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Biomedical subjects

N Stern

Publications and source records attributed to N Stern.

At least 19 recordsLinked to original sources

In vitro effects of insulin on aldosterone production in rat zona glomerulosa cells.

Though long standing diabetes mellitus is frequently accompanied by hypoaldosteronism, the role of insulin in this setting has never been clearly established. In the present study we have examined the direct effects of insulin on aldosterone production in rat zona glomerulosa cells in vitro. Insulin is shown to directly stimulate aldosterone production in a dose dependent manner, and to attenuate angiotensin II mediated aldosterone production, without affecting angiotensin II receptor binding kinetics. Insulin had no effect on aldosterone production mediated by the other physiological stimuli (K+ and ACTH). These data suggest a possible interaction between insulin and angiotensin II in the regulation of aldosterone secretion.

Adrenocorticotropic Hormone

Diabetes and hypertension.

Arterial hypertension is more common in diabetes mellitus than in nondiabetic subjects, and many metabolic and hemodynamic features of diabetes mellitus contribute to the etiology of hypertension. Control of hypertension in diabetes mellitus is extremely important as high blood pressure accelerates both macrovascular and microvascular complications of this disease. Most classes of antihypertensive agents are effective in blood pressure control in diabetes mellitus, so the choice of antihypertensive therapy is based on the differences in adverse effects of these agents on metabolic control and their effect on other cardiovascular risks.

Animals

Neurocirculatory asthenia revisited: elevated arterial pressure at presentation is a marker for subsequent hypertension.

Neurocirculatory asthenia (NCA) is a fairly common functional disorder often encountered among military recruits. Symptoms in NCA tend to appear in waves, and are believed to disappear completely with the passage of time. Elevated arterial pressure is known to occur as part of the various haemodynamic manifestations of NCA. However, the exact prevalence of hypertension, as well as its long-term prognosis, is still unknown. The present case-control study was designed to address these two issues. The target population consisted of 370 patients with NCA representing two separate cohorts: patients diagnosed in 1979, 10 years prior to this study, and patients diagnosed in 1983-84, 5 years prior to the study. An overall 20% prevalence rate of mild hypertension at diagnosis was calculated for the entire study population. In total, 100 patients representing equal numbers of hypertensive and matched normotensive subjects from each cohort were re-evaluated. At follow-up, hypertension was present in 27% (1979 cohort) and 30% (1983-84 cohort) of patients originally considered to be hypertensive. Hypertension was either non-existent (1979 cohort) or limited to a single case (1983-84 cohort) among originally normotensive individuals. In parallel, resting heart rate was higher in the hypertensive subjects of the 1979 cohort both at presentation (85.5 +/- 3.2 vs. 73.7 +/- 2.4 beats min-1; P less than 0.005) and at follow-up (79.6 +/- 3.2 vs. 70.0 +/- 2.5 beats min-1; P less than 0.01). These results indicate that hypertension complicates the diagnosis of NCA in 20% of patients and that, contrary to common belief, it cannot be regarded as another transient manifestation of this condition. Thus hypertension in this context is, as in the younger members of the population in general, a major risk factor for lifelong hypertension, rather than an inconsequential phenomenon.

Adolescent

12-Lipoxygenase products modulate calcium signals in vascular smooth muscle cells.

