PARP1 is required for adhesion molecule expression in atherogenesis

Aims Atherosclerosis is the leading cause of death in Western societies and a chronic inflammatory disease. However, the key mediators linking recruitment of inflammatory cells to atherogenesis remain poorly defined. Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme, which plays a role in acute inflammatory diseases. Methods and results In order to test the role of PARP in atherogenesis, we applied chronic pharmacological PARP inhibition or genetic PARP1 deletion in atherosclerosis-prone apolipoprotein E-deficient mice and measured plaque formation, adhesion molecules, and features of plaque vulnerability. After 12 weeks of high-cholesterol diet, plaque formation in male apolipoprotein E-deficient mice was decreased by chronic inhibition of enzymatic PARP activity or genetic deletion of PARP1 by 46 or 51%, respectively (P < 0.05, n ≥ 9). PARP inhibition or PARP1 deletion reduced PARP activity and diminished expression of inducible nitric oxide synthase, vascular cell adhesion molecule-1, and P- and E-selectin. Furthermore, chronic PARP inhibition reduced plaque macrophage (CD68) and T-cell infiltration (CD3), increased fibrous cap thickness, and decreased necrotic core size and cell death (P < 0.05, n ≥ 6). Conclusion Our data provide pharmacological and genetic evidence that endogenous PARP1 is required for atherogenesis in vivo by increasing adhesion molecules with endothelial activation, enhancing inflammation, and inducing features of plaque vulnerability. Thus, inhibition of PARP1 may represent a promising therapeutic target in atherosclerosi

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Poly(triacetylene)s: A New Class of Linearly π-Conjugated Oligomers and Polymers with an All-carbon Backbone

Linearly π-conjugated polymers are intensively investigated in both academia and industry for a diversity of advanced materials applications. Polyacetylenes (PAs) and poly(diacetylene)s (PDAs) were among the earliest investigated linearly π-conjugated polymers possessing an all-carbon backbone. They actually represent the first members in an entire progression of linear all-carbon polymers which starts with polyacetylene and ultimately extends to carbyne. Here, we describe the discovery and systematic investigation of poly(triacetylene)s (PTAs), the third class of compounds in this progression. We report both the preparation of longer-chain polydisperse PTA polymers as well as the synthesis, characterization, and physical study of monodisperse oligomers with record lengths extending up to 18 nm. We show how molecular properties evolve into the saturation range with increasing oligomeric length and report several direct determinations of the effective conjugation length (ECL), i.e. the oligomeric length at which saturation of molecular properties occurs. Finally, we present a new class of hybrid oligomers and polymers, with a diversity of chromophores inserted as functional spacers into the PTA backbone for further enhancement of optoelectronic properties

Intestinal parasitic infections in HIV-infected patients, Lao People's Democratic Republic

HIV infection is an emerging problem in Laos. We conducted the first prospective study on intestinal parasites, including opportunistic protozoa, in newly diagnosed HIV infected patients, with or without diarrhea. The aims were to describe the spectrum of infections, to determine their prevalence and to assess their associations with diarrhea, CD4 cell count, place of residence and living conditions.; One to three stool samples over consecutive days were obtained from 137 patients. The Kato thick smear method, formalin-ethyl concentration and specific stains for coccidia and microsporidia diagnosis were performed on 260 stool samples. Baseline characteristics regarding relevant demographics, place of residence and living conditions, clinical features including diarrhea, were collected using a standardized questionnaire.; The 137 patients were young (median age: 36 years) and severely immunocompromised (83.9% at WHO stage 3 or 4, median CD4 cell count: 41/mm3). Diarrhea was present in 43.0% of patients. Parasite infection was found in 78.8% of patients, infection with at least two species in 49.6%. Prevalence rates of protozoan and helminth infections were similar (54.7% and 58.4% respectively). Blastocystis sp. was the most frequent protozoa (26.3%). Cryptosporidium sp., Cytoisospora belli and microsporidia, found at low prevalence rates (6.6%, 4.4%, 2.9%, respectively), were described for the first time in Laos. Cryptosporidium sp. was associated with persistent diarrhea. Strongyloides stercoralis was the most prevalent helminth following Opisthorchis viverrini (20.4% and 47.5% respectively). The most immunocompromised patients, as assessed by a CD4 count ≤ 50 cells/mm3, were more likely to be infected with intestinal parasites.; HIV infection was mainly diagnosed at an advanced stage of immunosuppression in Lao patients. Intestinal parasite infections were highly prevalent regardless of their diarrheal status. Opportunistic infections were reported. Improving the laboratory diagnosis of intestinal parasite infections and the knowledge on their local risk factors is warranted

PARP1 is required for adhesion molecule expression in atherogenesis

AIMS: Atherosclerosis is the leading cause of death in Western societies and a chronic inflammatory disease. However, the key mediators linking recruitment of inflammatory cells to atherogenesis remain poorly defined. Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme, which plays a role in acute inflammatory diseases. METHODS AND RESULTS: In order to test the role of PARP in atherogenesis, we applied chronic pharmacological PARP inhibition or genetic PARP1 deletion in atherosclerosis-prone apolipoprotein E-deficient mice and measured plaque formation, adhesion molecules, and features of plaque vulnerability. After 12 weeks of high-cholesterol diet, plaque formation in male apolipoprotein E-deficient mice was decreased by chronic inhibition of enzymatic PARP activity or genetic deletion of PARP1 by 46 or 51%, respectively (P or= 9). PARP inhibition or PARP1 deletion reduced PARP activity and diminished expression of inducible nitric oxide synthase, vascular cell adhesion molecule-1, and P- and E-selectin. Furthermore, chronic PARP inhibition reduced plaque macrophage (CD68) and T-cell infiltration (CD3), increased fibrous cap thickness, and decreased necrotic core size and cell death (P or= 6). CONCLUSION: Our data provide pharmacological and genetic evidence that endogenous PARP1 is required for atherogenesis in vivo by increasing adhesion molecules with endothelial activation, enhancing inflammation, and inducing features of plaque vulnerability. Thus, inhibition of PARP1 may represent a promising therapeutic target in atherosclerosis

Association of intestinal parasites with acute and persistent diarrhea in HIV-infected patients, Laos (n = 59).

<p><i>P</i>-value of Fisher exact test.</p><p>n.a., not applicable.</p

Intestinal parasitic infections in HIV-infected patients by region of residence (Southern or Northern provinces), Laos (n = 137).

<p><i>P</i>-value of Fisher exact test.</p><p>n.a., not applicable.</p

Association of intestinal parasites with CD4 cell count in HIV-infected patients, Laos (n = 137).

<p>OR, Odds ratio.</p><p>CI, Confidence interval.</p

Demographic, clinical and laboratory characteristics of HIV-infected patients with regard to diarrhea, Laos (n = 137).

<p>OR, Odds Ratio.</p><p>CI, confidence interval.</p