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N Stern

Publications and source records attributed to N Stern.

At least 55 records · Page 3Linked to original sources
PubMed1997

Role of the lipoxygenase pathway in angiotensin II-induced vasoconstriction in the human placenta.

We have previously shown that the vasopressor effect of angiotensin II (Ang II) is inhibited by lipoxygenase (LO) blockers. To elucidate the specific mechanism involved, we studied the relationship between the contractile effect of Ang II and LO products in a human placental preparation. In perfused placental cotyledons, Ang II (boluses of 1 to 10 microg) increased perfusion pressure and 12-hydroxyeicosatetraenoic acid (12-HETE) release. The LO blockers phenidone and n-propyl gallate reduced the maximal Ang II-induced increment in pressure from 26+/-3 to 16+/-3 and 18+/-4 mm Hg, respectively (P<.05 for both). Ang II alone (10 microg) increased 12-HETE release from 8.9+/-3.6 to 37.6+/-0.4 ng/min, and this rise was entirely blocked by both phenidone and n-propyl gallate. Pressure increase generated by an increase in flow rate had no effect on 12-HETE formation. In deendothelialized umbilical artery segments, Ang II (10(-7) mol/L) increased 12-HETE formation by 47+/-5% (n=20). In cultured umbilical artery smooth muscle cells, Ang II increased 12-HETE formation from 48.1+/-7.2 to 75.1+/-15.3 ng/mg protein, and this effect was also blocked by the specific LO inhibitor baicalein (10(-6) mol/L). These results provide evidence that the vasopressor effect of Ang II is functionally coupled to 12-LO activation, which apparently takes place in arterial smooth muscle cells.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

Platelet lipoxygenase in spontaneously hypertensive rats.

We have previously reported that the nonselective lipoxygenase inhibitor phenidone is a potent hypotensive agent in the spontaneously hypertensive rat (SHR). In the present study, we examined the relationship between production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) and intra-arterial blood pressure in SHR and Wistar-Kyoto rats (WKY) using both a cross-sectional analysis and an acute pharmacological intervention. Basal generation rate of 12-HETE by platelets collected from the SHR was approximately 3.7-fold higher than in the WKY (0.86 +/- 0.24 versus 0.23 +/- 0.05 nmol/mL per 10 minutes, respectively; P < .01). Systolic arterial pressure was positively related to platelet 12-HETE formation rate when the entire rat population was considered (r = .70, P < .001). The specific 12-lipoxygenase inhibitor cinnamyl-3,4-dihydroxycyanocinnamate induced lowering of both arterial blood pressure and platelet 12-lipoxygenase activity in SHR. At 15 mg/kg, cinnamyl-3,4-dihydroxycyanocinnamate elicited a marked hypotensive effect in SHR but not in WKY. This reduction in arterial pressure was accompanied by an approximate 70% inhibition in platelet 12-HETE production rate. The return of high blood pressure to basal levels was associated with a significant rise in the production of platelet 12-HETE toward control values (baseline, 0.97 +/- 0.33 nmol/mL per 10 minutes; nadir of blood pressure, 0.19 +/- 0.03; resumption of basal pressure, 0.42 +/- 0.14). In contrast, captopril (15 mg/kg) induced a quantitatively similar decrease in blood pressure but had no effect on platelet 12-HETE generation rate. Thus, hypertension in SHR is linked to increased production rate of platelet 12-HETE. Acute blood pressure reduction attained during lipoxygenase inhibition but not by angiotensin converting enzyme inhibition leads to a concomitant reduction in the production of platelet 12-HETE. We speculate that since rat arterial tissue produces 12-HETE, increased 12-lipoxygenase activity in SHR may contribute to the maintenance of elevated arterial pressure in this strain.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

Erectile dysfunction in hypertensive subjects. Assessment of potential determinants.

