RESUMO
OBJECTIVE: To assess the diagnostic accuracy of ultrasound for detecting placenta accreta spectrum (PAS) during the first trimester of pregnancy and compare it with the accuracy of second- and third-trimester ultrasound examination in pregnancies at risk for PAS. METHODS: PubMed, EMBASE and Web of Science databases were searched to identify relevant studies published from inception until 10 March 2023. Inclusion criteria were cohort, case-control or cross-sectional studies that evaluated the accuracy of ultrasound examination performed at < 14 weeks of gestation (first trimester) or ≥ 14 weeks of gestation (second/third trimester) for the diagnosis of PAS in pregnancies with clinical risk factors. The primary outcome was the diagnostic accuracy of sonography in detecting PAS in the first trimester, compared with the accuracy of ultrasound examination in the second and third trimesters. The secondary outcome was the diagnostic accuracy of each sonographic marker individually across the trimesters of pregnancy. The reference standard was PAS confirmed at pathological or surgical examination. The potential of ultrasound and different ultrasound signs to detect PAS was assessed by computing summary estimates of sensitivity, specificity, diagnostic odds ratio and positive and negative likelihood ratios. RESULTS: A total of 37 studies, including 5764 pregnancies at risk of PAS, with 1348 cases of confirmed PAS, were included in our analysis. The meta-analysis demonstrated that ultrasound had a sensitivity of 86% (95% CI, 78-92%) and specificity of 63% (95% CI, 55-70%) during the first trimester, and a sensitivity of 88% (95% CI, 84-91%) and specificity of 92% (95% CI, 85-96%) during the second/third trimester. Regarding sonographic markers examined in the first trimester, lower uterine hypervascularity exhibited the highest sensitivity (97% (95% CI, 19-100%)), and uterovesical interface irregularity demonstrated the highest specificity (99% (95% CI, 96-100%)). In the second/third trimester, loss of clear zone had the highest sensitivity (80% (95% CI, 72-86%)), and uterovesical interface irregularity exhibited the highest specificity (99% (95% CI, 97-100%)). CONCLUSIONS: First-trimester ultrasound examination has similar accuracy to second- and third-trimester ultrasound examinations for the diagnosis of PAS. Routine first-trimester ultrasound screening for patients at high risk of PAS may improve detection rates and allow earlier referral to tertiary care centers for pregnancy management. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Placenta Acreta , Primeiro Trimestre da Gravidez , Sensibilidade e Especificidade , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Placenta Acreta/diagnóstico por imagem , Terceiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Trimestres da GravidezRESUMO
P-glycoprotein (P-gp) is an ABC transporter exhibiting high pharmacotoxicological relevance by extruding a wide range of cytotoxic compounds out of the cells. Previously, we demonstrated that the phytoestrogen genistein (GNT) modulates P-gp expression in hepatocellular carcinoma in vitro. Although several beneficial effects (e.g., antioxidant, antimutagenic, anticancer) have been attributed to GNT, the molecular mechanisms have not been totally elucidated. In the present work, we evaluated the effect of GNT on P-gp expression in rat liver, kidney and ileum. We found that GNT (5 mg/kg daily s.c. 3 days) increased hepatic P-gp expression and also Mdr1a (one of the genes encoding P-gp) mRNA levels. Renal and intestinal P-gp remained unchanged after GNT treatment. Hepatic P-gp activity measured with rhodamine-123 and digoxin, both well-known P-gp substrates, was also increased. In vitro experiments using hepatocyte primary cell culture demonstrated that inhibition of ER-α with ICI182/780 did not prevent Mdr1a mRNA up-regulation by GNT (10 µM). In contrast, Mdr1a induction was suppressed after pregnane X receptor (PXR) inhibition by sulforaphane and knockdown of this nuclear receptor. These findings were confirmed in vivo by using the PXR antagonist ketoconazole. In conclusion, we demonstrated the induction of hepatic P-gp expression and activity by GNT in vivo, with PXR being a likely mediator. This suggests that GNT, at concentrations observed in plasma of individuals consuming the phytoestrogen in the diet or through supplements, could affect the clearance of relevant P-gp substrates of therapeutic use as well as toxicity of environmental and food toxicants.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Anticarcinógenos/toxicidade , Genisteína/toxicidade , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , RNA Mensageiro/metabolismo , RatosRESUMO
