RESUMEN
A huge prepontine-suprasellar arachnoid cyst was identified by fetal sonography and magnetic resonance imaging. It was successfully treated with a two-stage operation using a neuroendoscope. The first operation during the neonatal period consisted of implantation of a cyst-peritoneal shunt. In the second operation, the cyst was fenestrated with the aid of a neuroendoscope. The cyst membrane was seen to cover the foramen magnum and to extend continuously to the ventral surface of the brain stem. At the foramen magnum, it was pulsating synchronously with the pulsation of the vertebral artery, which was suggestive of the mechanism of cyst growth. A ventriculo-peritoneal shunt was inserted to replace the cyst-peritoneal shunt. Endoscopic cyst fenestration is a less invasive alternative for the treatment of arachnoid cysts and can also be used for young children. In that case, however, special care should be taken to avoid complications, especially if the cyst exerts considerable pressure on the critical areas of the brain.
Asunto(s)
Quistes Aracnoideos/congénito , Quistes del Sistema Nervioso Central/congénito , Endoscopía , Puente , Adulto , Quistes Aracnoideos/diagnóstico , Quistes Aracnoideos/cirugía , Quistes del Sistema Nervioso Central/diagnóstico , Quistes del Sistema Nervioso Central/cirugía , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Puente/patología , Puente/cirugía , Complicaciones Posoperatorias/diagnóstico , Diagnóstico Prenatal , Reoperación , Derivación VentriculoperitonealRESUMEN
PURPOSE: To evaluate the mechanical properties of slow fibers and fast fibers which make up the extraocular muscles in rabbits. SUBJECTS AND METHOD: I studied the contractile properties and viscoelastic properties of the superior rectus muscle(SR) and the retractor bulbi muscle (RB) of rabbits using the quick release method and the frequency response method. RESULTS: In the quick release method, isometric tension transients were slower in the SR than in the RB. In the frequency response method, the muscle length is perturbed sinusoidally to measure kinetic viscoelasticity. In resting muscle, dynamic stiffness was not changed with increasing frequency. In contracted muscle, dynamic stiffness was increased with increasing frequency, and the rate of increase was greater in the SR than in the RB. CONCLUSION: It was concluded that the viscoelasticity of the activated cross bridge is greater in slow fibers than in fast fibers.
Asunto(s)
Fibras Musculares de Contracción Lenta/fisiología , Músculos Oculomotores/fisiología , Animales , Elasticidad , Contracción Isométrica/fisiología , Cinética , Contracción Muscular/fisiología , Fibras Musculares de Contracción Rápida/fisiología , ConejosRESUMEN
PURPOSE: We analyzed the clinical outcome of treatment with the expandable metallic stent (EMS) for the superior vena cava (SVC) syndrome associated with malignant tumors, and the results were compared with those of radiotherapy. MATERIAL AND METHODS: Of 33 patients with the SVC syndrome, 23 were treated by Gianturco EMS placement and 10 were treated by radiotherapy and/or chemotherapy alone. Of the 23 EMS patients, 11 had treatment before EMS placement and 12 had no treatment before EMS placement. RESULTS: After stenting, the clinical symptoms disappeared in 78% (18/23) of the patients, i.e. in 50% of the patients with intraluminal tumors, and in 93% of those with extrinsic compression. The clinical symptoms improved in 80% of patients who received radiotherapy. The mean duration of survival was 145 days in patients who underwent stenting, and 146 days in those receiving radiotherapy. However, the survival period differed significantly between patients with intraluminal tumors (44.9 days) and those with extrinsic compression (198.6 days). Between patients with previous treatment and those with no previous treatment, there was no significant difference in response rate or in survival period which were 82% versus 75%, and 127 days versus 162 days, respectively. CONCLUSION: The clinical symptoms showed similar improvement in patients receiving EMS placement or radiotherapy. EMS placement was effective in relieving clinical symptoms in patients who had failed to respond to radiotherapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/complicaciones , Stents , Síndrome de la Vena Cava Superior/terapia , Adulto , Anciano , Implantación de Prótesis Vascular , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Neoplasias/terapia , Flebografía , Radioterapia Adyuvante , Síndrome de la Vena Cava Superior/diagnóstico por imagen , Síndrome de la Vena Cava Superior/etiología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
