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Biomedical subjects

A Rahman

Publications and source records attributed to A Rahman.

At least 163 records · Page 9Linked to original sources
PubMed1998

E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation.

Because reactive oxygen species (ROS) can function as second messengers and regulate the activation of the transcription factor nuclear factor (NF)-kappaB, we investigated the possible role of tumor necrosis factor-alpha (TNF-alpha)-induced ROS generation in endothelial cells in signaling E-selectin gene transcription. We demonstrated that stimulation of human pulmonary artery endothelial cells with TNF-alpha (100 U/ml) resulted in ROS production using the oxidant-sensitive dye 5 (and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate bis(acetoxymethyl)ester. Pretreatment with N-acetyl-L-cysteine (NAC) or pyrrolidine dithiocarbamate (PDTC) for 0.5 h inhibited TNF-alpha-induced generation of ROS as well as activation of NF-kappaB and E-selectin mRNA and the cell surface protein expression. These findings indicate that TNF-alpha induces NF-kappaB activation and the resultant E-selectin gene expression by a pathway that involves formation of ROS and that E-selectin expression can be inhibited by the antioxidant action of NAC or PDTC. The results support the hypothesis that generation of ROS in endothelial cells induced by proinflammatory cytokines such as TNF-alpha is a critical signal mediating E-selectin expression.

Acetylcysteine↗
PubMed1998

Managing diabetes during glucocorticoid therapy. How to avoid metabolic emergencies.

Although glucocorticoid therapy carries a risk of promoting or exacerbating hyperglycemia, there are currently no established medical guidelines for detecting or managing diabetes in patients starting such therapy. The authors use three case reports to illustrate a relatively simple strategy that can be used to manage preexisting and new-onset diabetes in the primary care setting.

Aged↗
PubMed1998

Comparative in vivo studies with paclitaxel and liposome-encapsulated paclitaxel.

Our study was designed to evaluate the pharmacokinetics, tissue distribution, toxicity and therapeutic efficacy of liposome-encapsulated paclitaxel (LET) in comparison to conventional paclitaxel. In normal mice, LET was much less toxic than the conventional drug. A dose of 32.5 mg/kg of conventional paclitaxel administered i.v. on three consecutive days produced 100% mortality by day three, while liposomal paclitaxel exhibited no mortality. The control group which received Diluent 12 (Chremophor EL and ethanol; 1:1 v/v), a vehicle used in conventional paclitaxel, 30% mortality was observed at this dosage level. In murine ascitic L1210 leukemia model, liposomal paclitaxel and conventional paclitaxel showed comparable antitumor activity. The pharmacokinetics of conventional paclitaxel and LET was studied in mice at dose levels of 5 mg/kg and 20 mg/kg. After intravenous administration of conventional paclitaxel at a dose of 5 mg/kg, the area under the plasma-concentration-time curve (AUC) was 2-fold lower and, the elimination half-life was 2-times shorter compared to LET. At a dose of 20 mg/kg, the terminal half-lives were comparable, however, conventional paclitaxel displayed non-linear pharmacokinetics with disproportionate increase in AUC. At the two dose levels studied, LET demonstrated linear kinetics. Tissue distribution of paclitaxel after administration of LET showed levels 10-fold higher in spleen and 3.5-fold higher in liver as compared to conventional paclitaxel. The significant decrease in toxicity shown by LET, coupled with an increase in plasma AUC and half-life indicates that LET may be a viable alternative to the therapeutic use of the conventional preparation of paclitaxel.

Animals↗
PubMed1998

A global review of laws on induced abortion, 1985-1997.

CONTEXT: The legal status of induced abortion helps determine the availability of safe, affordable abortion services in a country, which in turn influences rates of maternal mortality and morbidity. It is important, therefore, for health professionals to know both the current status of abortion laws worldwide and the extent to which those laws are changing. METHODS: Abortion-related laws in 152 nations and dependent territories with populations of one million or more were reviewed, and changes in these laws since 1985 were documented. RESULTS: Currently 61% of the world's people live in countries where induced abortion is permitted either for a wide range of reasons or without restriction as to reason; in contrast, 25% reside in nations where abortion is generally prohibited. However, even in countries with highly restrictive laws, induced abortion is usually permitted when the woman's life is endangered; in contrast, even in nations with very liberal laws, access may be limited by gestational age restrictions, requirements that third parties authorize an abortion or limitations on the types of facilities that perform induced abortions. Since 1985, 19 nations have significantly liberalized their abortion laws; only one country has substantially curtailed legal access to abortion. CONCLUSIONS: A global trend toward liberalization of abortion laws observed before 1985 appears to have continued in more recent years. Nevertheless, women's ability to obtain abortion services is affected not just by the laws in force in a particular country, but also by how these laws are interpreted, how they are enforced and what the attitude of the medical community is toward abortion.

