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1.
Hernia ; 28(1): 199-209, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37934377

RESUMO

PURPOSE: The objective of this retrospective study was to assess safety and comparative clinical effectiveness of laparoscopic inguinal hernia repair (LIHR) and robot-assisted inguinal hernia repair (RIHR) from multi-institutional experience in Taiwan. METHODS: Medical records from a total of eight hospitals were retrospectively collected and analyzed. Patients primarily diagnosed of inguinal hernia, recurrent inguinal hernia or incarceration groin hernia patients who either underwent laparoscopic or robot-assisted inguinal hernia repair between January 2018 and December 2022 were included in the study. Baseline characteristics, intra-operative and post-operative results were analyzed. To compare two cohorts, overlap weighting was employed to balance the significant inter-group differences. We also conducted subgroup analyses by state of a hernia (primary or recurrent/incarceration) and laterality (unilateral or bilateral) that indicated complexity of surgery. RESULTS: A total of 1,080 patients who underwent minimally invasive inguinal hernia repair from 8 hospitals across Taiwan were collected. Following the application of inclusion criteria, there were 279 patients received RIHR and 763 patients received LIHR. In the baseline analysis, RIHR was more often performed in recurrent/incarceration (RIHR 18.6% vs LIHR 10.3%, p = 0.001) and bilateral cases (RIHR 81.4 vs LIHR 58.3, p < 0.001). Suturing was dominant mesh fixation method in RIHR (RIHR 81% vs LIHR 35.8%, p < 0.001). More overweight patients were treated with RIHR (RIHR 58.8% vs LIHR 48.9%, p = 0.006). After overlap weighting, there were no significant difference in intraoperative and post-operative complications between RIHR and LIHR. Reoperation and prescription rates of pain medication (opioid) were significantly lower in RIHR than LIHR in overall group comparison (reoperation: RIHR 0% vs. LIHR 2.9%, p = 0.016) (Opioid prescription: RIHR 3.34 mg vs LIHR 10.82 mg, p = 0.001) while operation time was significantly longer in RIHR (OR time: RIHR 155.27 min vs LIHR 95.30 min, p < 0.001). CONCLUSIONS: This real-world experience suggested that RIHR is a safe, and feasible option with comparable intra-operative and post-operative outcomes to LHIR. In our study, RIHR showed technical advantages in more complicated hernia cases with yielding to lower reoperation rates, and less opioid use.


Assuntos
Hérnia Inguinal , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Analgésicos Opioides , Hérnia Inguinal/cirurgia , Hérnia Inguinal/etiologia , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
2.
Int J Clin Pract ; 70(5): 372-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27039892

RESUMO

OBJECTIVES: To evaluate the safety and efficacy of low-dose desmopressin in elderly men with and without nocturnal polyuria (NP) in real-life practice. METHODS: Patients with lower urinary tract symptoms (LUTS)/ benign prostate hyperplasia (BPH) who were≧ 65 years old with refractory nocturia were enrolled in this study. We retrospectively analysed elderly men treated with adding desmopressin to current medications for nocturia according to category of the baseline nocturnal urine volume. The 48-h frequency volume chart (FVC), International Prostate Symptom Score (IPSS) and quality of life (QoL) were initially assessed and re-evaluated 12 weeks later. Serum sodium level was checked 1 week, 4 weeks, and 12 weeks after initiation of desmopressin therapy or suspected hyponatremia event. The mean change in numbers of nocturnal voids was evaluated for efficacy of treatment. RESULTS: A total of 136 patients were included with 55 in non-NP group and 81 in NP group. Hypertension was more common in NP group in regard of comorbidities. During treatment period, there were significant reductions of nocturnal voids from 4.22 ± 1.38 to 2.31 ± 0.98 (p < 0.001) in non-NP group and from 4.52 ± 1.23 to 2.07 ± 0.89 (p < 0.001) in NP group. The reduction in nocturnal voids was more significant in NP group (2.44 ± 1.15 vs. 1.91 ± 1.48, p = 0.003). The mean decrease in serum sodium levels were 3.89 ± 1.22 mmol/l (p < 0.001) in non-NP group and 4.69 ± 3.5 mmol/l (p < 0.001) in NP group at the extreme value. CONCLUSIONS: Long-term treatment with low-dose desmopressin is safe and effective for nocturia with or without NP in elderly patients with LUTS/BPH during real-life practice. Patients should be well informed about the disease and are closely followed.


