Transplantation of Human Adipose Mesenchymal Stem Cells in Non-Immunosuppressed GRMD Dogs is a Safe Procedure.

The possibility to treat Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, through cell therapy with mesenchymal stromal cells (MSCs) has been widely investigated in different animal models. However, some crucial questions need to be addressed before starting human therapeutic trials, particularly regarding its use for genetic disorders. How safe is the procedure? Are there any side effects following mesenchymal stem cell transplantation? To address these questions for DMD the best model is the golden retriever muscular dystrophy dog (GRMD), which is the closest model to the human condition displaying a much longer lifespan than other models. Here we report the follow-up of 5 GRMD dogs, which were repeatedly transplanted with human adipose-derived mesenchymal stromal cells (hASC), derived from different donors. Xenogeneic cell transplantation, which was done without immunosuppression, was well tolerated in all animals with no apparent long-term adverse effect. In the present study, we show that repeated heterologous stem-cell injection is a safe procedure, which is fundamental before starting human clinical trials.

In vitro Effects of Lemongrass Extract on Candida albicans Biofilms, Human Cells Viability, and Denture Surface.

The purpose of this study was to investigate whether immersion of a denture surface in lemongrass extract (LGE) has effects on C. albicans biofilms, human cell viability and denture surface. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were performed for LGE against C. albicans. For biofilm analysis, discs were fabricated using a denture acrylic resin with surface roughness standardization. C. albicans biofilms were developed on saliva-coated discs, and the effects of LGE at MIC, 5XMIC, and 10XMIC were investigated during biofilm formation and after biofilm maturation. Biofilms were investigated for cell counting, metabolic activity, and microscopic analysis. The cytotoxicity of different concentrations of LGE to peripheral blood mononuclear cells (PBMC) was analyzed using MTT. The effects of LGE on acrylic resin were verified by measuring changes in roughness, color and flexural strength after 28 days of immersion. Data were analyzed by ANOVA, followed by a Tukey test at a 5% significance level. The minimal concentration of LGE required to inhibit C. albicans growth was 0.625 mg/mL, while MFC was 2.5 mg/mL. The presence of LGE during biofilm development resulted in a reduction of cell counting (p < 0.05), which made the MIC sufficient to reduce approximately 90% of cells (p < 0.0001). The exposure of LGE after biofilm maturation also had a significant antifungal effect at all concentrations (p < 0.05). When compared to the control group, the exposure of PBMC to LGE at MIC resulted in similar viability (p > 0.05). There were no verified differences in color perception, roughness, or flexural strength after immersion in LGE at MIC compared to the control (p > 0.05). It could be concluded that immersion of the denture surface in LGE was effective in reducing C. albicans biofilms with no deleterious effects on acrylic properties at MIC. MIC was also an effective and safe concentration for use.

1-Deoxy-D-xylulose: synthesis based on molybdate-catalyzed rearrangement of a branched-chain aldotetrose.

1-Deoxy-D-xylulose has been prepared in seven steps and approximately 21% overall yield from 2,3-O-isopropylidene-D-erythrono-1,4-lactone. The key reaction involves transformation of a branched-chain aldotetrose to the 1-deoxy-2-ketopentose catalyzed by molybdic acid. Other branched-chain aldotetroses containing bulkier substituents at C2 also engage in the conversion, suggesting routes to protected 2-ketoses and alpha-ketoacids/esters. This synthetic route mimics reactions of the non-mevalonate isoprenoid pathway in plants and bacteria. [reaction: see text]

The anterior epitympanic recess: CT anatomy and pathology.

PURPOSE: To describe the variation in size and shape of the anterior epitympanic recess and to discuss pathologic processes that affect this space. METHODS: Axial CT scans of the temporal bones of 31 adults and 19 children were reviewed retrospectively to ascertain the morphology and size of the anterior epitympanic recess. Selected confirmed disease processes involving this space were studied. RESULTS: The anterior epitympanic recess, which is consistently identified on axial CT scans, is either single or multicelled. In our study, it was made up of a solitary cell in 61 of 100 ears. Side-to-side symmetry in shape was present in 78 of 100 cases. The size of a solitary air cell ranged from 1.0 to 7.0 mm. CONCLUSIONS: The configuration of the anterior epitympanic recess is readily affected by a persistent stapedial artery, by facial nerve schwannomas, by hemangiomas of the facial nerve canal in the geniculate region, and by congenital and acquired cholesteatomas. Familiarity with the CT anatomy of this space facilitates recognition of these pathologic processes at an early stage.

