6,577 research outputs found
Toxicological evaluation of lactose and chitosan delivered by inhalation
These days, inhalation constitutes a promising administration route for many drugs. However, this route exhibits unique limitations, and formulations aimed at pulmonary delivery should include as few as possible additives in order to maintain lung functionality. The purpose of this work was to investigate the safety of lactose and chitosan to the pulmonary tissue when delivered by inhalation. The study was carried out with 18 Wistar rats divided in three groups receiving distilled water, lactose or chitosan. A solution of each excipient was administered by inhalation at a dose of 20 mg. The lungs were excised and processed to determine several biochemical parameters used as toxicity biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and oxidized glutathione ( GSSG), myeloperoxidase ( MPO), cooper/zinc and manganese superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were determined. Results of myeloperoxidase activity and glutathione disulfide lung concentrations showed a relevant decrease for chitosan group compared to control: 4.67 +/- 2.27 versus 15.10 +/- 7.27 ( P = 0.011) for MPO and 0.89 +/- 0.68 versus 2.02 +/- 0.22 ( P = 0.014) for GSSG. The other parameters did not vary significantly among groups. Lactose and chitosan administered by inhalation failed to show toxic effects to the pulmonary tissue. A protective effect against oxidative stress might even be attributed to chitosan, since some biomarkers had values significantly lower than those observed in the control group when this product was inhaled. Nevertheless, caution must be taken regarding chemical composition and technological processes applied to incorporate these products during drug formulation, in particular for dry powder inhalators
Control of mucocutaneous leishmaniasis, a neglected disease: results of a control programme in Satipo Province, Peru.
Mucocutaneous leishmaniasis (MCL) is an important health problem in many rural areas of Latin America, but there are few data on the results of programmatic approaches to control the disease. We report the results of a control programme in San Martin de Pangoa District, which reports one of the highest prevalences of MCL in Peru. For 2 years (2001--2002), the technicians at the health post were trained in patient case management, received medical support and were supplied with antimonials. An evaluation after 2 years showed the following main achievements: better diagnosis of patients, who were confirmed by microscopy in 34% (82/240) of the cases in 2001 and 60% of the cases (153/254) in 2002; improved follow-up during treatment: 237 of 263 (90%) patients who initiated an antimonial therapy ended the full treatment course; improved follow-up after treatment: 143 of 237 (60%) patients who ended their full treatment were correctly monitored during the required period of 6 (cutaneous cases) or 12 (mucosal cases) months after the end of treatment. These achievements were largely due to the human and logistical resources made available, the constant availability of medications and the close collaboration between the Ministry of Health, a national research institute and an international non-governmental organization. At the end of this period, the health authorities decided to register a generic brand of sodium stibogluconate, which is now in use. This should allow the treatment of a significant number of additional patients, while saving money to invest in other facets of the case management
Assessment of conjunctival, episcleral and scleral thickness in healthy individuals using anterior segment optical coherence tomography
Purpose: To determine the thickness of the conjunctiva, episclera and sclera in healthy individuals using anterior segment optical coherence tomography (AS-OCT).Methods: We prospectively included 107 healthy individuals of different age groups (18-39 years, 40-54 years, 55-69 years and >= 70 years). For each eye, AS-OCT scans of four quadrants (temporal, nasal, superior and inferior) were acquired. The thickness of the conjunctiva, episclera and sclera was measured for each scan. In addition, the axial length of both eyes was measured, and general characteristics, including smoking, allergies and contact lens use, were collected.Results: The mean conjunctival thickness was significantly different between the nasal and superior quadrants (87 +/- 30 mu m vs. 77 +/- 16 mu m; p < 0.001), as well as the superior and inferior quadrants (77 +/- 16 mu m vs. 86 +/- 19 mu m; p = 0.001). The mean episcleral thickness was larger in the superior (174 +/- 54 mu m) and inferior (141 +/- 43 mu m) quadrants, compared to the nasal (83 +/- 38 mu m) and temporal quadrants (90 +/- 44 mu m). The mean scleral thickness of the inferior quadrant was the largest (596 +/- 64 mu m), followed by the nasal (567 +/- 76 mu m), temporal (516 +/- 67 mu m) and superior (467 +/- 52 mu m) quadrants (all p < 0.001). The averaged scleral thickness increased 0.96 mu m per age year (0.41-1.47 mu m, p < 0.001).Conclusions: This study provides an assessment of the thickness of scleral and adjacent superficial layers in healthy individuals determined on AS-OCT, which could enable future research into the use of AS-OCT in diseases affecting the anterior eye wall
