Presence Of DA Research Articles

Nanofiber-reinforced chitosan/gelatine hydrogel with photothermal, antioxidant and conductive capabilities promotes healing of infected wounds

The wound healing process was often accompanied by bacterial infection and inflammation. The combination of electrically conductive nanomaterials and wound dressings could accelerate cell proliferation through endogenous electrical signaling, effectively promoting wound healing. In this study, polypyrrole was modified with dopamine hydrochloride by an in situ polymerization to form dopamine-polypyrrole (DA-Ppy) conductive nanofibers which successfully enhanced the water dispersibility and biocompatibility of polypyrrole. The DA-Ppy nanofibers were dispersed in an aqueous solution for >48 h and still maintained good stability. In addition, the DA-Ppy nanofibers showed good photothermal properties, and the temperature could reach 59.7 °C by 1.5 W/cm2 near-infrared light irradiation (NIR) for 10 min. DA-Ppy conductive nanofibres could be well dispersed in 3,4-dihydroxyphenylpropionic acid modified chitosan-carboxymethylated β-cyclodextrin modified gelatin (CG) hydrogel due to the presence of DA, which endowed CG/DA-Ppy hydrogel with good adhesion properties, and the hydrogel adhered to the pigskin would not be dislodged by washing with running water. Under NIR, the CG/DA-Ppy hydrogel showed significant antimicrobial properties. Moreover, the CG/DA-Ppy hydrogel had excellent biocompatibility. In addition, CG/DA-Ppy hydrogel was effective in scavenging ROS, inducing macrophage polarization towards the M2 phenotype, and modulating the level of wound inflammation in vitro. Finally, it was confirmed in rat-infected wounds that the tissue regeneration effect and collagen deposition in the CG/DA-Ppy + NIR group were significantly better than the other groups in the repair of infected wounds, indicating better repair of infected wounds. The results suggested that the photothermal, antioxidant DA-Ppy conductive nanofiber had great potential for application in infected wound healing.

The prognostic value of ductal adenocarcinoma of the prostate in patients with advanced prostate cancer treated with abiraterone acetate.

167 Background: Previous studies have indicated that ductal adenocarcinoma of the prostate (DA) is associated with adverse prognosis in patients with localized prostate cancer (PCa). However, the clinical significance of DA in advanced PCa remains largely ambiguous. This study endeavors to investigate the relationship between the existence of DA in prostate biopsy specimens and treatment outcomes among patients with advanced PCa receiving abiraterone acetate (AA) therapy. Methods: We retrospectively analyzed data from 440 patients with advanced PCa who received AA at either the metastatic hormone-sensitive (mHSPC, N=123) or castration-resistant PCa (mCRPC, N=317) stage. The presence of DA and its proportion was evaluated based on prostate biopsy specimens. Kaplan-Meier curves and COX regression were used to evaluate the predictive significance of DA on AA efficacy, including PSA response, PSA progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS). Results: In aggregate, DA was detected in 35/440 (8.0%) patients, with 13/440 (3.0%) and 22/440 (5.0%) men harboring DA<5% and ≥5%, respectively, in the total tumors. The overall PSA response rate in the entire cohort was 302/440 (68.6%), and it was comparable for people with and without DA, with both groups having a response rate of 68.6%. Of note, compared with patients without DA, men with DA have significantly longer median PSA-PFS (mPSA-PFS, 12.1- vs. 25.0-Mo, P=0.005) and median rPFS (mrPFS, 19.8 vs. 38.2-Mo, P=0.034). Subgroup analysis based on DA proportion further revealed that in comparison with PCa without DA, DA≥5% was an indicator of favorable PSA-PFS (HR, 95%CI: 0.28, 0.14-0.56, p<0.001) and rPFS (HR, 95%CI: 0.35, 0.18-0.72, p=0.004), while DA<5% was not. In multivariate COX regression analysis, after adjusting by clinicopathological factors, including mCRPC/mHSPC stage, ISUP grading, metastatic burden, pain score and pretreatment hemoglobin, alkaline phosphatase, and lactate dehydrogenase, DA≥5% was still independently associated with better therapeutic efficacy of AA treatment (PSA-PFS: HR, 95%CI: 0.36, 0.17-0.74, p<0.001; rPFS: HR, 95%CI: 0.47, 0.23-0.96, p=0.040). Conclusions: A DA proportion ≥5% in the tumor is related to improved treatment efficacy for individuals with advanced PCa receiving AA. Thus, in the pathological diagnosis of PCa, it is necessary to routinely report the presence and proportion of DA in order to aid with treatment decision-making.

