Serotonin transporter binding in Tourette Syndrome

Recent studies provided evidence for an involvement of the dopaminergic system in the pathophysiology of Tourette Syndrome (TS). However, little is known about possible impairment of other neurotransmitter systems. In obsessive-compulsive disorder (OCD), a common comorbidity in TS, it is suggested that the serotonergic system plays a major role in the pathogenesis. We, therefore, used [I-123]2[beta]-carbomethoxy-3[beta]-(4-iodophenyl)tropane ([123I]beta-CIT) and single photon emission computed tomography (SPECT) to investigate serotonin transporter (SERT) binding capacity in 12 patients with TS with various degrees of associated obsessive compulsive behaviour (OCB) and 16 age-matched healthy controls. Binding ratios in TS patients not receiving serotonin reuptake inhibitors (SSRI) (n=8) were significantly reduced compared to age-adjusted ratios from normal controls (2.8 versus 3.2, p=0.003). Treatment with SSRI resulted in a significant reduction of SERT availability. Performing linear regression analysis for this small group, SSRI-free patients indicated trends for a negative correlation between [123I]beta-CIT binding on SERT and OCB (r=-0.78, p=0.023) as well as complex motor tics (r=-0.68, p=0.064). In healthy controls, but not in the TS group, we found an age-related decline in SERT binding capacity (0.28% decrease per year, p=0.038). Our data are in agreement with previous results suggesting an impairment of the serotonergic system in TS. It can be speculated that the reduction in SERT binding capacity is associated with the degree of comorbid OCB.     

Periodontitis is associated with a low concentration of vitamin C in plasma

This study aimed to clarify how concentrations of vitamin C in plasma relate to the serology of periodontitis. The random sample used comprised 431 men, 194 from Finland and 237 from Russia. The plasma vitamin C concentration was determined by o-phtaldialdehyde-fluorometry, and serum immunoglobulin G antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by a multiserotype enzyme-linked immunosorbent assay (ELISA). The mean plasma vitamin C concentration was higher (P < 0.001) in Finnish subjects (mean +/- standard deviation, 4.5 +/- 2.8 mg/liter) than in Russian subjects (1.4 +/- 1.8 mg/liter). Mean antibody levels to both A. actinomycetemcomitans (4.7 +/- 3.6 versus 5.2 +/- 3.1 ELISA units [P = 0.05]) and P. gingivalis (5.7 +/- 2.5 versus 7.6 +/- 2.9 ELISA units [P < 0.001]) were lower in Finnish men than in Russian men. In the combined Finnish and Russian population, the antibody levels to P. gingivalis were negatively correlated with vitamin C concentrations (r = -0.22; P < 0.001); this association remained statistically significant (P = 0.010) in a linear regression model after adjustment for confounding factors. The proportion of P. gingivalis-seropositive subjects decreased with increasing vitamin C concentrations (P for trend, <0.01), but no trend was seen among A. actinomycetemcomitans-seropositive subjects. In conclusion, P. gingivalis infection is associated with low concentrations of vitamin C in plasma, which may increase colonization of P. gingivalis or disturb the healing of the infected periodontium.     

The Bioperl toolkit: Perl modules for the life sciences

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.     

Experimental double infection of Biomphalaria glabrata snails with Angiostrongylus cantonensis and Schistosoma mansoni

Summary Two groups of Biomphalaria glabrata snails primarily infected with Angiostrongylus cantonensis were secondarily exposed to infection with Schistosoma mansoni. To investigate any antagonistic effect of a first infection on a superimposed one and to compare to singly and non-infected snails, a series of experiments was undertaken in which snails were individually exposed, variously, to 1,000 and 2,000 first-stage larvae of A. cantonensis and then to 5 and 10 miracidia of S. mansoni 1 day and 3 weeks later.Snails became infected with S. mansoni in both groups of snails with double infections and shed cercariae after the same incubation period as in the singly infected groups. The number of snails shedding cercariae simultaneously was similar in single and double infection groups during the first two weeks of shedding, after which this number decreased somewhat in doubly infected groups. Snails with double infection showed higher cumulative mortality rates than in snail groups with single infection with either A. cantonensis or S. mansoni. Therefore, initial infection of B. glabrata with A. cantonensis produced no inhibitory or retarding effect on subsequent infection of snails with S. mansoni.