Hypertension is often cited as a risk factor for erectile dysfunction. To clarify the relation between hypertension and erectile dysfunction, we evaluated 32 consecutive hypertensive and 78 normotensive impotent men with respect to multiple potential determinants and parameters of erectile function, including medical and sexual history, depression, hormonal profile, penile nocturnal tumescence, penile vascular supply, and pudendal nerve conduction. The hypertensive men were older, had higher body mass index, and used more medications than the normotensive men. The groups were not different with respect to the prevalence of smoking and peripheral vascular disease, but the hypertensive men had a marginally higher rate of ischemic heart disease (P = .06). The prevalence of depression, abnormal nocturnal penile tumescence, anomalous pudendal nerve conduction, and impairment in arterial supply as determined by penile brachial index were similar in the two groups. Testosterone and bioavailable testosterone levels were lower in the hypertensive men. After stratification by age and body mass index, hypertensive men younger than 50 years with body mass index less than 30 kg/m2 had significantly lower testosterone levels (12.0 +/- 1.7 versus 21.3 +/- 1.4 nmol/L, P < .02) but not bioavailable testosterone levels (3.9 +/- 0.7 versus 6.4 +/- 0.7 nmol/L, P < .17) than the corresponding normotensive group. Prolactin, follicle-stimulating hormone, and luteinizing hormone levels of the two groups were not significantly different. Contrary to common belief and with the exception of lower circulating testosterone levels, the overall analysis showed little difference between hypertensive and normotensive men with respect to a wide range of classic determinants of erectile function. Direct study of the local vascular erectile apparatus appears necessary for further elucidation of the mechanisms underlying erectile dysfunction in hypertensive men.

Adult↗
PubMed1996

Tonic inhibition of renin secretion by the 12 lipoxygenase pathway: augmentation by high salt intake.

Recent evidence suggests that lipoxygenase (LO) metabolites inhibit renin production in vitro. However, the physiological significance of this effect has not been determined. This study examined the role of the LO pathway in the regulation of plasma renin concentration (PRC) in vivo. The acute administration of two structurally unrelated LO inhibitors, phenidone (30 and 60 mg/kg) and esculetin (60 mg/kg), resulted in suppression of platelet 12 hydroxyeicosatetraenoic acid (12HETE) production, reduction in systemic arterial pressure and a 2- to 3-fold increase in PRC. To determine whether the esculetin-induced increase in PRC was secondary to hypotension, esculetin was also administered to rats preinfused with a pressor dose of norepinephrine. In these acutely hypertensive rats, esculetin still induced a 2.5-fold increase in PRC, whereas blood pressure remained over 40 mm Hg above basal levels. Further, esculetin (10(-6)M) increased renin release in renal slices from 150 +/- 10 to 310 +/- 20 ng/ml.h (P < 0.05) and this rise was entirely blocked in the presence of 12HETE (10(-7)M; 130 +/- 40 ng/ml.h). In rats placed on high salt intake, 12HETE concentration in renal slices from the outer cortex was considerably higher than in renal slices from salt-restricted rats (116.5 +/- 15.7 vs. 65 +/- 12 pg/mg protein; P < 0.05). Chronic administration of the LO inhibitor phenidone also resulted in an increase of PRC, which was independent of changes in blood pressure. On either high salt (3.15%0 or low salt (0.05%) diet phenidone-treated rats had higher PRC levels than the respective control groups [high salt 9.7 +/- 3.5 vs. 1.9 +/- 1.4 ng/ml.h; P < 0.05; low salt 33.2 +/- 5.3 vs. 19.4 +/- 3.10 ng/ml.h; P < 0.05]. The finding that LO blockers are potent stimulators of PRC in vivo suggests the existence of a physiological tonic inhibition of renin secretion by LO products that is operative under a wide range of salt intake. High salt intake enhances this inhibitory tone by increasing renal cortical 12 LO activity and, in fact, normal suppression of PRC during high salt diet does not occur in LO-blocked animals. Thus, the LO pathway exerts a tonic inhibitory effect on renin release, which appears particularly important for renin suppression during high salt intake.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

Prosthodontics--from craft to science.

Prosthodontics has evolved slowly from being an ancient craft into a modern science. The literature of the ancient world is replete with dental references which provide insights into the way dentistry was once practiced. The scientific breakthroughs of the past century have most prominently accelerated dentistry's modernization. The dentistry of the past has paved the way to modern day dental science and treatment.

Esthetics, Dental↗
PubMed1995

A CAD/CAM system for the production of metal copings for porcelain-fused-to-metal restorations.

A computer-aided design and manufacture system for the production of metal copings for porcelain-fused-to-metal restorations is described and evaluated. The three stages of production: digitizing, mathematical processing, and milling are described, with emphasis on the system's ability to produce metal copings for both single-unit and multiple-unit restorations. Evaluation of the marginal fit of the produced copings demonstrates the potential for clinically acceptable results.

Analog-Digital Conversion↗
PubMed1995

The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases.