Bile acid interactions with neurotransmitter transporters.

Synthesized in the liver from cholesterol, the bile acids (BAs) primary role is emulsifying fats to facilitate their absorption. BAs can cross the blood-brain barrier (BBB) and be synthesized in the brain. Recent evidence suggests a role for BAs in the gut-brain signaling by modulating the activity of various neuronal receptors and transporters, including the dopamine transporter (DAT). In this study, we investigated the effects of BAs and their relationship with substrates in three transporters of the solute carrier 6 family. The exposure to obeticholic acid (OCA), a semi-synthetic BA, elicits an inward current (IBA) in the DAT, the GABA transporter 1 (GAT1), and the glycine transporter 1 (GlyT1b); this current is proportional to the current generated by the substrate, respective to the transporter. Interestingly, a second consecutive OCA application to the transporter fails to elicit a response. The full displacement of BAs from the transporter occurs only after exposure to a saturating concentration of a substrate. In DAT, perfusion of secondary substrates norepinephrine (NE) and serotonin (5-HT) results in a second OCA current, decreased in amplitude and proportional to their affinity. Moreover, co-application of 5-HT or NE with OCA in DAT, and GABA with OCA in GAT1, did not alter the apparent affinity or the Imax, similar to what was previously reported in DAT in the presence of DA and OCA. The findings support the previous molecular model that suggested the ability of BAs to lock the transporter in an occluded conformation. The physiological significance is that it could possibly avoid the accumulation of small depolarizations in the cells expressing the neurotransmitter transporter. This achieves better transport efficiency in the presence of a saturating concentration of the neurotransmitter and enhances the action of the neurotransmitter on their receptors when they are present at reduced concentrations due to decreased availability of transporters.

TikTok, Digital Da’wa and Religious Authorities

This study explains the presence of da’wa influencers on social media. To narrow the discussion, the author takes a case study on TikTok social media. This study aims to determine whether new figures of da’wa on social media shift the old religious authority or traditional figures. The author describes this discussion using Heidi Campbell's digital religion concept approach. The author's analysis shows that these da’wa influencers do not claim to be scholars or religious scholars. The delivery of their da’wa is relaxed and not patronizing. The existence of this new da’wa figure belongs to the logic of continuity and complementarity, which means that their legitimacy is a form of continuity or as a successor of the old figure's authority.

3D flower-like β-Ni(OH)2 as an electrochemical sensor for sensitive determination of serotonin

Morphology studies of nanomaterials have attracted considerable attention in the field of catalysis because of their distinguishable properties and performances. In this context, we have developed a β-Ni(OH) 2 decorated para phenylenediamine (p-PDA) functionalized reduced graphene oxide (RGO) (denoted as RGO/p-PDA/β-Ni(OH) 2 ) electrochemical sensor for detecting serotonin (5-HT). The growth mechanism of a three-dimensional (3D) flower-like β-Ni(OH) 2 based on two-dimensional (2D) RGO nanosheets assembled with petals of the flower was investigated by field emission scanning electron microscopy (FESEM). The 3D flower-like morphology significantly enhanced the surface area and conductivity of RGO/p-PDA/β-Ni(OH) 2 modified glassy carbon electrode (GCE). The electrochemical performance of the material was studied using different techniques, including cyclic voltammetry (CV), linear sweep voltammetry (LSV), electrochemical impedance spectra (EIS), and amperometry. The higher oxidation current of RGO/p-PDA/β-Ni(OH) 2 /GCE was -134.8 µA at 0.383 V ( vs Ag / AgCl ) in CV. In amperometry, the modified electrode provided a wide linear range (5-325 µM), low limit of detection (0.0462 µM), high sensitivity (339.46 µA mM -1 cm -2 ), and fast response time (<2 s). Furthermore, the as-prepared electrode demonstrated high selectivity, long-term stability, reproducibility, and repeatability. The much better recovery range of urine (109.83-111.05%) than drinking water (98.15-101.02%) implied that the sensor is effective for 5-HT determination. • Thermally and chemically stable nanocomposite. • It demonstrated 3D flower-like morphology. • It responded within 2 s in CA. • Higher recovery range for urine sample. • It showed high selectivity in presence of DA and AA.

