Biomedical subjects

I Khan

Publications and source records attributed to I Khan.

At least 37 records · Page 2Linked to original sources

PubMed2002

The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent.

The effect of an aqueous extract of ginger (Zingiber officinale) on serum cholesterol and triglyceride levels as well as platelet thromboxane-B(2) and prostaglandin-E(2) production was examined. A raw aqueous extract of ginger was administered daily for a period of 4 weeks, either orally or intraperitoneally (IP) to rats. Fasting blood serum was investigated for thromboxane-B(2), prostaglandin-E(2), cholesterol and triglycerides. A low dose of ginger (50 mg/kg) administered either orally or IP did not produce any significant reduction in the serum thromboxane-B(2) levels when compared to saline-treated animals. However, ginger administered orally caused significant changes in the serum PGE(2) at this dose. High doses of ginger (500 mg/kg) were significantly effective in lowering serum PGE(2) when given either orally or IP. However, TXB(2) levels were significantly lower in rats given 500 mg/kg ginger orally but not IP. A significant reduction in serum cholesterol was observed when a higher dose of ginger (500 mg/kg) was administered. At a low dose of ginger (50 mg/kg), a significant reduction in the serum cholesterol was observed only when ginger was administered IP. No significant changes in serum triglyceride levels were observed upon administration of either the low or high dose of ginger. These results suggest that ginger could be used as an cholesterol-lowering, antithrombotic and anti-inflammatory agent.

Administration, Oral↗

PubMed2002

Cyclooxygenase-2 inhibition and experimental colitis: beneficial effects of phosphorothioated antisense oligonucleotide and meloxicam.

BACKGROUND: The effects of cyclooxygenase-2 (cox-2) inhibition by a cox-2 selective antisense phosphorothioated oligonucleotide (AS) and meloxicam were examined in experimental colitis. METHODS: Colitis was induced by trinitrobenzenesulphonic acid (TNBS) and acetic acid (Hac) separately in male Sprague-Dawley rats. Both groups of animals were treated daily intraperitoneally with AS and a mismatched control oligo (CO) (3 mg/kg), and orally with meloxicam (7.5 mg/kg) 1 h before induction of colitis. The animals were killed on day 4 (Hac) and on day 5 (TNBS). Tissue samples from colon, ileum, liver, kidney and spleen were collected for mRNA, myeloperoxidase activity (MPO), prostaglandin E2 (PGE2) estimation and for histology, and blood samples for PGE2, thromboxane B2 (TxB2) and TNF-alpha. RESULTS: Both TNBS and Hac increased colonic MPO activity, PGE2 concentrations and infiltration of colonic wall by inflammatory cells. Serum levels of TNF-alpha were increased in both models, whereas PGE2 was increased only in TNBS colitis. Only meloxicam suppressed the level of PGE2 significantly below the basal level. The animals in both models also showed splenomegaly. The colitis-induced changes were significantly suppressed by the treatment of the test compounds but not by the CO. Cox-2 mRNA but not cox-1 was decreased by the AS, but not by meloxicam or in CO-treated colitic animals. CONCLUSION: The findings demonstrate comparable beneficial effects of the cox-2 selective antisense oligonucleotide and meloxicam, which seem to be mediated by a combined inhibition of both PGE2 and TNF-alpha in the present models of colitis.

Animals↗

PubMed2001

Topology of the C-terminus of sodium hydrogen exchanger isoform-1: presence of an extracellular epitope.

In this study, the topology of the C-terminus of Na(+)/H(+) exchanger-1 (NHE-1) was examined using red blood cell (RBC) membrane vesicles. Specific polyclonal antibodies were raised against the C-terminus of the rat NHE-1 using a glutathione S-transferase fusion protein antigen. Enzyme-linked immunosorbent assay (ELISA) and flow cytometer analyses were employed. NHE-1 antibodies recognized a 110-kDa protein in the rats and mice, but not in the humans. RBC vesicles were resealed using 1 mM MgCl(2), and the right side out (RSOVs) and the inside out vesicles (ISOVs) were selected by concanavalin A. NHE-1 antibodies reacted strongly with the RSOVs and poorly with the ISOVs in an ELISA. The reaction with the unsealed vesicles was stronger than the resealed RSOVs. In contrast, the monoclonal alpha-actin antibodies reacted poorly with the RSOVs, but extremely strongly with the ISOVs. Flow cytometer analysis also showed a strong reaction of NHE-1 antibodies with the intact and permeabilized rat RBCs. The antibodies raised in this study also contain a population which reacts with the internal epitope in the NHE-1 C-terminus. These findings suggest that the NHE-1 C-terminus contains epitope(s) exposed extracellularly.

