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Biomedical subjects

H Ali

Publications and source records attributed to H Ali.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effect of 11 beta-substituents on the regioselective chlorination of estrogens with 2,3,4,5,6,6-hexachloro-2,4-cyclohexadienone.

The reaction of 11 beta-substituted estrogens with 2,3,4,5,6,6-hexachloro-2,4-cyclohexadienone affords exclusively ortho-substituted monochlorinated products including a major 4-chloro and a minor 2-chloro derivative. In the absence of an 11 beta-substituent, regioselectivity is lost, resulting in a mixture of 10 beta- and ortho-chlorinated products.

Chromatography, High Pressure Liquid↗
PubMed1994

Synthesis of (17 alpha,20E/Z)iodovinyl testosterone and 19-nortestosterone derivatives as potential radioligands for androgen and progesterone receptors.

To develop androgen and progesterone receptor-based radioligands for SPECT imaging we synthesized several radioiodinated 17 alpha-iodovinyl testosterone and 19-nortestosterone analogs and evaluated their biological properties. The synthesis of these compounds proceeds via the (17 alpha,20E/Z)stannyl intermediates and involves addition of tri-n-butyltin hydride to the 17 alpha-ethynyl group of the steroid using either azobisiso butyronitrile or triethylborane as a catalyst. The stannyl derivatives are stereospecifically converted to the corresponding (17 alpha,20E/Z)iodovinyl derivatives using molecular iodine, or to the [125I]iodovinyl analogs using [125I]NaI and H2O2. Androgen and progesterone receptor (AR and PgR) binding affinities were measured via a competitive in vitro binding assay. In general 19-nortestosterone derivatives showed higher receptor affinities as compared to the testosterone derivatives. In the latter series the highest PgR binding affinities were observed with the (17 alpha,20Z)iodovinyl-19-nortestosterone (IVNT) (92 vs 100 for R5020) followed by the 7 alpha-methyl analog, whereas the highest AR binding affinity was observed with the 7 alpha-Me-(17 alpha,20Z)IVNT (54 vs 100 for 5 alpha-dihydrotestosterone). These derivatives were also labeled with 125I and evaluated for their in vivo target organ uptake (prostate and estrogen-primed uterus). The highest PgR-mediated target tissue uptake was observed with the (17 alpha,20Z)-[125I]IVNT and its 7 alpha-methyl derivatives whereas only one derivative, the 7 alpha-Me-(17 alpha,20Z)-[125I]IVNT, showed AR-mediated dorsal prostate retention. Although some of the IVNT derivatives have interesting binding properties, the lack of in vivo selectivity does suggest that the 123I-labeled analogs are unlikely to be suitable for imaging of AR and PgR-rich tissues.

Animals↗
PubMed1994

Elimination of antipyrine and its metabolites in interferon treated hepatitis C.

1. To study the effect of interferon on hepatic drug metabolism in chronic hepatitis C, we examined nine patients before and at the end of 6 months of interferon treatment. 2. Routine liver function was determined together with the salivary clearance of antipyrine and the 48 h urinary excretion of the main metabolites of antipyrine: 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine before and after 6 months of interferon treatment. 3. Liver pathology, routine liver function, and antipyrine metabolism remained unchanged after patients were treated for 6 months with interferon for a histologically advanced but clinically compensated chronic hepatitis C.

Administration, Oral↗
PubMed1993

2- and 4-fluorinated 16 alpha(-)[125I]iodoestradiol derivatives: synthesis and effect on estrogen receptor binding and receptor-mediated target tissue uptake.

