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1.
Cells ; 10(4)2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917391

RESUMO

Cardiac fibroblasts and cardiomyocytes are the main cells involved in the pathophysiology of myocarditis (MCD). These cells are especially sensitive to changes in iron homeostasis, which is extremely important for the optimal maintenance of crucial cellular processes. However, the exact role of iron status in the pathophysiology of MCD remains unknown. We cultured primary human cardiomyocytes (hCM) and cardiofibroblasts (hCF) with sera from acute MCD patients and healthy controls to mimic the effects of systemic inflammation on these cells. Next, we performed an initial small-scale (n = 3 per group) RNA sequencing experiment to investigate the global cellular response to the exposure on sera. In both cell lines, transcriptomic data analysis revealed many alterations in gene expression, which are related to disturbed canonical pathways and the progression of cardiac diseases. Moreover, hCM exhibited changes in the iron homeostasis pathway. To further investigate these alterations in sera-treated cells, we performed a larger-scale (n = 10 for controls, n = 18 for MCD) follow-up study and evaluated the expression of genes involved in iron metabolism. In both cell lines, we demonstrated an increased expression of transferrin receptor 1 (TFR1) and ferritin in MCD serum-treated cells as compared to controls, suggesting increased iron demand. Furthermore, we related TFR1 expression with the clinical profile of patients and showed that greater iron demand in sera-treated cells was associated with higher inflammation score (interleukin 6 (IL-6), C-reactive protein (CRP)) and advanced neurohormonal activation (NT-proBNP) in patients. Collectively, our data suggest that the malfunctioning of cardiomyocytes and cardiofibroblasts in the course of MCD might be related to alterations in the iron homeostasis.


Assuntos
Fibroblastos/metabolismo , Regulação da Expressão Gênica , Ferro/metabolismo , Miocardite/sangue , Miócitos Cardíacos/metabolismo , Doença Aguda , Adulto , Estudos de Casos e Controles , Sobrevivência Celular , Células Cultivadas , Regulação para Baixo/genética , Feminino , Ferritinas/sangue , Perfilação da Expressão Gênica , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Miocardite/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , Resultado do Tratamento , Regulação para Cima/genética
2.
Pathogens ; 10(1)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450948

RESUMO

Yersinia enterocolitica, widespread within domestic and wild-living animals, is a foodborne pathogen causing yersiniosis. The goal of this study was to assess a genetic similarity of Y. enterocolitica and Y. enterocolitica-like strains isolated from different hosts using Multiple Locus Variable-Number Tandem Repeat Analysis (MLVA) and Pulsed-Field Gel Electrophoresis (PFGE) methods, and analyze the prevalence of virulence genes using multiplex-Polymerase Chain Reaction (PCR) assays. Among 51 Yersinia sp. strains 20 virulotypes were determined. The most common virulence genes were ymoA, ureC, inv, myfA, and yst. Yersinia sp. strains had genes which may contribute to the bacterial invasion and colonization of the intestines as well as survival in serum. One wild boar Y. enterocolitica 1A strain possessed ail gene implying the possible pathogenicity of 1A biotype. Wild boar strains, represented mainly by 1A biotype, were not classified into the predominant Variable-Number Tandem Repeats (VNTR)/PFGE profile and virulotype. There was a clustering tendency among VNTR/PFGE profiles of pig origin, 4/O:3, and virulence profile. Pig and human strains formed the most related group, characterized by ~80% of genetic similarity what suggest the role of pigs as a potential source of infection for the pork consumers.

3.
J Med Virol ; 93(3): 1599-1604, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32897549

RESUMO

Coronavirus disease 2019 (COVID-19) reinfections could be a major aggravating factor in this current pandemic, as this would further complicate potential vaccine development and help to maintain worldwide virus pockets. To investigate this critical question, we conducted a clinical meta-analysis including all available currently reported cases of potential COVID-19 reinfections. We searched for all peer-reviewed articles in the search engine of the National Center for Biotechnology Information. While there are over 30,000 publications on COVID-19, only about 15 specifically target the subject of COVID-19 reinfections. Available patient data in these reports was analyzed for age, gender, time of reported relapse after initial infection and persistent COVID-19 positive polymerase chain reaction (PCR) results. Following the first episode of infection, cases of clinical relapse are reported at 34 (mean) ± 10.5 days after full recovery. Patients with clinical relapse have persisting positive COVID-19 PCR testing results until 39 ± 9 days following initial positive testing. For patients without clinical relapse, positive testing was reported up to 54 ± 24 days. There were no reports of any clinical reinfections after a 70-day period following initial infection.


