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S Sigrist

Publications and source records attributed to S Sigrist.

At least 19 recordsLinked to original sources
PubMed2006

Antimicrobial and general toxicity activities of Gymnosperma glutinosum: a comparative study.

Gymnosperma glutinosum (Spreng.) Less (Asteraceae) is an important, and an effective herbal medicine which is wide used for the treatment of diarrhoea in Mexico. We examined and compared the antibacterial and antifungal activities through the dilution method and for general toxicity activity by the brine shrimp lethality assay of two samples of Gymnosperma glutinosum from two localities of Mexico: San Rafael-Coxcatlan (Puebla State) and Tepeji del Rio (Hidalgo State). In addition, two bioactive compounds (-)-17-hydroxy-neo-clerod-3-en-15-oic acid (1) and 5,7-dihydroxy-3,6,8,2',4',5'-hexamethoxyflavone (2) were isolated. From the hexane extract from both places was obtained a MeOH partition M(2). M(2) of Tepeji del Rio showed the least MICs (<125 microg/ml) in the majority of the bacterial strains. Sarcina lutea was the most sensitive bacteria (MIC< 125 microg/ml). The hexane extract of both localities showed antifungal activity against all tested fungi. San Rafael's hexane extract was significant more activity than Tepeji del Rio. Aspergillus niger (IC(50)=23.79 microg/ml) and Trichophyton mentagrophytes (IC(50)=90.25 microg/ml) were the more sensitive fungus strains. The strongest general toxicity activity was observed with the M(2) partition from Tepeji del Rio (LC(50)=503.7 microg/ml). The results obtained in this investigation, showed differences between the antimicrobial activities of the samples of plants collected in San Rafael (Puebla) and Tepeji del Rio (Hidalgo).

Animals↗
PubMed2006

Cardio protective effect of glucose-insulin infusion on acute digoxin toxicity in rat.

UNLABELLED: We recently observed a case of digoxin and insulin self-poisoning without cardiac repercussion. We raised the hypothesis that insulin may have a cardio-protective effect in case of digoxin toxicity. We have therefore evaluated the effect of glucose-insulin infusion on mortality and ECG abnormalities during acute digoxin toxicity in rats. Before and after a hyperinsulinemia-euglycemia clamp, rats in glucose-insulin-digoxin (GID) group (n=10) received an intravenous infusion of 12ml/h or 2,5ml/h digoxin (0.25mg/ml) respectively until death occured. Animals receiving digoxin or saline solution intravenously served as control (n=10). ECG recording was performed in all animals over the entire period. Serum insulin and digoxin concentrations were measured by ELISA method after digoxin administration. When digoxin was administered after the clamp, all animals in GID group were alive, whereas 80% of animals in the digoxin group were dead (p<0.001) after 30min. The administration of Digoxin provoked rapid death of rats in the digoxin group in 15+/-12min whereas in GID group the survival period was significantly increased to 38+/-3min (p<0.001). Twenty minutes after digoxin administration, P waves disappeared for 78% of animals in digoxin group while they were present in all rats of GID group (p<0.001). Animal death occurred after a digoxin infusion volume of 7.7+/-0.6ml and 3.0+/-2.4ml in GID and digoxin group respectively (p<0.001). Five minutes after digoxin administration, potassium plasmatic level increased significantly in digoxin group as compared to GID group: 7.1+/-2mmol/l versus 4.4+/-0.4mmol/l (p<0.001). When digoxin was infused before the clamp, 40% of animals in GID group were alive after 180min and the other 60% died after 137+/-40min whereas death of rats in the digoxin group occurred within 80+/-10min (p<0.001). The death of animals was preceded by the P waves disappearing. Thirty minutes after digoxin administration, the potassium plasmatic level increased significantly in the digoxin group as compared to the GID group: 6.9+/-0.5mmol/l versus 4.9+/-0.3mmol/l (p<0.001). At the time of death, both volume of digoxin infusion and serum digoxin concentration were increased in GID group as compared to digoxin group: 5.7+/-1.6ml versus 3.3+/-0.4ml (p<0.001) and 10.7+/-8.3mg/l versus 8.5+/-4.6mg/l. CONCLUSION: Glucose-insulin infusion delayed the abnormalities in cardiac conduction and improved rat survival after acute digoxin toxicity. These results suggest a cardioprotective effect of insulin in case of acute digoxin toxicity.

