Magnetic resonance imaging assessment of substantia nigral iron deposition in Parkinson's disease: a meta-analysis.

OBJECTIVE: The pathogenesis of Parkinson's disease (PD) is associated with abnormal iron accumulation. Magnetic resonance imaging (MRI) studies have shown that patients with Parkinson's disease have an increased amount of iron in their substantia nigra (SN). We have undertaken a meta-analysis of studies using MRI in PD, to explore the potential role of MRI in diagnosing PD using abnormal iron deposition in SN as a candidate biomarker. MATERIALS AND METHODS: Searches of PubMed, Embase, and Medline databases revealed 16 studies that compared PD patients and healthy controls (HC). A sensitivity analysis and subgroup analysis were performed to evaluate the reliability of our results. Estimates were pooled by the fixed-effects model. As an expression of I2, we computed the proportion of variation due to heterogeneity. RESULTS: We included 16 studies with sample sizes of 435 PD and 355 HC in our meta-analysis. Results showed that SN iron deposition was significantly elevated (p<0.00001) in patients with PD compared to HC ones (SMD=0.72, 95% confidence interval 0.57 to 0.87, p<0.00001). CONCLUSIONS: Our findings, based on a homogeneous group-level analysis, suggest that MRI-based SN iron deposition could be used to distinguish PD from HC. For a more rigorous investigation of SN iron deposition in PD, larger cohort studies are needed.

[Chi-liang Kwei and an unfulfilled plan of establishing a modern psychiatric hospital in China].

Church General Hospital in Wuchang, China planned to establish a psychiatric hospital in 1930. Chi-liang Kwei, received his PhD at Johns Hopkins Medical School of America and was appointed to be in charge of the preparation. After working out a draft plan for the hospital, Dr. Kwei applied for the Henderson Research Scholarship on Mental Diseases. She planned to study under the guidance of Dr. D.K. Henderson in the Glasgow Mental Royal Hospital for a full year in preparation for the establishment of the hospital. By drawing on the correspondence files of Chi-liang Kwei and psychiatrists Adolf Meyer and David Kennedy Henderson, the paper describes the background conditions and planning for the hospital establishment and interprets the significance and value of Chi-liang Kwei's efforts to establish a psychiatric hospital from the perspective of the historic development of modern psychiatry in China.

Voiding urosonography with second-generation ultrasound contrast versus micturating cystourethrography in the diagnosis of vesicoureteric reflux.

Vesicoureteric reflux has been associated with paediatric urinary tract infection. Fluoroscopic micturating cystourethrography (MCU) has been the gold standard of diagnostic test for decades; however, it has been criticized owing to its lower detection rate and radiation dose to children. Therefore, new radiation-free reflux imaging modalities have been developed, in which ultrasound-based contrast-enhanced voiding urosonography (ceVUS) is a good example. However, ultrasonography has been considered as an operator-dependent examination. Therefore, our study aimed to examine the inter-observer agreement of this sonographic technique, which has not been evaluated before. Moreover, the second-generation ultrasound contrast SonoVue has been recently marketed, and the data on its efficacy on intravesical use in ceVUS is relatively scarce. Thus, we also aimed to investigate the diagnostic performance and safety profile of SonoVue-enhanced VUS in the diagnosis of vesicoureteric reflux. Our prospective comparative study compared the diagnostic performance of ceVUS with MCU in young children presenting with first episode of urinary tract infection. We performed sequential ceVUS and MCU examinations in 31 patients (62 pelvi-ureter units). Perfect inter-observer agreement (Cohen's kappa statistics = 1.0, p < 0.001) was achieved in ceVUS, suggesting its good reliability in reflux detection and grading. Using MCU as reference, ceVUS had 100 % sensitivity and 84 % specificity and carried higher reflux detection rate than MCU (p < 0.001). There was no complication encountered. Conclusion: Voiding urosonography is a reliable, sensitive, safe and radiation-free modality in the investigation of vesicoureteric reflux in children. It should be incorporated in the diagnostic algorithm in paediatric urinary tract infection.

Scrotal antegradesclerotherapy demonstrates anatomical variations on venous drainage in paediatric, adolescent and young adult varicoceles.

