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Biomedical subjects

S Siddiqui

Publications and source records attributed to S Siddiqui.

At least 55 records · Page 3Linked to original sources

A sensitive fluorogenic enzyme linked immunosorbent assay for the detection of Vipera russelli venom.

A highly sensitive fluorogenic enzyme-linked immunosorbent assay (FELISA) has been adapted for the detection of Vipera russelli venom. The assay sensitivity was observed to be 0.1 pg/ml (1 x 10(-13) g/ml). Venoms from snakes of the Vipera group exhibited a high degree of cross-reactivity when tested with the antibody raised against V. russelli venom. With the exception of venom from Naja naja, all the tested venoms from unrelated families also showed cross-reactivity. This procedure is useful for detecting snake venom or its components in biological samples.

Animals↗

Elevated pyrogenic cytokines in heatstroke.

STUDY OBJECTIVES: Heatstroke, characterized by hyperthermia and neurologic abnormalities, can cause shock, adult respiratory distress syndrome, and multiorgan failure culminating in death. The mediation of metabolic changes and tissue damage is not fully understood. Recent evidence suggests the involvement of endotoxin, tumor necrosis factor alpha (TNF-alpha), and interleukin 1 alpha (IL-1 alpha) and we hypothesized that other pyrogenic cytokines may be implicated. DESIGN: Prospective analysis. SETTING: Heatstroke Center in Makkah (Mecca), Saudi Arabia. MEASUREMENTS AND RESULTS: We measured plasma IL-1 beta, IL-6, and interferon gamma (INF-gamma) concentrations by enzyme-linked immunosorbent assay in 28 heatstroke patients at the time of hospital admission (precooling) and after complete cooling (postcooling), and in 10 normal control subjects. We measured C-reactive protein (CRP) as a marker of acute phase response and calculated severity of illness using the simplified acute physiology score. Twenty-five male and 3 female subjects had mean (+/- SEM) rectal temperature of 41.2 +/- 0.2 degrees C. IL-6, IL-1 beta, and INF-gamma concentrations were elevated in 100 percent, 39 percent, and 50 percent of patients to (mean +/- SEM) 220 +/- 44 pg/ml, 42 +/- 14 pg/ml, and 1,180 +/- 879 pg/ml, respectively (normal control values: < 3.5 pg/ml, < 4.5 pg/ml, < 20 pg/ml). The CRP value was elevated in 72 percent of patients to 152 +/- 40 mg/L (control value: 0 to 17 mg/L). The IL-6 concentrations correlated with severity of illness (r = 0.516, p = 0.03); two patients with the highest concentrations died. There was no significant correlation between circulating levels of IL-6, IL-1 beta, INF-gamma, and temperature, or between IL-6, IL-1 beta, and CRP. Postcooling, IL-6, and IL-1 beta were still above normal control values; INF-gamma could be detected in one patient only. CONCLUSION: Our findings of elevated circulating IL-6, IL-1 beta, and INF-gamma in the presence of acute phase response, and correlation with severity of illness, suggest that these cytokines have a role in the pathogenesis of heatstroke, which could lead to new therapeutic strategies.

Body Temperature↗

Synthesis of alkyl catechols and evaluation of their antibacterial and cyfotoxic activity.

A series of potential biologically active mono-, di- and tetra- alkyl catechols were prepared through Friedel- Crafts alkylation of catechol, and evaluated for their antibacterial and cytotoxic activity. The mono-substituted alkyl derivatives showed maximum antibacterial activity in vitro which increased with the increasing length of the alkyl chains. Primary screening results indicated that all the monoalkyl derivatives except 4- (2-octyl) catechol inhibited the growth of B. bronchoseptica and maximum zones of inhibition were observed in case of monohexyl catechols (both n- and 2-hexyl) and monobenzyl derivative. In case of Gram-negative organisms growth of Kl. pneumoniae and A. calcoaceticus was inhibited by several derivatives. Mono-3-octyl-, monononyl- and monobenzyl catechols markedly inhibited the growth of Kl. pneumoniae. Mono-2-heptyl catechol inhibited the growth of six Gram-negative bacteria. Minimum inhibitory concentration of six most active compounds of the series was determined against Gram-positive and Gram-negative organisms; it ranged from < 100 mug/ml to l0 mug/ml. The antibacterial activity of catechol was not significant. Cytotoxicity test done by brine shrimp assays showed that the order of cytotoxicity decreases in going from mono- to tetra- alkyl catechols, and among the mono- alkyl products, a decrease in order of cytotoxicity was noted in going from mono-methyl catechol (LD(50) = 59) to monopentyl catechol (LD(50) = 173) after which the order of cytotoxicity gradually increased upto the largest alkyl substituent tested i.e. monononyl catechol (LD(50) = 114). Methyl and ethyl catechol, which were almost inactive in respect of their antibacterial activity possessed prononounced cytotoxicity as compared to higher homologues. Catechol itself did not show significant cytotoxicity (LD(50) = 393.27).