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Zusammenfassung Zwei Gruppen der Süßwasserschnecke Biomphalaria glabrata, die zuvor mit 1000 bzw. 2000 ersten Larven von Angiostrongylus cantonensis pro Schnecke infiziert worden waren, wurden zur Feststellung eines eventuellen antagonistischen Effekts zwischen beiden Parasiten, einen Tag und drei Wochen später mit 5 bzw. 10 Miracidien von Schistosoma mansoni infiziert. Nicht infizierte und mit jeweils nur einer der beiden Parasitenarten infizierte Schnecken dienten als Kontrolle.In beiden doppelt infizierten Gruppen ging die S. mansoni-Infektion sehr gut an, und die Ausscheidung von Cercarien begann nach der gleichen Entwicklungszeit wie bei den nur mit S. mansoni infizierten Kontrollgruppen. Die Anzahl Cercarien ausscheidender Schnecken war in den beiden ersten Wochen bei den jeweils einzeln und doppelt infizierten Gruppen sehr ähnlich, während sie sich in der Folgezeit in den doppelt infizierten Gruppen rasch verminderte. In Gruppen mit Doppelinfektion zeigte sich eine höhere Mortalität als bei den jeweils nur mit A. cantonensis oder S. mansoni infizierten Schnecken. Eine Beeinflussung der Entwicklung von S. mansoni durch die vorausgegangene Nematodeninfektion konnte nicht nachgewiesen werden.

     

Polymere imidazolcarbonsäuren, 2. Über das schwermetallionenbindungsvermögen von chelatharzen mit 4,5-sicarboxyimidazolyl-gruppen

The swelling behaviour, the time-dependence of the uptake of Cu²⁺-ions, and the pH-dependence of the uptake of Cu²⁺-, Ni²⁺-, Cd²⁺-, Zn²⁺- and Mg²⁺-ions of crosslinked poly[1-(4,5-dicarboxy-1-imidiazolyl)ethylene] ( 1 ) and poly{1-[p-(4,5-dicarboxy-2-imidazolyl)phenyl]ethylene} ( 2 ) were investigated. Both resins have a high selectivity for heavy metal ions. For resins 1 the uptake of heavy metal ions in the presence of an excess of EDTA was studied. Furthermore the possibility to remove Hg²⁺-ions from aqueous alkalichloride solutions by resin 1 was investigated.     

Über poly[1-N-(4-isothiocyanatophenyl)carbamoyloxy-methyläthylen-co-1-hydroxymethyläthylen]e als träger zur immobilisierung von papain

Poly[1-N-(4-isothiocyanatophenyl)carbamoyloxymethylethylene-co-1-hydroxymethylethylene]s ( 5a – c ) were obtained by reaction of poly(allyl alcohol) ( 2 ) with 4-isothiocyanatophenyl isocyanate ( 3 ). In some cases 1,4-phenylenediisocyanate ( 4 ) was used as crosslinking agent. These reactive carriers were found to be suitable to immobilize enzymes by covalent bonds. The binding abilities of these polymers 5a – e for butylamine, 3,4-dichloroaniline, peptone (from lactalbumin), and papain were investigated. The enzymatic activity, the pH-optimum, the apparent Michaelis-constant K_M(app), and the activity dependance on temperature were determined for the immobilized papain.     

Mathematical formulations of the fetal mass growth in cattle

After a short review of investigations into fetal weight growth of cattle, the first mathematical treatment of values gained by Swett and collaborators (1948) and approximated by simple power functions after a proposal from Bereskin and Touchberry (1967) is recalled. Thereafter values for the weight of fetus and uterus with content as summarized by Huth (1962) are approximated with growth functions applying nonlinear regressions. The 6 functions taken into consideration range from classical to quite recent types. Results as listed in 2 tables show remarkable improvements. Parameters and an evaluation of 4 components of fetal development are added. Finally a comparison for the fetus of cattle and the domestic pig shows a lagging behind of cattle by temporarily about 20 percent in relative weight.     

