PubMed Health⌕ Search

Biomedical subjects

N Mahmood

Publications and source records attributed to N Mahmood.

At least 19 recordsLinked to original sources
PubMed1999

Expression of cytokeratin 20 redefines urothelial papillomas of the bladder.

BACKGROUND: Most non-invasive urothelial tumours of the bladder are diagnosed as papillary carcinomas in accordance with the WHO classification and because the identification of papillomas is difficult by routine histology; some patients are therefore misdiagnosed. This practice is associated with psychological morbidity for the patient and may also skew cancer statistics. Cytokeratin 20 (CK20) is a sensitive marker of urothelial differentiation. We investigated whether this marker could be used in the identification of urothelial papillomas and used the rate of recurrence as an indicator to assess the biological behaviour of such tumours. METHODS: In a prospective study, immunocytochemistry for CK20 was done on tumours of all patients who presented for the first time with non-invasive papillary bladder tumours. We classified the expression pattern of CK20 as normal or abnormal at the time of initial diagnosis. We recorded time to first biopsy-proven recurrence or length of follow-up when no recurrence was observed. FINDINGS: Of 58 consecutive patients, ten had tumours with a normal pattern of CK20 expression. No patients developed further tumours during the follow-up (median 18 [range 13-28] months). By contrast, 30 (73%) of the 41 evaluable patients with tumours that showed abnormal CK20 expression developed further tumours; the median time to a second tumour was 6 (2-24) months. The only factor that had a significant effect on the outcome of patients in terms of recurrence was expression of CK20 (p<0.0001). INTERPRETATION: Normal urothelial differentiation, as evidenced by a normal pattern of CK20 expression, is retained in a proportion of non-invasive papillary urothelial tumours and thus justifies use of the term urothelial papilloma. A large-scale study is needed to investigate the outcome of patients with such tumours.

Adult↗
PubMed1999

Protection against oxidative damage and cell death by the natural antioxidant ergothioneine.

The natural antioxidant ergothioneine (EGT) was tested for its ability to inhibit cell death caused by hydrogen peroxide (H2O2) and to inhibit DNA oxidation by peroxynitrite (ONOO-) in human neuronal hybridoma cell line (N-18-RE-105). High concentrations of EGT (5 mM) were tolerated by the N-18-RE-105 cells. N-acetylcysteine (NAC) was not well tolerated by the cells at concentrations greater than 3 mM (cell viability averaged 50%). Increasing concentrations of EGT increases cell viability in the presence of NAC. EGT at concentrations up to 2 mM weakly improved cell viability in the presence of H2O2. NAC at concentrations up to 2 mM weakly decreased, but not significantly, the viability of the cells. At a higher concentration of 5 mM, NAC weakly protected the neuronal cells against the H2O2-induced cell death. The protection was significantly enhanced by preincubation with EGT. Ergothioneine inhibited ONOO(-)-induced oxidative damage in isolated calf thymus DNA and DNA in N-18-RE-105 cells. The concentration of EGT in human and mammalian tissue has been estimated to be 1-2 mM, which suggests that EGT may serve as a non-toxic thiol buffering antioxidant in vivo and may find applications in pharmaceutical preparations where oxidative stability is desired.

Animals↗
PubMed1999

Aspiration pneumonia in pediatric age group: etiology, predisposing factors and clinical outcome.

INTRODUCTION: Aspiration pneumonia in children is an important disease in terms of the morbidity and mortality associated with it. The objective of this study is to characterize the cases of aspiration pneumonia on the basis of the predisposing factors, types of aspiration syndromes, materials aspirated and their clinical outcome. METHODS: A total of 107 patients diagnosed as having aspiration pneumonia, were included in this study. Cases were between 0-15 years of age, admitted to the Aga Khan University Hospital (AKUH) over five years. RESULTS: The most common form of aspiration syndrome seen was chemical pneumonitis (52.1%). The three most common factors predisposing to pulmonary aspiration were accidental ingestion (37.4%), altered consciousness (34.6%) and neurologic disorders (29%). Children who aspirated oropharyngeal flora were at higher odds to require mechanical ventilation than those aspirating inert fluids and particulate matter (OR = 6.4, 95% CI: 1.5-29.2, p = 0.003). Milk (31.8%), kerosene (21.5%) and oral secretions (19.6%) were the most common materials aspirated. Betel nuts were the most commonly aspirated foreign body. Patients aspirating oral secretions and milk were seen to have a relatively worse clinical outcome than those aspirating kerosene oil. CONCLUSION: Aspiration pneumonia is a relatively uncommon clinical entity at AKUH in children. However, it does cause significant morbidity and mortality.

Adolescent↗
PubMed1999

[S]-AR-R 15896AR-A novel anticonvulsant: acute safety, pharmacokinetic and pharmacodynamic properties.