To investigate dopamine (DA) levels as well as DA metabolism by which the striatal DAergic grafts may bring the functional recovery to hemiparkinsonian model rats, a microdialysis study was performed in the striatum, and an autoradiographic analysis for DA transporter was made. In hemiparkinsonian model rats, the concentrations of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in striatal perfusates, decreased considerably (less than 5%, of control levels). In grafted rats that showed motor recovery, the concentration of DA recovered to almost control level, and DOPAC and HVA to about 20% of controls' suggesting that the rate of DA metabolism is low. L-DOPA loading to grafted rats induced a big release of DOPAC and HVA, thus the DOPAC/DA ratio was close to that of the controls'. Methamphetamine loading increased the concentration of DA but did not change the level of DOPAC and HVA. Haloperidol loading increased DA, DOPAC and HVA. [3H]mazindol binding that reflects the activity of the DA transporter decreased considerably in hemiparkinsonian model rats, but it reappeared more or less in grafted rats. Data indicated that in grafted striatum, the extracellular DA level is almost normal level while the rate of DA metabolism is low. By L-DOPA loading, the grafts show the capacity to synthesize, release and metabolize DA and then the DOPAC/DA ratio is normalized. Responses to methamphetamine and haloperidol, as well as the results of the autoradiographic study suggest that the grafts are under a good feedback regulation of DA metabolism.
Asunto(s)
Trasplante de Tejido Encefálico/fisiología , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Mesencéfalo/trasplante , Proteínas del Tejido Nervioso , Enfermedad de Parkinson Secundaria/metabolismo , Enfermedad de Parkinson Secundaria/cirugía , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Autorradiografía , Proteínas Portadoras/metabolismo , Cuerpo Estriado/efectos de los fármacos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Femenino , Trasplante de Tejido Fetal , Lateralidad Funcional , Haloperidol/farmacología , Ácido Homovanílico/metabolismo , Cinética , Levodopa/farmacología , Mazindol/metabolismo , Mesencéfalo/fisiología , Metanfetamina/farmacología , Microdiálisis , Actividad Motora/efectos de los fármacos , Oxidopamina , Enfermedad de Parkinson Secundaria/inducido químicamente , Ratas , Ratas Wistar , Rotación , Tritio , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
The reproducibility of bone mineral density (BMD) measurements with peripheral quantitative CT has been limited by the repositioning error. In this study, 1 mm-step 3-slice scan data were used to compensate for this error in trabecular BMD of the distal radius. The assessment was based on the liner relations between the cross-sectional area and trabecular bone mineral content and trabecular area ratio, on the condition that the trabecular bone is defined by a BMD value. The estimated reproducible errors of less than 2% under clinical conditions indicate that the method is reliable for follow-up examination.
Asunto(s)
Densidad Ósea/fisiología , Radio (Anatomía)/fisiología , Tomografía Computarizada por Rayos X , Adulto , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
Constitutive production of hydroxyl radicals from four established cancer cell lines was detected as spin adducts of 5,5-dimethyl-l-pyroline-N-oxide (DMPO), using an electron spin resonance spectrometer. The generated hydroxyl radicals was decreased in three out of four cancer cell lines when incubated in vitro for 3 h with TNF-alpha No direct scavenging effect of TNF-alpha on hydroxyl radicals or superoxide anions was observed in the in vitro radical generation system. The modulation of intracellular reactive oxygen species of these cancer cells by adding menadione or CuDIPS to the culture medium changed the antiproliferative effect of TNF-alpha on the cells. The ultrastructural localization of the radical-generating sites in cancer cells was visualized using the diaminobenzidine/horseradish peroxide histochemical system at the electron microscopic level. The hydrogen peroxide-dependent formation of electron-dense materials localized at the mitochondrial membranes was decreased after the treatment of the cancer cells with TNF-alpha. These data indicate that the reduction of radical generation in cancer cells by TNF-alpha may be an early mechanism that contributes to the antiproliferative effect of this cytokine on some cancer cells.
