Identification of Aspergillus tubingensis in a primary skin infection.

OBJECTIVE: Aspergillus section Nigri comprises a group of related species that include Aspergillus niger, A. welwitschiae, A. carbonarius, A. brasiliensis and A. tubingensis. Some of these species are morphologically very similar to A. niger but exhibit different patterns of susceptibility to antifungal agents; such is the case for A. tubingensis. Therefore, when diagnosing aspergillosis, it is important to identify the pathogen at the species level. This study aimed to identify the species of an Aspergillus spp. isolate (MM-82) obtained from a patient with a dermatosis localized to the right leg. MATERIALS AND METHODS: The MM-82 isolate was examined for macro- and microscopic morphology, conidia size and thermotolerance, and a phylogenetic analysis of a benA gene segment was performed for molecular identification. Susceptibility to antifungals was determined using antifungal microdilution according to the methodology of European Society of Clinical Microbiology and Infectious Diseases (EUCAST). RESULTS: Based on its phenotypic characteristics and the phylogenetic analysis of the sequence of a benA gene segment, the MM-82 isolate was identified as A. tubingensis. This fungus did not show resistance to antifungal agents commonly used for treatment. CONCLUSION: This study demonstrated that A. tubingensis can cause skin infection; this constitutes the first report of a case of aspergillosis caused by A. tubingensis in Mexico.

Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury.

Chronic neuropathic pain is a frequent comorbidity following spinal cord injury (SCI) and often fails to respond to conventional pain management strategies. Preventive administration of docosahexaenoic acid (DHA) or the consumption of a diet rich in omega-3 polyunsaturated fatty acids (O3PUFAs) confers potent prophylaxis against SCI and improves functional recovery. The present study examines whether this novel dietary strategy provides significant antinociceptive benefits in rats experiencing SCI-induced pain. Rats were fed control chow or chow enriched with O3PUFAs for 8weeks before being subjected to sham or cord contusion surgeries, continuing the same diets after surgery for another 8 more weeks. The paw sensitivity to noxious heat was quantified for at least 8weeks post-SCI using the Hargreaves test. We found that SCI rats consuming the preventive O3PUFA-enriched diet exhibited a significant reduction in thermal hyperalgesia compared to those consuming the normal diet. Functional neurometabolomic profiling revealed a distinctive deregulation in the metabolism of endocannabinoids (eCB) and related N-acyl ethanolamines (NAEs) at 8weeks post-SCI. We found that O3PUFAs consumption led to a robust accumulation of novel NAE precursors, including the glycerophospho-containing docosahexaenoyl ethanolamine (DHEA), docosapentaenoyl ethanolamine (DPEA), and eicosapentaenoyl ethanolamine (EPEA). The tissue levels of these metabolites were significantly correlated with the antihyperalgesic phenotype. In addition, rats consuming the O3PUFA-rich diet showed reduced sprouting of nociceptive fibers containing CGRP and dorsal horn neuron p38 mitogen-activated protein kinase (MAPK) expression, well-established biomarkers of pain. The spinal cord levels of inositols were positively correlated with thermal hyperalgesia, supporting their role as biomarkers of chronic neuropathic pain. Notably, the O3PUFA-rich dietary intervention reduced the levels of these metabolites. Collectively, these results demonstrate the prophylactic value of dietary O3PUFA against SCI-mediated chronic pain.

Evaluation of the effects of a new drug candidate (GEMSP) in a chronic EAE model.

Chronic Experimental Autoimmune Encephalomyelitis (EAE) was induced in rats to evaluate a new drug candidate (GEMSP) for the treatment of multiple sclerosis. This work is a part of preclinical studies on GEMSP, which is made up of fatty acids, vitamins and amino acids or their derivatives; all these compounds were linked to Poly-L-Lysine. In order to evaluate the effects of GEMSP, animals were divided into three experimental groups: 1) EAE rats treated with GEMSP; 2) EAE rats treated with NaCl; and 3) non-EAE rats. Using immunocytochemical techniques with a pan-leukocyte marker (anti-CD 45), differential leukocyte infiltration was compared in the central nervous systems of the different experimental groups. Antibodies directed against a component of GEMSP, the conjugated methionine, were used in all three groups. We found that: 1) GEMSP was effective in abolishing EAE. The crises and clinical scores were completely abolished in the animals of the first group, but not in the animals belonging to the second group; 2) the degree of leukocyte infiltration varied, depending on the different EAE stages, but was not related to the clinical score; and 3) after using anti-conjugated methionine antibodies, we observed immunoreactivity only in the motoneurons of the ventral horn of the spinal cord in the animals of the first group. This immunoreactivity was not found in the animals of the second or third groups. No methionine immunoreactivity was found in the brain. Our results suggest that GEMSP may be a potential drug candidate against the pathogenic processes involved in multiple sclerosis, inhibiting EAE episodes and brain leukocyte infiltration. Our results also show that one component of GEMSP, the methionine compound, is stored inside motoneurons. The possible physiological actions of GEMSP on spinal cord motoneurons are discussed.