Previous studies have shown that inhibition of the lipoxygenase pathway of arachidonic acid metabolism can prevent the development of elevated blood pressure in renin-dependent models of hypertension. Agents that inhibit the lipoxygenase pathway such as phenidone and the flavonoid baicalein can selectively attenuate contractile responses to angiotensin II in vivo as well as in isolated vascular tissue. In the present study, the effects of lipoxygenase inhibitors on pressor-induced changes in cytosolic calcium were examined in cultured rat vascular smooth muscle cells using the fluorescent dye fura-2. Two structurally unrelated lipoxygenase inhibitors, baicalein and 5,8,11-eicosatriynoic acid, attenuated angiotensin II-stimulated increases in cytosolic calcium in both normal and calcium-poor buffer. The addition of 5-, 12-, or 15(S)-hydroxyeicosatetraenoic acid alone to the cells had no acute effect on intracellular calcium concentration. However, the addition of 12(S)-hydroxyeicosatetraenoic acid but not 5- or 15(S)-hydroxyeicosatetraenoic acid restored the initial calcium response to angiotensin II in vascular smooth muscle cells pretreated with both inhibitors; 5,8,11-eicosatriynoic acid also reduced [Arg8]-vasopressin and endothelin-stimulated increases in intracellular calcium. The attenuation of vasopressor-induced calcium transients by agents that inhibit lipoxygenase may explain their observed hypotensive effects in vivo. Moreover, lipoxygenase products, in particular 12(S)-hydroxyeicosatetraenoic acid, may act as mediators for the intracellular actions of angiotensin II and possibly other pressor hormones in vascular tissue by regulation of intracellular calcium metabolism.

Angiotensin II

Clinical procedures in fabricating post and core restorations: case reports.

In this series of case reports, unusual clinical procedures in the implementation of post and core restorations are demonstrated and their difficulties are discussed. First a method for preparing an immediate post and amalgam core, while utilizing the provisional self-curing acrylic resin crown as a matrix for the condensation of amalgam, is presented. The second technique is the fabrication of a cast post and core restoration that fits an abutment root as well as the existing crown of a four-unit fixed restoration. The third case illustrates the clinical procedures involved in preparing an immediate post and core restoration through an opening in the crown, when the extended fixed restoration cannot be removed.

Dental Abutments

A predoctoral honors program in prosthodontics.

Over the last 25 years, the advent of new disciplines in dental education and the increasing body of knowledge in various dental specialties have led to a struggle for curriculum hours within many dental schools. At the same time, the amount of time available for teaching clinical skills in dental schools has not increased appreciably, and fewer patients require (or can afford) sophisticated prosthodontic treatment. As a result of these trends, there has been a general decline in the depth and range of clinical skills of recent dental school graduates, particularly in prosthodontics. New York University College of Dentistry has attempted to address this problem by establishing a predoctoral honors program in prosthodontics.

Education, Dental, Graduate

Clinically versus laboratory photocured facings.

Acrylic and composite resin facings may fracture or become detached from the metal framework. Insufficient retention, abrasion and trauma are among the causes of these phenomena. Clinical and laboratory techniques have been developed to fabricate facings by means of light-curing composite systems such as the Dentacolor (Kulzer, Inc.) system. The effect of different polishing methods, obtained in both techniques using the same material, was studied with SEM on samples. Finishing and polishing procedures were accomplished using fine finishing diamonds, diamond burs and sof-lex discs. Smooth and lustrous surfaces were obtained with finishing discs, in contrast to techniques using other finishing instruments. Little or no difference in surface texture was observed between samples finished by clinical and those finished by laboratory techniques.

Composite Resins

Angiotensin II directly increases rabbit renal brush-border membrane sodium transport: presence of local signal transduction system.

