Lavender and coriander essential oils and their main component linalool exert a protective effect against amyloid-ß neurotoxicity.

Alzheimer's disease (AD) is a neurodegenerative disorder leading to cognitive deficits and cognitive decline. Since no cure or preventing therapy is currently available to counteract AD, natural-derived compounds are investigated to find new potential neuroprotective agents for its treatment. In the present study, we tested the neuroprotective effect of lavender and coriander essential oils (EOs) and their main active constituent linalool, against the neurotoxicity elicited by Aß1-42 oligomers, a key molecular factor in the neurodegeneration of AD. Importantly, our findings on neuronally differentiated PC12 cells exposed to Aß1-42 oligomers are in accordance with previous in vivo studies reporting the neuroprotective potential of lavender and coriander EOs and linalool. We found that lavender and coriander EOs at the concentration of 10 µg/mL as well as linalool at the same concentration were able to improve viability and to reduce nuclear morphological abnormalities in cells treated with Aß1-42 oligomers for 24 hours. Lavender and coriander EOs and linalool also showed to counteract the increase of intracellular reactive oxygen species production and the activation of the pro-apoptotic enzyme caspase-3 induced by Aß1-42 oligomers. Our findings provide further evidence that these EOs and their main constituent linalool could be natural agents of therapeutic interest against Aß1-42 -induced neurotoxicity.

Discovery of novel multi-target indole-based derivatives as potent and selective inhibitors of chikungunya virus replication.

We recently identified indole derivatives (IIIe and IIIf) with anti-chikungunya virus (CHIKV) activities at lower micro molar concentrations and a selective index of inhibition higher than the lead compound Arbidol. Here we highlight new structural information for the optimization of the previously identified lead compounds that contain the indole chemical core. Based on the structural data, a series of indole derivatives was synthesized and tested for their antiviral activity against chikungunya virus in Vero cell culture by a CPE reduction assay. Systematic optimization of the lead compounds resulted in tert-butyl-5-hydroxy-1-methyl-2-(2-trifluoromethysulfynyl)methyl)-indole-3-carboxylate derivative IIc with a 10-fold improved anti-CHIKV inhibitory activity (EC50=6.5±1µM) as compared to Arbidol demonstrating a potent, selective and specific inhibition of CHIKV replication with only a moderate cell protective effect against other related alphaviruses. The reported computational insights, together with the accessible synthetic procedure, pave the road towards the design of novel synthetic derivatives with enhanced anti-viral activities.

Adult Acne: Prevalence and Portrayal in Primary Healthcare Patients, in the Greater Porto Area, Portugal.

INTRODUCTION: Though typically found in adolescents, acne frequently affects the adult population. In Portugal, no representative studies about acne prevalence in greater populational areas are known. This study had the following objectives: calculate acne prevalence in primary healthcare patients; its characteristics, including risk factors for onset and worsening; collect information concerning selfmedication and/or prescribed treatment. MATERIAL AND METHODS: Application of a questionnaire and physical examination into a convenience sample, composed by adults from20 - 60 years old that visited, in random days, five primary healthcare centers of the Greater Porto area. RESULTS: From the 1,055 evaluated adults, acne prevalence was estimated at 61.5%. Only 36.8% of acne suffering adults was awareof their condition. More than half of tobacco users (62.3%) had acne. Just 25% of acne sufferers sought treatment. The most affected areas were the malars, differing from the younger disease form. DISCUSSION: Acne prevalence was relatively higher than other studies. The results of this study have confirmed that acne seems to be related with increased calorie intake, tobacco smoking, whole milk and fat-reduced milk consumption, hirsutism, alopecia and seborrhea. CONCLUSION: In the primary healthcare set, more than half of adults were acne sufferers. These numbers show how important primary healthcare services can be in preventing and intervening when managing acne-related risk factors and psychosocial consequences.

Introdução: A acne, apesar de caraterística no adolescente, afeta frequentemente o adulto. Em Portugal, não são conhecidos estudos sobre a prevalência da acne no adulto, nomeadamente observada nos grandes centros populacionais. Os objetivos deste estudo foram estimar a prevalência da acne nos utentes dos serviços de cuidados de saúde primários, as suas características, incluindo fatores de risco para início e/ou agravamento, além de coletar informação relacionada com a automedicação e/ou tratamento prescrito. Material e Métodos: Aplicação de questionário e exame físico a amostra composta por adultos entre os 20 - 60 anos de idade que visitaram, em dias aleatórios, cinco centros de saúde da área do Grande Porto. Resultados: Dos 1 055 adultos avaliados, a prevalência estimada de acne foi de 61,5%. Apenas 36,8% dos portadores estavam cientes da sua condição e somente 25% afirmou ter procurado tratamento. Mais de metade dos fumadores (62,3%) apresentavam acne. A zona mais afetada foi a região malar, diferindo da forma adolescente da doença. Discussão: A prevalência encontrada de acne foi mais elevada do que em outros estudos. A acne aparentou estar relacionada com a ingestão calórica aumentada, tabagismo, consumo de leite gordo ou meio gordo, hirsutismo, alopécia e seborreia. Conclusão: No contexto dos cuidados de saúde primários, mais de metade dos adultos eram portadores de acne. Estes números demonstram o quão importante pode ser a prevenção e intervenção pelos profissionais dos cuidados de saúde primários, tanto para a redução de eventuais factores de risco como para a intervenção terapêutica e consequências psicossociais relacionadas com a acne. Palavras-chave: Acne Vulgaris/epidemiologia; Adulto; Cuidados de Saúde Primários; Portugal; Prevalência.