Efectos secundarios de los antidepresivos / Adverse events of antidepressants

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Cerebellar atrophy in Alzheimer's disease-clinicopathological correlations.

Morphometry of the cerebellum of 11 subjects who died in the severe, final stage of Alzheimer's disease (AD) and of five age-matched subjects without dementia revealed significant atrophy in the AD group, with a decrease in the volume of the molecular layer by 24% and of the granular layer by 22% in comparison with controls. The 32% decrease in the total number of Purkinje cells that was observed correlates with the atrophy of the molecular layer, whereas the 30% reduction in the total number of granule cells correlates with the atrophy of the molecular and granular layers. A unique pattern of Alzheimer-type pathology was observed in the cerebellum: (1) there were no neurofibrillary changes in the cerebellum of either the control or the AD subjects, (2) there was almost the same extent of leptomeningeal and cortical amyloid angiopathy in the normal aged subjects and in the AD patients, and (3) the presence of plaques was noted in the AD group, but not in the control group. This pattern of pathology suggests that two factors might be considered in the etiopathogenesis of cerebellar atrophy: (1) transneuronal degeneration and neuronal loss resulting from primary pathologic changes in cerebral structures and (2) parenchymal cerebellar ss-amyloidosis. The correlation between the temporal duration of AD and both the decrease of the total number of granule cells (r=0.86, p<0.01) and the volumetric loss of the molecular (r=0.73, p<0.05) and granular (r=0.93, p<0.001) layers of the cerebellar cortex indicates that these cerebellar atrophic changes are likely to be related to the basic pathologic process of AD. Similarly, the correlation between the most complex parameter the atrophy of the cerebellar cortex and the Functional Assessment Staging (FAST) measure of the clinical severity of AD at the time of demise (r=0.63, p<0.05) as well as with the duration of AD (r=0.78, p<0.01) indicates that cerebellar pathology, when viewed holistically, evolves continuously in association with clinical changes throughout the clinically manifest course of AD.

Anatomy of the central nervous system.

OBJECTIVES: To provide an overview of central nervous system anatomy. DATA SOURCES: Published books and articles. CONCLUSIONS: Classification of tumors, location of primary and metastatic tumors, and initial and progressive symptoms are best understood within a solid knowledge base of neuroanatomy. IMPLICATIONS FOR NURSING PRACTICE: It is essential for nurses caring for neuro-oncology patients to be familiar with normal central nervous system anatomy. This knowledge will enable them to anticipate symptoms, response to treatment, and prognosis for recovery. Understanding of the effects of central nervous system tumors on the function of the central nervous system will help nurses provide holistic care to both patients and significant others.

An immunocytochemical mapping of ACTH/CLIP in the cat diencephalon.

Using an indirect immunoperoxidase technique, the location of cell bodies and fibres containing adrenocorticotropin hormone/corticotropin-like intermediate lobe peptide (ACTH/CLIP) was studied in the cat diencephalon. Immunoreactivity was observed in several diencephalic nuclei of the cat in which no immunoreactivity has been previously reported. In this sense, a low density of immunoreactive cell bodies was found in the nucleus ventromedialis hypothalami; a high density of immunoreactive fibres was found in the medial preoptic area; a moderate density in the lateral preoptic area and in the nuclei centralis thalami (pars medialis), interventralis thalami, interanteromedialis thalami, parafascicularis and praemamillaris (pars ventralis and pars dorsalis); a low density in the nuclei habenularis lateralis and reuniens thalami, and single fibres were found in the nuclei lateralis thalami (pars anterior), habenularis medialis, parataenialis, corpus geniculatum mediale, ventralis thalami (pars medialis) and in the fornix. Our results point to a more widespread distribution of ACTH/CLIP immunoreactive structures in the cat diencephalon in comparison with previous studies carried out in the same region of this feline.

Fatty acid binding protein is induced in neurons of the dorsal root ganglia after peripheral nerve injury.

