Glucose Levels in Culture Medium Determine Cell Death Mode in MPP+-treated Dopaminergic Neuronal Cells

We previously demonstrated that 1-methyl-4-phenylpyridinium (MPP+) causes caspase-independent, non-apoptotic death of dopaminergic (DA) neuronal cells. Here, we specifically examined whether change of glucose concentration in culture medium may play a role for determining cell death modes of DA neurons following MPP+ treatment. By incubating MN9D cells in medium containing varying concentrations of glucose (5~35 mM), we found that cells underwent a distinct cell death as determined by morphological and biochemical criteria. At 5~10 mM glucose concentration (low glucose levels), MPP+ induced typical of the apoptotic dell death accompanied with caspase activation and DNA fragmentation as well as cell shrinkage. In contrast, MN9D cells cultivated in medium containing more than 17.5 mM (high glucose levels) did not demonstrate any of these changes. Subsequently, we observed that MPP+ at low glucose levels but not high glucose levels led to ROS generation and subsequent JNK activation. Therefore, MPP+-induced cell death only at low glucose levels was significantly ameliorated following co-treatment with ROS scavenger, caspase inhibitor or JNK inhibitor. We basically confirmed the quite similar pattern of cell death in primary cultures of DA neurons. Taken together, our results suggest that a biochemically distinct cell death mode is recruited by MPP+ depending on extracellular glucose levels.

Dietary Intakes of Older Adults with and without Dementia Compared to Healthy Eating Recommendations.

Background: The Alzheimer’s Research Trust (2012) report that 820,000 people are currently living with dementia in the UK with prevalence increasing in line with the ageing population and a new case estimated to occur every 3.2 minutes. Whilst there is currently no cure, early diagnosis and intervention may be essential in reducing the considerable health, economic and social burden of dementia. Although multifactorial in aetiology, diet and lifestyle factors have been identified as potentially protective and pathogenic for dementia development, Staehelin, [1]. The aim of this study was to compare the dietary intakes of a group of older adults early in their dementia disease to those of healthy controls in order to inform the development of future dietary intervention studies and service delivery to delay the onset and slow the progression of cognitive decline. Methods: Ethical approval was granted from the National Research Ethics Service Committee London. Participants with a diagnosis of dementia (Alzheimer’s, vascular or mixed type) were recruited from Memory Clinics across Sussex, with consent obtained from both the participant and their designated carer. Routine clinical data was extracted from the patient notes and any additional data collected during a 2hr initial interview. Healthy controls were recruited from community groups in the Brighton area. Anthropometric measurements were made according to standard age-appropriate procedures and dietary intakes were assessed using an adapted version of the EPIC Food Frequency Questionnaire (FFQ) Adamson et al. [2]. FFQ’s were coded and converted into nutritional information using the FETA software (Mulligan et al, unpublished). Relative nutrient intakes (expressed as a percentage of the age- and gender-appropriate dietary reference values (DRV) and adherence to a Mediterranean style diet Trichopoulou et al. [3] were compared between groups using independent t tests or non-parametric equivalents as appropriate. Results: Ninety-six cases and 53 controls had FFQ data available for analysis. Cases were more likely to be older (mean age 80.7[6.2] and 68.1[6.0] years), female (58% and 28% respectively) (p≤0.001) and of a higher BMI (26.4[3.8] and 25.0[3.2] kg/m2; p=0.02) than controls. Cases consumed significantly more energy in the form of saturated fat (13.8[2.6] and 12.2[3.2]% of energy) and significantly less as polyunsaturated fat (5.6[1.6] and 6.6[1.5]%) and alcohol (2.0[3.2] and 3.8[4.3]%) (p≤0.001). The differences in fat remained significant even when only healthy weight individuals were analysed (p<0.05). No significant differences in relative micronutrient intakes were observed, with the exception of magnesium (p=0.04). Food-based analyses suggested that adults with dementia were less likely to consume fruit and nuts and seeds (p≤0.007) and more likely to consume sugars and snacks (p<0.001) than controls. These differences remained significant, with the exception of fruit, when analysed within healthy weight adults only (p≤0.005). Controls showed greater adherence to a Mediterraean–style diet (p=0.001) and specifically higher scores for the fruit, vegetable and meat components of this score (p≤0.01). Discussion: The cross-sectional nature of this data limits the ability to draw conclusions regarding causality however it would appear that the current diet of older adults with dementia may fail to meet healthy eating recommendations, particularly with regard to the balance of fats. The cognitive benefits of a Mediterranean diet have been widely reportedSofrizzi et al, [4] and the food-based analyses would seem to support this theory, with potentially beneficial foods like fruits, nuts and alcohol underconsumed in a sample of adults with diagnosed cognitive impairment. Conclusion: This data would suggest that older adults with cognitive impairment have sub-optimal dietary intakes not solely explained by their greater age or BMI. Ongoing follow up of this cohort will confirm the impact of this on disease progression.

