Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
BJS Open ; 7(3)2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37151084

RESUMO

BACKGROUND: Parotidectomy is the standard procedure for treatment of many parotid lesions; however, it has several drawbacks. Facial asymmetry and Frey's syndrome are the most annoying complications to patients. Insertion of interpositioning grafts into the parotidectomy bed can decrease these complications significantly. Free dermal fat graft (FDFG) and superficial musculoaponeurotic system (SMAS) flap have very promising results. This RCT aimed to compare these two techniques regarding functional and aesthetic outcomes. METHODS: Between February 2016 and October 2021, adult patients undergoing superficial conservative parotidectomy in a single centre for a benign indication were randomized into two equal groups using a closed envelope method. In one group, FDFG was inserted at the parotidectomy bed, whereas, in the other group, SMAS flap was performed. Preoperative, operative, and postoperative data were recorded and analysed. The primary outcome was the development of Frey's syndrome. RESULTS: Seventy-eight patients were randomized into two equal groups of 39 patients. There was no significant difference between the two groups regarding development of Frey's syndrome. There was no significant statistical difference between study groups regarding demographic data, co-morbidities, parotid pathologies, specimen volumes, total operating time, and postoperative complications. A tendency for over correction was observed in FDFG and under correction in SMAS flap. There was no statistically significant difference between the study groups regarding the patients' aesthetic satisfaction with the majority displaying excellent satisfaction with no poor results. CONCLUSION: FDFG and SMAS flap are simple, rapid, and reliable procedures and are effective in improving both functional and aesthetic outcomes post-parotidectomy. They have comparable results; however, selection of either procedure can be determined according to patient and tumour characteristics. Registration number: NCT05452837 (http://www.clinicaltrials.gov).


Assuntos
Neoplasias Parotídeas , Sistema Musculoaponeurótico Superficial , Sudorese Gustativa , Adulto , Humanos , Sudorese Gustativa/etiologia , Sudorese Gustativa/patologia , Sudorese Gustativa/cirurgia , Sistema Musculoaponeurótico Superficial/cirurgia , Sistema Musculoaponeurótico Superficial/patologia , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/complicações , Neoplasias Parotídeas/patologia , Retalhos Cirúrgicos , Estética
2.
Int J Surg ; 89: 105950, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33887492

RESUMO

BACKGROUND: Seroma is one of the most commonly encountered morbidities after inguinal lymph node dissection (ILND). It causes much nuisance to both patients and doctors and its presence can lead to many complications. This study aimed to evaluate the role and impact of using fibrin glue to decrease seroma formation in patients undergoing ILND. MATERIALS AND METHODS: Thirty-two patients underwent ILND for various reasons. The patients were randomly divided into two groups; 16 in each group. In one group, fibrin glue sealant was applied with a dosage of 2 ml per 100 cm2 surface area. Drain placement was then performed. In the control group, only drain placement was used. Preoperative, operative and postoperative data were recorded and analyzed. RESULTS: There was a significant reduction in the incidence of seroma formation favoring the fibrin glue group when compared to the control group (P = 0.022). There was also a significant reduction of total cumulative amount of serous fluid (P < 0.001), time to remove drains (P < 0.001), and hospital stay (P = 0.012). There was no significant difference between the two groups in occurrences of hematoma, infection or superficial skin edge necrosis. CONCLUSION: Fibrin glue sealant has a role to play in ILND as it significantly reduced the incidence of seroma formation. Standardization of definition of seroma as well as dosage and technique of fibrin glue have to be reached in future studies to determine the true role of fibrin glue in ILND.


Assuntos
Adesivo Tecidual de Fibrina/administração & dosagem , Excisão de Linfonodo/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Seroma/prevenção & controle , Adesivos Teciduais/administração & dosagem , Adulto , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Seroma/epidemiologia , Seroma/etiologia , Resultado do Tratamento
3.
J Pediatr Surg ; 56(8): 1349-1355, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33092813

