Serum adiponectin is decreased in patients with familial combined hyperlipidemia and normolipaemic relatives and is influenced by lipid-lowering treatment.

BACKGROUND AND AIMS: Hypoadiponectinemia has been reported in patients with familial combined hyperlipidemia (FCHL) presenting increased waist circumference and insulin resistance. However, no studies have evaluated this association in non-obese FCHL patients. Moreover, it is unclear whether correction of lipoprotein abnormalities may influence adiponectin levels in FCHL. METHODS AND RESULTS: We have compared serum levels of adiponectin in 199 non-obese FCHL patients (BMI 25.96+/-3.7), 116 normolipaemic (NL) non-affected relatives (BMI 24.4+/-4.0) and 192 controls (BMI 28.0+/-7.4). In a subgroup of FCHL patients, changes in adiponectin levels after treatment with atorvastatin (n=22) or fenofibrate (n=26) were also evaluated. FCHL patients as well as their NL relatives showed lower serum adiponectin levels compared to controls (9.7+/-5.4 microg/mL, 10.7+/-5.3 microg/mL and 17.3+/-13.7microg/mL, respectively; p<0.0001 for all comparisons). After controlling for confounders, the strongest association with hypoadiponectinemia was observed with family history of FCHL, followed by HDL-C (negatively) and age (positively). These variables jointly explained 15% of the total variance of serum adiponectin levels. After 24-week of treatment, adiponectin was increased by 12.5% (p<0.05) by atorvastatin and was reduced by 10% by fenofibrate, resulting in a treatment difference of 22.5% in favor of atorvastatin (p<0.017). CONCLUSIONS: FCHL patients showed lower serum adiponectin levels compared to controls. Also normolipaemic relatives of FCHL patients presented decreased levels of adiponectin, suggesting a possible common background in the determination of this abnormality. Overall, these observations indicate that hypoadiponectinemia may be an inherent characteristic of the FCHL phenotype. In FCHL patients hypoadiponectinemia may be partially corrected by atorvastatin but not by fenofibrate treatment.

Myeloperoxidase overexpression in children with hypercholesterolemia.

BACKGROUND: Studies conducted in healthy children showed that biomarkers of oxidative stress decreased with increasing age from 1 to 11 years. No data have been reported concerning the behavior of age-related oxidative stress in hypercholesterolemic children. OBJECTIVE: Aim of this study was to test if children with hypercholesterolemia have prolonged exposure to enhanced oxidative stress and to study the underlying mechanism. METHODS: We performed a cross-sectional study comparing 8-hydroxy-2'deoxyguanosine, oxidized-LDL and myeloperoxidase plasma levels in 95 normocholesterolemic and 95 hypercholesterolemic children. RESULTS: Compared to normocholesterolemic children, those with hypercholesterolemia had higher 8-hydroxy-2'deoxyguanosine, oxidized-LDL and myeloperoxidase plasma levels. A correlation analysis of the overall population showed that total cholesterol was directly correlated with 8-hydroxy-2'deoxyguanosine, oxidized-LDL and myeloperoxidase. Stepwise linear regression showed that only total cholesterol, 8-hydroxy-2'deoxyguanosine and myeloperoxidase levels predicted oxidized-LDL plasma levels. In normocholesterolemic children oxidized-LDL and myeloperoxidase plasma levels significantly decreased from first (1-5 years) to second (6-9 years) quartile of age. In hypercholesterolemic children 8-hydroxy-2'deoxyguanosine, oxidized-LDL and myeloperoxidase plasma levels did not show significant differences among quartiles of age. CONCLUSION: This study shows that an early and persistent oxidative stress is detected in hypercholesterolemic children and that myeloperoxidase up-regulation might play a role.

Two thrush species as dispersers of Miconia prasina (Sw.) DC. (Melastomataceae): an experimental approach.

We carried out a seed germination experiment using two thrush species in captivity. We compared the number of germinated seeds and germination time of control seeds (manually removed from fruits) and ingested seeds of Miconia prasina by two bird species, Turdus albicollis and T. amaurochalinus, and also compared retention times of seeds by both thrush species. Control seeds germinated more frequently than those ingested for one species, T. albicollis. The germination time of ingested seeds by T. amaurochalinus was similar to the control seeds but seeds ingested by T. albicollis took longer to germinate than the controls. Both thrush species had a similar seed defecation pattern. The cumulative number of defecated seeds increased by 2 hours after fruit ingestion. At the end of the first 30 minutes both species had already defecated approximately 50% of the seeds ingested Our results suggest that both species could act as disperser agents of M. prasina.

