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1.
J Peripher Nerv Syst ; 3(3): 197-206, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-10959250

RESUMEN

More than one century after the epochal paper of Harald Hirschsprung, and in spite of fast and remarkable advances in the pathophysiology of congenital megacolon, our understanding of how bowels may become functionally obstructed, and especially its variability, remains largely incomplete. While much more needs to be known about normal gastrointestinal physiology, an interaction between genetic and environmental factors seems to be of paramount importance in the pathogenesis of Hirschsprung's disease. While reviewing the relevant literature, we came across a virtually unknown contribution by an Italian physician, Domenico Battini, who happened to follow-up for about 10 years a case of severe constipation. This contribution, published posthumously as a book in 1800, not only describes very carefully the clinical evolution of that patient, but also provides a detailed post-mortem examination of the abdominal viscera, with particular reference to the alterations occurred in the intestines. We conclude that Battini, nearly one century before Hirschsprung, had succeeded in reporting a typical case of congenital megacolon, and had perceived a number of features (familiarity, selective involvement of "neural layers" in the gut mucosa) that were to become characteristic of Hirschsprung's disease a few decades after Hirschsprung himself had published his article.


Asunto(s)
Enfermedad de Hirschsprung/historia , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/fisiopatología , Historia del Siglo XIX , Humanos , Italia , Masculino , Neurología/historia
2.
J Biol Chem ; 272(10): 6685-92, 1997 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-9045700

RESUMEN

Prodynorphin gene expression was investigated in adult ventricular myocytes isolated from normal (F1B) or cardiomyopathic (BIO 14.6) hamsters. Prodynorphin mRNA levels were higher in cardiomyopathic than in control myocytes and were stimulated by treatment of control cells with the protein kinase C (PKC) activator 1, 2-dioctanoyl-sn-glycerol. Both chelerythrine and calphostin C, two PKC inhibitors, abolished the stimulatory effect of the diglyceride and significantly reduced prodynorphin gene expression in cardiomyopathic myocytes. Nuclear run-off experiments indicated that the prodynorphin gene was regulated at the transcriptional level and that treatment of nuclei isolated from control cells with 1, 2-dioctanoyl-sn-glycerol increased prodynorphin gene transcription, whereas chelerythrine or calphostin C abolished this transcriptional effect. Direct exposure of nuclei isolated from cardiomyopathic myocytes to these inhibitors markedly down-regulated the rate of gene transcription. The expression of PKC-alpha, -delta, and -epsilon, as well as PKC activity, were increased in nuclei of cardiomyopathic myocytes compared with nuclei from control cells. The levels of both intracellular and secreted dynorphin B, a biologically active product of the gene, were higher in cardiomyopathic than in control cells and were stimulated or inhibited by cell treatment with 1,2-dioctanoyl-sn-glycerol or PKC inhibitors, respectively.


Asunto(s)
Cardiomiopatía Hipertrófica/genética , Encefalinas/genética , Miocardio/metabolismo , Proteína Quinasa C/fisiología , Precursores de Proteínas/genética , Animales , Núcleo Celular/enzimología , Cricetinae , Citosol/enzimología , Diglicéridos/metabolismo , Inhibidores Enzimáticos/farmacología , Regulación Enzimológica de la Expresión Génica , Isoenzimas/metabolismo , Masculino , Mesocricetus , Miocardio/enzimología , Proteína Quinasa C/antagonistas & inhibidores , ARN Mensajero/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo
3.
Clin Neuropathol ; 15(4): 240-7, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8836611