The effect of 2- and 4-fluoro substitution on the estrogen receptor-mediated tissue localization of radioiodinated 16 alpha-iodoestradiol (16 alpha-IE2) and its 11 beta-methoxy analogue (11 beta-OMe-16 alpha-IE2) was evaluated. Electrophilic substitution of estrone or 11 beta-methoxyestrone with N-fluoropyridinium salt gave the 2- and 4-fluoro derivatives which were subsequently converted to the 3,17 beta-enol diacetate and brominated to yield exclusively the 16 alpha-bromo analogues. Epimerization gave the corresponding 16 beta-bromoestrones which were reduced to the 17 beta-hydroxy derivatives. Halogen exchange with NaI or Na[125I]I provided the A-ring fluorinated 16 alpha-iodoestradiols. The 4-F analogue exhibited higher affinity for estrogen receptors than the corresponding 2-F analogue, and these differences were more pronounced at higher incubation temperatures. Biodistribution studies in immature female rats showed that 4-fluoro substitution had only a moderate effect on receptor-mediated tissue uptake of the parent molecules whereas 2-fluoro substitution resulted in strongly diminished tissue specificity. The lower target selectivity of the 2-F, compared to the 4-F, analogue correlates to some extent with their different receptor binding properties; however, the rate of catabolism may also be involved. Differences in blood clearance further accentuated the localization properties to yield particularly high uterus to blood ratios in the case of the 4-F-11 beta-OMe-16 alpha-IE2, suggesting the potential of the analog labeled with 123I as a radiopharmaceutical for receptor imaging in nuclear medicine. The isopotential maps of the fluorinated steroids, obtained via semiempirical computer modeling on the molecular structures, show striking differences between the 4-F and 2-F derivatives reflecting their varying biological properties.

Animals↗
PubMed1993

Differences in phosphorylation of formylpeptide and C5a chemoattractant receptors correlate with differences in desensitization.

To define the regulation of chemoattractant receptors, epitope-tagged human formyl peptide and C5a receptor cDNAs (ET-FR and ET-C5aR) were stably expressed in rat basophilic leukemia, RBL-2H3 cells. An antibody (12CA5) specific to "ET" was used to immunoprecipitate ET-FR and ET-C5aR. fMLP and C5a caused time- and dose-dependent phosphorylation of their respective receptors. Phosphorylated ET-FR migrated as a single broad band between 50 and 70 kDa on SDS-polyacrylamide gel electrophoresis, whereas ET-C5aR exhibited both fast (39-45 kDa) and broadly (39-52 kDa) migrating forms. Fast form phosphorylation alone was observed at low concentrations of C5a (0.001-0.01 microM), or at early times (5-30 s) with a higher concentration of C5a (0.1 microM). Phorbol 12-myristate 13-acetate, thrombin, or antigen caused no phosphorylation of ET-FR but stimulated exclusively fast form phosphorylation of ET-C5aR. The protein kinase C inhibitor staurosporine did not inhibit phosphorylation of ET-FR but blocked the fast migrating component of phosphorylated ET-C5aR. Homologous desensitization correlated with ligand-induced phosphorylation of both receptors. Of note, ET-C5aR but not ET-FR underwent heterologous desensitization by antigen, phorbol 12-myristate 13-acetate, and thrombin. The data suggest that protein kinase C mediates heterologous phosphorylation and desensitization of C5aR but not FR, yet, both receptors are homologously desensitized by a staurosporine-resistant kinase.

Alkaloids↗
PubMed1993

Synthesis of A-ring fluorinated derivatives of (17 alpha,20E/Z)-[125I]iodovinylestradiols: effect on receptor binding and receptor-mediated target tissue uptake.