Journal Article↗

Constituents of Azadirachta indica: isolation and structure elucidation of a new antibacterial tetranortriterpenoid, mahmoodin, and a new protolimonoid, naheedin.

Mahmoodin [1], a new limonoid, has been isolated from Azadirachta indica (neem) oil, along with seven known tetranortriterpenoids, azadirone, epoxyazadiradione, nimbin, gedunin, azadiradione, deacetylnimbin, and 17-hydroxyazadiradione. A new protolimonoid, naheedin [3], has been obtained from the neem fruits along with azadirachtol. Their structures have been elucidated through chemical and spectral analyses including 2D nmr studies. The absolute configuration of 1 was established by comparison of its cd spectrum with those of the known tetranortriterpenoids. Mahmoodin showed significant antibacterial activity against various Gram-positive and Gram-negative organisms. Four hydrocarbons, icosane, docosane, 2-methyltricosane, and docosene, have also been identified by gc-ms of the EtOH extract of the fruit coats. Only docosane has earlier been reported from neem, while the remaining three are unreported from this plant.

Anti-Bacterial Agents↗

Epidermoid cyst of the testicle in children.

Epidermoid cyst of the testicle is rare in children and only four previous cases have been reported. We add two cases and discuss their presentation and management. Both children presented with solid testicular masses, one of which was asymptomatic and the other was painful. Physical examination and ultrasound could not differentiate between a benign and malignant process. One child underwent radical orchiectomy and one child underwent local excision alone. Both are free of disease at follow-up.

Child↗

Tricyclic Diterpenes from the Stem Bark of Azadirachta indica.

Two new diterpenoids, margosone and margosolone, have been isolated from the stem bark of AZADIRACHTA INDICA A. Juss (neem) and their structures established as 12,13-dihydroxy-14-isoporpylpodocarpa-8,11,13-trien-7-one and 13-hydroxy-12-methoxypodocarpa-8,11,13-trien-7-one, respectively, through chemical and spectroscopic studies.

Journal Article↗

Neisseria meningitidis: heterogenicity in the outer membrane proteins released into the growth medium.

Eight strains of Neisseria meningitidis belonging to different serogroups were analysed for their virulence in mice and their release of outer membrane proteins into the medium during growth. All strains released proteins. No detectable lipopolysaccharide was observed. However, SDS-PAGE showed a heterogenicity in the protein number and profile among the different strains of N. meningitidis tested.

Animals↗

Receptor-mediated endocytosis of enterokinase by rat liver. Preliminary characterisation of low-density endosomes.

The endocytosis of enterokinase by rat hepatocytes has been studied both in a perfused liver system and in the intact, anaesthetised animal. 10 min after administration of the enzyme, only 70% of the activity was cleared by the perfused liver, whereas clearance was total in the intact animal. In both cases, about 85% of the internalised enzyme co-purified with the smooth microsomes and virtually all (more than 90%) of the catalytic activity was latent and could only be detected in the presence of detergent. After 10 min, 22.5% of the activity remained with the sinusoidal plasma membrane in the case of the perfused liver, while for the intact animal this figure was only 10%, confirming the more efficient clearance of enterokinase in the intact animal. Further subcellular fractionation showed that in the anaesthetised animal 8% of the internalised enzyme was associated with a low-density Golgi-like endosomal compartment (prepared from the mitochondrial pellet), whereas the corresponding value for the perfused liver was only 2.5%. Enterokinase specific activity was also up to 50-times greater in the low-density endosomes prepared from the intact animal. A second low-density Golgi-like compartment (purified from the smooth microsomes) also contained latent enterokinase, which together with the endosomes derived from the mitochondria accounted for 20% of the total enterokinase internalised by the liver 10 min after its administration to the intact animal. The passage of enterokinase through these two low-density compartments was shown not to be synchronous with its passage through the peripheral (sinusoidal membrane) and internal endosomes (smooth microsomes). There were qualitative differences in marker enzymes and polypeptide composition between the mitochondria and microsome-derived low-density endosomes. The sub-fractionation of low-density fractions on shallow sucrose gradients revealed a complex enzyme and polypeptide heterogeneity both between and within fractions. There was an apparent density-dependent separation of enterokinase from galactosyltransferase and the asialoglycoprotein receptor which was coincident with marked changes in the polypeptide composition of the endosomal membranes, particularly in the 30-45 kDa range.

