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1.
J Med Chem ; 66(20): 14241-14262, 2023 10 26.
Article in English | MEDLINE | ID: mdl-37800680

ABSTRACT

Urotensin II receptor (UT) modulators that differentiate the effects of the endogenous cyclic peptide ligands urotensin II (UII) and urotensin II-related peptide (URP) offer potential for dissecting their respective biological roles in disease etiology. Selective modulators of hUII and URP activities were obtained using 1,3,4-benzotriazepin-2-one mimics of a purported bioactive γ-turn conformation about the Bip-Lys-Tyr tripeptide sequence of urocontrin ([Bip4]URP). Considering an active ß-turn conformer about the shared Phe-Trp-Lys-Tyr sequence of UII and URP, 8-substituted 1,3,4-benzotriazepin-2-ones were designed to mimic the Phe-Bip-Lys-Tyr tetrapeptide sequence of urocontrin, synthesized, and examined for biological activity. Subtle 5- and 8-position modifications resulted in biased signaling and selective modulation of hUII- or URP-induced vasoconstriction. For example, p-hydroxyphenethyl analogs 17b-d were strong Gα13 and ßarr1 activators devoid of Gαq-mediated signaling. Tertiary amides 15d and 17d negatively modulated hUII-induced vasoconstriction without affecting URP-mediated responses. Benzotriazepinone carboxamides proved to be exceptional tools for elucidating the pharmacological complexity of UT.


Subject(s)
Peptide Hormones , Urotensins , Urotensins/pharmacology , Peptide Hormones/chemistry , Molecular Conformation , Signal Transduction , Receptors, G-Protein-Coupled
2.
ACS Chem Biol ; 18(9): 2050-2062, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37611227

ABSTRACT

Photoactivatable ligands remain valuable tools to study the spatiotemporal aspects of cellular signaling. However, the synthesis, handling, and biological validation of such compounds remain challenging, especially when dealing with peptides. We report an optimized synthetic strategy, where laborious preparation of dimethoxy-nitrobenzyl-tyrosine building blocks was replaced by direct functionalization of amino acid side chains while peptides remained coupled to resin, reducing both preparation time and cost. Our caged peptides were designed to investigate cellular responses mediated by intracellular angiotensin II receptors (iATR) upon interaction with known biased and unbiased ligands. The pathophysiological roles of iATRs remain poorly understood, and we sought to develop ligands to explore this. Initial validation showed that our caged ligands undergo rapid photolysis and produced functionally active peptides upon UV exposure. We also show, for the first time, that different biased ligands (ß-arrestin- vs G protein-biased analogues) evoked distinct responses when uncaged in adult rat myofibroblasts. Intracellularly targeted versions of Ang II (unbiased) or G protein-biased analogues (TRV055, TRV056) were more effective than ß-arrestin-biased Ang II analogues (SI, TRV026, and TRV27) in inducing collagen secretion, suggesting a divergent role in regulating the fibrotic response.


Subject(s)
Collagen , Myofibroblasts , Animals , Rats , Ligands , GTP-Binding Proteins , beta-Arrestins
3.
Rev. gaúch. enferm ; 44: e20210158, 2023. tab
Article in English | LILACS-Express | LILACS, BDENF - Nursing | ID: biblio-1423967

ABSTRACT

ABSTRACT Objective: To describe the reasons reported by individuals in hemodialysis that were not registered on kidney transplantation waiting lists. Methods: Cross-sectional study conducted in six renal replacement therapy services in Rio Grande do Sul, Brazil with 214 individuals undergoing hemodialysis who reported the reasons for not being registered on kidney transplantation waiting lists. The data collection was carried out through a questionnaire from March 2016 to March 2017. The Stata software was used to the statistical analysis and independence test. Results: The main reasons reported by the 214 individuals who were not registered on kidney transplantation waiting lists were due to the lack of information of the individuals, not wanting to be on list, due to morbidities and age. Conclusions: The lack of information was associated with the variables low education, male, ≤ 5 years of time since diagnosis and ≤ 5 years in renal replacement therapy. The reason for not wanting to be on the list was associated with the variables illiteracy and age.


