Intrauterine growth restriction modifies gene expression profiling in cord blood.

BACKGROUND: Small-for-gestational-age (SGA) newborns are at an increased risk for perinatal morbidity and mortality and development of metabolic syndromes such as cardiovascular disease and type 2 diabetes mellitus (T2DM) in adulthood. The mechanism underlying this increased risk remains unclear. In this study, genetic modifications of cord blood were investigated to characterize fetal change in SGA newborns. METHODS: Gene expression in cord blood cells was compared between 10 SGA newborns and 10 appropriate-for-gestational-age (AGA) newborns using microarray analysis. Pathway analysis was conducted using the Ingenuity Pathways Knowledge Base. To confirm the microarray analysis results, quantitative real-time polymerase chain reaction (RT-PCR) was performed for upregulated genes in SGA newborns. RESULTS: In total, 775 upregulated and 936 downregulated probes were identified in SGA newborns and compared with those in AGA newborns. Of these probes, 1149 were annotated. Most of these genes have been implicated in the development of cardiovascular disease and T2DM. There was good agreement between the RT-PCR and microarray analyses results. CONCLUSIONS: Expression of certain genes was modified in SGA newborns in the fetal period. These genes have been associated with metabolic syndrome. To clarify the association between modified gene expression in cord blood and individual vulnerability to metabolic syndrome in adulthood, these SGA newborns will be have long-term follow up for examination of genetic and postnatal environmental factors. Gene expression of cord blood can be a useful and non-invasive method of investigation of genetic alterations in the fetal period.

Continuous training in young athletes decreases hepcidin secretion and is positively correlated with serum 25(OH)D and ferritin.

Background: Iron deficiency is known to impair muscle function and reduce athletic performance, while vitamin D has been reported to induce iron deficiency. However, the mechanism underlying exercise-induced changes in iron metabolism and the involvement of vitamins in this mechanism are unclear. The present study examined changes in biological iron metabolism induced by continuous training and the effects of vitamin D on these changes. Methods: Diet, physical characteristics, and blood test data were collected from 23 female high school students in a dance club on the last day of each of a 2-month continuous training period and a 2-week complete rest periods. Results: Serum hepcidin-25 levels were significantly lower during the training period than the rest period (p = 0.013), as were the red blood cell count, hemoglobin, and hematocrit (all p < 0.001). Serum erythropoietin was significantly higher (p = 0.001) during the training period. Significant positive correlations were observed between 25(OH)D levels and serum iron, serum ferritin, and transferrin saturation during the training period. Multiple regression analysis with serum 25(OH)D level as the dependent variable and serum ferritin and iron levels as independent variables during the training period revealed a significant association with serum ferritin. Conclusion: Continuous training may promote hemolysis and erythropoiesis, contributing to the suppression of hepcidin expression. The relationship between serum 25(OH)D and iron in vivo may be closely related to metabolic changes induced by the exercise load.

[Omohyoid muscle syndrome in a patient with Parkinson's disease].

A 49-year-old man noticed a resting tremor in his right hand and was diagnosed with Parkinson's disease (PD) at the age of 43. Soon thereafter, he noticed a right neck mass that only appeared when he swallowed and was accompanied by an uncomfortable sensation. At the age of 49, he was admitted to our hospital to adjust his medication for PD and to examine the neck mass. The subcutaneous mass was round, soft, and approximately 3 cm in diameter. The symptoms in his neck showed no progression. Resting tremors and rigidity due to his PD were predominantly observed on his right side, but his postural reflex was intact. Cervical echogram revealed that the mass was the belly of the OM itself. Thus, the patient was diagnosed with omohyoid muscle syndrome (OMS). It can be surmised that some susceptibility of the OM itself and/or structural fragility in the surrounding tissues would be involved in the pathogenesis of OMS. In this case, considering that OMS occurred soon after symptoms of PD appeared, we speculated that muscle tone abnormalities due to PD played a role in the development of OMS.

L-dopa and dopamine enhance the formation of aggregates under proteasome inhibition in PC12 cells.

