Lanfranco R P Troncone | Instituto Butantan (original) (raw)
Papers by Lanfranco R P Troncone
Toxicon : official journal of the International Society on Toxinology, Jan 24, 2017
The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin prod... more The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin. Denervated mice showed intense fibrosis of the cavernosal tissue as well as absence of synaptophysin IHC staining; surprisingly mice showed toxin-induced priapism when tested 15, 30 or 60 days after denervation. While sham-operated mice presented full priapism, denervated animals showed only partial...
Behavioural Brain Research, 2014
Mammals respond to a real or perceived stress in an integrated physiological and psychological fa... more Mammals respond to a real or perceived stress in an integrated physiological and psychological fashion. Psychiatric disorders like major depression and anxiety have been associated to stressful events. In a previous study we demonstrated that the stress-induced ACTH secretion can be robustly inhibited by the concurrent use of CRF1 (CP154,526 - Pfizer) and V1B (SSR149415 - Sanofi-Aventis) non-peptide antagonists. A proof of mechanism was offered by substituting CP154,526 by SSR125543 and obtaining the same results on three stress models: forced swimming, ether vapor inhalation and restraint. SSR125543 effectively blocked only restraint stress-induced ACTH secretion. We then challenged the hypothesis that the concurrent use of both antagonists would have a potent effect on behavioral models of anxiety and depression. Decreasing doses (30-0.1 mg/kg s.c.) of both drugs were tested in three behavioral models: Porsolt forced swimming test, elevated plus maze and social interaction. Results showed that these drugs had no effect on anxiety models (plus maze and social interaction) but significantly reduced immobility time in the forced swimming test, suggesting anti-depressive action in a dose-range from 1 to 30 mg/kg, not different from the reported in the literature referring to one drug or the other. This negates the proposed hypothesis of summation/potentiation of effects as observed in stress-induced ACTH secretion. These results point toward the involvement of extra-hypothalamic sites for the anti-depressive effects. Recent Phase II clinical research on anti-depressive effects of these drugs has failed rising strong criticisms against the predictive value of behavioral tests currently employed.
1995.--Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimm... more 1995.--Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimming would result in suppression of apomorphine-, pilocarpine-, and physostigmine-induced yawning. Immobilization caused suppression of yawning, whereas foot shock and swimming resulted in increased number of yawns. Since interstressor interval was long in the two latter stressors, animals could have recovered and the increase in yawning could be due to the last (acute) exposure to stress. In Experiment 2 we recorded the number of yawns induced by pilocarpine in animals exposed to 1 h of swimming or foot shock. No differences between control and acutely stressed animals were detected. These results suggest that yawning is differently altered by constant and intermittent stressors (i.e., diminished by constant and increased by intermittent stress).
Archives of Medical Research, 2007
Background. Increased sympathetic drive to the heart might contribute to the development and prog... more Background. Increased sympathetic drive to the heart might contribute to the development and progression of myocardial damage in hypertensive patients (HTs). This study assessed the possible presence of abnormalities in myocardial uptake of 123 I-metaiodobenzylguanidine (MIBG), a marker of sympathetic activity, in HTs with left ventricular hypertrophy (LVH). Methods. Eleven HTs with LVH and 10 matched normotensive controls underwent clinical and laboratory examination, as well as LVH determination by echocardiography. The presence of myocardial ischemia was ruled out by exercise stress testing. Global and regional myocardial uptake of 123 I-MIBG was determined in both groups using planar and single proton emission tomography scintigraphy. In addition, thallium-201 (Tl-201) myocardial scintigraphy was performed in HTs. The heart/mediastinum (H/M) ratio on planar 123 I-MIBG images at different time points was compared between HTs and controls. Moreover, regional cardiac uptake of 123 I-MIBG was compared between groups and, within the HTs group, with regional Tl-201 uptake. Results. At all study times, the H/M ratio was lower in HTs than in controls (all p !0.05). A significant reduction in 123 I-MIBG uptake in the mid-inferolateral and midinferior segments was observed in HTs compared to controls. Also, a significant reduction in 123 I-MIBG uptake compared to Tl-210 uptake was observed in non-septal segments of HTs. Conclusions. Cardiac abnormalities in global and regional uptake of 123 I-MIBG, as well as impaired 123 I-MIBG compared to Tl-201 uptake, are present in HTs with LVH. Given the effect of sympathetic nervous system on the heart, these abnormalities might play a role in hypertension-related cardiac damage.