Abortion, Induced↗
PubMed1998

Single lung transplantation for emphysema: predictors for native lung hyperinflation.

BACKGROUND: Single lung transplantation is an established procedure for the treatment of respiratory failure resulting from emphysema. Initial concerns suggested that ventilation/perfusion mismatch may result in an unsatisfactory outcome, but good clinical results proved those concerns to be unfounded. However, a proportion of patients have had development of native lung hyperinflation (NLH), with increased morbidity and mortality rates. This study was undertaken to evaluate the factors that might predict those patients with emphysema who are at greatest risk for development of NLH. METHODS: We retrospectively analyzed data from 27 patients who underwent 31 single lung transplantations for emphysema. The patients were divided into two groups: group A, 12 patients with development of acute or chronic NLH, and group B, 15 patients without development of hyperinflation. NLH was defined as radiologic mediastinal shift with flattening of the ipsilateral diaphragm associated with respiratory dysfunction or hemodynamic instability. All preoperative and postoperative data from recipients and data from donors were analyzed. RESULTS: There were no differences between the two groups regarding age, preoperative partial pressure of oxygen, partial pressure of carbon dioxide, acid-base status, donor lung size and physiological structure, side of transplantation, primary pathologic condition, rejection score, infection episodes and obliterative bronchiolitis in the transplanted lung after operation. Patients with NLH had a significantly higher preoperative mean pulmonary artery pressure of 31.6 mm Hg (confidence interval [CI] 26.7 to 35.7), transpulmonary gradient of 20.5 mm Hg (CI 17.4 to 23.5), a lower mean forced expiratory volume in 1 second of 427 ml (CI 352 to 502), and higher mean residual volume of 4450 ml (CI 3769 to 5132). The duration of ventilation, 168 hours (CI 45 to 290), and the postoperative mean pulmonary artery pressure of 26 mm Hg (CI 23 to 28.7) are significantly higher in the hyperinflation group. Early death in group A (n = 5) was higher than in group B (no deaths) (p = 0.02). Six patients in group A required surgical treatment (two early native lung volume reductions, two early ipsilateral retransplantations, and two late contralateral transplantations). Group A patients tended to have poorer long-term lung function after transplantation, with reduced forced expiratory volume in 1 second, forced vital capacity, and higher residual volume (p = NS). CONCLUSION: Patients with end-stage emphysema and relative pulmonary hypertension, severe airway obstruction, and air trapping are at greatest risk for development of early and late NLH. In this subgroup of patients, an alternative treatment strategy may be considered.

Diaphragm↗
PubMed1997

Protective effect of liposome encapsulation on paclitaxel developmental toxicity in the rat.

Paclitaxel is an anticancer drug that has demonstrated severe embryotoxicity in chicks. This embryotoxicity is reduced by liposome encapsulation of the drug. The current study was designed to evaluate the potential of liposome encapsulation for reducing paclitaxel embryotoxicity in rats. Wistar rats were treated with paclitaxel on day 8 of pregnancy (plug = day 0) at doses of 0.67, 2.0, or 10.0 mg/kg intravenously. The same doses of paclitaxel encapsulated in liposomes were administered intravenously to other groups of animals. Control animals were given blank liposomes. Free paclitaxel produced maternal and embryotoxicity at 10.0 mg/kg with three of seven dams dying and resorption of all embryos in surviving dams. Liposome encapsulation at 10.0 mg/kg was not associated with maternal death and there were live fetuses on evaluation at term, although litter size was reduced and malformations occurred in surviving fetuses. At 2.0 mg/kg free paclitaxel, fetal weight was decreased and resorptions increased. Liposome encapsulation at 2.0 mg/kg produced litter results similar to those obtained in control animals given empty liposomes. Malformations were prominent at 2.0 mg/kg free paclitaxel and at 10.0 mg/kg paclitaxel in liposomes and included exencephaly/anencephaly, ventral wall defects, facial clefts, anophthalmia, diaphragmatic hernia, and defects of the kidney, cardiovascular system, and tail. Liposome encapsulation appeared to shift the developmental response to paclitaxel such that 10 mg/kg encapsulated drug produced effects similar to 2.0 mg/kg free drug. These results may have implications for drug delivery of therapeutic agents used during human pregnancy.

Abnormalities, Drug-Induced↗
PubMed1997

Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats.

