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1.
Commun Biol ; 6(1): 217, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36823431

RESUMO

Tissue mechanics determines tissue homeostasis, disease development and progression. Bladder strongly relies on its mechanical properties to perform its physiological function, but these are poorly unveiled under normal and pathological conditions. Here we characterize the mechanical fingerprints at the micro-scale level of the three tissue layers which compose the healthy bladder wall, and identify modifications associated with the onset and progression of pathological conditions (i.e., actinic cystitis and bladder cancer). We use two indentation-based instruments (an Atomic Force Microscope and a nanoindenter) and compare the micromechanical maps with a comprehensive histological analysis. We find that the healthy bladder wall is a mechanically inhomogeneous tissue, with a gradient of increasing stiffness from the urothelium to the lamina propria, which gradually decreases when reaching the muscle outer layer. Stiffening in fibrotic tissues correlate with increased deposition of dense extracellular matrix in the lamina propria. An increase in tissue compliance is observed before the onset and invasion of the tumor. By providing high resolution micromechanical investigation of each tissue layer of the bladder, we depict the intrinsic mechanical heterogeneity of the layers of a healthy bladder as compared with the mechanical properties alterations associated with either actinic cystitis or bladder tumor.


Assuntos
Cistite , Neoplasias da Bexiga Urinária , Ratos , Animais , Bexiga Urinária , Cistite/patologia , Matriz Extracelular , Neoplasias da Bexiga Urinária/patologia
3.
J Fluoresc ; 22(4): 1151-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22488046

RESUMO

Cellular membranes have relevant roles in processes related to proteases like human kallikreins and cathepsins. As enzyme and substrate may interact with cell membranes and associated co-factors, it is important to take into account the behavior of peptide substrates in the lipid environment. In this paper we report an study based on energy transfer in two bradykinin derived peptides labeled with the donor-acceptor pair Abz/Eddnp (ortho-aminobenzoic acid/N-[2,4-dinitrophenyl]-ethylenediamine). Time-resolved fluorescence experiments were performed in phosphate buffer and in the presence of large unilamelar vesicles of phospholipids, and of micelles of sodium dodecyl sulphate (SDS). The decay kinetics were analyzed using the program CONTIN to obtain end-to-end distance distribution functions f(r). Despite of the large difference in the number of residues the end-to-end distance of the longer peptide (9 amino acid residues) is only 20 % larger than the values obtained for the shorter peptide (5 amino acid residues). The proline residue, in position 4 of the bradykinin sequence promotes a turn in the longer peptide chain, shortening its end-to-end distance. The surfactant SDS has a strong disorganizing effect, substantially broadening the distance distributions, while temperature increase has mild effects in the flexibility of the chains, causing small increase in the distribution width. The interaction with phospholipid vesicles stabilizes more compact conformations, decreasing end-to-end distances in the peptides. Anisotropy experiments showed that rotational diffusion was not severely affected by the interaction with the vesicles, suggesting a location for the peptides in the surface region of the bilayer, a result consistent with small effect of lipid phase transition on the peptides conformations.


Assuntos
Bradicinina/química , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Fosfolipídeos/metabolismo , Lipossomas Unilamelares/metabolismo , Sequência de Aminoácidos , Dimiristoilfosfatidilcolina/metabolismo , Cinética , Micelas , Fosfatidilgliceróis/metabolismo , Ligação Proteica , Espectrometria de Fluorescência , Água/química
5.
Minerva Pediatr ; 60(6): 1401-9, 2008 Dec.
Artigo em Italiano | MEDLINE | ID: mdl-18971901

RESUMO

Contrary to common believing, the prevalence of the intolerance to food additives in the general population is rather low. Nowadays many doubts persist with regard both to the pathogenetic mechanisms and to the clinical and diagnostic aspects in this field. Symptoms due to, or exacerbated from, food additives usually involve non-IgE-mediate mechanisms (pseudo-allergic reactions, PAR) and are usually less severe of those induced by food allergy. The most frequent clinical feature of the intolerance to food additives still remains the urticaria-angioedema syndrome, although these substances are really involved only in a minority of patients. Other possible clinical features include anaphylaxis, atopic eczema, behaviour disturbances, asthma and non-allergic rhinitis. The diagnostic approach consists in diary cards, reporting symptoms and food habits, elimination diet and double blinded placebo-controlled oral challenge with suspected additives. However, such procedure still remains poorly standardized and numerous uncertainties persist with regard to optimal conditions for performing and interpret the challenge results. The therapeutic approach consists in the exclusion of foods and products containing the additive involved, and, in patients not compliant to the diet, in treatment with symptomatic drugs.