RESUMEN

A case of familial amyloidotic polyneuropathy (FAP) is reported in which peripheral nerve and skeletal muscle biopsies were obtained from the right leg to assess the severity of the relatively late-onset but rapid-evolving neuropathy. The present paper deals with some remarkable features found in the muscular biopsy, taken from peroneus brevis and extensor digitorum longus muscles. Several fibers contained amyloid masses characterized by Congo red positivity and birefringence on polarized light microscopy: histoenzymologic staining revealed that these fibers were always type 2B and appeared grossly hypertrophied. The presence of amyloid inside the muscle fibers was possibly dependent on the internalization of capillaries leading to direct deposition of amyloid fibrils into the sarcoplasm. Fiber vascularization occurred independently of fiber splitting, which appeared to be frequent in both muscles and was characterized by unusual segmental changes in the histochemical properties of the daughter fibers with respect to those of the parent fiber. Target/targetoid and degenerating areas were also observed in a large number of type 2 fibers, usually in close relationship with segmental splitting phenomena. These findings were interpreted as possible secondary myopathic changes accompanying chronic denervation-reinnervation episodes in the course of FAP.


Asunto(s)
Neuropatías Amiloides/patología , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Neuropatías Amiloides/genética , Biopsia , Capilares/patología , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/irrigación sanguínea
5.
J Peripher Nerv Syst ; 1(3): 241-9, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-10970114

RESUMEN

The incidental finding of four ectopic ganglion cells within the pelvic nerve of a normal rat prompted a thorough electron microscopic investigation of the ultrastructural features of these neurons. They were found to enwrap presynaptic terminals inside crater-like invaginations; the appositional surfaces were made more complex by the presence of slender dendritic appendages and sheet-like processes of glial cells. The presynaptic elements contained both clear and dense-cored vesicles, and appeared similar to those characterizing SIF (paraneuronal) cells. In addition, cilia were encountered in both the invaginated processes and most of the Schwann cells associated with the pre- and postsynaptic nerve cells and their processes. Overall, these features were deemed worth reporting because 1) of the unusual features of synaptic input from a SIF cell to a ganglion cell associated with the pelvic plexus, and 2) the ectopic ganglion cells possibly represent the sole example, other than ciliary neurones in the avian ciliary ganglion, of postsynaptic cells encasing presynaptic endings inside their perikarya.


Asunto(s)
Ganglios/ultraestructura , Pelvis/inervación , Animales , Cilios/ultraestructura , Ganglios/citología , Masculino , Microtúbulos/ultraestructura , Neuronas/ultraestructura , Terminales Presinápticos/ultraestructura , Ratas , Ratas Sprague-Dawley , Células de Schwann/ultraestructura
6.
J Peripher Nerv Syst ; 1(1): 65-72, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-10970121

RESUMEN

Spontaneous and evoked synaptic transmission were studied at the rat extensor digitorum longus (EDL) neuromuscular junction in the presence of CGIIIA mu-conotoxin, a peptide which suppresses action potential in the sarcolemma, while not affecting impulse conduction along motor nerve fibers. The binomial parameters m (mean quantal content) and n (number of units involved in evoked quantal release) increased as a function of extracellular Ca++ ([Ca++]o), up to the physiological concentration (2 mM). Additional Ca++ failed to induce a statistically significant increase in either m or n, while the probability of activation (p) did increase, approaching unity at 4 mM [Ca++]o. In cut EDL preparations, without CGIIIA, the relation between end-plate potential amplitude and [Ca++]o resembled that for quantal content in unlesioned, CGIIIA-treated muscles. In contrast, normal preparations exposed to 0.5 mg/ml d-tubocurarine were much more responsive to Ca++ variations, with a significant end-plate potential amplitude increase in the presence of 4 mM [Ca++]o. However, in curarized preparation the evoked release was remarkably affected by repetitive stimulation, while in the absence of postsynaptic blockers release levels were more stable. We suggest that the stimulatory effect of extracellular Ca++ on evoked release at the mammalian neuromuscular junction might normally be depressed under physiological conditions, possibly by a down-regulation mechanism involving presynaptic nicotinic receptors. Such inhibition would increase nerve transmission efficiency during prolonged motor terminal activity.