Structural and Biophysical Characterization of Stable Alpha-Synuclein Oligomers

The aggregation of α-synuclein (α-syn) into neurotoxic oligomers and fibrils is an important pathogenic feature of synucleinopatheis, including Parkinson's disease (PD). A further characteristic of PD is the oxidative stress that results in the formation of aldehydes by lipid peroxidation. It has been reported that the brains of deceased patients with PD contain high levels of protein oligomers that are cross-linked to these aldehydes. Increasing evidence also suggests that prefibrillar oligomeric species are more toxic than the mature amyloid fibrils. However, due to the heterogenous and metastable nature, characterization of the α-syn oligomeric species has been challenging. Here, we generated and characterized distinct α-syn oligomers in vitro in the presence of DA and lipid peroxidation products 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). HNE and ONE oligomer were stable towards the treatment with SDS, urea, and temperature. The secondary structure analysis revealed that only HNE and ONE oligomers contain β-sheet content. In the seeding assay, both DA and ONE oligomers significantly accelerated the aggregation. Furthermore, all oligomeric preparations were found to seed the aggregation of α-syn monomers in vitro and found to be cytotoxic when added to SH-SY5Y cells. Finally, both HNE and ONE α-syn oligomers can be used as a calibrator in an α-syn oligomers-specific ELISA.

Transition metal coordination frameworks as artificial nanozymes for dopamine detection via peroxidase-like activity

Herein, Cu–HMT and Ni–HMT were synthesized via a green synthetic method. Cu–HMT possesses formidable peroxidase-mimic activity compared to Ni–HMT. However, the peroxidase-like activity of Cu–HMT was strongly inhibited in the presence of DA.

Fabrication of a novel nanocomposite electrode with ZnO-MoO3 and biochar derived from mushroom biomaterials for the detection of acetaminophen in the presence of DA

A novel two-dimensional ZnO-MoO3-C nanocomposite was synthesized by the green thermal calcination method with the biochar of mushroom derived carbon nanosheets and Zn1.5PMo12O40 polyoxometallate. The nanocomposite was used to modify a glassy carbon electrode (GCE) for the first time to construct an acetaminophen (AP) electrochemical biosensor. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and nitrogen adsorption/desorption isotherm (BET) results showed that the synthesized ZnO-MoO3-C nanocomposite has many layered nanostructure and a large surface area. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) indicated that ZnO-MoO3-C/GCE presented highly effective and accurate toward the oxidation of AP due to the stable molecular structure of the electrode surface. The DPV response of the proposed sensor exhibited selectively and sensitively determination for AP with a wider linear dependence on the concentration of AP from 2.5 to 2000 μM, and lower limits of detection (LOD) 1.14 μM, compared with other carbon-base material modified GCE and GCE electrodes. In addition, the proposed sensor was applied to detection of AP in real samples, and the recovery was the range from 94.7 to 101.0%, and RSD was less than 5%. It indicates that the proposed sensor has a hopeful capacity of extensive applications in bioanalysis and tablets.

Translesion synthesis by AMV, HIV, and MMLVreverse transcriptases using RNA templates containing inosine, guanosine, and their 8-oxo-7,8-dihydropurine derivatives.

