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Biomedical subjects

S Bernasconi

Publications and source records attributed to S Bernasconi.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-6 and insulin-like growth factor system relationships and differences in the human placenta and fetus from the 35th week of gestation.

The integrity of the insulin-like growth factor (IGF) system is essential for normal fetal growth. Cytokine and IGF-IGFBP relationships have been shown in specific tissues, but it is unknown whether these occur in the placenta. We aimed to assess possible differences in the IGF system depending on gestational age (GA) from week 35 to 40, and to study relationships of IL-6 with components of the IGF system in the placenta and newborn infant. We followed 32 normal births and collected whole villous tissue and cord serum. Total RNA was extracted from the placenta samples, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins were assayed in placenta lysates and cord serum using specific commercial kits. Two groups of subjects (Group 1, 35-37 weeks GA, N=12 and Group 2, 38-40 weeks GA, N=20) were studied. In placenta, IGF-I mRNA was more abundant than IGF-II mRNA at all times and together with IGFBP-1mRNA were less expressed at term. IGFBP-2 and IL-6 mRNAs were higher after week 37 GA. IL-6 and IGFBP-2 gene expression were closely related. The corresponding proteins showed similar differences to the genes but IGF-I was undetectable in the lysates, whereas IGF-II was abundant. IGFBP-2 concentrations were very high and greater than those of IGFBP-1. In the newborn, no difference was seen in any cord serum protein after week 35 GA. IGFBP-1 was negatively correlated with parameters of neonatal size. In conclusion, this study reports new insights into IL-6, IGF-IGFBP relationships within the human placenta and shows the importance of comparing subjects with the same GA.

Adult↗
PubMed2006

High basal serum allopregnanolone levels in overweight girls.

OBJECTIVE: Several studies demonstrated that obese subjects have a hyperactive hypothalamic-pituitary-adrenal axis and that sex steroid hormones have been closely related to the regulation of adiposity, either through direct or indirect physiological mechanisms. Allopregnanolone (3alpha-hydroxy-5alpha-pregn-20-one; AP) is a circulating neuroactive steroid hormone involved in the modulation of behavioral functions, stress and neuroendocrine axis. The aim of our study was to evaluate basal serum AP levels in obese children. SUBJECTS AND MEASUREMENTS: We studied 27 normal weight (NW) and 23 overweight (OW) girls. Gonadotropins and steroid hormones were assessed in all patients. RESULTS: Basal AP concentrations in OW girls were significantly higher than in NW controls (P=0.013). There was no difference found between the other gonadal and adrenal hormones. Considering the pubertal stage, we demonstrated that obese pubertal girls presented higher AP concentrations than prepubertal and pubertal NW ones (P=0.020), and higher dehydroepiandrosterone sulfate (DHEAS) levels with respect to prepubertal obese girls, and prepubertal and pubertal NW patients (P=0.025). AP and DHEAS were significantly directly related to weight (r=0.31 and r=0.54, respectively) and body mass index (r=0.29 and r=0.34, respectively). In pubertal OW girls, a significant positive correlation between AP and DHEAS (r=0.60), A (r=0.72) and luteinizing hormone (r=0.64) levels was demonstrated. CONCLUSION: The present study demonstrates that AP is hypersecreted in children and adolescent with OW involving DHEAS concentrations, too. Our data suggest a possible role of AP in the regulation of neuroendocrine axis related to obesity. We can also speculate that in OW girls, who could manifest emotional and behavioral problems, a part of higher levels of this neuroactive steroid might act as gamma-aminobutyric acid agonist producing anxiolytic-sedative effects.

17-alpha-Hydroxyprogesterone↗
PubMed2006

Dioxygenation of naphthalene by Pseudomonas fluorescens N3 dioxygenase: optimization of the process parameters.

The bioconversion of naphthalene to the 1,2-dihydro-1,2-dihydroxy derivative was performed in good yield using an Escherichia coli recombinant strain carrying Pseudomonas fluorescens N3 dioxygenase. However, the efficiency of such transformation is affected by many process parameters, and their optimization is essential to the scaling up of the process. The following process parameters were considered for optimization: cell concentration together with the corresponding glucose concentration (DCW/L); pH of medium; temperature; stirring speed; air flow; substrate concentration; Fe(2+) concentration; microelements concentration; reaction volume. We used a two-step multivariate experimental design to select important variables and assign them optimal values. The most significant parameters were selected by adopting a Plackett-Burman design, and were then correlated, using a full factorial design, with the experimental results. The experimental results illustrate that the optimized process of recombinant whole cell biotransformation in two-liquid phase systems enhances the naphthalene dihydrodiol yield threefold. This biotransformation opens the way to future experiments involving different substrates.

