Mitochondrial DNA Copy Number Drives the Penetrance of Acute Intermittent Porphyria.

No published study has investigated the mitochondrial count in patients suffering from acute intermittent porphyria (AIP). In order to determine whether mitochondrial content can influence the pathogenesis of porphyria, we measured the mitochondrial DNA (mtDNA) copy number in the peripheral blood cells of 34 patients and 37 healthy individuals. We found that all AIP patients had a low number of mitochondria, likely as a result of a protective mechanism against an inherited heme synthesis deficiency. Furthermore, we identified a close correlation between disease penetrance and decreases in the mitochondrial content and serum levels of PERM1, a marker of mitochondrial biogenesis. In a healthy individual, mitochondrial count is usually modulated to fit its ability to respond to various environmental stressors and bioenergetic demands. In AIP patients, coincidentally, the phenotype only manifests in response to endogenous and exogenous triggers factors. Therefore, these new findings suggest that a deficiency in mitochondrial proliferation could affect the individual responsiveness to stimuli, providing a new explanation for the variability in the clinical manifestations of porphyria. However, the metabolic and/or genetic factors responsible for this impairment remain to be identified. In conclusion, both mtDNA copy number per cell and mitochondrial biogenesis seem to play a role in either inhibiting or promoting disease expression. They could serve as two novel biomarkers for porphyria.

KlMID1, a relevant key player between endoplasmic reticulum homeostasis and mitochondrial dysfunction in Kluyveromyces lactis.

The interplay between calcium metabolism and glycosylation in yeast is largely unknown. In order to clarify this relationship, the effect of a mutation in the KlOCH1 gene, encoding the Golgi α-1,6-mannosyltransferase, on calcium homeostasis was studied in the yeast Kluyveromyces lactis. In particular, the role of the KlMID1 gene, encoding one of the components of the plasma membrane calcium channel (Cch1-Mid1), was investigated. Almost complete suppression of the phenotypes occurring in the mutant strain, ranging from oxidative stress to cell wall alteration, was observed by increased dosage of KlMID1. In addition, the N-glycosylation mutant showed increased calcium accumulation and decreased transcription of KlMID1 and KlCCH1. Moreover, the calcium alterations included an increased expressional profile for the KlPMC1 gene, encoding the vacuolar calcium ion pump. Furthermore, perturbation of endoplasmic reticulum (ER) homeostasis was observed in Kloch1-1 cells. Similarly, down-modulation of calcium signalling genes as well as altered mitochondrial functionality were induced in wild-type cells after treatment with DTT. However, no mitochondrial alteration occurred in the treated cells when KlMID1 was overexpressed. Our results suggest that the ER stress taking place in Kloch1-1 cells appears to be the primary cause of the KlMID1 down-modulation and its resulting effects on the expression of calcium homeostasis genes.

[Cardiovascular risk factors among 7-and 14-year old schoolchildren in Cartagena, Colombia, 2009]. / Factores de riesgo cardiovascular en escolares entre 7 y 14 años en Cartagena, Colombia, 2009.

OBJECTIVE: Identifying family history, dyslipidaemia, hyperglycaemia, low physical activity and being overweight or suffering from obesity as cardiovascular risk factors in children aged 7 to 14 years in Cartagena, 2009. MATERIALS AND METHODS: A descriptive study of 173 children from Cartagena, Colombia, was designed. Biochemical serum parameters were determined by spectrophotometric methods. Habits were investigated through interviews and altered body weight was established using the body mass index (BMI). RESULTS: The sample consisted of 87 girls and 86 boys, and mean age was 9.9 years (9.6-10.3, 95 % CI). 75.1% (68.7-81.5, 95 % CI) had a family history of being overweight; 2.3 % (0.1-4.5, 95 % CI) were overweight and 1.7 % (0.0-3.6 95 %CI) were obese. More than half of the children had hightotal cholesterol levels (53.2 %; 45.8-60.695 %CI) and LDL (57.2 %; 49.8-64.6 95 % CI). Non-HDL cholesterol was found to be increased by 46.8 % (39.4-54.2 95 % CI). There was a significant difference between genders for triglyceridemia (females: 94.1 mg/dL; 87.0-101.2 mg/dL 95 % CI; males: 81.7 mg/dL; 75.0-88.5 mg/dL 95 % CI; p=0.005) and low physical activity (females: 83.8 %; 73.5-94.5 % 95 % CI; males: 44.2 %; 45.4-66.6 % 95 % CI; p=0,0001). CONCLUSIONS: Cardiovascular risk factors in these schoolchildren, even in those who were not obese, justify the need for the early detection of these factors as well as their strict controlto reduce their impact on people's future quality of life.