Calbindin-D28K Prevents Staurosporin-induced Bax Cleavage and Membrane Permeabilization

Calbindin-D28K has been implicated in the regulation of neuronal cell death. Previously, we demonstrated that calbindin-D28K prevents staurosporine (STS)-induced caspase activation and subsequent apoptosis in a neuronal cell line. However, the role of calbindin-D28K in STS-induced activation of calpain and necrotic cell death was not identified. Staurosporine induced the elevation of intracellular calcium after 1 hr of treatment. Overexpression of calbindin-D28K and presence of a calcium chelator, BAPTA, prevented the increase of calcium in STS-treated cells. Cleavage of Bax by calpain was prevented by the overexpressed calbindin-D28K. Permeabilization of the plasma membrane, a factor in necrosis, as well as apoptotic change of the nucleolus induced by STS, was prevented by calbindin-D28K. Thus, our study suggests that calbindin-D28K may exert its protective functions by preventing calpain activation in necrotic cell death, in addition to its effect on the caspase-apoptosis pathway.

Tumor Necrosis Factor-Associated Protein 1 (TRAP1) is Released from the Mitochondria Following 6-hydroxydopamine Treatment

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Most cases are sporadic and its etiology is incompletely understood. However, increasing evidence suggests that oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of Parkinson's disease. The aim of this study was to investigate changes in mitochondrial protein profiles during dopaminergic neuronal cell death using two-dimensional gel electrophoresis in conjunction with mass spectrometry. Several protein spots were found to be significantly altered following treatment of MN9D dopaminergic neuronal cells with 6-hydroxydopamine (6-OHDA). Among several identified candidates, TNF receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone, was released from the mitochondria into the cytosol in MN9D cells as well as primary cultures of dopaminergic neurons following 6-OHDA treatment. This event was drug-specific in that such apoptotic inducers as staurosporine and etoposide did not cause translocation of TRAP1 into the cytosol. To our knowledge, the present study is the first to demonstrate the drug-induced subcellular translocation of TRAP1 during neurodegeneration. Further studies delineating cellular mechanism associated with this phenomenon and its functional consequence may provide better understanding of dopaminergic neurodegeneration that underlies PD pathogenesis.

Promise of Neurorestoration and Mitochondrial Biogenesis in Parkinson's Disease with Multi Target Drugs: An Alternative to Stem Cell Therapy

There is an unmet need in progressive neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. The present therapeutics for these diseases at best is symptomatic and is not able to delay disease or possess disease modifying activity. Thus an approach to drug design should be made to slow or halt progressive course of a neurological disorder by interfering with a disease-specific pathogenetic process. This would entail the ability of the drug to protect neurons by blocking the common pathway for neuronal injury and cell death and the ability to promote regeneration of neurons and restoration of neuronal function. We have now developed a number of multi target drugs which possess neuroprotective, and neurorestorative activity as well as being able to active PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha), SIRT1 (NAD-dependent deacetylase protein) and NTF (mitochondrial transcription factor) that are intimately associated with mitochondrial biogenesis.

