[Therapeutic escalation in a case of nevoid hyperkeratosis of the areola and the nipple]. / Escalade thérapeutique devant un cas d'hyperkératose nævoïde de l'aréole et du mamelon.

Nevoid hyperkeratosis of the nipple areola complex (NAC) is a rare dermatological pathology of unknown etiology, first described in 1923. It is a benign condition characterized by verrucous thickening and brownish discoloration of the NAC. We described the case of a 26-year-old woman with bilateral nevoid hyperkeratosis of the NAC. Several lines of treatment have been used with varying efficacy: conservative (calcipotriol and local retinoids), semi-conservative (CO2 laser) and surgical (excision and total skin graft). The final result is very satisfactory and without recurrence at 1 year follow-up.

[Rose necrosis: Necrotizing granulomatous reaction with infected node at red pigment of a tattoo]. / La nécrose de la rose : réaction granulomateuse et nécrotique avec adénite au pigment rouge d'un tatouage.

INTRODUCTION: Nowadays, necrotizing cutaneous reaction after a tattoo is rare especially with the sterile tattoo equipment and antisepsis rules. We report the rare case of a necrotizing reaction secondary to a granulomatous reaction after a red tattoo, with a satellite node. CASE REPORT: A 40-year-old patient suffering from a granulomatous reaction to red dye of a large pectoral tattoo, with cutaneous and sub-cutaneous necrosis, and an infected axillary node. This pectoral tattoo also triggered a necrotizing granulomatous reaction on red-pigmented areas of other older tattoos. Local treatments (dressings, antibiotics, repeated excisions of necrotizing tissues) did not stop the allergic reaction, and an infectious origin was eliminated. The patient asked for a complete excision of the pectoral tattoo. Black intramacrophagic pigment was found in the black lymph node analysed. We did not experience any complications and the patient is satisfied with the results. DISCUSSION: Very few examples of cutaneous necrotizing secondary to a tattoo have been found in the literature. The hypothesis of a primitive infection that had secondarily led to necrosis is refuted by the lack of infective structures found in the analysed node, and most of all by the same reaction on other older tattoos on red-pigmented areas. This rare complication must be known by plastic surgeons, who will probably be called upon to take care of more and more tattooed patients. CONCLUSION: Even if it's rare, necrosis with a granulomatous reaction to red pigment after a tattoo must be known. This case illustrates a very violent immune reaction where infection was not proved.

[Gorlin syndrome: photodynamic therapy, as a useful adjunct to surgery]. / Syndrome de Gorlin : la photothérapie dynamique, technique complémentaire du traitement chirurgical.

Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is well known by dermatologists. Since its onset, 10 years ago, photodynamic therapy has found new applications and is now currently used to cure single or multiple basal cell carcinomas, with good results and without residual scars. We recall some of the basic principles of this technique, as well as its indications in Gorlin syndrome, which we illustrate with one case. Plastic surgeons must consider this relatively new technique, developed by dermatologists, as a useful adjunct to surgery in the management of Gorlin syndrome.

The effects of growth hormone on blood pressure and renin secretion in hypophysectomized rats.

The effects of hypophysectomy and GH on blood pressure and renin secretion were studied. Within 2 weeks after removal of the pituitary gland of rats, mean arterial blood pressure declined 30%, and heart rate fell 50%. No significant effect of hypophysectomy on blood volume or hematocrit was noted. Within 2 h after the iv administration of 10 micrograms ovine GH to hypophysectomized rats, blood pressure, but not heart rate, was restored to normal. Despite the hypotension, the PRA of hypophysectomized rats was not significantly greater than that of intact animals. This relatively low PRA could not be accounted for by a lack of renin per se, since kidneys of hypophysectomized rats contained at least as much renin as kidneys from intact rats. Neither the PRA of hypophysectomized rats nor the kidney renin content was significantly altered 24 h after a single injection of GH (100 micrograms, ip). When perfusions were performed at 100 mm Hg, the rate of renin secretion by isolated kidneys obtained from hypophysectomized rats was markedly lower than that of kidneys from intact rats. Reduction of mean perfusion pressure to 50 mm Hg or adding isoproterenol to the perfusate produced much smaller increases in renin secretion by kidneys of hypophysectomized rats than that observed in kidneys from intact rats. Kidneys obtained from hypophysectomized rats treated with GH 24 h earlier had a renin content similar to that of kidneys from untreated animals, but secreted renin at a much higher rate. Kidneys from hormone-treated hypophysectomized rats also exhibited a greater renin secretory response to low perfusion pressure or isoproterenol. These data indicate that hypophysectomy severely impairs the renin secretory response of the isolated kidney and that a single injection of GH can reverse this impairment. These observations suggest the possibility that the hypotension characteristic of hypophysectomized rats may, in part, reflect the lack of GH and alterations in the renin-angiotensin system.