RESUMEN Objetivo: Describir las razones informadas por personas en hemodiálisis que no estaban registradas en lista de espera para trasplante renal. Métodos: Estudio transversal realizado en Rio Grande do Sul, Brasil en seis servicios de terapia sustitutiva renal con 214 individuos en hemodiálisis que informaron los motivos de no estar registrados en listade espera para trasplante renal. La recolección de datos se realizó mediante un cuestionario entre marzo de 2016 y marzo de 2017. Para el análisis estadístico descriptivo y test de independencia se utilizó el software Stata. Resultados: Las principales razones reportadas por las 214 personas que no estaban inscritas en listade espera para trasplante renal fueron la falta de información de las personas, no querer estar en lista, impedimento por multimorbilidad y edad. Conclusiones: La falta de información se asoció con las variables baja escolaridad, género masculino, ≤ 5 años de tiempo desde el diagnóstico y ≤ 5 años en terapia de reemplazo renal. El motivo de no querer estar en la lista estuvo asociado a las variables no saber leer y edad.


RESUMO Objetivo: Descrever os motivos referidos pelos indivíduos em hemodiálise que não estavam cadastrados em lista de espera para o transplante renal. Métodos: Estudo transversal realizado no Rio Grande do Sul, Brasil em seis serviços de terapia de substituição renal com 214 indivíduos em hemodiálise que referiram os motivos de não estarem cadastrados em lista de espera para o transplante renal. A coleta de dados foi realizada por meio de questionário entre março de 2016 e março de 2017. Para a análise estatística descritiva e do teste de independência, utilizou-se o software Stata. Resultados: Os principais motivos referidos pelos 214 indivíduos que não estavam cadastrados em lista de espera para o transplante renal foram: a falta de informação dos indivíduos, não desejar estar em lista, o impedimento por multimorbidade e a idade. Conclusões: A falta de informação apresentou associação com as variáveis baixa escolaridade, sexo masculino, ≤ 5 anos de tempo de diagnóstico e ≤ 5 anos em terapia de substituição renal. O motivo não desejar estar em lista esteve associado com as variáveis não saber ler e idade.

4.
Am J Physiol Cell Physiol ; 323(3): C813-C822, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35938678

ABSTRACT

The role of different G protein-coupled receptors (GPCRs) in the cardiovascular system is well understood in cardiomyocytes and vascular smooth muscle cells (VSMCs). In the former, stimulation of Gs-coupled receptors leads to increases in contractility, whereas stimulation of Gq-coupled receptors modulates cellular survival and hypertrophic responses. In VSMCs, stimulation of GPCRs also modulates contractile and cell growth phenotypes. Here, we will focus on the relatively less well-studied effects of GPCRs in cardiac fibroblasts, focusing on key signaling events involved in the activation and differentiation of these cells. We also review the hierarchy of signaling events driving the fibrotic response and the communications between fibroblasts and other cells in the heart. We discuss how such events may be distinct depending on where the GPCRs and their associated signaling machinery are localized in these cells with an emphasis on nuclear membrane-localized receptors. Finally, we explore what such connections between the cell surface and nuclear GPCR signaling might mean for cardiac fibrosis.


Subject(s)
Fibroblasts , Receptors, G-Protein-Coupled , Cell Nucleus/metabolism , Fibroblasts/metabolism , Myocytes, Cardiac/metabolism , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Signal Transduction/physiology
5.
J Biol Chem ; 297(3): 101057, 2021 09.
Article in English | MEDLINE | ID: mdl-34389356

ABSTRACT

Over the last decade, the urotensinergic system, composed of one G protein-coupled receptor and two endogenous ligands, has garnered significant attention as a promising new target for the treatment of various cardiovascular diseases. Indeed, this system is associated with various biomarkers of cardiovascular dysfunctions and is involved in changes in cardiac contractility, fibrosis, and hypertrophy contributing, like the angiotensinergic system, to the pathogenesis and progression of heart failure. Significant investment has been made toward the development of clinically relevant UT ligands for therapeutic intervention, but with little or no success to date. This system therefore remains to be therapeutically exploited. Pepducins and other lipidated peptides have been used as both mechanistic probes and potential therapeutics; therefore, pepducins derived from the human urotensin II receptor might represent unique tools to generate signaling bias and study hUT signaling networks. Two hUT-derived pepducins, derived from the second and the third intracellular loop of the receptor (hUT-Pep2 and [Trp1, Leu2]hUT-Pep3, respectively), were synthesized and pharmacologically characterized. Our results demonstrated that hUT-Pep2 and [Trp1, Leu2]hUT-Pep3 acted as biased ago-allosteric modulators, triggered ERK1/2 phosphorylation and, to a lesser extent, IP1 production, and stimulated cell proliferation yet were devoid of contractile activity. Interestingly, both hUT-derived pepducins were able to modulate human urotensin II (hUII)- and urotensin II-related peptide (URP)-mediated contraction albeit to different extents. These new derivatives represent unique tools to reveal the intricacies of hUT signaling and also a novel avenue for the design of allosteric ligands selectively targeting hUT signaling potentially.


Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Peptide Hormones/metabolism , Peptides/metabolism , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/metabolism , Allosteric Regulation , Cell Proliferation , HEK293 Cells , Humans , Intracellular Signaling Peptides and Proteins/chemistry , Intracellular Signaling Peptides and Proteins/genetics , Ligands , Peptide Hormones/chemistry , Peptide Hormones/genetics , Peptides/chemistry , Protein Conformation, alpha-Helical , Receptors, G-Protein-Coupled/genetics , Signal Transduction
6.
Int J Biol Macromol ; 162: 599-608, 2020 Nov 01.
Article in English | MEDLINE | ID: mdl-32565303

ABSTRACT

This study investigates conformational aspects of ulvans (F2) and their polycarboxyl derivatives obtained through periodate-chlorite oxidation (C3) followed by DEAE-Sephacel fractioning (C3b and C3c). Size exclusion chromatography coupled with laser light scattering and viscometric detection, in addition to circular dichroism (CD) and molecular modeling analyses, suggested that F2 had a compact sphere conformation with a helical motif as secondary structure. In contrast, all the polycarboxyl ulvans showed a random coil conformation, although C3c (NaSO3- 21.0%; COO- 1.81 mmol·g-1; Mw 18 kg·mol-1) had a more rigid and constrained backbone than C3 (NaSO3- 21.0%; COO- 1.81 mmol·g-1; Mw 49 kg·mol-1), largely due to its higher sulfate and carboxyl content. Despite the higher ionic character of C3c, its anticoagulant activity (ACA), determined by activated partial thromboplastin time (APTT) assay, was not improved compared to that of C3. Moreover, C3b (NaSO3- 14.1%; COO- 1.23 mmol·g-1; Mw 8.1 kg·mol-1) had higher activity than F2 (NaSO3- 20.6.%; COO- 0.36 mmol·g-1; Mw 123 kg·mol-1), even with its lower sulfate content and molar mass. These results suggest that the ACA of polycarboxyl ulvans relies on carboxyl and sulfate content and may depend, in addition, on a proper flexible conformation.


Subject(s)
Anticoagulants , Ulva/chemistry , Anticoagulants/chemistry , Anticoagulants/isolation & purification , Anticoagulants/pharmacology , Humans , Molecular Conformation , Molecular Weight , Partial Thromboplastin Time
7.
Mol Cell Biol ; 40(15)2020 07 14.
Article in English | MEDLINE | ID: mdl-32366382

ABSTRACT

Rtf1 is a conserved RNA polymerase II (RNAPII) elongation factor that promotes cotranscriptional histone modification, RNAPII transcript elongation, and mRNA processing. Rtf1 function requires the phosphorylation of Spt5, an essential RNAPII processivity factor. Spt5 is phosphorylated within its C-terminal domain (CTD) by cyclin-dependent kinase 9 (Cdk9), the catalytic component of positive transcription elongation factor b (P-TEFb). Rtf1 recognizes phosphorylated Spt5 (pSpt5) through its Plus3 domain. Since Spt5 is a unique target of Cdk9 and Rtf1 is the only known pSpt5-binding factor, the Plus3/pSpt5 interaction is thought to be a key Cdk9-dependent event regulating RNAPII elongation. Here, we dissect Rtf1 regulation by pSpt5 in the fission yeast Schizosaccharomyces pombe We demonstrate that the Plus3 domain of Rtf1 (Prf1 in S. pombe) and pSpt5 are functionally distinct and that they act in parallel to promote Prf1 function. This alternate Plus3 domain function involves an interface that overlaps the pSpt5-binding site and that can interact with single-stranded nucleic acid or with the polymerase-associated factor (PAF) complex in vitro We further show that the C-terminal region of Prf1, which also interacts with PAF, has a similar parallel function with pSpt5. Our results elucidate unexpected complexity underlying Cdk9-dependent pathways that regulate transcription elongation.


