Synthesis of thiazole-4-carboxamide-adenine difluoromethylenediphosphonates substituted with fluorine at C-2'' of the adenosine

Stimulation in the nucleus raphe magnus (NRM) inhibits transmission of nociceptive information within the spinal cord through activation of bulbospinal pathways. This study used microdialysis in combination with high pressure liquid chromatography to measure the release of serotonin (5HT) and several amino acids, including glutamate, aspartate and glycine, from the lumbar dorsal horn during electrical stimulation within the NRM in the alpha-chloralose anesthetized cat. Observed release of putative neurotransmitters was correlated with inhibition of nociceptive projection neurons recorded from sites within 800 microns rostral or caudal to the dialysis fiber. NRM stimulus parameters considered to preferentially activate myelinated fibers caused inhibition of nociceptive evoked activity, and increased the release of excitatory amino acids and glycine within the spinal cord, with no detectable release of 5HT. When pulse widths were lengthened and unmyelinated fibers were also activated, increases in 5HT in the spinal dialysate were observed as well. Strychnine administered through the dialysis fiber (0.02-1 mM) antagonized NRM-induced inhibition when 5HT release was not detected. Inhibition produced by stimulation that increased 5HT concentrations was relatively strychnine resistant. These results point to a raphe-spinal inhibitory pathway that is not dependent on 5HT, the activation of which results in the spinal release of glycine.     

AP-3: an adaptor-like protein complex with ubiquitous expression

Equine herpesvirus type 2 (EHV-2) is a slow-growing, cytopathogenic gammaherpesvirus, which is suggested to be ubiquitous in the equine population. However, its precise role as a pathogen and its tissue tropism remains uncertain. To estimate the prevalence of EHV-2 in Germany and to investigate the possible pathogenicity of the virus, peripheral blood leucocytes (PBL) from 172 horses were examined for EHV-2 DNA by a sensitive and specific nested PCR based on the EcoRI-N genomic fragment and by classical cocultivation. PBL samples from 51% of the horses were positive by PCR and virus was isolated from 31% of the horses by cocultivation. However, almost all animals were seropositive for EHV-2. This may indicate that PBL do not harbour EHV-2 indefinitely after infection. Furthermore, a correlation between clinical signs and EHV-2 as a causative agent could not be determined. Nevertheless, the prevalence of virus was high among horses with upper respiratory tract disease, abortion and severe ataxia. The products of the second round of the PCR reactions showed size polymorphism. Sequencing of the products revealed that these size differences were due to repetition of the motif (AGACAGGGGCCATGCTGGC) between 9-16 times depending on the isolate, suggesting that the nested PCR might be a useful tool for the differentiation of EHV-2 isolates.     

Ferulic acid dehydrodimers from wheat bran: isolation, purification and antioxidant properties of 8-O-4-diferulic acid

Wheat bran contains several ester-linked dehydrodimers of ferulic acid, which were detected and quantified after sequential alkaline hydrolysis. The major dimers released were: trans-5-[(E)-2-carboxyvinyl]-2-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-2, 3- dihydrobenzofuran-3-carboxylic acid (5-8-BendiFA), (Z)-beta-[4-[(E)-2-carboxyvinyl]-2-methoxyphenoxy]-4-hydroxy-3-methox ycinnamic acid (8-O-4-diFA) and (E,E)-4,4'-dihydroxy-5,5'-dimethoxy-3,3'-bicinnamic acid (5-5-diFA). trans-7-hydroxy-1-(4-hydroxy-3methoxyphenyl)-6-methoxy-1,2-dihydro - naphthalene-2,3-dicarboxylic acid (8-8-diFA cyclic form) and 4,4'-dihydroxy-3,3'-dimethoxy-beta,beta'-bicinnamic acid (8-8-diFA non cyclic form) were not detected. One of the most abundant dimers, 8-O-4-diFA, was purified from de-starched wheat bran after alkaline hydrolysis and preparative HPLC. The resultant product was identical to the chemically synthesised 8-O-4-dimer by TLC and HPLC as confirmed by 1H-NMR and mass spectrometry. The absorption maxima and absorption coefficients for the synthetic compound in ethanol were: lambda max: 323 nm, lambda min: 258 nm, epsilon lambda max (M-1 cm-1): 24,800 +/- 2100 and epsilon 280 (M-1 cm-1): 19,700 +/- 1100. The antioxidant properties of 8-O-4-diFA were assessed using: (a) inhibition of ascorbate/iron-induced peroxidation of phosphatidylcholine liposomes and; (b) scavenging of the radical cation of 2,2'-azinobis (3-ethyl-benzothiazoline-6-sulphonate) (ABTS) relative to the water-soluble vitamin E analogue, Trolox C. The 8-O-4-diFA was a better antioxidant than ferulic acid in both lipid and aqueous phases. This is the first report of the antioxidant activity of a natural diferulate obtained from a plant.     

