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OBJECTIVE: Few studies have correlated pediatric endoscopic and histologic impressions of duodenal biopsies. Method: This is a retrospective study on children undergoing upper gastrointestinal endoscopy over a period of 11 years. We investigated concordance between the gross endoscopic and histopathologic characteristics of pediatric duodenal biopsies. Results: Of 1793 children enrolled in the study, duodenal pathology was observed in 72.3%. The gross endoscopic findings showed a low sensitivity of 38.9%, specificity of 99.2%, PPV of 99.2%, and NPV of 38.3%. Concordance between the gross endoscopic and histopathologic analysis was 55.6%. Conclusion: This study showed a higher rate of pediatric duodenal pathologies than gross assessment. This emphasizes the value for acquiring routine duodenal biopsies from grossly normal mucosa.
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Duodeno , Membrana Mucosa , Abdomen , Biopsia , Niño , Humanos , Estudios RetrospectivosRESUMEN
Although there is emerging evidence that mast cells are involved in infertility, their exact role has not been elucidated clearly. Here we carried out a retrospective case-control study to find out whether there is a correlation between mast cell (MC) count and proliferation (Ki67 index) of the spermatogenic epithelium as well as of the Sertoli cells (vimentin-positive) in non-obstructive azoospermia (NOA). We assessed MCs, Ki67 and vimentin expression in Sertoli cells in testicular biopsies of germ cell aplasia (GCA, n = 14) and maturation arrest (MA, n = 14) vs. normal spermatogenesis (n = 14) cases. There was a significant decrease in the spermatogonial Ki67 index (1.25 ± 0.91, 4.21 ± 1.81 vs. 39.57 ± 3.92) and Johnsen score (2.48 ± 0.65, 4.89 ± 1.05 vs. 9.75 ± 0.30) as well as a significant increase (P < 0.001) in MC count (29.00 ± 4.11, 7.57 ± 1.95 vs. 3.00 ± 1.30) in seminiferous tubules of infertile cases with GCA and MA vs. controls. On the other hand, the percentage of vimentin-expressing Sertoli cells was significantly decreased (P < 0.001) in biopsies of cases with MA (35.50 ± 15.62) compared to those of cases with GCA and controls (72.64 ± 10.67 and 98.57 ± 1.45 respectively). Additionally, a significant negative correlation was detected between MC count and Ki67 index as well as Johnsen score in the MA group which became more significant in the GCA group. The significant increase in MC count in the GCA group and to a lesser extent in the MA group indicates their possible role in NOA particularly at the spermatogonial proliferation level and this is supported by the significant negative correlation with the Ki67 index.
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Azoospermia/patología , Mastocitos/patología , Células de Sertoli/patología , Espermatogénesis , Espermatozoides/patología , Testículo/patología , Azoospermia/metabolismo , Azoospermia/fisiopatología , Biopsia , Proliferación Celular , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Estudios Retrospectivos , Células de Sertoli/química , Testículo/química , Testículo/fisiopatología , Vimentina/análisisRESUMEN
AIM OF THE STUDY: The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice. MATERIALS AND METHODS: Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured. Also, histological analysis was done. RESULTS: Asthmatic mice demonstrated apparent fibrotic changes. Significant airway fibrosis was demonstrated by hyperplasia of goblet cells and thickening of airway epithelium, increased content of lung collagen, lung and bronchoalveolar lavage of transforming growth factor beta-1 and interleukin-13 mutually accompanied by reduction in nitrate/nitrite generation. CONCLUSIONS: Beclomethasone influence on airway remodeling was mediated mainly via suppression of eosinophilic recruitment into the airways and reduction of interleukin-13 cytokine levels. Whereas, tranilast effects on airway remodeling was found to be mainly mediated via its inhibitory effect on transforming growth beta-1. Both beclomethasone and tranilast influence airway remodeling by different degrees and mechanisms.