![Research paper thumbnail of O uso de animais em pesquisas científicas: [carta ao editor]](https://attachments.academia-assets.com/66740150/thumbnails/1.jpg)
](Arq Bras Cienc Saude, Apr 1, 2008
N os países onde a ciência recebe tratamento prioritário esta discussão já se esgotou. O emprego ... more N os países onde a ciência recebe tratamento prioritário esta discussão já se esgotou. O emprego de animais em experimentação pode ser avaliado por vários ângulos. Um artigo abrangente sobre os aspectos técnicos e históricos desta questão foi publicado na edição de número 144, de fevereiro de 2008, da Revista Pesquisa Fapesp. Após a leitura desta matéria muitos concordarão que a discussão desse polêmico assunto já é coisa do passado. Para não deixar uma lacuna neste texto, só consigo acrescentar que não há nenhuma maneira de substituir um organismo vivo quando se trata de fazer ciência no campo da psicologia e do comportamento. Seres vivos se comportam. Até mesmo paramécios e amebas se comportam, aprendem e respondem a estímulos. Nisso o ser humano se parece com um unicelulado. Modelos animais de distúrbios psíquicos são largamente usados em todo o mundo e não há como substituí-los por modelos in vitro, como gostariam os críticos do uso de animais em experimentação. Talvez este tipo de investigação seja o que mais provoca as paixões, pois a incompreensão dos processos psíquicos humanos e a relutância em atribuir caracteres humanos a animais, que se chama de antropomorfisação, dificulta a avaliação fria dos fatos. Se uma pessoa pode ser levada à depressão ou à ansiedade, seja por um desequilíbrio neuroquímico (endógeno) ou por uma situação vivencial (reativa), é porque uma doença existe ou porque uma situação se impôs à pessoa e a levou ao desequilíbrio. Enquanto as bases fisiopatológicas desses distúrbios (e de todos os outros) não forem completamente conhecidas, não haverá maneira de substituir os modelos animais. Portanto, um dia a ciência conseguirá ter estas respostas apenas, e tão somente, se empregar modelos animais agora e ainda por muito tempo. Creio que uma questão ética como esta merece uma reflexão de caráter filosófico. A pergunta que se pretende responder é simples e direta: Nós temos o direito de usar animais para investigação científica? Se a resposta for sim a questão estará esgotada, mas se a resposta for não somos levados a refazer a pergunta com uma abrangência maior: Nós temos o direito de usar animais? Isso pode parecer uma regressão inútil mas evidencia um vício de raciocínio por parte daqueles que se opõem à experimentação animal. O vício está em achar que o que se faz com animais em laboratório é cruel, desnecessário e/ou dá prazer ao experimentador. Não há nada mais errado do que esta idéia. Nunca conheci em toda minha vida, ninguém que tivesse prazer em usar animais em seus experimentos na ciência (quase 30 anos no Brasil e exterior). Nenhum cientista sério usa animais sem um fim específico e finalmente, existe uma regulamentação que é imposta ao pesquisador quando este submete seus projetos a agências financiadoras ou revistas científicas. Essa regulamentação prevê limites claros ao que se pode fazer com animais, visando minimizar o sofrimento imposto a eles. Quanto a usar animais para nossos fins, várias espécies da escala zoológica, porque não dizer todos os seres vivos, fazem parte de uma cadeia alimentar e assim fazemos nós também. Este é, talvez, o argumento mais antigo dos defensores do uso de animais, mas ainda não se conseguiu mudar tal fato. Quero ir mais longe pois não vejo motivos para parar: não se pode negar que as plantas, fungos e microorganismos das mais diversas naturezas sejam entidades vivas; assim, usando a estratégia dos antigos, a reductio ad absurdum não poderíamos usar nenhum deles para nossos fins egoístas. Talvez, então, tenhamos que nos alimentar de carcaças de animais mortos por "causas naturais" e chegaríamos imediatamente à conclusão de que os únicos animais eticamente corretos são os urubus, hienas e bactérias decompositoras. Filósofos são treinados a expressar e defender suas idéias. Bertrand Russell é considerado por muitos o maior filósofo contemporâneo. Morreu em 1970 aos 98 anos. Em seu pequeno livro intitulado "No que acredito" (no Brasil, L&PM Editores, 2007) Russell advogava em 1925, ano de sua publicação, que o homem tem o dever de usar seu intelecto para o seu próprio bem. Para usar suas próprias palavras: "O respeito à natureza física é pura tolice; a natureza física deve ser estudada no intuito de se fazer com que sirva... aos propósitos humanos, ainda que, do ponto de vista ético, ela permaneça nem boa, nem má." Contam seus estudiosos, que Russell foi muito criticado por esta frase. É compreensível que um homem ilustrado perca a paciência diante do dogmatismo e autoritarismo e mude o tom do discurso, pois esta frase se encontra no final do livro. Entre seus argumentos iniciais está uma frase que precisa estar em nossas mentes: "A filosofia da natureza é uma coisa; a filosofia do valor é totalmente distinta. Confundi-las não gera senão prejuízo. O que consideramos bom, aquilo de que deveríamos gostar, não tem qualquer relação com o que é -questão esta concernente à filosofia da natureza."
