Paracoccidioidomicose: caso clínico / Paracoccidioidiomycosis: case report

Os autores reportam o caso clínico de um homem, 43 anos de idade, natural e residente na ilha da Madeira, emigrado na Venezuela até há 6 anos. Em Março 2009, observado por aparecimento de lesão pápulo-crostosa de bordos regulares eritematosos, indolor, pruriginosa, com dimensões de 4,5 x 3cm, localizada no dorso, com 2 meses de evolução. Como antecedentes, refere história de lesão da mucosa bucal, com exame histopatológico compatível com paracoccidioidomicose (PCM). Foram efectuadas duas biópsias da lesão cutânea para avaliação histopatológica e micológica. O exame histopatológico revelou a presença de múltiplas células circulares, sugerindo distribuição característica de "roda de leme". O estudo micológicos revelou,no exame directo, a presença de leveduras - algumas em gemulação. As culturas permitiram isolar o Paracoccidioides brasiliensis. A radiografia pulmonar apresentava infiltrado bilateral e simétrico, nos lobos centrais e basais. A Tomografia Axial Computadorizada torácica demonstrou múltiplosnódulos espiculados, áreas de opacidade e bronquiectasias.Foi efectuada broncofibroscopia (sem alterações) e simultaneamente foi obtido o lavado broncoalveolar (LBA). A cultura, a 25º C, revelou a presença de hifas e clamidósporos (forma filamentosa). Na cultura, a 37º C, não se obteve a forma leveduriforme.O tratamento efectuado foi o itraconazol 200 mg/dia, durante 6 meses, com regressão da lesão.Até à actualidade, nenhum caso de PCM foi reportado na ilha da Madeira, Portugal. Embora não seja frequente, fora das áreas endémicas, os dermatologistas devem ser capazes de reconhecer e diagnosticar micoses sistémicas, como a PCM (AU)

We report a case of a 43 years-old portuguese man, natural and resident in Madeira island, who was emigrated in Venezuela until 6 years ago. He was observed on March 2008 for a crusted papulo-nodular lesion with erythematous regular borders, pruritic and sized 4,5 x 3,0 cm, located on the dorsum, with a 2 month history. There was no palpable lymphadenopathy. He denied other simptomatology. On March of 1999, the patient had a mouthlesion which was compatible with paracoccidioidomycosis on histopathological examination. He was not aware of any associated pathologies. We performed two punch biopsies of the cutaneous lesion for histopathological and mycological examination. The histopathology showed the presence of multiple round cells of different size (yeast cells) in a narrow base suggesting the classic “pilot’s wheels”, on Hematoxiline & Eosine stain. On direct microscopic examination the mycology revealed yeast of different sizes - some of them on gemulation. The cultures, at 24º and 37º, isolated Paracoccidioides brasiliensis. The thoracic x-ray revealed a heterogeneous, bilateral and symmetric pattern located towards the central and basal portions. The CT scan of the chest showed multiple, micronodular and striated lesions (some of them with small cavities), with tendency to coalesce. To characterize better these lung abnormalities, the patient performed a fibrobronchoscopy of the respiratory tract which was normal. The culture, at 25 ºC, obtained from the sputum of the bronchoalveolar lavage fluid (BAL) showed Paracoccidioides brasiliensis. Routine laboratory studies were normal and serology negative for HIV and tuberculosis. The treatment of choice was itraconazol 200 mg/day, for 6months. As far as we know no case of PCM has been reported in Madeira. Although it is not a frequent disease outside the endemic areas, dermatologists should be able to recognise and diagnose systemic mycosis like PCM (AU)

Hypodynamia--hypokinesia induced variations in expression of fos protein in structures related to somatosensory system in the rat.