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Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Antialérgicos/uso terapéutico , Asma/tratamiento farmacológico , ortoaminobenzoatos/uso terapéutico , Animales , Antialérgicos/farmacología , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Asma/inmunología , Beclometasona/farmacología , Beclometasona/uso terapéutico , Líquido del Lavado Bronquioalveolar/química , Enfermedad Crónica , Colágeno/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Interleucina-13/metabolismo , Recuento de Leucocitos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Óxido Nítrico/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , ortoaminobenzoatos/farmacologíaRESUMEN
The tyrosine kinase inhibitors imatinib and nilotinib have been suggested to have promising antifibrotic activity in experimental models of liver fibrosis. The aim of the present study was to investigate new pathways underlying this beneficial effect. Hepatic injury was induced in male Wistar rats by intraperitoneal injection of CCl4 for 12 weeks. During the last 8 weeks of treatment, rats were also injected daily intraperitoneally with 20 mg/kg imatinib or 20, 10 or 5 mg/kg nilotinib. At the end of treatment, effects on fibrosis were assessed by measuring serum fibrotic markers and profibrogenic cytokines, as well as by histopathological examination. Possible anti-inflammatory effects were estimated by measuring levels of inflammatory cytokines in liver tissue. Liver expression of α-smooth muscle actin, transforming growth factor (TGF)-ß1 antibodies and platelet-derived growth factor receptor ß (PDGFRß) was evaluated by immunohistochemical staining techniques. Nilotinib (5 and 10 mg/kg) significantly (P < 0.05) decreased all serum fibrotic markers measured, but 20 mg/kg of either nilotinib or imatinib had limited effects. At all doses tested, nilotinib significantly (P < 0.05) decreased the CCl4 -induced increases in tissue inflammatory cytokines. Furthermore, 5 and 10 mg/kg nilotinib significantly decreased TGF-ß1 levels and tissue expression of its antibody, as well expression of PDGFRß. In conclusion, low doses (5 and 10 but not 20 mg/kg) of nilotinib, rather than imatinib, can control hepatic fibrosis by regulating levels of proinflammatory cytokines, primarily interleukin (IL)-1 and IL-6. Nilotinib also controls the signalling pathways of profibrogenic cytokines by lowering TGF-ß1 levels and decreasing expression of PDGFRß.
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Benzamidas/farmacología , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Piperazinas/farmacología , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacos , Actinas/metabolismo , Animales , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Mesilato de Imatinib , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Masculino , Ratas , Ratas Wistar , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
A liver biopsy is essential for the diagnostic workup of persistent neonatal cholestasis (NC). The differential diagnosis of NC is broad, including obstructive and non-obstructive causes. In addition, histologic features of certain disorders may be non-specific in the early course of the disease. To evaluate liver biopsies using a practical histopathologic approach for NC and to define a simple scoring system for biliary atresia (BA) for routine clinical practice. From June 2006 to December 2021, liver biopsy specimens from infants with persistent NC were examined by two independent pathologists. The cases diagnosed as BA were correlated with clinical, radiologic, and laboratory data to calculate the final score. Four hundred and fifty-nine cases were enrolled in the study. They had a mean age of 63.94 ± 20.62 days and were followed for a median time of 58 (1-191) months. They included 162 (35.3%) cases of BA. On multivariate analysis, portal edema, ductular proliferation, cholangiolitis, and bile duct/ductular plugs were the histopathologic predictors of BA. A liver biopsy did perform well with a 95.1% sensitivity, 91.6% specificity, 86% PPV, and 97.1% NPV. At a cutoff of 5 of the scoring system, diagnosis of BA could be done with a sensitivity of 95.1% and a specificity of 100%. We have shown detailed histopathologic features of BA with more depth to infants aged ≤ 6 weeks. We have developed a simple scoring system using a combination of liver biopsy with non-invasive methods to increase the diagnostic accuracy of BA.