Subject(s)
Chromosomal Proteins, Non-Histone/metabolism , Schizosaccharomyces pombe Proteins/metabolism , Schizosaccharomyces/metabolism , Transcriptional Elongation Factors/genetics , Phosphorylation , Positive Transcriptional Elongation Factor B/metabolism , RNA Polymerase II/metabolism , Transcription, Genetic/genetics , Transcriptional Elongation Factors/metabolism
8.
Carbohydr Polym ; 208: 152-160, 2019 Mar 15.
Article in English | MEDLINE | ID: mdl-30658786

ABSTRACT

Different hydrolysis conditions to produce κ-carrageenan oligosaccharide alditols were studied and the depolymerization process monitored by capillary electrophoresis (CE). Semisynthesis, ion-exchange and exclusion chromatography were used to obtain and isolate sulfated di-, tetra- and hexasaccharide alditols, the last being fully characterized for the first time. Those derivatives were used as standards to validate a new quantitative CE analytical method which was used to compare two different partial hydrolysis methodologies: an acid hydrolysis followed by reduction and a one-pot reductive hydrolysis using 4-methylmorpholine borane. The resulting depolymerization profiles were quite different from each other. Optimal hydrolysis conditions to produce high yields of specific sulfated oligosaccharides as well as particular mixtures of oligosaccharide alditols were determined. Moreover, using the novel CE method, we were able to distinguish up to eight different oligosaccharides in the hydrolysate mixtures.

9.
J Med Chem ; 61(7): 2875-2894, 2018 04 12.
Article in English | MEDLINE | ID: mdl-29544056

ABSTRACT

Targeting allosteric sites at M1 muscarinic acetylcholine receptors is a promising strategy for the treatment of Alzheimer's disease. Positive allosteric modulators not only may potentiate binding and/or signaling of the endogenous agonist acetylcholine (ACh) but also may possess direct agonist activity (thus referred to as PAM-agonists). Recent studies suggest that PAM-agonists with robust intrinsic efficacy are more likely to produce adverse effects in vivo. Herein we present the synthesis and pharmacological evaluation of a series of pyrrole-3-carboxamides with a diverse range of allosteric profiles. We proposed structural modifications at top, core, or pendant moieties of a prototypical molecule. Although generally there was a correlation between the degree of agonist activity and the modulatory potency of the PAMs, some derivatives displayed weak intrinsic efficacy yet maintained strong allosteric modulation. We also identified molecules with the ability to potentiate mainly the affinity or both affinity and efficacy of ACh.


Subject(s)
Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/pharmacology , Muscarinic Agonists/chemical synthesis , Muscarinic Agonists/pharmacology , Receptor, Muscarinic M1/agonists , Acetylcholine/pharmacology , Allosteric Regulation , Animals , CHO Cells , Cricetinae , Cricetulus , Drug Design , Humans , Inositol Phosphates/metabolism , Molecular Conformation , Structure-Activity Relationship
10.
Beilstein J Org Chem ; 13: 1222-1229, 2017.
Article in English | MEDLINE | ID: mdl-28694868

ABSTRACT

Agarose was herein employed as starting material to produce primary, secondary and tertiary C-glycoside glycamines, including mono- and disaccharide structures. The semisynthetic approach utilized was generally based on polysaccharide-controlled hydrolysis followed by reductive amination. All reactions were conducted in aqueous media and without the need of hydroxyl group protection. We were able to identify optimal conditions for the reductive amination of agar hydrolysis products and to overcome the major difficulties related to this kind of reaction, also extending it to reducing anhydrosugars. The excess of ammonium acetate, methyl- or dimethylamine, and the use of a diluted basic (pH 11) reaction media were identified as important aspects to achieve improved yields, as well as to decrease the amount of byproducts commonly related to reductive amination of carbohydrates. This strategy allowed the transposition of the 3,6-anhydro-α-L-galactopyranose unit (naturally present in the agarose structure) to all glycamines synthesized, constituting an amino-substituted C-threofuranoside moiety, which is closely related to (+)-muscarine.

