Rapid onset sodium appetite and orofacial responses to intraoral capsaicin and hypertonic NaCl in the rat.

Sodium appetite reverts from aversive to hedonic the orofacial responses to intraoral hypertonic NaCl in a taste reactivity test (TRT). An electrophysiological-based hypothesis suggests that aversion to salty taste results from oral nociception (e.g., like that produced by intraoral capsaicin). In the present work, we used the TRT to investigate whether sodium appetite and its sensitization produce similar effects on the orofacial responses to the intraoral infusion of either capsaicin or hypertonic NaCl. We produced rapid onset sodium appetite by subcutaneous injection of furosemide combined with a low dose of captopril (Furo/Cap) in adult rats instrumented with intraoral cannula. Then, the animals had 1-h free access to water (thirst test). Immediately after, they entered the TRT receiving a first intraoral infusion (1 ml for a total of 1 min) of (0.5 µM) capsaicin and, 20 min later, a second one of (0.3 M) NaCl. The sequence, Furo/Cap injection - thirst test - TRT, was repeated twice more every three days. The repetition of the Furo/Cap increased the frequency of hedonic responses, decreased the frequency of aversive responses, and increased the hedonic:neutral response ratio to NaCl. The repetition of Furo/Cap reduced transiently the neutral orofacial responses and ended decreasing the aversive:neutral response ratio to capsaicin. The results suggest that repeated Furo/Cap sensitizes the palatability of hypertonic NaCl. They also suggest that sensitization of sodium appetite involves increased sodium "liking". Finally yet importantly, we found that sensitization of sodium appetite can influence orofacial responses to capsaicin. Rapid onset sodium appetite and orofacial responses to intraoral capsaicin and hypertonic NaCl in the rat.

Inhibition of salty taste and sodium appetite by estrogens in spontaneously hypertensive rats.

Estrogen has a well-known effect of reducing salt intake in rats. This mini review focuses on recent findings regarding the interaction of estradiol with brain angiotensin II to control increased sodium palatability that occurs as a result of sodium appetite in spontaneously hypertensive rats.

Mineral preference in rats treated with muscimol into the lateral parabrachial nucleus.

Injection of muscimol, a GABAA receptor agonist, into the lateral parabrachial nucleus (LPBN) induces 0.3 M NaCl intake in rats. In the present work, we investigated whether such an effect applies to hypertonic (0.3 M) mineral solutions in general or is selective to sodium solutions in a 240 min intake test. Muscimol injection (0.5 nmol/0.2 µL) compared to vehicle injection into the LPBN of adult hydrated rats produced a preferential ingestion of 0.3 M NaCl (25.3 ± 10.2 mL) followed by a 0.3 M NaHCO3 intake (11.7 ± 5.6 mL), with no significant effect on water, KCl and CaCl2 intake. Only the effect of muscimol on NaCl intake (19.0 ± 10.4 mL) persisted in cell-dehydrated rats, with hardly any effect on water or other mineral solutions. The results suggest that the LPBN controls the ingestion of hypertonic NaCl and NaHCO3. They also suggest a selective mechanisms involving the LPBN to check hypertonic sodium intake.

Cardiovascular and hidroelectrolytic changes in rats fed with high-fat diet.

Obesity activates the renin-angiotensin and sympathetic systems facilitating hypertension and changes in the hydroelectrolytic balance. In the present study, in rats fed with high-fat diet (HFD), we investigated daily water intake and urinary excretion, prandial consumption of water and the changes in blood pressure and water intake to intracerebroventricular (icv) angiotensin II (ANG II). Male Holtzman rats (290-320 g) were fed with standard diet (SD, 11% calories from fat) or HFD (45% calories from fat) for 6 weeks. Part of the animals received a stainless steel cannula in the lateral ventricle (LV) at the 6th week after the beginning of the diets and the experiments were performed at the 7th week. The pressor effect, but not the dipsogenic response to acute icv injection of ANG II, was potentiated in the HFD rats. Daily water intake and urinary volume were reduced in rats fed with HFD with no significant changes in sodium excretion. Prandial water consumption was also reduced in rats ingesting HFD, an effect almost totally reverted blocking salivation with atropine. These results show a potentiation of the pressor response to icv ANG II in HFD-fed rats, without changing icv ANG II-induced water intake. In addition, prandial and daily water intake and urinary volume were reduced in HFD-fed rats, without changing sodium excretion. Salivation in rats ingesting HFD may play a role in the reduced prandial and daily water intake.

