Advances in basic research on choline and central nervous system development and related disorders / 中华预防医学杂志

Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.

FMO3-TMAO axis modulates the clinical outcome in chronic heart-failure patients with reduced ejection fraction: evidence from an Asian population / 医学前沿

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.

Dramatic polarization in genitourinary expert opinions regarding the clinical utility of positron emission tomography (PET) imaging in prostate cancer

ABSTRACT Objectives: To ascertain the opinions of North American genitourinary (GU) experts regarding inclusion of technologies such as prostate - specific membrane antigen (PSMA) and C - 11 choline positron emission tomography (PET) into routine practice. Materials and Methods: A survey was distributed to North American GU experts. Questions pertained to the role of PSMA and C - 11 PET in PCa management. Participants were categorized as "supporters" or "opponents" of incorporation of novel imaging techniques. Opinions were correlated with practice patterns. Results: Response rate was 54% and we analyzed 42 radiation oncologist respondents. 17 participants (40%) have been in practice for > 20 years and 38 (90%) practice at an academic center. 24 (57%) were supporters of PSMA and 29 (69%) were supporters of C - 11. Supporters were more likely to treat pelvic nodes (88% vs. 56%, p < 01) and trended to be more likely to treat patients with moderate or extreme hypofractionation (58% vs. 28%, p = 065). Supporters trended to be more likely to offer brachytherapy boost (55% vs. 23%, p = 09), favor initial observation and early salvage over adjuvant radiation (77% vs. 55%, p = 09), and to consider themselves expert brachytherapists (69% vs. 39%, p = 09). Conclusions: There is a polarization among GU radiation oncology experts regarding novel imaging techniques. A correlation emerged between support of novel imaging and adoption of treatment approaches that are clinically superior or less expensive. Pre - existing biases among GU experts on national treatment - decision panels and leaders of cooperative group studies may affect the design of future studies and influence the adoption of these technologies in clinical practice.

Pattern of Maxillofacial Fractures in Severe Multiple Trauma Patients: A 7-year Prospective Study

The incidence of facial trauma is high. This study has the primary objective of documenting and cataloging maxillofacial fractures in polytrauma patients. From a total of 1229 multiple trauma cases treated at the Emergency Room of the Santo Antonio Hospital - Oporto Hospital Center, Portugal, between August 2001 and December 2007, 251 patients had facial wounds and 209 had maxillofacial fractures. Aged ranged form 13 to 86 years. The applied selective method was based on the presence of facial wound with Abbreviated Injury Scale ≥1. Men had a higher incidence of maxillofacial fractures among multiple trauma patients (86.6%) and road traffic accidents were the primary cause of injuries (69.38%). Nasoorbitoethmoid complex was the most affected region (67.46%) followed by the maxilla (57.42%). The pattern and presentation of maxillofacial fractures had been studied in many parts of the world with varying results. Severe multiple trauma patients had different patterns of maxillofacial injuries. The number of maxillofacial trauma is on the rise worldwide as well as the incidence of associated sequelae. Maxillofacial fractures on multiple trauma patients were more frequent among males and in road traffic crashes. Knowing such data is elementary. The society should have a key role in the awareness of individuals and in prevention of road traffic accidents.

