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Biomedical subjects

A Papageorgiou

Publications and source records attributed to A Papageorgiou.

At least 19 recordsLinked to original sources

Estradiol induces expression of 5-hydroxytryptamine (5-HT) 4, 5-HT5, and 5-HT6 receptor messenger ribonucleic acid in rat anterior pituitary cell aggregates and allows prolactin release via the 5-HT4 receptor.

Serotonin [5-hydroxytryptamine (5-HT)] is known to control prolactin (PRL) release at a hypothalamic level, but a pituitary site of action remains poorly studied. The present study explores the acute effect of 5-HT on PRL release in rat anterior pituitary aggregate cell cultures, the influence of steroid and thyroid hormones, and the 5-HT receptor (5-HTR) subtype(s) involved. 5-HT elicited a prompt increase in basal PRL release, an effect strongly potentiated by estradiol (E(2)) in the culture medium (dose response 1-100 nm). In E(2) condition, the PRL response was not affected by the nonselective 5-HTR antagonists methysergide and methiothepin nor by 5-HTR1, 5-HTR2, 5-HTR3, 5-HTR6, and 5-HTR7/5 antagonists, but was fully blocked by the 5-HTR4 antagonist GR 113808. Among various agonist analogs, only the 5-HTR4 agonist cisapride and the 5-HTR2 agonist alpha-methyl-5-HT evoked PRL release. The effect of alpha-methyl-5-HT also required E(2) during culture and was abolished by GR 113808 but not by combined 5-HTR2A, B, and C blockade. In E(2)-treated aggregates, 5-HT caused a 5-fold increase in cAMP levels. The intact anterior pituitary expressed mRNA of all known members of the 5-HTR family. In aggregates, 5-HTR4, 5-HTR5, and 5-HTR6 mRNA expression required E(2) during culture. The effect of 5-HT on PRL release was not affected by blocking the serotonin transporter or the vesicular monoamine transporter. The present data suggest a widespread expression of 5-HTRs in the rat anterior pituitary, several of which are up-regulated by estrogen, and that, in the presence of estrogen, one of these, the 5-HTR4, mediates acute PRL release.

Animals↗

Adenoviral-mediated interferon alpha overcomes resistance to the interferon protein in various cancer types and has marked bystander effects.

We have previously shown that intravesical administration of adenovirus encoding human interferon alpha-2b (Ad-IFN) induced a marked regression of superficial human bladder tumors derived from cells that are resistant to over 1 million units/ml of IFNalpha protein in vitro. In addition, Ad-IFN appeared to produce strong bystander effects. In this study, we show that Ad-IFN causes marked inhibition of cell growth and apoptosis in cells of various tumor types, all of which are resistant to IFNalpha protein. In addition, strong perinuclear IFN staining was seen in all cell lines following Ad-IFN transfection and was never observed after exposure to the IFN protein. Ad-IFN induced proteolytic processing of caspases 3, 8 and 9, indicative of enzymatic activation. However, the caspase-8-selective inhibitor, IETDfmk, blocked apoptosis only in the cell lines that were sensitive to the IFNalpha protein and had minimal effect on Ad-IFN-induced caspase-3 or -9 processing and cell death, indicating that death receptor-independent mechanism(s) were involved in the cytotoxic effects observed for cancer cell lines resistant to the IFNalpha protein. Moreover, we document that a yet to be identified soluble factor(s) is responsible for causing the bystander effect observed following Ad-IFN treatment in IFN protein-resistant cancer cells.

Adenoviridae↗

Low-molecular-weight heparin (enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis: a randomized, controlled, comparative study.

BACKGROUND: Heparin could be beneficial to the treatment of active ulcerative colitis because of its anticoagulant, anti-inflammatory and immunomodulatory properties. AIM: To evaluate the tolerability, safety and efficacy of low-molecular-weight heparin as adjuvant therapy in patients with active ulcerative colitis. METHODS: Thirty-four adult patients with active ulcerative colitis were consecutively included in a prospective, randomized, comparative study, and were treated for 12 weeks. Eighteen patients in the 'standard therapy' group were treated with aminosalicylates and weekly tapered corticosteroids. Sixteen patients in the 'heparin therapy' group were treated with standard therapy plus enoxaparin 100 Anti-Xa IU/kg/day subcutaneously. RESULTS: Seventeen patients in the 'standard therapy' group and 15 patients in the 'heparin therapy' group completed the study. Tolerability and compliance to therapy were excellent and no withdrawals were noted because of complications. There was a significant improvement in the disease severity in both groups (P<0.001), without any difference between them (P=not significant). Both treatment groups showed similar proportions of disease improvement (65% and 73%, respectively; P=not significant). There were no significant differences in inflammation (fibrinogen, ESR, CRP) and coagulation (thrombin-antithrombin complex, F1+2, D-dimers) parameters during and at the end of the study between treatment groups. CONCLUSION: Adjuvant administration of low-molecular heparin in patients with active ulcerative colitis is safe and well tolerated, but no additive benefit over standard therapy for ulcerative colitis was noted.

