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Biomedical subjects

K Rahman

Publications and source records attributed to K Rahman.

At least 19 recordsLinked to original sources

Radiological impact of dietary intakes of naturally occurring radionuclides on Pakistani adults.

Daily dietary intakes of three naturally occurring long-lived radionuclides (232)Th, (238)U and (40)K were estimated for the adult population of Pakistan using neutron activation analysis (NAA), inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS), respectively. The daily intakes of (232)Th ranged from 4 to 29 mBq, (238)U ranged from 17 to 82 mBq and (40)K ranged from 51 to 128 Bq. The geometric means of these intakes were 10 mBqd(-1) for (232)Th, 33 mBqd(-1) for (238)U and 78.5 Bqd(-1) for (40)K. The measured values give annual committed effective doses of 0.80, 0.53 and 178.75 microSvyr(-1) for (232)Th, (238)U and (40)K, respectively to Pakistani population. The net radiological impact of these radionuclides is 180.08 microSvyr(-1). This value gives cancer risk factor of 4.5 x 10(-4) and loss of life expectancy of 0.87 days only. Whereas ICRP cancer risk factor for general public is 2.5 x 10(-3) and total risk involve from the all natural radiation sources based on global average annual radiation dose of 2.4 mSvyr(-1) is 6.0 x 10(-3). The estimated cancer risk shows that probability of increase of cancer risk from daily Pakistani diet is only a minor fraction of ICRP values. Therefore, the diet does not pose any significant health hazard and is considered radiologically safe for human consumption.

Diet↗

Antinociceptive activity and chemical composition of constituents from Caragana microphylla seeds.

This investigation was undertaken to ascertain the antinociceptive activity of Caragana microphylla Lam. seeds and isolate and characterize the constituents. Antinociceptive activity was screened using acetic acid-induced abdominal constriction in ICR mice. The 75% ethanol extract and some fractions showed analgesic activity, but the antinociceptive activity of chloroform fraction was the strongest and was more productive than other fractions. Seven compounds were isolated from it and identified as: (1) machaeric acid, (2) beta-sitosterol, (3) stigmasterol, (4) pratol, (5) dehydrocavidine, (6) formononetin and (7) sucrose. Caragana microphylla Lam. seeds showed analgesic activity, with the chloroform fraction showing the strongest analgesic activity among the fractions.

Acetic Acid↗

Failed tracheal intubation in obstetrics: no more frequent but still managed badly.

In the South-West Thames region of the United Kingdom, during a 5-year period from 1999 to 2003, there were 20 failed tracheal intubations occurring in 4768 obstetric general anaesthetics (incidence 1 : 238). In half of the 16 cases for which the patient's notes could be examined there was a failure to follow an accepted protocol for failed tracheal intubation.

Anesthesia, General↗

Sustainable urban development in Brisbane City--the Holy Grail?

Impacts from urban stormwater runoff on receiving environments have been well documented, particularly through specific regional scientific studies. Using various local government planning and management elements, urban developments in Brisbane City are now able to address stormwater management in an increasingly holistic context. One key initiative includes facilitating Water Sensitive Urban Design (WSUD) components within an Integrated Water Management Strategy that looks at policy formation, planning strategies, design option, community marketing and acceptance, maintenance programs and finally evaluation of various WSUD approaches. These can include the use of Natural Channel Designs, grassed swales, bio-filtration systems, porous pavements and roofwater tanks in several economic combinations. By linking with the Cooperative Research Centre for Catchment Hydrology, Brisbane City Council has influenced the design of WSUD planning tools and benefited the city with academic inputs into extensive evaluation programs. As well, it has also contributed to the Cooperative Research Centre's research outcomes. These evaluation programs are increasingly providing better understanding of various stormwater quality best management practices throughout Australia. As part of the overall implementation process, active involvement by a range of stakeholders has been crucial. These stakeholders have included internal planning, development assessment and design staff, external consultants, developers, and other local and state government agencies. The latter two groups are assisting in the important task of "regionalisation" of Brisbane City Council's policies and guidelines. Implementation of WSUD initiatives and stormwater re-use strategies under Council's new "Integrated Water Management" agenda are showing some excellent results, suggesting that sustainable urban development is no longer like the search for the Holy Grail.

