[Properties and evaluation of waste water from the damp oxidation of sewage sludge, with reference to water protection].
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Several new organogold(III) derivatives of the type [AuX(2)(damp)] (damp = o-C(6)H(4)CH(2)NMe(2)) have been prepared [X = CN, SCN, dtc, or X(2) = tm; dtc = R(2)NCS(2) (R = Me (dmtc) or Et (detc)); tm = SCH(CO(2))CH(2)CO(2)Na] together with [AuCl(tpca)(damp)]Cl (tpca = o-Ph(2)PC(6)H(4)CO(2)H), [Au(dtc)(damp)]Y (Y = Cl, BPh(4)) and K[Au(CN)(3)(damp)]. The (13)C NMR spectra of these and previous derivatives have been fully assigned. In [Au(dtc)(2)(damp)] and K[Au(CN)(3)(damp)], the damp ligand is coordinated only through carbon, as shown by X-ray crystallography and/or NMR. [Au(detc)(2)(damp)] has space group C2/c, with a = 29.884(4) Å, b = 13.446(2) Å, c = 12.401(2) Å, beta = 99.45(3)(o), V = 4915 Å(3), Z = 8, and R = 0.057 for 1918 reflections. The damp and one detc ligand are monodentate, the other detc is bidentate; in solution, the complex shows dynamic behavior, with the detc ligands appearing equivalent. The crystal structure of [Au(dmtc)(damp)]BPh(4) [Pna2(1), a = 26.149(5) Å, b = 11.250(2) Å, c = 11.921(2) Å, V = 3507 Å(3), Z = 4, R = 0.073, 1772 reflections] shows both ligands to be bidentate in the cation, but the two Au-S distances are nonequivalent. The crystal structure of [Au(tm)(damp)] has also been determined [P2(1)/n, a = 18.267(7) Å, b = 9.618(3) Å, c = 18.938(4) Å, beta = 113.45(3)(o), V = 3053 Å(3), Z = 8, R = 0.079, 1389 reflections]. The tm is bound through sulfur and the carboxyl group which allows five-membered ring formation. In all three structures, the trans-influence of the sigma-bonded aryl group is apparent. [AuCl(2)(damp)] has been tested in vitroagainst a range of microbial strains and several human tumor lines, where it displays differential cytotoxicity similar to that of cisplatin. Against the ZR-75-1 human tumor xenograft, both [AuCl(2)(damp)] and cisplatin showed limited activity.
Selected nasal symptoms were studied in personnel who worked in a damp office building that had microbial growth (including Stachybotrys sp.) in mineral fiber insulation and gypsum board. There were also signs of dampness in the floor. Clinical examinations included nasal lavage and peak expiratory flow measurements in 12 subjects in the damp building; an additional 8 subjects in a control building (i.e., no signs of dampness or microbial growth) were also examined. Hygienic air measurements of microorganisms and volatile organic compounds were performed in both buildings. The concentrations of eosinophil cationic protein, myeloperoxidase, and albumin, and the number of subjects with eosinophils in lavage fluid, were higher among office workers in the damp building than among controls. The damp biiilding had greater amounts of total molds and bacteria in its construction than the building materials in nondamp buildings. In addition, an increase of 2-ethyl-1-hexanol in the indoor air was detected in the damp building-a sign of dampness-related alkaline degradation of diethyl-hexyl phthalate in polyvinyl chloride floor coatings. In conclusion, the results of this study indicate that exposures in a damp office building may cause an inflammatory nasal mucosal response. The results also support conclusions of earlier studies, indicating that building dampness is related to respiratory inflammation.