Asunto(s)
Unión Neuromuscular/fisiología , Transmisión Sináptica/fisiología , Animales , Calcio/fisiología , Conotoxinas/farmacología , Curare/farmacología , Regulación hacia Abajo , Espacio Extracelular/metabolismo , Masculino , Unión Neuromuscular/efectos de los fármacos , Fármacos Neuromusculares no Despolarizantes/farmacología , Ratas , Ratas Sprague-Dawley
7.
Ann Neurol ; 38(2): 231-6, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7654071

RESUMEN

Vascular dementia is usually sporadic and associated with definite risk factors. Several cases also occur in a familial fashion, and may affect middle-aged or even younger subjects. Recently, an autosomal dominant inheritance was demonstrated in two unrelated French families, the members of which were affected by stroke-like episodes culminating in progressive dementia. Genetic linkage analysis assigned the disease locus to chromosome 19q12. We report an additional kindred of Italian origin in which at least 16 subjects presented leukoencephalopathic alterations. Recurrent strokes, psychiatric disturbances, dementia, and in 2 members, tetraplegia and pseudobulbar palsy were the hallmarks of this syndrome. Notably, 5 asymptomatic individuals had neuroradiological signs of leukoencephalopathy. Pathological examination of 1 subject revealed a widespread vasculopathy of the perforating arterioles, characterized by deposition of eosinophilic-congophilic material that did not immunostain with antibodies against prion protein, beta-amyloid, cystatin C, transthyretin, or heat-shock protein 70 and was similar to that described in the French families. Based on the maximum lod score, the most likely location for the disease locus was also mapped to chromosome 19q12, and found to coincide with the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) locus. The present results confirm the existence of a nosologically distinct, autosomal dominant cerebrovascular disease, presenting with recurrent subcortical ischemic strokes independent of vascular risk factors.


Asunto(s)
Trastornos Cerebrovasculares/genética , Esclerosis Cerebral Difusa de Schilder/genética , Adulto , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/genética , Infarto Cerebral/patología , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/patología , Esclerosis Cerebral Difusa de Schilder/diagnóstico por imagen , Esclerosis Cerebral Difusa de Schilder/patología , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Italia , Masculino , Persona de Mediana Edad , Linaje , Radiografía , Síndrome
8.
Toxicol Pathol ; 23(3): 248-55, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-7659949

RESUMEN

The lack of a suitable animal model for the peripheral neuropathy that often follows the systemic administration of the chemotherapeutic agent vincristine sulfate (VCR) has hampered the correlation between experimental and clinical patterns of this neuropathy. New Zealand rabbits have been recently found to develop, after iv injection of a VCR total dosage similar to that used in humans, a peripheral polyneuropathy characterized by electrophysiological changes that overlap those observed in the clinical setting. The present study was aimed at investigating the ultrastructural features of 3 different nerves (sural, peroneal, and medial gastrocnemius) in rabbits treated with 3 VCR doses that fall within the range (0.2-0.3 mg/kg i.v.) known to be efficacious chemotherapeutically and active neurotoxicologically. Regardless of the dose and the nerve under examination, histopathologic alterations appeared in the form of an overall loss of myelinated fibers, accompanied by successful attempts of regeneration and remyelination. Fibers undergoing Wallerian degeneration were characterized by an axoplasm, which was either watery-flocculent or divided in 2 or more regions as a consequence of ingrowing Schwann cell processes from the adaxonal surface. These ingrowths tended to isolate axoplasmic areas, retaining a fairly normal structure from other areas already crowded with altered organelles and cytoskeletal elements. In any event, neurofibrillary accumulations were rarely seen. These patterns are discussed with reference to those reported in the ultrastructural studies of human cases and confirm the suitability of rabbit as an animal model for VCR-induced peripheral neuropathy.


