Linseed, Baru, and Coconut Oils: NMR-Based Metabolomics, Leukocyte Infiltration Potential In Vivo, and Their Oil Characterization. Are There Still Controversies?

Different fatty acid proportions produce potential inflammatory and metabolic changes in organisms. However, the evidence for how each fatty acid mediates the metabolic pathway, and its lipid stability remains controversial. To resolve this controversy, the present study investigated the metabolic effects of cold-pressed linseed (LG), coconut (CG), and baru (BG) oils in comparison to those of soybean oil (SG) in mice, in terms of their oil characterization and stability. The quality analysis showed less oxidative behavior among PUFA-rich oils (SO, BO, and LO, with induction periods lower than 2 h compared to 39.8 h for CG), besides the high contents of tocopherols and carotenoids in SG and LG. In the experimental study, CG presented higher triglyceride (257.93 ± 72.30) and VLDL-cholesterol levels (51.59 ± 14.46, p < 0.05), while LG reduced LDL levels (59.29 ± 7.56, p < 0.05) when compared to SG (183.14 ± 22.06, 36.63 ± 4.41 and 131.63 ± 29.0, respectively). For visceral fats, the adiposity index was lower for BG (7.32 ± 3.13) and CG (9.58 ± 1.02, p < 0.05) in relation to SG (12.53 ± 2.80), and for leukocyte recruitment, CG presented lower polymorphonuclear (PMN) (p < 0.0001) and mononuclear (MN) (p < 0.05) cell infiltration, demonstrating anti-inflammatory potential. In NMR-based metabolomics, although CG presented higher values for the glucose, lactate, and LDL/VLDL ratio, this group also evidenced high levels of choline, a lipotropic metabolite. Our study emphasized the controversies of saturated fatty acids, which impair serum lipids, while alfa-linolenic acid presented cardioprotective effects. However, coconut oil also has a positive immunomodulatory pathway and was found to reduce visceral bodyfat in mice. Therefore, for future applications, we suggest a combination of lauric and al-fa-linolenic acid sources, which are present in coconut and linseed oil, respectively. This combination could be less obesogenic and inflammatory and exert cardioprotective action.

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.

Anti-inflammatory, antiproliferative and cytoprotective potential of the Attalea phalerata Mart. ex Spreng. pulp oil.

The anti-inflammatory, antiproliferative and cytoprotective activity of the Attalea phalerata Mart. ex Spreng pulp oil was evaluated by in vitro and in vivo methods. As for the chemical profile, the antioxidant activity was performed by spectrophotometry, and the profile of carotenoids and amino acids by chromatography. Our data demonstrated that A. phalerata oil has high carotenoid content, antioxidant activity and the presence of 5 essential amino acids. In the in vitro models of inflammation, the oil demonstrated the capacity to inhibit COX1 and COX2 enzymes, the production of nitric oxide and also induces macrophages to spreading. In the in vivo models of inflammation, the oil inhibited edema and leukocyte migration in the Wistar rats. In the in vitro model of antiproliferative and cytoprotective activity, the oil was shown inactive against the kidney carcinoma and prostate carcinoma lineage cells and with cytoprotective capacity in murine fibroblast cells, inhibiting the cytotoxic action of doxorubicin. Therefore, it is concluded that A. phalerata pulp oil has anti-inflammatory effects with nutraceutical properties potential due to the rich composition. Moreover, the oil also has cytoprotective activity probably because of its ability to inhibit the action of free radicals.

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

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.

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 Vitro antileishmania activity of sesquiterpene-rich essential oils from Nectandra species.

