Chemical and isotopic characterization of the thermal fluids emerging along the North-Northeastern Greece.

Hydrochemical and isotopic characteristics of fluids from major geothermal fields of middle/low temperature in N/NE Greece are examined [basins: Strymon River (SR), Nestos River Delta (ND), Xanthi-Komotini (XK), Loutros-Feres-Soufli (LFS) and Rhodope Massif]. The geodynamic context is reflected to isotopic/chemical composition of fluids, heat flow values and elevated CO2 concentrations in emitted fluids. B and Li are derived from leaching of the geothermal systems hosting rocks. δ18OH2O, δ18OSO4, δ13CCO2 values and chemical compositions of Cl, B and Li of geothermal discharges suggest two distinct source fluids. Fluids in SR exhibit high B/Cl and Li/Cl ratios, suggesting these constituents are derived from associated magmas of intermediate composition (andesitic rocks). Geothermal discharges in LFS exhibit low B/Cl and Li/Cl ratios, implying acid (rhyolitic) magmatism. δ13CCO2 and CO2/(CO2 + 105He) ratios in the west part, suggest fluids affected by addition of volatiles released from subducted marine sediments. For the eastern systems, these ratios suggest gas encountered in systems issued from mixing of crustal and mantle-derived volatiles. Isotopic geothermometers reflect, for the same direction, equilibrium processes more (LFS, XK) or less (SR) pronounced and discriminate the geothermal field from low to middle [SR, ND (Erasmio)] and middle to high enthalpy [ND (Eratino), LFS, XK].

Comparison of estimated creatinine clearance among five formulae (Cockroft-Gault, Jelliffe, Sanaka, simplified 4-variable MDRD and DAF) and the 24hours-urine-collection creatinine clearance.

BACKGROUND: GFR estimation is of major importance in everyday clinical practice. Usually it is done using one of the many eGFR equations available. In this study we compared in our population four widespread eGFR equations and our own empirical eGFR, with creatinine clearance calculated through a timed urine collection. PATIENTS AND METHODS: We collected laboratory data of 907 patients from our clinic and outpatient department through a ten-year period and statistically compared the eGFR results between them and with the timed urine collection creatinine clearances. RESULTS: All eGFR equations gave acceptable approximations to the timed urine collection creatinine clearances. However, in different subpopulations some equations did better than others, without any clear advantage of any equation overall. Surprisingly, our empirical equation named DAF also gave acceptable approximations regardless of age, weight and sex of the patient. CONCLUSIONS: In our population our empirical eGFR method (DAF) gave satisfactory results regarding the monitoring of renal function, compared with four other eGFR methods. We suggest that it could provide a very fast and easy to use means of eGFR calculation.

Oral administration of cyclosporin A in patients with severe alopecia areata.

Alopecia areata is a chronic, nonscarring hair loss condition with an unpredictable course that may cause emotional stress in affected patients. Regarding its pathogenesis, the most accepted theory is that alopecia areata is a T-cell-mediated autoimmune condition that is most likely to occur in genetically predisposed individuals. Cyclosporin A is an immunosuppressive agent that has provided new approaches in the treatment of autoimmune diseases. Hypertrichosis, one of the common side effects of orally administered cyclosporin A, encouraged a number of investigators to use the drug in the treatment of alopecia areata, but the reports on this subject have been controversial. We present a small series of patients with severe alopecia areata treated systemically with cyclosporin A at a dose of 3-5 mg/kg for 6 months as well as their 3-month follow-up after cessation of the drug.

Successful treatment of genital and facial psoriasis with tacrolimus ointment 0.1%.

Tacrolimus is an immunomodulatory agent that inhibits the activation and maturation of T-cells and blocks transcriptional activation of several cytokine genes. It also interferes with the function of Langerhans cells, basophil cells and mast cells. Recent studies have demonstrated the efficacy of topical tacrolimus in inflammatory skin disorders. Our objective was to assess the efficacy of topical treatment with tacrolimus ointment 0.1% in patients with psoriasis on the anogenital region and the face. Included in the study were 10 patients with a long-standing history of genital and facial psoriasis, partially controlled with periodic use of topical corticosteroids. Tacrolimus ointment 0.1% was applied twice daily for 10 days. The patients were followed-up every 3 weeks for a total period of 12 weeks. The severity of psoriasis was evaluated in all patients at baseline (day 0) and at the end of weeks 3, 6, 9 and 12. Clinical severity of erythema, scaling, infiltration and lesional extent were graded using a 0-3 scale indicating none, mild, moderate and severe expression, at baseline and at follow-ups. An overall severity score of 0 (clear), 1-4 (mild), 5-8 (moderate) or 9-12 (severe) was then assigned to each patient by adding the scores for the above parameters. On each visit, every patient was evaluated clinically. The decision to reapply the drug was determined by the clinical response of each patient at each visit. At the end of the study, patients also assessed efficacy, safety and tolerance after topical application of tacrolimus ointment using a 0-5 scale for each parameter: A marked improvement was noticed in all patients at the end of the first week without drug-related adverse effects. There were 15 recurrences during the 12-week period in all patients. In conclusion, tacrolimus ointment 0.1% seems to represent a safe new option for the treatment of genital and facial psoriasis. Further studies are probably needed to specify the therapeutic dosage and maintenance therapy

Pustular impetigo with good response to clarithromycin.