Zoo Biol, 2001
Habituation to captivity is difficult for some species. Understanding the motivational elements i... more Habituation to captivity is difficult for some species. Understanding the motivational elements involved in predation may ease this habituation. Seventy-one Brazilian jararaca snakes (Bothrops jararaca [Wied, 1824], Viperidae, Crotalinae) recently captured and never fed in captivity were tested for predatory behavior on rodents. Lighting was adapted to allow predatory sessions to occur during the first hours of the night when these animals are more active. Up to three prey subjects were presented in a session. In the first experiment, the preference for prey size and color was assessed using albino and dark-colored rodents. In a second experiment, a group of snakes was submitted to 12 sessions during a period of almost 2 years. The strike strategy was classified in one of two categories: envenomation (E) or seizing (S). Envenomation involved a bite delivered by the snake with prompt retrieval of the head; holding the rodent in the snake's jaws since the first strike, without retrieving the fangs and holding the prey during venom action, characterized S strike. Trailing and swallowing the dead prey always followed E strike. Results suggest that snakes fed more often on larger subjects. The color of the prey was not a relevant factor. E strike was predominant in the first predatory event in captivity. After habituation, S strike was predominant. Snakes may have a poor perception of the prey objects in captivity and adopt a strike strategy that assures the control of the prey. Also, the use of small prey subjects to ease feeding during adaptation to captivity may be less effective. Zoo Biol 20: 399-406, 2001.
Neuropsychobiology, 2016
Vasopressin and CRH have complementary roles in the secretion of ACTH following different stress ... more Vasopressin and CRH have complementary roles in the secretion of ACTH following different stress modalities. The concomitant use of V1b and CRF1 receptor antagonists completely inhibits ACTH secretion in response to different stress modalities. The combination of the CRF1 antagonist SSR125543 with the V1b antagonist SSR149415 effectively suppressed plasma ACTH 1.30 h after injection in rats stressed by ether vapor inhalation for 1 min, restraint stress for 1 h or forced swimming for 5 min. The duration of the effect was also studied. The CRF1 antagonist effectively suppressed ACTH secretion in restraint stress, while the V1b antagonist was effective against ether inhalation. Both antagonists were necessary to block the forced swimming stress response. SSR125543 induced a prolonged effect and can be used in a model of prolonged HPA axis blockade.
Toxicon Official Journal of the International Society on Toxinology, Jul 1, 2009
The peptides Tx2-5 and Tx2-6, isolated from the whole venom of ''armed-spider'' Phoneutria nigriv... more The peptides Tx2-5 and Tx2-6, isolated from the whole venom of ''armed-spider'' Phoneutria nigriventer venom, are directly linked with the induction of persistent and painful erection in the penis of mammals. The erection induced by Tx2-6 has been associated with the activation of nitric oxide synthases. There is a scarcity of studies focusing on the outcome of Tx2-6 at the molecular level, by this reason we evaluated the gene profile activity of this toxin at the nitric oxide (NO) pathway. After microarray analyses on cavernous tissue of mice inoculated with Tx2-6 we found that only 10.4% (10/96) of these genes were differentially expressed, showing a limited effect of the toxin on the NO pathway. We found the genes sparc, ednrb, junb, cdkn1a, bcl2, ccl5, abcc1 over-expressed and the genes sod1, s100a10 and fth1 under-expressed after inoculation of Tx2-6. The differential expressions of sparc and ednrb genes were further confirmed using real-time PCR. Interestingly, ednrb activates the L-arginine/NO/cGMP pathway that is involved in the relaxation of the cavernous body. Therefore the priapism induced by Tx2-6 is a consequence of a highly specific interference of this neurotoxin with the NO pathway.
Amb Rev Assoc Med Bras, Jun 1, 1987
... experimental, Documentos relacionados. Id: 42612. Autor: Carlini, Elisaldo Luiz de Araújo; Br... more ... experimental, Documentos relacionados. Id: 42612. Autor: Carlini, Elisaldo Luiz de Araújo; Braz, Sandra; Troncone, Lanfranco R. P; Tufik, Sergio; Romanach, Anna K; Pustiglione, Marcelo; Sposati, Mário Carlos Costa; Cudizio Filho, Oswaldo; Prado, Maria Isabel Almeida. ...
Animals deprived of REM sleep by the water tank technique show an important decrease in frequency... more Animals deprived of REM sleep by the water tank technique show an important decrease in frequency of yawning, induced by dopaminergic (apomorphine in low doses) and cholinergic (physostigmine and pilocarpine) agonists, if they are tested immediately after the 96 hr of deprivation. In order to understand the mechanisms underlying the effects of REM sleep deprivation on dopaminergic and cholinergic systems, we decided to test the animals after a recovery period of 24 hr. It was observed that apomorphine-induced yawning was still significantly reduced, whereas pilocarpine-induced yawning had returned to normal. The findings suggest that REM sleep deprivation alters dopaminergic and cholinergic systems in different ways: it seems that the interference on the dopaminergic system is prior and stronger than on the cholinergic system, thus its recovery demands more time.
