RESUMO
OBJECTIVE: To evaluate the detection rate of at least one sentinel lymph node (SLN) in patients with early cervical cancer who underwent open radical hysterectomy or trachelectomy using indocyanine green (ICG) with the SPY Portable Handler Imager (SPY-PHI) system. METHODS: We retrospectively reviewed patients with cervical cancer FIGO 2018 stage IA1 with lymphovascular invasion up to stage IIIC1p who underwent SLN mapping and open radical hysterectomy or trachelectomy from March 2018 through August 2022 at The University of Texas MD Anderson Cancer Center. ICG was the only tracer used with the SPY-PHI system. Patient demographics, surgical approach, and tumor factors were analyzed. Overall detection, bilateral detection, and empty lymph node packet rates were determined. RESULTS: A total of 106 patients were included. Ninety-four (88.7%) patients underwent open radical hysterectomy and 12 (11.3%) open radical trachelectomy. Median age was 40 years (range, 23-71). Median body mass index was 28.8 kg/m2 (range, 17.6-48.4). The most common FIGO 2018 stages were IB1 (35%) and IB2 (30%). The most common histologic subtypes were squamous cell carcinoma (45%) and adenocarcinoma (45%). Most patients had grade 2 disease (61%) and no lymphovascular invasion (58%). Median tumor size was 1.8 cm (range, 0.3-4). Median number of detected SLN was 4 (range, 0-12). An SLN was identified during surgery in 104 patients (98%), with bilateral mapping in 94 (89%) and unilateral mapping in 10 (9%). The empty lymph node packet rate was 4 (3.8%). The external iliac (73%) was the most common site of SLN detection. Fourteen patients had positive lymph nodes (13.5%); 3 (21.4%) had macrometastases, 9 (64.3%) had micrometastases, and 2 (14.3%) had isolated tumor cells. CONCLUSION: SLN mapping using ICG with the SPY-PHI system in open radical hysterectomy or trachelectomy is reliable and results in high overall and bilateral detection rates in patients with early cervical cancer.
Assuntos
Histerectomia , Verde de Indocianina , Linfonodo Sentinela , Traquelectomia , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Histerectomia/métodos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Idoso , Traquelectomia/métodos , Adulto Jovem , Corantes , Biópsia de Linfonodo Sentinela/métodos , Estadiamento de Neoplasias , Metástase LinfáticaRESUMO
Cervical cancer is the fourth most common cancer that affects women, mainly through human papilloma virus (HPV) infection with high-risk HPV16 and HPV18. The present study investigated the in vitro anticancer activity and mechanism of action of a proanthocyanidin polymer-rich fraction of Stryphnodendron adstringens (F2) in cervical cancer cell lines, including HeLa (HPV18-positive), SiHa (HPV16-positive), and C33A (HPV-negative) cells, and also evaluated in vivo anticancer activity. In vitro, cell viability was determined by the MTT assay. Cell migration was determined by the wound healing assay. The mechanism of action was investigated by performing ultrastructural analysis and evaluating reactive oxygen species (ROS) production, mitochondrial metabolism, lipoperoxidation, BCL-2 family expression, caspase expression, and DNA and cell membrane integrity. In vivo activity was evaluated using the murine Ehrlich solid tumor model. F2 time- and dose-dependently reduced cell viability and significantly inhibited the migration of cervical cancer cells. HeLa and SiHa cells treated with F2 (IC50) exhibited intense oxidative stress (i.e., increase in ROS and decrease in antioxidant species) and mitochondrial damage (i.e., mitochondrial membrane potential depolarization and a reduction of intracellular levels of adenosine triphosphate). Increases in the Bax/BCL-2 ratio and caspase 9 and caspase 3 expression, were observed, with DNA damage that was sufficient to trigger mitochondria-dependent apoptosis. Cell membrane disruption was observed in C33A cells (IC50 and IC90) and HeLa and SiHa cells (IC90), indicating progress to late apoptosis/necrosis. The inhibition of ROS production by N-acetylcysteine significantly suppressed oxidative stress in all three cell lines. In vivo, F2 significantly reduced tumor volume and weight of the Ehrlich solid tumor, and significantly increased lipoperoxidation, indicating that F2 also induces oxidative stress in the in vivo model. These findings indicate that the proanthocyanidin polymer-rich fraction of S. adstringens may be a potential chemotherapeutic candidate for cancer treatment.
