Lunatomalacia infantil o enfermedad de Kienböck con conformación tipo VISI en un niño: Descripción de un caso y revisión de la literatura / Childhood Lunatomalacia Or Kienböck Disease With VISI Conformation In A Child: A Case Report And Literature Review

La osteonecrosis del semilunar o enfermedad de Kienböck es una entidad de baja prevalencia, más frecuente en varones jóvenes entre 20 y 40 años. Todavía más exclusiva en pacientes en edad infantil. De etiología variable, se baraja la teoría traumática vascular y la teoría no traumática causada por otros diversos mecanismos. La afectación del semilunar puede presentarse con edema óseo, fragmentación, desalineación escafo-lunar y progresar hacia el colapso. Presentamos el caso de un adolescente con enfermedad de Kienböck, sin antecedente traumático atribuible que desarrolló una lesión de compleja clasificación en la escala de Litchman. Se consiguió mejoría parcial de la clínica con tratamiento conservador, pero sin eliminar el dolor de forma definitiva. El planteamiento quirúrgico se debate actualmente teniendo en cuenta su madurez esquelética y evolución fisiopatológica de la lesión (AU)

Semilunar osteonecrosis or Kienböck's disease has a low prevalence, usually occurring in young men aged between 20 and 40 years. This disease is even less common in childhood. The aetiology varies, with postulation of the vascular trauma theory and the non-traumatic theory, in which the disease is caused by various other mechanisms. Semilunar involvement can occur with bone oedema, fragmentation, and scapholunate misalignment and progresses towards collapse. We present the case of an adolescent boy with Kienböck's disease, with no attributable traumatic antecedent, who developed a complex classification injury on the Litchman scale. Partial improvement of symptoms was achieved with conservative treatment but without definitive pain elimination. Future surgery for this patient is currently being discussed, bearing in mind his skeletal maturity and the pathophysiological progression of the injury (AU)

Pharmacokinetic and pharmacodynamic properties of aerosolized ("vaped") THC in adolescent male and female rats.

RATIONALE: Adolescent exposure to ∆9-tetrahydrocannabinol (THC), the psychotropic constituent of cannabis, might affect brain development, and in rodent models leads to long-term behavioral and physiological alterations. Yet, the basic pharmacology of this drug in adolescent rodents, especially when ingested via ecologically relevant routes like aerosol inhalation, commonly referred to as "vaping," is still poorly characterized. Moreover, sex differences exist in THC metabolism, kinetics, and behavioral effects, but these have not been rigorously examined after vapor dosing in adolescents. OBJECTIVES: We investigated the pharmacokinetics and pharmacodynamics of aerosolized THC (30 min inhalation exposure, 25 or 100 mg/ml) in adolescent Wistar rats of both sexes. METHODS: Liquid chromatography/mass spectrometry analysis of THC and its major metabolites was conducted on blood plasma and brain tissue at 5, 30, 60, and 120 min following a 30-min aerosol dosing session. Effects on activity in a novel environment for 120 min after aerosol, and temperature, were measured in separate rats. RESULTS: We found sex-dependent differences in the pharmacokinetics of THC and its active (11-OH-THC) and inactive (11-COOH-THC) metabolites in the blood and brain, along with dose- and sex-dependent effects on anxiety-like and exploratory behaviors; namely, greater 11-OH-THC levels accompanied by greater behavioral effects in females at the low dose but similar hypothermic effects in both sexes at the high dose. CONCLUSIONS: These results provide a benchmark for dosing adolescent rats with aerosolized (or "vaped") THC, which could facilitate adoption by other labs of this potentially human-relevant THC exposure model to understand cannabis effects on the developing brain.

[Childhood Lunatomalacia Or Kienböck Disease With VISI Conformation In A Child: A Case Report And Literature Review]. / Lunatomalacia infantil o enfermedad de Kienböck con conformación tipo VISI en un niño: Descripción de un caso y revisión de la literatura.