Coronary heart disease, hypertension, non-insulin-dependent diabetes and obesity are major causes of ill health in industrial societies. Disturbances of carbohydrate and lipid metabolism are a common feature of these disorders. The bases for these disturbances and their roles in disease pathogenesis are poorly understood. The spontaneously hypertensive rat (SHR), a widely used animal model of essential hypertension, has a global defect in insulin action on glucose metabolism and shows reduced catecholamine action on lipolysis in fat cells. In our study we used cellular defects in carbohydrate and lipid metabolism to dissect the genetics of defective insulin and catecholamine action in the SHR strain. In a genome screen for loci linked to insulin and catecholamine action, we identified two quantitative trait loci (QTLs) for defective insulin action, on chromosome 4 and 12. We found that the major (and perhaps only) genetic determinant of defective control of lipolysis in SHR maps to the same region of chromosome 4. These linkage results were ascertained in at least two independent crosses. As the SHR strain manifests many of the defining features of human metabolic Syndrome X, in which hypertension associates with insulin resistance, dyslipidaemia and abdominal obesity, the identification of genes for defective insulin and catecholamine action in SHR may facilitate gene identification in this syndrome and in related human conditions, such as type-2 diabetes and familial combined hyperlipidaemia.

Animals↗
PubMed1997

Antisense raf oligodeoxyribonucleotide is protected by liposomal encapsulation and inhibits Raf-1 protein expression in vitro and in vivo: implication for gene therapy of radioresistant cancer.

We have redesigned cationic liposomes by using a combination of dimethyldioctadecyl ammonium bromide, phosphatidylcholine and cholesterol to enhance the in vitro and in vivo effectiveness of antisense raf oligodeoxyribonucleotide (ODN). Circulating ODNs carried in vivo by liposomes were intact for at least 24 h, while free ODNs were undetectable after 5 min. Liposome-encapsulated antisense raf ODN (LE-ATG-AS) inhibited Raf-1 protein expression in vitro and in vivo. Furthermore, radioresistant tumor cells treated with LE-ATG-AS raf ODN were sensitized to ionizing radiation. These data provide new information for the delivery and potency of antisense ODN in vivo, and support the use of LE-ATG-AS raf ODN for gene therapy of radioresistant cancer.

Animals↗
PubMed1997

A young woman with SLE: diagnostic and therapeutic challenges.

The presence of antiphospholipid antibodies, especially of the IgG isotype and in high titre, is associated with additional complications in patients with SLE. The thrombocytopaenia and cerebral events in the patient described are likely to have been linked to her lupus anticoagulant. However, the antibody and anticardiolipin antibodies are not necessarily synonymous and indeed we did not detect anticardiolipin antibodies in the patient, although her sister had them. It is likely that they represent overlapping sets of immunoglobulins. The production and analysis of further such antibodies, as described in this review, is awaited urgently. Much effort is also being expanded on identifying the precise targets for these antibodies. In a very recent report Hörkkö et al have shown that these antibodies may be directed against epitopes of oxidized phospholipids. The management of patients with complex disorders such as described here remain a challenge, although in the short term the patient's major locomotor, neurological, dermatological and haematological problems have been controlled. Long-term problems including impaired fertility and osteoporosis remain to be faced.

Adult↗
PubMed1997

Cardiac allograft rejection: do trough cyclosporine levels correlate with the grade of histologic rejection?

BACKGROUND: The introduction of cyclosporine to heart transplantation immunosuppressive protocols has been associated with an improvement in the long- and short-term survival rates. The ideal dose of cyclosporine that maximizes its immunosuppressive properties and minimizes its toxicity has remained an enigma since its introduction. This study was undertaken to evaluate which range of cyclosporine levels provided the most effective protection against graft rejection. METHODS: We studied the correlation between cyclosporine levels and histologic grade of rejection, cardiac function, and renal function by retrospectively analyzing the results of 1407 individual whole blood cyclosporine trough levels. One hundred seven heart transplant recipients were studied within 2 years of undergoing transplantation. As a historical comparison, we also studied 146 individual trough cyclosporine levels from a subgroup of patients (n = 14) who had acute cellular rejection with graft dysfunction or failure. We correlated trough cyclosporine levels with the histologic severity of cellular rejection, cardiac function (right cardiac catheterization), and serum creatinine in both groups. The correlation was performed within patient's own data rather than between patient groups to avoid interpatient variations. RESULTS: The mean cyclosporine level was significantly higher (206 ng/ml) when the patients had grade 0 cellular rejection in comparison to grade 3A, with a mean cyclosporine level of 173 ng/ml (p = 0.005). Patients with graft dysfunction or failure had higher mean cyclosporine level (230 ng/ml) when they had no rejection compared with 3A rejection with a mean cyclosporine level of 153 ng/ml (p = 0.001). Furthermore, lower cyclosporine levels were associated with graft dysfunction. There was no correlation between serum creatinine and cyclosporine levels (r = 0.059, r2 = 0.351%). CONCLUSION: We conclude that cyclosporine trough levels above 200 ng/ml in the first 2 years after heart transplantation are associated with reduced cellular rejection without deleterious effects on renal function.

