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1.
Scand J Clin Lab Invest ; 76(4): 309-12, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26985979

RESUMO

Background Gestational diabetes is one of the commonest metabolic problems associated with pregnancy and an accurate diagnosis is critical for the care. Research has shown that pregnant women have high levels of cortisol during the last stage of parturition. As cortisol is a diabetogenic hormone causing increased glucose levels, we wanted to study the association between cortisol and glucose levels during parturition. Materials and methods Glucose and cortisol were analyzed during parturition in 50 females divided according to slow (n = 11) and normal labors (n = 39). Blood samples were analyzed three times during the parturition and four times in the first day after delivery. Glucose levels were also measured once in each trimester. Results In the normal group, the glucose concentration increased from 6.2 (IQR 5.6-8.0) mmol/L in the latency phase to 11.6 (10.0-13.3) mmol/L at aftercare (p < 0.05). After parturition the glucose concentrations decreased gradually. There were significant Spearman rank correlations between glucose and cortisol values. Conclusions The changes associated with birth cause significant elevations of cortisol and glucose around parturition.


Assuntos
Diabetes Gestacional/sangue , Diabetes Gestacional/urina , Parto/sangue , Parto/urina , Adulto , Bioestatística , Glicemia/análise , Feminino , Glucose/análise , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Insulina/análise , Insulina/sangue , Insulina/urina , Período Pós-Parto/sangue , Período Pós-Parto/urina , Gravidez
2.
Acta Obstet Gynecol Scand ; 88(6): 639-46, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19412798

RESUMO

OBJECTIVE: To investigate associations between plasma oxytocin and vasopressin concentrations and renal water and sodium excretion during normal pregnancy in comparison with gestational hypertension. DESIGN: A prospective open trial conducted in the 12th, 24th, and 36th weeks of gestation. SETTINGS: Seven antenatal clinics in Sweden. PARTICIPANTS: Thirty-seven normotensive women, 15 women with gestational hypertension, and five women with mild preeclampsia. MAIN OUTCOME MEASURES: Hormones were analyzed with radioimmunoassay. Albumin, osmolality, sodium, and urea were analyzed by routine methods. RESULTS: Blood pressure was elevated in the hypertensive women and body mass index in mild preeclampsia from week 12. Renal sodium excretion did not differ between groups or weeks and mean renal free water clearance was negative. In normotensive women, the vasopressin concentration was 1.1+/-0.2 (week 12) and 0.7+/-0.1 pmol/L (week 36: p = 0.053). In hypertensive women, vasopressin concentration was 1.7+/-1.0 pmol/L, week 12, and 0.7+/-0.1 pmol/L in week 36 (ns). In normotensive women, oxytocin concentration increased from 23+/-1 pmol/L in week 12 to 48+/-3 pmol/L in week 36 (p<0.001). Corresponding values in hypertensive women were 36+/-11 (week 12) and 55+/-5 pmol/L (week 36: ns). In all groups, plasma estradiol concentration increased. Plasma progesterone increased until week 24 in normotensive and hypertensive women with further increase in normotensive women. CONCLUSIONS: The low plasma vasopressin and increasing plasma oxytocin concentrations with unchanged water and sodium excretion indicate that oxytocin assists vasopressin in concentrating urine during pregnancy.


Assuntos
Hipertensão Induzida pela Gravidez/fisiopatologia , Gravidez/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Estradiol/sangue , Estradiol/fisiologia , Feminino , Humanos , Hipertensão Induzida pela Gravidez/sangue , Rim/fisiologia , Ocitocina/sangue , Ocitocina/fisiologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/fisiopatologia , Progesterona/sangue , Progesterona/fisiologia , Vasopressinas/sangue , Vasopressinas/fisiologia
3.
Lab Anim ; 53(2): 137-147, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30041570