RESUMO
kin17 has been described as a protein involved in the processes of DNA replication initiation, DNA recombination, and DNA repair. kin17 has been studied as a potential molecular marker of breast cancer. This work reports the detection and localization of this protein in the murine melanoma cell line B16F10-Nex2 and in two derived subclones with different metastatic potential, B16-8HR and B16-10CR. Nuclear and chromatin-associated protein fractions were analyzed, and kin17 was detected in all fractions, with an elevated concentration observed in the chromatin-associated fraction of the clone with low metastatic potential, suggesting that the kin17 expression level could be a marker of melanoma.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Melanoma/metabolismo , Proteínas Nucleares/metabolismo , Animais , Movimento Celular , Cromatina/metabolismo , Reparo do DNA , Replicação do DNA , Isoenxertos , Melanoma/genética , Melanoma/patologia , Melanoma Experimental , Camundongos , Metástase NeoplásicaRESUMO
The population of Robinson Crusoe Island is estimated at 633 inhabitants. The current population has a common origin from the first eight families who colonized the island at the end of the 19th century. The objective of this study was to determine the rates of consanguinity, the average coefficients of inbreeding, the types of consanguineous marriages and the inbreeding evolution between 1900 and 2000 on the island. All marriages registered on the island, from the last colonization until 2000 (417 in total), were included in the analysis. In addition, extended genealogies were obtained. The consanguinity rate was 14.9% and the average coefficient of inbreeding (α) 54.05 × 10(-4). The most frequent type of consanguineous marriages was between second cousins, followed by first cousins. The average value of the first/second cousin ratio was 1.11. The population of Robinson Crusoe Island has a high rate of inbreeding. The unique characteristic of the island - its small current population, originating from just a few families, with small rate of gene flow - could explain the observed high and increasing consanguinity.
Assuntos
Consanguinidade , Ilhas , Grupos Populacionais/estatística & dados numéricos , Chile , Humanos , Masculino , Casamento , Linhagem , População RuralRESUMO
The classification and characterization of silkworm strains are important for sericulture, which is supported by the constant development of new hybrids. In this study, 16 parental strains of Bombyx mori L from the germplasm banks of the Universidade Estadual de Maringá--UEM, and Associação dos Criadores de Bicho-da-Seda de Nova Esperança e Regiões Sericícolas do Paraná--ACESP, were evaluated regarding biological and productive traits economically important. The Chinese C122-B and C121-A, and the Japanese HA-A and HA-B strains yielded the highest cocoon weight, which is related to the raw silk percentage. Our data will be useful in breeding programs for the production of superior silkworm strains and hybrids.
Assuntos
Bombyx/classificação , Têxteis/economia , AnimaisRESUMO
The classification and characterization of silkworm strains are important for sericulture, which is supported by the constant development of new hybrids. In this study, 16 parental strains of Bombyx mori L from the germplasm banks of the Universidade Estadual de Maringá - UEM, and Associação dos Criadores de Bicho-da-Seda de Nova Esperança e Regiões Sericícolas do Paraná - ACESP, were evaluated regarding biological and productive traits economically important. The Chinese C122-B and C121-A, and the Japanese HA-A and HA-B strains yielded the highest cocoon weight, which is related to the raw silk percentage. Our data will be useful in breeding programs for the production of superior silkworm strains and hybrids.
A classificação e caracterização de linhagens de Bombyx mori L é importante para a sericicultura, uma vez que essa atividade é sustentada pelo constante desenvolvimento de novos híbridos da espécie. Neste trabalho, 16 linhages parentais de B. mori do banco de germoplasma da Universidade Estadual de Maringá - UEM, e da Associação dos Criadores de Bicho-da-Seda de Nova Esperança e Regiões Sericícolas do Paraná - ACESP, foram avaliadas em relação às características biológicas e produtivas consideradas economicamente importantes. As linhagens C122-B e C121-A, de origem Chinesa, e as HA-A e HA-B, Japonesas, apresentaram o maior peso de casulo (CW), o qual é associado ao teor de seda (RSP). Os resultados apresentados neste trabalho podem ser utilizados em vários programas de melhoramento visando à produção de linhagens e híbridos geneticamente superiores.
