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Biomedical subjects

N Ahmed

Publications and source records attributed to N Ahmed.

At least 19 recordsLinked to original sources
PubMed1996

Peptides derived from C-reactive protein inhibit neutrophil alveolitis.

C-reactive protein (CRP) is the classic acute phase reactant in humans, with serum levels elevated up to 1000-fold after the onset of inflammation. CRP inhibits chemotaxis of complement (C5a)-, LTB4-, IL-8-, and FMLP-stimulated neutrophils in vitro, and rabbits and transgenic mice with elevated serum CRP levels exhibit diminished neutrophil infiltration and vascular permeability in models of chemotactic factor-induced alveolitis. To evaluate the mechanism of CRP inhibition on chemoattractant-induced neutrophil inflammation in vivo, experiments were performed in mice infused with peptides of human CRP shown to inhibit C5a- and FMLP-stimulated neutrophil chemotaxis in vitro. After direct tracheal instillation of FMLP, mice previously injected via the retro-orbital plexus with CRP peptide 77-82 or 201-206 showed significant reductions (up to 90%) of neutrophils in the bronchoalveolar lavage fluid compared with vehicle-treated mice. Both CRP peptides also significantly (up to 55%) inhibited the increase in alveolar total protein levels. Control injections of native rabbit CRP (3 microM) inhibited neutrophil influx by 93% and protein leak by 55% in mice intratracheally instilled with FMLP. Despite similar levels of inhibition, approximately 10-fold more peptide by weight than native CRP was required. These data suggest that CRP degradation products at sites of tissue injury, in particular CRP peptides 77-82 and 201-206, are anti-inflammatory and can diminish lung injury by a reduction in neutrophil influx and protein leakage into alveoli following FMLP-induced inflammation.

Amino Acid Sequence↗
PubMed1996

Interaction of reactive nitrogen and oxygen intermediates in HL60 and dimethylsulphoxide-differentiated HL60 cells.

The interaction of reactive nitrogen intermediates (RNI) with reactive oxygen intermediates (ROI) was inferred from the effect of added L-arginine on luminol-dependent chemiluminescence (LCL) and cytochrome C reduction in HL60 cells, dimethylsulphoxide (DMSO)-differentiated HL60 cells and human neutrophils. Phorbol myristate acetate (PMA)-stimulated HL60 cells had no effect on LCL and a decreased rate of cytochrome C reduction in the presence of increasing concentrations of L-arginine. Inhibition of L-arginine-mediated cytochrome C reduction was relieved by L-N(G)-monomethyl arginine (L-NMMA), an inhibitor of nitric oxide synthesis, in a concentration-dependent manner. In contrast, DMSO-differentiated cells and human neutrophils separated from blood showed decreased rates of LCL and cytochrome C reduction with increasing concentrations Of L-arginine, which were relieved to some extent by L-NMMA in a dose-dependent manner. These results are consistent with a 40% increase in the production of nitrate following stimulation of DMSO-differentiated cells and human neutrophils by PMA compared with only a 6% rise in undifferentiated HL60 cells. Possible inhibition of NADPH oxidase has been suggested to explain the responses of LCL, cytochrome C reduction and nitrate production by nitric oxide in the presence of L-arginine.

Catalysis↗
PubMed1996

Electrocardiogram in the ambulatory clinic in older patients with cardiac disease: an assessment of the contribution to management.

OBJECTIVE: To assess the value of the routine electrocardiogram (EKG) in the management of older (> 65 years) patients with cardiac disease during return visits to the ambulatory clinic. DESIGN: Retrospective chart analysis. SUBJECTS: Seventy-one patients older than 65 years of age, with cardiac diagnoses, presenting for follow-up visits. METHODS: Chart notes from 254 encounters with 71 patients in a cardiology clinic were analyzed. Excluded were new patients as well as patients followed in special arrhythmia clinics for pacemakers or significant arrhythmias. All patients underwent an EKG during each clinic visit, irrespective of their clinical status, according to the clinic's protocol. The frequency and nature of therapeutic decisions made in the clinic, the contribution of the EKG to the decision-making process, the appropriateness of the EKG, and the physician response to the EKG were assessed. MAIN RESULTS: Therapeutic decisions, the most common of which (28%) was medication changes, were made in 78 (31%) patients. The routine EKG was considered inappropriate in 60%. Unexpected diagnostic information not obtained from history or examination was not present in any encounter. EKG findings were not addressed by physicians in 22%. CONCLUSIONS: Most older patients seen in the cardiology clinic for return visits with stable symptoms do not benefit from EKGs. Unexpected diagnostic information from the EKG leading to major therapeutic decisions is rare in older people with stable symptoms.

Aged↗
PubMed1996

An investigation of the validity of attachment level measurements with an automated periodontal probe.

