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Biomedical subjects

D Bani

Publications and source records attributed to D Bani.

At least 37 records · Page 2Linked to original sources
PubMed1998

Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart.

Myocardial injury caused by ischemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, platelet and mast cell activation, and peroxidation of cell membrane lipids, which are followed by myocardial cell alterations resulting eventually in cell necrosis. The current study was designed to test the possible cardioprotective effect of the hormone relaxin, which has been found to cause coronary vessel dilation and to inhibit platelet and mast cell activation. Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the left anterior descending coronary artery; reperfusion (for 60 minutes or less if the rats died before this predetermined time) was induced by removal of the ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia. The results obtained showed that relaxin strongly reduces 1) the extension of the myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase activity, a marker of neutrophil accumulation, 6) production of malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule release, 8) calcium overload, and 9) morphological signs of myocardial cell injury. This study shows that relaxin can be regarded as an agent with a marked cardioprotective action against ischemia-reperfusion-induced myocardial injury.

Animals↗
PubMed1997

Relaxin: a pleiotropic hormone.

1. Relaxin is a peptide hormone of about 6000 Da belonging to the insulin family. Like insulin, relaxin is composed by two disulfide-linked chains, termed the A and B chains, the B chain bearing the receptor interaction site. 2. Relaxin is produced primarily by the corpus luteum, in both pregnant and nonpregnant females. It attains the highest plasma levels during pregnancy. In this condition, relaxin is also produced by the decidua and placenta. In males, relaxin is synthesized in the prostate and released in the seminal fluid. An additional source of relaxin has recently been identified in the heart atria. 3. Relaxin has a broad range of biologic activities, some of which have been known for a long time. These latter ones include: (a) the induction of collagen remodeling and consequent softening of the tissues of the birth canal in view of delivery; (b) the inhibition of uterine contractile activity; (c) the stimulation of growth and differentiation of the mammary gland. 4. In more recent years, novel sites of relaxin action have been recognized. In particular, it has been shown that relaxin: (a) regulates growth and differentiation of breast cancer cells in culture; (b) promotes dilation of blood vessels in several organs and tissues, including the uterus, the mammary gland, the lung and the heart; (c) has a chronotropic action on the heart; (d) inhibits the release of histamine by mast cells, thus being able to counteract experimental allergic asthma; (d) depresses aggregation of platelets and their release by megakaryocytes; (e) influences the secretion of hormones by the pituitary gland; and (f) contributes to the regulation of fluid balance. 5. Concerning the mechanisms of action of relaxin, stimulation of nitric oxide generation, with consequent rise in intracellular cyclic GMP levels, and stimulation of cyclic AMP production have been demonstrated to occur in the target cells and organs. 6. It may be expected that the next decade will provide answers about the utility of relaxin, in terms of insight into the actual physiologic functions of relaxin in the animal kingdom and especially in man, in view of possible therapeutic use of relaxin or relaxin-derived drugs in human disease, especially considering that human recombinant relaxin is now available for clinical experimentation.

Animals↗
PubMed1997

Relaxin counteracts myocardial damage induced by ischemia-reperfusion in isolated guinea pig hearts: evidence for an involvement of nitric oxide.

Relaxin was previously shown to cause coronary vasodilation and to inhibit mast cell activation through a stimulation of endogenous nitric oxide production. This suggests that relaxin may have beneficial effects on ischemia-reperfusion-induced myocardial injury, which is triggered by endothelial damage and impaired nitric oxide generation. In this study, we tested the effect of relaxin on isolated and perfused guinea pig hearts subjected to ischemia and reperfusion. Ischemia was induced by ligature of the left anterior descending coronary artery; removal of the ligature induced reperfusion. Relaxin, at the concentration of 30 ng/ml of perfusion fluid, causes: a significant increase in coronary flow and in nitric oxide generation; a significant decrease in malonyldialdehyde production and in calcium overload, both markers of myocardial injury; an inhibition of mast cell granule exocytosis and histamine release, which are known to contribute to myocardial damage; a reduction of ultrastructural abnormalities of myocardial cells; an improvement of heart contractility. The beneficial effects of relaxin were blunted by the NO synthase inhibitor L-NMMA. The current study provides first experimental evidence that relaxin has a powerful protective effect on the heart undergoing ischemia and reperfusion acting through a nitric oxide-driven mechanism.