RESUMO

BACKGROUND: Biofeedback and transcutaneous posterior tibial nerve stimulation (TPTNS) can be used in treatment of Functional non-retentive fecal incontinence (FNRFI). Aim of this study was to evaluate the early effect of Biofeedback versus (TPTNS) and treatment by Kegal exercises and dietetic regulations in management of (FNRFI) in children. METHODOLOGY: The current prospective randomized controlled study included 93 children with FNRFI who were randomly allocated into the 3 groups. Group A (n = 28) were treated by dietetic regulation and Kegal exercises. Group B (n = 34) received biofeedback while group C (n = 31) received (TPTNS) for 3 months. Follow up using St' Mark's incontinence score and high resolution manometry was done at 3 and 6 months and compared to the initial records. RESULTS: There was statistically significant decrease in the incontinence score in Group B and C compared to Group A at 3 and 6 months (p ˂ 0.001). Resting and squeeze pressures showed significant increase group B and C (p ˂ 0.001). Patients in Group B and C showed significant decrease volume of balloon required for 1st sensation (p ˂ 0.001 and 0.034) respectively. CONCLUSION: Biofeedback is more effective than TPTNS, Kegal exercises and dietetic regulations in treatment of FNRFI in children for short term follow-up. LEVEL OF EVIDENCE: Level I. TYPE OF STUDY: Treatment Study.


Assuntos
Incontinência Fecal , Estimulação Elétrica Nervosa Transcutânea , Biorretroalimentação Psicológica , Criança , Incontinência Fecal/terapia , Humanos , Nervo Tibial , Resultado do Tratamento
4.
Indian J Surg Oncol ; 11(3): 372-377, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33013113

RESUMO

According to recent clinical practice guidelines, enhanced recovery programs (ERP) have been practiced to improve surgical outcomes and decrease cost. However, these are still opposed by the traditional measures in the treatment of colorectal carcinoma that is still practiced with the concept of protection of anastomosis and decrease postoperative complications. The aim of this study was to report our experience in ERP in elective open left side colonic carcinoma surgery in comparison with the conventional perioperative care. The current prospective multicenter randomized controlled study included a total of 80 adult patients with left side colonic cancer who were eligible for elective colonic resection. Included patients were randomly divided into two equal groups: group (A) where conventional perioperative care was performed and group (B) where ERP were applied. Follow-up was designed for at least 1 month to evaluate and compare hospital stay and postoperative complications. There was no statistically significant difference between the two groups as regards demographic data and preoperative comorbidities. There were statistically significant less pain (P = 0.24), less postoperative nausea and vomiting (P = 0.045), and less hospital stay (P < 0.001) in group B than group A. Otherwise, there was no statistically significant difference in comparing the rest of postoperative surgical or non-surgical complications or rates of readmissions between the two groups. ERP are safe, reliable, simple, and applicable in open left side cancer colon surgery with no negative impact over the postoperative complications in comparison with the conventional care.

5.
Int J Surg Oncol ; 2020: 6789709, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685211

RESUMO

BACKGROUND: Malignant involvement of circumferential resection margin (CRM) and longitudinal resection margin (LRM) after surgical resection of colorectal cancer (CRC) are associated with higher rates of recurrence and development of distant metastasis. This can influence the overall patient's prognosis. The aim of the current study was to identify pathological factors as predictors for the involvement of resection margins in early T3 CRC. Patients and Methods. Fifty patients radiologically diagnosed to have cT3a/b (CRC) were included in the study. After resection, the pathological examination was performed to identify patients with positive CRM and/or LRM. Relations between the different pathological parameters and the CMR and LRM involvements were assessed. RESULTS: Positive CRM was present in 17 cases (34%), while positive LRM was found in 6 cases (12%). The involvement of both margins was significantly associated with rectal tumors and tumors with infiltrative gross appearance, grade III, deeper invasion, and positive lymph node metastases. Also, there was a significant association between both margins' positivity and other pathological parameters as signet ring carcinoma, tumor budding, perineural and vascular invasion, high microvessel density (MVD), and sinusoidal vascular pattern, while the presence of necrosis and infiltrative advancing tumor front was significantly associated with CRM involvement only. The depth of tumor invasion and signet ring carcinoma were identified as independent predictor factors for positive CRM and LRM, respectively. CONCLUSION: Preoperative identification of these pathological parameters can be a guide to tailor the management plan accordingly.


