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1.
Health Hum Rights ; 20(2): 105-122, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30568406

RESUMO

The Rohingya people of Myanmar have been subject to human rights violations through government-sponsored discrimination and violence. Since August 2017, an intensified assault by Myanmar authorities has resulted in a rapid increase of Rohingya pouring into Bangladesh, and the expansion of refugee settlements in the district of Cox's Bazar has strained humanitarian and government relief efforts. Assessing Rohingya and host community needs is critical for prioritizing resource allocations and for documenting the rights violations suffered by Rohingya refugees. From March 15 to 18, 2018, we conducted a rapid needs assessment of recently arrived Rohingya and host community households. We collected data on demographics, mortality, education, livelihoods, access to food and water, vaccination, and health care. Among other things, our survey found high levels of mortality among young Rohingya men, alarmingly low levels of vaccination among children, poor literacy, and rising poverty. Denied formal refugee status, the Rohingya cannot access due protections and find themselves in a state of insecurity in which they are unsure of their future and unable to formally seek work or send their children to school. While the government of Bangladesh explores the options of repatriation, relocation, and third-country resettlement for these refugees, it is important to ensure that they are not denied a life of dignity.


Assuntos
Necessidades e Demandas de Serviços de Saúde , Direitos Humanos , Racismo , Refugiados/estatística & dados numéricos , Adulto , Bangladesh , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Mianmar/etnologia , Pobreza , Populações Vulneráveis/estatística & dados numéricos , Adulto Jovem
2.
Curr Oncol ; 23(5): e481-e487, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27803609

RESUMO

BACKGROUND: Phase angle could be an alternative to subjective global assessment for the assessment of nutrition status in patients with head-and-neck cancer. METHODS: We prospectively evaluated a cohort of 75 stage iiib and iv head-and-neck patients treated at the Otolaryngology Department, Head and Neck Surgery, Medical University of Lublin, Poland. Bioelectrical impedance analysis was performed in all patients using an analyzer that operated at 50 kHz. The phase angle was calculated as reactance divided by resistance (Xc/R) and expressed in degrees. The Kaplan-Meier method was used to calculate survival. RESULTS: Median overall survival in the cohort was 32.0 months. At the time of analysis, 47 deaths had been recorded in the cohort (62.7%). The risk of shortened overall survival was significantly higher in patients whose phase angle was less than 4.733 degrees than in the remaining patients (19.6 months vs. 45 months, p = 0.0489; chi-square: 3.88; hazard ratio: 1.8856; 95% confidence interval: 1.0031 to 3.5446). CONCLUSIONS: Phase angle might be prognostic of survival in patients with advanced head-and-neck cancer. Further investigation in a larger population is required to confirm our results.

3.
Indian J Cancer ; 51(3): 209-213, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25494106

RESUMO

Context: Bioelectrical impedance analysis (BIA) detects changes in tissue electrical properties and has been seen as a prognostic tool in several chronic conditions, including cancer. AIMS: The study was conducted to investigate whether there are any tissue electrical differences in patients with head and neck cancer (H and NC) before and after surgery treatment. Settings and Design: The observational study was performed at the Otolaryngology Department, Head and Neck Oncology. Materials and Methods : Tissue electrical properties were assessed in 31 patients with H and NC before and 2 weeks after surgery treatment. Direct bioimpedance measures [resistance, reactance, phase angle (PA)] were determined by BIA. Statistical Analysis Used: The Shapiro-Wilk test was used to assess the distribution conformity of examined parameters with a normal distribution; the Fisher (F) test was used to assess variance homogeneity. For group comparisons of metric data we used the Mann-Whitney U test. P value < 0.05 was considered as statistically significant. The statistical analysis for this study was performed using the computer software STATISTICA v. 8.0 (StatSoft). Results: PA at 50 kHz was found to be significantly (P = 0.000009) lower after surgery in patients with H and NC than before treatment (4.69° ±0.71 vs. 4.22 ± 0.83, respectively). Resistance was significantly (P = 0.0005) greater after surgery in patients with H and NC than before (596.24 ± 96.31 ohm vs 647.64 ± 276.11 ohm, respectively). Conclusions: There are tissue electrical differences before and after surgery in patients diagnosed with H and NC. Further observations would be useful to feedback in support therapy planning of individual patients.