Semilunar osteonecrosis or Kienböck's disease has a low prevalence, usually occurring in young men aged between 20 and 40 years. This disease is even less common in childhood. The aetiology varies, with postulation of the vascular trauma theory and the non-traumatic theory, in which the disease is caused by various other mechanisms. Semilunar involvement can occur with bone oedema, fragmentation, and scapholunate misalignment and progresses towards collapse. We present the case of an adolescent boy with Kienböck's disease, with no attributable traumatic antecedent, who developed a complex classification injury on the Litchman scale. Partial improvement of symptoms was achieved with conservative treatment but without definitive pain elimination. Future surgery for this patient is currently being discussed, bearing in mind his skeletal maturity and the pathophysiological progression of the injury.

Adolescent cannabinoid exposure effects on natural reward seeking and learning in rats.

RATIONALE: Adolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like "Spice" cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc). OBJECTIVES AND METHODS: Here, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD) 30-43), on natural reward-seeking behaviors and ECB system function in adult male Long Evans rats (PD 60+). RESULTS: WIN ACRS increased palatable food intake, and altered attribution of incentive salience to food cues in a sign-/goal-tracking paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in increased anandamide and oleoylethanolamide levels in NAc after acute food restriction not seen in controls. ACRS did not affect food neophobia or locomotor response to a novel environment, but did increase preference for exploring a novel environment. CONCLUSIONS: These results demonstrate that ACRS causes long-term increases in natural reward-seeking behaviors and ECB system function that persist into adulthood, potentially increasing liability to excessive natural reward seeking later in life.

Short telomere length is associated with impaired cognitive performance in European ancestry cohorts.

The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (ß=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (ß=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (ß=-0.053; 95% CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (ß=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10-5), whereas carriers performed better in STROOP (ß=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal associations were found for STROOP only (ß=-0.598 per s.d.-increase of TL; 95% CI: -1.125, -0.072; P=0.026), with a larger effect in ɛ4-carriers (ß=-0.699; 95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.

Tortícolis muscular congénita en fase de adulto / Congenital muscular torticollis in adults

La tortícolis muscular congénita (TMC) es una enfermedad frecuente, que debido a su fácil reconocimiento y exitoso tratamiento en los primeros meses de vida no suelen mostrar alteraciones clínicas en edades infantiles tardías o adultos. El escaso número de casos que prevalecen por encima de los primeros años de vida hace que exista una menor información sobre las decisiones terapéuticas a seguir. Básicamente se relegan, tras fracasar la fisioterapia, al uso de toxina botulínica o de una cirugía específica. Presentamos el caso clínico de una paciente diagnosticada finalmente, ya en edad adulta de TMC, y que fue tratada mediante sección unipolar de la porción clavicular del esternocleidomastoideo seguida de una rehabilitación específica, intensa y precoz, con muy buenos resultados estéticos y funcionales (AU)

Congenital muscular torticollis is a common condition. Because it is easy to recognize and its successful treatment during the first months of life, clinical changes are not usually found in the late childhood or adult age. As few cases prevail after the first years of life, there is less information about treatment decisions to follow. When physical therapy fails, these treatments are basically relegated to botulinum toxin or specific surgery. We report the case of a patient who was finally diagnosed in adulthood of congenital muscular torticollis. This patient was treated by unipolar sectioning of the clavicular portion of the sternocleidomastoid muscle. This was followed by specific, early and intense rehabilitation, with very good esthetic and functional results (AU)

Telomeres as biomarkers for ageing and age-related diseases.

Telomeres in telomerase-negative cells shorten during DNA replication in vitro due to numerous causes including the inability of DNA polymerases to fully copy the lagging strand, DNA end processing and random damage, often caused by oxidative stress. Short telomeres activate replicative senescence, an irreversible cell cycle arrest. Thus, telomere length is an indicator of replicative history, of the probability of cell senescence, and of the cumulative history of oxidative stress. Telomeres in most human cells shorten during ageing in vivo as well, suggesting that telomere length could be a biomarker of ageing and age-related morbidity. There are two distinct possibilities: First, in a tissue-specific fashion, short telomeres might indicate senescence of (stem) cells, and this might contribute to age-related functional attenuation in this tissue. Second, short telomeres in one tissue might cause systemic effects or might simply indicate a history of high stress and damage in the individual and could thus act as risk markers for age-related disease residing in a completely different tissue. In recent years, data have been published to support both approaches, and we will review these. While they together paint a fairly promising picture, it needs to be pointed out that until now most of the evidence is correlative, that much of it comes from underpowered studies, and that causal evidence for essential pathways, for instance for the impact of cell senescence on tissue ageing in vivo, is still very weak.

