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PubMed1982

Improved medium for extraction of plasminogen activator from tissue.

Quantitation of plasminogen activators present in tissue may depend to a large extent on the extraction procedure used to solubilize the enzymes. Potassium thiocyanate solution is known to be an efficient solubilizer, but it can inhibit assay systems other than fibrin plates. An equally effective acetate-detergent extractant is reported here which can be used with the highly sensitive azocaseinolytic assay procedure. The results indicate that a three-fold increase in activator activity can be extracted from selected tissues relative to that previously reported for a phosphate-detergent extractant. The extraction medium contains 75 mM K acetate, 0.3 M NaCl, 0.1 M L-arginine, 10 mM EDTA, 0.25% Triton X-100, final pH 4.2.

Acetates↗
PubMed2001

Randomised trials of secondary prevention programmes in coronary heart disease: systematic review.

OBJECTIVE: To determine whether multidisciplinary disease management programmes for patients with coronary heart disease improve processes of care and reduce morbidity and mortality. DATA SOURCES: Randomised clinical trials of disease management programmes in patients with coronary heart disease were identified by searching Medline 1966-2000, Embase 1980-99, CINAHL 1982-99, SIGLE 1980-99, the Cochrane controlled trial register, the Cochrane effective practice and organisation of care study register, and bibliographies of published studies. DATA EXTRACTION: Studies were selected and data were extracted independently by two investigators, and summary risk ratios were calculated by using both the random effects model and the fixed effects model. DATA SYNTHESIS: A total of 12 trials (9803 patients with coronary heart disease) were identified. Disease management programmes had positive impacts on processes of care. Patients randomised to these programmes were more likely to be prescribed efficacious drugs (risk ratio 2.14 (95% confidence interval 1.92 to 2.38) for lipid lowering drugs, 1.19 (1.07 to 1.32) for beta blockers, and 1.07 (1.03 to 1.11) for antiplatelet agents). Five out of seven trials evaluating risk factor profiles showed significantly greater improvements with these programmes in comparison with usual care (with effect sizes in the moderate range). Summary risk ratios were 0.91 (0.79 to 1.04) for all cause mortality, 0.94 (0.80 to 1.10) for recurrent myocardial infarction, and 0.84 (0.76 to 0.94) for admission to hospital. Five of the eight trials evaluating quality of life or functional status reported better outcomes in the intervention arms. Only three of these trials reported the costs of the intervention-the interventions were cost saving in two cases. CONCLUSIONS: Disease management programmes improve processes of care, reduce admissions to hospital, and enhance quality of life or functional status in patients with coronary heart disease. The programmes' impact on survival and recurrent infarctions, their cost effectiveness, and the optimal mix of components remain uncertain.

Adrenergic beta-Antagonists↗
PubMed1997

New pharmacotherapy for Parkinson's disease.