Assuntos
Aditivos Alimentares/efeitos adversos , Hipersensibilidade Alimentar , Alérgenos , Criança , Aditivos Alimentares/análise , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/dietoterapia , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/terapia , Humanos , Prevalência , Testes Cutâneos , Fatores de Tempo , Urticária/etiologia
6.
Monaldi Arch Chest Dis ; 57(2): 147, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12357848

RESUMO

In the last few years the findings on allergic inflammation have improved, particularly in cellular signaling. Now we know that cytokines and other mediators are a network able to regulate the allergic inflammation (and inflammation in general). The new findings are important not only for basic science but also for the development of new therapeutic approaches to allergic diseases.


Assuntos
Hipersensibilidade/imunologia , Inflamação/imunologia , Humanos
8.
J Comput Biol ; 7(3-4): 537-58, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11108478

RESUMO

High-throughput, data-directed computational protocols for Structural Genomics (or Proteomics) are required in order to evaluate the protein products of genes for structure and function at rates comparable to current gene-sequencing technology. This paper presents the JIGSAW algorithm, a novel high-throughput, automated approach to protein structure characterization with nuclear magnetic resonance (NMR). JIGSAW applies graph algorithms and probabilistic reasoning techniques, enforcing first-principles consistency rules in order to overcome a 5-10% signal-to-noise ratio. It consists of two main components: (1) graph-based secondary structure pattern identification in unassigned heteronuclear NMR data, and (2) assignment of spectral peaks by probabilistic alignment of identified secondary structure elements against the primary sequence. Deferring assignment eliminates the bottleneck faced by traditional approaches, which begin by correlating peaks among dozens of experiments. JIGSAW utilizes only four experiments, none of which requires 13C-labeled protein, thus dramatically reducing both the amount and expense of wet lab molecular biology and the total spectrometer time. Results for three test proteins demonstrate that JIGSAW correctly identifies 79-100% of alpha-helical and 46-65% of beta-sheet NOE connectivities and correctly aligns 33-100% of secondary structure elements. JIGSAW is very fast, running in minutes on a Pentium-class Linux workstation. This approach yields quick and reasonably accurate (as opposed to the traditional slow and extremely accurate) structure calculations. It could be useful for quick structural assays to speed data to the biologist early in an investigation and could in principle be applied in an automation-like fashion to a large fraction of the proteome.


Assuntos
Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Proteínas de Neoplasias , Proteína Dissulfeto Redutase (Glutationa) , Estrutura Secundária de Proteína , Algoritmos , Biologia Computacional , Gráficos por Computador , Impressões Digitais de DNA , Proteínas de Ligação a DNA/química , Glutarredoxinas , Humanos , Modelos Moleculares , Oxirredutases/química , Proteoma/química , Alinhamento de Sequência , Software , Fatores de Transcrição/química
9.
Structure ; 7(10): 1247-56, 1999 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-10545320

RESUMO

BACKGROUND: CBFA is the DNA-binding subunit of the transcription factor complex called core binding factor, or CBF. Knockout of the Cbfa2 gene in mice leads to embryonic lethality and a profound block in hematopoietic development. Chromosomal disruptions of the human CBFA gene are associated with a large percentage of human leukemias. RESULTS: Utilizing nuclear magnetic resonance spectroscopy we have determined the three-dimensional fold of the CBFA Runt domain in its DNA-bound state, showing that it is an s-type immunoglobulin (Ig) fold. DNA binding by the Runt domain is shown to be mediated by loop regions located at both ends of the Runt domain Ig fold. A putative site for CBFB binding has been identified; the spatial location of this site provides a rationale for the ability of CBFB to modulate the affinity of the Runt domain for DNA. CONCLUSIONS: Structural comparisons demonstrate that the s-type Ig fold found in the Runt domain is conserved in the Ig folds found in the DNA-binding domains of NF-kappaB, NFAT, p53, STAT-1, and the T-domain. Thus, these proteins form a family of structurally and functionally related DNA-binding domains. Unlike the other members of this family, the Runt domain utilizes loops at both ends of the Ig fold for DNA recognition.


