RESUMO
In mammals, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are involved in cardiovascular and respiratory regulation. Several studies have demonstrated the presence of PACAP, VIP and their receptors in various tissues of teleost fish, including the brain, but little is known about their respiratory and cardiovascular effects. The present study was undertaken to compare the central and peripheral actions of graded doses (25-100 pmol) of trout PACAP and trout VIP on ventilatory and cardiovascular variables in the unanaesthetized rainbow trout. Compared with vehicle, only intracerebroventricular injection of PACAP significantly (P<0.05) elevated the ventilation frequency and the ventilation amplitude, but both peptides significantly increased the total ventilation (total ventilation). However, the maximum hyperventilatory effect of PACAP was approximately 2.5-fold higher than the effect of VIP at the 100 pmol dose (PACAP, (total ventilation)=+5407+/-921 arbitrary units, a.u.; VIP, (total ventilation)=+2056+/-874 a.u.; means +/- s.e.m.). When injected centrally, only PACAP produced a significant increase in mean dorsal aortic blood pressure (P(DA)) (100 pmol: +21%) but neither peptide affected heart rate (f(H)). Intra-arterial injections of either PACAP or VIP were without effect on the ventilatory variables. PACAP was without significant action on P(DA) and f(H) while VIP significantly elevated P(DA) (100 pmol: +36%) without changing f(H). In conclusion, the selective central hyperventilatory actions of exogenously administered trout PACAP, and to a lesser extent VIP, suggest that the endogenous peptides may be implicated in important neuroregulatory functions related to the central control of ventilation in trout.
Assuntos
Consumo de Oxigênio/efeitos dos fármacos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Truta/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Sequência de Aminoácidos , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Eletrocardiografia , Frequência Cardíaca/efeitos dos fármacos , Dados de Sequência Molecular , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Peptídeo Intestinal Vasoativo/genética , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
Although in most vertebrate species urotensin-II (UII) is synthesized in neurons of the central nervous system, little is known regarding the physiological actions of UII in the brain. We have investigated the effects of intracerebroventricular (ICV) administration of synthetic trout UII (1, 5, and 50 pmol) on total motor activity (ACT), ventilatory frequency (VF), ventilatory amplitude (VA), and heart rate (HR) in the unanesthetized trout. ICV injection of UII increased ACT in a dose-dependent manner, and the maximal effect was observed at a dose of 5 pmol. At doses of 1 and 5 pmol, UII did not affect VF, VA, or HR. At the highest dose tested (50 pmol), UII not only increased ACT, but also significantly activated VF, VA, and HR. In contrast, ICV injection of synthetic trout angiotensin-II (5 pmol) did not produce any effect on ACT, VF, or VA, but sharply increased HR. These data provide the first evidence that UII can act centrally to induce motor activity in a nonmammalian vertebrate species.
