Aromatase inhibitors: a useful additional therapeutic option for slowing down advanced bone age in boys with growth hormone deficiency.

INTRODUCTION: Aromatase inhibitors (AIs) have been used to slow down estrogen-dependent skeletal maturation in pubertal boys with short stature. In the literature, few data evaluate the effectiveness and safety of AIs in boys with growth hormone deficiency (GHD). This study aimed to evaluate the auxologic effects and short-term laboratory profiles of combined AI and rhGH therapy for 1 year in adolescent males with GHD. SUBJECTS AND METHODS: Male subjects between the ages of 10 and 16 with GHD from two different centers were included in the study. Patients were divided into two groups: (i) those who only used recombinant human growth hormone (rhGH) therapy (Group I; G-I) and (ii) those who also used AI therapy (anastrozole or letrozole) along with rhGH (Group II; G-II). RESULTS: Forty-one patients (G-I, 46%; G-II, 54%) were included in the study. All the subjects had isolated GHD. At the beginning of the treatment, the chronological ages (CAs) of the patients in the G-I and G-II groups were 11.8 (10.9-13.7) and 12.8 (12.0-14.3) years, respectively. The ratios of bone age (BA)/CA for the two groups were 0.8 (0.8-0.9) and 1.0 (0.9-1.1), respectively (p < 0.001). After the treatment, the height standard deviation (SD) scores and predicted adult height (PAH) significantly increased from baseline in all subjects in the G-I and G-II groups (p < 0.001; p < 0.001, respectively). There was no significant change in the ratio of BA/CA post-therapy in the G-I group (p = 0.1), while there was a significant decrease in the G-II group (p < 0.001). The growth velocities of the patients in the G-I and G-II groups were 9.1 (7.4-10.1) cm/year [1.5 (0.8-5.0) SD score] and 8.7 (7.5-9.9) cm/year [1.1 (0.3-3.1) SD score], respectively (p = 0.6). While post-therapy serum testosterone concentrations were seen to increase in the G-II group, none of the patients exhibited hematocrit above 50 percent, and the fasting glucose concentrations were normal. CONCLUSIONS: When used in addition to rhGH therapy in boys with GHD and advanced BA, AIs were observed to slow down the tempo of BA maturation after 1 year, compared to those who received rhGH treatment alone. AI therapy was found to be safe during the 1-year observation period and thus could be considered for preserving growth potential in these patients.

Studies on condensed 1,4-dihydropyridine derivatives and their calcium modulatory activities.

Hexahydroquinoline and furoquinoline derivatives were synthesized and their calcium modulatory activity was investigated on isolated rat ileum and lamb carotid artery. In addition, the in vitro hepatic microsomal biotransformation of one hexahydroquinoline derivative was studied in rat microsomes.

Synthesis and calcium antagonistic activity of 2,6,6-trimethyl-3-carbomethoxy(ethoxy)-4-aryl-1,4,5,6,7,8-hexahydroquinoline derivatives.

Twelve new 2,6,6-trimethyl-3-carbomethoxy(ethoxy)-4-aryl-1,4.5,6.7,8-hexahydroquinoline derivatives have been prepared. Their structures were confirmed by IR, 1H NMR, mass and elemental analysis. The calcium antagonistic activity of these compounds was tested in rat aortic rings precontracted with 30 mM K+. The compounds IVa, IVc, IVe, IVf, IVh-l induced concentration dependent relaxation response in precontracted aortic rings. The concentrations that cause 50% relaxation of K+-contraction were also calculated for the compounds IVe, IVf, IVj. According to pharmacological results, compound IVl exert the most activity and compound IVc has been found to be least active in this series. The methyl ester derivatives carrying mono halogensubstitutent in the phenyl ring, the activity order is F > Br > Cl. Replacement of the substituted phenyl ring with the pyridine ring increases the activity.

Synthesis and antimicrobial activity of some 2-(2-oxobenzothiazole-3-yl)-1-arylethanone derivatives.

The synthesis of new 2-(2-oxobenzothiazole-3-yl)-1-arylethanone derivatives is reported. The structure of these products is supported by their UV, IR and 1H-NMR spectra, as well as by elemental analysis. The new compounds were tested for antimicrobial activity.

Analgesic and antiinflammatory effects of some 2-mercaptobenzoxazole derivatives.