Assuntos
Animais , Bombyx/classificação , Têxteis/economiaRESUMO
Twelve cases of Reye's syndrome are presented with different degrees of encephalopathy, hyperammonemia and hypoglycemia; associated to acetyl salicylic acid (ASA) ingestion. The aim of the present retrospective study was to describe our experience in selected patients with Reye's syndrome associated to the ASA ingestion and to underline the influence of hyperammonemia on Reye's encephalopathy. All the cases presented moderate hyperbilirubinemia, elevated alanine aminotransferase, aspartate aminotransferase with an average of 302+/-205 UI/L and 285+/-149 UI/L respectively. Arterial blood ammonia averaged 172.4+/-71.3 micromol/L and glycaemia averaged 35.2+/-17.0 mg/dl. A high mortality was found in our series (41.7%). Considering that encephalopathy is the leading syndrome in these cases, the influence of ammonia on brain tissue was described. Glutamate is an excitotoxic neurotransmitter, capable to produce neuron and astrocyte damage and apoptosis. The presence of ASA could cause the onset of the mitochondrial permeability transition and the mitochondrial swelling in the astrocyte, leading to hyperammonemia. In Reye's syndrome, hyperammonemia and perhaps the increase of glutamate are the leading factors in the mechanism of brain damage and encephalopathy. Aspirin must be carefully administrated and controlled by professionals. Furthermore, parents must be informed about the risks in the use of this drug in children.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Hiperamonemia/induzido quimicamente , Síndrome de Reye/induzido quimicamente , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/metabolismo , Argentina/epidemiologia , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Criança , Pré-Escolar , Feminino , Ácido Glutâmico/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Humanos , Hiperamonemia/fisiopatologia , Hiperbilirrubinemia/induzido quimicamente , Masculino , Dilatação Mitocondrial/efeitos dos fármacos , Estudos Retrospectivos , Síndrome de Reye/mortalidade , Síndrome de Reye/fisiopatologiaRESUMO
1. The aim of the present study was to assess whether protection afforded by the Na(+)/H(+) exchanger blocker dimethylamiloride (DMA) is associated with inhibition of mitochondrial permeability transition (MPT). The effects of DMA were compared with those of cyclosporine (Cs) A, an inhibitor of MPT. 2. Rat hearts were Langendorff perfused with Krebs'-bicarbonate medium containing 10 mmol/L glucose and were subjected to 25 min no-flow global ischaemia and 30 min reperfusion in the presence or absence of 10 micromol/L DMA or 0.2 micromol/L CsA. Cell viability was measured using tetrazolium stain. The MPT was determined by loading hearts with 2-deoxy-[(3)H]-glucose (2DG), which enters mitochondria only during MPT. Total heart 2DG content as an estimation of the extent of tissue damage was also measured. To assess whether DMA has any direct effect on glycolysis, a cell-free heart extract containing all the glycolytic enzymes was used. 3. Dimethylamiloride improved functional recovery (rate-pressure product) from 24 +/- 7 to 68 +/- 11% (P < 0.01) at reperfusion end, attenuated the increase in left ventricular end-diastolic pressure (from 29 +/- 7 to 6 +/- 3% 10 min after reperfusion onset; P < 0.01), improved cell viability (from 21.2 +/- 6.6 to 69.6 +/- 7.1% at reperfusion end; P < 0.05) and lessened lactate accumulation at the end of ischaemia (119 +/- 15 vs 163 +/- 14 micromol/g dry weight; P < 0.05). Dimethylamiloride limited MPT: 2DG mitochondrial entrapment, being 33.1 +/- 14.2 and 96.3 +/- 14.0 at reperfusion end in the treated and control hearts, respectively (P < 0.05), and concomitantly raised total 2DG content (51.3 +/- 4.4 vs 86.8 +/- 1.7 x 10(3) d.p.m./g wet weight in control and treated groups, respectively; P < 0.05). Cyclosporine A improved functional recovery and attenuated the amplitude of ventricular diastolic pressure in ischaemic-reperfused hearts. It also reduced mitochondrial entrapment (67.3 +/- 7.7%; P < 0.05 vs control) and increased total cell 2DG content (162.3 +/- 1.3 x 10(3) d.p.m./g wet weight; P < 0.01 vs control) at the end of reperfusion. Dimethylamiloride did not affect glucose consumption and lactate production in the cell-free heart extract. 4. In conclusion, DMA protects against the noxious effects of ischaemia-reperfusion and inhibits MPT, coinciding with present and previous findings concerning the effects of CsA. Dimethylamiloride also diminished lactate accumulation, although it did not exhibit any direct effect on glycolysis. These data suggest that blockade of Na(+)/H(+) exchange by DMA attenuates the extent of MPT in ischaemic-reperfused rat heart.
