Endovascular model of ischemic stroke in swine guided by real-time MRI.

Modeling stroke in animals is essential for testing efficacy of new treatments; however, previous neuroprotective therapies, based on systemic delivery in rodents failed, exposing the need for model with improved clinical relevance. The purpose of this study was to develop endovascular approach for inducing ischemia in swine. To achieve that goal, we used intra-arterial administration of thrombin mixed with gadolinium and visualized the occlusion with real-time MRI. Placement of the microcatheter proximally to rete allowed trans-catheter perfusion of the ipsilateral hemisphere as visualized by contrast-enhanced perfusion MR scans. Dynamic T2*w MRI facilitated visualization of thrombin + Gd solution transiting through cerebral vasculature and persistent hyperintensities indicated occlusion. Area of trans-catheter perfusion dynamically quantified on representative slice before and after thrombin administration (22.20 ± 6.31 cm2 vs. 13.28 ± 4.71 cm2 respectively) indicated significantly reduced perfusion. ADC mapping showed evidence of ischemia as early as 27 min and follow-up T2w scans confirmed ischemic lesion (3.14 ± 1.41 cm2). Animals developed contralateral neurological deficits but were ambulatory. Our study has overcome long lasting challenge of inducing endovascular stroke model in pig. We were able to induce stroke using minimally invasive endovascular approach and observe in real-time formation of the thrombus, blockage of cerebral perfusion and eventually stroke lesion.

Giant cardiac tumours in the newborn: an unusual image.

Primary heart tumours in the paediatric population are very rare and they range from 0.01% to 0.04%. Most are benign lesions of which about half are rhabdomyomas. Rhabdomyoma tumour diagnosis is associated with a 75-80% risk of tuberous sclerosis complex (TSC). TSC are characterised with numerous changes of hamartoma-type located in the brain, kidneys, skin and other organs including the heart. More than two-thirds of newborns with TSC present rhabdomyomas in the heart. These changes may be asymptomatic, but in some cases they may cause heart failure, arrhythmias and death. We present a case report of an infant with giant rhabdomyoma tumours in the course of TSC.

Effects of morin-5'-sulfonic acid sodium salt (NaMSA) on cyclophosphamide-induced changes in oxido-redox state in rat liver and kidney.

Cyclophosphamide (CPX) is an anticancer drug with immunosuppressive properties. Its adverse effects are partly connected to the induction of oxidative stress. Some studies indicate that water-soluble derivative of morin-morin-5'-sulfonic acid sodium salt (NaMSA) exhibits strong antioxidant activity. The aim of present study was to evaluate the effect of NaMSA on CPX-induced changes in oxido-redox state in rat. Experiment was carried out on Wistar rats divided in three experimental groups (N = 12) receiving: 0.9% saline, CPX (15 mg/kg) or CPX (15 mg/kg) + NaMSA (100 mg/kg), respectively, and were given intragastrically for 10 days. Malondialdehyde (MDA) and glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were determined in liver and kidneys. Catalase (CAT) activity was assessed only in liver. Treatment with CPX resulted in significant decrease in MDA level in both tissues, which was completely reversed by NaMSA treatment only in liver. In comparison to the control group significant decrease in SOD activity were observed in both tissues of CPX receiving group. In kidneys this parameter was fully restored by NaMSA administration. CPX evoked significant decrease in GSH concentration in kidneys, which was completely reversed by NaMSA treatment. No significant changes were seen in GSH levels and CAT activity between all groups in liver. Results of our study suggest that CPX may exert significant impact on oxido-redox state in both organs. NaMSA fully reversed the CPX-induced changes, especially MDA level in liver, SOD activity and GSH concentration in kidneys and it may be done by enhancement of activity/concentration of endogenous antioxidants.

The Marfan syndrome - features, natural history and treatment options - our experiences.