Animals↗
PubMed1997

Relaxin counteracts asthma-like reaction induced by inhaled antigen in sensitized guinea pigs.

In previous studies, the peptide hormone relaxin (RLX) was found to inhibit mast cell secretion and platelet activation. It has been established that the release of mediators from these cells plays a central pathogenic role in allergic asthma. This prompted us to ascertain whether RLX may counteract the respiratory and histopathological abnormalities of the asthma-like reaction to inhaled antigen in sensitized guinea pigs. Guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received RLX (30 microg/kg BW, twice daily for 4 days) before antigen challenge. Other animals received inactivated RLX in place of authentic RLX. Respiratory abnormalities, such as cough and dyspnea, were analyzed as were light and electron microscopic features of lung specimens. RLX was shown to reduce the severity of respiratory abnormalities, as well as histological alterations, mast cell degranulation, and leukocyte infiltration in sensitized guinea pigs exposed to ovalbumin aerosol. RLX was also found to promote dilation of alveolar blood capillaries and to reduce the thickness of the air-blood barrier. This study provides evidence for an antiasthmatic property of RLX and raises the possibility of new therapeutic strategies for allergic asthma in humans.

Administration, Inhalation↗
PubMed1997

Relaxin and breast cancer.

Relaxin is a peptide hormone of luteal origin with a broad range of biological activities on tissues and organs of the female reproductive system as well as on other targets not directly related to the reproductive function. The mammary gland is one of the major targets for relaxin, which has been shown to promote growth and differentiation of mammary parenchyma and stroma. Based on the recognition of the mammotrophic action of relaxin, further research could show that this peptide also influences the behaviour of breast cancer cells in vitro. In fact, when relaxin was added to the culture medium of MCF-7 breast adenocarcinoma cells for short exposure times it had a biphasic effect on their growth, stimulating cell proliferation at low, nanomolar concentrations and inhibiting it at high, micromolar concentrations. In the longer times, relaxin had a marked growth-inhibitory effect on MCF-7 cells at any concentration assayed, and concurrently promoted cell differentiation and expression of adhesion molecules which are known to binder the spreading ability of cancer cells. The positive effect of relaxin on MCF-7 cell differentiation was even enhanced when these cells were cocultured with myoepithelial cells, thus recreating a microenvironment reminiscent of the tissue architecture of the mammary ducts in vivo. Concerning the mechanisms of action of relaxin on MCF-7 cells, it seems that the growth-inhibiting and differentiation-promoting effects of the peptide are mediated through the activation of the synthetic pathway of nitric oxide.

Adenocarcinoma↗
PubMed1995

Relaxin activates the L-arginine-nitric oxide pathway in human breast cancer cells.

Recently, we demonstrated that relaxin (RLX), a peptide hormone of ovarian origin, inhibits growth and promotes differentiation of MCF-7 breast adenocarcinoma cells. We also showed that RLX stimulates the production of nitric oxide (NO) in several cell types. NO has been reported to have antitumor activity by inhibiting proliferation, promoting differentiation, and reducing the metastatic spread of some tumor cell types. In this study, we aimed at evaluating whether RLX influences the L-arginine-NO pathway in MCF-7 cells. The cells were grown in the absence or presence of RLX at different concentrations, and cell proliferation, constitutive and inducible NO synthase activities, nitrite production, and intracellular levels of cyclic GMP were investigated. The results obtained indicate that RLX increases inducible NO synthase activity and potentiates NO production. This was accompanied by an elevation of intracellular cyclic GMP, which is known to mediate the cell response to NO. The RLX-induced activation of the L-arginine-NO pathway in the MCF-7 cells was inversely related to the rate of cell proliferation. These results suggest that the cytostatic effect of RLX on MCF-7 breast cancer cells may rely on its ability to stimulate endogenous production of NO.

Arginine↗
PubMed1995

P-glycoprotein is expressed in parathyroid epithelium and is regulated by calcium.

