Nerve lesions following apical extrusion of non-setting calcium hydroxide: a systematic case review and report of two cases.

We present two cases of apical extrusion of non-setting, calcium hydroxide paste which had been placed as an interappointment root canal dressing during routine endodontic treatment resulting in tissue necrosis of a large part of the mandible. Surgical intervention consisted of resections in both instances. In relation to the cases presented, a systematic review of similar cases in the literature between 1980 and April 2013 was conducted which resulted in eight cases meeting the criteria outlined. As with the two presented cases, half of these eight cases showed serious adverse effects and the use of an injectable system had most often been related to apical extrusion. Consequently, great care should be taken when applying the paste into the canal system.

Effect of acute and long-term treatment with 17-beta-estradiol on the vasomotor responses in the rat aorta.

1. This study sought to evaluate whether the effects of acute and long-term treatment with 17-beta-estradiol on the vasomotor responses in rat aortic rings are mediated through the same mechanism. 2. Ovariectomized rats were treated daily with either 17-beta-estradiol-3-benzoate (100 microg kg(-1)) or vehicle for 1 week. 3. The effect of long-term 17-beta-estradiol treatment on the responses to cumulative doses of phenylephrine, 5-HT, calcium, potassium and 17-beta-estradiol was determined in aortic rings. In the same rings, the effect of acute exposure to 17-beta-estradiol (5 and 10 microM) on the dose response curves for phenylephrine, 5-HT, calcium, potassium and acetylcholine were estimated. The measurements were made in rings with and without intact endothelium. The tone-related basal release of nitric oxide (NO) was measured in rings with intact endothelium. 4. Long-term 17-beta-estradiol treatment reduced the maximum developed contraction to all contracting agents studied. This effect was abolished in endothelium denuded vessels. Acute 17-beta-estradiol treatment also reduced maximal contraction. This effect, however, was independent of the endothelium. 5. Long-term 17-beta-estradiol treatment significantly increased the ability of the rings to dilate in response to acetylcholine whereas acute exposure to 17-beta-estradiol had no effect. The tone-related release of NO was significantly increased after long-term exposure to 17-beta-estradiol. 6. In conclusion, this study indicate that the acute and long-term effects of 17-beta-estradiol in the rat aorta are mediated through different mechanisms. The long-term effect is mediated through the endothelium most likely by increasing NO release. In contrast, the acute effect of 17-beta-estradiol seems to be through an effect on the vascular smooth muscle cells.

A partial estrogen receptor agonist with strong antiatherogenic properties without noticeable effect on reproductive tissue in cholesterol-fed female and male rabbits.

Estrogen replacement therapy retards the development of cardiovascular disease and osteoporosis in postmenopausal women. However, long-term unopposed use increases the risk of cancer in endometrium and possibly in breast. The racemic compound ormeloxifene, widely used in India as an antifertility agent, is a partial estrogen receptor agonist with antiosteoporotic properties. The present study was undertaken to investigate the effect of the L-enantiomer (levormeloxifene) and the d-enantiomer (d-ormeloxifene) on the development of atherosclerosis. In a short-term experiment (6 weeks), 4 x 10 ovariectomized female rabbits were fed a 0.25% cholesterol-enriched diet and the effect on plasma cholesterol levels was studied. In a long-term experiment (13 weeks), 4 x 15 ovariectomized female and 4 x 15 shamoperated male rabbits were maintained at a similar plasma cholesterol level of 25 mmol/L and the effect on undamaged and balloon-injured arterial wall was studied. In both experiments, the rabbits were treated with levormeloxifene, d-ormeloxifene, 17 beta-estradiol, or placebo, respectively. In the short-term experiment, levormeloxifene, in contrast to d-ormeloxifene, significantly reduced plasma cholesterol by 30% compared with the placebo group. In the long-term experiment, levormeloxifene, in contrast to d-ormeloxifene, significantly reduced atherosclerosis by 50% in the undamaged arterial wall of both female and male rabbits. Because these rabbits were cholesterol-clamped, the antiatherogenic effect was not mediated via plasma cholesterol lowering. Like estrogen, levormeloxifene did not inhibit atherosclerosis in the endothelium-denuded site of aorta. The antiatherogenic effects of levormeloxifene were thus similar to those of estrogen, but produced in the absence of any noticeable estrogenic effect on uterine or testicular tissue.