Influence of Asthma Epidemiology on the Risk for Other Diseases

Asthma is a multifactorial chronic disease affecting a significant proportion of people in the United States and worldwide. Numerous laboratory and epidemiological studies have attempted to understand the etiology and underlying mechanisms of asthma and to identify effective therapies. However, the impact of asthma on the risk for other diseases has drawn little attention. This paper discusses the potential effects of asthma as a risk factor for other diseases, explores the potential mechanisms, and reviews the implications of the findings to clinical practice, public health, and research.

Knowledge, perception and practices of healthcare professionals at tertiary level hospitals in Kingston, Jamaica, regarding neonatal pain management / Conocimientos, percepciones y prácticas de los profesionales de la salud en los hospitales de nivel terciario en Kingston, Jamaica, en relación con el tratamiento del dolor neonatal

OBJECTIVE: To determine knowledge, perception and practices of healthcare professionals at tertiary level hospitals in Kingston, Jamaica, regarding neonatal pain management. DESIGN AND METHODS: Physicians and nurses actively involved in providing neonatal care at three tertiary level hospitals were invited to participate. A 21-item self-administered questionnaire was used to obtain information on knowledge, perception and practice of neonatal pain management. Descriptive analyses were performed. RESULTS: A total of 147 healthcare workers participated giving a response rate of 85%. Male to female ratio was 1: 4.4. Nurses accounted for 76 (52%) of the respondents while 70 (48%) were physicians. Seventy-three (50%) individuals were unaware of the degree of pain neonates were capable of experiencing and only 38 (27%) knew that premature infants were capable of feeling pain. One hundred and four (71%) respondents were able to identify physiological markers of pain and most respondents were able to discriminate between painful and non-painful procedures. However, 100 (68%) respondents rarely prescribed analgesia for procedures previously rated as painful. Seventy-one (51%) respondents admitted to not using analgesia for alleviating procedural pain in neonates. Twenty-five (18%) individuals thought that the procedure was too short to require analgesic support while 41 (30%) stated that medication was not usually prescribed for procedural pain. Physician scores were significantly higher than those attained by nurses for knowledge (p = 0.003) and for pain perception (p = 0.001) but no significant differences were noted for practice (p = 0.18).> CONCLUSION : There is an overwhelming deficiency in the knowledge, perception and practice of neonatal pain management at tertiary level institutions in Kingston, Jamaica. There is the urgent need for the education of health professionals on neonatal pain management. This will in turn facilitate change in perception and eventually, along with the institution of local policies and protocols, influence practice.

OBJETIVO: Determinar los conocimientos, percepciones y prácticas de los profesionales de la salud en los hospitales de nivel terciario en Kingston, Jamaica, en relación con el tratamiento del dolor neonatal DISEÑO Y MÉTODOS: Los médicos y enfermeras comprometidos activamente en brindar atención neonatal en tres hospitales de nivel terciario, fueron invitados a participar. Se aplicó un cuestionario auto-administrado de 21 incisos a fin de obtener información sobre conocimientos, percepciones y prácticas del tratamiento del dolor neonatal. Se realizaron análisis descriptivos. RESULTADOS: Un total de 147 trabajadores de la salud participaron para una tasa de respuesta de 85%. La proporción de varones frente a hembras fue 1:4.4. Las enfermeras representaron 76 (52%) de los encuestados, mientras que 70 (48%) fueron médicos. Setenta y tres (50%) de los individuos no tenían noción del grado de dolor que los neonatos podían experimentar y sólo 28 (27%) sabían que los infantes prematuros podían sentir dolor. Ciento cuatro (71%) de los encuestados pudieron identificar los marcadores fisiológicos del dolor y la mayor parte de los encuestados pudieron discriminar entre procedimientos dolorosos y no dolorosos. Sin embargo, 100 (68%) encuestados raras veces prescribieron analgésicos para procedimientos previamente clasificados como dolorosos. Setenta y uno (51%) de los encuestados admitieron no usar analgésicos para aliviar el dolor en los procedimientos con los neonatos. Veinticinco (18%) individuos pensaron que el procedimiento era demasiado breve para requerir apoyo analgésico, en tanto que 41 (30%) plantearon que usualmente no se prescribían medicamentos para el dolor en los procedimientos. Las puntuaciones de los médicos fueron significativamente más altas que las alcanzadas por las enfermeras en relación con los conocimientos (p = 0.003) y la percepción del dolor (p = 0.001), pero no se observaron diferencias significativas en relación con la práctica (p = 0.18). CONCLUSIÓN: Existe una deficiencia abrumadora en cuanto a conocimientos, percepciones y prácticas en relación con el manejo de los dolores en neonatos en las instituciones de nivel terciario en Kingston, Jamaica. Hay una urgente necesidad de educar a los profesionales de la salud en el tratamiento del dolor en los neonatales. Esto a su vez facilitará un cambio en la percepción, y finalmente - junto con la institución de protocolos y políticas locales - influirá en la práctica.