The Marfan syndrome (MFS) is one of the most common (1:3000-1:4000) heritable connective tissue disorders. It's still a rarely diagnosed syndrome, especially in childhood. Near all cases MFS results from mutations in the fibrillin-1 (FBN1) gene on chromosome 15q21.1, which encodes for the glycoprotein fibrillin. The FBN1 gene is a large protein that can cause more than 500 mutations and molecular examinations, finally confirming the diagnosis, are conducted extremely rare. We present prospective data concerning 66 patients with clinically-diagnosed MFS who have been controlled in Department of Pediatric Cardiology and Congenital Heart Diseases Medical University in Gdansk in 2000 - 2010. 29 patients (44%) had mitral valve regurgitations, 19 (29%) aneurysmal dilatation of the aorta, 13 (20%) had both these irregularities. In 7 cases (11%) diagnosis of mitral valve prolapse preceded appearance of an aneurysmal dilalation of the aortic bulb. During the observation 11 patients (17%) underwent cardiosurgical procedures for the sake of stopping crucial progressive mitral valve dysfunction and/or aneurysmal dilatation of the aortic bulb, which threatened with a rupture of aortic aneurysm. In 39 cases (59%) prophylactic treatment with beta - blockers was administered. The patients with MFS need a multidisciplinary system of care and the psychological supporting. The cardiosurgical treatment, which nowadays is bringing better results, due to the technological advancements is a new hope for this patient population.

The course of the dilated cardiomyopathy in three siblings - a rare case of familial non-compact left ventricle.

The dilated cardiomyopathy still remains a big problem in infant's cardiology. Almost a third of patients with this diagnosis die in infancy, 30% will suffer from the chronic heart failure that forces constant treatment or/and heart transplantations, and in remaining 30% we notice improvement during infancy. We presented the clinical course and progress of dilated cardiomyopathy based on the case of three siblings. Signs of the heart failure were nonspecific. Concluding: diagnostic vigilance must be shown in the cases of positive familial history.

Fermi surface of an important nanosized metastable phase: Al3Li.

Nanoscale particles embedded in a metallic matrix are of considerable interest as a route towards identifying and tailoring material properties. Al-Li alloys, which form ordered nanoscale precipitates of Al(3)Li for a range of concentrations, have been deployed successfully in the aerospace industry owing to their superior strength-to-weight ratio. The precipitates are metastable and their electronic structure has so far been inaccessible through conventional techniques. Here, we take advantage of the strong positron affinity of Li to probe the Fermi surface of nanoscale Al(3)Li precipitates.

The Influence of prolonged beta-blockers treatment on male rabbit's sexual behavior and penile microcirculation.

The aim of the study was to assess the effect of the prolonged intake of three beta-blocking drugs (propranolol, metoprolol and nebivolol) on the sexual behavior and penile microcirculation of rabbits. Drugs were administered p.o. for 9 weeks and every three weeks in each group (n=13) one subgroup (n=7) performed behavioral tests, whereas in the second subgroup (n=6) penile microcirculation was measured with a laser Doppler flowmeter. The copulation studies revealed significant impairment of sexual function only in the propranolol treated group. The measured behavioral parameters suggest that at a given dose propranolol affects more performance rather than arousal aspects of rabbits' sexual behavior. In the course of the whole study no significant difference was observed among groups in penile blood flow. The data indicate that among the beta-blockers given only propranolol interferes with sexual behavior, and that beta-blockers do not appear to have a negative effect on penile microcirculation.

Anomalous electronic correlations in the ground state momentum density of Al(97)Li(3).

We report high resolution Compton scattering measurements on an Al(97)Li(3) disordered alloy single crystal for momentum transfer along the [100], [110], and [111] symmetry directions. The results are interpreted via corresponding Korringa-Kohn-Rostoker coherent potential approximation first-principles computations. By comparing spectra for Al(97)Li(3) and Al, we show that the momentum density in the alloy differs significantly from the predictions of the conventional Fermi-liquid picture and that the ground state of Al is modified anomalously by the addition of Li.

Atrioventricular septal defect: clinical and diagnostic problems in children hospitalised in 1993-1998.