We have prepared a series of 2- and 4-fluoro derivatives of the isomeric (17 alpha,20E)- and (17 alpha, 20Z)iodovinylestradiols (IVE2) and also the analogs substituted with either a 7 alpha-methyl (7 alpha-Me-IVE2) or 11 beta-methoxy group (11 beta-OMe-IVE2) and evaluated their in vitro and in vivo properties. Electrophilic substitution of the estrone derivatives with N-fluoropyridinium salt gave the 2- and 4-fluoro analogs which were subsequently converted to the 17 alpha-ethynyl derivatives. The tributylstannyl intermediates were obtained from the corresponding 17 alpha-ethynyl analogs using azobisisobutyronitrile or triethylborane as catalyst. All 12 products were also prepared as their no-carrier-added [125I]iodovinyl analogs via destannylation of the tributylstannyl precursors. Binding affinity for the estrogen receptor (ER) was in general higher for the 4-F derivatives as compared to the 2-F derivatives, while the 20Z isomers of the same compounds showed somewhat higher ER binding affinity as compared to the 20E isomers. The combination of an A-ring fluoro and 7 alpha- or 11 beta-substituent decreased ER binding affinity. Substitution of a fluoro atom at C-4 on either the 17 alpha-ethynylestradiol or isomeric 17 alpha-IVE2 enhanced the affinity of the parent molecule for the ER. A-ring fluorination of all other analogues tested had no effect or depressed ER binding affinity. Varying incubation conditions showed substantial differences in ER binding kinetics between the 20E and 20Z isomers. Tissue distribution in immature female rats showed that the highest uterus uptake and uterus to blood/nontarget ratios in the IVE2 series were obtained with the 4-F-(17 alpha,20Z)IVE2 isomer. The combination of A-ring fluoro and 7 alpha- or 11 beta-substitution decreased uterus uptake but had little or no effect on uterus to blood/nontarget ratios. The highest uterus to blood ratios were observed for the 4-F-(17 alpha,20E)11 beta-OMe-IVE2 (75 at 6 h and 125 at 12 h pi) reflecting rapid blood clearance and in vivo stability, as confirmed by the low levels of thyroid radioactivity. The lack of correlation between ER binding affinities and uterus uptake, and/or uptake ratios, suggests that other factors, including nonspecific binding and metabolic processes, also are involved in the tissue localization process. Our data suggest that 4-F substitution onto (17 alpha,20Z)IVE2 and (17 alpha,20E)11 beta-OMe-IVE2 enhances the potential of these compounds to function as SPECT imaging agents of ER-rich tissues.

Animals↗
PubMed1993

Interactions of chloroaluminium-tetramethyl-tetrapyridino-porphyrazine++ + with DNA.

The interaction of chloroaluminium-tetramethyl-tetrapyridinoporphyrazine (ClAlTMPyPa) with DNA was investigated by absorption/emission and circular-dichroic spectroscopy. Formation of a DNA-porphyrazine complex was evidenced by quenching of the ClAlTMPyPa fluorescence, a hypochromic red shift of the absorption band in the visible part of the spectrum and induction of a characteristic CD band with high positive ellipticity. Scatchard analysis of the spectral changes in low ionic strength buffer suggested an association constant of 9.7 +/- 0.6 x 10(7) M-1. Quenching of the fluorescence of a DNA-ethidium complex by added ClAlTMPyPa was shown to result from direct DNA-dye interaction rather than the displacement of ethidium from DNA. Our data suggest that porphyrazine binds to the outside of the DNA helix, involving interactions which are not limited to electrostatic forces only. The computer assisted modelling of ClAlTMPyPa-DNA interactions showed that the energy-minimized intermolecular orientation involves face-on binding of the ligand, preferably on the minor DNA groove.

Circular Dichroism↗
PubMed1993

The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells.