4.
Curr Oncol ; 21(1): e62-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24523622

RESUMO

BACKGROUND: The ratio of extracellular mass to body cell mass (ecm/bcm), determined by bioelectrical impedance analysis, has been found to be a potentially useful indicator of nutrition status. Subjective global assessment (sga) is a subjective method of evaluating nutrition status in head-and-neck cancer. The present study was conducted to investigate the association between ecm/bcm and sga in head-and-neck cancer. METHODS: Patients were classified as either well-nourished or malnourished by sga. Bioelectrical impedance analysis was conducted on a population of 75 patients with histologically confirmed head-and-neck cancer, and the ecm/bcm was calculated. Receiver operating characteristic curves were estimated using the nonparametric method to determine an optimal cut-off value of the ecm/bcm. RESULTS: Compared with malnourished patients, those who were well-nourished had a statistically significantly lower ecm/bcm (1.11 vs. 1.28, p = 0.005). An ecm/bcm cut-off of 1.194 was 76% sensitive and 63% specific in detecting malnutrition. CONCLUSIONS: The ecm/bcm can be an indicator that detects malnutrition in patients with head-and-neck cancer. Further observations are needed to validate the significance of the ecm/bcm and to monitor nutrition interventions.

5.
J Physiol Pharmacol ; 63(1): 101-4, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22460467

RESUMO

Direct bioimpedance measures (resistance, reactance, phase angle (PA)) determined by bioelectrical impedance analysis (BIA) detect changes in tissue electrical properties. The study was conducted to evaluate soft tissue hydration and mass through pattern analysis of vector plots as height, normalized resistance, and reactance measurements by bioelectric impedance vector analysis in patients with head and neck cancer. Whole-body measurements were made with ImpediMed bioimpedance analysis in 56 adult, white, male subjects 42 to 79 years old: 28 patients with head and neck squamous cell carcinoma (H&NC) and 28 healthy volunteers matched by sex, age and BMI as a control group. All patients were previously untreated and without active nutritional interventions. Mean vectors of H&NC group vs. the control group were characterized by an increased normalized resistance component with a reduced reactance component (separate 95% confidence limits, P<0.05), indicating a decreased ionic conduction (dehydration) with loss of dielectric mass (cell membranes and tissue interfaces) of soft tissue. Monitoring vector displacement trajectory toward the reference target vector position may represent useful feedback in support therapy planning of individual patients before surgery in patients with head and neck cancer in order to reduce post-operational complications.


Assuntos
Carcinoma de Células Escamosas/fisiopatologia , Neoplasias de Cabeça e Pescoço/fisiopatologia , Adulto , Idoso , Composição Corporal/fisiologia , Impedância Elétrica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço
6.
J Laryngol Otol ; 121(1): 5-8, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17076928

RESUMO

We studied the transmission of heat to the vestibule during revision stapes surgery with a piston in situ, using a CO2 laser, in an in vitro model. A type K thermocouple was placed around the medial end of stainless steel and fluoroplastic wire pistons in a 'vestibule' filled with saline. The effect of laser hits on fluoroplastic wire and stainless steel stapes prostheses was investigated. The effect of introducing a vein graft to seal the stapedotomy was also examined. Greater temperature rises occurred with stainless steel than with fluoroplastic wire pistons. The addition of the vein graft reduced heat transmission. Application of the CO2 laser to fluoroplastic wire pistons, using the power settings suggested by the manufacturer, is not likely to damage the inner-ear structures. Application of 6 W laser energy to stainless steel pistons can potentially disturb the inner-ear function.