In the present study, we have examined the direct actions of angiotensin II (AII) in rabbit renal brush border membrane (BBM) where binding sites for AII exist. Addition of AII (10(-11)-10(-7) M) was found to stimulate 22Na+ uptake by the isolated BBM vesicles directly. All did not affect the Na(+)-dependent BBM glucose uptake, and the effect of AII on BBM 22Na+ uptake was inhibited by amiloride, suggesting the involvement of Na+/H+ exchange mechanism. BBM proton permeability as assessed by acridine orange quenching was not affected by AII, indicating the direct effect of AII on Na+/H+ antiport system. In search of the signal transduction mechanism, it was found that AII activated BBM phospholipase A2 (PLA) and that BBM contains a 42-kDa guanine nucleotide-binding regulatory protein (G-protein) that underwent pertussis toxin (PTX)-catalyzed ADP-ribosylation. Addition of GTP potentiated, while GDP-beta S or PTX abolished, the effects of AII on BBM PLA and 22Na+ uptake, suggesting the involvement of G-protein in AII's actions. On the other hand, inhibition of PLA by mepacrine prevented AII's effect on BBM 22Na+ uptake, and activation of PLA by mellitin or addition of arachidonic acid similarly enhanced BBM 22Na+ uptake, suggesting the role of PLA activation in mediating AII's effect on BBM 22Na+ uptake. In summary, results of the present study show a direct stimulatory effect of AII on BBM Na+/H+ antiport system, and suggest the presence of a local signal transduction system involving G-protein mediated PLA activation.

Angiotensin II

Key role of diacylglycerol-mediated 12-lipoxygenase product formation in angiotensin II-induced aldosterone synthesis.

We have shown earlier that the 12-lipoxygenase product of arachidonic acid (AA), 12-hydroxyeicosatetraenoic acid (12-HETE), plays an important role in mediating angiotensin II (AII)-induced aldosterone secretion (J. Clin. Invest. (1987) 80, 1763). In the present study, we have evaluated whether diacylglycerol (DG) is the source of arachidonic acid giving rise to this 12-HETE. Treatment of rat adrenal glomerulosa cells with a DG lipase inhibitor, RHC 80267, which prevents conversion of DG to AA and HETEs, blocked AII-induced aldosterone and 12-HETE formation. In contrast, a DG kinase inhibitor, R59022, which prevents conversion of DG to phosphatidic acid, potentiated AII-induced aldosterone and 12-HETE formation. These two inhibitors block DG metabolism which would be expected to lead to increased DG levels and protein kinase C activity and AII-induced steroidogenesis. However, only R59022 potentiated AII action while RHC 80267 was inhibitory. This suggests that conversion of DG to AA and 12-HETE is important for AII action. Further proof for this was obtained by measuring [3H]AA-labeled DG levels. The combination of the inhibitors significantly potentiated AII-induced DG formation even though this same combination was inhibitory on AII-induced aldosterone and 12-HETE. Thus, the inhibitory effect of RHC 80267 is due to blockade of AA release and not of DG formation. These results suggest that DG plays a dual role in AII action, both as an activator of protein kinase C and as a source of AA for 12-HETE formation.

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

A survey of dentists practicing implant dentistry in Israel.

Due to the increasing interest in the field of implant dentistry, a first survey of dentists in Israel who used implants was conducted. Out of a total of 312 dentists questioned, 97 reported using dental implants in their practice. In spite of the team approach advocated in the literature, 40% of the dentists in the survey conducted both the surgical and the prosthetic phases of treatment. Over 60% of the respondents had less than 3 years' experience in the field, which is in keeping with the worldwide trend. A smaller number than expected regarded red gingival color and bone resorption based on radiographic findings as grounds for implant failure. In the view of at least 10 respondents, pain, discomfort, exudate, and fistulization did not indicate unsuccessful implants. A disparity was revealed between the dentists' practice methods and their hypothetical choice of self-treatment. Although the Core-Vent method was the most widely employed, only 50% of those using this system preferred it for themselves. Even fewer (25%) of those using blade implants considered it their self-treatment of choice. In contrast, although only 10% of the dentists had used the Branemark method, 30% preferred it for their own treatment.

Attitude of Health Personnel

Inhibition of lipoxygenase pathway reduces blood pressure in renovascular hypertensive rats.