Mast cells release the mediators of the immediate hypersensitivity reaction. Adenosine is known to modulate this process, but the receptor responsible for this is not the classical A1 or A2 adenosine receptors. This study was undertaken to determine whether the unique adenosine receptor (AR) previously postulated in a cultured mast cell line (RBL-2H3 cells) is the recently cloned A3AR. The receptors were quantitated by the agonist 125I-labeled APNEA (aminophenylethyladenosine), an A3AR agonist, which yielded Bmax and Kd values of 826 fmol/mg protein and 34 nM, respectively. A variety of adenosine analogs competed for 125I-APNEA binding sites with the following potency series: (R)-phenylisopropyladenosine = 5'-N-ethylcarboxamide adenosine > (S)-phenylisopropyladenosine. 125I-APNEA binding was relatively insensitive to the xanthine amine congener (XAC, 1 microM), a selective antagonist for the A1AR. Functionally, activation of these A3AR stimulated the production of inositol 1,4,5-triphosphate, leading to an increase in the level of intracellular Ca2+. Furthermore, while activation of these receptors alone produced little secretory response in RBL-2H3 cells, it enhanced antigen-induced secretion by 2-2.5-fold. Northern blotting studies using poly(A+) RNA from RBL-2H3 cells detected two transcripts of 2.0 and 3.5 kilobases, which hybridized to an A3AR cDNA but not to the A1 or A2AR cDNA probes. These data indicate that the unique AR that potentiates the secretory response to antigen in RBL-2H3 cells is exclusively the A3AR.

Amino Acid Sequence↗
PubMed1993

7 alpha-Methyl- and 11 beta-ethoxy-substitution of [125I]-16 alpha-iodoestradiol: effect on estrogen receptor-mediated target tissue uptake.

The 7 alpha-methyl and 11 beta-ethoxy derivatives of 16 alpha-[125I]iodoestradiol were prepared via halogen exchange with 125I of the corresponding 16 beta-bromoestradiol precursors. The 16 alpha-bromo derivatives were obtained via halogenation of the analogous 17-enol acetate, epimerization to the 16 beta-isomer, and hydride reduction. Stereochemical assignments were based on high resolution 1H NMR. To evaluate the effect of the nature and stereochemistry of the 16-halo substituent on the relative binding affinity for the estrogen receptor, the analogous 16-chloro derivatives were also prepared. The highest binding affinities were observed with the 7 alpha-methyl-16 alpha-haloestradiols, particularly the bromo and chloro derivatives while the 16 alpha-iodo derivatives gave somewhat lower values. Both the 11 beta-ethoxy and 7 alpha-methyl-16 alpha-[125I]iodoestradiols localize in the uteri of immature female rats via a receptor-mediated process. Rapid blood clearance of the 125I-labeled 7 alpha-methyl derivative results in lower 125I uptake by the uterus as well as nontarget organs as compared to the 11 beta-substituted estradiol analogs. However, uterus to blood and nontarget ratios are more favorable for the 7 alpha-methyl-16 alpha-[125I]iodoestradiol as compared to the analogous 11 beta-ethoxy derivatives suggesting that this compound substituted with 123I may be useful for the in vivo imaging of estrogen receptor-rich breast tumors by single photon emission computerized tomography.

Animals↗
PubMed1993

Synthesis, receptor binding and biodistribution of the gem-21-chloro-21-iodovinylestradiol derivatives.

Radioiodinated 11 beta-methoxy-(17 alpha,20E)iodovinylestradiol (11 beta-OMe-IVE2) shows high estrogen receptor (ER)-mediated uterus uptake and good potential as an ER-imaging agent. In order to examine the tolerance of the ER for modification about the iodovinyl substituent, we prepared the (17 alpha,20Z-chloro)21-chloro-21-iodovinylestradiol (4a) and several derivatives featuring 11 beta-methoxy (4b), 11 beta-ethoxy (4c) or 7 alpha-methyl (4d) substituents. All gem-dihalogen derivatives 4a-d were prepared from the 17 alpha-chloroethynyl precursors. The intermediate chlorostannylvinyl derivatives were obtained using tri-n-butyltin hydride and palladium acetate catalyst. Compounds 4a and 4b were labeled with 125I via their corresponding tin intermediates and their tissue distribution was studied in immature female rats. Addition of a 21-Cl to the 17 alpha-ethynylestradiols reduced ER binding affinity, except for the 11 beta-substituted analogs which showed a pronounced increase. Surprisingly, addition of a 21-Cl to the (17 alpha,20E)IVE2 resulted in increased ER binding affinities and augmented ER-mediated uterus uptake, which may result from the pronounced increase in the dipole moment of the molecule. Thus, further modifications at the C-21 position of IVE2 are well tolerated by the ER. However, addition of the 21-Cl also resulted in increased radioiodine uptake by the thyroid, much slower blood clearance and lower uterus to blood/nontarget ratios, suggesting increased in vivo instability of the C--I bond of the gem-chlorine-iodine atoms which may reflect the increase in steric and electronic interference.