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Atresia Biliar , Colestasis , Hepatopatías , Lactante , Recién Nacido , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Atresia Biliar/diagnóstico , Atresia Biliar/complicaciones , Atresia Biliar/patología , Hígado/patología , Sensibilidad y Especificidad , Colestasis/diagnóstico , Hepatopatías/patología , Biopsia , Diagnóstico DiferencialRESUMEN
Egypt has the highest prevalence of hepatitis C virus infection worldwide. CXCL10 is a potent chemoattractant that directs effector lymphocytes to sites of inflammation. It has been reported that plasma CXCL10 is processed by dipeptidylpeptidase IV (DPPIV) thus leading to the generation of an antagonist form. Using Luminex-based immunoassays we determined the concentration of different forms of CXCL10 (total, agonist, and antagonist). We also evaluated plasma soluble DPPIV (sDPPIV) concentration and plasma dipeptidylpeptidase (DPP) activity. Using flow cytometry and immunohistochemistry, we analyzed the distribution of lymphocyte subsets. Plasma CXCL10 was elevated in chronic HCV patients, however the agonist form was undetectable. Increased sDPPIV concentration and DPP activity supported the NH2-truncation of CXCL10. Finally, we demonstrated an increased frequency of CXCR3(+) cells in the peripheral blood, and low numbers of CXCR3(+) cells within the lobular regions of the liver. These findings generalize the observation of chemokine antagonism as a mechanism of immune modulation in chronic HCV patients and may help guide the use of new therapeutic immune modulators.
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Quimiocina CXCL10/sangre , Dipeptidil Peptidasa 4/sangre , Hepatitis C Crónica/inmunología , Adolescente , Adulto , Quimiocina CXCL10/antagonistas & inhibidores , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/sangre , Egipto , Femenino , Hepacivirus/inmunología , Hepatitis C Crónica/virología , Humanos , Inflamación/inmunología , Hígado/citología , Hígado/inmunología , Hígado/metabolismo , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Masculino , Persona de Mediana Edad , Receptores CXCR3/metabolismo , Adulto JovenRESUMEN
This study examined the effect of montelukast and beclomethasone on airway remodeling in murine model of asthma. Mice were sensitized by i.p. injection of ovalbumin (OVA) on days 0 and 14, and then challenged by nebulization of 1% OVA 3 days/week for 6 or 10 weeks. Results of 6-week OVA-challenged group showed moderate inflammation, but the 10-week OVA-challenged group exhibited mild inflammation. The OVA challenge (6 and 10 weeks) exhibited marked airway fibrosis, illustrated by significant increase in goblet cell hyperplasia and epithelial thickness, increased lung content of collagen and transforming growth factor-ß(1), together with a decrease in nitric oxide production; also, there was an increase in bronchoalveolar lavage fluid level of interleukin-13. Administration of montelukast or beclomethasone before each OVA challenge was capable of restoring most of the measured parameters to near normal levels. Inhalation of beclomethasone has a similar role in airway remodeling as montelukast, but its effects in regulating inflammatory changes is less pronounced than montelukast.
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Acetatos/farmacología , Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Beclometasona/farmacología , Quinolinas/farmacología , Acetatos/administración & dosificación , Administración por Inhalación , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Animales , Antiasmáticos/administración & dosificación , Asma/fisiopatología , Beclometasona/administración & dosificación , Ciclopropanos , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/patología , Masculino , Ratones , Ovalbúmina , Quinolinas/administración & dosificación , Índice de Severidad de la Enfermedad , Sulfuros , Factores de TiempoRESUMEN
Effective and well-tolerated anti-fibrotic drugs are currently lacking. Therefore, this study was carried out to investigate the potential anti-fibrotic effects of imatinib, nilotinib and silymarin on established hepatic fibrosis in the carbon tetrachloride (CCl(4)) rat model. Male Wistar rats received intraperitoneal injections of CCl(4) twice weekly for 8weeks, as well as daily intraperitoneal treatments of imatinib (10 and 20mg/kg), nilotinib (10 and 20mg/kg) and silymarin (100mg/kg) during the last 4weeks of CCl(4)-intoxication. At the end of the study, hepatic damage was evaluated by analysis of liver function tests and hepatic oxidative stress parameters. Hepatic fibrosis was evaluated by histopathology and morphometry, as well as collagen and 4-hydroxyproline contents. Nilotinib (20mg/kg) was the most effective treatment to counteract CCl(4)-induced hepatic injury as indicated by liver function tests and histopathology. Nilotinib (10mg/kg), nilotinib (20mg/kg) and silymarin (100mg/kg) treatments reduced the mean score of hepatic fibrosis by 31%, 68% and 47%, respectively, and hepatic collagen content by 47%, 49% and 18%, respectively in CCl(4)-treated rats. Hepatic morphometric evaluation and 4-hydroxyproline content revealed that CCl(4)-induced fibrosis was ameliorated significantly by nilotinib (20mg/kg) and imatinib (20mg/kg). Unlike nilotinib, imatinib (20mg/kg) showed some sort of hepatic injury evidenced by elevation of serum aminotransferases and total bilirubin levels, and hepatic total nitrate/nitrite content, as well as characteristic anisonucleosis visualized with the hematoxylin-eosin staining. In conclusion, this study provides the evidence that nilotinib exerts anti-fibrotic activity and suggests that it may be valuable in the treatment of hepatic fibrosis in humans.