Inosine is ubiquitous and essential in many biological processes, including RNA-editing. In addition, oxidative stress on RNA has been a topic of increasing interest due, in part, to its potential role in the development/progression of disease. In this work we probed the ability of three reverse transcriptases (RTs) to catalyze the synthesis of cDNA in the presence of RNA templates containing inosine (I), 8-oxo-7,8-dihydroinosine (8oxo-I), guanosine (G), or 8-oxo-7,8-dihydroguanosine (8-oxoG), and explored the impact that these purine derivatives have as a function of position. To this end, we used 29-mers of RNA (as template) containing the modifications at position-18 and reverse transcribed DNA using 17-mers, 18-mers, or 19-mers (as primers). Generally reactivity of the viral RTs, AMV / HIV / MMLV, towards cDNA synthesis was similar for templates containing G or I as well as for those with 8-oxoG or 8-oxoI. Notable differences are: 1) the use of 18-mers of DNA (to explore cDNA synthesis past the lesion/modification) led to inhibition of DNA elongation in cases where a G:dA wobble pair was present, while the presence of I, 8-oxoI, or 8-oxoG led to full synthesis of the corresponding cDNA, with the latter two displaying a more efficient process; 2) HIV RT is more sensitive to modified base pairs in the vicinity of cDNA synthesis; and 3) the presence of a modification two positions away from transcription initiation has an adverse impact on the overall process. Steady-state kinetics were established using AMV RT to determine substrate specificities towards canonical dNTPs (N = G, C, T, A). Overall we found evidence that RNA templates containing inosine are likely to incorporate dC > dT > > dA, where reactivity in the presence of dA was found to be pH dependent (process abolished at pH 7.3); and that the absence of the C2-exocyclic amine, as displayed with templates containing 8-oxoI, leads to increased selectivity towards incorporation of dA over dC. The data will be useful in assessing the impact that the presence of inosine and/or oxidatively generated lesions have on viral processes and adds to previous reports where I codes exclusively like G. Similar results were obtained upon comparison of AMV and MMLV RTs.

GERAKAN DAKWAH JAMA’AH TABLIGH DI KALANGAN WANITA DALAM PEMBINAAN KELUARGA MUSLIM DI KOTA BANDARLAMPUNG

Since the emergence of the Transnational Da'wah Movement such as the TablighiJama'at, it has created contradictions about the Law of Providing both birth and mentalityto the family left in the Khuruj fii sabilillah program (Exiting the Way of Allah) to preachthe ummah from house to house, mosque to mosque, inviting listen to Muslims (religiouslectures) and invite to pray in congregation in the mosque. From the development ofJama'ah Tabligh's missionary movement in Indonesia, this movement has experiencedquite rapid development. Not only is the movement that has a strong community, it ismarked by the presence of da'wah markers (da'wah centers) in each of the Provinces andDistricts of the City. But in the development of the da'wah movement there are severalthings that become contradictions in the family, in this case the provision of income forchildren and wives who are left behind when their head of household implements Khurujfii sabilillah for 3 days, 40 days and 4 months. Therefore, this paper takes the theme of theLaw of Livelihood Against Families in the Tabligh Jama Da'wah Movement in acomprehensive manner.

Hukum Nafkah Terhadap Keluarga pada Gerakan Transnasional Keagamaan

Abstract&#x0D; Since the emergence of the Transnational Da'wah Movement such as the Tablighi Jama'at, it has created contradictions about the Law of Providing both birth and mentality to the family left in the Khuruj fii sabilillah program (Exiting the Way of Allah) to preach the ummah from house to house, mosque to mosque, inviting listen to Muslims (religious lectures) and invite to pray in congregation in the mosque. From the development of Jama'ah Tabligh's missionary movement in Indonesia, this movement has experienced quite rapid development. Not only is the movement that has a Jama'at quite rapidly, it is marked by the presence of da'wah markers (da'wah centers) in each Province and District of the City. But in the development of the da'wah movement there are several things that become contradictions in the family, in this case the provision of income to children and wives who are left behind when their household heads implement Khuruj fi sabilillah for 3 days, 40 days and 4 months. Therefore, this paper takes the theme of the Law of Livelihood Against Families in the Tabligh Jama Da'wah Movement in a comprehensive manner.&#x0D; Keywords: Family Livelihood, Religious Transnational Movement.

Dechlorination of p-Chlorophenol by Fe-Pd Nanoparticles Promoted by Poly (γ-glutamic acid)–Dopamine Composite

Palladium-doped nanoscale zerovalent iron nanoparticles (Fe-Pd NPs) was fabricated and stabilized by poly (γ-glutamic acid)–Dopamine composite (PGA-DA). The fabricated nanoparticles had high dechlorination activity towards p-Chlorophenol (p-CP). PGA-DA modified Fe-Pd NPs significantly outperformed PGA modified ones in catalytic activities even in weak alkaline condition. Fe-Pd NPs@PGA-DA (10 mg PGA-DA and 0.4 wt% Pd loading) could achieve 100 % p-CP removal within 60 min. It is worth mentioning that the presence of DA alone could overwhelm dechlorination capacity of Fe-Pd NPs toward p-CP. The coordination bonding between catechol and Fe ions was also investigated in detail. This study demonstrated that PGA-DA is a promising modifier and stabilizer for Fe-Pd NPs, which was expected to be applied in real environmental remediation technology.