OBJECTIVE: To summarize the development, pharmacology, pharmacokinetics, efficacy, and safety of five investigational antiparkinsonian drugs that are in or have recently completed Phase III trials: three dopamine agonists, pramipexole, ropinirole, and cabergoline; and two catechol-O-methyltransferase (COMT) inhibitors, entacapone and tolcapone. The pathophysiology and the role of dopamine in Parkinson's disease are also reviewed. DATA SOURCES: A MEDLINE search of relevant English-language literature, clinical studies, abstracts, and review articles pertaining to Parkinson's disease was conducted. Manual searches of 1996/1997 meeting abstracts published by the American Academy of Neurology and the Movement Disorders Society were also performed. Manufacturers provided unpublished Phase III trial efficacy and pharmacokinetic data. STUDY SELECTION AND DATA EXTRACTION: Clinical trial investigations selected for inclusion were limited to human subjects. Interim analyses after 6 months for long-term clinical studies in progress were included. Pharmacokinetic data from animals were cited if human data were unavailable. Statistical analyses for all studies were evaluated. DATA SYNTHESIS: By selectivity targeting D2 receptors, the newer dopamine agonists (i.e., cabergoline, pramipexole, ropinirole) may delay the introduction of levodopa and thus the occurrence of levodopa-induced dyskinesias. In addition, they are efficacious as adjunctive therapies in patients with advanced Parkinson's disease. Unlike the currently available dopamine agonists, pramipexole and ropinirole are non-ergot derivatives and do not cause skin inflammation, paresthesias, pulmonary infiltrates, or pleural effusion. The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of levodopa by preventing its peripheral catabolism and increasing the concentration of brain dopamine; thus, these agents may reduce the incidence of "wearing-off" effects associated with the short half-life of levodopa and the progression of Parkinson's disease. CONCLUSIONS: Interim 6-month analyses of pramipexole, ropinirole, and cabergoline for symptomatic treatment of early Parkinson's disease have shown these drugs to be efficacious and relatively well-tolerated when used as monotherapy. Their role in delaying the development of motor fluctuations and delaying the addition of levodopa is the subject of long-term clinical studies. In advanced stages of Parkinson's disease, these medications were also efficacious; however, the main adverse effects included dyskinesias, somnolence, and hallucinations. The COMT inhibitors, entacapone and tolcapone, have also demonstrated efficacy in improving on-time in patients with stable disease. Tolcapone has also demonstrated efficacy in patients with motor fluctuations. Both drugs are relatively well-tolerated, with the exception of dyskinesias that require reduction of the levodopa dosage and occasional diarrhea.

Benzophenones↗
PubMed1976

Selective suppression of FSH by testicular extracts.

Studies were undertaken to determine the effects of intravenous infusions of bovine testicular extracts on plasma levels of FSH and LH in castrate male sheep. Decapsulated bovine testes were homogenized with phosphate buffer, the homogenates centrifuged at 30,000 X g for 30 min, and the supernatants extracted with diethyl ether. The aqueous extracts were filtered using Diaflo XM-100 membranes and the ultra-filtrates lyophilized. The extracts were infused over 24 hours, and plasma FSH and LH were measured prior to, during, and after the infusion. Control studies using infusions of saline and liver extracts demonstrated no decrease in FSH levels in 6 out of 7 controls, while LH levels tended to rise. Following infusions with the testicular extracts, the levels of FSH were selectively decreased to between 42% and 85% of baseline levels, and they subsequently remained suppressed for at least 24 hours. These results suggest that the testis is the site of production of a water-soluble, non-steroidal substance which exerts an inhibitory effect on the production and/or release of FSH.

Animals↗
PubMed1998

Toxicity management in patients receiving low-dose aldesleukin therapy.

OBJECTIVE: To review the pathophysiology and subsequent treatment options for low-dose aldesleukin-induced toxicity when administered via intravenous bolus infusion, continuous intravenous infusion, or subcutaneous injection. BACKGROUND: The adverse events associated with high-dose aldesleukin therapy (600,000 IU per kg i.v. every 8 h for a maximum of 14 doses) are well documented in the literature; however, the adverse event profile of lower doses and alternative administration routes are less well described. An understanding of the adverse event profile associated with these alternative regimens can enhance management of toxicity. DATA SOURCES: English-language clinical studies, abstracts, and review articles pertaining to low-dose intravenous, continuous intravenous infusion, or subcutaneous injection of aldesleukin, as well as aldesleukin-induced adverse events. STUDY SELECTION AND DATA EXTRACTION: Relevant studies were selected that assist with understanding the pathophysiology, clinical management, diagnosis, and management of aldesleukin-induced adverse events. CONCLUSIONS: Aldesleukin therapy initiates a cytokine-mediated proinflammatory process resulting in a toxicity profile that is different from traditional nonbiologic chemotherapeutic agents. The frequency and severity of adverse events associated with aldesleukin administration are dependent upon dose, route, and administration schedule. In addition, most adverse reactions are self-limiting. Alleviation of aldesleukin-induced adverse effects can usually be achieved on an outpatient basis with agents such as antiemetics, antipyretics, and topical creams or lotions, as well as nonmedication interventions. Aggressive and proactive management of aldesleukin associated toxicities can help facilitate completion of therapy.