Animals↗
PubMed1993

Chronic non-A, non-B hepatitis complicated by end-stage renal failure treated with recombinant interferon alpha.

Chronic non-A, non-B hepatitis occurs in 50% of Saudi patients with end-stage renal failure and requires long-term hemodialysis since it is a contraindication to renal transplantation. Thirteen patients with biochemical and histological documented chronic non-A, non-B hepatitis (11 with HCV antibodies) entered a double-blind placebo controlled cross-over study, in which Roferon A 3 MU or placebo were administered subcutaneously 3 times weekly after hemodialysis for 6 months. The mean ALT fell significantly from pretreatment levels of 74.7 (95% confidence interval (CI) 54.7, 92.5) (13 patients in the 6-month run-in period) and 66.8 (CI 47.7, 85.8) (7 patients in the run-in period + 6 patients in the placebo period) (difference NS) to 37.6 (CI 21.0, 54.2) during interferon treatment (P < 0.005). In 10/13 patients (77%) ALT levels became normal. In the 6-month follow-up period immediately after therapy, the mean ALT was 45.2 (CI 28.0, 62.0). Although this change was not significant (P = 0.49), only 7 of these 10 patients sustained biochemical remission in the 6-month follow-up period. The corresponding total Histological Activity Index improved from 8.9 (CI 7.5, 10.3), 8.9 (CI 7.2, 10.7) (difference NS) to 6.2 (CI 3.9, 8.5) (P < 0.05; P = 0.052, respectively). Intralobular inflammation and periportal inflammation showed the most significant changes. Five of 13 (39%) and 2/13 patients (15%) had complete resolution of piecemeal necrosis and intralobular inflammation, respectively. Toxic effects of interferon were mild, early and self-limiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Acute renal failure due to rhabdomyolysis associated with the extreme lithotomy position.

A patient who developed acute renal failure secondary to rhabdomyolysis associated with the use of the extreme lithotomy position for 6 hours during radical perineal prostatectomy is described. It appears that muscle ischemia due to compression of the lumbar and pelvic muscles resulted in muscle injury. Intense muscle uptake of technetium 99m methylene diphosphonate assisted in localizing the muscles involved and ascertaining the extent of the injury. Review of the literature disclosed seven other patients with a similar association. All patients complained of muscle pain shortly after recovery from anesthesia. Early recognition and aggressive treatment with intravenous fluids may prevent the development of acute renal failure.

Acute Kidney Injury↗
PubMed1993

Phthalocyanine-induced photohemolysis: structure-activity relationship and the effect of fluoride.

Phthalocyanine (Pc) containing A1, Ga or Zn as central metal ligand and substituted with a varying number of sulfonic acid residues as well as additional benzene rings were synthesized and their photodynamic activity was assayed using photohemolysis of human erythrocytes as an endpoint. The Pc derivatives varied > 300-fold in their photodynamic activity. Activity correlated with binding of the dye to the cell, with the exception of some of the amphiphilic dyes where cell uptake was an order of magnitude higher than expected from the observed activity. Fluoride was shown to inhibit A1PcSn-induced photohemolysis. This effect occurred also with other A1Pc and GaPc derivatives, but the concentration of F- required to slow photohemolysis by a factor of two (Ki) varied between 4 microM and 10 mM. Fluorescence spectral studies indicated complex formation between F- and the dye, which was stronger for A1Pc than GaPc derivatives. Ultrastructural studies using scanning electron microscopy showed that the photosensitized cells were converted to spherocytes and that F- prevented this to a large extent.

