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J Iqbal

Publications and source records attributed to J Iqbal.

At least 19 recordsLinked to original sources

Pharmacophoric 2-hydroxyalkyl benzenesulfonamide: a single-step synthesis from benzenesulfonamide via hemiaminal.

ortho-Acylation attempt of benzenesulfonamide afforded the corresponding hemiaminal as major product. The in situ reduction of the reaction mixture, reported herein, directly provided 2-hydroxyalkyl benzenesulfonamide, an important pharmacophoric element for designing drug-like scaffolds. Its application is demonstrated through designing a novel series of 1,5-diarylpyrazoles for cyclooxygenase-2 (COX-2) inhibition.

Aldehydes↗

Photochemistry of phenazopyridine hydrochloride.

Phenazopyridine hydrochloride (1) is an azo dye with local analgesic and anaesthetic effects on the urinary tract. Its photochemistry was studied in different reaction media including the drug adsorbed on silica gel. This resulted in photochemical cyclodehydrogenation, reductive photodegradation and rearrangement of the drug molecule. Four major products were isolated and identified on the basis of IR, NMR and mass spectral studies. The products are: pyrido[3,4-c]cinnoline-2,4-diamine (2), N3-phenylpyridine-2,3,4,6-tetraamine (3), pyridine-2,3,6-triamine (4), 2,6-diamino-1-(4-aminophenyl)pyridin-4(1H)-one (5).

Anesthetics, Local↗

Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial.

BACKGROUND: Estrogen has beneficial effects on lipid metabolism and bone preservation. The IMPACT trial evaluated neoadjuvant therapy with anastrozole or tamoxifen alone, or a combination. The comparative effects of these treatments on serum lipids and bone resorption were assessed. PATIENTS AND METHODS: Non-fasting clotted blood samples were taken from 176 postmenopausal patients at baseline, 2 and 12 weeks for assessment of serum levels of estradiol, the bone resorption marker CTx and lipid profiles [total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and non-HDL cholesterol (N-HDL-C)]. RESULTS: After 12 weeks, tamoxifen was associated with a significant increase in HDL-C (26.5%), and a decrease in TC (6.5%) and N-HDL-C (12.3%). Anastrozole was associated with a significant increase in HDL-C (11.2%), and a non-significant increase in TC (2.9%) and N-HDL-C (3.4%), both of which were significantly different from tamoxifen. The combination was associated with a significant increase in HDL-C (9.4%), and a decrease in TC (10.9%) and N-HDL-C (13.9%). For tamoxifen and the combination, there were non-significant decreases in CTx compared with a significant increase (45.6%) with anastrozole. No correlation between serum estradiol and CTx was seen in any of the treatment groups. CONCLUSION: Anastrozole did not have a detrimental effect on lipid profiles following 3 months of therapy. There was a significant increase in CTx with anastrozole in contrast to tamoxifen.

Aged↗

Evidence that projections from the bed nucleus of the stria terminalis and from the lateral and medial regions of the preoptic area provide input to gonadotropin releasing hormone (GNRH) neurons in the female sheep brain.