Animals↗
PubMed2005

Role of chemokine signaling pathways in pancreatic islet rejection during allo- and xenotransplantation.

During transplantation, pancreatic islets release chemokines promoting macrophage attraction, hampering engraftment of islets. The aim of this work was to examine the mechanism of macrophage-pancreatic islets interaction that mediates islet rejection during transplantation. Human macrophages exposed to supernates of human and porcine pancreatic islets for the allogeneic and xenogeneic models, respectively, were evaluated for chemotaxis and expression of chemokine receptors (CCR-5). To modulate migration and identify the signaling pathway of macrophages, we tested pertussis toxin (PTX) to block Gi protein, and staurosporin and wortmannin to inhibit the protein kinase, and phosphoinositol-3 kinase, respectively. The addition of these agents significantly reduced macrophage migration induced by human islet supernates from 3.2 +/- 0.5 to 1.5 +/- 0.2, 0.9 +/- 0.1, and 1 +/- 0.1, respectively (P < .001, n = 3). In a xenotransplantation model, the reduction was less decreased, from 4.1 +/- 0.4 to 2.7 +/- 0.3 (P < .01), to 2.5 +/- 0.3 (P < .01), or to 1 +/- 0.1 (P < .001). Western blot analysis of chemokine receptor expression showed increased CCR-5 expression with human pancreatic islet supernates. Moreover, decreased islet purity increased CCR-5 expression. Pharmacologic study showed that PTX induced an increase in CCR-5 expression in allogeneic transplantation, whereas only staurosporin induced an increased receptor expression in the xenogeneic model, suggesting that chemokines participate in islet rejection even though the chemokine signaling pathways differ between allo- and xenotransplantation. Understanding the molecular mechanisms of islet rejection may improve graft survival.

Adult↗
PubMed2003

Induction of angiogenesis in omentum with vascular endothelial growth factor: influence on the viability of encapsulated rat pancreatic islets during transplantation.

Transplantation of pancreatic islets is proposed as a treatment for type 1 diabetes, but insufficient blood supply can cause the loss of viable grafted islets. In the present study, we investigated the influence of vascular endothelial growth factor (VEGF) on the angiogenesis of omentum during encapsulated islet allotransplantation and consequently on islet survival. Fifty rat islets, cultured for 24 h, were encapsulated in the presence or absence of human VEGF and implanted in the peritoneal cavity of rats (n = 6). After 7, 14 and 28 days of implantation, encapsulation devices with surrounding omentum were removed. Histological analysis of this tissue was performed. Cellular adhesion at the membrane surface was characterized by a phagocytosis test. The morphological aspect of the islets was analyzed and their functionality was evaluated by measuring insulin secretion. At each step of the study, there was a two-fold increase in the number of vessels in the presence of VEGF. In addition, VEGF increased the vessel diameter and the surface area of the angiogenic pedicle. Moreover, the presence of VEGF significantly decreased the distance between the devices and vessels (16.2 +/- 5.6 vs. 51.6 +/- 10.1 microm, p < 0.001). Membrane surface analysis showed a decrease in macrophage adhesion in the presence of VEGF. Furthermore, islet structure and functionality was preserved in the presence of VEGF. Stimulation of angiogenesis of omentum induced by VEGF is associated with preservation of islet viability. Local delivery of VEGF proved to be a relevant approach to ameliorate the outcome of islet transplantation.

Animals↗
PubMed2003

Influence of VEGF on the viability of encapsulated pancreatic rat islets after transplantation in diabetic mice.