Bacterial Proteins↗
PubMed2006

Idiopathic thrombocytopenic purpura (ITP) in the elderly: clinical course in 178 patients.

Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly (age >or=65 yr), where it generally presents as a chronic disease. The objective of the present study was to describe the natural history of ITP in the elderly and to evaluate the risk of bleeding and the possible occurrence of other pathologies. We retrospectively evaluated 178 ITP patients (82 men, 96 women; mean age: 72 yr) diagnosed between 1981 and 1998. Therapy was started at diagnosis or during follow-up, depending on the platelet count and/or bleeding events. Sixty-six out of one hundred and seventy-eight patients (37%) initiated therapy at diagnosis; whereas in 11 of the 112 untreated patients (9.8%) therapy was necessary during the follow-up. Low-dose of prednisone was the first-line treatment in all patients (mean daily dose of 0.43 mg/kg). Forty-nine (63.6%) of the seventy-seven treated patients showed a response, 14 of these (28.6%) suffered a relapse. Another pathology occurred in 19 of the 178 patients (10.7%). We conclude that low-dose prednisone is an appropriate initial treatment for elderly persons. We also stress that an adequate follow-up is advisable, given that isolated thrombocytopenia could in some cases be the first sign of another underlying pathology.

Aged↗
PubMed2006

Decreased androgen receptor gene methylation in premature pubarche: a novel pathogenetic mechanism?

CONTEXT: Several studies found links between DNA methylation and gene expression. In patients with idiopathic hirsutism, a preferential methylation of the of shorter androgen receptor (AR) alleles was hypothesized to be responsible for the abnormal hair growth. OBJECTIVE: The objective of this study was to assess whether abnormalities in the AR function in both peripheral blood leukocytes (PBLs) and androgen target tissues are present in children with premature pubarche (PP). DESIGN: Human DNA was extracted from PBLs and pubic hair and CAG repeats length and methylation status of the AR gene were analyzed. SETTING: The study was performed at a Pediatric Endocrinology referral clinic. PATIENTS: Twenty-five girls with PP, 23 prepubertal children, and 10 girls with Tanner stage II pubertal development were studied. MAIN OUTCOME MEASURE: The main outcome measures were CAG repeat length and AR methylation pattern in PBLs and pubic hair. RESULTS: In PBLs from PP patients, AR gene methylation was significantly lower (P < 0.01) than that of prepubertal children and similar to that of girls with Tanner II stage pubertal development. A negative correlation between AR gene methylation in PBLs and the age of normal children was detected. PATIENTS with PP exhibited a hair follicle AR methylation pattern similar to that of Tanner stage II girls. The mean number of CAG repeats was lower in PP patients than in prepubertal and Tanner stage II girls, although it was within the normal range for the general population in both groups. CONCLUSIONS: The increased AR gene activity observed in PP patients, as indicated by the reduced AR gene methylation pattern, together with the presence of shorter CAG repeats, might lead to hypersensitivity of the hair follicles to steroid hormones and therefore to the premature development of pubic hair.

Child↗
PubMed2006

Cryptogenic stroke in children: possible role of patent foramen ovale.

Stroke is a rare disorder in childhood. The majority of these cases is of an ischemic nature. In spite of the long list of known causes, many strokes remain undetermined, so-called cryptogenic strokes. Increasing evidence indicates that, in the young adults, many cases of cryptogenic stroke are presumably due to paradoxical embolism. In childhood, this is usually not considered, unless in the context of a complex cyanotic heart disease. We present two cases, a 6-year-old boy and an 11-year-old girl who had an episode of cerebral ischemia documented by MRI, and in whom the only anomaly found was a patent foramen ovale (PFO) with intermittent left to right shunt at rest, but with a large right to left shunt during the Valsalva maneuvre. We assumed that, in our cases, in the absence of identifiable causes, the cerebral ischemia was most likely due to paradoxical embolism through the PFO. Of course, as in the adult, the paradoxical embolism could not be proved, but in our opinion it remains the most concrete possibility. Therefore, in presence of a cryptogenic stroke, a PFO should be investigated also in children.

Child↗
PubMed2006

Aromatase is differentially expressed in peripheral blood leukocytes from children, and adult female and male subjects.