The arcuate nucleus/ventromedial hypothalamic nucleus (ARC/VMH) region is thought to relay estrogen feedback signals to gonadotropin-releasing hormone (GnRH) cells in the sheep brain. This region sends major projections to the lateral preoptic area (lPOA), ventral bed nucleus of the stria terminals (vBnST) and the ventro-caudal division of the median preoptic nucleus (vcMePON) with little direct input to GnRH cell bodies, suggesting interneuronal relay to GnRH neurons. The brain stem also provides input to the POA. The present study aimed to identify possible relay circuits in the POA and BnST to GnRH neurons. Biotinylated dextran amine (BDA) was injected into lPOA (n=6), vBnST (n=2), vcMePON (n=3) and periventricular nucleus (PeriV; n=1) of ewes for anterograde tracing. GnRH immunoreactive (IR) perikarya appearing to receive input from BDA-containing varicosities were identified by fluorescence microscopy, with further analysis by confocal microscopy. When BDA was injected into rostral and caudal regions of lPOA (n=3), no tracer-filled varicose fibers were found in contact with GnRH-IR perikarya. Injections into the center of the lPOA (n=3) indicated direct projections to GnRH-IR cells. Injections into the vBnST, vcMePON and PeriV indicated that cells of these regions also provide input to GnRH cells. BDA-containing varicosities found in the MPOA were immunoreactive for NPY or were GABAergic or glutamatergic when the tracer was injected into vBnST and lPOA, but not when injections were placed in the vcMePON. With injection into the PeriV, tracer-filled varicosities in the MPOA were not immunoreactive for somatostatin or enkephalin. Injection of FluoroGold into ventral POA retrogradely labeled cells in the above mentioned areas, but few were also immunoreactive for estrogen receptor-alpha. Thus, cells of the vBnST, lPOA, vcMePON and PeriV project to GnRH neurons. These cells may provide an interneuronal route to GnRH neurons from the ARC/VMH, the brain stem and other regions of the brain.

Afferent Pathways↗

Co-localization and distribution of corticotrophin-releasing hormone, arginine vasopressin and enkephalin in the paraventricular nucleus of sheep: a sex comparison.

The paraventricular nucleus (PVN) is integral to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and contains cells producing corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and enkephalin. We used immunohistochemistry to map these peptides and to resolve the extent of co-localization within PVN cells in intact and gonadectomized male and female sheep. Immunoreactive (ir) CRH, AVP and enkephalin cells were mapped in two rams and two ewes at 180 mum intervals throughout the rostro-caudal extent of the PVN. Similar distributions of AVP-ir cells occurred in both sexes whereas CRH-ir and enkephalin-ir cells extended more rostrally in rams. In groups (n=4) of intact and gonadectomized sheep of both sexes, co-localization and distribution of neuropeptides was influenced by sex and gonadectomy. Males had more AVP and CRH cells than females. Intact animals had more AVP cells than gonadectomized animals. There were no differences between groups in the number or percentage of cells that stained for both CRH and AVP or in the number of cells that stained for both CRH and enkephalin. Differences were observed in the percentage of enkephalin cells that contained CRH with males having a greater percentage of co-localized cells than did females. Differences were also observed in the number and percentage of cells that stained for both enkephalin and AVP; the number of cells that stained for both neuropeptides was greater in males than in females and greater in intact animals than in gonadectomized animals. Differences were observed in the percentage of AVP cells that contained enkephalin, and in the percentage of enkephalin cells that contained AVP with males having a greater percentage of co-localized cells than did females. We conclude that sex and gonadal status affect peptide distribution in the PVN of the sheep which may provide an anatomical basis for sex differences in HPA axis responses to stress.

Animals↗

Changes in expression of the genes for the leptin receptor and the growth hormone-releasing peptide/ghrelin receptor in the hypothalamic arcuate nucleus with long-term manipulation of adiposity by dietary means.

Changes in leptin and ghrelin levels occur with alterations in adiposity, but signalling may be affected by levels of the relevant receptors. We measured expression of the leptin receptor (Ob-Rb) and the ghrelin/growth hormone releasing peptide receptor (GHS-R) in the arcuate nucleus of sheep held at either high or low levels of adiposity. Plasma growth hormone (GH) levels were lower in Fat animals and higher in Lean animals. Plasma insulin and leptin levels were higher in Fat animals and lower in Lean animals. Frozen hypothalamic sections of arcuate nucleus were extracted and mRNA levels measured for mRNA for Ob-Rb and GHS-R. Gene expression for both Ob-Rb and GHS-R was higher in Lean animals than in Fat animals, with no difference in expression between Fat and Normal animals. A second group of animals (n = 4 per group) was used for double-labelling immunohistochemistry to determine whether the increase in Ob-Rb gene expression was translated into Ob-Rb protein and to ascertain whether this effect is localised to the cells of the arcuate nucleus that produce either neuropeptide Y (NPY) and/or pro-opiomelanocortin-derived peptides. Lean animals displayed a 255% increase in immunoreactive NPY cells (P < 0.005), a 167% increase in cells with Ob-Rb (P < 0.037) protein and a 344% increase in cells that were staining for both NPY and Ob-Rb (P < 0.02). There was no difference between the Normal and Lean animals in the number of cells that were detected with an adrenocorticotrophic hormone (ACTH) antibody or the number of ACTH-immunoreactive cells that also stained for Ob-Rb. Finally, we measured plasma ghrelin levels in Normal, Fat and Lean ewes (n = 4/group); levels were higher (P < 0.05) in Fat animals than in Lean animals. We conclude that lowering body weight leads to increased expression of Ob-Rb, ghrelin/GHS-R expression and proportion of NPY cells that express Ob-Rb in the arcuate nucleus. This may be an adaptive mechanism to increase responsivity to both leptin and ghrelin.