There have been many reports describing modifications of the sensory and motor cortex following various types of disuse. Hypodynamia--hypokinesia is characterized by the absence of weight-bearing and by a decrease in motor activity. We have shown a reorganization of the cortical cartography after hypodynamia--hypokinesia. In order to give an anatomical account for this cortical plasticity, we set out to determine whether cerebral and spinal structures exhibited variations of their neuronal activation. For this purpose, immunocytochemical detection of Fos protein was performed in the rat brain and spinal cord. Following stimulation of the sciatic nerve, Fos protein was detected in the primary and secondary somatosensory cortex in control rats and in rats submitted to an episode of 14 days of hypodynamia--hypokinesia. Results showed that the stimulation of the sciatic nerve induced an increase in the number of Fos-immunoreactive neurons in all these structures. Moreover, after hypodynamia--hypokinesia, the number of Fos-immunoreactive neurons was increased in the primary and secondary somatosensory cortex and in the spinal cord. These results provide evidence for a higher activation of cortical cells after hypodynamia--hypokinesia in comparison to controls. These data support the hypothesis that hypodynamia--hypokinesia contributes to the development of functional plasticity.

Activation of ventrolateral medullary neurons projecting to spinal autonomic areas after chemical stimulation of the central nucleus of amygdala: a neuroanatomical study in the rat.

Several studies have shown that the central nucleus of amygdala is involved in cardiovascular regulation. The control of this function may be mediated by activation of the ventrolateral medulla neurons that project to preganglionic neurons located in the intermediolateral nucleus of the spinal cord. The aim of the present study was to examine whether stimulation of the central nucleus of amygdala activated ventrolateral medulla neurons projecting to the intermediolateral nucleus. For this purpose, the injection of a retrograde tracer, the cholera toxin b subunit (CTb), into the intermediolateral nucleus of the T2 segment was combined with immunohistochemical detection of Fos protein following chemical stimulation of the central nucleus of amygdala. Results showed that retrogradely labeled neurons were found throughout the ventrolateral medulla. Moreover, chemical stimulation of the central nucleus of amygdala induced: (1) a decrease of arterial blood pressure; (2) an expression of Fos protein mainly in sub-populations of neurons located in the intermediate and caudal parts of the ventrolateral medulla; (3) a significantly higher number of double labeled neurons (CTb-immunoreactive/Fos-immunoreactive) in the rostral part of the ventrolateral medulla than in the other parts of this region. These results show that the central nucleus of amygdala influences the activity of brainstem neurons projecting to the intermediolateral nucleus. Data were discussed in terms of descending amygdalofugal pathways involved in the hypotension.

Cortical control of somato-cardiovascular integration: neuroanatomical studies.

This paper will discuss experiments dedicated to the exploration of pathways linking the sensorimotor cortex (SMC) and the main bulbar nuclei involved in cardiovascular control: the nucleus tractus solitarius (NTS), the dorsal nucleus of the vagus (DMV) and the rostral ventrolateral medulla (RVLM). Results obtained through neurofunctional and neuroanatomical methods are presented in order to bring new answers to relevant points concerning somato-cardiovascular integration: firstly to show the ability of the SMC to influence neurons in bulbar cardiovascular nuclei, and secondly to identify pathways that transmit such influences. The neurofunctional approach, based on the identification of Fos-like immunoreactive neurons, indicated that the SMC has functional connections with cardiovascular bulbar nuclei. The neuroanatomical approach, which employed retrograde and anterograde axonal tracing methods, provided evidence of direct projections from the SMC to NTS/DMV and RVLM. Furthermore, experiments showed clearly that corticospinal neurons sent collaterals to bulbar cardiovascular nuclei, especially to the RVLM. Direct cortical projections to the NTS/DMV and the RVLM provide the anatomical basis for cortical influences on the baroreceptor reflex and sympathetic vasomotor mechanisms for blood pressure control, and support the hypothesis of cortical commands coupling somatic and cardiovascular outputs for action.

Double immunocytochemistry for the detection of Fos protein in retrogradely identified neurons using cholera toxin B subunit.