Analgesic and antiinflammatory effects of benzoxazole derivatives have been investigated in mice. In the acetic acid induced writhing test, the analgesic effect of two compounds were found to be stronger than that of diclofenac sodium. In the formaldehyde induced paw swelling edema test, two compounds were found to be more active than diclofenac sodium, another two were as potent as the control drug.

One pot synthesis of some new substituted hexahydro 2H-1,3-benzoxazine derivatives.

In this paper, we synthesized nineteen new compounds having 2,4-diaryl-5-oxohexahydro-2H-1,3-benzoxazine structure by the reaction of 1,3-cyclohexanedione, aromatic aldehyde and ammonium acetate. In addition, we evaluated calcium antagonistic activity of these compounds versus nicardipine.

2-methyl-3-acetyl-4-aryl-5-oxo-1,4-dihydro-5H indeno(1,2-b) pyridine derivatives studies and their calcium antagonistic activities.

Sixteen 2-methyl-3-acetyl-4-aryl-5-oxo-1,4-dihydro-5H-indeno(1,2-b)pyridine derivatives (3a-p) have been prepared. The structures of the compounds were characterised by IR, 1H-NMR, 13C-NMR, X-Ray and elemental analyses. The calcium antagonistic activity of these compounds were studied in rat taenia coli pre-contracted with 1 mmol/l Ca+2.

Microwave-assisted synthesis and spasmolytic activity of 4-indolylhexahydroquinoline derivatives.

In the present study a microwave-assisted one-pot method was applied for the synthesis of 18 novel condensed 1,4-dihydropyridines carrying the indole moiety. The compounds were achieved by the reaction of appropriate 1,3-cyclohexanedione, substituted indole carboxaldehyde derivative, alkyl acetoacetate and ammonium acetate in methanol, according to a modified Hantzsch reaction. The structure elucidation of the compounds was carried out by spectral methods including X-ray studies. Their spasmolytic activities through calcium channel blockade were assayed on isolated rat ileum. The obtained results indicated that the introduction of the brom atom on the indole ring altered the mentioned activity positively.

Synthesis of cyclopentapyridine and thienopyridine derivatives as potential calcium channel modulators.

In this study, novel condensed 1,4-dihydropyridines bearing cyclopentanone (1-21) or tetrahydrothiophene-1,1-dioxide ring (22-42) with various ester substituents were synthesized via a modified Hantzsch reaction and their calcium channel modulator activities were investigated on isolated rat ileum and rat thoracic aorta. The introduction of a cyclopentanone ring fused to the 1,4-dihydropyridine nucleus and methyl, ethyl and allyl moieties to the ester group led to more active calcium modulators.

Studies on calcium antagonist activities of 2-ethyl-3-carbmethoxy-4-aryl- 5-oxo-6,6-dimethyl-1,4,5,6,7,8-hexahydroquinoline derivatives.

In this study, 23 new compounds having 2-ethyl-3-carbmethoxy-4-aryl-5-oxo-6,6-dimethyl-1,4,5,6,7, 8-hexahydroquinoline structure have been synthesised and screened for their calcium antagonistic activities. The structure of the compounds were characterised by IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analyses. The calcium antagonistic activities of the compounds were determined by the tests performed on isolated rat ileum and lamb carotid artery. Although none of the synthesized compounds were as active as nicardipine in isolated rat ileum, the compounds 9, 10 and 19 have shown high activity. In screening studies on lamb carotid artery, compounds 10, 14 and 19 have been found active at a concentration of 10(-4) mol/l.

Relaxant effects of some benzothiazolinone derivatives on isolated rabbit corpus cavernosum.

In the present study, two 6-(fluorobenzoyl)-3-piperazinomethyl-2-benzothiazolinone derivatives were synthesized and their relaxant effects on isolated rabbit corpus cavernosum investigated. Compounds Y-16 and Y-21 can alter the ability of corpus cavernosum smooth muscle to contract. Strips of rabbit corpus cavernosum smooth muscle were mounted in isolated tissue baths for measurement of isometric contractile force. Compounds (10(-6) - 10(-3) M) did not cause contraction but induced relaxation in precontracted corpus cavernosum smooth muscle. Neither N-nitro-L-arginine methylester (L-NAME) nor indomethacin affected the relaxant effect of these compounds. Glibenclamide and tetraethylammonium chloride (TEA) also did not influence the relaxation induced by the compounds. In conclusion, in isolated rabbit corpus cavenosum, Y16 and Y21 have a relaxant potency equal or superior to known vasoactive agents. Further investigations are needed to show the importance of these effects for the diagnosis and treatment of erectile dysfunction.