Tratamiento de la neumonía del adulto adquirida en la comunidad / Treatment of community-acquired pneumonia in adults

Appropriate antibiotic treatment reduces the duration of symptoms associated to pneumonia, the risk of complications and mortality. In most cases, it is not possible to identify the etiologic agent so antibiotic treatment is empirically prescribed. In Chile, one third of Streptococcus pneumoniae strain isolates has diminished susceptibility to penicillin; in-vitro erythromycin resistance is about 10-15% and cefotaxime resistance 2-10%. It is recommended to classify patients with community acquired pneumonia in four risk categories: Group 1: patients under 65 years without co-morbidities, in ambulatory attendance. Treatment: oral amoxicillin 1 g TID, 7 days. Group 2: patients over 65 years and / or co-morbidities, in ambulatory attendance. Treatment: oral amoxicillin/clavulanate 500/125 mg TID or 875/125 mg BID, or cefuroxime 500 mg BID, 7 days. Group 3: patients admitted to general wards with criteria of moderate severity. Treatment: ceftriaxone 1-2 g once a day or cefotaxime 1 g TID, IV, 7-10 days. Group 4: patients with severe CAP that must be interned into ICU. Treatment: ceftriaxone 2 g once a day or cefotaxime 1 g TID, IV, associated to erythromycin 500 QID, levofloxacin 500-1.000 mg once a day, or moxifloxacin 400 mg/once a day, IV, 10-14 days. In the presence of allergy to or treatment failure with betalactam drugs and/or positive serology for Mycoplasma, Chlamydia or Legionella sp it is recommended to add: erythromycin 500 mg QID, IV or oral, oral clarithromycin 500 mg BID, or oral azythromycin 500 mg once a day...

El tratamiento antimicrobiano apropiado reduce la duración de la sintomatología asociada a la neumonía, el riesgo de complicaciones y la mortalidad. En la mayoría de los casos, no es posible identificar el agente microbiológico que ocasiona la infección y por esto el tratamiento antibacteriano se prescribe en forma empírica. En Chile, un tercio de las cepas de Streptococcus pneumoniae muestra susceptibilidad disminuida a penicilina; mientras que la resistencia a eritromicina fluctúa entre 10-15% y a cefotaxima entre 2-10%. Se recomienda clasificar a los pacientes con neumonía adquirida en la comunidad en cuatro categorías de riesgo: Grupo 1: pacientes bajo 65 años de edad, sin comorbilidad de manejo ambulatorio. Tratamiento: amoxicilina 1 gramo cada 8 horas vía oral durante 7 días. Grupo 2: pacientes sobre 65 años de edad y/o con comorbilidad de manejo ambulatorio. Tratamiento: amoxicilina/ácido clavulánico 500/125 mg cada 8 horas ó 875/125 mg cada 12 horas, o cefuroxima 500 mg cada 12 horas vía oral durante 7 días. Grupo 3: pacientes hospitalizados en sala de cuidados generales que tienen criterios de gravedad moderada. Tratamiento: ceftriaxona 1-2 g/día o cefotaxima 1 g cada 8 horas EV durante 7-10 días. Grupo 4: pacientes con neumonía grave adquirida en la comunidad que deben ser manejados en la UCI. Tratamiento: ceftriaxona 2 g/día o cefotaxima 1 g cada 8 horas EV asociado a eritromicina 500 mg cada 6 h, levofloxacina 500-1.000 mg/día, o moxifloxacina 400 mg/día EV durante 10-14 días. En presencia de alergia o fracaso de tratamiento con agentes b-lactámicos y/o serología positiva para Mycoplasma, Chlamydia o Legionella sp se recomienda agregar: eritromicina 500 mg cada 6 h EV o VO, claritromicina 500 mg cada 12 h VO, o azitromicina 500 mg/día VO

Molecular analysis of nicotinic receptor expression in autism.