After pancreatic islet transplantation, insufficient blood supply is responsible for the loss of islet viability. The aim of our study was: 1) to determine the influence of vascular endothelial growth factor (VEGF) on the survival of encapsulated rat islets transplanted into healthy and diabetic mice and 2) to evaluate the metabolic efficiency of the VEGF-supplemented grafts. Twenty-four hours after culture, 50 rat islets immobilized into collagen in the presence of VEGF (100 ng/ml) and encapsulated (AN69 membrane, HOSPAL) were grafted in the peritoneal cavity of healthy or streptozotocin-induced diabetic mice (n = 6). Seven, 14, and 28 days after implantation, the encapsulation device and tissue surrounding the device were removed and the following parameters were analyzed: the number and the diameter of buds, the distance between devices and buds, the amount of cellular adhesion on the capsule surface, and the level of insulin secreted by encapsulated islet. For reversal of diabetes, 1000 rat islets encapsulated in the presence of VEGF were implanted in the peritoneal cavity of diabetic mice and fasting glycemia was analyzed. After 7 days of islet implantation in the absence of VEGF, the bud diameter was 16.1 +/- 6.9 microm in diabetic mice and 34.4 +/- 3.9 microm in healthy mice. However, the number of buds increased by a factor 2.5 in the presence of VEGF in both types of mice. Furthermore, when islets were transplanted in the presence of VEGF, the distance between the device and the buds was significantly decreased in both types of mice (p < 0.001) after 7, 14, and 28 days of islet implantation. Capsule analysis showed a decrease in cellular adhesion when the islets were encapsulated in the presence of VEGF. Insulin secretion of the islets was higher in the presence of VEGF compared with islets alone at all steps of the study. When 1000 rat islets were transplanted in the presence of VEGF, the glycemia level decreased to 6.2 +/- 0.8 mmol/L after 3 days and remained stable until at least 28 days. In contrast, in the absence of VEGF, the initial decrease in the glucose level was rapidly followed by a relapse in hyperglycemia. In summary, VEGF increased the viability of engrafted encapsulated islets, increasing the duration of a normalized glycemia in diabetic mice following transplantation. Local adjunction of VEGF may therefore improve the clinical outcome of islet transplantation.

Animals↗
PubMed2001

Macrophage activation in type 1 diabetic patients with catheter obstruction during peritoneal insulin delivery with an implantable pump.

OBJECTIVE: The purpose of this study was to evaluate the activation of macrophages in type 1 diabetic patients during peritoneal insulin delivery with an implantable pump against two types of insulin: that which was collected from the pump reservoir and that which came straight fromn the bottle (i.e., vial insltlin). Macrophage activation was studied in patients with and without cathcter obstruction and compared with activation in healthy subjects. RESEARCH DESIGN AND METHODS: Human insulin (21 PH, 400 U/ml; Hoescht) was collected from the pump reservoir (Minimed) of diabetic patients with (n = 3) or without (n = 7) catheter obstruction, as assessed by histological examination of the catheter tip. Monocytes were obtained from venous blood samples from both kinds of diabetic patients and from healthy subjects (n = 5) and were differentiated into monocyte-derived macrophages in culture. Their chemotaxis and tumor necrosis factor-alpha (TNF-alpha) release were studied with respect to both types of insulin, as previously stated. Formyl-methionyl-leucyl-phenylalanine (fMLP) and lipopolysaccharide (LPS) were used as controls. RESULTS: Neither insulin recovered from the pump reservoir nor vial insulin proved chemotactic to macrophages from either healthy subjects or those diabetic patients with and without catheter obstruction. The migration toward fMLP of macrophages from patients presenting a catheter obstruction was significantly higher than that observed with macrophages from either diabetic patients without obstruction or healthy subjects, the chemotactic index (mean +/- SD) was 3.81 +/- 0.36 vs. 2.30 +/- 0.89 and 2.60 +/- 0.80, respectively (P < 0.05). LPS significantly stimulated the TNF-alpha secretion of macrophages from diabetic subjects with a catheter obstruction, whereas both native and reservoir-recovered insulin had no effect on this release (144.83 +/- 67.25 vs. 5.15 +/- 2.93 and 5.27 +/- 2.43 pg/ml, P < 0.001). CONCLUSIONS: The human insulin used in implantable pumps, regardless of how long it had remained in the pump reservoir, did not induce macrophage activation in diabetic patients treated through intraperitoneal insulin delivery. In some of these diabetic patients, catheter obstruction could be explained by their high capacity of macrophage chemotaxis.