Two thrush species as dispersers of Miconia prasina (Sw.) DC. (Melastomataceae): an experimental approach / Duas espécies de Turdus como dispersoras de Miconia prasina (Melastomataceae): uma abordagem experimental

We carried out a seed germination experiment using two thrush species in captivity. We compared the number of germinated seeds and germination time of control seeds (manually removed from fruits) and ingested seeds of Miconia prasina by two bird species, Turdus albicollis and T. amaurochalinus, and also compared retention times of seeds by both thrush species. Control seeds germinated more frequently than those ingested for one species, T. albicollis. The germination time of ingested seeds by T. amaurochalinus was similar to the control seeds but seeds ingested by T. albicollis took longer to germinate than the controls. Both thrush species had a similar seed defecation pattern. The cumulative number of defecated seeds increased by 2 hours after fruit ingestion. At the end of the first 30 minutes both species had already defecated approximately 50 percent of the seeds ingested Our results suggest that both species could act as disperser agents of M. prasina.

Realizamos um experimento de germinação utilizando duas espécies de Turdus em cativeiro. Comparamos o número de sementes germinadas e o tempo de germinação entre sementes controle (manualmente removidas dos frutos) e ingeridas de Miconia prasina por duas espécies de aves, Turdus albicollis e T. amaurochalinus, e também comparamos o tempo de retenção das sementes pelas duas espécies de Turdus. Sementes controle germinaram com maior freqüência do que as ingeridas por uma das espécies, T. albicollis. O tempo de germinação das sementes ingeridas por T. amaurochalinus foi semelhante ao das sementes controle, mas as sementes ingeridas por T. albicollis demoraram mais para germinar do que as sementes controle. Ambas as espécies de Turdus tiveram um padrão similar de defecação das sementes. O número acumulado de sementes defecadas aumentou por 2 horas após a ingestão dos frutos. Ao final dos primeiros 30 minutos ambas espécies já haviam defecado aproximadamente 50 por cento das sementes ingeridas Nossos resultados sugerem que as duas espécies de aves podem atuar como agentes dispersores de sementes de M. prasina.

Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis.

OBJECTIVES: The present study was planned to investigate the relationship between the plasma lipid profile and disease activity in patients with a first clinical episode suggestive of multiple sclerosis (MS). MATERIAL AND METHODS: Eighteen consecutive out-patients underwent a monthly brain magnetic resonance imaging (MRI), blood sample and neurological assessment over 6 months. Blood samples were used to evaluate total cholesterol and triglyceride levels as well as their lipoprotein fractions. Plasma total apolipoprotein E concentration was also determined. RESULTS: We found a significant correlation between the mean number of enhancing lesions and the mean plasma level of both total and low density lipoprotein cholesterol. The total plasma cholesterol level increased on average by 4.4 mg/dl for each enhancing lesion. CONCLUSION: Our preliminary data suggest a potential role of plasma cholesterol level as a biological marker of disease activity after a first demyelinating event. Further studies need, however, to be designed to determine whether the plasma cholesterol level is of practical use in monitoring the disease course.

Dieta cetogénica: fundamentos y resultados / The ketogenic diet: basics and results

