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1.
Proc Natl Acad Sci U S A ; 121(32): e2310917121, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39078681

RESUMEN

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has developed substantial antigenic variability. As the majority of the population now has pre-existing immunity due to infection or vaccination, the use of experimentally generated animal immune sera can be valuable for measuring antigenic differences between virus variants. Here, we immunized Syrian hamsters by two successive infections with one of nine SARS-CoV-2 variants. Their sera were titrated against 16 SARS-CoV-2 variants, and the resulting titers were visualized using antigenic cartography. The antigenic map shows a condensed cluster containing all pre-Omicron variants (D614G, Alpha, Delta, Beta, Mu, and an engineered B.1+E484K variant) and considerably more diversity among a selected panel of Omicron subvariants (BA.1, BA.2, BA.4/BA.5, the BA.5 descendants BF.7 and BQ.1.18, the BA.2.75 descendant BN.1.3.1, the BA.2-derived recombinants XBB.2 and EG.5.1, and the BA.2.86 descendant JN.1). Some Omicron subvariants were as antigenically distinct from each other as the wildtype is from the Omicron BA.1 variant. Compared to titers measured in human sera, titers in hamster sera are of higher magnitude, show less fold change, and result in a more compact antigenic map topology. The results highlight the potential of sera from hamsters for the continued antigenic characterization of SARS-CoV-2.


Asunto(s)
Variación Antigénica , COVID-19 , Mesocricetus , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , SARS-CoV-2/inmunología , SARS-CoV-2/genética , COVID-19/inmunología , COVID-19/virología , Cricetinae , Variación Antigénica/inmunología , Variación Antigénica/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Antígenos Virales/inmunología , Antígenos Virales/genética , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Humanos , Sueros Inmunes/inmunología
2.
Mol Ther ; 31(8): 2391-2407, 2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37263272

RESUMEN

Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmission of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV is a promising strategy to increase vaccine safety and prevent vaccine transmission without compromising vaccine efficacy.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Animales , Cricetinae , Humanos , COVID-19/prevención & control , Pandemias , SARS-CoV-2 , Vacunas Atenuadas , Anticuerpos Antivirales , Anticuerpos Neutralizantes
3.
Nucleic Acids Res ; 50(12): 6769-6785, 2022 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-35713540

RESUMEN

Antiviral innate immunity represents the first defense against invading viruses and is key to control viral infections, including SARS-CoV-2. Body temperature is an omnipresent variable but was neglected when addressing host defense mechanisms and susceptibility to SARS-CoV-2 infection. Here, we show that increasing temperature in a 1.5°C window, between 36.5 and 38°C, strongly increases the expression of genes in two branches of antiviral immunity, nitric oxide production and type I interferon response. We show that alternative splicing coupled to nonsense-mediated decay decreases STAT2 expression in colder conditions and suggest that increased STAT2 expression at elevated temperature induces the expression of diverse antiviral genes and SARS-CoV-2 restriction factors. This cascade is activated in a remarkably narrow temperature range below febrile temperature, which reflects individual, circadian and age-dependent variation. We suggest that decreased body temperature with aging contributes to reduced expression of antiviral genes in older individuals. Using cell culture and in vivo models, we show that higher body temperature correlates with reduced SARS-CoV-2 replication, which may affect the different vulnerability of children versus seniors toward severe SARS-CoV-2 infection. Altogether, our data connect body temperature and pre-mRNA processing to provide new mechanistic insight into the regulation of antiviral innate immunity.