OBJECTIVE: Aromatase, the key enzyme involved in estrogen synthesis, is expressed in a variety of cells and tissues including human peripheral blood leukocytes (PBLs). The present study was designed to evaluate PBL aromatase gene expression in male and female subjects of different age groups. In addition, differences in gene expression during the follicular and luteal phase of the menstrual cycle in women, and before and after testosterone administration in men, were estimated. DESIGN: Aromatase mRNA and protein were measured in PBLs obtained from young (n = 10) and postmenopausal women (n = 10), men (n = 15), and prepubertal children (n = 10). Aromatase mRNA and protein were also measured during the follicular and luteal phases of the menstrual cycle in women, and before and after the intramuscular administration of 250 mg testosterone enanthate in men. METHODS AND RESULTS: Aromatase mRNA measured by real-time PCR in PBLs from women during the follicular phase was significantly higher than during the luteal phase of the menstrual cycle (P < 0.05). In men, PBL aromatase mRNA values increased significantly following testosterone administration (P < 0.05). PBL mRNA aromatase levels in women during the follicular phase and men after testosterone administration were significantly higher (one-way ANOVA; P < 0.05) than in any other group. Children, postmenopausal women, and women during the luteal phase showed the lowest aromatase mRNA expression. The results of the immunoblot analysis confirmed the data obtained by real-time PCR. A positive correlation between PBL aromatase mRNA values and plasma estradiol and estrone levels during the follicular phase of the menstrual cycle was observed in the group of adult women. No other correlations were found. CONCLUSIONS: The aromatase gene is differentially expressed in PBLs from women, men, and prepubertal children, indicating a sexual dimorphism in the enzyme expression and an important role of sex steroids in the modulation of aromatase gene expression.

Adult↗
PubMed2006

Menstrual disorders in adolescence.

Altered frequency of the menstrual cycle accompanied by pain are manifestations of functional anomalies of the female reproductive system. These symptoms require prompt and accurate diagnosis and therapy to prevent a chronic condition that can seriously disturb the adolescent's psychic well being. The most common anomalies of the menstrual cycle and the causes of altered cycle frequency are outlined, as are useful criteria for diagnosing premenstrual syndrome dysmenorrhea and for distinguishing the causes and alterations in frequency and amount of menstrual discharge from other disturbances, including amenorrhea and abnormal uterine bleeding. The treatment of dysmenorrhea and quantitative alterations of the menstrual cycle is the focus of this article.

Adolescent↗
PubMed2006

Geometry and bone density.

Bone development is a key process in the growing child. It is, therefore, of paramount importance to survey this process, which is characterized by increasing length and size of the bone together with its progressive mineralization. The bone status can be evaluated by different techniques, each of them having its pros and cons. Furthermore, it should be underlined that the results of bone assessment depend not only from the employed technique but also from the auxological characteristics of the subjects. It is, therefore, the aim of this review to examine the characteristics of the various methods of bone evaluation, such as dual energy X-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), ultrasound and metacarpal index and to explain how changes in bone structure and geometry may influence the results.

Absorptiometry, Photon↗
PubMed2005

Genitourinary anomalies in Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B). Report of three Italian cases with hypospadias and review.

Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1,000 male births. It is a complex disorder associated with genetic and environmental factors and can be part of genetic syndromes. Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation. It is caused by mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1). To date, 68 deletion/mutation-positive cases have been reported. Genitourinary anomalies are common in MWS. Here we report that hypospadias is common in males with this syndrome. In 39 patients where this information was available, hypospadias was present in 46% of patients (18/39). In the 3 Italian male cases reported here, hypospadias was always present. MWS should be considered by endocrinologists in patients with hypospadias associated with developmental delays/mental retardation, in particular in the presence of a distinct facial phenotype.

Child, Preschool↗
PubMed2004

Bacterial communities and enzyme activities of PAHs polluted soils.