Assuntos
Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma/cirurgia , Carcinoma de Células em Anel de Sinete/cirurgia , Colectomia , Neoplasias do Colo/cirurgia , Margens de Excisão , Protectomia , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/patologia , Idoso , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias do Colo/patologia , Feminino , Humanos , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico
6.
Plast Reconstr Surg Glob Open ; 7(10): e2476, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31772899

RESUMO

BACKGROUND: Volume replacement oncoplastic breast techniques have become one of the standard lines in the treatment of early breast cancer. They have better cosmetic outcome and patient satisfaction. Latissimus dorsi (LD) flap is one of the most commonly used flaps for these techniques. Although it shows satisfactory surgical outcomes, postoperative shoulder dysfunction is an obvious drawback. The aim of this study was to compare LD flap with thoracodorsal artery perforator (TDAP) flap after breast-conserving surgery regarding surgical outcomes, patient satisfaction, and impact on shoulder function. METHODS: The study included 42 adult female patients with early breast cancer who were eligible for conservative breast surgery and immediate breast reconstruction. Patients were divided into 2 equal groups: group A where patients underwent immediate reconstruction using LD flap and group B where patients underwent reconstruction using TDAP flap. Follow-up was designed for 12 months for early outcome, patient satisfaction, and shoulder functions. RESULTS: The mean age of the included patients in group A and group B was 40.95 ± 5.06 and 40.33± 5.25 years, respectively. There was no significant difference in flap dimensions, postoperative complications, or cosmetic outcome in both groups. However, significantly less shoulder dysfunction was documented in cases of TDAP compared to LD flap at 3, 6, and 12 months postoperatively. CONCLUSIONS: TDAP flap is as reliable a technique as LD flap regarding the feasibility, postoperative complications, and the cosmetic outcome with significantly better functional outcome of the shoulder.

7.
Environ Toxicol ; 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29923357

RESUMO

A wide variety of natural products have powerful chemopreventive effects due to their antioxidant, antimutagenic, and anti-inflammatory activities that enable them to arrest cell proliferation in several cancer models. In the present study, we shed light on the protective mechanism of Nigella sativa extract against diethylnitrosamine (DENA)-induced preneoplastic stage of hepatocellular carcinoma (HCC) in rats. We studied the extract effect on EGFR/ERK1/2 signaling pathway as one of the major signaling pathways controlling cell proliferation during hepatocarcinogenesis as well as the investigation of its antioxidant activity. The study also compared the effects of NSEE to those of (thymoquinone) TQ and silymarin as hepatoprotective substances. Rats received daily doses of NSEE (150, 250, 350 mg/kg BW), a dose per three alternative days/week of TQ (20 mg/kg BW) and a daily dose of silymarin (100 mg/kg BW). The doses were administered orally by gavage for 12 days before DENA and CCl4 administration, and then the supply of NSEE, TQ or silymarin was continued until the end of the experiment (16 weeks). DENA administration activated EGFR/ERK1/2 signaling and caused a significant increase in P-EGFR and P-ERK1/2 as well as a significant up-regulation of expression of target genes such as PCNA, c-fos and Bcl2, which indicated the increase in cell proliferation. Furthermore, a significant elevation in alpha-fetoprotein (AFP) and hepatic enzymes was observed in DENA-treated rats in addition to a decrease in the antioxidant status. The protection with NSEE, TQ, or silymarin has the potential to inhibit the EGFR/ERK1/2 activation and improve the antioxidant status. Moreover, the action of NSEE against the hepatocarcinogenesis was supported by high antioxidant activity and the histopathological observations of the liver. These data suggest that NSEE has a chemopreventive role in DENA-induced HCC through the inhibition of the EGFR/ERK1/2 signaling pathway and their target genes in addition to its role as an antioxidant.

