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Since it has become possible to “read the book of life”, different approaches to the universe, revealed by genetic scientific advances, have come into being. On the one hand, the Human Genome Project (HGP) has opened the medical field to new treatments – or at least to the hope of new therapies – through, for instance, gene therapy. On the other hand, developments in genetics have allowed reductionism or genetic essentialism to make its way into the public and institutional perception of genetic advances. This paper will argue that the essentialist approach to genetics is inspired by the constant craving of humans to find, once and for all, those features and determinants that constitute identity: the human nature. I will argue against this trend by testing a particular field in which the concept of human nature could be the source of discrimination and inequalities, that being genetic human nature based law.

Background: Overweight and obesity prevention in childhood and adolescence represent a priority for public health; school is a privileged place for health promotion interventions. Objectives: The study aimed to test the effectiveness of a multicomponent 5-month intervention on the habits of primary school children, making the families aware of the importance of healthy choices. Methods: Two hundred nine children attending the fourth class of primary school, divided into interventional (n = 103) and control arm (n = 106) were included in the study. In the intervention group, parents and teachers received more intense lifestyle counseling, associated with weekly motivational telephone calls to families to motivate further their lifestyle changes. Standard deviation score (SDS) body mass index (BMI) was the primary outcome measure; on open-air games and TV watching were secondary outcomes. Results: At baseline, no differences were observed between groups. At 8-month follow-up, mean SDS BMI had decreased by 0.06 units in the intervention arm and increased by 0.12 in controls (time x treatment ANOVA, P < 0.002). Outdoor activities increased from 6.23 h week-1 to 9.93 in the intervention group (P < 0.001), not in controls. This change was associated differences in TV watching from baseline (intervention, -0.96 h week-1; P = 0.037; controls, +1.33 h week-1; P = 0.031). Conclusion: A multicomponent school-based intervention addressing the needs of children, teachers and families produced a significant and favourable short-term effect on overweight/obese schoolchildren.

A recombinant rat strain-Milan low-calpastatin strain (MLCS)-was derived from Milan hypertensive (MHS/Gib) and Milan normotensive (MNS/Gib) strains. The MLCS rats have normal blood pressure and low calpastatin activity, and this strain is proposed as a model for studies of the calpain-calpastatin system, which is involved in important cellular mechanisms. Calpastatin polymorphism was observed in 10 different strains of laboratory rats and a single locus hypothesis is suggested as the mode of inheritance.

Birth weight influences both postnatal growth and the initial response to GH therapy in GH-deficient subjects, but its relationship to final height is uncertain. Therefore, we examined final height results in a group of subjects treated for GH deficiency who were born small, appropriate or large for gestational age (GA).Retrospective study.108 GH-treated patients (age at diagnosis 11.1 +/- 2.0 years) affected by idiopathic and isolated GH deficiency (peak8 microg/l after pharmacological and/or nocturnal mean GH concentration/= 3.3 microg/l) were examined. Twenty-four had a birth weight3rd centile (2300 g +/- 268 - small for GA), 77 between the 3rd and 90th centile (3216 g +/- 317: appropriate for GA) and 7 above the 90th centile (4193 g +/- 143: large for GA).All subjects reached final height (growth velocity0.5 cm/year in the last year of treatment) after hGH treatment (range 33-96 months) at a dose of 20 U/m2/week. The 3 groups of subjects started therapy at a similar height for chronological and bone age.Final height in the small for GA group was - 1.71 +/- 0.93 standard deviation score (SDS), significantly lower than that of both appropriate (- 1.14 +/- 0.83 (P0.01)) and large (- 0.70 +/- 0.89 (P0.01)) for GA groups. Similarly, the small for GA group had a significantly lower height SDS increment from the start of therapy to adult height (0.54 +/- 0.84) than both the appropriate (0.99 +/- 0.78 (P0.05)) and the large (1.49 +/- 0.84 (P0.01)) for GA groups. The percentage of subjects with final height above target height was significantly different in the 3 groups: 21% for the small, 38% for the appropriate and 71% for the large for GA groups (P0.05). In the whole group of patients there was a positive correlation between birth weight and final height (r = 0.38; P0.0001).The present study showed that our patients, affected by isolated and idiopathic GH deficiency but with different birth weights, despite starting treatment with a similar height and bone age delay, had different auxological outcomes. It seems, therefore, that final height is strongly influenced by birth weight which penalizes the smaller newborns and assists the larger ones.

