Antitumor effect of depsidones from lichens on tumor cell lines and experimental murine melanoma

Abstract Lichens have exhibited numerous biological activities, including growth inhibition of tumor cells. This study evaluated the antiproliferative activity of hypostictic and salazinic acids against tumor cell lines (B16-F10, PC-03, MCF7, HT-29, HEP-G2, K562 and 786-0) by the SRB assay in vitro and antitumor activity in experimental murine melanoma in vivo. Activation of caspase-3 was quantified by flow cytometry. The murine experimental melanoma model B16-F10 was used in BALB/c mice for evaluation of antitumor activity. Hypostictic acid showed significant antiproliferative activity in K562 cells (GI50 2.20 µM), B16-F10 (GI50 13.78 µM) and 786-0 (GI50 14.24 µM), whereas salazinic acid was more active against K562 cells (GI50 64.36 µM), HT-29 (GI50 67.91 µM) and B16-F10 (GI5078.64 µM). Quantification of capase-3 revealed that the test compounds did not increase the expression of that enzyme. In the in vivo antitumor evaluation in B16-F10 melanoma, the isolated compounds inhibited tumor growth in relation to weight and volume. Hypostictic acid (16.7 mg/kg) inhibited 72% and salazinic acid 88% of tumor volume (p < 0.05). The results indicated that, both in the in vitro and in vivo models, the compounds evaluated showed antiproliferative and antitumor activities.

Effect of powdered shells treatment of the snail Megalobulimus lopesi on wounds of diabetic rats

Abstract Purpose: To analyzed the healing effect of the powdered shell of the Megalobulimus lopesi snail on wounds of diabetic rats, since in non-diabetic rats the powdered shell presented healing potential. Methods: Seventy-two Wistar rats (Rattus norvegicus albinus) were divided into three groups: Control group (GC.diab), no therapeutic intervention on the wound; Vehicle's Control group, topical via, in diabetic rats (GCvt.diab): Powder Shell Group (PC) applied topically (GPCvt.diab): Experimental group was administered topically shortly after wound dressing and once a day during the experimental period (3, 7, 14 and 21 days) the composition containing the powdered shell of the snail. The following variables related to the healing potential were analyzed: macroscopic one, where the capacity of reduction of the wound area was evaluated; histological analysis in HE, angiogenic activity, morphometric analysis (re-epithelization), leukocyte inflammatory infiltrate; leukocyte count and also differentiation in peripheral blood. Results: The topical application in wounds of diabetic rats presented healing activity, accelerating wound closure, stimulating angiogenesis and being pro-inflammatory in the early and anti-inflammatory stages in the final times of the healing process. Conclusion: The topical administration of the powdered shell on wounds of diabetic patients becomes a therapeutic option of low cost, with ease in the administration and access as well.

In vivo antileishmanial activity and chemical profile of polar extract from Selaginella sellowii

The polar hydroethanolic extract from Selaginella sellowii(SSPHE) has been previously proven active on intracellular amastigotes (in vitro test) and now was tested on hamsters infected with Leishmania (Leishmania) amazonensis (in vivo test). SSPHE suppressed a 100% of the parasite load in the infection site and draining lymph nodes at an intralesional dose of 50 mg/kg/day × 5, which was similar to the results observed in hamsters treated with N-methylglucamine antimonate (Sb) (28 mg/Kg/day × 5). When orally administered, SSPHE (50 mg/kg/day × 20) suppressed 99.2% of the parasite load in infected footpads, while Sb suppressed 98.5%. SSPHE also enhanced the release of nitric oxide through the intralesional route in comparison to Sb. The chemical fingerprint of SSPHE by high-performance liquid chromatography with diode-array detection and tandem mass spectrometry showed the presence of biflavonoids and high molecular weight phenylpropanoid glycosides. These compounds may have a synergistic action in vivo. Histopathological study revealed that the intralesional treatment with SSPHE induced an intense inflammatory infiltrate, composed mainly of mononuclear cells. The present findings reinforce the potential of this natural product as a source of future drug candidates for American cutaneous leishmaniasis.

In vitro activity of the hydroethanolic extract and biflavonoids isolated from Selaginella sellowii on Leishmania (Leishmania) amazonensis

This study is the first phytochemical investigation of Selaginella sellowii and demonstrates the antileishmanial activity of the hydroethanolic extract from this plant (SSHE), as well as of the biflavonoids amentoflavone and robustaflavone, isolated from this species. The effects of these substances were evaluated on intracellular amastigotes of Leishmania (Leishmania) amazonensis, an aetiological agent of American cutaneous leishmaniasis. SSHE was highly active against intracellular amastigotes [the half maximum inhibitory concentration (IC50) = 20.2 µg/mL]. Fractionation of the extract led to the isolation of the two bioflavonoids with the highest activity: amentoflavone, which was about 200 times more active (IC50 = 0.1 μg/mL) and less cytotoxic than SSHE (IC50 = 2.2 and 3 μg/mL, respectively on NIH/3T3 and J774.A1 cells), with a high selectivity index (SI) (22 and 30), robustaflavone, which was also active against L. amazonensis (IC50 = 2.8 µg/mL), but more cytotoxic, with IC50 = 25.5 µg/mL (SI = 9.1) on NIH/3T3 cells and IC50 = 3.1 µg/mL (SI = 1.1) on J774.A1 cells. The production of nitric oxide (NO) was lower in cells treated with amentoflavone (suggesting that NO does not contribute to the leishmanicidal mechanism in this case), while NO release was higher after treatment with robustaflavone. S. sellowii may be a potential source of biflavonoids that could provide promising compounds for the treatment of cutaneous leishmaniasis.