Asunto(s)
COVID-19 , SARS-CoV-2 , Niño , Humanos , Anciano , SARS-CoV-2/genética , Antivirales , Precursores del ARN/genética , Temperatura Corporal , COVID-19/genética
4.
Angew Chem Int Ed Engl ; 62(29): e202304010, 2023 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-37130003

RESUMEN

Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin-inspired nanostructure, produced via a synthetic methodology to prepare methacrylate-based dendronized polysulfates (MIP-1) on a multi gram-scale with high molecular weight (MW=450 kDa) and thiol end-functionalized mucin-inspired polymer (MIP) via RAFT polymerization. Cryo-electron tomography (Cryo-ET) analysis of MIP-1 confirmed a mucin-mimetic wormlike single-chain fiber structure (length=144±59 nm) in aqueous solution. This biocompatible fiber showed promising activity against SARS-CoV-2 and its mutant strain, with a remarkable low half maximal (IC50 ) inhibitory concentration (IC50 =10.0 nM). Additionally, we investigate the impact of fiber length on SARS-CoV-2 inhibition by testing other functional polymers (MIPs) of varying fiber lengths.


Asunto(s)
COVID-19 , Impresión Molecular , Humanos , Mucinas , SARS-CoV-2 , Polímeros/farmacología , Polímeros/química , Impresión Molecular/métodos
5.
Am J Pathol ; 186(4): 1025-35, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26877261

RESUMEN

Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post-transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition.


Asunto(s)
Carcinoma de Células de Merkel/metabolismo , Diferenciación Celular/fisiología , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , Neoplasias Cutáneas/metabolismo , Linaje de la Célula , Regulación hacia Abajo , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Receptor Notch2/metabolismo , Neoplasias Cutáneas/patología
6.
Implant Dent ; 25(1): 128-34, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26655097

RESUMEN

PURPOSE: The primary aim of this randomized, controlled, blinded clinical trial was to compare the effect of a resorbable collagen membrane (CM group) versus a nonresorbable high-density polytetrafluoroethylene membrane (PTFE group) on the clinical and histologic outcomes of a ridge preservation procedure. MATERIALS AND METHODS: All 24 sites received an intrasocket cancellous allograft and a buccal overlay bovine derived xenograft. RESULTS: The change in horizontal crestal ridge width was -1.4 ± 1.2 mm for the CM group, whereas the PTFE group lost -2.2 ± 1.5 mm, which was not statistically significant between groups (P > 0.05). Vertical ridge height change was -1.2 ± 1.5 for the CM group, whereas the PTFE group lost -0.5 ± 1.6, which was not significantly different between groups (P > 0.05). The percent vital bone was similar and not significantly different between groups. Primary closure was not obtained and the exposed membrane portion over the socket opening healed with keratinized tissue. CONCLUSION: The choice of a resorbable versus a nonresorbable barrier membrane did not affect the clinical or the histologic outcome of ridge preservation treatment.


Asunto(s)
Pérdida de Hueso Alveolar/prevención & control , Colágeno/uso terapéutico , Implantación Dental Endoósea/métodos , Membranas Artificiales , Politetrafluoroetileno/uso terapéutico , Adulto , Anciano , Aumento de la Cresta Alveolar/métodos , Femenino , Regeneración Tisular Guiada Periodontal , Humanos , Masculino , Persona de Mediana Edad
7.
Nat Commun ; 15(1): 995, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38307868

RESUMEN

The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways-the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Animales , Cricetinae , Masculino , Humanos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas de ARNm , SARS-CoV-2 , Mesocricetus , Anticuerpos Antivirales , Anticuerpos Neutralizantes
8.
ACS Biomater Sci Eng ; 9(6): 3712-3722, 2023 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-37256830