AIM OF THE STUDY: Anatomical variations on venous drainage in varicoceles are under-reported. We report our experience in scrotal antegrade sclerotherapy (SAS) for adolescent varicoceles. METHODS: Since 2011, 15 consecutive boys with left varicoceles were recruited. Under general anaesthesia, a 5-mm transverse incision was made at scrotal neck, testicular vein was cannulated at pampiniform plexus with venogram performed. Foam sclerosant by mixing sodium tetradecyl sulphate (STS), Lipiodol(®) and air was slowly injected under fluoroscopy. Postoperatively the patients were followed-up for varicocele grading, testicular size, and complications. MAIN RESULTS: Median age at operation was 14 (10-19) years. 80 % had grade three varicoceles, 33.3 % had smaller left testis before operation. Intra-operative venogram showed three different anatomical variations. Group I: eleven patients (73.3 %) had single distinct internal spermatic vein; Group II: two patients demonstrated duplication of internal spermatic vein draining into left renal vein; Group III: two patients had pampiniform plexus draining to iliac and/or paraspinal veins. SAS was performed in Group I and II patients. Sclerosant volume injected ranged from 1.5 to 4.5 ml. In Group III patients, surgical ligation of testicular veins was performed rather than SAS to avoid uncontrolled systemic sclerosant spillage. Mean length of stay was 1.13 day. One patient with scrotal haematoma and one other with minor wound dehiscence were managed conservatively. Mean follow-up period was 10.9 (1-22) months. Thirteen patients (86.7 %) achieved varicocele grading ≤ 1. There was no postoperative testicular atrophy, hydrocele and epididymo-orchitis. CONCLUSION: Scrotal antegrade sclerotherapy using STS foam is a safe and effective treatment for adolescent varicoceles. Anatomical variations on venous drainage in varicoceles are common.

Enzyme replacement therapy for mucopolysaccharidosis VI (Maroteaux-Lamy syndrome): experience in Hong Kong.

Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is a very rare inherited lysosomal storage disease. We evaluated the efficacy and safety of weekly infusions of recombinant human arylsulfatase B as enzyme replacement therapy for two patients in whom this condition was advanced. The primary outcome variables were the distance walked in a 6-minute walk test, forced vital capacity, and ejection fraction. The secondary outcome variables were the number of stairs climbed in a 3-minute stair climbing test, joint mobility, urinary glycosaminoglycan excretion, auto-continuous positive airway pressure study and liver size. After 24 weeks of treatment, patient A walked 40 m (36%) and patient B walked 66 m (58%) more in the walk test than at baseline. After 48 weeks, in patient A the corresponding improvements were 142 m (129%) in the walk test and 33 stairs (60%) in the 3-minute stair climbing test, and in patient B the respective improvements were 198 m (174%) and 77 stairs (140%). There was a significant decline in urinary glycosaminoglycan excretion and improvement in range of motion of joints in both patients. The auto-continuous positive airway pressure study revealed improvements in patient A, while other efficacy variables remained static. There were no drug-related adverse events or allergic reactions reported during and after the infusions of recombinant human arylsulfatase B. Recombinant human arylsulfatase B significantly improves endurance and reduces urinary glycosaminoglycan excretion. The drug is generally safe and well tolerated.

Relationships between sediment microbial communities and pollutants in two California salt marshes.

Salt marshes are important ecosystems whose plant and microbial communities can alter terrestrially derived pollutants prior to coastal water discharge. However, knowledge regarding relationships between anthropogenic pollutant levels and salt marsh microbial communities is limited, and salt marshes on the West Coast of the United States are rarely examined. In this study, we investigated the relationships between microbial community composition and 24 pollutants (20 metals and 4 organics) in two California salt marshes. Multivariate ordination techniques were used to assess how bacterial community composition, as determined by terminal restriction fragment length polymorphism and phospholipid fatty acid analyses, was related to pollution. Sea urchin embryo toxicity measurements and plant tissue metabolite profiles were considered two other biometrics of pollution. Spatial effects were strongly manifested across marshes and across channel elevations within marshes. Utilizing partial canonical correspondence analysis, an ordination technique new to microbial ecology, we found that several metals were strongly associated with microbial community composition after accounting for spatial effects. The major patterns in plant metabolite profiles were consistent with patterns across microbial community profiles, but sea urchin embryo assays, which are commonly used to evaluate ecological toxicity, had no identifiable relationships with pollution. Whereas salt marshes are generally dynamic and complex habitats, microbial communities in these marshes appear to be relatively sensitive indicators of toxic pollutants.

Synthesis and physico-chemical properties of peptides in soil humic substances.

