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1.
ChemMedChem ; 16(3): 467-471, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33197298

RESUMO

Inspired by the incorporation of metallocene functionalities into a variety of bioactive structures, particularly antimicrobial peptides, we endeavored to broaden the structural variety of quaternary ammonium compounds (QACs) by the incorporation of the ferrocene moiety. Accordingly, 23 ferrocene-containing mono- and bisQACs were prepared in high yields and tested for activity against a variety of bacteria, including Gram-negative strains and a panel of clinically isolated MRSA strains. Ferrocene QACs were shown to be effective antiseptics with some displaying single-digit micromolar activity against all bacteria tested, demonstrating yet another step in the expansion of structural variety of antiseptic QACs.


Assuntos
Antibacterianos/farmacologia , Compostos Ferrosos/farmacologia , Metalocenos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Compostos Ferrosos/química , Metalocenos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos de Amônio Quaternário/química , Relação Estrutura-Atividade
2.
ChemMedChem ; 14(1): 83-87, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30358105

RESUMO

Twenty-one mono- and biscationic quaternary ammonium amphiphiles (monoQACs and bisQACs) were rapidly prepared in order to investigate the effects of rigidity of a diamine core structure on antiseptic activity. As anticipated, the bioactivity against a panel of six bacteria including methicillin-resistant Staphylococcus aureus (MRSA) strains was strong for bisQAC structures, and is clearly correlated with the length of non-polar side chains. Modest advantages were noted for amide-containing side chains, as compared with straight-chained alkyl substituents. Surprisingly, antiseptics with more rigidly disposed side chains, such as those in DABCO-12,12, showed the highest level of antimicrobial activity, with single-digit MIC values or better against the entire bacterial panel, including sub-micromolar activity against an MRSA strain.


Assuntos
Anti-Infecciosos Locais/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Tensoativos/farmacologia , Anti-Infecciosos Locais/síntese química , Anti-Infecciosos Locais/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química , Relação Estrutura-Atividade , Tensoativos/síntese química , Tensoativos/química
3.
ChemMedChem ; 12(23): 1931-1934, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-29068517

RESUMO

Benzalkonium chloride (BAC) and cetyl pyridinium chloride (CPC) are two of the most common household antiseptics, but show weaker efficacy against Gram-negative bacteria as well as against methicillin-resistant Staphylococcus aureus (MRSA) strains, relative to other S. aureus strains. We prepared 28 novel quaternary ammonium compounds (QACs) that represent a hybrid of these two structures, using 1- to 2-step synthetic sequences. The biscationic (bisQAC) species prepared show uniformly potent activity against six bacterial strains tested, with nine novel antiseptics displaying single-digit micromolar activity across the board. Effects of unequal chain lengths of two installed side chains had less impact than the overall number of side chain carbon atoms present, which was optimal at 22-25 carbons. This is further indication that simple refinements to multiQAC architectures can show improvement over current household antiseptics.


Assuntos
Anti-Infecciosos Locais/farmacologia , Bactérias/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Anti-Infecciosos Locais/síntese química , Anti-Infecciosos Locais/química , Compostos de Benzalcônio/química , Compostos de Benzalcônio/farmacologia , Cátions/síntese química , Cátions/química , Cátions/farmacologia , Cetilpiridínio/química , Cetilpiridínio/farmacologia , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química
4.
Clin Nucl Med ; 39(1): 94-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24471190

RESUMO

A 59-year-old female patient was hospitalized with anemia from recurrent gastrointestinal bleeding. Planar (99m)Tc-tagged red blood cell bleeding scan suggested an active site of low-rate hemorrhage in the left upper quadrant, but after 60 minutes it could not conclusively define the bleeding as originating in small versus large bowel. SPECT/CT unequivocally localized the hemorrhage to the small bowel and deemed it reachable by extended version ("push"') endoscope. Subsequent push enteroscopy confirmed the bleeding in proximal jejunum and allowed effective treatment with electrocautery.