AIMS: The Algerian coastline is exposed to several types of pollution, including hydrocarbons. The aim of this work was to isolate oil-degrading bacteria and to explore the intrinsic bioremediation potential of part of its contaminated harbour. METHODS AND RESULTS: A collection of 119 strains, capable to grow on mineral medium supplemented with hydrocarbons, were obtained from polluted sediment and seawater collected from Sidi Fredj harbour (Algiers). Twenty-three strains were selected for further studies. Sequencing of the 16S rRNA gene showed that most isolates belong to genera of hydrocarbonoclastic bacteria (Alcanivorax), generalist hydrocarbons degraders (Marinobacter, Pseudomonas, Gordonia, Halomonas, Erythrobacter and Brevibacterium) and other bacteria not known as hydrocarbon degraders (Xanthomarina) but were able to degrade hydrocarbons. Strains related to Marinobacter and Alcanivorax were frequently isolated from our samples and resulted the most effective in degrading crude oil. Screening of catabolic genes alkB and xylA revealed the presence of alkB gene in several bacterial strains; one isolate harboured both catabolic genes while other isolates carried none of the studied genes. However, they grew in the presence of crude oil implying the existence of other biodegradation pathways. CONCLUSIONS: The samples of seawater and sediment from the Algerian coast contain high level of hydrocarbon-degrading bacteria that could be interesting and useful for future bioremediation purposes. SIGNIFICANCE AND IMPACT OF THE STUDY: This investigation demonstrates the diversity of hydrocarbon-degrading bacteria from a marine-contaminated area in Algeria, and their variable biodegradation abilities.
Assuntos
Bactérias/isolamento & purificação , Bactérias/metabolismo , Petróleo/metabolismo , Água do Mar/microbiologia , Argélia , Bactérias/classificação , Bactérias/genética , Biodegradação Ambiental , Biotecnologia , Hidrocarbonetos/metabolismo , Filogenia , RNA Ribossômico 16S/genéticaRESUMO
AIM: After the revolution in the surgery of gallbladder stones represented by the laparoscopic cholecystectomy, we tried a new technique that further maximize the aesthetic results and that at the same time is of easy learning for young surgeons. PATIENTS AND METHODS: From January 2011 to December 2012 we performed at our department 320 cholecystectomy: 27 in laparotomy and 293 in laparoscopy. Of these, 88 underwent to Single Incision Laparoscopic Surgery (SILS), namely the Single Incision Laparoscopic Cholecystectomy (SILC), in recruited patients aged between 19-65 years; 56 patients were females and 32 were males. RESULTS: The laparoscopic cholecystectomy with the SILS methodology is a safe technique. Respect to multi-port Laparoscopic Cholecystectomy (LC), we have cosmetic advances. The pain is less in extraumbilical sites, and the major umbilical pain can be prevented by local anaesthesia. The times are slightly longer, especially at the beginning of training, but after a few of operations it is reduced to about one hour. We didn't found any other difference in vantage and advantage between the two technics, only a case of postoperative umbilical hernia in SILS. CONCLUSION: We found the SILS a safe and effective technique for the cholecystectomy.
Assuntos
Colecistectomia Laparoscópica/métodos , Cálculos Biliares/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Children have an high risk of renal damage as a result of blunt trauma. Conservative management is always recommended for lower grades (I to III) but is rather controversial whenever high grade injuries (grade IV and V) are concerned. We describe a case of successful conservative management in grade IV renal injury occurred in a 9-years-old girl with blunt trauma.
Assuntos
Rim/lesões , Stents , Ferimentos não Penetrantes/complicações , Criança , Drenagem/métodos , Feminino , Humanos , Rim/patologia , Tratamentos com Preservação do Órgão/métodos , Ferimentos não Penetrantes/patologia , Ferimentos não Penetrantes/terapiaRESUMO
Lymphoma of cheek is a rare ad uncommon disease, representing 2,5% of malignant lymphoma. The cause is unknown but there are a lot of risk factors such as Helicobacter pylori and Epstein Barr virus. Symptoms are aspecific and may be confused with otolaryngological benign diseases. We present a case of B cell lymphoma of the cheek, which presented with a history of a slowly growing swelling of 3 months duration, resistant to NSAIDs and antibiotic therapy. Biopsy of the mass led to diagnosis of lymphoma. Blood investigations, ultrasonography and CT scan helped to reach this result. This case report shows that an accurate clinical examination, a cytohistological and immune-histochemical diagnosis by fine-needle aspiration biopsy (FNAB) are fundamental to obtain a diagnosis and to decide therapy.