We evaluated the distribution of TSH levels on dried blood spots (Delfia system-threshold value for recall 20 microU/ml) in 27,282 consecutive samples examined during 1993, in the Emilia-Romagna region. We also evaluated, by questionnaire, the frequency of iodine disinfection in the perinatal period in all centers that do blood spots. We also evaluated the distribution of TSH spot values according to the localization of the center in endemic or not endemic area of the region. Among the parameters we considered, only the sampling day (p0.02) and the maternity center (p0.0001) showed a significant influence on TSH spot values. With regard to the questionnaire, the centers which habitually used iodine disinfection in obstetrics (20/28) showed significantly higher percentages of TSH values over 10 microU/ml than the centers which did not use (3/28) or rarely used (4/28) this type of disinfection (p0.0001). The only center which used regular iodine disinfection of umbilical cord in all newborns, showed a percentage of TSH values over 10 microU/ml (25.8%) and a recall rate (2.5%) significantly higher than all other centers (p0.0001).

AIMS—To evaluate the developmental pattern of fetal growth hormone (GH), insulin-like growth factor I (IGF-I), GH binding protein (GHBP) and IGF binding protein-3 (IGF-3); to determine the implications for fetal growth. METHODS—Serum GH, IGF-I, GHBP and IGFBP-3 were measured in 53 fetuses, 41 aged 20-26 weeks (group A) and 12 aged 31-38 weeks (group B). Fetal blood samples were obtained by direct puncture of the umbilical vein in utero. Fetal blood samples were taken to rule out β thalassaemia, chromosome alterations, mother to fetus transmissible infections, and for maternal rhesus factor. GHBP was determined by gel filtration chromatography of serum incubated overnight with 125I-GH. GH, IGF-I and IGFBP-3 were determined by radioimmunoassay. RESULTS—Fetal serum GH concentrations in group A (median 29 µg/l, range 11-92) were significantly higher (P

The authors evaluate the different organizational strategies of a congenital hypothyroidism screening program. Positive and negative aspects of laboratory screening tests (TSH only, T4-supplemental TSH, TSH and T4), organization strategies (centralization or decentralization), recall and first follow-up criteria are examined. The authors consider that the necessity for an early diagnostic confirmation can be associated with a precise etiologic diagnosis and an evaluation of the prenatal severity of congenital hypothyroidism factors. Some European and North-American experiences are compared with the activity of a regional Italian screening center.

We evaluated, yearly, the neuro-psychological development in 16 out of the 27 children with phenylketonuria detected via neonatal screening in the years 1980-90. 14 children had the classical form, while 2 had "variant" type of phenylketonuria. Development quotients always were slightly lower in patients than in controls, but the greatest difference was seen at 1 year of age (92.5 +/- 6.7 vs 101.6 +/- 2.2). At age 6 years, 4 children out of 11 had a IQ equal or below 90.2 of them had neonatal asphyxia, while the others showed, after age 2-4, constantly elevated phenylalanine levels. Four children had a bad metabolic control, as from the age of 2-4 year, and only 1 of them showed a normal IQ at 6 years of age. Regression analyses were used to determine the best predictors of IQ. Parents' social level stood out as the best predictor of IQ at 6 years of age. If this parameter was excluded, phenylalanine level, especially at age 4, best predicted IQ. The following variables had no influence: age at start of diet (they were all begun on diet within the first month of life), pre-diet phenylalanine levels and phenylalanine levels at 1 year of age (all children were, at this age, on good control), DQ (Development Quotient) at age 1. A high percentage (10 out 14) of hyperactive and psychologically instable children was also found, but with no correlations with IQ levels.

