Dos casos de intoxicación por contaminación de maíz con Datura stramonium en ganado vacuno / Two cases of poisoning by Datura stramonium contaminated corn in cattle

Recientemente hemos observado dos intoxicaciones en ganado vacuno lechero, en granjas de Cataluña, debidas a la ingestión de estramonio (Datura stramonium). La planta había sido en ambos casos erróneamente recolectada junto con el maíz empleado para la alimentación de los animales. El cuadro fue leve y, básicamente, cursó con problemas digestivos y descenso en la producción lechera, y remitió con la retirada del alimento contaminado. Debido a factores ambientales y económicos, el problema podría estar en aumento(AU)

Recently, two poisoning episodes produced by Jimson weed (Datura stramonium) consumption have been observed in dairy cattle farms from Catalonia. The plant was mistakenly gathered, in both cases, together with corn used for animal feed. The set of symptoms were slight, basically gastrointestinal disorders and decrease of milk production, and animal recovery was observed as soon as the contaminated feed was removed. This problematic situation could be increasing in prevalence due to environmental and economic factors(AU)

In vitro capsaicin-induced cytological changes and alteration in calcium distribution in giant serotonergic neurons of the snail Helix pomatia: a light- and electron-microscopic study.

Morphological changes induced by capsaicin were studied in the serotonergic metacerebral giant neurons of the cerebral ganglia of Helix pomatia under in vitro conditions. Capsaicin at a concentration of 10(-4)M caused characteristic structural alterations in the giant serotonergic neurons but did not significantly influence serotonin immunoreactivity in the neurons. At the light-microscopic level, the most conspiciuous structural alterations were swelling of the cell bodies, which contained a swollen pale nucleus. Under the electron microscope, the nuclei, mitochondria and the cisternae of the endoplasmic reticulum were swollen in the capsaicin-affected metacerebral giant neurons. Electron-microscopic cytochemical techniques for calcium demonstration revealed electron-dense deposits in the swollen mitochondria and in the cisternae of the endoplasmic reticulum, suggesting an increased Ca2+ influx. The serotonergic metacerebral giant neurons could be labelled by cobalt (1mM) in the presence of capsaicin (10(-4)M) suggesting that capsaicin opens the cation chanels of the capsaicin-sensitive neuronal membrane. The morphological and cytochemical alterations induced by capsaicin in the serotonergic metacerebral giant neurons of Helix pomatia closely resemble those induced in sensory neurons of mammalian dorsal root ganglion.

The A-type potassium current: methoxybenzenes increase the rate of inactivation in snail neurons.

The effects of anisole (methoxybenzene) and veratrole (1,2-dimethoxybenzene) on the resting membrane potential (RMP), action potential (AP) and membrane potassium currents were investigated in snail neurons under current- and voltage-clamp conditions. Anisole (0.9-3 mM) scarcely influenced the AP, but it moderately depolarized the membrane and increased the neuronal excitability. Anisole accelerated the time-dependent inactivation of the A-current and decreased the time constant of the decay in a dose-dependent way (K1/2 = 1.2 mM). The potential-dependence of the steady-state activation or inactivation of the A-current was not influenced by anisole. An analysis of the Hill plot of anisole action on the time constant of decay of the A-current showed a one-to-two binding stoichiometry (nH = 2.1). Veratrole (2-8 mM) was effective similarly to anisole on the A-current, but proved less potent.

The A-type potassium current: catechol-induced blockage in snail neurons.

The effects of catechol (1-12.5 mM) on membrane properties, action potential and membrane ionic currents were investigated in identified snail neurons under current- and voltage-clamp conditions. Catechol hardly influenced the resting membrane potential, or the action potential amplitude and duration, but it increased the spike voltage threshold and slightly decreased the input resistance. Catechol specifically decreased the amplitude of the potassium A-currents in a dose-dependent way (Kd = 5 mM), without significant modulation of other potassium currents. The time constants of decay of A-current increased and the steady-state activation or inactivation curve shifted to more positive potentials in the catechol solutions. The blocking effect of catechol on A-currents followed a one-to-one binding stoichiometry (nH = 0.8).