The focus of this paper was to describe a method combining the neuroanatomical technique of retrograde transport of cholera toxin B subunit (CTB) with the technique of Fos functional labeling. This method allowed us to evaluate whether neurons identified by retrograde tracing were activated following chemical stimulation of another brain area. We have used this method at the light microscopic level to determine whether the stimulation of the rostral ventrolateral medulla activated retrogradely labeled adrenal sympathetic preganglionic neurons in the spinal cord. CTB-containing neurons, Fos immunoreactive neurons and double labeled neurons were observed in spinal autonomic areas. These results suggest that the rostral ventrolateral medulla exerts a descending activation upon identified adrenal preganglionic neurons. The method described in this protocol can be applied for other brain areas in order to establish if a given structure can activate an identified population of neurons linked with a particular target of central or peripheral nervous system.

Autonomic dysreflexia increases plasma adrenaline level in the chronic spinal cord-injured rat.

Autonomic dysreflexia (AD) occurs in up to 80% of quadriplegics and high paraplegics and is characterized by exaggerated sympathetic reflexes which induced paroxysmal hypertension. The aim of this study was to determine if plasma catecholamine levels increased during autonomic dysreflexia in the chronic spinal cord-injured (SCI) rats with special care to adrenaline. Catecholamine samples were collected before, during and 1 h after AD induced hypertension with colorectal distension. Results showed that plasma noradrenaline and adrenaline levels increased respectively 1.5-fold and 5-fold during AD in the chronic SCI rats. This suggests substantial roles for these two hormones in mediating the cardiovascular changes during AD. Knowledge of catecholamine levels during AD may thus aid in determining pathophysiology and potential pharmacologic treatments of this autonomic dysfunction.

Expression of Fos protein in adrenal preganglionic neurons following chemical stimulation of the rostral ventrolateral medulla of the rat.

The ventrolateral medulla is known to be involved in the regulation of arterial blood pressure, especially via its connections with sympathetic preganglionic neurons (SPNs) mainly located in the intermediolateral nucleus of the spinal cord. It has been shown that stimulation of the rostral part of the ventrolateral medulla (RVLM) elicits a release of catecholamines from the adrenal medulla. The aim of the present study was to demonstrate the existence of a functional pathway between the RVLM and adrenal SPNs using the combination of a retrograde tract tracing technique (cholera toxin B subunit) with the immunohistochemical detection of Fos protein following the chemical stimulation of RVLM. The data obtained showed that: (1) chemical stimulation of the RVLM induced Fos immunoreactivity in the intermediolateral nucleus and particularly in SPNs projecting to the adrenal medulla; (2) along the thoracic segments T2-T12, 26.1% of retrogradely identified adrenal SPNs were Fos-immunoreactive with the greatest percentage (30.9%) in the T8 segment. These results favored a functional control of the RVLM on adrenal SPNs which may contribute to a substantial activation of the cardiovascular system via the release of adrenal catecholamines.

Immunocytochemical detection of fos protein combined with anterograde tract-tracing using biotinylated dextran.

The present report deals with an axonal tract-tracing procedure in rat enabling visualization of anterogradely transported biotinylated dextran amine (BDA) combined with immnunocytochemical detection of Fos protein following electrical stimulation of the brain. This method allows us to evaluate whether a given structure, receiving both injection of BDA and electrical stimulation, elicits neuronal activation in another part of the brain via direct or indirect projections. We have used the method at the light microscopic level to determine the connectivity of the sensorimotor cortex in the rat. In various parts of the forebrain and brainstem, BDA-labeled fibers originating from the cortex were observed in close apposition to Fos-like immunoreactive cells (FLI) activated by stimulation. This result suggests a direct (probably monosynaptic) projection. On the contrary, FLI neurons were observed in areas devoid of direct afferents, indicating a cascade of activations. The method described in this protocol is applicable for functional anatomy purposes elsewhere within the central nervous system. It constitutes a preliminary step in identifying the validity of a pathway before examination of the reality of the monosynaptic relationship at the electron microscopic level.