É alta a incidência de traumas na face. Este estudo teve por objetivo documentar e catalogar as fraturas maxilofaciais em pacientes com politraumatismos. De um total de 1229 casos de politraumatizados tratados na Sala de Emergência do Hospital de Santo António - Centro Hospitalar do Porto, Portugal, entre Agosto de 2001 e Dezembro de 2007, 251 pacientes tiveram ferimentos na face e 209 apresentaram fraturas maxilofaciais. As idades variaram de 13 a 86 anos. O método de seleção baseou-se na presença de ferimentos na face com Abreviated Injury Scale ≥1. Os homens apresentaram maior incidência de fraturas maxilofaciais (86,6%) entre os pacientes com múltiplos traumatismos na face e os acidentes de trânsito foram a causa principal dos traumatismos (69,38%). A região mais afetada foi o complexo naso-órbito-etmoidal (67,46%), seguido pela maxila (57,42%). O padrão e a apresentação das fraturas maxilofaciais tem sido estudado em muitas regiões do mundo com resultados variados. Pacientes com politraumatizados graves apresentaram padrões diferentes de traumatismos maxilofaciais. O número de traumatismos maxilofaciais tem aumentado à escala mundial, assim como a incidência das sequelas associadas. Entre os pacientes com traumatismos múltiplos, a maioria pertencia ao sexo masculino, assim como a causa mais frequente foram os acidentes automobilísticos. É elementar o conhecimento destes dados. A sociedade tem um papel primordial nos cuidados individuais e na prevenção dos acidentes de trânsito.

Some current challenges in research on air pollution and health / Desafíos actuales de la investigación sobre contaminación del aire y salud

This commentary addresses some of the diverse questions of current interest with regard to the health effects of air pollution, including exposure-response relationships, toxicity of inhaled particles and risks to health, multipollutant mixtures, traffic-related pollution, accountability research, and issues with susceptibility and vulnerability. It considers the challenges posed to researchers as they attempt to provide useful evidence for policy-makers relevant to these issues. This commentary accompanies papers giving the results from the ESCALA project, a multi-city study in Latin America that has an overall goal of providing policy-relevant results. While progress has been made in improving air quality, driven by epidemiological evidence that air pollution is adversely affecting public health, the research questions have become more subtle and challenging as levels of air pollution dropped. More research is still needed, but also novel methods and approaches to address these new questions.

Este comentario aborda algunos de los temas de interés actual en relación con los efectos de la contaminación del aire sobre la salud, tales como las relaciones exposición-respuesta, la toxicidad y riesgos para la salud de las partículas inhaladas, las mezclas de contaminantes múltiples, la contaminación relacionada con el tráfico, la investigación sobre responsabilidad, y los problemas de susceptibilidad y vulnerabilidad. Considera los retos que se presentan a los investigadores que intentan proporcionar evidencia para los responsables políticos en estas cuestiones. Este texto acompaña otros trabajos con resultados del proyecto ESCALA, un estudio en varias ciudades de América Latina que tiene como objetivo general proporcionar resultados relevantes para la política pública. Aunque ha habido avances para mejorar la calidad del aire, gracias a la evidencia epidemiológica de que la contaminación aérea está afectando negativamente a la salud pública, las preguntas de investigación se han vuelto más sutiles y difíciles a medida que los niveles de contaminación se reducen. Se necesita más investigación, pero también nuevos métodos y enfoques capaces de enfrentar estas preguntas.

Initial Experiences with Proton MR Spectroscopy in Treatment Monitoring of Mitochondrial Encephalopathy

PURPOSE: Mitochondrial encephalopathy (ME) is a rare disorder of energy metabolism. The disease course can roughly be evaluated by clinical findings. The purpose of this study was to evaluate metabolic spectral changes using proton MR spectroscopy (MRS), and to establish a way to monitor ME by neuroimaging. MATERIALS AND METHODS: Proton MRS data were retrospectively reviewed in 12 patients with muscle biopsy-confirmed ME (M : F = 7 : 5, Mean age = 4.8 years). All received 1H-MRS initially and also after a ketogenic diet and mitochondrial disease treatment cocktail (follow up average was 10.2 months). Changes of N-acetylaspartate/creatine (NAA/Cr) ratio, choline/creatine (Cho/Cr) ratio, and lactate peak in basal ganglia at 1.2 ppm were evaluated before and after treatment. Findings on conventional T2 weighted MR images were also evaluated. RESULTS: On conventional MRI, increased basal ganglia T2 signal intensity was the most common finding with ME (n = 9, 75%), followed by diffuse cerebral atrophy (n = 8, 67%), T2 hyperintense lesions at pons and midbrain (n = 4, 33%), and brain atrophy (n = 2, 17%). Lactate peak was found in 4 patients; 2 had disappearance of the peak on follow up MRS. Quantitative analysis showed relative decrease of Cho/Cr ratio on follow up MRS (p = 0.0058, paired t-test, two-tailed). There was no significant change in NAA/Cr ratio. CONCLUSION: MRS is a useful tool for monitoring disease progression or impro-vement in ME, and decrease or disappearance of lactate peak and reduction of Cho/Cr fraction were correlated well with improvement of clinical symptoms.

