Neurons of the A5 region are required for the tachycardia evoked by electrical stimulation of the hypothalamic defence area in anaesthetized rats.

In order to assess the possible interactions between the pontine A5 region and the hypothalamic defence area (HDA), we have examined the pattern of double staining for c-Fos protein immunoreactivity (c-Fos-ir) and tyrosine hydroxylase, throughout the rostrocaudal extent of the A5 region in spontaneously breathing anaesthetized male Sprague-Dawley rats during electrical stimulation of the HDA. Activation of the HDA elicited a selective increase in c-Fos-ir with an ipsilateral predominance in catecholaminergic and non-catecholaminergic A5 somata (P < 0.001 in both cases). A second group of experiments was done to examine the importance of the A5 region in modulating the cardiorespiratory response evoked from the HDA. Cardiorespiratory changes were analysed in response to electrical stimulation of the HDA before and after ipsilateral microinjection of muscimol within the A5 region. Stimulation of the HDA evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (P < 0.001) due to a decrease in expiratory time (P < 0.01). The respiratory response was accompanied by a pressor response (P < 0.001) and tachycardia (P < 0.001). After muscimol microinjection within the A5 region, pressor and heart rate responses to HDA stimulation were reduced (P < 0.01 and P < 0.001, respectively). The respiratory response persisted unchanged. Finally, to confirm functional interactions between the HDA and the A5 region, extracellular recordings of putative A5 neurones were obtained during HDA stimulation. Seventy-five A5 cells were recorded, 35 of which were affected by the HDA (47%). These results indicate that neurones of the A5 region participate in the cardiovascular response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

Assessment of long-term cognitive dysfunction in older patients who undergo heart surgery.

INTRODUCTION: Older patients are more likely to have cognitive dysfunction, and a great proportion of patients undergone surgical procedures are older adults. Postoperative cognitive dysfunction (POCD) has been shown as a consistent complication after major surgical procedures such as heart surgery. AIM: To determine the presence of long-term POCD in ≥65-year-old patients undergoing coronary artery bypass grafting and aortic valve replacement, and to establish related risk factors. METHODS: We prospectively and sequentially included 44 patients with coronary disease and aortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized and a neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months after surgery. RESULTS: Patients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4% and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspects such as age (p<0.01), history of smoking (p<0.01), arterial hypertension (p=0.022), diabetes mellitus (p=0.024), heart failure (p=0.036) and preoperative cognitive dysfunction (p<0.01), and surgery-associated aspects such as EuroSCORE (p<0.01) and operation time (p<0.01) were identified as related risk factors. CONCLUSIONS: Older patients who underwent heart surgery had long-term POCD. Both patient- and surgery-related risk factors were established as related risk factors. These findings suggest that the prevalence of cognitive dysfunction after cardiac surgery in older patients could be related to a possible progression to dementia. In addition, many of the risk factors identified may be modifiable but in practice, these patients are not attended to for their possible cognitive impairment.

[Knowledge on stroke in Spanish population. A systematic review]. / Conocimiento sobre el ictus en la población española. Una revisión sistemática.

OBJECTIVES: To analyze by means of a systematic review the general knowledge about strokes of the Spanish population. MATERIALS AND METHODS: A systematic review is performed following PRISMA guidelines and with data from PubMed, Scopus and EMBASE. All studies carried out in Spain, centred around the knowledge of strokes are compiled (terminology, pathophysiology, signs and symptoms, risk factors, treatment, and willingness to make use of the Emergency Services). From the 4,627 articles collected, 21 were ultimately included in this review. RESULTS: In Spain, the term stroke is less known than others such as embolism or cerebrovascular accident. Loss of strength is the most widely recognized symptom, whereas arterial hypertension is the most widely identified risk factor. The least known symptom and risk factor are visual impairment and diabetes mellitus, respectively. When faced with a suspected stroke, the attitude of most respondents is adequate as they decide to go to the hospital or call the Emergency Services. However, in rural areas or in cases in which the symptoms suddenly stop, a greater number of participants choose to go to their family physician. The main sources of information of the participants are their family members and their doctors. CONCLUSIONS: General knowledge about strokes is scarce among the general population. Nonetheless, the attitude of most of the participants is adequate as they choose to contact specialized Emergency Services.