Chromosome 22 LD Map Comparison between Korean and Other Populations

Single nucleotide polymorphisms (SNPs) are the most abundant forms of human genetic variations and resources for mapping complex genetic traits and disease association studies. We have constructed a linkage disequilibrium(LD) map of chromosome 22 in Korean samples and compared it with those of other populations, including Yorubans in Ibadan, Nigeria (YRI), Centred'Etude du Polymorphisme Humain (CEPH) reference families (CEU), Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) in the HapMap database. We genotyped 4681 of 111,448 publicly available SNPs in 90 unrelated Koreans. Among genotyped SNPs, 4167 were polymorphic. Three hundred and five LD blocks were constructed to make up 18.6% (6.4 of 34.5 Mb) of chromosome 22 with 757 tagSNPs and 815 haplotypes(frequency > or = 5.0%). Of 3430 common SNPs genotyped in all five populations, 514 were monomorphic in Koreans. The CHB + JPT samples have more than a 72% overlap with the monomorphic SNPs in Koreans, while the CEU + YRI samples have less than a 38% overlap. The patterns of hot spots and LD blocks were dispersed throughout chromosome 22, with some common blocks among populations, highly concordant between the three Asian samples. Analysis of the distribution of chimpanzee-derived allele frequency (DAF), a measure of genetic differentiation, Fst levels, and allele frequency difference (AFD) among Koreans and the HapMap samples showed a strong correlation between the Asians, while the CEU and YRI samples showed a very weak correlation with Korean samples. Relative distance as a quantitative measurement based upon DAF, Fst, and AFD indicated that all three Asian samples are very proximate, while CEU and YRI are significantly remote from the Asian samples. Comparative genome-wide LD studies provide useful information on the association studies of complex diseases.

Chromosome 22 LD Map Comparison between Korean and Other Populations

Single nucleotide polymorphisms (SNPs) are the most abundant forms of human genetic variations and resources for mapping complex genetic traits and disease association studies. We have constructed a linkage disequilibrium(LD) map of chromosome 22 in Korean samples and compared it with those of other populations, including Yorubans in Ibadan, Nigeria (YRI), Centred'Etude du Polymorphisme Humain (CEPH) reference families (CEU), Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) in the HapMap database. We genotyped 4681 of 111,448 publicly available SNPs in 90 unrelated Koreans. Among genotyped SNPs, 4167 were polymorphic. Three hundred and five LD blocks were constructed to make up 18.6% (6.4 of 34.5 Mb) of chromosome 22 with 757 tagSNPs and 815 haplotypes(frequency > or = 5.0%). Of 3430 common SNPs genotyped in all five populations, 514 were monomorphic in Koreans. The CHB + JPT samples have more than a 72% overlap with the monomorphic SNPs in Koreans, while the CEU + YRI samples have less than a 38% overlap. The patterns of hot spots and LD blocks were dispersed throughout chromosome 22, with some common blocks among populations, highly concordant between the three Asian samples. Analysis of the distribution of chimpanzee-derived allele frequency (DAF), a measure of genetic differentiation, Fst levels, and allele frequency difference (AFD) among Koreans and the HapMap samples showed a strong correlation between the Asians, while the CEU and YRI samples showed a very weak correlation with Korean samples. Relative distance as a quantitative measurement based upon DAF, Fst, and AFD indicated that all three Asian samples are very proximate, while CEU and YRI are significantly remote from the Asian samples. Comparative genome-wide LD studies provide useful information on the association studies of complex diseases.

