RESUMO
Pancreatic cancer is a malignant tumor of the digestive system with occult onset, low early diagnosis rate, rapid progression and poor prognosis. Perineural invasion (PNI) of pancreatic cancer is considered as an important factor which leads to the poor prognosis of pancreatic cancer. Neural invasion models of pancreatic cancer can simulate the occurrence and development of neural invasion of pancreatic cancer under the complex tumor microenvironment, which is an important carrier to study the molecular mechanism, early diagnosis and treatment improvement of PNI of pancreatic cancer. The current PNI model could be broadly divided into in vivo model and in vitro model, and in vivo model could further be divided into ectopic model and in situ model. Recently, based on the in vivo and in vitro models, genetically engineered mouse models and patient-derived xenograft models have been applied. Here, the preparation methods, clinical uses and limitations of the commonly used neural invasion in vitro and in vivo models of pancreatic cancer are reviewed.
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Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/patologia , Nervos Periféricos/patologia , Animais , Progressão da Doença , Humanos , Camundongos , Pâncreas/patologia , Prognóstico , Microambiente TumoralRESUMO
INTRODUCTION: About 30% of haemophilia A (HA) patients are sporadic cases. It is important to confirm the mutation origin and carrier status in these families. AIM: To describe the spectrum and origin of the mutations in 393 Chinese sporadic HA families and identify potential mosaics among non-carrier mothers. METHODS: AccuCopy quantification combined with long-distance PCR was used for genotyping intron 22/1 inversion (Inv22/Inv1) and Inv22 mosaicism. F8 gene sequences were analysed by direct sequencing. Copy number variations of F8 gene were detected by AccuCopy method. Six short tandem repeats related to F8 gene were applied for linkage analysis. Mosaicism of point mutations/small deletions/insertions was determined by ddNTP primer extension method. RESULTS: Most of sporadic patients' mothers are carriers, in 257 cases with integral family members, 60% have the mutations tracing back to their fathers, 12% to their mothers. 28% had de novo mutations with non-carrier mothers as revealed by routine genetic studies. Mutation spectrum of sporadic families was different in groups with different origins of mutations. Point mutation (51%) was the predominant mutation type in pedigrees with de novo mutations. While, in families with mutations inherited from maternal grandfathers, Inv22 was the main type (51%). We found somatic mosaic in mothers of 30% (3/10) pedigrees with de novo Inv22 and 11.5% (3/26) pedigrees with point mutations. CONCLUSION: The spectrum of F8 genetic variants identified in sporadic families was fairly diverse. The high prevalence of chimaeras in carriers suggests that more cautions should be taken in genetic counselling of sporadic haemophilia families.
Assuntos
Hemofilia A/genética , China , Feminino , Hemofilia A/patologia , Humanos , Masculino , MutaçãoRESUMO
BACKGROUND: Tibiotalocalcaneal arthrodesis is most common and effective surgical treatment for severe hindfoot pathology, but the fusion rate is often lower than the ordinary tibiotalar arthrodesis because of the more serious joint disease associated with obvious deformity and osteoporosis. Recent literature describe tibiotalocalcaneal arthrodesis with reverse PHILOS plate with good clinical outcome result, though some patients non-union, due to eccentric force of the plate may be hidden. The purpose of this study was to evaluate clinical outcome of the lateral approach for tibiotalocalcaneal (TTC) arthrodesis with reverse PHILOS Plate and medial cannulated screw. METHODS: Between Jun, 2013 to April, 2015 12 patient with hindfoot pathology had TTC arthrodesis with a reverse PHILOS plate with medial cannulated screw through a lateral approach with resection of the distal fibula and bone graft. Perioperatively observe for wound and neurovascular status. Patients were follow-up from post-operative 1, 3, 6 and12 months, to observation of wound healing, ankle pain, subtalar Joint Fusion, internal fixation and ankle function. Ankle function were scored according to the American Orthopaedic Foot and Ankle Society(AOFAS) Ankle-Hindfoot Scale system. RESULTS: Twelve ankle fusion all patient follow-up, with mean time to surgery 18.6 months (12-36 month). No cases infection and issue necrosis; one patient complaint of lateral foot numbness we observe and follow-up was spontaneously recovery after 3 months. After 3 months of operation, no obvious pain of ankle joint and internal fixations loose were found. Almost fusion and good axial alignment of TTC joint also were found by X-ray and CT examination. After final fellow-up of each case, no case complain of pain of ankle joint, good fusion and axial alignment of TTC joint were also all found through Terminology. The mean American Orthopaedic Foot and Ankle society (AOFAS) score average was 77.5. CONCLUSION: TTC arthrodesis with reverse PHILOS Plate and medial cannulated screw have advantages of clear incision, effective bone orthopaedic and graft fully secure, stable internal fixation, high fusion rate and less complications, can effectively correct deformities, alleviate hindfoot pain and improve function, and is an effective method of treatment of after severe hindfoot disease. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov with reference number: ID: NCT02977910 . Registered 26 Nov 2016, retrospectively registered.