TITLE: Conocimiento sobre el ictus en la población española. Una revisión sistemática.Objetivos. Analizar mediante una revisión sistemática el estado de conocimiento sobre el ictus en la población española. Materiales y métodos. Se ha llevado a cabo una revisión sistemática siguiendo las directrices PRISMA en las bases de datos PubMed, Scopus y EMBASE. Se incorporaron todos los estudios realizados en España que versaran sobre el conocimiento del ictus (terminología, fisiopatología, síntomas y signos, factores de riesgo, tratamiento e intención de acudir a servicios de emergencias). Se identificaron 4.627 artículos, de los cuales 21 se incluyeron finalmente en la revisión. Resultados. El término ictus es menos reconocido que otros, como embolia o infarto cerebral. La pérdida de fuerza es el síntoma más reconocido y la hipertensión arterial es el factor de riesgo más identificado. El síntoma y el factor de riesgo menos reconocidos son los déficits visuales y la diabetes mellitus, respectivamente. Ante la sospecha de ictus, la actitud de la mayoría de los encuestados es adecuada, ya que eligen acudir al hospital o llamar a los servicios de emergencias. Sin embargo, en el medio rural, y ante síntomas que ceden espontáneamente, un mayor número de participantes elige acudir a su médico de familia. Las principales fuentes de información de los participantes son sus familiares y médicos. Conclusiones. El conocimiento global sobre el ictus es escaso entre la población española. Sin embargo, la actitud de la mayoría de los participantes es adecuada, ya que elige mayoritariamente contactar con servicios de emergencias especializados.

Atypical conduction aphasia and the right hemisphere: Cross-hemispheric plasticity of phonology in a developmentally dyslexic and dysgraphic patient with early left frontal damage.

We report the rare case of a patient, JNR, with history of mixed handedness, developmental dyslexia, dysgraphia, and attentional deficits associated with a Klippel-Trenaunay syndrome and a small subcortical frontal lesion involving the left arcuate fasciculus. In adulthood, he suffered a large right perisylvian stroke and developed atypical conduction aphasia with deficits in input and output phonological processing and poor auditory-verbal short-term memory. Lexical-semantic processing for single words was intact, but he was unable to access meaning in sentence comprehension and repetition. Reading and writing deficits worsened after the stroke and he presented a combination of developmental and acquired dysgraphia and dyslexia with mixed lexical and phonological processing deficits. This case suggest that a small lesion sustained prenatally or early in life could induce a selective rightward shift of phonology sparing the standard left hemisphere lateralisation of lexical-semantic functions.

Assessment of long-term cognitive dysfunction in older patients who undergo heart surgery.

INTRODUCTION: Older patients are more likely to have cognitive dysfunction, and a great proportion of patients undergone surgical procedures are older adults. Postoperative cognitive dysfunction (POCD) has been shown as a consistent complication after major surgical procedures such as heart surgery. AIM: To determine the presence of long-term POCD in ≥65-year-old patients undergoing coronary artery bypass grafting and aortic valve replacement, and to establish related risk factors. METHODS: We prospectively and sequentially included 44 patients with coronary disease and aortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized and a neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months after surgery. RESULTS: Patients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4% and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspects such as age (p<0.01), history of smoking (p<0.01), arterial hypertension (p=0.022), diabetes mellitus (p=0.024), heart failure (p=0.036) and preoperative cognitive dysfunction (p<0.01), and surgery-associated aspects such as EuroSCORE (p<0.01) and operation time (p<0.01) were identified as related risk factors. CONCLUSIONS: Older patients who underwent heart surgery had long-term POCD. Both patient- and surgery-related risk factors were established as related risk factors. These findings suggest that the prevalence of cognitive dysfunction after cardiac surgery in older patients could be related to a possible progression to dementia. In addition, many of the risk factors identified may be modifiable but in practice, these patients are not attended to for their possible cognitive impairment.