Hypertension and insulin resistant models have divergent propensities to learned helpless behavior in rodents.

The induction of learned helpless (LH) behavior in rats is a widely used model of unipolar depression. Recent studies have linked depression with hypertension and insulin resistance as observed in obesity, but the propensity of these disorders to manifest depression has not been reported. In this study, the LH behavioral paradigm was exploited in a model of hypertension (Dahl rat) and of insulin resistance (Zucker rat) to determine the propensity of these models to develop depression and to examine the profile of markers for the propensity of the cardiovascular system (plasma renin activity) and of the hypothalamus-pituitary-adrenal axis (corticosterone) in the display of propensity to depression. Results show that Zucker rats displayed the lowest propensity to the development of LH behavior (12%), followed by the control Sprague-Dawley rats (27%), and then Dahl rats (66%). In contrast, congenital learned helpless (cLH) rats, a genetically bred strain for animal depression, had the highest propensity (>90%). A gender effect was observed in the Zucker and cLH rats, with females showing an increased propensity to develop LH behavior. Plasma renin activity in the Dahl and Sprague-Dawley rats after the LH stress paradigm was not significantly different from baseline. In contrast, Zucker rats, with the lowest propensity to LH behavior, demonstrated a threefold increase in plasma renin activity after stress. Congenital LH rats, with the highest propensity to LH behavior, exhibited a significantly lower increase (43%) in plasma renin activity after stress. Hyporesponsive hypothalamus-pituitary-adrenal (HPA) axis functioning correlated with propensity of LH behavior. Stress-induced corticosterone levels increased under twofold in cLH rats, whereas they increased more than sevenfold in Zucker rats. Taken together, these studies suggest that whereas genetically prone hypertensive rats have a very high propensity to depression, insulin-resistant rats have a profound resistance to depression. Moreover, a hyporesponsive HPA axis may be a marker for disorders that are comorbid with depression, whereas a hyperresponsive renin-angiotensin system may be indicative of resilience.

Spontaneous pregnancy-induced hypertension and intrauterine growth restriction in rats.

The SHHF/Mcc-fa(cp) (spontaneous hypertension and heart failure) rat is advanced as a novel and suitable non-primate model of pregnancy-associated hypertension and fetal growth restriction because it simultaneously has spontaneous pregnancy-associated hypertension, small for gestational age (SGA) offsprings, and altered placental gene expression. Pregnancy-associated hypertension is a major contributor to maternal and fetal morbidity and mortality with the potential to result in maternal death and the need for iatrogenic preterm delivery. It has been reported to develop spontaneously in humans, but not in animals; consequently, progress in identifying the cause and pathogenesis of this disorder has been hampered. Spontaneous hypertension and heart failure rats develop hypertension spontaneously as they age, therefore we sought to determine whether these rats developed hypertension and SGA offsprings during pregnancy. Our results show that systolic blood pressure (BP) increased >40 mm Hg by the end of the first trimester and remained at this elevated level for the remainder of pregnancy, but decreased after parturition. Placenta weights of SHHF rats (0.60 +/- 0.02 g, n = 36) were significantly higher than Wistar-Kyoto (WKY) rats (0.42 +/- 0.01 g, n = 22, P < .05), but pup weights were significantly lower (2.68 +/- 0.06 g for SHHF rats compared to 3.24 +/- 0.06 g for WKY controls, P < .05). Histologic examination revealed pathologic lesions in neither heart, liver, placenta, nor kidney. L-Arginine administered in drinking water prevented the elevation of BP, particularly during the third trimester. Placentas from SHHF rats displayed altered expression of several genes whose protein products have been implicated in preeclampsia, including serotonin receptor, sodium channel, carbonic anhydrase, estrogen receptor regulator, major histocompatibility complex proteins, superoxide dismutase, and angiotensiogen. In addition, gene expression profiling showed alteration of a number of subcellular putative myristoylproteins not previously associated with preeclampsia, particularly those engaged in post-translational modifications in the placenta. Thus, SHHF rats may be a valuable tool, because it simultaneously has spontaneous pregnancy-associated hypertension, SGA offsprings, and altered placental gene expression.