Antineoplastic Agents↗
PubMed2003

Ramipril for the prevention and treatment of cardiovascular disease.

OBJECTIVE: To evaluate the effectiveness of ramipril in the prevention and treatment of cardiovascular disease and determine its need for inclusion on a formulary. DATA SOURCES: A MEDLINE and PubMed database search was conducted (1987-May 2002). Only journals written in the English language were selected for review. DATA EXTRACTION AND STUDY SELECTION: Articles reporting the use of ramipril in humans were evaluated. Emphasis was placed on randomized, controlled trials assessing efficacy. DATA SYNTHESIS: Ramipril is an angiotensin-converting enzyme (ACE) inhibitor that exerts its effects through inhibition of the renin-angiotensin-aldosterone system. It exhibits a safety profile that is similar to that of other ACE inhibitors and is comparable in cost to the majority of the available agents. Clinical trials have proven the effectiveness of ACE inhibitors in the treatment of hypertension, heart failure, and nephropathy. Ramipril, however, is the only ACE inhibitor currently approved for the prevention of cardiovascular events in high-risk patients without evidence of left-ventricular dysfunction or heart failure, based on the results of the HOPE (Heart Outcomes Prevention Evaluation) trial. Whether this effect is specific to ramipril has yet to be proven. This article emphasizes the major trials involving ramipril including the AIRE (Acute Infarction Ramipril Efficacy), REIN (Ramipril Efficacy in Nephropathy), and HOPE trials. CONCLUSIONS: Although similar to other ACE inhibitors in many aspects, it cannot be assumed that the benefits shown with ramipril in the HOPE trial are a class effect. Ongoing trials should help to clarify this matter. Until this time, current evidence justifies the inclusion of ramipril on a formulary.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

The role of cholesterol and statins in Alzheimer's disease.

OBJECTIVE: To briefly discuss the impact of elevated total and low-density-lipoprotein cholesterol levels, as well as the potential relationship of hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use, on the development of Alzheimer's disease (AD). DATA SOURCES: Biomedical literature was accessed through MEDLINE and International Pharmaceutical Abstracts (1966-June 2003). The authors independently reviewed literature for possible inclusion in this article. STUDY SELECTION AND DATA EXTRACTION: Clinical studies were selected and reviewed from the data sources, with special emphasis on those dealing with statin use and AD. DATA SYNTHESIS: The impact of AD is significant, as it is rapidly becoming one of our country's most debilitating and costly diseases. Data from epidemiologic trials indicate that statins may have some protective effect against the development of AD. These trials also allude to theories regarding possible mechanisms of action for this use, data implicating possible superiority of one statin over another, and their lack in certain populations, specifically the very old elderly population. CONCLUSIONS: Preliminary evidence suggests that statins may offer a protective effect against the development of AD. However, review of the literature does not lend credence to the use of statins in the general nondemented population without hyperlipidemia. Potential confounding variables have not been considered in the majority of trials. Placebo-controlled clinical trials are ongoing and should yield more definitive results.

Alzheimer Disease↗
PubMed1994

Selection of strain, culture conditions and extraction procedures for optimum production of beta-galactosidase from Kluyveromyces fragilis.

Among 47 tested yeast strains, belonging to different genera, only two cultures of Kluyveromyces fragilis and Fabospora fragilis showed beta-galactosidase activity in shaken flasks. Three types of extraction were used to release the enzyme from K. fragilis cells: solvent and detergent extraction, freezing and thawing extraction, and mechanical disintegration prior to extraction, using Triton X-100. The results indicate that the highest yield could be obtained by mechanical disintegration of cells. Factors affecting the enzyme production were studied using fermentation media of different chemical composition. The medium containing lactose, salts and yeast extract with initial pH 7.0 was selected as the best for enzyme production. Monobasic ammonium phosphate (2.0 g/dm3) was found to be the best inorganic nitrogen source for enzyme production. The effect of phosphorus level was also studied.