Diurnal variations of tonic electrodermal activity.

Diurnal variability of skin conductance level (SCL) was examined in two complementary experiments, simultaneously with variability of skin temperature (ST) and that of simple reaction time (RT) which was recorded as a behavioural index of arousal. In Experiment I, 6 subjects spent 6 days in the laboratory in homogeneous conditions. Three recording sessions, each lasting 2 h, began, respectively, at 9:00 a.m. (morning), 1:00 p.m. (afternoon) and 5:00 p.m. (evening). Results indicated that SCL increased linearly throughout the day. Experiment II was undertaken to test whether this effect could still be observed in more heterogeneous conditions. Subjects (n = 12) attended to their own activities between the two 30-min sessions beginning, respectively, at 9:30 a.m. and 6:00 p.m. during a single experimental day. Again, SCL was higher in the evening than in the morning. In both experiments the SCL pattern seemed to be asynchronous with ST and RT variations. Taken as a whole, these data bring additional evidence of temporal electrodermal variation, a phenomenon which should be further taken into account in EDA research.

Pyramidal control of heart rate and arterial pressure in cats.

The pyramidal control of the heart rate (HR) and the arterial pressure (AP) was investigated in the cat. Experiments were conducted in order to determine relative contribution of vagal and sympathetic components to this control. In eighteen anesthetized and curarized cats, electrical stimulations were applied to the pyramidal tract (PT), followed by pharmacological blockade of the sympathetic cardiac control or by bivagotomy. HR and mean arterial pressure (MAP) were recorded in response to pyramidal stimulations before and after bulbar transections sparing only the PT, beta 1-blockade by atenolol administration and/or bilateral vagotomy. Results showed that the stimulation of the PT elicits significant cardiac accelerations and MAP increases in all animals. Furthermore, bulbar transections allowed to conclude that pyramidal influences acted at bulbar level and not on spinal cardiovascular neurons. After beta 1-blockade by atenolol, HR increases were reduced by about 70% and those of MAP by about 30%; after bilateral vagotomy, cardioaccelerations were reduced by about 30% but no significant reductions of MAP were observed; finally, beta 1-blockade combined with vagal section suppressed cardioaccelerations and significantly reduced the MAP increases. These results suggest the existence of a direct cortical control, via the pyramidal tract, to cardiovascular centers of the medulla, probably mediated by pyramidal collaterals. This control appears to be organized following a reciprocal autonomic pattern where the suppression of the vagal inhibition is associated with a concomitant sympathetic excitation. The present work also provides data in favour of a central command coupling somatic programs and cardiac adjustments during motor acts.

Induction of c-Fos-like protein in bulbar catecholaminergic neurones by electrical stimulation of the sensorimotor cortex in the rat.

The sensorimotor cortex (SMC) establishes a functional connectivity with the nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla (RVLM). These bulbar nuclei are known to contain catecholaminergic neurones involved in the cardiovascular control. The aim of the present study was to establish the proportion of catecholaminergic neurones activated by electrical stimulation of SMC. For this purpose, double immunocytochemical procedures were used to reveal the distribution of Fos protein and tyrosine hydroxylase (TH). The results showed that, in the NTS, 7% of the neurones immunoreactive for TH expressed Fos-protein, versus 34% in the RVLM. These data provide evidence that the SMC activated preferentially catecholaminergic neurones of the RVLM which are known to be involved in cardiovascular control via spinal preganglionic neurones.

Distribution of cortical fibers and fos immunoreactive neurons in ventrolateral medulla and in nucleus tractus solitarius following the motor cortex stimulation in the rat.

The present study demonstrates that the motor cortex (MC) stimulation induces expression of Fos-like immunoreactivity (FLI) in the rostro-caudal parts of ventrolateral medulla (VLM) and nucleus tractus solitarius (NTS). The coupling of biotinylated dextran (BD) injections with the MC stimulation also permits to identify cortical labeled fibers in the vicinity of FLI neurons in the VLM. Results suggest that the MC is involved in a direct and an indirect modulation of bulbar cardiovascular nuclei.

