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Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, Pï¼0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.
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Neoplasias de la Mama , Gemcitabina , Femenino , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Desoxicitidina/uso terapéutico , Quimioterapia de Mantención , Resultado del Tratamiento , Adulto , AncianoRESUMEN
OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION: Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.
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Acrilamidas/uso terapéutico , Aminoquinolinas/uso terapéutico , Neoplasias de la Mama , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/tratamiento farmacológico , China , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Receptor ErbB-2 , Estudios Retrospectivos , Trastuzumab , Resultado del TratamientoRESUMEN
Objective: To describe the status of non-steroidal anti-inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods: This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High-risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)" . From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health-related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ(2) test and Cochran-Armitage trend analysis method. Results: Of 35 910 subjects, the mean age was (54.6±7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend <0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend <0.05 for all). Conclusion: The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.
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Antiinflamatorios no Esteroideos/efectos adversos , Anticarcinógenos/efectos adversos , Aspirina/efectos adversos , Neoplasias Gastrointestinales/epidemiología , Ibuprofeno/efectos adversos , Adulto , Anciano , Antiinflamatorios no Esteroideos/farmacología , Anticarcinógenos/farmacología , Aspirina/farmacología , China/epidemiología , Estudios Transversales , Femenino , Neoplasias Gastrointestinales/inducido químicamente , Neoplasias Gastrointestinales/etnología , Humanos , Ibuprofeno/farmacología , Incidencia , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Objectives: To investigate the efficacy and safety of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of 58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel were included between January 2014 to October 2017. Prophylactic use of PEG-rhG-CSF was administered.Patients were further divided into two groups according to the frequency of PEG-rhG-CSF use: frequent use group (≥3 cycles) and non-frequent use group (<3 cycles). Results: There were significant differences in the incidence rates of grade 3/4 neutropenia between the prophylactic group and non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was also noted in the prophylactic group compared with the non-prophylactic group in cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the frequent use of group compared with the non-frequent use group(P<0.001). The most common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for preventing neutropenia and febrile neutropenia in breast cancer patients receiving adjuvant chemotherapy with docetaxel regimen.
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Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adyuvante , Factor Estimulante de Colonias de Granulocitos , Humanos , Polietilenglicoles , Proteínas RecombinantesRESUMEN
OBJECTIVE: To investigate the role of SATB2 in stem cell-like properties of osteosarcoma and identify new strategies to eliminate cancer stem cells of osteosarcoma. MATERIALS AND METHODS: Osteosarcoma cancer stem cells were derived by sarcosphere generation or chemo drug enrichment. SATB2 and pluripotency-associated gene expression in osteosarcoma CSCs were analyzed using qRT-PCR and Western blotting. The sphere formation assay, cell counting kit-8 assay and anti-chemotherapy proteins were used to measure the effects of altered SATB2, N-cadherin expression or metformin treatment in CSCs. Nude mice were injected with SATB2-deficient U2OS/MTX cells to assess the role of SATB2 in osteosarcoma growth and chemoresistance in vivo. Bioinformatics analyses were performed to identify SATB2 downstream target genes and immunochemistry to determine the correlation between SATB2 expression and patient outcome. Western blotting and luciferase reporter assays were used to examine the effects of N-cadherin and SATB2 inhibition on the NF-kB pathway. RESULTS: SATB2 was upregulated in osteosarcoma stem cells. Knockdown of SATB2 decreased sarcosphere formation, cell proliferation and stem cell-like gene expression in vitro, meanwhile reduced tumor growth and chemoresistance in vivo. High SATB2 expression in osteosarcoma patient samples was associated with poor clinical outcome. N-cadherin was one critical downstream target gene of SATB2 that mediated the stem cell-like phenotype. Reduction of SATB2 or N-cadherin resulted in NF-kB inactivation, which led to impaired osteosarcoma sphere formation and tumor cell proliferation. Metformin treatment of osteosarcoma cells enhanced the effects of chemotherapy via suppression of N-cadherin. CONCLUSIONS: SATB2 plays an important role in regulating osteosarcoma stem cell-like properties and tumor growth. The combination of conventional chemotherapy and metformin may be a promising therapeutic strategy for osteosarcoma patients.