Asunto(s)
Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/ultraestructura , Enfermedades del Sistema Nervioso Periférico/patología , Vincristina/toxicidad , Animales , Inyecciones Intravenosas , Masculino , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Conejos , Vincristina/administración & dosificación
10.
Neurosci Lett ; 178(1): 127-30, 1994 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-7529383

RESUMEN

This study addressed the question as to whether the reduced activity of Na+,K(+)-ATPase reported to occur in diabetic nerves and to play a crucial role in the pathogenesis of diabetic neuropathy could be due to derangements in the axonal transport of the enzyme. A micromethod was developed to evaluate the ATPase accumulation in individual segments of ligated sciatic nerves from streptozotocin-induced diabetic rats. The results confirmed a approximately 40% decrease in the background activity, but showed that the enzyme was transported at similar rates in both anterograde and retrograde directions, suggesting that the decrease in its activity does not depend on an altered delivery along the axons.


Asunto(s)
Diabetes Mellitus Experimental/enzimología , Nervio Ciático/enzimología , Nervio Ciático/fisiopatología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Análisis de Varianza , Animales , Transporte Axonal , Diabetes Mellitus Experimental/fisiopatología , Masculino , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Nervio Ciático/fisiología
11.
J Comp Pathol ; 110(4): 413-7, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-8056876

RESUMEN

A case of symptomless, solitary lipoma of the choroid plexus is described. The tumour was found in the left lateral ventricle of an adult female baboon (Papio papio) in the course of post-mortem examination. Routine histological investigation showed that the tumour was composed exclusively of characteristic adipose cells with scarce collagen septa and without other hamartoma-like constituents, such as glial cells, neurons, cartilage or muscle fibres. The tumour mass was lined by a typical single layer of cuboidal cells; no calcifications were observed either inside the tumour or in the adjacent periventricular regions. This case is reported in view of the rarity of such tumours of the choroid plexus in man and animals, and to throw light on their possible origin.


Asunto(s)
Neoplasias del Plexo Coroideo/veterinaria , Lipoma/veterinaria , Enfermedades de los Monos/patología , Papio , Animales , Encéfalo/patología , Neoplasias del Plexo Coroideo/patología , Femenino , Lipoma/patología
13.
J Urol ; 151(3): 781-6, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8309006

RESUMEN

Urinary bladder dysfunction in the diabetic BB/W rat is characterized by infrequent irregular contractions of high amplitude. Initially these occur in the absence of detectable neuroanatomical lesions of sensory afferent and parasympathetic fibers of the pelvic nerve, which constitute the micturition reflex arc. Structural lesions consisting of progressive axonal atrophy of myelinated and unmyelinated fibers become detectable only after 4 months of diabetes. In the current study we evaluated the effect of ganglioside treatment (10 mg./kg. body weight) for one month. This drug regimen was initiated at 4 months of diabetes, when functional bladder abnormalities were well established, whereas structural lesions were yet to appear. Animals examined 1 or 3 months after termination of the one-month treatment protocol showed sustained normalization of the characteristic functional abnormalities, accompanied by prevention of the neuroanatomical lesions of sensory afferent and parasympathetic efferent myelinated fibers in the pelvic nerve. These data suggest that ganglioside treatment may be beneficial in delaying the progression of diabetic autonomic neuropathy in this experimental animal model.


Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Neuropatías Diabéticas/fisiopatología , Gangliósidos/uso terapéutico , Vejiga Urinaria Neurogénica/fisiopatología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/fisiopatología , Animales , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/patología , Femenino , Gangliósidos/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiopatología , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/patología , Ratas , Ratas Endogámicas BB , Vejiga Urinaria Neurogénica/tratamiento farmacológico
14.
Cardiology ; 85(3-4): 145-53, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7987869

RESUMEN

A case of severe cardiac involvement is reported in a patient affected with familial amyloidotic polyneuropathy due to the Portuguese type I variant (Val-->Met30) of the transthyretin (prealbumin) molecule. Echocardiographic and hemodynamic studies suggested the presence of a progressive infiltrative cardiomyopathy that was later confirmed by endomyocardial biopsy. Amyloid deposits were found in both intra- and extra-myofiber location and thought to be related to primary involvement of the heart. Norepinephrine content of myocardial bioptic specimens was about threefold lower than normal, indicating that autonomic denervation may contribute to the maintenance and progression of cardiomyopathy. A sample obtained from the sural nerve showed a loss of myelinated fibers along with accumulation of amyloid masses in the endoneurial space. This histopathologic pattern correlated with a sharp decrease in the activity of the enzyme subserving electrochemical conduction through the axonal membrane, Na+, K(+)-ATPase.