Assuntos
Proteínas de Ligação a DNA/química , Proteínas Proto-Oncogênicas , Proteínas de Protozoários , Fatores de Transcrição/química , Animais , Sítios de Ligação , Subunidade alfa 2 de Fator de Ligação ao Core , DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Imunoglobulinas/química , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Knockout , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Estrutura Terciária de Proteína , Termodinâmica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
J Mol Biol ; 292(1): 151-61, 1999 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-10493864

RESUMO

The reduction equivalents necessary for the ribonucleotide reductase (RNR)-catalyzed production of deoxyribonucleotides are provided by glutaredoxin (Grx) or thioredoxin (Trx). The initial location for transfer of reducing equivalents to RNR is located at the C terminus of the B1 subunit and involves the reduction of a disulfide between Cys754 and Cys759. We have used a 25-mer peptide corresponding to residues 737-761 of RNR B1 (C754-->S) to synthesize a stable mixed disulfide with Escherichia coli Grx-1 (C14-->S) resembling the structure of an intermediate in the reaction. The high-resolution solution structure of the mixed disulfide has been obtained by NMR with an RMSD of 0.56 A for all the backbone atoms of the protein and the well-defined portion of the peptide. The binding interactions responsible for specificity have been identified demonstrating the importance of electrostatic interactions in this system and providing a rationale for the specificity of the Grx-RNR interaction. The disulfide is buried in this complex, implying a solely intra-molecular mechanism of reduction in contrast to the previously determined structure of the glutathione complex where the disulfide was exposed; mutagenesis studies have shown the relevance of intermolecular reduction processes. Substantial conformational changes in the helices of the protein are associated with peptide binding which have significant mechanistic implications for protein disulfide reduction by glutaredoxins.


Assuntos
Dissulfetos/química , Oxirredutases , Proteínas/química , Proteínas de Bactérias/química , Escherichia coli/enzimologia , Glutarredoxinas , Glutationa/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Mutagênese , Oxirredução , Fragmentos de Peptídeos/química , Conformação Proteica , Estrutura Secundária de Proteína , Ribonucleotídeo Redutases/química , Eletricidade Estática
11.
Toxicol Pathol ; 27(3): 295-306, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10356706

RESUMO

Naproxen sodium was administered to cynomolgus monkeys (Macaca fascicularis) by oral gavage at daily doses of 44, 88, or 176 mg/kg for 2 wk (2 monkeys/gender) or of 44 mg/kg for 13 wk (4 monkeys/gender). Body weight loss occurred in at least one monkey in all naproxen sodium-dosed groups in the 2-wk (up to 16% loss) and 13-wk (up to 22% loss) studies. Increases in plasma naproxen concentrations were dose proportional between 44 and 88 mg/kg but were less than dose proportional between 88 and 176 mg/kg. Up to 2-fold increases in creatinine and/or serum urea nitrogen values as well as higher renal weights occurred in monkeys receiving 176 mg/kg for 2 wk or 44 mg/kg for 13 wk. Microscopically, renal changes were observed in all naproxen sodium-dosed groups. Renal findings after 2 wk of exposure included increased interstitial ground substance, tubular dilatation, and tubulointerstitial nephritis; in the 13-wk study, cortical tubular atrophy and interstitial fibrosis were also observed. These studies identify the kidney as the target organ of naproxen sodium in cynomolgus monkeys.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Túbulos Renais/efeitos dos fármacos , Naproxeno/toxicidade , Nefrite Intersticial/induzido quimicamente , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Nitrogênio da Ureia Sanguínea , Tecido Conjuntivo/efeitos dos fármacos , Tecido Conjuntivo/patologia , Creatinina/sangue , Relação Dose-Resposta a Droga , Feminino , Túbulos Renais/patologia , Macaca fascicularis , Masculino , Naproxeno/farmacocinética , Nefrite Intersticial/patologia , Tamanho do Órgão/efeitos dos fármacos , Projetos Piloto
12.
Int J Dev Neurosci ; 17(2): 121-30, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10221671