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Neoplasias Óseas/patología , Proliferación Celular/efectos de los fármacos , Proteínas de Unión a la Región de Fijación a la Matriz/metabolismo , Metformina/farmacología , Osteosarcoma/patología , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismo , Adolescente , Animales , Neoplasias Óseas/metabolismo , Neoplasias Óseas/mortalidad , Cadherinas/metabolismo , Femenino , Humanos , Masculino , Proteínas de Unión a la Región de Fijación a la Matriz/antagonistas & inhibidores , Proteínas de Unión a la Región de Fijación a la Matriz/genética , Ratones , Ratones Desnudos , FN-kappa B/metabolismo , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Osteosarcoma/metabolismo , Osteosarcoma/mortalidad , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Tasa de Supervivencia , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Adulto JovenRESUMEN
Objective: To investigate the overall incidence and age distribution of upper digestive tract cancer in Cixian county, and to provide a reliable basis of prevention and treatment for upper gastrointestinal cancer. Methods: Collected annual incidence rate among 2003-2012 from Cixian cancer registry and abstracted all incidence rate of upper digestive tract cancer. The age-standardized incidence rate by Chinese standard population (ASR China) was calculated using the national population composition of 2000. The age-standardized incidence rate by world standard population (ASR world) was calculated using the world population composition of 1964 of Segi's. The annual average change (APC) was used to estimate the growth rate of the last two years in comparision with the first two years, which was calculated by Joinpoint regression model. The data was divided into two sections (from 2003 to 2007, and from 2008 to 2012), and the rate difference of different age group was calculated. Results: The crude incidence rate of the digestive tract cancer from 2003 to 2012 was 165.36/100 000 (10 309/6 234 346), which dropped from 170.75/10 100 000 (1 029/602 638) of 2003 to 146.02/100 000 of 2012 (936/640 991).The PC and APC of the crude incidence rate of upper gastrointestinal cancer were-12.96%, and-1.54% (95%CI:-3.22%-0.07%), respectively. The PC and APC of ASR China were-10.83%, and-1.30% (95%CI: 2.54%-0.03%), respectively. The PC and APC of ASR world were-9.82%, and-1.13% (95%CI:-2.20%--0.03%), respectively. The incidence of upper gastrointestinal cancer decreased. The incidence rate of 2003-2007 and 2008-2012 were 171.55/100 000 (5 239/3 048 593), and 159.41/10 000 (5 070/3 180 514), respectively and the rate difference was-12.15/100 000. The decrease of rate difference of 70 to 74 years old was the most (-340.32/100 000) and the increase of rate difference over the age of 85 was the most (447.21/100 000). Conclusion: From 2003 to 2012, the crude incidence of upper digestive tract cancer in Cixian showed a decreasing trend, and the 70-74 years old age group shows the most obvious decline.