Soil humic substances (HS) are heterologous, polydispersive, and multi-functional organometallic macromolecules ubiquitous in soils and sediments. They are key players in the maintenance of the belowground ecosystems and in the bioavailability of both organic and inorganic contaminants. It is widely assumed that the peptidic substructures of HS are readily degraded and therefore do not contribute significantly to interactions with contaminants such as toxic metals. To investigate the turnover of humified peptides, laboratory soil aging experiments were conducted with 13C-glucose or 15N-nitrate for 8.5 months. Evidence for random-coil peptidic structures in the labeled HS was obtained from 2-D nuclear magnetic resonance (NMR), pyrolysis gas chromatography-mass spectrometry (pyro-GC-MS), and circular dichroism data. Interaction of metals with the peptidic carbonyls of labeled HS was rationalized from the solid-state NMR data. Detailed 13C and 15N labeling patterns of amino acid residues in the acid hydrolysates of HS acquired from NMR and GC-MS revealed two pools of peptides, i.e. one extant (unlabeled) and the other, newly humified with little isotopic scrambling (fully labeled). The persistence of pre-existing peptidic structures indicates their resistance to degradation while the presence of fully labeled peptidic amino acids suggests wholesale incorporation of newly synthesized peptides into HS. These findings are contrary to the general notion that humified peptides are readily degraded.

Ruptured adrenocortical carcinoma as a cause of paediatric acute abdomen.

Adrenocortical carcinoma (ACC) is rare in children. Its presentation is usually related to hormonal activity of the tumour. We report a case of childhood ACC that presented as an acute abdomen due to tumour rupture. This is the first reported case of a ruptured ACC as a cause of paediatric acute abdomen.

Comprehensive chemical profiling of gramineous plant root exudates using high-resolution NMR and MS.

Root exudates released into soil have important functions in mobilizing metal micronutrients and for causing selective enrichment of plant beneficial soil micro-organisms that colonize the rhizosphere. Analysis of plant root exudates typically has involved chromatographic methods that rely on a priori knowledge of which compounds might be present. In the research reported here, the combination of multinuclear and 2-D NMR with GC-MS and high-resolution MS provided de novo identification of a number of components directly in crude root exudates of different plant types. This approach was applied to examine the role of exudate metal ion ligands (MIL) in the acquisition of Cd and transition metals by barley and wheat. The exudation of mugineic acids and malate was enhanced by Fe deficiency. which in turn led to an increase in the tissue content of Cu, Mn, and Zn. The presence of elevated Cd maintained at a free activity pCd of 8.8 (10(-8.8) M), resulted in reduced phytosiderophore production by Fe deficient plants. The buffer morpholinoethane sulfonate (MES), which is commonly used in chelator-buffering nutrient solutions, was detected in the root exudate mixture, suggesting uptake and re-secretion of this compound by the roots. The ability to detect this compound in complex mixtures containing organic acids, amino acids, and other substances suggests that the analytical methods used here provide an unbiased method for simultaneous detection of all major components contained in root exudates.

Phytosiderophores influence on cadmium mobilization and uptake by wheat and barley plants.

A constant anthropogenic release of cadmium to the environment has resulted in a continuous buildup of Cd in soils. Uptake and accumulation of Cd in plant tissue and in grains may lead to food chain transfer to humans. Application of synthetic chelates was suggested to increase metal mobilization and facilitate phytoextraction as a means for the remediation of metal-polluted soils. However, most of the chelate-extracted metal may be leached rather than mobilized to plant roots. In contrast to the synthetic chelates added to soils, plant-produced chelators called phytosiderophores (PS) are excreted directly to the rhizosphere. Previous studies have shown that PS facilitate uptake of Zn and Fe by graminaceous plants. In this study, a two-step PS mediation of Cd uptake was hypothesized: (i) extraction and chelation in the soil solution, and (ii) delivery of the chelated Cd to the uptake system of the plant. We examined Cd extraction by PS, the synthetic chelate HEDTA [N-(2-hydroxyethyl)-ethylenediaminetriacetic acid], and a fungal siderophore rhizoferrin from solid-phase Cd phosphate at pH 7.3 with and without Fe competition in the presence of Ca and Mg as additional competing metals. While rhizoferrin did not extract Cd, PS and HEDTA did extract Cd even in the presence of Fe. Yet, uptake of Cd by wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) plants was not significantly influenced by Fe stress, but instead was controlled primarily by Cd2+ activity in solution. These results suggest that even though Cd may be mobilized by PS, there is no significant uptake of the Cd-PS complex by the plant roots.

Testicular volume of boys after inguinal herniotomy: combined clinical and radiological follow-up.

A total of 173 boys aged 10 to 179 months with previous unilateral inguinal herniotomy were called back for follow-up. Clinical and ultrasound examinations of the scrotum were performed. The interval between operation and follow-up was 6 to 123 months (mean 31.68 months). One boy (0.58%) had a more than 50% and 10 (5.8%) had a more than 25% decrease in testicular volume on the operated side when compared with the non-operated side.

