Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

Rotavirus serology and breast-feeding in young children in rural Guinea-Bissau

One hundred and forty-four children aged 9-20 months living in 14 villages in a rural area of Guinea-Bissau were examined for circulating rotavirus antibodies twice in a 15-month period. An immunofluorescence technique was used. About 3/4 of the children seroconverted, independent of age on entering the study. The age-specific proportion of seropositivity increased from 4/40 (10%) at 9-11 months to 26/29 (90%) at 33-35 months of age. All the initially seropositive children retained detectable antibodies to rotavirus. The relative risk of seroconversion was 1.4 times (95% confidence interval 1.0-2.0) more common among children living in villages by the mainroad as compared to those living off the road. Contact rate is probably dependent on population density and mobility but not on age. Breast-feeding, decreasing sharply through the age interval covered by the follow-up (9-35 months), had no apparent influence on seroconversion at the ages concerned.     

Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba.

We report here the antiproteolytic and antihemorrhagic properties of triterpenoid saponin inhibitors, named macrolobin-A and B, from Pentaclethra macroloba, against Bothrops snake venoms. The inhibitors were able to neutralize the hemorrhagic, fibrin(ogen)olytic, and proteolytic activities of class P-I and P-III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. Clotting and fibrinogenolytic activities induced by snake venoms and isolated thrombin-like enzymes were partially inhibited. Furthermore, the potential use of these inhibitors to complement antivenom therapy as an alternative treatment and/or used as molecular models for development of new therapeutical agents in the treatment of snake bite envenomations needs to be evaluated in future studies.     

Mifepristone in Italy: the case of a drug trapped between ethics and clinical practice

In Italy mifepristone is not yet marketed. Gynaecologists in our hospital asked to use this medication as a less traumatic method for voluntary abortions. We followed the standard procedure defined by the Italian Health Ministry (IMH) for purchasing drugs from abroad but encountered several unexpected barriers. Starting from this case, this paper is aimed at identifying these barriers which we found to be not only professional, but also ethical, religious and moral.     

Free insulin-like growth factor-I and cognitive function in older persons living in community.

CONTEXT: Increasing evidences from experimental and human studies suggest that the activity of the growth hormone (GH/insulin-like growth factor-I) axis may contribute to the age-related cognitive decline and poor cognition in late life. OBJECTIVE: The aim of the present study was to evaluate the relationship of total serum free IGF-I and its binding protein-3 with cognitive performance in older persons aged 80 years or older. DESIGN: Data are from baseline evaluation of the ilSIRENTE study (n=353). Cognitive performance was evaluated using five items enclosed in the Minimum Data Set for Home Care assessment form: short-term memory, procedural memory, cognitive skills in daily decision making, verbal expression, comprehension. Free insulin-like growth factor-I (free IGF-I) and IGF-binding protein-3 (IGFBP-3) in blood were measured. Analysis of covariance (ANCOVA) was used to examine the relationship between cognitive impairment and the serum free IGF-I and IGFBP-3 concentrations, after adjustment for potential confounding variables. RESULTS: After adjustment for potential confounders, which included age, gender, education, cerebrovascular disease, ischemic heart disease, congestive heart failure, hypertension, diabetes, depression, Parkinson diseases, thyroid diseases, smoking status, alcohol abuse, body mass index, and number of medications, individuals with verbal expression problems (n=20) and individuals with comprehension problems (n=24) had a significantly lower serum levels of readily dissociable IGF-I than participants without cognitive impairments. The serum IGFBP-3 presented the same behavior of free IGF-I. CONCLUSION: The present study suggests that among old-old subjects living in the community lower levels of total serum free IGF-I and IGFBP-3 are associated with impairment of cognitive performance. This finding suggests that the GH/IGF-I axis may play an important role in the age-related decline of cognitive performance.     

Activity of some naphthoquinones on blood stream forms of Trypanosoma cruzi

Accidental transmission of Chagas disease to man by blood transfusion is a serious problem in Latin America. This paper describes the testing of several naphthoquinones, some of which were active against blood trypomastigotes in vitro at 4 degrees C and might therefore warrant further study for preventing transmission of Chagas disease by blood transfusion.     

Efficacy of cefcanel on staphylocci

The minimum inhibitory concentration (MIC) of cefcanel, a new oral cephalosporin, has been tested against 153 staphylococci subdivided into the species Staphylococcus aureus. S. epidermidis sensu lato and S. saprophyticus, with and without beta-lactamase production. The concentration inhibiting 50% of the strains was 0.5 mg/l for all three species while the corresponding values for 90% of the strains were 1, 2 and 1 mg/l, respectively. These values apply to all the strains. The MICs of the non-beta-lactamase-producing strains were identical to the MICs of the beta-lactamase-producing strains for S. aureus, three twofold steps lower for S. epidermidis and one step higher for S. saprophyticus. Consequently, beta-lactamase production had no consistent consequences for the activity of cefcanel against S. aureus and S. saprophyticus. In contrast, the beta-lactamase production of S. epidermidis did influence the activity of cefcanel. Among the tested cephalosporins, cefcanel had the highest antistaphylococcal activity, and no strain was resistant to this new cephalosporin.     

Hemoglobin adducts of benzo[a]pyrene diolepoxide in newspaper vendors: association with traffic exhaust

Benzo[a]pyrene diol epoxide adducts with hemoglobin (Hb) weremeasured to detect human exposure to environmental benzo[a]pyrenefrom traffic exhaust. Benzo[a]pyrene tetrahydrotetrols (BPTs)released from Hb after acid hydrolysis were quantitated by gaschromatography-mass spectrometry after immunoaffinity chromatography.Fifty three newspaper vendors were enrolled. The median adductconcentration was 0.3 fmol BPTs/mg Hb in high density traffic-exposedvendors and