CONTEXT: New antileishmanias are needed because of toxicity, high cost and resistance problems associated with available drugs. Nectandra (Lauraceae) produces several classes of compounds but its essential oil has not previously been reported to have antileishmania activity. OBJECTIVE: We evaluated the cytotoxicity and antileishmania activity of essential oils from Nectandra amazonum Nees, N. gardneri Meisn., N. hihua (Ruiz & Pav.) Rohwer and N. megapotamica (Spreng.) Mez. MATERIALS AND METHODS: Nectandra oils were extracted from stem bark/leaves by hydrodistillation and compounds were identified by GC-MS. Oils were tested against Leishmania infantum and L. amazonensis intracellular amastigotes and nitric oxide production was evaluated. Cytotoxicity was achieved on NIH/3T3 and J774.A1 cells for the selectivity index (SI). RESULTS AND DISCUSSION: Nectandra gardneri was active against L. infantum and L. amazonensis (IC50 = 2.7 ± 1.3/2.1 ± 1.06 µg/mL) and contained 85.4% sesquiterpenes, of which 58.2% was intermediol. Besides low cytotoxicity (SI >11.3), N. gardneri induced a significant increase in NO production by L. infantum-infected macrophages. Nectandra hihua had the best activity on L. infantum amastigotes (IC50 = 0.2 ± 1.1 µg/mL). This oil was 89.0% sesquiterpenes, with 28.1% bicyclogermacrene. The two specimens of N. megapotamica had different activities on amastigotes. The one richer in sesquiterpenes (49.9%) was active against both species (IC50 = 12.5 ± 1.4/21.3 ± 1.2) and had phenylpropanoid E-asarone as the main compound (42.4%). Nectandra amazonum showed moderate activity on both the species (IC50 = 31.9 ± 2.0/22.1 ± 1.3 µg/mL) and low selectivity (0.9 < SI >2.6), probably due to the major presence of ß-caryophyllene (28.5%). CONCLUSIONS: Our data identify compounds that can now be isolated and used for the development of new antileishmanias.

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 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.

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.

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

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% were present on the REMUME, 76.8% on the National List of Essential Medicines (RENAME), and 63% 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% were available in the inspected facilities; for essential medicines, the availability increased to 88.1%. 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.

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.

Avaliação das prescrições médicas provenientes das unidades básicas de saúde de Campo Grande, Mato Grosso do Sul, Brasil / Evaluation of medical prescriptions from health basic units of Campo Grande, Mato Grosso do Sul, Brazil

Introdução: A prescrição medicamentosa é um recurso terapêutico utilizado nos cuidados à saúde. Na prática, observa-se que a prescrição inadequada e o modo como os medicamentos são utilizados geram consequências para a saúde pública e para a utilização dos recursos disponíveis. Objetivo: Avaliar as prescrições médicas provenientes de Unidades Básicas de Saúde do município de Campo Grande ­ MS, segundo os indicadores de prescrição propostos pela Organização Mundial de Saúde (OMS). Materiais e métodos: A pesquisa realizada foi do tipo transversal, quantitativa e descritiva. Foram analisadas as prescrições provenientes da Clínica Médica, obtidas nas farmácias internas das Unidades Básicas de Saúde, durante os meses de abril a junho de 2008. Para tanto, os indicadores avaliados foram: número médio de medicamentos por prescrição; porcentagem de medicamentos prescritos pelo nome genérico; porcentagem de prescrições que contém um antibiótico; porcentagem de prescrições em que se prescreve um medicamento injetável; porcentagem de medicamentos prescritos que constam na RENAME; na REMUME e na 14ª Lista Modelo de Medicamentos Essenciais da OMS. Resultados: Foram analisadas 367 prescrições (n=1044 medicamentos). O número médio de medicamentos por prescrição foi 2,8. 81,5% foram prescritos pelo nome genérico. Do total de prescrições, 12,7% continham antibióticos e 5,7% injetáveis. 94,2% dos medicamentos constavam na lista de medicamentos padronizados pelo município (REMUME), 84% na RENAME e 64,6% na 14ª lista Modelo de Medicamentos Essenciais (OMS). Conclusão: Os dados indicaram a adequação das prescrições na promoção do uso racional de medicamentos.

Introduction: Medical prescriptions are therapeutic resources used in health care. In the practice, it is observed that inadequate prescription and the manner as drugs are used cause consequences to public health and to the use of available resources. Objective: Evaluate medical prescription of Basic Health Units of the city of Campo Grande ­ MS, according to prescription indicators proposed by World Health Organization (WHO). Methods: This was a transversal, quantitative and descriptive study that evaluated prescriptions of Medical Clinic received by the pharmacy of Basic Health Units during april to june of 2008. The analysed indicators were averange number of drugs per prescription; percentage of drugs prescribed for the generic name; prescription's percentage that contains at least one antibiotic; prescription's percentage with an injectable drug prescribed; percentage of prescribed drugs that are included in the Municipal. National and 14ª Essential Medicine Model List of WHO. Results: 367 medical prescriptions were analyzed (n=1044 medicines) and the averange number of drugs perprescription was 2,8. Medication by its generic name was in 81,5% of prescriptions. Antibiotics and injectable drugs were prescribed in 12,81% and 5,72% situations, respectively. 94,2% of drugs were included in Municipal, 84% in National and 64,6% in 14ª Essential Medicine Model List of WHO. Conclusion: Data indicated that medical prescriptions was adequate to the promotion of rational use of medicines.