Adjuvants, Pharmaceutic↗

In vivo anticancer, anti-inflammatory, and toxicity studies of mixed-ligand Cu(II) complexes of dien and its Schiff dibases with heterocyclic aldehydes and 2-amino-2-thiazoline. Crystal structure of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O).

A new series of complexes of the type [Cu(dien)(2a-2tzn)Y(2)] and [Cu(dienXX)(2a-2tzn)Y(2)], where dien=diethylenetriamine and dienXX=Schiff dibase of diethylenetriamine formed with 2-furaldehyde (dienOO), 2-thiophenecarboxaldehyde (dienSS), or pyrrol-2-carboxaldehyde (dienNN); Y=Cl, Br or NO(3); and 2a-2tzn=2-amino-2-thiazoline, were synthesized and their structure established by C, H, N and Cu analysis; IR and electronic spectra; magnetic susceptibility; and molar conductivity. The isolated complexes are monomers, paramagnetic, and electrolytes of types 1:1 or 1:2. In both types of solid state complexes, [Cu(dien)(2a-2tzn)Y(2)] and [Cu(dienXX)(2a-2tzn)Y(2)], dien and its Schiff dibases are bonded to Cu(II) in a tridentate fashion through 3N atoms. The coordination sphere is completed by the endocyclic nitrogen of the thiazoline moiety and by two Cl, Br, or NO(3) groups with distorted octahedral geometry. The proposed structure of these compounds was supported by X-ray analysis of [Cu(dien)(Br)(2a-2tzn)](Br)(H(2)O). The coordination polyhedron around the copper atom can be described as a distorted square pyramid [Cu(dien)(Br)(2a-2tzn)](+). Its basal plane is occupied by the four nitrogen atoms of the dien and thiazoline ligands with Cu-N distances ranging between 1.996(6) and 2.032(3)A, and the axial position is occupied by one of the two bromine atoms (Br1) with a Cu1-Br1 bond distance of 2.782(1)A. The second bromine atom (Br2) is 4.694(2)A from the copper atom, which exists as a discrete anion and is responsible for the cationic nature of the complex. Results regarding toxicity, antitumor, and anti-inflammatory activities of the investigated compounds are promising and allow the selection of a lead compound for further biological studies.

Animals↗

Endometriosis and infertility: a multi-cytokine imbalance versus ovulation, fertilization and early embryo development.

Endometriosis is tightly linked to infertility which is manifested at very early or more advanced stages of the gestational cycle. Alteration on the production of a great number of cytokines/growth factors can be accused for problems on ovum maturation, fertilization or implantation. Yet, macroscopically these stages are characterized by the inability of conception. A closer look of the cytokinic profile during the conceptional and early gestational cycle could, however, localize the problem and allow a therapeutic approach. In this commentary, going through the cytokine requirement during ovulation, fertilization and the early stages of pregnancy, it became possible to specifically define the harmful endometriosis-induced cytokines for each of the conceptional and early gestational stages. Thus, regulating the levels of interferon-gamma and tumor necrosis-alpha will facilitate ovulation and fertilization, whereas adjusting the levels of interleukin-1beta and colony stimulating gactor-1 will facilitate implantation.

Animals↗

Melanocortin peptides stimulate prolactin gene expression and prolactin accumulation in rat pituitary aggregate cell cultures.

