A high-cholesterol diet promotes the intravasation of breast tumor cells through an LDL-LDLR axis.

Most metastases in breast cancer occur via the dissemination of tumor cells through the bloodstream. How tumor cells enter the blood (intravasation) is, however, a poorly understood mechanism at the cellular and molecular levels. Particularly uncharacterized is how intravasation is affected by systemic nutrients. High levels of systemic LDL-cholesterol have been shown to contribute to breast cancer progression and metastasis in various models, but the cellular and molecular mechanisms involved are still undisclosed. Here we show that a high- cholesterol diet promotes intravasation in two mouse models of breast cancer and that this could be reverted by blocking LDL binding to LDLR in tumor cells. Moreover, we show that LDL promotes vascular invasion in vitro and the intercalation of tumor cells with endothelial cells, a phenotypic change resembling vascular mimicry (VM). At the molecular level, LDL increases the expression of SERPINE2, previously shown to be required for both VM and intravasation. Overall, our manuscript unravels novel mechanisms by which systemic hypercholesterolemia may affect the onset of metastatic breast cancer by favouring phenotypic changes in breast cancer cells and increasing intravasation.

Morphological and molecular effects of cortisol and ACTH on zebrafish stage I and II follicles.

Oogenesis in zebrafish (Danio rerio) is controlled by the hypothalamus-pituitary-gonadal axis and reproductive hormones. In addition, an interference of stress hormones is known with reproductive biology. In the presented work, we aimed to explore the hypothesis that cortisol (Cort) and ACTH may affect early oogenesis in zebrafish, given the presence of the specific receptors for glucocorticoids and ACTH in the zebrafish ovary. Follicles at stages I and II were exposed in vitro to 1  µM Cort and ACTH for 48 h, then ultrastructural and molecular effects were analyzed. The comet assay demonstrated increased tail moments for Cort and ACTH treatment indicative of DNA damage. The mRNA expression of apoptotic genes (bax, bcl-2) was not altered by both treatments, but Cort increased significantly the expression of the ACTH receptor (mc2r). Cort stimulated the presence of the endoplasmic reticulum, predominantly at stage II, while ACTH induced a strong vacuolization. Viability of oocytes was not affected by both treatments and fluorescent staining (monodansylcadaverine/acridine orange) indicated a reduced quantity of autophagosomes for ACTH, and lower presence of nucleic acids in ooplasm for Cort and ACTH. Concluding, different responses were observed for stress hormones on early stages of zebrafish oocytes, which suggest a role for both hormones in the stress-mediated adverse effects on female gametogenesis.

Mucocutaneous manifestations of Behçet's disease.

Behçet's disease is a relapsing multisystem polysymptomatic disease with exacerbations and remissions defined by the presence of the major symptom, recurrent oral aphthous ulcers, plus two of the following: recurrent genital ulceration, eye lesions, skin lesions or a positive pathergy test. Mucocutaneous manifestations like oral and genital ulcers, and cutaneous lesions (papulopustular lesions, erythema nodosum-like lesions, cutaneous ulcers, superficial thrombophlebitis), are considered the \"fingerprint\" of the disease, being the most common and often the first signs to appear. Although the exact etiopathogenesis is still not known, genetic predispose and environmental factors may influence and contribute to the development of this disease. Diagnosis is based in the International Study Group criteria. During the last years, this disease has been largely studied and new immunological data and treatment strategies have been postulated. Despite that, further studies and attention to new data are needed.

Fungal meningitis in an immunocompetent patient.

Cryptococcal meningitis is a rare entity among immunocompetent hosts but, when it occurs, it is associated with significant morbidity and mortality. Clinical presentation as well as the course of the disease is usually subtle and indolent with headache and altered mental status. The authors present the case of a 59-year-old man, who sought medical help with a 2-week history of headaches accompanied by nausea and visual and hearing disturbances. On admission the patient was afebrile, presented visual and hearing deficits and had a normal magnetic resonance image of the brain. A lumbar puncture was performed and microscopic examination of the cerebrospinal fluid revealed yeasts that were identified as Cryptococcus spp. and later, by means of molecular biology techniques, as Cryptococcus neoformans, var. grubii. The patient was treated with liposomal amphotericin B plus fluconazole for 28 weeks. At follow-up after 1 year the patient was asymptomatic and received fluconazole 400 mg/day as prophylactic therapy. The outcome of Cryptococcus infections in immunocompetent hosts is reported to be poor as a result of a delayed diagnosis and suboptimal initial antifungal therapy. The influence of the normal immune response is unclear.

Mechanisms of action of topical corticosteroids in psoriasis.

Psoriasis is a lifelong, chronic, and immune-mediated systemic disease, which affects approximately 1-3% of the Caucasian population. The different presentations of psoriasis require different approaches to treatment and appropriate prescriptions according to disease severity. The use of topical therapy remains a key component of the management of almost all psoriasis patients, and while mild disease is commonly treated only with topical agents, the use of topical therapy as adjuvant therapy in moderate-to-severe disease may also be helpful. This paper focuses on the cutaneous mechanisms of action of corticosteroids and on the currently available topical treatments, taking into account adverse effects, bioavailability, new combination treatments, and strategies to improve the safety of corticosteroids. It is established that the treatment choice should be tailored to match the individual patient's needs and his/her expectations, prescribing to each patient the most suitable vehicle.

Cutaneous manifestations of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. The skin is one of the target organs most variably affected by the disease. The American College of Rheumatology (ACR) established 11 criteria as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. Cutaneous lesions account for four of these 11 revised criteria of SLE. Skin lesions in patients with lupus may be specific or nonspecific. This paper covers the SLE-specific cutaneous changes: malar rash, discoid rash, photosensitivity, and oral mucosal lesions as well as SLE nonspecific skin manifestations, their pathophysiology, and management. A deeper thorough understanding of the cutaneous manifestations of SLE is essential for diagnosis, prognosis, and efficient management. Thus, dermatologists should cooperate with other specialties to provide optimal care of SLE patient.

Pathogenic fungi: an unacknowledged risk at coastal resorts? New insights on microbiological sand quality in Portugal.

Whilst the potential impact on beach users from microorganisms in water has received considerable attention, there has been relatively little investigation into microbial contaminants in sand. Thirty three beaches across Portugal were analyzed during a five year period (2006-2010) to determine the presence of yeasts, pathogenic fungi, dermatophytes, total coliforms, Escherichia coli and intestinal enterococci in sand. Our results showed that 60.4% of the samples were positive for fungi and that 25.2% were positive for the bacterial parameters. The most frequent fungal species found were Candida sp. and Aspergillus sp., whereas intestinal enterococci were the most frequently isolated bacteria. Positive associations were detected among analyzed parameters and country-regions but none among those parameters and sampling period. Regarding threshold values, we propose 15 cfu/g for yeasts, 17 cfu/g for potential pathogenic fungi, 8 cfu/g for dermatophytes. Twenty-five cfu/g for E. coli, and 10 [corrected] cfu/g for intestinal enterococci.