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Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Estrés Oxidativo/fisiología , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Silimarina/uso terapéutico , Animales , Benzamidas , Intoxicación por Tetracloruro de Carbono/metabolismo , Intoxicación por Tetracloruro de Carbono/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Relación Dosis-Respuesta a Droga , Mesilato de Imatinib , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Piperazinas/farmacología , Pirimidinas/farmacología , Ratas , Ratas Wistar , Silimarina/farmacología , Resultado del TratamientoRESUMEN
This study aimed to investigate the influence of low-power gallium-aluminium-arsenide (GaAlAs) laser [830 nm, continuous wave (CW), 40 mW and fluence 4 J/cm(2)] on the healing of surgically created bone defects in rats treated with bioactive glass graft material. Surgical bone defects were created in the mandibles of 36 Wistar rats divided into two groups, each consisting of 18 rats. Group I was treated with bioactive glass plus laser irradiation. Group II was treated with graft material only. The animals were killed at 4 weeks, 8 weeks and 12 weeks postoperatively for histological examination. Laser irradiation had significantly accelerated bone healing at 4 weeks and 8 weeks in comparison with that at the sites not irradiated. However at 12 weeks, complete healing of the defects had occurred with no difference detected. Our results have confirmed the positive effect of soft laser in accelerating bone regeneration.
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Regeneración Ósea/efectos de los fármacos , Regeneración Ósea/efectos de la radiación , Cerámica/uso terapéutico , Láseres de Semiconductores/uso terapéutico , Terapia por Luz de Baja Intensidad , Animales , Sustitutos de Huesos , Huesos/efectos de los fármacos , Huesos/lesiones , Huesos/patología , Huesos/efectos de la radiación , Regeneración Tisular Dirigida/métodos , Oseointegración/efectos de los fármacos , Oseointegración/efectos de la radiación , Ratas , Ratas Wistar , Factores de Tiempo , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/efectos de la radiaciónRESUMEN
This study aimed to investigate the influence of low-power 830 nm gallium-aluminium-arsenide (GaAlAs) laser [continuous wave (CW) 40 mW and fluence 4 J/cm(2), with total energy density of 16 J/cm(2)] on the healing of human infra-bony defects treated with bioactive glass graft material. Twenty patients with chronic periodontitis and bilateral infra-bony defects were included. Using a split mouth design, we treated 20 defects with bioactive glass plus laser irradiation during surgical procedures and on days 3, 5, 7 postoperatively; 20 contra-lateral defects were treated with bioactive glass only. Clinical probing pocket depths, clinical attachment levels and standardized periapical radiographs were recorded at baseline and at 3 months and 6 months postoperatively. At 3 months there was a statistically significant difference between the laser and non-laser sites in the parameters investigated. However, at 6 months, no difference was observed. Our results have confirmed the positive effect of soft laser in accelerating periodontal wound healing.