Asunto(s)
Neuropatías Amiloides/metabolismo , Amiloide/metabolismo , Miocardio/metabolismo , Prealbúmina/metabolismo , Neuropatías Amiloides/complicaciones , Neuropatías Amiloides/genética , Neuropatías Amiloides/patología , Amiloidosis/genética , Amiloidosis/metabolismo , Amiloidosis/patología , Cardiomiopatías/complicaciones , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Humanos , Masculino , Persona de Mediana Edad , Miocardio/patología , Norepinefrina/análisis , ATPasa Intercambiadora de Sodio-Potasio/análisis , Nervio Sural/enzimología , Nervio Sural/patología
15.
J Neurol Sci ; 120(2): 159-67, 1993 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-8138805

RESUMEN

A decrease in Na+,K(+)-ATPase activity is claimed to play a central role in the pathogenesis of electrophysiological and morphological abnormalities that characterize the neuropathic complications in different animal models of diabetes mellitus. The peripheral nerves from 17 patients with either type I or type II diabetes mellitus were studied to assess the importance of changes in Na+,K(+)-ATPase activity in chronic human diabetic neuropathy. Sixteen nerves from age- and sex-matched normal individuals, and 12 nerves from non-diabetic neuropathic subjects undergoing vascular or orthopedic surgery served as negative and positive controls, respectively. All specimens were processed blind. Ouabain-sensitive ATPase activity was measured by a modified spectrophotometric coupled-enzyme assay. Standard histology, fiber teasing and electron microscopy were used to establish the normal or neuropathological patterns of surgical material. Morphometric analysis permitted calculation of fiber density in each nerve specimen and correlation of this figure with the relevant enzymatic activity. Na+,K(+)-ATPase activity was approximately 59% lower in nerves from diabetic patients than in normal controls (P < 0.01) and approximately 38% lower in nerves from non-diabetic patients with neuropathy (P < 0.01). Although nerves from both neuropathic conditions had significantly fewer fibers than those from normal individuals (diabetic -33%, and non-diabetic -22%), the decreases in Na+,K(+)-ATPase activity and fiber density were not correlated only in specimens from diabetic patients (r2 = 0.096; P = 0.22). Taken together with data from experimental animal models, these results suggest that the reduction in Na+,K(+)-ATPase activity in diabetic nerves is not an epiphenomenon secondary to fiber loss; rather, it may be an important factor in the pathogenesis and self-maintenance of human diabetic neuropathy.


Asunto(s)
Neuropatías Diabéticas/enzimología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/patología , Femenino , Histocitoquímica , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/enzimología , Fibras Nerviosas Mielínicas/ultraestructura , Enfermedades del Sistema Nervioso Periférico/enzimología , Enfermedades del Sistema Nervioso Periférico/patología
16.
Invest Radiol ; 28(9): 821-7, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8225888

RESUMEN

RATIONALE AND OBJECTIVES: The use of the newest nonionic, water-soluble, low-osmolar radiographic contrast media (CM) is still associated with occasional adverse reactions affecting the neural tissues. Because these CM display lipophilic potential in their interactions with biological membranes when diffusing within the brain parenchyma, they could affect neurotransmitter binding to the receptors. Two representative nonionic CM, iopamidol and iohexol, were studied to assess whether CM-related neurotoxicity derived from their interactions with specific receptors on neural membranes. METHODS: Binding assays were carried out in vitro on crude total membrane or crude synaptic membrane preparations from selected brain areas (cortex, striatum, hippocampus, cerebellum). The concentrations of CM and reference drugs that reduce specific binding of each ligand by 50% of its maximum value (IC50) were determined using radioligands to the receptors of the most common neurotransmitters in the central nervous system, including excitatory amino acids. RESULTS: Neither iopamidol nor iohexol inhibited the (3H) ligand binding to any kind of receptor up to very high concentrations (100 microM). CONCLUSIONS: The nonionic, low-osmolar CM did not influence the normal functions of neural membranes in our model. This suggests that occasional neurotoxic effects do not occur as a consequence of specific action on brain receptors. These CM may have an indirect, postmembrane site of action.