The impact of antenatal care on pregnancy performance between adolescent girls and older women / Impacto del cuidado prenatal en el desenvolvimiento del embarazo entre niñas adolescentes y mujeres mayores

OBJECTIVE: To investigate pregnancy performance and newborn outcome between adolescents and older women receiving adequate and similar antenatal care. METHODS: Four hundred and twenty-five women attending the antenatal clinic at the University Hospital of the West Indies, Kingston, Jamaica, participated in a prospective study. Recruitment included women 19 years and younger (adolescents) and 20 years and older (older women). Anthropometric measurements of the women and their newborn were made. During the pregnancy, all admissions to hospital and the diagnoses were recorded. Neonatal admissions were also recorded. RESULT: Three hundred and sixty-one women each (84.9%) delivered a live infant of which 175 (87.5%) women were less than 20 years old and comprised the adolescent group and 186 (82.7%) of these women were 20 years and older and comprised the women in the older age group. Thirty-nine (9.2%) had early pregnancy losses; twelve among the adolescents (6%) and twenty-seven (12%) among the older women (p = 0.03). There was one intrauterine death and one stillbirth in the adolescent group and two intrauterine deaths and no stillbirth in the older group. The attendance rate at the antenatal clinic for both groups was high throughout the study with each group having greater than 96% attendance. There were 53 (26.5%) admissions among the adolescent girls and 70 (31.1%) admissions among the older women. This was not statistically significant. There was a significant difference in the occurrence of urinary tract infections where 17% of the adolescents had a urinary tract infection compared to 1% of older women (p < 0.0001). There was a lower Caesarean section rate among the adolescent. No significant difference between the number of neonatal admissions for the two groups (p = 0.19) was seen. CONCLUSION: This study showed that with similar and adequate antenatal care there were minimal differences in pregnancy performance between the two groups with...

OBJETIVO: Investigar el desempeño del embarazo y el resultado neonatal entre adolescentes y mujeres mayores que reciben cuidado prenatal similar y adecuado. MÉTODOS: Cuatrocientos veinticinco mujeres que asistían a la clínica de atención prenatal en el Hospital Universitario de West Indies, Kingston, Jamaica, participaron en un estudio prospectivo. El reclutamiento incluyó mujeres de 19 años y más jóvenes (adolescentes) y 20 años y mayores (mujeres mayores). Se hicieron mediciones antropométricas de las mujeres y sus recién nacidos. Durante el embarazo, se registraron todos los ingresos al hospital y los diagnósticos. También se registraron los ingresos neonatales. RESULTADO: Trescientos sesenta y uno mujeres (84.9%) dieron a luz a un infante vivo. De ellas, 175 (87.5%) eran menores de 20 años, incluido el grupo de adolescentes, en tanto que 186 (82.7%) tenían 20 años o más, y abarcaban las mujeres en el grupo etario de más edad. Treinta y nueve (9.2%) tuvieron pérdidas de embarazo tempranas - doce de entre las adolescentes (6%) y veintisiete (12%) de entre las mujeres mayores (p = 0.03). Hubo una muerte intrauterina y un parto de mortinato en el grupo de adolescentes, dos muertes intrauterinas y ningún parto de mortinatos en el grupo de más edad. La tasa de asistencia a la clínica de atención prenatal para ambos grupos fue alta a lo largo del estudio, teniendo cada de grupo una asistencia superior al 96%. Hubo 53 (26.5%) ingresos entre las adolescentes y 70 (31.1%) ingresos entre las mujeres de más edad. Esto no fue estadísticamente significativo. Hubo una diferencia significativa en la ocurrencia de infecciones del tracto urinario, donde el 17% de las adolescentes tuvieron una infección del tracto urinario en comparación con el 1% de las mujeres mayores (p < 0.0001). Hubo una proporción de cesáreas menor entre las adolescentes. No se observó diferencia significativa alguna entre el número de ingresos neonatales en los dos grupos (p = 0.19)...