Amino Acid Sequence↗

PubMed2001

Beta 93 modified hemoglobin: kinetic and conformational consequences.

The reactive sulfhydryl on Cys beta93 in human adult hemoglobin (HbA) has been the focus of much attention. It has purported functional roles such as a transporter of nitric oxide and a detoxifier of super oxide. In addition, it has a proposed role in the allosteric mechanism. The present study addresses the functional and conformational consequences of modifying the beta93 sulfhydryl using either maleimide or disulfide-based reactions. The geminate and bimolecular recombination of CO derivatives of several different beta93-modified Hbs in both solution and sol-gel matrixes provide a window into functional modifications associated with both the R and T states of these proteins. Nanosecond time-resolved visible resonance Raman spectroscopy is used to probe conformational consequences associated with the proximal heme environment. The results show functional and conformational consequences that depend on the specific chemistry used to modify beta93. Maleimide-based modification show the most significant alterations of R-state properties including a consistent pattern of a reduced geminate yield and a loss of the favorable heme-proximal histidine interaction normally seen for liganded R-state HbA. A mechanism based on a displacement of the side chain of Tyr beta145 is explored as a basis for this effect as well as other situations where there is loss of the quaternary enhancement effect. The quaternary enhancement effect refers to the enhancement of ligand binding properties of the alphabeta dimers when they are associated into the R-state tetramer.

Carboxyhemoglobin↗

PubMed2001

Double bag or Y-set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end-stage renal disease.

BACKGROUND: Peritonitis is the most frequent serious complication of continuous ambulatory peritoneal dialysis (CAPD). It has a major influence on the number of patients switching from CAPD to haemodialysis and has probably restricted the wider acceptance and uptake of CAPD as an alternative mode of dialysis. OBJECTIVES: This systematic review sought to determine if modifications of the transfer set (Y-set or double bag systems) used in CAPD exchanges are associated with a reduction in peritonitis and an improvement in other relevant outcomes. SEARCH STRATEGY: A broad search strategy was employed which attempted to identify all RCTs or quasi-RCTs relevant to the management of end-stage renal disease (ESRD). Five electronic databases were searched (Medline 1966-1999, EMBASE 1984-1999, CINAHL 1982-1996, BIOSIS 1985-1996 and the Cochrane Library), authors of included studies and relevant biomedical companies were contacted, reference lists of identified RCTs and relevant narrative reviews were screened and Kidney International 1980-1997 was hand searched. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing double bag, Y-set and standard CAPD exchange systems in patients with ESRD. DATA COLLECTION AND ANALYSIS: Data were abstracted by a single investigator onto a standard form and subsequently entered into Review Manager 4.0.4. Odds Ratio (OR) for dichotomous data and a (Weighted) Mean Difference (WMD) for continuous data were calculated with 95% confidence intervals (95% CI). MAIN RESULTS: Twelve eligible trials with a total of 991 randomised patients were identified. In trials comparing either the Y-set or double bag systems with the standard systems significantly fewer patients (OR 0.33, 95% CI 0.24 to 0.46) experienced peritonitis and the number of patient-months on CAPD per episode of peritonitis were consistently greater. When the double bag systems were compared with the Y-set systems significantly fewer patients experienced peritonitis (OR 0.44, 95% CI 0.27 to 0.71) and the numbers of patient-months on CAPD/ episode of peritonitis were also greater. REVIEWER'S CONCLUSIONS: Double bag systems should be the preferred exchange systems in CAPD.

Humans↗

PubMed2001

Comparison of cellulose, modified cellulose and synthetic membranes in the haemodialysis of patients with end-stage renal disease.