Assuntos
Frequência Cardíaca/fisiologia , Atividade Motora/fisiologia , Oncorhynchus mykiss/fisiologia , Urotensinas/administração & dosagem , Animais , Frequência Cardíaca/efeitos dos fármacos , Injeções Intraventriculares , Atividade Motora/efeitos dos fármacos , Ventilação Pulmonar/efeitos dos fármacos , Ventilação Pulmonar/fisiologia , Fatores de Tempo , Urotensinas/fisiologiaRESUMO
The present investigation assessed the ability of the neurohypophysial nonapeptide arginine vasotocin (AVT) to centrally regulate the cardiovascular activity in fish. Intracerebroventricular (ICV) injection of AVT (0.4 to 50 ng/kg b.wt.) in anesthetized trout resulted in a dose-related increase in blood pressure (BP) without any consistent changes in heart rate. For doses of AVT ranging from 2 to 50 ng/kg b.wt., BP remained elevated during at least 25 min after ICV injection. Systemic (intraarterial) administration of the same doses of AVT appeared to be less efficient than ICV injection, except for the highest dose (50 ng/kg) which evoked a similar rise in BP as that observed after ICV administration. In contrast to AVT, a high concentration of neuropeptide Y (10 micrograms/kg b.wt., ICV) caused only a slight increase of BP. The results suggest that AVT acts centrally to regulate BP in fish. These data, together with the widespread distribution of AVT-immunoreactive fibers and AVT binding sites in the brain, support the notion that, in fish, AVT may play neuromodulator and/or neurotransmitter functions.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Truta/fisiologia , Vasotocina/administração & dosagem , Animais , Pressão Sanguínea/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Injeções Intra-Arteriais , Injeções Intraventriculares , Masculino , Neuropeptídeo Y/administração & dosagem , Vasotocina/fisiologiaRESUMO
Previous work has shown that incubation of heat-denatured plasma from the rainbow trout Oncorhynchus mykiss with porcine pancreatic kallikrein generates [Lys0, Trp5, Leu8]bradykinin (trout [Lys0]BK). We have now isolated a second BK-related peptide from kallikrein-treated trout plasma with the primary structure: Arg-Arg-Pro-Gly-Trp-Ser-Pro-Leu-Arg (trout [Arg0]BK). Bolus injections of both trout [Arg0]BK and [Lys0]BK (> 100 pmol/kg) into the dorsal aorta of conscious trout produced multiphasic effects on arterial blood pressure. An initial pressor response of short duration (1-2 min) was followed by a fall in pressure (to below basal values in 11 out of 15 animals) and then by a sustained rise in pressure lasting up to 60 min. The maximum rise in pressure produced by trout [Arg0]BK (10 nmol/kg) was approximately one-fourth of the maximum rise produced by angiotensin II in the same animals. Intracerebroventricular injections of trout [Arg0]BK (500 pmol) into conscious trout had no effect on arterial blood pressure or heart rate. Trout [Arg0]BK did not affect the tension of vascular rings from trout efferent branchial and caeliacomesenteric arteries and anterior cardinal vein. Trout des [Arg9]BK had no effect on cardiovascular parameters, either in vivo or in vitro, indicating that the C-terminal arginine residue of the peptide is important in interaction with the trout kinin receptor(s).
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Bradicinina/análogos & derivados , Fármacos Cardiovasculares/farmacologia , Oncorhynchus mykiss , Sequência de Aminoácidos , Animais , Artérias/efeitos dos fármacos , Bradicinina/isolamento & purificação , Bradicinina/farmacologia , Fármacos Cardiovasculares/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Técnicas In Vitro , Injeções Intra-Arteriais , Sistema Calicreína-Cinina , Dados de Sequência Molecular , Veias/efeitos dos fármacosRESUMO
The central effect of angiotensin II on cardiovascular activity has been investigated in conscious trout bearing an intracerebroventricular (i.c.v.) cannula and an intra-arterial catheter. I.c.v. injection of the angiotensin II agonist [Asn1,Val5]AII (6.2-50 pmol) induced a dose-dependent increase in heart rate and arterial blood pressure. Central administration of the angiotensin II antagonist DuP 753 (5 nmol) 30 min before i.c.v. injection of [Asn1,Val5]AII totally prevented the tachycardia and reduced the hypertension induced by the angiotensin II agonist. Intra-arterial injection of arginine-vasotocin (12.5 pmol) caused a bradycardia associated with a marked increase in arterial blood pressure. I.c.v. injection of [Asn1,Val5]AII totally blocked the bradycardia induced by arginine-vasotocin and this effect was prevented by central administration of DuP 753. In contrast, [Asn1,Val5]AII did not affect the increase in blood pressure induced by arginine vasotocin. Suppression of the vagal tone by atropine treatment totally blocked the central effect of [Asn1,Val5]AII. These results show that angiotensin II acts directly on the trout brain to increase blood pressure and heart rate. The effect of angiotensin II is mediated through a receptor related to the mammalian AT1 receptor type.