RESUMEN

Triboelectric nanogenerators (TENGs) are associated with several drawbacks that limit their application in the biomedical field, including toxicity, thrombogenicity, and poor performance in the presence of fluids. By proposing the use of a hemo/biocompatible hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), this study bypasses these barriers. In contact-separation mode, using polytetrafluoroethylene (PTFE) as a reference, pHEMA generates an output of 100.0 V, under an open circuit, 4.7 µA, and 0.68 W/m2 for an internal resistance of 10 MΩ. Our findings unveil that graphene oxide (GO) can be used to tune pHEMA's triboelectric properties in a concentration-dependent manner. At the lowest measured concentration (0.2% GO), the generated outputs increase to 194.5 V, 5.3 µA, and 1.28 W/m2 due to the observed increase in pHEMA's surface roughness, which expands the contact area. Triboelectric performance starts to decrease as GO concentration increases, plateauing at 11% volumetric, where the output is 51 V, 1.76 µA, and 0.17 W/m2 less than pHEMA's. Increases in internal resistance, from 14 ΩM to greater than 470 ΩM, ζ-potential, from -7.3 to -0.4 mV, and open-circuit characteristic charge decay periods, from 90 to 120 ms, are all observed in conjunction with this phenomenon, which points to GO function as an electron trapping site in pHEMA's matrix. All of the composites can charge a 10 µF capacitor in 200 s, producing a voltage between 0.25 and 3.5 V and allowing the operation of at least 20 LEDs. The triboelectric output was largely steady throughout the 3.33 h durability test. Voltage decreases by 38% due to contact-separation frequency, whereas current increases by 77%. In terms of pressure, it appears to have little effect on voltage but boosts current output by 42%. Finally, pHEMA and pHEMA/GO extracts were cytocompatible toward fibroblasts. According to these results, pHEMA has a significant potential to function as a biomaterial to create bio/hemocompatible TENGs and GO to precisely control its triboelectric outputs.


Asunto(s)
Electrónica Médica , Hidrogeles , Electrones , Polihidroxietil Metacrilato
9.
Nat Microbiol ; 8(5): 860-874, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37012419

RESUMEN

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Cricetinae , Humanos , Vacunas Atenuadas , COVID-19/prevención & control , Vacunas contra la COVID-19 , Vacuna BNT162 , Pandemias , Mesocricetus
10.
Implant Dent ; 19(1): 81-90, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20147820

RESUMEN

AIMS: The primary aim of this study was to evaluate the 1-year crestal bone loss and success rate of an immediately placed single-stage implant placed and restored by novice operators. A secondary aim was to determine the patient's assessment of the appearance of the final restoration. METHODS: Fifty-one patients received a tooth extraction and placement of at least 1 immediate implant by a Graduate Periodontics resident. Clinical and radiographic measurements were taken at the surgical, 4-month, and 1-year follow-up visits. After at least 3 months healing, dental students restored the implants with either a crown or an overdenture. Patient satisfaction was assessed using 5 categories: excellent, very good, good, fair, or poor. RESULTS: Sixty-two immediate implants were placed. The success rate was 100% at the 12-month visit and was subclassified as grade 3 because of the mean first year bone loss of 1.3 +/- 1.0 mm. Using the 2008 classification of Misch et al, 42 implants were classified as success optimum health, 19 as survival satisfactory health, and 1 as survival compromised health. Radiographic bone loss was stratified by implant platform position relative to the alveolar crest and changed from time 0 to time 12 by -1.0 +/- 1.2 mm for the supracrestal group (n = 25, P < 0.05), -1.5 +/- 0.9 mm for the crestal group (n = 31, P < 0.05), and -1.3 +/- 1.2 mm for the subcrestal group (n = 6, P < 0.05). The supracrestal group had significantly less bone loss than either the crestal or the subcrestal group (P < 0.05). The appearance of the final restoration at 1 year was rated excellent by 82% of patients, very good by 16%, and good by 2%. CONCLUSIONS: Immediate implant placement by novice operators using routine dental school procedures was a highly predictable procedure as indicated by the 100% success rate at 12 months. Most patients rated the restoration appearance as excellent.


Asunto(s)
Implantación Dental Endoósea/métodos , Implantación Dental Endoósea/estadística & datos numéricos , Implantes Dentales de Diente Único/estadística & datos numéricos , Prótesis Dental de Soporte Implantado/estadística & datos numéricos , Alveolo Dental/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/prevención & control , Análisis de Varianza , Competencia Clínica/estadística & datos numéricos , Coronas/estadística & datos numéricos , Implantación Dental Endoósea/efectos adversos , Análisis del Estrés Dental , Prótesis de Recubrimiento/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Internado y Residencia , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Prostodoncia/educación , Radiografía , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
11.
Carbohydr Polym ; 229: 115525, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31826510