Adult↗
PubMed2000

Down-regulation by troglitazone of hepatic tumor necrosis factor-alpha and interleukin-6 mRNA expression in a murine model of non-insulin-dependent diabetes.

Troglitazone, a novel thiazolidinedione drug used to treat non-insulin-dependent diabetes mellitus, is a selective ligand for the peroxisome proliferator-activated receptor-gamma (PPARgamma). Recent results indicate that PPARgamma activation by thiazolidinediones regulates adipose tissue- and monocyte/peritoneal macrophage-derived cytokine expression in vitro. We evaluated whether troglitazone may also negatively regulate cytokine expression in the liver, which harbors the majority of the body's resident macrophages but which only weakly expresses PPARgamma. Lean C57BL6 mice and genetically obese KKA(y) mice were chronically treated with troglitazone (100 mg/kg/day for 2 weeks). At the end of treatment, hepatic expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNA was quantitatively determined by kinetic polymerase chain reaction both under basal conditions and after stimulation with lipopolysaccharide (LPS). Both untreated lean and obese mice exhibited low levels of baseline TNF-alpha and IL-6 mRNA expression and responded with a dramatic increase in hepatic cytokine transcripts and TNF-alpha protein expression following a challenge with LPS. Similar to the effects on white adipose tissue, troglitazone not only down-regulated the baseline levels of hepatic TNF-alpha and IL-6, but also greatly attenuated the inducing effects of LPS. The extent of this inhibitory effect of troglitazone was higher in obese KKA(y) mice than in lean mice and was also reflected by markedly down-regulated hepatic TNF-alpha protein expression. These data demonstrate that chronic administration of troglitazone is associated with a greatly attenuated responsiveness towards inducers of hepatic TNF-alpha and IL-6 production. The possible biological consequences of these effects, however, have not yet been assessed.

Animals↗
PubMed1998

Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts.

The Xenopus homologue of Drosophila Fizzy and budding yeast CDC20 has been characterized. The encoded protein (X-FZY) is a component of a high molecular weight complex distinct from the APC/cyclosome. Antibodies directed against FZY were produced and shown to prevent calmodulin-dependent protein kinase II (CaMKII) from inducing the metaphase to anaphase transition of spindles assembled in vitro in Xenopus egg extracts, and this was associated with suppression of the degradation of mitotic cyclins. The same antibodies suppressed M phase-promoting factor (MPF)-dependent activation of the APC/cyclosome in interphase egg extracts, although they did not appear to alter the pattern or extent of MPF-dependent phosphorylation of APC/cyclosome subunits. As these phosphorylations are thought to be essential for APC/cyclosome activation in eggs and early embryos, we conclude that at least two events are required for MPF to activate the APC/cyclosome, allowing both chromatid segregation and full degradation of mitotic cyclins. The first one, which does not require FZY function, is the phosphorylation of APC/cyclosome subunits. The second one, that requires FZY function (even in the absence of MAD2 protein and when the spindle assembly checkpoint is not activated) is not yet understood at its molecular level.

Amino Acid Sequence↗
PubMed1996

Novel members of the cdc2-related kinase family in Drosophila: cdk4/6, cdk5, PFTAIRE, and PITSLRE kinase.

In addition to the previously identified Drosophila cdc2 and cdc2c genes, we have identified four additional cdc2-related genes with low stringency and polymerase chain reaction approaches. Sequence comparisons suggest that the four putative kinases represent the Drosophila homologues of vertebrate cdk4/6, cdk5, PCTAIRE, and PITSLRE kinases. Although the similarity between human and Drosophila homologues is extensive in the case of cdk5, PCTAIRE, and PITSLRE kinases (78%, 58%, and 65% identity in the kinase domain), only limited conservation is observed for Drosophila cdk4/6 (47% identity). However, like vertebrate cdk4 and cdk6, Drosophila cdk4/6 binds also to a D-type cyclin according to the results of two-hybrid experiments in yeast. Northern blot analysis indicated that the four Drosophila kinases are expressed throughout embryogenesis. Expression in early embryogenesis appeared to be ubiquitous according to in situ hybridization. Abundant expression already at the start of embryogenesis and long before neuron differentiation was also observed in the case of cdk5 protein, which has been described as predominantly neuron specific in mice. Sequence conservation and expression pattern, therefore, suggest that all of these kinases perform important cellular functions.