Assuntos
Artrodese/métodos , Placas Ósseas , Parafusos Ósseos , Articulação Talocalcânea/cirurgia , Tíbia/cirurgia , Adulto , Artrodese/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Articulação Talocalcânea/diagnóstico por imagem , Tíbia/diagnóstico por imagemRESUMO
BACKGROUND: Tumor-specific immunity of insulin-like growth factor-binding protein-2 (IGFBP-2) has been reported in several cancers. We aimed to assess the role of serum IGFBP-2 antibodies (IGFBP-2 Abs) in early cancer detection. PATIENTS AND METHODS: Glioma and colorectal carcinoma (CRC) were used as models. Serum IGFBP-2 and IGFBP-2 Abs were measured in 260 tumor patients (145 gliomas, 45 colorectal polyps, and 70 CRCs) and 141 controls. Receiver operating characteristic curves were applied. RESULTS: Serum IGFBP-2 Ab levels were significantly elevated in tumors (mean: 82 ng/ml, median: 17 ng/ml, range: 0-1387 ng/ml) compared with controls (11, 0, 0-212 ng/ml) (P < 0.0001) and higher in early than advanced cancers opposite of serum IGFBP-2 levels. IGFBP-2 Abs effectively discriminated between controls and grade II and III gliomas [area under the curve (AUC): 0.821-0.864; 95% confidence interval (CI) = 0.762-0.936; P < 0.0001], and CRC I-II (AUC: 0.668; 95% CI = 0.566-0.770; P = 0.002) as well as indicative of advanced polyps at high risk of CRC (AUC: 0.72; 95% CI = 0.630-0.811; P < 0.0001). The sensitivity and specificity for diagnosing grade II-III gliomas reached 66%-84% and 81%. Combined serum IGFBP-2 and IGFBP-2 Abs augmented the discriminative power of all stage tumors (AUC: 0.823), gliomas (AUC: 0.800), and CRCs (AUC = 0.917). CONCLUSION: Our results first demonstrate IGFBP-2 Abs for early cancer detection and in combination of serum IGFBP-2 for improved cancer diagnosis.
Assuntos
Astrocitoma/sangue , Autoanticorpos/sangue , Carcinoma/sangue , Neoplasias do Sistema Nervoso Central/sangue , Neoplasias Colorretais/sangue , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Astrocitoma/diagnóstico , Astrocitoma/metabolismo , Carcinoma/diagnóstico , Carcinoma/metabolismo , Estudos de Casos e Controles , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Detecção Precoce de Câncer , Feminino , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Estatísticas não Paramétricas , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Seizures are a common symptom of patients with primary brain tumors, particularly low-grade gliomas (LGGs). Poor seizure control after surgery has a great adverse impact on quality of life in these patients. The present study aimed to identify clinical and molecular genetic factors that influence postoperative seizure control. METHODS: A series of 183 LGGs were analyzed by denaturing high-performance liquid chromatography (DHPLC) for 1p and 19q status and by immunohistochemical staining for expression of several molecular markers (P53, Ki-67, MMP-9 and MGMT), with particular emphasis on correlations with postoperative seizure control. Univariate and multivariate logistic regression analyses were used for statistic analysis. RESULTS: Of the 183 patients, 134 (73.2%) patients presented with seizures. Most of oligodendrogliomas and oligoastrocytomas had LOH 1p and LOH 19q, which were rarely seen in combination in astrocytomas (P<0.001). Oligodendroglial tumors were more likely to locate in frontal lobe (P=0.011) and present calcification on MRI (P=0.024). Temporal location (P=0.014), and high expression of mutated P53 (P=0.011) were associated with astrocytomas. Patients achieved much better seizure control after gross-total resection (P<0.001) than after subtotal resection. Patients without LOH 19q were more likely to have poor seizure control (P=0.004) than those with this alteration. Ki-67 was an independent molecular marker predicting poor seizure control (P=0.016) if over expressed. CONCLUSIONS: Gross total resection of the tumor, LOH 19q and low Ki-67 expression were associated with favorable seizure control after surgery for the patients with LGGs. The possible involvement of other factors should be investigated further.
Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Convulsões/genética , Adolescente , Adulto , Idoso , Povo Asiático/genética , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 19 , Feminino , Glioma/complicações , Glioma/patologia , Glioma/cirurgia , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/patologia , Convulsões/cirurgiaRESUMO
The study analysed healthcare workers' (HCWs) knowledge, practices, and attitudes regarding coronavirus disease 2019 (COVID-19). A cross-sectional survey was conducted from February 4th to February 8th, 2020, involving a total of 1357 HCWs across 10 hospitals in Henan, China. Of those surveyed, 89% of HCWs had sufficient knowledge of COVID-19, more than 85% feared self-infection with the virus, and 89.7% followed correct practices regarding COVID-19. In addition to knowledge level, some risk factors including work experience and job category influenced HCWs' attitudes and practice concerning COVID-19. Measures must be taken to protect HCWs from risks linked to job category, work experience, working hours, educational attainment, and frontline HCWs.
Assuntos
Atitude do Pessoal de Saúde , Betacoronavirus , Infecções por Coronavirus/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Pneumonia Viral/psicologia , Competência Profissional/estatística & dados numéricos , COVID-19 , China , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Hospitais , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The pathogenesis of NSCLC has not yet been fully understood, and the therapeutic efficacy of current anti-NSCLC medication remains unsatisfactory. Previous studies indicated that miR-296-3p was down-regulated in NSCLC, suggesting that miR-296-3p may participate in the pathogenesis of NSCLC; however, the specific mechanisms still need to be further explored. The aim of this work is to investigate the roles of miR-296-3p in NSCLC and the related mechanism. PATIENTS AND METHODS: Thirty NSCLC tissue and paired adjacent tissue were collected, and Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to examine the expression of miR-296-3p in cancer tissue and the adjacent tissue. Next, A549 cells were cultured and transfected with miR-296-3p mimics, and cell migration and invasion were determined using scratch wound-healing and transwell assays. Moreover, Western blot assay was performed to determine the effect of miR-296-3p on the expression of Rab-like 3 (RABL3), Matrix metallopeptidase (MMP)-2, Janus kinase (JAK) and Signal transducer and activator of transcription 3 (STAT3); next, Dual-Luciferase reporter assay has been conducted to prove the direct targeting relationship between miR-296-3p and RABL3. Finally, the cells of different treatments were subcutaneously implanted into nude mice to investigate the effect of miR-296-3p mimics in the xenograft mice tumor models. RESULTS: Our data indicated that miR-296-3p was significantly down-regulated and RABL3 was markedly up-regulated in NSCLC tissue compared with the adjacent tissue. Moreover, transient over-expression of miR-296-3p in A549 cells induced a significant decrease in the proliferation and invasion ability of A549 cells, as well as decreased expression of RABL3, MMP-2, JAK and STAT3. Furthermore, the Dual-Luciferase reporter assay confirmed that RABL3 is a direct target of miR-296-3p. Finally, the results of animal studies indicated that miR-296-3p can regulate the tumorigenesis of A549 cells in vivo. CONCLUSIONS: Our findings proved that miR-296-3p may play a role as a tumor suppressor in NSCLC both in vitro and in vivo, and we first reported that miR-296-3p can regulate the migration and invasion of A549 cells via targeting RABL3. Our data suggested that miR-296-3p may serve as a potential therapeutic target for treating NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Movimento Celular , Proliferação de Células , Células Cultivadas , Regulação para Baixo/genética , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/cirurgia , Proteínas rab de Ligação ao GTP/genéticaRESUMO
An Advanced spent fuel Conditioning Process Facility (ACPF) has recently been constructed by a modification of previously unused cells. ACPF is a hot cell with two rooms located in the basement of the Irradiated Materials Experiment Facility (IMEF) at the Korea Atomic Energy Research Institute. This is for demonstrating the advanced spent fuel conditioning process being proposed in Korea, which is an electrolytic reduction process of spent oxide fuels into a metallic form. The ACPF was designed with a more than 90 cm thick high density concrete shield wall to handle 1.38 PBq (37,430 Ci) of radioactive materials with dose rates lower than 10 muSv h in the operational areas (7,000 zone) and 150 muSv h in the service areas (8,000 zone). In Monte Carlo calculations with a design basis source inventory, the results for the bounding wall showed a maximum of 3 muSv h dose rate at an exterior surface of the ACPF for gamma radiation and 0.76 muSv h for neutrons. All the bounding structures of the ACPF were investigated to check on the shielding performance of the facility to ensure the radiation safety of the facility. A test was performed with a 2.96 TBq (80 Ci) 60Co source unit and the test results were compared with the calculation results. A few failure points were discovered and carefully fixed to meet the design criteria. After fixing the problems, the failure points were rechecked and the safety of the shielding structures was confirmed. In conclusion, it was confirmed that all the investigated parts of the ACPF passed the shielding safety limits by using this program and the ACPF is ready to fulfill its tasks for the advanced spent fuel conditioning process.