Conformational analysts of the three homologous series, from dipeptide to heptapeptide of monodisperse, N- and C-protected oligopeptides derived from the β-branched α-amino acid residues L -valine, L -isoleucine, and D -allo-isoleucine is reported. Occurrence of intermolecular β conformations in the higher oligopeptides in the solid state was established by means of infrared absorption. The extent of intramolecularly hydrogen-bonded folded structure formation was assessed as a function of chain length in solvents of low polarity at high dilution. Statistical coil and intermolecular β-conformations were shown to exist in alcohols and aqueous alcoholic mixtures. The results obtained indicate that, branching positions being equal, configuration of the asymmetric carbon atom in the lateral chain, overall bulkiness and lyophobic character of the amino acid side chains are all important factors in determining the stability of the ordered conformations of oligopeptides.

Activation of semipurified human kidney prorenin was found to occur in vitro in presence of a mixture of lipids that mimics the composition of the inner human cell membrane. The lipid-dependent activation was indeed only partial (38 +/- 4%) when compared to that obtained by trypsin in liquid phase (100 micrograms/mL) used as a control of maximal activation (100%) under our experimental conditions (semipurified human kidney prorenin in presence of semipurified human plasma renin substrate at a concentration of 1400 ng/mL, at pH 7.2). The phenomenon was time-dependent up to 60 min whereas the angiotensin I generated after 120 min was virtually the same as that generated after 60 min thus indicating a possible reversible activation of human prorenin. We speculate that prorenin may be reversibly activated by contact with the lipidic portion of the cell membrane either inside or outside the cells thus allowing a limited angiotensin II-generating cascade at a local site initiated by prorenin independently from the presence of active renin.

Classic homocystinuria is an autosomal recessive metabolic disease due to a cystathionine-β-synthase deficiency with consequent blocking of homocysteine and serine condensation for producing cystathionine. The characteristic biochemical abnormalities in the blood and urine are: abnormal accumulation of methionine, abnormal presence of homocystine and low values of cystathionine, cysteine or cystine (disulfide of the cysteine). The most frequent clinical signs are: subluxation of the lenses, mental retardation of different degrees, long bones excessively lengthened, scoliosis, susceptibility to arterial and venous thromboembolism. The latter is frequent after surgery, and may be life-threatening. This disease must be differentiated from Marfan’s syndrome via laboratory tests.

Evidence indicates that an alteration in kidney function has a causal role in the pathogenesis of hypertension in the Milan hypertensive strain (MHS) rat. At the prehypertensive stage, these animals have increased glomerular filtration rate and 24-hour urinary output, whereas plasma renin activity and urinary kallikrein are lower. After transplantation, the MHS kidney increases the blood pressure of a normotensive recipient. Micropuncture experiments, where single nephron filtration rate, tubuloglomerular feedback, proximal tubular reabsorption, micro-pressures in tubuli, and interstitium and interstitial oncotic pressure were measured, suggest that the intrinsic ability of MHS proximal tubular epithelium to reabsorb solute and water is greater in prehypertensive MHS rats than in Milan normotensive strain (MNS) rats. Also rheogenic Na transport across the brush-border vesicles isolated from proximal tubular cells is faster. When erythrocytes and proximal tubular cells of MHS rats are compared to those of MNS rats, the former have smaller volume and Na content, whereas the Na transport is faster and the Ca ATPase at Vmax is lower. This indicates that the genetic cellular abnormality responsible for the renal functional abnormality and hypertension is also present in erythrocytes. Moreover, MHS erythrocyte abnormalities are genetically determined within the stem cells and are genetically associated with hypertension. Because a correlation was also found in human hypertension between erythrocyte Na transport abnormality and renal function, it is proposed that the erythrocyte may be used for studying the genetic molecular mechanisms of hypertension.

Essential hypertension develops from the interaction of genetic and environmental factors. In the Milan hypertensive strain (MHS) rat before the development of hypertension, there is a genetically inherited increase of tubular reabsorption which is the cause of the following increase of blood pressure. Also in young normotensive humans, predisposed to develop essential hypertension later in life, there is an abnormal pattern of renal function that may be explained by increase of tubular reabsorption. The studies of the erythrocyte membrane transport support these data and suggest that at least a subset of essential hypertensive humans may develop a form of hypertension that has pathogenetic mechanisms similar to the ones of MHS rats.