Assessment of long-term cognitive dysfunction in older patients who undergo heart surgery / Deterioro cognitivo a largo plazo tras cirugía cardiaca en pacientes de edad avanzada

Introduction: Older patients are more likely to have cognitive dysfunction, and a great pro-portion of patients undergone surgical procedures are older adults. Postoperative cognitivedysfunction (POCD) has been shown as a consistent complication after major surgical proceduressuch as heart surgery.Aim: To determine the presence of long-term POCD in ≥65-year-old patients undergoing coro-nary artery bypass grafting and aortic valve replacement, and to establish related risk factors.Methods: We prospectively and sequentially included 44 patients with coronary disease andaortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized anda neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months aftersurgery.Results: Patients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4%and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspectssuch as age (p < 0.01), history of smoking (p < 0.01), arterial hypertension (p = 0.022), diabetesmellitus (p = 0.024), heart failure (p = 0.036) and preoperative cognitive dysfunction (p < 0.01),and surgery-associated aspects such as EuroSCORE (p < 0.01) and operation time (p < 0.01) wereidentified as related risk factors. Conclusions: Older patients who underwent heart surgery had long-term POCD. Both patient-and surgery-related risk factors were established as related risk factors. These findings suggestthat the prevalence of cognitive dysfunction after cardiac surgery in older patients could berelated to a possible progression to dementia. In addition, many of the risk factors identifiedmay be modifiable but in practice, these patients are not attended to for their possible cognitiveimpairment.(AU)

Introducción: Los pacientes de edad avanzada tienen más riesgo de sufrir deterioro cognitivo, yson cada vez más frecuentemente sometidos a una cirugía. El deterioro cognitivo posquirúrgico(DCP) tras cirugía cardiaca se ha mostrado como una complicación importante.Objetivos: Determinar la presencia del DCP a largo plazo en pacientes ≥ 65 a˜nos intervenidosde derivación coronaria y reemplazo de válvula aórtica, y establecer los factores de riesgorelacionados.Métodos: Se realizó un estudio en el que se incluyeron de forma prospectiva y secuen-cial 44 pacientes con enfermedad coronaria y estenosis aórtica programados para cirugía. Elseguimiento fue estandarizado y se realizaron evaluaciones neuropsicológicas preoperatoria-mente a los 1, 6 y 12 meses postoperatorios.Resultados: Se observó la presencia de un DCP significativo (33,5, 63,4 y 38,9% a 1, 6 y 12 meses,respectivamente) respecto al nivel basal (20,5%). Se identificaron como factores de riesgo varia-bles asociadas al paciente como la edad (p < 0,01), el tabaquismo (p < 0,01), la hipertensiónarterial (p = 0,022), la diabetes mellitus (p = 0,024), la insuficiencia cardiaca (p = 0,036) y el dete-rioro cognitivo preoperatorio (p < 0,01), y variables quirúrgicas como el EuroSCORE (p < 0,01) yel tiempo de intervención (p < 0,01).Conclusiones: Los pacientes de edad avanzada sometidos a cirugía cardiaca presentaron DCP alargo plazo. Variables asociadas al paciente y quirúrgicas se mostraron como factores de riesgo,muchas de ellas modificables. Estos hallazgos sugieren que la presencia de DCP en pacientes demás edad podría suponer mayor riesgo de evolución a demencia. En la práctica clínica habitualno es evaluado el rendimiento cognitivo.(AU)

Glutamate receptors of the A5 region modulate cardiovascular responses evoked from the dorsomedial hypothalamic nucleus and perifornical area.

To assess the possible function of glutamate in the interaction between the dorsomedial hypothalamic nucleus-perifornical area (DMH-PeF) and the A5 pontine region (A5), cardiovascular and respiratory changes were studied in response to electrical stimulation of the DMH-PeF (1 ms pulses, 30-50 µA given at 100 Hz for 5 s) before and after the microinjection of kynurenic acid (non-specific glutamate receptor antagonist; 50 nl, 5 nmol), MK-801 (NMDA receptor antagonist; 50 nl, 50 nmol), CNQX (non-NMDA receptor antagonist; 50 nl, 50 nmol) or MCPG (metabotropic glutamate receptor antagonist; 50 nl, 5 nmol) within the A5 region. DMH-PeF electrical stimulation elicited a pressor (p < 0.001) and tachycardic response (p < 0.001) which was accompanied by an inspiratory facilitation characterised by an increase in respiratory rate (p < 0.001) due to a decrease in expiratory time (p < 0.01). Kynurenic acid within the A5 region decreased the tachycardia (p < 0.001) and the intensity of the blood pressure response (p < 0.001) to DMH-PeF stimulation. After the microinjection of MK-801 and CNQX into the A5 region, the magnitude of the tachycardia and the pressor response were decreased (p < 0.05 and p < 0.01; p < 0.001 and p < 0.05, respectively). After MCPG microinjection into the A5 region, a decrease in the tachycardia (p < 0.001) with no changes in the pressor response was observed during DMH-PeF stimulation. The respiratory response elicited by DMH-PeF stimulation was not changed after the microinjection of kynurenic acid, MK-801, CNQX or MCPG within the A5 region. These results suggest that A5 region glutamate receptors play a role in the cardiovascular response elicited from the DMH-PeF. The possible mechanisms involved in these interactions are discussed.