RESUMO

THE FOUR EU FUNCTIONS AND BEYOND: FELASA accredits courses that fulfil the requirements of Functions A, B, C and D as defined by EU Directive, Article 23, as well as for designated veterinarians and specialists in laboratory animal science. MODULARITY AND MOBILITY: Cohesive courses for Functions and for very specific topics are accredited, but flexibility and mobility are possible: a researcher can start his/her training with one FELASA accredited course and complete other modules with another. A course organizer will deliver a FELASA certificate relating to the successfully completed modules. ACCREDITATION PROCESS: The process consists of two major steps: (1) a review of full course documentation provided by the applicant will lead, if successful, to FELASA accreditation. The course is posted on the FELASA website as 'FELASA accredited' and the course provider can deliver FELASA certificates upon successful completion of the course; (2) successful accreditation is followed by an on-site course audit. In the case of a negative outcome of the audit, FELASA accreditation is withdrawn, the course is deleted from the list of FELASA accredited courses and FELASA certificates cannot be issued. To ensure that quality is maintained, continuation of accreditation requires regular revalidation.


Assuntos
Acreditação/estatística & dados numéricos , Ciência dos Animais de Laboratório/normas , Bem-Estar do Animal , Animais , Europa (Continente) , União Europeia , Ciência dos Animais de Laboratório/educação , Ciência dos Animais de Laboratório/legislação & jurisprudência
4.
Clin Exp Hypertens ; 30(2): 151-8, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18293170

RESUMO

A possible natriuretic mechanism of action of oxytocin was investigated in male Sprague-Dawley rats. The effects of an intravenous bolus injection of amiloride on urine volume, potassium and sodium excretion, and osmolality were measured with and without an intravenous infusion of oxytocin in saline. Control values were obtained during the infusion of saline. Amiloride administered during an oxytocin infusion increased sodium excretion from 0.1 +/- 0.0 to 16.6 +/- 2.1 micromol/min. In animals treated with amiloride only, the sodium excretion was 4.5 +/- 0.8 micromol/min. The administration of oxytocin only resulted in a sodium excretion of 1.2 +/- 0.3 micromol/min. After the administration of oxytocin, amiloride increased urinary flow from 4.3 +/- 0.6 microl/min to 48.8 +/- 6.1 microl/min. In animals treated with amiloride only, the flow after the bolus dose was 17.7 +/- 1.8 microl/min. The administration of oxytocin only resulted in a flow of 8.5 +/- 1.6 microl/min. The amiloride-caused change in potassium excretion was not inhibited by oxytocin. In summary, the effects of amiloride were not inhibited by the actions of oxytocin. Amiloride administrated after reaching a near steady-state effect of oxytocin was found to give rise to an effect far greater than that after the administration of oxytocin or amiloride alone. It is concluded that the intrarenal natriuretic mechanisms of oxytocin do not emanate from the amiloride-sensitive sodium channels.


Assuntos
Amilorida/farmacologia , Rim/efeitos dos fármacos , Natriuréticos/farmacologia , Ocitocina/farmacologia , Amilorida/administração & dosagem , Animais , Diurese/efeitos dos fármacos , Sinergismo Farmacológico , Injeções Intravenosas , Masculino , Natriurese/efeitos dos fármacos , Natriuréticos/administração & dosagem , Concentração Osmolar , Ocitocina/administração & dosagem , Potássio/urina , Ratos , Ratos Sprague-Dawley
5.
Am J Hypertens ; 20(7): 743-50, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17586408

RESUMO

BACKGROUND: The catalytic activity of semicarbazide-sensitive amine oxidase (SSAO) is increased in diabetes, as well as in other disorders of cardiovascular origin. Our hypothesis is that SSAO is involved in the synthesis or maturation of elastin in vascular tissue. An increased SSAO activity can thereby be involved in the development of vascular damage. METHODS: Elastin quantification was performed in aorta of transgenic mice overexpressing the human form of SSAO, using electron microscopy. Furthermore, lung capacity was measured using a spirometry-mimicking method, developed for mice. The effect of vasoactive substances was estimated by measuring mean arterial pressure and pulse pressure under anesthesia. RESULTS: No differences in elastin quantity or lung capacity could be observed between transgenic or nontransgenic littermates. Pulse pressure was higher in transgenic mice, and electron microscopy of aorta showed elastin fibers parallel with the aorta wall (ie, straight fibers instead of folded compared with control mice). No difference in the response to adrenaline or sodium chloride was observed between the transgenic and control mice. The control mice had a clear decrease in blood pressure (BP) with a longer duration as a response to injection of a nitric oxide (NO) donor, sodium nitroprusside, compared with transgenic mice where only a minor response was observed. The SSAO activity in serum of control mice was elevated in response to injection of the NO donor, but not in response to a ganglion blocker. CONCLUSIONS: An elevated pulse pressure, together with an abnormal elastin structure in the aorta, suggests a rigidity of large arteries as a result of an elevated SSAO activity as well as a physiologic role for SSAO in elastin maturation.


