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1.  Membranoproliferative Glomerulonephritis due to Visceral Leishmaniasis in an HIV Patient 
Patient: Male, 47
Final Diagnosis: Membranoproliferative glomerulonephritis
Symptoms: Nephrotic syndrome
Medication: —
Clinical Procedure: Renal biopsy
Specialty: Nephrology
Rare disease
Visceral leishmaniasis is an important opportunistic disease in HIV-positive patients. The information available on the effects of such co-infection in the kidney is limited. We describe a patient with HIV/leishmania coinfection who developed nephrotic syndrome and membranoproliferative glomerulonephritis. As far as we know, only 2 cases of this nephropathy in HIV/leishmania coinfection have been reported.
Case Report:
A 47-year-old man developed nephrotic syndrome. He had been diagnosed with HIV infection and visceral leishmaniasis and was treated with antiretroviral therapy, antimonial compounds, liposomal amphotericin B and miltefosine, but the leishmania followed a relapsing course.
Renal biopsy disclosed membranoproliferative glomerulonephritis and leishmania amastigotes were seen within glomerular capillary lumens. He was given miltefosine and liposomal amphotericin B but the leishmaniasis persisted. Stage 3B chronic renal disease and nephrotic range proteinuria tend to become stable by 15-month follow-up.
Our case illustrated some aspects of leishmaniasis in HIV patients: its relapsing course, the difficulties in therapy, and the renal involvement.
PMCID: PMC4299756  PMID: 25575099
Glomerulonephritis; Membranoproliferative; HIV; Leishmania; Nephrotic Syndrome
2.  The Regulation of Coenzyme Q Biosynthesis in Eukaryotic Cells: All That Yeast Can Tell Us 
Molecular Syndromology  2014;5(3-4):107-118.
Coenzyme Q (CoQ) is a mitochondrial lipid, which functions mainly as an electron carrier from complex I or II to complex III at the mitochondrial inner membrane, and also as antioxidant in cell membranes. CoQ is needed as electron acceptor in β-oxidation of fatty acids and pyridine nucleotide biosynthesis, and it is responsible for opening the mitochondrial permeability transition pore. The yeast model has been very useful to analyze the synthesis of CoQ, and therefore, most of the knowledge about its regulation was obtained from the Saccharomyces cerevisiae model. CoQ biosynthesis is regulated to support 2 processes: the bioenergetic metabolism and the antioxidant defense. Alterations of the carbon source in yeast, or in nutrient availability in yeasts or mammalian cells, upregulate genes encoding proteins involved in CoQ synthesis. Oxidative stress, generated by chemical or physical agents or by serum deprivation, modifies specifically the expression of some COQ genes by means of stress transcription factors such as Msn2/4p, Yap1p or Hsf1p. In general, the induction of COQ gene expression produced by metabolic changes or stress is modulated downstream by other regulatory mechanisms such as the protein import to mitochondria, the assembly of a multi-enzymatic complex composed by Coq proteins and also the existence of a phosphorylation cycle that regulates the last steps of CoQ biosynthesis. The CoQ biosynthetic complex assembly starts with the production of a nucleating lipid such as HHB by the action of the Coq2 protein. Then, the Coq4 protein recognizes the precursor HHB acting as the nucleus of the complex. The activity of Coq8p, probably as kinase, allows the formation of an initial pre-complex containing all Coq proteins with the exception of Coq7p. This pre-complex leads to the synthesis of 5-demethoxy-Q6 (DMQ6), the Coq7p substrate. When de novo CoQ biosynthesis is required, Coq7p becomes dephosphorylated by the action of Ptc7p increasing the synthesis rate of CoQ6. This critical model is needed for a better understanding of CoQ biosynthesis. Taking into account that patients with CoQ10 deficiency maintain to some extent the machinery to synthesize CoQ, new promising strategies for the treatment of CoQ10 deficiency will require a better understanding of the regulation of CoQ biosynthesis in the future.
PMCID: PMC4112530  PMID: 25126044
Coenzyme Q; Mitochondria; Protein complex; 
Respiration; Ubiquinone; Yeast
3.  Human Infection with Rickettsia sibirica mongolitimonae, Spain, 2007–2011 
Emerging Infectious Diseases  2013;19(2):267-269.
Human infection with Rickettsia sibirica mongolitimonae was initially reported in 1996, and reports of a total of 18 cases have been published. We describe 6 additional cases that occurred in the Mediterranean coast region of Spain during 2007–2011. Clinicians should consider this infection in patients who have traveled to this area.