AMB; revista da Associação Médica Brasileira
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the author's institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: a b s t r a c t The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin. Denervated mice showed intense fibrosis of the cavernosal tissue as well as absence of synaptophysin IHC staining; surprisingly mice showed toxin-induced priapism when tested 15, 30 or 60 days after denervation. While sham-operated mice presented full priapism, denervated animals showed only partial priapism possibly due to the fibrosis. These results reveal that erection caused by Tx2-6 toxin may not depend on cavernosal nerves integrity. The effect of this toxin on sodium channels seem not directly involved in priapism as many toxins have identical effects but do not induce priapism. Discussion approaches the many different potential sites of intervention listed in the signaling cascades of NO/cGMP, RhoA/Rho-Kinase, as well as the emerging new gasotransmitter H 2 S. The pharmacological inhibition of Rho-kinase and toxin Tx2-6 have similar effects in vivo.
Toxicon, 2007
Crotamine is a peptide toxin from the venom of the rattlesnake Crotalus durissus terrificus that ... more Crotamine is a peptide toxin from the venom of the rattlesnake Crotalus durissus terrificus that induces a typical hindlimb paralysis of unknown nature. Hind limbs have a predominance of fast-twitching muscles that bear a higher density of sodium channels believed until now to be the primary target of crotamine. Hypothetically, this makes these muscles more sensitive to crotamine and would explain such hind-limb paralysis. To challenge this hypothesis, we performed concentration vs. response curves on fast (extensor digitorum longus (EDL)) and slow (soleus) muscles of adult male rats. Crotamine was tested on various human Na + channel isoforms (Na v 1.1-Na v 1.6 a-subunits) expressed in HEK293 cells in patch-clamp experiments, as well as in acutely dissociated dorsal root ganglion (DRG) neurons. Also, the behavioral effects of crotamine intoxication were compared with those of a muscle-selective sodium channel antagonist m-CgTx-GIIIA, and other sodium-acting toxins such as tetrodotoxin aand b-pompilidotoxins, sea anemone toxin BcIII, spider toxin Tx2-6. Results pointed out that EDL was more susceptible to crotamine than soleus under direct electrical stimulation. Surprisingly, electrophysiological experiments in human Na v 1.1 to Na v 1.6 Na + channels failed to show any significant change in channel characteristics, in a clear contrast with former studies. DRG neurons did not respond to crotamine. The behavioral effects of the toxins were described in detail and showed remarkable differences. We conclude that, although differences in the physiology of fast and slow muscles may cause the typical crotamine syndrome, sodium channels are not the primary target of crotamine and therefore, the real mechanism of action of this toxin is still unknown. r
Arquivos Brasileiros de Ciências da Saúde, 2008
Opinião 1925, ano de sua publicação, que o homem tem o dever de usar seu intelecto para o seu pró... more Opinião 1925, ano de sua publicação, que o homem tem o dever de usar seu intelecto para o seu próprio bem. Para usar suas próprias palavras: "O respeito à natureza física é pura tolice; a natureza física deve ser estudada no intuito de se fazer com que sirva... aos propósitos humanos, ainda que, do ponto de vista ético, ela permaneça nem boa, nem má." Contam seus estudiosos, que Russell foi muito criticado por esta frase. É compreensível que um homem ilustrado perca a paciência diante do dogmatismo e autoritarismo e mude o tom do discurso, pois esta frase se encontra no fi nal do livro. Entre seus argumentos iniciais está uma frase que precisa estar em nossas mentes: "A fi losofi a da natureza é uma coisa; a fi losofi a do valor é totalmente distinta. Confundi-las não gera senão prejuízo. O que consideramos bom, aquilo de que deveríamos gostar, não tem qualquer relação com o que é -questão esta concernente à fi losofi a da natureza." O texto continua defendendo que dar valor a coisas não é errado e mesmo, admirar a beleza da natureza não tem signifi cado, pois nós fazemos parte dela. Esses argumentos são intrigantes e expõem Arquivos Brasileiros de Ciências da Saúde, v.33, n. 1, p. 0-0
BJU International, 2008
smooth muscle, thus causing penile erection. Thirty-five mice were divided in two groups; 10 cont... more smooth muscle, thus causing penile erection. Thirty-five mice were divided in two groups; 10 control mice were injected 20 µ L of saline solution, and in the treated group, 25 mice were divided into groups of five and each subgroup received eretina in decreasing doses (0.024, 0.012, 0.006, 0.003 and 0.0015 µ g/kg) until the minimum dose that produced an erection was determined. After treatment all mice were monitored to determine the response and any collateral effects.
