RESUMEN

Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility. This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin.

Asunto(s)

Nifedipino , Piel , Administración Cutánea , Emulsiones/química , Nifedipino/metabolismo , Dispersión del Ángulo Pequeño , Piel/metabolismo , Tensoactivos/química , Agua/química , Difracción de Rayos X

RESUMEN

Neuropathic pain develops due to injury to the somatosensory system, affecting the patient's quality of life. In view of the ineffectiveness of the current pharmacotherapy, substances obtained from natural products (NPs) are a promising alternative. One NP that has been discussed in the literature is hecogenin acetate (HA), a steroidal sapogenin with anti-inflammatory and antinociceptive activity. However, HA has low water solubility, which affects its bioavailability. Thus, the objective of this study was to evaluate the anti-hyperalgesic activity of pure and complexed hecogenin acetate (HA/ßCD) in an animal model of chronic neuropathic and inflammatory pain. The inclusion complex was prepared at a molar ratio of 1:2 (HA:ßCD) by the lyophilization method. For the induction of chronic inflammatory pain, the mice received an intraplantar injection of CFA (complete Freund's adjuvant), and were evaluated for mechanical hyperalgesia and for the levels of myeloperoxidase (MPO) in the skin of the paw after eight days of treatment. HA and HA/ßCD reduced mechanical hyperalgesia in relation to the vehicle group until the fourth and fifth hours, respectively, in the acute evaluation, with a superior effect of the complexed form over the pure form in the second and third hour after treatment (p < 0.001). In the chronic evaluation, HA and HA/ßCD reduced hyperalgesia in relation to the vehicle in the eight days of treatment (p < 0.001). Both pure (p < 0.01) and complexed (p < 0.001) forms reduced myeloperoxidase activity in the skin of the animals' paw. Groups of animals subjected to the same pharmacological protocol were submitted to the partial sciatic nerve ligation (PSNL) model and evaluated for mechanical and thermal hyperalgesia, and cold allodynia. HA and HA/ßCD reduced mechanical hyperalgesia until the fourth and sixth hours, respectively, and both reduced hyperalgesia in relation to the vehicle in the chronic evaluation (p < 0.001). HA and HA/ßCD also reduced thermal hyperalgesia and cold allodynia (p < 0.05 and p < 0.001, respectively). The analysis of the spinal cord of these animals showed a decrease in the levels of the pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 and a reduction in the phosphorylation of NFκB and p38MAPK, as well as a decrease in microglioses compared to the vehicle group. In addition, HA/ßCD reduced the nociception induced by intraplantar injection of agonist TRPA1 (p < 0.01) and TRPM8 (p < 0.05). Treatment for eight days with HA and HA/ßCD showed no signs of gastric or liver damage. HA and HA/ßCD were, therefore, shown to have antinociceptive effects in chronic pain models. Based on our exploration of the mechanisms of the action of HA, these effects are likely to be related to inhibited leukocyte migration, interaction with the TRPA1 and TRPM8 receptors, reduced pro-inflammatory cytokines levels, microglial expression and suppression of NF-κB p65 and p38 MAPK pathway signaling. Therefore, HA/ßCD has great potential for use in the treatment of chronic pain.

Asunto(s)

Hiperalgesia/tratamiento farmacológico , FN-kappa B/antagonistas & inhibidores , Sapogeninas/administración & dosificación , Compuestos de Espiro/administración & dosificación , Esteroides/administración & dosificación , beta-Ciclodextrinas/administración & dosificación , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Acetilación , Animales , Combinación de Medicamentos , Hiperalgesia/metabolismo , Masculino , Ratones , FN-kappa B/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo

RESUMEN

OBJECTIVE: To provide an overview of sensors incorporated into wound dressings that can be used to assess and manage healing parameters. DATA SOURCES: Authors conducted an extensive literature search of the Science Direct, Scopus, MEDLINE-PubMed, and Web of Science databases. STUDY SELECTION: A total of 587 studies that evaluated dressings used to manage wound healing parameters were identified in the search, but only 16 met all of the review criteria and were included in the final analysis. DATA EXTRACTION: Chronic wounds were the most common type of injury among studies. Six articles involved a wireless transmission system. DATA SYNTHESIS: All studies evaluated the physical and chemical characteristics of the dressings. CONCLUSIONS: This review demonstrates the lack of studies examining wound dressing sensors. New studies are required to assess sensors that allow not only wound monitoring, but also the application of drugs in a single dressing, providing a better and more cost-effective treatment for wounds.