Assuntos
COVID-19/diagnóstico , Reinfecção/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , SARS-CoV-2 , Adulto Jovem
4.
Sci Rep ; 10(1): 18889, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144661

RESUMO

The oral cavity may comprise a significant reservoir for Staphylococcus aureus but the data on molecular epidemiology and clonal distribution of oral strains are really scarce. This study aimed to evaluate the clonal relatedness in S. aureus isolated from oral cavity and their relationship with carriage of virulence genes, and antimicrobial resistance profiles. A total of 139 oral S. aureus isolates were obtained from 2327 analysed oral samples of dental patients. Antimicrobial susceptibility testing was performed. Isolates were characterized using protein A gene (spa) typing, spa-CC clonal complexes, toxin genes and SCCmec typing for MRSA. High resistance rates for penicillin, tetracycline and gentamicin were detected, respectively 58.3%, 42.4%, and 35.2%. Twelve (8.6%) S. aureus isolates were identified as MRSA. All of MRSA isolates were mecA-positive and mecC-negative. SCCmec IV was the most common type (66.7%), which was typical for community-acquired MRSA (CA-MRSA). Overall, the enterotoxin gene cluster (egc) was the most frequent detected virulence factor (44.9%), both in MSSA and MRSA isolates. Presence of genes encoding for the enterotoxins (sea, seb, sec, seh, sek), exfoliative toxin A (eta), and toxic shock syndrome toxin-1 (tst) was also observed. Strains carrying lukS-PV/lukF-PV genes belonged to SCCmecV- spa type t437. The most prevalent spa types were t091, t015, t084, t002, t571, and t026 among all 57 identified. Spa types, including 3 new ones, grouped in 6 different spa-CC clonal complexes, with four major dominated; CC45, CC30, CC5, and CC15. This study demonstrated that both methicillin-susceptible and methicillin-resistant major European clones of S. aureus could be isolated from the oral cavity of dental patients, with the emergence of PVL-positive CA-MRSA strains. The oral cavity should be considered as a possible source of toxigenic egc-positive S. aureus strains, in terms of potential risk of cross-infection and dissemination to other body sites.


Assuntos
Resistência a Meticilina , Tipagem Molecular/métodos , Boca/microbiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/farmacologia , Proteínas de Bactérias/genética , Evolução Clonal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Proteínas de Ligação às Penicilinas/genética , Prevalência , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Fatores de Virulência/genética , Adulto Jovem
5.
Cell Transplant ; 29: 963689720949244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32967455

RESUMO

Aerosolized drug delivery has recently attracted much attention as a possible new tool for the delivery of complex nanoparticles. This study aims to investigate whether catheter-based aerosolization of islets via endobronchial systems is a feasible option in islet transplantation. Besides investigating the feasibility of islet aerosolization, we also examined cluster cell vitality and structural integrity of the islets following aerosolization. Using an ex vivo postmortem swine model, porcine pancreatic islets were isolated and aerosolized with an endoscopic spray catheter. Following aerosolization, islet cell vitality and function were assessed via Calcein AM and propidium iodide as well as insulin production after glucose exposure. In the final step, the overall feasibility of the procedure and structural integrity of cells were analyzed and evaluated with respect to clinical applicability. No significant difference was detected in the viability of control islets (90.67 ± 2.19) vs aerosolized islets (90.68 ± 1.20). Similarly, there was no significant difference in control islets (1.62 ± 0.086) vs aerosolized islets (1.42 ± 0.11) regarding insulin release after stimulation. Indocyanine green marked islets were transplanted into the lung without major difficulty. Histological analysis confirmed retained structural integrity and predominant location in the alveolar cavity. Our ex vivo data suggest that catheter-based aerosolized islet cell delivery is a promising tool for the application of cell clusters. According to our data, islet cell clusters delivery is feasible from a mechanical and physical perspective. Moreover, cell vitality and structural integrity remain largely unaffected following aerosolization. These preliminary results are encouraging and represent a first step toward endoscopically assisted islet cell implantation in the lung.


