RESUMO
Hamburg is a growing metropolitan city. The increase in sealed surfaces of about 0.36% per year and the subsequent increased runoff impacts on the city's wastewater infrastructure. Further potential risks to the drainage infrastructure arise also from effects of climate change, e.g. increased intensity and frequency of heavy rainfalls. These challenges were addressed in the Rain InfraStructure Adaption (RISA) project conducted 2009-2015 by HAMBURG WASSER and the State Ministry for Environment and Energy, supported by several municipal stakeholders. RISA addressed intensifying conflicts in the context of urban development and stormwater management at that time. Major results of the project are improvements and recommendations for adequate consideration of stormwater management issues during urban planning as well as new funding mechanisms for stormwater management measures. The latter topic resulted in the introduction of a separated stormwater charge based on the amount of sealed area connected to the sewer system of each property. For both undertakings - the RISA project and the introduction of the separated stormwater charge - a novel, comprehensive, digital database was built. Today, these geographical information system (GIS)-based data offer various scale-independent analysis and information opportunities, which facilitate the day-to-day business of HAMBURG WASSER and stormwater management practice in Hamburg.
Assuntos
Cidades , Planejamento de Cidades , Engenharia Sanitária/economia , Engenharia Sanitária/métodos , Movimentos da Água , Mudança Climática , Meio Ambiente , Monitoramento Ambiental , Sistemas de Informação Geográfica , Alemanha , Chuva , Eliminação de Resíduos Líquidos/métodosRESUMO
Giant papillary conjunctivitis is an inflammation of the conjunctiva, which is associated with immunological-allergic disorders, but is difficult to integrate as a defined type of illness. The deposits of contact lenses are responsible in predisposed wearers. They induce a special immune answer to their biochemical ingredients. In addition, roughness of the superficial corneal layers and the conjunctiva, even without any contact lenses after filtrating glaucoma surgery, leads to mechanically induced papillary formations. In former days these symptoms of building giant papillae were seen mostly in wearers of soft hydrogel contact lenses. Nowadays manufacturers have developed contact lens systems with a variety of material components, with an increase of protein and lipid deposits. In combination with the observed non-compliance of wearers regarding lens exchange and contact lens hygiene, GPC is an issue which should be taken into consideration again.
Assuntos
Conjuntivite Alérgica/etiologia , Conjuntivite Alérgica/prevenção & controle , Lentes de Contato/efeitos adversos , Doenças Palpebrais/etiologia , Doenças Palpebrais/prevenção & controle , Imunossupressores/uso terapêutico , Soluções Oftálmicas/administração & dosagem , Conjuntivite Alérgica/diagnóstico , Doenças Palpebrais/diagnóstico , HumanosRESUMO
A 49-year-old woman presented with unspecific symptoms including polydipsia, increasing fatigue for several weeks, and vague abdominal pain. Serum calcium (5.30 mmol/l; normal range 2.00-2.60) and parathyroid hormone levels (> 2500.0 ng/l; normal range 15.0-68.0) were extremely elevated. Imaging studies showed a huge mediastinal tumor. Based on these findings a hypercalcemic crisis caused by primary hyperparathyroidism was diagnosed. After intensive care treatment and further diagnostic procedures, the patient's parathyroid adenoma was removed by parathyroidectomy. The postoperative course was uneventful.
Assuntos
Dor Abdominal/etiologia , Adenoma/complicações , Adenoma/diagnóstico , Fadiga/etiologia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico , Polidipsia/etiologia , Dor Abdominal/diagnóstico , Dor Abdominal/prevenção & controle , Adenoma/cirurgia , Diagnóstico Diferencial , Fadiga/diagnóstico , Fadiga/prevenção & controle , Feminino , Humanos , Neoplasias do Mediastino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Polidipsia/diagnóstico , Polidipsia/prevenção & controle , Resultado do TratamentoRESUMO
Keratitis is a rare but important and possibly sight threatening complication of Contact Lens wearing. Despite of the number of only about 1.7 keratitis cases per ophthalmolgist per year, this serious side effect needs knowledge and special diagnosis and treatment. Global changes of infectious agents and increase of previously unsuspicious pathogens in combination with a high degress of non-compliance indicate that Contact Lens wearing must be accompanied careful ophthalmologist's medical care and after-care.