The role of the low dose (1 microgram) ACTH stimulation test in the evaluation of patients with pituitary diseases was systematically assessed by relating its results to those obtained on gold standard tests of hypothalamo-pituitary-adrenal (HPA) reserve, such as insulin-induced hypoglycemia or a metyrapone challenge. Ten patients with pituitary diseases (8 men and 2 women) and proven impairment of HPA function and 9 patients (5 men and 4 women) with similar pituitary pathologies but preserved HPA function were studied (pituitary controls). A group of 7 normal volunteers (3 men and 4 women) served as normal controls. None of the subjects was taking glucocorticoids on a chronic basis or had been taking any recently. All subjects underwent ACTH tests at 0800 h with 3 different levels of stimulation (1, 5, and 250 micrograms), and serum cortisol was assayed 0, 30, and 60 min after injection. A pass result was defined as a peak cortisol value of 497 nmol/L or more. Basal cortisol values were indistinguishable among the groups. Pituitary controls did not differ from normal controls for any of the challenges. In healthy controls, peak cortisol levels attained with the low dose stimulation were clearly lower than with the standard dose (670 +/- 39 vs. 919 +/- 50 nmol/L; P = 0.002). However, every normal control passed the low dose stimulation, whereas none of the patients with impaired HPA function did (P = 0.00005). Although the cortisol values achieved on the standard (250 micrograms) dose by the subjects with impaired HPA function were significantly lower than those in normal controls (P < 0.005), they were generally normal in absolute terms. Indeed, using the peak value criterion, 7 of these 10 patients would have qualified as pass on the 5-micrograms challenge, and 9 of 10 would have passed the 250-micrograms test. Thus, the low dose ACTH test appears to perform better than the standard pharmacological test. As we have shown that this test correlates well with reference tests of HPA function, it is suggested that it should replace the standard ACTH test in the diagnosis of secondary adrenal insufficiency.

Adrenocorticotropic Hormone↗
PubMed1995

Relative sparing of anterior pituitary function in patients with growth hormone-secreting macroadenomas: comparison with nonfunctioning macroadenomas.

Pre- and postoperative anterior pituitary function was assessed in 26 subjects with nonfunctioning macroadenoma (NFMA) and in 15 acromegalic subjects with macroadenomas. Preoperatively, NFMA patients had a higher prevalence of secondary hypogonadism (78% vs. 40%; P < 0.05), hypothyroidism (23% vs. 0%; P = 0.06), and hypoadrenalism (43% vs. 7%; P = 0.02) compared to individuals with GH-secreting macroadenoma (GHMA). Patients with NFMA also had a higher prevalence of more severe pituitary failure compared with acromegalic patients; 56% of the patients in this group had more than one pituitary hormone axis impaired compared to only 8% in the acromegalic group. These differences could not be accounted for by tumor grade and/or stage. Transsphenoidal pituitary surgery led to a significant improvement in anterior pituitary function in the NFMA group. Nevertheless, the prevalence of pituitary deficiency postoperatively was still significantly greater in NFMA patients than in the acromegalic group (68% vs. 17%, respectively; P < 0.04). The results suggest that anterior pituitary function is better preserved in GHMA than in NFMA and that this difference is independent of tumor size. The mechanism underlying the lower rate of hypopituitarism in acromegalics with macroadenomas remains to be elucidated.

Acromegaly↗
PubMed1994

Effect of impression materials and techniques on the marginal fit of metal castings.

The effect of two impression materials used in three different techniques was tested for the accuracy of the marginal fit of metal castings. Sixty identically prepared Ivorine teeth were divided into groups of 20. The following methods were selected to make impressions: (1) putty in a metal stock tray with simultaneous elastomeric impression wash, (2) copper band relined with autopolymerizing acrylic resin and subsequent light-body elastomeric impression material, and (3) copper bands with modeling compound. Faciolingual sections of the Ivorine teeth with cemented metal castings were examined by scanning electron microscopy (SEM) at x 100 magnification. Measurements of the thickness of cement layers were calculated both manually and by use of a recently developed computerized method. The differences in the gingival marginal gaps between various impression materials and techniques at both the facial and lingual surfaces were not statistically significant.

Acrylic Resins↗
PubMed1994

Dexamethasone enhances active cation transport in cultured aortic smooth muscle cells.

Previous studies have indicated that ouabain-sensitive cation transport is increased in arteries obtained from rats with glucocorticoid-induced hypertension. However, it remained unclear whether this effect reflected direct glucocorticoid activation or rather depended on the elevated arterial pressure per se. In the present study, we examined the effect of dexamethasone on cultured rat aortic smooth muscle cells. Dexamethasone (10(-9) mol/L) increased ouabain-sensitive 86Rb uptake by about 50% (control: 16.5 +/- 1.6 pmol/mg protein/10 min; dexamethasone 10(-9) mol/L: 24.4 +/- 1.3 pmol/mg protein/10 min). The effect was not apparent until 18 h of incubation and was partly inhibited by the mineralocorticoid antagonist spironolactone. Dexamethasone also increased membrane potential in these cells by an average of 9.5 mV (control: -43.3 +/- 4 mV; dexamethasone: -52.8 +/- 4 mV), presumably reflecting increased intracellular K+ activity as a result of dexamethasone's effect on the Na,K pump. These results suggest a direct effect of glucocorticoids on arterial Na,K pump. The physiopathological significance of this effect remains to be determined.