Electrodermal level asymmetry in a unilateral brain-damaged patient.

The purpose of this article is to report on a patient with right frontal damage who exhibited a strong left > right asymmetry of skin conductance levels (SCLs). Comparison with a control group indicates that this asymmetry resulted only from a higher SCL on the left hand. Such a result suggests that the frontal lesion has induced a contralateral disinhibition and is consistent with the idea of a contralateral inhibitory control of tonic electrodermal activity in the case of a healthy hemisphere. Peripheral factors, such as sweating or temperature seem unrelated to the SCL asymmetry and a possible influence of motor weakness is also rejected following comparison with a second patient who presented the same motor disorder without atypical SCL asymmetry. In contrast to SCLs, no asymmetry in skin conductance response amplitudes was observed in the former patient. This discrepancy is in line with previous observations showing that tonic and phasic EDA could depend on different neurophysiological controls.

Opioid peptide involvement in the bulbar inhibition of electrodermal activity in the cat.

By analogy with supraspinal and spinal inhibitory controls of pain, it was hypothesized that an opioid mechanism could be involved in the bulbar inhibitory control of the electrodermal activity. This activity was evoked as skin potential responses on the footpads of 13 cats by the central tegmental field stimulation (control responses) and inhibited by the simultaneous stimulation of bulbar reticular formation (experimental responses). Then, naloxone, an opioid peptide antagonist, was injected intravenously or intrathecally and its effects were analyzed on both control and experimental responses. Intravenous injections of naloxone increased significantly the amplitude of experimental responses from 6 to 12 min after the injection and had no effect on the amplitude of control responses. Intrathecal injections of naloxone induced significant increases of amplitude of experimental responses from 6 to 42 min after the injection. These results showed that a spinal opioid peptide link could be involved in bulbar inhibition mechanisms of electrodermal activity.

Expression of c-fos in bulbar nuclei involved in cardiovascular control following the electrical stimulation of sensorimotor cortex in the rat.

Previous studies have shown that electrical stimulation of the sensorimotor cortex (SMC) induces responses of the autonomic nervous system such as variations in heart rate and arterial pressure. Neuroanatomical studies have shown the existence of monosynaptic projections from the SMC to the nucleus tractus solitarius (NTS), the rostral ventrolateral medulla (RVLM) and the dorsal nucleus of the vagus nerve (DNV), which are bulbar nuclei involved in cardiovascular control. The aim of the present study was to establish whether there exists a functional connectivity between the SMC and these nuclei. Electrical stimulation applied to the SMC of 7 rats for 1 h induced the expression of c-fos-protein-like immunoreactivity in the nucleus of some neurons in NTS, RVLM and DNV. These data support the view that the SMC has functional connections with bulbar neurons involved in cardiovascular control.

Corticospinal collaterals to medullary cardiovascular nuclei in the rat: an anterograde and a retrograde double-labeling study.