Assuntos
Arquitetura de Instituições de Saúde , Raios gama , Física Médica/métodos , Proteção Radiológica/métodos , Resíduos Radioativos , Humanos , Coreia (Geográfico) , Método de Monte CarloRESUMO
The major reabsorptive mechanism for D-glucose in the kidney is known to involve a low affinity high capacity Na+/glucose cotransporter, which is located in the early proximal convoluted tubule segment S1, and which has a Na+ to glucose coupling ratio of 1:1. Here we provide the first molecular evidence for this renal D-glucose reabsorptive mechanism. We report the characterization of a previously cloned human kidney cDNA that codes for a protein with 59% identity to the high affinity Na+/glucose cotransporter (SGLT1). Using expression studies with Xenopus laevis oocytes we demonstrate that this protein (termed SGLT2) mediates saturable Na(+)-dependent and phlorizin-sensitive transport of D-glucose and alpha-methyl-D-glucopyranoside (alpha MeGlc) with Km values of 1.6 mM for alpha MeGlc and approximately 250 to 300 mM for Na+, consistent with low affinity Na+/glucose cotransport. In contrast to SGLT1, SGLT2 does not transport D-galactose. By comparing the initial rate of [14C]-alpha MeGlc uptake with the Na(+)-influx calculated from alpha MeGlc-evoked inward currents, we show that the Na+ to glucose coupling ratio of SGLT2 is 1:1. Using combined in situ hybridization and immunocytochemistry with tubule segment specific marker antibodies, we demonstrate an extremely high level of SGLT2 message in proximal tubule S1 segments. This level of expression was also evident on Northern blots and likely confers the high capacity of this glucose transport system. We conclude that SGLT2 has properties characteristic of the renal low affinity high capacity Na+/glucose cotransporter as previously reported for perfused tubule preparations and brush border membrane vesicles. Knowledge of the structural and functional properties of this major renal Na+/glucose reabsorptive mechanism will advance our understanding of the pathophysiology of renal diseases such as familial renal glycosuria and diabetic renal disorders.