The formation of inclusion bodies in dopaminergic neurons is associated with the pathogenesis of Parkinson's disease. In order to clarify the role of dopamine/L-dopa in the formation of protein aggregates, we investigated dopamine/L-dopa-related aggregation using an experimental inclusion model. The inhibition of tyrosine hydroxylase (TH) by alpha-methyltyrosine dramatically decreased MG132-induced aggregate formation. In addition, the inhibition of TH caused the upregulation of proteasomes in cultured cells and the dopamine/L-dopa induced non-enzymatic polymerization of ubiquitin. This inhibition did not affect cell viability. These results suggest that dopamine/L-dopa might enhance aggregate formation, and that intracellular aggregates may not be toxic to cells.

Transcriptional activation of p62/A170/ZIP during the formation of the aggregates: possible mechanisms and the role in Lewy body formation in Parkinson's disease.

Formation of intracellular inclusion bodies due to defects in the protein degradation machinery is associated with the pathogenesis of neurodegenerative diseases. Sequestosomal protein p62/A170/ZIP, which is an oxidative stress-related protein and a ubiquitin-binding protein, is a component protein of Lewy bodies that are observed in patients with Parkinson's disease. The association of p62 with poly-ubiquitinated proteins may be an important step in the formation of intracellular protein aggregates like Lewy bodies. To study the role of p62 in the formation of protein aggregates in PC12 cells, we monitored the intracellular localizations of p62 and ubiquitinated proteins and the levels of both components during treatment with MG132, a proteasome inhibitor. In the early stage of aggregate formation, p62 did not always co-localize with ubiquitin. In contrast, these proteins were always co-localized in later stages. After the treatment of the cells with MG132, we found that the expression level of p62 increased due to the transcriptional activation of the gene and that higher molecular sizes of p62, corresponding to mono- and di-ubiquitinated formes, were also formed. Both the transcriptional inhibitor actinomycin D and an antisense oligonucleotide of p62 inhibited the MG132-mediated increase of p62, the sequestration of ubiquitinated proteins, and the enlargement of the aggregates. Furthermore, p62-positive aggregates were observed primarily in surviving cells. Together, these results suggest that p62 plays an important role in the protection of cells from the toxicity of misfolded proteins by enhancing aggregate formation especially in the later stages.

p53-mediated mitochondrial dysfunction by proteasome inhibition in dopaminergic SH-SY5Y cells.

Decreased proteasome activity is an important pathology in Parkinson's disease (PD), which is related to cell death and Lewy body formation. In this study, we show that p53-activity may correlate with neuronal death via the mitochondrial pathway in PD model. The proteasome inhibitor, MG132, induced the accumulation of p53 in human dopaminergic neuroblastoma SH-SY5Y cells. The increased stabilization of p53 upregulated the level of Bax and mitochondrial depolarization. These events were inhibited by the p53 inhibitor, pifithrin-alpha (PFT). Cell viability analyzes demonstrated that PFT partially prevented MG132-induced cell death. These results suggest that p53 is a candidate as an intermediary between the proteasome system and mitochondria-related neuronal death in PD.

Hypertrophy of IMC of carotid artery in Parkinson's disease is associated with L-DOPA, homocysteine, and MTHFR genotype.

In recent years, an intense interest has developed in the association between Parkinson's disease (PD) and hyperhomocysteinemia. Homocysteine (Hcy) is a neuronal excitotoxic amino acid, and is well known as a risk factor for vascular diseases. Some reports suggest that the administration of L-DOPA may promote hyperhomocysteinemia and idiopathic atherosclerosis. In this study, we report that a mild hypertrophy of the intima-media complex (IMC) of the carotid artery, which has been established as a marker for systemic atherosclerosis, is observed in PD patients compared with normal subjects. PD patients that were treated with L-DOPA for long durations showed a hypertrophic IMC, while the patients that were not treated with L-DOPA did not show any hypertrophic changes in the IMC. These hypertrophic changes were observed primarily in patients with a Hoehn-Yahr stage of 3-5. PD patients with hypertrophic IMC of the carotid artery also exhibited elevated plasma levels of Hcy associated with the C677T genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR). Moreover, a prolonged duration of treatment with L-DOPA in patients with MTHFR T/T genotype enhanced the hypertrophy of IMC, compared with patients with the C/C or C/T genotype. These results suggest that hyperhomocysteinemia promoted by the C677T genotype of MTHFR and prolonged treatment with L-DOPA enhances atherosclerosis in PD patients and affects their general condition.

[A case of non-paralytic pontine exotropia with vertical dissociated nystagmus in the contralateral eye].