Asunto(s)
Depuradores de Radicales Libres/farmacología , Factor de Necrosis Tumoral alfa/farmacología , División Celular/efectos de los fármacos , Óxidos N-Cíclicos , Espectroscopía de Resonancia por Spin del Electrón , Radicales Libres/metabolismo , Humanos , Radical Hidroxilo/metabolismo , Microscopía Electrónica , Especies Reactivas de Oxígeno/metabolismo , Salicilatos/farmacología , Marcadores de Spin , Superóxidos/metabolismo , Células Tumorales Cultivadas , Vitamina K/farmacologíaRESUMEN
We report here the time-course of electron microscopic changes induced by gamma-interferon (IFN-gamma) in the human erythromyeloid leukemia cell line K562. In K562 cells treated with IFN-gamma for 6h, the nuclei were polygonal in shape and microvilli were far more abundant on cell membranes compared with control K562 cells, and invaginations were often seen in the cell membranes. There was a reduction in the number of cell-membrane microvilli and an increase in the number of lysosomal bodies in the cytoplasm of K562 cells treated with IFN-gamma for 12h. After treatment with IFN-gamma for 24h, the cell membrane microvilli disappeared, large numbers of cellular organelles were observed, such as mitochondria and lysosomes, and the cytoplasm became electron-dense. Cytoplasmic vesicles and vacuoles were also observed. These vesicles may correspond to an intermediate step in the ultimate cellular disintegration associated with apoptosis caused by IFN-gamma.
Asunto(s)
Apoptosis/efectos de los fármacos , Interferón gamma/farmacología , Monocitos/ultraestructura , División Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Núcleo Celular/ultraestructura , Supervivencia Celular/efectos de los fármacos , Humanos , Microscopía Electrónica , Microvellosidades/efectos de los fármacos , Microvellosidades/ultraestructura , Monocitos/efectos de los fármacos , Orgánulos/efectos de los fármacos , Orgánulos/ultraestructura , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
The time-course of changes in the plasma-membrane lipid bilayer induced by tumour necrosis factor-alpha (TNF) were investigated in cultured cells using spin-label electron-spin-resonance techniques. Treatment of K 562 cells, a human chronic myelocytic leukaemia cell line, in suspension culture with TNF for up to 6 h caused an initial increase in cell-membrane fluidity, which returned to the control level after 12 h of treatment. After 24 h of treatment, the cell-membrane fluidity had decreased and this decrease was maintained after 48 h of treatment. In Daudi cells, a human malignant lymphoma cell line, TNF, did not induce any changes in cell-membrane fluidity, indicating that the effect of TNF on membrane structure is cell-specific. The early and transient change in membrane fluidity in K 562 cells is probably related to signal generation, while the later, persistent change may reflect the phenotype of TNF-treated cells, in particular, changes in the plasma membrane-cytoplasmic complex. Histochemical electron microscopic studies indicated that the membrane fluidity changes induced by TNF have an ultrastructural correlate.
Asunto(s)
Membrana Celular/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Espectroscopía de Resonancia por Spin del Electrón , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Linfoma/metabolismo , Fluidez de la Membrana/efectos de los fármacos , Microscopía Electrónica , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
We examined by morphological methodology the effect of (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713), an acetylcholinesterase (AChE) inhibitor, on ischemia-induced neuronal death in the gerbil hippocampus due to a 5-min ligation of bilateral common carotid arteries after light ether anesthesia. Pyramidal cells had been decreased to 27% of sham-operated controls and the number of hypertrophic astrocytes expressing glial fibrillary acidic protein (GFAP) markedly increased in the hippocampal CA1 subfield 14 days after ischemia. However, post-ischemic administration of ENA-713 (three times 0.2 mg/kg, i.p.) significantly ameliorated this ischemia-induced decrease in the number of pyramidal cells by 47% of sham-operated controls, furthermore, it reduced the ischemia-induced accumulation of GFAP-positive astrocyte in the CA1 region. Together with previous results showing that ENA-713 protected against the ischemia-induced cholinergic abnormalities in the gerbil brain and improved cholinergic dysfunctions in the senescent rat brain, our present findings suggest that ENA-713 prove to be useful for treatment with senile dementia such as cerebrovascular dementia.