Assuntos
Angiotensina II/análogos & derivados , Compostos de Bifenilo/farmacologia , Ventrículos Cerebrais/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Imidazóis/farmacologia , Tetrazóis/farmacologia , Angiotensina II/agonistas , Angiotensina II/antagonistas & inibidores , Angiotensina II/farmacologia , Animais , Atropina/administração & dosagem , Atropina/farmacologia , Compostos de Bifenilo/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Ventrículos Cerebrais/efeitos dos fármacos , Estado de Consciência , Relação Dose-Resposta a Droga , Imidazóis/administração & dosagem , Injeções Intra-Arteriais , Injeções Intraventriculares , Losartan , Tetrazóis/administração & dosagem , TrutaRESUMO
The cardiovascular activity of neurohypophyseal peptides has been investigated in conscious trout bearing an intracerebroventricular guide cannula and a permanent intraarterial catheter. Changes in diastolic pressure, systolic pressure and heart rate were monitored during the 25-min period following intracerebroventricular or intraarterial administration of arginine vasotocin and related neuropeptides, including arginine vasopressin, oxytocin, hydrin-2, mesotocin, isotocin and conopressin-S. Intracerebroventricular injection of increasing doses of arginine vasotocin (0.62-5 pmol) induced a dose-dependent increase of diastolic and systolic pressures. The onset of the response occurred within 3-5 min after intracerebroventricular administration of arginine vasotocin and the maximal increase was reached at 10-15 min. Central administration of vasopressin and oxytocin induced a significant rise in diastolic and systolic pressures at a dose of 5 pmol while hydrin-2 only caused a significant elevation of blood pressure at a dose of 50 pmol. Central administration of mesotocin, isotocin and conopressin-S (5-500 pmol each) had no significant effect on blood pressure. No changes in heart rate occurred after intracerebroventricular injection of any of the seven neuropeptides tested. Intraarterial injection of arginine vasotocin (50 pmol) induced a significant rise in blood pressure and bradycardia. Peripheral injection of the other neuropeptides did not cause any modification of the cardiovascular activity, whatever the doses administered (5-500 pmol). The V1A receptor antagonist [d(CH2)5, Tyr(OMe)2]arginine vasopressin had no intrinsic effect on blood pressure and heart rate when injected centrally (50 pmol) or in the peripheral circulation (200 pmol). At the same doses, [d(CH2)5, Tyr(OMe)2]arginine vasopressin reduced by 50 and 66%, respectively, the increase in blood pressure evoked by intracerebroventricular (5 pmol) or intraarterial (50 pmol) injections of arginine vasotocin.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Neuropeptídeos/administração & dosagem , Receptores de Angiotensina/fisiologia , Receptores de Vasopressinas , Truta/fisiologia , Vasotocina/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Cateterismo Periférico , Injeções Intra-Arteriais , Injeções IntraventricularesRESUMO
Responses of heart rate (HR) and mean arterial blood pressure (MABP) were examined following microinjection of angiotensin II ([Asn1,Val5]AI) within the dorsal vagal motor nucleus (DVN) of the conscious trout's brainstem. AII (15-125 fmol) preferentially and significantly increased HR in a dose-dependent manner, but the rise in MABP was not dose-dependent and was only significant (P < 0.05) after injection of AII at a dose of 62.5 fmol. The cardiovascular action of AII was site-specific, since administrations of the peptide at a dose of 62.5 fmol, but outside the boundaries of the DVN, were devoid of any effect on HR or MABP. All the responses to DVN injections of AII were totally prevented by DVN injection of 1 nmol of losartan, a mammalian non-peptide AII subtype 1 (AT1) receptor antagonist. The ability of DVN injection of AII to induce a tachycardic response was negatively correlated to HR basal values. In conclusion, these results indicate that, at femtomolar doses, AII exerts a central neurocardioregulatory role, involving a localized receptor closely related to the mammalian AT1 receptor subtype within the DVN of the trout.