Peripheral nerve trauma induces the expression of genes presumed to be involved in the process of nerve degeneration and repair. In the present study, an in vivo paradigm was employed to identify molecules which may have important roles in these processes. A cDNA library was constructed with RNA extracted from rat dorsal root ganglia (DRG) 3 days after a sciatic nerve crush. After differential hybridization to this library, several cDNAs were identified that encoded mRNAs that were upregulated in the DRG ipsilateral to the crush injury, as opposed to the contralateral or naive DRG. Approximately 0.15% of all the clones screened were found to be induced. This report presents the types of induced sequences identified and characterizes one of them, DA11. The 0.7 kb DA11 full length cDNA clone contains a 405 nucleotide open reading frame that encodes a putative protein of 15.2 kDa (135 amino acid residues) and is a member of the family of fatty acid binding proteins (FABP). The DA11 protein differs by one amino acid residue from the sequence of the C-FAPB protein and by eight residues from the sequence of mal1, proteins found in rat and mouse skin, respectively. Northern and Western blot analyses showed that the DA11 mRNA and protein were induced in the injured DRG. Furthermore, studies using antibodies generated against DA11 found that the DA11-like immunoreactivity was more pronounced in the nuclei of neurons located in the DRG ipsilateral to the sciatic cut than those located in the contralateral DRG. The induction of DA11 mRNA and protein in DRG neurons suggests, for the first time, the involvement of a neuronal FABP in the process of degeneration and repair in the nervous system.

Mapping of alpha-melanocyte-stimulating hormone-like immunoreactivity in the cat diencephalon.

Using an indirect immunoperoxidase technique, we studied the location of alpha-melanocyte-stimulating hormone-like fibers and cell bodies in the cat diencephalon. In the thalamus, almost all the immunoreactive fibers were found in the midline region, whereas in the hypothalamus immunoreactive fibers were observed in the whole structure. The hypothalamus showed a higher density of both immunoreactive fibers and cell bodies; no immunoreactive neurons were found in the thalamus. The densest network of immunoreactive fibers was observed in the epithalamus (nucleus periventricularis anterior) and in the hypothalamic nuclei filiformis, hypothalami ventromedialis, arcuatus, periventricularis hypothalami, area hypothalamica dorsalis, and hypothalamus posterior. A high density of immunoreactive neurons was found in the nucleus arcuatus, in the hypothalamus lateralis, and in the area hypothalamica dorsalis; a low density was found in the nucleus hypothalami ventromedialis and in the hypothalamus dorsomedialis. By comparison with the studies of previous researchers, these data showed a more widespread distribution of alpha-melanocyte-stimulating hormone-like immunoreactive fibers and perikarya in the feline hypothalamus. Moreover, our findings indicate that the peptide is widely distributed in the cat diencephalon, suggesting that alpha-melanocyte-stimulating hormone might be involved in several physiological functions.

Distribution of parvalbumin immunoreactivity in the cat diencephalon.

The distribution of parvalbumin-immunoreactive cell bodies and fibers in the cat diencephalon has been analyzed by using the avidin-biotin immunoperoxidase technique. The thalamus showed a higher density of immunoreactive cell bodies than the hypothalamus. A high or moderate density of perikarya and a high density of fibers containing parvalbumin was observed in the nuclei lateralis posterior, lateralis dorsalis, pulvinar, corpus geniculatum laterale, reticularis, medialis dorsalis, centrum medianum, subparafascicularis, ventralis postero-medialis, ventralis postero-lateralis, habenularis medialis, parafascicularis, corpus geniculatum mediale, centralis lateralis, rhomboidens, reuniens, centralis medialis, ventralis medialis, ventralis lateralis, parataenialis, anterior ventralis, anterior medialis, ventralis anterior, hypothalamus posterior, corpus mamillare, area hypothalamica dorsalis, and in the nucleus suprachiasmaticus. Moreover, a high or moderate density of immunoreactive fibers and a low density of parvalbumin-immunoreactive cell bodies was observed in the nuclei periventricularis anterior, anterior dorsalis, habenularis lateralis, corpus geniculatum laterale (pars ventralis), periventricularis hypothalami, hypothalamus lateralis, hypothalamus anterior, and in the hypothalamus dorsomedialis.

Quantification of axotomy-induced alteration of neuropeptide mRNAs in dorsal root ganglion neurons with special reference to neuropeptide Y mRNA and the effects of neonatal capsaicin treatment.