8.
Environ Toxicol ; 32(9): 2212-2220, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28573719

RESUMO

N-nitrosamines are widely spread environmental pollutants of well-known toxicity and carcinogenicity in various animal species. These compounds are metabolically activated by cytochrome P450 system predominantly in the liver and in other tissues into more active metabolites leading to generation of both alkylating agents that alkylate DNA and reactive oxygen species. In the current study, we investigated the influence of four types of N-nitrosamines that are commonly present in the environment [methyethylnitrosamine, (MEN), diethylnitrosamine (DEN), diphenylnitroasamine (DPN) and dimethylnitrosamine (DMN)] on both livers and testes of male rabbits through assessment of 17 ß-hydroxysteroid dehydrogenase (17 ß-HSD) activity. The protein expression of the three cytochrome P450s (CYP11A1, CYP19A1, and CYP21A2) is involved in the steroidogenesis. The levels of testosterone (T) and estradiol (E2) were also determined in the plasma of N-nitrosamines-treated rabbits after one, four-, eight- and twelve weeks of treatment of male New Zealand rabbits with an oral dose of 0.5 mg/kg B.W/day of each compound. In addition, activities of glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and levels of free radicals measured as thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) level were quantified in both livers and testes. The present study showed that levels of free radicals (TBARS) were markedly increased, whereas GSH levels were depleted in the tissues of both livers and testes after treatment of rabbits with any of N-nitrosamines. In addition, all tested N-nitrosamines inhibited the activities of antioxidant enzyme activities (GR, GST, SOD, and CAT) in hepatic and testicular tissues of rabbits after 12 weeks of treatment. Histopathological examination showed that N-nitrosamines caused lymphocytic infiltration with vascular degeneration and necrosis, congestion of central vein with RBCs hemolysis, dilated sinusoids, as well as fibrosis around portal areas were seen in hepatic tissues. In the testes, histopathological examination displayed disorganized seminiferous tubules with degeneration of germinal epithelium and Sertoli cells. Also, spermatogenic cells had pyknotic nuclei and others were detached from basement membranes of seminiferous tubules, edema was seen between seminiferous tubules. Moreover, the present data showed that MEN and DEN down-regulated the protein expression of both CYP19A1 and 21A2 in both livers and testes of male rabbits. In addition, both MEN and DEN decreased levels of testosterone and estradiol in plasma of treated rabbits. On the one hand, DMN and DPN markedly up-regulated the protein expression of CYP19A1 in both hepatic and testicular tissues of treated rabbits. These compounds potentially increased estradiol and decreased testosterone levels. On the other hand, no correlation was found between the expression of CYP11A1 and levels of both testosterone and estradiol. It is concluded that most of tested N-nitrosamines induce different changes, which could be a new mechanism of infertility due to exposure to N-nitrosamines from different environmental sources.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infertilidade/induzido quimicamente , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Estradiol/metabolismo , Radicais Livres/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Infertilidade/metabolismo , Masculino , Nitrosaminas/metabolismo , Oxirredução , Estresse Oxidativo , Coelhos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Testosterona/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
9.
Trop Biomed ; 33(4): 632-640, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33579059

RESUMO

In the current study, tyrosine aminotransferase (TAT) as a target enzyme was purified from the liver of control and Schistosoma-infected mice that was subjected to catalytic investigation. The purified enzyme has a single band on SDS-PAGE with a molecular mass of almost 100 KD from control and infected mice. The kinetic studies of hepatic TAT towards its substrates showed no change in Km, whereas Vmax value was increased from 2.3 to 2.9 fold in the enzyme isolated from Schistsoma- infected mice. In addition, the Kcat/ Km ratio displayed a higher value for the enzyme from infected mice, indicating that it is more efficient and specific. On the other hand, the in vitro effect of praziquantel showed a slight activation of hepatic TAT in both control and infected mice, whereas mirazid (MZD) has an inhibitory effect in a concentration-dependent manner. The response of TAT from infected mice towards MZD inhibition is less than that from controls. These data suggest that there is a change in the catalytic properties of hepatic TAT in schistosomiasis and the in vitro effect of the schistosomicidal drugs appears to have inductive or inhibitory effect.

10.
J Enzyme Inhib ; 16(3): 259-67, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11697046

RESUMO

Mammalian and hepatic aspartate transcarbamylase is inhibited by phenobarbital p-nitrophenylhydrazone in a reversible and non-competitive type with Ki values 8.45 x 10(-5) and 9.64 x 10(-5) M in the reactions toward carbamyl phosphate and aspartate, respectively. In vivo inhibition occurred in a dose-dependent manner in which less than 50% of the activity was retained. These observations suggest that this inhibitor may interfere with the in vivo regulation of this enzyme and lead to an additional biological effect of phenobarbitals.