Asunto(s)

Vendajes , Monitoreo Fisiológico/instrumentación , Úlcera Cutánea/terapia , Dispositivos Electrónicos Vestibles , Cicatrización de Heridas/fisiología , Humanos

RESUMEN

Information on the risk factors for COVID-19 mortality in low- and middle-income countries is still scarce. In this retrospective cohort study, we analyzed the factors associated with COVID-19 mortality in hospitalized patients in a poor area of Brazil. Logistic regression was used to identify factors independently associated with mortality, including gender, age, and the presence of underlying medical conditions. A total of 1,207 patients were included in the analysis, and a 1.5-fold increase in COVID-19 mortality was found among patients aged > 65 years with hypertension and diabetes (odds ratio [OR]: 1.50, 95% CI: 1.02-2.19). Moreover, infectious disease (OR: 4.31, 95% CI: 1.39-13.39), kidney disease (OR: 2.59, 95% CI: 1.27-5.27), and heart disease (OR: 2.00, 95% CI: 1.31-3.04) were also predictive for COVID-19 in-hospital death. This large cohort provides important data on potential factors associated with COVID-19 mortality in Brazil.

Asunto(s)

COVID-19/epidemiología , COVID-19/mortalidad , Pacientes Internos , SARS-CoV-2 , Brasil/epidemiología , Estudios de Cohortes , Humanos , Pobreza , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

Diarrhea is a condition in which the individual has about three or more daily bowel movements, followed by changes in stool consistency. It is currently considered as one of the worst public health problems due to the number of cases and deaths involved and difficulty of treatment. Thus, the use of natural products is an alternative for new treatments. Among these possibilities is Farnesol (C15H26O), a sesquiterpene found in different herbal species that has known biological activities. The objective of this study was to evaluate the antidiarrheal activity of Farnesol (FOH). Initially, FOH activity was evaluated in models of diarrhea and enteropooling induced by castor oil and PGE2. To evaluate motility, the opioid and cholinergic pathways were studied. In addition, the effect of FOH was investigated in the secretion model in intestinal loops treated with cholera toxin. FOH was evaluated for the ability to absorb fluids in intestinal loops and interact with GM1 receptors using the ELISA method and molecular docking. The dose of 50 mg/kg of FOH showed the best results in all antidiarrheal activity tests with castor oil and PGE2, being considered as the standard dose, reducing motility by anticholinergic mechanisms. There was a reduction in fluid secretion when FOH interacted directly with GM1 receptors; cholera toxin and molecular docking showed strong interaction between farnesol and these targets. In view of the results presented, the antidiarrheal activity occurs through anticholinergic, anti-inflammatory and anti-secretory action, making farnesol a potential candidate for the development of a new drug to treat diarrheal diseases.

Asunto(s)

Antidiarreicos/farmacología , Antidiarreicos/uso terapéutico , Diarrea/tratamiento farmacológico , Diarrea/metabolismo , Farnesol/farmacología , Farnesol/uso terapéutico , Animales , Aceite de Ricino , Cloruros/metabolismo , Toxina del Cólera , Diarrea/inducido químicamente , Dinoprostona , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Secreciones Intestinales/metabolismo , Masculino , Ratones , Simulación del Acoplamiento Molecular , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Receptores de Superficie Celular/metabolismo

RESUMEN

Nerolidol is naturally occurring sesquiterpene has wide range of biological properties including anti-inflammatory activity. However, it has high volatility with low solubility in nature. The present study aimed to develop and characterized nano-encapsulated nerolidol and evaluated its activity on zymosan-induced arthritis model. Nano-capsules were produced by interfacial deposition of preformed polymer method and characterized by particle size, pH, polydispersity index (PDI), zeta potential, drug content and transmission electron microscopy (TEM). In vitro cytotoxicity of formulations was evaluated by alamar blue and MTT assays. In vivo neutrophils migration assay was performed on intra-articular zymosan-induced arthritis model in mice. Nano-encapsulated nerolidol suspensions presented adequate properties: mean diameter of particles 219.5 ±â€¯8.4 nm, pH: 6.84 ±â€¯0.5, PDI≤0.2, the zeta potential was -20.3 ±â€¯3.6 mV and drug content 71,2 ±â€¯1.3%. The formulations did not demonstrated cytotoxicity under the conditions assessed. Nerolidol 300 mg/kg inhibited neutrophils migration into joint cavity by 18.8% remains compared with control group, and nano-encapsulated nerolidol 3 mg/kg inhibited (26.7% remains) similar to free nerolidol 10 mg/kg (27.4% remains). Histological, quantification of pro-inflammatory and anti-inflammatory cytokines proves the same results. In conclusion the data suggests that nanoencapsulation of nerolidol improved its anti-inflammatory effect on arthritis in mice.