RESUMEN

The extracellular polysaccharides produced by cyanobacteria have distinctive characteristics that make them promising for applications ranging from bioremediation to biomedicine. In this study, a sulfated polysaccharide produced by a marine cyanobacterial strain and named cyanoflan was characterized in terms of morphology, chemical composition, and rheological and emulsifying properties. Cyanoflan has a 71 % carbohydrate content, with 11 % of sulfated residues, while the protein account for 4 % of dry weight. The glycosidic-substitution analysis revealed a highly branched complex chemical structure with a large number of sugar residues. The cyanoflan high molecular mass fractions (above 1 MDa) and entangled structure is consistent with its high apparent viscosity in aqueous solutions and high emulsifying activity. It showed to be a typical non-Newtonian fluid with pseudoplastic behavior. Altogether, these results confirm that cyanoflan is a versatile carbohydrate polymer that can be used in different biotechnological applications, such as emulsifying/thickening agent in food or cosmetic industries.


Asunto(s)
Cianobacterias/metabolismo , Emulsionantes/química , Polisacáridos Bacterianos/química , Óxidos de Azufre/química , Peso Molecular , Parafina/química , Aceites de Plantas/química , Reología , Viscosidad
12.
J Periodontol ; 80(3): 397-404, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19254123

RESUMEN

BACKGROUND: The primary aim of this randomized, controlled, blinded clinical pilot study was to compare the percentage of recession defect coverage obtained with a coronally positioned tunnel (CPT) plus an acellular dermal matrix allograft (ADM) to that of a CPT plus ADM and platelet-rich plasma (CPT/PRP) 4 months post-surgically. METHODS: Eighteen patients with Miller Class I or II recession >or=3 mm at one site were treated and followed for 4 months. Nine patients received a CPT plus ADM and were considered the positive control group. The test group consisted of nine patients treated with a CPT plus ADM and PRP. Patients were randomly selected by a coin toss to receive the test or positive control treatment. RESULTS: The mean recession at the initial examination for the CPT group was 3.6 +/- 1.0 mm, which was reduced to 1.0 +/- 1.0 mm at the 4-month examination for a gain of 2.6 +/- 1.5 mm or 70% defect coverage (P <0.05). The mean recession at the initial examination for the CPT/PRP group was 3.3 +/- 0.7 mm, which was reduced to 0.4 +/- 0.7 mm at the 4-month examination for a gain of 2.9 +/- 0.5 mm or 90% defect coverage (P <0.05). There were no statistically significant differences between the groups (P >0.05). CONCLUSIONS: The CPT plus ADM and PRP produced defect coverage of 90%, whereas the CPT with ADM produced only 70% defect coverage. This difference was not statistically significant, but it may be clinically significant.


Asunto(s)
Colágeno/uso terapéutico , Encía/trasplante , Recesión Gingival/cirugía , Plasma Rico en Plaquetas , Piel Artificial , Colgajos Quirúrgicos , Raíz del Diente/cirugía , Adulto , Anciano , Índice de Placa Dental , Femenino , Estudios de Seguimiento , Encía/patología , Recesión Gingival/clasificación , Gingivoplastia/métodos , Humanos , Queratinas , Masculino , Persona de Mediana Edad , Pérdida de la Inserción Periodontal/clasificación , Índice Periodontal , Bolsa Periodontal/clasificación , Proyectos Piloto , Método Simple Ciego , Movilidad Dentaria/clasificación , Adulto Joven
13.
J Periodontol ; 79(6): 1022-30, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18533779