Primary paraganglioma of the facial nerve canal.

We report two cases of primary paraganglioma of the facial nerve canal. This entity should be considered in patients presenting with facial paresis or pulsatile tinnitus. Paraganglioma should be considered when a lesion appears to arise from the facial nerve canal.

Spontaneous CSF otorrhea caused by abnormal development of the facial nerve canal.

In two patients with surgically proved CSF fistula through the facial nerve canal, MR and CT examinations showed smooth enlargement of the geniculate fossa with CSF signal. In the clinical setting of CSF otorrhea or rhinorrhea, the presence of an enlarged labyrinthine facial nerve canal and enlarged geniculate fossa on CT scans and CSF intensity on MR images strongly suggests a CSF fistula through the facial nerve canal.

Iatrogenically induced cortical blindness associated with leptomeningeal enhancement.

Leptomeningeal enhancement is usually infective or neoplastic in origin. We present a case in which a patient received total parenteral nutrition via a catheter unknowingly placed within the right vertebral artery. We postulate that the hyperosmolar nature of the infused solution induced temporary osmotic disruption of the blood-brain barrier, resulting in cortical blindness associated with localized leptomeningeal enhancement.

Chronic lymphocytic leukemia presenting as a pituitary mass lesion.

We describe a unique case of chronic lymphocytic leukemia (CLL) in a patient who presented with bitemporal hemianopsia, adrenal insufficiency, and gonadotrophin deficiency. Studies revealed an enhancing intrasellar mass with suprasellar extension and displacement of the optic chiasm. Peripheral blood and cerebrospinal fluid (CSF) studies disclosed a monoclonal IgM kappa expressing B-cell CLL. Biopsy of the pituitary mass revealed dense infiltration of the pituitary gland by leukemic cells. This is, to our knowledge, the first reported case of CLL presenting as a pituitary mass lesion.

A nitro sugar derivative route to 2-thioepisophorose and 2-thiosophorose and their remarkable facile epimerization.

The addition of 1-thio-D-glucose sodium salt to per-O-acetylated 1,2-dideoxy-1-nitro-D-arabino-hex-1-enitol, readily available from D-arabinose, afforded the corresponding 2-S-glycosylated 1-deoxy-1-nitro-D-mannitol and -D-glucitol peracetates. These, after deacetylation, were transformed by the Nef reaction to 2-thioepisophorose and 2-thiosophorose, respectively. The 2-thiodisaccharides easily epimerize in aqueous sodium bicarbonate at ambient temperature to a 1:4 equilibrium mixture. The predominant 2-thiosophorose was obtained crystalline. A 1H NMR study of the epimerization in deuterium oxide showed that the reaction involves an H-2 proton exchange mechanism.

Crystal and molecular structures of beta-cellobiosylnitromethane and of beta-maltosylnitromethane heptaacetate.

The structures of the title compounds have been determined by X-ray crystallography, using direct methods, and have been refined to conventional final residual factors of R = 0.063 and R = 0.046, respectively.

Current role of CT in pediatric neuroimaging.

MR imaging is now the premier imaging modality for the evaluation of neurological disorders in children; however, CT remains a cost effective tool for the investigation of most disorders of the brain, neck, and spine.

Pulmonary edema and fluid mobilization as determinants of the duration of ECMO support.