Assuntos
Temperatura Alta , Terapia a Laser/efeitos adversos , Cirurgia do Estribo/efeitos adversos , Terapia a Laser/instrumentação , Terapia a Laser/métodos , Reoperação , Cirurgia do Estribo/instrumentação , Cirurgia do Estribo/métodos , Condutividade Térmica , Vestíbulo do Labirinto
7.
Otolaryngol Pol ; 55(1): 29-33, 2001.
Artigo em Polonês | MEDLINE | ID: mdl-11355473

RESUMO

Human papillomavirus (HPV) is a small DNA virus. HPV is can be divided into two groups: mucosal and cutaneous. HPV have various oncogenic potential. The correlation between presence of high oncogenic type of HPV and carcinogenesis was confirmed in human anogenital tract and cervical carcinoma. The latest studies suggest HPV infection involvement in benign and malignant lesions of aerodigestive tract. The aim of our study was to determine the presence of the HPV genes E6/E7. The specimens were taken after total laryngectomy from 20 patients with squamous cell carcinoma. The fresh tissue specimens were frozen at -70 degrees C until DNA extraction and HPV detection. The presence of HPV DNA was assessed by polymerase chain reaction using specific primers for HPV 16 and 18 E6/E7. There were 7 (35%) HPV positive specimens in our group. 5 (25%) specimens were HPV 16 positive, 4 (20%) specimens were HPV-18 positive. In two cases HPV 16 and HPV 18 was present. The results suggest that high oncogenic types of HPV may play a role in pathogenesis of laryngeal carcinoma.


Assuntos
Neoplasias Laríngeas/diagnóstico , Proteínas Oncogênicas Virais/isolamento & purificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Adulto , Idoso , DNA Viral/isolamento & purificação , Feminino , Humanos , Recém-Nascido , Neoplasias Laríngeas/virologia , Masculino , Pessoa de Meia-Idade , Proteínas E7 de Papillomavirus , Reação em Cadeia da Polimerase
8.
Artigo em Inglês | MEDLINE | ID: mdl-11977350

RESUMO

Otosclerosis in children and teenagers is very uncommon. Typical otosclerosis presents as a slowly progressive conductive hearing loss and tinnitus in the third to fourth decade of life. Stapedectomy is a well-established procedure for correction of conductive hearing loss in adult patients with otosclerosis. The aim of this work is to assess short- (6 months) and long-term (7 years) results after stapedectomy performed in 10 patients under 20 years of age. In 1 patient cochlear otosclerosis was diagnosed and in 1 patient incus anomaly was found during the operation. Pure tone audiograms obtained 6 months after stapedectomy showed air-bone gap closure to 10 dB in 6 patients, to 15 dB in 8 patients and in all patients to 20 dB. Average air conduction threshold improved by 26.5 dB and average bone conduction threshold by 5.9 dB. 7 years after stapedectomy air-bone gap was similar to the one measured 6 months postoperatively. Stapedectomy in children provides good and stable hearing results.


Assuntos
Otosclerose/cirurgia , Cirurgia do Estribo , Adolescente , Adulto , Condução Óssea , Criança , Feminino , Humanos , Bigorna/anormalidades , Masculino , Próteses e Implantes , Resultado do Tratamento
9.
Otolaryngol Pol ; 55(4): 421-3, 2001.
Artigo em Polonês | MEDLINE | ID: mdl-11766322

RESUMO

In a group of 15 patients with malignant melanoma of the nasal cavity and paranasal sinuses the place of origin was nasal mucosa in 11 patients, the ethmoid cells in 2 cases and the maxillary sinus in 2 cases. Only 5 patients had tumour limited to infrastructure of the nasomaxillary complex, in 10 patients tumour occupied also suprastructure. Total maxillectomy was performed in 4 patients, partial maxillectomy in 8 patients with orbital exenteration in 3 patients. Of 12 patients operated on three patients died one year, two patients two years and one patient 6 years after surgery. One patient is alive 12 years, three patients are alive three years and one patient is alive one year after surgery.