Whole body sodium depletion modifies AT1 mRNA expression and serotonin content in the dorsal raphe nucleus.

Angiotensin II (Ang II) acts on Ang II type 1 (AT1) receptors located in the organum vasculosum and subfornical organ (SFO) of the lamina terminalis as a main facilitatory mechanism of sodium appetite. The brain serotonin (5-HT) system with soma located in the dorsal raphe nucleus (DRN) provides a main inhibitory mechanism. In the present study, we first investigated the existence of Ang II AT1 receptors in serotonergic DRN neurones. Then, we examined whether whole body sodium depletion affects the gene expression of the AT1a receptor subtype and the presumed functional significance of AT1 receptors. Using confocal microscopy, we found that tryptophan hydroxylase-2 and serotonin neurones express AT1 receptors in the DRN. Immunofluorescence quantification showed a significant reduction in 5-HT content but no change in AT1 receptor expression or AT1/5-HT colocalisation in the DRN after sodium depletion. Whole body sodium depletion also significantly increased Agtr1a mRNA expression in the SFO and DRN. Oral treatment with the AT1 receptor antagonist losartan reversed the changes in Agtr1a expression in the SFO but not the DRN. Losartan injection into either the DRN or the mesencephalic aqueduct had no influence on sodium depletion-induced 0.3 mol L-1 NaCl intake. The results indicate the expression of Agtr1a mRNA in the DRN and SFO as a marker of sodium depletion. They also suggest that serotonergic DRN neurones are targets for Ang II. However, the function of their AT1 receptors remains elusive.

Damage of the medial preoptic area impairs peripheral pilocarpine-induced salivary secretion.

The existence of neural connections between the medial preoptic area (MPOA) and the salivary glands and the increase in salivation by thermal or electrical stimulation of the MPOA have suggested an important role of MPOA in the control of salivary gland function. Although direct cholinergic activation of the salivary glands induces salivation, recent studies have suggested that salivation produced by i.p. pilocarpine may also depend on the activation of central mechanisms. Therefore, in the present study, we investigated the effects of bilateral electrolytic lesions of the MPOA on the salivation induced by i.p. pilocarpine. Adult male Holtzman rats (n = 11-12/group) with bilateral sham or electrolytic lesions of the MPOA were used. One, five, and fifteen days after the brain surgery, under ketamine anesthesia, the salivation was induced by i.p. pilocarpine (1 mg/kg of body weight), and saliva was collected using pre-weighed small cotton balls inserted into the animal's mouth. Pilocarpine-induced salivation was reduced 1 and 5 days after MPOA lesion (341 +/- 41 and 310 +/- 35 mg/7 min, respectively, vs. sham lesions: 428 +/- 32 and 495 +/- 36 mg/7 min, respectively), but it was fully recovered at the 15th day post-lesion (561 +/- 49 vs. sham lesion: 618 +/- 27 mg/7 min). Lesions of the MPOA did not affect baseline non-stimulated salivary secretion. The results confirm the importance of MPOA in the control of salivation and suggest that its integrity is necessary for the full sialogogue effect of pilocarpine. However, alternative mechanisms probably involving other central nuclei can replace MPOA function in chronically lesioned rats allowing the complete recovery of the effects of pilocarpine.

Cardiovascular effects of felypressin.