Assuntos
Antidiuréticos/uso terapêutico , Desamino Arginina Vasopressina/uso terapêutico , Noctúria/tratamento farmacológico , Poliúria/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Noctúria/etiologia , Poliúria/etiologia , Hiperplasia Prostática/complicações , Estudos Retrospectivos
3.
Nuklearmedizin ; 54(1): 36-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25345433

RESUMO

UNLABELLED: Oral hydration with large volume of fluid, high dose of diuretics and maximum bladder distension are frequently required to achieve an adequate urinary FDG clearance in an FDG PET/CT protocol for bladder cancer or pelvic tumour evaluation. Although most patients tolerated these procedures for eliminating urinary FDG activity, these procedures may be still unpleasant. AIM: Is there a more patient-friendly protocol which is less burdensome and yet provides a satisfactory FDG clearance in urine? In this study, we established a patient-friendly FDG PET/CT protocol without compromising urinary FDG clearance. PATIENTS, METHODS: 23 patients with biopsy-proven urinary bladder cancers were recruited to evaluate the effectiveness of this patient-friendly protocol on reducing urinary bladder FDG activity. The patient-friendly protocol includes encouraging patients to take a tolerable amount of fluid, delaying the administration of low dose diuretic, shortening the urine holding time and using delayed imaging. RESULTS: All of the patients tolerated this patient-friendly procedure well. In addition, the patient-friendly protocol was effective in reducing FDG activity in the urine. One hundred percent of primary bladder cancer were visualized on the FDG PET/CT images using this patient-friendly protocol. CONCLUSIONS: This patient-friendly FDG PET/CT protocol is less intrusive yet effective in reducing urinary FDG activity.


Assuntos
Fluordesoxiglucose F18 , Imagem Multimodal/métodos , Satisfação do Paciente , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/metabolismo , Bexiga Urinária/metabolismo , Adulto , Idoso , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Assistência Centrada no Paciente/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos , Micção
4.
Transplant Proc ; 46(10): 3335-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25498047

RESUMO

OBJECTIVES: High terminal serum creatinine level in a deceased donor has been reported as the second most frequent cause of refusal for kidney transplantation. A growing body of evidence has shown a comparable outcome of kidney transplantation from deceased donors with acute kidney injury (AKI). However, the influence of the severity of AKI on graft outcomes remains to be elucidated. METHODS: In this retrospective cohort study, 84 consecutive kidney transplants from 57 standard-criteria donors were classified into 4 groups by RIFLE (Risk, Injury, Failure, Loss of function, and End-stage renal disease) classification according to donor AKI severity before kidney procurement. The donor and recipient characteristics and graft outcomes were compared. RESULTS: Of 84 kidney transplants, 56, 11, 10, and 7 recipients were in the Non-AKI, Risk, Injury, and Failure groups. The mean terminal creatinine was 1.1, 1.6, 2.3, and 4.4 mg/dL in these 4 groups. However, the graft outcomes, including primary nonfunction rate, delayed graft function rate, acute rejection rate, renal function, graft survival and overall survival over the first 5 years had no statistical difference. A trend toward increasing delayed graft function rate as the severity of AKI increased was observed (Non-AKI, Risk, Injury, and Failure: 26.8%, 36.4%, 60.0%, and 57.1%, P = .099). CONCLUSIONS: Our study demonstrates that AKI before procurement does not cause adverse long-term graft outcomes. Standard-criteria donors with AKI are suitable for kidney transplantation, even with a high severity of AKI.