Treatment for 40 h of reaggregate pituitary cell cultures from 14-day-old female rats with nanomolar concentrations of gamma3-melanocyte-stimulating hormone (MSH) increased prolactin mRNA but not growth hormone (GH) mRNA expression levels as measured by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). During the 40 h incubation, gamma3-MSH stimulated prolactin accumulation in the culture medium. alpha-MSH, a potent agonist of the rat melanocortin-3 receptor (MC3R) and Ala(8)-gamma2-MSH, a very weak agonist of the MC3R, increased prolactin mRNA expression at a similar concentration range as gamma3-MSH. The effect of gamma3-MSH on prolactin mRNA expression was abolished when aggregates were cultured in the presence of thyroid or glucocorticoid hormones, but not of oestradiol. By contrast, oestradiol abolished the stimulatory effect of Ala(8)-gamma2-MSH on prolactin mRNA expression. In GH3 cells stably transfected with the enhanced green fluorescent protein (eGFP) gene under control of a 3-kb prolactin promoter fragment, a dose as low as 1 nMgamma3-MSH, added for 24 h, significantly increased eGFP fluorescence. Agouti-related protein (AgRP(83-132)), a known endogenous MC3R and MC4R antagonist, did not reduce the stimulation of prolactin mRNA expression by gamma3-MSH or Ala(8)-gamma2-MSH. On its own, AgRP(83-132) significantly increased prolactin mRNA expression level and prolactin accumulation. Both gamma2-MSH and Ala(8)-gamma2-MSH increased [S(35)]GTPgammaS binding in membrane preparations of 14-day-old rat pituitaries and of GH3 cells. Whereas MC3R and MC5R mRNA were detectable by RT-PCR in normal pituitary, these receptor mRNAs were undetectable in GH3 cells using various oligonucleotide primer sets. The present findings indicate that melanocortin peptides stimulate prolactin gene expression and production and that, at least in part, a receptor different from the classic MCR is involved. AgRP appears to have other actions than its known antagonistic activity on the MC3R and MC4R.

Agouti-Related Protein↗

Comparison of risks from percutaneous central venous catheters and peripheral lines in infants of extremely low birth weight: a cohort controlled study of infants < 1000 g.

OBJECTIVE: To evaluate in infants of < 1000 g (extremely low birth weight; ELBW) the success rate of insertion of percutaneous central venous catheters (PCVC) and their duration; and the short- and long-term complications, i.e. mechanical and infectious, when compared to a control group of infants of the same age treated only with peripheral venous access. STUDY DESIGN: A cohort of 44 ELBW infants managed with PCVC (study group) was compared to a cohort of 44 infants managed only with peripheral venous access (control group). The two groups were matched for birth weight, gestational age and gender, and were comparable for severity of illness (CRIB scores). RESULTS: The success rate of PCVC insertion was 74% with the right axillary vein being the most frequently used site. The mean duration of PCVC treatment was 28 +/- 13 days. The reasons for removal of the catheter were: cessation of the total parenteral nutrition administration in 75% of the cases and occlusion in 25%. There were three infectious episodes for a total of 1138 catheter days in the PCVC group vs. 12 episodes for a total of 1114 days (p = 0.03) in the control group. Three infants died in the study group and 11 infants died in the control group (p = 0.05) of infants of ELBW. CONCLUSION: Insertion of PCVC is successful in the vast majority of cases and carries a lower risk of infection than multiple insertions of peripheral lines in infants of ELBW. It prevents repeat and painful introductions of intravenous needles.

Bacteremia↗

On the use of genetic algorithms for response surface modeling in high-performance liquid chromatography and their combination with the Microsoft Solver.

Four genetic algorithms--the classical, Haupt's, Brunetti's and a modification of the classical algorithm suggested in the present paper--are examined when they are used for the modeling of response surfaces in high-performance liquid chromatography (HPLC). We found that the best results are obtained from our modification and the worst by Haupt's algorithm. The classical genetic algorithm gives satisfactory results, better than those of Brunetti's algorithm. We also ascertained that all genetic algorithms may get stuck in a local minimum other than the global one, except for our modification, which can be considered to approach a global method. Finally, the time needed for the optimization of a genetic algorithm and the combination of a genetic algorithm with a non-linear least-squares routine are considered and discussed.

Algorithms↗

Study on the electrochemical detection of the macrolide antibiotics clarithromycin and roxithromycin in reversed-phase high-performance liquid chromatography.