BACKGROUND: When the kidney fails the blood borne metabolites of protein breakdown and water cannot be excreted. The principle of haemodialysis is that such substances can be removed when blood is passed over a semipermeable membrane. Natural membrane materials can be used including cellulose or modified cellulose, more recently various synthetic membranes have been developed. Synthetic membranes are regarded as being more "biocompatible" in that they incite less of an immune response than cellulose-based membranes. OBJECTIVES: To assess the effects of different haemodialysis membrane material in patients with end-stage renal disease (ESRD). SEARCH STRATEGY: We searched Medline (1966 to December 2000), Embase (1981 to November 2000), PreMedline (29 November 2000), HealthStar (1975 to December 2000), Cinahl (1982 to October 2000), The Cochrane Controlled Trials Register (Issue 1, 1996), Biosis (1989 to June 1995), Sigle (1980 to June 1996), Crib (10th edition, 1995), UK National Research Register (September 1996), and reference lists of relevant articles. We contacted biomedical companies, investigators and we hand searched Kidney International (1980 to 1997). Date of the most recent searches: November 2000. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials comparing different haemodialysis membrane material in patients with ESRD. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of studies. Data was abstracted from included studies onto a standard form by one reviewer and checked by another. MAIN RESULTS: Twenty seven studies met our inclusion criteria and where possible data from these were summated by meta-analyses (Peto's odds ratio (OR) and weighted mean difference (WMD) with 95% confidence intervals (CI)). Twenty two outcome measures were sought in 10 broad areas. For two (number of episodes of significant infection per year and quality of life) no data were available. For the comparison of cellulose with synthetic membranes, data for 12/20 outcome measures were available in only a single trial. For modified cellulose and synthetic membranes, data for three outcome measures were available in one trial only and for 12 of the outcomes no data were found, crossover studies were analysed separately and studies which randomised by patient yet analysed by dialysis sessions adjusted for clustering. Pre-dialysis beta2 microglobulin concentrations were significantly lower at the end of the studies in patients treated with synthetic membranes (WMD - 14.5; 95% CI -17.4 to -11.6). One crossover study showed a lowering of beta2 microglobulin when low flux synthetic membranes were used. When analysed for a change in beta2 microglobulin across a trial a fall was only noted when high flux membranes were used. In one very small study the incidence of amyloid was less in patients who were dialysed for six years with high flux synthetic membranes (OR 0.05; 95% CI 0.01 to 0.18). In the single study which measured triglyceride values there was a significant difference in favour of the synthetic (high flux) membrane (WMD -0.66; 95% CI -1.18 to -0.14). Serum albumin was higher in patients treated with synthetic membranes (both low and high flux) although this just bordered statistical significance (WMD -0.09; 95% CI -0.18 to 0.00). Dialysis adequacy measured by Kt/V was marginally higher when cellulose membranes were used (WMD 0.10; 95% CI 0.04 to 0.16). There was no significant difference between these membranes for any of the other clinical outcomes measures but confidence intervals were generally wide. No differences were found between modified cellulose and synthetic membranes although many fewer trials were carried out for this comparison. REVIEWER'S CONCLUSIONS: For clinical practice This systematic literature review has generated no evidence of benefit when synthetic membranes were used compared with cellulose/modified cellulose membranes in terms of reduced mortality nor reduction in dialysis related adverse symptoms. Despite the relatively large number of RCTs undertaken in this area none of the included studies reported any measures of quality of life. End-of-study beta2 microglobulin values, and possibly the development of amyloid disease, were less in patients treated with synthetic membranes compared with cellulose membranes. Plasma triglyceride values were also lower with synthetic membranes in the single study that measured this outcome. Differences in these outcomes may have reflected the high flux of the synthetic membrane. Serum albumin was higher when synthetic membranes of both high and low flux were used. Kt/V and urea reduction ratio were higher when cellulose or modified cellulose membranes were used in the few studies that measured these outcomes. We are hesitant to recommend the universal use of synthetic membranes for haemodialysis in patients with ESRD because of; the small number of trials (particularly for modified cellulose membranes, most with low patient numbers), the heterogeneity of many of the trials compared, the variations in membrane flux, the differences in exclusion criteria, particularly relating to comorbidity and the relative lack of patient-centred outcomes studied. Such evidence as we have favours synthetic membranes but even if we assume extra benefit it may be at considerable cost, particularly if high flux synthetic membranes were to be used. For further research A further systematic review of RCTs comparing high and low flux haemodialysis membranes, subgrouped according to membrane composition (cellulose, modified cellulose, synthetic) and reporting clinical outcomes of major importance to patients needs to be undertaken. Further pragmatic RCTs are required to compare the different dialysis membranes available. We recommend that they: - Take into account other properties including flux as well as the material from which the membrane is made and test modified cellulose membranes as well as standard ones. - Record an agreed minimum dataset on primary outcomes of major importance to patients. - Explicitly record whether symptoms are patient- or staff-reported recognising that generally patient reporting will be more appropriate for evaluating effectiveness but staff reported data may be necessary for calculating the cost of treating complications. - Be multi-centre (and possibly multinational) to have sufficient patients to complete the study to allow for a considerable number of withdrawals and dropouts. - Have sufficient length of follow up to draw conclusions for important clinical outcome measures and continue to follow patients who have renal transplants. - Include older patients and those with comorbid illnesses and take into account age and comorbidity when assessing outcomes (possibly by stratification at trial entry). - Carry out, in parallel, an economic evaluation of the different policies being compared in the trial.