Increased basal activity of the HPA axis and renin-angiotensin system in congenital learned helpless rats exposed to stress early in development.

Learned helpless behavior has been successfully bred in rats and designated as a genetic animal model of human depression and/or anxiety. Since congenital learned helpless animals have an impaired stress response in adulthood, we examined the effects of early stressors (at postnatal day 7, 14 or 21) on the hypothalamic-pituitary-adrenal axis and the renin-angiotensin system. The functioning of the hypothalamic-pituitary-adrenal axis was monitored through changes in corticosterone plasma levels in the adult animals after acute exposure to cold stress and maternal deprivation early in development. Renin-angiotensin system functioning was assessed by plasma renin activity. Unstressed congenital learned helpless rats had corticosterone levels that were similar to control animals (congenital non-learned helpless rats not stressed during development), but unstressed plasma renin activity levels of congenital learned helpless rats were lower than congenital non-learned helpless rats. There was a step-wise increase in corticosterone plasma levels in the congenital learned helpless rats with age of acute presentation of either cold stress or maternal deprivation stress (day 7, 49%; day 14, 84%; and day 21, 543% for cold stress). However, these baseline corticosterone levels were significantly lower in congenital learned helpless rats compared to congenital non-learned helpless controls. Similarly, in response to early exposure to cold stress and maternal deprivation, there was an increase in plasma renin activity levels of congenital learned helpless rats with age of presentation to either stressors. However, this increase in plasma renin activity levels was not evident in congenital non-learned helpless controls. Taken together, these results suggest that exposure to stress early in development has long-term effects on both the hypothalamic pituitary-adrenal axis and the renin-angiotensin system, two neuroendocrine indicators of stress responsivity.

Mechanism for low renin in blacks: studies in hypophysectomised rat model.

Black people have a lower plasma renin activity (PRA) than is appropriate for the level of blood pressure, but the mechanism remains unknown. Studies in our laboratory, using the hypophysectomised (Hypox) rat model, have provided a partial explanation of the inappropriately low PRA with respect to BP. Kidneys were isolated and perfused and renin secretion responsiveness studied with isoproterenol (Iso) infusion, calcium (Ca) depletion, and pressure reduction; an enriched preparation of juxtaglomerular (JG) cells was prepared for determination of cellular renin content (CRC); and preparations of isolated renin granules (IRG) and plasma membrane vesicles (PMV) from the purified JG cells were used to assess the storage and compartmentalisation of renin. Renin secretion was lower in Hypox than in normal and sodium (Na) deprived rats. On the other hand, CRC, IRG, and PMV were identical (statistically) in Hypox and Na deprived rats. Despite identical content and storage, kidneys from Hypox rats secreted significantly less renin in response to Iso, Ca depletion, and low pressure. One interesting observation is that upon stimulation, PMV of Hypox rats stored a much larger percentage of renin than normal or Na deprived rats, suggesting that the PMV may play a role as a renin sink in the low PRA levels observed in the Hypox rats. Since black people have renin profiles and responsiveness similar to those in Hypox rats, this model may be useful in studying the mechanisms responsible for their lower PRA.

Internal-external locus of control and performance on a vigilance task.

Previous studies have demonstrated there are large individual differences in subjects' ability to perform on vigilance or watch-keeping tasks. This study used Rotter's Internal-External (I-E) Locus of Control Scale to resolve some of the variance attributed to individual differences and tested the hypothesis that the internally controlled person is a better monitor on a vigilance task than an externally controlled person. There were 64 subjects who performed a visual watch-keeping task for a 1-hr. period. The results indicated that the external subjects made significantly more incorrect responses and missed significantly more signals during the entire task. The internal-external dimension was effective in differentiating performance on a vigilance task.

Mechanism by which renin secretion from perfused rat kidneys is stimulated by isoprenaline and inhibited by high perfusion pressure.