Cutaneous Lymphangioma circumscriptum - dermoscopic features.

Lymphangiomas are congenital lymphatic malformations and cutaneous lymphangioma circumscriptum is the most common type. It is clinically characterized by clusters of translucent vesicles and the presence of dermoscopically yellow lacunae surrounded by pale septa, as well as reddish to bluish lacunae. In our case, the recently described hypopyon-like feature manifested, aiding in the sometimes difficult differential diagnosis of cutaneous lymphangioma circumscriptum with vascular lesions, further highlighting the importance of dermoscopy in what can be a diagnostic challenge.

Cutaneous Lymphangioma circumscriptum - dermoscopic features*

Lymphangiomas are congenital lymphatic malformations and cutaneous lymphangioma circumscriptum is the most common type. It is clinically characterized by clusters of translucent vesicles and the presence of dermoscopically yellow lacunae surrounded by pale septa, as well as reddish to bluish lacunae. In our case, the recently described hypopyon-like feature manifested, aiding in the sometimes difficult differential diagnosis of cutaneous lymphangioma circumscriptum with vascular lesions, further highlighting the importance of dermoscopy in what can be a diagnostic challenge.

Titanium mesh in the reconstruction of a malar defect: a case report.

BACKGROUND: Increasing rates of non-melanoma skin cancer support the use of prosthetic materials for the closure of post-surgical defects with cartilage or bone involvement. The use of allografts, especially titanium, is well established in maxillofacial procedures but is uncommon in dermatologic surgery. METHODS: A 92-year-old man presented with a basal cell carcinoma measuring 2×3 cm on the right cheek. Computed tomography showed infiltration of the anterior maxillary sinus wall. The tumor was excised under general anesthesia. The final defect comprised skin, muscle, the central portion of the maxillary bone and part of the maxillary sinus mucous. The defect was closed with titanium mesh and covered with a rotation flap from the right cheek. The secondary defect created by the preauricular rotation was closed with a free skin graft from the supraclavicular area. RESULTS: The use of titanium mesh enabled satisfactory esthetic and functional results to be achieved safely and quickly. CONCLUSIONS: Titanium mesh facilitates the repair of large defects and avoids the second intervention and increased risk for infection associated with bone grafting. Reconstruction with titanium mesh is considered a valuable technique in post-trauma fractures and post-oncologic defects but remains underused in dermatologic surgery. The present experience supports its use as a reliable option in bone replacement.

Circumscribed morphea and breast asymmetry in an adolescent.

Morphea is a rare fibrosing disorder of the skin and underlying tissues. Circumscribed morphea presents with less than three discrete indurated plaques and breasts are commonly affected in women. We report the case of a 12-year-old female with a right infra-areolar, nontender, brownish patch and asymmetry of the right breast with 2 years of evolution. Skin biopsy showing thickening of the dermal collagen bundles confirmed the clinical diagnosis of morphea. After a 3-year follow-up period without progression of disease, reconstructive surgery is scheduled. Plaque morphea can involve all layers of the skin but associated breast deformity is rare. It can mimic benign and malignant breast disorders justifying the benefit for early tissue biopsy. Breast morphea generally has a good prognosis but hyperpigmentation and breast deformity in young girls have been rarely described. An early diagnosis can possibly lead to a therapeutic intervention with a different outcome, as it can be the source of severe psychological and social issues in a delicate period of development such as adolescence.

Cyclohexa-2,5-diene-1,4-dione-based antiproliferative agents: design, synthesis, and cytotoxic evaluation.

BACKGROUND: Tumors are diseases characterized by uncontrolled cell growth and, in spite of the progress of medicine over the years, continue to represent a major threat to the health, requiring new therapies. Several synthetic compounds, such as those derived from natural sources, have been identified as anticancer drugs; among these compounds quinone represent the second largest class of anticancer agents in use. Several studies have shown that these act on tumor cells through several mechanisms. An important objective of this work is to develop quinoidscompounds showing antitumor activity, but with fewer side effects. The parachinone cannabinol HU-331, is a small molecule that with its core 4-hydroxy-1,4-benzoquinone, exhibits a potent and selective cytotoxic activity on different tumor cell lines. A series of derivatives 3-hydroxy-1,4-benzochinoni were thus developed through HU-331 chemical modifications. The purpose of the work is to test the ability of the compounds to induce proliferative inhibition and study the mechanisms of cell death. METHODS: The antitumor activities were evaluated in vitro by examining their cytotoxic effects against different human cancer cell lines. All cell lines tested were plated in 96-multiwell and treated with HU-100-V at different concentrations and cell viability was evaluated byMTT assay. Subsequently via flow cytometry (FACS) it was possible to assess apoptosis by the system of double labeling with PI and Annexin-V, and the effect of the compounds on ROS formation by measuring the dichlorofluorescein fluorescence. RESULTS: The substitution by n-hexyl chain considerably enhanced the bioactivity of the compounds. In details, 2-hexyl-5-hydroxycyclohexa-2,5-diene-1,4-dione (V), 2,5-Dimethoxy-3-hexyl-2,5-cyclohexadiene-1,4-dione (XII) and 2-hydroxy-5-methoxy-3-hexyl-cyclohexa-2,5-diene-1,4-dione (XIII) showed most prominent cytotoxicity against almost human tumour cell lines. Compound V was further subjected to downstream apoptotic analysis, demostrating a time-dependent pro-apoptotic activity on human melanoma M14 cell line mediated by caspases activation and poly-(ADP-ribose)-polymerase (PARP) protein cleavage. CONCLUSIONS: These findings indicate that 2-hexyl-5-idrossicicloesa-2,5-diene-1,4-dione can be a promising compound for the design of a new class of antineoplastic derivatives.Carmen Petronzi, Michela Festa, Antonella Peduto and Maria Castellano: equally contributed equally to this work.

