Room-temperature conductance spectroscopy of CdSe quantum dots using a modified scanning force microscope.
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Journal Article↗
Biomedical subjects
I Rubinstein
Publications and source records attributed to I Rubinstein.
Neurotensin stimulates neutrophil adherence to bronchial epithelial cells in vitro.
Neutrophils and neuropeptides have both been implicated in airway inflammation. We hypothesized that neurotensin, a neuropeptide found in the airways, would stimulate neutrophil adherence to bronchial epithelial cells. Adherence was assessed using 51Cr-labelled human neutrophils added to confluent monolayers of bovine bronchial epithelial cells. Neurotensin added to bronchial epithelial cells produced a time-and concentration-dependent increase in adherence which was maximal at 4 h and 10(-10)M (17.6 +/- 1.4% vs. 6.1 +/- 0.4%, p < 0.01). Conversely, neurotensin stimulation of neutrophils induced a concentration-dependent and rapid ( < 5 min) increase in adherence which was also maximal at 10(-10)M (27.1 +/- 1.9% vs. 10.1 +/- 1.4%, p < 0.01). The effects were reproduced by the carboxy portion of the molecule. Anti-CD11a, -CD11b or -ICAM-1 antibodies significantly decreased the neurotensin-induced increase in adherence. These data suggest an important role for neurotensin in modulating airway inflammation.
Animals↗
Short-term exposure to lipopolysaccharide is associated with microvascular contractile dysfunction in vivo.
The purpose of this study was to determine whether short-term exposure of resistance arterioles to lipopolysaccharide in situ is associated with changes in vasomotor tone. Using intravital microscopy, we found that suffusion of Escherichia coli lipopolysaccharide (3 micrograms/ml) over hamster cheek pouch arterioles for 1 h was associated with a significant immediate biphasic response: vasoconstriction followed by vasodilation (p < 0.05). The former was attenuated by indomethacin, and the latter by SK&F 108566, a selective, non-peptide angiotension II receptor antagonist (p < 0.05). The nitric oxide synthase inhibitor, NG-L-nitro arginine, had no significant effects on lipopolysaccharide-induced responses. Allopurinol, a scavenger of reactive oxygen species, significantly attenuated lipopolysaccharide-induced vasodilation. Acetylcholine- and nitroglycerin-induced vasodilation were significantly potentiated after lipopolysaccharide. These responses were recorded in the absence of any significant changes in systemic arterial blood pressure. Collectively, these data suggest that short-term exposure of the peripheral microcirculation to lipopolysaccharide in situ is associated with an ischemia-reperfusion-like injury. These changes may contribute to end organ failure observed several hours after exposure to lipopolysaccharide.
Acrylates↗
Tissue angiotensin I-converting enzyme activity in aging hamsters with and without cardiomyopathy.
The purpose of this study was to determine tissue angiotensin I-converting enzyme (ACE) activity in aging hamsters with and without cardiomyopathy, and the factors that regulate its activity in vitro. We found that ACE activity was significantly increased in the heart and significantly decreased in the lung of aging hamsters with hereditary cardiomyopathy in comparison to age/genetically-matched controls (P < 0.05). Kidney and cheek pouch ACE activity was similar in both groups. Lisinopril inhibition curves of tissue ACE activity were similar in aging hamsters with and without cardiomyopathy. In both groups, tissue ACE activity was dependent on chloride anion concentration in the assay buffer. Substituting citrate for chloride abrogated, in part, this response. We conclude that cardiomyopathy is associated with significant changes in cardiac and lung ACE activity in aging hamsters in comparison to age/genetically-matched controls. However, regulation of tissue ACE activity in vitro is similar in both groups.
Aging↗
Encapsulation of vasoactive intestinal peptide into liposomes: effects on vasodilation in vivo.
The purpose of this study was to determine whether encapsulation of vasoactive intestinal peptide (VIP) into liposomes potentiated its vasorelaxant effects in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (53 +/- 1 microns) in the hamster cheek pouch before, during and after suffusion of VIP, liposomes and VIP encapsulated into liposomes for 7 min. We found that VIP (0.05, 0.1 & 1.0 nmol) induced significant, time- and concentration-dependent vasodilation (9 +/- 1%, 13 +/- 3% and 14 +/- 1% increase from baseline values, respectively; mean +/- SEM; n = 12; p < 0.05). Arteriolar diameter returned to baseline values within 1-4 min after suffusion was stopped. These effects were significantly potentiated when VIP (0.05, 0.1 & 1.0 nmol) was encapsulated into liposomes (26 +/- 6%, 38 +/- 7% and 34 +/- 3% increase from baseline values, respectively; n = 12; p < 0.05). In addition, arteriolar diameter returned to baseline values 5-13 min after suffusion was stopped. Suffusion of liposomes alone had no significant effects on arteriolar diameter (n = 12; p > 0.5). We conclude that encapsulation of VIP into liposomes potentiates and prolongs of its vasorelaxant effects in the peripheral microcirculation in vivo.
Acetylcholine↗
Impaired nasal mucociliary clearance in long-distance runners.
For years physicians have observed a high incidence of upper respiratory tract infections (URTI) after strenuous exercise. Mucosal surfaces represent a first-line-of-defense against infections, and pollutants or organisms entrapped in respiratory secretions are cleared by mucociliary transport. Little is known about this mechanism during exercise. The purpose of this study was to examine the nasal mucociliary clearance (MMCC) in amateur runners competing in a marathon race. Twelve amateur runners entered in an inner-city marathon race and 10 healthy sedentary subjects participated in the study. On the day of the race the outside temperature was 3 degrees C. Nasal mucociliary transit time (NMTT) was measured daily for 1 week before and 1 week after the race by the saccharin sodium/indigo carmine method. Nasal tissue biopsies were taken, and cilia beat frequency (CBF) was measured as viability and function of ciliated epithelial cells were determined. NMTT was significantly prolonged after the race (17.1 +/- 1.2 min vs 8.9 +/- 0.9 min; athletes vs control group; mean +/- SEM) and returned to baseline over several days. CBF was significantly reduced only in the first 24 hours after the race (7.31 +/- 0.65 Hz for athletes vs 9.94 +/- 0.45 Hz, controls. After the race, athletes showed a higher percentage of ciliated cells with immotile cilia (37.1 +/- 1.3% vs 27.8 +/- 1.1%, athletes vs controls) or dead ciliated cells (7.3 +/- 0.9% vs 4.1 +/- 0.8%). The findings suggest impairment of NMCC up to several days after strenuous exercise, which might be partially caused by abnormally functioning ciliated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The stable VIP analogue, Ro 24-9981, potentiates bradykinin-induced increases in clearance of macromolecules.
The purpose of this study was to determine whether the stable cyclic peptide analogue of human vasoactive intestinal peptide, Ro 24-9981, modulates bradykinin-induced plasma exudation in the oral mucosa and if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that suffusion of Ro 24-9981 had no significant effects on leaky site formation and clearance of fluorescein-isothiocyanate-dextran (mol mass 70 kDa) in the hamster cheek pouch. However, Ro 24-9981 significantly potentiated bradykinin-induced increases in leaky site formation and clearance of fluorescein-isothiocyanate-dextran (P < 0.05). These effects were specific because Ro 24-9981 had no significant effects on adenosine and calcium ionophore A23187-induced increases in leaky site formation and clearance of fluorescein-isothiocyanate-dextran. Furthermore, they were not mediated by cyclooxygenase products of arachidonic acid metabolism because indomethacin was ineffective. NG-nitro-L-arginine methyl ester, a selective inhibitor of nitric oxide synthase, but not NG-nitro-D-arginine methyl ester, significantly attenuated the effects of both bradykinin and Ro 24-9981 with bradykinin (P < 0.05). These responses were restored by L-arginine but not D-arginine. Collectively, these data indicate that bradykinin-induced plasma exudation in the oral mucosa was potentiated by Ro 24-9981 in a specific receptor-mediated fashion. These responses were mediated, in part, by the L-arginine/nitric oxide biosynthetic pathway.
Adenosine↗
TNF-alpha and IL-1 beta upregulate nitric oxide-dependent ciliary motility in bovine airway epithelium.
Airway epithelial cells can be modulated by cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta that are released from inflammatory cells. Since ciliary motility is an important host defense function of airway epithelium, we hypothesized that cytokines, released from lung macrophages, upregulate ciliary motility. To test this hypothesis, ciliary beat frequency (CBF) was measured by video microscopy in cultured ciliated bovine bronchial epithelial cells (BBECs) incubated for 24 h with bovine alveolar macrophage-conditioned medium (AM-CM). Exposure to AM-CM resulted in a delayed (> or = 2 h) increase in CBF that was maximal after 24 h exposure (13.70 +/- 0.43 for AM-CM vs. 9.44 +/- 0.24 Hz for medium; P < 0.0001) and which was largely blocked by either anti-TNF-alpha or anti-IL-1 beta antibodies. rTNF-alpha or rIL-1 beta similarly increased CBF, which could be blocked by preincubation with either anti-rTNF-alpha or anti-rIL-1 beta antibodies. Preincubation of BBECs with actinomycin D or dexamethasone also blocked rTNF-alpha- and rIL-1 beta-induced cilia stimulation, suggesting that new protein synthesis is required for cytokine-induced upregulation of CBF. Since NO is known to upregulate ciliary motility and cytokines can induce NO synthase (NOS), we hypothesized that TNF-alpha and IL-1 beta increase CBF by inducing NOS in BBECs. The cilia stimulatory effects of TNF-alpha or IL-1 beta were inhibited by NG-monomethyl-L-arginine, a competitive NOS inhibitor, and restored by the addition of either L-arginine, an NOS substrate, or sodium nitroprusside, an NO donor.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Oxidoreductases↗
Neutral endopeptidase modulates substance P-induced vasodilation in vivo.
The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44-70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1-9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.
Animals↗
Stable VIP analogue Ro-24-9981 potentiates substance P-induced plasma exudation in hamster cheek pouch.
The purpose of this study was to determine whether vasoactive intestinal peptide (VIP; 300 nM) and a stable cyclic analogue of VIP, Ro-24-9981 (226 nM), modulated neurogenic plasma exudation in the oral cavity in situ and, if so, to determine the mechanisms that mediated these responses. With the use of intravital microscopy, we found that suffusion of substance P induced a significant concentration-dependent formation of fluorescein-isothiocyanate-dextran (mol wt 70 kDa) leaky sites in the hamster cheek pouch (P < 0.05). These effects were significantly and stereospecifically attenuated by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, and restored by L-arginine, the substrate for NO synthase (P < 0.05). Topical application of human VIP and Ro-24-9981 had no significant effects of leaky site formation. In addition, human VIP had no significant effects on substance P-induced responses. By contrast, Ro-24-9981 significantly potentiated substance P- and capsaicin-induced leaky site formation (P < 0.05). The effects of Ro-24-9981 on substance P-induced responses were significantly attenuated by NG-nitro-L-arginine methyl ester and restored by L-arginine (P < 0.05). Indomethacin had no significant effects on Ro-24-9981-induced responses. Ro-24-9981 had no significant effects on adenosine- and calcium ionophore A-23187-induced leaky site formation. Collectively, these data suggest that VIP plays no significant role in modulating neurogenic plasma exudation in the oral mucosa. By contrast, Ro-24-9981 amplified this response in a specific receptor-mediated fashion.
Animals↗
Differential expression of annexins I and II in bovine bronchial epithelial cells.
Annexins I and II have been proposed to participate in regulation of inflammation and cell proliferation. In the present study, we examined the expression of annexins I and II in various levels of the bovine respiratory tract and in cultured bovine bronchial epithelial cells. Immunoblot analysis of whole-tissue extracts revealed low-level expression of annexins I and II in bronchial mucosa mainstem to fourth generation. In contrast, high levels of annexins I and II (15- to 20-fold higher than in the bronchial mucosa) were seen in the distal lung parenchyma. Immunohistochemical staining of tracheobronchial tissue sections with anti-annexin I antibody revealed an uneven positive reaction of about 30 to 40% of the columnar differentiated ciliated and secretory cells, with no obvious positivity within the nondifferentiated basal epithelial cell layer. In contrast, anti-annexin II antibody reacted nearly uniformly within the basal cell layer, with no obvious decoration of the differentiated cell types. These results were confirmed by immunoblot analysis of annexin I and II in density fractionated populations of basal and secretory/ciliated epithelial cells. Both annexins I and II were expressed at constitutive levels in bovine bronchial epithelial cells grown in glucocorticoid- and serum-free medium, and dexamethasone increased expression of both proteins in a concentration-dependent manner. We conclude that annexins I and II are differentially expressed in the differentiated ciliated cells and undifferentiated basal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Nasal inflammation in patients with obstructive sleep apnea.
The purpose of this study was to determine whether nasal inflammation is present in patients with obstructive sleep apnea (OSA). The number of polymorphonuclear leukocytes (PMNs) and the concentrations of bradykinin and vasoactive intestinal peptide (VIP) were quantified in nasal lavage fluid of eight nonsmoking patients with OSA and in six matched controls before sleep and the next morning. The total number of cells and the percentage of PMNs was significantly higher in patients with OSA in comparison to controls before and after sleep (P < .05). Likewise, bradykinin and VIP concentrations were significantly higher in patients with OSA in comparison to controls before and after sleep (P < .05). These findings indicate that nasal inflammation is present in patients with OSA. We suggest that nasal inflammation plays a role in upper airway obstruction in OSA.
Adult↗
Phagocytosis and oxidative burst of blood phagocytes in chronic obstructive airway disease.
Acute diseases and chronic conditions might be associated with altered blood neutrophil functions. The aim of this study was to investigate teh effects of stable chronic obstructive pulmonary disease (COPD) and superimposed acute bacterial bronchopneumonia (ABP) on the phagocytosis and oxidative metabolism of blood phagocytes. The 129 participants were assigned to 6 groups: group 1, healthy controls; group 2, previously healthy controls with ABP; group 3, patients with stable COPD on inhaled corticosteroids (IC); group 4, individuals with stable COPD on IC and ABP; group 5, patients with stable COPD requiring oral corticosteroids (OC); group 6, individuals with COPD on OC and ABP. Phagocytosis and oxidative burst was measured. Both tests showed a significant difference between the groups without acute infection when compared to the patients with ABP. No differences were observed between patients with stable COPD without ABP (groups 3 and 5) and group 1. The number of phagocytized E. coli/cell was 9.1 +/- 0.37, 7.9 +/- 0.27 and 8 .2 +/- 0.28 (groups 2, 4, and 6, respectively) reversed the observed changes. We conclude, that acute bacterial bronchopneumonia is associated with an impairment of phagocytosis and oxidative metabolism in blood. We suggest, that stable COPD has no influence on phagocytosis and oxidative burst.
Acute Disease↗
Phagocytosis and oxidative burst of granulocytes in the upper respiratory tract in chronic and acute inflammation.
Acute diseases and chronic conditions may be associated with altered neutrophil functions. The aim of this investigation was to study the number and function of granulocytes in the upper respiratory tract in acute and chronic airway inflammation. The 136 participating subjects were assigned to 6 groups; group 1: controls; group 2: smokers, < 10 cigarettes/day; group 3: smokers, > 10 cigarettes/day; group 4: patients with allergic rhinitis; group 5: patients with obstructive sleep apnea; group 6: patients with acute viral upper respiratory tract infection. Whole blood and nasal lavage fluid were obtained and a cell count was performed. Phagocytosis of opsonized bacteria and the oxidative burst was measured. Total cell counts and absolute number of neutrophils in nasal lavage (NAL), but not in blood, were elevated in all groups compared to controls. Highest increases of neutrophils were observed in group 4 (7-fold) and group 6 (25-fold), p < .01. Phagocytosis and oxidative burst of granulocytes recovered by NAL were found to be increased in group 4 (25% and 15%, respectively) and group 6 (35% and 21%) only, but decreased in the other groups. We conclude that conditions leading to acute or chronic inflammation in the upper respiratory tract are associated with altered functions of granulocytes recovered by NAL but not blood, suggesting local modulating factors. We speculate that chronic inflammation, in contrast to acute conditions, is associated with impaired granulocyte function.
Adult↗
L-arginine dilates cheek pouch arterioles in hamsters with hereditary cardiomyopathy but not in controls.
The purpose of this study was to determine whether suffusion of L-arginine alone induces vasodilation in the cheek pouch of hamsters with hereditary cardiomyopathy in comparison with controls, and whether these effects are mediated by the L-arginine/nitric oxide biosynthetic pathway. Using intravital microscopy, we found that suffusion of L-arginine for 20 minutes induced a significant, stereospecific concentration-dependent vasodilation in hamsters with hereditary cardiomyopathy but not in controls (p < 0.05). These responses were abrogated by suffusion of the nitric synthase inhibitor NG-L-arginine methyl ester (L-NAME) but not by suffusion of D-NAME. Suffusion of nitroglycerin, a nitric oxide donor, induced significant vasodilation of similar magnitude in both groups (p < 0.05). L-NAME had no significant effects on nitroglycerin-induced responses in both groups. We conclude that direct application of L-arginine alone to the peripheral microcirculation in cardiomyopathy induces significant vasodilation that is mediated, most likely, via a nitric oxide-dependent mechanisms(s). We suggest that a reversible, L-arginine-responsive impairment in the constitutive L-arginine/nitric oxide biosynthetic pathway is present in the peripheral microcirculation in cardiomyopathy.
Animals↗
[Stereology of the human epididymis in different groups of age: fetus, children, adolescents and elderly].
The importance of abnormalities of function and epididymis structure in the etiology of male infertility is still not well understood. We studied 52 individuals distributed in five age groups: fetuses, children, adolescents, adults and the elderly. The region of the body of epididymis was obtained by autopsy and immediately fixed by immersion in a solution of 10% buffered formaldehyde, embedded in paraffin and histologically prepared. The samples were observed under an optic microscope. Test-points were counted in 12 random microscopic fields with the M42 test-system. The following stereological parameters were determined: ductal area, volumetric densities (Vv) of the duct, smooth muscle, connective tissue, epithelial duct and blood vessels. The main results distinguished by those whose averages were statistically significant (p < 0.05), showed that the ductal area is 9.7 times greater in the adolescent/adult/elderly group than the children's group. The Vv of the lumen of the epididymis duct occupies 11.7% of the epididymis body in the fetal period, 5.3% in the child and in individuals after puberty this figures reaches more than 15%. The Vv of smooth muscle occupies 28.3% of the body of the epididymis in the fetus and 35.9% in children, but after puberty this figures stays around 22%. The Vv of the connective tissue occupies 26% in prenatal life, 37% in children, and after puberty these figures range from 21 to 27.5%. Comparing the results of the adult group with that of the elderly group there is an increase in the volumetric density of the connective tissue by 18.1%. In conclusion, the epididymal duct area and the Vv of the ductal lumen, smooth muscle and connective tissue were significant comparing the different groups. However, the quantitative relative differences of the duct's epithelium and the blood vessels were not significant comparing these groups. The study of quantitative aspects of the normal human epididymis can increase our knowledge about male fertility.
Adolescent↗
Differential effect of endothelin-1 on renal regional blood flow: role of nitric oxide.
This study evaluated the effects of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively) and the interactions with other local vasoactive systems in the regulation of renal regional blood flow. CBF and MBF were measured simulataneously by laser-Doppler flowmetry in anesthetized Wistar rats. Administration of ET-1 (1.0 nmol/kg, i.v.) produced a decrease in CBF (delta = -20%) and at the same time increased MBF (delta = +24%). In the presence of nitric oxide (NO) blockade by L-NAME, the vasodilatory effect of ET-1 on MBF was completely blocked and actually reversed (delta = -19%), whereas the cortical vasconstrictor effect was potentiated (delta = -31%). Cycloxygenase inhibition with indomethacin attenuated the vasodilator effect of ET-1 on MBF (delta = +12%) but did not affect the changes in CBF. Therefore, ET-1 exerts a differential effect on intrarenal regional blood flow, i.e., a decrease in CBF and an increase in MBF. The medullary vasodilator action of the peptide is dependent on an intact NO system and, to a lesser extent, on prostaglandin synthesis.
Animals↗
Substance P increases neutrophil adhesion to bronchial epithelial cells.
Polymorphonuclear neutrophils (PMNs) accumulate within the airways during acute and chronic bronchitis and can adhere to bronchial epithelium. Substance P (SP), a neuropeptide released from the primary afferent nerve endings, has been shown to have a proinflammatory effect on PMNs. To test the hypothesis that SP could modulate PMN bronchial epithelial cell adherence, bovine bronchial epithelial cells (BBECs) were isolated and cultured, and the capacity of SP to modulate PMN-BBEC adherence was evaluated. SP interacted with BBECs to induce an increase in PMN adhesion (14.7 +/- 1.2% vs 5.3 +/- 0.7% adherence, p < 0.01). The effect of SP was both time- and dose-dependent with maximal responses at 6 h and 10(-10) M. The effect was reproduced by the carboxyl-terminal sequence of the molecule (SP 6-11). Importantly, pretreatment of the BBECs with the tachykinin SP receptor (NK1) antagonist, CP-96,345, significantly reduced the increase in adhesion induced by SP (p < 0.01). Furthermore, treatment of the BBECs with antibodies against CD11a (LFA-1), CD11b (MAC-1), or ICAM-1 significantly decreased SP-induced adherence (p < 0.01 all comparisons). Conversely, SP stimulation of PMN induced a dose-dependent, rapid (within 5 min) increase in adherence. This effect was also mediated by the carboxy end of the molecule and was decreased by CP-96,345, again suggesting that this effect was NK1 mediated. These data demonstrate the SP has the capacity for modulating PMN-BBEC interactions and suggest an important role for SP in modulating airway inflammation.
Animals↗