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1.
Front Med (Lausanne) ; 10: 1179350, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404809

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event in patients treated with antiresorptives. Management of MRONJ is challenging, and no non-antibiotic, established medical treatment exists. Intermittent parathyroid hormone (iPTH) has been used off-label to treat MRONJ with favorable results. However, its medical efficacy has rarely been substantiated in clinical or preclinical experiments. Using a validated rice rat, infection-based model of MRONJ, we evaluated the effects of iPTH on established MRONJ. We hypothesize that iPTH contributes to MRONJ resolution by enhancing alveolar bone turnover and healing oral soft tissues. Eighty-four rice rats began a standard rodent chow diet at age 4 weeks to induce localized periodontitis. Rats were simultaneously randomized to receive saline (vehicle, VEH) or zoledronic acid (ZOL, 80 µg/kg IV) every 4 weeks. Oral exams were conducted bi-weekly to assign a gross quadrant grade (GQG, 0-4) to evaluate any lesion at the lingual aspect of the interdental space between maxillary molar (M2) and M3. 14 of 20 VEH-treated rice rats (70%) developed maxillary localized periodontitis with GQG 2-3 after 30 ± 10 weeks of saline. Additionally, 40 of 64 ZOL-treated rice rats with periodontitis developed MRONJ-like lesions after 30 ± 10 weeks of ZOL treatment. Rice rats with localized periodontitis or MRONJ-like lesions were treated with saline or iPTH (40 µg/kg) subcutaneously (SC) 3 times/week For 6 weeks until euthanasia. We found that iPTH -treated ZOL rats had a lower prevalence of MRONJ (p < 0.001), with lower severity extent of oral lesions (p = 0.003) and percentage of empty osteocyte lacunae (p < 0.001). ZOL rats treated with iPTH displayed a higher osteoblast surface (p < 0.001), more osteoblasts (p < 0.001), higher osteoclast surface (p < 0.001) and more osteoclasts (p = 0.002) at alveolar bone surfaces than ZOL/VEH rats. Greater gingival epithelial thickness and epithelial cell proliferation rate was found in the oral mucosa and gingiva of ZOL/PTH rats than in ZOL/VEH rats (p < 0.001). Our data suggest that iPTH is an efficacious non-operative medicinal therapy that accelerates oral healing and enhances the resolution of MRONJ lesions in ZOL-treated rice rats.

2.
Phys Chem Chem Phys ; 19(31): 21174-21184, 2017 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-28752877

RESUMO

Recent studies suggest that graphene decorated with light metal atoms is a feasible alternative for the design of the next generation of hydrogen storage systems, that is, materials which require a gravimetric content of at least 7.5 wt%, and an adsorption energy of 0.2-0.6 eV per H2. We present a first principles study of hydrogen adsorption in titanium, and bimetallic Ti5-xAlx (x = 1-3) and Ti7-xAlx (x = 1-4) clusters supported on graphene. Our results for Ti5, Ti4Al, Ti7, and Ti6Al show that doping titanium clusters with small amounts of aluminum does not influence the cluster stability on graphene, but that notably, it enhances its hydrogen gravimetric content up to 3.2-3.6 wt%. A further increment of the aluminum concentration was found to reduce the cluster stability and to favor hydrogen desorption, as shown by our calculations for supported Ti3Al2, Ti2Al3, TiAl4 and Ti5Al2. An analysis of atomic charges and density of states reveals the role of charge transfer and orbital interactions in the stability of hydride and dihydrogen complexes in the studied systems. Our results support the hypothesis that a controlled introduction of small metal clusters to graphene is a feasible way to enhance its hydrogen gravimetric content, and it opens up the possibility of investigating other binary TMx-Ay (TM = transition metal and A = main group) clusters supported on graphene as promising candidates for hydrogen storage.

3.
Clin Microbiol Infect ; 9(9): 964-5, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14616687

RESUMO

We describe an atypical presentation of bacteremia caused by N. meningitidis serogroup X. By multilocus sequence typing the isolate was characterized to the sequence type 2139, which is not related with the clonal complex recently isolated in Africa. Since 1984, only six cases of serogroup X N. meningitidis infections have been diagnosed in Spain. Nevertheless, after the application of the conjugated vaccine, attention should be paid to the emergence of infections caused by unusual serogroups of N. meningitidis.


Assuntos
Infecções Meningocócicas/microbiologia , Neisseria meningitidis/crescimento & desenvolvimento , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/imunologia , Bacteriemia/microbiologia , Criança , Feminino , Humanos , Infecções Meningocócicas/tratamento farmacológico , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Penicilina G/uso terapêutico , Sorotipagem , Espanha , Vacinas Conjugadas/imunologia
6.
Am J Trop Med Hyg ; 59(1): 49-52, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9684627

RESUMO

The Leishmaniases are a group of diseases whose clinical presentation is in part determined by the infecting species. Until recently, mucosal leishmaniasis was attributed exclusively to Leishmania (Viannia) braziliensis; however, the capacity of other species of the subgenus Viannia to invade mucosal tissue has been documented. This report examines the clinical characteristics of 23 parasitologically diagnosed patients with mucosal leishmaniasis due to L. (V.) panamensis from the Pacific Coast of Colombia seen at CIDEIM between 1985 and 1996. Most of the mucosal lesions 74% (17 of 23) were mild, with a short time of evolution (median = 2.5 months) and were present concomitantly with an active cutaneous lesion in 61% (14 of 23) of the cases. The simultaneous presentation of mucosal and active cutaneous lesions contrast with classical descriptions of mucosal leishmaniasis caused by L. (V.) braziliensis, and highlights the importance of early diagnosis of mucosal disease by the examination of mucosa in all cases of cutaneous leishmaniasis.


Assuntos
Leishmania guyanensis , Leishmaniose Mucocutânea/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Animais , Criança , Colômbia/epidemiologia , Feminino , Humanos , Laringe/patologia , Leishmania guyanensis/classificação , Leishmania guyanensis/isolamento & purificação , Leishmaniose Mucocutânea/parasitologia , Leishmaniose Mucocutânea/patologia , Masculino , Pessoa de Meia-Idade , Mucosa/parasitologia , Mucosa Nasal/patologia , Fenótipo , Fatores Sexuais , Pele/parasitologia
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