A Bernard o que é de Bernard: resgatando o significado de “vida livre”

A recent critique on “homeostasis”, as elaborated by Walter Cannon (1871-1945), identifies contradictions intrinsic to the conditional association made by Claude Bernard (1813-1878) between “constancy of the internal environment” and “free life”. On the one hand, the critique reiterates the importance of the “internal environment” - the liquid where tissue cells live, extending to the evolution of the body’s fluid compartments. However, it also shows that the conditional association made by Bernard has neither empirical nor logical support. Therefore, assuming that “constancy of the internal environment” is the condition for “free life” is invalid. Apart from its intrinsic contradiction, other works have criticized the conditional on the assumption that Bernard, followed by Cannon, was referring to a rigid regulation of biological (life) variables in general. The objective of the present work is to show that this criticism is also invalid because, in our view, Bernard does not make this type of generalization when referring to “free life”. We conclude that avoiding ambiguities is necessary to appreciate Bernard’s theoretical contribution to physiology effectively.Uma avaliação crítica recente da “homeostase”, elaborada por Walter Cannon (1871-1945), identifica contradições intrínsecas à associação condicional, feita por Claude Bernard (1813-1878), entre “constância do meio interno” e “vida livre”. Por um lado, a avaliação reitera a importância do “meio interno” - líquido onde vivem as células dos tecidos, estendendo-a à evolução dos compartimentos líquidos corporais. Entretanto, ela também mostra que a associação condicional não tem suporte empírico nem lógico. Portanto, é inválido assumir que “constância do meio interno” seja condição para “vida livre”. À parte de sua contradição intrínseca, outros trabalhos têm criticado o condicional presumindo que Bernard seguido por Cannon estava se referindo a uma rigidez regulatória das variáveis biológicas (da vida) em geral.  O objetivo do presente trabalho é mostrar que essa crítica é também inválida, pois a nosso ver Bernard não faz esse tipo de generalização ao se referir a “vida livre”. Concluímos que evitar ambiguidades torna-se necessário para uma efetiva apreciação da contribuição teórica de Bernard para a fisiologia

Anatomopathological analysis of sentinel and nonsentinel lymph nodes in breast cancer: Hematoxylin-eosin versus immunohistochemistry

The authors compare the detection of metastases in sentinel lymph nodes (SLNs) and nonsentinel lymph nodes (NSLNs) using hematoxvlin-eosin (HE) staining versus immunohistochemistry (IHC). Thirty-six patients with breast carcinoma undergo exeresis of the primary tumor and of 50 SLNs and 491 NSLNs. Sentinel lymph nodes are sectioned into transverse slices of 2- to 3-mm thickness, and a cytologic smear and a frozen section were obtained from each slice. The slices are completely cut into serial sections at 100-mu m intervals. Two consecutive 4-mu m-thick sections are then obtained from each level and were prepared for HE staining and IHC. Nonsentinel lymph nodes are evaluated similarly to SLNs. The authors obtain 4076 SLN sections and 32 012 NSLN sections, fora total of 36 088 sections. A comparison of HE staining versus IHC based on the total number of sections shows a sensitivity of 93.8%, a negative predictive value of 98.9%, and an accuracy of 99.1 %. The values obtained by HE staining are similar to those obtained by IHC

Role of central α1- and α2-adrenoceptors on the dipsogenic and cardiovascular effect of angiotensin II

We investigated the effects of previous central treatment with prazosin (an α1-adrenoceptor antagonist) or clonidine (an α2-adrenoceptor agonist) on the dipsogenic, pressor and tachycardic responses produced by intracerebroventricular (ICV) injection of angiotensin II (AII) in conscious rats. Holtzman rats with a chronic cannula implanted in the lateral ventricle were tested for dipsogenic and cardiovascular (arterial pressure and heart rate) responses in separate experiments. Previous ICV treatment with clonidine (20, 40, 80 and 120 nmol) abolished the pressor, tachycardic and dipsogenic effects of ICV AII. After all doses of prazosin (40, 80 and 120 nmol), AII induced bradycardic responses, but only the 80 and 120 nmol doses of prazosin reduced the pressor responses to AII. Prazosin produced no alteration in the dipsogenic effect of AII. The results show that the periventricular α1-adrenoceptors are involved only in the cardiovascular responses produced by central AII, whereas clonidine acting through α2-adrenergic and/or imidazole receptors can modulate all actions of AII. © 1990

Episodes of water deprivation enhance daily hypertonic NaCl intake in rats

Water and 1.8% NaCl intake was recorded daily in adult male rats (N = 6) submitted to four water deprivations plus four sodium appetite tests, each at the end of each 7-day interval, or in controls (non-deprived, N = 6). Water deprivation was achieved by removing water and 1.8% NaCl for 24 h. Water was then offered for 2 h. At the end of this period, 1.8% NaCl was also offered in addition to water (sodium appetite test). Average daily 1.8% NaCl intake was enhanced from 5.2 ± 1.0 to 15.7 ± 2.5 ml from the first to the fifth week in the experimental group and was unchanged in the control group. Daily water intake was not altered in either group. Thus, repeated episodes of water deprivation enhance daily NaCl intake

Role of the alfa1- and alfa2-adrenoceptors of the lateral hypothalamus in the dipsogenic response to central angiotensin II in rats