Asunto(s)

Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Portadores de Fármacos/química , Nanocápsulas/química , Sesquiterpenos/uso terapéutico , Animales , Articulación del Tobillo/efectos de los fármacos , Articulación del Tobillo/patología , Artritis Experimental/inducido químicamente , Artritis Reumatoide/inducido químicamente , Línea Celular Tumoral , Femenino , Ratones , Tamaño de la Partícula , Zimosan

RESUMEN

Eplingiella fruticosa (Lamiaceae), formally known as Hyptis fruticosa, is an important aromatic medicinal herb used in folk medicine in northeastern Brazil. We aimed to evaluate the anti-hyperalgesic effect of essential oil obtained from E. fruticosa (HypEO) complexed with ßCD (HypEO-ßCD) in a chronic widespread non-inflammatory muscle pain animal model (a mice fibromyalgia-like model, FM). The HypEO was extracted by hydro distillation and its chemical composition was determined by GC-MS/FID. Moreover, Fos protein expression in the spinal cord was assessed by immunofluorescence. (E)-caryophyllene, bicyclogermacrene, 1,8-cineole, α-pinene, ß-pinene and 21 other compounds were identified in the HypEO. The treatment with HypEO-ßCD produced a longer-lasting anti-hyperalgesic effect compared to HypEO, without alterations in motor coordination or myorelaxant effects. Moreover, HypEO and HypEO-ßCD produced a significant anti-hyperalgesic effect over 7 consecutive treatment days. Immunofluorescence assay demonstrated a decrease in Fos protein expression in the spinal cord (p < 0.001). We demonstrated that the anti-hyperalgesic effect produced by HypEO was improved after complexation with ß-CD and this seems to be related to the central pain-inhibitory pathway, suggesting the possible use of E. fruticosa for chronic pain management.

Asunto(s)

Analgésicos/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Lamiaceae/química , Mialgia/tratamiento farmacológico , Aceites Volátiles/uso terapéutico , beta-Ciclodextrinas/uso terapéutico , Analgésicos/aislamiento & purificación , Animales , Masculino , Ratones , Aceites Volátiles/aislamiento & purificación , Hojas de la Planta/química , Proteínas Proto-Oncogénicas c-fos/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Polyphenolics (flavonoid and phenolic) rich plants are the effective source for the treatment of acute and chronic degenerative diseases including inflammatory bowel disease. OBJECTIVE: This study was aimed to examine the effects of polyphenolics rich leaf acetone extract of P. subpeltata against the indomethacin induced ulcerative colitis in rats. MATERIALS AND METHODS: Two consecutive days administration of indomethacin produced chronic inflammation in GIT tissues of rats. Further, the plant extract 200 and 400 mg/kg treatment were continued until 11th day. Then hematological, enzymatic antioxidants, MPO and histological evaluations were analyzed. Moreover, the extracts were treated with RAW267.4 cells for the cytotoxicity, NO and TNF-α analysis. RESULTS: The obtained results revealed, that higher dose of the plant extract dropped neutrophil infiltration followed by inhibiting the MPO enzyme levels and controls the enzymatic antioxidants such as SOD, CAT, GSH and LPO. RAW cells study also proved that the plant extract effectively inhibits NO and TNF-α production. CONCLUSIONS: Thus, these results suggest that P. subpeltata extract may have therapeutic potential for the treatment of IBD although further clinical research is still warranted.