RESUMEN

BACKGROUND: The primary aim of this randomized, controlled, masked clinical trial was to compare the percentage of root coverage obtained with a coronally positioned flap plus acellular dermal matrix (ADM) allograft to that of a tunnel technique plus ADM 4 months post-surgically. METHODS: Twenty-four subjects with one site with > or =3 mm Miller Class I or II recession were treated and followed for 4 months. Twelve patients received a coronally positioned flap plus ADM and were considered the positive control group (CPF). The test group consisted of 12 subjects treated with a coronally positioned tunnel technique plus ADM (TUN). Subjects were randomly selected by a coin toss to receive the test or control treatment. RESULTS: The mean facial recession defect at the initial examination for the TUN group was 3.1 +/- 0.3 mm; this was reduced to 0.7 +/- 0.9 mm at the 4-month examination for a gain of 2.4 +/- 1.0 mm or 78% defect coverage (P <0.05). The mean facial recession defect at the initial examination for the CPF group was 3.4 +/- 0.8 mm; it was reduced to 0.2 +/- 0.3 mm at the 4-month examination for a gain of 3.2 +/- 0.9 mm or 95% defect coverage (P <0.05). There was no statistically significant difference between groups (P >0.05). CONCLUSIONS: The coronally positioned flap plus ADM produced a defect coverage of 95%, whereas the tunnel technique plus ADM produced only 78% coverage. This difference was considered clinically significant but was not statistically significant.


Asunto(s)
Recesión Gingival/cirugía , Gingivoplastia/métodos , Piel Artificial , Colgajos Quirúrgicos , Adulto , Anciano , Colágeno , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice Periodontal , Resultado del Tratamiento
14.
J Mol Diagn ; 18(3): 362-369, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26941049

RESUMEN

Germline mutations in breast and ovarian cancer are rare, with approximately 5% to 10% and 13% being hereditary in origin, respectively. In 2001, the Ontario Ministry of Health and Long Term Care, in an effort to contain costs, defined criteria to determine an individual's eligibility for BRCA genetic screening. We studied a cohort of individuals that have undergone genetic testing at Kingston General Hospital between 2001 and late 2013. We focused on determining whether the 13 risk criteria, defined by an expert working group for the Ontario Ministry of Health and Long Term Care, have performed according to expectations in this cohort. Our findings show that all of the criteria perform well by identifying carriers at the expected 10% rate defined by the guidelines. We demonstrate that loose application of the risk criteria does not further enrich for BRCA variant carriers. Our assessment of the established risk criteria that have been in use in Ontario for more than a decade, provide evidence for their effectiveness, and offer insights into how they may be expanded or improved.


Asunto(s)
Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Síndrome de Cáncer de Mama y Ovario Hereditario/diagnóstico , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama Masculina/diagnóstico , Neoplasias de la Mama Masculina/genética , Estudios de Cohortes , Femenino , Genes BRCA1 , Genes BRCA2 , Asesoramiento Genético , Mutación de Línea Germinal , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Tasa de Mutación , Ontario , Factores de Riesgo , Adulto Joven
15.
Clinics (Sao Paulo) ; 60(2): 85-92, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15880243

RESUMEN

PURPOSE: To evaluate the repair process in rats with experimentally induced arterial hypertension. This study aimed to evaluate lesions in the ventricular myocardium and the repair process during experimental hypertension induced by systemic blockage of nitric oxide using N-omega-nitro-L-arginine methyl ester hydrochloride (L-NAME). Nitric oxide is an endothelial vasorelaxing factor and is necessary for the maintenance of normal arterial pressure, and L-NAME is an analog and antagonist of L-arginine, the substrate of the nitric oxide synthase. MATERIALS AND METHODS: We used 26 normotensive young male Wistar rats belonging to several litters. Animals were treated with oral administration of L-NAME dissolved in water (75 mg/100 mL) for 43 days. Hearts were weighed and processed by routine methods. Special stains utilized were Gomori's trichrome (aniline blue), picrosirius red polarization to identify fibrillar collagen, alcian blue technique (pH 0.5 and pH 2.5) to identify glycosaminoglycans, periodic acid-Schiff technique (with and without amylases) to identify proteoglycans, and Weigert's resorcinol fuchsin solution (with and without oxone) to identify elastic fibers. RESULTS: The results showed significant elevation of the arterial pressure (P <0.01) and significant increase of cardiac weight (P <.0001) in the L-NAME (hypertensive) treated group, as compared to an untreated control group. The histological analysis demonstrated wide infarcted myocardial areas in animals with nitric oxide blockade; several vascular changes such as thickening of the muscular tunica with fibrosis; thickening in the wall of small arteries and arterioles; and fibrinoid necrosis in the wall to nearly complete luminal obliteration. Reparative fibrosis involved mainly oxytalan elastic and collagen fibers. CONCLUSION: Oxytalan elastic and collagen fibers are of great importance for the postinfarct repair process occurring during experimental nitric oxide inhibition.


