ASSOCIATION OF COL1A1 SP1 AND FOK-I VDR GENETIC POLYMORPHISMS IN YOUNG MALE IDIOPATHIC OSTEOPOROSIS.

INTRODUCTION: Primary osteoporosis during childhood and adolescence represents an uncommon condition, and secondary forms are more likely to manifest at this age due to chronic disease and adverse effects of medical treatment. CASE REPORT: The authors report the case of a young male patient with a history of multiple idiopathic non-vertebral fragility fractures in addition to a family history of maternal osteoporosis and fracture, in whom osteoporosis was confirmed according to 2013 International Society for Clinical Densitometry (ISCD) criteria. Bone markers indicated low bone formation marker osteocalcin. Genetic testing revealed homozygosity for Sp1 COL1A1 gene polymorphism in combination to Fok-I vitamin D receptor (VDR) heterozygous polymorphism, to contribute to low bone mass and increased fracture risk. Severe premenopausal osteoporosis was present in the patient's mother, who was also tested positive for both gene polymorphisms. CONCLUSION: This case report highlights the association between COL1A1 and VDR candidate gene polymorphisms and fragility fractures in a family. Individual genetic testing might be of clinical value in idiopathic osteoporosis in young patients, identifying subjects at increased fracture risk.

Genetic diversity and antimicrobial resistance in Streptococcus agalactiae strains recovered from female carriers in the Bucharest area

For the first time, we used multilocus sequence typing (MLST) to understand how Romanian group B streptococcus (GBS) strains fit into the global GBS population structure. Colonising isolates recovered from adult human females were tested for antibiotic resistance, were molecularly serotyped based on the capsular polysaccharide synthesis (cps) gene cluster and further characterised using a set of molecular markers (surface protein genes, pilus-encoded islands and mobile genetic elements inserted in the scpB-lmb intergenic region). Pulsed-field gel electrophoresis was used to complement the MLST clonal distribution pattern of selected strains. Among the 55 strains assigned to six cps types (Ia, Ib, II-V), 18 sequence types (STs) were identified by MLST. Five STs represented new entries to the MLST database. The prevalent STs were ST-1, ST-17, ST-19 and ST-28. Twenty molecular marker profiles were identified. The most common profiles (rib+GBSi1+PI-1, rib+GBSi1+PI-1, PI-2b and alp2/3+PI-1, PI-2a) were associated with the cps III/ST-17 and cps V/ST-1 strains. A cluster of fluoroquinolone-resistant strains was detected among the cps V/ST-19 members; these strains shared alp1 and IS1548 and carried PI-1, PI-2a or both. Our results support the usefulness of implementing an integrated genotyping system at the reference laboratory level to obtain the reliable data required to make comparisons between countries.

Infertility in a new 46, XX male with positive SRY confirmed by fluorescence in situ hybridization: a case report.

The 46, XX male syndrome (de la Chapelle syndrome or 46, XX testicular disorder of sex development) is a rare form of sex reversal with complex mechanisms leading to a large spectrum of clinical manifestations ranging from ambiguous genitalia in the newborn to normal male phenotype. Therefore, diagnosis is established either pre- or early postnatal, or in adult life due to male infertility. In some cases, subtle clinical signs during childhood and puberty may be overlooked. A 28-year-old married man presented with azoospermia without erectile dysfunction. Between 9-14 years he was examined for the small testes and under-masculinized external genitalia but the diagnosis was not further clarified. At presentation, hormonal laboratory evaluation revealed hypergonadotropic hypogonadism. Chromosome analysis showed a 46, XX karyotype and translocation of SRY (testis-determining factor) from chromosome Y to chromosome X was identified by fluorescence in situ hybridization (FISH). Despite early subtle clinical signs of abnormal sexual development in this new 46, XX male syndrome, medical investigations were triggered by infertility.

On the significance of chemiluminescence induced by the blood polymorphonuclear leukocytes. I. Normal values.

In spite of the fact that chemiluminescence (CL) produced by the in vitro stimulated polymorphonuclear leukocytes is now a current method for the quantitative measurement of phagocytosis, its clinical use is still limited due to some controversies mostly technical. By comparing the different forms of presentation of the results, we proposed as stimulation index, the ratio of CL in the stimulated sample to that in the nonstimulated as measured at the same time interval and in the same number of cells (1 x 10(6)/ml). Measurements performed in a group of 200 healthy individuals, aged 20-70 years, with various occupations showed wide large variations of both the stimulation index of 23.5 +/- 12.3 and in a lesser degree of the CL kinetics. We suggest different possibilities of interpretation of the results obtained by this method (both the stimulated index and the CL kinetics) in order to obtain maximum information concerning the cellular immunity for clinical use.

The changes of peroxides and total antioxidants in the plasma of patients who received 131I therapeutically.

