Effects of war aggression in Croatia on some forms and manifestations of breast cancer

The aim of this study was to determine the differences in epidemiological and clinical manifestations of breast cancer in time of war in Croatia and in peacetime before and after the war, in the defined population of Pozesko-Slavonska County. The methods used in this study were the evaluation of relative predictive value of variables by means of chi 2-test and the analysis of variance, while the survival studies were tested by Long Rank test according to Kaplan-Meier analysis of survival. This work encompasses 660 patients who had breast cancer. The differences between three time periods were evaluated: the war period (1991-1995), and two control periods: before the war (1981-1990) and after the war (1996-2000). The patients were grouped by age, localization of tumor and survival. During the war period the patients were, on the average, 4.2 years younger than those who acquired the disease in control periods, and the mean age of patients was between 50 and 59 years (36.5% of patients). Although the difference in tumor distribution by sides (left or right breast) and quadrants was statistically significant (war period vs. control periods; p < 0.001), there was no statistically significant difference in the survival of patients according to the results of Kaplan-Meier analysis of localization of tumor (p > 0.05). The length of survival in terms of age of patients in time of surgical procedure was significantly different (p < 0.001). This study confirms the effects of war on some epidemiological and clinical manifestation of breast cancer in the defined population of Pozesko-Slavonska County.     

Lacustrine basin to delta evolution in the Zagorje Basin,a Pannonian sub-basin (Late Miocene: Pontian,NW Croatia)

Pontian deposits of the Zagorje Basin constitute a coarsening-upward succession, which reflects the infilling style of this Pannonian sub-basin, i.e. the progradation of clastic systems into the brackish lake. Six facies differentiated correspond to lake floor, channelled slope, distal and proximal pro-delta, distal and proximal mouth bars, and lagoon/bay to swamp and alluvial environments. The deposition in the mouth-bar area was dominated by frictional forces. The upper-stage plane-bed sands are the main mouth-bar facies, which is uncommon in the geological record. The main factors for the origin of such bars include an abundant sand supply by the high-energy fluvial system(s), low-energy of the receiving basin and shallow depositional depth. Prolonged, catastrophic floods generated sustained hyperpycnal flows, which bypassed the mouth-bar area and fed the slope/pro-delta. The high ratio between sediment supply and subsidence rate resulted in a fast moving progradational wave, which involved the entire SW Pannonian Basin, including the Zagorje Basin.     

Ex vivo gingival-biofilm consortia

AIMS: To develop a protocol for harvesting ex vivo samples of gingival-biofilm consortia and to investigate their basic characteristics. METHODS AND RESULTS: Gingival epithelial cells with attached biofilm were collected from healthy subjects by taking a smear. The bacterial viability was estimated via the alteration of the membrane permeability and metabolic activity via the double/single-stranded nucleic acid ratio using a confocal laser-scanning microscope. Morphological analysis was performed by scanning and transmission electron microscopy. Additionally, microbiological estimations were made. The electron microscopy revealed fimbriae-mediated adhesion and the formation of a biofilm matrix. Most bacteria were viable and had a high metabolic activity. CONCLUSIONS: The presented study offers an easy to follow approach for harvesting samples of gingival-biofilm consortia. The latter differs considerably from the supragingival plaque in viability and zonal distribution. Related to free-living and in vitro-grown biofilms, the gingiva-associated biofilm revealed an atypically high metabolic activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofilm fragments should possess the basic features of the entire gingiva-associated biofilm; which as yet cannot be simulated in vitro. Thus, samples of ex vivo gingival-biofilm consortia can be used to investigate the resistance of oral biofilms against antibiotics and biocides.     

Screening for depression disorders in patients with chronic somatic illness

Depression is one of the most common complications in patients with chronic somatic illnesses. Comorbidity of depression with physical illness often remains unrecognized and untreated, additionally aggravating the somatic illness itself, its treatment and prognosis. The aim of this study was to investigate the prevalence of depression in chronic somatic patients suffering from diabetes, epilepsy, asthma, chronic obstructive pulmonary disease (COPD) and hypothyroidism. Patients, who were regularly attending control examinations in neurological and internal medicine out-patient departments, were tested for the presence of depression with Beck Depression Inventory. The sample comprised 2153 chronic somatic patients aged between 18 and 80 years. Out of this total, 228 patients (10.6%) did not complete the study, (5.12%) refused to participate, and (5.5%) of the patients were technical failures. 1925 patients completed the study, and 1383 of them were not depressive. In 542 patients (28.5%) depression was confirmed, being almost twice more frequent in women, 346 (64%) vs. 196 (36%) male. Among these depressed examinees, mild depression was found in 284 (52.4%), major in 186 (34.3%) and severe in 72 (13.3%) chronic somatic patients. The majority of patients were aged over 55 yrs (49%). This population contained the largest number of depressed examinees (49.9%). The prevalence of depression with regard to subgroups shows that (25.6%) of asthma patients were depressed, as well as (26.6%) of those with COPD. These two groups did not present statistically significant differences regarding gender. The depression level of (32.2%) was found in patients with diabetes, of (29.6%) in patients with epilepsy and of (24.2%) among those with hypothyroidism. As for gender, statistically significant difference was found in the last three groups of patients (p < 0.001).     