There is a need for information on the validity of probing depth and attachment level measurements made with automated probes. In this study, 34 teeth in 9 patients were measured with the Florida probe from points marked with a bur prior to extraction. After extraction, connective tissue attachment levels were measured from the same points with a dissecting microscope. Mean measurements of attachment level were similar with probing (5.13 +/- 2.08 mm) and laboratory (5.18 +/- 2.26 mm) assessments. The correlation between these measurements was 0.72 (p < 0.001), and a t-test of the paired measurements showed no difference (t = 0.44; p = 0.66). The Florida probe thus showed satisfactory validity for this group of measurements of advanced periodontitis. However, there was substantial lack of agreement between individual probing measurements and the validity criterion of laboratory attachment level measurements, and the intra-class correlation coefficient was 0.46. It was concluded that the Florida probe was suitable for studies in which measurements were averaged, but not for longitudinal study of individual sites.

Adult↗
PubMed1996

Transgenic mice expressing rabbit C-reactive protein exhibit diminished chemotactic factor-induced alveolitis.

The acute phase protein, C-reactive protein (CRP), can increase more than a thousandfold during acute inflammatory states, and it is known to modulate neutrophil-mediated inflammatory responses. We have previously shown that CRP inhibits chemotaxis of C5a-stimulated neutrophils in vitro and that rabbits with elevated CRP blood levels exhibit diminished pulmonary vascular permeability and neutrophil infiltration in a model of alveolitis. To study the effect of CRP on alveolitis induced by different chemoattractants, transgenic mice capable of expressing rabbit CRP in a dietary-inducible fashion were treated with inflammatory doses of the chemoattractants. Intratracheal installation of FMLP (8 x 10(-10) mol), LTB4 (2 x 10(-11) mol), or IL-8 (5 x 10(-12) mol) in normal CF1 mice resulted in significant (p<0.05) influx of neutrophils and protein into the alveolar space. Transgenic mice with elevated plasma levels of CRP showed significantly (p<0.05) diminished infiltration of neutrophils into bronchoalveolar lavage fluid (BALF) and significant reduction in BALF protein compared with that in normal mice. Rabbit CRP (10 to 500 micrograms/ml) inhibited in vitro neutrophil chemotaxis in a concentration-dependent fashion when stimulated by the various chemoattractants examined. These data show that rabbit CRP can modify both in vivo and in vitro neutrophil responses to several classes of chemoattractants and that CRP has a significant protective effect in alveolitis by reducing neutrophil influx and protein leakage into the lung.

Animals↗
PubMed1995

Biochemical effect of three different inhibitors of purine/pyrimidine metabolism on differentiation in HL60 cells.

The effects of three different nucleotide biosynthesis inhibitors were tested on differentiation and purine/pyrimidine metabolism in HL60 cells. On the three nucleotide biosynthesis inhibitors, acivicin and mycophenolic acid were able to differentiate HL60 cells, while alanosine failed to do so. Differentiation of HL60 cells by acivicin and mycophenolic acid was associated with substantial decreases in both the guanylate and adenylate pools and appeared to be dependent on the state of depletion of intracellular GTP. Simultaneous addition of guanosine or guanine to mycophenolic acid-treated cells restored the GTP pool and prevented differentiation from occurring. Adenine or adenosine had no such effect, while hypoxanthine and inosine partially reversed the differentiation. In acivicin-treated cells, simultaneous addition of guanine caused partial prevention of differentiation. Even though treatment of HL60 cells with alanosine resulted in the depletion of guanylates, this effect was secondary to the depletion of adenylates and developed only upon prolonged exposure. In all the inhibitor-treated cells the activities of the key regulatory enzymes of de novo purine biosynthesis were affected. Even though the measurable activity of hypoxanthine/guanine phosphoribosyl transferase was enhanced in inhibitor-treated cells, the activity of the salvage pathway was inhibited in mycophenolic acid and alanosine-treated cells. Besides de novo purine nucleotide biosynthesis, de novo pyrimidine nucleotide biosynthesis was also inhibited in inhibitor-treated cells. The inhibition of purine and pyrimidine nucleotide biosynthesis in mycophenolic acid, acivicin and alanosine-treated cells resulted in an increase in the steady-state concentration of PRPP. Since purine and pyrimidine nucleotides play an important role in the synthesis of important macromolecules, it can be suggested that depletion of guanine ribonucleotide as a result of inhibition of early de novo purine biosynthesis, or due to specific inhibition of de novo guanine nucleotide biosynthesis, may be an obligatory step in the initiation of differentiation in mycophenolic acid and acivicin-treated HL60 cells.

Alanine↗
PubMed1995

HPLC investigation on Ni(II)-mediated DNA damage in the presence of t-butyl hydroperoxide and glutathione.