The physiological variables that govern recovery of pulmonary function during neonatal extracorporeal membrane oxygenation (ECMO) remain poorly understood. We hypothesized that pulmonary hypertension (PHN) resolves soon after starting ECMO and that neonatal weight gain, pulmonary edema, and fluid mobilization are major determinants of recovery of pulmonary function and the ability to decrease ECMO support. To evaluate this, 17 consecutive neonates requiring ECMO for severe respiratory failure were reviewed. PHN was studied by daily echocardiography to assess the direction of ductal shunting. To evaluate fluid flux, pulmonary function, and edema during ECMO, we measured body weight, urine output, and ECMO flow every 12 hours. To evaluate pulmonary edema, serial chest radiographs obtained every 12 hours were randomly reviewed and scored by two radiologists with a semiquantitative chest radiograph index score (CRIS). By 25% of bypass time, PHN had resolved in all patients. However, at that time, weight had increased to 9.16% +/- 1.78% above birth weight, and the CRIS was 44% worse than the value just prior to ECMO. From 25% time on bypass, as urine output increased, patient weight and CRIS progressively decreased, allowing ECMO support to be weaned. At the time of discontinuation of ECMO support, weight had decreased to 2.0% +/- 1.3% above birth weight, and urine output remained steady at 3.0 +/- 0.3 mL/kg/h. Within 24 hours of stopping ECMO, the CRIS showed a 58% improvement compared to maximal scores during ECMO. We conclude that PHN decreases early in ECMO and that edema and its mobilization are important determinants of the improvement in pulmonary function and duration of ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival and echocardiographic evaluation of dogs with idiopathic dilated cardiomyopathy treated with carvedilol / Avaliação ecocardiográfica e de sobrevida de cães com cardiomiopatia dilatada idiopática tratados com carvedilol

Sixty dogs with idiopathic dilated cardiomyopathy were randomly treated with traditional therapy - digitalis, diuretics, angiotensin-converting inhibitors - (group A) or treated with these drugs plus carvedilol (group B). Echocardiographic variables were measured before and after 3, 13, 26, and 52 weeks of treatment or until death. Comparisons between groups and time were performed. No significant differences between groups were found in the most of the echocardiographic variables. The left ventricular end-systolic diameter indexed to body surface area (LVESDi) increased significantly in the group A dogs compared to the group B animals. The survival of groups A and B dogs were not different (P-value=0.1137). In conclusion, the stability of the LVESDi observed in the group treated with carvedilol may represent the beneficial effect over the ventricular remodeling.

Sessenta cães com cardiomiopatia dilatada idiopática receberam, aleatoriamente, tratamento convencional - digitálicos, diuréticos, inibidores da enzima conversora de angiotensina - (grupo A) ou esses fármacos mais carvedilol (grupo B). As variáveis ecocardiográficas foram avaliadas antes e depois de três, 13, 26 e 52 semanas de tratamento ou até o óbito. Não foram encontradas diferenças significativas entre os grupos de animais quanto à maioria das variáveis ecocardiográficas. O diâmetro sistólico final do ventrículo esquerdo indexado à superfície corpórea (DSVEi) aumentou de forma significativa no grupo A quando comparado ao grupo B. Não se observou diferença na sobrevida dos grupos A e B (P=0,1137). Concluiu-se que a estabilização do DSVEi no grupo tratado com carvedilol pode representar o efeito benéfico deste fármaco sobre o remodelamento ventricular.

Partial ACL rupture: an MR diagnosis?

PURPOSE: We sought to clarify the ability of magnetic resonance imaging (MR) to show partial anterior cruciate ligament (ACL) ruptures and to allow distinction of partial from complete ACL ruptures. MATERIALS AND METHODS: Eighty-eight patients were studied by arthroscopy and MR (36 with normal ACLs, 21 with partial ACL ruptures, and 31 with complete ACL ruptures). MR studies were interpreted by an experienced, blinded reader. MR examinations were also independently scored with respect to four primary and seven secondary signs, and these data were analyzed using discriminant analysis. RESULTS: The sensitivity of MR is lower for partial than for complete ACL ruptures. Most detected partial ACL ruptures resemble complete ruptures on MR. Secondary signs do not significantly improve detection of partial ACL ruptures, but they do help to distinguish partial from complete ACL ruptures. Displacement of the posterior horn of the lateral meniscus and popliteus muscle injury are indicative of complete ACL rupture. CONCLUSIONS: The majority of partial ACL ruptures are shown by MR, but MR is less sensitive for partial than for complete ACL rupture. The distinction of partial from complete ACL rupture on MR examination, while problematic, is slightly improved by assessment of secondary signs.

Endoscopic evaluation of dysphagia in the elderly.