Assuntos
Aspartato Carbamoiltransferase/antagonistas & inibidores , Aspartato Carbamoiltransferase/metabolismo , Inibidores Enzimáticos/metabolismo , Fenobarbital/análogos & derivados , Animais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Cinética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Fenobarbital/química , Fenobarbital/metabolismo , Fenobarbital/farmacologia
11.
J Enzyme Inhib ; 16(4): 381-90, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11916144

RESUMO

Succinate-cytochrome c reductase (SCR) from mouse liver was inhibited strongly and reversibly by an iron (II) macrocyclic complex 3. The inhibition was observed for the enzyme toward the reduction of both 2,6-dichlorophenol indophenol (DCIP) and cytochrome c (cyt c). The inhibition was a mixed type and noncompetitive with respect to the reduction of DCIP and cyt c, respectively. Values of the inhibition constant ranged from 6.6 to 8.3 microM. The IC50 for the complex 3 was found to be 16.6 +/- 0.8 and 12.1 +/- 0.5 microM for the enzyme toward DCIP and cyt c, respectively. The reduced form of complex 3 also exhibited enzyme inhibition but to a less extent. Complex 3, at a lower level, equal to 25% of its LD50 showed about 50% inhibition of the enzyme through in vivo dose-dependent effect. These findings suggested that the structure of the equatorial benzoquinoid macrocyclic ligand of the Fe(II) complex is involved in the enzyme inhibition.


Assuntos
Inibidores Enzimáticos/química , Compostos Ferrosos/farmacologia , Succinato Citocromo c Oxirredutase/antagonistas & inibidores , Administração Oral , Animais , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/química , Heme/química , Cinética , Ligantes , Camundongos , Mimetismo Molecular , Relação Estrutura-Atividade , Taxa de Sobrevida
12.
Carbohydr Res ; 317(1-4): 100-9, 1999 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-10466209

RESUMO

The hepatic lysosomal glycosidases alpha-glucosidase and beta-glucuronidase were inhibited in vitro and in vivo by mono- and diethanolamines. The in vivo inhibition is dose dependent and occurs at a value less than LD50. Phenyl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside inhibited alpha-glucosidase both in vitro and in vivo. The treatment of the enzymes in vitro by ethanolamine exhibited a reversible inhibition of the mixed and competitive types for alpha-glucosidase and beta-glucuronidase, respectively. Diethanolamine showed a reversible inhibition of the competitive type for both enzymes. It is a potent inhibitor for beta-glucuronidase, in vitro, whose inhibition constant (Ki) is 5 x 10(-5) M. Phenyl 6-deoxy-6-(morpholin-4-yl)-beta-D-glucopyranoside is a potent inhibitor only for hepatic alpha-glucosidase with a Ki value of 1.6 x 10(-5) M. The pattern of the pH dependence of enzymic activity was not affected by ethanolamine inhibition. The magnitude of the inhibition of enzymes is dependent on the structure of the inhibitor.


Assuntos
Inibidores Enzimáticos/farmacologia , Etanolaminas/farmacologia , Glucosídeos/farmacologia , Glucuronidase/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases , Fígado/enzimologia , Lisossomos/enzimologia , Morfolinas/farmacologia , Animais , Inibidores Enzimáticos/química , Etanolaminas/química , Glucosídeos/química , Glucuronidase/isolamento & purificação , Concentração de Íons de Hidrogênio , Cinética , Camundongos , Morfolinas/química , alfa-Glucosidases/isolamento & purificação
13.
Biochim Biophys Acta ; 1299(1): 141-5, 1996 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-8555246

RESUMO

Glycolipid sulfotransferase activity in a human renal cancer cell line, SMKT-R3, is enhanced by the action of growth factors such as EGF, TGF-alpha and HGF, whose receptors possess tyrosine kinase domains. We investigated whether tyrosine kinases are involved in the regulation of the sulfotransferase in the cells by using specific tyrosine kinase inhibitors. Genistein and tyrphostin 51 not only cancelled the enhancement of the sulfotransferase by EGF but also reduced the enzyme level to a point much lower than that seen in non-treated cells, whereas they did not affect the sulfotransferase activity in vitro. The activity-reducing effects of genistein were dose- and time-dependent. Genistein also inhibited the cell growth of SMKT-R3 cells. Western blotting using anti-phosphotyrosine monoclonal antibody revealed a tyrosine-phosphorylated protein with an apparent molecular mass of 116 kDa in the non-treated cells. The EGF receptor was tyrosine-phosphorylated by the addition of EGF. The phosphorylations of the 116 kDa protein and EGF receptor were attenuated by co-incubation with genistein. These results indicate that tyrosine kinases including the EGF receptor are involved in the growth of SMKT-R3 cells and in the regulatory mechanisms of glycolipid sulfotransferase in the cells.