GABA antagonists potentiate the cardioinhibitory reflex induced by capsaicin in the cat.

The GABA antagonists picrotoxin (PX) and bicuculline (BIC) were given intravenously (i.v.) or applied topically to the region of the nucleus of the solitary tract (NTS) in intact or in precollicularly decerebrate cats under chloralose-urethane anaesthesia, and their effects on capsaicin (CAP)-induced reflex bradycardia were studied. The administration of PX or BIC was found to result in a decrease of the resting heart rate and a significant increase of the cardioinhibitory reflex evoked by CAP. The maximum effects of these GABA antagonists developed within 3-10 min and lasted for about 40-60 min. Neither the resting heart rate nor the response to CAP was affected by strychnine. It is concluded that the CAP-sensitive unmyelinated barosensory afferents and/or the interneurons in the NTS are under a tonically active GABA-ergic inhibitory control originating in the brain stem.

Intracellular and voltage clamp studies of capsaicin induced effects on a sensory neuron model.

The acute effects of capsaicin (CAP) were studied on membrane properties, the action potential (AP) and the membrane ionic currents in the giant serotoninergic neuron of the cerebral ganglion (MCC) in the snail of Helix pomatia L. CAP (30-300 microM) depolarized the MCC, decreased the amplitude, the rate of rise and the rate of fall of the action potential. CAP prolonged the AP-duration, increased the membrane slope resistance, decreased the hyperpolarizing afterpotential and the posttetanic hyperpolarization both in normal and Na-free media. All the effects were reversible and could be evoked repeatedly. CAP attenuated the outward membrane currents with decreasing potency in the sequence of the transient potassium (IA) voltage-dependent potassium (IK), Ca-dependent potassium (IC) and leakage currents (IL). CAP decreased or increased the peak amplitude of the Ca-current (ICa), depending on the extracellular Ca concentration. CAP increased the inactivation of the ICa, decreased the Ca-conductance (GCa) in normal and high Ca solutions and shifted the Ca-equilibrium potential (VCa) to more positive voltage in 30 mM Ca-solution. CAP decreased the electrically activated Na-current and blocked the acetylcholine (ACh) activated increase in Na-K conductances. It is concluded that CAP profoundly affects the electrically and some transmitter-activated cationic conductances. Further studies are needed to clarify the significance of these changes with respect to the mechanism of the selective neurotoxic effects of CAP.

Neurotoxic effect of capsaicin in mammals.

Capsaicin is now widely used to explore and/or prove the role of peptide-containing primary afferent neurones in different somato- and viscerosensory functions. The present paper deals with the morphological effects of capsaicin administered according to currently used experimental paradigms. As it has been repeatedly confirmed in the recent literature, administration of capsaicin to newborn mammals results in a highly selective degeneration of a particular population of small sized, B-type primary afferent neurones located in spinal and cranial sensory ganglia. Chemosensitive i.e. capsaicin sensitive primary sensory neurones (CPSNs) correspond to primary sensory ganglion cells which contain neuropeptides. The permanent functional impairments and the decrease in the peptide contents of the sensory neurones observed after neonatal capsaicin treatment may be accounted for an irreversible loss of CPSNs. Direct application of capsaicin to peripheral nerves results in an apparently irreversible functional impairment of unmyelinated afferent fibres implicated in nociceptive, viscerosensory and neurogenic inflammatory mechanisms. Morphological observations indicate that perineural treatment with capsaicin initiates a selective but delayed degeneration process of unmyelinated afferent nerve fibres presumably due to an inhibition of intraneuronal transport mechanisms. In contrast with perineural capsaicin treatment affecting the chemistry and function of the whole sensory neurone, injection of capsaicin into the subarachnoid space results in an irreversible abolition of the "afferent" but not the "efferent" function of CPSNs. Accordingly, noxious thermal or chemical stimuli applied to the peripheral innervation areas of the trigeminal nucleus caudalis or the affected segments of the spinal cord fail to induce nociceptive reflexes because of the degeneration of the central terminals of CPSNs. However, in these same skin areas, application of chemical irritants invariably evoked the neurogenic inflammatory response, indicating that CPSNs deprived of their central terminals maintain their capacity to synthesize and release the peptide(s) responsible for the initiation of that response. In contrast with previous findings, our recent studies furnished evidence for a selective neurodegenerative action of systemically injected capsaicin in adult mammals, as well. Therefore, some of the irreversible functional impairments produced by capsaicin in adult animals may result from the degeneration of a particular subpopulation of CPSNs.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of capsaicin on molluscan neurons: an intracellular study.