Significant reduction of the antiatherogenic effect of estrogen by long-term inhibition of nitric oxide synthesis in cholesterol-clamped rabbits.

The purpose of this study was to investigate whether endothelium-derived nitric oxide (NO) is involved in the plasma lipid-independent antiatherogenic effect of estrogen and levormeloxifene, a partial estrogen receptor agonist. 85 rabbits were ovariectomized and balloon-injured in the middle thoracic aorta. The rabbits were fed a cholesterol-enriched diet supplemented with 17beta-estradiol, levormeloxifene, or placebo, either alone, or together with 160 microg/ml NG-nitro- -arginine methyl ester (-NAME), an NO synthase inhibitor, in their drinking water for 12 wk. Plasma cholesterol was maintained at 25-30 mmol/liter by individualized cholesterol feeding. In the undamaged aorta, the extent of atherosclerosis in the estrogen group was only one-third that in the placebo group. Simultaneous administration of -NAME, however, significantly reduced the antiatherogenic effect of estrogen (P < 0.01). There was no significant difference between the placebo group given -NAME and the group treated with placebo alone. At the previously endothelium-denuded site, estrogen had no effect on atherosclerosis development, whereas -NAME combined with estrogen significantly increased atherogenesis (P < 0.05). The effects of levormeloxifene were almost similar to those of estrogen. Active vascular concentrations of -NAME were demonstrated in an additional study, in which maximal aortic/coronary endothelium-dependent relaxation was significantly inhibited in rabbits given -NAME. Thus, in this study a considerable part of the plasma lipid-independent antiatherogenic effect of estrogen was mediated through its effect on endothelial NO in cholesterol-fed rabbits. The results for levormeloxifene suggest a common mechanism of action for estrogen and partial estrogen receptor agonists on atherogenesis.

The preferential dopamine D3 receptor agonist cis-8-OH-PBZI induces limbic Fos expression in rat brain.

The affinity, selectivity and agonistic properties of a constrained dopaminergic compound, the benz[e]indole cis-8-hydroxy-3-(n-propyl)1,2,3a.4,5,9b-hexahydro-1H-benz[e]indole (cis-8-OH-PBZI), for the dopamine D3 receptor were evaluated in competition binding experiments with cloned human dopamine receptor subtypes and, to further extend its profile, in in vitro radioligand binding assays. The Ki value measured for competition binding of this compound to the dopamine D3 receptor was 27.4+/-3.1 nM; this was 775-fold, 550-fold, 90-fold and 10-fold higher affinity than that measured at dopamine D1A, D5, D2s and D4 receptors, respectively. Evidence of dopamine receptor activation by cis-8-OH-PBZI was obtained by measuring dose-dependent increases in extracellular acidification rates and decreases in cAMP synthesis. In vivo, cis-8-OH-PBZI potently induced Fos protein immunoreactivity in the rat medial prefrontal cortex and shell region of the nucleus accumbens, but only marginally in the motor dorsolateral striatum, indicating a selective limbic site of action. In conclusion, the present data identify cis-8-OH-PBZI as having preference for the dopamine D3 receptor in vitro, and as having dopamine agonist activity and limbic sites of action in vivo.

The effect of clozapine on Fos protein immunoreactivity in the rat forebrain is not mimicked by the addition of alpha 1-adrenergic or 5HT2 receptor blockade to haloperidol.