The optimal conditions of the amperometric detection of the macrolide antibiotics clarithromycin and roxithromycin were found by cyclic voltammetric studies and HPLC-electrochemical detection responses obtained in different temperatures (25.5-60 degrees C) and different but almost isoelutropic binary, ternary and quaternary mixtures of aqueous buffer (pH 7), methanol, acetonitrile and isopropanol. These conditions were also proved to be applicable for the quantitative detection of clarithromycin in human plasma using roxithromycin as an internal standard and vice versa. It was demonstrated that increased attention has to be paid to eluent composition and column temperature to ensure sensitive and reproducible electrochemical responses as well as regularly shaped peaks for both macrolides tested.

Anti-Bacterial Agents↗

On the equations describing chromatographic peaks and the problem of the deconvolution of overlapped peaks.

The problem of the appropriate choice of the function that describes a chromatographic peak is examined in combination with the deconvolution of overlapped peaks by means of the non-linear least-squares method. It is shown that the majority of the functions proposed in the literature to describe chromatographic peaks are not suitable for this purpose. Only the polynomial modified Gaussian function can describe almost every peak but it is mathematically incorrect unless it is redefined properly. Two new functions are proposed and discussed. It is also shown that the deconvolution of an overlapping peak can be done with high accuracy using a non-linear least-squares procedure, like Microsoft Solver, but this target is attained only if we use as fitted parameters the position of the peak maximum and the peak area (or height) of every component in the unresolved chromatographic peak. In case we use as fitted parameters all the parameters that describe each single peak enclosed in the multi-component peak, then Solver leads to better fits, which though do not correspond to the best deconvolution of the peak. Finally, it is found that Solver gives much better results than those of modern methods, like the immune and genetic algorithms.

Artifacts↗

Platinum(II) and palladium(II) complexes with 2-acetylpyridine thiosemicarbazone: cytogenetic and antineoplastic effects.

The effect of three novel complexes of Pt(II) and three complexes of Pd(II) with 2-acetylpyridine thiosemicarbazone (HAcTsc) on sister chromatid exchange (SCE) rates and human lymphocyte proliferation kinetics on a molar basis was studied. Also, the effect of Pt(II) and Pd(II) complexes against leukemia P388 was investigated. Among these compounds, the most effective in inducing antitumor and cytogenetic effects were the complexes [Pt(AcTsc)2] x H2O and [Pd(AcTsc)2] while the rest, i.e. (HAcTsc), [Pt(AcTsc)Cl], [Pt(HAcTsc)2]Cl2 x 2H2O, [Pd(AcTsc)Cl] and [Pd(HAcTsc)2]Cl2, displayed marginal cytogenetic and antitumor effects.

Animals↗

Legal pitfalls of psychiatric research.

BACKGROUND: The increasing complexity of psychiatric research, including recent attempts to evaluate mental health legislation, suggests legal advice may be valuable in a wide range of research contexts. AIMS: We aim to illustrate both the legal pitfalls of research in psychiatry and the potential for solutions if the methods are carefully chosen. METHOD: Two examples of research are subject to legal analysis, one involving advance directives, the other the random discharge of compulsory out-patients. RESULTS: This analysis illustrates that participation in research may expose clinicians to additional forms of liability, but the legal risks can be minimised through changes in the methods or additional safeguards. CONCLUSIONS: Collaboration between academic law and psychiatry can enrich research agendas and avoid serious legal pitfalls. We argue that sound legal advice should be sought at the planning stage of research in psychiatry, but the fear of liability should not lead to overly defensive research practices. The aim should be to strike the right balance between avoiding unacceptable exposure to liability and stifling innovative research.

Advance Directives↗

The grading of hallux valgus. The Manchester Scale.

This article describes a new, noninvasive method of assessing the severity of hallux valgus deformity by means of a set of standardized photographs. Six podiatrists were independently asked to grade the level of deformity of 13 subjects (26 feet) on a scale of 1 (no deformity) to 4 (severe deformity). The reliability of the four-point scale for the severity of hallux valgus was investigated by means of kappa-type statistics for more than two raters. The results showed that the grading method had excellent interobserver repeatability with a combined kappa-type statistic of 0.86, making it a suitable instrument for clinical and research purposes.

Foot↗

A comparative study on cytogenetic and antineoplastic effects induced by two modified steroidal alkylating agents.