Conservation of Natural Resources↗

Historical perspective on garlic and cardiovascular disease.

Cardiovascular disease is a complex and multifactorial disease characterized by such factors as high cholesterol, hypertension, reduced fibrinolysis, increase in blood-clotting time and increased platelet aggregation. Dietary therapy is the first step in the treatment of hyperlipidemia; garlic has been used medicinally for centuries and is still included in the traditional medicine of many cultures. Historically, there has been great interest in the role of garlic in reducing cardiovascular risk factors. Evidence from numerous studies points to the fact that garlic can bring about the normalization of plasma lipids, enhancement of fibrinolytic activity, inhibition of platelet aggregation and reduction of blood pressure and glucose. However, some contradictory results have also emerged as a result of methodological shortcomings, the use of different formulations/preparations of garlic and different time scales of the studies. Accordingly, further clinical studies are required in which standardized formulations of garlic with known compositions can be used. Such formulations (e.g., Aged Garlic Extract) are now available and are being investigated. Evidence obtained from these studies indicates that garlic has potential in the prevention and control of cardiovascular disorders and is beneficial when taken as a dietary supplement.

Arteriosclerosis↗

Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans.

Garlic has been widely reported to protect against cardiovascular disease by reducing serum cholesterol concentrations and blood pressure and by inhibiting platelet aggregation. However, most of these studies have been performed in hypercholesterolemic subjects or in animal models. We performed a 13-wk study in normolipidemic subjects who ingested 5 mL of aged garlic extract (AGE, Kyolic) per day. Blood was drawn from these subjects at the beginning and end of the study. Aggregation of platelet-rich plasma was induced by ADP; full lipid profiles and liver function tests were determined on serum, and plasma concentrations of eicosanoids were also measured. Dietary supplementation with AGE significantly inhibited both the total percentage and initial rate of platelet aggregation at concentrations of ADP up to 10 micromol/L. The K:(M) for ADP-induced aggregation were approximately doubled after supplementation with AGE, whereas the maximum rate of aggregation was unaffected. No significant changes in plasma thromboxane B(2) and 6-ketoprostaglandin F(1alpha) concentrations or serum lipid profiles were observed. We conclude that AGE, when taken as a dietary supplement by normolipidemic subjects, may be beneficial in protecting against cardiovascular disease as a result of inhibiting platelet aggregation.

6-Ketoprostaglandin F1 alpha↗

Treatment with aged garlic extract protects against bromobenzene toxicity to precision cut rat liver slices.

Precision-cut liver slices from phenobarbital-induced rats were incubated for 6 h with the model hepatotoxin bromobenzene (BB) at a final concentration of 1 mM. Severe toxicity was indicated by a decreased K+, adenosine triphosphate and glutathione (GSH) content of the slices, increased release of alanine aminotransferase and lactate dehydrogenase into the medium, and increased formation of thiobarbituric acid reacting substances. Pretreatment of animals for 7 days with aged garlic extract (AGE) (Kyolic) at doses of 2 and 10 ml/kg/day dramatically reduced the toxicity of BB in a dose-dependent manner. The GSH content of liver slices from rats treated with AGE at 2 or 10 ml/kg/day increased by 50 and 80%, respectively. The BB-induced decrease in GSH content was less in slices derived from AGE-treated rats compared with slices from control rats. Pretreatment with AGE did not affect cytochrome P450 when assayed as 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities in hepatic microsomes. Thus, the mechanism by which pretreatment with AGE protects against BB hepatotoxicity involves both an elevation of hepatic GSH content, and a GSH sparing effect, possibly due to conjugation of organosulphur compounds in AGE with toxic BB metabolites. Only this GSH sparing effect was seen in our earlier study on the in vitro hepatoprotective effect of AGE [Wang et al., 1998. Toxicology 126, 213-222].

Adenosine Triphosphate↗

Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome.