An electrochemical sensor for determination of tryptophan in the presence of DA based on poly(l-methionine)/graphene modified electrode

Electrocatalytic oxidation of l-Trp at poly(l-methionine)/graphene composite film modified glassy carbon electrode (PLME/GR/GCE) were investigated by differential pulse voltammetry.

DOPAMINE MODULATES FLOW‐DEPENDENT TRANSPORT BY NHE3, BUT NOT H + ‐ATPASE, IN MOUSE PROXIMAL TUBULES

Mechanism of flow dependence of NaCl and HCO3− absorption were studied in microperfused mouse kidney proximal tubules in vitro under the conditions of low (5nl/min) and high (20 nl/min) luminal perfusion rates. Similar to our previous report, the transition from low to high flow increased reabsorption of fluid (Jv) and Na+ (JNa) by 53%, and of HCO3− (JHCO3) by 100%. Flow did not affect Cl− transport, as JCl was 47.8 and 40.5 pmol/min/mm at high and low flow rates, respectively. Luminal dopamine (DA; 10μM) did not change JNa and JHCO3 at low flow rate but completely abolished the increments of JNa and partially inhibited (60%) the increment of JHCO3 induced by high flow rate. The remaining flow-stimulated JHCO3 in the presence of DA was completely abolished by luminal bafilomycin, an inhibitor of H+-ATPase. The effect of DA was largely blocked by DA1 inhibitor SCH23390 and completely blocked when both DA1 and DA2 inhibitors, SCH23390 and sulpiride, were added together. The effect of DA was abolished by the protein kinase A inhibitor H89; however, 8-Br-cAMP had no effect on flow-dependent stimulation of proximal tubule transport. 8-Br-cAMP had a similar inhibitory effect on JNa and JHCO3 at both low and high flow rates. JNa was reduced by 21% and 24.5 % and JHCO3 by 16% and 16.5% compared with control at low and high perfusion rates, respectively. These results show that flow dependence of NHE3 and H+-ATPase is cAMP independent and dopamine interferes with the flow dependence of NHE3 largely by a DA1- and PKA-mediated mechanism but has no impact on H+-ATPase, indicating flow dependence of NHE3 and H+-ATPase activity may be modulated by different signaling mechanisms.

Inhibition of energy metabolism in cerebral cortex of young rats by the medium-chain fatty acids accumulating in MCAD deficiency

Patients affected by medium-chain acyl CoA dehydrogenase (MCAD) deficiency, a frequent inborn error of metabolism, suffer from acute episodes of encephalopathy. However, the mechanisms underlying the neuropathology of this disease are poorly known. In the present study, we investigated the in vitro effect of the medium-chain fatty acids (MCFA), at concentrations varying from 0.01 to 3 mM, accumulating in MCAD deficiency on some parameters of energy metabolism in cerebral cortex of young rats. 14CO 2 production from [U 14] glucose, [1- 14C] acetate and [1,5- 14C] citrate was evaluated by incubating cerebral cortex homogenates from 30-day-old rats in the absence (controls) or presence of octanoic acid, decanoic acid or cis-4-decenoic acid. OA and DA significantly reduced 14CO 2 production from acetate by around 30–40%, and from glucose by around 70%. DA significantly reduced 14CO 2 production from citrate by around 40%, while OA did not affect this parameter. cDA inhibited 14CO 2 production from all tested substrates by around 30–40%. The activities of the respiratory chain complexes and of creatine kinase were also tested in the presence of DA and cDA. Both metabolites significantly inhibited cytochrome c oxidase activity (by 30%) and complex II–III activity (DA, 25%; cDA, 80%). Furthermore, only cDA inhibited complex II activity (by 30%), while complex I–III and citrate synthase were not affected by these MCFA. On the other hand, only cDA reduced the activity of creatine kinase in total homogenates, as well as in mitochondrial and cytosolic fractions from cerebral cortex (by 50%). The data suggest that the major metabolites which accumulate in MCAD deficiency, with particular emphasis to cDA, compromise brain energy metabolism. We presume that these findings may contribute to the understanding of the pathophysiology of the neurological dysfunction of MCAD deficient patients.