INTRODUCTION: Atrioventricular septal defect (AVSD) is one of the most frequent congenital heart diseases, making up 7.5% of all developmental anomalies of circulatory system. MATERIAL AND METHODS: Sixty-seven children with the diagnosis of atrioventricular septal defect were hospitalised at the Department of Paediatric Cardiology, Medical University in Gdansk, in 1993-1998. Patients' age ranged at diagnosis between 3 days and 17 years (mean age 35 months). The analysed group included 20 children with partial atrioventricular septal defect (group I) and 47 children with complete AVSD (group II). The diagnosis was based on anamnesis, physical examination, ECG, chest x-ray and echocardiography. Cardiac catheterisation and angiocardiography were performed in 28 children. RESULTS: On the basis of the results obtained, 6 children with Down syndrome were disqualified from the surgery due to persistent pulmonary hypertension. Fifty-nine children--including all the patients from group I (20) and 39 children from group II were qualified for operations in extracorporeal circulation. Two children from group II required ventilation with the mixture containing NO in the early post-operative period. There were 8 deaths (12%). Three children from group II died preoperatively due to severe generalised infection in early infancy and 5 infants from group II died immediately after operation. No deaths occurred in group I. In one case of a 4 year-old boy with partial atrioventricular septal defect, atrioventricular block developed immediately after surgery and required constant stimulation of the heart. In two children it was necessary to replace mitral valve (2 and 5 years after ASD I surgery). CONCLUSIONS: 1. Children with Down syndrome require screening echocardiography. 2. Non-invasive diagnostic examinations of atrioventricular septal defect are usually sufficient for the full assessment of the defect and the choice of further treatment. 3. The correction of the congenital heart disease such as atrioventricular septal defect should be completed in the first 6 months of life, particularly in children with complete AVSD.

Effects of pamidronate on the development of changes in bone mechanical properties and bone structure caused by the administration of prednisolone in rats.

The purpose of the study was to investigate the influence of pamidronate on mechanical properties, growth, and structural changes in bones of rats in which experimental osteopenia was induced by administration of prednisolone. The experiment was carried out on male WAG rats divided into three groups: I. Control, II. Prednisolone (5 mg/kg im daily) and III. Disodium pamidronate (3 mg/kg sc daily) + prednisolone (5 mg/kg im daily). After three weeks of the experiment, the animals were sacrificed and their femoral and tibial bones were prepared. The administration of prednisolone resulted in morphological and metabolic changes in the osseous system, characteristic of osteopenia. The increased osteopsathyrosis was noted, manifesting in lowered resistance to fractures and lesser deformability in comparison with the control group. The administration of pamidronate resulted in the reduction of the destructive action of prednisolone on bones.

[Molecular-genetic characteristics of mutations in dystrophin gene and clinical symptoms in Duchenne muscular dystrophy]. / Molekularno-genetyczna charakterystyka mutacji w genie dystrofiny (DMD), a obraz kliniczny dystrofii miesniowej Duchenne'a.

The purpose of this paper is the estimation of the interrelationship of molecular findings with clinical studies on Duchenne muscular dystrophy (DMD), the estimation of molecular genetic findings efficiency focused on the diagnosis and the prognosis and carrier detection in relatives with recommendation of prenatal diagnosis possibilities. DNA isolated from peripheral blood lymphocytes of 100 patients was examined. DNA analyses was performed by multiplex PCR for promoter and 21 exons of DMD gene in regions where mutations are most frequent. Deletions were detected in 55% of the cases. In cases with no deletions detected, PCR-SSCP and PCR-HD analysis were performed in order to detect point mutations. For selected introns and exon 48 the occurrence of the previously described polymorphism was confirmed. Mutation causing formation of shortened protein was detected in exon 6 of two patients. Point mutation analysis is important complement of molecular diagnostics of Duchenne muscular dystrophy in patients with no deletions. For each family at risk of DMD the analysis of mutant allele was performed and carrier status evaluated.

Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance.