Assuntos
Injúria Renal Aguda/diagnóstico , Função Retardada do Enxerto/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Rim/patologia , Doadores de Tecidos , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Rim/fisiopatologia , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Masculino , Estudos Retrospectivos
5.
Opt Express ; 22(7): 7473-91, 2014 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-24718122

RESUMO

The generalized tight-binding model with exact diagonalization method is developed to calculate the optical properties of monolayer graphene in the presence of composite magnetic fields. The ratio of the uniform magnetic field and the modulated one accounts for a strong influence on the structure, number, intensity and frequency of absorption peaks, and thus the extra selection rules that are subsequently induced can be explained. When the modulated field increases, each symmetric peak, under a uniform magnetic field, splits into a pair of asymmetric peaks with lower intensities. The threshold absorption frequency exhibits an obvious evolution in terms of a redshift. These absorption peaks obey the same selection rule that is followed by Landau level transitions. Moreover, at a sufficiently strong modulation strength, the extra peaks in the absorption spectrum might arise from different selection rules.

7.
Eur J Surg Oncol ; 39(1): 107-13, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23085148

RESUMO

BACKGROUND: To analyze the trifecta outcome (continence, potency, and cancer control) in 300 cases of robotic-assisted laparoscopic radical prostatectomy (RARP). METHODS: A prospective assessment of outcomes in 300 consecutive patients that underwent a RARP performed by a single surgeon. Patients were grouped according to D'Amico risk criteria: Group I consisted of 'low-risk' cases (n = 64), Group II consisted of 'intermediate-risk' cases (n = 88), and Group III consisted of 'high-risk' cases (n = 148). Patients were evaluated for perioperative complications and the trifecta outcome. RESULTS: The operation time, blood loss, post-operative stay, duration of urethral catheterization, and perioperative complication rate were similar among all groups. The incidence of bilateral neurovascular bundle (NVB) preservation was significantly decreased with the increasing risk of cases (P < 0.001). The continence rates at the 1-week, 1-month, 3-month, 6-month, and 12-month follow-ups did not differ significantly between groups. The potency rates at the 12-month follow-up were not significantly different. The positive surgical margin and positive lymph node metastasis rate increased with the increasing risk of cases (P < 0.001). The biochemical recurrence rate (BCR, PSA >0.2 ng/mL) was 3.1, 11.36, and 19.59% in Groups I, II and III, respectively (P = 0.004). The trifecta outcome for RARP with bilateral NVB preservation showed no significant differences among groups. CONCLUSIONS: Undergoing a RARP is safe and feasible in high-risk prostate cancer patients. Compared to low-risk and intermediate-risk groups, the high-risk group had a significant higher incidence of positive surgical margin, positive lymph node metastasis, and BCR rate.


Assuntos
Ereção Peniana , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Robótica , Incontinência Urinária/etiologia , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Prospectivos , Prostatectomia/efeitos adversos , Prostatectomia/instrumentação , Prostatectomia/métodos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
9.
Nanotechnology ; 20(28): 285401, 2009 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-19546498

RESUMO

Interdot Coulomb interactions and collective Coulomb blockade were theoretically argued to be a newly important topic, and experimentally identified in semiconductor quantum dots, formed in the gate confined two-dimensional electron gas system. Developments of cluster science and colloidal synthesis accelerated the studies of electron transport in colloidal nanocrystal or quantum-dot solids. To study the interdot coupling, various sizes of two-dimensional arrays of colloidal PbSe quantum dots are self-assembled on flat gold surfaces for scanning tunneling microscopy and scanning tunneling spectroscopy measurements at both room and liquid-nitrogen temperatures. The tip-to-array, array-to-substrate, and interdot capacitances are evaluated and the tunneling spectra of quantum-dot arrays are analyzed by the theory of collective Coulomb blockade. The current-voltage of PbSe quantum-dot arrays conforms properly to a scaling power law function. In this study, the dependence of tunneling spectra on the sizes (numbers of quantum dots) of arrays is reported and the capacitive coupling between quantum dots in the arrays is explored.