Proton MR spectroscopy of the foramen of Monro region in patients with tuberous sclerosis complex / Espectroscopia de prótons por RM da região do forame de Monro em pacientes com complexo esclerose tuberosa

PURPOSE: To evaluate with 1H-magnetic resonance spectroscopy (MRS) the metabolites rations of the foramen of Monro's region in patients with tuberous sclerosis complex (TSC). METHOD: Twelve patients with TSC and an age and gender-matched control group underwent MR imaging at a 1.5T scanner, and 1H-MRS at the foramen of Monro level with a multivoxel acquisition. Similar volumes of interest were selected in each side of the foramen of Monro and in the basal ganglia (lentiform nuclei). The obtained N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) peak amplitude values and ratios were studied. The statistical analysis was performed and p<0.05 was considered statically significant. RESULTS: There was no significant difference between the NAA/Cr and Cho/Cr ratios near to the foramen of Monro and basal ganglia of the TSC patients compared with the controls (p>0.05). CONCLUSION: The NAA/Cr and Cho/Cr ratios near to the foramen of Monro and basal ganglia of TSC patients are similar to the rations obtained in the control group.

OBJETIVO: Avaliar através de espectroscopia de prótons as relações dos metabólitos da região do forame de Monro em pacientes com complexo esclerose tuberosa (CET). MÉTODO: Doze pacientes com CET e um grupo controle pareado por sexo e idade realizaram RM em aparelho de 1,5T, e a espectroscopia de prótons foi obtida ao nível do forame de Monro com aquisição multi-voxel. Volumes de interesse similares foram posicionados em cada lado do forame de Monro e nos gânglios da base (núcleos lentiformes). Os valores das relações e amplitudes de pico do N-acetilaspartato (NAA), creatina (Cr) e colina (Cho) foram estudados. A análise estatística foi realizada e valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: Não houve diferença significativa entre as relações NAA/Cr e Cho/Cr na região do forame de Monro e nos gânglios da base dos pacientes com CeT comparados com os controles (p>0,05). CONCLUSÃO: As relações NAA/Cr e Cho/Cr na região do forame de Monro e nos gânglios da base de pacientes com CET são semelhantes àquelas obtidas no grupo controle.

Espectroscopia multivoxel com tempo de eco curto: a razão colina/N-acetil-aspartato e a graduação dos astrocitomas cerebrais / Multivoxel spectroscopy with short echo time: choline/N-acetyl-aspartate ratio and the grading of cerebral astrocytomas

Avaliou-se a relação colina/N-acetil-aspartato (Co/NAA), obtida pela espectroscopia multivoxel com tempo de eco (TE) curto, na graduação histológica dos astrocitomas encefálicos (graus I, II e III-IV), comparando com o parênquima cerebral normal. Observou-se aumento significativo (p<0,05) das relações médias de Co/NAA nos três grupos de astrocitomas estudados em relação ao tecido normal, havendo tendência de elevação com o aumento da graduação, sem significância estatística, que correspondeu a: 0,53±0,24 no grupo controle, 1,19±0,49 no grau I, 1,58±0,65 no grau II e 5,13±8,12 no grupo de alto grau (graus III-IV). Houve aumento da relação Co/NAA em 4/5 (80 por cento) dos pacientes com grau I, 5/6 (83 por cento) com grau II e 10/20 (50 por cento) com graus III e IV. Concluiu-se que a espectroscopia multivoxel com TE curto pode ser usada na discriminação entre o parênquima normal e o tecido neoplásico. Entretanto, nem todo tecido neoplásico estudado apresentou aumento da relação Co/NAA, principalmente o grupo com maior malignidade.

