Biomechanical properties of bones from rats treated with sevelamer.

Sevelamer hydrochloride is used for ten years in patients on dialysis as a phosphate binder. We have previously shown that oral application of sevelamer prevents the bone loss and increases the bone volume in ovariectomized rats. In this study we further analysed the biomechanical properties of bones from rats treated with sevelamer utilizing a threepoint bending test to determine the mechanical properties of the cortical bone of the mid-shaft femur, while the indentation test was used to determine the mechanical properties of cancellous bone in the marrow cavity of the distal femoral metaphysis. Parameters analyzed included: maximum load (F(u)), stiffness (S), energy absorbed (W), toughness (T) and ultimate strength (sigma). The intrinsic properties, stress, elastic modulus and toughness were determined from measured maximum load, strains, stiffness, energy absorbed, outer and inner diameters, and calculated bone cross-sectional moment of inertia. Sevelamer was given to rats for 25 weeks with a content of 3% of sevelamer in a standard diet, starting immediately following ovariectomy (OVX). Animals were divided to the following groups: (1) Sham; (2) Sham + sevelamer 3%; (3) OVX; (4) OVX + sevelamer 3%. Our results showed that sevelamer particularly influenced the rat trabecular bone by increasing the maximum load for 26.2%, energy absorbed for 24.2% and the ultimate strength for 26.2% in sham animals treated with sevelamer 3%, as compared to sham rats. Sevelamer 3% in OVX rats also increased the maximum load for 71.4%, stiffness for 70.7%, energy absorbed for 55.9% and the ultimate strength for 71.3% as compared to OVX controls. In the three bending test sevelamer had a very little effect on preventing loss of bone strenght in the cortical bone. These results collectively suggest that sevelamer improves bone biomechanical properties, mainly affecting trabecular bone quality in both normal and ovariectomized rats.

[Diagnostic and therapeutic algorithm for the treatment of premenstrual dysphoric disorder]. / Dijagnosticke i terapijske smjernice za lijecenje predmenstruacijskog disforicnog poremecaja.

Many women experience psychological and physical symptoms associated with menstrual cycle. In 3% to 5% of women that meet the criteria for premenstrual dysphoric disorder, the symptoms are severe and impair their social and occupational functioning. Although the etiology of premenstrual dysphoric disorder is unknown, the symptoms of dysphoria, including depression and anxiety, have been associated with serotonergic dysregulation. Selective serotonin reuptake inhibitors, taken only during the symptomatic luteal phase, are considered as first-line therapy for premenstrual dysphoric disorder.

[The organization of mental health care in community]. / Organizacija zastite mentalnog zdravlja u zajednici.

Integration of the psychiatry in primary care is beneficial for the early detection of mental disorder, better outcome of mental disorder and reduction of stigma. Psychiatry is a leading profession in organisation of mental health services. General practitioners (GPs) in Europe deal with mental disorders in their everyday practice, so the same is expected in Croatia. Graduate and postgraduate education of our GPs is insufficient for this new role. The paper compares actual situation in Croatia with forthcoming needs. The paper suggests that community psychiatry, anti-stigma program, continuing medical education of GPs and network of consultant psychiatrists give the best results in the early detection and treatment of mental disorder.

The comparison of fetal behavior in high risk and normal pregnancies assessed by four dimensional ultrasound.

OBJECTIVE: We compared fetal behavior (FB) in high risk and normal pregnancies using four dimensional ultrasound (4DUS). METHODS: For assessment of FB in high risk and normal pregnancies, we used a scoring system of Kurjak's antenatal neurological test (KANET). The newborns were assessed by a postnatal neurological test, Amiel-Tison neurological assessment at term (ATNAT). The scores of KANET in high risk (N=116) and in normal pregnancies (N=110) were compared. After delivery, the results of KANET from both groups were compared with ATNAT test. RESULTS: There was a statistically significant difference between group of high risk and normal pregnancies, for 8 out of 10 parameters in KANET: isolated anteflection of the head, eye blinking, facial expressions, mouth movements, isolated hand movement, hand to face movement, fist and finger movements, general movements. There was no difference for cranial sutures and isolated leg movements. Comparison of KANET and ATNAT showed statistically significant, moderate correlation between the two tests, which means that the neuropediatric exam (ATNAT) confirmed the prenatal 4DUS finding (KANET). CONCLUSION: The difference of FB between the high risk and normal pregnancies was evident. These preliminary results are promising but further studies have to be done before the test could be recommended for wider clinical practice.