Toxicon : official journal of the International Society on Toxinology, Jan 24, 2017
The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin prod... more The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin. Denervated mice showed intense fibrosis of the cavernosal tissue as well as absence of synaptophysin IHC staining; surprisingly mice showed toxin-induced priapism when tested 15, 30 or 60 days after denervation. While sham-operated mice presented full priapism, denervated animals showed only partial...
Behavioural Brain Research, 2014
Mammals respond to a real or perceived stress in an integrated physiological and psychological fa... more Mammals respond to a real or perceived stress in an integrated physiological and psychological fashion. Psychiatric disorders like major depression and anxiety have been associated to stressful events. In a previous study we demonstrated that the stress-induced ACTH secretion can be robustly inhibited by the concurrent use of CRF1 (CP154,526 - Pfizer) and V1B (SSR149415 - Sanofi-Aventis) non-peptide antagonists. A proof of mechanism was offered by substituting CP154,526 by SSR125543 and obtaining the same results on three stress models: forced swimming, ether vapor inhalation and restraint. SSR125543 effectively blocked only restraint stress-induced ACTH secretion. We then challenged the hypothesis that the concurrent use of both antagonists would have a potent effect on behavioral models of anxiety and depression. Decreasing doses (30-0.1 mg/kg s.c.) of both drugs were tested in three behavioral models: Porsolt forced swimming test, elevated plus maze and social interaction. Results showed that these drugs had no effect on anxiety models (plus maze and social interaction) but significantly reduced immobility time in the forced swimming test, suggesting anti-depressive action in a dose-range from 1 to 30 mg/kg, not different from the reported in the literature referring to one drug or the other. This negates the proposed hypothesis of summation/potentiation of effects as observed in stress-induced ACTH secretion. These results point toward the involvement of extra-hypothalamic sites for the anti-depressive effects. Recent Phase II clinical research on anti-depressive effects of these drugs has failed rising strong criticisms against the predictive value of behavioral tests currently employed.
1995.--Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimm... more 1995.--Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimming would result in suppression of apomorphine-, pilocarpine-, and physostigmine-induced yawning. Immobilization caused suppression of yawning, whereas foot shock and swimming resulted in increased number of yawns. Since interstressor interval was long in the two latter stressors, animals could have recovered and the increase in yawning could be due to the last (acute) exposure to stress. In Experiment 2 we recorded the number of yawns induced by pilocarpine in animals exposed to 1 h of swimming or foot shock. No differences between control and acutely stressed animals were detected. These results suggest that yawning is differently altered by constant and intermittent stressors (i.e., diminished by constant and increased by intermittent stress).
Archives of Medical Research, 2007
Background. Increased sympathetic drive to the heart might contribute to the development and prog... more Background. Increased sympathetic drive to the heart might contribute to the development and progression of myocardial damage in hypertensive patients (HTs). This study assessed the possible presence of abnormalities in myocardial uptake of 123 I-metaiodobenzylguanidine (MIBG), a marker of sympathetic activity, in HTs with left ventricular hypertrophy (LVH). Methods. Eleven HTs with LVH and 10 matched normotensive controls underwent clinical and laboratory examination, as well as LVH determination by echocardiography. The presence of myocardial ischemia was ruled out by exercise stress testing. Global and regional myocardial uptake of 123 I-MIBG was determined in both groups using planar and single proton emission tomography scintigraphy. In addition, thallium-201 (Tl-201) myocardial scintigraphy was performed in HTs. The heart/mediastinum (H/M) ratio on planar 123 I-MIBG images at different time points was compared between HTs and controls. Moreover, regional cardiac uptake of 123 I-MIBG was compared between groups and, within the HTs group, with regional Tl-201 uptake. Results. At all study times, the H/M ratio was lower in HTs than in controls (all p !0.05). A significant reduction in 123 I-MIBG uptake in the mid-inferolateral and midinferior segments was observed in HTs compared to controls. Also, a significant reduction in 123 I-MIBG uptake compared to Tl-210 uptake was observed in non-septal segments of HTs. Conclusions. Cardiac abnormalities in global and regional uptake of 123 I-MIBG, as well as impaired 123 I-MIBG compared to Tl-201 uptake, are present in HTs with LVH. Given the effect of sympathetic nervous system on the heart, these abnormalities might play a role in hypertension-related cardiac damage.