The choline/N-acetyl-aspartate (Cho/NAA) ratio, obtained by the multivoxel spectroscopy with short echo time (TE), was evaluated, in the histological grading of the brain astrocytomas (grades I, II and III-IV) in comparison with the normal cerebral parenchyma. A significant increase (p<0.05) in the average ratios of Cho/NAA was observed in the three astrocytoma groups studied in relation to normal tissue, having a tendency to increase with the increase in grading, without any statistic significance, which corresponded to: 0.53±0.24 in the control group, 1.19±0.49 in grade I, 1.58±0.65 in grade II and 5.13±8.12 in the high grade group (grades III-IV), with variation in the values encountered. There was an increase in the Cho/NAA ratio in 4/5 (80 percent) in grade I, 5/6 (83 percent) in grade II and 10/20 (50 percent) in grades III and IV. We conclude that multivoxel spectroscopy with short TE can be used in discriminating between normal parenchyma and neoplasm tissue. However, not all neoplasm tissue studied presented an increase in Cho/NAA, especially in the group with higher grade of malignancy.

Estimation of postmortem interval with multivoxel-voxel proton 1H-MR spectroscopy / 法医学杂志

OBJECTIVE@#The purpose of our study was to evaluate the postmortem interval with multi-voxel 1H-MR spectroscopy.@*METHODS@#Twelve healthy rabbits were studied and the quantities of N-acetylaspartate, total choline, phosphocreatine and creatine were measured by 1H-MR spectroscopy after death at 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 h.@*RESULTS@#The levels of Naa/Cr and Naa/Ch decreased following death, while the level of Ch/Cr increased initially and then decreased following death.@*CONCLUSION@#Multi-voxel proton MR spectroscopy for Naa/Cr and Ch/Cr metabolic ratio could be used in future postmortem interval studies.

Espectroscopia de prótons na doença de Alzheimer e no comprometimento cognitivo sem demência: estudo de uma amostra comunitária / Proton spectroscopy in Alzheimer's disease and cognitive impairment not dementia: a community study

OBJETIVO: Descrever os achados da espectroscopia de prótons (¹H-ERM) na doença de Alzheimer (DA) e no comprometimento cognitivo sem demência (CIND) em uma amostra da comunidade. MÉTODO: Foram avaliados seis pacientes com DA, sete com CIND e sete controles normais, originários da comunidade. ¹H-ERM foi realizada com voxel de 8 cm³ nas regiões temporal direita, parietal esquerda e occipital medial e estudados os metabólitos: N-acetilaspartato (NAA), creatina (Cr), colina (Cho) e mio-inositol (mI). RESULTADOS: O NAA foi maior nos indivíduos controles do que nos DA e intermediário no CIND. Análise de função discriminante mostrou que as associações Cr parietal-Cr occipital e Cr parietal-Cho occipital identificaram corretamente 92,3 por cento da amostra comparando Controle vs DA. Na comparação Controle vs CIND O mI temporal identificou corretamente 78,6 por cento dos indivíduos. CONCLUSÃO: A espectroscopia pode contribuir para o diagnóstico e seguimento de indivíduos com comprometimento cognitivo; avaliações de pacientes da comunidade podem revelar achados diferentes quanto à distribuição dos metabólitos cerebrais.

Evaluation of dietary essentiality of vitamins for Penaeus monodon (Fabricius).