Assuntos
Glucose/metabolismo , Túbulos Renais/metabolismo , Rim/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Animais , Transporte Biológico , Linhagem Celular , Chlorocebus aethiops , Feminino , Transportador de Glucose Tipo 2 , Humanos , Hibridização In Situ , Cinética , Metilglucosídeos/metabolismo , Proteínas de Transporte de Monossacarídeos/biossíntese , Oócitos/metabolismo , Oócitos/fisiologia , RNA Complementar/metabolismo , Transfecção , Xenopus laevisRESUMO
In mammals, urea is the predominant end-product of nitrogen metabolism and plays a central role in the urinary-concentrating mechanism. Urea accumulation in the renal medulla is critical to the ability of the kidney to concentrate urine to an osmolality greater than systemic plasma. Regulation of urea excretion and accumulation in the renal medulla depends on the functional state of specialized phloretin-sensitive urea transporters. To study these transporters and their regulation of expression we isolated a cDNA which encodes the rat homologue (rUT2) of rabbit UT2 (You, G., C.P. Smith, Y. Kanai, W.-S. Lee, M. Stelzner, and M.A. Hediger, et al. Nature (Lond.). 1993. 365:844-847). Rat UT2 has 88% amino acid sequence identity to rabbit UT2 and 64% identity to the recently cloned human erythrocyte urea transporter, HUT11 (Olives, B., P. Neav, P. Bailly, M.A. Hediger, G. Rousselet, J.P. Cartron, and P. Ripoch J. Biol. Chem. 1994. 269:31649-31652). Analysis of rat kidney mRNA revealed two transcripts of size 2.9 and 4.0 kb which had spatially distinct distributions. Northern analysis and in situ hybridization showed that the 4.0-kb transcript was primarily responsive to changes in the protein content of the diet whereas the 2.9-kb transcript was responsive to changes in the hydration state of the animal. These studies reveal that the expression levels of the two rUT2 transcripts are modulated by different pathways to allow fluid and nitrogen balance to be regulated independently. Our data provide important insights into the regulation of the renal urea transporter UT2 and provide a basis on which to refine our understanding of the urinary concentrating mechanism and its regulation.
Assuntos
Proteínas de Transporte/biossíntese , Proteínas Alimentares , Regulação da Expressão Gênica , Rim/fisiologia , Glicoproteínas de Membrana/biossíntese , Proteínas de Membrana Transportadoras , Sequência de Aminoácidos , Animais , Proteínas de Transporte/química , Proteínas de Transporte/fisiologia , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Clonagem Molecular , DNA Complementar/metabolismo , Diurese , Feminino , Hibridização In Situ , Rim/citologia , Medula Renal/metabolismo , Masculino , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/fisiologia , Modelos Biológicos , Modelos Estruturais , Dados de Sequência Molecular , Oócitos/fisiologia , Estrutura Secundária de Proteína , Coelhos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Transcrição Gênica , Ureia/metabolismo , Xenopus laevis , Transportadores de UreiaRESUMO
Bovine calmodulin analogues, spin-labeled at either methionine or tyrosine residues, have been utilized in electron paramagnetic resonance (EPR) studies to investigate possible calmodulin interactions with aluminum ion. The study attempts to clarify a previous report in the literature (H. Siegel, R. Coughlin, and A. Haug, Biochem. Biophys. Res. Commun. 115, 512 (1983)) which indicated, on the basis of EPR experiments on methionine spin-labeled protein, significant interaction between calmodulin and aluminum ion at pH = 6.5. In EPR metal ion titration experiments we have found that the signal line-shape (from both methionine and tyrosine spin labels) changed dramatically with the addition of calcium ion, but was virtually unchanged with the addition of aluminum ion at pH = 6.5. Experiments performed at pH = 5.5, where significantly more "free" aluminum ion (i.e., Al(H2O)6(3+) = Al3+) is present, also failed to produce the line-narrowing effect observed in the earlier study. Based on our EPR experiments, in the pH range 5.5 to 6.5, we find no evidence for significant interaction between calmodulin and aluminum ion.
Assuntos
Alumínio/metabolismo , Cálcio/metabolismo , Calmodulina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Química Encefálica , Bovinos , Espectroscopia de Ressonância de Spin Eletrônica , Metionina/química , Ligação Proteica , Marcadores de Spin , Tirosina/químicaRESUMO
Bovine calmodulin, spin-labeled at tyrosine-99, has been utilized in electron paramagnetic resonance (EPR) studies to investigate calmodulin interactions with Ca(II), Cd(II), and Mg(II). The addition of either Ca(II) or Cd(II) to apo-calmodulin results in a complex capable of activating target enzymes, such as 3', 5'-cyclic nucleotide phosphodiesterase (J. M. Buccigross, C. L. O'Donnell, and D. J. Nelson, Biochem. J. 235 677 [1986]), while Mg(II) is known to be incapable of activating calmodulin toward any of its target enzymes. Additions of Ca(II) and Cd(II) to spin-labeled apo-calmodulin gave rise to very similar changes in the EPR spectrum of the bound label, consistent with a dramatic decrease in the mobility of the nitroxide spin-label covalently attached to tyrosine-99. Addition of Mg(II) to spin-labeled apo-calmodulin caused no change in the EPR spectrum of the bound label. Thus, the conformational changes induced by Ca(II) and Cd(II) ion binding to calmodulin, which lead to decreased tyrosine-99 spin label mobility, are clearly not occurring when Mg(II) ion binds. These results are consistent with the results of other spectroscopic studies, which indicate that "activating" metal ions, such as Ca(II) and Cd(II), produce calmodulin conformers that are different from those produced by "inactivating" metal ions, such as Mg(II).