Conocimiento sobre el ictus en la población española. Una revisión sistemática / Knowledge on stroke in Spanish population. A systematic review

Objetivos: Analizar mediante una revisión sistemática el estado de conocimiento sobre el ictus en la población española. Materiales y métodosSe ha llevado a cabo una revisión sistemática siguiendo las directrices PRISMA en las bases de datos PubMed, Scopus y EMBASE. Se incorporaron todos los estudios realizados en España que versaran sobre el conocimiento del ictus (terminología, fisiopatología, síntomas y signos, factores de riesgo, tratamiento e intención de acudir a servicios de emergencias). Se identificaron 4.627 artículos, de los cuales 21 se incluyeron finalmente en la revisión. Resultados: El término ictus es menos reconocido que otros, como embolia o infarto cerebral. La pérdida de fuerza es el síntoma más reconocido y la hipertensión arterial es el factor de riesgo más identificado. El síntoma y el factor de riesgo menos reconocidos son los déficits visuales y la diabetes mellitus, respectivamente. Ante la sospecha de ictus, la actitud de la mayoría de los encuestados es adecuada, ya que eligen acudir al hospital o llamar a los servicios de emergencias. Sin embargo, en el medio rural, y ante síntomas que ceden espontáneamente, un mayor número de participantes elige acudir a su médico de familia. Las principales fuentes de información de los participantes son sus familiares y médicos. Conclusiones: El conocimiento global sobre el ictus es escaso entre la población española. Sin embargo, la actitud de la mayoría de los participantes es adecuada, ya que elige mayoritariamente contactar con servicios de emergencias especializados.(AU)

Objectives: To analyze by means of a systematic review the general knowledge about strokes of the Spanish population. Materials and methods: A systematic review is performed following PRISMA guidelines and with data from PubMed, Scopus and EMBASE. All studies carried out in Spain, centred around the knowledge of strokes are compiled (terminology, pathophysiology, signs and symptoms, risk factors, treatment, and willingness to make use of the Emergency Services). From the 4,627 articles collected, 21 were ultimately included in this review. Results: In Spain, the term stroke is less known than others such as embolism or cerebrovascular accident. Loss of strength is the most widely recognized symptom, whereas arterial hypertension is the most widely identified risk factor. The least known symptom and risk factor are visual impairment and diabetes mellitus, respectively. When faced with a suspected stroke, the attitude of most respondents is adequate as they decide to go to the hospital or call the Emergency Services. However, in rural areas or in cases in which the symptoms suddenly stop, a greater number of participants choose to go to their family physician. The main sources of information of the participants are their family members and their doctors. Conclusions: General knowledge about strokes is scarce among the general population. Nonetheless, the attitude of most of the participants is adequate as they choose to contact specialized Emergency Services.(AU)

Molecular cloning, expression pattern and chromosomal mapping of pig CD9 antigen.

CD9 is a member of the transmembrane-4 superfamily of surface molecules that seems to have a relevant role in cell migration and adhesion, as well as malignant progression. This work describes the isolation of the cDNA coding for the porcine CD9 molecule. Pig CD9 cDNA was isolated from a smooth muscle cDNA library and contains a 678-bp open reading frame with its predicted polypeptide sequence of 226 amino acids. The deduced amino acid sequence conserves the main characteristics of TM4 proteins, including the presence of four transmembrane domains. Like their homologous molecules from other species, pig CD9 has two extracellular regions of a different size with the minor loop bearing two possible glycosylation sites. The pig CD9 gene was localized to chromosome 5q25 by using a somatic cell hybrid panel. Analysis of CD9 expression in different porcine cells and tissues demonstrated that CD9 mRNA is ubiquitously expressed.