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Pueblo Asiatico/estadística & datos numéricos , Neoplasias Esofágicas/etnología , Distribución por Edad , China/epidemiología , Humanos , Incidencia , Estándares de ReferenciaRESUMEN
BACKGROUND: Esomeprazole is an S-enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in humans. However, the pharmacokinetics and effects on intragastric pH of esomeprazole in dogs have not been reported. OBJECTIVE: To determine the pharmacokinetics of esomeprazole administered via various routes (PK study) and to investigate the effect of esomeprazole on intragastric pH with a Bravo pH monitoring system (PD study). ANIMALS: Seven adult male Beagle dogs and 5 adult male Beagle dogs were used for PK and PD study, respectively. METHODS: Both studies used an open, randomized, and crossover design. In the PK study, 7 dogs received intravenous (IV), subcutaneous (SC), and oral doses (PO) of esomeprazole (1 mg/kg). Each treatment period was separated by a washout period of at least 10 days. Esomeprazole plasma concentrations were measured by HPLC/MS/MS. In the efficacy study, intragastric pH was recorded without medication (baseline pH) and following IV, SC, and PO esomeprazole dosing regimens (1 mg/kg) in 5 dogs. RESULTS: The bioavailability of esomeprazole administered as PO enteric-coated granules and as SC injections was 71.4 and 106%, respectively. The half-life was approximately 1 hour. Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 58.9 ± 21.1% and 40.9 ± 17.3% for IV group, 75.8 ± 16.4% and 62.7 ± 17.7% for SC group, 88.2 ± 8.9% and 82.5 ± 7.7% for PO group, and 12.5 ± 3.6% and 3.7 ± 1.8% for baseline. The mean percent time with intragastric pH was ≥3 or ≥4 was significantly increased regardless of the dosing route (P < .05). CONCLUSION: The PK parameters for PO and SC esomeprazole administration were favorable, and esomeprazole significantly increased intragastric pH after IV, PO, and SC administration. IV and SC administration of esomeprazole might be useful when PO administration is not possible. No significant adverse effects were observed.
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Antiulcerosos/farmacocinética , Esomeprazol/farmacocinética , Administración Oral , Animales , Antiulcerosos/administración & dosificación , Antiulcerosos/sangre , Antiulcerosos/farmacología , Área Bajo la Curva , Estudios Cruzados , Perros , Esomeprazol/administración & dosificación , Esomeprazol/sangre , Esomeprazol/farmacología , Esófago/efectos de los fármacos , Femenino , Concentración de Iones de Hidrógeno/efectos de los fármacos , Inyecciones Intravenosas/veterinaria , Inyecciones Subcutáneas/veterinaria , Masculino , Valores de ReferenciaRESUMEN
OBJECTIVE: To detect the proportion of lymphocyte subsets in peripheral blood of the advanced breast cancer patients before and after chemotherapy with docetaxel and thiotepa, as well as the association between the proportion of peripheral blood lymphocyte subsets with the response rate and prognosis. METHODS: The proportions of lymphocyte subsets (CD3+ T cell, CD3+/CD4+ T cell, CD3+/CD8+ T cell, CD3-/CD16+56+ NK cell, CD3+/CD16+56+ T cell, CD19+ B cell, CD4+/CD25+ T cell, CD8+/CD28- T cell, CD8+/CD28+ T cell) in the peripheral blood of 86 patients were analyzed with flowcytometry before and after chemotherapy. The result was analyzed in combination with clinicopathological data. RESULTS: The proportion of regulatory T cells (Treg) after chemotherapy in the disease control patients decreased significantly compared with that of the progressive patients (P=0.034). The difference of the proportions of Treg before and after chemotherapy affected significantly the overall survival (OS). The OS of the patients with decreased proportion of Treg was significantly longer than that of the patients with increased proportion of Treg, which was 23.5 and 9.4 months respectively (P<0.05). CONCLUSION: The patients with decreased proportion of Treg after chemotherapy had higher response rate and better survival benefit.
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Neoplasias de la Mama/sangre , Subgrupos de Linfocitos T/citología , Linfocitos T Reguladores/citología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Docetaxel , Femenino , Citometría de Flujo , Humanos , Recuento de Linfocitos , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/inmunología , Pronóstico , Tasa de Supervivencia , Taxoides/uso terapéuticoRESUMEN
According to traditional Chinese medicine, the symptoms of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CNP/CPPS) may be treated using a cocktail of herbs that stimulate blood circulation ('activating blood circulation formula'). We investigated the effect of three doses of this formula on a rat model of CNP/CPPS. Male Wistar rats were injected with a saline extract of male sex accessory glands on days 0 and 30 to induce prostatitis and then treated daily by gavage between days 32 and 60. Treatment with low, medium and high doses of activating blood circulation formula resulted in an almost total rescue of paw withdrawal threshold at day 60, and treatment with the highest dose also significantly decreased prostate inflammation (assessed histopathologically). We further observed elevated serum prostaglandin E2 levels in the CNP/CPPS model which decreased upon high-dose treatment, and increased Cox-2 expression in the prostate and spinal cord dorsal horn which was rescued in both tissues in the high-dose group and in the prostate in the medium-dose group. These results shed light on a possible mechanism by which activating blood circulation therapy may alleviate pain in a rat model of CNP/CPPS by downregulating Cox-2 expression in the spinal cord, thereby raising the pain threshold. Further research will be needed to fully characterise the mechanism by which activating blood circulation therapy produces this therapeutic effect.