The symptoms of restless legs syndrome (RLS) worsen while patients are sitting or lying and also worsen at night. The current study was designed to determine if the periodic limb movements (PLMs) and sensory symptoms of RLS are modulated by an independent circadian factor. We recorded sleeping and waking PLMs and waking sensory symptoms in eight volunteers with RLS for 3 successive nights and days, starting with a polysomnographic recording of 2 nights, followed by a third night of sleep deprivation and the day after sleep deprivation. This study showed that both the PLMs and sensory symptoms were worst at night with a maximum for both between midnight and 1:00 AM and a minimum between 9:00 and 11:00 AM. Sleep and drowsiness had a tendency to worsen PLMs and sensory symptoms after the night of sleep deprivation. Circadian temperature curves were normal in all four patients with adequate data collection. The highest PLM counts occurred on the falling phase of the circadian temperature curve whereas the lowest PLM counts occurred on the rising phase of the curve. We conclude that the PLM and sensory symptoms in RLS are influenced by a circadian rhythm, and that the "worsening at night" criterion of the RLS Definition Criteria is, at least in part, distinct from the "worsening while lying or sitting" criterion.

Adult↗

Protective effects of aged garlic extract against bromobenzene toxicity to precision cut rat liver slices.

Precision-cut liver slices from phenobarbital-treated rats were incubated for up to 8 h with the industrial solvent and hepatotoxin bromobenzene at a final concentration of 1 mM. Phenobarbital pretreatment potentiates bromobenzene hepatotoxicity by inducing those P450 isoforms responsible for the formation of the active hepatotoxin, namely bromobenzene-3,4-oxide. A reduction in cell viability was indicated by a decrease in the K+, ATP and glutathione content of the slices and the increased release of the intracellular enzymes, lactate dehydrogenase and alanine aminotransferase, into the medium. Furthermore, levels of lipid peroxidation as judged by the formation of thiobarbituric acid reactive substances, were increased approximately 5-fold. Aged garlic extract (AGE) at concentrations of 1-5% (v/v) reduced the toxicity of bromobenzene in a concentration-dependent manner as judged by all of the parameters of viability studied, with the exception of lipid peroxidation which was reduced to control levels even at the lowest concentration of garlic extract used. AGE was found to cause partial inhibition of cytochrome P450 when assayed as both 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities, but even the highest concentration used inhibited both activities by less than 50%. It is suggested that the hepatoprotective effects of AGE are due primarily to the reduced glutathione-sparing properties of its constituents, most probably its organosulphur compounds.

7-Alkoxycoumarin O-Dealkylase↗

The effect of priming with vecuronium and rocuronium on young and elderly patients.

UNLABELLED: The priming principle consists of administering a subparalyzing dose of nondepolarizing neuromuscular blocking drug 3-6 min before giving a second dose for tracheal intubation. This study was performed to observe the effects of priming doses of vecuronium and rocuronium on pulmonary function tests and muscular weaknesses in young (25-35 yr of age) and elderly (65-73 yr of age) patients. Ten young and 10 elderly patients were each placed in vecuronium and rocuronium groups. Oxygen saturation and train-of-four (TOF) ratio were determined, and pulmonary function tests were performed. Then 20% of the 95% effective dose (ED95) of the muscle relaxants was given intravenously. All tests were performed again 4 min after vecuronium and 3 min after rocuronium. Other signs of muscular weaknesses were also recorded. Elderly patients showed more signs of muscle weakness in both groups. The TOF ratio was 0.77 and 0.79 in the elderly rocuronium and vecuronium groups, respectively, and 0.89 and 0.90 in the young rocuronium and vecuronium groups, respectively. Dynamic spirometry revealed decreases in forced expiratory volume in 1 s and forced vital capacity in both groups, and no significant changes in peak expiratory flow rate. The expiratory reserve volume was reduced more in the elderly groups. Oxygen saturation decreased in both groups. We conclude that oxygen saturation, pulmonary function, and muscle strength decrease more in the elderly than in their younger counterparts from priming doses of vecuronium or rocuronium. IMPLICATIONS: The priming principle consists of giving a subparalyzing dose of muscle relaxant 3-6 min before giving a second dose for tracheal intubation. We found that priming doses of vecuronium and rocuronium produced greater decreases in oxygen saturation and pulmonary function in the elderly (aged 65-73 yr) than their younger (aged 25-35 yr) counterparts. Priming may not be a safe approach in elderly patients.