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Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/radioterapia , Regeneración Ósea/efectos de los fármacos , Regeneración Ósea/efectos de la radiación , Sustitutos de Huesos/uso terapéutico , Cerámica/uso terapéutico , Terapia por Luz de Baja Intensidad/métodos , Adulto , Pérdida de Hueso Alveolar/patología , Periodontitis Crónica/diagnóstico por imagen , Periodontitis Crónica/tratamiento farmacológico , Periodontitis Crónica/radioterapia , Femenino , Humanos , Láseres de Semiconductores/uso terapéutico , Masculino , Persona de Mediana Edad , RadiografíaRESUMEN
INTRODUCTION: The adrenal gland is a rare site for hepatocellular carcinoma (HCC) recurrence after living-donor liver transplantation (LDLT). Solitary adrenal recurrence can be managed by surgical excision, with expected better survival outcomes. We describe a rare case of successful left adrenalectomy of solitary recurrent HCC in the left adrenal gland 5 years after LDLT. PRESENTATION: 59 years male patient with HCC complicating chronic HCV infection received a right hemi-liver graft from his son. The actual graft weight was 1208 g and GRWR was 1.5. The patient started oral direct acting antiviral drugs for recurrent HCV 2 years after LDLT. A left adrenal mass was detected on follow up radiology. No other metastatic lesions were detected on metastatic workup. Left adrenalectomy was done by an anterior approach. The postoperative course was uneventful and was discharged a week after operation. Postoperative pathological and immune-histochemical examinations confirmed the metastatic HCC nature of the mass. The patient is under regular follow up with no recurrences 6 month after resection. DISCUSSION: There is no consensus regarding the management of HCC recurrence after LDLT. Most patients had multi-organ recurrences and usually offered palliative or supportive care. Solitary HCC recurrence offers a better chance for more aggressive therapy, offering better prognosis. CONCLUSION: Solitary adrenal recurrence of HCC after LDLT is extremely rare. Strict follow up protocol is necessary to allow early detection of tumor recurrence. Curative surgical resection is a safe option associated with low morbidity and expected to have a good long-term survival.
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BACKGROUND: The impact of chronic hepatitis C (CHC) on bone mineral density (BMD) has been well studied in adults with a relative paucity of data in children, especially concerning effect of treatment with pegylated interferon (PEG-IFN) plus ribavirin (RV). In the current work, we assessed prospectively changes in BMD in children with CHC before, during, and after treatment. METHODS: Forty-six consecutive children with noncirrhotic genotype 4 CHC were subjected to dual-energy X-ray absorptiometry at baseline, 24 weeks, 48 weeks of therapy and 24 weeks after treatment. BMD, bone mineral content (BMC), and Z score of lumbar spine (L2-L4) were reported. Tanner pubertal stage, viral load, liver function tests, serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and liver histopathology were assessed in all included children. RESULTS: Thirty (65.2%) patients had normal BMD, 10 (21.7%) were at risk for low BMD, and 6 (13.1%) had low BMD for chronological age. Patients with low BMD were significantly older (P=0.001), with higher frequency of delayed puberty than other groups (P=0.002). Baseline densitometric parameters (BMD & BMC) were significantly positively correlated with patients' age, weight, height, body mass index and hemoglobin level; while they were insignificantly correlated with basal viral load, histopathology activity index and fibrosis score. Densitometric parameters improved significantly on PEG-IFN plus RV treatment, this improvement was found to be sustainable 24 weeks after therapy. CONCLUSIONS: Low BMD is detectable in a proportion of CHC children. Antiviral therapy leads to a sustainable increase in BMD.
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Densidad Ósea/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Ribavirina/administración & dosificación , Absorciometría de Fotón/métodos , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Quimioterapia Combinada , Egipto , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/genética , Humanos , Masculino , Estudios Retrospectivos , Factores Sexuales , Resultado del TratamientoRESUMEN
Liver biopsy is still recommended in most patients with chronic hepatitis C (CHC). Due to its limitations and risks, the use of non-invasive blood biomarkers has been suggested for predicting liver cirrhosis in these patients. Here, we analyzed a panel of routine blood biochemical and hematological markers of 455 Egyptians (272 males and 183 females aged 26-67 years; mean age of 47.25 years) with clinically confirmed CHC. The multivariate discriminant analysis (MDA) selected a function based on absolute values of the four routine biomarkers; score=[albumin (g/L)x0.3+platelet count (10(9)/L)x0.05]-[alkaline phosphatase (IU/L)x0.014+AST/ALT ratiox6+14]. The MDA function correctly classified 98% of the cirrhotic patients at a discriminant cut-off score=0 (i.e. less than 0 indicated liver cirrhosis and greater than 0 indicated CHC without cirrhosis) with high degrees of specificity (97%), positive predictive value (99%) and negative predictive value (92%). The MDA of the absolute values of a combination of four routine tests can efficiently indicate liver cirrhosis in CHC patients. Based on individual patient MDA score value, each patient can be simply and efficiently classified into a cirrhotic or a non-cirrhotic liver patient.