To assess the potential role of the lipoxygenase (LO) pathway in the vasculature in an angiotensin II (ANG II)-dependent model of hypertension, we investigated the effect of LO pathway inhibition on blood pressure in the two-kidney, one-clip (2K,1C) Goldblatt hypertensive rat. The development of renovascular hypertension in 2K,1C rats was attenuated by oral administration of phenidone (Phe, 60 mg.kg-1.day-1), a nonselective LO inhibitor, throughout the 3 wk of observation after renal artery constriction. In contrast, the same treatment protocol had no effect on the evolution of hypertension in the deoxycorticosterone acetate-salt rat, which is considered to be an ANG II-independent form of hypertension. The hypotensive effect of Phe was not associated with changes in plasma renin or aldosterone concentration (PRC and PAC, respectively). In vitro synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) by aortic segments was increased in 2K,1C hypertensive rats compared with sham-operated rats. In addition, the synthesis of 12-HETE was suppressed by the in vitro addition of Phe (10(-4) M) to aortic-segment incubates obtained from 2K,1C rats and sham-operated rats. Acute administration of Phe (30 or 60 mg/kg) in 2K,1C hypertensive rats produced a rapid and sustained decrease in mean blood pressure (MBP). This decrease in MBP was accompanied by a brisk rise in PRC and PAC. In contrast, bolus administration of indomethacin, a selective cyclooxygenase inhibitor, did not affect MBP, PRC, or PAC.(ABSTRACT TRUNCATED AT 250 WORDS)

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

A graphic comparison of mandibular border movements generated by various articulators. Part II: Results.

A method was described in Part I in which mandibular border movements of a subject can be compared with the movements generated by various articulators (fully adjustable Denar SE and semiadjustable Denar Mark II) by using an electronic pantograph, the Pantronic. The mean values of 12 sets of plots from this device were calculated and graphs were generated. For the subject studied, differences were detected by the Pantronic pantograph between human border movements and those generated by each articulator and method of adjusting it. In the horizontal table, the semiadjustable articulator without immediate side shift always showed the potential of greater errors, especially as excursions started. When the semiadjustable instrument was programmed with immediate side shift, its movements were comparable with the fully adjustable articulator. Neither articulator exactly simulated the subjects' movements.

Dental Articulators

Hypotensive effects of the lipoxygenase inhibitor phenidone in two-kidney, one clip Goldblatt hypertension.

This study examined the role of the lipoxygenase (LO) pathway in the maintenance of hypertension in rats with two-kidney, one clip (2K,1C) Goldblatt hypertension. A single dose of the lipoxygenase blocker phenidone was injected intraperitoneally to 2K,1C rats during the early phase (14 days) of the development of hypertension (mean intraarterial blood pressure 137 +/- 3.9 mm Hg). Phenidone (60 mg/kg) markedly decreased arterial pressure to nadir levels of 58.9% of resting blood pressure. The maximal changes were observed 15 min after injection and the hypotensive response was sustained for at least 2 h. Plasma renin concentration (PRC) increased from 74.3 +/- 18.9 to 281.0 +/- 6.5 ng/mL/h after injection (P less than .05). Thus, the hypotensive effect of phenidone was not due to suppression of renin secretion but presumably due to inhibition of its effects. It is suggested that arachidonate metabolites of the LO pathway at the vascular bed may be involved in maintenance of high arterial pressure in 2K,1C renovascular hypertension in rat.

Animals

The effect of dietary salt ingestion on blood pressure of old-old subjects. A double-blind, placebo-controlled, crossover trial.

To study the effect of dietary salt restriction and supplementation on blood pressure of elderly subjects, we performed a randomized, placebo-controlled, double-blind, crossover trial. Seven healthy subjects living in a long-term care facility, with a mean age of 85 and normal to borderline-hypertensive blood pressures, completed a 16-week protocol. During the double-blind cycles, subjects consumed either a low sodium (43 mmol/day) or a high sodium diet (175 mmol/day) for four weeks supplemented with placebo or salt capsules, with crossover to the other diet. Sitting diastolic blood pressure was significantly lower during the low sodium diet (69.86 mmHg +/- 3.80 vs 78.71 mmHg +/- 3.99, P less than .01), with all subjects showing decreases. Supine plasma renin activity and plasma aldosterone were significantly lower during the high sodium diet. Both low and high sodium diets were well-tolerated by subjects. Symptomatic postural hypotension and hyponatremia were not observed. We conclude that old-old subjects with borderline hypertension demonstrate salt-dependent increases in blood pressure. Without additional supportive studies, however, these results should not be generalized to any specific cohort of elderly individuals.

