36 research outputs found

    Renal function in HIV-infected children and adolescents treated with tenofovir disoproxil fumarate and protease inhibitors

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    <p>Abstract</p> <p>Background</p> <p>Kidney disease is an important complication in HIV infected people, and this may be related to infection or antiretroviral therapy (ART). Our aim is to assess renal function in HIV infected paediatric patients, who may be particularly affected and are likely to take ART for longer than adults, and investigate the long term role of Tenofovir Disoproxil Fumarate (TDF) alone or co-administered with Ritonavir-boosted Protease Inhibitors (PI).</p> <p>Methods</p> <p>Serum creatinine, phosphate and potassium levels, with estimated Glomerular Filtration Rate (eGFR), had been prospectively evaluated for 2 years in a cohort of HIV infected children and adolescents (age 9-18) on ART, and data analyzed according to the exposure to TDF or simultaneous TDF and PI.</p> <p>Results</p> <p>Forty-nine patients were studied (57% female, mean age 14). Sixty-three percent were treated with ART containing TDF (Group A), and 37% without TDF (Group B); 47% with concomitant use of TDF and PI (Group C) and 53% without this combination (Group D). The groups didn't differ for age, gender or ethnicity. The median creatinine increased in the entire cohort and in all the groups analyzed; eGFR decreased from 143.6 mL/min/1.73 m<sup>2 </sup>at baseline to 128.9 after 2 years (<it>p </it>= 0.006) in the entire cohort. Three patients presented a mild eGFR reduction, all were on TDF+PI. Phosphatemia decreased significantly in the entire cohort (<it>p </it>= 0.0003) and in TDF+PI group (<it>p </it>= 0.0128) after 2 years. Five patients (10%) developed hypophosphatemia (Division of Acquired Immune Deficiency AE grade 1 or 2), and four of them were on TDF+PI.</p> <p>Conclusions</p> <p>Renal function decrease and hypophosphatemia occur over time in HIV infected children and adolescents on ART. The association with co-administration of TDF and PI appears weak, and further studies are warranted.</p

    Therapeutic DNA vaccination of vertically HIV-infected children: Report of the first pediatric randomised trial (PEDVAC)

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    Subjects: Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm³. Intervention: Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results: Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions: The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration: clinicaltrialsregister.eu 2007-002359-18; 2007-002359-18/I

    Loss of miR-204 expression is a key event in melanoma

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    Cutaneous melanoma (CM) is a malignancy with increasing occurrence. Its microRNA repertoire has been defined in a number studies, leading to candidates for biological and clinical relevance: miR-200a/b/c, miR-203, miR-205, miR-204, miR-211, miR-23b and miR-26a/b. Our work was aimed to validate the role of these candidate miRNAs in melanoma, using additional patients cohorts and in vitro cultures. miR-26a, miR-204 and miR-211 were more expressed in normal melanocytes, while miR-23b, miR-200b/c, miR-203 and miR-205 in epidermis and keratinocytes. None of the keratinocyte-related miRNAs was associated with any known mutation or with clinical covariates in melanoma. On the other hand, the loss of miR-204 was enriched in melanomas with NRAS sole mutation (Fisher exact test, P = 0.001, Log Odds = 1.67), and less frequent than expected in those harbouring CDKN2A mutations (Fisher exact test, P = 0.001, Log Odds − 1.09). Additionally, miR-204 was associated with better prognosis in two independent melanoma cohorts and its exogenous expression led to growth impairment in melanoma cell lines. Thus, miR-204 represents a relevant mechanism in melanoma, with potential prognostic value and its loss seems to act in the CDKN2A pathway, in cooperation with NRAS

    Archaeometric study of punic amphorae from the underwater recoveries of Pantelleria Island (Sicily).

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    In the frame of an extensive research project concerning the study of archaeological finds from the sea of Pantelleria Island (Sicily, Italy), about two hundred Punic, Greek-Italic, and Roman amphorae have been examined. In particular, thirty five Punic amphorae belonging to six different typologies of the second century BC have been studied. They were probably produced in that Punic-Tunisian area comprising Carthage and other Punic sites nearby the Sahel area. These ceramic artifacts were recovered from shipwrecks dating back to the II century BC, belonging to a shipload, i.e. associated with Greek-Italian amphorae (first half of the second century BC) and with Roman- Tyrrhenian amphorae (second half of the second century BC). Selected amphorae underwent archaeometric studies which are aimed at identifying their origin, at validating the archaeological hypothesis, at identifying the production technology, and at studying their conservation status. Results obtained allowed to recognize three ceramic-body groups characterized by different relative distributions of grain size fractions. Furthermore chemical composition results show some analogies with sherds from Carthage. Diatoms, algae and bryozoa encrustations have been identified as well, together with surface chromatic alterations (i.e. black areas), probably ascribable to chemical reduction processes, due to the activity of sulphur- bacteria.Dans le contexte d'un vaste projet de recherche concernant le matériel archéologique de Pantelleria, on a étudié près de deux cents amphores puniques, gréco-italiques et romaines. En particulier on a sélectionné trente-cinq amphores puniques qu'on associe à six typologies du IIème siècle av. J.-C. (Torres, 1996) produites sans doute dans la région punique-tunisienne comprenant Carthage et les centres puniques de la côte aux environs de la région du Sahel. Il s'agit de produits céramiques récupérés dans des épaves du IIème siècle av. J.-C, qui appartiennent à une charge de genre mixte, c'est-à-dire associés à d'autres amphores gréco-italiques (première moitié du IIème siècle av. J.-C.) et à des amphores romaines tyrrhénéennes (seconde moitié du IIème siècle av. J.-C). Le groupe d'amphores sélectionnées a été soumis à des études archéométriques afin d'identifier leur origine et de confirmer, éventuellement, les hypothèses archéologiques, pour identifier la technologie de production et pour connaître leur état de conservation. Les résultats de ces recherches ont permis de créer trois groupes de pâte caractérisés par différentes distributions des fractions granulomètrique. Les résultats de l'analyse chimique montrent des similitudes avec les obtenues sur les matériaux céramiques de Carthage. De plus, on a mis en évidence des incrustations de diatomées, algues et bryozoaires, ainsi que des altérations superficielles de la pâte de genre chromatique (noircissements) qu'on peut ramener à une activité de réduction de la part de sulphobactéries.Amadori Maria Letizia, Baldassari Roberta, Lanza Stefania, Maione Michela, Penna Antonella, Acquaro Enrico. Archaeometric study of punic amphorae from the underwater recoveries of Pantelleria Island (Sicily).. In: Revue d'Archéométrie, n°26, 2002. pp. 79-91

    Patient data at enrolment.

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    <p>ART signifies antiretroviral treatment with PI = protease inhibitors, NRTI = nucleoside reverse transcriptase inhibitors, NNRTI = non nucleoside reverse transcriptase inhibitors.</p

    Viral dynamics during the vaccination schedule for the control Group A (n = 10) (A) and vaccine Group B (n = 10) (B).

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    <p>HIV-RNA with a limit of detection of 50 copies/ml is shown as black dots, HIV-RNA ultrasensitive assay with a limit of detection of 1 copy/ml plasma is shown as circles and cell associated HIV-DNA of PBMC shown as triangles indicating number of total HIV-proviral DNA copies/10<sup>6</sup> PBMC. Black arrows show vaccinations (weeks 0, 4, 12 and 36).</p
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