Factores de riesgo cardiovascular en escolares entre 7 y 14 años en Cartagena, Colombia, 2009 / Cardiovascular risk factors among 7-and 14-year old schoolchildren in Cartagena, Colombia, 2009

Objetivo Identificar antecedentes familiares, dislipidemias, hiperglucemia, escasa actividad física y sobrepeso u obesidad como factores de riesgo cardiovascular en niños entre 7 y 14 años de Cartagena, 2009. Materiales y Métodos Se realizó un estudio descriptivo en 173 niños de Cartagena, Colombia. Se determinaron los parámetros bioquímicos en suero mediante técnicas espectrofotométricas. Los hábitos fueron indagados mediante entrevista y las alteraciones de peso fueron establecidas utilizando el índice de masa corporal. Resultados La muestra quedó conformada por 87 niñas y 86 niños con edad promedio de 9,9 años (IC95 por ciento 9,6-10,3). El 75,1 por ciento (IC95 por ciento 68,7-81.5) presentaron antecedentes familiares; 2,3 por ciento (IC95 por ciento 0,1-4,5) tuvieron sobrepeso y 1,7 por ciento (IC95 por ciento 0,0-3,6) obesidad. Más de la mitad de los niños presentaron niveles elevados de colesterol total (53,2 por ciento; IC95 por ciento 45,8-60,6) y LDL (57,2 por ciento; IC95 por ciento 49,8-64,6). El colesterol no HDL se halló incrementado en el 46,8 por ciento (IC95 por ciento 39,4-54,2). Las niñas presentaron mayor concentración de triglicéridos (94,1 mg/dL; IC95 por ciento 93,0-95,2 mg/dL) que los niños (81,7 mg/dL; IC95 por ciento 80,6-82,8 mg/dL) con diferencia significativa (p=0,005) y también presentaron con mayor frecuencia baja actividad física (niñas: 83,8 por ciento; IC95 por ciento 73,5-94,5 por ciento; varones: 44,2 por ciento; IC95 por ciento 45,4-66,6; p=0,0001). Conclusión Los factores de riesgo cardiovascular presentes en esta población, inclusive en ausencia de obesidad, muestran la necesidad de implementar programas que los identifiquen e intervengan de manera oportuna para disminuir su impacto en la calidad de vida futura.

Objective Identifying family history, dyslipidaemia, hyperglycaemia, low physical activity and being overweight or suffering from obesity as cardiovascular risk factors in children aged 7 to 14 years in Cartagena, 2009. Materials and Methods A descriptive study of 173 children from Cartagena, Colombia, was designed. Biochemical serum parameters were determined by spectrophotometric methods. Habits were investigated through interviews and altered body weight was established using the body mass index (BMI). Results The sample consisted of 87 girls and 86 boys, and mean age was 9.9 years (9.6-10.3, 95 percent CI). 75.1 percent (68.7-81.5, 95 percent CI) had a family history of being overweight; 2.3 percent (0.1-4.5, 95 percent CI) were overweight and 1.7 percent (0.0-3.6 95 percentCI) were obese. More than half of the children had hightotal cholesterol levels (53.2 percent; 45.8-60.695 percentCI) and LDL (57.2 percent; 49.8-64.6 95 percent CI). Non-HDL cholesterol was found to be increased by 46.8 percent (39.4-54.2 95 percent CI). There was a significant difference between genders for triglyceridemia (females: 94.1 mg/dL; 87.0-101.2 mg/dL 95 percent CI; males: 81.7 mg/dL; 75.0-88.5 mg/dL 95 percent CI; p=0.005) and low physical activity (females: 83.8 percent; 73.5-94.5 percent 95 percent CI; males: 44.2 percent; 45.4-66.6 percent 95 percent CI; p=0,0001). Conclusions Cardiovascular risk factors in these schoolchildren, even in those who were not obese, justify the need for the early detection of these factors as well as their strict controlto reduce their impact on people's future quality of life.