Cardiovascular effects of felypressin (FEL) were studied in Wistar rats. Heart rate and mean arterial pressure measurements were taken in awake rats treated with vasopressin (AVP), FEL, or epinephrine (EPI). Each group received either an intravenous (IV) or an intracerebroventricular V1 receptor antagonist, saline, area postrema removal, or sham surgery. Analysis of variance and Student-Newman-Keuls (P < .05) were applied. Felypressin and AVP induced a pressor effect, and bradycardia was inhibited by IV V1 antagonist. Intracerebroventricular V1 antagonist and area postrema removal enhanced their pressor effects. Epinephrine induced a higher pressor effect and a similar bradycardia that was not affected by the treatments. It was concluded that FEL depends on V1 receptors to induce pressor and bradycardic effects, and that it produces a high relationship between bradycardia and mean arterial pressure variation depending on area postrema and central V1 receptors. These effects are potentially less harmful to the cardiovascular system than the effects of EPI.

Effects of AV3V lesion on pilocarpine-induced pressor response and salivary gland vasodilation.

The cholinergic agonist pilocarpine injected intraperitoneally (ip) increases mean arterial pressure (MAP) and superior mesenteric (SM) vascular resistance and reduces submandibular/sublingual gland (SSG) vascular resistance. In the present study, we investigated the effects of electrolytic lesions of the anteroventral third ventricle (AV3V) region on the changes in MAP, SM, and SSG vascular resistances induced by ip pilocarpine. Male Holtzman rats anesthetized with urethane (1.0 g/kg) and chloralose (60 mg/kg) were submitted to sham or electrolytic AV3V lesions and had pulsed Doppler flow probes implanted around the arteries. Contrary to sham rats, in 1-h and 2-day AV3V-lesioned rats, pilocarpine (4 micromol/kg) ip decreased MAP (-41 +/- 4 and -26 +/- 4 mm Hg, respectively, vs. sham: 19 +/- 4 mm Hg) and SM (-48 +/- 11 and -45 +/- 10%, respectively, vs. sham: 41 +/- 10%) and hindlimb vascular resistances (-65 +/- 32 and -113 +/- 29%, respectively, vs. sham: 19 +/- 29%). In 7-day AV3V-lesioned rats, pilocarpine produced no changes on MAP and SM and hindlimb vascular resistances. Similar to sham rats, pilocarpine reduced SSG vascular resistance 1 h after AV3V lesions (-46 +/- 6%, vs. sham: -40 +/- 6%), but it produced no effect 2 days after AV3V lesions and increased SSG vascular resistance (37 +/- 6%) in 7-day AV3V-lesioned rats. The responses to ip pilocarpine were similar in 15-day sham and AV3V-lesioned rats. The cholinergic antagonist atropine methyl bromide (10 nmol) iv slightly increased the pressor response to ip pilocarpine in sham rats and abolished for 40 min the fall in MAP induced by ip pilocarpine in 1-h AV3V-lesioned rats. The results suggest that central mechanisms dependent on the AV3V region are involved in the pressor responses to ip pilocarpine. Although it was impaired 2 and 7 days after AV3V lesions, pilocarpine-induced salivary gland vasodilation was not altered 1 h after AV3V lesions which suggests that this vasodilation is not directly dependent on the AV3V region.

Moxonidine and central alpha2 adrenergic receptors in sodium intake.

Central injections of the alpha(2) adrenergic/imidazoline receptor agonist moxonidine inhibit water and NaCl intake in rats. In the present study, we investigated the possible involvement of central alpha(2) adrenergic receptors on the inhibitory effect of moxonidine in 0.3 M NaCl intake induced by 24 h sodium depletion. Male Holtzman rats with stainless-steel cannulas implanted into the lateral ventricle (LV) were used. Sodium depletion was produced by the treatment with the diuretic furosemide (20 mg/kg of body weight) injected subcutaneously +24 h of sodium-deficient diet. Intracerebroventricular (icv) injections of moxonidine (20 nmol/1 microl) reduced sodium depletion-induced 0.3 M NaCl intake (6.6+/-1.9 ml/120 min vs. vehicle: 12.7+/-1.7 ml/120 min). Pre-treatment with the alpha(2) adrenoreceptor antagonists RX 821002 (80 nmol/1 microl), SK&F 86466 (640 nmol/1 microl) and yohimbine (320 nmol/3 microl) injected icv abolished the inhibitory effect of icv moxonidine on sodium depletion-induced 0.3 M NaCl intake (13.3+/-1.4, 15.7+/-1.7 and 11.8+/-2.2 ml/120 min, respectively). The results show that the activation of alpha(2) adrenoreceptors is essential for the inhibitory effect of central moxonidine on sodium depletion-induced NaCl intake.