Assuntos
Melanoma/diagnóstico , Melanoma/cirurgia , Neoplasias Nasais/diagnóstico , Neoplasias Nasais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal , Mucosa Nasal , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/cirurgia , Resultado do Tratamento
10.
Toxicol Sci ; 46(2): 410-7, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10048145

RESUMO

Propylene glycol (propane-1,2-diol; PD) is a widely used solvent for intravenous drugs. Clinical studies have reported serious side effects, including the development of renal insufficiency in patients receiving PD as drug vehicle. Despite such clinical reports, the data on the toxicity of PD in isolated renal cells are limited. Using primary cultured human proximal tubule (HPT) cells as an in vitro model, we have previously shown the acute toxic effects of PD in HPT cells (Morshed et al., Fundam. Appl. Toxicol. 23, 38-43, 1994). Since most cases of clinical toxicity are noted after prolonged administration of PD, the current studies were designed to investigate the toxicity of repeated exposure of PD in HPT cells. The onset of toxicity was determined using 10-50 mM racemic, sinister, and rectus PD (rac-, S-, and R-PD, respectively) for periods up to 6 days. Cytotoxicity was noted by decreases in thymidine incorporation, in mitochondrial metabolic activity, and in lysosomal accumulation of neutral red. Exposure of HPT cells to 50 mM PD produced toxic responses, while at 10 mM, responses were not significantly greater than those of osmotic controls. The toxicity was caused by a PD-specific mechanism and by a secondary mechanism without any enantiomeric specificity. The HPT cell toxicity was associated with a 35% increase in cellular thiobarbituric acid-reactive substances and a 20% decrease in glutathione. These findings suggest the development of a mild, subacute toxicity in normally proliferating HPT cells at concentrations that could be achieved in human plasma when PD is used as a drug vehicle.


Assuntos
Túbulos Renais/efeitos dos fármacos , Mitocôndrias/metabolismo , Vermelho Neutro/farmacocinética , Propilenoglicol/toxicidade , Timidina/metabolismo , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Estereoisomerismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
11.
Artigo em Polonês | MEDLINE | ID: mdl-10761233

RESUMO

The study of registered morbidity of patients suffering from laryngeal cancer in the Lublin macro-region in the years 1991-95 was carried out. Morbidity rates in the population in consecutive years of investigated 5-year age groups were examined. In clinical investigations the conditions of clinical advancement of the disease in particular organs was determined and environmental factors and occupation were also revealed.


Assuntos
Neoplasias Laríngeas/epidemiologia , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Neoplasias Laríngeas/classificação , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida
12.
J Nutr ; 127(6): 1137-47, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9187628

RESUMO

Although reabsorption across the apical (AP) membrane of the renal proximal tubule cell plays a vital role in the conservation of plasma 5-methyltetrahydrofolate, basolateral (BL) membrane-directed secretory pathways may also be important in regulating the urinary excretion of folate. Folate transport proteins, folate receptor and the reduced folate carrier have been implicated in the renal conservation of folate across the AP membrane, but their role in BL membrane-directed folate transport has not been studied. 5-Methyltetrahydrofolate transport across the AP and BL membranes of human proximal tubule cells was studied in cells grown on membrane inserts to allow optimum differentiation of AP and BL domains. Colchicine, an inhibitor of vesicular-mediated endocytosis, inhibited AP binding and AP-directed transport without affecting BL transport. Probenecid, an inhibitor of anion exchange, did not affect binding, but inhibited both AP and BL-directed transport with a greater effect on BL transport. Folic acid abolished AP binding of 5-methyltetrahydrofolate, but diminished AP-mediated transport by only 50%. These data suggest that both the folate receptor and the reduced folate carrier participate in AP uptake of folates by human kidney cells, but that BL-mediated uptake occurs primarily by the reduced folate carrier. Folate transport from the secretory direction occurred as readily as that from the reabsorptive direction, indicating that altered secretion could mediate excess urinary folate excretion.