Assuntos
Chumbo/química , Microscopia de Tunelamento/métodos , Nanoestruturas/química , Nanotecnologia/métodos , Pontos Quânticos , Compostos de Selênio/química
11.
Arch Androl ; 52(2): 117-21, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16443588

RESUMO

The aim of the study was to report our experiences in the treatment of chronic prostatitis using combination regimen including ciprofloxacin, doxazosin, allopurinol and biofeedback perineal massage. From May 2003 to April 2004, 7 patients with NIH Category II-chronic bacterial prostatitis and 7 patients with NIH Category IIIA-inflammatory chronic pelvic pain syndrome were treated. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) was scored by the patient before and after the treatment, 6 months later. In Category II patients, the bacterial eradication rate was 71% after ciprofloxacin treatment during a follow-up of 6 months. The beneficial response rate to allopurinol, doxazosin and biofeedback perineal massage was 50%, 42% and 85%, respectively. In NIH Category IIIA patients, the individual beneficial response rate to ciprofloxacin, allopurinol, doxazosin and biofeedback perineal massage was 57%, 100%, 71% and 100%, respectively. Comparing pre-treatment and post-treatment results of the combination regimen, there was a statistically significant improvement in the 3 domains of pain score, urinary symptoms and quality of life impact of the NIH-CPSI. Combination regimen including ciprofloxacin, doxazosin allopurinol and biofeedback perineal massage in the treatment of chronic prostatitis is a safe and effective modality in our limited experience.


Assuntos
Prostatite/terapia , Antagonistas Adrenérgicos alfa/uso terapêutico , Adulto , Idoso , Alopurinol/uso terapêutico , Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Terapia Combinada , Doxazossina/uso terapêutico , Quimioterapia Combinada , Supressores da Gota/uso terapêutico , Humanos , Masculino , Massagem , Pessoa de Meia-Idade , Prostatite/tratamento farmacológico
12.
J Chem Phys ; 121(17): 8175-8, 2004 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-15511134

RESUMO

Based on the standard transfer matrix, a formally exact quantization condition for arbitrary potentials, which outflanks and unifies the historical approaches, is derived. It can be used to find the exact bound-state energy eigenvalues of the quantum system without solving an equation of motion for the system wave functions.

13.
Zhonghua Yi Xue Za Zhi (Taipei) ; 64(3): 183-6, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11458625

RESUMO

Primary renal sarcoma represents approximately one per cent of all primary tumors of the kidney in adults. We report an unusual case of primary renal sarcoma with inferior vena cava (IVC) thrombus. This patient presented with hemorrhagic shock due to tumor rupture. Emergent radical nephrectomy and vena caval thrombectomy were performed. Histological examination proved a clear cell sarcoma.


Assuntos
Neoplasias Renais/complicações , Sarcoma de Células Claras/complicações , Veia Cava Inferior , Trombose Venosa/complicações , Adulto , Humanos , Masculino , Ruptura Espontânea , Choque Hemorrágico/etiologia
14.
Zhonghua Yi Xue Za Zhi (Taipei) ; 64(4): 215-22, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11458759