Arq Bras Cienc Saude, Apr 1, 2008
N os países onde a ciência recebe tratamento prioritário esta discussão já se esgotou. O emprego ... more N os países onde a ciência recebe tratamento prioritário esta discussão já se esgotou. O emprego de animais em experimentação pode ser avaliado por vários ângulos. Um artigo abrangente sobre os aspectos técnicos e históricos desta questão foi publicado na edição de número 144, de fevereiro de 2008, da Revista Pesquisa Fapesp. Após a leitura desta matéria muitos concordarão que a discussão desse polêmico assunto já é coisa do passado. Para não deixar uma lacuna neste texto, só consigo acrescentar que não há nenhuma maneira de substituir um organismo vivo quando se trata de fazer ciência no campo da psicologia e do comportamento. Seres vivos se comportam. Até mesmo paramécios e amebas se comportam, aprendem e respondem a estímulos. Nisso o ser humano se parece com um unicelulado. Modelos animais de distúrbios psíquicos são largamente usados em todo o mundo e não há como substituí-los por modelos in vitro, como gostariam os críticos do uso de animais em experimentação. Talvez este tipo de investigação seja o que mais provoca as paixões, pois a incompreensão dos processos psíquicos humanos e a relutância em atribuir caracteres humanos a animais, que se chama de antropomorfisação, dificulta a avaliação fria dos fatos. Se uma pessoa pode ser levada à depressão ou à ansiedade, seja por um desequilíbrio neuroquímico (endógeno) ou por uma situação vivencial (reativa), é porque uma doença existe ou porque uma situação se impôs à pessoa e a levou ao desequilíbrio. Enquanto as bases fisiopatológicas desses distúrbios (e de todos os outros) não forem completamente conhecidas, não haverá maneira de substituir os modelos animais. Portanto, um dia a ciência conseguirá ter estas respostas apenas, e tão somente, se empregar modelos animais agora e ainda por muito tempo. Creio que uma questão ética como esta merece uma reflexão de caráter filosófico. A pergunta que se pretende responder é simples e direta: Nós temos o direito de usar animais para investigação científica? Se a resposta for sim a questão estará esgotada, mas se a resposta for não somos levados a refazer a pergunta com uma abrangência maior: Nós temos o direito de usar animais? Isso pode parecer uma regressão inútil mas evidencia um vício de raciocínio por parte daqueles que se opõem à experimentação animal. O vício está em achar que o que se faz com animais em laboratório é cruel, desnecessário e/ou dá prazer ao experimentador. Não há nada mais errado do que esta idéia. Nunca conheci em toda minha vida, ninguém que tivesse prazer em usar animais em seus experimentos na ciência (quase 30 anos no Brasil e exterior). Nenhum cientista sério usa animais sem um fim específico e finalmente, existe uma regulamentação que é imposta ao pesquisador quando este submete seus projetos a agências financiadoras ou revistas científicas. Essa regulamentação prevê limites claros ao que se pode fazer com animais, visando minimizar o sofrimento imposto a eles. Quanto a usar animais para nossos fins, várias espécies da escala zoológica, porque não dizer todos os seres vivos, fazem parte de uma cadeia alimentar e assim fazemos nós também. Este é, talvez, o argumento mais antigo dos defensores do uso de animais, mas ainda não se conseguiu mudar tal fato. Quero ir mais longe pois não vejo motivos para parar: não se pode negar que as plantas, fungos e microorganismos das mais diversas naturezas sejam entidades vivas; assim, usando a estratégia dos antigos, a reductio ad absurdum não poderíamos usar nenhum deles para nossos fins egoístas. Talvez, então, tenhamos que nos alimentar de carcaças de animais mortos por "causas naturais" e chegaríamos imediatamente à conclusão de que os únicos animais eticamente corretos são os urubus, hienas e bactérias decompositoras. Filósofos são treinados a expressar e defender suas idéias. Bertrand Russell é considerado por muitos o maior filósofo contemporâneo. Morreu em 1970 aos 98 anos. Em seu pequeno livro intitulado "No que acredito" (no Brasil, L&PM Editores, 2007) Russell advogava em 1925, ano de sua publicação, que o homem tem o dever de usar seu intelecto para o seu próprio bem. Para usar suas próprias palavras: "O respeito à natureza física é pura tolice; a natureza física deve ser estudada no intuito de se fazer com que sirva... aos propósitos humanos, ainda que, do ponto de vista ético, ela permaneça nem boa, nem má." Contam seus estudiosos, que Russell foi muito criticado por esta frase. É compreensível que um homem ilustrado perca a paciência diante do dogmatismo e autoritarismo e mude o tom do discurso, pois esta frase se encontra no final do livro. Entre seus argumentos iniciais está uma frase que precisa estar em nossas mentes: "A filosofia da natureza é uma coisa; a filosofia do valor é totalmente distinta. Confundi-las não gera senão prejuízo. O que consideramos bom, aquilo de que deveríamos gostar, não tem qualquer relação com o que é -questão esta concernente à filosofia da natureza."