Analysis of phosphorylated metabolites in crayfish extracts by two-dimensional 1H-31P NMR heteronuclear total correlation spectroscopy (heteroTOCSY).

In vivo and extract analyses by one-dimensional 31P NMR have been a key tool in investigating energy-related metabolism. Although many phosphorylated metabolites have been observed, many of them have yet to be identified. This reflects the difficulty in identifying them using 31P NMR alone. Two-dimensional 1H-31P correlation experiments have been shown to be useful for assigning phosphorylated metabolites. To obtain better sensitivity and structure information, 1H-detected 31P-1H heteronuclear total correlation spectroscopy (heteroTOCSY) was implemented and a complete chemical shift assignment for a number of phosphorylated standards was made. The time courses of 1D heteroTOCSY signal intensity versus spin-locking time were established for these standards to aid the optimization of the 2D experiment. This method was applied to crayfish extracts for the assignment of glucose 6-phosphate, alpha-glycerophosphate, ribose 5-phosphate, fructose 1,6-bisphosphate, phosphocholine, phosphoethanolamine, glucose 1-phosphate, glycerophosphoethanolamine, glycerophosphocholine, ATP, ADP, and AMP. An alkyl phosphate, a hexose 1-phosphate, and a UDP-hexose were also observed. These assignments allowed the identification of many changes in the 31P NMR spectra of crayfish extracts elicited by treatment with the organophosphate pesticide chlorpyrifos. The assignment of an in vivo 31P spectrum of a live crayfish was also made based on the extract assignment. This approach should be a powerful tool for examining stress-associated changes in the metabolism of phosphorylated compounds.

Comprehensive analysis of organic ligands in whole root exudates using nuclear magnetic resonance and gas chromatography-mass spectrometry.

Root exudates in the rhizosphere are vital to the normal life cycle of plants. A key factor is phytometallophores, which function in the nutritional acquisition of iron and zinc and are likely to be important in the uptake of pollutant metals by plants. Unraveling the biochemistry of these compounds is tedious using traditional analyses, which also fall short in providing the overall chemical composition or in detecting unknown or unexpected organic ligands in the exudates. Here, we demonstrate a comprehensive analysis of the exudate composition directly by 1H and 13C multidimensional NMR and silylation GC-MS. The advantages are (a) minimal sample preparation, with no loss of unknown compounds, and reduced net analysis time; (b) structure-based analysis for universal detection and identification; and (c) simultaneous analysis of a large number of constituents in a complex mixture. Using barley root exudates, a large number of common organic and amino acids were identified. Three derivatives of mugineic acid phytosiderophores were also determined, the major one being 3-epihydroxymugineic acid, for which complete 1H and 13C NMR assignments were obtained. Quantification of all major components using these methods revealed a sevenfold increase in total exudation under moderate iron deficiency, with 3-epihydroxymugineic acid comprising approximately 22% of the exudate mixture. As iron deficiency increased, total quantities of exudate per gram of root remained unchanged, but the relative quantity of carbon allocated to phytosiderophore increased to approximately 50% of the total exudate in response to severe iron deficiency.

In vivo 13C NMR analysis of acyl chain composition and organization of perirenal triacylglycerides in rats fed vegetable and fish oils.

Lipid composition of body fat can be a key indicator of nutritional status and a number of human disorders. In vivo 13C NMR provides for repeated, noninvasive analysis of fatty acyl chain composition on individuals, which circumvents classical problems of individual variation and repetitive invasive sampling. It also offers a unique opportunity to examine acyl chain organization in situ. This approach was used to examine the fatty acyl chain composition in the perirenal fat pads of rats fed olive, safflower, and menhaden oil-containing diets. These changes were then monitored during a diet switch between olive and menhaden oil-fed rats. The fatty acid composition of perirenal fat pads and livers was also analyzed using gas chromatography for comparison with the in vivo NMR analysis. Both tissues assumed the general characteristics of diet fatty acyl chain and fatty acid composition and the diet switch induced a switchover of the perirenal composition in 30-45 days. These results indicate that a large portion of the diet fatty acyl chains were incorporated directly into adipose and liver tissues although some were also metabolized, particularly in menhaden oil-fed rats. Furthermore, changes in the in vivo spin-lattice relaxation times (T1) of fatty acyl carbons in the perirenal fat pads and their lipid extracts were followed and effective correlation times (tau eff) were calculated from the T1 data. The result indicated that the in vivo segmental mobility of acyl carbons was sensitive to changes in diet-derived fatty acyl chain composition and that the central region of the acyl chain was more sensitive to these changes. There was a qualitative similarity but quantitative differences in the tau eff of acyl carbons acquired in vivo and from extracts. These results suggest that adipose triacylglycerides experience an overall liquid-like microenvironment in vivo but with more restriction in their mobility, and that different factors may exist in governing their organization in situ versus in extracts.