Asunto(s)
Carbamatos/farmacología , Muerte Celular/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Hipocampo/patología , Ataque Isquémico Transitorio/patología , Neuronas/patología , Fenilcarbamatos , Animales , Astrocitos/efectos de los fármacos , Astrocitos/patología , Gerbillinae , Proteína Ácida Fibrilar de la Glía/análisis , Proteína Ácida Fibrilar de la Glía/biosíntesis , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipertrofia , Neuronas/citología , Neuronas/efectos de los fármacos , Células Piramidales/efectos de los fármacos , Células Piramidales/patología , RivastigminaRESUMEN
This study evaluated the adhesion of composite resin to five different surface conditions of porcelain samples that were treated with three kinds of silane agents. Two of these were commercially available Porcelain Liner M and Tokuso Ceramic Primer, and one was an experimental agent. The commercially available silane agents gave high bond strengths without hydrofluoric acid etching, which gave the greatest roughness on the porcelain surface. One component of these commercially available silane agents was gamma-methacryloxypropyl trimethoxysilane, and the other was the carboxylic acid. As a result of the effective formation of siloxane bonds by mixing with acid solution, porcelain surface conditions did not affect the bond strengths.
Asunto(s)
Resinas Compuestas/química , Recubrimiento Dental Adhesivo/métodos , Porcelana Dental/química , Silanos/química , Análisis de Varianza , Ácido Fluorhídrico , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Ácidos Fosfóricos , Propiedades de Superficie , Resistencia a la TracciónRESUMEN
A 74-year-old female presented with intraventricular and subarachnoid hemorrhage due to probable rupture of a basilar artery (BA) aneurysm or a superior cerebellar artery (SCA) aneurysm. She was treated by endovascular therapy using detachable coils through the BA. The BA aneurysm was completely occluded, but part of a coil migrated into the BA from the SCA aneurysm during the procedure. The migrated coil was retrieved using a snare type endovascular retrieving device. The snare loop required concentric closure around the coil by simultaneous pulling of the corewire and a slight forward movement of the tip of the snare catheter. The SCA aneurysm was successfully occluded 1 week later using a shorter coil.
Asunto(s)
Arteria Basilar/fisiopatología , Cuerpos Extraños/cirugía , Aneurisma Intracraneal/fisiopatología , Hemorragia Subaracnoidea/fisiopatología , Anciano , Angiografía Cerebral , Femenino , Cuerpos Extraños/diagnóstico , HumanosRESUMEN
The distribution of atrial natriuretic polypeptide (ANP) and atrial specific granules in the myocytes of the atria and ventricles of an experimental animal model, stroke-prone spontaneously hypertensive rats (SHRSP) and a control, Wistar Kyoto rats (WKY), was examined using immunocytochemical and electron microscopic techniques. In the atria of both SHRSP and WKY, ANP-immunoreactivity was recognized in the perinuclear regions of essentially all cardiac myocytes. In the ventricles of WKY, ANP-immunoreactivity was hardly seen except for the impulse-conducting system. However, in the ventricles of SHRSP, almost all cardiac myocytes possessed immunoreaction products which were scattered evenly throughout the cytoplasm; this distribution pattern differed from that of the atrial wall of this strain.