Effects of capsaicin (CAP) on membrane properties and action potentials (AP) were studied (30-300 microM, at 22 degrees C, pH 7.4) in Helix and Aplysia neurons. CAP (100-300 microM) depolarized the cell membrane and increased the slope resistance. The neuronal firing increased and/or the spike threshold decreased. CAP differentially affected the APs generated in A- and B-cells in Helix or S- and F-cells in Aplysia. Plateau-like prolongation of the APs with a concomitant increase of the hump duration was observed in A-cells, while a significant prolongation of the spike duration was at 90% repolarization time in B-cells. The electrophysiological changes proved to be similar when CAP acted in homologous Helix and Aplysia neurons, but were less pronounced in the latter animal. CAP decreased the rate of rise and the rate of fall of the APs and shortened the action potential duration (APD) in Na-free (TEA) solution. CAP-induced events were dose-dependent and reversible.

Effects of capsaicin on molluscan neurons: a voltage clamp study.

The effects of capsaicin (CAP) on membrane ionic currents of identified and non-identified neurons were investigated by use of the single electrode clamp (SEC). CAP (300 microM, 22 degrees C, pH 7.4) caused a 25-50% reduction of the inward current and a 50-80% reduction of the outward current in normal or Na-free (Tris) solution. The Na current (INa) was moderately decreased (about 10%) in LPa2 neuron, but a 50% reduction of the peak Ca current (ICa) was observed. The action of CAP on ICa varied from cell to cell but an enhanced inactivation of the fast calcium current was found in all neurons studied. CAP (150 microM, 10 min) highly attenuated the long-lasting component of the inward current in LPa2 recorded in Na-free (TEA) Ba solutions. CAP attenuated the fast outward current (IA) and voltage-dependent outward current (IK) in 100 and 300 microM concentrations for the half blocking dose (ID50) in LPa2 neuron, respectively. CAP decreased the slow outward tail currents but hardly influenced the leakage current (IL). We suggest that the acute action of CAP coupled with a series of events in the neuronal membrane can modify the conductance via electrically excitable calcium, potassium and sodium channels differentially.

Axonal effects of capsaicin: an electrophysiological study.

The effects of axonally applied capsaicin on the discharge activity and compound action potential of the cat vagus, saphenous and phrenic nerves and the cervical sympathetic trunk were studied under in vivo and in vitro conditions. Application of capsaicin (10(-4) M) to the vagus, saphenous and phrenic nerves resulted in the appearance of intense discharge activity which reached its maximum after 3-4 min and lasted for 15-20 min. Parallel with the increase in discharge activity, elicited by orthodromic activation induced by capsaicin, the amplitudes of the A delta and C components of an antidromically evoked compound action potential were significantly reduced. After the excitatory action of capsaicin vanished, an increase in the latency and duration and a decrease in the amplitudes of the components of the compound action potential were observed which might have led to the development of a local block of impulse propagation. These changes proved to be reversible after the removal of capsaicin from the nerve. Compound action potentials recorded from the saphenous or vagus nerves pretreated with capsaicin 3-5 days before the experiments failed to show any significant changes. It is concluded that upon direct axonal application capsaicin results in the excitation of both A delta and C fibres which is followed by a nonspecific but reversible blockade of impulse propagation. The possible significance of these transient effects of axonally applied capsaicin in term of the development of the highly specific functional impairment occurring a few days after perineural capsaicin treatment remains to be elucidated.