Alteration in mRNA expression in dorsal root ganglia (DRG) neurons encoding 5 neuropeptides was quantitatively compared in normal rats and in those neonatally treated with capsaicin, a selective neurotoxin which destroys a subpopulation of DRG neurons with unmyelinated axons. Adult rats received a unilateral transection of the sciatic nerve and were killed 7 days later. Oligonucleotide probes specific for the genes encoding neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), galanin (GAL), somatostatin (SOM), and calcitonin gene-related peptide (CGRP) were used for in situ hybridization and RNA blot analysis. Following the nerve cut, RNA blot analysis demonstrated a dramatic induction of NPY, VIP, and GAL mRNA levels from the undetectable constitutive level of expression. Conversely, CGRP and SOM mRNAs, which are constitutively expressed, were reduced 55% and 70%, respectively, following the nerve cut. A unimodal size distribution for neurons expressing NPY mRNA was determined, with a mean cross-sectional area of 1700 microns2 representing 24.4% of DRG neurons ipsilateral to the nerve cut. Neurons expressing VIP mRNA were mainly small sized, with a cross-sectional area of approximately 700 microns2, while those expressing GAL mRNA were both small (approximately 700 microns2) and medium (approximately 1,300 microns2) sized. The percentages of neurons expressing VIP or GAL mRNA were 19.9% and 33.7%, respectively. In neonatal capsaicin-treated rats, there was a 10% reduction in neurons expressing NPY mRNA, a 37% reduction for VIP, and a 27% for GAL mRNA compared to vehicle-treated rats after nerve cut. Capsaicin-sensitive neurons comprised 37% of CGRP neurons and 83% of SOM neurons. These observations suggest that NPY is primarily induced in myelinated primary afferent neurons, while VIP and GAL mRNA induction occurs in a mixed population, a sizeable percentage of which has unmyelinated axons. Additionally, SOM mRNA expression is associated mainly with unmyelinated primary afferents.

Somatostatin-28 (1-12)-like immunoreactivity in the cat diencephalon.

Using an indirect immunoperoxidase technique, the location of somatostatin-28 (1-12)-like immunoreactive fibres and cell bodies in the cat diencephalon was studied. The hypothalamus was richer in somatostatin-28 (1-12)-like immunoreactive structures than the thalamus. A high density of immunoreactive fibres was observed in the nuclei habenularis lateralis, paraventricularis anterior (its caudal part), filiformis, hypothalami ventromedialis, and regio praeoptica, whereas a moderate density was found in the nuclei paracentralis, supraopticus, supra chiasmaticus, hypothalamus posterior and area hypothalamica dorsalis. The nuclei lateralis dorsalis, lateralis posterior, medialis dorsalis, rhomboidens, centralis medialis, ventralis medialis, reuniens, anterior dorsalis, parataenialis, interanteromedialis, hypothalamus lateralis, hypothalamus dorsomedialis and arcuatus had the lowest density of immunoreactive fibres. In addition, a high or moderate density of somatostatin-28 (1-12)-like immunoreactive cell bodies was observed in the nuclei paraventricularis hypothalami, supraopticus, supra chiasmaticus, area hypothalamics dorsalis, subparafascicularis, hypothalamus posterior and hypothalamus anterior, whereas scarce immunoreactive perikarya were visualized in the nuclei lateralis dorsalis and parafascicularis. The distribution of somatostatin-28 (1-12)-like immunoreactive structures is compared with the location of other neuropeptides in the cat diencephalon.

Distribution of parvalbumin-immunoreactivity in the rat thalamus using a monoclonal antibody.

1. The distribution of parvalbumin cell bodies and fibers in the thalamus of the rat was studied using a monoclonal antibody and the avidin-biotin-peroxidase method. The densest clusters of immunoreactive perikarya were observed in the nuclei ventralis posterior, reticularis, ventralis anterior and zona incerta, whereas the nuclei habenularis lateralis, lateralis posterior, lateralis, centralis lateralis and ventralis lateralis had the lowest density. In the nucleus geniculatum laterale ventralis, the density of parvalbumin cell bodies was intermediate. In all these thalamic nuclei, small, round or fusiform immunoreactive cells with short immunolabeled dendritic processes were observed. 2. The densest network of immunoreactive fibers was observed in the nuclei geniculatum laterale ventralis, reticularis and zona incerta. The nuclei geniculatum laterale dorsalis, ventralis posterior, medialis ventralis, ventralis anterior, anterior ventralis, anterior dorsalis and rhomboidens contained a moderate number of parvalbumin fibers, whereas the nuclei lateralis posterior, habenularis lateralis, parataenialis, centrum medianum, lateralis, centralis lateralis, ventralis lateralis, medialis dorsalis, anterior medialis, ventralis medialis and lateralis anterior had the lowest density of immunoreactive fibers. In addition, a large number of immunoreactive fibers was found in the lemniscus medialis and a scarce number in the stria medullaris. 3. No immunoreactive structure was observed in the nuclei habenularis medialis, paraventricularis, reuniens and geniculatum mediale. 4. Thus, perikarya and fibers containing parvalbumin are widely distributed throughout the thalamus of the rat, suggesting that parvalbumin might play a role, directly or indirectly, in limbic, visual and somatosensory mechanisms.