Asunto(s)
Factor Natriurético Atrial/análisis , Trastornos Cerebrovasculares/metabolismo , Gránulos Citoplasmáticos/química , Hipertensión/metabolismo , Miocardio/química , Animales , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Atrios Cardíacos , Ventrículos Cardíacos , Hipertensión/patología , Inmunohistoquímica , Masculino , Microscopía Electrónica , Miocardio/citología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKYRESUMEN
The effects of pre-treatment with ENA-713, an acetylcholinesterase (AChE) inhibitor, on changes in pre- and postsynaptic cholinergic indices in gerbil brain following transient ischemia were studied at 4 and 14 days after recirculation. In the ischemic group, hippocampal acetylcholine (ACh) level was significantly reduced (to 23% of sham-operated controls) at 4 days post-ischemia, but this reduction was completely prevented by ENA-713 treatment. Choline acetyltransferase (ChAT) and cholinesterase (ChE) activities were not significantly changed at 4 and 14 days post-ischemia. Although the maximum number (Bmax) of muscarinic ACh receptor (mACh-R) binding in the hippocampus was decreased (to 44%) without any change in affinity at 14 days post-ischemia, this decrease was also inhibited by ENA-713 treatment. In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions. Thus, these findings suggest that ENA-713 has protective, neurotrophic and therapeutic effects on cerebrovascular type dementia due to cerebral ischemia.
Asunto(s)
Acetilcolina/metabolismo , Carbamatos/uso terapéutico , Inhibidores de la Colinesterasa/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Fenilcarbamatos , Sinapsis/metabolismo , Animales , Gerbillinae , Ataque Isquémico Transitorio/metabolismo , Ataque Isquémico Transitorio/patología , Estructura Molecular , Receptores Muscarínicos/efectos de los fármacos , Receptores Muscarínicos/metabolismo , RivastigminaRESUMEN
Two types of beta-galactosidase genes, whose products are distributed in the nucleus (N beta-gal) or cytoplasm (C beta-gal), were injected with fructose intramuscularly into the quadriceps of adult mice. Regionally restricted and overlapped distributions of both gene products were observed in the myofibres. These findings indicate that N beta-gal is incorporated into the nucleus responsible for its synthesis and that C beta-gal becomes located in the vicinity of the nucleus after its synthesis. This restricted location of C beta-gal in myofibres remained unchanged during the development of infant mouse muscle. Thus, the gene products directed by the nucleus of myofibres seem to show limited diffusibility, suggesting a universal localization of subcellular domains in myofibres.
Asunto(s)
Núcleo Celular/enzimología , Citoplasma/metabolismo , Técnicas de Transferencia de Gen , Músculos/ultraestructura , beta-Galactosidasa/genética , Animales , ADN/metabolismo , Difusión , Distrofina/genética , Terapia Genética , Cinética , Luciferasas/genética , Ratones , Ratones Endogámicos ICR , Microscopía Electrónica , Músculos/enzimología , Distrofias Musculares/terapia , Plásmidos , beta-Galactosidasa/metabolismoRESUMEN
We grafted fetal striatal cells in ischemic rat models, and investigated graft survival/growth, GABA release, GABAA receptor reorganization and functional recovery. One hour intraluminal occlusion of the middle cerebral artery (MCA) induced ischemic infarct in the lateral part of the striatum and adjacent cortex. In ischemic rats, the acquisition of Morris' water-maze learning was significantly slower than that of control rats. In these animals GABA level in the globus pallidus, detected by microdialysis, was about the half of that of controls. However, after the grafts of fetal striatal cells in the striatopallidum, the acquisition was improved, thus no difference was observed in the time course of learning curves in control and grafted animals. GABA level recovered to almost normal level by the graft. It further increased by the treatment of a GABA uptake blocker (nipecotic acids) in the perfusion. In the grafts, GABAA receptor organization detected by autoradiography using [3H] labeled SR95531 was restored for more than 1 year after the graft. Data suggest that fetal striatal cell grafts in infarct striatum may partially reconstruct striatopallidal GABA projection and reorganize GABAA receptor. This might be a basis of improvement of function.