Assuntos
Neoplasias Renais/enzimologia , Proteínas Tirosina Quinases/fisiologia , Sulfotransferases/metabolismo , Divisão Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Fator de Crescimento Epidérmico/antagonistas & inibidores , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/antagonistas & inibidores , Genisteína , Humanos , Isoflavonas/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Células Tumorais Cultivadas
14.
Indian J Biochem Biophys ; 31(2): 136-7, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7927435

RESUMO

The synthetic peptides AC-Glu-Phe-Phe (NO2)-Arg-amide (peptide VP) and AC-Ile-Glu-Phe-Phe (NO2)-Arg-amide (peptide VIP) are more readily hydrolyzed by human pepsin in gastric juice of patients of gastritis than those of duodenal ulcer and normal subjects. The kinetic parameters suggest that S3 subsite of the enzyme plays a role in the elevation of enzyme activity in gastric disease.


Assuntos
Úlcera Duodenal/enzimologia , Suco Gástrico/enzimologia , Gastrite/enzimologia , Oligopeptídeos/metabolismo , Pepsina A/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Humanos , Cinética , Dados de Sequência Molecular , Valores de Referência , Especificidade por Substrato
15.
Int J Biochem ; 26(1): 35-42, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8138045

RESUMO

1. The tetrapeptide Ala2-Nph2 (where Nph = p-nitrophenylalanyl) is treated by porcine pepsin to study the mechanism of aminotranspeptidation reactions. 2. The major initial product is Ala2-Nph and the major transpeptidation products are Nph2 and Nph3 accompanied by some Nph, a little Nph4, Ala2-Nph3 and Ala2-Nph4. 3. Oligomers of Nph greater than tetramers are formed near the end of the reaction. 4. In presence of [3H]Nph, no incorporation of Nph into the transpeptidation products is observed. 5. 18O-labeling shows extensive incorporation of 18O atoms from [18O]water in the carbonyl oxygens of Nph residues.


Assuntos
Aminoácidos/química , Pepsina A , Sequência de Aminoácidos , Animais , Catálise , Cromatografia Líquida de Alta Pressão , Dados de Sequência Molecular , Isótopos de Oxigênio , Fenilalanina/análogos & derivados , Suínos
16.
Arch Biochem Biophys ; 306(2): 297-303, 1993 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8215428

RESUMO

The kinetic parameters kcat and Km were determined at 25 degrees C and pH 5.5 for endothiapepsin and rhizopuspepsin acting on the series of substrates Ac-Ala(m)-Lys-Nph-Ala(n)-amide where Nph is p-nitrophenylalanine, and m and n equal 0-4. Kinetic parameters were also determined at 25 degrees C and pH 3.5 for pig pepsin acting on the series of substrates Ac-Ala(m)-Phe-Nph-Argn-Ala(n)-amide, where m equals 0 to 2 and n equals 0 or 1, and another series based on -Ile-Glu-Phe-Nph-Arg-, which is the core of a series of peptides designed by Dunn et al. (1986, Biochem. J. 237, 899-906). Km values were found to be largely independent of increases in the chain length of the substrates whereas kcat values showed large increases with increasing chain length. With endothiapepsin and rhizopuspepsin the largest increases (between 13-fold and over 150-fold) were obtained when alanine residues were added in positions P3 and P'2 and thus are similar to those observed previously with penicillopepsin. Additions of alanines to positions P2, P'3, and P'4 gave much smaller increases. In the case of pig pepsin the results were not as clearcut. Whereas the largest increases were seen for positions P3 and P'2 only with some of the peptides, the increases were strongly dependent on the length of the peptides. With some of the longer peptides the increases were comparable to those seen for positions P2 and P'3. Thus, whereas the addition of two alanines in position P3 to the dipeptide Ac-Phe-Nph-amide caused a large proportional increase in kcat, the increase was much smaller when the addition was made to the homologous tetrapeptide and even smaller when made to the pentapeptide Ac-Ala-Phe-Nph-Arg-Ala-amide. Additions of arginine in position P'2 gave large increases in kcat for all three peptides of the series.