Assuntos
Amina Oxidase (contendo Cobre)/metabolismo , Artérias/fisiologia , Pressão Sanguínea/fisiologia , Elastina/metabolismo , Músculo Liso Vascular/metabolismo , Animais , Artérias/ultraestrutura , Elasticidade , Feminino , Frequência Cardíaca , Pulmão/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica , Músculo Liso Vascular/fisiologia , Pulso Arterial , Respiração
6.
Cancer Res ; 62(19): 5476-84, 2002 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-12359756

RESUMO

Lowering of tumor interstitial hypertension, which acts as a barrier for tumor transvascular transport, has been proposed as a general strategy to enhance tumor uptake and therapeutic effects of anticancer drugs. The tyrosine kinase platelet-derived growth factor (PDGF) beta-receptor is one mediator of tumor hypertension. The effects of PDGF antagonists on chemotherapy response were investigated in two tumor models that display PDGF receptor expression restricted to the tumor stroma, and in which PDGF antagonists relieve tumor hypertension. Inhibitory PDGF aptamers and the PDGF receptor tyrosine kinase inhibitor STI571 enhanced the antitumor effect of Taxol on s.c. KAT-4 tumors in SCID mice. Treatment with only PDGF antagonists had no effect on tumor growth. Taxol uptake in tumors was increased by treatment with PDGF antagonists. Cotreatment with PDGF antagonists and Taxol was not associated with antiangiogenic effects, and PDGF antagonists did not enhance the Taxol effect on in vitro growth of KAT-4 cells. STI571 also increased the antitumor effects of 5-fluorouracil on s.c. PROb tumors in syngeneic BDIX rats, without increasing the effect of 5-fluorouracil on cultured PROb cells. Expression of PDGF receptors in tumor stroma, as well as tumor hypertension, occurs in most common solid tumors. Therefore, our results have implications for treatment regimens for large patient groups and merit clinical testing. In conclusion, our study identifies inhibition of PDGF signaling in tumor stroma as a novel, possibly general strategy for enhancement of the therapeutic effects chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Piperazinas/farmacologia , Pirimidinas/farmacologia , Receptores do Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Benzamidas , Sinergismo Farmacológico , Fluoruracila/administração & dosagem , Fluoruracila/farmacocinética , Fluoruracila/farmacologia , Mesilato de Imatinib , Camundongos , Camundongos SCID , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Ratos , Receptores do Fator de Crescimento Derivado de Plaquetas/biossíntese , Receptores do Fator de Crescimento Derivado de Plaquetas/fisiologia , Transdução de Sinais/fisiologia , Células Estromais/patologia , Suínos , Neoplasias da Glândula Tireoide/irrigação sanguínea , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
7.
FASEB J ; 17(12): 1756-8, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12958200

RESUMO

Chemotherapy of solid tumors is presently largely ineffective at dosage levels that are compatible with survival of the patient. Here, it is argued that a condition of raised interstitial fluid pressure (IFP) that can be observed in many tumors is a major factor in preventing optimal access of systemically administered chemotherapeutic agents. Using prostaglandin E1-methyl ester (PGE1), which is known transiently to reduce IFP, it was shown that 5-fluorouracil (5-FU) caused significant growth inhibition on two experimental tumors in rats but only after administration of PGE1. Furthermore, timing experiments showed that only in the period in which IFP is reduced did 5-FU have an antitumor effect. These experiments uniquely demonstrate a clear and, according to the starting hypothesis, logical, synergistic effect of PGE1 and 5-FU that offers hope for better treatment of many tumors in which raised IFP is likely to be inhibiting optimal results with water-soluble cancer chemotherapeutic agents.