Molluscum contagiosum eyelid lesions in an HIV-patient.

Molluscum contagiosum (MC) lesions on the face are mainly observed in HIV patients and are related to low CD4 cells counts. We report a 41-year-old female patient infected with human immunodeficiency virus who had a CD4 count of 22 cells/mm³. She developed molluscum contagiosum lesions at the right upper eyelid. Skin biopsy was performed to exclude other serious conditions, such as dimorphic fungal infections. A good response was observed with three sessions of curettage and topical application of 70 percent trichloroacetic acid. Facial molluscum contagiosum lesions can be a cutaneous marker of severe immunosuppression in HIV patients and skin biopsy is important in ruling out the diagnosis of dimorphic fungal infections.

Design, synthesis, biophysical and biological studies of trisubstituted naphthalimides as G-quadruplex ligands.

A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)(3) binding was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex with compounds showing the best affinity has been studied by isothermal titration calorimetry and UV-melting experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell proliferation was observed for all cellular lines during short-term treatment.

Structure-based design, synthesis and preliminary anti-inflammatory activity of bolinaquinone analogues.

As a part of our drug discovery efforts we developed a series of simplified derivatives of bolinaquinone (BLQ), a hydroxyquinone marine metabolite, showing potent anti-inflammatory activity. Thirteen new hydroxyquinone derivatives closely related to BLQ were synthesized and tested on mouse macrophage-like RAW 264.7 cell line in order to investigate their ability to modulate the production of Prostaglandin E2 (PGE2). This optimization process led to the identification of three strictly correlated compounds with comparable and higher inhibitory potency than BLQ on PGE2 production. To evaluate the affinity of BLQ and its analogues for hsPLA2, surface plasmon resonance (SPR) experiments were performed.

Atopic dermatitis-like non-erythrodermic leukemic variant of CD3(-/+dim) CD4(+) cutaneous T-cell lymphoma preceded by cutaneous papular xanthomatosis.

We report a patient with cutaneous papular xanthomatosis who 4 years later developed a CD3(-/+dim)/CD4(+) T-cell lymphoma. Pruritic xerotic non-erythrodermic skin, eosinophilia and hyper-IgE were present and erroneously classified as atopic dermatitis. Flow cytometry and DNA ploidy analysis of both blood and skin lymphocytes, skin histology and blood T-cell receptor gene rearrangement studies confirmed diagnosis of T-cell lymphoma. Monoclonal CD3(-/+dim)/CD4(+) T-cells were especially prone to the synthesis of IL-13, a cytokine that is involved in IgE-secretion, and comprised both a medium (diploid) and large (hyperploid) sized T-cell populations with a similar immunophenotype. The majority of the normal residual T-cells were large granular lymphocytes, expressed activation-related and natural-killer-associated markers and secreted high levels of interferon gamma, suggesting that they might correspond to active cytotoxic cells directed against the neoplastic T-lymphocytes.

Non-cytotoxic gamma-delta peripheral T-cell lymphoma affecting the mandibular and parotidal lymph nodes and the skin.

In contrast to the majority of alphabeta peripheral T cell lymphomas (PTCL), which usually originate in lymph nodes and do not express NK-associated molecules, most gammadelta PTCL express a cytotoxic phenotype and originate at extranodal sites. We report a case of a patient with a gamma-delta PTCL who presented with large mandibular and parotidal lymphadenopathy and skin lesions. CD3(+)/TCR-Vdelta1 (+) lymphoma cells did not express the cell surface (CD11b, CD11c, CD16, CD56 and CD57) and cytoplasmic granule molecules (Perforin and Granzyme B) that usually characterize the cytotoxic T-cells, a phenotype that fulfils the criteria for diagnosis of a rare non-cytotoxic variant of a gammadelta T-cell lymphoma. "In situ" hybridization for Epstein-Barr virus-encoded RNA and latent membrane protein-1 gave negative results. The disease had an aggressive course and was resistant to chemotherapy and the patient died 4 months after diagnosis.