Asunto(s)
Colágeno/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Hipertensión/patología , Miocardio/patología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Animales , Inhibidores Enzimáticos/farmacología , Fibrosis/patología , Hipertensión/inducido químicamente , Masculino , Miocardio/enzimología , NG-Nitroarginina Metil Éster/farmacología , Tamaño de los Órganos , Ratas , Ratas Wistar
16.
Artículo en Inglés | MEDLINE | ID: mdl-26133146

RESUMEN

The purpose of this article is to present a surgical and restorative protocol for the replacement of missing teeth in the esthetic zone. The ABC protocol consists of digitally guided implantation, autogenous bone graft (A), followed by bovine bone xenograft (B) and connective tissue graft (C). Autogenous bone is placed in contact with the implant surface to induce osseointegration; bovine bone xenograft is then applied to augment the ridge dimension and provide long-term stability. Connective tissue is used to provide additional volume. The ABC biomaterial sequence offers favorable hard and soft tissue dimensions and immediate provisional restoration predictably leads to an esthetically pleasing definitive prosthesis.


Asunto(s)
Aumento de la Cresta Alveolar/métodos , Trasplante Óseo/métodos , Implantes Dentales de Diente Único , Adulto , Animales , Bovinos , Terapia Combinada , Pilares Dentales , Estética Dental , Femenino , Gingivoplastia/métodos , Xenoinjertos , Humanos , Incisivo , Arcada Parcialmente Edéntula/cirugía , Masculino , Oseointegración
17.
J Periodontol ; 85(5): 661-8, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-23895252

RESUMEN

BACKGROUND: Platelet-rich plasma (PRP) contains a number of biologically active growth factors, and previous studies have reported conflicting ridge augmentation results. The primary aim of this randomized, controlled, masked, clinical trial was to determine if PRP combined with a rapidly resorbing cancellous allograft would enhance the regenerative result compared with an allograft without PRP. METHODS: Thirty-two patients with an edentulous ridge defect were sequentially entered into the study; four were excluded from data analysis. Fourteen patients received a cancellous allograft (CAN group) and the other 14 received a cancellous allograft mixed with PRP (PRP group). All 28 grafted sites were covered with a resorbable polylactide membrane. After elevation of a full-thickness flap, horizontal ridge dimensions were measured with a digital caliper at the crest and 5 mm apical to the crest. Vertical ridge dimensions were measured from a tooth-supported stent. All sites were reentered at 4 months, and a trephine core was obtained for histologic analysis before implant placement. RESULTS: The crestal ridge width for the CAN group had a mean gain of 2.0 ± 1.2 mm, whereas the PRP group gained 2.9 ± 1.0, and the difference was statistically significant between groups (P <0.05). The percent vital bone was 36% ± 14% for the CAN group compared with 51% ± 15% for the PRP group and was statistically significant between groups (P <0.05). Loss of augmented ridge width was 34% ± 17% for the CAN group and 28% ± 17% for the PRP group (P >0.05). CONCLUSION: These clinical and histologic findings suggest that PRP enhanced bone regeneration and resulted in increased horizontal bone gain and percentage vital bone.