Adipose Tissue↗

Noradrenergic regulation of hypothalamic cells that produce growth hormone-releasing hormone and somatostatin and the effect of altered adiposity in sheep.

The growth hormone (GH) axis is sensitive to alteration in body weight and there is evidence that central noradrenergic systems regulate neurones that produce growth hormone-releasing hormone (GHRH) and somatostatin (SRIF). This study reports semiquantitative estimates of the noradrenergic input to neuroendocrine GHRH and SRIF neurones in the sheep of different body weights. We also studied the effects of altered body weight on expression of dopamine beta-hydroxylase (DBH), the enzyme that produces noradrenalin from dopamine. Ovariectomised ewes were made Lean (39.6 +/- 2.6 kg; Mean +/- SEM) by dietary restriction, whereas Normally Fed animals (61.2 +/- 0.8 kg) were maintained on a regular diet. Brains were perfused for immunohistochemistry and in situ hybridisation. The Mean +/- SEM number of GHRH-immunoreactive (-IR) cells was lower in Normally Fed (65 +/- 7) than in Lean (115 +/- 14) animals, whereas the number of SRIF-IR cells was similar in the two groups (Normally Fed, 196 +/- 17; Lean 230 +/- 21). Confocal microscopic analysis revealed that the percentage of GHRH-IR cells (Normally Fed 36 +/- 1.5% versus Lean 32 +/- 4.6%) and percentage of SRIF-IR cells (Normally Fed 30 +/- 40.4% versus Lean 32 +/- 2.3%) contacted by noradrenergic fibres did not change with body weight. FluoroGold retrograde tracer injections confirmed that noradrenergic projections to the arcuate nucleus are from ventrolateral medulla and noradrenergic projections to periventricular nucleus arise from the ventrolateral medulla, nucleus of solitary tract, locus coeruleus (LC) and the parabrachial nucleus (PBN). DBH expressing cells were identified using immunohistochemistry and in situ hybridisation and the level of expression (silver grains/cell) quantified by image analysis. The number of DBH cells was similar in Normally Fed and Lean animals, but the level of expression/cell was lower (P < 0.02) in the PBN and LC of Lean animals. These results provide an anatomical basis for the noradrenergic regulation of GHRH and SRIF cells and GH secretion. Altered activity or noradrenergic neurones in the PBN and LC that occur with reduced body weight may be relevant to the control of GH axis.

Adipose Tissue↗

Photooxidation of acyclovir in aqueous solution.

Photodegradation of an aqueous solution of acyclovir in phosphate buffer (pH 7) under aerobic conditions was studied with light of wavelength > 270 nm. Three major products were isolated and identified on the basis of IR, NMR and mass spectral studies. The products are: (2-hydroxyethoxy)methyl spiroiminodihydantoin (2), (2-hydroxyethoxy)methyl(amino)-2-imino-1,2-dihydroimidazole-5-one (3), and 2,2-diamino-4-[(2-hydroxyethoxy)methyl]amino)-5-[2H]-oxazolone (4). Furthermore the effects of D2O as reaction medium, addition of sodium azide and absence of oxygen on the photodegradation of acyclovir were examined, the observations indicating the involvement of singlet oxygen. The formation of the products is explained by the photooxidation of acyclovir.