A rational, chemical, synthetic effort to identify promising low-affinity uncompetitive N-methyl-D-aspartic acid receptor antagonists for use as antiepileptic drugs led to the discovery of AR-R 15035AR, or [RS]-alpha-phenyl-2-pyridine-ethanamine.2HCl. Chiral separation followed by intensive in vivo screening resulted in the selection of the [S] enantiomer, AR-R 15896AR, as the best compound for further preclinical development. AR-R 15896AR prevented tonic seizures in rodents for up to 6 to 8 h in response to maximal electroshock (MES), 4-aminopyridine, bicuculline, or strychnine, as well as characteristic seizures following injections of N-methyl-DL-aspartic or kainic acids. AR-R 15896AR was ineffective in two kindling models of epilepsy, did not produce tolerance to MES, and was devoid of proconvulsant and phencyclidine-like properties in mice and rats, respectively. Therapeutic indices for AR-R 15896AR were comparable to or exceeded those for standard anticonvulsants. Orally administered AR-R 15896AR rapidly entered the rat brain and was eliminated in parallel from the plasma and plasma-free compartment. A dose-response relationship between plasma and brain levels after p.o. or i.v. administration of AR-R 15896AR and protection against MES was highly correlative. The time course for loss of protection against MES mirrored the elimination of the compound from brain and plasma. The total brain concentration (25 microM) of drug at the ED50 value (approximately 3 mg/kg) for protection against MES seizures was consistent with the reported affinity of AR-R 15896AR at the N-methyl-D- aspartic acid binding site (IC50 value = 1.3 microM). The present findings demonstrated the attractiveness of AR-R 15896AR as a candidate for further development to treat epilepsy.

4-Aminopyridine↗
PubMed1998

The patients perspective of extracorporeal shock wave lithotripsy.

We studied the effect of a single analgesic regime for outpatient lithotripsy on the patient's perception of pain and the disruption of their normal activities by sending a postal questionnaire to 200 patients. Results showed that 15% of patients received insufficient analgesia during ESWL, 25% considered treatment painful, 6.8% had side effects from analgesia, 18% had delayed return to their normal activities and 33% contacted their doctor within a week of lithotripsy with problems related to it. This study shows that analgesic requirements of patients treated with modern lithotriptors are underestimated. This can be avoided by tailoring analgesia to individual needs and better patient communication.

Adolescent↗
PubMed1998

Anti-HIV activity and mechanism of action of macrocyclic diamide SRR-SB3.

The importance of cyclic compounds as anti-cancer and anti-viral agents has been recognized for some time. We have studied a series of macrocyclic amide derivatives for activity against HIV infection of T lymphocytes in-vitro. Compounds containing aromatic rings and sulphur atoms were generally active, however the selectivity was greatly enhanced when two benzene rings were bridged by a disulphide linkage to produce 7-methyl-6,7,8,9-tetrahydrodibenzo[c,k][1,2,6,9]-dithiadiazacyc lododecine-5,10-dione (SRR-SB3). This compound was studied in detail with different cell and virus infections including macrophages and chronically infected H9 cells. It was active with an EC50 (the dose affording 50% inhibition of infection) of 0.05-01 microg mL(-1) and a TC50 (concentration reducing uninfected cell growth by 50%) of 50 microg mL(-1). The compound did not inhibit protease, but seemed to act by inhibiting maturation of progeny virus, by interfering with precursor protein processing. It was synergistic with AZT (3'-azido-3'-deoxythymidine; zidovudine) when tested in-vitro. The unusual mode of action and potent anti-HIV activity in T lymphocytes and macrophages makes this compound a potential candidate for clinical trials.

Anti-HIV Agents↗
PubMed1997

Flavonol and chalcone ester glycosides from Bidens leucantha.

Four new flavonol 7-O-glycosides 1-4 and a new chalcone ester glycoside 5 have been isolated from the leaves of Bidens leucantha along with four known chalcone ester glycosides 6-9. Their structures were elucidated using a combination of spectroscopic techniques. The in vitro anti-HIV activity of all the compounds was tested as part of our screening of potential anti-AIDS agents from medicinal plants. Although none of the flavonol glycosides was active, a moderate inhibitory effect on viral replication was exerted by chalcone ester glycoside 9.

Anti-HIV Agents↗
PubMed1997

Mechanism of asbestos-mediated DNA damage: role of heme and heme proteins.