Assessment of conjunctival, episcleral and scleral thickness in healthy individuals using anterior segment optical coherence tomography
Purpose: To determine the thickness of the conjunctiva, episclera and sclera in healthy individuals using anterior segment optical coherence tomography (AS-OCT).Methods: We prospectively included 107 healthy individuals of different age groups (18-39 years, 40-54 years, 55-69 years and >= 70 years). For each eye, AS-OCT scans of four quadrants (temporal, nasal, superior and inferior) were acquired. The thickness of the conjunctiva, episclera and sclera was measured for each scan. In addition, the axial length of both eyes was measured, and general characteristics, including smoking, allergies and contact lens use, were collected.Results: The mean conjunctival thickness was significantly different between the nasal and superior quadrants (87 +/- 30 mu m vs. 77 +/- 16 mu m; p < 0.001), as well as the superior and inferior quadrants (77 +/- 16 mu m vs. 86 +/- 19 mu m; p = 0.001). The mean episcleral thickness was larger in the superior (174 +/- 54 mu m) and inferior (141 +/- 43 mu m) quadrants, compared to the nasal (83 +/- 38 mu m) and temporal quadrants (90 +/- 44 mu m). The mean scleral thickness of the inferior quadrant was the largest (596 +/- 64 mu m), followed by the nasal (567 +/- 76 mu m), temporal (516 +/- 67 mu m) and superior (467 +/- 52 mu m) quadrants (all p < 0.001). The averaged scleral thickness increased 0.96 mu m per age year (0.41-1.47 mu m, p < 0.001).Conclusions: This study provides an assessment of the thickness of scleral and adjacent superficial layers in healthy individuals determined on AS-OCT, which could enable future research into the use of AS-OCT in diseases affecting the anterior eye wall
Fiber-optic lossy mode resonance sensors
In the last 4 years, experimental evidences about the potential use of optical sensors based on Lossy Mode Resonances (LMR) have been presented in the literature. These LMR sensors have some similarities with Surface Plasmon Resonance (SPR) sensors, the gold standard in label-free, real-time biomolecular interaction analysis. In these new LMR sensors, if the non-metallic nanocladding of an optical waveguide fulfills the conditions explained in this work, coupling of light to the cladding modes happens at certain resonance wavelengths, which enables the use of LMR devices as refractometers and opens the door to diverse applications such as in biology and proteomics research. These highly sensitive refractometers have already shown sensitivities higher than 20,000 nm/RIU or 5x10-7 RIU and, given the youth of this field, it is expected to achieve even better values
Physiological and transcriptomic characterization of a fliA mutant of Pseudomonas putida KT2440
Pseudomonas putida KT2440 encodes 23 alternative sigma factors. The fliA gene, which encodes σ28, is in a cluster with other genes involved in flagella biosynthesis and chemotaxis. Reverse transcriptase-PCR revealed that this cluster is comprised of four independent transcriptional units: flhAF, fleNfliA, cheYZA and cheBmotAB. We generated a nonpolar fliA mutant by homologous recombination and tested its motility, adhesion to biotic and abiotic surfaces, and responses to various stress conditions. The mutant strain was nonmotile and exhibited decreased capacity to bind to corn seeds, although its ability to colonize the rhizosphere of plants was unaffected. The mutant was also affected in binding to abiotic surfaces and its ability to form biofilms decreased by almost threefold. In the fliA mutant background expression of 25 genes was affected: two genes were upregulated and 23 genes were downregulated. In addition to a number of motility and chemotaxis genes, the fliA gene product is also necessary for the expression of some genes potentially involved in amino acid utilization or stress responses; however, we were unable to assign specific phenotypes linked to these genes since the fliA mutant used the same range of amino acids as the parental strain, and was as tolerant as the wild type to stress imposed by heat, antibiotics, NaCl, sodium dodecyl sulfate, H2O2 and benzoate. Based on the sequence alignment of promoters recognized by FliA and genome in silico analysis, we propose that P. putidaσ28 recognizes a TCAAG-t-N12-GCCGATA consensus sequence located between −34 and −8 and that this sequence is preferentially associated with an AT-rich upstream region