Alrededor de un tercio de los pacientes con epilepsia no controlan satisfactoriamente las crisis, a pesar de recibir un tratamiento farmacológico adecuado. La dieta cetogénica (DC) se ha utilizado en el tratamiento de las epilepsias refractarias, sobre todo en niños, desde 1920. Su empleo cayó en desuso con la aparición de los fármacos anticomiciales hasta recientemente. Consiste, de manera esencial, en una dieta rica, en grasas y pobre en hidratos de carbono y proteínas, que se traduce en la aparición de cetosis y un mejor control de las crisis. Se desconoce el mecanismo último de acción de la dieta, aunque la mayoría de hipótesis indican la modificación del metabolismo cerebral, que varía de estar basado en la glucosa a depender de los cuerpos cetónicos. Las tres variantes más conocidas de la dieta se apoyan en este principio: la dieta cetogénica clásica, la más utilizada, proporciona 1 g de hidratos de carbono + proteínas por cada 3, 4 ó 5 g de grasa; la dieta con triglicéridos de cadena media (TCM) incorpora grandes cantidades de estos aceites y es peor tolerada, y la dieta cetogénica combinada, con TCM, consiste en el 30 por ciento del aporte energético como TCM, el 41 por ciento como rasas de la dieta el 10 por ciento proteínas y el 19 por ciento hidratos de carbono. Esta última es la empleada en nuestro Centro. Las complicaciones asociadas al uso de la dieta son, por lo general, de pequeña magnitud y bien toleradas. La instauración de la dieta ha de hacerse con el paciente ingresado y con la estrecha supervisión del dietista, que ajustará la dieta a las particularidades de cada niño, al mismo tiempo que educará a los padres en el control de la dieta y en la prevención de complicaciones. Desde 1998, 15 niños (7 niños y 8 niñas) con una mediana de edad de 3 años y medio (rango: 18 meses-9 años) han recibido la dieta. Todos nuestros pacientes habían sido diagnosticados de síndrome de Lennox-Gastaut; 7 de ellos con retraso mental profundo. A los 6 mese de iniciada la dieta, la mitad de los niños presentó una reducción en el número diario de crisis igual o superior al 50 por ciento. La mitad de ellos no tenía ninguna crisis o alguna muy ocasional. Tras 2 años, la mitad de los pacientes continuaba con la dieta, con una reducción en el número diario de crisis >90 por ciento. La dieta fue bien tolerada en todos los casos, manteniendo cetonuria superior a dos cruces en la mayoría de pacientes. Sólo se observaron efectos adversos. Conclusiones: La dieta cetogénica, generalmente en combinación con fármacos antiepilépticos, es eficaz en el control de la epilepsia refractaria de la infancia, sobre todo en pacientes diagnosticados de síndrome de Lennox-Gastaut. Hasta el 50 por ciento de los que comenzaron la dieta mantenía un buen control de las crisis al cabo de 2 años de tratamiento con la dieta. Su excelente tolerancia y los escasos efectos adversos animan al empleo de la dieta en los casos de difícil control (AU)

Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by intramuscular injection of plasmid DNA.

We report on systemic delivery and long-term biological effects of apolipoprotein E (apoE) obtained by intramuscular (i.m.) plasmid DNA injection. ApoE plays an important role in lipoprotein catabolism and apoE knock-out mice develop severe hypercholesterolemia and diffuse atherosclerosis. We have injected apoE-deficient mice with 80 microg of a plasmid vector (pCMV-E3) encoding the human apoE3 cDNA under the control of the CMV promoter-enhancer in both posterior legs. Local expression of the transgene was demonstrated throughout 16 weeks. Human apoE3 recombinant protein reached 0.6 ng/ml serum level. After i.m. injection of pCMV-E3 expression vector the mean serum cholesterol concentrations decreased from 439 +/- 57 mg/dl to 253 +/- 99 mg/dl (P < 0.05) 2 weeks after injection and persisted at a significantly reduced level throughout the 16 weeks observation period (P < 0.005). Serum cholesterol was unaffected and reached an absolute level of 636 +/- 67 mg/dl in control groups. Finally, injection of pCMV-E3 into apoE-deficient mice resulted in a redistribution of cholesterol content between lipoprotein fractions, with a marked decrease in VLDL, IDL and LDL cholesterol content and an increase in HDL cholesterol. These results demonstrate that severe hypercholesterolemia in apoE-deficient mice can be effectively reversed by i.m. DNA injection, and indicate that this approach could represent a useful tool to correct several hyperlipidemic conditions resulting in atherosclerosis.

Identification of aminoethylcysteine ketimine decarboxylated dimer in human plasma.

Aminoethylcysteine ketimine decarboxylated dimer (AECK-DD) is a natural sulfur-containing tricyclic compound detected, until now, in human urine and bovine cerebellum. Recently, the antioxidant properties of this compound, and particularly its protective effect on the in vitro oxidation of low-density lipoproteins, have been demonstrated. In this paper, the identification of AECK-DD in human plasma by means of gas chromatography, high-performance liquid chromatography and gas chromatography-mass spectrometry, performed after a simple and fast purification procedure, is reported.