Asunto(s)
Encéfalo/efectos de los fármacos , Yohexol/toxicidad , Yopamidol/toxicidad , Animales , Unión Competitiva , Encéfalo/metabolismo , Yohexol/metabolismo , Yopamidol/metabolismo , Masculino , Concentración Osmolar , Ensayo de Unión Radioligante , Ratas , Ratas Sprague-Dawley , Receptores de Neurotransmisores/metabolismo
17.
Electroencephalogr Clin Neurophysiol ; 87(3): 97-104, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7691546

RESUMEN

Visual processing of sinusoidally modulated gratings was studied in a group of patients (n = 11) with Alzheimer's disease (AD) and an elderly normal control group (n = 9). Spatial square wave gratings (1.47 c/d) were reversed at a temporal frequency of 4 or 8 Hz. EEG recordings at rest and during visual stimulation were obtained from 20 channels using the 10/20 international system. The power spectrum of the 2nd and 4th harmonic of the stimulation frequency was calculated by Fast Fourier Transform (FFT) at a resolution of 0.25 Hz. Association of activity between occipital, temporal, parietal and central regions was measured by intra- and inter-hemispheric coherence and phase at harmonics of the stimulation frequency. A significant difference (P < 0.01) in evoked activity of the 4th harmonic at O1 and O2 was found between the two groups with less activity in the AD patients. In the AD group there was a significant correlation (P < 0.05) between evoked activity at the 2nd harmonic of the 8 Hz visual stimulation and Mini-Mental State (MMS) score. This correlation was independent of the age effect on MMS. Response phase between O1 and O2 for both 4 and 8 Hz stimuli was close to 0 degree C and coherence had similar values in both groups. Occipital and central regions showed a phase reversal for all harmonic responses to both visual stimuli. The AD patients showed statistically significant (P < 0.05) phase dispersion at O1-P3 and O2-P4 not seen in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiopatología , Electroencefalografía , Percepción Visual , Anciano , Electrofisiología , Potenciales Evocados Visuales , Femenino , Análisis de Fourier , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Vías Visuales
18.
Eur J Pharmacol ; 239(1-3): 55-61, 1993 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-8223914

RESUMEN

The effects of ganglioside treatment on 1,2-diacylglycerol content and on molecular species in 1,2-diacylglycerol, phosphatidic acid and total diacylglycerolipids, as well as Na+,K(+)-ATPase activity, were examined in sciatic nerves from streptozotocin-induced diabetic rats. Beginning 2 weeks after induction of diabetes, animals were administered mixed bovine brain gangliosides, AGF1, an inner ester derivative of this mixture, or saline for 5 weeks. The levels of 1,2-diacylglycerol and arachidonoyl-containing molecular species in age-matched non-diabetic animals were not affected by ganglioside treatment. In nerves from saline-treated diabetic animals, 1,2-diacylglycerol levels were not reduced, but both Na+,K(+)-ATPase activity and all arachidonyl-containing species except for 18:0/20:4 1,2-diacylglycerol were significantly decreased. The content of 1,2-diacylglycerol was lowered by 23 and 16% in bovine brain ganglioside and AGF1-treated diabetic animals, respectively, and the quantity of 18:0/20:4 1,2-diacylglycerol was also selectively reduced. Ganglioside administration did not affect the diminished levels of arachidonoyl-containing molecular species in 1,2-diacylglycerol, phosphatidic acid or diacylglycerolipids in nerve from diabetic rats. In the same nerves, bovine brain gangliosides partially and AGF1 completely restored Na+,K(+)-ATPase activity. The results suggest that gangliosides depress the content of total 1,2-diacylglycerol and the quantity of 18:0/20:4 1,2-diacylglycerol, specifically, in diabetic nerve. The possible relationship between the corrective action of gangliosides on Na+,K(+)-ATPase activity and the effect of these substances on 1,2-diacylglycerol molecular species composition and metabolism is discussed.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Diglicéridos/metabolismo , Gangliósidos/farmacología , Nervio Ciático/efectos de los fármacos , Animales , Diabetes Mellitus Experimental/enzimología , Gangliósidos/administración & dosificación , Masculino , Ouabaína/farmacología , Ácidos Fosfatidicos/metabolismo , Ratas , Ratas Sprague-Dawley , Nervio Ciático/enzimología , Nervio Ciático/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo
19.
Aging (Milano) ; 5(2): 123-33, 1993 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8323999