Rational use of medicines: prescribing indicators at different levels of health care

This multicenter study aimed to investigate prescribing patterns of drugs at different levels of health care delivery in university-affiliated outpatient clinics located in eight cities in the South and Midwest of Brazil. All prescriptions collected were analyzed for various items, including WHO prescribing indicators. A total of 2,411 prescriptions were analyzed, and 469 drugs were identified. The number of drugs prescribed per encounter, the frequency of polypharmacy, and the percentage of encounters with at least one injection or antibiotic prescribed were higher in centers providing primary health care services, compared to those where this type of care is not provided. Most drugs (86.1%) were prescribed by generic name. In centers with primary health care services, drug availability was higher, drugs included in the National and Municipal Lists of Essential Medicines were more frequently prescribed, and patients were given more instructions. However, warnings and non-pharmacological measures were less frequently recommended. This study reveals trends in drug prescribing at different levels of health care delivery in university-affiliated outpatient clinics and indicates possible areas for improvement in prescribing practices.

Este estudo multicêntrico teve como objetivo investigar o padrão de prescrição de medicamentos para pacientes ambulatoriais atendidos em serviços de saúde vinculados a universidades com diferentes níveis de atenção, em oito cidades do sul e centro-oeste do Brasil. As prescrições coletadas foram submetidas à análise de diversos itens, incluindo os indicadores de prescrição propostos pela OMS. No total, 2.411 prescrições foram analisadas e 469 medicamentos foram identificados. O número de medicamentos prescritos por consulta, a frequência de polifarmácia e a porcentagem de consultas com pelo menos um medicamento injetável ou um antimicrobiano prescrito foram maiores em centros de saúde que ofereciam cuidados de atenção básica, em comparação com aqueles que não dispunham desse tipo de atendimento. A maioria dos medicamentos foi prescrita pelo nome genérico (86,1%). Em unidades com cuidados de atenção básica, a acessibilidade foi maior, a prescrição de medicamentos presentes nas Listas Nacional e Municipais de Medicamentos Essenciais foi mais frequente e instruções foram fornecidas aos pacientes mais comumente. Entretanto, advertências e medidas não farmacológicas foram indicadas com menor frequência. Este estudo revela tendências de prescrição de medicamentos em serviços de saúde ligados a universidades, com diferentes níveis de atenção, e indica possíveis áreas de melhoria na prática da prescrição.

Adesão a listas de medicamentos essenciais em municípios de três estados brasileiros / Adherence to essential medicines in cities from three Brazilian states

Este estudo comparou as Relações Municipais de Medicamentos Essenciais (REMUME), analisou a adesão dos prescritores e a disponibilidade de medicamentos essenciais em unidades de saúde vinculadas ao Sistema Único de Saúde (SUS). Foram coletados dados sobre as REMUME e os medicamentos prescritos a 2.411 pacientes arrolados consecutivamente em oito serviços de atenção primária ou secundária de municípios da região centro-sul do país. A disponibilidade dos medicamentos foi verificada por meio da existência de estoque na farmácia. De um total de 5.222 medicamentos prescritos, 76,4 por cento constavam nas REMUME, 76,8 por cento na Relação Nacional de Medicamentos Essenciais (RENAME) e 63 por cento na lista da Organização Mundial da Saúde (OMS). Entre os medicamentos mais prescritos, um ou mais não pertenciam às respectivas REMUME. Do total de medicamentos prescritos, 76,1 por cento estavam disponíveis nos locais pesquisados; entre os medicamentos essenciais, a disponibilidade aumentou para 88,1 por cento. A prescrição em desacordo com as REMUME pode ser resultado da indisponibilidade dos medicamentos nos locais investigados ou da inadequação das listas frente ao nível de complexidade da atenção.

This study compared the Municipal Essential Medicines Lists (REMUME) and examined adherence by prescribers and availability of essential medicines in the health units affiliated with the Unified National Health System (SUS). Data were collected on lists and medicines prescribed to 2,411 patients enrolled consecutively in primary or secondary care services in Brazilian municipalities. Of 5,222 prescribed medicines, 76.4 percent were present on the REMUME, 76.8 percent on the National List of Essential Medicines (RENAME), and 63 percent on the World Health Organization (WHO) list. Among the most frequently prescribed medications, one or more did not belong to the respective REMUME. Of all medicines prescribed, 76.1 percent were available in the inspected facilities; for essential medicines, the availability increased to 88.1 percent. Prescription in disagreement with the REMUME may result from the unavailability of medicines in the inspected facilities or the lists' inadequacy for the level of care.