RESUMO

BACKGROUND: The value of lymphadenectomy in the management of renal cell carcinoma (RCC) remains controversial. Most would agree that lymphadenectomy (LD) provides accurate pathologic staging for prognostic data. The question remains whether there is any significant therapeutic benefit from extensive lymph node dissection with radical nephrectomy. The aim of this study was to compare outcomes in sampled lymphadenectomy (SLD) and extensive lymphadenectomy (ELD) with radical nephrectomy for RCC. METHODS: One hundred and thirty-seven patients with RCC were enrolled in this study from Oct. 1982 to Dec. 1996. Eighty-one patients received radical nephrectomy with SLD (stage I: 43, II: 16, III: 22). Fifty-six patients received radical nephrectomy with ELD (stage I: 30, II: 11, III: 15). RESULTS: The mean number of lymph nodes removed by SLD was 4 (ranged from 1 to 8). The mean number of lymph nodes removed by ELD was 16.1 (ranged from 9 to 32). Overall 5-year survivals for SLD in stages I, II and III were 98%, 80% and 38%, respectively. Overall 5-year survivals for ELD in stages I, II and III were 92%, 84% and 40%, respectively. CONCLUSIONS: There is no significant therapeutic benefit from ELD in patients with RCC receiving radical nephrectomy.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Excisão de Linfonodo , Nefrectomia , Adulto , Idoso , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
15.
Gene ; 271(2): 143-50, 2001 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-11418235

RESUMO

Osteocalcin (OC) is known to be a bone tissue-specific protein, expression of which is believed to be controlled by the OC promoter. In this communication, we provided evidence to demonstrate that tissue-specific expression of OC was also regulated at the RNA splicing level. We identified incompletely spliced variants of human OC mRNA, which retain one or more introns during RNA splicing, existing dominantly in non-osseous organs. Northern blot analysis identified two OC RNA transcripts expressed in normal human tissues, but the expression level of the transcripts varied between the tissues. Most non-osseous tissues expressed transcripts with higher molecular weight, prominent in ovary, kidney, pancreas, spleen, thymus, prostate, and testis, than the expected size of OC mRNA as seen in bone marrow. RT-PCR analysis identified up to six OC transcripts in most tissues tested except bone marrow. Sequence analysis showed that four of five RNA variants contained intron 1 in common and the dominant one contained all three introns. MG63, an osteoblastic osteosarcoma cell, expressed only the completely-spliced form of OC, whereas incompletely spliced RNA was dominant in most prostate tumor cells. Combined study of in situ hybridization and immunohistochemistry revealed that OC RNA was highly expressed in prostate tumor epithelial cells while only very low levels of protein were detected, which confirms that there are OC RNA variants in non-osseous tissues. In conclusion, we demonstrated that OC mRNA is also expressed in several non-osseous tissues. However, only bone preferentially underwent the complete splicing event of all three introns. The function of other splicing variants of OC mRNA needs to be further investigated.


Assuntos
Processamento Alternativo , Osteocalcina/genética , Northern Blotting , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Osteocalcina/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Distribuição Tecidual , Transcrição Gênica , Células Tumorais Cultivadas
16.
Transplantation ; 71(7): 992-4, 2001 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11349737

RESUMO

BACKGROUND: Nephroid metaplasia is a benign and rare lesion that is confined to the lamina propria of the urinary tract. The leading cause of these lesions is previous trauma to the urothelium. METHOD: We report a case of nephroid metaplasia of a graft kidney from a living-unrelated donor. This patient presented to our clinics due to painless gross hematuria 1 month after renal transplantation. RESULT: Although malignancy was suspected in the beginning due to a filling defect demonstrated by urography, only percutaneous excision of the tumor was performed to preserve the renal function. However, the pathological result disclosed nephroid metaplasia. CONCLUSION: Hematuria warrant aggressive evaluation because underlying malignancy in a immunocompromised patient might be relatively progressive.


Assuntos
Transplante de Rim , Rim/patologia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Feminino , Humanos , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Metaplasia , Pessoa de Meia-Idade , Período Pós-Operatório , Urografia
17.
Zhonghua Yi Xue Za Zhi (Taipei) ; 64(1): 64-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11310374