The assessment of fetal neurobehavior by three-dimensional and four-dimensional ultrasound.

The development of three-dimensional (3D) and four-dimensional ultrasound (4D) has provided new opportunities to study fetal and even embryonic behavior. These techniques enable simultaneous spatial imaging of the entire fetus and its movements. Recently, multicenter studies of fetal brain function have been carried out, the aim of which is to establish the standards of embryonic and fetal peripheral and body movements and facial expression as additional diagnostic criteria for prenatal brain development. Additional studies have been conducted in order to provide more information on specific movement patterns and quality of movement in the high-risk fetus. The purpose of this paper is to review and analyze the published literature on the use of 3D and 4D ultrasound in the assessment of fetal behavior.

Nitric oxide synthesis in placenta is increased in intrauterine growth restriction and fetal hypoxia.

In order to study the possible role of nitric oxide (NO) in the human placenta, we measured the concentration of its stable metabolite nitrite (NO2-) in the placentas of women with normal pregnancies and those from pregnancies complicated by intrauterine growth restriction (IUGR) with or without fetal hypoxia. We have measured nitrites by the Griess reaction in 15 placentas from IUGR pregnancies and 12 controls. Cerebroumbilical ratio (C:U) was recorded by color Doppler ultrasound and values below 1 were considered to be a predictor for fetal hypoxia. NO2- levels measured in pathological placentas were increased for at least 93% as compared to control. Subjects from pregnancies complicated by IUGR and fetal hypoxia had increased NO2- as compared to the placentas from pregnancies with IUGR and normal fetal oxygenation. NO production in placenta is increased in pregnancies with IUGR. This effect is more pronounced in those with compromised fetal oxygenation.

Sevelamer restores bone volume and improves bone microarchitecture and strength in aged ovariectomized rats.

Sevelamer hydrochloride, a noncalcium phosphate binder, has been shown to reduce coronary artery and aortic calcification, and to improve trabecular bone mineral density in hemodialysis patients with chronic kidney disease. Here, we examined whether sevelamer given orally for 12 wk with normal food could restore bone volume (BV) and strength in aged ovariectomized (OVX) rats starting at 4 wk after OVX. Dual-energy x-ray absorptiometry, microcomputerized tomography, and bone histomorphometry analyses showed that OVX animals receiving sevelamer had increased trabecular BV (51%), trabecular number (43%), trabecular thickness (9%), cortical thickness (16%), mineral apposition rate (103%), bone formation rate (25%), and enhanced cortical and trabecular bone mechanical strength as compared with OVX rats. Sevelamer decreased collagen C telopeptide, increased osteocalcin levels, and decreased phosphate and magnesium levels without affecting calcium levels in the blood. Although sevelamer was not absorbed systemically, it stimulated osteoblast differentiation in BM-derived mesenchymal stem cell cultures, as evaluated by alkaline phosphatase positive colony-forming units, and inhibited recombinant human soluble receptor activator of nuclear factor-kappaB ligand-induced osteoclast differentiation, as evaluated by tartrate-resistant acid phosphatase positive cells in bone mineral-hematopoietic stem cell cultures. Surface enhanced laser desorption/ionization time-of-flight mass spectrometry analysis revealed that 69 proteins were differently expressed after OVX, of which 30% (20 of 69) were reversed to sham activity after sevelamer intake. PTH, fibroblast growth factor-23, and cytokine profile in serum were not significantly changed. Together, these results suggest that sevelamer in food increases the BV and improves biomechanical properties of bone in OVX rats.