Central moxonidine on salivary gland blood flow and cardiovascular responses to pilocarpine.

Peripheral treatment with the cholinergic agonist pilocarpine induces intense salivation that is inhibited by central injections of the alpha2-adrenergic/imidazoline receptor agonist moxonidine. Salivary gland blood flow controlled by sympathetic and parasympathetic systems may affect salivation. We investigated the changes in mean arterial pressure (MAP) and in the vascular resistance in the submandibular/sublingual gland (SSG) artery, superior mesenteric (SM) artery and low abdominal aorta (hindlimb) in rats treated with intraperitoneal (i.p.) pilocarpine alone or combined with intracerebroventricular (i.c.v.) moxonidine. Male Holtzman rats with stainless steel cannula implanted into lateral ventricle (LV) and anesthetized with urethane were used. Pilocarpine (4 micromol/kg of body weight) i.p. reduced SSG vascular resistance (-50+/-13% vs. vehicle: 5+/-3%). Pilocarpine i.p. also increased mesenteric vascular resistance (15+/-5% vs. vehicle: 2+/-3%) and MAP (16+/-3 mmHg, vs. vehicle: 2+/-3 mmHg). Moxonidine (20 nmol) i.c.v. increased SSG vascular resistance (88+/-12% vs. vehicle: 7+/-4%). When injected 15 min following i.c.v. moxonidine, pilocarpine i.p. produced no change on SSG vascular resistance. Pilocarpine-induced pressor responses and increase in mesenteric vascular resistance were not modified by i.c.v. moxonidine. The treatments produced no change in heart rate (HR) and hindlimb vascular resistance. The results show that (1) i.p. pilocarpine increases mesenteric vascular resistance and MAP and reduces salivary gland vascular resistance and (2) central moxonidine increases salivary gland vascular resistance and impairs pilocarpine-induced salivary gland vasodilatation. Therefore, the increase in salivary gland vascular resistance may play a role in the anti-salivatory response to central moxonidine.

Central alpha(2) adrenergic receptors and cholinergic-induced salivation in rats.

Salivation induced by intraperitoneal (i.p.) injections of pilocarpine (cholinergic agonist) is reduced by intracerebroventricular (i.c.v.) injections of moxonidine (alpha(2) adrenergic and imidazoline receptor agonist). In the present study, we investigated the involvement of central alpha(2) adrenergic receptors in the inhibitory effect of i.c.v. moxonidine on i.p. pilocarpine-induced salivation. Male Holtzman rats with stainless steel cannula implanted into the lateral ventricle (LV) were used. Saliva was collected using pre-weighted small cotton balls inserted into the animal's mouth under ketamine (100 mg x kg(-1)) anesthesia. Salivation was induced by i.p. injection of pilocarpine (4 micromol x kg(-1)). Pilocarpine-induced salivation was reduced by i.c.v. injection of moxonidine (10 nmol) and enhanced by i.c.v. injections of either RX 821002 (160 nmol) or yohimbine (320 nmol). The inhibitory effect of i.c.v. moxonidine on pilocarpine-induced salivation was abolished by prior i.c.v. injections of the alpha(2) adrenergic receptor antagonists, RX 821002 (160 nmol) or yohimbine (160 and 320 nmol). The alpha(1) adrenergic receptor antagonist prazosin (320 nmol) injected i.c.v. did not change the effect of moxonidine on pilocarpine-induced salivation. The results suggest that moxonidine acts on central alpha(2) adrenergic receptors to inhibit pilocarpine-induced salivation, and that this salivation is tonically inhibited by central alpha(2) adrenergic receptors.

