Is identification of malignant lesions of the liver and of hemangiomas possible by Doppler ultrasonography and radionuclide angiography?

The aim of this study was to try to diagnose malignant liver lesions and hemangiomas by means of vascularisation and perfusion studies. The study was performed in 32 patients with hepatocellular carcinoma (HCC), in 74 with metastatic liver carcinoma (MLC) and in 40 with hemangiomas (H). Color Doppler ultrasonography (DUS) was done with an ATL Ultramark 9 apparatus with convex probe 2.5 MHz using pulse and DUS. Hepatic radionuclide angiography (HRA) was performed with bolus injection of 740 MBq (99m)Tc-pertechnetate, (1 min, 1 f/s), using ROTA scintillation camera and MicroDelta computer. Hepatic perfusion index (HPI) indicated the percentage of the portal blood inflow to the liver. Our results showed that in HCC and MLC there was a decrease of portal inflow while arterial inflow was increased resulting in pulse arterial wave velocity increase and in continuous venous waves velocity in the tumors. There was significant linear correlation between the increase of the arterial inflow and the arterial pulse wave found in the center and in the margin of the tumors. In hemangiomas, hepatic perfusion index related to arterial inflow was within normal range. In conclusion, our results suggest that HCC and MLC have specific characteristics in vascular and/or perfusion studies while hemangiomas show normal liver parenchyma findings.     

A rare case of enteropathy-associated T-cell lymphoma presenting as acute renal failure

Enteropathy-associated T-cell lymphoma (EATCL) is a high grade, pleomorphic peripheral T-cell lymphoma usually with cytotoxic phenotypes. We describe a first case of patient with EATCL that is remarkable for its fulminant course and invasion of both kidneys manifested as acute renal failure. The patient was a 23 year old woman with a long history of celiac disease. She was presented with acute renal failure and enlarged mono-nuclear infiltrated kidneys. Diagnosis of tubuloi-nterstitial nephritis and polyserositis was confirmed with consecutive pulse doses of steroid therapy. After reco-very, she had disseminated disease two months later. Magnetic resonance imaging showed thickened intestine wall, extremely augmented kidneys, enlarged intra-abdominal lymph nodes with extra-luminal compression of common bile duct. Laparotomy with mesenterial adipous tissue and lymph glands biopsy was done. Consecutive pathophysiological and immunohistochemical analyses confirmed the diagnosis of EATCL: CD45RO , CD43 , CD3 . The revision of renal pathophysiology sub-stanti-ated the diagnosis. The patient received chemotherapy, but unfortunately she died manifesting signs of pulmonary embolism caused by tumor cells.     

Correlation between uroflowmetry parameters and treatment outcome in children with dysfunctional voiding

PurposeTo investigate the correlation between subjective (clinical) treatment outcome and objective uroflowmetry parameters and curve pattern in children with dysfunctional voiding.MethodSeventy-five children were randomly allocated to two urotherapy programs. Group A was submitted to standard urotherapy and pelvic floor exercises while group B received conservative treatment. Constipation and recurrent urinary tract infections (UTIs) were treated in both groups. Selected children from both groups received pharmacotherapy (anticholinergics or desmopressin). Uroflowmetry with electromyography of the pelvic floor and ultrasound post-void residual (PVR) urine volumes were obtained before and at the end of the 12-month treatment period. Uroflowmetry findings were stratified into two categories based on clinical treatment outcome: ‘cured’ and ‘unchanged’. Uroflowmetry findings were compared between categories at the beginning and the end of the investigation.ResultsVoided volume, average and peak flow rates were significantly increased while PVR urine was decreased in children with cured urinary incontinence and nocturnal enuresis compared with ‘unchanged’ category. Significant decrease of PVR urine was noted in children with cured UTIs. The frequency of a bell-shaped curve was significantly higher compared to other curve patterns in children with cured urinary incontinence and UTIs.ConclusionPost-treatment improvement in clinical symptoms correlated with improvement in uroflowmetry parameters and curve pattern. Correction of voiding phase is necessary for urinary continence achievement and resolution of UTIs.     

Helicobacter pylori eradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura

We prospectively investigated the prevalence of Helicobacter pylori (H. pylori) infection in a cohort of 54 adult Serbian patients with chronic idiopathic thrombocytopenic purpura (ITP), and examined the effects of its eradication on their platelet counts. H. pylori infection was diagnosed in 39/54 (72.2%) patients, using the 14C-urea breath test; and was significantly higher than in the healthy Serbian population (55% P < 0.05). H. pylori-positive patients were significantly older than H. pylori-negative patients (P = 0.006), though there were no significant differences regarding gender, disease duration, mean platelet counts, previous therapies and spleen status between H. pylori-positive and H. pylori-negative patients. Successful eradication was confirmed in 23/30 (77%) treated patients. Stable platelet recovery was registered in 6/23 eradicated patients (26.1%) and maintained for 18 months. Complete and partial remissions were achieved in two and four patients, respectively, including one highly refractory patient. A significant mean platelet recovery was seen 6 months after successful H. pylori eradication in the group of 23 patients (P < 0.05). No platelet recovery was registered in either H. pylori-negative (n = 15), untreated H. pylori-positive patients (n = 9) or H. pylori-positive non-eradicated patients (n = 7). Even though the pathogenetic mechanisms of H. pylori-induced thrombocytopenia remain obscure, the results of this small prospective study support the use of H. pylori eradication as an effective non-immunosuppressive treatment for chronic ITP.     

Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats

To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCRalphabeta and (ii) Thy-1, which is supposed to be a regulator of TCRalphabeta signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCRalphabeta signalling in the development of CD4+25+T(reg)-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRalphabeta-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCRalphabeta(low) thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more efficient differentiational transition from the DP TCRalphabeta(high) to the SP TCRalphabeta(high) developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+T(reg)-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing.     

A new approach to the compartmental analysis in pharmacokinetics: fractional time evolution of diclofenac

This study presents a new two compartmental model and its application to the evaluation of diclofenac pharmacokinetics in a small number of healthy adults, during a bioequivalence trial. In the model the integer order derivatives are replaced by derivatives of real order often called fractional order derivatives. Physically that means that a history (memory) of a biological process, realized as a transfer from one compartment to another one with the mass balance conservation, is taken into account. This kind of investigations in pharmacokinetics is founded by Dokoumetzidis and Macheras through the one compartmental models while our contribution is the analysis of multi-dimensional compartmental models with the applications of the two compartmental model in evaluation of diclofenac pharmacokinetics. Two experiments were preformed with 12 healthy volunteers with two slow release 100 mg diclofenac tablet formulations. The agreement of the values predicted by the proposed model with the values obtained through experiments is shown to be good. Thus, pharmacokinetics of slow release diclofenac can be described well by a specific two compartmental model with fractional derivatives of the same order. Parameters in the model are determined by the least-squares method and the Particle Swarm Optimization (PSO) numerical procedure is used. The results show that the fractional order two compartmental model for diclofenac is superior in comparison to the classical two compartmental model. Actually this is true in general case since the classical one is a special case of the fractional one.     

The pituitary-adrenal axis of fetal rats after maternal dexamethasone treatment

Elevated glucocorticoid level in the gravid female circulation affects number of endocrine functions in fetuses and offspring. In this research female rats were injected with dexamethasone (Dx) in three consecutive daily doses of 1.0, 0.5, 0.5 mg/kg body weight, starting from day 16 of pregnancy. The influence of this treatment on the pituitary adrenocorticotrophic (ACTH) cells and adrenal glands of 19-day-old fetuses was examined immunocytochemically and by morphometric analysis. Moreover, the proliferative activity of adrenocortical cells was estimated after application of the mitotic inhibitor Oncovine. Administration of Dx to pregnant rats induced a decline of fetal ACTH cell immunopositivity and significant decreases of ACTH cell volume (23%, p<0.05), volume density (41%, p<0.05), and its number per unit area (17%, p<0.05) in comparison to the control 19-day-old fetuses. Reduced proliferative activity of adrenocortical cells (31%; p<0.05) in zona glomerulosa, as well as the volume of this zone were detected. The volume and number of fetal adrenocortical cells in the inner zone and chromoblasts were not significantly reduced after Dx treatment of pregnant rats. These results show that maternal Dx administration in the period when the fetal hypothalamo-pituitary-adrenal (PA) axis begins its function inhibited the PA axis. Reduced ACTH cell function and mitotic activity led to suppression of adrenocortical cell multiplication in zona glomerulosa, the region of the adrenal cortex where most proliferating cells were found in control 19-day-old fetuses. Thus, increased glucocorticoid levels during late pregnancy caused developmental modifications involving the fetal PA axis, which could be the basis of the altered endocrine responsiveness in adult life.     

Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds

We report that the functional assembly of engineered cardiac muscle can be enhanced by oxygen supply provided by mechanisms resembling those in normal vascularized tissues. To mimic the capillary network, cardiomyocytes and fibroblasts isolated from the neonatal rat hearts were cultured on a highly porous elastomer with a parallel array of channels that were perfused with culture medium. To mimic oxygen supply by hemoglobin, culture medium was supplemented with a perfluorocarbon (PFC) emulsion; constructs perfused with unsupplemented culture medium served as controls. In PFC-supplemented medium, the decrease in the partial pressure of oxygen in the aqueous phase was only 50% of that in control medium (28 mmHg vs. 45 mmHg between the construct inlet and outlet at a flow rate of 0.1 mL/min). Consistently, constructs cultivated in the presence of PFC contained higher amounts of DNA and cardiac markers (troponin I, connexin-43) and had significantly better contractile properties as compared to control constructs. In both groups, electron microscopy revealed open channels and the presence of cells at the channel surfaces as well as within constructs. Improved properties of cardiac constructs could be correlated with the enhanced supply of oxygen to the cells, by a combined use of channeled scaffolds and PFC.     

The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain

In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.     

New RB1 oncogenic mutations and intronic polymorphisms in Serbian retinoblastoma patients: genetic counseling implications

The purpose of this work was to identify germ line RB1 mutations in 16 Serbian retinoblastoma patients for genetic counselling. Mutation analysis was carried out by PCR directed sequencing of the 27 exons. Loss of heterozygosity for two RB1 intragenic markers was also analyzed in 14 tumour samples. Five new RB1 oncogenic mutations (g.2078 del C, g.77047_48 del GC, g.78117_8 del TT, g.160797 del T, and g.64439+2 T>C) and two recurrences (R445X and Q383X) have been found in this study. In addition, four intronic variants were observed germ line in some unilateral patients. Two of these variants (g.44668-15T/G, and g.166204-8T/A) are discussed as potential oncogenic mutation candidates. The results show the relevance of studies aimed to investigate the role of intronic variants in exon splicing regulation. Such studies will help to disclose hidden retinoblastoma susceptibilities, important for accurate genetic counselling.