Impetigo is a contagious superficial pyogenic infection of the skin caused by Staphylococcus aureus and/or by group A Streptococcus. Two main clinical forms are recognized: bullous impetigo and non-bullous impetigo. We present an unusual case of pustular impetigo in a 35-year-old man. The pustules were localized symmetrically in the groin and the patient was successfully treated with clarithromycin. In bullous impetigo, exfoliative toxins produced by Staphylococcus aureus are accepted as the basis for the bulla formation just below the stratum granulosum. Although clarithromycin is considered to be a second-choice therapy for bullous impetigo, it was highly effective in our case.

Preclinical evaluation of the homo-aza-steroid ester 13beta-hydroxy-13alpha-amino-13,17- seco-5alpha-androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl)aminophenoxy acetate for the treatment of malignant melanoma.

PURPOSE: To investigate the in vitro and in vivo activity of an homo-aza-steroid alkylating ester, namely 13beta-hydroxy- 13alpha-amino-13,17-seco-5alpha-androstan-17-oic-13,17- lactam-p-bis (2-chloro ethyl) aminophenoxy acetate (HASE), in comparison with dacarbazine (DTIC) in the treatment of malignant melanoma. MATERIALS AND METHODS: Cytotoxicity was assessed in vitro by the MTT assay using a panel of 6 malignant melanoma human cell lines, with or without the presence of rat liver microsome assay. B16 melanoma-bearing mice were used to evaluate in vivo the antitumor activity of the tested compounds. RESULTS: In all cases of in vitro screening, HASE displayed significantly higher (p <0.0001) cytostatic and cytotoxic activity than DTIC. Moreover, the antitumor activity of HASE in B16 melanoma-bearing mice was satisfactory, prolonging the mice lifespan at 67%, compared to 43% achieved by DTIC. Furthermore, HASE significantly inhibited the tumor growth (tumor growth rate: <42%) as this was defined by tumor volume and weight differences, presenting higher antitumor effect than DTIC. CONCLUSION: HASE displayed superior in vitro and in vivo activity than DTIC in the treatment of melanoma. Thus, HASE may be considered as a significant candidate anticancer agent for further development.

An epidemiological study of syphilis incognito, an emerging public health problem in Greece.

BACKGROUND: Syphilis incognito is a subtype of latent syphilis (early or late) characterized by no signs or symptoms of primary or secondary syphilis and diagnosed by positive serologic results for syphilis during routine screening. OBJECTIVE: To study the epidemiological characteristics, causes, and implications of syphilis incognito in Greece. PATIENTS AND METHODS: All new adult patients diagnosed as having syphilis in Andreas Sygros Hospital for Skin and Venereal Diseases, Athens, Greece, from 1989 through 1996 were studied prospectively and retrospectively (history, physical examination, serologic tests, cerebrospinal fluid examination, and imaging) to determine the stage of their disease. The epidemiological, clinical, and serologic characteristics of patients with syphilis incognito were recorded and analyzed. RESULTS: During the 8-year period, 711 new syphilis cases were detected; of these, 480 cases (67.5%) fulfilled the definition criteria of syphilis incognito. The male-female ratio was 1.8:1. Patients with syphilis incognito were most commonly heterosexual, had a median socioeconomic status, and were aged 20 to 39 years, and their conditions were diagnosed during routine screening for syphilis (prenatal care, hospital admission, or blood donation). However, the number of syphilis incognito cases appeared to decline during the period studied. CONCLUSIONS: The incidence of syphilis in Greece has decreased dramatically, following the trends in western Europe. The most common form of syphilis is syphilis incognito, affecting adults who are older and have a higher socioeconomic status than those in the past. Improved hygiene and wide use of antibiotics that minimize or abolish symptoms of early disease may have contributed to the frequency of syphilis incognito in recent years. Screening of asymptomatic persons, especially those at high risk, should continue and be reenforced to prevent the devastating consequences of unrecognized and untreated syphilis.

Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists.

A series of purin-8-ones was prepared and discovered to have excellent binding affinity to the CRH-R1 receptor. Structure-activity studies focused on amine side-chain optimization, urea substitution and pyridyl isostere incorporation. Thus, the highly potent purin-8-ones show promise as a new class of potential anxiolytics and/or antidepressants.

Non-peptide corticotropin-releasing hormone antagonists: syntheses and structure-activity relationships of 2-anilinopyrimidines and -triazines.

