West syndrome with periventricular leukomalacia: ten-year clinical study

The aim of the study was to evaluate magnetic resonance imaging (MRI) findings in infants with periventricular leukomalacia (PVL) and West syndrome (WS) and determine the neurodevelopmental outcome in children with West syndrome and PVL. Ultrasound and brain MRI were performed in 37 infants with recognized PVL. PVL was categorized according to De Vries, whereas West syndrome was categorized according to International League Against Epilepsy 1989. West syndrome in our patients developed during the first 2 years of life. The most common interictal abnormality was hypsarrhythmia. All, except two patients had delayed development and various degrees of mental retardation. The most characteristic neuroimaging findings were major reduction in cerebral cortical gray matter volume, reduction in the volume of brain myelin, and delayed myelination. These findings may explain the anatomical association between the West syndrome onset and PVL and intellectual and cognitive deficit in premature infants with PVL.     

Fatty-Acid Profile of Total and Polar Lipids in Cultured Rainbow Trout (Oncorhynchus mykiss) Raised in Freshwater and Seawater (Croatia) Determined by Transmethylation Method

Fatty acids from total lipids and polar lipids in cultured rainbow trout (Oncorhynchus mykiss) raised in seawater (SW) and freshwater (FW) were identified and quantified from the muscle samples in January, April, and July. The highest total lipid and polar lipid amounts were found in April. July contents of total lipids were low, but percent of the polyunsaturated fatty acids (PUFAs) was high in SW and FW environment (particularly n-3 PUFAs). Variety of 17 fatty acids was identified by GC-FID after transmethylation. The predominant fatty acids in rainbow trout from SW and FW were: docosahexaenoic acid among n-3 PUFAs, palmitic acid among saturated fatty acids (SFAs), and oleic acid among monounsaturated fatty acids (MUFAs). Appreciably higher n-3/n-6 ratio was found in total lipids in April (6.40, FW fish) and in polar lipids in July (18.76; SW fish). High n-3/n-6 ratio in total lipids and polar lipids of rainbow trout from SW and FW, besides beneficial n-3/n-6 ratio in the commercial fish food, could be characteristic for the local environmental conditions (Croatia).     

Phenylcyclobutyl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I

3-(Phenylcyclobutyl)-1,2,4-triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). These were active both in vitro and in an in vivo mouse pharmacodynamic (PD) model. Fluorine substitution of the cyclobutane ring improved the pharmacokinetic profile significantly. The synthesis and structure-activity relationships are presented.     

Nail position has an influence on anterior knee pain after tibial intramedullary nailing

Our aim was to determine the possible relationship between anterior knee pain (AKP) and nail position marked as a distance from tip of nail to tibial plateau (NP) and to the tuberositas tibiae (NT). Nail position has an influence on anterior knee pain after tibial intramedullary nailing. We evaluated postoperative outcome results of 50 patients in the last 3 years with healed fractures initially treated with intramedullary (IM) reamed nails with 2 or 3 interlocking screws on both parts of the nail and with the use of medial paratendinous incision for nail entry portal. Patients marked a point on the visual analog scale (VAS) that corresponded to the level of postoperative AKP felt. Two groups of patients were formed on the basis of AKP (pain level was neglected): groups A and B, with and without pain, respectively. The difference between the two groups concerning NP measurements was statistically significant (p < 0.05), but not concerning NT measurements at the p < 0.05 level. Patients were classified by pain with high accuracy (98%) according to a classification tree. Symptoms of AKP did not appear if the tip of the nail position was more than 6.0 mm from the NP and more than 2.6 mm from the NT. However, for better evaluation of these results it will be necessary to examine a larger number of postoperative patients with AKP.     

Hepatic and pancreatic glycosphingolipid phenotypes of the neurological different rat strains

Among three commonly used strains of laboratory rats, Wistar rats perform more neurological tasks better then Lewis and Sprague-Dawley (SD) rats. Liver is the main site of insulin-like growth factor (IGF) production and pancreas is the exclusive site of insulin production. Insulin stimulates neuronal development and appropriate IGF-I input is critical in brain growth. Glycosphingolipids (GSLs) are important mediators of insulin secretion and action. Therefore, this study investigated GSL phenotypes of liver and pancreas with hypothesis that they are different in three rat strains. Total GSL fractions (neutral and gangliosides) were analysed by high performance thin-layer chromatography (HPTLC). Complex gangliosides were detected by HPTLC immunostaining using cholera toxin B subunit after neuraminidase pretreatment. Wistar rats had the highest liver weight/body weight ratio and SD rats had the highest pancreas weight/body weight ratio. Ganglioside GM3 was more expressed in the liver of Wistar compared to Lewis and SD rats. SD rats contained scarce quantities of GD1a and b-series gangliosides in the liver compared to Wistar and Lewis rats. Pancreatic b-series ganglioside content was also the lowest in SD rats. This study represents differences in the hepatic and pancreatic ganglioside phenotypes of three rat strains that could influence IGF and insulin secretion and action.     

Absolutely conserved tryptophan in M49 family of peptidases contributes to catalysis and binding of competitive inhibitors

The role of the unique fully conserved tryptophan in metallopeptidase family M49 (dipeptidyl peptidase III family) was investigated by site-directed mutagenesis on human dipeptidyl peptidase III (DPP III) where Trp300 was subjected to two substitutions (W300F and W300L). The mutant enzymes showed thermal stability equal to the wild-type DPP III. Conservative substitution of the Trp300 with phenylalanine decreased enzyme activity 2-4 fold, but did not significantly change the K_m values for two dipeptidyl 2-naphthylamide substrates. However, the K_m for the W300L mutant was elevated 5-fold and the k_cat value was reduced 16-fold with Arg-Arg-2-naphthylamide. Both substitutions had a negative effect on the binding of two competitive inhibitors designed to interact with S1 and S2 subsites.These results indicate the importance of the aromatic nature of W300 in DPP III ligand binding and catalysis, and contribution of this residue in maintaining the functional integrity of this enzyme’s S2 subsite.