11.
Bioorg Med Chem Lett ; 27(2): 156-161, 2017 01 15.
Article in English | MEDLINE | ID: mdl-27956348

ABSTRACT

Sixteen porphyrins, including neutral, anionic and cationic meso-(aryl)porphyrins and meso-(1-methyl-4-pyridinium)porphyrins were herein evaluated in terms of their photosensitizing properties against HaCaT keratinocytes. After an initial screening, the cationic porphyrins were studied in more details, by both determining their log POW and performing PDT assays in lower porphyrin concentrations. Porphyrins presenting two or more adjacent positively charged groups, directly linked to the macrocycle meso positions, appeared to be the most effective photosensitizers. The present study also included the dicationic 5,10-diphenyl-15,20-di(1-methylpyridinium-4-yl)porphyrin (14b), which has previously shown promising results on a psoriasis-like in vivo model. Overall results indicated that the beneficial effect related to porphyrins on psoriasis can be related to the decreasing of keratinocyte viability. Furthermore, some of the cationic porphyrins studied appeared as candidates to be utilized as photosensitizers for psoriasis treatment.


Subject(s)
Keratinocytes/drug effects , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Pyridinium Compounds/pharmacology , Cell Line , Humans , Keratinocytes/cytology , Light , Photosensitizing Agents/chemical synthesis , Porphyrins/chemical synthesis , Psoriasis/drug therapy , Pyridinium Compounds/chemical synthesis
12.
J. bras. patol. med. lab ; 48(1): 59-65, fev. 2012. graf
Article in Portuguese | LILACS | ID: lil-617020

ABSTRACT

INTRODUÇÃO: A core biopsy (CB) tem ganhado espaço cada vez mais importante no diagnóstico e no manejo do câncer de mama devido a seu baixo custo e alta acurácia. Entretanto, devemos nos perguntar se esse método realmente é adequado para a caracterização do tipo histológico e do grau de diferenciação tumoral, uma vez que a região biopsiada pode não ser representativa do tumor como um todo. OBJETIVO: Avaliar a concordância entre o anatomopatológico da biópsia e o encontrado na peça cirúrgica. MATERIAL E MÉTODOS: Realizamos um estudo retrospectivo envolvendo todos os pacientes com câncer de mama submetidos à mastectomia radical modificada ou à quadrantectomia em nosso serviço, entre janeiro de 2007 a dezembro 2009, analisando a taxa de concordância entre o resultado da CB do tumor de mama e o anatomopatológico da peça cirúrgica. Estudamos como variáveis o tipo histológico e o grau de diferenciação tumoral e de invasão linfovascular. RESULTADOS: Os resultados mostraram taxa de concordância para tipo histológico de 76 por cento entre os métodos. Já a concordância para o grau tumoral foi de 50 por cento, observando-se uma tendência da CB a subestimar o grau. Em relação à presença de invasão linfovascular, ocorreram 62,09 por cento de concordância, sendo 100 por cento seu valor preditivo positivo (VPP), mas com baixa sensibilidade (29 por cento). CONCLUSÃO: Esses achados sugerem que a CB seja o método adequado para o diagnóstico histológico do câncer de mama, porém apresenta alta taxa de discordância para grau tumoral e invasão linfovascular com o exame anatomopatológico da peça cirúrgica, tendendo a subestimar a agressividade do tumor.


INTRODUCTION: Core biopsy (CB) has increasingly gained importance in the diagnosis and management of breast cancer due to its cost effectiveness and high accuracy. However, it is debatable whether this method is particularly suitable for the characterization of histological type and tumor differentiation, since the biopsied region may not be representative of the tumor as a whole. OBJECTIVE: To evaluate the concordance between the biopsy and the surgical specimen anatomopathological findings. MATERIAL AND METHODS: We carried out a retrospective study involving all patients with breast cancer undergoing modified radical mastectomy or quadrantectomy in our service from January 2007 to December 2009, thus analyzing the concordance rate between the results of breast tumor CB and surgical specimen anatomopathology. Histological type, tumor differentiation grade and lymphovascular invasion were assessed as variables. RESULTS: The results show a concordance rate of 76 percent for the histological type between both methods. As to tumor grade, concordance rate was 50 percent, in which CB was prone to underestimate grade. Regarding the presence of lymphovascular invasion, the concordance was 62.09 percent, with 100 percent positive predictive value but low sensitivity (29 percent). CONCLUSION: These findings suggest that CB is a suitable method for histological diagnosis of breast cancer, although it has a high discordance rate for tumor grade and lymphovascular invasion in comparison with specimen anatomopathologic exam, tending to underestimate tumor aggressiveness.