Assuntos
Angiotensina II/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Neurônios Motores/fisiologia , Oncorhynchus mykiss/fisiologia , Nervo Vago/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Losartan/farmacologia , Masculino , Microinjeções , Nervo Vago/citologiaRESUMO
A 60-year-old woman with acromegaly associated with sleep apnea was treated with the somatostatin analogue SMS 201-995 (Sandoz) for several months. Growth hormone levels were normalized and a rapid improvement in sleep apnea was controlled with polygraphic nocturnal monitoring. Hypophysectomy seems to have variable effects on sleep apnea in acromegaly. The origin of obstructive apnea in acromegaly is therefore unclear.
Assuntos
Acromegalia/complicações , Octreotida/uso terapêutico , Síndromes da Apneia do Sono/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Síndromes da Apneia do Sono/complicações , Fatores de TempoRESUMO
Ten subjects from 2 families with adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN), hereditary X-linked diseases, were systematically explored. We performed endocrinological, biochemical assays and neurophysiological tests; the latter consisted of nerve conductions (CNV), Hoffmann's reflex and multimodal evoked potentials: visual (flash and pattern, VEP), brainstem auditory (BAEP) and somesthetic (SEP) using median nerve stimulation at the wrist. We only considered values above 2 SD. The purpose of our study was to determine the correlation between neurophysiological and endocrinological perturbations and the presence of pathological traits. Our results suggest that the correlation is high in diseased male patients, lower for the ALD carriers (BAEP, SEP and CNV were more frequently abnormal) and very low for the AMN carriers. Only the biochemical assays appeared to have any value for the characterization of female carriers of ALD and AMN.
Assuntos
Doenças das Glândulas Suprarrenais/genética , Adrenoleucodistrofia/genética , Esclerose Cerebral Difusa de Schilder/genética , Doenças da Medula Espinal/genética , Adolescente , Doenças das Glândulas Suprarrenais/fisiopatologia , Adrenoleucodistrofia/fisiopatologia , Adulto , Criança , Pré-Escolar , Potenciais Evocados Auditivos , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Nervo Mediano/fisiopatologia , Pessoa de Meia-Idade , Condução Nervosa , Linhagem , Doenças da Medula Espinal/fisiopatologiaRESUMO
Gigantism, an extremely rare condition, develops before puberty or in subjects in whom puberty is not yet completed. Hypersecretion of somatotropic hormone results in a tremendous surge in growth (our patient was 2.36 m tall). Among other clinical symptoms disabling peripheral neuropathy predominates and changes in nerve conduction velocity are not merely due to the increase in height. The increase in growth hormone concentrations combined with hypogonadotrophic hypogonadism with normal prolactinaemia is associated with peculiar cutaneous symptoms and with low levels of sex hormone-binding protein.
Assuntos
Adenoma/metabolismo , Gigantismo/etiologia , Hormônio do Crescimento/metabolismo , Doenças do Sistema Nervoso Periférico/etiologia , Neoplasias Hipofisárias/metabolismo , Adenoma/complicações , Adulto , Gigantismo/fisiopatologia , Humanos , Hipogonadismo/etiologia , Perna (Membro)/inervação , Masculino , Neoplasias Hipofisárias/complicações , Fatores de TempoRESUMO
The present study was undertaken to determine the central and peripheral actions of trout angiotensin III (ANG III) on heart rate (HR) and mean dorsal aortic blood pressure (P(DA)) in the unanaesthetized rainbow trout. Intracerebroventricular injection of ANG III (5-100 pmol) produced a significant and dose-dependent increase in HR without significant change in P(DA). In contrast, when injected peripherally ANG III (5-50 pmol) evoked a significant and dose-dependent increase in P(DA). The hypertensive responses were accompanied by a bradycardia that reached significance only for the highest dose of ANG III tested. In conclusion, our results have shown that ANG III has potent and contrasting cardiovascular actions depending on whether its site of action is the brain or the peripheral circulation. Endogenous ANG III may have important physiological functions in teleost fishes.