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BACKGROUND AND AIMS: Oncogenes and tumor suppressor genes expression are well described in bladder cancer associated with schistosomiasis especially in Egypt. Scarce studies were directed to colorectal cancer (CRC) associated with Schistosoma mansoni (S. mansoni). Apoptosis (programmed cell death) and the genes regulating this process (e.g., Bcl-2) have recently become a focus of interest in the study of cancer development and progression. In the present study, we aimed to investigate the expression pattern of p53, Bcl-2 and C-Myc in CRC tissues obtained from Egyptian colorectal cancer patients divided in two different groups, one associated with Schistosoma mansoni (CRC-Sm) and the other without Schistosoma mansoni (CRC-NSm). METHODS: Seventy-five CRC tumors containing 36 draining lymph node metastatic tumors were immunohistochemically stained using specific monoclonal antibodies for p53, Bcl-2 and C-Myc, in addition the apoptotic activity of these tumors were analyzed. RESULTS AND CONCLUSIONS: Regardless of the S. mansoni infection, the obtained results showed that the apoptotic activity was more evident in p53 diffuse positive tumors (P = 0.021). There was a significant correlation between p53 diffuse positive staining and Bcl-2 positive immunostaining (P = 0.011). Signet ring cell carcinoma and mucinous adenocarcinoma exhibited both intense C-Myc expression than non-mucinous carcinoma (P = 0.001). When adjusting for S. mansoni infection, 58.3% of CRC-Sm cases were Bcl-2 positive compared to only (33.3%) of CRC-NSm (P = 0.046). Apoptotic activity was more evident in the latter group than of CRC-Sm tumors (P = 0.009). p53 and C-Myc expressions were found insignificantly different in CRC-Sm compared with CRC-NSm (P > 0.05). These observations suggest that the genotoxic agents produced endogenously through the course of schistosomiasis mansoni may play a role in CRC-Sm pathogenesis through the dysregulation of apoptosis by alteration the expression pattern of Bcl-2 protein differently from CRC-NSm suggesting a different biological behavior.
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Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Esquistosomiasis/complicaciones , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Neoplasias Colorrectales/patología , Egipto , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND/AIMS: p53 gene mutation occurs in about 50-60% of colorectal carcinoma cases. This mostly occurs as a late event in the adenoma-carcinoma sequence. These late stages are associated with more aneuploidy compared to adenomas and early carcinomas. However there is a controversy regarding the relation between p53 overexpression and DNA index. This study was designed to investigate the relationship between p53 status and DNA ploidy pattern. METHODOLOGY: Nuclear DNA content of paraffin-embedded material from 83 colectomy specimens for colorectal carcinoma was measured by flow cytometry. Also, p53 was detected by immunohistochemistry in 73 out of the 83 tumor cases using a monoclonal antibody that detects both wild and mutant p53 proteins (Biogenex 1801). RESULTS: Aneuploidy was identified in 37 cases (46.25%). Tumors with rectal location were significantly more aneuploid in comparison to other sites (P = 0.009), p53 staining showed three patterns: diffuse staining (29 cases), focal (13 cases), and negative (31 cases). Diffuse p53 staining was associated with aneuploidy (P = 0.04). The majority of DNA indices fell within the range 1.1-2.2 (32 out of 37). Twenty-one of these had DNA index = 1.1-1.8 (aneuploidy short of tetraploidy) significantly associated with diffuse p53 staining compared with peritetraploid cases (DNA index 1.8-2.2) (P = 0.034). CONCLUSIONS: p53 immunohistochemistry demonstrates two distinct patterns in colorectal carcinoma. Diffuse p53 staining, which is associated with aneuploidy short of tetraploidy (DNA index 1.1-1.8), a finding which is different from previously published work. Focal p53 staining pattern, in contrast, is related to high G2M and more abnormal tetraploid peaks but less aneuploidy.