Zoo Biol, 2001
Habituation to captivity is difficult for some species. Understanding the motivational elements i... more Habituation to captivity is difficult for some species. Understanding the motivational elements involved in predation may ease this habituation. Seventy-one Brazilian jararaca snakes (Bothrops jararaca [Wied, 1824], Viperidae, Crotalinae) recently captured and never fed in captivity were tested for predatory behavior on rodents. Lighting was adapted to allow predatory sessions to occur during the first hours of the night when these animals are more active. Up to three prey subjects were presented in a session. In the first experiment, the preference for prey size and color was assessed using albino and dark-colored rodents. In a second experiment, a group of snakes was submitted to 12 sessions during a period of almost 2 years. The strike strategy was classified in one of two categories: envenomation (E) or seizing (S). Envenomation involved a bite delivered by the snake with prompt retrieval of the head; holding the rodent in the snake's jaws since the first strike, without retrieving the fangs and holding the prey during venom action, characterized S strike. Trailing and swallowing the dead prey always followed E strike. Results suggest that snakes fed more often on larger subjects. The color of the prey was not a relevant factor. E strike was predominant in the first predatory event in captivity. After habituation, S strike was predominant. Snakes may have a poor perception of the prey objects in captivity and adopt a strike strategy that assures the control of the prey. Also, the use of small prey subjects to ease feeding during adaptation to captivity may be less effective. Zoo Biol 20: 399-406, 2001.
Neuropsychobiology, 2016
Vasopressin and CRH have complementary roles in the secretion of ACTH following different stress ... more Vasopressin and CRH have complementary roles in the secretion of ACTH following different stress modalities. The concomitant use of V1b and CRF1 receptor antagonists completely inhibits ACTH secretion in response to different stress modalities. The combination of the CRF1 antagonist SSR125543 with the V1b antagonist SSR149415 effectively suppressed plasma ACTH 1.30 h after injection in rats stressed by ether vapor inhalation for 1 min, restraint stress for 1 h or forced swimming for 5 min. The duration of the effect was also studied. The CRF1 antagonist effectively suppressed ACTH secretion in restraint stress, while the V1b antagonist was effective against ether inhalation. Both antagonists were necessary to block the forced swimming stress response. SSR125543 induced a prolonged effect and can be used in a model of prolonged HPA axis blockade.
Toxicon Official Journal of the International Society on Toxinology, Jul 1, 2009
The peptides Tx2-5 and Tx2-6, isolated from the whole venom of ''armed-spider'' Phoneutria nigriv... more The peptides Tx2-5 and Tx2-6, isolated from the whole venom of ''armed-spider'' Phoneutria nigriventer venom, are directly linked with the induction of persistent and painful erection in the penis of mammals. The erection induced by Tx2-6 has been associated with the activation of nitric oxide synthases. There is a scarcity of studies focusing on the outcome of Tx2-6 at the molecular level, by this reason we evaluated the gene profile activity of this toxin at the nitric oxide (NO) pathway. After microarray analyses on cavernous tissue of mice inoculated with Tx2-6 we found that only 10.4% (10/96) of these genes were differentially expressed, showing a limited effect of the toxin on the NO pathway. We found the genes sparc, ednrb, junb, cdkn1a, bcl2, ccl5, abcc1 over-expressed and the genes sod1, s100a10 and fth1 under-expressed after inoculation of Tx2-6. The differential expressions of sparc and ednrb genes were further confirmed using real-time PCR. Interestingly, ednrb activates the L-arginine/NO/cGMP pathway that is involved in the relaxation of the cavernous body. Therefore the priapism induced by Tx2-6 is a consequence of a highly specific interference of this neurotoxin with the NO pathway.
Amb Rev Assoc Med Bras, Jun 1, 1987
... experimental, Documentos relacionados. Id: 42612. Autor: Carlini, Elisaldo Luiz de Araújo; Br... more ... experimental, Documentos relacionados. Id: 42612. Autor: Carlini, Elisaldo Luiz de Araújo; Braz, Sandra; Troncone, Lanfranco R. P; Tufik, Sergio; Romanach, Anna K; Pustiglione, Marcelo; Sposati, Mário Carlos Costa; Cudizio Filho, Oswaldo; Prado, Maria Isabel Almeida. ...
Animals deprived of REM sleep by the water tank technique show an important decrease in frequency... more Animals deprived of REM sleep by the water tank technique show an important decrease in frequency of yawning, induced by dopaminergic (apomorphine in low doses) and cholinergic (physostigmine and pilocarpine) agonists, if they are tested immediately after the 96 hr of deprivation. In order to understand the mechanisms underlying the effects of REM sleep deprivation on dopaminergic and cholinergic systems, we decided to test the animals after a recovery period of 24 hr. It was observed that apomorphine-induced yawning was still significantly reduced, whereas pilocarpine-induced yawning had returned to normal. The findings suggest that REM sleep deprivation alters dopaminergic and cholinergic systems in different ways: it seems that the interference on the dopaminergic system is prior and stronger than on the cholinergic system, thus its recovery demands more time.