RESUMO

L1 is a murine multidomain glycoprotein implicated in cell aggregation, fasciculation. neurite outgrowth and synaptogenesis. Laminin, a trimeric polypeptide, is implicated in neuronal survival, growth cone guidance, neurite outgrowth and cell differentiation. Laminin can also interact with the cell adhesion molecule L1. Their expressions were investigated from embryonic day 15 (E15) to adult in the rat hypophysis, and in adult neurohemal zones. Detected in the neural lobe from E17, the L1 immunoreactivity increased during prenatal development and persisted in adulthood mainly related to the neuropeptidergic fibers. Pituicytes were only labelled on the plasmalemma apposed to axons. In the intermediate lobe, L1 appeared at birth on folliculo-stellate cells extensions, constituting a network which densified during postnatal development. L1 is also expressed in all neurohemal areas on neuronal profiles. Laminin was clearly detectable in the hypophysis at E15 before the first blood vessels penetrate the Rathke pouch. At E20, all the basal membranes of the blood vessels were stained. In the intermediate lobe, a spotted laminin immunoreactivity was detected at E21. At this stage, we observed the staining of intercellular spaces and the intracellular labelling of melanotrophs, concerning reticulum or vesicles. The staining of melanotrophs seemed to maintain during adulthood. In contrast with blood vessels of the adult cerebral tissue, adult capillaries of the neural lobe and the others neuro-hemal zones were intensely labelled with the anti-laminin antibody. These results suggest that neurite outgrowth and neurite guidance could be promoted by L1 and laminin in the neurointermediate lobe. The "intercellular tunnels" could also be an important guidance cue for migrating cells in the intermediate lobe. These data also demonstrate that melanotrophic cells. secreting the laminin, have a role in the ontogenesis of the gland. Finally, we suggest that L1 and laminin can collaborate to reinforce "neurons-capillaries" interactions in neurohemal zones.


Assuntos
Proteínas Fetais/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Laminina/biossíntese , Glicoproteínas de Membrana/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Moléculas de Adesão de Célula Nervosa/biossíntese , Sistemas Neurossecretores/embriologia , Hipófise/embriologia , Animais , Movimento Celular , Proteínas Fetais/genética , Idade Gestacional , Hipotálamo/embriologia , Hipotálamo/crescimento & desenvolvimento , Hibridização In Situ , Laminina/genética , Complexo Antígeno L1 Leucocitário , Glicoproteínas de Membrana/genética , Neovascularização Fisiológica , Proteínas do Tecido Nervoso/genética , Moléculas de Adesão de Célula Nervosa/genética , Neuritos/fisiologia , Sistemas Neurossecretores/crescimento & desenvolvimento , Sistemas Neurossecretores/metabolismo , Hipófise/irrigação sanguínea , Hipófise/crescimento & desenvolvimento , Hipófise/inervação , Hipófise/metabolismo , Ratos , Ratos Wistar
13.
Ann Ital Chir ; 69(4): 421-5, 1998.
Artigo em Italiano | MEDLINE | ID: mdl-9835114

RESUMO

Epidemiology for diverticular disease of the colon is rather difficult to assess because of the almost regularly selection of the patients submitted to analysis and described in literature. Therefore data extracted from different experiences are useful only for orientative epidemiologic implications. In the meanwhile these studies have been very useful to understand the possible reasons of its insurgence and evolution. Actually for etiopathogenesis the more diffuse opinion is to give importance to low fibre diet and to intrinsic motor derangement of the colon.


Assuntos
Divertículo do Colo/epidemiologia , Divertículo do Colo/etiologia , Divertículo do Colo/patologia , Divertículo do Colo/fisiopatologia , Saúde Global , Humanos , Incidência
14.
J Mol Biol ; 280(4): 687-701, 1998 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-9677297

RESUMO

The determination of the nuclear magnetic resonance (NMR) solution structure of fully reduced human glutaredoxin is described. A total of 1159 useful nuclear Overhauser effect (NOE) upper distance constraints and 187 dihedral angle constraints were obtained as the input for the structure calculations for which the torsion angle dynamics program DYANA has been utilized followed by energy minimization in water with the AMBER force field as implemented in the program OPAL. The resulting 20 conformers have an average root-mean-square deviation value relative to the mean coordinates of 0.54 A for all the backbone atoms N, Calpha and C', and of 1.01 A for all heavy atoms. Human glutaredoxin consists of a four-stranded mixed beta-sheet composed of residues 15 to 19, 43 to 47, 72 to 75 and 78 to 81, and five alpha-helices composed of residues 4 to 9, 24 to 34, 54 to 65, 83 to 91, and 94 to 100. Comparisons with the structures of Escherichia coli glutaredoxin-1, pig liver glutaredoxin and human thioredoxin were made. Electrostatic calculations on the human glutaredoxin structure and that of related proteins provide an understanding of the variation of pKa values for the nucleophilic cysteine in the active site observed among these proteins. In addition, the high-resolution NMR solution structure of human glutaredoxin has been used to model the binding site for glutathione and for ribonucleotide reductase B1 by molecular dynamics simulations.