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Medicamentos Herbarios Chinos/uso terapéutico , Inflamación/tratamiento farmacológico , Medicina Tradicional China , Dolor/tratamiento farmacológico , Prostatitis/tratamiento farmacológico , Animales , Ciclooxigenasa 2/metabolismo , Dinoprostona/sangre , Modelos Animales de Enfermedad , Inflamación/sangre , Masculino , Dolor/sangre , Dimensión del Dolor , Fitoterapia , Prostatitis/sangre , Ratas , Ratas Wistar , Médula Espinal/metabolismo , Resultado del TratamientoRESUMEN
The Shanyi inbred A and E strains of the Chinese hamster are widely used in biomedical research, but detailed genetic characterization has been lacking. We developed microsatellite markers that could be used for genetic diversity analysis and linkage map construction. We isolated and characterized 16 novel microsatellite loci from a microsatellite-enriched genomic DNA library. These loci were genotyped in 48 animals from the two strains, and the polymorphic information content was determined. In the Shanyi A and E populations, 14 and 15 loci were found to be polymorphic, respectively, with polymorphic information content ranging from 0.1393 to 0.8082 and from 0.1109 to 0.7397, respectively. A total of 115 alleles were found for the 16 microsatellite loci in the two populations; the mean observed heterozygosity (H(O)) was 0.5191 and 0.4333 for the A and E populations, respectively, indicating marked genetic variation within the two populations. Correspondingly, the F(ST) values ranged from 0.002 to 0.9253, with an overall mean of 0.1935, indicating significant genetic difference between the two strains. The population differentiation levels were substantiated by Nei's genetic distance and full Bayesian analyses computed with STRUCTURE. Despite the genetic diversity and differentiation within and between the two inbred populations, the 48 individuals were correctly allocated into their original populations with high statistical confidence based on these 16 microsatellite loci. These novel microsatellite loci should be useful genetic markers for these two Chinese hamster inbred strains.
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Cricetinae/genética , Variación Genética , Repeticiones de Microsatélite , Polimorfismo Genético , Alelos , Animales , ADN/genética , Marcadores Genéticos , Genoma , Genotipo , Heterocigoto , EndogamiaRESUMEN
Melatonin is known to alleviate stress and modulate gut motility. We investigated the modulating effects of melatonin on stress-induced gut dysfunction. One hundred Wistar rats were randomly assigned to five equal groups, receiving intraperitoneal injections of 0, 1, 10, 100 or 1000 microg kg(-1) melatonin, respectively. Fifteen minutes later, each group was divided again into four subgroups receiving no treatment, 0.25 mg luzindole (a non-selective melatonin receptor antagonist) intraperitoneally, wrap-restraint stress, and 10 mg kg(-1) serotonin intraperitoneally, respectively. Two hours later, serum serotonin, corticotropin-releasing factor (CRF) and melatonin levels, and faecal output were recorded. Results showed that intraperitoneal melatonin increased faecal output, but this effect was abolished by luzindole. In wrap-restraint group, prior intraperitoneal melatonin at doses of 100 or 1000 microg kg(-1) significantly inhibited stress-induced defecation. This effect was associated with corresponding reductions in serum serotonin and CRF concentrations. In serotonin-treated group, serotonin-induced defecation was also inhibited by melatonin. In conclusion, melatonin exhibited an excitatory effect on bowel output in rats placed under resting state, while attenuated defecation in those subjected to wrap-restraint stress or serotonin treatment. The inhibitory effects of melatonin on stress-induced defecation may stem from its antagonistic effect on stress-induced enhancement of serotonin and CRF secretion.