Asunto(s)

Antiinflamatorios/farmacología , Colitis Ulcerosa/prevención & control , Colon/efectos de los fármacos , Flavonoides/farmacología , Fármacos Gastrointestinales/farmacología , Passiflora , Extractos Vegetales/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colon/metabolismo , Colon/patología , Modelos Animales de Enfermedad , Flavonoides/aislamiento & purificación , Fármacos Gastrointestinales/aislamiento & purificación , Indometacina , Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Infiltración Neutrófila/efectos de los fármacos , Óxido Nítrico/metabolismo , Passiflora/química , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7 , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Chronic pain is a continuous or recurring pain which exceeds the normal course of recovery to an injury or disease. According to the origin of the chronic pain, it can be classified as inflammatory or neuropathic. This study aimed to evaluate the antinociceptive and anti-inflammatory effect of (-)-α-bisabolol (BIS) alone and complexed with ß-cyclodextrin (ßCD) in preclinical models of chronic pain. Chronic pain was induced by Freund's Complete Adjuvant (FCA) or partial lesion of the sciatic nerve (PLSN). Swiss mice were treated with BIS, BIS-ßCD (50 mg/kg, p.o) or vehicle (control) and mechanical hyperalgesia, thermal hyperalgesia, muscle strength and motor coordination were evaluated. In addition, levels of TNF-α and IL-10 and expression of the ionized calcium-binding adapter protein (IBA-1) were assessed in the spinal cord of the mice. The complexation efficiency of BIS in ßCD was evaluated by High-Performance Liquid Chromatography. BIS and BIS-ßCD reduced (p < 0.001) mechanical and thermal hyperalgesia. No alterations were found in force and motor coordination. In addition, BIS and BIS-ßCD inhibited (p < 0.05) TNF-α production in the spinal cord and stimulated (p < 0.05) the release of IL-10 in the spinal cord in PLSN-mice. Further, BIS and BIS-ßCD reduced IBA-1 immunostaining. Therefore, BIS and BIS-ßCD attenuated hyperalgesia, deregulated cytokine release and inhibited IBA-1 expression in the spinal cord in the PLSN model. Moreover, our results show that the complexation of BIS in ßCD reduced the therapeutic dose of BIS. We conclude that BIS is a promising molecule for the treatment of chronic pain.

Asunto(s)

Citocinas/metabolismo , Gliosis/tratamiento farmacológico , Hiperalgesia/inducido químicamente , Inflamación/tratamiento farmacológico , Sesquiterpenos Monocíclicos/uso terapéutico , Neuralgia/tratamiento farmacológico , beta-Ciclodextrinas/uso terapéutico , Animales , Proteínas de Unión al Calcio/biosíntesis , Adyuvante de Freund , Calor , Hiperalgesia/metabolismo , Inflamación/metabolismo , Masculino , Ratones , Proteínas de Microfilamentos/biosíntesis , Fuerza Muscular/efectos de los fármacos , Neuralgia/inducido químicamente , Neuralgia/metabolismo , Desempeño Psicomotor/efectos de los fármacos , Neuropatía Ciática/tratamiento farmacológico , Médula Espinal/metabolismo , Estereoisomerismo

RESUMEN

Leprosy is a granulomatous disease, infectious and transmissible, which affects the skin and peripheral nerves, having Mycobacterium leprae as causative agent. The manifestation of this disease causes cutaneous lesions, peripheral neuropathies and, in more extreme cases, may generate deformities and disabilities in affected individuals. Patents were identified using the descriptor 'leprosy' and code A61K of the international patent classification, which indicates only products that meet human needs. The analysis was made using the WIPO, ESPACENET and USPTO databases, until the month of September 2016. Through this review, we found a variety of in vitro, pre-clinical and clinical studies relating to the treatment of leprosy with different types of compounds and forms of administration. New treatment proposals should include pain reduction capabilities, prevention or limitation of the appearance of cutaneous lesions, as well as prevention of the progression of the disease to more severe stages that may lead to loss of function or potentiate the individual's immune response to the M. leprae bacillus in order to prevent bacterial spread. We concluded that any patents developed with natural products were not found in the treatment of leprosy. All the deposited products were synthetic origin, mostly tested in humans and of varied forms of administration.

Asunto(s)

Desarrollo de Medicamentos , Lepra/tratamiento farmacológico , Patentes como Asunto , Antibacterianos/uso terapéutico , Anticuerpos/uso terapéutico , Humanos , Péptidos/uso terapéutico , Drogas Sintéticas/uso terapéutico