Assuntos
Oxirredutases , Conformação Proteica , Proteínas/química , Glutarredoxinas , Glutationa/química , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Oxirredução , Ribonucleotídeo Redutases/química
15.
Biochemistry ; 37(17): 5849-57, 1998 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-9558318

RESUMO

The first committed step in de novo DNA biosynthesis involves the conversion of ribonucleotides to the corresponding deoxyribonucleotides catalyzed by the enzyme ribonucleotide reductase. Reduction of disulfides in ribonucleotide reductase is essential and is catalyzed by the protein disulfide reductants glutaredoxin or thioredoxin. The interaction region between Escherichia coli glutaredoxin-1 and E. coli ribonucleotide reductase has been localized to the C-terminal end of the B1 subunit of ribonucleotide reductase. We have demonstrated that a 25-residue peptide corresponding to this C-terminal sequence is a very good substrate for glutaredoxin via a fluorescence assay and that this peptide binds in a specific manner via isothermal titration calorimetric measurements. By selectively mutating the two cysteines in the peptide, we have identified the electrophilic cysteine as C759 (B1 numbering) and prepared a mixed disulfide between E. coli glutaredoxin-1 (C14 --> S) and the C759 monothiol form of the peptide. The peptide and the protein have been labeled with 13C and 15N, and complete heteronuclear NMR resonance assignments have been completed for both the peptide and the protein in the complex. By using half-filtered NOESY spectra, intermolecular NOEs between the protein and the peptide have been identified and the binding site on glutaredoxin has been mapped. The electrostatic charge distribution of the protein in this region is very positive, thus providing an excellent match for the highly negatively charged peptide. In addition, the electrostatic potential of the peptide provides a rationale for the observed cysteine selectivity in the reaction between glutaredoxin and the B1 peptide.


Assuntos
Cisteína/química , Dissulfetos/química , Oxirredutases , Proteínas/química , Ribonucleotídeo Redutases/química , Sequência de Aminoácidos , Sítios de Ligação , Escherichia coli/enzimologia , Glutarredoxinas , Modelos Moleculares , Dados de Sequência Molecular , Ressonância Magnética Nuclear Biomolecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Mapeamento de Peptídeos , Estrutura Secundária de Proteína , Proteínas/metabolismo , Ribonucleotídeo Redutases/genética , Ribonucleotídeo Redutases/metabolismo , Eletricidade Estática
16.
Cell Tissue Res ; 280(2): 463-72, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7781043

RESUMO

Neural cell adhesion molecules (NCAMs) can undergo post-translational modifications, such as the addition of polysialic acid chains, thus generating PSA-NCAMs, which are expressed mainly during development. Since polysialylation considerably modifies NCAM adhesivity, expression of NCAMs and PSA-NCAMs has been investigated in the developing hypophysis by immunohistochemistry. At embryonic day 13 (E13), an antibody against NCAM outlined all cellular profiles in the entire Rathke's pouch; this labelling persisted until adulthood. NCAM expression increased in all lobes during development and concerned all pituitary cell types. In contrast, at E13, PSA-NCAMs were only detected in the neural lobe, solely constituted of pituicytes at this stage, and the tuberal lobe, the only lobe expressing hormonal mRNA at the same stage. PSA-NCAMs expression increased in the neural lobe at E17 with the arrival of the neurosecretory fibres and persisted into adulthood. In the anterior lobe, PSA-NCAMs appeared at E15 where their distribution was similar to that of the differentiating corticotrophic cells; at subsequent stages, their expression extended to the whole anterior lobe. Only two cell types, corticotrophic and somatotrophic cells, remained labelled in the adult gland. In the intermediate lobe, melanotrophic cells never expressed PSA-NCAMs but these were expressed on folliculo-stellate cells at birth, preceding the onset of innervation. These results suggest that NCAMs and PSA-NCAMs play a role in pituitary histogenesis, cell differentiation and neurointermediate lobe innervation.


Assuntos
Moléculas de Adesão Celular Neuronais/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Hipófise/metabolismo , Ácidos Siálicos/análise , Animais , Moléculas de Adesão Celular Neuronais/genética , Diferenciação Celular , Idade Gestacional , Hibridização In Situ , Hipófise/citologia , Hipófise/embriologia , Hipófise/crescimento & desenvolvimento , Hipófise/inervação , Splicing de RNA , Ratos , Ratos Wistar , Tirosina 3-Mono-Oxigenase/análise
17.
Minerva Chir ; 48(19): 1069-71, 1993 Oct 15.
Artigo em Italiano | MEDLINE | ID: mdl-8309603

RESUMO

Current option in managing obstructive colorectal carcinoma is a one stage procedure. Between 1987 and 1991, 47 cases of obstructive colorectal cancer were managed. A statistical analysis showed no significant difference in mortality, morbidity and hospital stay when comparing elective and emergency one staged resection and reconstruction.