Acyclovir↗

Methylation of the asparagine synthetase promoter in human leukemic cell lines is associated with a specific methyl binding protein.

We have examined the methylation profiles of the asparagine synthetase (ASY) promoter in a number of human leukemic cell lines in relation to their asparagine (ASN) requirements in vitro. Cells in which the promoter is highly methylated are auxotrophs and express ASY at very low levels. Electromobility shift assays (EMSA) of nuclear extracts with oligomers from the promoting region show, in addition to recognized transcription factor binding, a novel methyl binding protein specific for a 12 base consensus sequence, which includes a single methylated CpG. This sequence overlaps that of the amino-acid response unit of the ASY promoter, which is activated byATF4 and C/EBP. Competition by the methyl binding protein could account for the observed failure of the methylated promoter to bind these transcription factors and consequently, although other mechanisms can also be operative, for the specific repression of the gene. The ASY methyl binding protein (ASMB) is present in leukemic lymphoid and myeloid cells irrespective of their methylation status, and in normal lymphocytes after phytohemagglutinin stimulation. It has been purified by affinity chromatography and has a molecular size of 40 kDa in 10% SDS-polyacrylamide gels.

Aspartate-Ammonia Ligase↗

Removal and recovery of nickel(II) from aqueous solution by loofa sponge-immobilized biomass of Chlorella sorokiniana: characterization studies.

The biosorption process for the removal of nickel(II) by loofa sponge-immobilized biomass of Chlorella sorokiniana (LIBCS), a newly developed immobilized biosorbent, was characterized. Effects of environmental factors on metal uptake capacity of LIBCS were studied and compared with free biomass of C. sorokiniana (FBCS). Nickel(II) removal by LIBCS was found to be influenced by pH of the solution, initial metal concentration, and biomass concentration. The biosorption of nickel(II) ions by both LIBCS and FBCS increased as the initial concentration of nickel(II) ions increased in the medium. No loss to biosorption capacity of LIBCS for nickel(II) was found due to the presence of loofa sponge, indeed as compared to FBCS an increase of 25.3% was noted in the biosorption capacity of LIBCS. Maximum biosorption capacities for FBCS and LIBCS were found as 48.08 and 60.38 mg nickel(II)/g, respectively, whereas the amount of nickel(II) ions adsorbed on the plain loofa sponge was 6.1mg/g. During these biosorption studies, LIBCS exhibited excellent physical and chemical stability without any significant release/loss of microalgal biomass from loofa sponge matrix. The kinetics of nickel(II) removal was extremely fast reaching at equilibrium in about 15 min for LIBCS and 20 min for FBCS. The biosorption equilibrium was well described by the Langmuir and Freundlich adsorption isotherms. The biosorption capacities were found to be solution pH dependent and the maximum adsorption was found at a solution pH 4-5. The LIBCS could be regenerated using 75 mM HCl, with up to 98% recovery. The LIBCS were shown to be robust and stable with little decrease in the nickel(II) uptake capacity when used in consecutive seven biosorption-desorption cycles. Continuous removal of nickel(II) from electroplating effluent by LIBCS packed in fixed bed column bioreactor confirm the possibility of developing a biological treatment process for the removal of toxic metals from authentic wastewater.

Adsorption↗

Effect of matrix depleting agents on the expression of chondrocyte metabolism by equine chondrocytes.