Assuntos
Bochecha/patologia , Linfoma de Células B/diagnóstico , Idoso , Biópsia por Agulha Fina , Feminino , Citometria de Fluxo , Humanos , Linfoma de Células B/patologia , Tomografia Computadorizada por Raios XRESUMO
Extraskeletal osteosarcoma (ESOS) is a rare malignant mesenchymal neoplasm that accounts for less than 4% of all osteosarcomas and approximately 1-2% of all soft tissue sarcomas. The tumor is typically located in the deep soft tissues, without attachment to skeletal bones. Although ESOS has been found todevelop virtually in every organ, its most common locations are the limbs. In the case of abdominal or pelvic lesions the diagnosis can be very difficult, thus it necessarily requires confirmation after exploratory laparotomy and histopathology. Such tumors may reach enormous sizes before detection because the enlarging mass may not be associated with pain. ESOS may be one of the differential diagnoses to be considered in the case of calcified masses arising in retroperitoneal space. Here we describe a bulky, bilateral, metastatic ESOS arising from the retroperitoneum and causing obstructive uropathy with consequent hydronephrosis.
Assuntos
Calcinose/complicações , Hidronefrose/etiologia , Osteossarcoma/complicações , Neoplasias Retroperitoneais/complicações , Idoso , Calcinose/patologia , Calcinose/terapia , Feminino , Humanos , Hidronefrose/terapia , Neoplasias Pulmonares/secundário , Invasividade Neoplásica , Osteossarcoma/secundário , Osteossarcoma/terapia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/terapia , Resultado do Tratamento , Obstrução Ureteral/etiologiaRESUMO
Primary intestinal lymphoma is rare representing about 0.5% of all colonic malignancies. It can be classified into two principal categories: follicular B cell lymphomas and intestinal T cell lymphomas. Other intestinal diseases are very important such as immunoproliferative small intestinal disease (IPSID), a prelymphomatous process, and MALT lymphomas, caused by infection of Helicobacter pylori (H. Pylori). We present a 79-year-old male patient which presented with abdominal pain in the upper parts of abdomen of four months' duration, colic timpanists, tenderness, distention, weight loss. Sometimes the abdominal pain decreased expelling diarrheal dejections. Histological and immune-histochemical tests on bioptic piece helped to reach the diagnosis of lymphoma but only after histological investigation on operative piece was made the diagnosis of B-cell lymphoma. This case report shows that an accurate diagnosis, the evaluation of the extension and the presence of particular infections and/or co morbidities (H. Pylori positive, age, performance status) are fundamental to decide the therapeutic protocol.
Assuntos
Neoplasias Intestinais/patologia , Linfoma de Células B/patologia , Idoso , Antígenos CD/análise , Biópsia , Colectomia , Infecções por Helicobacter/complicações , Humanos , Neoplasias Intestinais/cirurgia , Linfoma de Células B/cirurgia , Masculino , Linfócitos T/imunologia , Tomografia Computadorizada por Raios XRESUMO
Gastrointestinal Stromal Tumor (GIST) is a rare intra-abdominal tumor, characterized by a specific histological and immunohistochemical pattern. These tumors affect with higher frequency stomach and small bowel and occur at a median age of 60 years with a slight male predominance. An early stage of GIST often don't cause any symptoms, so most GISTs are diagnosed in later stages of the disease. We report a case of GIST diagnosed only with clinical data and positron emission tomography (PET). We demonstrate the usefulness of neoadjuvant treatment with Imatinib mesylate, a newly developed tyrosine kinase receptor inhibitor. The neoadjuvant treatment with Imatinib reduced the mass size and vascularization, making possible a surgical approach.