Assuntos
Cádmio , Cálcio , Calmodulina , Magnésio , Tirosina , Animais , Bovinos , Espectroscopia de Ressonância de Spin Eletrônica , Conformação ProteicaRESUMO
AIM: To further evaluate the antifertility effects of tripchlorolide, a derivative of triptolide produced at the extraction procedure of Tripterygium wilfordii Hook. f., in male rats and to investigate its sites and possible mechanisms of action. METHODS: In male rats, tripchlorolide was given by oral garage at a dose of 50 micrograms.kg-1.d-1 for 5 weeks, fertility was assessed by mating tests, and biochemical indices and light microscopic observation of the epididymides and testes were also performed. RESULTS: Administration of tripchlorolide at 50 micrograms.kg-1.d-1 for 3 weeks did not influence the fertility of male rats, but 5-week treatment rendered the rats infertile. The density and motility of spermatozoa collected from cauda epididymides were reduced significantly. The epididymal weights, as well as the L-carnitine concentration and alpha-glucosidase content in the epididymal fluid were decreased. There were no significant differences in alpha-glucosidase and acid phosphatase (ACP) in caput epididymal homogenates between the control and the experimental rats. Obvious morphological changes were observed in the epididymal spermatozoa, mainly including head and tail separation or acrosome curving. Sloughed spermatids were found in the seminifeous and epididymal tubules. In testicular homogenates, tripchlorolide had no influence on the lactate dehydrogenase-C4 (LDH-C4) and hyaluronidase activities. No apparent lesions were observed in the seminiferous and epididymal epithelium. CONCLUSION: At the dose level employed, tripchlorolide has a significant effect on the fertility in male rats and the primary sites of action may be spermatids and testicular and epididymal spermatozoa.
Assuntos
Diterpenos/farmacologia , Epididimo/efeitos dos fármacos , Fenantrenos , Testículo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Anticoncepcionais Masculinos/farmacologia , Fertilidade/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Motilidade dos Espermatozoides/efeitos dos fármacos , Testículo/anatomia & histologiaRESUMO
AIM: To ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose reduction. METHODS: Seventy-seven male volunteers were divided into 3 groups: control (22 cases), 10 mg gossypol (29 cases) and 12.5 mg (26 cases). Serum levels of testosterone, FSH and LH were measured by RIA and potassium by flame photometry. Sperm counts and motility were examined before and regularly after treatment for the evaluation of contraceptive efficacy. RESULTS: The average sperm density and motility started to decrease significantly by the end of month 2 of medication and gradually reached the infertility levels (< 4 million/mL) in both treated groups. After that the 10 mg group was asked to take the same dose every other day for up to a total observation period of 16-18 months for the maintenance of infertility. Subjects in the 12.5 mg group did not take gossypol any more so as to observe the length of the loading dose required, but in a few, a maintenance dose of 12.5 mg every other day was instituted for a few more months. In both treated groups, none of the spouses was pregnant during the maintenance dose period. Serum levels of potassium, FSH, LH and testosterone were not significantly changed and not a single volunteer complained of myoasthenia. After cessation of drug administration, the semen data returned to pretreatment levels. CONCLUSION: A regimen with 10 or 12.5 mg of gossypol as the daily loading dose and 35 or 43.75 mg as the weekly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility.