Assuntos
Alprostadil/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Fluoruracila/uso terapêutico , Animais , Pressão Sanguínea , Carcinoma/irrigação sanguínea , Carcinoma/patologia , Divisão Celular , Sinergismo Farmacológico , Espaço Extracelular/efeitos dos fármacos , Modelos Biológicos , Pressão , Ratos
8.
Clin Biochem ; 48(13-14): 837-42, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26102343

RESUMO

OBJECTIVES: To investigate how water balance is regulated during labor and 27h postpartum. DESIGN AND METHODS: A prospective open trial with 49 women giving birth vaginally. Ringer-acetate was infused intravenously and combined with epidural analgesia in seven women (fluid group). Intravenous infusions of oxytocin in 5% glucose were given to 12 women (oxytocin group). Thirty women delivered their babies without infusion (nofluid group). Blood and urine samples were collected at arrival, at early stage 1, at early stage 2, and at aftercare, and 9, 15, and 27h postpartum. Plasma osmolality, sodium, cystatin C, vasopressin, oxytocin, urine flow, urine osmolality, and urine sodium were measued. RESULTS: The oxytocin group had significantly lower plasma osmolality than the nofluid group before parturition, and they had lower plasma sodium concentration at early stage 1 and 2. Plasma vasopressin concentration was low and did not differ between groups or before and after parturition. Water diuresis developed postpartum in all groups. The cystatin C concentration decreased significantly after parturition in the oxytocin and nofluid groups. CONCLUSIONS: The vasopressin levels were suppressed during parturition irrespective of the P-osmolality and the nongravid regulation of water balance had not returned within 27h postpartum.


Assuntos
Período Pós-Parto/fisiologia , Equilíbrio Hidroeletrolítico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Cistatina C/sangue , Eletrólitos/sangue , Feminino , Humanos , Recém-Nascido , Concentração Osmolar , Ocitocina/farmacologia , Período Pós-Parto/sangue , Gravidez , Estudos Prospectivos , Sódio/sangue , Micção/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
9.
Brain Res ; 961(1): 15-21, 2003 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-12535772

RESUMO

This study investigates the effects of cerebral microembolism on motor performance and risk assessment behavior in the rat. Cerebral infarcts were produced in rats by injecting small plastic beads into the left heart ventricle under short-acting anesthesia. The functional outcome was tested 24 h later by subjecting the animals to a series of consecutive behavioral tests. Thereafter, the rats were anesthetized and underwent magnetic resonance imaging. On average about seven infarcts per brain were found. The volume of the individual infarcts was largest in the hippocampus (mean=4.26 mm(3)) and smallest in the white matter (mean=0.83 mm(3)). Embolized animals performed spontaneous and evident locomotion. The activity was, however, significantly decreased compared to rats treated with vehicle. More specific tests for motor ability revealed reduced gait capacity and muscular strength. A significant relationship was found between behaviors reflecting motor ability and the total volume of infarcted tissue in the brain stem, cortex and cerebellum. Also the behavioral profile of risk and benefit assessment was found to be altered by the microembolization. It is concluded that the combination of the microembolization method and behavioral tests provides a valuable tool for further studies of the pathophysiology of, and potential treatment for, cerebral infarction.


Assuntos
Comportamento Animal , Embolia Intracraniana/fisiopatologia , Embolia Intracraniana/psicologia , Atividade Motora , Animais , Encéfalo/patologia , Infarto Cerebral/diagnóstico , Infarto Cerebral/etiologia , Embolia Intracraniana/complicações , Imageamento por Ressonância Magnética , Masculino , Ratos , Ratos Sprague-Dawley
10.
Am J Physiol Regul Integr Comp Physiol ; 294(3): R836-41, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18077505