Assuntos
Aerossóis/administração & dosagem , Endoscopia , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/citologia , Pulmão/diagnóstico por imagem , Animais , Broncoscopia , Cateteres , Agregação Celular , Sobrevivência Celular , Estudos de Viabilidade , Glucose/metabolismo , Suínos
6.
Sci Rep ; 10(1): 10341, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32587302

RESUMO

For decades, intraperitoneal chemotherapy (IPC) was delivered into the abdominal cavity as a liquid solution. This preliminary study aims to evaluate foam as a potential new drug carrier for IPC delivery. Foam-based intraperitoneal chemotherapy (FBIC) was produced with taurolidine, hydrogen peroxide, human serum, potassium iodide and doxorubicin/ oxaliplatin for both ex vivo and in vitro experiments. Analysis of FBIC efficacy included evaluation of cytotoxicity, tissue penetration, foam stability, temperature changes and total foam volume per time evaluation. FBIC showed penetration rates of about 275 ± 87 µm and higher cytotoxicity compared to controls and to conventional liquid IPC (p < 0.005). The volume of the generated foam was approximately 50-times higher than the initial liquid solution and temporarily stable. Foam core temperature was measured and increased to 47 °C after 9 min. Foam ingredients (total protein content) were evenly distributed within different locations. Our preliminary results are quite encouraging and indicate that FBIC is a feasible approach. However, in order to discuss a possible superior effect over conventional liquid or aerosolized chemo applications, further studies are required to investigate pharmacologic, pharmacodynamic and physical properties of FBIC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Portadores de Fármacos/química , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias Peritoneais/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Portadores de Fármacos/farmacologia , Estudos de Viabilidade , Células HT29 , Humanos , Peróxido de Hidrogênio/química , Masculino , Peritônio/metabolismo , Permeabilidade/efeitos dos fármacos , Iodeto de Potássio/química , Soro/química , Suínos , Testes de Toxicidade
7.
Food Microbiol ; 90: 103482, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32336356

RESUMO

In this study, 53 Staphylococcus (S.) aureus strains were typed by 16S-23S rDNA intergenic spacer region (ISR) typing and staphylococcal enterotoxin gene (SEg) typing for all the staphylococcal enterotoxin (se) and staphylococcal enterotoxin-like toxin (sel) genes known to date, revealing a higher discriminatory power than that of multi locus sequence typing. Six strains, one of each ISR- and SEg-type, were genome sequenced and the ability to produce some classical and new SEs when growing in milk was investigated. The manual analysis of the six genomes allowed us to confirm, correct and expand the results of common available genomic data pipelines such as VirulenceFinder. Moreover, it enabled us to (i) investigate the actual location of se and sel genes, even for genes such as selY, whose location (in the core genome) was so far unknown, (ii) find novel allelic variants of se and sel genes and pseudogenes, (iii) correctly annotate se and sel genes and pseudogenes, and (iv) discover a novel type of enterotoxin gene cluster (egc), i.e. the egc type 5 in strains 356P and 364P, while S. argenteus MSHR1132 harbored the egc type 6. Four of the six S. aureus strains produced sufficient amounts of SEA, SEC, SED and SEH in milk to cause staphylococcal food poisoning (SFP), with S. aureus 372 P being the highest producer of SED in milk found to date, producing as much as ca. 47,300 ng/mL and 49,200 ng/mL of SED, after 24 and 48 h of incubation in milk at 37 °C, respectively. S. aureus 372 P released a low amount of SER in milk, most likely because the seR gene was present as a pseudogene, putatively encoding only 51 amino acids. These findings confirm that not only the classical SEs, but also the new ones can represent a potential hazard for the consumers' health if produced in foods in sufficient amounts. Therefore, the detection of SEs in foods, especially if involved in SFP cases, should focus not only on classical, but also on all the new SEs and SEls known to date. Where reference methods are unavailable, the presence of the relevant genes, by using the conventional and real time PCR protocols we exhaustively provided herein, and their nucleotide sequences, should be investigated.


Assuntos
Enterotoxinas/genética , Genoma Bacteriano , Leite/microbiologia , Alimentos Crus/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/patogenicidade , Animais , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Microbiologia de Alimentos/métodos , Família Multigênica , Tipagem de Sequências Multilocus , Intoxicação Alimentar Estafilocócica/prevenção & controle , Staphylococcus aureus/isolamento & purificação , Sequenciamento Completo do Genoma
8.
J Travel Med ; 27(3)2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32181488