Selective degeneration by capsaicin of a subpopulation of primary sensory neurons in the adult rat.

The morphological effects of systemic capsaicin treatment have been studied in adult rats. Light and electron microscopy revealed that a subpopulation of small-to-medium sized B-type primary sensory neurons, representing about 17% of the total neuronal population in the 4th lumbar spinal ganglion, underwent rapid degeneration after the administration of capsaicin. Quantitative electron microscopy demonstrated a decrease of about 45% in the number of unmyelinated axons in the saphenous nerve. Light microscopy showed extensive axon terminal degeneration in the brainstem and spinal cord confined to the central projection areas of capsaicin-sensitive afferent fibers, as has already been revealed in the newborn rat. The present results furnish evidence for a hitherto unrecognized selective neurodegenerative action of capsaicin in the adult rat.

The effects of capsaicin on action potential and outward potassium currents in a bursting neuron of the snail, Helix pomatia L.

The effects of capsaicin (CAP) on membrane properties, action potentials (APs) and outward membrane currents were investigated using the single electrode current and voltage clamp. CAP (60-300 microM) depolarized the cell membrane and increased the input resistance (Rin). The burst frequency of the neuron simultaneously increased. CAP prolonged the APs and attenuated the outward currents with decreasing potency in the sequence of the early outward current (IA), an early and a late component of the delayed outward current.

Evidence for a capsaicin-sensitive vasomotor mechanism in the ventral medullary chemosensitive area of the cat.

The effects of capsaicin applied to the exposed ventral surface of the medulla were studied on the mean arterial blood pressure, heart rate, respiration and sympathetic efferent nerve activity in chloralose-urethane-anaesthetized cats. The application of capsaicin produced a marked increase in the mean arterial blood pressure and sympathetic nerve activity, but not in the heart rate. The "intermediate area" proved to be the most sensitive to capsaicin. Pressor responses could be elicited repeatedly; tachyphylaxis was not noted provided a time interval of 30 min elapsed between consecutive applications. Repeated applications of capsaicin at intervals of less than 30 min led to tachyphylaxis. However, pressor responses evoked by either topical application of glutamate or pentamethylene-tetrazole or bilateral carotid occlusion could invariably be demonstrated during this period of tachyphylaxis. Histological studies revealed the existence of a hitherto unrecognized termination of capsaicin-sensitive nerve endings within the ventral medullary chemosensitive area of the cat. The results provide both functional and morphological evidence for the presence of a capsaicin-sensitive vasomotor mechanism in the ventral medullary chemo-sensitive area of the cat. It is suggested that the pressor effects of capsaicin applied to the ventral medullary chemo-sensitive area may be mediated by an activation of capsaicin-sensitive primary sensory afferents terminating in this area. Accordingly, capsaicin-sensitive neuronal mechanisms located in the ventral medullary chemosensitive area may play an important role in the central nervous regulation of blood pressure.

The effects of capsaicin on the early outward current in identified snail neurones.

An investigation of the action of capsaicin (CAP) on the early outward current (IA) in identified neurones of Helix pomatia was performed using the single electrode clamp. CAP (60-300 microM) caused a dose-dependent reduction of the IA-currents in LPa3 and RPa3 neurones both in normal and Na-free solutions. There was also a marked shortening of the time constant for the inactivation of IA, and a 5-10 mV shift in the hyperpolarizing direction of the curve relating the steady-state inactivation of IA to membrane potential. The equilibrium potential for IA was not changed in up to 300 microM CAP solutions.

Capsaicin blocks synaptically activated potassium conductance in snail neurone.