There is little evidence allowing the hypothesis of the existence of direct pathways from the sensorimotor cortex (SMC) to main cardiovascular medullary nuclei: the dorsal motor nucleus of the vagus (DMV), the nucleus of the solitary tract (NTS) and the rostral ventrolateral medulla (RVLM). The purpose of this study was to identify in the rat direct SMC-NTS/DMV and-RVLM projections descending through the pyramidal tract (PT) and corticospinal neurones projecting to spinal somatic centers and sending collaterals to the NTS/DMV and the RVLM. The first group of animals (N = 15) received injections of anterograde tracers into the SMC: wheat germ agglutinin conjugated to horseradish peroxydase (WGA-HRP) or rhodamine-conjugated dextran (DR). In the second group (n = 35), retrograde tracers were injected: fluorogold (FG) into the NTS/DMV or into the RVLM and DR into the lateral thoracic cord (Th2-Th4). Anterograde transport of WGA-HRP and DR allowed corticofugal fibers to be followed inside the PT ipsilaterally to the site of cortical injection and showed bilateral labeled projections to the NTS/DMV and RVLM. After retrograde transport, bilateral FG or DR labeled cells were distributed in the SMC, mainly in the medial (AGm) and lateral (AGl) agranular cortex. After spinal and bulbar injections, double-labeled cells were distributed in same cortical areas. After injections in RVLM, 49% of labeled cells showed a double-labeling in the frontal cortex (rostral AGm and premotor cortex) while only 24% were observed in the posterior SMC (caudal AGl). On the contrary, when injections were done in NTS/DMV, double-labeled neurons were respectively of 11% in the frontal cortex and 4% in the posterior SMC. In the present work it was shown that the SMC sent direct projections to bulbar cardiovascular nuclei by means of fibers descending through the PT and corticospinal collaterals. The hypothesis which may be drawn from this study is that cortical motor areas probably program cardiovascular adjustments, preparatory or concomitant to the control of striate muscles.

Fronto-parietal control of electrodermal activity in the cat.

The aim of this work was to investigate the direct involvement of the fronto-parietal cortex in the control of spinal autonomic centers eliciting electrodermal activity (EDA). This autonomic response, linked with the activity of sweat glands, was recorded as skin potential responses (SPRs) from forepaws in the cat. Animals were paralyzed by gallamine and SPRs were obtained under halothane anaesthesia. For each animal, a transection of the medulla sparing only pyramidal tracts was carried out. SPRs were elicited by direct electrical stimulation of pericruciate and posterior parietal cortical areas before and after such a transection. Results showed that in intact preparations, stimulation of the pericruciate cortex evoked SPRs at lower thresholds than the posterior parietal cortex. After the bulbar transection, only the stimulation of pericruciate areas still elicited SPRs at low intensities. Results are interpreted as indicating that fronto-parietal control of EDA is probably mediated by a double descending system: one involving corticoreticulospinal pathways and a direct corticospinal one. We hypothesized that the somatic motor cortex initiates descending programs to autonomic centers at bulbar and spinal levels, and that these centers are involved in autonomic adjustments to somatomotor movements.

Bilateral electrodermal activity during sleep and waking in the cat.

Electrodermal activity (EDA) was recorded as skin potential responses (SPRs), on the hindpaws of cats during waking and sleep. SPRs recorded on both paws showed an overall parallelism during all stages of vigilance. SPRs on both paws significantly decreased in amplitude and in frequency from wakefulness to sleep. Most SPRs were synchronous but showed bilateral differences larger than 0.1 mV. However, this asymmetry did not show any significant variation as a function of sleep stages. Electrical stimulation of the reticular central tegmental field at levels below the thresholds for behavioral and cortical arousal thresholds evoked SPRs during wakefulness and all stages of sleep. Bilateral differences between evoked SPR amplitudes did not show significant variations as a function of the stages of vigilance. Moreover, the bilateral asymmetry of the evoked SPRs was significantly lower than that of the spontaneous SPRs. These results are discussed in relation to the variations in bilateral EDA recorded in humans during waking and sleep; the influence of central and peripheral factors on EDA laterality is also discussed.

Sensorimotor cortex projections to the ventrolateral and the dorsomedial medulla oblongata in the rat.

After small pressure injections of Fluorogold (FG), and Dextran-tetramethylrodamine (DR) into the dorsal motor nucleus of the vagus/nucleus of the solitary tract (DMV/NTS) and the rostral ventrolateral medulla (RVLM), respectively, retrograde FG-labelled cells were found mainly in the sensorimotor cortex; retrograde DR-labelled cells were located in the same cortical areas and in the prefrontal cortex. Double-labelled cells were also found in the sensorimotor cortical areas. These results provide evidence of direct projections from the sensorimotor cortex to the DMV/NTS and RVLM and suggest that somatic cortical areas directly control cardiovascular output during sensory and somatic processes.