Ciprofibrate--racemate and enantiomers: effects of a four-week treatment on male inbred Fischer rats. A biochemical and morphological study

Ciprofibrates (racemate and both enantiomers, Raccip, R- and Scip) were administered orally in doses of 1 and 10 mg/kg once daily over 28 days to male inbred Fischer 344 rats, age 90-110 days at the beginning of the experiment. Body mass gain was observed in all groups. The 1 mg groups showed almost no difference to the control group. The 10 mg groups exhibited less body mass gain, most pronounced in the Scip group. Liver masses were increased in a dose dependent manner up to more than 200%, only the 10 mg Scip group was not significantly different from the 1 mg group which exhibited an increase in liver weight to about 175%. Also the kidney weights increased to 130%, whereas thymus and spleen weights were decreased in the high dose groups. Liver microsomal cytochromes P450 (P450) concentrations were not altered in the 1 mg groups and distinctly lowered in the 10 mg groups. Ethoxyresorufin and ethoxycoumarin O-deethylations were lowered in all experimental groups in a dose dependent manner, after administration of the high doses down to 30% of the control levels or less. Pentoxyresorufin O-depentylation, however, was increased in all 1 mg groups. In the high dose groups it was not altered. Ethylmorphine N-demethylation was decreased after administration of the high doses by about 50%, but only Scip decreased this reaction also after administration of the low dose. NADPH/Fe2+-stimulated microsomal luminol and lucigenin amplified chemiluminescence was increased, whereas hydrogen peroxide formation was depressed even by the low doses to 50% of the normal values, to about 25% by the high doses. Microsomal lipid peroxidation, however, was only slightly or not influenced. Glutathion concentrations (in the reduced and the oxidized form) were increased in a dose dependent manner by about 20 to 30%, the concentration of lipid peroxides was not significantly influenced. Thus, the effects of the enantiomers were not different and were similar to those of the racemate. In serum, cholesterol and triglycerides were only moderately lowered. Albumin concentrations were significantly enhanced in all groups, total proteins after 1 mg/kg Raccip only. Serum bilirubins were not altered, and among the indicator enzymes for liver damage only ALAT, alkaline phosphatase and the dehydrogenases were increased, in no case higher than twofold. Histologically distinct effects were seen after administration of both doses, more pronounced after 10 mg/kg, but with no differences between the enantiomers and Raccip: marked hypertrophy of the hepatocytes, reduced staining of the nuclei, strongly acidophilic granulated cytoplama, no basophilia of the cell bodies, loss of glycogen. These changes were most pronounced around the central veins. Hepatocyte apoptoses also were observed. By immunohistochemistry an increased staining was seen for all P450 isoforms tested (1A1, 2B1, 2E1, 3A2 and 4A1), predominantly perivenously and most pronounced after administration of the high doses without differences between Rcip, Scip or Raccip (preliminary results). By electron microscopy a moderate proliferation of peroxisomes after treatment with 1 mg/kg Cips with a ratio between mitochondria and peroxisomes of about 1:1 (controls: 10:1) was observed, and the peroxisomes were a more heterogeneous population. The relative portions of glycogen and both forms of the ER decreased. Treatment with 10 mg/kg Rcip, Scip or Raccip led to a strong increase in the number of peroxisomes, in some hepatocytes the ratio between mitochondria and peroxisomes was 1:3 with an increased heterogeneity among the peroxisomes evidenced by a broad range of electron densities. Most peroxisomes lacked a nucleoid. Thus, the biochemical effects differed only slightly and the morphological effects of the enantiomers were not different and were similar to those of the racemate.     