Autism is a developmental disorder of unknown aetiopathology and lacking any specific pharmacological therapeutic intervention. Neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA) and acetylcholine have been implicated. Abnormalities in nicotinic acetylcholine receptors have been identified including cortical loss of binding to the alpha4/beta2 subtype and increase in cerebellar alpha7 binding. Receptor expression (mRNA) has not so far been systematically examined. This study aims to further explore the role of nicotinic receptors in autism by analysing nicotinic receptor subunit mRNA in conjunction with protein levels and receptor binding in different brain areas. Quantitative RT-PCR for alpha4, alpha7 and beta2 subunit mRNA expression levels; alpha3, alpha4, alpha7 and beta2 subunit protein expression immunochemistry and specific radioligand receptor binding were performed in adult autism and control brain samples from cerebral cortex and cerebellum. Alpha4 and beta2 protein expression and receptor binding density as well as alpha4 mRNA levels were lower in parietal cortex in autism, while alpha7 did not change for any of these parameters. In cerebellum, alpha4 mRNA expression was increased, whereas subunit protein and receptor levels were decreased. Alpha7 receptor binding in cerebellum was increased alongside non-significant elevations in mRNA and protein expression levels. No significant changes were found for beta2 in cerebellum. The data obtained, using complementary measures of receptor expression, indicate that reduced gene expression of the alpha4beta2 nicotinic receptor in the cerebral cortex is a major feature of the neurochemical pathology of autism, whilst post-transcriptional abnormalities of both this and the alpha7 subtype are apparent in the cerebellum. The findings point to dendritic and/or synaptic nicotinic receptor abnormalities that may relate to disruptions in cerebral circuitry development.

Immunohistochemical localisation of nicotinic acetylcholine receptor subunits in human cerebellum.

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel superfamily composed of alpha and beta subunits with specific structural, functional and pharmacological properties. In this study we have used immunohistochemistry to investigate the presence of nicotinic acetylcholine receptor subunits in human cerebellum. Tissue was obtained at autopsy from eight adult individuals (aged 36-56 years). Histological sections were prepared from formalin-fixed paraffin-embedded material. alpha 3, alpha 4, alpha 6, alpha 7, beta 2, and beta 4 subunits were present in this brain area associated with both neuronal and non-neuronal cell types. Most Purkinje cells were immunoreactive for all the above subunits, but most strongly for alpha 4 and alpha 7. A proportion of granule cell somata were immunoreactive for all subunits except alpha 3. Punctate immunoreactivity in Purkinje cell and granule cell layers was evident with antibodies against alpha 3, alpha 4, alpha 6, and alpha 7 in parallel with synaptophysin immunoreactivity, suggesting the presence of these subunits on nerve terminals in the human cerebellum. All subunits were present in the dentate nucleus associated with neurones and cell processes. Strong immunoreactivity of neuropil in both the molecular and granule cell layers and within the dentate nucleus was noted with alpha 4, alpha 7 and beta 4 subunits. Astrocytes and astrocytic cell processes appeared to be immunoreactive for alpha 7 and cell processes observed in white matter, also possibly astrocytic, were immunoreactive for beta2. Immunoreactivity to all subunits was noted in association with blood vessels. We suggest that nicotinic acetylcholine receptor subunits may be involved in the modulation of cerebellar activity. Further investigations are warranted to evaluate the participation of nicotinic acetylcholine receptors in cerebellar pathology associated with both developmental and age-related disorders.

Algunas claves para la enseñanza en la educación superior de veterinaria / Some keys to teach Veterinary Sciences in the higher education

Se analizan algunos de los factores que inciden en el aprendizaje en el contexto universitario a partir de un enfoque constructivista. Comenzábamos planteándonos algunos de los factores que inciden sobre la labor docente del profesor y sobre el aprendizaje de los alumnos. El profesor no sólo debe enseñar contenidos y procedimientos, sino despertar el espíritu científico del alumno y generar en ellos actitudes entusiastas ante el conocimiento. En esta misma línea, queremos apuntar la importancia de las estrategias que debemos utilizar si queremos ser “profesores eficaces”. Nuestra experiencia docente nos ha enseñado la necesidad de hacer una presentación significativa de los contenidos, que además debe ser activa, clara, estructurada y redundante. Asimismo, resulta útil favorecer la iniciativa del alumno, y plantear preguntas adaptadas a su conocimiento previo, proporcionando además abundante retro-alimentación. Cuidar el clima afectivo, mostrando respeto por los alumnos, y fomentar el aprendizaje cooperativo son otros aspectos que contribuyen a mejorar el proceso de enseñanza/aprendizaje. (AU)

Human brain nicotinic receptors, their distribution and participation in neuropsychiatric disorders.

