Nonactivated titanium-dioxide nanoparticles promote the growth of Chlamydia trachomatis and decrease the antimicrobial activity of silver nanoparticles.

AIMS: Chlamydia trachomatis and herpes simplex virus (HSV) are the most prevalent bacterial and viral sexually transmitted infections. Due to the chronic nature of their infections, they are able to interact with titanium-dioxide (TiO2 ) nanoparticles (NPs) applied as food additives or drug delivery vehicles. The aim of this study was to describe the interactions of these two prevalent pathogens with the TiO2 NPs. METHODS AND RESULTS: Chlamydia trachomatis and HSV-2 were treated with nonactivated TiO2 NPs, silver NPs and silver decorated TiO2 NPs before infection of HeLa and Vero cells. Their intracellular growth was monitored by quantitative PCR. Unexpectedly, the TiO2 NPs (100 µg ml-1 ) increased the growth of C. trachomatis by approximately fourfold, while the HSV-2 replication was not affected. Addition of TiO2 to silver NPs decreased their antimicrobial activity against C. trachomatis up to 27·92-fold. CONCLUSION: In summary, nonactivated TiO2 NPs could increase the replication of C. trachomatis and decrease the antimicrobial activity of silver NPs. SIGNIFICANCE AND IMPACT OF THE STUDY: The food industry or drug delivery use of TiO2 NPs could enhance the growth of certain intracellular pathogens and potentially worsen disease symptoms, a feature that should be further investigated.

Antiinflammatory activity of 5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazoles. Isomeric 4-pyridyl and 4-substituted phenyl derivatives.

Isomeric 5(6)-(4-pyridyl)- and 6(5)-(4-substituted-phenyl)-2,3-dihydroimidazo[2,1-b]thiazoles were prepared by a mixed benzoin-imidazothione route, and their structures were assigned by spectral comparison to compounds of established substitution pattern. The structural assignment was confirmed by X-ray analysis. Examination of the compounds for antiinflammatory activity by an adjuvant arthritic rat assay revealed strikingly higher potencies for one analogous series than for their isomers. This selectivity was paralleled in the ability to stimulate cell-mediated immunity, as reflected in an oxazolone-induced contact sensitivity model. A drug-receptor complex is proposed that requires at least three sites of interactions.

A highly enantioselective conjugate reduction of 3-arylinden-1-ones using bakers' yeast for the preparation of (S)-3-arylindan-1-ones.

[formula: see text] The bakers' yeast reduction of 3-(1,3-benzodioxol-5-yl)-6-propoxy-1H-inden-1-one 4 has been shown to give (S)-3-(1,3-benzodioxol-5-yl)-2,3-dihydro-6-propoxy-1H-indan-1-one 6 in 65% yield with high enantioselectivity (> 99.0% ee), a key intermediate for the synthesis of the endothelin receptor antagonist SB 217242. In addition, the substituted 3-arylinden-1-ones 10a-e gave equally high enantioselectivity for the 3-arylindan-1-one products 13a-e. Mechanistic studies of the reaction indicate the operative pathway to be an asymmetric conjugate reduction, wherein the hydride transfer from NAD(P)H occurs from the Re-face of the indenone substrate.

Screening the familial accumulation of kidney malposition and malrotation.

Sacral dystopic kidneys have been found in a couple of brothers and sisters. By screening all the first-grade relatives in one generation, 5 brothers and sisters showed kidney malposition and malrotation. This is the first report in the literature about family screening for this developmental anomaly. Based on the results an autosomal recessive character of the clinical pattern was suggested; it is pointed out that the final clearing of the hereditary process requires further family screenings.

Horseshoe kidney and its therapeutic problems. (A review of seventy-one clinical cases).

A review of 71 cases of horseshoe kidney accounting for 0.12% of the total number of patients seen at the Department of Urology, Semmelweis University Medical School, Budapest, over 25 years is presented. The incidence of the abnormality has been found twice as high in males as in females. The proportion of surgical cases has been 57.8%, in agreement with published data. The radiodiagnostic investigations, particularly the functional diagnostic studies, are dealt with in detail. Their decisive importance in the considerations for or against surgery is emphasized.

Efficient solution phase synthesis of [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)- 2-(O-ethyl-D-tyrosine)-4-valine-9-desglycine]arginine vasopressin.

A convergent synthesis of the peptide [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)- 2-(O-ethyl-D-tyrosine)-4-valine-9-desglycine]arginine vasopressin (1), based on the classical solution phase method, was developed. The molecule is assembled by a 3 + 4 coupling via the azide method; then the disulfide bridge is installed by iodine treatment of the bis-acetamidomethyl protected thiols, and the terminal arginine amide added by a 7 + 1 coupling. The method has been used to prepare gram quantities of 1 in more than 98% purity and in 13% yield (based on tetrapeptide intermediate 13) after a single stage purification. The method appears to be particularly suitable for the large scale preparation of 1 and other vasopressin congeners. A novel, albeit low level, transfer of acetamidomethyl group from the sulfur of cysteine to the asparagine amide side-chain was detected following hydrogen chloride treatment of Boc-containing intermediates.

The Hungarian periconceptional service as a model for community genetics.

OBJECTIVES: This review describes the methods and results of the Hungarian periconceptional service consisting of counselling, examinations and medical interventions. (The term periconceptional is used instead of preconceptional because the early postconceptional period is also involved to this service.) METHODS: The service was based on three steps: check-up examination of reproductive health (i.e., preconceptional screenings), a 3-month preparation for conception, dispensed and/or supervised by qualified nurses, and a better protection in early pregnancy for the most sensitive early development of the embryo for voluntary and eligible couples. RESULTS: Experiences from the coordinating centre of the Hungarian periconceptional service are summarized between February 1, 1984, and January 31, 1999, thus 15 years. Participants with positive family histories, case histories and subjects with genito-urinary infections had a more effective flow towards secondary care. Infertile couples were diagnosed and treated sooner. The periconceptional service is effective for the introduction of periconceptional folic acid-containing multivitamin supplementation and for the reduction of smoking and alcohol consumption in females in the preconceptional period. The rate of major congenital abnormalities (20.6 per 1,000) was significantly lower than expected. CONCLUSIONS: The periconceptional service is feasible and has many benefits. Thus, proper preparation for conception is the earliest and probably the most important effort to prevent genetic diseases.

Large-scale synthesis of hematoregulatory nonapeptide SK&F 107647 by fragment coupling.

Linear and convergent routes for the large-scale preparation of the hematoregulatory nonapeptide (Glp-Glu-Asp)2-DAS-(Lys)2 (2, SK&F 107647) were investigated. A convergent approach ('3 + 2'-route employing Boc-and benzyl ester protecting groups) was selected for the preparation of multihundred-gram quantities of 2. Key steps were the preparation and the coupling of tripeptide hydrochloride (HCl.H)2-DAS-(Lys(Z)-OBn)2 (6, DAS-2,7-L,L-diaminosuberic acid) and tripeptide Glp-Glu(OBn)-Asp(OBn)-OH (26). Several coupling reagents were investigated in order to reduce the amount of epimerization of this fragment coupling. TDBTU [O-(3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl-1,1,3,3-tetrameth yluronium tetrafluoroborate] was identified as the condensation reagent of choice. Using this synthetic route > 97% pure final product in an overall yield of 35% calculated on di-Boc protected 2,7-L,L-diaminosuberic acid was prepared.