Molecular cloning and characterization of the pig homologue to human CD29, the integrin beta1 subunit.

BACKGROUND: CD29 is the beta1 subunit, a member of the integrin gene superfamily that function as receptor for cell adhesion molecules of the extracellular matrix. Porcine integrin beta1 subunit is involved in rejection of pig-to-human tissue xenografts as target of the natural antibodies present in the human serum. Moreover since CD29, as part of the beta1 integrins very late antigen 4 (VLA-4) and VLA-6, is involved in homing and differentiation of haematopoietic progenitor cells, its characterization in pig is critical to study the interaction of porcine adhesion molecules with human ligands in the induction of donor-specific tolerance toward porcine antigens, a process extremely desirable to prevent rejection of xenogeneic organs. METHODS: The porcine CD29 cDNA has been isolated from a cDNA library and its structure determined. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine the expression of CD29 in different tissues. RESULTS: The nucleotide sequence of the porcine cDNA includes an open reading frame encoding a polypeptide of 798 amino acids. Expression analysis showed that porcine CD29 is expressed in all lymphoid tissues tested and, in lower amounts, in nonlymphoid tissues. Pig CD29 deduced amino acid sequence displays extensive conservation compared with CD29 sequences from other species and a common structural feature with all the other CD29 molecules analyzed in mammals, including the 12 potential N-glycosilation sites. Punctual changes between human and swine CD29 molecule into the ligand binding domain, and/or into the regulatory domain, suggest potential differences between human and porcine CD29 relative to the human CD29 ligands. CONCLUSIONS: Cloning of the swine CD29 gene offers a new tool for an alternative protocol of removing xenoreactive antibodies in the recipient. In addition, the determination of the differences between human and swine CD29 will help to understand the adhesion molecule-ligand interactions and their function across the swine-human barrier in xenotransplantation.

Aldehyde dehydrogenase (ALDH) activity in Drosophila melanogaster adults: evidence for cytosolic localization.

The subcellular localization of the aldehyde dehydrogenase activity from the ALDH (EC 1.2.1.3) enzyme has been studied in nutritionally manipulated Drosophila melanogaster adults from a wild (LRC) and an ADH-null (bAdhn4) strain. ALDH activities from ALDH or ADH (EC 1.1.1.1) enzymes were selectively inhibited by prefeeding respectively the flies sucrose solutions supplemented with either cyanamide or acetone respectively. ALDH, ADH (as a cytosolic marker) and succinate dehydrogenase (EC 1.3.9.1) (as a mitochondrial marker) activities were assayed in both the mitochondrial and cytosolic fractions isolated from flies subjected to each treatment. Total ALDH activity in the cytosolic fraction was found to be between five (ADH strain) and ten (ADH strain) times higher than that in the mitochondrial fraction. Prefeeding cyanamide resulted in a 64% (ADH strain) and a 90% (ADH strain) reduction of the cytosolic ALDH activity, whereas prefeeding acetone resulted in a 38% (ADH strain) reduction of this activity. Prefeeding both cyanamide and acetone resulted in a total inhibition of ALDH activity, which was also observed after an extended cyanamide treatment. In conclusion, our results support that, contrary to what occurs in larvae, in adults the ALDH activity from ALDH enzyme is mainly localized in the cytosolic fraction: about 85% in ADH+ and 90% in ADH- strains. Although larvae and adults use different ALDH activities to detoxify acetaldehyde (from ADH and ALDH enzymes, respectively) both of them are cytosolic. Reasons for these different uses are discussed in relation to the subcellular localization of ALDH activity.

Study of the causes of direct-acting mutagenicity in coffee and tea using the Ara test in Salmonella typhimurium.