We investigated the effects of two newly synthesized steroidal derivatives of nitrogen mustard on sister chromatid exchange rates and on human lymphocyte proliferation kinetics. The compound 33-hydroxy-5alpha,22alpha-spirostan- 12-one-p-(N,N-bis(2-chloroethyl)amino)phenylacetate(1) was, on a molar basis, less effective in inducing sister chromatid exchange and suppressing cell proliferation rate indices than compound 3beta-hydroxy-12alpha-aza-C-homo-5alpha,22alpha-spirostan-12-one-p-(N,N-bis(2-chloroethyl)amino)phenylacetate(2). A correlation was observed between the magnitude of the sister chromatid exchange response and the depression of cell proliferation index. We also studied the effects of the aforementioned compounds on Lewis lung carcinoma. The order of the percent inhibition of tumor growth achieved by the compounds coincides with the order of the cytogenetic effects they induce.

Animals↗

Comparative study of sister chromatid exchange induction and antitumor effects by homo-aza-steroidal esters of [p-[bis(2-chloroethyl)amino]phenyl]butyric acid.

The present work was undertaken in order to test the hypothesis that the Sister Chromatid Exchange (SCE) assay in vitro can be used for the prediction of in vivo tumor response to newly synthesized potential chemotherapeutics. The effect of three homo-aza-steroidal esters containing the -CONH- in the steroidal nucleus, 1, 2, and 3 on SCE rates and on cell kinetics in cultured human lymphocytes was studied. The antitumor activity of these compounds was tested on leukemia P388- and leukemia L1210-bearing mice. The three substances induced statistically significant enhancement of SCEs and of cell division delays. Compounds 1 and 3 were identified, on a molar basis, as more effective inducers of SCEs and of cell division delays compared with compound 2. Compounds 1 and 3 had upon both experimental tumors better therapeutic effects compared with compound 2 at equitoxic doses. Therefore, the order of the antitumor effectiveness of the three compounds coincided with the order of the cytogenetic effects they induced.

Animals↗

Ranitidine versus ranitidine plus octreotide in the treatment of acute non-variceal upper gastrointestinal bleeding: a prospective randomised study.

AIM: To compare the efficacy of ranitidine with that of ranitidine plus octreotide in the treatment of non-variceal upper gastrointestinal (UGI) bleeding. DESIGN: Prospective, randomised, open study. PATIENTS AND METHODS: Upper GI endoscopy was carried out during the first 24 hours in all patients with UGI bleeding who had been admitted within a period of 18 months. Patients with variceal bleeding, and those who had undergone any type of gastric operation, were excluded. Eighty-four patients (58 men and 26 women) aged 21-92 years (mean age: 61.2 +/- 15.0 SD) were included. Patients were randomised to receive ranitidine 50 mg tid intravenously alone (Group A: 44 patients, 29 men), or in combination with octreotide 100 micrograms tid subcutaneously, the second drug given for three days only (Group B: 40 patients, 29 men). The study end-points were discharge without operation, emergency surgical intervention or death. The number of blood units given and the days of hospitalization were also recorded. RESULTS: Aspirin and non-aspirin NSAID use before bleeding was reported by 16/44 (36%) patients in Group A and by 19/40 (47.5%) patients in Group B (p = 0.38, OR = 0.63, 95% CI = 0.26-1.51). The endoscopically detected pathology and bleeding stigmata did not differ between the groups (p = 0.86, p = 0.64, OR = 0.78, 95% CI = 0.3-1.99, respectively). Mean use of blood units (p = 0.16) and days of hospitalization (p = 0.25) did not differ. Three patients in Group A (6.8%) and three in Group B (7.5%) required surgical intervention (p = 1.0, OR = 1.1, 95% CI = 0.21-5.84). CONCLUSION: Ranitidine plus subcutaneous octreotide is not superior to ranitidine alone in the management of patients with acute non-variceal UGI bleeding.

Adult↗

Changes in public attitudes towards mental illness in the Athens area (1979/1980-1994).

Opinions about mental illness were measured, in 1994, in a probability sample consisting of 360 residents of two boroughs in greater Athens. These boroughs represent the catchment area of a community mental health centre. The aim of this study was to compare the differences in attitudes towards mental illness with a matched sample of 360 respondents drawn from the sample of the 1979/1980 attitudinal study, conducted in the same area. The instrument used was the Opinion about Mental Illness scale, which yields five factors. In all five factors statistically significant differences between the two samples were observed. The recent study sample expressed more positive attitudes towards the social integration of the mentally ill, and did not favour the social discrimination against and restriction of mental patients. These results could be explained in the context of a positive and tolerant social climate in the Athens area, strengthened by the implementation of local community mental health intervention programmes.

Adult↗