The involvement of alpha 1-adrenergic and 5HT2-receptor blockade in the induction of Fos protein produced by the 'atypical' neuroleptic clozapine was investigated in the rat forebrain. The Fos protein immunohistochemical technique has been used to identify the anatomical substrate underlying the effects of typical and atypical neuroleptics. Clozapine (20 mg/kg) induced a significantly higher Fos protein immunoreactivity response in the medial prefrontal cortex and a significantly lower response in the dorsolateral striatum compared to the effect of haloperidol (1 mg/kg). The alpha 1-adrenergic antagonist prazosin (0.3 and 1.0 mg/kg) and the 5HT2 antagonist ritanserin (1 and 3 mg/kg) did not increase Fos protein immunoreactivity by themselves and did not mimic the clozapine response when co-administered with haloperidol (1 mg/kg). Consequently, this study suggests that neither alpha 1-adrenergic receptor blockade nor the 5HT2-receptor blockade accounts for the unique Fos protein expression pattern produced by clozapine.

Number and size of renal glomeruli in spontaneously hypertensive rats.

OBJECTIVE: A reduced number of nephrons, whether acquired or congenital, as has been observed in certain inbred rat strains, may lead to systemic hypertension. The present study estimated the total number of glomeruli and mean glomerular size in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. METHODS: Unbiased stereological methods were used on immersion-fixed kidneys from 12-week-old male SHR (n = 9) and age-matched WKY rats (n = 11). RESULTS: The total number of glomeruli was significantly reduced in the SHR compared with in the WKY rats. Sclerotic glomeruli were not found in either group. No significant difference in mean glomerular volume was observed, but the total glomerular volume was reduced by 25% in the SHR compared with in the WKY rats. CONCLUSION: SHR have fewer glomeruli than WKY rats, but of similar size, resulting in a reduced total glomerular volume in adult SHR. These findings are consistent with the hypothesis that the kidney plays an important role in the pathogenesis of genetic hypertension.

Early narrowed afferent arteriole is a contributor to the development of hypertension.

The kidney is probably critically involved in the development of essential hypertension, as in many genetic models of hypertension. We have investigated whether a narrowed renal afferent arteriole is involved in the pathogenesis of hypertension in spontaneously hypertensive rats. Systolic blood pressure of 37 F2 generation spontaneously hypertensive rats/Wistar-Kyoto rats was measured at age 7 weeks. The right kidney was removed, and lumen diameter and media cross-sectional area of the afferent arterioles were measured after having been fixed while relaxed and under a transmural pressure of 100 mm Hg. The uninephrectomized rats continued until age 23 weeks, when mean blood pressure was measured. Mean blood pressure at 23 weeks was negatively correlated with lumen diameter at 7 weeks. Quartile analysis based on lumen diameter at 7 weeks showed that compared with rats in the top lumen diameter quartile, rats in the bottom lumen diameter quartile had a reduced media cross-sectional area at 7 weeks (17%), the same systolic blood pressure at 7 weeks, and an increased (16%) mean blood pressure at 23 weeks. We conclude that in spontaneously hypertensive rats a narrowed lumen of distal afferent arterioles at 7 weeks contributes to later development of increased blood pressure. This reduced lumen could be caused by inhibited renal afferent arteriole growth.

Dose-dependent effects of perindopril on blood pressure and small-artery structure.

Long-term treatment of young spontaneously hypertensive rats (SHR) with angiotensin-converting enzyme (ACE) inhibitors has a persistent effect on blood pressure when treatment is withdrawn. The aim of the present study was to determine whether this effect could be mediated by the effect of treatment on resistance-artery structure. We determined the dose dependence of ACE-inhibitor therapy on blood pressure and small-artery structure during treatment and on the recovery of blood pressure when treatment was withdrawn. SHR (40 per group) were treated from age 4 to 24 weeks with one of three doses of perindopril (0.4, 0.8, or 1.5 mg/kg per day). Control groups were untreated SHR and Wistar-Kyoto rats. At 24 weeks, treatment was stopped and small arteries were taken from half of the rats from the mesenteric, femoral, cerebral, and coronary vascular beds for morphological and functional measurements. The blood pressure of the other half of the rats was followed until 36 weeks of age. During treatment, perindopril caused a dose-dependent reduction in blood pressure and in the media-lumen ratio and media area of the small arteries, whereas there was a dose-dependent increase in lumen diameter. The effect of treatment on the structure of arteries from the different vascular beds was homogeneous. Compared with values from Wistar-Kyoto rats, blood pressure normalization in SHR was not associated with full normalization of structure. After withdrawal of treatment, there was an inverse relation between perindopril dose and the persistent effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Histology of subcutaneous small arteries from patients with essential hypertension.