The effect of exclusion of individual water-soluble (thiamine, riboflavin, pyridoxine, cyanocobalamin, pantothenic acid, folic acid, niacin, biotin, choline, inositol, ascorbic acid) and fat-soluble vitamins (vit. A, D, K and E) in semi-purified diets on growth and survival of juvenile shrimp, P. monodon was studied in the laboratory for 8 weeks. Diets lacking riboflavin and vitamin K did not affect growth and survival of shrimp. However, deletion of inositol and choline resulted in poor growth. Maximum growth was observed in the control diet (C1) which was supplemented with all vitamins. Diet deficient in ascorbic acid, biotin, folic acid, niacin, thiamine and alpha-tocopherol resulted in poor appetite and poorer feed conversion efficiency. All treatments except the control (C1) resulted in histological changes in the digestive gland cells. Detachment or destruction of the epithelial cells was observed in all treatments lacking individual vitamins but more severely in the treatment without a vitamin supplement followed by inositol, choline and ascorbic acid deficient diets.

Multifocal Inflammatory Leukoencephalopathy: Use of Thallium-201 SPECT and Proton MRS

In a patient receiving 5-fluorouracil and levamisole, neurologic deficits suggest the cerebral demyelinating syndrome as a differential diagnosis. The authors report a patient diagnosed as multifocal inflammatory leukoencephalopathy for which thallium-201 ((201)Tl) single photon emission computed tomography (SPECT) and proton magnetic resonance spectroscopy (MRS) were employed as noninvasive diagnostic tools. (201)Tl SPECT study was negative and proton MRS showed an increase of choline and lactate and well preserved N-acetylaspartate. These findings support histopathologic findings of multifocal inflammatory leukoencephalopathy revealing demyelination with relative axonal sparing in the patient.

Metabolic Alterations in Parkinson's Disease after Thalamotomy, as Revealed by 1H MR Spectroscopy

OBJECTIVE: To determine, using proton magnetic resonance spectroscopy (1H MRS) whether thalamotomy in patients with Parkinson's disease gives rise to significant changes in regional brain metabolism. MATERIALS AND METHODS: Fifteen patients each underwent stereotactic thalamotomy for the control of medically refractory parkinsonian tremor. Single-voxel 1H MRS was performed on a 1.5T unit using a STEAM sequence (TR/TM/TE, 2000/14/20 msec), and spectra were obtained from substantia nigra, thalamus and putamen areas, with volumes of interest of 7-8ml, before and after thalamotomy. NAA/Cho, NAA/Cr and Cho/Cr metabolite ratios were calculated from relative peak area measurements, and any changes were recorded and assessed. RESULTS: In the substantia nigra and thalamus, NAA/Cho ratios were generally low. In the substantia nigra of 80% of patients (12/15) who showed clinical improvement, decreased NAA/Cho ratios were observed in selected voxels after thalamic surgery (p < 0.05). In the thalamus of 67% of such patients (10/15), significant decreases were also noted (p < 0.05). CONCLUSION: Our results suggest that the NAA/Cho ratio may be a valuable criterion for the evaluation of Parkinson's disease patients who show clinical improvement following surgery. By highlighting variations in this ratio, 1H MRS may help lead to a better understanding of the pathophysiologic processes occurring in those with Parkinson's disease.

Crotoxin, the major toxin from the rattlesnake Crotalus durissus terrificus, inhibits 3H-choline uptake in guinea pig ileum

We examined the effect of crotoxin, the neurotoxic complex from the venom of the South American rattlesnake Crotalus durissus terrificus, on the uptake of 3H-choline in minces of smooth muscle myenteric plexus from guinea pig ileum. In the concentration range used (0.03-1 ÁM) and up to 10 min of treatment, crotoxin decreased 3H-choline uptake by 50-75 percent compared to control. This inhibition was time dependent and did not seem to be associated with the disruption of the neuronal membrane, because at least for the first 20 min of tissue exposure to the toxin (up to 1 ÁM) the levels of lactate dehydrogenase (LDH) released into the supernatant were similar to those of controls. Higher concentrations of crotoxin or more extensive incubation times with this toxin resulted in elevation of LDH activity detected in the assay supernatant. The inhibitory effect of crotoxin on 3H-choline uptake seems to be associated with its phospholipase activity since the equimolar substitution of Sr2+ for Ca2+ in the incubation medium or the modification of the toxin with p-bromophenacyl bromide substantially decreased this effect. Our results show that crotoxin inhibits 3H-choline uptake with high affinity (EC25 = 10 +/- 5 nM). We suggest that this inhibition could explain, at least in part, the blocking effect of crotoxin on neurotransmission