Several observations, including studies from this laboratory, demonstrate that asbestos generates free radicals in the biological system that may play a role in the manifestation of asbestos-related cytotoxicity and carcinogenicity. It has also been demonstrated that iron associated with asbestos plays an important role in the asbestos-mediated generation of reactive oxygen species. Exposure to asbestos leads to degradation of heme proteins such as cytochrome P450-releasing heme in cytosol. Our simulation experiments in the presence of heme show that such asbestos-released heme may increase lipid peroxidation and can cause DNA damage. Further, heme and horseradish peroxidase (HRP) can cause extensive DNA damage in the presence of asbestos and hydrogen peroxide/organic peroxide/hydroperoxides. HRP catalyzes oxidation reactions in a manner similar to that of prostaglandin H synthetase. Iron released from asbestos is only partially responsible for DNA damage. However, our studies indicate that DNA damage mediated by asbestos in vivo may be caused by a combination of effects such as the release and participation of iron, heme, and heme moiety of prostaglandin H synthetase in free radical generation from peroxides and hydroperoxides.

Animals↗
PubMed1997

Management of acute respiratory infections by mothers in the community.

Home treatments are important in the management of acute respiratory infection (ARI). In order to examine how urban mothers in Lahore, managed ARI, a study was carried out within 1-km radius of a teaching hospital. A total of 50 mothers who had at least one child aged 2 months-5 years with an ARI from each of three settings-a lower class locality, a middle class locality and the outpatient department of the hospital were interviewed during the winters of 1992-93. A substantial proportion of mothers, particularly those from the lower class locality (44%), did not use home treatment for acute respiratory infection. The majority of mothers indicated that they would not use home treatment if their child had an ARI in the future. The importance of home treatment has to be introduced into the community probably by programmes conducted by health professionals.

Acute Disease↗
PubMed1996

The anti-HIV activity and mechanisms of action of pure compounds isolated from Rosa damascena.

Water and methanol extracts of Rosa damascena exhibited moderate anti-HIV activity. The anti-viral activities of 9 compounds isolated from the methanol extract were compared. The tetrahydroxyflavanone (kaempferol, 1), was effective in reducing the maturation of infectious progeny virus apparently due to selective inhibition of the viral protease. On the other hand the pentahydroxyflavone (quercetin, 2) and two 3-substituted derivatives of kaempferol appeared to inhibit HIV-infection by preventing binding of gp120 to CD4. 2-Phenylethanol-O-(6-O-galloyl)-beta-D-glucopyranoside 8 interacted irreversibly with gp120 and neutralized virus infectivity. The differences in the modes of action of 1 and 8 can account for the apparent synergy of their anti-viral activities.

Anti-HIV Agents↗
PubMed1996

An evaluation of the antioxidant and antiviral action of extracts of rosemary and Provençal herbs.

Extracts of herbs and spices are increasingly of interest in the food industry because they retard oxidative degradation of lipids. There is also increasing interest in the antiviral activity of plant products. A liquid, deodorized rosemary extract and an oily extract of a mixture of Provençal herbs were tested for antioxidant and antiviral action in vitro. The rosemary extract (Herbor 025) and the extract of Provençal herbs (Spice Cocktail) inhibited peroxidation of phospholipid liposomes with 50% inhibition concentration values of 0.0009% (v/v) and 0.0035% (v/v), respectively. Herbor 025 and the spice cocktail (at 0.2%, v/v) reacted with trichloromethylperoxyl radical with calculated rates of 2.7 x 10(4) s-1 and 1.5 x 10(3) s-1, respectively. The main active components in the herbal preparations, carnosol and carnosic acid, at 0.05% (v/v) react with rate constants of (1-3) x 10(6) M-1 sec-1 and 2.7 x 10(7) M-1 sec-1, respectively. Both extracts show good antioxidant activity in the Rancimat test, especially in lard. Herbor 025 and the spice cocktail inhibited human immunodeficiency virus (HIV) infection at very low concentrations which were also cytotoxic. However, purified carnosol exhibited definite anti-HIV activity at a concentration (8 microM) which was not cytotoxic. Both preparations promoted some DNA damage in the copper-phenanthroline and the bleomycin-iron systems. The two herbal preparations possess antioxidant properties that may make them useful in the food matrix.

Abietanes↗
PubMed1996

Constituents of Ardisia japonica and their in vitro anti-HIV activity.

As part of our screening of anti-AIDS agents from medicinal plants, the MeOH extract of the aerial parts of Ardisia japonica was tested, and it showed moderate in vitro anti-HIV activity. Reexamination to identify the compounds responsible for the anti-HIV activity revealed several known compounds and a new triterpenoid saponin (4) whose structure elucidation was accomplished by 1H-1H correlation spectroscopy (COSY, HOHAHA, ROESY) and 1H-13C heteronuclear correlation (HETCOR) NMR experiments. All of the isolated compounds were tested and, although none of the triterpenoid saponins was active, bergenin and norbergenin showed weak anti-HIV activity.

Antiviral Agents↗
PubMed1995

Synthesis and biological evaluation of N6-cycloalkyl derivatives of 1-deazaadenine nucleosides: a new class of anti-human immunodeficiency virus agents.