Assuntos
Ácido Fólico/metabolismo , Túbulos Renais Proximais/metabolismo , Receptores de Superfície Celular , Tetra-Hidrofolatos/farmacocinética , Antídotos/metabolismo , Membrana Basilar/fisiologia , Transporte Biológico , Proteínas de Transporte/fisiologia , Células Cultivadas , Receptores de Folato com Âncoras de GPI , Ácido Fólico/urina , Humanos , Leucovorina/metabolismo , Tetra-Hidrofolatos/metabolismo
13.
Am J Physiol ; 272(3 Pt 2): F380-8, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9087682

RESUMO

Decreases in plasma folate levels leading to folate deficiency can result from increased urinary loss of folate, due to changes in either the renal reabsorption or secretion of folate. Hence, human proximal tubule (HPT) cells were cultured on microporous membranes to separate apical (AP) and basolateral (BL) domains and to assess the transport of 5-methyltetrahydrofolate from AP-to-BL (i.e., reabsorptive) and BL-to-AP (secretory) directions. Cellular uptake of alpha-methylglucoside occurred specifically from the AP direction, and transport of p-aminohippurate occurred more readily from the BL direction, demonstrating cell polarity similar to that in vivo. Under tight monolayer conditions, binding of folate to the AP membrane occurred more readily from the AP direction, although AP binding also occurred from the BL chamber. Intracellular transport occurred equally from both AP and BL directions. When loaded from either direction, folate was effluxed from HPT cells into both AP and BL chambers. About 20-30% of the internalized substrate was converted to nonfolate catabolites. Thus HPT cells readily take up folate via both the AP and BL membranes, metabolize it intracellularly and secrete the products across both membranes. These studies suggest that renal folate homeostasis is regulated bidirectionally.


Assuntos
Córtex Renal/metabolismo , Túbulos Renais Proximais/metabolismo , Tetra-Hidrofolatos/farmacocinética , Absorção , Transporte Biológico , Membrana Celular/metabolismo , Células Cultivadas , Técnicas de Cultura/métodos , Humanos , Cinética , Metilglucosídeos/farmacocinética
14.
Mol Cell Biochem ; 162(1): 11-6, 1996 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-8905620

RESUMO

This study has examined whether elevated glucose can induce lipid peroxidation and contribute to the inhibition of cell growth in human kidney proximal tubule(HPT) cells. HPT cells were cultured in media containing glucose concentrations of 8 mM (control), 25 mM, and 50 mM. Lipid peroxidation was assessed by the thiobarbituric acid reactivity and cell growth was assessed by 3H-thymidine uptake. Results show decreased (59%, p < 0.01) growth of HPT cells cultured in 50 mM glucose. Cells cultured in 50 mM mannitol did not show any growth inhibition, suggesting that the decreased cell growth associated with glucose is not due to osmolarity changes. There was an increase (108%, p < 0.02) in lipid peroxidation in cells cultured with high levels of glucose (50 mM) compared with controls and cells cultured with 50 mM mannitol. To examine if membrane lipid peroxidation or malondialdehyde (MDA, an end product of lipid peroxidation) has any role in the inhibition of cell growth, we examined the effect of tertiary butylhydroperoxide (TBH, known to cause lipid peroxidation and generate MDA) on the growth of HPT cells. TBH decreased cell growth (49, 17 and 3% of controls at 0.1, 0.25, and 0.5 mumole TBH/ml medium). Similarly, a marked reduction in the growth was observed with exogenous MDA (72, 69 and 34% of controls at 0.1, 0.25, and 0.5 mumole MDA/ml medium). This suggests that elevated glucose can induce membrane lipid peroxidation and accumulation of MDA, which in turn can inhibit cellular growth and contribute to the altered structure and function of HPT cells in diabetes.