Secondary attachment site lambda-lysogens were isolated in an Escherichia coli strain carrying multiple tandem 9.8 kb repeats. The repeat carried the structural gene for chromosomal beta-lactamase, ampC. One lysogen produced lysates with amp-transducing activity. Three types of phages with different densities were obtained from this lysogen. The one with the lowest density was found to be a helper lambda cI857S7 phage. The other two phage showed identical restriction endonuclease fragmentation patterns. The difference in density was due to the presence or absence of phage tail. In lambda damp the right cohesive end segment was deleted in a random fashion with the majority ending between 81.0% and 82.4% of lambda. The chromosomal segment of lambda damp was most likely located at the lambda attachment site. The lambda damp DNA was compared to that of ColE1 hybrid carrying the chromosomal amp segment and a ColE1 hybrid carrying the same 9.8 kb amp repeat as the lysogen from which lambda damp was isolated. It was found that the chromosomal part of lambda damp constituted 9.8 kb, i.e. the size of one repeat. Moreover, the novel joint between adjacent repeats was present. In a lambda attB-deleted E. coli K-12 strain, lysogenic for lambda damp, highly ampicillin-resistant mutants occurred at an exceedingly high frequency. They were found to contain in the chromosome an amplified 9.8 kb repeat. This suggested that integration of the novel joint for lambda damp into the amp region gives rise to an amplifiable duplication. In E. coli lysogenized for lambda damp at lambda attB highly ampicillin-resistant clones were also found at a high frequency. These clones carried multiple tandem repeats of lambda damp DNA, each with an intact right end segment.
The aim of the present study was to elucidate the role of the non-M1 muscarinic receptors, in the extrinsic and intrinsic nerve control of in vivo colonic motility. Experiments were performed on the proximal colon of anaesthetized rabbits. In this species, the parasympathetic innervation of the proximal colon originates from the vagus nerves. The action of methoctramine and 4-diphenyl-acetoxy-N-methylpiperidine methobromide (4-DAMP) was studied on excitatory junction potentials (EJPs), and on inhibitory junction potentials (IJPs) elicited in smooth muscle cells by stimulating parasympathetic efferents. The effects of the same drugs on spontaneous spiking activity were also investigated. The EJPs either decreased or disappeared after intra-arterial (i.a.) administration of 4-DAMP (45 pg to 450 ng). In the presence of 4-DAMP, further intravenous (i.v.) administration of pirenzepine (0.1 mg.kg-1) had facilitatory effects on the inhibitory pathway, i.e., after abolition of the EJPs, vagal stimulation elicited IJPs. With the highest dose of 4-DAMP, vagal stimulation immediately elicited IJPs the amplitude of which still increased after pirenzepine. In the presence of 4-DAMP, the spontaneous spike discharge was not noticeably altered. Methoctramine (0.37 to 75 micrograms, i.a. or 50 micrograms to 0.2 mg.kg-1, i.v.) increased the amplitude of the EJPs, whereas it decreased that of the IJPs. In addition, at the same doses, it either initiated or increased spike discharges that were not altered by pirenzepine up to 0.2 mg.kg-1, i.v. The so-called rebound excitation occurring after IJPs was not affected by methoctramine. No change in the EJP or IJP amplitude was observed with gallamine at sufficiently high doses to paralyse striated muscles (up to 3 mg.kg-1.h-1). It is concluded that the parasympathetic excitatory pathway to smooth muscle is blocked by 4-DAMP, whereas it is facilitated by methoctramine. 4-DAMP has no effect on the inhibitory pathway which is strongly depressed by methoctramine; however, the fact that these two drugs have opposite effects indicates that 4-DAMP and methoctramine may act on different muscarinic receptor subtypes. In addition, the facilitatory effects of pirenzepine on IJPs observed in animals pre-treated with 4-DAMP, indicates that the latter drug may act on non-M1 and non-M2 (presumably M3) muscarinic receptors. Methoctramine acts on non-M1 and non-M3 (presumably M2) receptors. The spike discharge induced by methoctramine is presumably due to an increased release of acetylcholine, and possibly also of a non-cholinergic transmitter which has excitatory effects on smooth muscle, the identification of which requires further investigations.(ABSTRACT TRUNCATED AT 400 WORDS)
AIMS: To analyse the contribution of certain social, familial, prenatal, perinatal, and developmental background factors in the pathogenesis of deficits in attention, motor control, and perception (DAMP). METHODS: A population based case-control study was carried out with 113 children aged 6 years, 62 diagnosed with DAMP and 51 controls without DAMP. The children's health and medical records were studied and their history with regard to background factors was taken at an interview with the mother using a standardised schedule. Familial factors, possible non-optimal factors during pregnancy (including smoking), developmental factors (including early language development), and medical and psychosocial data were scored in accordance with the reduced optimality method. RESULTS: Low socioeconomic class was common in the group with DAMP. Familial language disorder and familial motor clumsiness were found at higher rates in the DAMP group. Neuropathogenic risk factors in utero were also more common in the children with DAMP. Maternal smoking during pregnancy appeared to be an important risk factor. Language problems were present in two thirds of the children with DAMP. Sleep problems and gastrointestinal disorders, but not atopy or otitis media, were significantly more common in the DAMP group. CONCLUSIONS: Prenatal familial and neuropathogenic risk factors contribute to the development of DAMP. Primary prevention, such as improved maternal health care and early detection or treatment, or both, of associated language problems appear to be essential.
