RESUMEN
Corticosteroid-resistant asthma (CRA) is a severe form of disease and clinically important, since patients do not respond to mainstay corticosteroid therapies. Thus, new therapies are needed. However, a big limiting factor in the understanding of CRA is the existence of different immunological and inflammatory phenotypes, a fact that makes it difficult to reproduce experimentally. Photobiomodulation (PBM) emerges as an alternative therapy based on earlier studies. This study aims to evaluate the effect of PBM using infrared light-emitting diode (ILED) on the development of corticosteroid-resistant asthma. Therefore, groups of rats were sensitized and challenged with ovalbumin plus Freund's adjuvant for the induction of CRA, and treated or not with ILED directly in the respiratory tract on the skin (wavelength 810 nm; power 100 mW; density energy 5 J/cm; total energy 15 J; time 150 s). Our experimental model was capable to induce neutrophilic asthma. Besides that, the corticosteroid treatment did not reverse the lung cell migration as well as the levels of leukotriene B4, and interleukins 17 and 6. The treatment with ILED reduced the lung cell migration; myeloperoxidase activity; mast cell degranulation; and the levels of leukotriene B4, thromboxane B2, prostaglandin E2, tumoral necrosis factor alpha, and interleukins 17 and 6. Still, ILED increased the level of interleukin 10. In conclusion, we showed promisor effects of ILED when irradiated directly in the respiratory tract as adjuvant treatment of corticosteroid-resistant asthma.
Asunto(s)
Asma , Terapia por Luz de Baja Intensidad , Corticoesteroides , Animales , Asma/tratamiento farmacológico , Asma/radioterapia , Humanos , Pulmón , Mastocitos , Ratas , PielRESUMEN
Two platforms based on reduced graphene oxide (rGO) functionalized with Pluronic® P123 (rGO-P123) and polyethyleneimine - PEI (rGO-PEI) polymers and loaded with amphotericin B (AmB) were fabricated and tested against Leishmania amazonensis, which can cause cutaneous and diffuse cutaneous leishmaniasis. The materials rGO-P123 and rGO-PEI were efficiently loaded with AmB - a polyene antibiotic - which resulted in rGO-P123-AmB (0.078 mg per mg of material) and rGO-PEI-AmB (0.086 mg per mg of material). Under near-infrared (NIR) light irradiation, the amount of AmB released from rGO-PEI-AmB at pH 5.0 and 7.4 doubled in comparison to AmB released in the absence of NIR light under identical conditions. It was accompanied by a photothermal effect. Otherwise, rGO-P123-AmB did not show a significant change in AmB released in the presence and absence of NIR light. Cytotoxicity studies in mammalian host macrophages revealed that rGO-PEI and rGO-PEI-AmB were nontoxic to the host cells, whereas rGO-123 and rGO-P123-AmB were very toxic, particularly the latter. Therefore, only rGO-PEI and rGO-PEI-AmB were tested against L. amazonensis promastigotes in the presence and absence of NIR light. In vitro antiproliferative effects revealed that rGO-PEI-AmB showed a more pronounced activity against the parasite than rGO-PEI, which was improved under NIR light irradiation. Scanning-transmission electron microscopy of L. amazonensis promastigotes after incubation with rGO-PEI or rGO-PEI-AmB suggested autophagic and necrotic cell death. Thus, the facile synthesis, high AmB loading capacity and good photothermal effect make the rGO-PEI-AmB platform a promising candidate for the topical treatment of cutaneous leishmaniasis.
Asunto(s)
Grafito , Leishmania , Anfotericina B/farmacología , Animales , Óxidos , Terapia Fototérmica , PolímerosRESUMEN
OBJECTIVE: To evaluate the accuracy of the near-infrared light transillumination (NILT) for the detection of interproximal dental caries in permanent dentition when compared to bitewing X-ray (BW). DATA: In vivo studies that detected interproximal primary caries in permanent teeth by using NILT and BW were selected. QUADAS-2 was used to assess the risk of bias. Pooled sensitivity and specificity forest plots were calculated, summary receiver operator characteristics (SROC) curves were constructed. The certainty of the evidence was rated using the GRADE system. SOURCES: Pubmed, Cochrane Library, Web of Science, Scopus, Lilacs/BBO and grey literature databases were surveyed. STUDY SELECTION: From 1594 retrieved articles, 13 studies were included. Six studies had a low risk of bias and a low level of concern regarding applicability. Four studies had an unclear risk of bias, while three presented a high risk of bias. The meta-analysis of six studies demonstrated that NILT presented good overall accuracy. Of 6110 teeth, 92.3 % (5639) were accurately classified (776 as true positive and 4863 as true negative). The pooled sensitivity was 0.97 (0.96 to 0.98; pâ¯=â¯0.0000; I2â¯=â¯93.2 %) with moderate certainty of evidence, and the pooled specificity was 0.91 (0.91 to 0.92; pâ¯=â¯0.0000; I2â¯=â¯98.3 %) with high certainty of evidence. Symmetric (0.9837) and asymmetric (0.9836) SROC showed a high discrimination and determination effect of NILT. CONCLUSION: The current literature, with moderate certainty and a middling quality of evidence, demonstrates that NILT presents a reasonably comparable accuracy to that of BW for detecting interproximal carious lesions in the permanent dentition. CLINICAL SIGNIFICANCE: Since NILT presented good overall accuracy for the detection of interproximal primary caries, it could be routinely used in dental check-ups, especially in high-risk caries populations and in patients where the use of radiation should be reduced, like pregnant women or children.
Asunto(s)
Caries Dental , Dentición Permanente , Transiluminación , Niño , Caries Dental/diagnóstico por imagen , Femenino , Humanos , Embarazo , Radiografía de Mordida Lateral , Diente PrimarioRESUMEN
Stimuli-responsive drug-delivery nanocarriers (DDNs) have been increasingly reported in the literature as an alternative for breast cancer therapy. Stimuli-responsive DDNs are developed with materials that present a drastic change in response to intrinsic/chemical stimuli (pH, redox and enzyme) and extrinsic/physical stimuli (ultrasound, Near-infrared (NIR) light, magnetic field and electric current). In addition, they can be developed using different strategies, such as functionalization with signaling molecules, leading to several advantages, such as (a) improved pharmaceutical properties of liposoluble drugs, (b) selectivity with the tumor tissue decreasing systemic toxic effects, (c) controlled release upon different stimuli, which are all fundamental to improving the therapeutic effectiveness of breast cancer treatment. Therefore, this review summarizes the use of stimuli-responsive DDNs in the treatment of breast cancer. We have divided the discussions into intrinsic and extrinsic stimuli and have separately detailed them regarding their definitions and applications. Finally, we aim to address the ability of these stimuli-responsive DDNs to control the drug release in vitro and the influence on breast cancer therapy, evaluated in vivo in breast cancer models.
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Neoplasias de la Mama , Nanopartículas , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Humanos , Oxidación-ReducciónRESUMEN
A method for the synthesis of a linear block copolymer (PNIPAM-b-PANI), containing a thermoresponsive block (poly(N-isopropylacrylamide), PNIPAM) and a Near Infrared (NIR) light-absorbing block (polyaniline, PANI), is reported. The synthetic approach involves a two-step successive polymerization reaction. First, the radical polymerization of NIPAM is done using 4-aminothiophenol as a chain transfer agent for the obtention of thermosensitive block terminated with an aniline (ANI) moiety. Second, the oxidative polymerization of ANI is initiated in ANI moiety of thermosensitive block to grow the second conductive PANI block. 1H nuclear magnetic resonance (NMR) and FT-IR spectroscopy shows the characteristics peaks of both polymeric blocks revealing the successful copolymerization process. Static Light Scattering (SLS) and UV-Visible combined measurements allowed the determination of the Mw for PNIPAM-b-PANI macromolecule: 5.5 × 105 g mol-1. The resulting copolymer is soluble in water (8.3 g L-1) and in non-aqueous solvents, such as ethanol, formic acid, acetonitrile, and others. Both polymer blocks chains show the properties of the polymer chains. The block copolymer shows a lower critical solution temperature (LCST) at the same temperature (32-34 °C) than PNIPAM, while the copolymer shows pH dependent UV-vis-NIR absorption similar to PANI. The PNIPAM block suffers a coil to globule transition upon NIR light irradiation (785 nm, 100 mW), as shown by turbidimetry and Atomic Force Microscopy (AFM), due to local heating (more than 9 °C in 12 min) induced by the NIR absorption at the PANI block. Furthermore, the electrical conductivity of PNIPAM-b-PANI thin films is demonstrated (resistivity of 5.3 × 10-4 Ω-1 cm-1), indicating that the PANI block is present in its conductive form.