RESUMO

OBJECTIVE: an increased glomerular filtration rate (GFR) has been postulated as a potential mechanism involved in the progression of diabetic nephropathy. Studies suggest that C-peptide exerts a renoprotective effect on diabetes. The peptide decreases hyperfiltration in patients with type 1 diabetes, as well as in diabetic animal models. In this study, we investigated whether C-peptide causes a change in arteriolar diameter. RESEARCH DESIGN AND METHODS: C57-Bl mice were made diabetic by means of a single intravenous injection of alloxan 2 wk prior to the experiment. Age-matched normoglycemic mice served as controls. Afferent arterioles, intact with the glomeruli, were dissected and microperfused. The effect of luminal application of C-peptide, compared with scrambled C-peptide or vehicle, was investigated. The effect of the Rho-kinase inhibitor Y-27632 was also investigated. RESULTS: C-peptide constricted afferent arterioles in diabetic mice by -27% compared with the control value. Normoglycemic arterioles administered C-peptide displayed a delayed and minute response (-4%). Scrambled C-peptide or vehicle administration, whether administered to hyperglycemic or normoglycemic mice, did not induce any effect. Addition of Y-27632 abolished the effect of C-peptide. CONCLUSION: C-peptide induces constriction of afferent arterioles in diabetic mice. This can reduce enhanced GFR and may be one of the mechanisms in the renoprotective action of C-peptide in diabetes.


Assuntos
Peptídeo C/farmacologia , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/patologia , Glomérulos Renais/irrigação sanguínea , Vasoconstrição/efeitos dos fármacos , Amidas/farmacologia , Angiotensina II/farmacologia , Animais , Arteríolas/anatomia & histologia , Arteríolas/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glomérulos Renais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Piridinas/farmacologia , Fator Rho/metabolismo , Vasoconstritores/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismo
11.
Diabetes Metab Res Rev ; 24(2): 165-8, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18157793

RESUMO

BACKGROUND: Pancreatic islet blood flow is regulated separately from that of the exocrine pancreas, and a consistent finding during impaired glucose tolerance is an increased blood perfusion. The aim of the present study was to investigate whether C-peptide affects pancreatic islet arterioles in normal and diabetic mice. MATERIALS AND METHODS: Control and diabetic C57-Bl mice were studied after 2 weeks of alloxan-induced diabetes. Islet arterioles were dissected and microperfused with Dulbecco's modified Eagle medium (DMEM) solution. The effect of luminal application of mouse C-peptide was investigated. RESULTS: C-peptide reduced the diameter of islet arterioles from diabetic mice (-10+/-4%, P<0.05) compared to base-line values, whilst arterioles from normoglycaemic animals did not respond to C-peptide (P=0.2). CONCLUSION: These findings suggest a role for C-peptide in the regulation of islet blood flow, especially during conditions with impaired glucose tolerance.


Assuntos
Arteríolas/efeitos dos fármacos , Peptídeo C/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Ilhotas Pancreáticas/irrigação sanguínea , Vasoconstrição/efeitos dos fármacos , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fluxo Sanguíneo Regional/efeitos dos fármacos
12.
Diabetes Metab Res Rev ; 23(5): 400-5, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17103462

RESUMO

BACKGROUND: Initially, diabetes is commonly associated with an increased glomerular filtration rate (GFR), a potential mechanism involved in the progression of diabetic nephropathy. Several studies have reported reno-protective effects of C-peptide. C-peptide reduces diabetes-induced hyperfiltration, as well as renal hypertrophy and albuminuria. In order to gain further understanding of these effects, it is very important to localize the active sites within the C-peptide molecule. This study was designed to elucidate the effects of the C-peptide fragment EVARQ on kidney function, blood pressure and blood glucose levels in diabetic rats in vivo. METHODS: The study was performed on adult inactin-anaesthetized male Sprague-Dawley rats. Two weeks prior to the experiment, diabetes was induced by a single intravenous injection of streptozotocin (55 mg/kg BW). After recovery and recording of baseline values, vehicle, C-peptide (50 pmol . kg BW(-1).h(-1)) or EVARQ (500 pmol.kg BW(-1).h(-1)) was continuously administered for a total of 100 min. RESULTS: Before substance administration, all diabetic groups displayed a pronounced hyperfiltration as compared to the control rats. Continuous administration of both C-peptide and EVARQ reduced the diabetes-induced hyperfiltration within an hour. Furthermore, blood pressure was only reduced in diabetic rats that were given C-peptide, whereas the blood glucose decreased in the diabetic groups that were given either C-peptide or EVARQ. CONCLUSIONS: The present study shows that administration of the C-peptide fragment EVARQ has similar effects on GFR and blood glucose levels as the intact C-peptide molecule, suggesting at least one active site within this region.