This study was carried out to investigate the effect of two enzymes (collagenase and chondroitinase) and two cytokines/metabolites (interleukin-1beta and retinoic acid) of known catabolic activity on the expression of cartilage metabolism/phenotype in equine articular cartilage. Articular cartilage explants from 11 horses (5-13 years old) were treated for 48 h and assayed for total sulphated glycosaminoglycan (GAG), the incorporation of 35S-sulphate, collagen degradation and mRNA expression of the proteoglycans collagen II, collagen IIA, collagen III, collagen IX, collagen X, collagen XI and glyceraldehyde-3-phosphate (GAPDH). Purified collagenase and retinoic acid were responsible for increased GAG loss from the tissues. Chondroitinase, responsible for catalysing the elimination of glucuronate residues from chondroitin A, B and C (Chondroitinase ABC) and retinoic acid treatment induced an inhibition of proteoglycan synthesis, whereas collagenase treatment did not. Collagenase activity was correlated with increased appearance of the CB11B epitope and type II collagen denaturation. By RT-PCR there was evidence of expression of altered collagen type IIA in purified collagenase treated tissues.

Animals↗

Suppression of diethylnitrosamine and 2-acetylaminofluorene-induced hepatocarcinogenesis in rats by tocotrienol-rich fraction isolated from rice bran oil.

The anticancer efficacy of tocotrienol-rich fraction (TRF) was evaluated during diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)-induced hepatocarcinogenesis in male Sprague-Dawley rats. TRF treatment was carried out for 6 months, and was started 2 weeks before initiation phase of hepatocarcinogenesis. Morphological examination of the livers from DEN/AAF rats showed numerous off-white patches and few small nodules, which were significantly reduced by TRF treatment. Cytotoxic damage by DEN/AAF was estimated by alkaline phosphatase (ALP) release into the plasma from the cell membranes. DEN/AAF caused a twofold increase in the activity of ALP in plasma as compared with normal control rats, and this increase was prevented significantly by TRF treatment. We observed an increase of 79% in liver ALP activity in DEN/AAF rats, which was further increased by another 48% after the administration of TRF. Hepatic activity of glutathione S-transferase (GST) was also increased (3.5-fold) during the induction of hepatic carcinogenesis. Lipid peroxidation and low-density lipoprotein (LDL) oxidation increased threefold following initiation by DEN/AAF as compared with normal control rats. However, TRF treatment to DEN/AAF-treated rats substantially decreased (62-66%) the above parameters and thus limited the action of DEN/AAF. We conclude that long-term intake of TRF could reduce cancer risk by preventing hepatic lipid peroxidation and protein oxidation damage due to its antioxidant actions.

2-Acetylaminofluorene↗

Strongyloidiasis: challenges in diagnosis and management in non-endemic Kuwait.

Among immunocompromised individuals, hyper-infection with Strongyloides stercoralis may occur and lead to fatal strongyloidiasis. To clinicians and laboratory diagnosticians in non-endemic countries such as Kuwait, this severe infection poses a particular problem. The clinical histories and signs and symptoms of four Kuwaiti cases of S. stercoralis hyper-infection were reviewed. Each of the four was found not only to have lived in an area where S. stercoralis was endemic but also to have been treated with immunosuppressive steroids (for medical problems unrelated to the nematode infection). When they presented with undiagnosed hyper-infections their clinical features were confusing. Three of the cases, all with low eosinophil counts, died but the other, who was treated with thiabendazole, survived. In the light of these observations, healthy medical examinees who had recently moved from endemic zones were checked for asymptomatic S. stercoralis infection, both by stool examination and ELISA-based serology. Of 381 stool samples investigated over a 3-month period, 183 (48%) were found positive for helminths, 7% for S. stercoralis. Of 198 individuals from endemic zones who were screened after another medical examination, 71 (35.8%) were found positive for intestinal helminth parasites, including one (1.45%) infected with S. stercoralis. Although ELISA appear reliable in making a presumptive diagnosis of strongylodiasis, the results of such assays are not very specific and are best interpreted in conjunction with the patient's clinical status. The concurrent administration of anthelminthics to patients prescribed steroids who, because they live or have lived in an area where S. stercoralis is endemic, are at risk of infection with the nematode, should be considered.

Adult↗

Long-term alteration in bodyweight and food restriction does not affect the gene expression of either preproorexin or prodynorphin in the sheep.