Cellulose↗

PubMed2001

Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients.

BACKGROUND: Treatment with recombinant human erythropoietin (rHu EPO) in dialysis patients has been shown to be highly effective in terms of correcting anaemia and improving quality of life. There is debate concerning the benefits of rHu EPO use in pre-dialysis patients. There is a concern that rHu EPO may accelerate the deterioration in renal function, however the opposing view is that if rHu EPO is as effective in pre-dialysis patients that by improving the patients sense of well-being the onset of dialysis could be delayed. OBJECTIVES: To assess the effects of rHu EPO use in pre-dialysis patients with renal anaemia. SEARCH STRATEGY: We searched MEDLINE (1980 to May Week 3 2001), EMBASE (1984 to Week 24 2001), BIOSIS (1985 to January 1997), CINAHL (1982 to October 1997), The Cochrane Library (Issue 1, 1997), CHEMABS (1984 to November 1996), SIGLE (1980 to June 1996), CRIB (10th edition, 1995), UK NRR (14TH consolidation, September 1996), RSC ( 1980 to February 1997), HealthSTAR (1995 to October 1997), IBSS (1984 to July 1997), NEED (July 1997) and reference lists of relevant articles. We contacted biomedical companies and investigators in the field and we hand searched Kidney International (including all supplements but excluding all conference proceedings except for 1994) July 1983 to May 1997 inclusive. The internet was also searched on: August 1997. We had also identified some studies from a previous broad search for all randomised controlled trials (RCTs) relevant to the management of end-stage renal disease. Date of the most recent search: June 2001. SELECTION CRITERIA: RCTs or quasi-RCTs comparing the use of rHu EPO with no rHu EPO or placebo in pre-dialysis patients. DATA COLLECTION AND ANALYSIS: Only published data were used. Data were abstracted by a single investigator onto a standard form. A sample of the data abstracted was double-checked by another reviewer. The data abstracted were relevant to the predetermined outcome measures. Some authors were contacted to clarify how patients were allocated to groups. All authors from included studies were contacted for missing information. MAIN RESULTS: Twelve studies with a total of 232 participants met the inclusion criteria and where possible data from these were summated by meta-analyses (Peto's Odds Ratio (OR) and Weighted Mean Difference (WMD)). The majority of the trials included small numbers and were of short duration (8-10 weeks) with the exception of three trials. There was a marked improvement in haemoglobin (mean difference 2.3g/dL, 95% CI 1.37 to 3.23) and haematocrit (WMD 9.92%, 95% CI 8.78 to 11.05) with the treatment and a decrease in the number of patients requiring blood transfusion (OR 0.25, 95% CI 0.09 to 0.69). The data from all studies which reported quality of life or exercise capacity demonstrated an improvement in the rHu EPO group. None of the measures of progression of renal disease (when a summary statistic was calculated) demonstrated a statistically significant difference. Though the requirement for antihypertensive treatment appears to be increased by rHu EPO (OR 1.84, 95% CI 1.02 to 3.32), there was no other statistically significant increase in adverse events. Based on the limited current evidence, decisions therefore have to be made on whether the putative benefits in terms of quality of life identified in the review are worth the extra costs of pre-dialysis rHu EPO. REVIEWER'S CONCLUSIONS: This review has shown that treatment with rHu EPO in pre-dialysis patients corrects anaemia and avoids the requirement for blood transfusions. There are also improvements in quality of life and exercise capacity. There may be increased hypertension. Most of the trials were not of sufficient duration to assess the effects of rHu EPO on progression of renal disease. In the long term, questions still remain about whether pre-dialysis rHu EPO either speeds up or delays the onset of dialysis. Thus there is insufficient evidence on the total costs and benefits of treating pre-dialysis patients with rHu EPO.