Assuntos
Tumores do Estroma Gastrointestinal/terapia , Terapia Neoadjuvante/métodos , Tomografia por Emissão de Pósitrons/métodos , Idoso , Benzamidas , Terapia Combinada , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib , Masculino , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
Malignant skin cancer of the scalp with skull invasion, dural infiltration and brain involvement is a uncommon lesion. This scenario is most often encountered in patients where initial scalp lesions are not appropriately diagnosed or their extent is underestimated by the patient and/or the doctor. Our study is a retrospective review of 25 patients treated using a multidisciplinary approach (combined plastic surgery/neurosurgery procedure and neuro-oncological management). After a mean follow-up of 7 years, 22 patients did not show local recurrence or distant metastases of their primary disease. Overall, these 22 patients had excellent quality of life; however, three patients died from causes not related to their primary pathology. To obtain a complete and definitive cure, prompt diagnosis of scalp cancers followed by appropriate multidisciplinary management is strongly advised.
Assuntos
Carcinoma/secundário , Carcinoma/terapia , Invasividade Neoplásica/patologia , Couro Cabeludo/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Idoso , Neoplasias da Mama/secundário , Carcinoma/mortalidade , Cavidades Cranianas/patologia , Cavidades Cranianas/cirurgia , Dura-Máter/patologia , Dura-Máter/cirurgia , Feminino , Humanos , Comunicação Interdisciplinar , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Invasividade Neoplásica/fisiopatologia , Invasividade Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/normas , Equipe de Assistência ao Paciente/normas , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/normas , Estudos Retrospectivos , Couro Cabeludo/cirurgia , Neoplasias Cutâneas/mortalidade , Crânio/patologia , Crânio/cirurgia , Retalhos Cirúrgicos , Taxa de SobrevidaRESUMO
The use of dermic substitutes is a valid and effective choice in the treatment of the cutaneous defects with loss of substance. In our experience, the aesthetic and functional results of dermic substitutes is really positive and encouraging, with better tolerance by patients than the autologue grafts.
Assuntos
Pele Artificial/estatística & dados numéricos , Úlcera Varicosa/cirurgia , Idoso , Curetagem , Feminino , Seguimentos , Humanos , Fatores de Tempo , Resultado do TratamentoRESUMO
Microsomal membranes from rat small intestine exhibit a higher cholesterol/phospholipid ratio and a lower phosphatidyl-choline/sphingomyelin ratio than those of the liver, which could negatively influence membrane-bound enzymes like bilirubin UDP-glucuronosyltransferase. To study the effect of in vitro modifications in the lipid composition of intestinal microsomes on bilirubin glucuronidating activity, two strategies were employed. On one hand, microsomal lipids were modified in order to mimic those of the liver tissue; on the other hand, cholesterol content of microsomal membranes was increased or decreased with respect to the normal value. Lipid changes were carried out by both an enzyme-mediated and a detergent-mediated procedure. Irrespective of the methodology employed, when a depletion in the cholesterol content was produced, enzyme activity increased about 40%, and when lipid composition approached that of the liver tissue, which not only decreased cholesterol but also modified phospholipid classes, enzyme activity increased about 80%. Both lipid modifications produced a 'fluidification' of microsomal membranes measured by fluorescence anisotropy of 1,6-diphenylhexatriene, being the effect of the approach to the liver higher than that of the decrease of cholesterol. In turn, the enrichment in cholesterol of microsomal membranes led to a decrease of enzyme activity of about 20% and to a 'rigidization' of the membranes. The present findings suggest that in rat intestine, bilirubin glucuronidation is strongly influenced by microsomal lipids. In particular, there seems to be an inverse association between enzyme activity and the cholesterol content of membrane.
Assuntos
Glucuronosiltransferase/metabolismo , Mucosa Intestinal/metabolismo , Lipídeos/análise , Microssomos/metabolismo , Animais , Ativação Enzimática , Intestinos/ultraestrutura , Masculino , Microssomos Hepáticos/metabolismo , Ratos , Ratos WistarRESUMO
To evaluate whether a temporary hepatic insufficiency may affect intestinal glucuronidation, we determined UDP-glucuronosyltransferase activity towards bilirubin and p-nitrophenol in rat jejunum and liver after partial hepatectomy. Enzyme assays were performed in native, and in UDP-N-acetylglucosamine- or palmitoyl lysophosphatidylcholine-activated microsomes at different times post-hepatectomy. Content of enzyme was analyzed by Western blot. Microsomal cholesterol/phospholipid ratio, phospholipid and total fatty acid classes were also determined to evaluate the possible influence on enzyme activity. The results show that while hepatic microsomes exhibited no change in UDP-glucuronosyltransferase activity (for both substrates) with respect to shams at any time of study, intestinal activities increased significantly 48 h after surgery, returning to sham values 96-h post-hepatectomy. Western blotting confirmed the increase (about 50% for both substrates 48-h post-hepatectomy) in intestinal UDP-glucuronosyltransferase activity. No variations were observed in hepatic and intestinal microsomal lipid composition in agreement with the absence of modification in the percent of activation by palmitoyl lysophosphatidylcholine. In conclusion, jejunum but not liver, was able to produce a compensatory increase in conjugation capacity during a transitory loss of hepatic mass. The phenomenon is associated to a modification in the amount of UDP-glucuronosyltransferase, rather than to changes in the characteristics of the enzyme environment.