Assuntos
Glucose/farmacologia , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Peroxidação de Lipídeos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Túbulos Renais Proximais/efeitos dos fármacos , Malondialdeído/metabolismo , Malondialdeído/farmacologia , Peróxidos/farmacologia , Espécies Reativas de Oxigênio , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , terc-Butil Hidroperóxido
15.
In Vitro Cell Dev Biol Anim ; 31(2): 107-14, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7735562

RESUMO

Primary cultures of human proximal tubule (HPT) cells possess the characteristics of a tight epithelium and retain the characteristics of in vivo renal function. HPT cells form confluent monolayers when grown on collagen-coated polycarbonate inserts in a hormonally defined serum-free medium. However, initial studies of transepithelial transport observed large bidirectional fluxes of the paracellular probe inulin. The present studies were designed to assess the transformation of HPT cell tight junctions to a "leaky" state and subsequent recovery. The apparent transepithelial electrical resistance of HPT cells at confluence was 952.0 +/- 70.0 ohms*cm2, suggesting a well-developed tight junction-mediated paracellular pathway in this epithelium. However, replacement of the growth media produced an immediate 90% drop in the initial resistance, which was paralleled by an increased flux of inulin and of phenol red. This transient abolition of barrier function spontaneously reestablished over 1-2 h by a process that was dependent on the ionic composition of the added media. Complete recovery of cellular resistance was paralleled by markedly decreased fluxes of inulin and of phenol red. The recovery of cellular barrier function was inhibited by cytochalasin B suggesting an intracellular action, not a physical disruption of the monolayer. These results suggest that the tight junctions in these cells appear to transiently produce a leaky state during removal of the media, but rearrange to a "tight conformation" when incubated in the appropriate media.


Assuntos
Permeabilidade da Membrana Celular , Túbulos Renais Proximais/metabolismo , Transporte Biológico , Cátions , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , Citocalasina B/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Inulina/metabolismo , Túbulos Renais Proximais/citologia , Fenolsulfonaftaleína/metabolismo
16.
Otolaryngol Pol ; 49 Suppl 20: 29-31, 1995.
Artigo em Polonês | MEDLINE | ID: mdl-9454163

RESUMO

Investigations of larynx cancer rate of Lublin population were carried out in the years 1991-1994. Factors of the community rates in each year and in five-years age group were determined. 681 suffering people were examined clinically. The clinical stage and degree of organ involvement were appointed.


Assuntos
Neoplasias Laríngeas/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polônia/epidemiologia , Distribuição por Sexo
17.
Otolaryngol Pol ; 49 Suppl 20: 373-6, 1995.
Artigo em Polonês | MEDLINE | ID: mdl-9454184

RESUMO

In the group of 42 patients after maxillectomy face deformation and function defects were assessed. The best cosmetic and functional result was observed after maxillectomy without orbital exenteration, with preservation of lateral part of the zygomatic bone and at least a half of nasal skeleton. Severe face deformation developed after orbital exenteration, resection of the palpebrae, cheek and external nose.


Assuntos
Face/anormalidades , Neoplasias Maxilares/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Adolescente , Adulto , Idoso , Bochecha/cirurgia , Face/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nariz/cirurgia , Órbita/cirurgia , Resultado do Tratamento
18.
Fundam Appl Toxicol ; 23(1): 38-43, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7958561

RESUMO

The present study assess the acute toxicity of propylene glycol (propane-1,2-diol, PD) using cultured human proximal tubule (HPT) cells as the model. Confluent monolayers of HPT cells were treated with 0-263 mM (0-2%) isotonic solutions of racemic, sinister, and rectus PD (rac-, S-, and R-PD, synonym: DL-, L-, and D-PD, respectively). Release of lactate dehydrogenase (LDH) and of preloaded 51Cr as markers of in vitro toxicity, were increased by PD in a time- and concentration-related manner, suggesting significant PD-induced damage of the HPT cell membrane. These toxic effects reached an apparent maximum within 2 hr. Further studies were performed to determine whether adverse effects of PD may occur prior to development of membrane damage. Because significant membrane damage was not apparent during the first 15 min of PD exposure, cellular release of lactate and accumulation of glucose were studied after preincubating cells in PD (treated) or pH 7.4 buffer (control) for 10 min. PD significantly increased the subsequent release of lactate by concentration- and enantiomer-dependent mechanisms with R-PD being the most potent agent. PD also inhibited the Na(+)-independent, carrier-mediated glucose accumulation without significant effects on the Na(+)-dependent pathway. These data suggest a rapid onset of cellular toxicity even when the plasma membrane integrity and viability remained apparently normal. The present studies show significant toxic effects of PD and suggest that a primary culture of HPT cells may be useful in evaluating the toxicity of xenobiotics.