[Oral rehydration solutions with 60 or 90 nmol/L of sodium for infants with acute diarrhea in accord with their nutritional status]. / Soluciones de rehidratación oral con 60 ó 90 mmol/L de sodio en niños con diarrea aguda de acuerdo a su estado nutricional.

A total of 186 infants suffering from dehydration due to acute diarrhea were studied and divided into two groups: 84 children were placed in group A and received the oral rehydration solution (ORS) recommended by the World Health Organization (WHO), know as ORS-90 and those placed in group B were given an ORS with 60 and 90 mmol/L of sodium and glucose, respectively, with an osmolality of 240 mOsm/kg (ORS-60). Seven patients from group A (8.3%) and two from group B (2.5%) could not be orally rehydrated and required intravenous rehydration. The children were divided according to their weight for their age into eutrophics, grade I malnutrition (10 to 25% deficit), grade II (26 to 40% deficit) and grade III (more than 40% deficit). In those patients who evolved favorably, the average rehydration time was 4.5 to 5.3 hours, independently from their nutritional state. In the same way, no important variations were seen in the average sodium and potassium serum levels once the dehydration was corrected, in either of the groups. Yet, both groups showed a persistence in hypokalemia and hyperkalemia seen when admitted, once the dehydration was corrected, demonstrating that the short time needed for the correction of the dehydration was insufficient to completely corrected the changes in serum potassium. Closer studies must be conducted on the hydric balance to adequately demonstrate if the new ORS-60 induces lesser losses through vomiting and feces when compared to the ORS-90 recommended by the WHO.

Frequency of upper gastrointestinal lesions in patients with liver cirrhosis.

The frequency of gastroduodenal lesions has been investigated in 142 patients with liver cirrhosis of various degrees of severity and in 63 patients with mild liver disease (controls) in whom liver biopsy excluded nodular regeneration. Cirrhotic patients were subdivided in three groups according to the Pugh modification of the Child-Turcotte criteria. Although the frequency of peptic ulcer was not different, gastroduodenal erosions were observed more frequently in cirrhotics than in controls (29.6% vs 11.1%, P less than 0.01). The occurrence of erosions was related to the severity of the disease: in Child A and B patients their frequency was 21 and 26% respectively, but rose to 48.4 (15 of 31 vs 7 of 63 in controls, P less than 0.001) in the Child C group. Both mild and severe gastroduodenitis occurred more frequently, although not significantly, in patients with liver cirrhosis. All together one or more endoscopic lesions were observed in almost 60% of cirrhotics but only in 25.4% of controls (P less than 0.001). In conclusion, our data do not show an increased prevalence of peptic ulcer in cirrhotic patients; in contrast, liver cirrhosis is significantly associated with the endoscopic finding of gastroduodenal erosions, especially in the more advanced stages of the disease. These findings would suggest a cautious use, in cirrhotic patients, of drugs which may damage the gastroduodenal mucosa; moreover, long-term administration of antacids or of other drugs with a protective effect on gastroduodenal mucosa might be taken into consideration for Child C patients.

Regional correlation of PET and CT in senile dementia of the Alzheimer type.

Alzheimer disease is manifested by both widespread and regionally restricted brain changes, some of which have recently been identified in vivo with computed tomography (CT) and positron emission tomography (PET). This is a report of the regional correlation of CT and PET measurements in 19 carefully diagnosed subjects comprising 11 controls and eight patients with senile dementia of the Alzheimer type. Regional CT attenuation values did not discriminate between the two groups, but PET using 18F-2-deoxy-2-fluoro-D-glucose demonstrated significant regional reductions (range, 21%-28%) in glucose utilization in the Alzheimer group. PET measures were also more consistently related to cognitive decline. The correlation between CT structural measures and PET metabolic measures demonstrated consistent relations between widespread PET regions and CT changes in the thalamus, posterior limb of the internal capsule, and temporal lobes. However, CT changes in the frontal white matter, caudate nucleus, and anterior limb of the internal capsule were not related to any regional PET changes. These data support previous findings of temporal lobe involvement in Alzheimer disease and suggest the involvement of structures in the region of the third ventricle.