Assuntos
Glucuronosiltransferase/metabolismo , Hepatectomia , Mucosa Intestinal/enzimologia , Animais , Bilirrubina/sangue , Ativação Enzimática/efeitos dos fármacos , Glucuronosiltransferase/fisiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Jejuno , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Ratos , Ratos Wistar , Uridina Difosfato N-Acetilglicosamina/farmacologiaRESUMO
The effect of lactation on UDP-glucuronosyltransferase (UGT) and Glutathione S-transferase (GST) activities was studied in jejunum from mother rats, 14 (LM14) and 21 (LM21) days after delivery. p-Nitrophenol glucuronidation rate was increased in LM14 and LM21 rats while conjugation of bilirubin and estrone was not affected and androsterone glucuronidation was decreased. Additional studies, including Western blotting and microsomal lipid analysis, revealed that the enhancement in p-nitrophenol UGT activity is most likely associated with an inductive process rather than with a modification in enzyme constraint. GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was also increased in LM14 and LM21 while activity towards 1,2-dichloro-4-nitrobenzene (DCNB) was not affected. Western blotting revealed a significant increase in the cytosolic content of mu (rGSTM2) and pi (rGSTP1) class subunits in LM14 and LM21 groups, while the alpha class subunit rGSTA2 remained unchanged. To evaluate the potential modulatory role of prolactin on the same enzyme systems, ovariectomized rats were treated with ovine prolactin (oPRL) at doses of 100, 200 and 300 microg/100 g body wt. per day for 4 days. Hormone administration affected UGT activities towards p-nitrophenol and androsterone and GST activity towards CDNB in a way and magnitude consistent with those produced in lactating rats, while conjugation of estrone, bilirubin and DCNB were unchanged. Western blotting data were also consistent with those of lactating rats. These results indicate that UGT and GST activities are increased in rat jejunum during lactation, due to induction of some specific isoforms, and that prolactin is the likely mediator of these effects.
Assuntos
Glucuronosiltransferase/biossíntese , Glutationa Transferase/biossíntese , Jejuno/enzimologia , Lactação , Prolactina/fisiologia , Animais , Biotransformação , Western Blotting , Indução Enzimática , Feminino , Glucuronosiltransferase/metabolismo , Glutationa Transferase/metabolismo , Metabolismo dos Lipídeos , Microssomos/enzimologia , Gravidez , Ratos , Ratos WistarRESUMO
AIM OF THE STUDY: to value the appropriateness and the efficacy of non-operative treatment in children with blunt abdominal trauma. PATIENTS AND METHODS: in this research 14 children with abdominal trauma, secondary mostly to road accidents, were studied; 9 of these had single organ injury while 5 had multiple organ injuries. Spleen has been the most injured organ (9 children), followed by liver (5 cases) and kidney (2 cases). Five children were admitted at emergency department in hypovolemic conditions, promptly corrected by resuscitative measures. All patients underwent abdominal ultrasound and/or C.T. scans in order to detect any intraperitoneal free fluid or organic injuries. Six children (43%) were followed by non-operative treatment, while other eight underwent surgery. RESULTS: all children, those treated conservatively as well as those operated, were cured, without any important complication. DISCUSSION AND CONCLUSIONS: nowadays, with the great help of ultrasound and C.T. scans, is possible to treat 40-50% of children affected by abdominal trauma with non-operative measures, with return to normal functions by the injured organs. The surgical approach is today accomplished only in presence of severe injuries or haemodynamic instability resistant to resuscitative treatment. The majority of Authors in the literature agree on the usefulness of non-operative treatment, especially for children. Regarding surgical treatment, in the near future probably we'll see a larger application of laparoscopic techniques also in the field of abdominal traumatology.