Assuntos
Amilorida/análogos & derivados , Fármacos Cardiovasculares/farmacologia , Ciclosporina/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Amilorida/farmacologia , Amilorida/uso terapêutico , Animais , Fármacos Cardiovasculares/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Ciclosporina/uso terapêutico , Feminino , Glicólise/efeitos dos fármacos , Técnicas In Vitro , Ácido Láctico/metabolismo , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Perfusão , Permeabilidade , Ratos , Ratos Wistar , Trocadores de Sódio-Hidrogênio/metabolismo , Fatores de Tempo , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacosRESUMO
The number of patients over 65 years of age with chronic renal failure has increased. Peritoneal dialysis (PD) is an effective mode of treatment for such patients. In the present study, we report our experience with automated PD in patients over 65. We recorded the demographic and clinical characteristics of the patients and the exit-site infection rate, the peritonitis rate, and the mortality rate, comparing those parameters with the same parameters in patients under 65. We followed 36 patients (30% of the total study population) who were over 65 years of age (mean: 74.5 +/- 7.3 years). Of the 36 patients, 34 (94.4%) had another chronic disease--arterial hypertension and heart disease being the more common. Eleven of the patients (31%) had diabetes. Duration of PD therapy in the group was 31.5 +/- 20.7 months. Ten of the patients (27.8%) had at least 1 catheter-related complication, including exit-site infection (n = 3), tunnel infection (n = 1), or a noninfectious complication (n = 6). The rate of catheter-related infection was 0.22 episodes/patient-year. Two catheter were lost: 1 in a case of hematoma, and 1 in a case of catheter obstruction. The rate of peritonitis was 0.16 episodes/patient-year, and the most common infectious agent was methicillin-susceptible Staphylococcus aureus. Actuarial survival of our elderly patients was 51.8% at 4 years of follow-up as compared with 81.7% in the younger patients (p = 0.01). All cases of death were related to comorbid conditions, not to PD therapy. Two patients were transferred to hemodialysis. We conclude that PD has proven to be a safe and comfortable therapy for renal replacement in patients over 65 years of age. Results are similar to results in younger patients.
Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cateteres de Demora/efeitos adversos , Feminino , Humanos , Masculino , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/mortalidade , Peritonite/etiologia , Taxa de SobrevidaRESUMO
Loss of the peritoneal dialysis (PD) catheter is a major cause of PD technique failure and transfer to hemodialysis. In the present study, we report our experience with permanent peritoneal catheters. We prospectively analyzed 125 double-cuff coiled, swan-neck catheters implanted by the open surgical method in 120 patients from January 1996 to June 2003. The patients were evaluated monthly and followed for a total of 2806 patient-months. The mean age of the patients was 55 +/- 17 years (range: 22 - 91 years); 52% were men; 20% had diabetes; 10% were receiving immunosuppressive treatment; 45% were Staphylococcus aureus nasal carriers; and 93.3% were on automated PD. Catheter survival was 97% at 2 years and 92.2% at 5 years. A total of 59 early and late catheter complications were observed in 36 patients. These included exit-site infection at a rate of 0.125 episodes/ patient-year. The most frequent noninfectious complications were herniation (8%), leakage (6%), and bloody dialysate (3%). Statistical analysis did not identify variables that predicted the development of exit-site infection. The overall peritonitis rate was 0.149 episodes/patient-year. Our data suggest that the main catheter complication is infection. The low incidence of infection in our study is probably related more to good installation technique and aftercare than to the clinical characteristics of the patients.
Assuntos
Cateteres de Demora/efeitos adversos , Diálise Peritoneal/instrumentação , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/etiologia , Infecções Bacterianas/microbiologia , Feminino , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Peritonite/etiologia , Peritonite/microbiologia , Análise de SobrevidaRESUMO
AIM: To study the blood-brain barrier integrity, brain edema, animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication. METHODS: Adults male Wistar rats were divided into four groups. Group I: sham operation; II: Prehepatic portal hypertension, produced by partial portal vein ligation; III: Acetaminophen intoxication and IV: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded. RESULTS: Portal hypertension was significantly elevated in groups II and IV. Liver enzymes and ammonia plasma levels were increased in groups II, III and IV. Prehepatic portal hypertension (group II), acetaminophen intoxication (group III) and both (group IV) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups III and IV. Behavioral test (rota rod) was altered in group IV. CONCLUSION: These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group IV, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.