Espectroscopia de prótons (1H) por ressonância magnética, neuroquímica cerebral e diagnóstico de doenças neurológicas / Proton (1H) magnetic resonance spectroscopy, brain neurochemistry, and diagnosis of neurological diseases

A técnica de espectroscopia de prótons (1H) por ressonância magnética do cérebro permite identificar, in vivo e de modo näo-invasivo, neurometabolitos pertencentes a diversas vias do metabolismo intermediário. A análise desses achados é o objetivo da presente revisäo. As bases do método e os principais metabolitos que constituem o espectro säo considerados, assim como as vias neuroquímicas relacionadas com importantes funçöes metabólicas e os neurometabolitos representativos das mesmas, possíveis de serem observados no espectro em condiçöes normais e patológicas. O conhecimento dessas relaçöes aponta para aspectos neuroquímicos da amostra de tecido nervoso examinada e permite hipóteses fisiológicas e fisiopatológicas relativas às variaçöes dos principais metabolitos. Säo descritas variaçöes regionais e em relaçäo ao envelhecimento normal, importantes na seleçäo e comparaçäo de amostras adequadamente pareadas, sobretudo em situaçäo de pesquisa. A aplicaçäo da técnica no diagnóstico em neurologia também é considerada, com ênfase em doenças degenerativas. Conclui-se ser uma técnica de grande utilidade clínica e que contribui de modo significativo no aprofundamento disgnóstico, assim como na monitorizaçäo terapêutica e no acompanhamento evolutivo de doenças neurológicas

Espectroscopia por ressonância magnética em epilepsia / Magnetic resonance spectroscopic imaging in epilepsy

A evoluçäo da cirurgia para epilepsia vem sendo acompanhada por novos métodos de neuroimagem, näo só morfológicos, como, também, funcionais. Dentre esses últimos, destacamos a espectroscopia por ressonância magnética (ERM), de especial interesse deste artigo. A ERM parece ser promissora na definiçäo da identificaçäo do foco epileptogênico, pela demonstraçäo das alteraçöes dos metabólicos do fósforo (31P-ERM) e avaliaçäo pelo próton de H+ (1H-ERM). Reconhece-se a variaçäo da 1H-ERM normal, segundo alteraçöes idade-relacionadas, para localizaçäo do foco epileptogênico, no período interictal, pelas taxas de NAA (N-acetilaspartato), Cr (creatina) e Co (colina), e relaçöes NAA: Co e NAA: Cr; e no ictal, pelas mesmas taxas e pela avaliaçäo do lactato. A estimativa de aminoácidos neurotransmissores também auxilia nessa topografia. A ERM, em especial, a 1H-ERM, é de grande potencialidade no estudo bioquímico do cérebro, in vivo, e poderá vir a ter crescente importância no diagnóstico topográfico da regiäo epileptogênica dos pacientes com epilepsia, na dependência da idade e do local do foco

Caffeine causes glycerophosphorylcholine accumulation through ryanodine-inhibitable increase of cellular calcium and activation of phospholipase A2 in cultured MDCK cells