1. Rat kidneys were completely isolated and perfused to determine the ionic mechanism whereby isoprenaline stimulates and high perfusion pressure inhibits renin secretion. 2. Isoprenaline (2.43 microM) stimulated renin secretion, but K-free medium and ouabain also reduced perfusate flow. 3. Removing Ca from the perfusion medium increased renin secretion threefold when perfusion pressure was 100 mmHg and fourfold when pressure was raised to 150 mmHg. Simultaneously raising the perfusion pressure to 150 mmHg and the Ca concentration to 5 mM inhibited renin secretion. Verapamil (50 microM) prevented this inhibition. Raising Ca also caused vasoconstriction at a pressure of 150 mmHg, but verapamil partially prevented the vasoconstriction. 4. High concentration of K (50 mM) in the perfusion medium also stimulated renin secretion when Ca was removed and inhibited secretion when Ca concentration was raised to 5 mM. Verapamil (50 microM) prevented this inhibition. High K induced vasoconstriction in the presence of high Ca, but verapamil partially prevented the constriction. 5. High concentration of K (50 mM) and high perfusion pressure (150 mmHg) stimulated renin secretion in the absence of Ca and 20 mM-Mg potentiated this effect. This suggests that both sets of stimuli activate renin secretion by different cellular mechanisms, but that both act to lower cytoplasmic Ca in the juxtaglomerular cell. This is discussed. 6. High perfusion pressure inhibited renin secretion and reduced perfusate flow when Na was lowered from 145 to 14.5 or 0 mM whether or not Ca was present. 7. K-free medium and ouabain blocked the elevated renin secretion and reduced the high flow stimulated by high perfusion pressure when Ca was removed from the perfusion medium. 8. These observations suggest that isoprenaline stimulates renin secretion by a mechanism coupled to the Na-K pump. These observations are also consistent with the hypothesis that high renal perfusion pressure inhibits renin secretion by promoting Ca movement into the juxtaglomerular cell and stimulates secretion by a mechanism coupled to the Na-K pump. High perfusion pressure also causes renal vasoconstriction by increasing the Ca permeability of the smooth muscle cells in the afferent arteriole.

Stretch receptor model for renin release with evidence from perfused rat kidney.

Control of renin release was studied in isolated rat kidneys perfused with Krebs-Henseleit solution containing albumin. Cumulative perfusate renin activity (PRA) as measured by radioimmunoassay was increased by low perfusion pressure and suppressed by high pressure. Renal vasoconstriction induced by infusion of phenylephrine or methoxamine increased PRA, whereas vasodilatation by papaverine suppressed renin activity. The increased renin activity induced by phenylephrine was blocked by high pressure or papaverine. Changing sodium concentration in the perfusion medium had no effect on basal renin release. A mathematical analysis for an intrarenal stretch receptor indicates that renin release is related to the elastic modulus, the internal and external hydrostatic pressures, and the internal and external radii. Calculations based on this model also indicate that renin release is most sensitive to changes in the ratio of the radii. It is proposed that basodilatation or high perfusion pressure may increase the stretch of the afferent arteriole and depolarize the granular cell membrane, whereas vasoconstriction or low pressure may decrease stretch and thus hyperpolarize the cell.

Stimulation of renin release in perfused kidney by low calcium and high magnesium.

These experiments were designed to test whether changing perfusate calcium or magnesium concentrations affected renin release in the isolated perfused rat kidney, and whether kidneys removed from sodium-loaded or sodium-deprived rats released the same amount of renin in response to identical stimuli. Kidneys were perfused with Kreb-Henseleit solution containing albumin. Renin release was inversely related to perfusate calcium concentration, whereas renin release was directly related to perfusate magnesium. Although a low calcium medium or low perfusion pressure (50 mmHg) stimulated renin release, the release was substantially greater in the sodium-deprived rats. Increasing the perfusate sodium concentration from 85 to 206 mM increased excretion, but did not alter renin release. It is concluded that a) low perfusate calcium and high magnesium concentrations stimulate renin release, b) kidneys removed from sodium-deprived rats released substantially more renin thatn those from sodium-loaded rats, and c) changing perfusate sodium concentration alters sodium excretion, but does not affect renin release.