Erythrocytes↗
PubMed1992

Synthesis, receptor binding and target-tissue uptake of carbon-11-labeled carbamate derivatives of estradiol and hexestrol.

Carbon-11-labeled estradiol and hexestrol derivatives were prepared via the reaction of [11C]ethylchloroformate with the 2- and 4-amino derivatives of estradiol, the 3'-amino derivatives of hexestrol, and the 1-aminophenoxy derivatives of hexestrol and 1-norhexestrol. The corresponding nonradioactive carbamates were prepared for chemical characterization and in vitro receptor binding assays. The positions of the substituents on the parent molecules were selected with a view to minimize interference with the receptor binding process. In spite of this, affinity for the estrogen receptor was strongly impaired for all carbamate derivatives. Likewise, in vivo, the [11C]carbamate analogs failed to localize in receptor rich tissue via an estrogen receptor mediated process.

Amines↗
PubMed1992

Concurrent post-streptococcal carditis and glomerulonephritis: serial echocardiographic diagnosis and follow-up.

The two non-suppurative post-streptococcal events, acute rheumatic fever and acute glomerulonephritis, rarely occur simultaneously. We describe such a patient, a 16-year-old male who was admitted with fever, agitation and confusion. Blood work-up showed high antistreptolysin O titre, raised serum creatinine and low complement levels. Urinalysis showed RBC casts. Echocardiographic examination demonstrated markedly impaired left ventricular systolic and diastolic function and three large thrombi in the apex. Serial echocardiographic examinations revealed improvement of cardiac function and the resolution of the thrombi and both cardiac and renal function returned to normal after 3 weeks of treatment.

Acute Disease↗
PubMed1992

Photosensitizing activity of water- and lipid-soluble phthalocyanines on prokaryotic and eukaryotic microbial cells.

The photosensitizing activity of lipophilic zinc-phthalocyanine (Zn-Pc) and its water-soluble sulphonated derivative (Zn-PcS) towards Streptococcus faecium and Candida albicans was studied and correlated with the amount of cell-bound photosensitizer. With both micro-organisms Zn-PcS was more tightly bound in larger amounts than Zn-Pc in the protoplasts of the cytoplasmic membrane. As a consequence, the photoinduced damage in S. faecium initially involved membrane proteins, while DNA was modified only upon prolonged irradiation. For C. albicans only Zn-PcS showed a preferential affinity for the spheroplasts and the decrease in cell survival was not accompanied by detectable modifications of the electrophoretic pattern of membrane proteins. The photoinduced ultrastructural alteration of both micro-organisms suggests damage at membrane level. This would indicate the involvement of different targets in bacteria and yeast for phthalocyanine photosensitization.

Candida albicans↗
PubMed1992

[Multicomponent reconstructive operations on the mitral valve].

Between 1978 and 1990, 134 reconstructive operations were conducted on the mitral valve in its predominant incompetence. 50% of patients were related to functional class IV (NYHA), 76.1% had atrial fibrillation. In 44 (32.8%) patients interventions were conducted at the same time on other valves. The valvular disease was caused by rheumatism in 78.3%, congenital pathology in 10.4%, and impaired connective-tissue structure in 10.4% of cases. Hospital mortality was 5.9% (8 patients). Mortality in the group of patients with isolated annulovalvuloplasty was 4.4%. The immediate results were good in 93.3% of patients. The late results were studied in 120 patients during a maximum follow-up period of 12 years. The actuarial survival value by the 12th follow-up year was 83.5%. By that time there was no need for a repeated operation in 88.4% of patients, thrombolytic complications did not develop in 91.2% of cases, 96.7% of patients belong to functional classes I and II.

Actuarial Analysis↗