Mapping of nicotinic acetylcholine receptor (nAChR) subtypes and subunits in human brain is far from complete, however it is clear that multiple subunits are present (including alpha3, alpha4, alpha5, alpha6 and alpha7, beta2, alpha3 and beta4) and that these receptors are not solely distributed on neurones, but also on cerebral vasculature and astrocytes. It is important to elucidate subunit composition of receptors associated with different cell types and pathways within the human CNS in terms of potential nicotinic therapy for a range of both developmental and age-related disorders in which nAChR attenuation occurs. Reductions in nAChRs are reported in Alzheimer's and Parkinson's diseases, dementia with Lewy bodies, schizophrenia and autism, but may not be associated with reduced cortical cholinergic innervation observed in vascular dementia or occur at an early stage in Down's syndrome. Changes in nAChR expression in neuropsychiatric disorders appear to be brain region and subtype specific and have been shown in some instances to be associated with pathology and symptomatology. It is likely that deficits in alpha4-containing receptors predominate in cortical areas in Alzheimer's disease and autism, whereas reduction of alpha7 receptors may be more important in schizophrenia. Changes in astrocytic and vascular nAChR expression in neurodegenerative diseases should also be considered. Studies using both animal models and human autopsy tissue suggest that nAChRs can play a role in neuroprotection against age-related pathology. It is possible that the development of nAChR subtype specific drugs may lead to advances in therapy for both age-related and psychiatric disorders.

Nicotinic receptor subtypes in human brain related to aging and dementia.

Neuronal nicotinic receptors are attracting increasing interest, beyond their role in relation to tobacco use, in the areas of human brain aging and disorders associated with dementia. Of the different receptor subtypes in the mammalian brain, many decline with normal aging in several different areas, including particularly cerebral cortex and hippocampus. There are further select subtype changes in the two most common forms of dementia in the elderly: Alzheimer's disease and dementia with Lewy bodies. The alpha4 subunit is most extensively reduced in the cortex in Alzheimer's disease, reflected in the loss of the high affinity binding site. There are also reductions in the low affinity binding site (alpha-bungarotoxin binding) in the thalamus in both disorders, which are likely to reflect the loss of the homomeric (most commonly alpha7) receptor subtype. Correlations exist between some of these receptor abnormalities and clinical and pathological features of the diseases. Targeting such receptors is a current therapeutic objective.

Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain.

OBJECTIVE: Measures of cholinergic transmitter activity were investigated in patients with autism because of reported neuropathological abnormalities in cholinergic nuclei in the basal forebrain. METHOD: Levels of cholinergic enzyme and receptor activity were measured in the frontal and parietal cerebral cortex of deceased autistic adults, similarly aged normal adults without mental retardation, and nonautistic mentally retarded adults. The immunoreactivity levels of brain-derived neurotrophic factor and nerve growth factor were measured in the basal forebrain. RESULTS: There were no differences between the autistic and comparison groups in choline acetyltransferase or acetylcholinesterase activity in the cerebral cortex and basal forebrain or in muscarinic M(2) receptor or alpha-bungarotoxin binding within the cortex. Cortical M(1) receptor binding was up to 30% lower than normal in the autistic subjects, and the difference reached significance in the parietal cortex. In both the parietal and frontal cortices, differences in nicotinic receptors assessed by [(3)H]epibatidine binding were significant and extensive (65%-73% lower in the autistic group than in the normal subjects); there were no differences in nicotine binding in the basal forebrain. Immunochemical analysis indicated lower levels of both the alpha(4) and beta(2) nicotinic receptor subunits in the parietal cortex. The M(1) receptor abnormality was not evident in the nonautistic group with mental retardation, although the lower [(3)H]epibatidine binding was apparent. In the basal forebrain, the level of brain-derived neurotrophic factor in the autistic group was three times as high as the level of the normal group. CONCLUSIONS: These neurochemical abnormalities implicate the cholinergic system in developmental disorders such as autism and suggest the potential for intervention based on cholinergic receptor modulation.

Alpha and beta nicotinic acetylcholine receptors subunits and synaptophysin in putamen from Parkinson's disease.