Adult↗

Biliary lipid output by isolated perfused rat livers in response to cholyl-lysylfluorescein.

The biliary output of bile acids and lipids is tightly coupled. The ability of the natural bile acid glycocholate to trigger biliary lipid secretion was compared with that of the fluorescent bile acid analogue cholyl-lysylfluorescein (cholyl-lys-F). When administered as a 5 min pulse of 2.5 mumol/min to bile acid-depleted rat livers perfused under recycling conditions, glycocholate produced well-defined peaks of phospholipid and cholesterol output, and of bile flow, which were coincident with the peak of bile acid output. Although cholyl-lys-F did trigger biliary lipid secretion, its time course of appearance was delayed and well-defined peaks of output were not observed. However, the increased biliary output of phospholipid and cholesterol was coincident with that of bile acids and, as judged by phospholipid/bile acid and cholesterol/bile acid ratios, cholyl-lys-F was as effective as glycocholate in triggering biliary lipid output. When administered to livers perfused under single pass conditions, perfusate to bile transfer of glycocholate was > 85% at infusion rates of up to 5 mumol/min whereas transfer of cholyl-lys-F showed saturation at infusion rates of > 0.2 mumol/min; the time course of biliary output of both bile acids was similar. Thus, under recycling conditions, cholyl-lys-F not taken up during first pass will be continually represented for transfer to bile, explaining why bile acid and lipid output did not occur as well-defined peaks.

Animals↗

Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen.

Human DNA helicase II (HDH II) is a novel ATP-dependent DNA unwinding enzyme, purified to apparent homogeneity from HeLa cells, which (i) unwinds exclusively DNA duplexes, (ii) prefers partially unwound substrates and (iii) proceeds in the 3' to 5' direction on the bound strand. HDH II is a heterodimer of 72 and 87 kDa polypeptides. It shows single-stranded DNA-dependent ATPase activity, as well as double-stranded DNA binding capacity. All these activities comigrate in gel filtration and glycerol gradients, giving a sedimentation coefficient of 7.4S and a Stokes radius of approximately 46 A, corresponding to a native molecular weight of 158 kDa. The antibodies raised in rabbit against either polypeptide can remove from the solution all the activities of HDH II. Photoaffinity labelling with [alpha-32P]ATP labelled both polypeptides. Microsequencing of the separate polypeptides of HDH II and cross-reaction with specific antibodies showed that this enzyme is identical to Ku, an autoantigen recognized by the sera of scleroderma and lupus erythematosus patients, which binds specifically to duplex DNA ends and is regulator of a DNA-dependent protein kinase. Recombinant HDH II/Ku protein expressed in and purified from Escherichia coli cells showed DNA binding and helicase activities indistinguishable from those of the isolated protein. The exclusively nuclear location of HDH II/Ku antigen, its highly specific affinity for double-stranded DNA, its abundance and its newly demonstrated ability to unwind exclusively DNA duplexes, point to an additional, if still unclear, role for this molecule in DNA metabolism.

Adenosine Triphosphatases↗

Human DNA helicase V, a novel DNA unwinding enzyme from HeLa cells.