Assuntos
Traumatismos Abdominais/cirurgia , Ferimentos não Penetrantes/cirurgia , Traumatismos Abdominais/diagnóstico , Acidentes de Trânsito , Adolescente , Algoritmos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Centros de Traumatologia , Resultado do Tratamento , Ferimentos não Penetrantes/diagnósticoRESUMO
In the present study, hepatic p-nitrophenol glucuronidation was analyzed comparatively in virgin female, lactating mother and nonlactating mother rats (the last two groups 19-21 days post-partum). Enzyme assays were performed in native and activated microsomal suspensions. Activation was achieved either by including UDP-N-acetylglucosamine in the incubation mixtures or by preincubating native microsomes with optimal concentrations of Triton X-100 or palmitoyl-lysophosphatidylcholine. When UDP-N-acetylglucosamine was used as activator, enzyme activity increased in both lactating (about 80% increment) and nonlactating mothers (about 30% increment) as compared with virgin females. From an analysis of the degree of activation by Triton X-100 and palmitoyl-lysophosphatidylcholine, it can be inferred that the pregnancy-delivery event decreased the latency of UDP-glucuronosyltransferase activity that was detectable even 3 weeks post-partum, irrespective of whether suckling newborns were or were not kept with their mothers (lactating and nonlactating mothers, respectively). The estimation of apparent Vmax toward UDP-glucuronic acid in palmitoyl-lysophosphatidylcholine-activated microsomes, which allows an estimation of the amount of the enzyme, showed that lactation increased the number of catalytic units (about 40%). Hepatic UDP-glucuronic acid content was 70% higher in lactating rats than in other groups. The lipid composition and membrane fluidity (using 1,6-diphenyl-1,3,5-hexatriene as probe) were also analyzed in microsomes from all groups. A significant decrease in the unsaturation index that correlated with the rigidization of microsomal membranes was consistent with the changes in the degree of enzyme latency observed in lactating and nonlactating mothers. In conclusion, lactating rats exhibited enhanced p-nitrophenol UDP-glucuronosyltransferase activity as well as an increase in the hepatic content of UDP-glucuronic acid. These findings and the fact that lactation increased the liver to body weight ratio emphasize the role of the liver in the metabolism of planar phenolic derivatives in these circumstances.
Assuntos
Glucuronosiltransferase/metabolismo , Lactação , Microssomos Hepáticos/metabolismo , Nitrofenóis/metabolismo , Animais , Ácidos Graxos/análise , Feminino , Lisofosfatidilcolinas , Fluidez de Membrana , Lipídeos de Membrana/análise , Octoxinol , Ratos , Ratos WistarRESUMO
The basis for gender-dependent differences in rates of glucuronidation of xenobiotics is uncertain. To clarify this issue, the glucuronidation of p-nitrophenol was compared in liver microsomes from adult male and female rats. The activity of native UDP-glucuronosyltransferase was 47% higher in microsomes from male than from female rats. Immunoblotting of microsomal protein with anti-UDP-glucuronosyltransferase antiserum revealed 66% more immunoreactive protein in male microsomes. A kinetic method for measuring glucuronidating enzyme content confirmed the result of the immunoblot. Responses of UDP-glucuronosyltransferase to activation by palmitoyllysophosphatidylcholine or high pressure indicated that the activity of the enzyme was more latent in male than in female microsomes. Differences in enzyme latency could be due to differences in membrane structure. A comparison of microsomal fatty acid composition revealed significantly higher levels of oleic and linoleic acids and lower levels of stearic and docosahexaenoic acids in male than in female microsomes. The phospholipid composition, ratio of cholesterol:phospholipid, and membrane fluidity were similar in male and female microsomes. These results indicate that gender-dependent differences in UDP-glucuronosyltransferase activity are due to differences in both the amount and functional state of the enzyme.