Age-related changes in uterine and ovarian morphology and size were studied in 114 normal premenarcheal girls using a real-time mechanical sector scanner. Reference growth values were obtained for total uterine length, anteroposterior diameters of the corpus and cervix, corpus/cervix ratio, and uterine and ovarian volumes. Up to 7 years of age uterine size was not influenced by age and there was a relative predominance of the cervix over the corpus. Thereafter the uterus underwent a regular increase in size and the corpus gradually became larger than the cervix. Ovarian volume was relatively stable up to 5 years, when regular age-related growth started, associated with an increase in cystic functional changes in the ovary. As uterine and ovarian morphology and size are reliable indicators of the degree of sex-hormone stimulation, real-time ultrasound offers a rapid method of studying normal and abnormal pubertal development in girls.

We examined 107,670 infants born in the Italian region Emilia-Romagna. Capillary blood samples for contemporary T4 and TSH radioimmunoassay were collected on the 3rd, 4th, 5th, 6th, 7th or between the 7th and the 15th day of life on filter paper. In our method the threshold value for recall for a second assay was calculated taking into account the mean - 2 SD of each session for T4, and fixing between 30 and 50 microU/ml the threshold value for TSH. The re-call percentage was 0.74%. 21 subjects confirmed to be affected by congenital hypothyroidism; this corresponds to a frequency in our region of 1 case every 5,127 infants. 12 subjects had a TBG deficiency, this corresponds to a frequency of 1 case every 8,972 infants. No cases of secondary hypothyroidism were found up to date.

High blood pressure (HBP) in man is considered a major risk factor in cardiovascular heart disease; the most frequent cause of death in modern civilizations. Most states of HBP are classifed as “essential hypertension” as distinct from “secondary hypertension” which is due to some known organ dysfunction or other cause.

The skin diseases observed in 41 children affected by type-1 diabetes and in 1,273 children unaffected by diabetes were compared to evaluate the dermatoses that are associated to type-1 diabetes. A high prevalence of vitiligo, psoriasis and herpes simplex infections was found in diabetics. These data are confirmed by statistical comparison.

The role of genetic factors in essential hypertension is supported by studies of subjects with known genetic relationships (family studies) (41–43) monozygotic twins (25, 26, 37, 38), natural vs adopted children (18) and experimental models of spontaneous or “genetic” hypertension in rats (6, 24, 45). The demonstration that genetic factors are involved in this disease has stimulated many investigators to look for possible biochemical-functional alterations that could be considered as the direct phenotypic expression of genetic abnormalities underlying hypertension. Thus many studies have been performed on human hypertension to investigate alterations of transmembrane ionic transport, intracellular ion content and molecular characteristics of cellular membranes. However, these studies (1, 18, 21, 22, 33, 61) have not resulted in a consistent picture characteristic of the hypertensive patient. This is not surprising considering that essential hypertension is a polygenic disease, phenotypically expressed in different ways depending on the interaction between many environmental factors and a polygenic substrate. When approaching the problem of the etiology of human essential hypertension, it is therefore important to study the same patients with different techniques of physiology, biochemistry, molecular biology and population genetics in order to clarify the sequence of events from genetic alteration to the cellular and organ alteration responsible for the disease in the individual patient or family.

Alterations of cell function and structure have been described both in man with essential hypertension (Garay and Meyer 1975; Canessa et al. 1980; Cusi et al. 1981) and rat models with genetic types of hypertension (De Mendoca et al. 1982; Duhm et al. 1983). Possible cause-effect relationships between these cell abnormalities and the development of hypertension have therefore been proposed. The polygenic character of the human disease, the influence of environmental factors and methodological limitations to applying the best experimental design in humans, however, make it difficult to distinguish between those alterations that may be direct phenotypic expressions of the primary genetic defect and those which are secondary readjustments of the cell homeostasis.

An approach to evaluating the genetic components of essential hypertension using an animal model, the Milan hypertensive strain (MHS) of rats, and studies in human families with positive and negative histories for high blood pressure are described and discussed. Differences at renal and cellular levels between MHS and its normotensive control strain, MNS, show many similarities to those between offspring from hyper- and normotensive families in humans. These include, with respect to the former group of each species, lower erythrocyte volume and Na content, higher Na-K cotransport across red blood cell (RBC) membranes higher Na excretion after load, and greater pressor effect in transplanted kidneys. A novel protein found in rat RBC cytoskeleton appears to have a function in Na-K cotransport and it may, eventually, be possible to demonstrate in man.