Aldosterone↗
PubMed1994

Assessment of 5 alpha-reductase activity in hirsute women: comparison of serum androstanediol glucuronide with urinary androsterone and aetiocholanolone excretion.

OBJECTIVE: Recent evidence suggests that androstanediol glucuronide (AG), a metabolite of dihydrotestosterone (DHT) formed in skin, is frequently elevated in hirsute women, presumably reflecting enhanced 5 alpha-reductase activity. An alternative method of demonstrating 5 alpha-reductase activity is the androsterone (A)/aetiocholanolone (E) ratio in urine. A and E are the 5 alpha- and 5 beta-reduced metabolites, respectively, of androstenedione, which is the principal metabolite of dehydroepiandrosterone (D). Although serum AG and the urinary A/E ratio have both been considered valid methods for assessing 5 alpha-reductase activity, the two have not been previously compared in hirsute women. The present study was undertaken to assess 5 alpha-reductase activity in hirsute patients as determined by these two different methods. PATIENTS AND MEASUREMENTS: We surveyed 47 untreated women (ages 17-33) with various degrees of hirsutism. Serum testosterone, bioavailable testosterone, dehydroepiandrosterone sulphate, and AG were determined. Additionally, A, E and D were measured in 24-hour collections of urine. RESULTS: For the 47 women, 37 had elevated blood levels of AG (17.4 +/- 2.2, mean +/- SEM; normal < 8 nmol/l), but only 18 of these had an increased urinary A/E ratio (> 1.5). All but one of the remainder had elevated urinary and/or serum androgen levels. Overall, no significant correlation between AG and A/E was observed. There was a highly significant correlation between AG in serum and A in urine (r = 0.82, P < 0.001). AG was also positively related to dehydroepiandrosterone sulphate (r = 0.64; P < 0.005), bioavailable testosterone (r = 0.6; P < 0.001), aetiocholanolone (r = 0.58; P < 0.001) and total testosterone (r = 0.52; P < 0.01). In contrast, A/E was not significantly related to androgen production. CONCLUSIONS: There is a poor correlation between AG and the A/E ratio in hirsute women. Although AG may be raised by increased 5 alpha-reductase activity, it is probably also affected by the presence of elevated androgens regardless of 5 alpha-reductase activity.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Effect of 5-alpha-reductase inhibition on sex-hormone-binding globulin in elderly men.

In this study we examined the possibility that chronic reduction in serum dihydrotestosterone (DHT) attained by pharmacologic inhibition of 5 alpha-reductase modulates serum sex-hormone-binding globulin (SHBG) levels in elderly men. Twenty-one men, ages 58-79 years (mean 66) with benign prostatic hypertrophy were treated with the 5 alpha-reductase inhibitor finasteride (5 mg daily) for 12 months. Serum DHT declined by 80% (p < 0.001) and total testosterone rose by 14% (p < 0.05). Serum SHBG concentration remained unchanged (44.1 +/- 4.5 vs 45.2 +/- 5.7 nmol/l for pre- and post-therapy levels, respectively). Thus, the conversion of testosterone to DHT is not required to maintain the androgenic effect on serum SHBG concentration in elderly men.

Aged↗
PubMed1993

Octadecatetraenoate synthesis in the unicellular alga Isochrysis galbana: studies with intact and broken chloroplasts.