Screening of our chemical library using a rat corticotropin-releasing hormone (CRH) receptor assay led to the discovery that 2-anilinopyrimidine 15-1 weakly displaced [125I]-0-Tyr-oCRH from rat frontal cortex homogenates when compared to the known peptide antagonist alpha-helical CRH(9-41) (Ki = 5700 nM vs 1 nM). Furthermore, 15-1 weakly inhibited CRH-stimulated adenylate cyclase activity in the same tissue, but it was less potent than alpha-helical CRH(9-41) (IC50 = 20 000 nM vs 250 nM). Systematic structure-activity relationship studies, using the cloned human CRH1 receptor assay, defined the pharmacophore for optimal binding to hCRH1 receptors. Several high-affinity 2-anilinopyrimidines and -triazines were discovered, some of which had superior pharmacokinetic profiles in the rat. This paper describes the structure-activity studies which improved hCRH1 receptor binding affinity and pharmacokinetic parameters in the rat. Compound 28-17 (mean hCRH1 Ki = 32 nM) had a significantly improved pharmacokinetic profile in the rat (19% oral bioavailability at 30 mg/kg) as well as in the dog (20% oral bioavailability at 5 mg/kg) relative to the early lead structures.

Corticotropin-releasing hormone receptor antagonists: framework design and synthesis guided by ligand conformational studies.

As described in the preceding paper (Arvanitis et al. J. Med. Chem. 1999, 42), anilinopyrimidines I were identified as potent antagonists of corticotropin-releasing hormone-1 receptor (CRH1-R, also referred to as corticotropin-releasing factor, CRF1-R). Our next goal was to understand the receptor-bound conformation of the antagonists and to use this information to help guide preclinical optimization of the series and to develop new leads. Since receptor structural information was not available, we assumed that these small, high-affinity antagonists would tend to bind in conformations at or energetically close to their global minima and that rigid analogues that maintained the important stereoelectronic features of the bound anilinopyrimidine would also bind tightly. Conformational preferences and barriers to rotation of the anilinopyrimidines were determined by semiempirical methods, and X-ray and variable-temperature NMR spectroscopy provided experimental results that correlated well with calculated structures. Using these data, a key dihedral angle was constrained to design fused-ring analogues, substituted N-arylpyrrolopyridines II, synthesis of which provided CRH1 receptor antagonists with potency equal to that of the initial congeneric leads (Ki = 1 nM) and which closely matched the conformation held by the original compound, as determined by crystallography. In addition to providing a useful template for further analogue synthesis, the study unequivocally determined the active conformation of the anilinopyrimidines. Theoretical and spectroscopic studies, synthesis, and receptor binding data are presented.

Synthesis, corticotropin-releasing factor receptor binding affinity, and pharmacokinetic properties of triazolo-, imidazo-, and pyrrolopyrimidines and -pyridines.

The synthesis and CRF receptor binding affinities of several new series of N-aryltriazolo- and -imidazopyrimidines and -pyridines are described. These cyclized systems were prepared from appropriately substituted diaminopyrimidines or -pyridines by nitrous acid, orthoester, or acyl halide treatment. Variations of amino (ether) pendants and aromatic substituents have defined the structure-activity relationships of these series and resulted in the identification of a variety of high-affinity agents (Ki's < 10 nM). On the basis of this property and lipophilicity differences, six of these compounds (4d,i,n,x, 8k, 9a) were initially chosen for rat pharmacokinetic (PK) studies. Good oral bioavailability, high plasma levels, and duration of four of these compounds (4d,i,n,x) prompted further PK studies in the dog following both iv and oral routes of administration. Results from this work indicated 4i,x had properties we believe necessary for a potential therapeutic agent, and 4i1 has been selected for further pharmacological studies that will be reported in due course.

Change in the epidemiology of Reiter's syndrome (reactive arthritis) in the post-AIDS era? An analysis of cases appearing in the Greek Army.

OBJECTIVE: During the last 5 years we observed a significant decrease in the incidence of newly established cases of Reiter's syndrome (reactive arthritis) in Greek Army personnel. Our study was initiated to validate this observation and to evaluate a possible change in the prevalence of Reiter's syndrome (RS) associated infections. METHODS: The case records of patients with reactive arthritis (ReA) admitted during the periods 1980-83 and 1989-92 at a large Army Hospital were studied retrospectively and the cases of RS were reviewed. In addition, the prevalence of cases with urethritis and dysentery that presented to the hospital in the same periods was studied in retrospect, as these infections are known to participate in the etiopathogenesis of RS. RESULTS: A significant decrease in the overall incidence of the randomly presented RS cases during the second 4 year period was detected (27 versus 4 cases, p < 0.0001, chi 2 test). A similar significant decrease in the number of cases with gonococcal and nongonococcal urethritis was observed while the prevalence of dysentery was not significantly altered during the defined intervals. CONCLUSION: We suggest that the anti-AIDS campaign which began after the years 1984-85 is the principal cause of the observed change of epidemiology of RS cases appearing in the Greek Army.