P-glycoprotein (Pgp), the multidrug resistance (mdr) gene product, has been described in normal tissues with diverse physiologic functions. A broad role as a transporter protein for toxins, hormones, and physiologic metabolites has been provisionally deduced, based on structural analysis and immunoanatomic localization. Recently, significant levels of Pgp have been demonstrated in endocrine and hormonally responsive tissues and tumors. We examined calcium-regulated, clonal parathyroid epithelial (PT-r) and endothelial cells (BPE-1) and frozen parathyroid tissue from normal human parathyroid, parathyroid hyperplasia, parathyroid adenoma, and parathyroid carcinoma for expression of the multidrug resistance gene (Mdr1) and Pgp utilizing Northern and Western analysis and immunohistochemistry. We also investigated the effect of extracellular calcium (eCa) on Pgp expression in PT-r cells at the molecular/cellular level. Immunohistochemistry, utilizing three murine monoclonal antibodies (MAbs)--C494, JSB-1, and C219--which recognize spatially distinct cytoplasmic epitopes of Pgp, revealed strong immunoreactivity in PT-r cells, normal parathyroid, and parathyroid hyperplasia, and weak immunostaining in parathyroid adenomas. BPE-1 cells, endothelial cells, and parathyroid carcinoma were negative. PT-r cells showed a single 130 kDa band (120 KDa after glycosidase treatment) on Western blot and a 4.6 kb transcript on Northern analysis, consistent with Pgp. Western and Northern blot analysis of PTr cells cultured in different eCa concentrations showed that eCa up-regulated Pgp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Relaxin-induced increased coronary flow through stimulation of nitric oxide production.

1. Relaxin (RLX) is a multifunctional hormone which, besides its role in pregnancy and parturition, has also been shown to influence the cardiovascular system. In this study, we investigated the effect of RLX on coronary flow of rat and guinea-pig hearts, isolated and perfused in a Langendorff apparatus. RLX was either added to the perfusion fluid at a concentration of 5 x 10(-9) M for a 20-min perfusion, or given as a bolus into the aortic cannula at concentrations of 10(-9) M, 5 x 10(-8) M dissolved in 1 ml of perfusion fluid. 2. RLX, given either for a 20-min perfusion or as a bolus in the aortic cannula to guinea-pig and rat isolated hearts, increased the coronary flow and the amount of nitrite, a stable end-product of nitric oxide (NO) metabolism, that appeared in the perfusates in a concentration-dependent fashion. 3. The increase in coronary flow and in nitrite in the perfusates induced by RLX was significantly reduced by pretreatment with the nitric oxide synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA, 10(-4) M). 4. The effects of RLX on coronary flow and nitrite amounts in the perfusates were compared with those induced by the endothelium-dependent vasodilator agent, acetylcholine (ACh, 10(-8)-10(-7) M), and by the endothelium-independent vasodilator agent, sodium nitroprusside (SNP, 10(-7)-10(-6) M). The results obtained show that RLX is more effective than ACh and SNP in increasing coronary flow. 5 The results of this study show that RLX increases coronary flow through stimulation of NO production; hence this hormone should be regarded as a novel agent capable of improving myocardial perfusion.

Acetylcholine↗
PubMed1995

Relaxin depresses platelet aggregation: in vitro studies on isolated human and rabbit platelets.