Various hypothalamic neuropeptides are involved in central regulation of food intake and expression of genes encoding these peptides changes with alterations in the bodyweight/metabolic status/nutritional status. Orexin(s) and dynorphin have been implicated in the regulation of appetite and neuroendocrine systems, but the function of these peptides is not well understood. We have employed in situ hybridization to examine the effects of long-term alterations in the bodyweight on expression of mRNA for preproorexin and prodynorphin in the putative feeding centers of the ovine hypothalamus. Expression of preproorexin was localized to the dorsomedial hypothalamic nucleus, perifornical area and lateral hypothalamic area. Cells expressing prodynorphin were localized to the periventricular, supraoptic, paraventricular, ventromedial hypothalamic nuclei and the thalamus. Small numbers of single scattered cells were seen in other brain areas. A few scattered prodynorphin-expressing cells were found in the lateral hypothalamic area but, in contrast to observations in the rat, there was no colocalization with preproorexin. Long-term alterations in the bodyweight did not influence the level of expression of preproorexin or prodynorphin. These findings suggest that orexin and dynorphin may not play a direct role in appetite regulation in sheep, although regulation at the level of the receptors for these peptides remains a possibility.

Animals↗

Effect of volume of culture medium on enhanced citric acid productivity by a mutant culture of Aspergillus niger in stirred fermentor.

AIMS: The present study deals with the effect of volume of culture medium on enhanced citric acid productivity by a mutant culture of Aspergillus niger. METHODS AND RESULTS: A laboratory scale stirred fermentor of 15-l capacity was employed for all microbial cultivations. Blackstrap molasses, a by-product of sugar industries is easily and abundantly available for its exploitation as a carbon source in fermentation processes. The parental culture of A. niger was improved by mutation using ultraviolet radiations and N-methyl N-nitro N-nitroso guanidine, i.e. mutagen MNNG. Six MUV and eight MNNG-treated mutant strains were isolated after extensive screening and optimization. Mutant strain of A. niger MNNG-2 showed enhanced citric productivity (87.60 g l-1) over the parental strain BTL-45 (19.53 g l-1) and other mutant derivatives (49.85 g l-1 citric acid in case of mutant MUV-5 and 76.82 g l-1 in case of mutant MNNG-7). The optimal sugar level was found to be 150 g l-1 (optimum volume of the medium, 60%) after 6 days of inoculation, which is economically significant. Specific productivity of the mutant culture MNNG-2 (qp = 0.057 g/g cells h-1) was several folds higher than other strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study are of commercial level. All kinetic parameters including yield coefficients and volumetric rates revealed the hyper-producibility of citric acid by mutant MNNG-2 using blackstrap molasses as the basal medium in stirred fermentor.

Aspergillus niger↗

Microalgal-luffa sponge immobilized disc: a new efficient biosorbent for the removal of Ni(II) from aqueous solution.

AIMS: The aim was to develop a new, efficient and cost-effective biosorbent for the removal of heavy metals from aqueous solution. METHODS AND RESULTS: A new biosorbent was developed by immobilizing a unicellular green microalga Chlorella sorokiniana within luffa sponge discs and used for the removal of metal ions from aqueous solution. Microalgal-luffa sponge immobilized discs (MLIDs) removed Ni(II) very rapidly, with 97% of equilibrium loading being reached in 5 min. MLIDs were tested for their potential to remove Ni(II) from aqueous solution in fixed-bed column bioreactor. The regenerated MLIDs retained 92.9% of the initial binding capacity for Ni(II) up to five cycles of reuse. CONCLUSIONS: In this study for the first time, C. sorokiniana biomass immobilized within luffa sponge disc was successfully used as a metal biosorbent for the removal of Ni(II). It appears that MLIDs can be used as an effective biosorbent for efficient removal of Ni(II) or other metals from aqueous solution. SIGNIFICANCE AND IMPACT OF THE STUDY: MLIDs biosorption system was shown to have good biosorption properties with respect to Ni(II). Efficient metal removal ability of MLIDs, low cost and simplicity of the technique used for the preparation of MILDs could provide an attractive strategy for developing high-affinity biosorption system for heavy metal removal.

Biomass↗