Anemia↗

PubMed2001

Ambulatory blood pressure monitoring after renal transplantation in children.

Hypertension occurs commonly following renal transplantation and may cause end organ damage, such as cardiac hypertrophy. This study seeks to determine which features of hypertension are related to cardiac hypertrophy in children after renal transplantation. Ambulatory blood pressure monitoring (ABPM) was performed in 45 pediatric patients, 4.9+/-3.0 years after renal transplantation. ABPM data were related to clinical features and echocardiographic measurements. Hypertension was demonstrated in 33% of patients by casual blood pressure (BP) measurement and in 40% by ABPM. The mean percentage nighttime decline in BP (dipping) was 8.9+/-5.0% for systolic and 13.9+/-7.7% for diastolic BP. Abnormal dipping (<10%) was seen in 58% of patients. BP load (percentage of BP recordings above 95th percentile) was >30% in 44% of patients. Patients taking antihypertensive medication had more abnormal dipping and greater nighttime BP load. The prevalence of left ventricular hypertrophy was 72% before transplantation, 75% after transplantation, and 54% near to ABPM. Left ventricular mass (LVM) indexed to height(3) decreased significantly after transplantation. (40.2+/-14.7 vs. 35.0+/-8.3 g/m(3), P=0.0002). There was no significant relationship between ABPM data and LVM. ABPM was not able to differentiate those patients with persistently elevated LVM. The results suggest that hypertension is not always associated with cardiac hypertrophy following pediatric renal transplantation.

Adolescent↗

PubMed2001

Antiinflammatory effects of Cordia myxa fruit on experimentally induced colitis in rats.

Products of certain species of Cordia are reported to have antiinflammatory properties. In the present study we examined the effects of Cordia myxa fruit on experimentally induced colitis in rats. Colitis was induced by intrarectal administration of 4% acetic acid. Colitic, normal, and corresponding control animals were included. Body weight was recorded daily. All the animals were sacrificed 4 days after the fruit treatment. Colitis was monitored histologically and by activity of myeloperoxidase. Glutathione peroxidase, superoxide dismutase, as well as total antioxidant status and concentrations of zinc, copper, manganese, selenium, and iron were assayed in plasma, liver, and colon using standard methods. Histology of the colon of colitic rats showed acute colitis that was confirmed by a significant increase in the myeloperoxidase activity. Colitis was associated with significant decreases in the tissue activities of glutathione peroxidase and superoxide dismutase and lower concentrations of trace elements. Histologic examination and myeloperoxidase activity showed that the fruit treatment reversed the above findings in the inflamed colon, and in liver and plasma of colitic rats. The present results suggest that the observed antiinflammatory effect of the Cordia myxa may be attributed partly to its antioxidant property and to restoration of the levels of trace elements in the inflamed colon, liver, and plasma.

Acetic Acid↗

PubMed2001

Drug absorption in vitro model: filter-immobilized artificial membranes. 2. Studies of the permeability properties of lactones in Piper methysticum Forst.