BACKGROUND: Relaxin, a peptide hormone of ovarian origin, has been shown to cause a striking dilatory action on microvessels in different organs. In our recent studies, relaxin has been shown to stimulate the production of nitric oxide, a powerful vasodilatory agent, in several targets. Nitric oxide also inhibits platelet aggregation. This prompted us to search for a role of relaxin in platelet function. EXPERIMENTAL DESIGN: The effect of relaxin on platelet aggregation was studied in isolated human and rabbit platelets. The samples were incubated with relaxin at different concentrations and then stimulated with collagen or thrombin. Aggregation and intracellular levels of cGMP and Ca2+ were determined. In some experiments, inhibitors or potentiators of nitric oxide activity were also used to clarify whether the mechanism of action of relaxin involves the L-arginine-nitric-oxide pathway. Electron microscopy of platelets treated and not treated with relaxin was also carried out. RESULTS: Preincubation of the platelets with relaxin before stimulation with proaggregants resulted in a significant, concentration-dependent inhibition of platelet aggregation, accompanied by an elevation of intraplatelet cGMP and a decrease in the rise of cytosolic Ca2+ levels. The effect of relaxin appeared to be mediated through nitric oxide. Ultrastructurally, relaxin was shown to hinder the conformational changes and granule exocytosis usually occurring in platelets during aggregation. CONCLUSIONS: This newly recognized antiaggregatory property of relaxin, together with the vasodilatory and hypotensive activities of the peptide demonstrated in previous studies, allows for this hormone to be regarded as a protective agent against thrombotic and hypertensive disorders of pregnancy and cardiovascular diseases.

Adult↗
PubMed1994

Relaxin influences growth, differentiation and cell-cell adhesion of human breast-cancer cells in culture.

The effects of different concentrations of relaxin (RLX) on growth and differentiation of a human breast-cancer cell line (MCF-7) have been studied after various times of exposure. The cells were cultured for 4 and 7 days in the absence (control) and the presence of highly purified porcine RLX at concentrations of 10(-9) M and 10(-6) M. (3H)-Thymidine uptake assay was used to evaluate cell proliferation. Electron microscopy and immunocytochemistry for the cell-cell adhesion molecule E-cadherin were carried out to evaluate cell differentiation. Analysis of DNA changes associated with apoptosis was performed to clarify whether RLX induces active cell death in the MCF-7 cells. The findings obtained show that RLX, when applied at micromolar concentrations, or even at nanomolar concentrations for long exposure times, suppresses proliferation, stimulates differentiation, and enhances expression of the surface molecule E-cadherin. Growth inhibition is not accompanied by apoptosis. The results of this study show that RLX can be recognized as a novel agent active in influencing growth and differentiation of MCF-7 breast-cancer cells. When applied at appropriate concentrations and exposure times, the peptide has a growth-inhibitory action, thus reversing the growth-stimulatory effect exerted at low concentrations for short exposure times, and promotes differentiation and cell-cell adhesion. These last-mentioned properties might result in a decrease in invasiveness of breast adenocarcinoma cells.

Adenocarcinoma↗
PubMed1994

Effects of portacaval anastomosis on pancreatic islets of the rat.

The pancreatic islets of rats with surgically constructed end-to-side portacaval anastomosis were studied immunocytochemically, morphometrically, and ultrastructurally, and the plasma levels of glucose, insulin, and glucagon determined. The results of the current study show that, four weeks after surgery, hypoglycemia, normal insulinemia, and hyperglucagonemia occur and that these hematologic changes are associated with immunocytochemical and ultrastructural signs of impairment of the secretory activity of islet B cells and normal secretion pattern of the remaining islet cell types. The causes and the meaning of the hematologic and islet cell changes are discussed, and the hypothesis has been drawn that they are primarily related to the functional deterioration of the liver, which follows the diversion of the portal blood in the systemic circulation.

Animals↗
PubMed1994

Spontaneous in vitro differentiation of a myoepithelial cell line (PA 16/23) from a pleomorphic adenoma of the parotid gland is associated with reduced production of the autocrine growth factor interleukin 6.

A myoepithelial cell line (PA 16/23) was derived from a pleomorphic adenoma of the parotid gland. PA 16/23 cells have light microscopic, immunophenotypical and ultrastructural features of immature myoepithelial cells, i.e. they are of fusiform or stellate shape and show keratin and actin cytofilaments located mainly in the perinuclear cytoplasm, desmosomes and tracts of basal lamina. The PA 16/23 cells grew actively and expressed mRNA for and produced interleukin 6 (IL-6) which was released into the culture medium. This cytokine, in turn, acted as an autocrine growth factor on the cells. PA 16/23 cells also expressed high-affinity IL-6 receptors. In these cells, both IL-6 production and proliferation could be modulated by exogenous stimulants, such as IL-6 itself, IL-1, IL-4, tumour necrosis factor alpha, interferon gamma and lipopolysaccharide. From the 40th culture passage onwards, the PA 16/23 cells ceased to grow, either spontaneously or in response to exogenous stimulants. Moreover, they strongly reduced IL-6 production, and underwent morphological differentiation into more mature myoepithelial cells, with an increased amount and a different arrangement of the keratin and actin cytofilaments, which formed thick bundles in the peripheral cytoplasm. These findings suggest a role for IL-6 in modulating the proliferation and, possibly, the differentiation of the PA 16/23 cells.