Fifty patients with thyroid cancer were studied during administration of high doses of 131I (5-50 mCi). Peroxides, total antioxidants and free sulphydryl-groups were measured in the blood samples obtained before and after administration of radioactive iodine. After the administration of iodine, significant increases of peroxides and free SH groups were observed, as well as the decrease of total antioxidants. These biochemical changes were in agreement with significant decreases of blood platelets and lymphocytes. The data obtained brought forward again the much debated problem of peroxidation and antioxidants in cancer, since comparatively, the patients with other localizations of tumors presented decreases of peroxides and variable amounts of antioxidants. The influence of iodine and thyroid hormones is discussed, with reference to a previous paper in which high levels of peroxides had been found both in hyper- and in hypothyroidism but with different mechanisms. The biochemical changes observed in the patients treated with radioactive iodine confirmed the involvement of peroxides in the consequences of internal irradiation.

Evaluation of the therapeutic efficiency of Voltarene by using the in vitro chemiluminescence emitted by leukocytes polymorphonuclear.

It is known that antiinflammatory drugs inhibit the chemiluminescence produced by polymorphonuclear leukocytes (PMNL). In this respect, we studied in vitro, in standardized conditions (1.0 x 10(6) PMNL), the inhibitory effect of Voltarene on the chemiluminescence produced by PMNL from patients with rheumatic diseases, before and after treatment with the above drug. The stimulation index, as a quantitative measure of PMNL phagocytosis is higher in patients with rheumatic diseases than in controls. After treatment with Voltarene, the stimulation index further increases, especially in the patients with arthritis, suggesting a raised PMNL reactivity. A great differentiation of the in vitro inhibitory effect of Voltarene was observed especially for higher concentrations, function of age and the severity of disease. According to our results, Voltarene acts mainly by increasing the PMNL reactivity. The in vitro inhibitory effect of Voltarene on PMNL seems to be correlated with the in vivo action, the younger patients showing the greatest reactivity.

The significance of the peroxides increase in the plasma of the patients with liver failure.

200 patients with varied types of liver failure were biochemically and clinically investigated. Beside the usual biochemical analyses (transaminases, glutamyl transpeptidase, triglycerides, bilirubin), some special parameters such as lipid peroxides, glutathione, ceruloplasmin and the total antioxidative capacity of plasma were measured. High levels of lipid peroxides appear especially in severe cases of liver failure such as acute viral hepatitis, coma. The persistence of a high level of peroxides in plasma suggests the presence of severe, irreversible lesions. The increase of peroxides in the plasma is mainly due to the overridden production of antioxidative systems, localized especially in the liver. In severe liver failure, the mechanism of the increased formation of peroxides seems to involve bilirubin, due to induction of liver heme oxygenase. The data presented showed inverse correlations between the increase of peroxides and the decrease of glutathione and ceruloplasmin.

Plasma renin activity, aldosterone and cortisol in relation with postural changes in dogs.

Experiments were carried out in six dogs anesthetized with chloralose, fixed on a tilting table and moved from the supine to the vertical posture. In one dog this postural change was done after cutting both Hering nerves, and in another one after bilateral nephrectomy (BN), these experiments being orientative. Changing the supine to the vertical posture was followed by increase in plasma renin activity (PRA) and in aldosterone and cortisol plasma concentration (p.c.) Between PRA and aldosterone p.c., there was a slight correlation, but between aldosterone and cortisol this was evident. Therefore it may be supposed that aldosterone hypersecretion is produced by ACTH hypersecretion, a common stimulatory pathway for both hormones. This stimulatory mechanism is sustained by the orientative experiment on dogs, with BN, in which supine to vertical changed posture was followed by an important aldosterone hypersecretion despite minimal values of PRA.

Renin and aldosterone reactions after acute hemorrhage.

Among the pressor homeostatic mechanisms that appear after hemorrhage are renin-angiotensin response and aldosterone hypersecretion. Plasma renin activity (PRA) may decrease initially but increase always after a certain interval. Aldosterone secretion increases or decreases in a higher or lower degree. It is generally accepted that Ang II is one of the principal factors that stimulates aldosterone secretion, but from our material it resulted that after hemorrhage it evolves independently. This discrepancy is more evident if hemorrhage is followed by bilateral nephrectomy (BN), when PRA significantly decreases but aldosterone secretion increases. After a simple BN, PRA decreases significantly but aldosterone plasma concentration increases, a discrepancy that is more evident if BN are followed by hemorrhage. Thus, it appears that after hemorrhage, the aldosterone secretion is not stimulated by the renin-angiotensin system.

Small intestine biopotentials in rats after hypokinesia.

In order to study the effect of hypokinesia on rats' small intestine biopotentials it was first necessary to characterize it. Biopotentials were recorded by intracellulary microelectrodes from oral and caudal segments of the small intestine. The morphology of rat's small intestine biopotentials differs from that of other species (man, cat, rabbit, dog, e.a.) the slow waves being smaller and the frequency of basal electrical rhythm higher (approximately 31.23 c/min oraly and approximately 24.50 aboraly), and by waxing and waning waves that are more frequently encountered suggesting a greater number of plateaus potentials. Spike potentials are inscribed on the descending slope of the slow waves but delayed in each successive wave with a regular interval. Hypokinesia obtained by introducing rats in small cages for two weeks, increases the slow waves amplitude. Frequency of basic electric rhythm and other parameters are not specifically changed.