Three soils (i.e. a Belgian soil, B-BT, a German soil, G, and an Italian agricultural soil, I-BT) with different properties and hydrocarbon-pollution history with regard to their potential to degrade phenanthrene were investigated. A chemical and microbiological evaluation of soils was done using measurements of routine chemical properties, bacterial counts and several enzyme activities. The three soils showed different levels of polycyclic aromatic hydrocarbons (PAHs), being their contamination strictly associated to their pollution history. High values of enzyme activities and culturable heterotrophic bacteria were detected in the soil with no or negligible presence of organic pollutants. Genetic diversity of soil samples and enrichment cultures was measured as bands on denaturing gradient gel electrophoresis (DGGE) of amplified 16S rDNA sequences from the soil and enrichment community DNAs. When analysed by Shannon index (H'), the highest genetic biodiversity (H'=2.87) was found in the Belgian soil B-BT with a medium-term exposition to PAHs and the poorest biodiversity (H'=0.85) in the German soil with a long-term exposition to alkanes and PAHs and where absence, or lower levels of enzyme activities were measured. For the Italian agricultural soil I-BT, containing negligible amounts of organic pollutants but the highest Cu content, a Shannon index=2.13 was found. The enrichment of four mixed cultures capable of degrading solid phenanthrene in batch liquid systems was also studied. Phenanthrene degradation rates in batch systems were culture-dependent, and simple (one-slope) and complex (two-slope) kinetic behaviours were observed. The presence of common bands of microbial species in the cultures and in the native soil DNA indicated that those strains could be potential in situ phenanthrene degraders. Consistent with this assumption are the decrease of PAH and phenanthrene contents of Belgian soil B-BT and the isolation of phenanthrene-degrading bacteria. From the fastest phenanthrene-degrading culture C(B-BT), representative strains were identified as Achromobacter xylosoxidans (100%), Methylobacterium sp. (99%), Rhizobium galegae (99%), Rhodococcus aetherovorans (100%), Stenotrophomonas acidaminiphila (100%), Alcaligenes sp. (99%) and Aquamicrobium defluvium (100%). DGGE-profiles of culture C(B-BT) showed bands attributable to Rhodococcus, Achromobacter, Methylobacterium rhizobium, Alcaligenes and Aquamicrobium. The isolation of Rhodococcus aetherovorans and Methylobacterium sp. can be consistent with the hypothesis that different phenanthrene-degrading strategies, cell surface properties, or the presence of xenobiotic-specific membrane carriers could play a role in the uptake/degradation of solid phenanthrene.

Bacteria↗
PubMed2004

Functional transfer of CD40L gene in human B-cell precursor ALL blasts by second-generation SIN lentivectors.

Three different second-generation lentiviral self-inactivating vectors containing CMV, EF1alpha and PGK promoter, respectively, and all carrying the exogenous GFP gene, were compared for expression in human B-cell precursor ALL blasts. At a comparable percentage of transduction and vector DNA copy number, CMV clearly showed better efficiency of transcription. Human bone marrow stromal cells were favored compared to the MRC-5 cell line, as support for cell viability during infection. Cells were infected and analyzed after variable culture times ranging from 4 to 12 days, to reduce the possibility of pseudotransduction. In 10/14 samples, we detected more than 20% GFP-positive cells after exposure to high-titer viral supernatants. We then tested a similar vector carrying the human CD40L cDNA and, in similar infection conditions, obtained more than 20% transduction in 6/6 samples. The levels of transduction obtained were sufficient to induce the upregulation of CD83 molecule in cocultured immature dendritic cells.

CD40 Ligand↗
PubMed2004

Bone mass evaluated by calcaneous ultrasound and radial peripheral computed tomography in 726 youngsters.

AIM: To compare the results of ultrasound and computed peripheral tomography in evaluating bone mass in a population of normal children. METHODS: Seven hundred and twenty-six healthy school children (260 males; age 8.3-20.9 y) underwent calcaneous ultrasound and peripheral computed tomography at the ultradistal radius. Broadband ultrasound attenuation (BUA) and areal and volumetric bone mineral density (aBMD and vBMD) were evaluated. The results were compared and correlated among them and with auxological parameters (height, BMI and pubertal stages) using the software package SPSS for Windows. RESULTS: The three variables examined (BUA, aBMD and vBMD) all showed a progressive increase with age and a positive correlation with age, height and BMI. When the population was subdivided according to pubertal stages, all variables showed a progressive increase, the difference being significant when stages 1-2 were compared with stages 4-5. A significant correlation was present among BUA, aBMD and vBMD even if the Pearson correlation coefficient was not high. CONCLUSIONS: The similar pattern of BUA, aBMD and vBMD with respect to age, height and pubertal stages indicates that ultrasound could be a reliable method to screen bone mass abnormalities in children. The low correlation coefficient, however, suggests that the methods employed measure different bone parameters. Moreover, the different skeletal locations could also account for these results.

Adolescent↗
PubMed2004

Hyperparathyroidism.

Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (>12 <13.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (>13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca >13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.

Calcium↗