Acute lead poisoning associated with backyard lead smelting in Jamaica / Envenenamiento agudo con plomo asociado con la fundición casera de plomo en Jamaica

Long-term backyard smelting of lead in a district known as Mona Commons, Kingston, Jamaica, has produced lead burdens as high as 30 000 mg/kg in soils near to the smelter, and indoor dust loadings of 373 microg/f2 in the residents' home. The blood lead levels (BPb) of 107 children from the district were in the range 2.2-202 microg/dL. Fifty-nine per cent of these had BPb levels above 10 microg/dL and the population mean was an unacceptably high 25.1 microg/dL. The highest levels were observed for five siblings, two of whom presented with lead encephalopathy. This severe chronic exposure to lead was exacerbated by a significant history of pica, and chronic nutritional anaemia. Chelation therapy significantly reduced the BPb levels but due to lead storage in other organs, the values after several months were still higher than desirable. This study emphasizes the importance of reducing the exposure of children to lead.

An unusual presentation of group B streptococcal sepsis

This paper describes the devastating outcome of a neonate who presented with severe late onset group B beta-haemolytic streptococcal (GBS) disease. There were extensive infarcts of the brain and gangrene of the toes. The purpose of this report is to alert healthcare workers of the unusual presentation and that fatal late onset group B beta-haemolytic streptococcal disease may occur despite early and effective management

Additional Diagnosis of Brain Death by Transcranial Doppler

Ever since transplant surgery became a common procedure. The early diagnosis of irreversible cessation of cerebral function has become an important need We analysed the findings of transcranial doppler of five cases. Two was diagnosed brain death by currently accepted criteria. Two cases showed absence of intracranial blood flow and normal to disturbed flow status of the cervical carotid artery. Three cases showed reverberating flow pattern with reflux phenomenon. Transcranial doppler investigation seems to provide a practical, non-invasive. And reliable disgnostic evidence for the arrest of cerebral circulation.

Computerized optic disc analysis with adjunct stereoscopic viewing of disc photographs

We have investigated the potential usefulness of stereoscopic viewing of optic disc photographs in marking the disc margin in computerized analysis with the Rodenstock Analyzer in 48 eyes of 26 patients with ocular hypertension or primary open-angle glaucoma. Marking of the disc margin without Method 1) and with the aid of stereoscopic viewing of disc photographs (Method 2) three consecutive times by one observer at the same sitting, and three subsequent topographic analyses of each method were done on each 48 eyes. The mean intraphotographic variabilities of such optic disc parameters as rim area, and cup volume with Method 2 were significantly less than those with Method 1 overall and in 16 eyes (33%) with poor video images having an ill-defined disc margin (p less than 0.05 for each), but not in 32 eyes (67%) with clear video images having a well-defined disc margin. Furthermore, the mean paired differences of rim area, disc area and cup volume between the two methods (Method 1 minus Method 2) were also statistically significant overall and in eyes with poor video images (p less than 0.05 for each).

Atencion de salud en minorias etnicas rurales. Algunas observaciones antropologicas. / Health care among rural ethnic minorities. Some anthropological observations

Se examina la importancia que para los educadores de salud tienen las observaciones antropologicas al estudiar factores y necesidades culturales en relacion con el diagnostico de enfermedades, su evaluacion y el proceso de decision terapeutica. Se ponen de relieve nuevas tendencias en los modelos de adopcion de decisiones que muestran la logica subyacente a las elecciones em materia de salud