The effect of capsaicin was studied on non-cholinergic inhibitory postsynaptic currents (IPSC). The experiments were performed on an identified snail neurone using the single electrode voltage-clamp technique. The IPSC decayed with a bi-exponential time course. Capsaicin (200 microM) reversibly blocked both components of the transmitter-activated potassium conductance similarly to other potassium channel blockers such as Ba2+, quinine or 4-aminopyridine. Externally applied TEA+ exclusively attenuated the slow phase. Capsaicin prolonged the action potential duration and decreased the membrane outward current in the postsynaptic neurone.

Effects of capsaicin applied perineurally to the vagus nerve on cardiovascular and respiratory functions in the cat.

The effects of capsaicin applied perineurally to the cervical vagus nerves have been studied on cardiovascular and respiratory functions in urethane anaesthetized cats. Application of capsaicin resulted in a moderate but significant decrease in the mean arterial blood pressure and in changes of the heart rate whose direction and magnitude depended on the initial cardiac frequency. Subsequent to these alterations, which may be attributed to a direct stimulation by capsaicin of vagal afferents, a transient block of impulse propagation was observed. Three to five days after pre-treatment of the cervical vagus nerves with capsaicin, phenyldiguanidine and veratrine given intravenously invariably evoked bradycardia, hypotension and apnoea, while the reflex responses to intravenous injection of capsaicin and some of its pungent congeners were greatly reduced or even abolished. It is suggested that vagal afferent fibres mediating cardiovascular and respiratory chemo-reflexes are separated into chemo-specifically different populations. Perineural application of capsaicin may be a useful tool for elucidating the role of different populations of peptide-containing vagal afferent fibres in the regulation of cardiovascular and respiratory functions.

Spatial interactions of opposite vasomotor reflexes.

The simultaneous interactions of pressor and depressor reflexes evoked by stimulation of the central ends of the vagal, tibial and median nerves were studied in urethan and chloralose-urethan anaesthetized cats. The responses obtained to simultaneous activations of opposite reflexes differed from the algebraic sum of the separately evoked ones. The direction and the extent of the differences were determined by the type of the prevailing neural process and by the size of the individual reflex responses. The relations between the responses evoked simultaneously and separately may be characterized by multiple linear regression.

Spatial interactions and stimulus-response relations of unit responses evoked by somato-sensory stimuli in the feline caudal medullary reticular formation.

Responses of neurons in the bulbar reticular area to separate and simultaneous stimulation of the forelimbs were recorded extracellularly in chloralose-anaesthetized cats. On increasing the stimulus intensity the number of spikes per response increased while the initial latency and interspike intervals decreased in accordance with the functional property of the neuron. Responses evoked by simultaneous stimulation displayed more spikes and a shorter latency than those evoked by separate stimuli of corresponding intensities. The differences in the responses evoked simultaneously and the sums of responses evoked separately showed characteristic distributions as a function of the latter. Three types of distribution were distinguished. The results indicate that stimulus-response relations play a determining role in the mechanism of spatial integration.

The role of "the law of initial value" and the levels of the central nervous system in the spatial interactions of blood pressure reflexes.

In experiments carried out on cats it has been found that various anaesthesia (chloralose, pentobarbital or urethan, given in doses of 50 mg/kg, 45 mg/kg and 800 mg/kg, respectively) did not influence the parameters of regression lines describing the spatial interactions of depressor reflexes of somatic and visceral origin. The individual differences showed a correlation with the "mean basal blood pressure" only. There was a linear relationship between the "mean basal blood pressure" and the X-axis intercepts of the regression lines. The size of the latters determined the extent of the facilitatory zone. No differences could be demonstrated between spatial interactions of depressor reflexes evoked by stimulation of somatic or visceral afferents. It seems that the depressor reflex-mechanism operates identically, independently of the input level. The interactions of pressor reflexes were shown to be of the additive type in the case of chloralose or pentobarbital anaesthesia, while of the facilitatory type under urethan anaesthesia. The distribution of spatial interactions of pressor reflexes observed in spinal cats was similar to that observed in animals anaesthetized with chloralose or pentobarbital. The role or various levels of the central nervous system in the organization of spatial interactions of blood pressure reflexes is discussed.