Assuntos
Peptídeo C/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomérulos Renais/fisiopatologia , Fragmentos de Peptídeos/uso terapêutico , Animais , Glomérulos Renais/efeitos dos fármacos , Masculino , Oligopeptídeos/uso terapêutico , Ratos , Ratos Sprague-Dawley
13.
Neurobiol Dis ; 25(3): 455-63, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17223348

RESUMO

The calcium-binding Mts1/S100A4 protein plays an important role in motility and metastatic activity of tumor cells. Recently we showed that Mts1/S100A4 is expressed in white matter astrocytes and influences their migration in vitro and in vivo. Here, we have investigated the role of Mts1/S100A4 expression in C6 glioma cells or surrounding astrocytes for migration of C6 cells on astrocytes, using short interference (si) RNA to silence Mts1/S100A4 expression. We find that in vitro, the migration of Mts1/S100A4 expressing and silenced C6 cells on astrocytes is predominantly dependent on the expression of Mts1/S100A4 in astrocytes, i.e. C6 cells preferably migrate on Mts1/S100A4-silenced astrocytes. In vivo, Mts1/S100A4-positive C6 cells preferably migrate in white matter. In contrast Mts1/S100A4-silenced C6 cells avoid white matter and migrate in gray matter and meninges. Thus, the migration pattern of C6 cells is affected by their intrinsic Mts1/S100A4 expression as well as Mts1/S100A4 expression in astrocytes. To investigate if Mts1/S100A4 has a significant role on brain tumor progression, we made quantitative RT-PCR analysis for the expression of S100A4/Mts1 in various grades of astrocytic tumors. Our data showed that high-grade glioblastomas express higher amount of S100A4/Mts1 than low-grade astrocytic tumors.


Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Movimento Celular , Proteínas S100/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Comunicação Celular , Linhagem Celular Tumoral , Corpo Caloso/metabolismo , Corpo Caloso/patologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Metaloproteases/metabolismo , Invasividade Neoplásica , Transplante de Neoplasias , Fibras Nervosas Mielinizadas/metabolismo , Fibras Nervosas Mielinizadas/patologia , RNA Interferente Pequeno , Ratos , Proteína A4 de Ligação a Cálcio da Família S100 , Proteínas S100/genética
14.
Exp Physiol ; 90(6): 847-53, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16091405

RESUMO

To identify defects in the salt-sensitive Dahl rat (Dahl-S), the natriuretic, catecholaminergic and pressor responses to 60-min elevation of the cerebroventricular sodium concentration (CNS-induced natriuresis) were compared between prehypertensive salt-sensitive Dahl-S and salt-resistant Dahl rats (Dahl-R). The plasma concentrations of the rat natriuretic hormone oxytocin, which has implications for the development of hypertension, and vasopressin (AVP) were also measured. Basal sodium and catecholamine excretion and mean arterial blood pressure (MAP) were similar in both strains. Sodium excretion during CNS stimulation increased more than 15-fold in Dahl-R but only 10-fold in Dahl-S. Dopamine excretion increased only transiently and similarly in both strains. Noradrenaline excretion and response to CNS stimulation were similar, suggesting a comparable sympathetic nervous activity between the strains. MAP increased comparably in Dahl-R and Dahl-S. Plasma AVP concentration was similar in both strains while plasma oxytocin concentration after CNS stimulation was more than 2-fold higher in Dahl-S than in Dahl-R. In conclusion, the prehypertensive Dahl-S has an attenuated natriuretic response to elevations of the cerebroventricular fluid sodium concentration and a higher plasma level of the natriuretic hormone oxytocin. Dopamine is not a mediator of CNS-induced natriuresis in neither strain. The attenuated natriuretic response may partly explain the salt-sensitivity in Dahl-S, and the higher plasma oxytocin value may either represent an effort to compensate for the deficient natriuretic response or reflect a primary defect in this system. Due to the known involvement of oxytocin in central MAP regulation in some hypertensive animal models, the findings warrant further investigation.