The assessment of transport properties of 23 drug and natural product molecules was made using the in vitro model based on filter-immobilized artificial membranes (filter-IAM), assembled from phosphatidylcholine in dodecane, in buffer solutions at pH 7.4. Five of the compounds were lactones extracted from the roots of the kava-kava plant. Experiments were designed to test the effects of stirring (0-600 rpm) during assays and the effects of varying the assay times (2-15 h). The highly mobile kava lactones permeated in the order dihydromethisticin (40)>yangonin (37)>kavain (34)>methisticin (32)>desmethoxyyangonin (26), the numbers in parentheses being the measured effective permeabilities in units of 10(-6) cm/s. By comparison, commercial drugs ranked: phenazopyridine (35)>testosterone (19)>propranolol (13)>ketoconazole (6.3)>piroxicam (2.2)>caffeine (1.7)>metoprolol (0.8)>terbutaline (0.01). In addition to permeability measurements, membrane retention of compounds was determined. Yangonin, desmethoxyyangonin, ketoconazole, and phenazopyridine were more than 60% retained by the artificial membranes containing phospholipids. Stirring during assay significantly increased the observed permeabilities for highly mobile molecules, but had minimal impact on the poorly permeable molecules. The influence of hydrogen bonding was explored by determining permeabilities using filters coated with dodecane free of phospholipids. In the filter-IAM method, concentrations were determined by microtitre plate UV spectrophotometry and by LC-MS. Higher-throughput was achieved with direct UV by the use of 96-well microtitre plate formats and with LC-MS by the use of cassette dosing (five-in-one).

Absorption↗

PubMed2001

Blood purine and energy status in rats with colitis.

Colitis reduces the blood and tissue levels of adenosine deaminase and adenylate deaminase. Whether this has any effect on blood purines remains to be determined. The aim of this study was to measure the adenylate pool, substrates of the above enzymes, and energy status in blood from rats with colitis. Colitis was induced by intrarectal administration of acetic acid and followed over a period of seven days. The levels of ATP, ADP, AMP, adenosine, inosine, and uric acid were analyzed by HPLC, and energy status was estimated. Myeloperoxidase was used as a marker of colitis. Concentrations of ATP, ADP, AMP and adenosine decreased during days 1-5, whereas energy status decreased on day 2. The concentrations of inosine, uric acid, and hemoglobin remained unaltered, whereas colonic myeloperoxidase activity increased. These, findings demonstrate colitis-induced reduction of the circulating purines, which may be due to their enhanced usage for the repair of the inflamed colon.

Acetic Acid↗

PubMed2001

Levels of IL-8 and myeloperoxidase in the lungs of pneumonia patients.

Interleukin-8 (IL-8) is considered as the major polymorphonuclear neutrophils (PMNs) chemoattractant cytokine in lung diseases such as asthma and adult respiratory distress syndrome (ARDS). However, controversial results were obtained regarding the involvement of IL-8 in the pathogenesis of pneumonia. This study examines the role of IL-8 in the recruitment and activation of PMNs in the lung of pneumonia patients. The interesting aspect of this study is that it is a site- specific analysis of the infected and uninfected lungs of the same patient. The level of IL-8 mRNA, protein and myeloperoxidase present in the cells of the bronchioalveolar lavages (BALs) taken from the areas of known pneumonic consolidations on chest X-ray (infected lung) are compared with the BALs obtained from areas of no obvious infiltrate (non-infected lung). The results obtained from the infected and non-infected lungs of pneumonic patients were further compared with that of a control group of non-smoking patients. The level of IL-8 mRNA and protein were determined by RT-PCR and ELISA respectively. There was a significant increase in the level of IL-8 mRNA in the infected lung as compared to its level in the non-infected lung (p < 0.001). In correlation with the increase in mRNA, IL-8 protein concentrations in BAL fluids from the infected lung were 6 fold higher than those taken from the non-infected lung (p < 0.0001). This pattern was also consistent with MPO activity in the BALs (4.5 fold more MPO activity in the infected lung as compared to that of the non-infected lung), indicating that IL-8 is directly implicated in neutrophil accumulation that follows acute respiratory infection. The results of the present study, therefore, indicate the involvement of IL-8 in the pathogenesis of pneumonia.

Adult↗

PubMed2001

Expression and sub cellular localization of the sodium hydrogen exchanger isoform-1 in rat tissues: a possible functional relevance.