Assuntos
Ácido Aspártico Endopeptidases/metabolismo , Pepsina A/metabolismo , Sequência de Aminoácidos , Animais , Ácido Aspártico Endopeptidases/química , Sítios de Ligação , Cinética , Dados de Sequência Molecular , Oligopeptídeos/síntese química , Oligopeptídeos/metabolismo , Especificidade por Substrato , Suínos
17.
Hokkaido Igaku Zasshi ; 63(2): 277-92, 1988 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3384398

RESUMO

Previous studies from this laboratory have demonstrated that arylsulfatase B (ASB) is phosphorylated by a protein kinase, which is the first finding of phosphorylation in lysosomal hydrolases. The present study was undertaken to characterize the sites of phosphorylation in ASB from transplanted human lung cancer and from normal human tissues, and to identify type of tumor protein kinase responsible for the phosphorylation of ASB. When ASB purified from liver and placenta was phosphorylated in vitro by a cAMP-dependent protein kinase, it gave a single tryptic phosphopeptide (X) and phosphothreonine. On the other hand, the tumor ASB which had been phosphorylated in vivo demonstrated two phosphopeptides X and Y. Since the tumor ASB had been shown to be phosphorylated both at threonine and serine residues, phosphorylation at threonine residue of peptide X, which is phosphorylated by a cAMP-dependent protein kinase, will be cancer-associated. Through photoaffinity labeling with a labeled cAMP analogue to detect regulatory subunits of cAMP-dependent protein kinase subtypes, it was found that the cAMP-dependent protein kinase in the transplanted lung tumor was largely type II which can be ascribed to the appearance of highly phosphorylated ASB in the tumor.


Assuntos
Condro-4-Sulfatase/metabolismo , Lisossomos/enzimologia , Neoplasias/enzimologia , Sulfatases/metabolismo , Humanos , Fígado/enzimologia , Neoplasias Pulmonares/enzimologia , Fosforilação , Proteínas Quinases/metabolismo
18.
Biochem Biophys Res Commun ; 150(1): 163-9, 1988 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-2827663

RESUMO

Since a lysosomal arylsulfatase B has been shown to be phosphorylated by a cAMP-dependent protein kinase (cAMP-PK) in transplantable human lung tumor, protein kinase isozymes were investigated in the tumor. Although the kinase of normal human lung comprised both type I and II isozymes at lower level, the tumor kinase was elevated in the activity and occupied almost exclusively by the type II which was responsible for the phosphorylation of arylsulfatase B. The isozyme deviation was also observed in the casein kinase of the tumor with predominance of type II in the tumor in contrast to the coexistence of both types I and II in normal lung.


Assuntos
Condro-4-Sulfatase/metabolismo , AMP Cíclico/farmacologia , Isoenzimas/metabolismo , Neoplasias Pulmonares/enzimologia , Proteínas Quinases/metabolismo , Sulfatases/metabolismo , Caseína Quinases , Cromatografia , Citosol/enzimologia , Histonas/metabolismo , Humanos , Fosforilação
19.
J Biol Chem ; 262(3): 1230-8, 1987 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-2433276

RESUMO

We previously demonstrated that an acidic variant (B1) of lysosomal arylsulfatase B from transplanted human lung cancer is phosphorylated on its protein and carbohydrate moieties (Gasa, S., and Makita, A. (1983) J. Biol. Chem. 258, 5034-5039). The present study identifies that a cAMP-dependent protein kinase is responsible for phosphorylation of arylsulfatase B. The protein kinase activity toward the sulfatase was considerably higher in the transplanted lung cancer than in normal lung in the presence of cAMP. B enzyme purified from normal human liver was found to contain 0.6 mol/mol B enzyme, and protein kinase treatment added further 1.3 mol of Pi to give a single phosphopeptide (X). On the other hand, B1 enzyme purified from the transplanted human lung cancer which had been labeled in vivo with 32Pi revealed at least two phosphopeptides (X and Y). Assuming that the sulfatase from normal liver and lung cancer possesses the same number of available phosphorylation sites, phosphorylation of site X which was available only by deliberate phosphorylation of the native, ordinary B enzyme appears to be cancer-associated. Increasing phosphorylation of the sulfatase resulted in a maximum 50% elevation in arylsulfatase activity, followed by a decrease of the activity upon overphosphorylation, using an artificial substrate.


Assuntos
Condro-4-Sulfatase/metabolismo , AMP Cíclico/farmacologia , Neoplasias Pulmonares/enzimologia , Lisossomos/enzimologia , Proteínas Quinases/metabolismo , Sulfatases/metabolismo , Animais , Anticorpos/imunologia , Sítios de Ligação , Condro-4-Sulfatase/imunologia , Epitopos/imunologia , Humanos , Ponto Isoelétrico , Fígado/enzimologia , Pulmão/enzimologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fosfatos/metabolismo , Fosforilação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA