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Biomedical subjects

I Rubinstein

Publications and source records attributed to I Rubinstein.

At least 73 records · Page 4Linked to original sources
PubMed1997

Purified ACE attenuates smokeless tobacco-induced increase in macromolecular efflux from the oral mucosa.

The purpose of this study was to determine whether purified angiotensin I-converting enzyme (ACE) attenuates smokeless tobacco extract (STE)-induced increase in macromolecular efflux from the in situ oral mucosa. By using intravital microscopy, we found that suffusion of an aqueous extract of smokeless tobacco elicited significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass, 70 kDa) from the hamster cheek pouch (P < 0.05). Suffusion of purified rabbit lung ACE significantly attenuated these responses in a concentration-dependent fashion (P < 0.05). These effects were specific because purified ACE also significantly attenuated the increase in macromolecular efflux elicited by bradykinin, which is produced in the cheek pouch during suffusion of STE, but did not attenuate the increase elicited by adenosine. Moreover, suffusion of heat-inactivated purified ACE and purified superoxide dismutase had no significant effects on STE- and bradykinin-induced responses. Collectively, these data suggest that exogenous ACE attenuates STE-induced increase in macromolecular efflux from the in situ oral mucosa, in part, by promoting local bradykinin catabolism.

Animals↗
PubMed1997

Initial characterization of hamsters with spontaneous hypertension.

The purpose of this study was to begin to characterize a new inbred strain of adult male hamsters with established spontaneous hypertension along with their genetically/age-matched normotensive controls. We found that mean arterial pressure was 162+/-3 mm Hg in hypertensive hamsters and 94+/-4 mm Hg in controls (mean+/-SEM; P<.05). Body weight was significantly lower in hypertensive hamsters relative to normotensive hamsters (P<.05). Hypertension was associated with a significant increase in heart weight, thickness of the left ventricular wall, and amplitude of the QRS complex in standard electrocardiographic leads I and aVR (P<.05). No gross or microscopic abnormalities were observed in other organs. Plasma renin activity and the number of circulating neutrophils were significantly increased in hypertensive hamsters relative to controls (P<.05). Serum concentrations of creatinine, blood urea nitrogen, sodium, potassium, and calcium as well as urinalysis were similar in both groups. Overall, these data suggest that the spontaneously hypertensive hamster could be a suitable model for the study of spontaneous hypertension.

Animals↗
PubMed1997

Decrease in immunoreactive neutral endopeptidase in uvula epithelium of patients with obstructive sleep apnea.

The purpose of this study was to determine whether neutral endopeptidase (NEP; EC3.4.24.11) is decreased in the uvula epithelium of patients with obstructive sleep apnea (OSA). Tissues were obtained by uvulopharyngopalatoplasty in seven patients with moderate OSA and by autopsy in five individuals not known to have OSA. Using antisera to human NEP and immunoperoxidase staining, we found that NEP was localized in uvula epithelial cells of both patients with OSA and controls. However, there was a significant decrease in the number of epithelial cells staining for NEP in patients with OSA relative to controls (67 +/- 10 cells versus 261 +/- 33 cells, in 5 randomly selected high-power microscopic fields, respectively; mean +/- SEM; p < .05). The intensity of staining for NEP was similar in both groups. We conclude that immunoreactive NEP is significantly decreased in the uvula epithelium of patients with OSA.

Adult↗
PubMed1997

Exhaled pentane levels in acute asthma.

BACKGROUND: Exhaled pentane, a product of lipid peroxidation, has been proposed as an objective, nonspecific, and noninvasive marker of active inflammation. Reactive oxygen species, which elicit lipid peroxidation, are increased in asthma and contribute to airway dysfunction. OBJECTIVE: To determine whether exhaled pentane levels are increased in acute asthma, and whether they decrease once acute asthma subsides. METHODS: Expired air was collected through a mouthpiece into a pentane-impermeable collection bag from 12 patients (40+/-5 years; mean+/-SEM) presenting to the emergency department of the University of Illinois Hospital in Chicago with acute asthma. Exhaled air was also collected after discharge from the hospital once acute asthma subsided. Eleven patients with stable asthma (40+/-5 years) and 17 healthy volunteers (31+/-5 years) served as control subjects. Exhaled air and ambient room air were analyzed for pentane content by gas chromatography. Peak expiratory flow rates were determined in each subject. RESULTS: Peak expiratory flow rates were 202+/-29 L/min during acute asthma and 327+/-26 L/min once acute asthma subsided (p<0.05). Exhaled pentane levels were 8.4+/-2.9 nmol/L during acute asthma and decreased significantly to 3.5+/-0.5 nmol/L once acute asthma subsided (p<0.05). Exhaled pentane levels were similar in patients with stable asthma and normal control subjects (3.6+/-0.4 nmol/L and 2.6+/-0.2 nmol/L, respectively; p>0.05). No pentane was detected in ambient air. CONCLUSION: Exhaled pentane levels are increased in patients with acute asthma and decrease significantly once acute asthma subsides.

Acute Disease↗
PubMed1997

Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea.

BACKGROUND: Upper airway inflammation is present in patients with obstructive sleep apnea (OSA). OBJECTIVE: To determine whether exhaled pentane and nitric oxide (NO) levels, two nonspecific markers of inflammation, are increased in patients with OSA. METHODS: Exhaled nasal and oral pentane and NO levels were determined before and after sleep in 20 patients with OSA (apnea-hypopnea index, 48+/-7; mean+/-SEM) and eight healthy control subjects. RESULTS: In patients with OSA, exhaled nasal and oral pentane levels after sleep were significantly higher than presleep values (6.1+/-1.2 nM vs 3.4+/-0.4 nM, and 7.0+/-1.3 nM vs 4.2+/-0.4 nM, respectively; p<0.05). Likewise, exhaled nasal and oral NO levels after sleep were significantly higher than presleep values in patients with OSA (39.7+/-3.8 ppb vs 28.4+/-2.9 ppb and 10.9+/-1.5 ppb vs 6.6+/-0.8 ppb, respectively; p<0.05). By contrast, there were no significant differences in exhaled nasal and oral pentane, and nasal NO levels before and after sleep in control subjects. Exhaled oral NO levels were significantly increased after sleep in comparison to presleep values in control subjects (p<0.05). CONCLUSION: Exhaled nasal pentane and NO levels are increased after sleep in patients with moderate-severe OSA. These data suggest that upper airway inflammation is present in these patients after sleep.

Adult↗
PubMed1997

Management of shock and acute renal failure in casualties suffering from the crush syndrome.

Widespread muscle crush injury is often associated with profound hemodynamic shock and myoglobinuric acute renal failure (ARF). The main reason for the shock is rapid uptake by the injured muscles of a substantial portion of extracellular fluid. The shock is aggravated by NO-dependent vasodilation in the injured muscles and by hyperkalemia and hypocalcemia, which suppress the entire cardiovascular tree. Treatment consists of early massive volume replacement and forced alkaline solute (mannitol) diuresis. With this regimen it is possible to increase survival of life and limbs, and prevent myoglobinuric ARF. Our preliminary experience suggests that i.v. hypertonic mannitol is protective also to the injured muscle and can be used as a noninvasive adjunct in the management of compartment syndrome in man. Moreover, by preserving muscular integrity, mannitol can conceivable reduce leakage of the nephrotoxic myoglobin and urate and thus further defend kidney function.

Acute Kidney Injury↗
PubMed1996

Mechanisms of smokeless tobacco-induced oral mucosa inflammation: role of bradykinin.

The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) increases clearance of macromolecules from postcapillary venules in the in situ oral mucosa and, if so, whether bradykinin mediated this response. Using intravital microscopy, we found that 20-min suffusion of the extract elicited significant concentration-dependent leaky site formation and increase in clearance of FITC-dextran (molecular mass, 70 kDa) from the hamster cheek pouch (p < 0.05). These responses were associated with a significant increase in bradykinin-like immunoreactivity in the suffusate. Smokeless tobacco extract-induced leaky site formation and increase in clearance of FITC-dextran were significantly attenuated by NPC 17647 and Hoe 140 (p < 0.05), two bradykinin B2 receptor antagonists, but not by desArg9,[Leu8]bradykinin, a bradykinin B1 receptor antagonist. Both bradykinin B2 receptor antagonists had no significant effects on adenosine-induced responses. Indomethacin had no significant effects on smokeless tobacco extract-induced responses. Exposure to smokeless tobacco extract was associated with a significant decrease in angiotensin I-converting enzyme activity and a small, but significant, increase in neutral endopeptidase 24.11 activity in the cheek pouch, two peptidases widely distributed in the microcirculation that cleave and inactivate bradykinin (p < 0.05). Overall, these data suggest that smokeless tobacco elicits plasma exudation in the oral mucosa in vivo in a specific fashion, and that this response is mediated by bradykinin.

Animals↗
PubMed1996

Bosentan improves renal regional blood flow in rats with experimental congestive heart failure.

The effects of the mixed endothelin receptor antagonist bosentan on renal regional haemodynamics were investigated in rats with aorto-caval fistula, an experimental model of congestive heart failure. A matched group of normal rats served as control. Injection of bosentan (10 mg/kg i.v.) to the rats with decompensated congestive heart failure produced an increase in cortical (+20%) and medullary (+12%) blood flow, and a decrease in vascular resistance in the cortex (-30%) and medulla (-23%), while reducing mean arterial pressure by approximately 10 mm Hg. In rats with compensated congestive heart failure and in normal animals, infusion of bosentan did not affect blood pressure and cortical perfusion. These findings indicate that 1) endothelin receptor blockade produces beneficial effects on renal haemodynamics in rats with experimental congestive heart failure and 2) endothelin-1 may be involved in the pathogenesis of renal hypoperfusion only in decompensated congestive heart failure.

Animals↗
PubMed1996

Neutrophil chemotactic activity is increased in nasal secretions of long-distance runners.

For years physicians have observed a high incidence of infections after strenuous exercise. Recent observations suggest an increase of neutrophils in the upper airways following a long-distance race. In order to elucidate mechanisms responsible for the influx of neutrophils in airway mucosa, we tested neutrophil chemotactic activity (NCA) in nasal lavages of amateur runners. Thirty-six amateur runners entered in a marathon race (42.2 km) and 24 healthy sedentary subjects participated in the study. Nasal lavages (NAL) were performed several times before and after the race. The total number of recovered neutrophils was measured and the NCA was determined using a modified Boyden chamber. The number of PMNs in NAL of the runners immediately after the race was increased 2.7-fold (p < 0.01) compared to the values obtained on the same day prior to the race (128 +/- 19 vs. 48 +/- 16, x 10(3)), remained elevated several days after the race and returned to baseline after 1 week. The race resulted also in a 2.5-fold (p < 0.01) increase of NCA immediately after the competition compared to the pre-race values of the same day (78 +/- 5.2 cells/8 High Power Fields, HPF vs. 31 +/- 3.4 cells/8 HPF). The findings suggest that NCA might play an important role in attracting neutrophils to the airways. The nature and origin of NCA in airway secretions is presently not known.

Adult↗
PubMed1996

Inflammation in the uvula mucosa of patients with obstructive sleep apnea.

This study was conducted to determine whether inflammation is present in the uvula mucosa of patients with obstructive sleep apnea (OSA). Uvulas were obtained by uvulopalatopharyngoplasty in 21 patients with moderate OSA (mean apnea/hypopnea index and standard error of the mean: 32 +/- 4) and by autopsy in 5 individuals not known to have OSA. Using point counting in five randomly selected high-power microscopic fields (X100), the authors found that the number of leukocytes in the lamina propria of the uvula mucosa was significantly higher in patients with OSA than in the controls (179 +/- 12 cells vs. 71 +/- 4 cells, respectively; P < .05). This was due to a significant increase in the number of plasma cells in patients with OSA as compared with controls (89 +/- 15 cells vs. 21 +/- 5 cells, respectively; P < .05). The thickness of the lamina propria (an index of interstitial edema) was also significantly increased in patients with OSA compared with controls (0.99 +/- 0.12 mm vs. 0.27 +/- 0.02 mm, respectively; P < 0.05). The authors conclude that inflammation, characterized by plasma cell infiltration and interstitial edema, is present in the uvula mucosa of patients with moderate OSA. They also suggest that soft palate inflammation contributes to upper airway occlusion observed during sleep in these patients.

Adult↗
PubMed1996

Physician reporting of and referral for patient complaints about sleep disorders.

The first goal of this Nebraska-based study was to determine physician reporting of patient complaints about sleep. The second goal was to determine the patterns of referral to sleep disorders laboratories by geographic location and specialty practice. A total of 299 Nebraska physicians (177 in urban areas and 122 in rural areas) completed a questionnaire concerning sleep complaints among patients. We found no statistically significant differences between urban and rural physicians in the percentage of patients reporting insomnia, excessive daytime sleepiness, snoring, or other sleep complaints. Psychiatrists reported on significantly more patients with insomnia and excessive daytime sleepiness than did other physicians; however, they tended to refer fewer patients to sleep disorders laboratories than did physicians practicing internal medicine. Urban physicians referred significantly more patients to sleep disorders laboratories than did rural physicians. We concluded that physician reporting of patient complaints about sleep is similar in urban and rural areas of Nebraska. However, physicians in rural areas tend to refer fewer patients to sleep disorders laboratories than do physicians in urban communities.

Family Practice↗
PubMed1996

Encapsulation of VIP into liposomes restores vasorelaxation in hypertension in situ.

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) elicits vasodilation in the in situ peripheral microcirculation of hamsters with spontaneous hypertension and whether encapsulation of VIP into liposomes modulates this response. Using intravital microscopy, we found that suffusion of VIP (0.05 and 0.1 nmol) alone over cheek pouch resistance arterioles of normotensive hamsters elicited significant vasodilation that was potentiated and prolonged by encapsulation of the peptide into liposomes (P < 0.05). By contrast, VIP (0.5 and 0.1 nmol) had no significant effects on arteriolar diameter in hamsters with spontaneous hypertension. However, encapsulation of VIP into liposomes restored its vasorelaxant effects in hypertensive animals, although the duration of vasodilation was significantly shorter in comparison with controls (P < 0.05). Empty liposomes had no significant effects on arteriolar diameter in either group. These data indicate that VIP-induced vasodilation in the peripheral microcirculation in situ is impaired in essential hypertension and that encapsulation of VIP into liposomes restores, in part, this response.

Acetylcholine↗
PubMed1996

Neutral endopeptidase modulates VIP-induced vasodilation in hamster cheek pouch vessels in situ.

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) dilates resistance arterioles in the in situ systemic circulation and whether inhibitors of neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE), two membrane-bound metalloenzymes that are widely distributed in the microcirculation and cleave and inactive VIP, potentiate this response. Using intravital microscopy, we found that VIP (0.05 and 0.1 nmol) induced significant vasodilation in the hamster cheek pouch (13 +/- 1 and 20 +/- 2% increase from baseline, respectively; mean +/- SE; P < 0.05). These responses were significantly potentiated by topical application of phosphoramidon and thiorphan, two relatively selective NEP inhibitors, but not by captopril, a relatively selective ACE inhibitor. Furthermore, suffusion of a mixture of proteinase inhibitors consisting of leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid to inhibit serine proteinases, including mast cell tryptase, aminopeptidases, and carboxypeptidase N, respectively, had no significant effects on VIP-induced responses. These data indicate that VIP elicits vasodilation in the in situ systemic microcirculation and that NEP modulates this response.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Differential regulation of renal regional blood flow by endothelin-1.

The present study evaluated the effects and mechanisms of action of endothelin-1 (ET-1) on medullary and cortical blood flow (MBF and CBF, respectively). CBF and MBF were measured simultaneously by laser-Doppler flowmetry in anesthetized male Wistar rats. Bolus injection of ET-1 (1.0 nmol/kg iv) produced a sustained decrease in CBF (delta = -30%) and a transient increase in MBF (delta = +35%). The medullary vasodilation induced by ET-1 was observed with doses lower than that required to produce cortical vasoconstriction; was completely blocked by bosentan, a mixed ETA/B-receptor antagonist; and was mimicked by IRL-1620, a specific ETB-receptor agonist. In contrast, BQ-123, an ETA-receptor antagonist, failed to inhibit the ET-1-dependent medullary vasodilation but effectively blocked the cortical vasoconstriction induced by the peptide. Finally, inhibition of nitric oxide (NO) synthase completely abolished, whereas cylooxygenase inhibition attenuated, the effect of ET-1 on MBF. The data demonstrate that ET-1 exerts opposite effects on renal cortical and medullary circulation, i.e., ETA-receptor-mediated cortical vasoconstriction and ETB-mediated medullary vasodilation. Furthermore, the medullary vasodilation induced by ET-1 is dependent on the NO system and, to a lesser extent, on prostaglandin generation.

Animals↗
PubMed1996

Loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa.

The purpose of this study was to determine whether loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa in situ and, if so, to start to determine the mechanisms that mediated these responses. By using intravital microscopy, we found that bradykinin induced a significant concentration-dependent increase in fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) leaky site formation in the hamster cheek pouch. These responses were significantly attenuated by topical application of two structurally distinct loop diuretics, furosemide and ethacrynic acid, onto the cheek pouch (P < 0.05). Hydrochlorothiazide, a nonloop diuretic, had no significant effects on bradykinin-induced responses. Furosemide had no significant effects on adenosine-induced leaky site formation. Application of bradykinin after furosemide, but not after hydrochlorothiazide, was associated with a significant concentration-dependent decrease in bradykinin-like immunoreactivity in the cheek pouch suffusate (P < 0.05). Prostaglandins and changes in vasomotor tone did not modulate the effects of furosemide on bradykinin-induced responses. These data indicate that loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa in a specific fashion, probably by amplifying local bradykinin catabolism. We suggest that topical loop diuretics could be useful in the treatment of oral mucosa inflammation elicited by bradykinin.

Adenosine↗
PubMed1996

Aqueous smokeless tobacco extract impairs endothelium-dependent vasodilation in the oral mucosa.

The purpose of this study was to determine whether an aqueous extract of smokeless tobacco (moist snuff) modulates vasomotor tone in the oral mucosa in situ and, if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that the extract had no significant effects on diameter of resistance (second-order) arterioles [44 +/- 5 (SD) microns] in the hamster cheek pouch. However, it significantly attenuated vasodilation elicited by two endothelium-dependent agonists, acetylcholine and bradykinin (P < 0.05). These effects were specific because smokeless tobacco extract had no significant effects on vasodilation elicited by nitroglycerin, an endothelium-independent agonist. Indomethacin, a cyclooxygenase inhibitor, and SQ-29548, a thromboxane A2/prostaglandin H2-receptor antagonist, abrogated the attenuating effects of smokeless tobacco extract on acetylcholine- and bradykinin-induced vasodilation. These data indicate that an aqueous extract of smokeless tobacco impairs endothelium-dependent vasodilation in the oral mucosa in situ in a specific fashion and that these effects are mediated, in part, by cyclooxygenase products of arachidonic acid metabolism that stimulate thromboxane A2/prostaglandin H2 receptors.

Animals↗
PubMed1996

Measurement of exhaled nitric oxide by three different techniques.

The purpose of the study was to compare exhaled nitric oxide (NO) determined by three techniques. Ninety-one subjects performed a slow vital capacity maneuver: (1) through the mouth directly into a NO chemiluminescence analyzer (peak oral NO), (2) through the mouth into a collection bag (mean oral NO), and (3) through the nose into a collection bag (mean nasal NO). Peak oral NO was higher in patients with asthma (n = 18, 174.2 +/- 27.0 ppb), but lower in smokers (n = 36, 39.6 +/- 4.8 ppb) compared with nonsmoking control subjects (n = 23, 105.5 +/- 8.4 ppb, p < 0.05 both comparisons). Mean oral NO levels were significantly lower than peak oral NO levels (p < 0.05), but still higher in patients with asthma in comparison with nonsmoking healthy control subjects and asymptomatic smokers (27.2 +/- 3.5 versus 14.5 +/- 1.1 and 7.3 +/- 0.7 ppb, respectively, p < 0.05). In contrast, there was no significant difference in mean nasal NO levels between the three groups. Peak oral NO and mean oral NO levels correlated (r = 0.772, p < 0.0001). Determination of exhaled oral NO levels is qualitatively independent of the technique used, but nasal exhalation may affect NO determination in conditions associated with airway inflammation.

Adult↗