13.
Rev. bras. ortop ; 47(1): 118-123, jan.-fev. 2012. ilus
Article in Portuguese | LILACS | ID: lil-624815

ABSTRACT

As cirurgias radicais para tratamento dos tumores da cintura pélvica e escapular (hemipelvectomias e desarticulações interescapulotorácicas) constituem-se, em geral, em procedimentos extensos com grandes áreas de perda de substância local após ressecção do tumor. A utilização do retalho que inclui toda a musculatura anterior e posterior da coxa após dissecção do fêmur, pediculado pelos vasos femorais superficiais, foi descrita apenas uma vez na literatura. O retalho similar utilizando toda a musculatura anterior e posterior do braço após dissecção do úmero, pediculado pelos vasos subclávios para reconstrução após desarticulação interescapulotorácica, não apresenta relatos. Descrevemos dois casos - um de hemipelvectomia e outro de desarticulação interescapulotorácica - utilizando estes dois retalhos para fechamento do defeito.


Radical surgeries for treatment of scapular and pelvic girdle tumors (hemipelvectomy and interscapulothoracic amputation) are generally extended procedures, with large areas of local tissue loss after tumor resection. The use of a flap that includes all the anterior and posterior thigh musculature after femur dissection, pedicled in the superficial femoral vessels, has been described was only once in the medical literature, and there have been no reports on a similar flap using the whole anterior and posterior musculature of the arm after humerus dissection, pedicled in the subclavian vessels, for reconstruction after interscapulothoracic amputation. Here, we describe two cases - one hemipelvectomy and one interscapulothoracicl amputation - using these two the flaps to close the defect.


Subject(s)
Humans , Male , Middle Aged , Bone Neoplasms , Disarticulation , Hemipelvectomy , Pelvic Neoplasms , Scapula , Surgical Flaps
14.
Rev Bras Ortop ; 47(1): 118-23, 2012.
Article in English | MEDLINE | ID: mdl-27027091

ABSTRACT

Radical surgeries for treatment of scapular and pelvic girdle tumors (hemipelvectomy and interscapulothoracic amputation) are generally extended procedures, with large areas of local tissue loss after tumor resection. The use of a flap that includes all the anterior and posterior thigh musculature after femur dissection, pedicled in the superficial femoral vessels, has been described was only once in the medical literature, and there have been no reports on a similar flap using the whole anterior and posterior musculature of the arm after humerus dissection, pedicled in the subclavian vessels, for reconstruction after interscapulothoracic amputation. Here, we describe two cases - one hemipelvectomy and one interscapulothoracicl amputation - using these two the flaps to close the defect.

15.
Article in Portuguese | LILACS-Express | LILACS | ID: lil-621047

ABSTRACT

Introdução: O câncer de cabeça e pescoço é o quinto câncermais comum no mundo. Apesar dos importantes avanços nodiagnóstico e tratamento, um pequeno aumento na sobrevida em5 anos foi observado nas últimas décadas. Objetivo: Analisar aepidemiologia dos pacientes com câncer da cabeça e pescoço,atendidos no Hospital Erasto Gaertner, que foram a óbito antes dereceber tratamento. Método: Revisão de dados epidemiológicosde 164 pacientes, admitidos entre janeiro de 2001 e dezembro de2006. Resultados: A idade média foi de 61,6 anos e a localizaçãomais comum foi à orofaringe, em 36,6%. 83% dos pacientesapresentavam Estádio Clínico IV, e o emagrecimento foiobservado em 76,6% dos pacientes. 38,4% dos pacientes eramZubrod 2, 16,5% Zubrod 3 e 7,3% com Zubrod 4. O tempo médioentre a primeira consulta e o óbito foi de 68,7 dias. Conclusão:O estádio clínico avançado e o atraso no reconhecimento dossintomas e na procura da assistência médica parecem ser fatoresdeterminantes dos óbitos dos pacientes estudados.