Amino Acid Sequence↗
PubMed1996

The relation of fibrous degeneration to menopausal status in small uterine leiomyomas with evidence for postmenopausal origin of seedling myomas.

It is well known that uterine leiomyomas shrink after the menopause. Fibrosis is the most common type of myomatous degeneration, but its relationship to menopause has not been studied. We evaluated fibrosis in 237 small myomas (< 1 cm) in relation to menopause, tumor size, intrauterine location, and patient age. Substantial fibrosis was seen in 33 (21%) of 159 small premenopausal myomas versus 39 (50%) of 78 small postmenopausal myomas (P < 0.001). This relationship was even stronger for women between 40 and 60 years of age: 27 (21%) of 126 premenopausal women versus 12 (71%) of 17 postmenopausal women (P < 0.001). Only 23 (23%) of 101 2- to 4-mm myomas had substantial fibrosis versus 45 (40%) of 112 5- to 9-mm myomas (P < 0.01). Small postmenopausal myomas that were inframucosal had less frequent fibrosis (3 [27%] of 11) than their intramural and subserosal counterparts (36 [54%] of 67) (P = 0.05). There was a significant increase in seedling myomas (fully cellular myomas < 1 cm) from postmenopausal women aged 60 to 70 years (13 [35%] of 37) compared with younger postmenopausal women (1 [6%] of 17) (P < 0.01). We conclude that fibrosis is strongly associated with menopausal status in small uterine myomas, that size and location are also related to fibrosis in small myomas, and that seedling myomas may arise after the menopause. Our interpretation of these findings is that the most likely cause of fibrosis in small myomas is senescence and that there may be heterogeneity in the molecular basis of senescence.

Adolescent↗
PubMed1995

Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction of cyclins A, B and B3.

While entry into mitosis is triggered by activation of cdc2 kinase, exit from mitosis requires inactivation of this kinase. Inactivation results from proteolytic degradation of the regulatory cyclin subunits during mitosis. At least three different cyclin types, cyclins A, B and B3, associate with cdc2 kinase in higher eukaryotes and are sequentially degraded in mitosis. We show here that mutations in the Drosophila gene fizzy (fzy) block the mitotic degradation of these cyclins. Moreover, expression of mutant cyclins (delta cyclins) lacking the destruction box motif required for mitotic degradation affects mitotic progression at distinct stages. Deltacyclin A results in a delay in metaphase, deltacyclin B in an early anaphase arrest and deltacyclin B3 in a late anaphase arrest, suggesting that mitotic progression beyond metaphase is ordered by the sequential degradation of these different cyclins. Coexpression of deltacyclins A, B and B3 allows a delayed separation of sister chromosomes, but interferes wit chromosome segregation to the poles. Mutations in fzy block both sister chromosome separation and segregation, indicating that fzy plays a crucial role in the metaphase/anaphase transition.

Anaphase↗
PubMed1995

Dmcdc2 kinase is required for both meiotic divisions during Drosophila spermatogenesis and is activated by the Twine/cdc25 phosphatase.

We have analyzed the requirement for Drosophila cdc2 kinase during spermatogenesis after generating temperature-sensitive mutant lines (Dmcdc2ts) by re-constructing mutations known to result in temperature sensitivity in fission yeast cdc2+. While meiotic spindles and metaphase plates were never formed in Dmcdc2ts mutants at high temperature, chromosomes still condensed in late spermatocytes and spermatid differentiation (sperm head and tail formation) continued. The same phenotype was also observed in twine and twine, Dmcdc2ts double mutant testes, consistent with the idea that the cdc2 kinase activity required for meiotic divisions is activated by the Twine/cdc25 phosphatase. Confirming this notion, we find that ectopic expression of the String/cdc25 phosphatase, which is known to activate the cdc2 kinase before mitosis, results in a partial rescue of meiotic divisions in twine mutant testis.