The purpose of the present study was to determine the cellular basis for the increased ratio of media thickness to lumen diameter (media-lumen ratio) consistently found in the peripheral resistance arteries from patients with essential hypertension using an unbiased stereological principle (the "disector"). Segments of subcutaneous resistance arteries (approximately 200 microns internal diameter) were isolated from gluteal biopsies of skin and subcutaneous fat taken from 16 untreated patients with essential hypertension and 16 age- and sex-matched normotensive control subjects. Measured under standardized conditions (ie, relaxed and under controlled mechanical conditions) on an isometric myograph, vessels from hypertensive patients had a significant (P < .05) reduction in lumen diameter and an increase in media-lumen ratio (P < .05) compared with vessels from normotensive control subjects. These changes were not associated with alterations in the estimated media volume per segment length. After these measurements had been made, the arteries were fixed, serial sectioned, and stained. The volume fraction of smooth muscle cells within the media was estimated by point counting on photomicrographs of the vessels. Using the disector principle, we determined the numerical density (number per unit volume) of smooth muscle cells within the media of each vessel and calculated the average smooth muscle cell volume (1775 +/- 122 [mean +/- SEM] and 1532 +/- 112 microns 3, hypertensive and normotensive, respectively, P > .05) on the basis of these measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphology of renal afferent arterioles in spontaneously hypertensive rats.

We present a new perfusion technique that allows arteries down to the level of capillaries to be fixed while relaxed and under a known intravascular pressure. Through a catheter inserted into the right renal artery of 12-week-old male spontaneously hypertensive rats (n = 9) and control Wistar-Kyoto rats (n = 11), the kidney vessels were rinsed with human plasma, relaxed by papaverine, and perfused with a casting resin containing microspheres. The microspheres (12 microns) became trapped in the glomeruli of the kidney and, together with a closing of the venous outflow, they caused the flow through the kidney to stop, so that the intravascular pressure was raised to the level of the input perfusion pressure (100 mm Hg). The resin material was allowed to harden, and the kidney was immersion-fixed and prepared for histomorphometrical investigations. This technique made it possible to measure both the structurally determined lumen diameter and the corresponding media thickness under clearly defined conditions. The lumen diameter of afferent arterioles close to the glomeruli showed a 17% reduction in spontaneously hypertensive rats (15.4 +/- 0.6 microns; mean +/- SEM) compared with Wistar-Kyoto rat arterioles (18.5 +/- 0.3 microns, p < 0.001). However, this was not due to media hypertrophy, because media cross-sectional area was smaller (p < 0.001) in spontaneously hypertensive rats (210 +/- 6 microns 2) compared with Wistar-Kyoto rats (274 +/- 16 microns 2). We conclude that the lumen reduction in renal afferent arterioles in spontaneously hypertensive rats is not the result of an encroachment on the lumen by a hypertrophic media.

Morphology and function of mesenteric resistance arteries in transgenic rats with low-renin hypertension.

OBJECTIVE: The renin-angiotensin system plays an important role in blood pressure control. Recently the mouse Ren-2 renin gene was introduced into the genome of rats, producing low-renin hypertensive animals. The aim of the present study was to characterize the pharmacological and morphological properties of mesenteric resistance arteries from transgenic rats. DESIGN: Segments of small arteries were taken from the mesenteric bed of 13-week-old transgenic rats and from age-matched Sprague-Dawley controls. METHODS: Vessels were mounted on an isometric myograph permitting direct measurements of vessel isometric wall tension. Vessel morphology was measured with a microscope using a water-immersion objective. RESULTS: The transgenic versus Sprague-Dawley rat comparison is similar to that seen previously for spontaneous hypertensive rats (SHR) versus Wistar-Kyoto (WKY) rats as regards active effective pressure (increased), lumen diameter (decreased) and media thickness (increased). However, in contrast to SHR vessels, where media cross-sectional area has previously been shown to be increased compared with WKY vessels, vessels from transgenic rats had the same media cross-sectional area as those from Sprague-Dawley rats. There was neither cellular hypertrophy nor hyperplasia. However, an increased number of smooth muscle layers was found, indicating a rearrangement of existing material. CONCLUSION: Although the structural changes found in transgenic rats may account for the increased pressure response, hypertension in this animal is apparently not caused by general vascular growth.