Glycerophosphrylocholine (GPC) is a renal medullary compatible organic osmolyte that is derived from choline via phosphatidylcholine, which is catalyzed in part by phospholipase A2 (PLA2) and its degradation by GPC: choline phosphodiesterase (GPC: choline PDE). We found that caffeine elevated intracellular free calcium ([Ca2+]i) and GPC level in cultured MDCK cells, canine kidney epithelial cells, and propose a possible biochemical mechanism. When MDCK cells were incubated for 3 h with 1 to 10 mM caffeine, cellular GPC was elevated in a dose-dependent manner, and this occurred independently of the extracellular osmolality. Caffeine stimulated the rate of [14C]choline incorporation into [14C]GPC and PLA2 activity. Whereas, GPC: choline PDE activity was accompanied by less of increase. These enzyme changes demonstrate the increased net synthesis of MDCK GPC. In order to identify what triggers the PLA2 activation, [Ca2+]i was measured by using a fluorescence dye, Fura-2. Caffeine (10 mM) resulted in a typical transient increase in MDCK [Ca2+]i concentration, and this increase was greatly inhibited by pretreatment of MDCK cells with 10 mM ryanodine for 5 min. Ryanodine (10 mM) also inhibited the caffeine-induced stimulation of PLA2 activity. These findings provide the first evidence that caffeine in MDCK cells causes a ryanodine-inhibitable increase of [Ca2+]i and PLA2 activity, resulting in cellular GPC accumulation.

Influence of cyclic AMP on the biosynthesis of phosphatidylcholine in Microsporum gypseum.

The influence of intracellular cAMP on phosphatidylcholine biosynthesis in Microsporum gypseum has been examined using radiolabelled precursors. The incorporation of labelled choline, methionine and ethanolamine into total lipids, phospholipids and choline containing phospholipids increased in aminophylline and decreased in atropine grown cells as a result of rise and fall in cAMP levels in these cells. The enhanced uptake of labelled methionine and ethanolamine in comparison to labelled choline in choline containing phospholipids in aminophylline grown cells suggests that methylation pathway is more influenced by cAMP than CDP-choline pathway.

Trimetilaminuria: Síndrome del olor a pescado: descripción de un nuevo caso y revisión de la bibliografía / Trimethylaminuria: fish odor syndrome: description of a new case and bibliographic review

Se describe el decimocuarto caso del síndrome de olor a pescado, en un niño de 7 años, cuya única manifestación clínica es desprender dicho olor, fenómeno que se acentúa con la transpiración y al ingerir alimentos ricos en colina. Se trata de un error congénito del metabolismo por una falla en el sistema oxidante de la trimetilamina del hígado que permite el pasaje a la sangre, secreciones, aliento y orina de esta amina volátil cuyo olor es característico, por lo que también se denomina a esta enzimopatía trimetilaminemia o trimetilaminuria. La trimetilamina se determinó en el suero del paciente por medio de la cromatografía en fase gaseosa. Se aportan datos sobre sus dermatoglifos y se contribuye a delimitar la afección, desligándola de manifestaciones accidentales

Efflux of acetylcholine in dimorphic skeletal muscle from castrated male rats

The effect of testosterone on motor neurons of dimorphic muscles is demostrable by increased frequency of miniature end-plate potentials (mepp) and decreased end-plate acetylcholinesterase activity observed in castrated rats. No change occurs in induced acetylcholine (ACh release. Although these muscles atrophy after castration there is no loss of muscle fibers. In the present study we reinvestigate the neuromuscular transmission in levator ani (LA) muscles from normal (N) adult (120 days) male rats and from rats castrated (C) 30 days before. The measurement of radioactive [3H]-choline was used to evaluate ACh release since it permits simultaneous estimation of quantal and non-quantal and non-quantal ACh release. The LA muscle was incubated with [3H]-choline (1µCi/ml) for 30 min and ACh efflux was measured after washout. The basal release of [3H]-choline (dpm total tissue radioactivity-1 number of fibers-1) was 296 ñ 33 and 156 ñ 24 in N and C, respectively. Induced ACh release (25 Hz, 5 min) was the same in N and C (653.19 ñ 66.46) and 496.62 ñ 68.67, respectively). These results indicate that castration increased nepp frequency buth reduced the total spontaneous release of ACh