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Adenocarcinoma/genética , Neoplasias Colorrectales/genética , Genes p53/genética , Ploidias , Adenocarcinoma Mucinoso/genética , Adulto , Anciano , Anciano de 80 o más Años , Egipto , Femenino , Citometría de Flujo , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
This study was designed to investigate the potential effects of omega-3, olmesartan and their combination on established hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. Male Wistar rats received subcutaneous injections of CCl4 twice weekly for 12weeks, as well as daily oral treatments of olmesartan (1 and 3mg/kg), omega-3 (75 and 150mg/kg) and their combination during the last 4weeks of intoxication. Our results indicated that omega-3 and, to a lesser extent, olmesartan dose-dependently blunted CCl4-induced necroinflammation scoring and elevation of liver injury parameters in serum. Besides, omega-3 and, to a lesser extent, olmesartan treatments in a dose dependent manner attenuated CCl4-induced liver fibrosis, as demonstrated by hepatic histopathology scoring and 4-hydroxyproline content. The mechanisms behind these beneficial effects of both omega-3 and olmesartan were also elucidated. These include (1) counteracting hepatic oxidative stress and augmenting hepatic antioxidants; (2) preventing the activation of hepatic stellate cells (HSCs), as denoted by reducing α-smooth muscle actin (α-SMA) expression in the liver; (3) inhibiting the proliferation and chemotaxis of HSCs, as evidenced by downregulating platelet-derived growth factor receptors-ß (PDGFR-ß) expression in the liver; and (4) inhibiting the fibrogenesis response of HSCs, as indicated by inhibiting the secretion of transforming growth factor-ß1 (TGF-ß1). Unexpectedly, when olmesartan was co-administered with omega-3, it interfered with the hepatoprotective and anti-fibrotic activities of omega-3. In conclusion, this study introduces the first evidence regarding the pronounced anti-fibrotic activity of omega-3 and suggests that it may be beneficial in the treatment of hepatic fibrosis in humans.
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Ácidos Grasos Omega-3/uso terapéutico , Imidazoles/uso terapéutico , Cirrosis Hepática Experimental/tratamiento farmacológico , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Tetrazoles/uso terapéutico , Actinas/metabolismo , Animales , Biomarcadores/metabolismo , Tetracloruro de Carbono , Quimioterapia Combinada , Ácidos Grasos Omega-3/farmacología , Hidroxiprolina/metabolismo , Imidazoles/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática Experimental/sangre , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Masculino , Ratas , Ratas Wistar , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Tetrazoles/farmacología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Neonatal cholestasis syndrome is considered as a major challenge in pediatric practice. This study was undertaken to investigate the value of morphometric assessment of hepatic fibrosis in early diagnosis of biliary atresia. METHODS: We studied liver biopsy specimens from 53 patients with neonatal cholestasis. The patients were assigned to two groups: group 1 (25 patients with biliary atresia) and group 2 (28 patients with non-obstructive cholestasis). Morphometric assessment of fibrosis was performed for all biopsies; in addition, another twelve histological parameters were estimated and scored on a scale of 0 to 4. Biopsies of infants aged 60 days or younger were characterized and analyzed separately. RESULTS: Morphometric value of fibrosis was significantly higher in group 1 than in group 2 (16.8 ± 8.4% vs. 5.9 ± 2.3%, respectively; P<0.001). By multiple regression analysis, bile ductular plugs, morphometric assessment of fibrosis, rosetting, portal tract inflammation and pattern of cholestasis were found to be significant in discriminating the two groups. In infants aged 60 days or younger, a cutoff value for morphometric assessment of fibrosis of 7.5% was the discriminating point between the two groups with a sensitivity of 80% and a specificity of 84%. CONCLUSION: Morphometric assessment of hepatic fibrosis could enhance the value of liver biopsy in early diagnosis of biliary atresia.