Optical sensors based on lossy-mode resonances
Lossy-mode resonance (LMR)–based optical sensing technology has emerged in the last two decades as a nanotechnological platform with very interesting and promising properties. LMR complements the metallic materials typically used in surface plasmon resonance (SPR)–based sensors, with metallic oxides and polymers. In addition, it enables one to tune the position of the resonance in the optical spectrum, to excite the resonance with both transverse electric (TE) and transverse magnetic (TM) polarized light, and to generate multiple resonances. The domains of application are numerous: as sensors for detection of refractive indices voltage, pH, humidity, chemical species, and antigens, as well as biosensors. This review will discuss the bases of this relatively new technology and will show the main contributions that have permitted the optimization of its performance to the point that the question arises as to whether LMR–based optical sensors could become the sensing platform of the near future
La vid silvestre en México. Actualidades y potencial
En ocho capítulos se aborda el estado del arte de la vid silvestre en MéxicoEl estudio de las especies vegetales nativas de México representa un reto que cada día más investigadores mexicanos asumen. Durante muchos años, el apoyo a la investigación pública ha sido mínimo; desde el punto de vista agronómico es insuficiente para avanzar a la velocidad que requiere nuestro país para afrontar problemas de producción y distribución de alimentos. Por esa razón, entre otras, me es grato presentar esta obra que compila parte de los trabajos de la Red de Vid Silvestre patrocinada por el Sistema Nacional de Recursos Fitogenéticos (sinarefi) dependiente de la sagarpa; trabajos apuntalados por investigadores que sin pertenecer a la red han colaborado en el estudio de las plantas del género Vitis. En este libro se muestra el potencial del país para aprovechar el recurso vid, empleado desde antes de la conquista española por nativos mexicanos que conocían sus bondades. Es necesario continuar el avance en el conocimiento de este recurso, por ello el presente libro pretende invitar a toda persona interesada en contribuir con el rescate y conservación de las vides mexicanas. Los autores y editores, así como las instituciones en donde laboramos y aquellas que patrocinan estas investigaciones, esperamos se cumpla este objetivo y que el lector, alumno, profesor, investigador, público en general, disfrute esta lectura y, sobre todo, se interese en el recurso VitisSEP, SINAREFI, UAEME
Beneficial effect of ursodeoxycholic acid in patients with acyl-CoA oxidase 2 (ACOX2) deficiency-associated hypertransaminasemia
Background and aims: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3?,7?,12?-trihydroxy-5?-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration.
Methods and results: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by high-performance liquid chromatography-mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH-7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1-S/XBP1-U ratio), and BAX? expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt-based cell viability test). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH.
Conclusions: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.Funding information: This study was supported by the following grants: CIBERehd (EHD15PI05/2016); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819 and PI20/00189), co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”; “Junta de Castilla y León” (SA074P20); Fundació Marato TV3 (201916–31); AECC Scientific Foundation (2017/2020), Spain; and “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from grants PID2019-111669RBI-100, PID2020-115055RB-I00 from Plan Nacional de I+D funded by the “Agencia Estatal de Investigación” (AEI) and the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH, as well as support from AGAUR of the “Generalitat de Catalunya” SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network. Marta Alonso-Peña was the recipient of a predoctoral fellowship from “Ministerio de Educación, Cultura y Deporte” (BOE-A-2015-9456; FPU-14/00214) and a Mobility Grant for Short Stays from “Ministerio de Ciencia, Innovación y Universidades” (EST17/00186). Ricardo Espinosa-Escudero is the recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). The funding sources were not involved in the research design or preparation of the article
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