Histochemical detection of lymphatic drainage pathways in the middle nasal meatus

AIM: Assessment of the antihypertensive effect of doxazosin, alpha-1 blocker, as well as its action on lipid and carbohydrate metabolism, microcirculation and platelet function in patients with non-insulin-dependent diabetes mellitus (NIDDM). MATERIALS AND METHODS: Doxazosin (tonocardin) treatment was given for 11 weeks to 33 NIDDM patients with concomitant hypertension. The clinical examination comprised evaluation of central hemodynamics, vessels of the fundus of eye, lipid and carbohydrate metabolism, renal function, platelet aggregation. RESULTS: Tonocardin produced a fall in the systolic blood pressure (BP) by 14%, in the diastolic BP--by 17%. The 24-h profile of BP, lipid and purine metabolism, microcirculation of the vessels of the fundus of eye also improved. Total peripheral vascular resistance, left ventricular myocardial mass and platelet aggregation. Carbohydrate metabolism remained unchanged. CONCLUSION: Monotherapy with tonocardin (2-8 mg/day) is effective and safe in the treatment of arterial hypertension in NIDDM patients.     

KINETICS OF GROWTH OF MAGNESIUM HYDROXIDE CRYSTALS

The kinetics of growth of Mg(OH)₂, seed crystals at 298, 308 and 318 K from an a~ueous supersaturated solution of initial concentrations of Mg(OH)₂ 0,48, 0.60 and 0.73 mol-3 were determined. The growth was followed by measuring the conductivity of a seeded system as a function of time. The growth kinetics satisfied a first order kinetic equation. Within the examined range of variables the kinetic constant is independent of temperature and the initial concentration and dependenl on the surface area of seeds added at the start of the experiment. The growth of crystals under the studied conditions is controlled by the surface reaction mechanism.     

Compact cryogenic source of periodic hydrogen and argon droplet beams for relativistic laser-plasma generation

We present a cryogenic source of periodic streams of micrometer-sized hydrogen and argon droplets as ideal mass-limited target systems for fundamental intense laser-driven plasma applications. The highly compact design combined with a high temporal and spatial droplet stability makes our injector ideally suited for experiments using state-of-the-art high-power lasers in which a precise synchronization between the laser pulses and the droplets is mandatory. We show this by irradiating argon droplets with multi-terawatt pulses.     

Enzymatic Addition of Alcohols to Terpenes by Squalene Hopene Cyclase Variants

Squalene–hopene cyclases (SHCs) catalyze the polycyclization of squalene into a mixture of hopene and hopanol. Recently, amino-acid residues lining the catalytic cavity of the SHC from Alicyclobacillus acidocaldarius were replaced by small and large hydrophobic amino acids. The alteration of leucine 607 to phenylalanine resulted in increased enzymatic activity towards the formation of an intermolecular farnesyl–farnesyl ether product from farnesol. Furthermore, the addition of small-chain alcohols acting as nucleophiles led to the formation of non-natural ether-linked terpenoids and, thus, to significant alteration of the product pattern relative to that obtained with the wild type. It is proposed that the mutation of leucine at position 607 may facilitate premature quenching of the intermediate by small alcohol nucleophiles. This mutagenesis-based study opens the field for further intermolecular bond-forming reactions and the generation of non-natural products.     

Substituierte Alkinyle als axiale Liganden an häminähnlich gebundenem Eisen(III) - Einordnung in eine spektrochemische Serie

Substituted Alkinyles as Axial Ligands at Hemine Like Bound Iron(III) - Incorporation into a Spectrochemical Series . Substituted lithium alkynyles Li CC R (R = ^tBu, Ph, p-Cl C₆H₄, Me₃Si, ⁱPr₃Si, Ph₃Si) react with the hemine like macrocyclic iron(III) complex 6,13-di(ethoxycarbonyl)-5, 14-dimethyl-1, 4, 8, 11-tetraazatetradeca-4,6,12,14-tetraenato[2⁻]iron(III)-iodide (formula 2 ;) in tetrahydrofuran to form anionic low-spin di-adducts [fe(CC R)₂]⁻. The incorporation of the alkynyles into a spectrochemical series of the axial ligands (studied by the sharp equatorial-ligand-to-metal CT absorption band) results in the wavelength-sequence (nm): OH⁻ (≈︁ 510) « N₃⁻ (≈︁ 625) < ^tBu CC⁻ (664) < NH₃ (666) < Ph CC⁻ (692) < Ph NH₂ (695) < Me₃Si CC⁻ (698) < SCN⁻ (713) < Ph₃Si C  C⁻ (716) < CN⁻ (739) < 4-picoline (759) < pyridine (765) < nicotinamide (776) < methylnicotinat (788) < pyrazine (798) and points to a significant π-acceptor ability of the silyl substituents.     