RESUMO

BACKGROUND: With its epicenter in Wuhan, China, the COVID-19 outbreak was declared a Public Health Emergency of International Concern by the World Health Organization (WHO). Consequently, many countries have implemented flight restrictions to China. China itself has imposed a lockdown of the population of Wuhan as well as the entire Hubei province. However, whether these two enormous measures have led to significant changes in the spread of COVID-19 cases remains unclear. METHODS: We analyzed the available data on the development of confirmed domestic and international COVID-19 cases before and after lockdown measures. We evaluated the correlation of domestic air traffic to the number of confirmed COVID-19 cases and determined the growth curves of COVID-19 cases within China before and after lockdown as well as after changes in COVID-19 diagnostic criteria. RESULTS: Our findings indicate a significant increase in doubling time from 2 days (95% CI: 1.9-2.6) to 4 days (95% CI: 3.5-4.3), after imposing lockdown. A further increase is detected after changing diagnostic and testing methodology to 19.3 (95% CI: 15.1-26.3), respectively. Moreover, the correlation between domestic air traffic and COVID-19 spread became weaker following lockdown (before lockdown: r = 0.98, P < 0.05 vs after lockdown: r = 0.91, P = NS). CONCLUSIONS: A significantly decreased growth rate and increased doubling time of cases was observed, which is most likely due to Chinese lockdown measures. A more stringent confinement of people in high risk areas seems to have a potential to slow down the spread of COVID-19.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Quarentena , Viagem/legislação & jurisprudência , Aeronaves , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/epidemiologia , SARS-CoV-2
9.
J Microbiol Immunol Infect ; 53(3): 454-458, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32205091

RESUMO

BACKGROUND: With its epicenter in Wuhan, China, the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO). While many countries have implemented flight restrictions to China, an increasing number of cases with or without travel background to China are confirmed daily. These developments support concerns on possible unidentified and unreported international COVID-19 cases, which could lead to new local disease epicenters. METHODS: We have analyzed all available data on the development of international COVID-19 cases from January 20th, 2020 until February 18th, 2020. COVID-19 cases with and without travel history to China were divided into cohorts according to the Healthcare Access and Quality Index (HAQ-Index) of each country. Chi-square and Post-hoc testing were performed. RESULTS: While COVID-19 cases with travel history to China seem to peak for each HAQ-cohort, the number of non-travel related COVID-19 cases seem to continuously increase in the HAQ-cohort of countries with higher medical standards. Further analyses demonstrate a significantly lower proportion of reported COVID-19 cases without travel history to China in countries with lower HAQ (HAQ I vs. HAQ II, posthoc p < 0.01). CONCLUSIONS: Our data indicate that countries with lower HAQ-index may either underreport COVID-19 cases or are unable to adequately detect them. Although our data may be incomplete and must be interpreted with caution, inconsistencies in reporting COVID-19 cases is a serious problem which might sabotage efforts to contain the virus.


Assuntos
Doenças Transmissíveis Importadas/epidemiologia , Infecções por Coronavirus/epidemiologia , Notificação de Doenças/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Viagem/estatística & dados numéricos , Betacoronavirus , COVID-19 , Acesso aos Serviços de Saúde , Humanos , Pandemias , SARS-CoV-2
10.
J Cancer ; 11(6): 1308-1314, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047537

RESUMO

Background: Nanocrystallization is a promising field for the development of new drugs. This study aims to present the use of nanocrystallization via intraperitoneal nanoaerosol therapy (INAT) for the treatment of peritoneal metastases. Methods: A continuous aerosol generation device was used to aerosolize a highly concentrated doxorubicin solution within a dry CO2 environment. The produced nanoaerosol was directed into an ex vivo abdominal model and collision of aerosol particles with placed samples was subject to further analysis via scanning-electron microscopy (SEM). SEM detected structural changes of particles caused by migration to different locations. Results: It was possible to visualize the contact of doxorubicin aerosol particles with the surface. Larger particles as well as particles closer to the aerosol generation chamber collided with the glass sample creating liquid drops, while smaller particles with more distance to the aerosol chamber collided as highly concentrated nanocrystals. The amount of nanocrystal particles outweighed the amount of fluid aerosol particles by far. Conclusions: Under optimal conditions, the formation of nanocrystals via aerosol creation device is possible. While a wide range of possible applications of nanocrystals is conceivable, surface coating with drug particles is especially interesting as it may serve as an alternative to conventional liquid intraperitoneal chemotherapy. Further studies are required to investigate nanocrystallization of chemotherapeutic solutions as well as its physical and pharmacological properties and side effects.