By use of HPLC with UV and electrochemical detection, the present study demonstrates that reaction of Ni2+ with t-butyl hydroperoxide in the presence of glutathioine (GSH) generates 8-hydroxy-2'-deoxyguanosine (8-OH-dG) from 2'-deoxyguanosine (dG) and from dG residues in calf thymus DNA at physiological pH. No significant amount of 8-OH-dG was generated in the absence of GSH, indicating an important role of GSH in enhancing the reactivity of Ni2+ toward lipid hydroperoxide to oxidize dG or dG residues in DNA. The rate of dG conversion to 8-OH-dG depends on the concentration of the reagents. During a two hour incubation of 0.75 mM dG, 10 mM t-butyl hydroperoxide, 1 mM Ni2+, and 2 mM GSH at room temperature under ambient air, dG was converted to 8-OH-dG with a yield of about 0.2%. For dG residues in DNA, 24 hour incubation at 37 degrees C yielded 0.1% 8-OH-dG. The 8-OH-dG generation from both dG and dG residues in DNA was inhibited by superoxide dismutase, catalase, and ethanol (hydroxyl radical scavenger), implying the involvement of oxygen free radicals in the 8-OH-dG generation process. The metal ion chelators, deferoxamine and EDTA, efficiently inhibited the 8-OH-dG formation. Similar results were obtained for the conversion of dG residues in calf thymus DNA to 8-OH-dG. Electrophoretic assays of DNA strand breaks showed that Ni2+ caused DNA double-strand breaks in the presence of t-butyl hydroperoxide and GSH. Because GSH is ubiquitously present in cellular systems at relatively high concentration, and the exposure of cells to Ni2+ results in the generation of lipid hydroperoxides, the 8-OH-dG generation and DNA double-strand breaks caused by the reaction of Ni2+ with lipid hydroperoxides in the presence of GSH may be an important mechanism in Ni(2+)-induced carcinogenesis. The inhibitory effect of chelators suggests a possible prevention strategy against Ni(2+)-induced toxicity and carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Comparison of phenytoin with auranofin and chloroquine in rheumatoid arthritis--a double blind study.

OBJECTIVE: To evaluate efficacy of phenytoin in modifying the course of rheumatoid arthritis (RA) by comparing it to gold (auranofin) and chloroquine. METHODS: A double blind, randomized study of 6 months' duration was conducted at the Nizam Institute of Medical Sciences, Hyderabad, India. One hundred and thirty-two patients with active RA (defined by the 1987 ARA criteria) were entered into the study and randomized into 3 groups: phenytoin, chloroquine, or auranofin. RESULTS: Full data were evaluable in 100 patients who satisfactorily completed the protocol (phenytoin, 35; auranofin, 30; and chloroquine, 35). Twenty-four patients were noncompliant and did not take medication or return for evaluation; 8 patients had the drug withdrawn because of side effects before study completion. For each of the 3 drugs all clinical and laboratory variables improved when pre and posttreatment values (p < 0.05 to 0.001) were compared. There was a greater reduction in posttreatment mean morning stiffness in the chloroquine group than in the phenytoin and auranofin groups (p < 0.05). Posttreatment grip strength was also greatest in the chloroquine group. On the other hand, there were statistically significant decreases in IgM levels in both the phenytoin and auranofin groups (p < 0.001), but not with chloroquine. Among the 53 patients with a disease history of 3-6 months, global outcome was best with phenytoin (16/17), compared to chloroquine (12/18) and auranofin (12/18) (p < 0.03). However, there was no such difference in the 47 patients in all 3 groups with a disease history longer than 6 months. Eight patients had side effects (phenytoin, auranofin, 2; chloroquine, 1) requiring withdrawal of the drug. However, the incidence of side effects was not significantly different for the 3 drugs. CONCLUSION: Our data indicate that phenytoin is comparable to auranofin and chloroquine in its efficacy in RA and may be considered an alternative disease modifying agent for RA.

Adult↗
PubMed1995

Initial experience with telebrachytherapy treatment in palliation of advanced oesophageal cancer.

Ten patients with advanced metastatic squamous cell carcinoma of the middle third of the oesophagus were treated with palliative external radiotherapy and intraluminal brachytherapy. All patients had long lesions, 8-15 cm in length, and narrow lumens that did not allow the passage of a guidewire for dilatation. Improvement in dysphagia by more than 2 grades was seen in 9 of 10 patients. This finding was correlated with an increase in the size of the oesophageal lumen at the end of 6 weeks following treatment by barium swallow. No complications of treatment were noted in any patient. Low doses of external beam radiotherapy and high-dose-rate intraluminal brachytherapy can provide quick and effective palliation in advanced metastatic oesophageal carcinoma.

Adult↗
PubMed1995

Evaluation of oral midazolam as pre-medication in day care surgery in adult Pakistani patients.