We performed a comprehensive analysis for mutations in the TSC1 gene using Southern blot analysis, and SSCP and heteroduplex analysis of amplified exons in 13 families with genetic linkage to the TSC1 region, 22 small families without linkage information, and 126 sporadic patients. 17 unique mutations were identified in 21 patients. Mutations were found in 7/13 (54%) TSC1-linked families, 1/22 (5%) small families without linkage, and 13 of 126 (10%) sporadic cases. The mutations were all chain-terminating, with 14 small deletions, 1 small insertion, and 6 nonsense mutations. In families with mutations, all individuals carrying a mutation met formal diagnostic criteria for TSC, apart from a 3-year-old girl who had inherited a deletion mutation, and who had no seizures, normal intelligence, normal abdominal ultrasound, and hypomelanotic macules only on physical exam. We assessed the incidence and severity of mental retardation in the 13 sporadic patients with TSC1 mutations versus the entire sporadic cohort, and found no significant difference. The observations indicate that TSC1 mutations are all inactivating, suggest that TSC1 disease occurs in only 15-20% of the sporadic TSC population, and demonstrate that presymptomatic TSC does occur.

Human XPMC2H: cDNA cloning, mapping to 9q34, genomic structure, and evaluation as TSC1.

XPMC2 is a Xenopus gene identified on the basis of its ability to correct a mitotic defect in fission yeast. Here we report the identification of cDNA clones for human XPMC2H, its mapping to the tuberous sclerosis gene TSC1 region on 9q34, determination of genomic structure, and identification of several coding region polymorphisms. The predicted protein has strong sequence similarity to the Xenopus gene. Through SSCP and heteroduplex analysis of genomic DNA, we found two intragenic polymorphisms but no evidence for significant mutations in patients with tuberous sclerosis in this gene.

Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.

Cloning and evaluation of RALGDS as a candidate for the tuberous sclerosis gene TSC1.

RALGDS is a 115 kDa protein which was identified by its ability to enhance guanine nucleotide exchange for the ras family member ral. It also binds to activated ras and rap1, and appears to function as part of a signalling complex in downstream events following rap1 activation. Here we report the identification of full-length cDNA clones for human RALGDS, isolated from a brain cDNA library. The predicted protein has strong sequence homology to rat and murine isoforms of RALGDS in the N- and C-terminal regions, but an internal region (aa 250-380) shows relatively high divergence with only 42% identical amino acid residues. The human RALGDS gene is contained within a 30 kb region of 9q34, approximately 200 kb proximal to the ABO gene, within the current critical region for the tuberous sclerosis gene TSC1. Partial genomic structure was determined; it consists of at least 11 exons. Based upon analysis of Southern blots from 110 TSC patients, genomic DNA SSCP analysis, and RT-PCR analysis which demonstrated RNA expression of both alleles in patients from 9q34-linked TSC families using intragenic polymorphisms, we conclude that RALGDS is not likely to be TSC1.

Deletion screening and carrier detection in Duchenne muscular dystrophy in Polish population via direct analysis of DNA and RNA transcripts.

Analysis of 102 Polish Duchenne/Becker muscular dystrophy (D/BMD) patients was performed by 'multiplex' amplification of 22 fragments of the DMD/BMD gene and deletions were found in 55% of the patients. The data obtained using PCR were compared with results of 25 Southern blotting and hybridization experiments with cDNA probes and with immunostaining using anti-dystrophin antibodies. In order to determine more precise deletion breakpoints, additional experiments were performed on dystrophin transcripts isolated from peripheral blood lymphocytes. These data found direct application in carrier analysis in the respective families by detection or exclusion of aberrant cDNA fragments. Carrier detection was also performed by RFLP-PCR, analysis of polymorphic (CA)n repeats and single stranded conformational polymorphism (SSCP) for selected exons of the DMD gene.

[Analysis of angiotensin converting enzyme (ACE) polymorphism in patients with myocardial infarction in the Polish population]. / Analiza polimorfizmu Genu knowertazy angiotensynowej (ACE) u chorych z przebytym zawalem miesnia sercowego w populacji polskiej.

Analysis is presented of polymorphism of gene specifying angiotensin converting enzyme in Polish population and its comparison with results obtained for control group. Insertion/deletion polymorphism was detected by polymerase chain reaction. Frequencies of I/D alleles in control group were similar to those reported in French population but different frequencies were observed in patients with myocardial infarction.