Adult↗
PubMed1997

Use of betel quid and cigarettes among Bangladeshi patients in an inner-city practice: prevalence and knowledge of health effects.

BACKGROUND: Betel quid chewing, often combined with tobacco chewing, is a common habit in the Indian subcontinent. It is associated with the development of malignancy of the oral mucosa and foregut. Among Asian communities in the United Kingdom (UK), Bangladeshis are particularly likely to retain this habit. AIM: To investigate the prevalence of betel quid chewing, smoking, and knowledge of health hazards associated with these habits among the Bangladeshi population in an east London general practice. METHOD: A bilingual postal questionnaire to all 306 adults (25 years and over) identified as being of Bangladeshi origin within one practice in east London. RESULTS: The questionnaire response rate was 46%. The prevalence of betel quid chewing was over 80% with no sex difference. Men were more likely to smoke tobacco than women (men = 57%, women = 11%, X2 = 33.3, P < 0.001), but over half the women added tobacco to their quid for chewing. Whereas over 80% of both male and female respondents identified the health risk of smoking, only one third identified oral cancer as a risk. In all, 25% of respondents started chewing in the UK. CONCLUSIONS: The low response rate is discussed. The findings indicate that the majority of Bangladeshi respondents are unaware of the health risks of a common social habit, although well informed about smoking risks. A government health warning should be introduced for betel quid sold in the UK.

Adult↗
PubMed1997

Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins.

Grapefruit juice increases the oral availability of a variety of CYP3A4 substrates. It has been shown that recurrent grapefruit juice ingestion results in a loss of CYP3A4 from the small bowel epithelium. We now show that the reduction in intestinal CYP3A4 concentration is rapid; a 47% decrease occurred in a healthy volunteer within 4 hr after consuming grapefruit juice. To identify the specific components of the juice responsible for this effect, we used a recently developed Caco-2 cell culture model of human intestinal epithelium that expresses catalytically active CYP3A4. We found that grapefruit oil and two furanocoumarin constituents (6', 7'-dihydroxybergamottin and a closely related dimer) caused a dose-dependent fall in CYP3A4 catalytic activity and immunoreactive CYP3A4 concentration. The effect was selective in that concentrations of CYP1A1 and CYP2D6 did not fall, consistent with previous results obtained in vivo. Assays of various juices confirmed that 6',7'-dihydroxybergamottin is the major furanocoumarin present and, although its concentration varies significantly among types and brands of grapefruit juice, it is consistently present in concentrations exceeding the IC50 (1 microM) for loss of midazolam 1'-hydroxylase activity determined in the Caco-2 cells. Studies with recombinant CYP3A4 revealed that 6', 7'-dihydroxybergamottin is a mechanism-based inactivator, which supports the idea that loss of CYP3A4 results from accelerated degradation of the enzyme. We conclude that the effect of grapefruit juice on oral availability of CYP3A4 substrates can be largely accounted for by the presence of 6',7'-dihydroxybergamottin although other furanocoumarins probably also contribute.

Biological Availability↗
PubMed1996

Sequences of monoclonal antiphospholipid antibodies: variations on an anti-DNA antibody theme.

Antiphospholipid antibodies (aPL) are recognized increasingly as a probable cause of clinical features such as thrombosis and recurrent miscarriages, particularly in a subset of patients with systemic lupus erythematosus (SLE) and those with the antiphospholipid antibody syndrome (APS). A powerful method of studying the origin of these antibodies and delineating their binding sites is to sequence monoclonal aPL. The few reports of mouse aPL sequences suggest that gene families J558 and Vk23 may be used preferentially but without extensive mutation of complementarity determining regions (CDR). Polyreactive human aPL, which bind DNA as well as phospholipids, generally use germline genes with few mutations. Specific immunoglobulin (Ig) M aPL also tend to use relatively unmutated genes but often have high concentrations of positive residues in CDR, which may enhance binding to anionic phospholipids. IgG aPL show many more antigen-selected mutations, particularly in heavy chain CDR. This difference between isotypes is similar to that seen in anti-DNA antibodies, but the role of positively charged residues in aPL is less evident, and additional motifs are likely to be important in antigen binding.

Animals↗