Assuntos
Líquido Cefalorraquidiano/fisiologia , Dopamina/urina , Natriurese/fisiologia , Norepinefrina/urina , Ocitocina/sangue , Ácido 3,4-Di-Hidroxifenilacético/urina , Animais , Hipertensão/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos Dahl , Solução Salina Hipertônica/farmacologia , Sódio/urina , Vasopressinas/sangue
15.
Mol Cell Biochem ; 271(1-2): 61-7, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15881656

RESUMO

Bikunin is a chondroitin sulfate-containing plasma protein synthesized in the liver. In vitro, it has been shown to inhibit proteases and to have additional activities, but its biological function is still unclear. Here we have studied the dynamics of plasma bikunin in rats and mice. A half-life of 7 +/- 2 min was obtained from the time course of the decrease of the plasma level of bikunin following hepatectomy. Clearance experiments with intravenously injected radiolabeled bikunin with or without the chondroitin sulfate chain showed that the polysaccharide had little influence on the elimination rate of the protein. The uptake of bikunin by different tissues was studied using bikunin labeled with the residualizing agent 125I-tyramine cellobiose; 60 min after intravenous injection, 49% of the radioactivity was recovered in the kidneys and 6-11% in the liver, bones, skin, intestine and skeletal muscle. The uptake in the liver was analyzed by intravenous injection of radiolabeled bikunin followed by collagenase perfusion and dispersion of the liver cells. These experiments indicated that bikunin is first trapped extracellularly within the liver before being internalized by the cells.


Assuntos
Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/farmacocinética , Inibidor da Tripsina de Soja de Kunitz/sangue , Inibidor da Tripsina de Soja de Kunitz/farmacocinética , Animais , Celobiose/química , Sulfatos de Condroitina/química , Sulfatos de Condroitina/metabolismo , Meia-Vida , Hepatectomia , Injeções Intravenosas , Radioisótopos do Iodo , Marcação por Isótopo , Rim/metabolismo , Fígado/citologia , Fígado/metabolismo , Masculino , Glicoproteínas de Membrana/administração & dosagem , Glicoproteínas de Membrana/química , Taxa de Depuração Metabólica , Camundongos , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Inibidor da Tripsina de Soja de Kunitz/administração & dosagem , Inibidor da Tripsina de Soja de Kunitz/química , Tiramina/química
16.
Nephrol Dial Transplant ; 20(3): 532-8, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15665028

RESUMO

BACKGROUND: There is accumulating evidence that C-peptide exerts beneficial renal effects in type-1 diabetes by reducing glomerular hyperfiltration, albuminuria and glomerular hypertrophy in the early stage of nephropathy. The aim of this study was to clarify further the effects of C-peptide on renal structural changes in type-1 diabetic rats. METHODS: The effects of C-peptide or placebo on glomerular volume, mesangial expansion, glomerular basement membrane thickness, albuminuria and glomerular filtration rate (GFR) were studied in three groups of rats: a non-diabetic group (N, n=9) and two groups that, during 8 weeks of diabetes, were left untreated for 4 weeks and then given a subcutaneous infusion of either placebo (D, n=11) or C-peptide (DCp, n=11) during the next 4 weeks. Furthermore, GFR was studied after 4 weeks of diabetes in an additional diabetic group (D-early, n=9) and in an age-matched non-diabetic group (N-early, n=9). RESULTS: After 4 weeks, GFR in the D-early group was 102% higher than in the N-early group. GFR after 8 weeks did not differ between the study groups. The D group presented with a 33% larger glomerular volume than the N group (P<0.001), while glomerular volume in the DCp group was similar to that in the N-group. Total mesangial and mesangial matrix fractions were increased by 46% (P<0.001) and 133% (P<0.001), respectively, in the D group. The corresponding values in the DCp group did not differ from those for the non-diabetic animals. Neither the thickness of the glomerular basement membrane nor the level of albuminuria differed significantly between the study groups. CONCLUSIONS: C-peptide administration in replacement dose to streptozotocin-diabetic rats serves to limit or prevent the glomerular hypertrophy and the mesangial matrix expansion seen in the post-hyperfiltration phase of early diabetic nephropathy.