Simultaneous high-performance liquid chromatographic determination of adenosine and dopamine in rat striatal tissue with combined ultraviolet absorbance and electrochemical detection.

A method is described for the simultaneous determination of biogenic amines, adenosine and their metabolites in rat striatal tissue using high-performance liquid chromatography with ultraviolet spectrophotometric and electrochemical detection. Peaks in the chromatograms of striatal tissue extracts were identified by retention times and by on-line analysis of peak spectra for adenosine and its metabolites, and by comparing current ratios of the dual-electrode coulometric detector for monoamines and metabolites. The assay gives a linear response over the concentration range of 0.15-0.60 micrograms/ml for biogenic amines, 0.5-2.0 micrograms/ml for serotonin, 5-20 micrograms/ml for hypoxanthine, adenosine and N-methyladenosine, and 10-40 micrograms/ml for inosine. The limit of detection for striatal homogenates was 3.5 ng/g for monoamines, 9 ng/g for serotonine, 140 ng/g for hypoxanthine, 290 ng/g for inosine and 80 ng/g for adenosine. The recovery ranged from 88.5% for vanillylmandelic acid to 110.3% for dopamine. The method was used to measure biogenic amines, adenosine and related metabolites in rat striatal tissues.

Effects of hypobaric hypoxia on the middle-latency and steady-state auditory evoked potentials.

The aim of the present paper was the investigation of middle-latency responses (MLRs) and steady-state responses (SSRs) during and after a 30-min exposure to hypobaric hypoxia (5182 m above sea level). The test was performed in a hypobaric chamber on 8 male audiologically normal volunteers. The auditory stimulus (500-Hz tone burst), delivered at rates of 10 and 40/s for MLRs and SSRs, respectively, was recalibrated in the hypobaric condition because of the reduced air density. Absolute latencies of waves Na and Pa and their interpeak amplitude were the MLR parameters investigated; for the SSRs, the first positive wave (P1) absolute latency and the interpeak amplitude between P1 and the first negative wave (N1) were considered. The results showed an absence of statistically significant modification of the MLRs. On the contrary, the SSRs showed a significant (p < 0.025) latency increase during hypoxia, with an immediate recovery upon return to ground level. No significant changes of SSR amplitudes were observed. One possible data interpretation is related to the higher stimulation rate adopted for the SSRs; a second possibility could be a different electrogenesis between MLRs and SSRs.

Abdominal colpopexy for complete prolapse of the vagina.

A comparative study of abdominal colpopexy using rectus fascia and sacral fixation for the treatment of prolapsed vagina following hysterectomy was performed. The abdominal approach yields better results than the vaginal route. Fixation of the vaginal vault using a Dacron prosthesis is more rational and was the method of choice, resulting in a complete cure in 10 of 11 patients. The Brady technique failed in 25% of cases.

Uso do piroxicam injetável em cirurgia bucomaxilofacial / Use of piroxicam in bucomaxilofacial surgery

Os autores conduziram um estudo aberto, näo comparativo, sobre o uso do Piroxicam intramuscular como analgésico e antiinflamatório no pós-operatório de cirurgia para a remoçäo de terceiros molares inclusos. Vinte e cinco pacientes submetidos à cirurgia receberam após as mesmas, a partir do momento em que acusavam dor intensa ou moderada, 40 mg da droga, por via intramuscular, repetidos 24 horas depois. A forma injetável foi administrada por um período máximo de dois dias, sendo substituída, se necessário, pela forma supositório, do terceiro ao quinto dia. Os pacientes foram avaliados quanto aos seguintes parâmetros: dor expontânea, intensidade da dor, seu alívio com a medicaçäo , edema e temperatura corporal, segundo intervalos predeterminados. Nenhum paciente apresentou reaçöes adversas durante o estudo. Os autores notaram uma significativa diminuiçäo da dor e do edema no pós-operatório

A form of familial hypobetalipoproteinaemia not due to a mutation in the apolipoprotein B gene.