The present experiments were conducted to investigate the role of the α1- and α2-adrenergic receptors of the lateral hypothalamus (LH) on the drinking response elicited by intracerebroventricular (i.c.v) injections of carbachol and angiotensin II (AII) in rats. Clonidine (an α2-adrenergic agonist) injected into the LH produced a dose-dependent reduction of the drinking responses elicited by i.c.v. administration of carbachol and AII. The α1-adrenergic agonist phenylephrine injected into the LH reduced the dipsogenic response to i.c.v. AII, but not to carbachol. Injection of yohimbine (an α2-adrenergic antagonist) and prazosin (an α1-adrenergic antagonist) into the LH also reduced the water intake produced by i.c.v. injection of AII. Previous injection of α1- or α2-adrenergic antagonists into the LH increased the antidipsogenic effect of clonidine or phenylephrine injected into the same area on the water intake induced by i.c.v. AII. These results show that the α1- and α2-adrenergic receptors of the LH are involved in the control of drinking responses elicited by i.c.v. injection of AII in rats. They also show that clonidine, but not phenylephrine, suppresses the drinking induced by i.c.v. carbachol. The data suggest that the discharge of central α-adrenergic receptors has a dual (inhibitory and excitatory) effect on water intake induced by central AII. © 1991

Carbachol injection into the medial preoptic area induces natriuresis, kaliuresis and antidiuresis in rats

The microinjection of carbachol into the medial preoptic area (MPO) of the rat induced natriuresis, kaliuresis and anti-diuresis in a dose-related manner. Atropine blocked all responses to carbachol. Hexamethonium impaired the dose-response effect of carbachol on kaliuresis, but had no effect on natriuresis and enhanced the antidiuretic effect of carbachol. Nicotine alone had no effects, but pre-treatment with nicotine enhanced the responses to carbachol. These data show that activity of the muscarinic receptors of the MPO increases renal electrolyte and reduces water excretion. They also suggest that nicotinic receptors have an inhibitory effect on water excretion. Nicotine could act through mechanisms unrelated to nicotinic receptors to enhance the effect of the carbachol. © 1989

Clonidine and phenylephrine injected into the lateral preoptic area reduce water intake in dehydrated rats

In the present study, we investigated the effect of phenylephrine and clonidine (α1- and α2-adrenoceptor agonists, respectively) injected into the lateral preoptic area (LPOA) on the water intake induced by water deprivation in rats. In addition, the effects of prior injections of prazosin and yohimbine (α1- and α2-adrenoceptor antagonists, respectively) into the LPOA on the antidipsogenic action of phenylephrine and clonidine were investigated. After 30 h of water deprivation, the water intake of rats in a control experiment (saline injection) was 10.5 ± 0.8 ml/h. Injection of clonidine (5, 10, 20, and 40 nmol) into the LPOA reduced water intake to 6.3 ± 0.9, 4.9 ± 0.8, 3.6 ± 1.0, and 2.2 ± 0.7 ml/h, respectively. Similar reductions occurred after injection of 80 and 160 nmol phenylephrine into the LPOA (6.2 ± 1.6 and 4.8 ± 1.3 ml/h, respectively). Pretreatment with prazosin (40 nmol) abolished the antidipsogenic action of an 80-nmol dose of phenylephrine (11.3 ± 1.1 ml/h) and reduced the effect of a 20-nmol dose of clonidine (7.4 ± 1.4 ml/h). Yohimbine (20, 40, and 80 nmol), previously injected, produced no significant changes in the effects of either phenylephrine or clonidine. The present results show that phenylephrine and clonidine injected into the LPOA induce an antidipsogenic effect in water-deprived rat. They also suggest an involvement of α1-adrenoceptors in this effect. A possible participation of imidazole receptors in the effect of clonidine should also be taken into account. © 1993

Pressor, dipsogenic, natriuretic and kaliuretic responses to central carbachol in rats with lesion of the medial septal area

In the present study we investigated the effect of electrolytic lesion of the medial septal area (MSA) on the dipsogenic, natriuretic, kaliuretic and pressor responses elicited by intracerebroventricular (i.c.v.) injection of the cholinergic agonist carbachol. Freely moving rats with sham or MSA lesion (1-7 days and 14-18 days) and a stainless steel cannula implanted into the lateral ventricle were studied. In sham rats, i.c.v. injection of carbachol (7.5 nmol) produced an increase in water intake (10.2 ± 1.5 ml/h), mean arterial pressure (MAP) (35 ± 5 mmHg) and urinary Na+ and K+ excretion (551 ± 83 and 170 ± 17 μEq 120 min, resp.). The pressor (18 ± 3 and 14 ± 4 mmHg, resp.) and natriuretic responses (178 ± 58 and 172 ± 38 μEq 120 min) produced by i.c.v. carbachol in acute or chronic MSA-lesioned rats were reduced. No change was observed in urinary K+ excretion and a reduced water intake (5 ± 1.3 ml/h) was observed only in acute MSA-lesioned rats. These results suggest that the MSA plays an important role for the pressor and natriuretic responses induced by central cholinergic activation in rats. A small influence of this structure on water intake may also be suggested. © 1991

Alterations in the water intake caused by central inhibition of angiotensin-converting enzyme in the rat

In the present study we investigated the effects of central (i.c.v.) and subcutaneous (s.c.) injections of a 2 μg dose of lisinopryl, an inhibitor of angiotensin I(ANGI)-converting enzyme (CE), on water intake. I.c.v. but not s.c. injection of lisinopryl abolished drinking in response to s.c. isoprenaline (100 μg/kg) and significantly reduced drinking in response to 24 h water deprivation or s.c. polyethylene glycol (30% w/v, 10 ml/kg). Lisinopryl had no effect on water intake induced by cellular dehydration (s.c. injection of hypertonic saline (2 M NaCl)). These results are consistent with the hypothesis that lisinopryl acts as a CE blocking agent in the brain. The thirst challenge induced by hypotension using isoprenaline acts primarily by generating ANGII systemically and centrally. The other thirst challenges such as cellular dehydration are independent of the ANGII in the brain. This conclusion was made possible by utilizing a new CE blocking agent at a smaller dose than normally used for other ANG I-CE inhibitors. © 1992