11.
APMIS ; 128(3): 211-219, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31692060

RESUMO

The aim of this study was to analyze the prevalence of Staphylococcus aureus in the tonsils of children subjected tonsillectomy due to recurrent tonsilitis and to determine the spa types of the pathogens, carriage of virulence genes and antimicrobial resistance profiles. The study included 73 tonsillectomized children. Bacteria, including S. aureus were isolated from tonsillar surface prior to tonsillectomy, recovered from tonsillar core at the time of the surgery, and from posterior pharynx 2-4 weeks after the procedure. Staphylococcus aureus isolates were compared by spa typing, tested for antimicrobial susceptibility and for the presence of superantigenic toxin genes (sea-seu, eta, etb, tst, lukS/lukF-PV) by multiplex polymerase chain reaction. Seventy-three patients (mean 7.1 ± 4.1 years, 61.6% male) were assessed. The most commonly isolated bacteria were S. aureus. The largest proportion of staphylococcal isolates originated from tonsillar core (63%), followed by tonsillar surface (45.1%) and posterior pharynx in tonsillectomized children (18.2%, p = 0.007). Five (6.3%) isolates were identified as MRSA (mecA-positive). Up to 67.5% of the isolates synthesized penicillinases (blaZ-positive isolates), and 8.8% displayed MLSB resistance. The superantigenic toxin genes were detected in more than half of examined isolates (56.3%). spa types t091, t084, and t002, and clonal complexes (CCs) CC7, CC45, and CC30 turned out to be most common. Staphylococcus aureus associated with RT in children showed pathogenicity potential and considerable genetic diversity, and no clones were found to be specific for this condition although further studies are needed.


Assuntos
Farmacorresistência Bacteriana/genética , Variação Genética/genética , Staphylococcus aureus/genética , Tonsilite/microbiologia , Adolescente , Anti-Infecciosos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Tonsila Palatina/microbiologia , Prevalência , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Tonsilectomia/métodos , Tonsilite/tratamento farmacológico , Virulência/genética , Fatores de Virulência/genética
12.
Curr Pharm Des ; 25(45): 4813-4819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692422

RESUMO

BACKGROUND: Ethylenediaminetetraacetic acid (EDTA), a commonly used compound in laboratory medicine, is known for its membrane-destabilization capacity and cell-detaching effect. This preliminary study aims to assess the potential of EDTA in removing residual tumor cell clusters. Using an in-vitro model, this effect is then compared to the cytotoxic effect of oxaliplatin which is routinely administered during HIPEC procedures. The overall cell toxicity and cell detaching effects of EDTA are compared to those of Oxaliplatin and the additive effect is quantified. METHODS: HT-29 (ATCC® HTB-38™) cells were treated with A) EDTA only B) Oxaliplatin only and C) both agents using an in-vitro model. Cytotoxicity and cell detachment following EDTA application were measured via colorimetric MTS assay. Additionally, detached cell groups were visualized using light microscopy and further analyzed by means of electron microscopy. RESULTS: When solely applied, EDTA does not exhibit any cell toxicity nor does it add any toxicity to oxaliplatin. However, EDTA enhances the detachment of adherent colon carcinoma cells by removing up to 65% (p<0.05) of the total initial cell amount. In comparison, the sole application of highly concentrated oxaliplatin induced cell mortality by up to 66% (p<0.05). While detached cells showed no mortality after EDTA treatment, cell clusters exhibited a decreased amount of extracellular and adhesive matrix in-between cells. When combined, Oxaliplatin and EDTA display a significant additive effect with only 30% (mean p <0.01) of residual vitality detected in the initial well. EDTA and Oxaliplatin remove up to 81% (p <0.01) of adhesive HT-29 cells from the surface either by cytotoxic effects or cell detachment. CONCLUSION: Our data support EDTA's potential to remove microscopical tumor cell clusters from the peritoneum and possibly act as a supplementary agent in HIPEC procedures with chemotherapy. While adding EDTA to HIPEC procedures may significantly decrease the risk of PM recurrence, further in-vivo and clinical trials are required to evaluate this effect.


Assuntos
Antineoplásicos , Procedimentos Cirúrgicos de Citorredução , Ácido Edético/farmacologia , Hipertermia Induzida , Oxaliplatina/farmacologia , Terapia Combinada , Células HT29 , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual/terapia , Neoplasias Peritoneais/terapia
13.
Oncol Lett ; 17(6): 4921-4927, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31186701

RESUMO

Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has been introduced to the clinical setting as a novel approach for the treatment of peritoneal metastasis. The local interaction of chemoaerosol droplets with the peritoneal surface as well as their distribution pattern is considered the main advantage over conventional liquid intraperitoneal chemotherapy. The aim of the present study was to investigate the behavior of these aerosol particles during PIPAC application via electron microscopy. Solutions of doxycycline, liposomal doxorubicin and macrophage cells were aerosolized using an established ex-vivo model. PIPAC was performed on peritoneum samples via microcatheter (MC) at a pressure of 12 mmHg C02 at 27°C. Following PIPAC the surface structure of applied particles was measured via electron microscopy. The aerosol particle contact of doxycyclin created a nanofilm of ~200 nm height on the peritoneal surface, and this height was revealed to be independent of the size of the initial particle hitting. These nanofilm blocks of 'cylinders' are of different diameters depending on the initial aerosol particle hitting that spot. Diameters of these 'cylinders' are far wider than the original diameter of the initial aerosol particle. However, coated particles such as liposomal doxorubicin and macrophages remained intact following contact with the peritoneal surface. Based on this and other data, the concept that aerosol particles exhibit a gas-like behavior in the abdomen creating a therapeutic capnoperitoneum should be revised. Fluid aerosol particles collide with the peritoneum creating a nanofilm. The interaction of pressurized intraperitoneal aerosol on the peritoneum is therefore closer to the distribution of a liquid film than to that of a gas. Further studies are required to further analyze the interaction of this nanofilm on the peritoneum.

14.
World J Surg Oncol ; 17(1): 93, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159819

RESUMO

BACKGROUND: Besides its known antibacterial effect commonly used in intraperitoneal lavage, taurolidine has been observed to possess antineoplastic properties. In order to analyse this antineoplastic potential in a palliative therapeutic setting, taurolidine (TN) was compared to mitomycin C (MMC) and oxaliplatin (OX), known antineoplastic agents which are routinely used in intraperitoneal applications, following pressurized intra-peritoneal aerosol chemotherapy (PIPAC). METHODS: An in vitro model was established using a colon adenocarcinoma cell line (HT-29 human cells). Different experimental dosages of TN and combinations of TN, MMC, and OX were applied via PIPAC. To measure cell proliferation, a colorimetric tetrazolium reduction assay was utilized 24 h after PIPAC. RESULTS: We demonstrated a cytotoxic effect of TN and OX (184 mg/150 mL, p < 0.01) on tumor cell growth. An increasing dosage of TN (from 0.5 g/100 mL to 0.75 g/150 mL) correlated with higher cell toxicity when compared to untreated cells (p < 0.05 and p < 0.01, respectively). PIPAC with OX and both OX and TN (0.5 g/100 mL) showed the same cytotoxic effect (p < 0.01). No significant impact was observed for MMC (14 mg/50 mL, p > 0.05) or MMC with OX (p > 0.05) applied via PIPAC. CONCLUSIONS: The intraperitoneal application of TN is mostly limited to lavage procedures in cases of peritonitis. Our results indicate a substantial antineoplastic in vitro effect on colon carcinoma cells following PIPAC application. While this effect could be used in the palliative treatment of peritoneal metastases, further clinical studies are required to investigate the feasibility of TN application in such cases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Neoplasias Peritoneais/patologia , Aerossóis , Neoplasias do Colo/tratamento farmacológico , Humanos , Técnicas In Vitro , Mitomicina/administração & dosagem , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Pressão , Taurina/administração & dosagem , Taurina/análogos & derivados , Tiadiazinas/administração & dosagem , Células Tumorais Cultivadas
15.
J Cancer ; 9(23): 4301-4305, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519333

RESUMO

Background: This ex-vivo study was performed to compare the impact of doxorubicin vs. liposomal doxorubicin on penetration depth in peritoneal tissue during Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) via microcatheter (MC). Methods: Fresh post mortem swine peritoneum was cut into proportional sections. One group of samples was treated with PIPAC with Doxorubicin (D), and the other was treated with PIPAC with liposomal doxorubicin (LD). Tissue specimens were placed as follows: at the bottom of the plastic box (1), at the side wall (2), at the top cover (3) and the side of the box covered by a plastic tunnel (4). In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. Results: Medium penetration levels with D were 325 µm (1), 152 µm (2), 84 µm (3) and 71 µm (4), respectively. Medium penetration levels with LD were significantly lower with 10 µm (1), 2 µm (2), 0 µm (3) and 0 µm (4), respectively. In most samples that were treated with LD no doxorubicin could be detected at all. Conclusion: Our data indicate that liposomal coating of doxorubicin and possibly other chemotherapeutical drugs might inhibit their interaction with the peritoneal surface. This inhibition appears to be relatively strong, since doxorubicin is partially undetectable due to liposomal coating. Further studies are warranted to investigate this interaction and its potential benefit in peritoneal applications.

16.
In Vivo ; 32(6): 1369-1372, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30348690

RESUMO

BACKGROUND: Pressurized aerosol chemotherapy (PAC) is a novel approach to the treatment of surface malignancies. This study aimed to investigate whether PAC is a feasible treatment of early-stage bladder cancer. MATERIALS AND METHODS: PAC via inserted microcatheter was performed on a fresh urinary bladder in a post-mortem swine model (n=3), creating a pressurized doxorubicin chemoaerosol. Drug penetration of aerosolized doxorubicin at different concentrations (3 mg/50 ml, 9 mg/50 ml and 15 mg/50 ml) and different locations on the mucosa was measured via fluorescence microscopy. RESULTS: Mean endoluminal penetration rates for the urothelium following PAC reached 149±61 µm (using 15 mg/50 ml). Doxorubicin penetration was significantly increased with higher drug concentration (15 vs. 3 mg/50 ml: p<0.01). This study demonstrated the feasibility of PAC for intravesical use. CONCLUSION: PAC is a feasible minimally-invasive approach to the treatment of early-stage bladder cancer.


Assuntos
Aerossóis , Antineoplásicos/administração & dosagem , Pressão , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Animais , Modelos Animais de Doenças , Humanos , Microscopia de Fluorescência , Suínos , Distribuição Tecidual
17.
Anticancer Res ; 38(8): 4645-4649, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30061231

RESUMO

BACKGROUND/AIM: Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) is a new approach in the treatment of peritoneal carcinomatosis. With PIPAC currently limited to liquid chemotherapeutic solutions, this study aims to investigate whether the application range may be extended to the delivery of therapeutic nano- or microparticles. MATERIALS AND METHODS: Human serum, bacteria cultures and macrophage cells were aerosolized in an established ex vivo model. Human serum composition was analyzed via gel electrophoresis. The viability of bacteria and macrophage cells was measured prior to and following PIPAC. RESULTS: No structural disintegration of the plasma solution was detected. While the concentration and viability of Escherichia coli and Salmonella Enteritidis did not significantly change following aerosol formation, macrophage cells showed structural disintegration. CONCLUSION: Our ex vivo data suggest that PIPAC can be used to deliver complex particles. The delivery of small and less complex particles was feasible, yet the mechanical and physical properties of PIPAC might alter the stability of larger and more complex particles.


Assuntos
Aerossóis/administração & dosagem , Aerossóis/química , Neoplasias Peritoneais/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Humanos , Injeções Intraperitoneais/métodos , Macrófagos/efeitos dos fármacos , Nanopartículas/administração & dosagem , Nanopartículas/química , Peritônio/efeitos dos fármacos
18.
Anticancer Res ; 38(6): 3447-3452, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29848695

RESUMO

BACKGROUND/AIM: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is becoming an increasingly widespread approach for delivering intra-peritoneal chemotherapy (IPC) by means of a chemoaerosol. Currently, the aerosol dispersion is achieved by using a special micropump (MIP®). However, the delivery of a chemoaerosol into the abdominal cavity is not limited to the MIP®. This study aimed to investigate the feasibility, drug penetration and distribution of PIPAC via an established endoscopical microcatheter (MC). MATERIALS AND METHODS: An established ex vivo PIPAC model containing native fresh tissue samples of swine peritoneum was used to aerosolize doxorubicin at a pressure of 12 mm Hg CO2 at 27° degrees Celsius. On the top cover of the PIPAC chamber a MC device was installed via trocar. Tissue specimens were placed as follows: at the bottom of the plastic box (A), at the side wall (B), at the top (C) and the covered bottom (D) of the box. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. RESULTS: The mean depth of doxorubicin penetration was found to be significantly higher in tissue directly exposed to the aerosol jet. All samples had contact with doxorubicin. Penetration rates were: A: 348 (+/- 47 µm), B: 174 (+/- 64 µm), C: 92 (+/- 27 µm) and D: 84 (+/- 45) µm. CONCLUSION: Our ex vivo data suggest that PIPAC can be delivered via MC device. While local drug penetration is practically congruent to known PIPAC performance with MIP®, the MC offers a feasible, flexible, easy to handle and economic improvement compared to conventional PIPAC.