Assuntos
Neoplasias Colorretais/complicações , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Idoso , Humanos , Complicações Pós-Operatórias
18.
Ann Ital Chir ; 64(5): 545-7; discussion 548, 1993.
Artigo em Italiano | MEDLINE | ID: mdl-8010583

RESUMO

Sixty-three carcinomas of the lower third of the rectum operated of anterior resection with low colorectal or coloanal anastomosis are presented. Handsewn anastomoses were performed in 33 patients, while staplers were used in 30 cases. The average distance of the tumor from the anal verge is 10.8 cm. in hand sutured anastomoses and 7.8 cm. in stapled ones. Dehiscences, stenosis and temporary incontinence are observed more frequently after stapled anastomosis, while the incidence of neoplastic recurrences is higher in sutured anastomosis; hospital stay and mortality are similar in the two series. Our results and literature review show that both techniques are comparable though maintaining their own specific identity and precise indication.


Assuntos
Colo/cirurgia , Neoplasias Retais/cirurgia , Reto/cirurgia , Grampeadores Cirúrgicos , Técnicas de Sutura , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/cirurgia , Anastomose Cirúrgica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Fatores de Tempo
19.
Drugs ; 46 Suppl 1: 215-8, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-7506175

RESUMO

The pharmacokinetic profile and efficacy of nimesulide were assessed in 2 separate studies that recruited children with hypoglycaemia or upper respiratory tract infection and fever, respectively. A single dose of nimesulide 50mg (granules) administered orally to 14 hypoglycaemic children was rapidly absorbed. A mean maximum nimesulide plasma concentration of 3.5 mg/L was achieved within 2 hours of administration, which subsequently declined over the following 12 hours. Nimesulide was metabolised to its principal hydroxy metabolite, which was detectable in samples obtained 0.5 hours after giving the parent drug. Levels of this metabolite steadily increased, surpassing those of intact nimesulide at the 9-hour sampling point. In a randomised nonblind clinical investigation, 100 hospitalised children with acute upper respiratory infections and fever received nimesulide oral suspension (5 mg/kg/day) or paracetamol (26 mg/kg/day) for 3 to 9 days. The antipyretic and anti-inflammatory effects of nimesulide were superior to those observed with paracetamol (p < 0.01) and both drugs were equally well tolerated.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Infecções Respiratórias/tratamento farmacológico , Sulfonamidas/farmacocinética , Sulfonamidas/uso terapêutico , Acetaminofen/uso terapêutico , Doença Aguda , Criança , Pré-Escolar , Feminino , Humanos , Hipoglicemia/metabolismo , Masculino
20.
Clin Ther ; 13(6): 687-94, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1790543

RESUMO

A series of tests was used to compare two formulations of the topical steroid beta-methasone dipropionate, Diprolene (manufactured by the innovator, Schering Corp.) and Topilene (a generic formulation, manufactured by Technilab). Cream and ointment formulations produced by both manufacturers were compared with respect to physicochemical characteristics, skin sensitivity in rabbits, and a vasconstrictor assay indicative of topical availability in man. The physicochemical tests revealed no differences between innovator and generic ointment formulations, whereas excipients varied widely for the cream products. Similarly, the ointment formulations were comparable on the skin sensitivity tests in rabbits, whereas the generic cream product was much more irritating than the innovator cream in this test. On the vasoconstrictor assay in man the ointments were comparable, while the activity of the generic cream was much lower (approximately 30%) than that of the innovator cream; this difference was highly statistically significant. The difference in vasoconstrictor activity of the two cream products is discussed in relation to the differences in their physicochemical properties. It is concluded that the generic Topilene cream is not interchangeable with the innovator Diprolene cream, and that both pharmacists and physicians should be very careful when substituting one topical steroid formulation for another.


Assuntos
Anti-Inflamatórios/farmacocinética , Betametasona/análogos & derivados , Medicamentos Genéricos/farmacocinética , Administração Tópica , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Betametasona/administração & dosagem , Betametasona/química , Betametasona/farmacocinética , Química Farmacêutica , Medicamentos Genéricos/administração & dosagem , Medicamentos Genéricos/química , Feminino , Glucocorticoides , Humanos , Masculino , Pomadas , Coelhos , Testes Cutâneos , Equivalência Terapêutica
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