Familial hypobetalipoproteinaemia (FHBL) is a dominant disorder of lipoprotein metabolism characterized by levels of apolipoprotein B-carrying lipoproteins (VLDL, IDL and LDL) which are 50% of the normal levels in the heterozygotes and almost absent in the homozygotes. Several reports have recently shown that the underlying defect in FHBL involves different mutations in the apo B gene which lead to reduced levels of apo B mRNA or to the production of truncated forms of apo B having either a lower synthetic rate or a higher catabolic rate than normal apo B. We here present a three-generation family with several FHBL members in which the linkage analysis shows absence of co-segregation between apo B gene alleles and the hypocholesterolaemic phenotype. We conclude that a dominantly transmitted mutation in a gene other than that for apo B is responsible for the low plasma cholesterol levels.

Variation at the apolipoprotein (apo) AI-CIII-AIV gene cluster and apo B gene loci is associated with lipoprotein and apolipoprotein levels in Italian children.

We have used RFLPs of the apolipoprotein (apo) B gene and apo AI-CIII-AIV gene cluster to estimate the genetic contribution of variation at these loci to the variability of plasmid lipid, lipoprotein, and apolipoprotein levels in 209 children from Sezze in central Italy. The sample was randomly divided into group I (107 children) and group II (102 children). Four site polymorphisms (PvuII, XbaI, MspI, and EcoRI) of the apo B gene and five site polymorphisms (XmnI, PstI, SstI, PvuII-CIII, and PvuII-AIV) of the apo AI-CIII-AIV gene cluster were examined in group I children. After adjustment for gender, age, and body-mass index, polymorphisms at both gene loci (PvuII-B, PvuII-CIII, and PvuII-AIV) were associated with significant effects on the levels of plasma apo AI, apo B, or high-density lipoprotein-cholesterol. RFLPs that showed significant effects in group I were genotyped in group II. All three polymorphisms were associated with similar effects on apolipoprotein levels, though for all RFLPs the magnitude of the effects was smaller in the group II children and only statistically significant for the effect of the PvuII-B genotype on apo AI levels. In the total sample of 209 children 7.4% of the sample variance in apo AI levels was explained by variation associated with the apo B PvuII-B RFLP. In addition, the PvuII-B RFLP was associated with significant effects on plasma apo B levels and explained 5.7% of the sample variance. The PvuII-CIII and PvuII-AIV polymorphisms were both associated with differences in apo AI levels, explaining 3.7%-5.7% of the sample variance. Taken together, the three PvuII polymorphisms explained 17.7% of the phenotypic variance in apo AI levels. There was significant evidence for an effect of nonlinearity of the PvuII-CIII genotypes on apo AI levels, with the individuals heterozygous for the polymorphism having the highest apo AI levels. No evidence of interaction between genotype and gender, age, and body-mass index was shown by covariance analysis. The molecular explanation of this effect is unclear. Our data show that variation at both the apo AI-CIII-AIV and apo B loci are associated with lipoprotein and apolipoprotein levels in this sample of Italian children.

Serum lipoprotein pattern variations in dementia and ischemic stroke.

Blood levels of triglycerides, total cholesterol, isolated lipoprotein fractions (VLDL-LDL- and HDL-cholesterol) and apoproteins (Apo-A1 and Apo-B) were examined in multi-infarct dementia, senile dementia of the Alzheimer type, ischemic stroke associated with carotid atherosclerosis and in control subjects. Forty patients divided into 10 consecutive patients for each group were studied. Alzheimer patients showed mean total cholesterol and Apo-B values significantly higher than control subjects. Apo-B was significantly higher in stroke patients than in controls. The mean lowest HDL-cholesterol (HDL-c) value was observed in stroke patients. No significant differences in mean HDL-c levels were found between patients with multi-infarct and Alzheimer dementia.

[Oncocytoma of the kidney: a diagnostic and therapeutic dilemma]. / Oncocitoma renale: un dilemma diagnostico e terapeutico.

Renal oncocytic tumours are uncommon and controversial in both their diagnosis and therapy. The need for correct cytological diagnosis is emphasised and total nephrectomy proposed as the elective surgical treatment owing to the real possibility of malignancy and multicentric diffusion. Conservative management should be reserved for bilateral tumours or where the tumour occurs in a solitary kidney.