New catalysts for the oxidative polymerization of 2,6-dimethylphenol, 2. Copper complexes containing the dicyanoethenedithiolatocuprate structure as the ligand

It was found that the reaction of 1,2-dicyano-1,2-ethenedithiolate, resp. of bis(1,2-dicyano-1,2-ethenedithiolato)cuprate(2-), with Cu²⁺ does not lead to copper bis(1,2-dicyano-1,2-ethenedithiolato)cuprate(2-) dihydrate ( 1a ) as described in the literature but to a reaction product which has a complex structure containing mainly Cu⁺. This compound as well as complexes with the same ligand, but with Cu⁺, Cu²⁺ or Cu³⁺ as the central atom, were synthesized and tested with and without added cuprous chloride as catalysts for the oxidative polymerization of 2,6-dimethylphenol. Included in this investigation were some copper complexes with the isomeric ligand 2,2-dicyano-1,1-ethenedithiolate.     

Amphotere ionenaustauscher, 5

Amphoteric ion exchangers with uniform structure were obtained by copolymerization of aziridinyl monomers followed by alkaline saponification of the ester groups of the polymers. The following compounds were copolymerized: Diethyl 2,4-di(1-aziridinyl)glutarate ( 1 ) with either diethyl (1-aziridinyl)succinate ( 4 ), diethyl (1-aziridinyl)fumarate ( 5 ) or dimethyl (1-aziridinylmethyl)succinate ( 6 ); diethyl ester of 3,3′-(1,4-phenylene) and 3,3′-(1,3-phenylene)di[3-(1-aziridinyl)propionic acid] ( 2a ) and ( 2b ), respectively, with either methyl (1-aziridinyl) acetate ( 7 ) or methyl (1-aziridinyl)propionate ( 8 ); dimethyl 3,6-di(1-aziridinyl)cyclohexane-1,2-dicarboxylate ( 3 ) with dimethyl 6-(1-aziridinyl)cyclo-2-hexene-1,2-dicarboxylate ( 9 ). Further the dioctylester of 3,3′-(1,4-phenylene)di[3-(1-aziridinyl)propionic acid] ( 10 ) was homopolymerized. The properties of the amphoteric resins were investigated. In particular the binding ability for Cu^2⊕, Ni^2⊕, Zn^2⊕, and Mg^2⊕ ions and the swelling ability were studied as function of the pH of the solution. The uptake of CU²⁺ ions was determined as a function of time. An average capacity for Cu²⁺ ions of 2,5 to 3,75 mmol/g of dry resin was found at pH 5,5–6.     

Clonogenicity of normal and malignant hematopoietic progenitor cells after exposure to synthetic alkyl-lymphospholipids

Summary Alkyl-lysophospholipids (ALP) are synthetic analogues of natural lysophosphatidylcholine and represent a new class of anti-tumor agents. They are cytotoxic in vitro with a high selectivity for neoplastic cells which, in contrast to normal cells, lack an alkyl-cleavage enzyme to degrade the adsorbed ALP molecules. As ALP accumulates, it interferes with normal membrane phospholipid turnover and eventually causes disruption of membrane integrity. To evaluate the potential value of ALP in eliminating leukemic cells from remission marrows prior to autologous transplantation, we tested the effect of various ALPs on the clongenicity of normal human marrow cells and on promyelocytic leukemia HL-60. A remarkable difference in the dose response to ALP of normal marrow cells an HL-60 was observed. After an incubation period of 24 h, the same inhibition of clonogenicity in HL-60 occurred at ALP concentrations 4 times lower than in normal marrow cells. Reducing the exposure time to 6 h enhanced the selectivity further: whereas HL-60 colonies were nearly completely inhibited at 16 g ALP/ml, more than 50% of normal CFU-c and BFU-E were recovered after incubation with 48 g/ml. No further increase in selectivity was achieved by changing the incubation temperature. Both thioether- and alkyl-analogues were active and no difference was observed between methoxy- and acylamino-substituted ALPs. We conclude that this selective cytotoxicity makes ALP compounds worth further study as purging agents in autologous bone marrow transplantation programs.Supported by the Deutsche Forschungsgemeinschaft An 111/3