16.
Rev. Col. Bras. Cir ; 33(2): 74-78, mar.-abr. 2006. ilus, graf
Article in Portuguese | LILACS | ID: lil-430592

ABSTRACT

OBJETIVO: Reconhecer a interferência do captopril na cicatrização de feridas cutâneas de ratos hipertensos. MÉTODOS: Distribuíram-se 111 ratos em quatro grupos: controle normotenso (N=30); controle hipertenso (N=30), os quais receberam 1 ml/dia de solução de cloreto de sódio a 0.9 por cento por via oral; grupo experimento (N=31), hipertensos que receberam 7,5mg/kg/dia de captopril e um grupo aferição (N=20), 10 hipertensos e 10 normotensos, nos quais aferiu-se a pressão na aorta abdominal, no último dia de experimento. Após 15 dias de medicação, fez-se uma incisão da pele e da tela subcutânea, na região médio-dorsal dos grupos I, II e III, seguida de síntese. Ressecaram-se as cicatrizes de 10 animais de cada grupo, no 4.°, 7.° e 14.° dias após a operação, que divididas em duas partes foram enviadas para a tensiometria e para análise histológica. RESULTADOS: A pressão arterial média de 83,18 ± 7,51 mmHg nos normotensos e 151,36 ± 10,51 mmHg nos hipertensos. As cicatrizes dos hipertensos tratados e não tratados eram menos resistentes que as dos normotensos, nos tempos iniciais (p<0,05) e que ao 14.° dia as resistências se igualaram. Não houve diferença entre o grupo tratado e o não tratado. A densidade de colágeno total foi maior nos normotensos em todos os tempos (p<0,05) e não houve diferença entre hipertensos tratados e não tratados. A epitelização, a reação inflamatória e a formação do tecido de granulação foi semelhante nos três grupos. CONCLUSÕES: O captopril, em ratos, não modifica a cicatrização, ficando as diferenças relacionadas à hipertensão.

17.
Rev. Col. Bras. Cir ; 30(3): 224-229, maio-jun. 2003.
Article in Portuguese | LILACS | ID: lil-492772

ABSTRACT

OBJETIVOS: Determinar o impacto financeiro do trauma em um hospital universitário em Curitiba. MÉTODO: Estudo retrospectivo de pacientes vítimas de trauma, internados no Hospital Universitário Cajuru, divididos de acordo com o mecanismo de trauma. Foram analisados o número de dias de internamento e o custo assistencial total de cada paciente declarados na ficha de Autorização de Internação Hospitalar (AIH). A partir daí, calculou-se o custo médio, a média de dias de internamento e o custo médio paciente/dia. RESULTADOS: O custo médio de 349 pacientes estudados foi de US$ 568,22; das vítimas por ferimento por arma de fogo (FAF), US$ 692,50; das vítimas de ferimento de arma branca (FAB), US$ 676,9; das vítimas de agressão, US$ 412,3; das vítimas de queda, US$ 503,05 e das vítimas de acidente de trânsito, US$ 600,30. A média de dias de internamento da amostra total foi de 6,2; das vítimas de FAF, 7,7; das vítimas de FAB, 5,3; das vítimas de agressão, 6,7; das vítimas de queda, 7 e das vítimas de acidente de trânsito 6. O custo médio paciente/dia da amostra total foi de US$ 91,65; das vítimas de FAF, US$ 89,99; das vítimas de FAB, US$ 127,66; das vítimas de agressão, US$ 61,54; das vítimas de queda, US$ 71,86 e das vítimas de acidente de trânsito, US$ 100,05. CONCLUSÃO: Este estudo, como tantos outros, mostra que o trauma é uma doença negligenciada, importante para a saúde publica por seu grande impacto social e econômico e passível de redução através de medidas de prevenção.


BACKGROUND: The aim of this study is to determine the economic impact of trauma in an university hospital in Curitiba. METHODS: A retrospective study of medical registries was carried out and they were divided in accordance to trauma mechanism, number of in-hospital days and total medical assistance costs were also considered for each patient on the In-Hospital Authorization Form. From these data, the average cost, average in-hospital days and average patient/day costs were calculated. RESULTS: The average cost for the 349 patients was US$ 568.22; for fire gun victims, US$ 692.50; for blade victims, US$ 676.90; aggression victims, US$ 412.30; fall victims and traffic accident victims, US$ 600.03. The average in-hospital days for the total sample was 6.2; fire gun victims, 7.7; blade victims, 5.3; aggression victims, 6.7; fall victims, 7 and traffic accident victims was of 6. The average patient/day cost, for the total sample, was US$ 91.65; fire gun victims, US$ 89.99; blade victims, US$ 127.66; aggression victims, US$ 61.54; fall victims, US$ 71.86 and traffic accident victims, US$100.05. CONCLUSIONS: This study corroborates with many others that show that trauma is a neglected disease, important to public health due to its enormous social and economic wich can be avoided by means of preventive measures.

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