Asunto(s)
Aumento de la Cresta Alveolar/métodos , Regeneración Tisular Guiada Periodontal/métodos , Plasma Rico en Plaquetas/fisiología , Implantes Absorbibles , Adulto , Anciano , Aloinjertos/trasplante , Proceso Alveolar/patología , Regeneración Ósea/fisiología , Trasplante Óseo/métodos , Cefalometría/métodos , Implantación Dental Endoósea/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Membranas Artificiales , Persona de Mediana Edad , Osteotomía/métodos , Poliésteres/química , Método Simple Ciego , Colgajos Quirúrgicos/cirugía , Adulto Joven
18.
J Periodontol ; 84(11): 1567-75, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23339378

RESUMEN

BACKGROUND: Previous studies of ridge preservation showed a loss of ≈18% or 1.5 mm of crestal ridge width in spite of treatment. The primary aim of this randomized, controlled, masked clinical trial is to compare a socket graft to the same treatment plus a buccal overlay graft, both with a polylactide membrane, to determine if loss of ridge width can be prevented by use of an overlay graft. METHODS: Twelve patients who served as positive controls received an intrasocket mineralized cancellous allograft (socket group), and 12 patients received the same socket graft procedure plus buccal overlay cancellous xenograft (overlay group). Horizontal ridge dimensions were measured with a digital caliper, and vertical ridge changes were measured from a stent. Before implant placement, at 4 months, a trephine core was obtained for histologic analysis. RESULTS: The mean horizontal ridge width at the crest for the socket group decreased from 8.7 ± 1.0 to 7.1 ± 1.5 mm for a mean loss of 1.6 ± 0.8 mm (P <0.05), whereas the same measurement for the overlay group decreased from 8.4 ± 1.4 to 8.1 ± 1.4 mm for a mean loss of 0.3 ± 0.9 mm (P >0.05). The overlay group was significantly different from the socket group (P <0.05). Histologic analysis revealed that the socket group had 35% ± 16% vital bone, and the overlay group had 40% ± 16% (P >0.05). CONCLUSIONS: The overlay treatment significantly prevented loss of ridge width and preserved or augmented the buccal contour. The socket and overlay groups healed with a high percentage of vital bone.


Asunto(s)
Aloinjertos/trasplante , Aumento de la Cresta Alveolar/métodos , Trasplante Óseo/métodos , Xenoinjertos/trasplante , Alveolo Dental/cirugía , Implantes Absorbibles , Adulto , Anciano , Proceso Alveolar/patología , Animales , Biopsia , Bovinos , Cefalometría/instrumentación , Implantación Dental Endoósea/métodos , Femenino , Estudios de Seguimiento , Regeneración Tisular Guiada Periodontal/métodos , Humanos , Masculino , Mandíbula/patología , Mandíbula/cirugía , Maxilar/patología , Maxilar/cirugía , Membranas Artificiales , Persona de Mediana Edad , Poliésteres/química , Método Simple Ciego , Stents , Colgajos Quirúrgicos/cirugía , Alveolo Dental/patología , Resultado del Tratamiento
19.
Rev. cuba. oftalmol ; 31(3)jul.-set. 2018.
Artículo en Español | CUMED, LILACS | ID: biblio-1508353

RESUMEN

Objetivo: Determinar la efectividad de la terapia visual con el uso del PlayStation PortableTM en la ambliopía. Método: Se incluyeron 40 pacientes de 5-10 años de edad con ambliopía estrábica, anisometrópica o ambas, aleatorizados en 4 grupos según el tipo de terapia a utilizar (10 pacientes por grupo): grupo 1, PlayStation PortableTM y lentes rojo-verde; grupo 2, PlayStation PortableTM y lentes con vidrio esmerilado en el ojo fijador (no ambliope); grupo 3, PlayStation PortableTM y parche oclusivo en el ojo fijador; grupo 4, parche oclusivo en el ojo fijador sin el PlayStation PortableTM. Todos los pacientes utilizaron su refracción. Las actividades de los grupos 1 al 3 incluyeron jugar videojuegos y ver películas 1-2 horas al día; el grupo 4 podía realizar cualquier actividad. Se valoró la agudeza visual mejor corregida semanalmente, hasta completar 3 meses de tratamiento. En el postratamiento se valoró la agudeza visual mejor corregida mensualmente durante 3 meses. Resultados: En total se estudiaron 40 pacientes, de los cuales el 60 por ciento fueron del sexo femenino, con un promedio de edad de 8,2 años, rango de 5-10 años. El tipo más frecuente de ambliopía fue la estrábica (55 por ciento), seguido de la anisometrópica (37,5 por ciento) y ambas (7,5 por ciento). En cuanto al ojo afectado, en el 62,5 por ciento fue el ojo izquierdo y en el 37,5 por ciento el ojo derecho. Conclusiones: En este estudio el grupo con mejores resultados fue el de filtro rojo-verde. Al suspender la terapia se observó un deterioro visual en los cuatro grupos, sin regresar a la basal. Se demuestra que el PlayStation PortableTM funciona como terapia en la ambliopía con una mejoría en la agudeza visual mejor corregida(AU)