PMCID: PMC3559030  PMID: 23343524
Rickettsia sibirica mongolitimonae; rickettsiosis; LAR; spotted fever; rickettsiae; infection; bacteria; Hyalomma asiaticum; ticks; vector-borne infections; lymphangitis-associated rickettsiosis; Spain
4.  Contribution of Interferon gamma release assays testing to the diagnosis of latent tuberculosis infection in HIV-infected patients: A comparison of QuantiFERON-TB Gold In Tube, T-SPOT.TB and tuberculin skin test 
BMC Infectious Diseases  2012;12:169.
Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection. The tuberculin skin test (TST) was the only available method to identify LTBI. The aim of the present work was to evaluate the usefulness of the interferon-gamma release assays (IGRAs): QuantiFERON-tuberculosis (TB) Gold-In-Tube test (QFG) and T-SPOT.TB for the diagnosis of LTBI in a diverse cohort of HIV-infected patients.
A prospective study was carried out in consecutive patients cared for in a single institution in Spain from January 2009 to October 2010. IGRAs and TST were performed simultaneously. TST induration ≥ 5 mm was considered positive.
QFG, T-SPOT.TB and TST were performed in 373 subjects. Median CD4 cell count was 470/μl with a median nadir of 150/μl. TST, QFG and T-SPOT.TB were positive in 13.3%, 7.5% and 18.5% cases respectively. Among 277 patients with neither past or current TB nor previous treatment for LTBI and who had TST results, a positive TST result was obtained in 20 (7.2%) cases. When adding QFG results to TST, there were a total of 26 (8.6%) diagnoses of LTBI. When the results of both IGRAs were added, the number of diagnoses increased to 54 (17.9%) (incremental difference: 10.7% [95% confidence interval [CI]:5.3-16.2%] [p < 0.001]), and when both IGRAs were added, the number of diagnoses reached 56 (18.5%) (incremental difference: 11.3% [95% CI:5.7%–16.9%] [p < 0.001]). Patients with a CD4 cell count greater than 500 cells/μl and prior stay in prison were more likely to have a diagnosis of LTBI by TST and/or QFG and/or T-SPOT.TB (adjusted odds ratio [aOR]: 3.8; 95% CI, 1.4 – 9.9; and aOR: 3.3; 95% CI, 1.3 – 8.3, respectively).
IGRAs were more sensitive than TST for diagnosis of M. tuberculosis infection in HIV-infected patients. Dual sequential testing with TST and IGRAs may be the optimal approach for LTBI screening in this population.
PMCID: PMC3482589  PMID: 22849726
5.  Evaluation of endothelial function and subclinical atherosclerosis in association with hepatitis C virus in HIV-infected patients: a cross-sectional study 
BMC Infectious Diseases  2011;11:265.
Relationship of hepatitis C virus (HCV) infection with an increased risk of cardiovascular disease (CVD) in HIV-infected patients remains controversial. We evaluated endothelial function and subclinical atherosclerosis in HIV-infected patients with and without HCV.
Flow-mediated dilatation (FMD) of the brachial artery and circulating levels of cell adhesion molecules (CAM) were measured in HCV/HIV-coinfected and HIV-monoinfected patients. Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT).
63 (31%) HCV/HIV-coinfected and 138 (69%) HIV-monoinfected patients were included. Median soluble vascular CAM-1 (sVCAM-1) and intercellular CAM-1 (sICAM-1) levels were significantly higher in HIV/HCV-coinfected patients (P < 0.001 for both cases). Median (interquartile range) FMD was 6.21% (2.86-9.62) in HCV/HIV-coinfected and 5.54% (2.13-9.13) in HIV-monoinfected patients (P = 0.37). Adjustment for variables associated with HCV and FMD disclosed similar results. FMD correlated inversely with cIMT and age. Carotid IMT did not differ between HCV/HIV-coinfected and HIV-monoinfected patients in unadjusted (0.61 [0.55-0.65] mm vs 0.60 [0.53-0.72] mm; P = 0.39) or adjusted analyses.
HCV infection was associated with higher levels of sICAM-1 and sVCAM-1, but no evidence of increased subclinical atherosclerosis was found when endothelial function was evaluated through FMD, or when assessing the cIMT.