Spektroskopie und Photochemie indigoider Verbindungen. V. Quantenchemische Berechnungen zum unterschiedlichen UV/S-Spektralverhalten der trans- und cis-Isomeren thioindigoider Verbindungen

Spectroscopy and Photochemistry of Indigoid Compounds. V. Quantum Chemical Calculations on the Different UV/VIS Spectral Behaviour of trans- and cis-Isomers of Thioindigoid Compounds The concept of non-bonding S…O-interaction [3] has been proved for some thioindigoid compounds. The different spectral behaviour of trans- and cis-isomers with regard to the long wave absorption band is mainly dependent on the number of S…O-structural units and on the S…O-distance. As compared to a coplanar structure twisting about the central double bond can result both in an increasing and a decreasing spectral shift.     

Magnetic resonance imaging with implanted neurostimulators: an in vitro and in vivo study

OBJECTIVE: The goal was to assess the safety of magnetic resonance imaging (MRI) with implanted neurostimulators, in an in vitro and in vivo study. METHODS: Two different implantable pulse generators (IPGs) (ITREL II and 3; Medtronic, Minneapolis, MN) and different leads (separately and connected to an IPG) were tested in three different MRI scanners (0.2, 0.25, and 1.5 T). Measurements of the induced voltages (using an external oscilloscope) and the induced heat (using an infrared camera) were performed in an in vitro study. Finally, 38 patients with implanted neurostimulator systems (leads and IPGs) underwent MRI in 50 examinations, with continuous monitoring by a physician with uninterrupted visual and vocal contact with the patient. Twenty-five patients were studied prospectively, with documented printouts of the parameter settings before and after MRI. RESULTS: An induced voltage of 2.4 to 5.5 V was measured in the experimental configuration with a lead connected to an IPG. The voltage was higher with the leads alone, compared with the leads connected to the IPG, and was dependent on the MRI scanner, the sequences, and the type of lead. No heat induction was observed in any part of the hardware. No change of pulse shape or change of IPG parameters was observed during MRI. No adverse effects occurred in patients with chronically implanted deep brain leads connected to an IPG. CONCLUSION: MRI can be safely performed in patients with implanted neurostimulation systems with the tested deep brain leads connected to an IPG (ITREL II and 3), with running parameters. No heat induction was detected, and the experimentally measured induced voltage did not seem to harm the patients. Only the reed switch of the IPGs was activated; the other parameters remained unchanged. Further investigations must be performed to study the local electrical effects in larger plate electrodes; these effects might cause slight discomfort. There is no danger with any type of electrode during MRI examinations if the electrodes lie outside the region of interest. These observations are restricted to the tested devices. A conscientious estimation of the risks and benefits of MRI for patients with implanted devices is recommended. If the type of device is not known to the examiner, MRI should still be considered to be contraindicated.     

Alterations of the enteric nervous system in neonatal necrotizing enterocolitis revealed by whole-mount immunohistochemistry

We report the results of a comprehensive search of Drosophila melanogaster DNA sequences in GenBank for di-, tri-, and tetranucleotide repeats of more than four repeat units, and a DNA library screen for dinucleotide repeats. Dinucleotide repeats are more abundant (66%) than tri- (30%) or tetranucleotide (4%) repeats. We estimate that 1917 dinucleotide repeats with 10 or more repeat units are present in the euchromatic D. melanogaster genome and, on average, they occur once every 60 kb. Relative to many other animals, dinucleotide repeats in D. melanogaster are short. Tri- and tetranucleotide repeats have even fewer repeat units on average than dinucleotide repeats. Our WorldWide Web site (http://www.bio.cornell.edu/genetics/aquadro/+ ++aquadro.html) posts the complete list of 1298 microsatellites (> or = five repeat units) identified from the GenBank search. We also summarize assay conditions for 70 D. melanogaster microsatellites characterized in previous studies and an additional 56 newly characterized markers.