A series of 1-deazaadenine nucleosides with the N6 nitrogen unsubstituted or bearing methyl or cycloalkyl substituents, with or without a chloro group in the 2-position, and with the glycosylic moiety being ribose (1-16), 2'-deoxyribose (17-32), or 2', 3'-dideoxyribose (33-48) were designed and synthesized starting from 5,7-dichloro-3H-imidazo[4,5-b] pyridine (50). These compounds were evaluated for their in vitro activity against human immunodeficiency virus type-1 (HIV-1) and herpes simplex virus type-1 (HSV-1). In addition they were tested for their ability to inhibit adenosine deaminase (ADA) from calf intestine. While the parent compounds 1-deazaadenosine (9), 2'-deoxy-1-deazaadenosine (25), and 2',3'-dideoxy-1- deazaadenosine (41) and the corresponding 2-chloro derivatives were inactive, nucleosides bearing cycloalkyl substituents on N6 exhibited moderate to good anti-HIV-1 activity, compared to 2',3'-dideoxyadenosine, with the degree and pattern of improvement depending on the structure of the sugar moiety. In general, 2'-deoxy- and 2',3'-dideoxy derivatives were more potent compounds than the corresponding ribose nucleosides. Compounds bearing a 6-cycloheptyl or cyclooctylamine were the most active in every series. The presence of a chloro group in the 2-position improved both activity and therapeutic index in every series, the most active compound being 2'-deoxy-2-chloro-N6-cycloheptyl-1-deazaadenosine (23; ED50 = 0.2 microM). On the other hand, most of these derivatives were inactive as anti-HSV-1 agents, showing a high degree of virus selectivity. The 1-deazaadenine derivatives were not substrates of adenosine deaminase, and some of them proved to be good inhibitors of the enzyme. However, the ADA inhibitory activity does not account for the antiviral potency since increased lipophilicity and steric hindrance of substituents resulted in derivatives much less active than the parent compounds.

Adenosine↗
PubMed1995

Anti-(human immunodeficiency virus) activity of polyoxotungstates and their inhibition of human immunodeficiency virus reverse transcriptase.

Heteropolyoxotungstates of the Keggin class containing different heteroatoms were tested for inhibition of two strains of human immunodeficiency virus 1 (HIV-1); they exhibited varying antiviral activity. Compounds containing boron were inactive, only one of those containing phosphorus showed selective anti-viral activity, whereas all silicon-containing compounds exhibited significant anti-viral activity in C8166 cells infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silicotungstates were effective inhibitors of HIV reverse transcriptase, showing greater inhibition with RNA/DNA template primers than with DNA/DNA template.primer. Kinetic analysis demonstrated that they inhibit the enzyme by different mechanisms, as, of the four compounds examined, two competed with template.primer and two competed with deoxynucleoside triphosphate. Inhibition of DNA polymerase activity by these compounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse transcriptase, they did not inhibit all DNA polymerases to a similar degree.

Antiviral Agents↗
PubMed1995

Augmentation of chrysotile-induced oxidative stress by BHA in mice lungs.

Asbestos is known to induce oxidative stress in the lung. The consumption of butylated hydroxyanisole (BHA) in preserved food and soft drinks is increasing in the general population, which includes workers in asbestos factories. Because there is no information on the effect of co-exposure to chrysotile and BHA, the time-dependent effects of a single intratracheal dose of chrysotile (1 mg per mouse) and a single ip dose of BHA (350 mg/kg body weight) on various indices of oxidative stress such as lipid peroxidation, hydrogen peroxide generation, glutathione peroxidase (GPX), glutathione reductase (GR), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione (GSH) were followed for up to 14 days. Microsomal lipid peroxidation (as well as that induced by NADPH) was significantly enhanced by BHA in the chrysotile-exposed group. GPX and GR activities in the same group were gradually decreased by BHA. Non-significant modulation of catalase activity by BHA was also noted. BHA induces GSH to a significant extent in lungs exposed with chrysotile. An increase in the G6PDH activity was maximal (19%; P < 0.05) at day 3. The results clearly demonstrate that BHA enhances chrysotile-induced oxidative stress in the lung.

Animals↗
PubMed1994

Certain phosphoramidate derivatives of dideoxy uridine (ddU) are active against HIV and successfully by-pass thymidine kinase.

As part of our effort to deliver masked phosphates inside living cells we have discovered that certain phosphate triester derivatives of the inactive nucleoside analogue, dideoxy uridine (ddU) are inhibitors of HIV replication at microM levels. Moreover, we note that certain phosphoramidate derivatives retain their activity in thymidine kinase-deficient cells, which indicates that they do indeed act by intracellular release of the free nucleotide, and that they successfully by-pass the nucleoside kinase. The increased structural freedom in drug design which this allows may have implications for dealing with the emergence of resistance and may stimulate the discovery of improved therapeutic agents.

Antiviral Agents↗