The mutagenic activities of 6 of the chemicals identified in coffee solutions were assayed with the Salmonella Ara test, under experimental conditions optimized for coffee mutagenicity. Caffeine was the only non-mutagenic compound. Among the other 5 chemicals, hydrogen peroxide was the strongest mutagen and chlorogenic acid the weakest; methylglyoxal, glyoxal and caffeic acid exhibited intermediate mutagenicities. The minimal mutagenic doses of these components correlated negatively with their relative concentrations in coffee. It was concluded that chlorogenic acid, caffeic acid, glyoxal and methylglyoxal cannot contribute alone to the mutagenicity of coffee in the Ara test, since their minimal mutagenic concentrations were much higher than their respective levels in the coffee samples assayed. By contrast, 40-60% of the mutagenic activity in coffee and also in tea could be attributed to their H2O2 contents. Catalase abolished more than 95% of the mutagenic activity of coffee, as detected by the Ara test. A similar sensitivity to catalase has been reported by other authors in relation to the coffee mutagenicity identified by the Salmonella His test. Nevertheless, the results presented in this paper suggest that the Ara forward and the His reverse mutation tests are sensitive to the mutagenicity of different constituents in coffee solutions. We propose that the His test, sensitive at high coffee doses, mainly recognizes the mutagenicity of methylglyoxal, whilst the Ara test, sensitive at low coffee doses, mainly detects the mutagenic activity of hydrogen peroxide. The data reported also suggest that the direct-acting mutagenicity(ies) detected by the Ara test in tea solutions is (are) based on similar, if not identical, mechanisms.

Swine platelet antigens: section report.

A total of 14 antibodies were found to label resting and/or activated swine platelets. Six recognized CD previously characterized for swine (CD29, CD41/61 and CD46). One had been characterized for human cells (CD47). Two antibodies with CD14 and SLA class I specificity suggested by the donor as well as five blind antibodies were also positive on platelets. One antibody appeared to recognize the swine homologue to human CD47, and four remained unclustered.

[Leptin: physiological and clinical role]. / Leptina: implicaciones fisiológicas y clínicas.

Leptin is a protein that has been identified three years ago, but its role, or at least its deficiency, was suspected from 1950. Dickie and coworkers reported the appearance of a mutant rat in one of their colonies with morbid obesity. The genetic defect was autosomal recessive and was manifested early in life. In December 1994, the gen ob was cloned, which stated the first step for the later identification of the gen product leptin, as a protein of 167 aminoacids expressed in adipose tissue. Since then, leptin has been implicated in many neuroendocrine regulatory pathways. The recent research in leptin roles worth an update review, and so its current and future clinical relevance.

[Prevalence and comorbidity of neuropsychiatric symptoms in Alzheimer's disease]. / Prevalencia y comorbilidad de síntomas neuropsiquiátricos en la enfermedadde Alzheimer.

INTRODUCTION: The objective of this study is to describe the frequency and severity of behavioral and psychological symptoms (BPS) in a group of 125 patients diagnosed of Alzheimer's disease (AD) (DSM-IV-TR and NINCDSADRDA criteria). METHODS: The evaluation of the BPS was carried out using the Neuropsychiatric Inventory (NPI; Cummings et al., 1994). The sociodemographic and personal background data of the patients were gathered and the dementia stage was established with the Global Deterioration Scale (GDS Reisberg, 1982). RESULTS: A total of 122 patients (98%) presented BPS, with an average of five symptoms per patient. Frequency of presentation was the following: apathy (75%), irritability (66%), depression (60%), agitation (55%), anxiety (54%), aberrant motor activity (47%), delirium (38%), sleeping disorders (36%), disinhibition (29%), eating disorders (28%), hallucinations (20%) and euphoria (4%). CONCLUSIONS: These results show the high incidence of BPS in AD patients and point to the necessity and importance of treating these disorders appropriately.

Tolerance to 1-pentene-3-ol and to 1-pentene-3-one in relation to alcohol dehydrogenase (ADH) and aldo keto reductase (AKR) activities in Drosophila melanogaster.

The detoxification of 1-pentene-3-ol (pentenol) and 1-pentene-3-one (pentenone) by Drosophila melanogaster adult flies has been studied in two homozygous lines for the AdhF and AdhS alleles (LRC lines), in their respective lines selected for tolerance to ethanol (LRSe lines) and in a homozygous strain for the Adhn4 null allele. For each line, the genotype and sex LDs50 of both compounds were estimated. Then, in order to explain the differences in LD50, both alcohol dehydrogenase (ADH) and aldo keto reductase (AKR) activities were assayed. In addition, the effects of pentenone on AKR activity were also studied. Our results show that ADH-positive flies exhibit a much higher sensitivity to pentenol than ADH-null flies. However, both ADH-positive and ADH-null flies show a similar tolerance to pentenone. Our results show that flies selected for improving tolerance to ethanol also have increased tolerance to pentenol (FF and SS flies) and pentenone (SS flies). However, this improved ability to tolerate pentenol and/or pentenone cannot be explained by changes in ADH or AKR activities. On the other hand, we have observed a beneficial effect of pentenol, but not of pentenone, in n4 flies. We also show that AKR activity is not modified by the administration of pentenone. These results suggest that, in the absence of ADH activity, pentenol may be transformed into a compound that is less toxic than pentenone and that pentenone itself might also be transformed into a less toxic compound.