We report a 74-year-old woman presenting non-paralytic pontine exotropia (NPPE) with vertical monocular nystagmus in her contralateral eye, due to a small infarction in the upper pons. On forward gaze, the ocular position of the right eye was fixed at the midline, while the left eye was abducted. On the leftward gaze, the left eye was abducted and monocular nystagmus was noted, but the right eye was not able to pass midline, which indicated NPPE. Neither a skew deviation nor an alternating exotropia was observed. In the acute phase of this case, disturbances in the vertical eye movement of her right eye and the monocular upper gaze-evoked nystagmus of her left eye were observed. On the 7th hospital day, the monocular nystagmus disappeared simultaneously with an improvement of vertical eye movement. This finding suggests that the patient's vertical monocular nystagmus occurred due to an adaptive increase in the innervation to the left eye according to Hering's law of equal innervation, which indicates either horizontal dissociated nystagmus in MLF syndrome or NPPE.

Obesity, bone status and dietary intake of Palauan elderly congregating in a Senior Citizen's Center.

A health survey of obesity and bone density measured by an Achilles Ultrasound bone densitometer (Lunar, USA) and nutritional intake was carried out for 15 male and 30 female Palauan elderly persons congregating in a Senior Citizens' Center. The subjects had high obesity values with mean BMI of 27.0 in males and 28.9 in females, and with mean body fat % of 22.3 in males and 39.8 in females (p < 0.01). The females showed a great decline in bone density from 60 to 70 years of age, with mean Stiffness index of 65.0 compared with that of 80.0 for males of the same age group. The subjects have all undergone a certain acculturation in their dietary habits, influenced by traditional Palauan, East-Asian, and Western food and dietary patterns. While all subjects had high carbohydrate intakes, and males had significantly greater intakes of energy, protein, calcium, phosphorus, iron, vitamin B1 and niacin than females. To determine the association of nutritional intake with obesity and Stiffness index, principal component analysis was carried out for amounts of intake of each food group. Correlation analysis between the scores of each principal food component and the body fat %, the BMI and the stiffness index was done. The score of the fourth principal component named "greater variety of food intake" was found to have significant positive correlation with body fat %. However, between the nutritional intake and body fat %, only a relationship could be identified. The findings indicate a need develop appropriate nutrition education and, particularly to address the problem of obesity.

Detecçäo de termonuclease de estafilocócica em leite através de método rápido e barato / A rapid and low cost adaptation of staphylococal tnase detection in milk

Resumo: Um método visndo detecçäo direta de termonuclease (TNase) em leite foi desenvolvido, coma finalidade de triagem de alimentos contaminados com estafilococos enterotoxigênicos. A substituiçäo de soroalbumina bovina (BSA) do tampäo tris por proteose peptona número 3 concedeu melhor proteçäo à TNase em caldo BHI e leite ontaminado com estafilococos enterotoxigênicos, embora seja inferior ao método de preciptaçäo com tricloroacético seguida de centrifugaçäo. estas modificaçöes poderäo ser úteis em condiçöes onde existem dificuldades referentes à disponibilidade de BSA e centrifugaçäo a alta rotaçäo para detecçäo direta de TNase estafilocócica em alimentos (au)

Aflatoxicose em cunicultura de Londrina, PR / Aflatoxicosis in rabit farm in Londrina, Paraná, Brazil

Resumo: No período de dezembro de 1986 a abril de 1987,a ocorrência de aflatoxicose casou a morte de 560 coelhos na regiäo de Londrina - PR. PAra a diagnose do problema foram analisadoas 6 amostras de raçäo coletadas em diferentes propriedades. A presença de aflatoxina B1, foi detectada em uma amostra de triguilho na concentraçäo de 33 ugKg, duas amostras de raçäo granulada na concentraçäo de 110 e 44 ugKg, e a contagem total de bolores foi de 8,2 x 10(elevado a +6); 2,8 x 10(elevado a +6) e 8,0 x 10(elevado a +3) UFC/G, respectivamente. Na amostra de triguilho predominou Aspergillus flavuis com 6,7 x 10(elevado a +6) UFC/G, enquanto que nas amostras de raçäo granulada, indica que o tratamento térmico pode ter eliminado o fungo, mas näo inativou a toxina (au)