Assuntos
Angiotensina III/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Truta , AnimaisRESUMO
Extracellular antidromic potentials recorded from the neurosecretory cell body were characterized by the following criteria: constant latency, the ability to follow a high frequency rate of stimulation and the collision test. The latency of the antidromic potentials ranged from 12 to 24 ms (17.46 +/- 3.10 SD) which gave a mean conduction velocity of 0.19 m/s, typical of unmyelinated nerve fibers. Two components could be clearly distinguished in the antidromic potential. A small "A" spike which showed constant latency and a large "B" spike with a variable latency and amplitude. A delay of 6.5 ms between the two spikes could occur and sometimes the "B" spike was blocked leaving only the "A" spike. Four patterns of spontaneous activity seem to emerge: Type I (26% of units, M +/- SD = 0.77 +/- 0.32 sp/s) corresponds to a slow and irregular pattern of activity; Type II (28% of units, M = 1.58 +/- 0.47 sp/s) is hard to classify and may be related to an irregular bursting pattern of activity; Type III (28% of units, M = 2.59 +/- 1.19 sp/s) corresponds to a continuous pattern of activity; Type IV (18% of units) represents a rhythmic pattern of activity with an active phase of about 3 min (M = 2.42 +/- 0.90 min), a silent phase of about 4 min (M = 3.89 +/- 3.02 min) and a maximal frequency of unit discharge in the range 2-18 sp/s. No statistical differences exist for the mean dorsal aortic pressure (DAP) between the four types of neurosecretory cell activity.
Assuntos
Sistemas Neurossecretores/fisiologia , Área Pré-Óptica/fisiologia , Salmonidae/fisiologia , Truta/fisiologia , Animais , Estimulação Elétrica , Potenciais Evocados , Microeletrodos , Sistemas Neurossecretores/citologia , Área Pré-Óptica/citologiaRESUMO
Multiple unit activity (MUA) from the preoptic nucleus (NPO) blood pressure and heart rate were recorded in 41 anaesthetized and curarized rainbow trout. Mayer waves were frequently observed in blood pressure recordings (83%). Rhythmic MUA from the NPO, recorded in 46% of the experimented trout, occurred preferentially during Mayer waves. The initiation of the period of MUA occurred during low pressure vasomotor tone and large vasomotor pulse pressure inhibited MUA. Sustained decrease in blood pressure induced proportional rise in MUA. These results suggest that cardiovascular inputs influence the electrical activity of neurosecretory cells within the NPO and so may modulate the neurohypophysial hormones secretion.
Assuntos
Pressão Sanguínea , Área Pré-Óptica/fisiologia , Animais , Diencéfalo/citologia , Condutividade Elétrica , Frequência Cardíaca , Fatores de Tempo , TrutaRESUMO
This study describes a technique which allows continuous recording of MUA (Multiple Unit Activity), from the NPO (Preoptic Nucleus), DAP (Dorsal Aortic blood Pressure) and ECG (Electrocardiogram) in freely swimming rainbow trout. From the 21 trout tested, six trout (29%) clearly showed rhythmic patterns of MUA during the five post-operative days (D2-D6). The mean length of rhythmic MUA was about 18 hr (range 6-33 hr) among the six trout during the recording days. Periodic MUA occurred approximately eight times/hr and lasted about 2 min. The maximal frequency of discharges was 20-30 spikes per sec. No change occurred in the mean level of blood pressure from the first operative day to the following post-operative days, where rhythmic MUA appeared or reappeared. These results demonstrate the existence of biorhythmicity within the NPO of freely swimming trout and suggest parallel oscillations in neurohormones secretion.