A survey of 100 consecutive endoscopies on elderly patients with suspected obstructive dysphagia is reported. Seventy-eight patients had positive findings and one to three lesions were reported in these cases. Benign stricture of the oesophagus was the commonest finding, and led to active treatment (dilation) in most cases either with Hurst bougies or Eder dilators. Fifteen patients had upper gastro-intestinal malignancy (12 oesophagus, three stomach). All of those with oesophageal carcinoma received some form of active treatment, either in the form of radiotherapy, surgery, dilation or Celestin tube insertion. Six patients with negative endoscopies had diagnoses established by other means and in 14 no cause was identified, but in four of these symptoms settled after endoscopy. The duration of dysphagia was not particularly helpful clinically. Two thirds of 'endoscopically normal' patients had short histories with dysphagia for less than 1 year, as did half of the patients with benign stricture. Most patients who were found to be malignant had experienced dysphagia for only a short time although one patient had a 4-year history! Upper gastro-intestinal endoscopy is a safe and valuable procedure in elderly patients with dysphagia and often leads to positive therapeutic intervention even in quite frail subjects.

Growth of Candida albicans on artificial D-glucose derivatives.

Growth of Candida albicans on artificial D-glucose derivatives (amino-, methyl-, acylglycosides and N-acetyl-D-glucosamine derivatives) was examined with the aim to find new inducers of the mycelial growth form. For representatives of particular groups (alpha-D-glucopyranosylamine, D-glucose and N-acetyl-D-glucosamine) some physiological (growth, doubling time, specific growth rate, oxygen uptake and CO2 production, respiration quotients), biochemical (dry weight yield, protein content, ethanol production), and morphological parameters (length-width quotient, volume, percentage of budding cells) of cultures in different growth phases were determined with regard to the type and concentration of carbon source. The results obtained may be valuable for studies of the structure-utilization relationships of carbohydrate derivatives as well as for the elucidation of yeast-mycelial transition in Candida albicans induced by unphysiological hexoses degradable intracellularly.

The pediatric patient with suspected adrenal neoplasm: which radiological test to use?

To establish which radiological test to use in a pediatric patient with suspected neoplasm, we retrospectively studied 19 children with proven adrenal neoplasm who had a combination of ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). The results show that US should remain the initial imaging modality for evaluating abdominal masses in children but that MRI is more accurate than CT and US in detecting the organ of origin and the extent of an adrenal lesion and should, therefore, be the modality of choice for the definitive evaluation of adrenal neoplasm in children.

Toward an optimal oligosaccharide ligand for rat natural killer cell activation receptor NKR-P1.

Aminosugars have a good affinity for the NKR-P1A protein, the major activating receptor at the surface of rat natural killer cells. We have systematically investigated the structural requirements of the recombinant soluble dimeric form of the receptor for its optimal carbohydrate ligands. While N-acetylD-mannosamine was the best neutral monosaccharide ligand, its participation in the context of an extended oligosaccharide sequence was equally important. The IC(50) value for the GalNAcbeta1 --> ManNAc disaccharide was nearly 10(-10) M with a further possible increase depending on the type of the glycosidic linkage and the aglycon nature. From the point of view of its availability, stability, and affinity for the receptor and a potential in vivo use, these studies are pivotal for the design of an oligosaccharide or glycomimetics suitable for further clustering into the multivalent glycodendrimers.

Chemical ionization mass spectra of acetals of beta-D-glycopyranosylnitromethanes

O-Isopropylidene and O-benzylidene acetals of common 2, 6-anhydro-1-deoxy-1-nitroalditols (beta-D-glycopyranosylnitromethanes) derived from D-glucose, D-galactose and D-mannose were studied by chemical ionization mass spectrometry (CIMS) using methane, isobutane, ammonia or pyridine as reaction gas. Production of [M+H](+) adduct ions dominates in the case of methane or isobutane possessing proton affinity values PA = 552 or 683 kJ mol(-1), respectively. The collision-induced dissociation time-of-flight product ion spectra of [M+H](+) ions differ characteristically according the stereochemical arrangement of the pyranoid ring. These differences can be helpful when assigning stereochemical arrangements for the pyranoid ring. The dominant process in ammonia (PA = 853 kJ mol(-1)) CIMS for most of the compounds studied is the production of the cluster ions [M+NH(4)](+). The cluster [M+pyridineH](+) ions are observable only for substances possessing the O-benzylidene group (PA of pyridine = 924 kJ mol(-1)). Copyright 2000 John Wiley & Sons, Ltd.