(1) Monogalactosyldiacylglycerol (MGD) is the major lipid component of Isochrysis galbana. In cells incubated for 3 h with [1-14C]]acetate or [1-14C]oleate. MGD contained 35.9% and 52.8%, respectively, of the label incorporated into cellular lipids. (2) 18:4 amounted to 50-60% of the total FA of MGD. Separation of MGD species of cells grown with [1-14C]oleate on AgNO3 impregnated plates revealed 20 distinct spots. The slowest spot was identified as dioctadecatetraenoyl MGD. Fast moving species were enriched with 18:1. (3) In cells incubated for 3 h with [1-14C]oleate, approx. 60% of the radioactivity was associated with 18:1. Subsequent chase resulted in a gradual shift of label and after 48 h [14C]18:1 declined to 10% and [14C]18:4 reached 52%. This shift was also reflected in the labeling pattern of the MGD-species. Dioctadecatetraenoyl-MGD became labelled only after 24 h. (4) Addition of the substituted pyridazinone herbicide (SAN 9785) during the chase period inhibited [14C]18:4 formation; [14C]18:2 and [14C]18:3 accumulated instead. (5) Isolated chloroplast readily incorporated [14C]oleate into MGD and PA. Considerable amounts of [14C]18:1 were desaturated to 18:2 and 18:3. Only very small amounts of 18:4 were formed. O2 was required for desaturation. Cofactor requirement could not be shown. (6) Membranes isolated from broken chloroplasts retained the ability to incorporate [14C]oleate into MGD and PA and desaturate 18:1 to 18:2 and 18:3.

Chloroplasts↗
PubMed1993

The lipoxygenase inhibitor phenidone is a potent hypotensive agent in the spontaneously hypertensive rat.

Previous studies from our laboratory indicated that the lipoxygenase inhibitor phenidone markedly attenuates angiotensin II (AII) induced vascular contractility. Phenidone was also shown to inhibit the formation of vascular lipoxygenase products and to reduce blood pressure in the AII-dependent renovascular hypertensive rat. We have now examined the effects of phenidone in the spontaneously hypertensive rat (SHR). A single dose of phenidone lowered intraarterial systolic pressure in a dose dependent manner in both SHR and Wistar-Kyoto (WKY) [(max 74 +/- 15 and 22 +/- 3 mm Hg, respectively; P < .001)], but the effect was substantially greater in SHR. Long-term oral phenidone administration arrested the evolution of hypertension in 6 week old SHR treated over a period of 4 weeks (control 190 +/- 2 mm Hg; phenidone treated rats 164 +/- 4 mm Hg; P < .01). To assess the role of AII related mechanisms in the hypotensive effect of phenidone, the acute effect was studied in SHR on high and low sodium intake. In addition, the effect of captopril was compared to that of phenidone alone or captopril and phenidone in salt restricted SHR. While a single dose of phenidone (30 mg/kg, intraperitoneally) elicited similar maximal effects in SHR on high and low sodium intake (54 +/- 6 and 52 +/- 5 mm Hg compared to basal blood pressure, respectively), the hypotensive effect in sodium restricted rats was more sustained. Phenidone had no further hypotensive effect in captopril treated, salt restricted SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Potential role of 12 hydroxyeicosatetraenoic acid in angiotensin II-induced calcium signal in rat glomerulosa cells.

Recent evidence suggests that 12 hydroxyeicosatetraenoic acid (12HETE), a product of the 12 lipoxygenase (LO) pathway of arachidonic acid metabolism, may have a role in mediating angiotensin II (AII)-induced aldosterone secretion. The present study examined the possible role of the 12 LO product 12HETE in AII-induced calcium ([Ca++]i) signals in rat glomerulosa cells. The addition of 12HETE to glomerulosa cells induced a dose-dependent (10(-6)-10(-8) M) rise in [Ca++]i levels that was sustained over 15 min. The effects of 12HETE on [Ca++]i were attenuated but not blocked by nifedipine (5 x 10(-6) M) and were preserved in a calcium-free medium, suggesting mobilization of intracellular calcium stores. Furthermore, the 12HETE-mediated rise in [Ca++]i was almost entirely abolished by dantrolene. In parallel, 12HETE reversed the inhibitory effect of nifedipine on AII-induced aldosterone secretion [AII (10(-9) M) - 36 +/- 7, AII + nifedipine (5 x 10(-6) M) - 13 +/- 2, AII + nifedipine + 12HETE (5 x 10(-8) M) - 27 +/- 4 ng/10(6) cells]. Dantrolene also inhibited AII-dependent aldosterone secretion (AII 10(-9) M - 75.8 +/- 5.6, AII + dantrolene 10(-6) M 45.5 +/- 8.8 ng/10(-6) cells), but this inhibition could not be reversed by 12HETE 10(-8) M (45.4 +/- 10.6 ng/10(6) cells). The LO blockers baicalein and BW755C inhibited the effect of AII on aldosterone production and on [Ca++]i in a parallel fashion. During LO blockade, the addition of 12HETE (10(-7) M) restored the AII-induced rise in [Ca++]i. Collectively, these observations suggest that activation of the LO pathway in the rat adrenal glomerulosa contributes to change in cytosolic calcium, which may be important for the steroidogenic effect of AII.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