Autoxidation and MAO-mediated metabolism of dopamine as a potential cause of oxidative stress: role of ferrous and ferric ions

The autoxidation and monoamine oxidase (MAO)-mediated metabolism of dopamine (3-hydroxytyramine; DA) cause a continuous production of hydroxyl radical ( OH), which is further enhanced by the presence of iron (ferrous iron, Fe 2+ and ferric ion, Fe 3+). The accumulation of hydrogen peroxide (H 2O 2) in the presence of Fe 2+ appears to discard the involvement of the Fenton reaction in this process. It has been found that the presence of DA significantly reduces the formation of thiobarbituric acid reagent substances (TBARS), which under physiological conditions takes place in mitochondrial preparations. The presence of DA is also able to reduce TBARS formation in mitochondrial preparations even in the presence of iron (Fe 2+ and Fe 3+). However, DA boosted the carbonyl content of mitochondrial proteins, which was further increased in the presence of iron (Fe 2+ and Fe 3+). This latter effect is also accompanied by a significant reduction in thiol content of mitochondrial proteins. It has also been observed how the pre-incubation of mitochondria with pargyline, an acetylenic MAO inhibitor, reduces the production of OH and increases the formation of TBARS. Although, the MAO-mediated metabolism of DA increases MAO-B activity, the presence of iron inhibits both MAO-A and MAO-B activities. Consequently, DA has been shown to be a double-edged sword, because it displays antioxidant properties in relation to both the Fenton reaction and lipid peroxidation and exhibits pro-oxidant properties by causing both generation OH and oxidation of mitochondrial proteins. Evidently, these pro-oxidant properties of DA help explain the long-term side effects derived from l-DOPA treatment of Parkinson’s disease and its exacerbation by the concomitant use of DA metabolism inhibitors.

Synthesis and structure determination of the adducts formed by electrochemical oxidation of 1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene in the presence of deoxyribonucleosides or adenine.

Study of DNA adducts formed with aromatic hydrocarbons is part of the strategy to elucidate the mechanisms of tumor initiation by these compounds. 1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene (THDMBA) is of special interest because it allows discrimination between the pathways of bioactivation by one-electron oxidation and monooxygenation. To study and identify adducts formed biologically, synthetic adducts are needed as reference standards. THDMBA was electrochemically oxidized in the presence of deoxyadenosine (dA), adenine (Ade), deoxyguanosine (dG), or deoxycytidine (dC). In the presence of dA, four adducts were isolated: 7-methyl-1,2,3,4-tetrahydrobenz[a]anthracene-12-CH2-N7Ade (7-MTHBA-12-CH2-N7Ade, 3.6%), 12-MTHBA-7-CH2-N7Ade (4.2%), 7-MTHBA-12-CH2-N6dA (5.8%), and 12-exo-methylene-7-MTHBA-7-N6dA (22.8%); a dehydrogenated product, 7,12-di-exo-methylene-THBA (44.2%), was also obtained. In the presence of Ade, nine adducts were synthesized: 7-MTHBA-12-CH2-N7Ade (1.1%), 12-MTHBA-7-CH2-N7Ade (2.4%), 7-MTHBA-12-CH2-N1Ade (10.2%), 12-MTHBA-7-CH2-N1Ade (13.2%), 7-MTHBA-12CH2-N3Ade (1.7%), 12-MTHBA-7-CH2-N3Ade (1.7%), 7-exo-methylene-12-MTHBA-12-N3Ade (11.2%), 12-exo-methylene-7-MTHBA-7-N3Ade (27.9%), and 12-exo-methylene-7-MTHBA-7-N6Ade (12.1%), as well as the dehydrogenated product 7,12-di-exo-methylene-THBA (16.7%). In the presence of dG, three adducts were produced: 7-MTHBA-12-CH2-N7Gua (24.2%), 12-MTHBA-7-CH2-N7Gua (12.2%), and 7-MTHBA-12-CH2-N2dG (3.7%), as well as the dehydrogenated product 7,12-di-exo-methylene-THBA (38.9%). Anodic oxidation in the presence of dC yielded a large amount of 7,12-di-exo-methylene-THBA (80.4%), but no adducts. The structure of the adducts was elucidated by using UV, NMR, and MS. The N-7 positions in dG, dA, and Ade, the 2-NH2 in dG, and the N-1 position in Ade form exclusively methyl-linked adducts. In contrast, the 6-NH2 group of dA and Ade and the N-3 of Ade prefer to attack the meso-anthracenic positions rather than the methyl groups. The order of reactivity of dG and dA in the formation of methyl-linked THDMBA adducts agrees well with that previously found for 7,12-dimethylbenz[a]anthracene [RamaKrishna et al. (1992) J. Am. Chem. Soc. 114, 1863-1874.