Assuntos
Túbulos Renais Proximais/efeitos dos fármacos , Propilenoglicóis/toxicidade , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , Cromo/metabolismo , Glucose/metabolismo , Humanos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , L-Lactato Desidrogenase/metabolismo , Lactatos/metabolismo , Ácido Láctico , Propilenoglicol , Estereoisomerismo , Testes de Toxicidade/métodos
19.
Adv Exp Med Biol ; 338: 745-8, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8304220

RESUMO

Initial attempts to model urinary folate reabsorption using cultures of HPT cells on porous filter inserts produced disappointing results in that large amounts of 5M were transported across the epithelial monolayer in a nonspecific manner. Since the impermeable molecule inulin was also transported, there apparently existed a significant leakage pathway in the way that the cultured cells were used for transport studies. 5M was bound to the AP membrane and taken up into the HPT cell by specific processes, while inulin was excluded, suggesting that the HPT cells were nevertheless operating functionally. TER values from cultured HPT cells plateaued at a high level when cells became confluent, suggesting an epithelial layer with functional tight junctions. However, when growth media were removed and replaced with transport buffers, there was an immediate loss of TER that fully recovered if the transport buffers were preincubated for 60 min. Under these conditions, transport studies showed the expected results--no movement of inulin through the cell layer and much reduced transfer of folate through the paracellular pathway. These results suggest that a transient opening of tight junctions occurs when growth media are replaced with biological buffers (or with fresh growth media), but that recovery of tight junction function occurs with time.


Assuntos
Ácido Fólico/metabolismo , Túbulos Renais/metabolismo , Tetra-Hidrofolatos/metabolismo , Tetra-Hidrofolatos/urina , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular , Células Cultivadas , Humanos , Junções Intercelulares/metabolismo , Inulina/metabolismo , Cinética , Modelos Biológicos , Fatores de Tempo , Ácido p-Aminoipúrico/metabolismo
20.
J Nutr ; 122(12): 2415-23, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1453227

RESUMO

The renal regulation of folate excretion is an important component in maintaining the body burden of folate. The tubular processes for folate disposition have been examined by a variety of methods to elucidate the mechanism by which renal folate excretion is regulated. Accordingly, the isolated perfused rat kidney technique was evaluated by investigating the clearance and metabolic patterns of 5-methyltetrahydrofolate (5-CH3-H4PteGlu). Kidneys from male Sprague-Dawley rats were perfused in vitro with [3H]5-CH3-H4PteGlu (1-2000 nmol/L). Linear regression analysis of 5-CH3-H4PteGlu excretion vs. filtered load revealed a tubular transport maximum of 7.5 pmol x min-1.g-1. A dual component system for tubular transport of 5-CH3-H4PteGlu was found: a high capacity, nonsaturable system and a low capacity, saturable system represented by the transport maximum. Furthermore, HPLC analysis of urine demonstrated renal uptake and metabolism of the labeled tracer. Tetrahydrofolate was identified as one metabolic product that indicated secretion of this compound. Additional metabolites were identified from kidney samples. Results suggest that 5-CH3-H4PteGlu undergoes net reabsorption by a dual component transport system; some of the reabsorbed 5-CH3-H4PteGlu is metabolized to other products that may be secreted in the urine.


Assuntos
Rim/metabolismo , Tetra-Hidrofolatos/metabolismo , Absorção , Animais , Transporte Biológico , Cromatografia Líquida de Alta Pressão , Taxa de Filtração Glomerular , Técnicas In Vitro , Túbulos Renais/metabolismo , Cinética , Masculino , Perfusão , Ratos , Ratos Sprague-Dawley , Análise de Regressão
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