Asunto(s)
Trasplante de Tejido Encefálico/fisiología , Trasplante de Células/fisiología , Globo Pálido/fisiología , Aprendizaje/fisiología , Neostriado/trasplante , Prolina/análogos & derivados , Receptores de GABA-A/fisiología , Ácido gamma-Aminobutírico/metabolismo , Animales , Autorradiografía , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/psicología , Arterias Cerebrales/fisiología , Infarto Cerebral/fisiopatología , Infarto Cerebral/psicología , Antagonistas de Receptores de GABA-A , Globo Pálido/fisiopatología , Masculino , Microdiálisis , Neostriado/fisiología , Neostriado/fisiopatología , Ácidos Nipecóticos/farmacología , Piridazinas/farmacología , Ratas , Ratas WistarRESUMEN
We investigated alterations in protein kinase C (PKC) activity of PANC-1 cells following treatment with tumour necrosis factor (TNF)-alpha or TNF-beta by an in vitro autoradiographic method. Binding studies performed on whole cells using [3H]phorbol-12,13-dibutyrate (PDBu) as a ligand revealed strong activation of PKC by TNFs within 30 min. The effect was similar to that seen after 30 min treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). After treatment for 24 h, TNF-beta caused a marked down-regulation of PKC similar to that seen after 24 h treatment with TPA; significant activation persisted, however, in the cells treated for 24 h with TNF-alpha. Our data suggest that PKC activation may play a more important role in the TNF-alpha signal transduction pathway than in that of TNF-beta.
Asunto(s)
Linfotoxina-alfa/farmacología , Neoplasias Pancreáticas/metabolismo , Proteína Quinasa C/biosíntesis , Transducción de Señal , Factor de Necrosis Tumoral alfa/farmacología , Autorradiografía , Inducción Enzimática , Humanos , Técnicas In Vitro , Células Tumorales CultivadasRESUMEN
Several studies have shown that swinglock removable partial dentures are effective for stability of the abutment teeth and the surrounding tissues including alveolar bone. This efficacy has been thought to be due to the dynamic structure of the swinglock attachment. Individual biting force was measured to determine the physiological efficacy of teeth splints by use of the attachment. The results showed that individual biting forces with the swinglock removable partial denture were 10-25% higher than those without the denture. Furthermore, statistical analysis showed that the individual biting forces with the swinglock removable partial denture were significantly higher. The swinglock attachment can stabilize partially edentulous dentition by splinting all residual teeth. In addition, when physical forces are applied to the abutment teeth and the artificial teeth, this attachment can deliver and distribute the stress to the other abutment teeth and alveolar mucosa. The present findings suggest that the swinglock attachment augments the ability to withstand physical forces such as those occurring during biting and mastication.
Asunto(s)
Fuerza de la Mordida , Análisis del Estrés Dental , Dentadura Parcial Removible , Arcada Parcialmente Edéntula/fisiopatología , Pilares Dentales , Diseño de Dentadura , Retención de Dentadura/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Receptor binding assays and in vitro macroautoradiography were used to analyze muscarinic cholinergic receptors (MCR) in the cerebral frontal cortex of Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT), and age-matched control brains at autopsy. Total MCR binding, detected by [(3)H]quiniclinidyl benzilate binding, did not differ significantly between the 3 groups. The concentrations of M1 subtype (M1-R), detected by [(3)H]pirenzepine binding, and high affinity state MCRs, however, were significantly lower in AD than in control and SDAT frontal cortices. No differences were detected in the affinity of these receptors for their ligands. The MCRs in AD frontal cortex were more sensitive to the agonist carbachol than were control MCRs. Autoradiography revealed a complete destruction of the laminar distribution of MCR and M1-R in AD and SDAT frontal cortices. Forskolin and phorbol ester binding sites, used to analyze second messenger systems, were significantly and markedly reduced in AD frontal cortex. In addition, coupling between MCR and second messenger systems was supersensitive in AD frontal cortex. Our findings that there are alterations in the structural distribution of MCR as well as reductions and abnormalities in second messenger systems in AD cerebral frontal cortex, suggest that drug therapy with acetylcholine precursors, choline esterase inhibitors and muscarinic agonists cannot eliminate symptoms in dementia patients. Furthermore, they point out the need for techniques to diagnose the disease prior to disintegration of the neuronal network, and the need for therapies to delay or prevent the progression of structural changes.