Actins↗
PubMed1994

Differentiation of breast cancer cells in vitro is promoted by the concurrent influence of myoepithelial cells and relaxin.

Our previous studies showed that relaxin promotes differentiation of MCF-7 breast adenocarcinoma cells. In the current investigation, we aimed to elucidate whether the effect of the hormone is potentiated when MCF-7 cells are grown together with myoepithelial cells, thus creating a microenvironment reminiscent of the organised tissue architecture of the mammary parenchyma in vivo. The findings obtained reveal that most MCF-7 cells cultured alone have an undifferentiated, blast-like phenotype, only a minority showing a more differentiated phenotype with more organelles and rudimentary intercellular junctions. When co-cultured with myoepithelial cells more MCF-7 cells acquire ultrastructural features consistent with a more differentiated phenotype, such as a rich organellular complement, apical microvilli and intercellular junctions. When relaxin was added to the co-cultures, the ultrastructural signs of differentiation could be observed in even more MCF-7 cells and became more pronounced than in the absence of the hormone, judged by the appearance of a clear-cut polarisation of cytoplasmic organelles, an almost continuous coat of apical microvilli and numerous intracellular pseudolumina.

Adenocarcinoma↗
PubMed1994

Effects of relaxin on mast cells. In vitro and in vivo studies in rats and guinea pigs.

The results of the current study demonstrate that relaxin inhibits histamine release by mast cells. This effect is related to the peptide concentrations, and could be observed in both isolated rat serosal mast cells stimulated with compound 48/80 or calcium ionophore A 23187, and in serosal mast cells isolated from sensitized guinea pigs and challenged with the antigen. The morphological findings agree with the functional data, revealing that relaxin attenuates calcium ionophore-induced granule exocytosis by isolated rat serosal mast cells. Similar effects of relaxin have also been recognized in vivo by light microscopic and densitometric analysis of the mesenteric mast cells of rats which received the hormone intraperitoneally 20 min before local treatment of the mesentery with calcium ionophore. Moreover, evidence is provided that relaxin stimulates endogenous production of nitric oxide and attenuates the rise of intracellular Ca2+ concentration induced by calcium ionophore. The experiments with drugs capable of influencing nitric oxide production also provide indirect evidence that the inhibiting effect of relaxin on mast cell histamine release is related to an increased generation of nitric oxide. It is suggested that relaxin may have a physiological role in modulating mast cell function through the L-arginine-nitric oxide pathway.

Animals↗
PubMed1994

Intraepithelial lymphocyte subpopulations and dendritic accessory cells in normal and hypertrophic adenoids.

The adenoids have been studied by immunocytochemistry and electron microscopy in children with and without adenoidal enlargement. Compared with normal adenoids, the enlarged ones showed a marked increase in the number of intraepithelial gamma-delta TCR+ lymphocytes and a slight increase in the number of intraepithelial CD8+ lymphocytes. This was accompanied by large amounts of dendritic human lymphocyte antigen (D related) (HLA-DR+) S-100+ accessory cells in the lymphoid tissue underlying the epithelium. By electron microscopy, dead epithelial cells apposed to intraepithelial lymphocytes, and clefts of the epithelial lamina, could be seen frequently in the enlarged adenoids, whereas, in the normal ones, they could not. Based on these findings, the hypothesis is drawn that imbalance of the system of the intraepithelial cytotoxic lymphocytes may lead to increased killing of epithelial cells and uncontrolled penetration of exogenous agents, and hence be involved in the pathogenesis of adenoidal hypertrophy.

Adenoids↗