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Defecación/efectos de los fármacos , Melatonina/farmacología , Estrés Psicológico , Animales , Hormona Liberadora de Corticotropina/sangre , Habituación Psicofisiológica , Masculino , Ratas , Ratas Wistar , Restricción Física , Serotonina/sangreRESUMEN
BACKGROUND AND AIMS: Melatonin, a sleep promoting agent, is involved in the regulation of gastrointestinal motility and sensation. We aimed to determine if melatonin was effective in improving bowel symptoms and sleep disturbances in irritable bowel syndrome (IBS) patients with sleep disturbance. METHODS: Forty IBS patients (aged 20-64 years; 24 female) with sleep disturbances were randomly assigned to receive either melatonin 3 mg (n = 20) or matching placebo (n = 20) at bedtime for two weeks. Immediately before and after the treatment, subjects completed bowel, sleep, and psychological questionnaires, and underwent rectal manometry and overnight polysomnography. RESULTS: Compared with placebo, melatonin taken for two weeks significantly decreased mean abdominal pain score (2.35 v 0.70; p<0.001) and increased mean rectal pain threshold (8.9 v -1.2 mm Hg; p<0.01). Bloating, stool type, stool frequency, and anxiety and depression scores did not significantly differ after treatment in both groups. Data from sleep questionnaires and polysomnography showed that the two week course of melatonin did not influence sleep parameters, including total sleep time, sleep latency, sleep efficiency, sleep onset latency, arousals, duration of stages 1-4, rapid eye movement (REM) sleep, and REM onset latency. CONCLUSIONS: Administration of melatonin 3 mg at bedtime for two weeks significantly attenuated abdominal pain and reduced rectal pain sensitivity without improvements in sleep disturbance or psychological distress. The findings suggest that the beneficial effects of melatonin on abdominal pain in IBS patients with sleep disturbances are independent of its action on sleep disturbances or psychological profiles.
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Dolor Abdominal/prevención & control , Síndrome del Colon Irritable/tratamiento farmacológico , Melatonina/uso terapéutico , Trastornos del Sueño-Vigilia/fisiopatología , Dolor Abdominal/etiología , Dolor Abdominal/fisiopatología , Adulto , Defecación/fisiología , Método Doble Ciego , Femenino , Humanos , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/fisiopatología , Masculino , Persona de Mediana Edad , Polisomnografía/métodos , Presión , Recto/fisiopatología , Umbral Sensorial/fisiología , Sueño/efectos de los fármacos , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/psicologíaRESUMEN
OBJECTIVE: To determine sequence of sporogony stage-specific (S type) 18S ribosomal RNA gene of Plasmodium yoelii (P. y) By265 strain, and by using it to detect the malaria parasites within vector mosquito. METHODS: A pair of conserved DNA primers, universe primer (Pu) and reverse transcription one (Pr), was designed and synthesized according to sequence of the 18S rRNA gene of Plasmodium berghei (P. b). The segment of the S type 18S rDNA of P. y was amplified by reverse transcript-polymerase chain reaction (RT-PCR) from dissected midguts of Anopheles stephensi infected with P. y on the 7th day after infective blood-meal, and its sequence was then determined. One P. y sporogony stage-specific primer (Pys) was selected according to the sequence. Using this primer and Pr, the parasites within mosquitoes were semi-quantitatively detected through RT-PCR between 1-7 d post-infection. RESULTS: The length of the amplified segment was 920 bp. Alignment in match region of the 18S rDNA among S type of P. y (PyS), S type of P. b (PbS) and asexual blood stage-specific one of P. y (PyA) revealed that the similarity between the former and the latter two reached 95.3% and 94.0% respectively. The density of amplified band was significantly concordance with the intensity of oocyst in the midgut. Sensitivity of RT-PCR method was higher than that of the traditional dissection and oocyst observation also. The assay could detect the 18S rRNA molecule of the parasites on the third day post-infection while their oocysts were difficult to be recognized under an optical microscope at that time. CONCLUSION: This S type 18S rDNA sequence in P. y species was first reported (AF266261). As a molecular marker, it could be applied to monitoring the parasite development in its vector at an earlier stage semi-quantitatively with an adequate sensitivity and specificity.