Myocardial ultrastructure in the isolated rabbit heart exposed to dopamine, dobutamine, isoprenaline, G-strofanthin, xamoterol and hypoxia.

The isolated spontaneously beating heart was used for comparing the effects of hypoxia and positive inotropic drugs on myocardial ultrastructure. Hypoxia gives a significant decrease in the volume fractions of mitochondrial cristae relative to the total mitochondrial volume (Vvmcristae) and a significant increase in the volume fraction of mitochondrial matrix relative to the total mitochondrial volume (Vvmmatrix), but changes in volume fractions of mitochondria (Vvmitochondria) and myofibrils (Vvmyofibrils) were absent. Significant changes in ultrastructure in hearts treated with dopamine (0.6 microM), dobutamine (90 nM), G-strofanthin (0.25 microM), xamoterol (32 nM) and isoprenaline (0.15 microM or 15 nM) were absent. Furthermore, myocardial effects in the isolated rabbit heart without exposure to any treatment showed a significantly decrease in oxygen consumption after 90 min. and a significant decrease in frequency of contractions after 120 min. perfusion time, but no change in contractility was seen. We conclude that this experimental model is useful in studies of positive inotropic drugs.

Remodeling and reparation of the cardiovascular system.

Growth or altered metabolism of nonmyocyte cells (cardiac fibroblasts, vascular smooth muscle and endothelial cells) alters myocardial and vascular structure (remodeling) and function. However, the precise roles of circulating and locally generated factors such as angiotensin II, aldosterone and endothelin that regulate growth and metabolism of nonmyocyte cells have yet to be fully elucidated. Trials of pharmacologic therapy aimed at preventing structural remodeling and repairing altered myocardial structure to or toward normal in the setting of hypertension, heart failure and diabetes are reviewed. It is proposed that these are therapeutic goals that may reduce cardiovascular morbidity and mortality. Although this hypothesis remains unproved the primary goal of therapy should be to preserve or restore tissue structure and function.

Effect of induced hypercholesterolemia in rabbits on functional responses of isolated large proximal and small distal coronary arteries.

We studied the effects of hypercholesterolemia on the vascular responses of proximal and distal parts of the rabbit coronary circulation in two consecutive studies. For 12 weeks, New Zealand White rabbits were fed a control diet or a diet with 1% cholesterol dissolved in either 3% coconut oil (study A) or ether (study B). Isolated proximal epicardial and distal intramyocardial coronary arteries from control and hypercholesterolemic rabbits were mounted for isometric tension recording in a double myograph. In study A for hypercholesterolemic rabbits (n = 12), the maximal relaxation and sensitivity to acetylcholine (ACh) were significantly decreased in proximal coronary segments contracted with 30 mmol/l potassium solution compared with segments from control rabbits (n = 13). The only change observed in distal coronary segments was a slight decrease in relaxation in response to low ACh concentrations (10(-8) and 3 x 10(-8) mol/l). However, in study B for proximal coronary and distal coronary segments from hypercholesterolemic rabbits (n = 13), the area under the ACh relaxation curve was increased compared with that of control rabbits (n = 12). Other parameters that were similarly affected in studies A and B include the following: 1) proximal coronary segments from hypercholesterolemic rabbits were more sensitive to sodium nitroprusside (SNP) than were those from control rabbits, but this was not true for distal coronary segments; 2) endothelial removal from arterial segments of control rabbits induced a significant increase in sensitivity and maximal relaxation to SNP of proximal coronary and distal coronary arteries; 3) in segments from hypercholesterolemic rabbits, the absence of endothelium did not alter the response of proximal coronary segments to SNP but did augment the relaxation of distal coronary segments to SNP; 4) the maximal response to 5-hydroxytryptamine in proximal coronary arteries from hypercholesterolemic rabbits was increased compared with those from control rabbits, whereas such changes were not observed in distal coronary arteries; and 5) histological examination showed the presence of atheromatous plaques in proximal coronary but not in distal coronary segments from treated animals. In conclusion, the present investigation demonstrates that induced hypercholesterolemia alters both the structure and function of proximal parts of the coronary circulation. In distal coronary arteries of hypercholesterolemic rabbits, the only change observed was an impaired endothelium-dependent cholinergic relaxation, but even this change appeared to be dependent on the manner in which cholesterol was added to the diet, although parallel studies are required to confirm this.