Amino Acid Sequence↗
PubMed1987

Comparison of binding sites for the calcitonin gene-related peptides I and II in man.

Specific and saturable binding sites of the synthetic human calcitonin gene-related peptide-I (CGRP-I) and -II (CGRP-II) have been identified in membrane homogenates of the human central nervous system, heart and spleen. Half maximal inhibition of the binding of 125I-CGRP-II was achieved with 0.25 nM and 1.7 nM of non-radioactive CGRP-I or -II, and with 260 and 850 nM salmon calcitonin in the spinal cord and cerebellum, respectively, but 1 microM human calcitonin was not recognized. Autoradiographs of diencephalic sections revealed different distribution of 125I-CGRP-I and -II binding sites.

Autoradiography↗
PubMed1986

Specific receptor and cardiovascular effects of calcitonin gene-related peptide.

Specific binding sites for calcitonin gene-related peptide (CGRP) were demonstrated in the rat heart and spleen. Autoradiography revealed rat [125I]iodo CGRP binding associated with the intima and media of the aorta, the coronary arteries and the heart valves, and the red pulp of the spleen. Half-maximal inhibition of rat [125I]iodo-CGRP binding to membranes of the rat atria and the spleen was obtained with, respectively, 5 and 0.35 nM unlabeled rat CGRP; these values correspond to EC50 values of 3 and 0.14 nM for activation of adenylate cyclase by CGRP. In the isolated, spontaneously beating right atrium, the EC50 values of stimulation of the force and rate of contraction by rat CGRP were 120 and 70 nM, respectively. Rat CGRP caused relaxation of splenic strips, precontracted with noradrenaline; the EC50 was 50 nM. The beta-adrenergic blocking agent metoprolol, while obliterating the increase in the force and rate of contraction evoked by noradrenaline in the right atrium, did not significantly change the action of CGRP. Similarly, preserved action of CGRP in the presence of indomethacin as well as mepyramine and cimetidine argues against a role of prostaglandins or histamine in the functional responses of CGRP. Much like CGRP, capsaicin, which releases mediators from sensory neurons, caused stimulation of the force and rate of contraction of the isolated right rat atrium. After tachyphylaxis to CGRP, the response to noradrenaline was intact, while the positive chronotropic and inotropic effects of capsaicin were suppressed. The results indicate that the cardiac effects of capsaicin may be due to the release of endogenous CGRP through a local mode of action.

Animals↗
PubMed1982

Action of costal and crural parts of the diaphragm on the rib cage in dog.

We studied the action of the costal and crural (vertebral) parts of the diaphragm on the lower rib cage in normal supine dogs. The two parts of the diaphragm were separately stimulated by electrodes directly implanted in the muscle or via the different phrenic nerve roots in the neck. The results of the experiments indicate the following. 1) The costal and crural parts of the diaphragm have a different segmental innervation and a different mechanical action on the rib cage. 2) The costal diaphragm expands the lower rib cage when it contracts. This rib-cage expansion is due mostly to the fulcrum of the abdominal contents and partly to the rise in abdominal pressure that takes place during diaphragmatic contraction. The pericardial attachments play no role in this action of the diaphragm. 3) The action of the crural diaphragm on the lower rib cage depends only on the balance between the inspiratory force exerted by the rise in abdominal pressure and the expiratory force exerted by the fall in pleural pressure. In the intact animal at functional residual capacity, these two opposite effects cancel each other. 4) The inflationary action of both parts on the rib cage decreases progressively as lung volume increases. The findings also suggest that the rise in abdominal pressure which occurs when the diaphragm contracts expands the lower rib cage by acting through the area of apposition of the diaphragm to the rib cage. These findings also strengthen the idea that the diaphragm actually consists of two muscles.

Abdomen↗