Assuntos
Glucuronosiltransferase/metabolismo , Microssomos Hepáticos/enzimologia , Animais , Colesterol/análise , Detergentes , Ativação Enzimática/efeitos dos fármacos , Ácidos Graxos/análise , Feminino , Membranas Intracelulares/química , Cinética , Lisofosfatidilcolinas/farmacologia , Masculino , Nitrofenóis/metabolismo , Fosfolipídeos/análise , Pressão , Ratos , Ratos Wistar , Fatores SexuaisRESUMO
Gender-related differences and the regulation by testosterone of glutathione S-transferase were studied in rat jejunum. We analyzed enzyme activity and the relative content of GST subunits. Four experimental groups of adult rats were studied: normal males, castrated males, castrated males injected with testosterone and normal females. Glutathione S-transferase activity was assayed using 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates. Differences in subunit composition among groups were evaluated by western blot analysis. The results demonstrated that 1-chloro-2,4-dinitrobenzene conjugation rate is higher in normal males than in normal females and castrated males. Testosterone administration to castrated males raised the activity up to the level observed in normal males. No significant difference in glutathione S-transferase activity towards 1,2-dichloro-4-nitrobenzene was observed among groups. Western blot analysis revealed that males and females differ in all subunits tested that is, rGSTA2, rGSTM1, rGSTM2 and rGSTP1, and that testosterone regulates the content of rGSTM1, rGSTM2 and rGSTP1. In conclusion, jejunal GST shows a gender-dependent regulation affecting both enzyme activity and subunit composition, and testosterone appears to be one of the factors involved.
Assuntos
Glutationa Transferase/metabolismo , Jejuno/enzimologia , Testosterona/farmacologia , Animais , Western Blotting , Citosol/metabolismo , Dinitroclorobenzeno/metabolismo , Feminino , Jejuno/efeitos dos fármacos , Masculino , Nitrobenzenos/metabolismo , Ratos , Ratos Wistar , Caracteres Sexuais , Testosterona/sangueRESUMO
The effect of spironolactone pretreatment on glutathione S-transferase activity and on the relative content of the principal subunits (Ya, Yc, Yb1, Yb2 and Yp or 1, 2, 3, 4 and 7 respectively) was studied in rat liver, jejunum and colon. Male Wistar rats were injected with spironolactone i.p. at daily doses of 50, 100 and 200 micromol/kg body wt for 3 consecutive days. Glutathione S-transferase activities were assayed using 1-chloro-2,4-dinitrobenzene as substrate. Changes in subunit composition were evaluated by Western blot analysis in rats treated with the highest dose of spironolactone. The results demonstrated a dose-dependent increase in enzyme activity in liver, while in jejunum the three tested doses exhibited the same magnitude of induction. No significant difference in glutathione S-transferase activity was observed between control and treated rats for the colon. Immunoblot analysis revealed more Ya and Yp protein in liver (140 and 118% increase respectively) and jejunum (45 and 145% increase respectively) from treated rats. While Ya and Yp relative contents were similar in jejunum, the latter subunit slightly contributed to total GST in liver, even in SL-treated animals. The inducer produced no change in subunit composition in colon. In conclusion, spironolactone was able to increase glutathione S-transferase activity mainly by induction of Ya subunit in liver and Yp subunit in jejunal mucosa, without affecting colonic enzyme.
Assuntos
Colo/enzimologia , Glutationa Transferase/biossíntese , Jejuno/enzimologia , Fígado/enzimologia , Espironolactona/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Ursodeoxycholic acid and its endogenous metabolite tauroursodeoxycholic acid inhibited in vitro the microsomal bilirubin UDP-glucuronosyltransferase from rat liver. The magnitude of the inhibition correlated well with the loss of integrity of microsomal vesicles, suggesting that bile salts needed to reach the lumen to exert their inhibitory effects. The endogenous bile acids cholic acid, chenodeoxycholic acid and deoxycholic acid also exhibited inhibitory effects on bilirubin glucuronidation in digitonin-disrupted microsomes. Ursodeoxycholic acid inhibitory capacity was similar to that of chenodeoxycholic acid and deoxycholic acid but greater than that of cholic acid, the major endogenous bile salt. Kinetic studies, performed in detergent-activated preparations, showed that the inhibitions produced by ursodeoxycholic and tauroursodeoxycholic acids were competitive toward both bilirubin and UDP-glucuronic acid. The estimated Ki(app) for both substrates did not differ statistically between ursodeoxycholic and tauroursodeoxycholic acids. Both bile salts were weak inhibitors toward bilirubin but rather strong inhibitors toward UDP-glucuronic acid.