Assuntos
Lentes de Contato/efeitos adversos , Ceratite/etiologia , Ceratite/prevenção & controle , Humanos , Ceratite/diagnósticoRESUMO
OBJECTIVES: To determine the effectiveness of a structured multidisciplinary non-surgical obesity therapy program on the basis of a temporary low-calorie-diet for 12 weeks, and additional intervention modules to enhance nutritional education, to increase physical activity and to modify eating behavior. DESIGN: Prospective multicenter observational study in obese individuals undergoing a medically supervised outpatient-based 52-week treatment in 37 centers in Germany. SUBJECTS: A total of 8296 participants with a body mass index (BMI) of >30 kg m(-2) included within 8.5 years. MEASUREMENTS: Main outcome measures were body weight loss, waist circumference (WC), blood pressure, quality of life and adverse events. RESULTS: In females, initial body weight was reduced after the 1-year-intervention by 19.6 kg (95% confidence intervals 19.2-19.9 kg) and in males by 26.0 kg (25.2-26.8) according to per protocol analysis of 4850 individuals. Intention-to-treat (ITT) analysis revealed a weight reduction of 15.2 kg (14.9-15.6) in females and 19.4 kg (18.7-20.1) in males. Overall, the intervention resulted in mean reduction in WC of 11 cm; it reduced the prevalence of the metabolic syndrome by 50% and the frequency of hypertension from 47 to 29% of all participants (ITT, all P<0.001). The beneficial effects could be documented for up to 3 years and comprised significant improvement of health-related quality of life. The incidence of adverse effects was low; the only event repeatedly observed and possibly related to either the intervention or the underlying disease was biliary disorders. CONCLUSION: The present non-surgical intervention program is a highly effective treatment of obesity grades I-III and obesity-related diseases, and therefore, could be a valuable basis for future weight maintenance strategies required for sustained success.
Assuntos
Peso Corporal , Restrição Calórica , Hipertensão/epidemiologia , Comunicação Interdisciplinar , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Qualidade de Vida , Programas de Redução de Peso/métodos , Adolescente , Adulto , Idoso , Restrição Calórica/métodos , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Hipertensão/dietoterapia , Masculino , Síndrome Metabólica/dietoterapia , Pessoa de Meia-Idade , Obesidade/dietoterapia , Estudos Prospectivos , Circunferência da Cintura , Adulto JovemAssuntos
Ceratocone/diagnóstico , Ceratocone/terapia , Lentes de Contato , Córnea/patologia , Substância Própria/patologia , Topografia da Córnea , Estudos Transversais , Progressão da Doença , Diagnóstico Precoce , Humanos , Incidência , Ceratocone/epidemiologia , Educação de Pacientes como Assunto , Fatores de Risco , Síndrome , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologiaRESUMO
The objective of this study was to investigate the pharmacokinetics of cefuroxime in wound secretion and the antibacterial activity of the traumatic wound secretion in patients receiving cefuroxime and in those not receiving antibiotics. Included in the present controlled, prospective, non-randomized study were 12 patients with an open fracture who needed vacuum therapy (group A) and 12 patients with a closed fracture, who, due to soft tissue damage, also underwent treatment with vacuum therapy (group B). Wound secretion was obtained on the first, third and fifth postoperative days and exposed to the test bacteria, Staphylococcus aureus and Staphylococcus epidermidis. Patients in group A underwent systemic antibiotic treatment with cefuroxime administered intravenously at a dose of 1.5 g every 8 hours. Patients in group B did not receive antibiotics. Cefuroxime concentrations were determined using high-performance liquid chromatography (HPLC). Antibacterial activity was determined using the inhibition test. Maximum cefuroxime concentrations in wound secretion were measured at 4-5 hours following intravenous administration and, with a mean concentration of 10 mg/l, remained consistently above the minimum inhibitory concentration (MIC) for the test bacteria at all points during the measurement period. As expected, the antibacterial activity of the wound secretion in patients in group A (cefuroxime) was higher than that in group B (no antibiotics). In group A, antibacterial activity against S. aureus was 94.6% and 100% against S. epidermidis. In group B, antibacterial activity against S. aureus was 61% and 81% against S. epidermidis. Cefuroxime reaches the highest level in wound secretion after 4 hours. The high antibacterial activity of the wound secretion in traumatic closed fractures is elevated by cefuroxime. in addition, our findings show that vacuum therapy of wounds is suitable as a non-invasive method for studying the pharmacokinetics of antibiotics.
Assuntos
Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Cefuroxima/farmacocinética , Cefuroxima/uso terapêutico , Fraturas Fechadas/terapia , Fraturas Expostas/terapia , Vácuo , Antibacterianos/administração & dosagem , Cefuroxima/administração & dosagem , Cromatografia Líquida de Alta Pressão , Fraturas Fechadas/microbiologia , Fraturas Expostas/microbiologia , Humanos , Infusões Intravenosas , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Infecção dos Ferimentos/prevenção & controleRESUMO
INTRODUCTION: Bronchial stump insufficiency (BSI) remains one of the most feared complications with an incidence of 0-12% in the literature. PATIENTS AND METHOD: The present retrospective study reviewed the medical records of 11 patients with BSI. Patients were divided into two groups, depending on treatment. In group A, 5 patients were treated initially unsuccessfully using other therapeutic procedures such pectoralis flap transposition, omentum majus transposition and fibrin glue applications and subsequently treated successfully with vacuum therapy (VT). In 6 patients (group B), only VT (a combination of bronchial suture, thoracoplasty, latissimus muscle transposition and VT) was performed. VT represents a closed dressing system allowing moist wound treatment in full contact with the wound surface as well as protection against contamination with nosocomial pathogens by means of continuous drainage of wound secretions. RESULTS: Of the 11 patients reviewed in this study, closure of the bronchial stump with VT was achieved in 8 patients. Of the 8 patients with successful closure of the bronchial stump, 4 patients were in group A and 4 in group B. CONCLUSION: Based on this preliminary experience, the combination of bronchial suture, thoracoplasty, latissimus muscle transposition and VT appears to be a promising concept for the management of bronchial stump insufficiency.
Assuntos
Fístula Brônquica/terapia , Tratamento de Ferimentos com Pressão Negativa , Pneumonectomia/efeitos adversos , Retalhos Cirúrgicos , Técnicas de Sutura , Toracoplastia , Fístula Brônquica/etiologia , Terapia Combinada , Feminino , Adesivo Tecidual de Fibrina/uso terapêutico , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Hybrid procedures for thoracoabdominal aortic aneurysms (TAAA) have been previously described as an attractive alternative to open reconstruction. PATIENTS AND METHODS: Between 1999 and 2009, 16 patients with a median age of 67years underwent hybrid repair of a TAAA (Crawford type I: 3, type II: 3, type III: 1, and type IV: 9). In 94%, 3 and more severe comorbidities were present, with previous aortic surgery in 56% of the patients; elective/urgent repair was done in 10 and emergent surgery in 6 patients. RESULTS: Primary technical success was 100%, with 31 vessels grafted. Elective/urgent mortality was 20% (2 of 10) and emergent mortality 50% (3 of 6). During follow-up time (median: 12 months) 2 patients died and 2 patients had to undergo secondary interventions. CONCLUSION: In high-risk patients especially after prior aortic surgery hybrid repair of TAAA is feasible. However, due to high mortality rates especially in the emergent situation this procedure should be reserved only for decidedly selected patients.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular , Adulto , Idoso , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Procedimentos Cirúrgicos Eletivos , Tratamento de Emergência , Estudos de Viabilidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Reoperação , Medição de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Contact lens fitting for presbyotic patients needs more than simple fitting shill; patients need additional psychological support. The wearer has to accept optical quality reduction due to the multifocality of the lens design. In general, the technical fitting of presbyotic contact lenses is comparable to monofocal systems. They work with the same rules of performance. The difference lies in the principles of correction by the lens itself. Simple presbyotic systems use uncorrected optical aberration to widen depth perception. These lenses are suitable for young presbyopes, up to a need of 1 diopter plus power for near vision. Uncorrected aspherical designs have a multifocal effect which can be used for presbyotic lenses. There are contact lenses on the market with simultaneous imaging, which is based on concentric rings around the near or distance centre. Another principles are based on segmented reading portions in the lower part of the lens, also called alternating systems. These very few design variations are the basis for the various specific models which are sold on the market today. The results of the fitting can never be foreseen as subjective and psychological aspects of the wearer overlay the objective results. Thus, the fitter needs experience and patient understanding, combined with fundamental knowledge of the specific lens type used.
Assuntos
Lentes de Contato , Presbiopia/diagnóstico , Presbiopia/reabilitação , Ajuste de Prótese/métodos , Humanos , Satisfação do Paciente , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Desenho de PróteseRESUMO
Treating obesity can significantly reduce morbidity and mortality. Successful treatments comprise interdisciplinary long-term programs. The combined skills of physicians, psychologists, physiotherapists and dieticians are necessary to modify the patient's eating habits. With regard to dietetic measures, the combination of formula diets followed by reduction diets (CLD) has proved successful. Behavioral therapy in combination with professional physiotherapy can reduce the failure rate. In the event that dietetic measures fail, the medications sibutramine, orlistat and rimonabant are available.
Assuntos
Dieta Redutora , Jejum , Alimentos Formulados , Obesidade/dietoterapia , Terapia Combinada , Ingestão de Energia , Exercício Físico , HumanosRESUMO
Information on the regulation of steroid hormone receptors and their distinct functions within the human endometrial epithelium is largely unavailable. We have immortalized human primary endometrial epithelial cells (EECs) isolated from a normal proliferative phase endometrium by stably transfecting the catalytic subunit (hTERT) of the human telomerase complex and cultured these hTERT-EECs now for over 350 population doublings. Active hTERT was detected in hTERT-EECs employing the telomerase repeat amplification assay protocol. hTERT-EECs revealed a polarized, non-invasive epithelial phenotype with apical microvilli and production of a basal lamina when grown on a three-dimensional collagen-fibroblast lattice. Employing atomic force microscopy, living hTERT-EECs were shown to produce extracellular matrix (ECM) components and ECM secretion was modified by estrogen and progesterone (P4). hTERT-EECs expressed inducible and functional endogenous estrogen receptor-alpha (ER-alpha) as demonstrated by estrogen response element reporter assays and induction of P4 receptor (PR). P4 treatment down-regulated PR expression, induced MUC-1 gene activity and resulted in increased ER-beta transcriptional activity. Gene activities of cytokines and their receptors interleukin (IL)-6, leukemia inhibitory factor (LIF), IL-11 and IL-6 receptor (IL6-R), LIF receptor and gp130 relevant to implantation revealed a 17 beta-estradiol (E2)-mediated up-regulation of IL-6 and an E2- and P4-mediated up-regulation of IL6-R in hTERT-EECs. Thus, hTERT-EECs may be regarded as a novel in vitro model to investigate the role of human EECs in steroid hormone-dependent normal physiology and pathologies, including implantation failure, endometriosis and endometrial cancer.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Endométrio/citologia , Células Epiteliais/fisiologia , Receptor alfa de Estrogênio/metabolismo , Receptores de Progesterona , Receptores de Esteroides/metabolismo , Telomerase/metabolismo , Biomarcadores , Domínio Catalítico , Técnicas de Cultura de Células , Polaridade Celular , Células Cultivadas , Células Epiteliais/citologia , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Estrogênios/metabolismo , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Feminino , Genes Reporter , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Ligantes , Mucina-1/genética , Mucina-1/metabolismo , Fenótipo , Progesterona/metabolismo , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismoRESUMO
The interaction of synthetic polynucleotide double strands with a natural lipid, oleic acid, was examined in diluted aqueous solutions by circular dichroism spectra, UV-absorption measurements, and surface plasmon resonance biosensor investigations. The investigations were performed with defined double and triple stranded oligo- and polydeoxyribonucleotides. Whereas duplexes are influenced by oleic acid ligandation, which could not be removed by ethanol dialysis procedure, no binding occurs to triple stranded DNA. The spectroscopic results indicate that oleic acid shows molecular recognition to AT b.p. motifs by groove binding. GC tracts - in particular alternating d[G-C] motifs - are strongly influenced by ligand interaction up to a ratio of one molecule per two base pairs. Likewise, the spectroscopic and morphologic changes in the supramolecular association of the complexes after treatment occur even after dialysis procedure. This was monitored with scanning force microscopy (SFM) as well. Additionally, monolayers of biotinylated DNA duplexes were immobilized on a streptavidin sensor-layer for surface plasmon resonance (SPR) observations. Small portions of the ligand were injected in continuous flow. Loosely bound molecules were removed by washing procedure. Injections of sodium hydroxide denature the DNA, releasing the tightly bound effectors. The amount of tightly bound oleic acid molecules was determined at one molecule per 2-3 base pairs. As consequence, a new mechanism of regulation of gene expression at nuclear membrane or by lipids inside DNA double helix has to be discussed.
Assuntos
DNA Complementar/metabolismo , Ácido Oleico/química , Ressonância de Plasmônio de Superfície , Pareamento de Bases , Dicroísmo Circular , DNA Complementar/química , DNA Complementar/efeitos dos fármacos , Ligantes , Substâncias Macromoleculares , Microscopia de Força Atômica , Conformação de Ácido Nucleico , Desnaturação de Ácido Nucleico , Ácidos Nucleicos Heteroduplexes/química , Ácidos Nucleicos Heteroduplexes/metabolismo , Ácido Oleico/metabolismo , Oligonucleotídeos/química , Polidesoxirribonucleotídeos/química , Polidesoxirribonucleotídeos/metabolismo , Hidróxido de Sódio/farmacologia , Soluções , Espectrofotometria Ultravioleta , Estreptavidina/química , Estreptavidina/metabolismo , Água/metabolismoRESUMO
The structures and formation energies of nucleic acid-phospholipid complexes both in the absence and in the presence of Mg(2+) ions were calculated taking double-stranded trinucleoside diphosphates NpNpN or heptanucleotides ApAp(NpNpN)pApA, composed of 64 possible combinations of genetic code, and phosphatidylcholine (PC) and sphingomyelin (SM) as model compounds. The dependence of intramolecular interactions on the primary structure of nucleic acid molecules and on the presence of a cationic bridge was revealed. The formation energies and structure of oligonucleotides were found by molecular mechanics calculations with the AMBER force field. The structures of phospholipid and MgCl(2) molecules were calculated by the semiempirical PM3 method, while the energies of phospholipid-oligonucleotide complexes were calculated by the molecular mechanics method. Calculations of complexes were carried out with consideration of solvation effects. Considerable gain in the formation energy of triple complexes is achieved due to the presence of the electroneutral metal bridge. A tendency toward increasing the stability of "triple" PC complexes (but not SM ones), containing guanosine- and cytidine-enriched triplets was revealed. Depending on the structure of NpNpN trinucleotides, the formation energy values of NpNpN-MgCl(2)-PC and ApAp(NpNpN)pApA-MgCl(2)-PC complexes differ by 1.7-2.6 kcal mol(-1), which can be considered as the atomic-scale manifestation of the recognition phenomenon. Presence of metal (II) ion bridge results in a greater stabilization of the phospholipid-nucleic acid complexes for SM in comparison to PC (the total energy difference equals to 4-16 kcal mol(-1)). Depending on the structure of NpNpN trinucleotides, the formation energies of NpNpN-MgCl(2)-SM and ApAp(NpNpN)pApA-MgCl(2)-SM complexes differ by 1.7-2.1 kcal.mol(-1), which is essential at physiological conditions and can also be considered as the recognition effect.
Assuntos
DNA/metabolismo , Magnésio/metabolismo , Fosfolipídeos/metabolismo , Sequência de Bases , Cátions Bivalentes , DNA/química , Metabolismo dos Lipídeos , Lipídeos/química , Magnésio/química , Modelos Moleculares , Conformação de Ácido Nucleico , Oligodesoxirribonucleotídeos/química , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Esfingomielinas/química , Esfingomielinas/metabolismo , TermodinâmicaRESUMO
The interactions of various low-molecular weight substances with DNA are naturally relevant mechanisms in the cellular cycle and so also used in medicinal treatment. Depending on the particular drug structure, DNA-binding modes like groove-binding, intercalating and/or stacking, give rise to supramolecular assemblies of the polynucleotides, as well as influence the DNA-protein binding. In this review, we compare the underlying molecular structures, including general aspects of DNA sequences, with the benefit in medicinal treatment. While so far interest in this field had mainly been devoted to isolated nucleic acid/drug interactions, the present paper will focus on drug efficiencies generating and influencing supramolecular organizations and their complex sequence-dependent structure-activity codes. In particular, the attention will be directed to stereoelectronic relationships. Spatial enantioselective properties are discussed in details. As examples, the drug self-assemblies, as well as the influence of drugs on supramolecular DNA formations are described. A hypothetical connection between drug-influenced DNA-toroids and the formation of micronuclei in tissues will be interpreted.
Assuntos
Proteínas de Ligação a DNA/química , DNA/metabolismo , Desenho de Fármacos , Substâncias Intercalantes/química , Ligação Competitiva , Modelos Moleculares , Relação Estrutura-AtividadeRESUMO
BACKGROUND: The microbiological examination of contact lens storage solutions may reveal the etiological organisms responsible for keratitis and additionally harbour environmental contaminants. PATIENTS AND METHODS: From 1995 to 1998, conjunctival and corneal smears and scrapes, as well as the storage solutions of 55 soft contact lens wearers were examined microbiologically in a prospective non-randomised cohort study involving 53x unilateral and 2x bilateral cases of keraitis. RESULTS: In 42 of the in-use contact lens storage solutions, the following organisms were found: 8x Bacillus sp., 7x P. aeruginosa and 8x other pseudomonads, 6x Alcaligenes xylosans, 4x Serratia liquefaciens, 4x Enterobacter sp., 4x coagulase negative staphylococci, 3x Serratia marcescens, 3x S. aureus, 2x Streptococcus faecalis, 1x Klebsiella oxytoca and 5x Acanthameba. A significant correlation of ocular cultures was found for Pseudomonas, Enterobacter, Serratia, S. aureus, S. faecalis and Acanthameba, but not for Bacillus, Alcaligenes, and coagulase negative staphylococci. Fungi were not found. The more pronounced the clinical picture, the more Gram-negative bacteria were isolated. CONCLUSIONS: The microbiological examination of soft contact lens storage solutions of 55 keratitis patients confirmed that the microbes responsible were to be found in the fluid, in addition to environmental contaminants.
Assuntos
Bactérias/isolamento & purificação , Túnica Conjuntiva/microbiologia , Soluções para Lentes de Contato/efeitos adversos , Lentes de Contato Hidrofílicas/microbiologia , Córnea/microbiologia , Ceratite/etiologia , Ceratite por Acanthamoeba/etiologia , Estudos de Coortes , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Estudos Prospectivos , Fatores de RiscoRESUMO
Cells from human head-neck squamous cell carcinoma (hypopharynx, UMSCC11, and UMSCC22) and lung tumor (alveolus, UMSCC7) were investigated by light and scanning force microscopy (SFM) observation. In the present study a less-invasive contact mode was used to scan living cells in air covered with a thin fluid layer. The investigations were done without any pretreatment of the specimens for such observations as chemical fixation, or staining. Untreated tumor cells, and those treated with the antitumor drug hematoporphyrin IX derivative (HpD) were studied without photosensitizing. Additionally, the temperature influence on cell proliferation was studied. Three-dimensional topographic images and their magnifications offer highly informative insights into the untreated cell surface. In the present study, the cell structure destruction and cell death could partly be visualized by observing the head-neck tumor cells incubated with HpD. Most of the drug-treated head-neck tumor cells died (only 2%-5% of survivors). However, HpD could not affect cells of the lung tumor cell type. They, well known as more resistant against oxidation processes, survived to a great extent. Also, no distortion of the membrane under drug treatment could be observed. The possibilities and limits in the use of SFM for studying the topography of cell surfaces are presented in many details.
Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/patologia , Éter de Diematoporfirina/farmacologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Pulmonares/patologia , Microscopia de Força Atômica/métodos , Artefatos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Divisão Celular/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Fotorradiação com Hematoporfirina , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Temperatura , Células Tumorais CultivadasRESUMO
Several 2.7-bis-[(dialkylamino)-acetylamino]-fluoren-9-one derivatives (fluoramides) were synthesized as analogues of the DNA binding compound tilorone (2,7-bis[(diethylamino)-ethoxy]-fluoren-9-one). Previous studies showed the drugs to induce cytokines and inhibit reverse transcription. Here, their binding to DNA was evaluated using UV and circular dichroism studies. Like tilorone, the fluoramides derivatives also intercalate resulting in increased Tm values and new CD signatures. A preference to alternating A-T and G-C sequences was detected; only minor interaction to homologous sequences was observed. Moreover, no upper limit in the drug/DNA ratio was found, testing limit being the precipitation of the drug. However, surface plasmon resonance (SPR) studies of tilorone and 2,7-bis-[(dipropylamino)-acetyl-amino]-fluoren-9-one, indicate an astonishing drug/base pair ratio (r > 1), which point to a multitude of interactions under SPR conditions. Molecular modeling calculations, where the geometries of the complexes optimized under the assumption of intercalative and multitude of suprahelical arrangements, rationalize the observations. Based on the thermodynamic and biological studies, a structure-function model is proposed.
Assuntos
DNA/metabolismo , Fluorenos/química , Ácidos Nucleicos/química , Animais , Bovinos , Dicroísmo Circular , Simulação por Computador , Ligantes , Modelos Químicos , Modelos Moleculares , Espectrofotometria , Relação Estrutura-Atividade , Ressonância de Plasmônio de Superfície , Termodinâmica , Timo/metabolismo , Raios UltravioletaRESUMO
Amphiphilic complementary nucleobase derivatives, containing n-octadecyloxymethyl substituents at the N1 position of pyrimidine and N9 of purine, dissolved in chloroform form non-specific lyotropic mesophases, which were analyzed by optical polarizing microscopy. Molecular modeling studies visualize hypothetical horizontal and vertical nucleobase hydrogen-bonding and stacking arrangements, as well as aliphatic long-chain interstrand interaction.
Assuntos
DNA/química , DNA/síntese química , Nucleosídeos/síntese química , Clorofórmio/química , Ligação de Hidrogênio , Microscopia de Polarização , Modelos Moleculares , Conformação de Ácido NucleicoRESUMO
The bifunctionally reactive nucleoside and distant nucleoside analogs adenosine (Ado), S-[(adenine-9-yl)methoxyethyl]-L-cysteine (Na-salt) (cysA) and 9-vinyladenine (vA) in aqueous solutions assemble on complementary polyuridylic acid templates to form complex lyomesophases. The systems are investigated by polarizing microscopy, differential scanning calorimetry (DSC) and 1H- and 31P-nmr spectroscopies, assisted by molecular modeling studies. The results indicate the importance of biomesogenic (pre)ordering in nucleic acid native and artificial matrix reactions.