Animals↗

Selective transcription and DNase I protection of the rat prolactin gene by GH3 pituitary cell-free extracts.

Prolactin (PRL) is a member of the growth hormone gene family that is specifically expressed in the lactotroph cells of the anterior pituitary. Whole cell extracts have been prepared from cultured GH3 rat pituitary tumor cells to study lactotroph-specific expression of the rat PRL (rPRL) gene in an in vitro transcription assay. The human alpha 1-globin and Rous sarcoma virus promoters efficiently initiate transcription in both HeLa and GH3 cell extracts, whereas the rPRL promoter containing 425 base pairs of 5' flanking DNA is active only in GH3 pituitary cell-free extracts. Transcription of the rPRL gene was reconstituted in HeLa cell extracts by the addition of GH3 cell extracts. DNase I digestion of the rPRL promoter reveals two protected regions centered at positions -55 (I) and -160 (III) that are GH3 cell-specific and rPRL promoter-selective. These "footprints" overlie a highly conserved 8-base-pair motif, CCTGATAATA. By contrast, footprint II at position -125 is common to both HeLa and GH3 cell extracts and overlies a 15-base-pair sequence found in all members of the growth hormone gene family. Thus, GH3 pituitary cell-free extracts selectively transcribe the rPRL gene and contain cell-specific factors that directly interact with the rPRL promoter. These studies provide useful assays to further identify, purify, and characterize pituitary-specific transcription factors and to address the biochemical mechanisms involved in rPRL gene expression.

Animals↗

Cardiac function in alcohol-associated systemic hypertension.

The pathogenesis of alcohol cardiomyopathy is obscure. Because systemic hypertension is observed in one-third of alcoholics, the relation of this finding to left ventricular (LV) function was analyzed in 66 alcoholics (26 with a blood pressure of 160/95 mm Hg or higher) 4 to 5 days after alcohol withdrawal. Hypertensive alcoholics had a more abnormal ratio of preejection period/LV ejection time (PEP/ET) (0.398 +/- 0.01 vs 0.35 +/- 0.01, p less than 0.02) than normotensive alcoholics (matched normal 0.290 +/- 0.01). Hypertensive alcoholics (transitory hypertension) with blood pressures of 120/80 mm Hg or less at time of study also had more abnormal PEP/LVET than matched normotensive alcoholics (0.415 +/- 0.03 vs 0.331 +/- 0.01, p less than 0.05). In both hypertensive (77 +/- 6 dynes/cm2 X 10(3)) and normotensive alcoholics (67 +/- 4 dynes/cm2 X 10(3) LV stress was elevated (normal 46 +/- 3 dynes/cm2 X 10(3), both p less than 0.02). However, LV mass was not increased (hypertensive 96 +/- 4 g/m2; vs normotensive 100 +/- 4 g/m2; (normal 92 +/- 5 g/m2), resulting in a markedly increased stress to mass ratio (hypertensive 0.8 +/- 0.06; Normal 0.05 +/- 0.05, p less than 0.02). Hypertensive alcoholics also had LV "hyperfunction," with an increased stress/LV end-systolic volume ratio (1.7 +/- 0.1 vs 1.3 +/- 0.1 dynes/cm2 X 10(3)/ml, p less than 0.02). Thus, hypertensive alcoholics, even those with transitory hypertension, have more abnormal cardiac function than normotensive alcoholics. Presence of hypertension with hyperdynamic LV features may be a prelude to heart failure.

Adult↗