Carbohydrate Metabolism↗
PubMed1997

HIV-1 protease inhibitors. A review for clinicians.

OBJECTIVE: The clinical care of people infected with human immunodeficiency virus (HIV) has been substantially affected by the introduction of HIV-specific protease inhibitors (PIs). The 4 PIs available are saquinavir mesylate, ritonavir, indinavir sulfate, and nelfinavir mesylate. Comparison studies have not been reported; therefore, an assessment of the available data to aid clinicians and patients in choosing appropriate treatment will be presented. DATA SOURCES: A systematic review of peer-reviewed publications, abstracts from national and international conferences, and product registration information through September 1996. STUDY SELECTION AND DATA EXTRACTION: Criteria used to select studies include their relevance to PIs, having been published in the English language, and pertinence for clinicians. Data quality and validity included the venue of the publication and relevance to clinical care. DATA SYNTHESIS: Oral adminstration of ritonavir, indinavir, or nelfinavir generates sustainable drug serum levels to effectively inhibit the protease enzyme; however, saquinavir may not generate sustained levels necessary to inhibit the protease enzyme. Patients treated with ritonavir, indinavir, or nelfinavir experience similar reductions in viral load and increases in CD4+ lymphocytes; smaller effects occur among those treated with saquinavir. Two randomized placebo-controlled studies conducted among patients with severe immune system suppression and substantial zidovudine treatment experience demonstrated reduced HIV disease progression and reduced mortality with PI treatment. Genotypic resistance to PIs occurs; the clinical relevance of resistance is unclear. The costs of these agents including required monitoring impose new and substantial costs. CONCLUSIONS: The PIs have emerged as critical drugs for people with HIV infection. Optimal use involves combination with reverse transcriptase inhibitors. Resistance develops to each agent, and cross-resistance is likely. These agents must be used at full doses with attention to ensuring patient compliance. The expense of these agents may be offset by forestalling disease progression and death and returning people to productive life. Selecting the initial PI must be individualized, and factors to consider include proven activity, possible toxicities, dosing regimens, drug interactions, and costs.

Anti-HIV Agents↗
PubMedDate not supplied

Optimisation of conditions for the extraction of casearins from Casearia sylvestris using response surface methodology.

Optimal conditions for the extraction of casearins from Casearia sylvestris were determined using response surface methodology. The maceration and sonication extraction techniques were performed using a 3 x 3 x 3 full factorial design including three acidity conditions, three solvents of different polarities and three extraction times. The yields and selectivities of the extraction of casearins were significantly influenced by acidity conditions. Taking into account all variables tested, the optimal conditions for maceration extraction were estimated to involve treatment with dichloromethane saturated with ammonium hydroxide for 26 h. Similar yields and selectivities for casearins were determined for sonication extraction using the same solvent but for the much shorter time of 1 h. The best results for stabilisation of the fresh plant material were obtained using leaves that had been oven dried at 40 degrees C for 48 h.

Casearia↗
PubMed2002

On-line solid-phase extraction and fluorescence detection of selected endocrine disrupting chemicals in water by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed to analyse selected endocrine disrupting chemicals in water by using automated on-line solid-phase extraction with a fluorescence detector. The excitation and emission wavelengths of the fluorescence detector were 230 nm and 290 nm, respectively. The selected endocrine disrupting chemicals include hormone steroids such as estradiol (E2), estriol (E3), ethynylestradiol (EE2), and ethynylestradiol 3-methyl ether (MeEE2) as well as nonylphenols (NP), octylphenols (OP), POE(1-2) nonyl phenol (NPE) and bisphenol A (BP). Three types of on-line cartridges (C18, PLRP-s and PRP-1) were tested to pre-concentrate the endocrine disruptors in deionised water. It was found that the recoveries of these chemicals at 1 microg/L were close to 100% except for 4-octyl phenol and 4-n-nonyl phenol, which had recoveries of about 40% to 80%. The two polymer cartridges (PLRP-s and PRP-1) gave higher recoveries than the C18 cartridges. The addition of methanol at 5% to 10% in water significantly improved the recovery of 4-octyl phenol and 4-n-nonyl phenol. The addition of methanol also led to an improvement in the recovery with C18 cartridges. With the addition of methanol in water samples, these three types of cartridges gave similar recoveries for the chemicals. The detection limits of this method ranged from 20 ng/L to 50 ng/L. A river water sample spiked with these chemicals was analysed using the above method and we found no interference with the peaks of the selected endocrine disrupting chemicals. The recoveries for these chemicals were more than 92% except for 4-NP with a recovery of 61%. This relatively simple method is useful for laboratory studies on the environmental fate of these endocrine disrupting chemicals in water.