STUDY DESIGN: Descriptive, case-matched comparison. OBJECTIVES: To compare the knee joint stiffness and damping coefficients of individuals with knee osteoarthritis (KOA) to those of age- and gender-matched individuals without KOA. A secondary purpose was to investigate relationships between these coefficients and complaints of stiffness in individuals with KOA. BACKGROUND: KOA is a leading cause of disability, and stiffness is a common complaint in individuals with KOA. Yet the most common method of assessing knee joint stiffness is through a self-report questionnaire. METHODS AND MEASURES: Stiffness and damping coefficients at the knee were calculated in 10 volunteers (mean age +/- SD, 64.1+/-15.5 years) with KOA and compared to coefficients from age-and gender-matched individuals without KOA, collected in a previous study (mean age +/- SD, 62.1+/-13.9 years). Stiffness and damping coefficients were calculated from the angular motion of the knee during a relaxed oscillation. Spearman correlation coefficients were calculated between stiffness and damping coefficients and WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores for subjects with KOA. RESULTS: Independent 2-tailed t tests revealed significantly larger damping coefficients (P = .035) among those with KOA (95% CI, 0.10-2.32 Nm s/rad). Spearman rank correlations revealed a significant positive relationship (r = .85, P = .003) between the damping coefficient and the stiffness subscore of the WOMAC. CONCLUSION: This study offers preliminary data demonstrating the feasibility of measuring stiffness and damping coefficients in individuals with KOA. Additionally, the damping coefficient is increased in people with KOA when compared to age- and gender-matched individuals without KOA. The damping coefficient appears to be associated with the complaints of stiffness reported by the WOMAC.
A new family of oxoruthenium(IV) complexes based on [(DAMP)(L)RuO](2+) have been prepared where DAMP = 2,6-bis((dimethylamino)methyl)pyridine and L = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), or dipyridophenazine (dppz). The structures of [(DAMP)(bpy)RuO](2+) and [(DAMP)(phen)RuO](2+) were determined by X-ray crystallography. The Ru-O bond lengths (1.805(3) and 1.814(4) Å, respectively) are indicative of multiple bonding, as expected for oxoruthenium(IV), and clear steric protection of the Ru=O moiety is provided by the DAMP ligand. Cyclic voltammetry shows that the tertiary amine functionalities of the DAMP ligand stabilize both the Ru(IV)O(2+) and Ru(III)OH(2+) redox forms relative to other (polypyridyl)oxoruthenium(IV) complexes. As a result, the oxidations of both sec-phenylethanol and trans-stilbene are approximately 100 times slower for [(DAMP)(bpy)RuO](2+) than for [(bpy)(2)(py)RuO](2+). Accordingly, the reaction mechanisms involve oxidation of substrate only by the Ru(IV)O(2+) form with no contribution from direct oxidation by the Ru(III)OH(2+) intermediate, which greatly simplifies the kinetic analysis. The Ru(IV)O(2+) forms are not effective oxidants of the sugar moiety of mononucleotides; however, the base functionality of guanosine 5'-monophosphate is oxidized at detectable rates. In contrast, cleavage of a hairpin oligonucleotide is detected at both guanine and sugar functionalities, indicating that the oligomer promotes sugar oxidation by increasing the local concentration of the metal complex. The Ru(III)OH(2+) form of the DAMP complexes is stable in the absence of DNA but is reduced following a zero-order rate law in the presence of calf thymus DNA. Analysis using a model that resembles Michaelis-Menten kinetics indicates that the binding domain on DNA catalyzes the disproportionation of the complex. The model yields a binding constant and a calculated first-order rate constant that are in good agreement with independent measurements.