RESUMEN

This double-blind study assesses the therapeutic efficacy and the safety of oral treatment with phosphatidylserine (BC-PS) vs placebo (300 mg/day for 6 months) in a group of geriatric patients with cognitive impairment. A total of 494 elderly patients (age between 65 and 93 years), with moderate to severe cognitive decline, according to the Mini Mental State Examination and Global Deterioration Scale, were recruited in 23 Geriatric or General Medicine Units in Northeastern Italy. Sixty-nine patients dropped out within the 6-month trial period. Patients were examined just before starting therapy, and 3 and 6 months thereafter. The efficacy of treatment compared to placebo was measured on the basis of changes occurring in behavior and cognitive performance using the Plutchik Geriatric Rating Scale and the Buschke Selective Reminding Test. Statistically significant improvements in the phosphatidylserine-treated group compared to placebo were observed both in terms of behavioral and cognitive parameters. In addition, clinical evaluation and laboratory tests demonstrated that BC-PS was well tolerated. These results are clinically important since the patients were representative of the geriatric population commonly met in clinical practice.


Asunto(s)
Anciano , Trastornos del Conocimiento/prevención & control , Fosfatidilserinas/uso terapéutico , Actividades Cotidianas , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Anciano Frágil , Humanos , Masculino , Procesos Mentales/efectos de los fármacos , Escala del Estado Mental , Pacientes Desistentes del Tratamiento , Fosfatidilserinas/farmacología , Escalas de Valoración Psiquiátrica
20.
Scand J Immunol ; 37(3): 308-13, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8441917

RESUMEN

Gangliosides have been shown to modulate autoimmune phenomena in experimental diabetes. The effects of a pancreatic ganglioside preparation or of a commercial brain ganglioside mixture on the insulitis and blood glucose levels in the low-dose streptozotocin mouse model of diabetes have been investigated. Fifty-five C57BL/6J male mice were grouped as follows: Group 1 (n = 20) was injected intraperitoneally with repeated low doses of streptozotocin; Group 2 (n = 10) received streptozotocin as above but was also injected with a pancreatic ganglioside preparation equivalent to 2 micrograms sialic acid 2 h before each streptozotocin dose; Group 3 (n = 15) received streptozotocin and brain-derived gangliosides in the same dose as that of pancreatic gangliosides; Group 4 (n = 10) consisted of normal animals. Half of the mice were killed on day 12 and the others on day 24 from the beginning of treatment. On day 12, among the streptozotocin-injected animals only those treated with pancreatic gangliosides remained normoglycaemic, whereas on day 24 all streptozotocin mice were hyperglycaemic. Such a result paralleled the data pertaining to insulitis scores. In conclusion, pancreatic gangliosides have a short-term protective role on the development of diabetes in the low-dose streptozotocin model, an effect therefore linked to tissue-related differences in the glycosphingolipid composition.


Asunto(s)
Diabetes Mellitus Experimental/inducido químicamente , Gangliósidos/farmacología , Pancreatitis/inducido químicamente , Animales , Química Encefálica , Masculino , Ratones , Ratones Endogámicos C57BL , Páncreas/química , Estreptozocina/administración & dosificación , Factores de Tiempo
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