Chromatography, High Pressure Liquid↗
PubMed1984

Cytochemical changes in lactate dehydrogenase isoenzymes in human brain tumours.

The lactate dehydrogenase (LDH) isoenzyme patterns in benign and malignant brain tumours were determined by means of electrophoresis of the cell extracts and selective cytochemical stain of the smears. The LDH isoenzyme distribution of the cell extracts showed a pronounced cathodal shift in the malignant gliomas and metastatic carcinomas. Normal brain tissues and histologically benign gliomas, however, showed an anodal pattern with a dominance of the H-type LDH. Schwannomas and meningiomas had a midzone isoenzyme pattern with a dominant LDH3 fraction. Pituitary adenomas usually showed the LDH pattern similar to that of the normal cerebrum. The LDH M fraction could be cytochemically verified using an inhibitory effect by 2.6 M urea in staining. Astrocytomas grades 3-4 and metastatic carcinomas were characterized by loss or marked reduction of stainability by urea treatment, while astrocytomas grades 1-2 and oligodendrogliomas were resistant to urea inhibition.

Adenoma↗
PubMed1991

Hepatoprotective effects of Andrographis paniculata against carbon tetrachloride-induced liver damage.

Alcoholic extract of the leaves of Andrographis paniculata Ness (= AAP) was obtained by cold maceration. A dose of 300 mg/kg (1/6 of LD50) of the extract was selected to study hepatoprotective action against carbon tetrachloride-induced liver damage. The extract was found to be effective in preventing liver damage which was evident by morphological, biochemical and functional parameters.

Animals↗
PubMed2000

Hot phosphate-buffered water extraction coupled on-line with liquid chromatography/mass spectrometry for analyzing contaminants in soil.

We evaluated the feasibility of analyzing rapidly traces of polar and medium polar contaminants in soil by coupling on-line a hot phosphate-buffered water extraction apparatus to a liquid chromatography/mass spectrometer system. Coupling was accomplished by using a small C-18 sorbent trap for collecting analytes and two six-port valves. The efficiency of this device was evaluated by extracting 13 selected pesticides from 200 mg of laboratory-aged soils by varying the extraction temperature, the extractant volume, and the flow rate at which the extractant passed through the extraction cell and the sorbent trap. In terms of extraction efficiency, robustness of the method, and extraction time, the best compromise was that of using 8 mL of extractant at 90 degrees C and 0.5 mL/min flow rate. Under these conditions, recoveries of 11 out of 13 analytes ranged between 82 and 103%, while those of the least hydrophilic pesticides, i.e., neburon and prochloraz, were 73 and 63%, respectively. By increasing the extractant volume to 60 mL, additional amounts of the two latter compounds could be recovered. Under this condition, however, the most hydrophilic analytes were in part no more retained by the C-18 sorbent trap. From a naturally 1.5-year aged soil, hot phosphate-buffered water removed larger amounts of three herbicides and hydroxyterbuthylazine (a terbuthylazine degradation product) than pure water and Soxhlet extraction. This result seems to confirm that hot phosphate buffer is also able to remove from soil those fractions of contaminants that, on aging, are sequestered into the humic acid framework.

Buffers↗
PubMed2001

Atrial fibrillation after cardiac surgery.