OBJECTIVE: To explore the relationship between the portal hemodynamics or the indices of liver fibrosis and the liver function score in patients with different traditional Chinese medical syndromes of liver cirrhosis. METHODS: One hundred and forty-seven cases of liver cirrhosis with different syndromes were included in the study. Diameters and blood flow velocities of the portal vein and splenic vein were tested by color Doppler sonarography. The indices of liver function (TBIL, ALT, AST, Alb, Glb, PTA) and the indices of hepatic fibrosis (HA, PC-III, LN, VI-C) were tested. RESULTS: The diameters of portal vein in liver cirrhosis patients with different syndromes (internal accumulation of of damp-heat, stagnation of liver-qi, superabundance of dampness due to spleen-asthenia, asthenia of liver and kidney yin, asthenia of spleen and kidney yang, blood stasis) were not significantly different. The blood flow velocities and flow volumes of portal vein in patients with the blood stasis syndrome and the internal accumulation of damp-heat syndrome were significantly different (P < 0.05). The diameter of splenic vein in patients with the internal accumulation of damp-heat syndrome was significantly different to that of the asthenia of liver and kidney yin syndrome, or the blood stasis syndrome, or the asthenia of spleen and kidney yang syndrome, respectively (P < 0.05 or P < 0.01). The blood flow velocity of splenic vein in patients with the blood stasis syndrome or the asthenia of spleen and kidney yang syndrome was significantly different to that of the internal accumulation of damp-heat syndrome, or the stagnation of liver-qi syndrome, or the asthenia of liver and kidney yin syndrome, respectively (P < 0.01). The blood flow volume of splenic vein in patients with the internal accumulation of damp-heat syndrome was significantly different to that of the asthenia of liver and kidney yin syndrome, or the asthenia of spleen and kidney yang syndrome, or the blood stasis syndrome, respectively (P < 0.01). The liver cirrhosis indices HA and PC-III in patients with the asthenia of liver and kidney yin syndrome were significantly different to those of the internal accumulation of damp-heat syndrome (P < 0.05). In Child-Pugh classification, the incidence of Child-Pugh C was the highest in the asthenia of spleen and kidney yang syndrome, while the incidence of Child-Pugh A was the highest in the stagnation of liver qi syndrome. CONCLUSION: The changes of portal vein dynamics in liver cirrhosis patients with the asthenia of liver and kidney yin syndrome, or the asthenia of spleen and kidney yang syndrome, or the blood stasis syndrome are significantly different to those of the internal accumulation of damp-heat syndrome and the stagnation of liver-qi syndrome.
OBJECTIVE: To study the relationship between two different Syndromes (Cold-Damp Syndrome and Damp-Heat Syndrome) and three soluble cytokine receptors (sCKR, soluble interleukin-2 receptor, sIL-2R, soluble interleukin-6 receptor, sIL-6R, soluble tumor necrosis factor receptor 1, sTNFR1) in rheumatoid arthritis (RA). METHODS: The serum levels of three soluble receptors were measured by ELISA in patients with RA. RESULTS: The serum levels of 3 sCKR were significantly elevated in RA patients compared to healthy controls and obviously lowered after treatment (P < 0.01). The level of sIL-2R was significantly higher in Cold-Damp Syndrome than that in Damp-Heat Syndrome (P < 0.01), but serum sTNFR1 was significantly higher in Damp-Heat Syndrome than that in Cold-Damp Syndrome, there was no obvious difference between sIL-6R of two Syndromes. CONCLUSION: The high serum sIL-2R and low sTNFR1 might be a criterion of Cold-Damp Syndrome, but the high sTNFR1 and low sIL-2R might be a criterion of Damp-Heat Syndrome, these criteria reflected some states of different functions in immune system in patients with RA.