Inhibition of pilocarpine-induced salivation in rats by central noradrenaline.

Peripheral treatment with cholinergic or adrenergic agonists results in salivation and the possibility of synergy between cholinergic and adrenergic efferent mechanisms in the control of salivation has been proposed. Central injections of the cholinergic agonist pilocarpine also induce salivation, while the effects of central injections of noradrenaline (norepinephrine) are not known. Here (a) the effects of intracerebroventricular (i.c.v.) injection of noradrenaline on the salivation induced by i.c.v. or intraperitoneal (i.p.) injection of pilocarpine and (b) the receptors involved in the effects of central noradrenaline on pilocarpine-induced salivation were investigated. Male Holtzman rats with a stainless-steel guide cannula implanted into the lateral ventricle were used. Rats were anaesthetized with tribromoethanol (200mg/kg body weight) and saliva was collected on small, preweighed cotton balls inserted into the animal's mouth. Noradrenaline (40, 80 and 160 nmol/1 microl) injected i.c.v. reduced the salivary secretion induced by pilocarpine (0.5 micro mol/1 microl) injected i.c.v.. Noradrenaline (80 and 160 nmol/1 microl) injected i.c.v. also reduced the salivation induced by pilocarpine (4 micromol/kg) injected i.p. Previous treatment with the alpha(2)-adrenergic receptor antagonists RX 821002 (40, 80 and 160 nmol/1 microl) or yohimbine (160 and 320 nmol/1 microl) abolished the inhibitory effect produced by i.c.v. injection of noradrenaline on pilocarpine-induced salivation in rats. Prazosin (alpha(1)-adrenergic receptor antagonist) injected icv did not change the effect of noradrenaline on pilocarpine-induced salivation. Prior icv injection of only RX 821002 (80 or 160 nmol/1 microl) or yohimbine (320 nmol/1 microl) increased pilocarpine-induced salivation. The results show that (1) contrary to its peripheral effects, noradrenaline acting centrally inhibits cholinergic-induced salivation in rats; (2) central mechanisms involving alpha(2)-adrenergic receptors inhibit pilocarpine-induced salivation.

[Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast]. / Imunoexpressão do c-erbB-2 nas lesões epiteliais proliferativas intraductais da mama de mulheres.

OBJECTIVES: Genetic modifications are related to genesis and development of cancer. Neoplasias in various organs express the c-erbB-2 oncogene. In intraductal proliferations of the breast it has been assessed as a risk factor for subsequent development of carcinoma. The c-erbB-2 immunoexpression in intraductal epithelial proliferations and the relationship with histopathological characteristics of ductal carcinoma in situ (DCIS) were evaluated. METHODS: File material from 88 women, which were tissue samples formalin-fixed, paraffin-embedded blocks, was used. Of these 51 presented with DCIS and 37 with ductal hyperplasia without atypia. Ages of the women ranged from 35 to 76 years. All cases were reviewed and nuclear grade, presence of necrosis, preponderance of histological subtype and its extension were verified. Specimens were obtained for the c-erB-2 immunohistochemical study of 84 of the women in question. RESULTS: No expression of the oncogene was verified in the hyperplasias without atypias and in tissues adjacent to all tissue samples. Expression of c-erbB-2 was verified in 9 (19.1%) of the DCIS (p = 0.0001). Immunoexpression was not related to the extension of the lesions. The c-erbB-2 immunoexpression in DCIS was correlated to the histological subtype (p = 0.019), necrosis (p = 0.0066), nuclear grade (p = 0.0084) and Van Nuys Classification (p = 0.039). CONCLUSIONS: Expression of c-erbB-2 was significant in proliferative lesions with risk (DCIS) and was correlated to histopathological characteristics: high nuclear grade, presence of necrosis and comedy subtype. There was no expression in the hyperplasias without atypias and adjacent tissues.