RESUMO

A rare case of ureteral stump metastasis 3 months after nephrectomy for a renal cell carcinoma is presented. A 62-year-old female had undergone right radical nephrectomy 3 months earlier because of renal cell carcinoma in our hospital, and she came back due to gross hematuria. Cystoscopy revealed a papillary mass with a vascular pedicle protruding from the right ureteral orifice. Transurethral resection of the bladder tumor over right ureteral orifice was performed and the pathologic result showed clear cell adenocarcinoma, which argued in favor of a metastatic lesion from the previous renal cell carcinoma. Ureterectomy and a bladder cuff excision were then adopted for this patient, but no residual tumor was found over the remaining ureter. Nevertheless, the patient died of cancer 36 months after the event of ureteral stump metastasis.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias Ureterais/secundário , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/cirurgia , Pessoa de Meia-Idade
18.
Cancer Res ; 61(5): 1879-89, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11280742

RESUMO

A combination of experimental and simulation approaches were used to analyze the clonal growth of preneoplastic, enzyme-altered foci during liver carcinogenesis in an initiation-promotion regimen. Male Fisher 344 rats, 8 weeks of age, were initiated with a single dose (200 mg/kg, i.p.) of diethylnitrosamine (DEN). Beginning 2 weeks later, animals were exposed to daily gavage consisting of 0.1 mmol/kg pentachlorobenzene (PECB) or hexachlorobenzene (HCB) in corn oil vehicle for 6 weeks. Partial hepatectomy was performed 3 weeks after initiation. Experimental data including liver weight, hepatocyte density (number of hepatocytes/unit volume), 5-bromo-2'-deoxyuridine-labeling index for analysis of cell division rate, and number and volume of glutathione-S-transferase pi-positive foci were collected 23, 26, 28, 47, or 56 days after initiation. Model parameters describing liver growth were obtained directly from the experimental data. The probability of mutation/division of normal cells and the growth rate of initiated cells were inferred by a comparison of model outcomes with the observed time courses of foci development. To describe the time-dependent increases in foci volume and the concomitant reduction of foci number observed in all treatment groups, the calibrated model for the DEN controls incorporated the hypothesis of two initiated cell populations (referred to as A and B cells) within the framework of the two-stage model. The B cells are initiated cells that have a selective growth advantage under conditions that inhibit the growth of A cells and normal hepatocytes. The parameter values defined in the DEN controls were used to evaluate experiments involving the administration of PECB or HCB. Both PECB and HCB caused a significant increase in foci volume compared with the DEN controls. HCB treatments resulted in increased proliferation of normal hepatocytes, which was not observed for PECB under the same treatment regimen. The best description of the data resulted from the model incorporating the hypothesis that PECB and HCB promoted the growth of foci via increased net growth rates of B cells. We present here a biologically based clonal growth simulation platform to describe the growth of preneoplastic foci under experimental manipulations of initiation-promotion studies. This simulation work is an example of quantitative approaches that could be useful for the analysis of other initiation-promotion studies.


Assuntos
Carcinógenos/toxicidade , Clorobenzenos/toxicidade , Hexaclorobenzeno/toxicidade , Neoplasias Hepáticas Experimentais/patologia , Modelos Biológicos , Lesões Pré-Cancerosas/patologia , Animais , Bioensaio , Peso Corporal/efeitos dos fármacos , Calibragem , Contagem de Células , Divisão Celular/fisiologia , Células Clonais , Simulação por Computador , Dietilnitrosamina/toxicidade , Fungicidas Industriais/toxicidade , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Inseticidas/toxicidade , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Neoplasias Hepáticas Experimentais/induzido quimicamente , Masculino , Tamanho do Órgão/efeitos dos fármacos , Lesões Pré-Cancerosas/induzido quimicamente , Ratos , Ratos Endogâmicos F344
19.
Neurotoxicology ; 20(5): 793-804, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10591515