Phosphatidylcholine transfer protein from bovine liver contains highly unsaturated phosphatidylcholine species

The jejunum was able to metabolize p-nitrophenol (PNP) rapidly and to transport the metabolites efficiently back into the luminal solution. About 21, 16, 6 and 3.5% of recirculated amount of PNP could be detected in 90 minutes as glucuronide in the lumen of jejunal loop, when 20, 100, 500 or 1,000 microM PNP was perfused, which shows that the luminal appearance of p-nitrophenol-glucuronide (PNP-G) tended to saturability. Biliary excretion rate of PNP-G was lower than the luminal appearance of this metabolite, when PNP was recirculated at 20 or 100 microM concentrations, however, at higher concentrations (500, 1,000 microM) the biliary excretion exceeded the luminal appearance of this conjugate and no saturability was observed in the biliary glucuronidation of PNP. Biliary excretion of sulfate conjugate of p-nitrophenol (PNP-S) exceeded the luminal appearance of this metabolite.     

The implementation of external cephalic version at term for singleton breech presentation--how can we further increase its impact?

The aim was to investigate if extent and time course of acute radiation damage to epidermis and intestine could be moderated by epidermal growth factor (EGF). Twelve-to-sixteen weeks old female CDF1 mice were treated either by single dose local irradiation to the right hind leg or total body irradiation (TBI). The endpoints were skin score and lethality, respectively. Human recombinant EGF was given s.c. or i.p. at a dose of 5-10 microg/day either before or after irradiation. Body weight was significantly higher for EGF treated animals compared with controls treated with saline. However, EGF did not reduce the median skin score following local irradiation and did not increase LD50 (days 1-6) following TBI. Further studies using more specific assays are necessary to determine if radiation damage to less toxic levels can be ameliorated by EGF.     

Functional outcome after coloanal versus low colorectal anastomosis for rectal carcinoma

The ocular dimensions and refraction of the eye were measured for accommodation stimulus levels of 0.0, 1.5, 3.5, 5.5, and 8.0 D for 11 subjects aged 18 to 28 years, mean 21.2 +/- 2.62 years using keratometry, autorefraction, A-Scan ultrasonography, and video phakometry techniques. The subjects had refractive errors in the range + 0.50 to -4.25 D, mean -1.88 +/- 1.64 D. With the maximum level of accommodation the anterior chamber depth decreased by 0.23 +/- 0.09 mm, the lens thickness increased by 0.28 +/- 0.09 mm, and no significant differences were recorded in axial length or vitreous chamber depth. The radius of curvature of the anterior surface of the crystalline lens decreased from 11.54 +/- 1.27 to 6.59 +/- 0.97 mm and the posterior surface from -6.67 +/- 0.97 to -5.30 +/- 0.4 mm. We determined the equivalent refractive index to be 1.4277 +/- 0.0011, with no significant differences at different levels of accommodation. When the crystalline lens was modeled as a gradient refractive index (GRIN) structure with elliptical iso-indicial lines, the mean surface refractive index of the lens was 1.3859 +/- 0.0009 for an assumed central refractive index of 1.406. The power of the anterior surface of the lens increased from 4.38 +/- 0.49 to 7.59 +/- 0.34 D, the posterior surface increased from 7.67 +/- 1.28 to 9.32 +/- 0.64 D, and the GRIN power increased from 9.70 +/- 1.31 to 13.74 +/- 0.77 D for the maximum accommodative stimulus of 8.00 D. On the basis of the model used, a substantial part of the increase in power of the crystalline lens with accommodation resulted from the change in refractive index distribution within the lens.