Assuntos
Anticoncepcionais Masculinos/administração & dosagem , Genitália Masculina/efeitos dos fármacos , Gossipol/administração & dosagem , Infertilidade Masculina/induzido quimicamente , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fertilização/efeitos dos fármacos , Hormônio Foliculoestimulante/sangue , Genitália Masculina/citologia , Genitália Masculina/metabolismo , Humanos , Hipopotassemia/induzido quimicamente , Hipopotassemia/fisiopatologia , Infertilidade Masculina/metabolismo , Hormônio Luteinizante/sangue , Masculino , Potássio/sangue , Gravidez , Taxa de Gravidez , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/fisiologia , Testosterona/sangueRESUMO
A long-term follow-up study of 21 patients with 24 attacks of acute non-Q-wave myocardial infarction admitted to Beijing Hospital was carried out and clinicopathological correlation was made in 9 by autopsy. The results revealed that in patients with non-Q-wave myocardial infarction the mortality rate in acute stage was 14.3%, the 2-year aggregate mortality rate 33.3% and the rate of reinfarction 38%, while in patients with Q-wave myocardial infarction admitted in the same period the rate was 18.9%, 26.2% and 17.3%, respectively. It was thus shown that non-Q-wave myocardial infarction was an unstable condition. Although its prognosis in the acute stage was slightly better than that of Q-wave myocardial infarction, yet its outcome in the long run was poorer. Clinicopathological correlation showed that the diagnostic criteria for acute non-Q-wave myocardial infarction used at present are practical and a negative serum enzyme does not preclude the possibility of this disease.
Assuntos
Eletrocardiografia , Infarto do Miocárdio/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , PrognósticoRESUMO
In order to understand the magnitude and trends of both under- and over-nutrition problems in Asian countries, we reviewed data available in a number of selected countries. In general, the prevalence of under-nutrition is declining in this region but is still heavy in many countries. The trends varied with complexity of individual countries. In China, the prevalence of underweight, stunting and wasting was 21.6%, 30.5% and 2.6% in children of 0-4 years old (90,662 subjects, 1987) . Another large-scale survey in 1992 (176,976 subjects) presented a prevalence of 17.1% , 33.5% and 4.5%, respectively. Recent studies showed a remarkable improvement in both underweight and stunting. The National Student Survey in 1995, however, showed that the prevalence of under-nutrition was 26.9% for schoolboys and 38.3% for schoolgirls (7-18 yr). There was an increase of 4.7% and 3 .5%, respectively, compared with the results of a similar survey conducted in 1985. The proportion of malnutrition in Chinese adults (BMI < 18.5) was 11.6% in 1982 and 9.0% in 1992 for urban areas, and 12.9% and 8.0% for rural areas, indicating a descending trend over the 10 years. The prevalence of underweight was the highest, over 50% among children below 6 years old, in both Bangladesh and India, between 50% and 20% in Malaysia, the Philippines, Thailand and Vietnam, and below 20% in Mongolia, Kazakhstan and Fiji. It showed a declining trend from the 1970s to the 1990s with an average annual reduction of 0.8 to 1.9 percentage points in these countries. The problem of over-nutrition is emerging quickly in this region, not only in some better-off countries but also in countries in economy transition. In China, the prevalence of overweight and obesity in young adults (BMI > 25) was increased from 9.7% to 14.9% for urban areas and from 6.15% to 8.4% for rural areas in a 10-year period (1982 - 1992), and the prevalence of overweight jumped from 3.38% and 2.75% in 1985 to 7.18% and 8.65% in 1995 for schoolboys and schoolgirls. In India, the increase of overweight and obesity in female adults was 5.0 percentage points from 1989 to 1994. The prevalence of overweight was 24.5% for male and 21.4% for female in Japan (1995), and 28.7% and 26.0% in Malaysia (1990). These results indicate that over-nutrition is a growing problem in this region. Many Asian countries are facing double challenges. They have to deal with both under-nutrition and over-nutrition problems. Among many possible interventions, the further strengthening mass education on healthy diet practice should be emphasized.
Assuntos
Distúrbios Nutricionais/epidemiologia , Fenômenos Fisiológicos da Nutrição , Saúde Pública , Adolescente , Adulto , Idoso , Ásia/epidemiologia , Peso Corporal , Criança , Proteção da Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Política Nutricional , Obesidade/epidemiologia , Prevalência , Magreza/epidemiologiaRESUMO
The effect of the somatostatin analogue, octreotide, on gastric fluid pH was investigated in 4 ponies. Gastric fluid pH was determined after SC administration of octreotide or physiologic saline solution (control). A baseline sample of fluid was obtained, the agent was given, and 8 additional samples were collected hourly. Administration of octreotide at all dosages tested (0.1, 0.5, 1.0, and 5.0 micrograms/kg of body weight) increased gastric pH to > 5.0. Baseline values were consistently < 2.7. Administration of octreotide at these same dosages induced gastric pH values > 4.0 for 2.4 +/- 1.2, 4.8 +/- 0.8, 5.7 +/- 1.3, and 5.4 +/- 2.6 (mean +/- SD) continuous hours, respectively. Treatment at all dosages increased the pH of gastric fluid, compared with control values. The duration of the increase in pH was significantly (P < 0.05) different than that of the control treatment, even for the lowest dosage, 0.1 microgram/kg.
