological and quantitative changes triggered by high-risk HPV infection. Cervical DC reduction in early, premalignant high-risk HPV infection might represent viral subversion strategies interfering with efficient antigen handling by the immune system's peripheral sentinels, the DC, perhaps hampering appropriate recruitment and subsequent development of effector (cytotoxic) T cells.