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ADN Protozoario/química , ADN Ribosómico/química , Plasmodium yoelii/genética , Animales , Anopheles/parasitología , Secuencia de Bases , Insectos Vectores/parasitología , Datos de Secuencia Molecular , Plasmodium yoelii/aislamiento & purificación , ARN Ribosómico 18S/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To isolate and identify genes related to malaria parasite infection in vector mosquito, and to explore the mechanisms. METHODS: Anopheles stephensi infected with Plasmodium yoelii was used as tester (T) group, while uninfected but normal blood fed as driver (D) one. Engorged female mosquitoes of two groups were collected separately at 24 hours after biting. An enriched subtractive cDNA pool was generated through the course of suppression subtractive hybridization (SSH) and selective PCR amplification. The subtracted library was screened by hybridization using T and D cDNA mixture as probes, respectively. The positive clones, which produced stronger signal when probed with T than with D, were sequenced and their sequence homologues in GenBank database were searched with BLAST by internet. RESULTS: The analysis of subtraction efficiency showed that the differentially expressed genes in T comparing to in D were enriched significantly. In dot blot screening, 24 of 58 randomly selected clones (41.4%) were shown up-regulation in malaria infected mosquitoes. The BLAST search of 23 genes revealed that 12 were homologous to functionally known genes, 4 were homologous to functionally unknown entries, and 7 were novel without any relatives. Nine of the 23 genes (39.1%) also hit homologous sequences in the An. gambiae EST database generated from an immune competent cell line treated with lipopolysaccharide (LPS). CONCLUSION: An enriched cDNA pool of the mosquito genes which up-regulated responsively at the early stage of malaria parasite infection was obtained. Expression screening against the pool indicated that various biochemical processes and mechanisms might be involved in the response of mosquito to parasite infection, especially those related with the innate immune system and energy metabolism.
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Anopheles/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Insectos Vectores/genética , Plasmodium yoelii , Animales , Anopheles/parasitología , Clonación Molecular , Femenino , Insectos Vectores/parasitología , Ratones , Ratones Endogámicos ICR , Reacción en Cadena de la PolimerasaRESUMEN
OBJECTIVE: To compare the pharmacokinetic differences of chloroquine in normal mice and the mice infected with the N and the RC strains of Plasmodium berghei. METHODS: The concentrations of chloroquine in the plasma of normal mice and the mice infected with the N or the RC strains of P. berghei were analyzed by reverse-phase HPLC. The pharmacokinetic parameters were measured with software 3P87. RESULTS: The t1/2 beta value was significantly lower in the mice infected with the RC strain than in normal mice and the mice infected with the N strain(P < 0.05), however, there were no significant differences between the mice infected with the N strain and normal mice. CONCLUSION: Elimination of chloroquine in the mice infected with the RC strain of P. berghei speed up significantly comparing with the mice infected with the N strain.