Aged

Effects of central and peripheral dopamine antagonism on aldosterone secretion: evidence for adrenal mechanism.

Both domperidone (DOMP) and metoclopramide (MCP) are D2 receptor antagonists, MCP being a central and peripheral dopamine antagonist, whereas DOMP is exclusively a peripheral antagonist. MCP, but not DOMP, has been shown to stimulate aldosterone production. To elucidate whether aldosterone stimulation by dopamine antagonism is centrally mediated, we injected DOMP (28 micrograms/kg body wt) via a cannula into the third ventricle in Sprague-Dawley rats. Plasma aldosterone and renin concentration were measured before and 15 min after the injection. Centrally administered DOMP resulted in an increment in plasma aldosterone (23.8 +/- 7.4 ng/dl) that was not significantly greater than that induced by vehicle alone (15.8 +/- 4.5 ng/dl). This increase was inhibited by pretreatment with dexamethasone (100 micrograms three times daily) and attenuated by captopril (1 mg/kg ip) but not by L-beta-3,4-dihydroxyphenylalanine (30 mg/kg), thus reflecting a stress effect. Similarly, central administration of MCP (21 micrograms/kg) resulted in a significant rise in plasma aldosterone. This increase, however, was eliminated by pretreatment with dexamethasone and attenuated by captopril. Peripherally administered DOMP (280 micrograms/kg) had no effect on plasma aldosterone. The effect of DOMP and MCP on aldosterone secretion by freshly obtained adrenal capsules was also tested. Angiotensin II and MCP, but not DOMP, induced a dose-dependent increase in aldosterone secretion, with a maximal increment (15.7 +/- 5.8 ng.mg capsular protein-1.10 min-1; 50% increase) with MCP at 10(-7) M (P less than 0.01 compared with controls). Dopamine completely inhibited this MCP-induced rise in aldosterone release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex

Selective inhibition of angiotensin II-mediated vasoconstriction by lipoxygenase blockade.

We have previously demonstrated that the lipoxygenase (LO) pathway has a specific role in the effect of angiotensin II (ANG II) on aldosterone secretion. To elucidate whether the LO pathway also participates in the vascular effects of ANG II, the nonselective LO inhibitor phenidone (PHE; 30 mg/kg) was administered to rats 1 h before graded dose ANG II infusion. PHE reduced the LO product 12-hydroxyeicosatetraenoic acid (12-HETE) in deendothelialized aortas by an average of 36% as determined by radiometric detection with high-performance liquid chromatography and radioimmunoassay methods. In parallel, the peak systolic pressor response to ANG II was lowered from 36.2 +/- 3.7 to 16.8 +/- 2.0 mmHg. The peak pressor responses to ANG II were also reduced by two other LO inhibitors, baicalein (30 mg/kg) and esculetin (60 mg/kg) (13.9 +/- 2.4 and 22.1 +/- 4.7 mmHg, respectively; P less than 0.01 compared with control rats for both), but not by the cyclooxygenase inhibitor indomethacin. The LO inhibitors baicalein (7.5 X 10(-5) M) and PHE (10(-4) M) markedly attenuated the in vitro contractile response to ANG II of femoral artery rings. In contrast, neither the in vivo nor in vitro constrictor responses to norepinephrine were affected by baicalein. Thus lipoxygenase blockade induces a direct and selective inhibition of ANG II-induced vasoconstriction. The LO pathway may have an important role in mediating the pressor effect of ANG II.

Angiotensin II