PMCID: PMC3198698  PMID: 21967471
6.  Predictors of Pneumococcal Co-infection for Patients with Pandemic (H1N1) 2009 
Emerging Infectious Diseases  2011;17(8):1475-1478.
We conducted a systematic investigation of pneumococcal co-infection in patients with a diagnosis of pandemic (H1N1) 2009 and any risk factor for complications or with severity criteria. We found 14% prevalence, with one third of patients having nonpneumonic infections. A severity assessment score >1 and high C-reactive protein levels were predictors of pneumococcal co-infection.
PMCID: PMC3381536  PMID: 21801627
respiratory infections; viruses; bacteria; influenza; pneumococcal; pandemic; Streptococcus pneumoniae; influenza A; H1N1; dispatch
7.  Performance of Genotypic Algorithms for Predicting HIV-1 Tropism Measured against the Enhanced-Sensitivity Trofile Coreceptor Tropism Assay ▿  
Journal of Clinical Microbiology  2010;48(11):4135-4139.
The objectives of this study were to assess the performance of genotypic algorithms for predicting CXCR4-using virus, with enhanced sensitivity Trofile HIV coreceptor tropism assay (ES Trofile) as the reference, and to compare the concordance/accuracy of genotypic tests with ES Trofile and with the original Trofile assay. Paired phenotypic and genotypic determinations of HIV-1 coreceptor usage were compared in plasma samples from HIV-1-infected patients. Sequencing of the third hypervariable (V3) loop of the viral gene and phenotypic assays were performed for each sample. Genotypic rules used to predict tropism were Geno2pheno (false-positive rate at 1 to 20%), position-specific scoring matrix X4R5 (PSSMX4R5) and PSSMsinsi (where “sinsi” stands for syncytium inducing and non-syncytium inducing), and the 11/25, 11/24/25, and net charge rules. Two hundred forty-four phenotypic and genotypic samples were tested. Coreceptor usage was obtained from ES Trofile for 145 (59%) samples and from Trofile for 99 (41%) samples. The highest concordance (82.6%) was obtained with PSSMX4R5 when ES Trofile was used as the reference. Geno2pheno at a 20% false-positive rate showed the highest sensitivity (76.7%) for CXCR4-using virus detection with ES Trofile. Samples from naïve subjects and those with CD4 cell counts between 200 and 500 cells/mm3 showed the best predictive performance. Overall, the accuracy of the bioinformatics tools to detect CXCR4-using virus was similar for ES Trofile and Trofile; however, the negative predictive values for genotypic tools with ES Trofile were slightly higher than they were with Trofile. The accuracy of genotypic algorithms for detecting CXCR4-using viruses is high when using ES Trofile as the reference. Results are similar to those obtained with Trofile. The concordance with ES Trofile is better with higher CD4 cell counts and nonexposure to antiretroviral therapy.
PMCID: PMC3020874  PMID: 20861336
8.  NQR1 controls lifespan by regulating the promotion of respiratory metabolism in yeast 
Aging cell  2009;8(2):140-151.
The activity and expression of plasma membrane NADH coenzyme Q reductase is increased by calorie restriction (CR) in rodents. Although this effect is well established and is necessary for CR's ability to delay aging, the mechanism is unknown. Here we show that the Saccharomyces cerevisiae homolog, NQR1, resides at the plasma membrane and when overexpressed extends both replicative and chronological lifespan. We show that NQR1 extends replicative lifespan in a SIR2-dependent manner by shifting cells towards respiratory metabolism. Chronological lifespan extension, in contrast, occurs via a SIR2-independent decrease in ethanol production. We conclude that NQR1 is a key mediator of lifespan extension by CR through its effects on yeast metabolism and discuss how these findings could suggest a function for this protein in lifespan extension in mammals.
PMCID: PMC2699585  PMID: 19239415
Plasma membrane; coenzyme Q reductase; NQR1; coenzyme Q; replicative lifespan; chronological lifespan; dietary restriction
9.  Clinical Outcome of HIV-Infected Patients with Sustained Virologic Response to Antiretroviral Therapy: Long-Term Follow-Up of a Multicenter Cohort 
PLoS ONE  2006;1(1):e89.
Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART.
Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models.
Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9%) patients died (mortality rate 0.86 per 100 person-years), and 40 (5.3%) died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68–10.83]; P = .002), and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02–1.09; P = .001). Initial antiretroviral regimen chosen was not associated with different risk of clinical progression.
Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.
PMCID: PMC1762396  PMID: 17183720

Results 1-9 (9)