It is well established that nicotinic receptors in the mammalian striatum are involved in modulation of the release of several neurotransmitters, including dopamine. In addition, nicotinic receptors with high affinity for agonists have generally been found to be reduced in the striatum in Parkinson's disease. In the present study antibodies have been used to examine which subunits contribute to the striatal nicotinic receptor loss in Parkinson's disease, and whether the reduction in [(3)H]nicotine binding correlates with synaptic loss. Autopsy tissue from the putamen of 12 Parkinson's disease cases and 12 age-matched control subjects was analysed by immunoblotting using antibodies against recombinant peptides specific for alpha3, alpha4, alpha7, beta2 and beta4 nicotinic acetylcholine receptor (nAChR) subunits and the synaptic marker synaptophysin, in conjunction with assessment of [(3)H]nicotine binding by autoradiography. The data indicate that there is no loss of alpha3, alpha4, alpha7 and beta2 immunoreactivity in the putamen in Parkinson's disease, despite a highly significant reduction in [(3)H]nicotine binding. An intense signal of beta4 immunoreactivity was found in human dorsal root ganglia, but not in temporal cortex or putamen samples. Synaptophysin immunoreactivities were also similar in Parkinson's disease and control cases. These results suggest that the loss of nicotine binding in the putamen in Parkinson's disease may involve an nAChR subunit (e.g., alpha5 and/or alpha6) other than those investigated. Alternatively, the results could reflect impaired subunit assembly at the plasma membrane.

Effects of ethanol, acetaldehyde, and acetic acid on histamine secretion in guinea pig lung mast cells.

We studied the direct effects of ethanol and its metabolites on the guinea pig lung mast cell, and the alterations caused in the histamine release induced by different stimuli. Guinea pig lungs cells dispersed by collagenase were used throughout. High concentrations of ethanol (100 mg/ml), acetaldehyde (0.3-3 mg/ml) and acetic acid (3 mg/ml) induced histamine release that was not inhibited by sodium cyanide (0.3 mM). Lower concentration of ethanol (10 mg/ml) and acetic acid (0.3 mg/ml), but not acetaldehyde, inhibited the histamine release induced by antigen and ionophore A23187. The histamine release induced by phorbol 12-miristate 13-acetate (1 microM) was also inhibited by ethanol (10 mg/ml). Changes in the levels of calcium, glucose and phosphatidic acid did not influence the effect of ethanol. We conclude that high doses of ethanol, acetaldehyde, and acetic acid cause a cytotoxic histamine release by independent mechanisms. Low concentrations of acetic acid inhibit the histamine release by pH reduction. Ethanol acts by a generalized effect that is independent of calcium and glucose suggesting a nonspecific effect that, nevertheless, is not cytotoxic since it can be reversed by washing the cells.

Alpha4 but not alpha3 and alpha7 nicotinic acetylcholine receptor subunits are lost from the temporal cortex in Alzheimer's disease.

Neuronal nicotinic acetylcholine receptors labelled with tritiated agonists are reduced in the cerebral cortex in Alzheimer's disease (AD), but to date it has not been demonstrated which nicotinic receptor subunits contribute to this deficit. In the present study, autopsy tissue from the temporal cortex of 14 AD cases and 15 age-matched control subjects was compared using immunoblotting with antibodies against recombinant peptides specific for alpha3, alpha4, and alpha7 subunits, in conjunction with [3H]epibatidine binding. Antibodies to alpha3, alpha4, and alpha7 produced one major band on western blots at 59, 51, and 57 kDa, respectively. [3H]Epibatidine binding and alpha4-like immunoreactivity (using antibodies against the extracellular domain and cytoplasmic loop of the alpha4 subunit) were reduced in AD cases compared with control subjects (p < 0.02) and with a subgroup of control subjects (n = 9) who did not smoke prior to death (p < 0.05) for the former two parameters. [3H]Epibatidine binding and cytoplasmic alpha4-like immunoreactivity were significantly elevated in a subgroup of control subjects (n = 4) known to have smoked prior to death (p < 0.05). There were no significant changes in alpha3- or alpha7-like immunoreactivity associated with AD or tobacco use. The selective involvement of alpha4 has implications for understanding the role of nicotinic receptors in AD and potential therapeutic targets.