Coffee is highly mutagenic in the L-arabinose resistance test in Salmonella typhimurium.

The present study shows that the L-arabinose resistance test in Salmonella typhimurium detects coffee as a strong mutagen in the absence of mammalian microsomal activation. The response of the Ara forward mutation assay was 8.5 times higher than that of TA104, which is the most sensitive to coffee of the tester strains of the Ames test. Both the mutagenesis protocol (preincubation test) and the additional genetic characteristics of the bacterial tester strain (excision repair deficiency, normal lipopolysaccharide barrier, and the presence of plasmid pKM101) were critical factors in the optimal induction by coffee of forward mutations to L-arabinose resistance. All ten samples of roasted coffee analyzed with the Ara assay were highly mutagenic: one cup of coffee (150 ml) was calculated to induce 3-4 X 10(6) AraR mutants. In contrast, coffee prepared from unroasted beans (green coffee) had no mutagenic activity. Regular- and sugar-roasted coffees showed similar mutagenicities, but the specific mutagenic activity of instant coffees (1559 AraR mutants/mg) was almost 2 times that of noninstant ones (834 AraR mutants/mg). The Ara assay allowed the direct testing of coffee, although it was demonstrated that lyophilization has no effect on the mutagenicity of this beverage. Like roasted coffee, roasted barley induced a large number of AraR mutants per mg (227), though its specific mutagenic activity was approximately 4 and 7 times lower than that of noninstant and instant coffees, respectively.

Participation of Drosophila melanogaster alcohol dehydrogenase (ADH) in the detoxification of 1-pentene-3-ol and 1-pentene-3-one.

The participation of the ADH enzymes in the detoxification by D. melanogaster of 1-pentene-3-ol (also called pentenol) and its oxidized product, 1-pentene-3-one (usually known as ethyl-vinyl-ketone or pentenone) have been studied using the LR lines. For this purpose flies of AdhS AdhS (SS) and AdhF AdhF (FF) genotypes were independently pretreated with a 2 per cent isopropanol (2-propanol) solution and the survivors exposed to water, to a 0.0075 per cent pentenol solution or to a 0.00375 per cent pentenone solution. After one day in these solutions, the ability to tolerate both compounds was checked and the ADH activity of the surviving flies was measured and compared with those of control flies not pretreated with isopropanol. Additionally, the effects of pentenone on ADH enzymes have been studied by comparing them with those of acetone. Our results show that, in contrast to acetone, pentenone neither reduced significantly the ADH activity in vivo nor altered the normal proportion of ADH isozymes of either SS or FF flies. Our findings also demonstrate that the isopropanol pretreatment implied a considerable decrease in sensitivity not only to pentenol (60 and 91 per cent for SS and FF flies, respectively) but also to pentenone (72 and 80 per cent for SS and FF flies, respectively). After isopropanol pretreatment, FF flies continued exhibiting higher ADH activities than SS ones. However, FF pretreated flies displayed higher tolerance to pentenol and a similar tolerance to pentenone than SS animals. Our results suggest that pentenol (unsaturated secondary alcohol) and isopropanol (saturated secondary alcohol) may be detoxified by slightly different processes (both ADH-activity-dependent), and that pentenone could not be accumulated in the fly but transformed into another compound(s) by means of some ADH-independent mechanism(s).

Electrophoretic types of leucine aminopeptidase in sheep serum.

Leucine aminopeptidase in sheep serum was studied by starch gel electrophoresis. Two phenotypes, A and B, were observed, of which the former was present in 70-90% of all the sheep examined. These two phenotypes have been shown to be controlled by a single autosomal locus, with two alleles LapA and LapB. The LapA allele is dominant. The frequencies of Lap phenotypes and alleles were determined in eleven Spanish and two foreign breeds. Serum alkaline phosphatase and serum leucine aminopeptidase are electrophoretically distinct.