Assuntos
Periodicidade , Área Pré-Óptica/fisiologia , Salmonidae/fisiologia , Truta/fisiologia , Animais , Pressão Sanguínea , Eletrocardiografia , Feminino , Frequência Cardíaca , Hematócrito , Masculino , Atividade MotoraRESUMO
We show modifications in the hypothalamic CRF activity and plasma ACTH concentration in adult rats of both sexes, which were five day sham-operated or adrenalectomized and killed either under basal conditions or after a 3 min period or psychological stress. 1. Under basal conditions, the inhibition of the basal release of ACTH is suppressed in 5 day adrenalectomized rats and a sex difference appears: plasma ACTH concentration is twice as great in females than in males. 2. After a 3 min period of psychological stress, the usual increase in hypothalamic CRF activity observed in sham-operated rats, which seems to be sex-related, does not appear in adrenalectomized male or female rats. However, in adrenalectomized rats, the maximal increase in plasma ACTH concentration occurred more rapidly, with a rate 10 times as great in males and 4 times as great in females, than in sham-operated rats. Differences between the sexes in the maximal increase in plasma ACTH concentration remains 1,6 times as great in females than in males. 3. Our results confirm that corticosteroids exert: (1) a tonic feedback inhibition of the basal release of ACTH, (2) a fast feedback inhibition of the stress induced release of ACTH; the promote an increase in the hypothalamic CRF content. Relative intensity of these two inhibitory mechanisms seems to be sex-related.
Assuntos
Adrenalectomia , Hormônio Adrenocorticotrópico/sangue , Hormônio Liberador da Corticotropina/análise , Estresse Psicológico/fisiopatologia , Animais , Corticosterona/sangue , Feminino , Humanos , Hipotálamo/fisiologia , Masculino , Ratos , Fatores Sexuais , Fatores de TempoRESUMO
Brain-stem auditory evoked potentials (BAEPs) were obtained from 25 chronic alcoholic patients. The patients had been drinking heavily for an average of 15 years and a minimum of 5 years. All patients were totally abstinent for a minimum of 3 weeks. The morphology of waves were often altered. All presented prolonged I-III, III-V, inter-peak latencies (IPLs) and a loss of amplitude of wave V. The I-III, III-V and I-VIPLs were increased between 30 and 40 years, and III-V and I-VIPLs between 40 and 50 years. The incidence of abnormal BAEPs in patients with alcoholic epilepsy was not different from that of patients without a history of alcoholic seizures. Patients with clinical manifestations of alcoholic polyneuropathy had the highest incidence of abnormal BAEPs. BAEPs are more reliable in chronic alcoholic patients than EEG. The mechanisms of the increase in neural transmission time within the auditory brain-stem are discussed.
Assuntos
Alcoolismo/fisiopatologia , Tronco Encefálico/fisiopatologia , Adulto , Alcoolismo/complicações , Epilepsia/etiologia , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/etiologia , Polineuropatias/fisiopatologia , Tempo de Reação/fisiologiaRESUMO
The visual evoked potentials (VEPs), somatosensory evoked potentials (SEPs) and the electroencephalogram (EEG) have been studied in 16 subjects presenting chronic respiratory insufficiency (CRI) with normal consciousness. The SEPs latencies were increased but the VEPs latencies were not. The EEG was little disturbed and did not seem to provide useful information in CRI without encephalopathy.
Assuntos
Eletroencefalografia , Potenciais Evocados , Sistema Nervoso/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Idoso , Doença Crônica , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Humanos , Pessoa de Meia-Idade , Tempo de ReaçãoRESUMO
Eleven patients with bronchial epidermoid carcinoma and undergoing treatment with cis-D.D.P. (II) were kept under electrophysiological and clinical surveillance. No other neurotoxic medication was added. The total dose of cis-D.D.P. was 300 mg/m2 over a period of three months: namely, three courses of 100 mg/m2 distributed over 5 days. Following the pretreatment check-up, the patients were divided into two groups: those without any electrophysiological abnormality (group A), and those without clinical abnormality but with a delayed latency H of the Hoffmann Reflex (group B). Patients in group A showed a slowing down of the motor nerve conduction velocity of the Median and Peroneal Nerves after a course of 100 mg, without accompanying worsening of the conduction velocity after 300 mg/m2, and prolongation of the distal latency of the sensory Median Nerve after 300 mg/m2; in group B, no significant change of electrophysiological clinical features were noted. In the two groups a non-significant reduction in amplitude of evoked responses were noted. These findings are more consistent with an axonal injury than with functional myelin injury. The authors review the existing literature and discuss the physiopathologic mechanisms of cis-D.D.P. peripheral neuropathies.