Assuntos
Albuminúria/patologia , Peptídeo C/farmacologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomérulos Renais/efeitos dos fármacos , Albuminúria/fisiopatologia , Animais , Membrana Basal/efeitos dos fármacos , Membrana Basal/patologia , Mesângio Glomerular/efeitos dos fármacos , Mesângio Glomerular/patologia , Glomérulos Renais/patologia , Glomérulos Renais/fisiopatologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Estreptozocina
17.
Nephrol Dial Transplant ; 19(6): 1385-91, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15004258

RESUMO

BACKGROUND: C-peptide has been shown to reduce glomerular hyperfiltration, glomerular hypertrophy and urinary albumin excretion in type 1 diabetes, but its effect has not been compared with that of an angiotensin-converting enzyme inhibitor (ACEI) in the early stage of renal involvement in diabetes. METHODS: Glomerular filtration rate (GFR) was measured in terms of inulin clearance and renal blood flow, using ultrasound technique, in four groups of streptozotocin-induced diabetic rats before and after a 60 min infusion of C-peptide (D-Cp), captopril (D-ACEI), C-peptide and captopril (D-Cp-ACEI) or placebo (D-placebo). In addition, a non-diabetic control group was studied before and after captopril infusion (C-ACEI). RESULTS: GFR was 37-51% higher in the diabetic groups than in the control animals. GFR decreased after treatment in the D-Cp, D-ACEI and D-Cp-ACEI groups, but did not change in the D-placebo group. Blood flow increased by 26-32% in the three groups receiving captopril and by 5% in the diabetic groups treated with C-peptide alone or placebo. The increase in blood flow in the three ACEI-treated groups was significantly greater than in the D-placebo group. Filtration fraction fell significantly in all groups, but only in the combined D-Cp-ACEI group did it fall significantly more than in the D-placebo group. CONCLUSIONS: C-peptide and captopril lower diabetes-induced glomerular hyperfiltration to a similar extent, but the influence of captopril on blood flow is greater than that of C-peptide, suggesting different mechanisms of action. No statistically significant additive effects of C-peptide and captopril were shown in this acute infusion study.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Peptídeo C/farmacologia , Captopril/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/fisiopatologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/efeitos dos fármacos
18.
Am J Pathol ; 163(5): 1921-8, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14578191

RESUMO

Elevated semicarbazide-sensitive amine oxidase (SSAO) activity has been observed in several human conditions, eg, diabetes, and it has been speculated that SSAO contributes to the development of vasculopathies associated with this disease. To investigate in vivo consequences of elevated expression of SSAO in vascular tissues, we have developed a transgenic model for overexpression of human SSAO in mice. A smooth muscle-specific promoter, smooth muscle alpha-actin promoter 8 (SMP8) was used. Transgenic expression of human SSAO in tissues with a high content of smooth muscle cells was confirmed by Northern blot analysis. Enzymatic analysis of homogenates from transgenic tissues showed elevated levels of SSAO activity compared to non-transgenic littermates. Furthermore, when plasma SSAO activity was analyzed, much higher activity was detected compared to plasma from control mice, indicating that plasma SSAO may originate from smooth muscle cells. Histopathological evaluation of aorta and renal artery from transgenic mice revealed an abnormal structure of the elastin tissue. Instead of the regularly folded elastic laminae normally found in tunica media of sacrificed mice, the elastic laminae were straight and unfolded with irregularly arranged elastic fibers, forming tangled webs, between the intercalating elastic laminae. These alterations of the elastin structures suggest that overexpression of SSAO has led to a reduced elasticity of the arteries. Moreover, the mean femoral arterial pressure of the SMP8 SSAO transgenic mice was significantly lower in comparison to non-transgenic littermates. This suggests that the transgenic mice have a defect in their ability to regulate blood pressure.


Assuntos
Amina Oxidase (contendo Cobre)/biossíntese , Aorta/patologia , Miócitos de Músculo Liso/enzimologia , Amina Oxidase (contendo Cobre)/sangue , Amina Oxidase (contendo Cobre)/genética , Animais , Aorta/enzimologia , Aorta/ultraestrutura , Artérias/patologia , Artérias/fisiopatologia , Pressão Sanguínea/genética , Pressão Sanguínea/fisiologia , Northern Blotting , Elastina/ultraestrutura , Humanos , Camundongos , Camundongos Transgênicos , Regiões Promotoras Genéticas , Regulação para Cima
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