Electrophoretic separation, characterization, and quantification of biologically active lignin-derived macromolecules.

Degraded macromolecular lignin, which was isolated from the effluents of commercial pulp processing and known to inhibit early development in marine organisms, was separated and characterized using several polyacrylamide gel electrophoresis (PAGE) techniques. This lignin-derived macromolecule (LDM), when subjected to native PAGE and stained with alcian blue, appeared as a single band. On sodium dodecyl sulfate (SDS)-PAGE, LDM appeared to consist of two subcomponents with apparent molecular weights of 11 and < 1 kDa. When subjected to isoelectrofocusing--PAGE of pH 3-9, LDM consisted of two major bands in the basic region of the gel, with less distinct banding in the more acidic region. Two-dimensional PAGE of LDM indicated that the higher molecular weight subcomponent corresponded to the more basic constituents, while the lower molecular weight subcomponent corresponded to acidic constituents. When the two subcomponents of LDM were isolated from SDS gels by electroelution and assessed for their effects on successful fertilization and early development, the higher molecular weight subcomponent possessed most of the inhibitory activity. This is the first report of the application of a variety of electrophoretic techniques to both structurally and biologically characterize lignin-derived macromolecules.

Determination of metabolites by 1H NMR and GC: analysis for organic osmolytes in crude tissue extracts.

World-wide salinity and drought problems necessitate the understanding of biological adaptation to water deficit. Osmotic adjustment via organic solutes is a common strategy for organisms to deal with water deficit problems. Numerous water-soluble organic metabolites across several chemical classes are commonly utilized as osmolytes, including betaines, sulfonium and sulfonate compounds, amino acids, carbohydrates, and polyols. To deal with the complexity and variability in osmolyte composition, we have devised an analytical approach that combines high-resolution 1H NMR and GLC to provide both structure identification and quantification of a broad spectrum of compounds. This combined approach also facilitated direct analyses of crude tissue extracts without extensive sample preparation, making it well-suited for a convenient screening of potential osmolytes. The structures of known osmolytes were confirmed from two-dimensional total correlation 1H NMR spectra, which also yielded structural information about unknown compounds. Five each terrestrial plant and marine animal species were examined for 41 metabolites, including osmolyte candidates glycinebetaine, dimethylsulfoniopropionate, taurine, proline, glycine, asparagine, alanine, glutamine, glucose, and sucrose. The osmotic function of glycinebetaine, proline, asparagine, glutamine, glucose, and sucrose was also demonstrated in leaves of Distichlis spicata under different salinity treatments.

Identification of glycerophosphorylcholine in mussel ovarian extracts by two-dimensional nuclear magnetic resonance.

The abundance of the "phosphodiester" peak in differentiating or proliferating tissues, including reproductive organs and tumors, warrants further investigations of its metabolic role(s), which would require a rigorous confirmation of its identity. The assignment of this peak to glycerophosphorylcholine in 31P NMR spectra of biological samples has been largely based on chemical shift, which can result in ambiguities. We employed a combination of two-dimensional 31P-1H heteronuclear shift correlation and 1H total correlation spectroscopies to trace the spin connectivities of glycerophosphorylcholine and thus to identify its structure directly from crude ovarian extracts of mussels without ambiguities and the need for extensive purification. This approach can be applied generally to the identification of molecules containing heteroatoms in crude tissue extracts.

Hypoxia does not affect rate of ATP synthesis and energy metabolism in rice shoot tips as measured by 31P NMR in vivo.

The cytoplasmic pH, concentrations of phosphate metabolites, and rate of ATP synthesis were measured in vivo in excised rice shoot tips under normoxic and hypoxic conditions using 31P NMR. When supplied with glucose, the shoot tips grew rapidly and were relatively unaffected by hypoxia. The cytoplasmic pH decreased transiently by only 0.2 units during hypoxia, and the concentration of ATP was maintained to at least 90% of the normoxic level. Most importantly, the unidirectional rate constant of ATP synthesis from free phosphate decreased less than 25% during hypoxia. This is in contrast to other actively growing tissues such as the maize root tip. gamma-Aminobutyrate was the major nonvolatile fermentation end product after 22 h of hypoxia. Other hypoxia-induced changes included a modest increase in [Ala] and [succinate] as well as a substantial decrease in [malate].