AMB; revista da Associação Médica Brasileira
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the author's institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: a b s t r a c t The Phoneutria nigriventer spider toxin Tx2-6 causes priapism in humans and mice. This toxin produces a delay in Sodium channel inactivation, generalized vascular congestion and death by respiratory failure. NO-Synthase inhibitors seem to abolish toxin-induced priapism. The understanding of the ultimate molecular mechanism involved in toxin-induced priapism may shed light on aspects of erectile function/dysfunction. This study investigates if cavernosal denervation can abolish the toxin-induced priapism. Surgical cavernosal nerve excision/denervation was performed in mice and confirmed by infertility, histological assessment of fibrosis and immunohistochemical staining for synaptophysin. Denervated mice showed intense fibrosis of the cavernosal tissue as well as absence of synaptophysin IHC staining; surprisingly mice showed toxin-induced priapism when tested 15, 30 or 60 days after denervation. While sham-operated mice presented full priapism, denervated animals showed only partial priapism possibly due to the fibrosis. These results reveal that erection caused by Tx2-6 toxin may not depend on cavernosal nerves integrity. The effect of this toxin on sodium channels seem not directly involved in priapism as many toxins have identical effects but do not induce priapism. Discussion approaches the many different potential sites of intervention listed in the signaling cascades of NO/cGMP, RhoA/Rho-Kinase, as well as the emerging new gasotransmitter H 2 S. The pharmacological inhibition of Rho-kinase and toxin Tx2-6 have similar effects in vivo.
Toxicon, 2007
Crotamine is a peptide toxin from the venom of the rattlesnake Crotalus durissus terrificus that ... more Crotamine is a peptide toxin from the venom of the rattlesnake Crotalus durissus terrificus that induces a typical hindlimb paralysis of unknown nature. Hind limbs have a predominance of fast-twitching muscles that bear a higher density of sodium channels believed until now to be the primary target of crotamine. Hypothetically, this makes these muscles more sensitive to crotamine and would explain such hind-limb paralysis. To challenge this hypothesis, we performed concentration vs. response curves on fast (extensor digitorum longus (EDL)) and slow (soleus) muscles of adult male rats. Crotamine was tested on various human Na + channel isoforms (Na v 1.1-Na v 1.6 a-subunits) expressed in HEK293 cells in patch-clamp experiments, as well as in acutely dissociated dorsal root ganglion (DRG) neurons. Also, the behavioral effects of crotamine intoxication were compared with those of a muscle-selective sodium channel antagonist m-CgTx-GIIIA, and other sodium-acting toxins such as tetrodotoxin aand b-pompilidotoxins, sea anemone toxin BcIII, spider toxin Tx2-6. Results pointed out that EDL was more susceptible to crotamine than soleus under direct electrical stimulation. Surprisingly, electrophysiological experiments in human Na v 1.1 to Na v 1.6 Na + channels failed to show any significant change in channel characteristics, in a clear contrast with former studies. DRG neurons did not respond to crotamine. The behavioral effects of the toxins were described in detail and showed remarkable differences. We conclude that, although differences in the physiology of fast and slow muscles may cause the typical crotamine syndrome, sodium channels are not the primary target of crotamine and therefore, the real mechanism of action of this toxin is still unknown. r
Arquivos Brasileiros de Ciências da Saúde, 2008
Opinião 1925, ano de sua publicação, que o homem tem o dever de usar seu intelecto para o seu pró... more Opinião 1925, ano de sua publicação, que o homem tem o dever de usar seu intelecto para o seu próprio bem. Para usar suas próprias palavras: "O respeito à natureza física é pura tolice; a natureza física deve ser estudada no intuito de se fazer com que sirva... aos propósitos humanos, ainda que, do ponto de vista ético, ela permaneça nem boa, nem má." Contam seus estudiosos, que Russell foi muito criticado por esta frase. É compreensível que um homem ilustrado perca a paciência diante do dogmatismo e autoritarismo e mude o tom do discurso, pois esta frase se encontra no fi nal do livro. Entre seus argumentos iniciais está uma frase que precisa estar em nossas mentes: "A fi losofi a da natureza é uma coisa; a fi losofi a do valor é totalmente distinta. Confundi-las não gera senão prejuízo. O que consideramos bom, aquilo de que deveríamos gostar, não tem qualquer relação com o que é -questão esta concernente à fi losofi a da natureza." O texto continua defendendo que dar valor a coisas não é errado e mesmo, admirar a beleza da natureza não tem signifi cado, pois nós fazemos parte dela. Esses argumentos são intrigantes e expõem Arquivos Brasileiros de Ciências da Saúde, v.33, n. 1, p. 0-0
BJU International, 2008
smooth muscle, thus causing penile erection. Thirty-five mice were divided in two groups; 10 cont... more smooth muscle, thus causing penile erection. Thirty-five mice were divided in two groups; 10 control mice were injected 20 µ L of saline solution, and in the treated group, 25 mice were divided into groups of five and each subgroup received eretina in decreasing doses (0.024, 0.012, 0.006, 0.003 and 0.0015 µ g/kg) until the minimum dose that produced an erection was determined. After treatment all mice were monitored to determine the response and any collateral effects.