Pulmonary lymphatic vessel morphology: a review.

Our understanding of lymphatic vessels has been advanced by the recent identification of relatively specific lymphatic endothelium markers, including Prox-1, VEGFR3, podoplanin and LYVE-1. The use of lymphatic markers has led to the observation that, contrary to previous assumptions, human lymphatic vessels extend deep inside the pulmonary lobule, either in association with bronchioles, intralobular arterioles or small pulmonary veins. Pulmonary lymphatic vessels may thus be classified into pleural, interlobular (in interlobular septa) and intralobular. Intralobular lymphatic vessels may be further subdivided in: bronchovascular (associated with a bronchovascular bundle), perivascular (associated with a blood vessel), peribronchiolar (associated with a bronchiole), and interalveolar (in interalveolar septa). Most of the intralobular lymphatic vessels are in close contact with a blood vessel, either alone or within a bronchovascular bundle. A minority is associated with a bronchiole, and small lymphatics are occasionally present even in interalveolar septa, seemingly independent of blood vessels or bronchioles. The lymphatics of the interlobular septa often contain valves, are usually associated with the pulmonary veins, and connect with the pleural lymphatics. The large lymphatics associated with bronchovascular bundles have similar characteristics to pleural and interlobular lymphatics and may be considered conducting vessels. The numerous small perivascular lymphatics and the few peribronchiolar ones that are found inside the lobule are probably the absorbing compartment of the lung responsible for maintaining the alveolar interstitium relatively dry in order to provide a minimal thickness of the air-blood barrier and thus optimize gas diffusion. These lymphatic populations could be differentially involved in the pathogenesis of diseases preferentially involving distinct lung compartments.

A Reduction Grade of Lipodystrophy and Limited Side Effects after HAART Regimen with Raltegravir, Lamivudine, Darunavir and Ritonavir in an HIV-1 Infected Patient after Six Years of Antiretroviral Therapy.

HIV-associated lipodystrophy commonly presents with fat loss in the face, buttocks, arms and legs, hypocomplementaemia, glomerulonephritis, and autoimmune disorders. The exact mechanism of HIV-associated lipodystrophy is not fully elucidated. There is evidence indicating that it can be caused by both antiretroviral medications and HIV infection in the absence of antiretroviral medication. Lipodystrophy seems to be mainly due to HIV-1 protease inhibitors. Interference with lipid metabolism is postulated as pathophysiology. Also, the development of lipodystrophy is associated with specific nucleoside reverse transcriptase inhibitors (NRTI). Mitochondrial toxicity is postulated to be involved in the pathogenesis associated with NRTI. Here, we analyse the side effects and examine the impact of the highly active antiretroviral therapy (HAART) regimen including raltegravir, lamivudine, darunavir and ritonavir in an HIV-1 infected patient with severe lipodystrophy after six years of antiretroviral therapy.

Efficacy and safety of a salvage regimen based on tipranavir, enfuvirtide and three nucleoside analogues in HIV1 infected patients with clinical progression: 96-week evaluation.

In recent years, novel antiretroviral drugs have become available for multi-experienced HIV-infected patients with limited options. We enrolled seven advanced HIV-patients, failing multiple previous HAART regimens, in virological failure on their current HAART regimen and showing recent clinical and immunological progression. All patients were prescribed a double-boosted tipranavir plus enfuvirtide based regimen, in addition to zidovudine, tenofovir and lamivudine for salvage therapy. To assess susceptibility to tipranavir, the tipranavir genotypic resistance score was calculated and two years later this was re-evaluated on an updated tipranavir genotypic score algorithm. At baseline, CD4 were 139/mcL (more or less 145), HIV-1 RNA was 822,700 cp/mL. All patients achieved HIV-1 RNA levels less than 400 cp/mL between 12 weeks and 24 weeks of observation; two reached less than 50 cp/mL during this period. At 48 weeks three patients had reached less than 50 cp/mL; three other patients had HIV RNA less than 200 cp/mL. At 72 and 96 weeks HIV viraemia was less than 50 cp/mL in six patients; CD4 T-cell counts 285/mcL (more o less 198). No AIDS-defining events were recorded. Adverse events did not need to stop or change HAART. Strong 3 NRTI backbone could help efficacy and durability, and frequent evaluations in complex patients can help to manage toxicity.