Assuntos
Aerossóis/administração & dosagem , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Peritônio/efeitos dos fármacos , Aerossóis/farmacocinética , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Cateteres , Doxorrubicina/farmacocinética , Endoscopia , Microscopia de Fluorescência , Peritônio/metabolismo , Pressão , Suínos , Distribuição Tecidual
19.
Foodborne Pathog Dis ; 14(4): 223-230, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28072918

RESUMO

Seventeen Staphylococcus aureus strains were tested for production of staphylococcal enterotoxin D (SED) and staphylococcal enterotoxin R (SER) in milk and meat juice. SED was secreted in milk by 12 S. aureus strains at 6-54 ng/mL at 24 h and 9-98 ng/mL at 48 h. Another five strains secreted SED at 0.9-1.9 µg/mL at 24 h and at 1.2-2.4 µg/mL at 48 h. Strains producing high levels of SED in milk secreted 77-666 µg/mL of SED in meat juice at 24 h and 132-1225 µg/mL at 48 h. Strains producing lower amounts of SED in milk secreted 228-1109 ng/mL of SED at 24 h and 377-1782 ng/mL at 48 h in meat juice. Tested S. aureus strains produced SER in milk at 33-183 ng/mL at 24 h and 41-832 ng/mL at 48 h. Fourteen strains produced more SER in meat juice than in milk (17- to 232-fold and 15- to 269-fold more at 24 and 48 h, respectively). Three S. aureus strains secreted less than 74 ng/mL of SER in meat juice. Expression pattern of known enterotoxin regulators, that is, agrA, sarA, hld, rot, and sigB, was similar in selected strong and weak SED producers grown in both food matrices and could not explain differences in enterotoxin protein level. This suggests that enterotoxin regulation is more complex than previously thought. We demonstrated that in a number of tested S. aureus strains, production of SED and SER was significantly decreased in milk when compared with meat juice, supporting previous reports. However, certain strains secreted high amounts of SED and SER, irrespective of environment, likely contributing to higher food safety risk.


Assuntos
Enterotoxinas/metabolismo , Carne/microbiologia , Leite/microbiologia , Staphylococcus aureus/isolamento & purificação , Animais , Enterotoxinas/genética , Análise de Alimentos , Contaminação de Alimentos/análise , Microbiologia de Alimentos , RNA Bacteriano/isolamento & purificação , Staphylococcus aureus/metabolismo
20.
Int J Food Microbiol ; 235: 36-45, 2016 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-27400451

RESUMO

Twenty Staphylococcus aureus strains harboring seh gene, including one carrying also sec gene and 11 sea gene, were grown in BHI+YE broth and milk and were tested for SEA, SEC and SEH production. All strains decreased pH of BHI+YE broth at 24h and increased them at 48h. Seventeen S. aureus strains grown in milk changed pH for no >0.3 unit until 48h. Three other S. aureus strains significantly decreased pH during growth in milk. All S. aureus produced SEH in BHI+YE broth in amounts ranging from 95 to 1292ng/ml, and from 170 to 4158ng/ml at 24 and 48h, respectively. SEH production in milk by 17 strains did not exceed 23ng/ml at 24h and 36ng/ml at 48h. Three S. aureus strains able to decrease milk pH produced 107-3029ng/ml and 320-4246ng/ml of SEH in milk at 24 and 48h, respectively. These strains were grown in milk and BHI+YE broth with pH stabilized at values near neutral leading to a significant decrease of SEH production. Representative weak SEH producers were grown in milk at reduced pH resulting in moderate increase in SEH production. SEA was produced in milk by 10S. aureus strains at 24-151ng/ml at 24h, and 31-303ng/ml at 48h. SEA production in milk was higher or comparable as in BHI+YE broth in 3 strains and lower for remaining strains. Production of SEC by sec-positive S. aureus strains was lower in milk than in BHI+YE broth, ranging from 131 to 2319ng/ml at 24 and 48h in milk and 296-30,087ng/ml in BHI+YE at 24 and 48h. Both lacE and lacG transcripts involved in lactose metabolism were significantly up-regulated in milk in strong SEH producers. In these strains hld, rot and sarA transcripts were up-regulated in milk as compared to weak SEH producers. Stabilization of milk pH at a value of raw milk significantly down-regulated hld, rot and sarA RNA in strong SEH producers. Milk was generally found unfavorable for enterotoxin production. However, certain S. aureus strains were not restricted in SEH and SEA expression in milk, unlike SEC which remained down-regulated in this environment. Therefore, low safety risk related to S. aureus producing SEC in milk, as suggested previously, may not pertain to certain SEA and SEH-producing strains.


Assuntos
Enterotoxinas/metabolismo , Leite/microbiologia , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidade , Animais , Enterotoxinas/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética
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