Using the acidotrophic amine 3-(2,4-dinitroanillino)-3'-amino-N-methyldipropylamine (DAMP) as a marker for low pH and immunofluorescence cytochemistry, we examined acidic compartments of osteoclasts cultured on cover glasses or bone slices, where they could resorb the bone surface, forming resorptive lacunae. DAMP-positive structures were seen as vesicular and tubular forms in the cytoplasm, indicating lysosomes and endosomes. Not only the osteoclastic cytoplasm but also the extracellular area around the ruffled border and resorptive lacunae were stained with DAMP, suggesting acidic regions. Immunofluorescence was localized predominantly on the substratum side of actively resorbing osteoclasts, whereas an evenly distributed staining pattern was seen in the nonactive cell. The most intensive reaction was seen at the advancing front of resorptive lacunae within the actively resorbing osteoclasts. The distribution pattern of DAMP seemed to be correlated with the osteoclastic activity, since osteoclasts exhibit alternating resorption and migration phases during the bone-remodeling cycle. In this culture system, the resorptive lacunae were left behind after the osteoclasts had completed resorption and migrated along the bone surface. These exposed resorptive lacunae were also stained with DAMP, which were presumably kept at an acidic pH. The effect of treatment with monensin, chloroquine, ammonium chloride, or nigericin was varied in terms of the immunoreactivity for DAMP, but not complete abolition of the staining was obtained. Weak bases such as chloroquine or ammonium chloride inhibited both intra- and extracellular immunoreactivity. Immunoreactivity for the vacuolar type of proton ATPase (V-ATPase) was demonstrable in the cytoplasm of the osteoclasts but was weakened by the addition of bafilomycin. Immunofluorescence of the resorptive lacunae was still retained even after the treatment with bafilomycin and acetazolamide. Besides, both bafilomycin and acetazolamide reversibly inhibited cellular acidity as judged by DAMP immunocytochemistry, which agrees with the fact that ostoeclastic acidification results from the action of vacuolar proton-pump ATPase coupled with carbonic anhydrase.
Several studies have shown that d-amphetamine (DAMP) speeds mean reaction time (RT). However, the use of mean RT may obscure important aspects of the drug response. Therefore we applied the Poisson-Erlang (PE) stochastic model of choice reaction time proposed by Pieters (1985) to the RT distribution. This model proposes that the RT distribution is generated by two states: Processing (P) and Distraction (D). RT represents the sum of the time spent in each of these states. P is the time taken to complete a set of cognitive operations which are required to give a correct response. D represents the time taken by all other activities. RTs were collected using a task (SERS) in which stimulus and response complexity each had two levels, easy and hard. Subjects were tested pre- and postdrug. Drug conditions were: placebo, 10 mg d-amphetamine (DAMP), 4 mg of the dopamine agonist, pimozide, and a combination of DAMP and pimozide (COMBO). Parameters of the model were derived using methods described by Pieters. Four measures were analyzed: Processing Time (PT); Mean Time per distraction (XTD); Distraction Rate (DR); and Total Distraction Time per trial (TDT). Mean RT is also presented. Analyses of the effects of task conditions on the parameters of the model were made using the predrug sessions. Mean RT was increased by both stimulus and response complexities as was PT. TDT was increased by the task conditions. The PE measures did not change over days. DAMP speeded mean RT. However, this effect did not interact with the task factors. DAMP speeded processing and reduced distraction. Processing was speeded only in the hard response condition, distraction time was reduced only in the easy response condition. The results indicate that the PE model can be successfully applied to fast RT tasks. More importantly, the parameters of the model revealed important pharmacological effects that were not apparent in mean RT. DAMP speeds cognitive operations related to motor preparation and reduces the effects of distraction. Consistent with past studies there are no indications that DAMP interacted with stimulus processing. The distraction effect appears to be mediated by an increase in the rate of distraction and a decrease in the average time of these distractions.
