Fatal Naegleria fowleri Meningoencephalitis, Italy

We report the first case of primary amebic meningoencephalitis in Italy, in a 9-year-old boy. Clinical course was fulminant, and diagnosis was made by identifying amebas in stained brain sections and by indirect immunofluorescence analysis. Naegleria fowleri was characterized as genotype I on the basis of polymerase chain reaction test results

De novo fatty acid synthesis at the mitotic exit is required to complete cellular division

Although the regulation of the cell cycle has been extensively studied, much less is known about its coordination with the cellular metabolism. Using mass spectrometry we found that lysophospholipid levels decreased drastically from G2/M to G1 phase, while de novo phosphatidylcholine synthesis, the main phospholipid in mammalian cells, increased, suggesting that enhanced membrane production was concomitant to a decrease in its turnover. In addition, fatty acid synthesis and incorporation into membranes was increased upon cell division. The rate-limiting reaction for de novo fatty acid synthesis is catalyzed by acetyl-CoA carboxylase. As expected, its inhibiting phosphorylation decreased prior to cytokinesis initiation. Importantly, the inhibition of fatty acid synthesis arrested the cells at G2/M despite the presence of abundant fatty acids in the media. Our results suggest that de novo lipogenesis is essential for cell cycle completion. This "lipogenic checkpoint" at G2/M may be therapeutically exploited for hyperproliferative diseases such as cancer.Instituto de Investigaciones Bioquímicas de La Plat

De novo fatty acid synthesis at the mitotic exit is required to complete cellular division

Although the regulation of the cell cycle has been extensively studied, much less is known about its coordination with the cellular metabolism. Using mass spectrometry we found that lysophospholipid levels decreased drastically from G2/M to G1 phase, while de novo phosphatidylcholine synthesis, the main phospholipid in mammalian cells, increased, suggesting that enhanced membrane production was concomitant to a decrease in its turnover. In addition, fatty acid synthesis and incorporation into membranes was increased upon cell division. The rate-limiting reaction for de novo fatty acid synthesis is catalyzed by acetyl-CoA carboxylase. As expected, its inhibiting phosphorylation decreased prior to cytokinesis initiation. Importantly, the inhibition of fatty acid synthesis arrested the cells at G2/M despite the presence of abundant fatty acids in the media. Our results suggest that de novo lipogenesis is essential for cell cycle completion. This "lipogenic checkpoint" at G2/M may be therapeutically exploited for hyperproliferative diseases such as cancer.Instituto de Investigaciones Bioquímicas de La Plat

Chronic Giardia intestinalis infection presenting with clinical features mimicking lichen planus.

Sir, Human giardiasis, caused by Giardia intestinalis, a agellate protozoan parasite that colonizes the small bowel, is a worldwide infection (1). Giardia infection is usually asymptomatic but intestinal illness may occur (2–5). Several reports describe the association of allergy with increased levels of total serum IgE antibodies and of speci c IgE antibodies against food allergens in patients aVected by giardiasis, and Giardia infection may determine altered absorption of food antigens causing allergic sensitization (6). Cutaneous signs may be virtually indistinguishable from those of atopic dermatitis (7, 8). Acute reactions such as urticaria or asthma have also been described (9–11). We here report a patient aVected by giardiasis, with lichen-planus-like lesions as the sole clinical feature

AKT1 and MYC Induce Distinctive Metabolic Fingerprints in Human Prostate Cancer

Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry–based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our findings show how prostate tumors undergo a metabolic reprogramming that reflects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.Fil: Priolo, Carmen. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Pyne, Saumyadipta. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Rose, Joshua. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Regan, Erzsébet Ravasz. Harvard Medical School; Estados UnidosFil: Zadra, Giorgia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Photopoulos, Cornelia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Cacciatore, Stefano. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados UnidosFil: Schultz, Denise. Johns Hopkins University; Estados UnidosFil: Scaglia, Natalia. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: McDunn, Jonathan. Metabolon Inc.; Estados UnidosFil: de Marzo, Angelo M.. Johns Hopkins University; Estados UnidosFil: Loda, Massimo. Department of Pathology. Brigham and Women's Hospital; Estados Unidos. Department of Medical Oncology. Dana Farber Cancer Institute. Brigham and Women's Hospital; Estados Unidos. University of Cambridge; Estados Unidos. King's College London. Division of Cancer Studies; Estados Unido

A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis

5′AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth remains to be determined. A small molecule screening was performed and identified MT 63–78, a specific and potent direct AMPK activator. Here, we show that direct activation of AMPK inhibits PCa cell growth in androgen sensitive and castration resistant PCa (CRPC) models, induces mitotic arrest, and apoptosis. In vivo, AMPK activation is sufficient to reduce PCa growth, whereas the allelic loss of its catalytic subunits fosters PCa development. Importantly, despite mTORC1 blockade, the suppression of de novo lipogenesis is the underpinning mechanism responsible for AMPK-mediated PCa growth inhibition, suggesting AMPK as a therapeutic target especially for lipogenesis-driven PCas. Finally, we demonstrate that MT 63–78 enhances the growth inhibitory effect of AR signaling inhibitors MDV3100 and abiraterone. This study thus provides a rationale for their combined use in CRPC treatment

De novo fatty acid synthesis at the mitotic exit is required to complete cellular division

Although the regulation of the cell cycle has been extensively studied, much less is known about its coordination with the cellular metabolism. Using mass spectrometry we found that lysophospholipid levels decreased drastically from G2/M to G1 phase, while de novo phosphatidylcholine synthesis, the main phospholipid in mammalian cells, increased, suggesting that enhanced membrane production was concomitant to a decrease in its turnover. In addition, fatty acid synthesis and incorporation into membranes was increased upon cell division. the rate-limiting reaction for de novo fatty acid synthesis is catalyzed by acetyl-CoA carboxylase. As expected, its inhibiting phosphorylation decreased prior to cytokinesis initiation. Importantly, the inhibition of fatty acid synthesis arrested the cells at G2/M despite the presence of abundant fatty acids in the media. our results suggest that de novo lipogenesis is essential for cell cycle completion. this “lipogenic checkpoint” at G2/M may be therapeutically exploited for hyperproliferative diseases such as cancer.Fil: Scaglia, Natalia. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tyekucheva, Svitlana. Harvard University. Harvard School of Public Health; Estados UnidosFil: Zadra, Giorgia. Harvard Medical School; Estados UnidosFil: Photopoulos, Cornelia. Harvard Medical School; Estados UnidosFil: Loda, Massimo. Harvard Medical School; Estados Unido

Trichomoniasi in gravidanza . Indagine colturale e colpocitologica su 208 gestanti asintomatiche.

[Trichomoniasis in pregnancy. Cultural and colpocytologic research on 208 asymptomatic pregnant women]