Asunto(s)
Atresia Biliar/diagnóstico , Cirrosis Hepática/patología , Biopsia , Colestasis/patología , Diagnóstico Precoz , Femenino , Humanos , Lactante , Recién Nacido , Hígado/patología , Masculino , Análisis Multivariante , Sensibilidad y EspecificidadRESUMEN
Schistosomiasis still represents a major threat to women's health in many developing countries. The frequency in developed countries is increasing among immigrants and tourists who have a history of freshwater exposure in endemic areas. This is a case of 43-year-old immunocompetent Egyptian woman presented by abnormal vaginal bleeding. The gynecological examination revealed an endocervical polyp measuring 3 x 2 x 1 cm. Polypectomy was done. Histopathological examination revealed several granulomas containing viable eggs of Schistosoma hematobium. Schistosomiasis is rarely presented with endocervical polyp. In developing countries, schistosomiasis may be considered in differential diagnosis of patient with endocervical polyp.
Asunto(s)
Pólipos/patología , Schistosoma haematobium/aislamiento & purificación , Esquistosomiasis Urinaria/diagnóstico , Esquistosomiasis Urinaria/patología , Útero/patología , Adulto , Animales , Egipto , Femenino , Histocitoquímica , Humanos , Pólipos/cirugía , Esquistosomiasis Urinaria/cirugía , Hemorragia Uterina/etiología , Útero/cirugíaRESUMEN
Breast carcinoma may be classified into distinct molecular subtypes based on immunohistochemical markers for estrogen, progesterone and Her-2/neu receptors. The aim of the study was to identify the clinicopathological features of the molecular subtypes of breast carcinoma in our locality. A total of 274 surgically resected breast carcinomas were selected from the files of the Dr. KRZ referral pathology laboratory, Mansoura, Egypt, and the Pathology Department of Mansoura University. Molecular subtypes were classified into luminal A, luminal B, Her-2/neu-expressing and triple-negative. Clinicopathological and histological features of molecular subtypes were analyzed. Luminal A subtype was the most prevalent (41.2%), followed by triple-negative subtype (28.5%), then Her2-expressing subtype (19.4%) and luminal B subtype (13.9%). The commonest histological type was infiltrating duct carcinoma (83.2%), followed by infiltrating lobular carcinoma (9.1%) and medullary carcinoma (3.2%). The luminal A subtype was significantly correlated to low tumor grade, lower number of positive lymph nodes metastasis, absence of both necrosis and syncytial growth pattern. We concluded that the commonest molecular subtype of invasive breast carcinoma among Egyptian women is luminal subtype A, which displayed favorable features. Triple-negative subtype and medullary carcinomas are present in a ratio higher than in western countries.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Carcinoma Medular/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/química , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/etnología , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/clasificación , Carcinoma Ductal de Mama/etnología , Carcinoma Lobular/química , Carcinoma Lobular/clasificación , Carcinoma Lobular/etnología , Carcinoma Medular/química , Carcinoma Medular/clasificación , Carcinoma Medular/etnología , Egipto/etnología , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Clasificación del Tumor , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisisRESUMEN
BACKGROUND: Tissue microarray technology has provided a high throughput means of evaluating potential biomarkers in archival pathological specimens. This study was carried out in order to produce tissue microarray blocks using mechanical pencil tips without high cost. METHOD: Conventional mechanical pencil tips (Rotring Tikky II Mechanical Pencil 1.0 mm) were used to cut out 1 mm wax cylinders from the recipient block, creating from 36 to 72 holes. Three cores of tumor areas were punched out manually by using the mechanical pencil tips from donor paraffin embedded tissue blocks and transferred to the holes of the paraffin tissue microarrays. RESULTS: This technique was easy and caused little damage to the donor blocks. We successfully performed H&E slides and immunodetection without substantial tissue cylinder loss. CONCLUSION: Our mechanical pencil tip technique is the most inexpensive easy technique among the literature. It also takes a reasonable amount of time and reduces antibody consumption during immunohistochemistry.