Accuracy of (99m)Tc-sestamibi scintimammography for breast cancer diagnosis.

Scintimammography using (99m)Tc-sestamibi is a noninvasive and painless diagnostic imaging method that is used to detect breast cancer when mammography is inconclusive. Because of the advantages of labeling with (99m)Tc-sestamibi and its high efficiency in detecting carcinomas, it is the most widespread agent for this purpose. Its accumulation in the tumor has multifactorial causes and does not depend on the presence of architectural distortion or local or diffuse density variation in the breast. The objective of this study was to evaluate the accuracy of scintimammography for detecting breast cancer. One hundred and fifty-seven patients presenting 158 palpable and non-palpable breast nodules were evaluated. Three patients were male and 154 were female, aged between 14 and 81 years. All patients underwent scintimammography, and the nodule was subjected to cytological or histological study, i.e., the gold standard for diagnosing cancer. One hundred and eleven malignant and 47 benign nodules were detected, with predominance of ductal carcinomas (n=94) and fibroadenoma/fibrocystic condition (n=11/n=11), respectively. The mean size was 3.11 cm (7-10 cm) among the malignant nodules and 2.07 cm among the benign nodules (0.5-10 cm). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 89, 89, 95, 78 and 89%, respectively. Analysis on the histological types showed that the technique was more effective on tumors that were more aggressive, such as ductal carcinoma. In this study, (99m)Tc-sestamibi scintimammography was shown to be an important tool for diagnosing breast cancer when mammography was inconclusive.

Oxytocinergic and serotonergic systems involvement in sodium intake regulation: satiety or hypertonicity markers?

Previous studies demonstrated the inhibitory participation of serotonergic (5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD-induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD-induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5-HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and non-depleted animals. The OT plasma levels significantly increased only in the PD-induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.

Serotonergic mechanisms of the lateral parabrachial nucleus and cholinergic-induced sodium appetite.

Central cholinergic mechanisms are suggested to participate in osmoreceptor-induced water intake. Therefore, central injections of the cholinergic agonist carbachol usually produce water intake (i.e., thirst) and are ineffective in inducing the intake of hypertonic saline solutions (i.e., the operational definition of sodium appetite). Recent studies have indicated that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nucleus (LPBN) markedly increases salt intake in models involving the activation of the renin-angiotensin system or mineralocorticoid hormones. The present studies investigated whether sodium appetite could be induced by central cholinergic activation with carbachol (an experimental condition where only water is typically ingested) after the blockade of LPBN serotonergic mechanisms with methysergide treatment in rats. When administered intracerebroventricularly in combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused water drinking but insignificant intake of hypertonic saline. In contrast, after bilateral LPBN injections of methysergide (4 microg), intracerebroventricular carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by intracerebroventricular carbachol was not changed by LPBN methysergide injections. The results indicate that central cholinergic activation can induce marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the LPBN are attenuated.

Serum zinc levels and breast intraductal neoplasm

Objective: To verify whether patients with microcalcifications in mammography (BI-RADS 3 or 4) and diagnosis of breast intraductal neoplasm had serum zinc levels lower than those patients with benign diagnosis. Methodology: Analyzed were patients with first-time attendance in the IBCC clinic who presented microcalcifications and submitted to biopsy investigation. Before the biopsy was performed, patients responded to a questionnaire with questions that included age, menarche age, age at first childbirth, total time of breast-feeding and breast cancer antecedents. Patients were also submitted to preoperative examinations, including serum zinc level assessment by atomic absorption method. Statistical analysis between the two groups (control group with benign results; study group with breast intraductal neoplasm) was done through Student's t-test and chi-square test, with an admitted 5% level of significance. Results: Forty-seven patients met the study adopted criteria. The control group enrolled 28 subjects and the study group included 19 patients. The authors did not find significant differences between the two groups in the studied parameters. The serum zinc levels did not show significant differences. However, of all studied parameters of both groups, the serum zinc levels were of higher significance. Conclusion: In spite of the tendency of lower levels of serum zinc in the study group (patients with intraductal breast cancer), no statistically significant differences (p=0.25) were found in the present study. Therefore, this parameter could not be used as a conclusive predictive marker for risk assessment. Since the number of studied cases was small, a larger number of cases should be studied in order to clarify this tendency of slightly lower levels of serum zinc in patients.