Assuntos
Hemorragia Gastrointestinal/diagnóstico por imagem , Intestino Delgado , Imagem Multimodal , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Feminino , Hemorragia Gastrointestinal/terapia , Humanos , Pessoa de Meia-Idade
5.
Case Rep Radiol ; 2013: 595341, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23607033

RESUMO

A 53-year-old male presented with complaints of abdominal pain and weight loss. On physical exam he was noted to have mucocutaneous pigmentation around his lips and oral mucosa. Radiologic and endoscopic investigations demonstrated an obstructing mass in the second portion of the duodenum along with additional smaller soft tissue masses throughout the bowel. Histology of biopsied specimens revealed architectural disorganization without dysplasia, suggestive of Peutz-Jeghers hamartomatous polyps.

6.
Anat Sci Educ ; 2(4): 143-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19637291

RESUMO

Reciprocal peer teaching (RPT), wherein students alternate roles as teacher and learner, has been applied in several educational arenas with varying success. Here, we describe the implementation of a reciprocal peer teaching protocol in a human gross anatomy laboratory curriculum. We compared the outcomes of the RPT class with those of previous classes in which RPT was not employed. Objective data (i.e., course grades) show no significant differences in gross anatomy laboratory grades between students in the RPT and non-RPT classes. To subjectively evaluate the relative success of RPT in the laboratory, we analyzed student opinions obtained through anonymous surveys. These data show that a powerful majority of student respondents felt that RPT was beneficial and should be used in future classes. The greatest disadvantage was unreliable quality of teaching from peers; however, most students still felt that RPT should be continued. Students who felt that they had insufficient hands-on experience (by virtue of dissecting only half the time) were significantly more likely to recommend abandoning RPT. These results underscore the importance of active student dissection, and suggest that a modified version of the described RPT protocol may satisfy more of the needs of large, diverse student populations. Several hidden benefits of RPT exist for faculty, administration, and students, including reduced need for large numbers of cadavers, attendant reduction in operating costs, and smaller student-to-teacher ratios.


Assuntos
Anatomia/educação , Dissecação/educação , Educação de Graduação em Medicina , Laboratórios , Grupo Associado , Estudantes de Medicina , Anatomia/normas , Cadáver , Compreensão , Currículo , Dissecação/normas , Educação de Graduação em Medicina/normas , Avaliação Educacional , Humanos , Relações Interpessoais , Laboratórios/normas , Modelos Educacionais , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Controle de Qualidade , Estudantes de Medicina/psicologia , Inquéritos e Questionários
7.
Clin Anat ; 20(7): 799-807, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17583582

RESUMO

Osteoarthritis is manifested both by macroscopically visible lesions and by specific histological indicators. Although traditional views of the disease process invoke physical abrasion of joint surfaces, recent studies indicate that tissue-level changes may precede grossly visible lesions of articular cartilage. This study investigates the association between gross and histological indicators of osteoarthritis at the manual interphalangeal joints, and examines a sequence of events that may lead to the onset of cartilage degeneration. Interphalangeal joints from the hands of nine cadavers were dissected, of which 52 joints were collected and further evaluated. Gross degradation of the proximal articular surface was graded on a scale of 0-3 (with 0 representing normal cartilage with no visible lesions). Osteoarthritic lesions were found in 86% of specimens and showed no preferential occurrence between males and females or right and left hands. Histological analysis indicated that known microscopic indicators of osteoarthritis always occur in Grade 1-3 specimens, but can also be recognized in some macroscopically normal specimens. Many macroscopically normal specimens exhibited chondrocyte clustering (28.6%) and/or tide mark irregularities (57%), indicating that these features are most likely the earliest to develop in the progression of osteoarthritis. It is possible that the initiating etiology is thickening of the subchondral bone, but this was not directly observed. Results indicate significant thinning of the cartilage as macroscopic degradation progresses. Our study supports, with slight modification, a previously proposed cascade of histological changes that may ultimately lead to the physical destruction of articular cartilage.


Assuntos
Cartilagem Articular/patologia , Condrócitos/patologia , Articulações dos Dedos/patologia , Osteoartrite/patologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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