In an attempt to understand the mechanism underlying the tissue-dependent function, the expression of NHE-1 protein and its sub cellular localization was examined in the rat GI-tract and other tissues. Rat NHE-1 polyclonal antibodies were raised in rabbits using a NHE-1 fusion protein antigen. The antibodies recognized a 110 kD protein in rats and mice, but not in human or rabbit RBCs. Colon, stomach, brain, spleen and kidney expressed NHE-1 protein abundantly, whereas the skeletal muscle the least abundant. Ouabain-sensitive-K+-stimulated p-nitrophenylphosphatase (PNPPase), the partial activity of the sodium pump and alkaline phosphatase (Apase) were used as the markers of the basolateral and apical membranes. NHE-1 was detected predominantly in the PNPPase enriched membrane fractions, but was also detected in the apical membrane enriched fractions in the kidney cortex, jejunum and colon at a lower level. NHE-1 was detected in the plasma membrane enriched fractions from the skeletal muscle and ventricle. Immunofluorescence data showed a similar localization pattern of NHE-1 in the colon and kidney sections. These findings suggest that NHE-1 is localized both on the apical and basolateral membrane. In view of its similar sub cellular localization in the GI-tract and kidney, but a different level of expression, might suggest that the level of protein, but not the sub cellular distribution is important to regulate its tissue-dependent function.

4-Nitrophenylphosphatase↗

PubMed2001

Mental health nurses' perceptions of nurse prescribing.

AIMS: This study aimed to ascertain mental health nurses' perceptions of the advantages and disadvantages of nurse prescribing and to identify the educational needs of mental health nurse prescribers. DESIGN: A questionnaire was designed and administered to a convenience sample in the UK of 73 mental health nurses in clinical practice, 14 working in in-patient settings and 59 in the community. Questions included both closed and open-ended items. Descriptive statistics were used for numerical data, and category analysis of the open-ended questions was undertaken by two of the researchers independently and then conjointly. FINDINGS: The majority of respondents felt that mental health nurse prescribing would significantly improve clients' access to medication, improve compliance, prevent relapse and prove cost effective. However, many were anxious that they did not have sufficient knowledge and skills to assume responsibility for prescribing. CONCLUSIONS: Although there would be benefits to clients and patients, further training, rigorous supervision and the co-operation of doctors will be required if mental health nurse prescribing is to yield the anticipated benefits.

Attitude of Health Personnel↗

PubMed2001

Thromboxane-B2, prostaglandin-E2 and hypertension in the rat 2-kidney 1-clip model: a possible mechanism of the garlic induced hypotension.

Serum collected from unilaterally clipped and unclipped rats before and after treatment with water, garlic or cilazapril and subsequent to measuring blood pressure was assayed for thromboxane-B2 and prostaglandin-E2. The unclipped rats' thromboxane-B2 and prostaglandin-E2 levels were about 23 ng/ml and 2 ng/ml, respectively, and blood pressure was 126+/-3 mmHg. These values were not affected by either water or garlic administration. The clipped rats' thromboxane-B2 and prostaglandin-E2 concentrations were close to 34 ng/ml and 4 ng/ml, respectively, and declined only in response to garlic (by 15 ng/ml and 3 ng/ml) and cilazapril (by 12 ng/ml and 1.5 ng/ml). The blood pressure of these rats was 196+/-7 mmHg and again was reduced only by garlic to 169+/-14 mmHg and cilazapril to 137+/-5 mmHg. The no-treatment and water-treatment readings were significantly higher in the clipped rats. The data suggest that prostanoid system activity in the 2-kidney 1-clip rat is enhanced and mostly toward maintaining the hypertension. Furthermore, the blood pressure lowering effects of garlic and cilazapril might have been induced partially by a greater reduction in the synthesis of vasoconstrictor prostanoids.

Animals↗

PubMed2001

Self-expanding oesophageal stents: strategies for re-intervention.