Tratamento clínico e seguimento das hiperplasias de endométrio / Clinical treatment and follow-up of endometrial hyperplasia

Objetivos: avaliar a eficácia do acetato de medroxiprogesterona e do acetato de megestrol nas hiperplasias de endométrio. Métodos: foram incluídas, retrospectivamente 47 pacientes com sangramento uterino anormal, submetidas a curetagem uterina diagnóstica e/ou biópsia de endométrio, cujo achado histopatológico foi de hiperplasia de endométrio. Nas pacientes com hiperplasia sem atipia foi iniciado a terapêutica com acetato de medroxiprogesterona por via oral, na dose de 10 mg/dia durante 10-12 dias por mês. Nas com atipia, era utilizado o acetato de megestrol por via oral, dose de 160 mg/dia, uso contínuo. O período de tratamento variou de 3 a 18 meses. Biópsia de endométrio e/ou curetagem uterina de controle foram realizadas entre três e seis meses do início do tratamento e periodicamente para avaliar a resposta terapêutica. Resultados: foram analisadas 42 pacientes com hiperplasia endometrial sem atipia e cinco com atipia. A média de idade das pacientes foi de 49,5 mais ou menos 10,6 anos, sendo 70,2 por cento com idade superior a 45 anos. O acetato de medroxiprogesterona foi eficaz em fazer regredir as hiperplasias sem atipias em 83,2 por cento (35/42) e o acetato de megestrol em 80 por cento (4/5) das hiperplasias com atipia. Em 16,8 por cento (7 casos) das hiperplasias sem atipia e em 20 por cento (1 caso) das com atipia, ocorreu persistência das lesões, apesar do tratamento. Em nenhum caso ocorreu progressão para câncer de endométrio, durante o período de seguimento que foi de 3 meses a 9 anos. No acompanhamento dessas pacientes, verificamos que 18 (38,3 por cento) apresentaram amenorréia, em 12 (25,5 por cento) ocorreu regularização do ciclo menstrual e 17 (36,2 por cento) permaneceram com sangramento uterino anormal, sendo submetidas a histerectomia total abdominal. O exame anatomopatológico mostrou a persistência da lesão hiperplásica em oito casos, leiomioma em quatro, adenomiose em três, mio-hipertrofla uterina difusa em um caso e útero normal em outro, tendo havido regressão das lesões hiperplásicas nesses últimos nove casos. Conclusões: o tratamento das hiperplasias de endométrio com acetato de medroxiprogesterona e/ ou acetato de megestrol, representa uma alternativa satisfatória para mulheres que desejam preservar o útero ou que tenham risco cirúrgico elevado. Entretanto, é necessário monitorização cuidadosa do endométrio, o que deve ser realizado pela avaliação dos sintomas, ultra-sonografia transvaginal e biópsia periódica.

Prevençäo de aderências pélvicas: estudo experimental em ratas com diferentes modalidades terapêuticas / Pelvic adhesion prevention: experimental study on rats with different therapeutic agents