PURPOSE: To review the epidemiology, mechanisms, complications, predictors, prevention, and treatment of atrial fibrillation following cardiac surgery. DATA SOURCES: MEDLINE search of English-language reports published between 1966 and 2000 and a search of references of relevant papers. STUDY SELECTION: Clinical and basic research studies on atrial fibrillation after cardiac surgery. DATA EXTRACTION: Relevant clinical information was extracted from selected articles. DATA SYNTHESIS: Atrial fibrillation occurs in 10% to 65% of patients after cardiac surgery, usually on the second or third postoperative day. Postoperative atrial fibrillation is associated with increased morbidity and mortality and longer, more expensive hospital stays. Prophylactic use of beta-adrenergic blockers reduces the incidence of postoperative atrial fibrillation and should be administered before and after cardiac surgery to all patients without contraindication. Prophylactic amiodarone and atrial overdrive pacing should be considered in patients at high risk for postoperative atrial fibrillation (for example, patients with previous atrial fibrillation or mitral valve surgery). For patients who develop atrial fibrillation after cardiac surgery, a strategy of rhythm management or rate management should be selected. For patients who are hemodynamically unstable or highly symptomatic or who have a contraindication to anticoagulation, rhythm management with electrical cardioversion, amiodarone, or both is preferred. Treatment of the remaining patients should focus on rate control because most will spontaneously revert to sinus rhythm within 6 weeks after discharge. All patients with atrial fibrillation persisting for more than 24 to 48 hours and without contraindication should receive anticoagulation. CONCLUSIONS: Atrial fibrillation frequently complicates cardiac surgery. Many cases can be prevented with appropriate prophylactic therapy. A strategy of rhythm management for symptomatic patients and rate management for all other patients usually results in reversion to sinus rhythm within 6 weeks of discharge.

Adrenergic beta-Antagonists↗
PubMed2005

The spatial frequency and orientation selectivity of the mechanisms that extract motion-defined contours.

The human visual system can undertake a specialized form of motion integration, one that enables the presence of extended spatial contours to be disambiguated from their backgrounds. We have shown previously that the visual system can selectively integrate local motion signals when their directions are along spatial contours and its efficiency is inversely related to the curvature of the contour involved (Ledgeway, T., & Hess, R. F. (2002). Vision Research, 42, 653-659). This integration primarily involves the direction, rather than the speed, of local motion signals. In the present study, we sought to investigate both the spatial frequency and orientation tuning of this specialized contour integration process, using a path detection paradigm. The results show that the tuning for spatial frequency is very broad, in line with previous studies that have examined this issue. In contrast, the orientation selectivity of the mechanism mediating contour extraction under these conditions is relatively narrowband. Thus, spatial frequency but not orientation pooling appears to take place prior to the extraction of motion-defined contours, a situation that is different from that previously shown for spatial contours composed of static, oriented elements.

Form Perception↗
PubMedDate not supplied

Selective cytotoxic activity of grape peel and seed extracts against oral tumor cell lines.

Grape seed extracts were more cytotoxic than grape peel extracts. Methanol and 70% methanol extracts of grape seed selectively killed two human oral tumor cell lines, more efficiently than human gingival fibroblasts. ESR spectroscopy revealed that these extracts produced radicals under alkaline conditions and enhanced the radical intensity of sodium ascorbate at higher concentrations. On the other hand, lower concentration of these extracts slightly reduced the radical intensity of sodium ascorbate, and scavenged superoxide anion, generated by hypoxanthine and xanthine oxidase reaction. These properties of grape seed extracts suggest their possible application for cancer prevention.

Anticarcinogenic Agents↗
PubMed1991

Hepatoprotective effect of Vitex negundo against carbon tetrachloride-induced liver damage.

Alcoholic extract of the seeds of Vitex negundo Linn. was obtained by cold maceration. A dose of 250 mg/kg (1/6 of LD50) of the extract was selected to study the hepatoprotective action against carbon tetrachloride-induced liver damage. The extract was found to be effective in preventing liver damage which was evident by morphological, biochemical and functional parameters.

Animals↗