P2-124 - presence of DA in the guinea-pig stomach

P2-124 - presence of DA in the guinea-pig stomach

Synthesis and structure determination of the adducts formed by electrochemical oxidation of the potent carcinogen dibenzo[a,I]pyrene in the presence of nucleosides.

Because dibenzo[a,l]pyrene (DBP) is the most potent known carcinogenic aromatic hydrocarbon, reference adducts formed by reaction of deoxyribonucleosides with electrophilic intermediates of DBP are essential for identifying the structures of adducts formed in biological systems. Electrochemical oxidation of DBP in the presence of nucleosides leads to adducts from DBP.+. When 6.8 equiv of charge are consumed, three adducts are formed with dG: 7-(DBP-10-yl)Gua (89%), 8-(DBP-10-yl)dG (2%), and 8-(DBP-10-yl)Gua (2%). With 10 equiv of charge, however, only two adducts are formed: 7-(DBP-10-yl)Gua (89%) and 8-(DBP-10-yl)Gua (4%). Anodic oxidation of 8-(DBP-10-yl)dG yields 8-(DBP-10-yl)Gua. Anodic oxidation of DBP in the presence of G produces 7-(DBP-10-yl)Gua (27%) and 8-(DBP-10-yl)G (9%). Anodic oxidation of DBP in the presence of dA affords two adducts, N6-(DBP-10-yl)dA (28%) and 7-(DBP-10-yl)Ade (12%), whereas anodic oxidation in the presence of A produces only N6-(DBP-10-yl)A (24%). The structures of the adducts were elucidated by using UV, NMR, and MS. Formation of these adducts demonstrates that DBP.+ reacts at C-10 with nucleophiles. The most reactive nucleophilic groups for the Gua moiety are the N-7 and C-8, whereas for the Ade moiety they are N-7 and the 6-amino group.

The influence of interleukin-2 on the release of somatostatin and growth hormone-releasing hormone by mediobasal hypothalamus.

Interleukin-2 (IL-2), which plays a major role in the bidirectional intercellular communication between the neuroendocrine and immune systems, suppressed the release of GH from anterior pituitary halves at femtomolar concentrations. It is well established that the release of GH from the anterior pituitary is regulated by growth hormone releasing hormone (GRH) and growth hormone release-inhibiting hormone (somatostatin). Consequently, we studied the possible effect of IL-2 on the release of somatostatin and GRH from the mediobasal hypothalamus (MBH) in vitro. Single MBHs were incubated with fresh Krebs-Ringer bicarbonate (KRB) buffer alone or KRB containing different concentrations of IL-2 (10(-15)-10(-10) M) for 30 min. After collection of the media, the MBHs were incubated with KRB containing high potassium (high K+ = 56 mM) without IL-2 for a period of 30 min to study the effect of pretreatment with IL-2 on depolarization-induced somatostatin and GRH release. Experiments were also undertaken to study the effect of IL-2 in the presence of high K+ or IL-2 in the presence of DA (60 microM), a potent stimulator of somatostatin and GRH release. The minimal effective dose of IL-2 which significantly stimulated the release of somatostatin was 10(-14) M. Depolarization-induced release of somatostatin was reduced significantly by prior treatment with all the concentrations of IL-2 tested (10(-13)-10(-10) M).(ABSTRACT TRUNCATED AT 250 WORDS)