Using a strand-displacement assay with 32P labeled oligonucleotide annealed to M13 ssDNA we have purified to apparent homogeneity and characterized a novel DNA unwinding enzyme from HeLa cell nuclei, human DNA helicase V (HDH V). This is present in extremely low abundance in the cells and has the highest turnover rate among other human helicases. From 300 grams of cultured cells only 0.012 mg of pure protein was isolated which was free of DNA topoisomerase, ligase, nicking and nuclease activities. The enzyme also shows ATPase activity dependent on single-stranded DNA and has an apparent molecular weight of 92 kDa by SDS-polyacrylamide gel electrophoresis. Only ATP or dATP hydrolysis supports the unwinding activity. The helicase requires a divalent cation (Mg2+ > Mn2+) at an optimum concentration of 1.0 mM for activity; it unwinds DNA duplexes less than 25 bp long and having a ssDNA stretch as short as 49 nucleotides. A replication fork-like structure is not required to perform DNA unwinding. HDH V cannot unwind either blunt-ended duplex DNA or DNA-RNA hybrids; it unwinds DNA unidirectionally by moving in the 3' to 5' direction along the bound strand, a polarity similar to the previously described human DNA helicases I and III (Tuteja et al. Nucleic Acids Res. 18, 6785-6792, 1990; Tuteja et al. Nucleic Acid Res. 20, 5329-5337, 1992) and opposite to that of human DNA helicase IV (Tuteja et al. Nucleic Acid Res. 19, 3613-3618, 1991).

Adenosine Triphosphatases↗

Effects of niacin on biliary lipid output in the rat.

The mechanisms for the hypocholesterolaemic action of niacin (nicotinic acid) were examined in rats administered niacin at a dose of 400 mg/kg body wt/day for either 2 or 4 weeks. Another group of rats were administered diosgenin, an inhibitor of acyl-CoA:cholesterol acyltransferase, as a 1% (w/w) supplement in the diet for 7 days. Both agents produced small increases in bile flow rates (up to 40%) and mild hepatotoxicity evidenced by small increases in serum transaminase activities. Niacin treatment for 2 or 4 weeks lowered serum cholesterol concentrations by 13% or 29%, respectively, with the greatest decrease occurring in the low density lipoprotein fraction. This was accompanied by relatively large increases in biliary cholesterol output (114% and 130% after 2 and 4 weeks treatment, respectively) with smaller increases in the biliary output of phospholipid (18% and 45%) and bile acid (26% and 14%). Diosgenin treatment increased serum cholesterol by 29% and increased the biliary output of cholesterol, phospholipid and bile acid by 800%, 10% and 45%, respectively. Thus, both agents increased the cholesterol saturation of bile (100% by niacin, 500% by diosgenin). Cholesterol and phospholipid in fistula bile from control rats were present in lamellar and micellar forms. Niacin treatment did not alter the physical form of biliary lipids whilst diosgenin caused the appearance of vesicular lipid in fistula bile. Thus, increased biliary secretion of cholesterol explains, at least in part, the hypocholesterolaemic action of niacin. In addition, since aggregation of biliary vesicles is involved in cholesterol gallstone formation in humans, the non-appearance of vesicular material in fistula bile from niacin-treated rats may be of some importance.

Animals↗

DNA helicase III from HeLa cells: an enzyme that acts preferentially on partially unwound DNA duplexes.

Human DNA helicase III, a novel DNA unwinding enzyme, has been purified to apparent homogeneity from nuclear extracts of HeLa cells and characterized. The activity was measured by using a strand displacement assay with a 32P labeled oligonucleotide annealed to M13 ssDNA. From 305 grams of cultured cells 0.26 mg of pure protein was isolated which was free of DNA topoisomerase, ligase, nicking and nuclease activities. The apparent molecular weight is 46 kDa on SDS polyacrylamide gel electrophoresis. The enzyme shows also DNA dependent ATPase activity and moves unidirectionally along the bound strand in 3' to 5' direction. It prefers ATP to dATP as a cofactor and requires a divalent cation (Mg2+ > Mn2+). Helicase III cannot unwind either blunt-ended duplex DNA or DNA-RNA hybrids and requires more than 84 bases of ssDNA in order to exert its unwinding activity. This enzyme is unique among human helicases as it requires a fork-like structure on the substrate for maximum activity, contrary to the previously described human DNA helicases I and IV, (Tuteja et al. Nucleic Acids Res. 18, 6785-6792, 1990; Tuteja et al. Nucleic Acids Res. 19, 3613-3618, 1991).

Adenosine Triphosphate↗