Objective: Determine the effectiveness of visual therapy with PlayStation PortableTM for amblyopia. Methods: The study sample was composed of 40 patients aged 5-10 years with strabismic amblyopia, anisometropic amblyopia or both, randomized to 4 groups according to the therapy to be used (10 patients per group): Group 1: PlayStation PortableTM and red-green lenses; Group 2: PlayStation PortableTM and frosted glass lenses on the fixating (non-amblyopic) eye; Group 3: PlayStation PortableTM and occlusive patch on the fixating eye; Group 4: occlusive patch on the fixating eye without PlayStation PortableTM. All the patients used their refraction. The activities performed by Groups 1-3 included playing video games and watching movies 1-2 hours per day; Group 4 could perform any activity. Best corrected visual acuity was measured weekly until completing 3 months of treatment. In the post-treatment period best corrected visual acuity was measured monthly for 3 months. Results: A total 40 patients were studied, of whom 60 percent were female, with a mean age of 8.2 years, range of 5-10 years. Strabismic amblyopia was the most common type (55 percent), followed by anisometropic amblyopia (37,5 percent) and both (7.5 percent). The affected eye was the left eye in 62.5 percent and the right eye in 37.5 percent. Conclusions: It was found that PlayStation PortableTM is effective as therapy for amblyopia, improving best corrected visual acuity. The group with the best results was the red-green filter group. Upon suspension of the therapy, visual deterioration was observed in the 4 groups, without returning to baseline values(AU)


Asunto(s)
Humanos , Femenino , Niño , Ambliopía/terapia , Juegos de Video/efectos adversos , Estrabismo/etiología
20.
J Biomed Mater Res A ; 99(3): 344-53, 2011 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-22021182

RESUMEN

Helicobacter pylori (H. pylori) is one of the most common infectious agents in the world and it is thought to colonize the gastric mucosa of about half of the world's population causing several gastric diseases. In this work, the effect of surface chemistry on H. pylori nonspecific adhesion, viability, and morphology was evaluated using three H. pylori strains with different adhesins expression profile. Self-assembled monolayers (SAMs) of alkanethiols on gold were used to obtain surfaces exposing different functional groups: OH, CH3, and ethylene glycol (EG4). Bacterial adhesion onto the surfaces reached a plateau at 2 h. There was a correlation between adhesion and the exposed surface group, with bacterial cells adhering preferentially to CH3-SAMs while EG4-SAMs prevented H. pylori adhesion during the entire adhesion test (24 h). Surfaces that presented the EG4 group were also the only ones that significantly reduced the viability of adhered bacteria. Surface chemistry also influenced the morphology of adhered bacteria. The H. pylori rod shape observed in the control (Tissue Culture Polyethylene-TCPE) was only retrieved on CH3-SAMs. This work demonstrates that surface chemistry, namely specific functional groups on the material, influence the nonspecific adsorption of H. pylori. Moreover, the features of the bacterial strain and the surface chemistry can alter the adhesion kinetics, as well as the morphology and viability of attached bacteria.


Asunto(s)
Adhesión Bacteriana , Helicobacter pylori/citología , Viabilidad Microbiana , Adhesión Bacteriana/efectos de los fármacos , Recuento de Colonia Microbiana , Oro/farmacología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/crecimiento & desarrollo , Helicobacter pylori/ultraestructura , Cinética , Viabilidad Microbiana/efectos de los fármacos , Microscopía de Fuerza Atómica , Propiedades de Superficie/efectos de los fármacos , Agua/química
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