A placebo controlled randomized double blind study was designed to assess the suitability of oral Midazolam as a premedication in day care surgery in adult Pakistani patients. Fifty ASA I and II patients aged between 20-60 years received either Midazolam 7.5 mg or a placebo approximately one hour prior to surgery. Midazolam 7.5 mg produced significant anxiolysis and sedation (p < 0.001) in comparison to placebo after one hour of premedication. There was a significant difference (p < 0.001) in the mean heart rate and blood pressure in both groups after 1 hour of premedication with a lesser rise in blood pressure and heart rate in the Midazolam group. Psychomotor performance assessed by 'n' deletion test was impaired by Midazolam (p < 0.001) and recall of pictures revealed differences (p < 0.05) in the groups at one hour after premedication. However, at four hours after surgery there were no differences in both groups. These findings indicate that rapidly acting oral Midazolam in doses of 7.5 mg provided safe and effective premedication in terms of anxiolysis, sedation, amnesia and psychomotor performance and is suitable for day surgery.

Administration, Oral↗
PubMed1994

Generation of thiyl and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH.

Electron spin resonance (ESR) spin trapping was utilized to investigate the reaction of peroxynitrite with thiols and ascorbate at physiological pH. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The reaction of peroxynitrite with DMPO generated 5,5-dimethylpyrrolidone-(2)-oxy-(1) (DMPOX). Formate enhanced the peroxynitrite decomposition but did not generate any detectable amount of formate-derived free radicals. Thus, the spin trapping measurements provided no evidence for hydroxyl (.OH) radical generation in peroxynitrite decomposition at physiological pH. Thiols (glutathione, cysteine, and penicillamine) and ascorbate reacted with peroxynitrite to generate the corresponding thiyl and ascorbyl radicals. The one-electron oxidation of thiols by peroxynitrite may be one of the important mechanisms for peroxynitrite-induced toxicity and ascorbate may provide a detoxification pathway.

Ascorbic Acid↗
PubMed1994

A microassay for urinary phenol using capillary gas chromatography and optimised enzymic hydrolysis.

An improved capillary gas chromatography method is described for the assay of urinary phenol for the assessment of benzene exposure. Enzymatic hydrolysis with an extract of Helix pomatia is used to liberate phenol from its glucuronide and sulphate conjugates in urine and has the advantage in that complete hydrolysis occurs and clean chromatograms are produced. Furthermore, an internal standard (2,4-xylenol) has been incorporated in the method enabling rapid and single step extraction of phenol. The microassay can be used to measure phenol concentrations as low as 1 mg/l in urine thus making it a suitable method for monitoring benzene exposure.

Benzene↗
PubMed1994

Purine metabolism in promyelocytic HL60 and dimethylsulphoxide-differentiated HL60 cells.

Purine metabolism was studied in the human promyelocytic leukaemic cell line HL60 both before and after differentiation by dimethylsulphoxide (DMSO) treatment in vitro. DMSO-induced differentiation had no effect on the steady-state concentration of 5-phosphoribosylpyrophosphate (PRPP), even though the activity of the oxidative segment of the pentose phosphate pathway (OPP) increased two-fold and the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were enhanced 3-6 times. [14C]-formate incorporation, on the other hand, showed that undifferentiated HL60 cells produced purines by the de novo pathway at six-fold the rate of the differentiated cells and at three times the rate measured in polymorphonuclear leukocytes (PMNs) separated from human blood. This is consistent with significantly higher activities (two to five-fold) of the key regulatory enzymes of the de novo purine synthesis pathway (PRPP synthetase, amido-phosphoribosyl transferase and adenylosuccinate synthase) in the undifferentiated cells. Labelling the cells with [14C]-hypoxanthine showed that there was an active salvage pathway in the HL60 cells which remained unaltered by differentiation. The activities of the salvage enzymes were also the same, although hypoxanthine was taken up at twice the rate by the undifferentiated cells. Human PMNs had an active salvage pathway, but their rate was five times lower than that of the HL60 cells, consistent with much lower activities (three to eight-fold) of the salvage pathway enzymes. These observations suggest that regulation of the synthesis and activities of the purine nucleotide synthesis enzymes may play an important role in the regulation of differentiation of myeloid cells.

Cell Differentiation↗
PubMed1994

Management of tuberculosis by practitioners of Peshawar.

In this report the drug prescribing practices of practitioners are described. The results indicate that a high proportion (80%) of practitioners still prescribe long duration chemotherapy. The most frequently prescribed drugs are rifampicin (87%), isoniazid (89%) and streptomycin (73%). Despite the use of these highly effective drugs the duration of illness after diagnosis in 31% is over three years. The possible reasons for the poor control of the disease are noncompliance with treatment and multidrug resistance of mycobacterium tuberculosis. The prescribing practices of the practitioners indicate that they are not receiving continuing education and training on the case management of TB.

Child↗