Assuntos
Suco Gástrico/efeitos dos fármacos , Cavalos/metabolismo , Octreotida/farmacologia , Animais , Feminino , Determinação da Acidez Gástrica/veterináriaRESUMO
We studied ultrastructural alterations caused by intravenous infusion of 150 ml/kg of irrigating fluid containing mannitol and/or sorbitol in 15 rabbits. The osmolality of the solutions varied between 165 and 350 mosmol/kg. Specimens for electron microscopic examination were obtained from the kidney, brain and lung. Regardless of the choice of solute, the hypo-osmotic solutions caused damage to kidney and brain tissue by inducing marked interstitial and cellular oedema. No such changes were observed after administration of isosmotic irrigating fluid. We conclude that ultrastructural changes following overhydration with irrigating fluid vary with the osmolality of the solution but not with the choice of solute. Moreover, the consistent absence of tissue damage in the lungs suggests that the lung is not a primary target organ for the "TUR syndrome".
Assuntos
Encéfalo/ultraestrutura , Rim/ultraestrutura , Pulmão/ultraestrutura , Irrigação Terapêutica/efeitos adversos , Animais , Encéfalo/efeitos dos fármacos , Diuréticos Osmóticos/administração & dosagem , Diuréticos Osmóticos/efeitos adversos , Edema/induzido quimicamente , Edema/patologia , Soluções Hipotônicas/administração & dosagem , Soluções Hipotônicas/efeitos adversos , Infusões Intravenosas , Rim/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Manitol/administração & dosagem , Manitol/efeitos adversos , Microscopia Eletrônica , Coelhos , Sorbitol/administração & dosagem , Sorbitol/efeitos adversosRESUMO
OBJECTIVE: Recent studies have demonstrated that acetylcholine receptor antibodies (AChRab) present in the serum of the patients with myasthenia gravis (MG) not only block acetylcholine transmission at the neuromuscular junction, but also cause dysfunction of central nervous system (CNS). The mechanism remains unclear. In the present study the concentration of interleukin-1 in the brain, thymus and blood was investigated to reveal the mechanism of CNS dysfunction in MG. METHODS: The concentration of interleukin-1 in brain, thymus and blood was detected after establishing the experimental MG model of central nervous system dysfunction induced by injection of AChRab purified from MG sera into the rat cerebral ventricular system. RESULTS: Interleukin-1 level in brain, thymus and blood started to increase one week after injection of AChRab. The level of interleukin-1 in brain tissue showed a very significant increase, as compared to that in thymus and blood till the end of 2 weeks after injection, where as in thymus and blood the increasing rate was relatively slow. CONCLUSION: It is concluded that interleukin-1 increased in rat brain, thymus and blood may play an important role in generating dysfunction of CNS in MG.
Assuntos
Sistema Nervoso Central/fisiopatologia , Interleucina-1/metabolismo , Miastenia Gravis/metabolismo , Animais , Encéfalo/metabolismo , Humanos , Imunoglobulina G/administração & dosagem , Masculino , Miastenia Gravis/fisiopatologia , Ratos , Ratos Sprague-Dawley , Timo/metabolismoRESUMO
OBJECTIVE: To study the pathology, incidence and etiology of Binswanger's disease. METHODS: Autopsied brains from 9 cases of Binswanger's disease and 13 cases of non-demented elderly individuals were studied by clinico-pathological, immunohistochemical and micrometer methods. RESULTS: The lesions of Binswanger's disease were mainly located in the subcortical white matter, periventrical regions, brainstem and cerebellum. The pathological changes were demyelination, lacunar infarction, gliosis and dilatation of perivascular space (Virchow-Robin space, VR space, P < 0.01). The wall thickness of deeply penetrating arteries in the white matter was significantly increased (P < 0.01). CONCLUSION: Binswanger's disease is not a rare entity. The findings of this study suggest that arteriosclerosis is a primary factor in the pathogenesis of Binswanger's disease.