Difference between aortic and renal vascular reactivity in cyclosporin A treated rats and the effect of cicletanine.

4 Groups of 2 month-old male Wistar rats were treated with a) cyclosporin A (CyA) 30 mg/kg/day alone, b) CyA plus cicletanine (Cic) 60 mg/kg/day, c) vehicle (vegetable oil) 1 ml/100 g rat/day and d) no treatment for 8 weeks. The reactivity of isolated papillary muscle to isoprenaline and Ca2+ was not altered in any of the treated groups. Endothelium-dependent relaxation induced by acetylcholine was inhibited in aorta ring segments from CyA-treated rats as compared to that of control and CyA + Cic-treated rats. The relaxation induced by acetylcholine in rat aortas was similar in all groups in the presence of 10 microM indomethacin. Noradrenaline sensitivity of aortic segments was not affected by any treatments applied. The Ca(2+)-concentration response curves of aorta segments from CyA-treated and CyA + Cic-treated rats were shifted to the right as compared to control rats. In interlobar renal arteries the endothelium-dependent relaxation induced by acetylcholine was not affected by any form of treatment. In renal arteries 10 microM indomethacin increased the maximal relaxation induced by acetylcholine about 50%. In these vessels noradrenaline sensitivity in CyA and CyA + Cic treated rats was higher than in controls. Cocaine, 3 microM, shifted the noradrenaline concentration response curve to the left about 0.4 log units in all renal vessel groups, thus renal vascular smooth muscle sensitivity to noradrenaline was significantly greater in vessels from rats receiving CyA than in vessels from control rats. Administration of CyA induced only slight renal morphological changes. Cic was without effect on CyA induced morphological abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hepatitis C antibody in hematological patients who underwent multiple transfusions]. / Hepatitis C antistof hos multitransfunderede haematologiske patienter.

The frequency of hepatitis C virus antibodies in serum as detected by the "Ortho Antibody Elisa Test System", was investigated in a consecutive series of multitransfused haematological patients who had received a total of 3,627 transfusions. Two out of 43 patients (4.6%; 95% confidence interval 0.6-15.8%) were found seropositive. Among Danish blood donors the frequency of seropositivity has been reported to 0.2-0.3%. The clinical significance of the seropositivity is underlined by the finding at autopsy of chronic active hepatitis in one of the two patients found anti-HCV positive.

Microcirculatory and trophic effects of short chain fatty acids in the human rectum after Hartmann's procedure.

Short chain fatty acids (acetic, propionic and butyric) were instilled into the rectum of patients who had undergone Hartmann's procedure. The following parameters were examined before and after a 2-week treatment period with short chain fatty acids (100 ml twice daily at a total concentration of 150 mM): (1) microcirculatory effects in vivo using a laser Doppler flow technique, and (2) morphometrical changes in mucosal biopsies. The following parameters were significantly increased in all patients after treatment: (1) mucosal blood flow, (2) the fractional crypt cell epithelium plus surface epithelium volume in relation to total tissue volume down to the muscularis mucosa, (3) nuclear volume in the crypt and the surface epithelium, and (4) the fractional nuclear volume to total cell volume in the crypt and the surface epithelium. These data suggest that short chain fatty acids in the human colon have trophic and vasodilatory effects.