OBJETIVOS: avaliar o grau de aderências pélvicas em funçäo do tempo e da utilizaçäo de diferentes substâncias empregadas na sua profilaxia. MATERIAL E MÉTODOS: estudo prospectivo com 120 ratas Wistar, albinas, virgens, 3 a 4 meses de idade, pesando aproximadamente 250 gramas, divididas aleatoriamente em 10 grupos de 12 animais cada: controle, sem lesäo; lesöes e sem tratamento; lesöes + soluçäo fisiológica 0,9 por cento; lesöes + Ringer-lactato; lesöes + dextrano 70 a 32 por cento; lesöes + Ringer-lactato/heparina; lesöes + Ringer-lactato/dexametasona; lesöes + Ringer-lactato/hidrocortisona/dexametasona/ampicilina; lesöes + Ringer-lactato/albumina e lesöes + carboximetilcelulose 1 por cento. Após anestesiados os animais, realizaram-se dois tipos de lesöes nos cornos uterinos (escarificaçäo e eletrocauterizaçäo), seguidos de tratamento profilático intraperitoneal com as soluçöes citadas. No 7º, 14º e 28º dia pós-operatório, momentos M1, M2 e M3, respectivamente, avaliaram-se quatro ratas de cada grupo quanto à presença de aderências. Os métodos empregados na quantificaçäo das aderências encontradas basearam-se na classificaçäo de Cohen, com escores variando de 0 a 4+ de acordo com a quantidade, características e localizaçäo das aderências. Foram usadas provas paramétricas para análise da variância e Kruskal-Wallis. RESULTADOS: os melhores tratamentos para prevençäo de aderência pélvica em ratas foram: Ringer-lactato/dexametasona (predomínio do escore 1+), dextrano 70 a 32 por cento (predomínio do escore 2+) e Ringer-lactato/hidrocortisona/dexametasona/ampicilina (predomínio do escore 2+). O período pós-operatório, representado pelo momento M3, e a técnica cirúrgica, predominantemente com escore 0, influíram na adesiólise e manutençäo de aderências pélvicas em ratas. CONCLUSÖES: a prevençäo de aderências pélvicas em ratas inicia-se no processo cirúrgico de baixo dano tecidual; o uso de substâncias profiláticas (soluçöes) tem eficácia variada, sendo que algumas mostraram-se mais eficazes que outras

Imunoexpressão do c-erbB-2 nas lesões epiteliais proliferativas intraductais da mama de mulheres / Immunoexpression of c-erbB-2 in intraductal proliferative lesions of the female breast

OBJETIVOS: Alterações genéticas são relacionadas à gênese e progressão do câncer. Neoplasias de vários órgãos expressam o oncogene c-erbB-2. Nas proliferações intraductais da mama tem sido avaliado como fator de risco para o desenvolvimento de câncer. Foram avaliadas a imunoexpressão do c-erbB-2 em lesões epiteliais proliferativas intraductais e as possíveis correlações com características anatomopatológicas do carcinoma ductal "in situ" (CDIS). MÉTODOS: Foi utilizado material de arquivo, amostras teciduais fixadas em formalina e incluídas em blocos de parafina de 88 mulheres. Destas, 51 com CDIS e 37 com hiperplasia ductal sem atipias (HDT). A idade variou de 35 a 76 anos. Revisados todos os casos, verificou-se: o grau nuclear, a presença de necrose, o subtipo histológico predominante e sua extensão. Obteve-se material suficiente para o estudo imunohistoquímico do c-erbB-2 de 84 sujeitos do estudo. RESULTADOS: Não foi observada a expressão do oncogene nas hiperplasias sem atipias e nos tecidos adjacentes a todas amostras teciduais. A expressão do c-erbB-2 foi verificada em nove (19,1 por cento) dos CDIS (p= 0,0001). A imunoexpressão não se relacionou à extensão das lesões. A imunoexpressão do c-erbB-2 no CDIS correlacionou-se com subtipo histológico (p=0,019), com a presença de necrose (p=0,0066), com o grau nuclear (p=0,0084) e com a Classificação de Van Nuys (p=0,039). CONCLUSÕES: A expressão do c-erbB-2 foi estatisticamente significante nas lesões proliferativas de risco (CDIS) e correlacionou-se com características histopatológicas: alto grau nuclear, presença de necrose, subtipo comedo. Não houve expressão nas hiperplasias sem atipias e tecidos adjacentes.