Fimbria-mediated bacterial adhesion to human oral epithelium

The white-rot fungus Marasmius quercophilus C30 is able to produce several laccases. The proportion of the enzymes produced depends on culture conditions. On malt medium, LAC1 was produced continuously over the 14 days of the cultivation period and was the only activity detectable. Copper increased total laccase activity by a factor 10 and induced the transient expression of one or more extra laccases in the culture medium. A combination of copper and p-hydroxybenzoic acid made it possible to extend the expression of induced laccase activities over the cultivation period and to reach a maximum activity 30 times higher than in non-induced culture. Extracellular laccases produced in this last condition were eluted as four peaks on an anion exchange column and were partially characterized.     

Effect of Peroral Administration of Chromium on Insulin Signaling Pathway in Skeletal Muscle Tissue of Holstein Calves

The objective of this study was to investigate the effects of peroral administration of chromium-enriched yeast on glucose tolerance in Holstein calves, assessed by insulin signaling pathway molecule determination and intravenous glucose tolerance test (IVGTT). Twenty-four Holstein calves, aged 1 month, were chosen for the study and divided into two groups: the PoCr group (n = 12) that perorally received 0.04 mg of Cr/kg of body mass daily, for 70 days, and the NCr group (n = 12) that received no chromium supplementation. Skeletal tissue samples from each calf were obtained on day 0 and day 70 of the experiment. Chromium supplementation increased protein content of the insulin β-subunit receptor, phosphorylation of insulin receptor substrate 1 at Tyrosine 632, phosphorylation of Akt at Serine 473, glucose transporter-4, and AMP-activated protein kinase in skeletal muscle tissue, while phosphorylation of insulin receptor substrate 1 at Serine 307 was not affected by chromium treatment. Results obtained during IVGTT, which was conducted on days 0, 30, 50, and 70, suggested an increased insulin sensitivity and, consequently, a better utilization of glucose in the PoCr group. Lower basal concentrations of glucose and insulin in the PoCr group on days 30 and 70 were also obtained. Our results indicate that chromium supplementation improves glucose utilization in calves by enhancing insulin intracellular signaling in the skeletal muscle tissue.     

In vivo osteoinductive effect and in vitro isolation and cultivation bone marrow mesenchymal stem cells

Bone marrow contains cell type termed mesenchymal stem cells (MSC), first recognized in bone marrow by a German pathologist, Julius Cohnheim in 1867. That MSCs have potential to differentiate in vitro in to the various cells lines as osteoblast, chondroblast, myoblast and adipoblast cells lines. Aims of our study were to show in vivo capacity of bone marrow MSC to produce bone in surgically created non critical size mandible defects New Zeland Rabbits, and then in second part of study to isolate in vitro MSC from bone marrow, as potential cell transplantation model in bone regeneration. In vivo study showed new bone detected on 3D CT reconstruction day 30, on all 3 animals non critical size defects, treated with bone marrow MSC exposed to the human Bone Morphogenetic Protein 7 (rhBMP-7). Average values of bone mineral density (BMD), was 530 mg/cm3, on MSC treated animals, and 553 mg/cm3 on control group of 3 animals where non critical size defects were treated with iliac crest autologue bone graft. Activity of the Alkaline Phosphatase enzyme were measurement on 0.5, 14, 21, 30 day and increased activity were detected day 14 on animals treated with bone marrow MSCs compared with day 30 on iliac crest treated animals. That results indicates strong osteoinduction activity of the experimental bone marrow MSCs models exposed to the rhBMP-7 factor Comparing ALP activity, that model showed superiorly results than control group. That result initiates us in opinion that MSCs alone should be alternative for the autolologue bone transplantation and in vitro study we isolated singles MSCs from the bone marrow of rat's tibia and femora and cultivated according to the method of Maniatopoulos et all. The small initial colonies of fibroblast like cells were photo-documented after 2 days of primary culture. Such isolated and cultivated MSCs in future studies will be exposed to the growth factors to differentiate in osteoblast and indicate their clinically potential as alternative for conventional medicine and autologue bone transplantation. That new horizons have potential to minimize surgery and patient donor morbidity, with more success treatment in bone regenerative and metabolism diseases.     

N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: A novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors

A series of N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting c-Met and VEGFR2 tyrosine kinases was designed and synthesized. The compounds were potent against these two enzymes with IC₅₀ values in the low nanomolar range in vitro, possessed favorable pharmacokinetic profiles and showed high efficacy in vivo in several human tumor xenograft models in mice.     

N-(4-(6,7-Disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: A novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors

A series of N-(4-(6,7-disubstituted-quinolin-4-yloxy)-3-fluorophenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting c-Met and VEGFR2 tyrosine kinases was designed and synthesized. The compounds were potent against these two enzymes with IC₅₀ values in the low nanomolar range in vitro, possessed favorable pharmacokinetic profiles and showed high efficacy in vivo in several human tumor xenograft models in mice.     

Premenstrual dysphoric disorder--a neglected diagnosis? Preliminary study on a sample of Croatian students

The aims of this study were to assess prevalence and symptom profile of premenstrual dysphoric disorder (PMDD) in a sample of Croatian students and young university graduates. We obtained data for 87 healthy women, aged 18-30, at their regular gynecologic outpatient visits over the period of 2003 to 2004. The severity of premenstrual symptoms were assessed daily, during two cycles, with the Daily Record of Severity of Problems (DRSP) and criteria for PMDD according to DSM-IV were applied. Fifteen out of 87 women fulfilled PMDD criteria and reported statistically significantly higher prevalence of co morbid disorders in their medical history compared to non-PMDD group. The most common symptoms in the PMDD group were psychological, while in non-PMDD group were vegetative. Overall, relatively high prevalence of PMDD in studied group indicates the need to continue the study.