RESUMO

Previous studies indicate that the ability of cells to up-regulate levels of intracellular glutathione (GSH) synthesis may determine their sensitivity to MeHg exposure. The purpose of the current study is two-fold. First, we determined whether the vulnerability of the developing central nervous system (CNS) to MeHg lies in its intracellular GSH content. The intracellular GSH content and the activity of gamma-glutamyl cysteine synthetase (GCS) were determined with and without MeHg exposure in primary cultures of rat embryonic CNS cells. In addition, the effect of GSH modulation on MeHg-induced cytotoxicity was determined. Second, we characterized the mechanism of GCS regulation, initially by studying the GCS heavy chain subunit (GCS-HC). Primary embryonic limb bud cells were used as a reference cell type for comparing the response of CNS cells. The results indicate that constitutive intracellular GSH content, GCS activity, and GCS-HC mRNA and protein levels of CNS cells were approximately ten-, two-, five-, and ten-fold higher, respectively, than those in limb bud cells. A dose-dependent increase in GSH levels and GCS activity was observed in CNS and limb bud cells following 1 and 2 microM MeHg exposure for 20 hr. Further characterization of GCS up-regulation in CNS cells showed that the increase in GCS activity following MeHg exposure, unlike limb bud cells, was not accompanied by an elevation of GCS-HC mRNA and protein levels. Pretreatment with N-acetylcysteine led to a significant increase in intracellular GSH, while L-buthionine-(S,R)-sulfoximine (BSO) resulted in decreased GSH levels, however neither pretreatment had a significant impact on MeHg-induced cytotoxicity in either cell type. Our results suggest that although oxidative stress may mediate aspects of MeHg toxicity, disruption of GSH homeostasis alone is not responsible for the sensitivity of embryonic CNS cells to MeHg.


Assuntos
Sistema Nervoso Central/patologia , Embrião de Mamíferos/citologia , Glutationa/fisiologia , Compostos de Metilmercúrio/toxicidade , Neurônios/efeitos dos fármacos , Acetilcisteína/farmacologia , Aminoaciltransferases/biossíntese , Animais , Butionina Sulfoximina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sistema Nervoso Central/embriologia , Embrião de Mamíferos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Extremidades/embriologia , Extremidades/inervação , Citometria de Fluxo , Sequestradores de Radicais Livres/farmacologia , Homeostase/fisiologia , Neurônios/patologia , Estresse Oxidativo/fisiologia , Pirazóis , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
20.
Toxicol Appl Pharmacol ; 157(3): 203-12, 1999 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-10373404

RESUMO

Methylmercury (MeHg) is recognized as a significant environmental hazard, particularly to the development of the nervous system. To study the molecular mechanisms underlying cell cycle inhibition by MeHg, we assessed the involvement of p21 (Waf1, Cip1), a cell cycle regulatory gene implicated in the G1 and G2 phases of cell cycle arrest, in primary embryonic cells and adult mice following MeHg exposure. Previous literature has supported the association of increased p21 expression with chondrocyte differentiation. In support of this finding, we observed an increasing p21 expression during limb bud (LB), but not midbrain central nervous system (CNS) cell differentiation. Both embryonic LB and CNS cells responded to MeHg exposure with a concentration-dependent increase in p21 mRNA. In the parallel adult study, C57BL/6 female mice were chronically exposed to 10 ppm MeHg via drinking water for 4 weeks. While there was limited or absent induction of Gadd45, Gadd153, and the gamma-glutamylcysteine synthetase catalytic subunit, p21 was markedly induced in the brain, kidney, and liver tissues in most of the animals that showed MeHg-induced behavioral toxicity such as hyperactivity and tremor. Furthermore, the induction of p21 mRNA was accompanied by an increase in p21 protein level. The results indicate that the activation of cell cycle regulatory genes may be one mechanism by which MeHg interferes with the cell cycle in adult and developing organisms. Continued examination of the molecular mechanisms underlying cell cycle inhibition may potentially lead to utilization of this mechanistic information to characterize the effects of MeHg exposure in vivo.


Assuntos
Ciclinas/genética , Regulação da Expressão Gênica , Compostos de Metilmercúrio/toxicidade , Animais , Northern Blotting , Western Blotting , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21 , Extremidades/embriologia , Feminino , Mesencéfalo/citologia , Mesencéfalo/embriologia , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Testes de Precipitina , Ratos , Ratos Sprague-Dawley
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