The effects of cetyltrimethylammonium bromide (CTAB) micelles and dioctadecyldimethylammonium bromide (DODAB) bilayers on molecular conformation of 2'-deoxyadenosine 5'-monophosphate (dAMP) were evaluated from circular dichroism spectroscopy (CD) and molecular modeling of dAMP conformations of minimal energy upon varying torsion angles for the glycosidic bond (t(1)) for four different conditions of dielectric constant of the medium (E) and negative charge on the phosphate moiety (C), namely, E80_C2, E80_C0, E1_C2, and E1_C0. Upon decreasing medium polarity, a decreased intensity of the negative band over the 190-210 nm region for the dAMP CD spectrum was observed. Upon increasing relative proportion dAMP: DODAB, an increased intensity of the positive band over the 210-230 nm region plus a red shift were obtained that could be attributed to an increased nitrogenous base stacking, similar to A stacking in poly(A). Concomitant base stacking and insertion in the cationic aggregates were observed for DODAB bilayers but not for CTAB micelles. Thereby, the nucleotide extended, anti conformation in pure water typical for nucleotides in DNA was forced by the cationic bilayer to become syn. dAMP conformational modeling upon simultaneous changes in the nucleotide environment (from water to a hydrocarbon phase) and in the charge on phosphate moiety (-2 to zero) allowed to simulate dAMP conformation in the cationic bilayer/dAMP complex. Modeling confirmed the dAMP anti-to-syn conformational change experimentally characterized from CD spectroscopy. This nucleotide conformational change would possibly be at the root of DNA denaturation upon complexation with cationic lipids.
Our laboratory previously reported the identification and quantification of depurinating DNA adducts of dibenzo[a,l]pyrene (DB[a,l]P) in vitro, which comprise about 84% of all the DNA adducts that are formed [Li, K.-M., et al. (1995) Biochemistry 34, 8043-8049]. To determine a complete adduct profile and identify both stable and depurinating DNA adducts, we have developed a relatively simple, nonradioactive method for the identification of stable DNA adducts by combining enzymatic digestion, HPLC, and fluorescence line-narrowing spectroscopy (FLNS) techniques. Calf thymus DNA, bound to either (+/-)-anti- or (+/-)-syn-DB[a,l]PDE or rat liver microsome-activated DB[a,l]P, was first digested to 3'-mononucleotides with micrococcal nuclease and spleen phosphodiesterase. The adducts were then separated by HPLC with an ion-pair column and identified by FLNS by using the spectra of standards for comparison. In reactions with (+/-)-anti-DB[a,l]PDE, three adducts, an anti-cis-DB[a,l]PDE-dGMP, an anti-trans-DB[a, l]PDE-dAMP, and an anti-cis-DB[a,l]PDE-dAMP, were identified by HPLC and FLNS. In reactions with (+/-)-syn-DB[a,l]PDE, a pair of syn-trans-DB[a,l]PDE-dGMP adducts as well as a syn-cis-DB[a, l]PDE-dGMP, a syn-cis-DB[a,l]PDE-dAMP, and a pair of syn-trans-DB[a, l]PDE-dAMP adducts were identified. From the digest of microsome-activated DB[a,l]P-bound DNA, a syn-trans-DB[a,l]PDE-dGMP, an anti-cis-DB[a,l]PDE-dGMP, a syn-trans-DB[a,l]PDE-dAMP, and a syn-cis-DB[a,l]PDE-dAMP adduct were identified. An anti-cis-DB[a, l]PDE-dAMP adduct was identified only by (32)P-postlabeling. A total of five of the stable adducts formed by DB[a,l]P and nine of the stable adducts formed by DB[a,l]PDE in vitro have been identified. These adducts were also correlated to adduct spots in the (32)P-postlabeling method by cochromatography with standards. Approximately 93% of the stable adducts formed in reactions with (+/-)-anti-DB[a,l]PDE, 90% of adducts with (+/-)-syn-DB[a,l]PDE, and 85% of adducts formed with microsome-activated DB[a,l]P have been identified as Gua or Ade adducts. Equal amounts of stable Gua and Ade adducts were observed in the microsome-catalyzed binding of DB[a, l]P to calf thymus DNA, while 1.4 times more Gua adducts than Ade adducts were obtained in reactions with (+/-)-anti- or (+/-)-syn-DB[a,l]PDE.