BACKGROUND AND STUDY AIMS: Self-expanding metal stents have become accepted palliation for inoperable malignant oesophageal obstruction, the cost of the devices being offset against the ease of insertion and the reduced complication rate. However, re-intervention is often required for obstruction, malposition, migration and tumour progression. The marginal cost of re-stenting is generally higher than other modalities. This study aims to determine the rate of re-intervention and the effectiveness of the various intervention modalities. PATIENTS AND METHODS: A population of 165 patients, treated in a tertiary referral oesophageal centre, (132 with oesophageal cancer, 31 with mediastinal metastases from other tumours, two with benign conditions) whose initial stent placement was performed between January 1994 and December 1998 was followed-up through July 1999 or till death. RESULTS: A total of 75 re-interventions were required in 44 patients and were successful in 51 (68%). Rigid oesophagoscopy and removal of food bolus was successful in three out of three, dilation in one of 11, rigid oesophagoscopy and physical debridement in 12 of 17 and laser debridement in 12 of 20. Re-stenting was the primary re-intervention in 10 cases and was ultimately necessary in 14 patients (with 11 self-expanding metal stents, three Celestin) who had previously undergone other forms of re-intervention. It was not successful in one case. The median survival following first re-intervention was 9.8 weeks (compared with 14.3 weeks for initial stenting) and was longer in those receiving radiotherapy (23.6 weeks) or chemotherapy (14.4 weeks). CONCLUSIONS: While repeated stenting is usually successful, debridement and laser vaporization are viable alternatives for proximal tumour overgrowth or ingrowth in the upper or middle third of the oesophagus. Distal tumour growth or ingrowth at the oesophagogastric junction are best treated with a second stent. Repeated treatment is justified, as survival following first re-intervention is comparable to that after initial stenting, particularly in those patients who are able to undergo chemotherapy or radiotherapy.

Equipment Design↗

PubMed2001

In vivo inhibition of cyclooxygenase-2 by a selective phosphorothioated oligonucleotide.

Inhibition of cyclooxygenase-2 (cox-2) is considered to be anti-inflammatory, whereas inhibition of the constitutive isozyme cox-1 causes renal and gastrointestinal toxicity. Therefore, to achieve an optimal anti-inflammatory effect, an inhibitor should be cox-2 selective without inhibiting cox-1. For this purpose, 10 different cox-2-selective phosphorothioated oligonucleotides (S-oligos) were tested to inhibit the cox-2 enzyme selectively in vivo. An aqueous solution of these S-oligos (3 mg/kg body weight) was injected intraperitoneally (i.p.) into male Sprague-Dawley rats with colitis induced by trinitrobenzene sulfonic acid (TNBS). The colonic levels of cox-2 protein, mRNA, myeloperoxidase (MPO), and prostaglandin E2 (PGE2) were increased significantly on day 1 and remained significantly elevated until day 7 post-TNBS administration, whereas cox-1 remained unaltered. Two S-oligos were found to be effective in reducing the level of cox-2 protein selectively without any effect on the cox-1. The effective S-oligo, but not the mismatched control oligo, reduced the tissue levels of PGE2 and MPO activity significantly. The effective S-oligo reduced the level of cox-2 but not the cox-1 mRNA significantly, whereas a mismatched or a sense control oligo did not affect the levels of these isoforms. M-fold analysis demonstrated extensive secondary structure formation in the cox-2 mRNA. These findings demonstrate that only a few selected sites in the cox-2 target mRNA are accessible in vivo, probably because of the presence of secondary structures. Suppression of cox-2 protein, PGE2, and MPO activity by the S-oligo might prove to be an anti-inflammatory property.

Animals↗

PubMed2001

Differences in repair responses between immature and mature cartilage.

Cartilage has a poor reparative capacity although it is unclear as to what extent this may be dependent on age or maturation. In the current study, the cellular responses of chondrocytes to experimental wounding in vitro using embryonic, immature, and mature cartilage have been compared. In all cases, the response was consistent (a combination of cell death that included apoptosis and proliferation). The speed of response varied in terms of cell death with embryonic cartilage showing the most rapid response and mature cartilage showing the slowest response. Intrinsic repair as assessed by the ability to heal the lesion was not detected in any of the culture systems used. It was concluded that the poor repair potential of cartilage is not maturation dependent in the systems studied.

Animals↗