Asunto(s)
Antimaláricos/farmacocinética , Cloroquina/farmacocinética , Malaria/metabolismo , Animales , Antimaláricos/farmacología , Cloroquina/farmacología , Cromatografía Líquida de Alta Presión , Resistencia a Medicamentos , Femenino , Malaria/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Plasmodium berghei/efectos de los fármacosRESUMEN
We investigated whether chloroquine- or mefloquine-resistant Plasmodium berghei could be selected through drug pressure applied during continuous cyclical transmission in Anopheles stephensi mosquitoes. Mosquitoes were infected by feeding them on mice previously inoculated with a drug-sensitive clone of P. berghei ANKA. Mosquitoes ingested mefloquine or chloroquine with the infectious blood-meal, or by feeding on a drug-treated (uninfected) mouse 4 or 10 days after the infectious blood-meal. Twenty-two days after being infected, mosquitoes transmitted sporozoites to uninfected mice. Blood from these animals was used to infect naive mice that were then used to reinitiate the mouse/mosquito/mouse cycle. A total of 20 passages through mosquitoes were completed while under drug pressure. Drug-resistance levels were assessed in the initial clone and after 20 passages through mosquitoes. None of 18 "sub-clones" of parasites showed significant increases in chloroquine or mefloquine resistance, suggesting that exposure of sporogonic stage Plasmodium to chloroquine or mefloquine will not result in the development of drug resistance.
Asunto(s)
Anopheles/parasitología , Antimaláricos/farmacología , Cloroquina/farmacología , Insectos Vectores/parasitología , Mefloquina/farmacología , Plasmodium berghei/efectos de los fármacos , Animales , Resistencia a Medicamentos , Malaria/parasitología , Ratones , Parasitemia/sangre , Plasmodium berghei/crecimiento & desarrolloRESUMEN
Differences in sensitivities of chloroquine-sensitive and chloroquine-resistant strains of Plasmodium berghei were observed following irradiation of the parasites. A dose of 15 kilorads from a cobalt-60 source killed the erythrocytic stages of the chloroquine-sensitive strain and no parasitemias were observed when mice were injected with these irradiated parasites. In contrast, when the chloroquine-resistant strain was irradiated with the same dose of cobalt-60 and injected into mice, an infection rate of 12.5% was observed, indicating that the latter strain was more resistant to inactivation by irradiation. Following injection of these irradiated strains of P. berghei into mice, significant decreases in mouse hepatic cytochrome P450 and benzo(a)pyrene hydroxylase activity, with no significant effect on N-demethylase activity, were observed. Serum glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) levels of mice injected with the irradiated parasites fell within the range of the serum enzyme levels in normal laboratory mice.
Asunto(s)
Antimaláricos/farmacología , Cloroquina/farmacología , Malaria/enzimología , Oxigenasas de Función Mixta/metabolismo , Plasmodium berghei/efectos de los fármacos , Plasmodium berghei/efectos de la radiación , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Resistencia a Medicamentos/efectos de la radiación , Eritrocitos/enzimología , Eritrocitos/efectos de la radiación , Femenino , Hígado/enzimología , Malaria/sangre , Malaria/parasitología , Ratones , Ratones Endogámicos ICR , Tamaño de los Órganos/fisiología , Plasmodium berghei/enzimología , Bazo/enzimologíaRESUMEN
The sporontocidal activity of three 8-aminoquinolines, a 1,4-naphthoquinone, and three dihydroacridine-diones was determined against the ANKA clone of Plasmodium berghei and both chloroquine-sensitive (NF54) and chloroquine-resistant (7G8) P. falciparum. Anopheles stephensi mosquitoes previously fed on P. berghei--infected mice or P. falciparum--infected cultures were refed on uninfected mice treated previously with a given drug. Sporontocidal activity was determined by assessing both oocyst and sporozoite development. Neither primaquine nor menoctone exhibited sporontocidal activity against P. berghei or either strain of P. falciparum at a dose of 100 mg base drug/kg mouse body weight, whereas the other five compounds each effectively interrupted the sporogonic development of all three parasite strains at this dose. These data clearly demonstrate that experimental dihydroacridine-diones and 8-aminoquinolines are capable of interrupting the sporogonic development of P. berghei and chloroquine-sensitive and chloroquine-resistant P. falciparum. These data also suggest that the P. berghei model may be used to accurately predict sporontocidal activity against P. falciparum.