Persistent oscillation in constant conditions is a defining characteristic of circadian rhythms. However, in plants transferred into extended dark conditions, circadian rhythms in mRNA abundance commonly damp in amplitude over two or three cycles to a steady state level of relatively constant, low mRNA abundance. In Arabidopsis, catalase CAT3 mRNA oscillations damp rapidly in extended dark conditions, but unlike catalase CAT2 and the chlorophyll a/b binding protein gene CAB, in which the circadian oscillations damp to low steady state mRNA abundance, CAT3 mRNA oscillations damp to high steady state levels of mRNA abundance. Mutational disruption of either phytochrome- or cryptochrome-mediated light perception prevents damping of the oscillations in CAT3 mRNA abundance and reveals strong circadian oscillations that persist for multiple cycles in extended dark conditions. Damping of CAT3 mRNA oscillations specifically requires phytochrome A but not phytochrome B and also requires the cryptochrome1 blue light receptor. Therefore, we conclude that synergistic signaling mediated through both phytochrome A and cryptochrome1 is required for damping of circadian CAT3 mRNA oscillations in extended dark conditions.
UNLABELLED: PET studies of the serotonin (5-hydroxytryptamine, or 5-HT) transporter are increasingly using (11)C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile (DASB). We noted that the percentage of unmetabolized (11)C-DASB is often lower at 2 min after injection than at 12 min. We hypothesized that this is due to initial "trapping" of the unmetabolized (11)C-DASB compound in the lung, a major 5-HT transporter site and dose-limiting organ. To determine whether binding to an extracranial pool of 5-HT transporters contributes to the lower initial level of unmetabolized (11)C-DASB, we examined the effects of sertraline. METHODS: Eleven healthy volunteers had 2 (11)C-DASB PET scans on the same day, and 6 of the 11 had a third scan after sertraline administration. The unmetabolized (11)C-DASB fraction was measured in arterial plasma as a function of time and was fit with 2 exponentials with no damping, power function damping, or no damping with the first point removed. RESULTS: Power function damping best fit the data as assessed by visual inspection and residuals and resulted in greater distribution volumes than did no damping with the first point removed. Test-retest reproducibility improved when power function damping was used, as compared with no damping with the first point removed. Oral sertraline raised the 2-min unmetabolized (11)C-DASB percentage. CONCLUSION: Measurement and fitting of early metabolism time points improves curve fitting, significantly affects volume-of-distribution determination, and improves test-retest reproducibility. Saturation of lung 5-HT transporters by sertraline prevents the initial trapping of (11)C-DASB. Initial trapping of high-affinity radioligands may be important in the quantification of the binding of other ligands with a high concentration of binding sites in the lungs.
The performance of a new albumin-impregnated, knitted vascular graft stored damp in saline was assessed by a comparative study in the canine aorta. Knitted grafts interposed into the descending thoracic aorta for 4 weeks included: albumin-coated and stored damp in saline (damp albuminated) (n = 6), albumin-coated and freeze-dried (dry albuminated) (n = 5), collagen-coated (n = 4), and uncoated (n = 4). The results of macroscopic and microscopic evaluation were subjected to one-way analysis of variance (Newman-Keuls). Damp albuminated grafts had significantly less transinterstitial blood loss than uncoated grafts (P less than 0.05). No significant differences in thrombogenicity, thrombus-free surface area, tissue ingrowth, or endothelial coverage existed between the damp albuminated and the uncoated grafts. However, significantly less thrombogenicity (P less than 0.05) and more endothelial cell coverage (P less than 0.05) were present in the damp albuminated grafts than in the collagen-coated grafts. No evidence for delayed graft hemorrhage or distal embolization was found in any group. The new damp albuminated graft is a minimally thrombogenic prosthesis combining low implantation porosity with relative ease of handling. It should function well as a low porosity graft for great vessel replacement.