Stretch receptor control of renin release in perfused rat kidney: effect of high perfusate potassium.

1. These studies were conducted in the isolated perfused rat kidney to determine the effect of high perfusate K on the renin release induced by low perfusion pressure, renal vasoconstriction and isoprenaline, and to determine whether the magnitude of the K-induced inhibition equalled that observed with renal vasodilation and high perfusion pressure. 2. Raising perfusate K concentration from 4.2 to 56 mM suppressed basal renin release, and the 56 mM-K inhibited the renin release induced by low perfusion pressure (50 mmHg) or phenylephrine (0.83 micrometers). 3. Isoprenaline (0.79 micrometers) induced a marked increase in renin release; but high perfusate K, propranolol (0.28 mM), papaverine (0.39 mM), or high perfusion pressure (150 mmHg) inhibited this effect. 4. It is concluded that high perfusate K has a powerful inhibitory effect on the renin release induced by renal hypotension, vasoconstriction, and isoprenaline infusion, and that this effect may be mimicked by high perfusion pressure or renal vasodilation. A mechanism is proposed whereby these signals may inhibit renin release by depolarizing the juxtaglomerular granular cells.

Hydrogen and potassium regulation of (pro)renin processing and secretion.

H and K ions play central roles in prorenin processing and secretion, and prorenin is abnormally expressed in H and K disorders. At the surface membrane of juxtaglomerular (JG) cells, K is sensed and regulated by K channels (coupled to Cl channels and activated by excess Ca), Na-K-adenosinetriphosphatase, and a KCl/H exchange transporter (regulated by Ca). In JG cell granular membrane, K flux is regulated by K channels and a KCl/H exchange transporter (activated by Ca). H channels and a H pump reside in the granular membrane, which maintain H concentration in the granular matrix at least two orders of magnitude greater than in cytosol. The H pump may also be responsible for maintaining the acidic matrix required for maximal prorenin processing to renin by prohormone convertase for human renin (PCren), the prorenin convertase. These molecules form the core of a chemiosmotic system, which appears to regulate both prorenin processing and renin secretion. Renin secretion and prorenin processing appear to be of more than causal significance in clinical disorders characterized by chemiosmotic imbalance. A critical review of the literature supports the following general conclusions. First, hyperrenin state defines the initial phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension. Second, low-renin syndrome defines the transition-to-establish phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension in which the key feature is renin secretory hyporesponsivity. Third, renin disorders are usually associated with other endocrine disorders (polyendocrinopathies types I, II, and III), suggesting that renin may be an important molecule in the processing of chemiosmotic forces. The key chemiosmotic molecules (K and H) are also important in the processing and export of most (if not all) hormones. Thus, by regulating K and H homeostasis, renin may regulate the endocrine system.

Chemiosmotic control of renin release from isolated renin granules of rat kidneys.

1. Renin-containing granules were isolated, characterized, and used to gain insight into a possible chemiosmotic mechanism of renin secretion. 2. Renin granules were obtained by a modification of the sucrose gradient method, which yielded a 67-fold purification of renin granules as assessed by marker enzymes, or a modification of the Percoll gradient, which yielded a 230-fold enrichment of renin granules. 3. Granular renin content was increased by chronic sodium deprivation and hypophysectomy. 4. Renin release from granules was inversely related to osmotic strength (150-900 mosmol l-1). pH had a biphasic effect on renin release, with greater stimulation at both acidic (pH 5) and alkaline (pH 8 and 9) pH. The pH effect was dependent on Cl-; raising Cl- stimulated release. This effect was abolished by-oligomycin and N,N'-dicyclohexylcarbodiimide (DCCD) at pH 5, but not at pH 8; the effect was enhanced by NH4+. 5. Either valinomycin or carbonyl cyanide m-chlorophenylhydrazone (CCCP) alone was without effect; but in combination they caused a potent stimulation at all pHs. Nigericin stimulated renin release at all pHs, but its effect required K+. 6. Raising K+ stimulated renin release from granules, whereas raising Na+ was without effect. Lowering Ca2+ below 10(-6) M significantly stimulated renin release. 7. Taken together, the evidence is consistent with the chemiosmotic hypothesis for the control of renin release from granules and may have some implications for the regulation of renin secretion from juxtaglomerular cells.