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Tolerance to organic nitrates: evidence, mechanisms, clinical relevance, and strategies for prevention.

OBJECTIVE: To review the available information about nitrate tolerance, its potential mechanisms, clinical implications, and strategies for prevention. DATA IDENTIFICATION: A survey of the National Library of Medicine MEDLINE database and bibliographies of the reviewed articles. STUDY SELECTION AND DATA EXTRACTION: Studies were selected from the English language literature with an emphasis on recent studies and, when available, randomized placebo-controlled studies. Old studies were selected on the basis of their historical value and originality. A total of 134 retrieved articles were considered relevant and were reviewed in depth. RESULTS: The available information about the experimental as well as the clinical evidence for tolerance to organic nitrates has been summarized. In addition, information related to potential mechanisms, clinical implications, and possible methods for prevention have been reviewed. CONCLUSIONS: Evidence indicates that prolonged in-vitro exposure to organic nitrates, continuous intravenous or topical administration of nitrates, and frequent in-vivo oral dosing result in the rapid development of tolerance to the peripheral as well as to the coronary vasodilatory effects of the drugs. This phenomenon leads to the rapid attenuation of the hemodynamic and anti-ischemic effects of nitrates in patients with ischemic heart disease or congestive heart failure, or both. Tolerance development seems to be dose- and time-dependent, and its main mechanism seems to be a depletion of sulfhydryl groups at the vascular cell. Although the repletion of sulfhydryl groups with the use of sulfhydryl-containing drugs may help to prevent tolerance, the efficacy and safety of this approach requires further evaluation. Intermittent therapy allowing a sufficiently long, daily nitrate-washout interval seems to be the most effective and the most safe strategy currently available for the prevention of nitrate tolerance.

Cardiovascular Agents↗

Reducing the risk for transfusion-transmitted cytomegalovirus infection.

OBJECTIVE: To define the groups of patients at risk for transfusion-transmitted cytomegalovirus infection and to define the methods to reduce this risk. DATA SOURCES: English-language publications on transfusion medicine. STUDY SELECTION AND DATA EXTRACTION: Studies were selected that described cytomegalovirus infection in transfusion-dependent patients. Special attention was paid to reports that included observations about the prevalence and clinical manifestations of cytomegalovirus infection and recommendations for the prevention of infection. DATA SYNTHESIS: Some patients with impaired immune responses who have never been exposed to cytomegalovirus are at risk for transfusion-transmitted cytomegalovirus infection. This infection, which is associated with substantial morbidity and mortality, can be avoided by additional screening of blood donors or by special processing of components for transfusion. CONCLUSIONS: Transfusion products that are unlikely to transmit cytomegalovirus infection can be prepared by filtration to remove leukocytes or can be obtained by selecting donors who are seronegative for antibodies to cytomegalovirus. These products are indicated for certain groups of immunosuppressed patients, including pregnant women who are cytomegalovirus seronegative, premature infants of low birth weight who are born to cytomegalovirus-seronegative mothers, cytomegalovirus-seronegative recipients of allogeneic bone marrow transplants from cytomegalovirus-seronegative donors, and cytomegalovirus-seronegative patients with the acquired immunodeficiency syndrome (AIDS).

Cytomegalovirus Infections↗

Hepatosplenic schistosomiasis: a review.

BACKGROUND: Schistosomiasis is a granulomatous disease that is caused by infection with schistosomes. It is a major health threat in tropical and subtropical countries. Due to increased movement, all residents of the universe are at risk of contracting this infection. The infection goes through several stages, but the most life-threatening form and leading cause of mortality is hepatosplenic schistosomiasis (HSS). It is a chronic complication, which develops as a consequence of inflammatory response. This complication has not been adequately addressed or attended the and as a consequence most of patients presenting with this complication in our settings die. OBJECTIVES: To review literature on hepatosplenic schistosomiasis, to give the state-of-the-art management of HSS, to give our own experience on management of this complication and hence impart knowledge to medical personnel on HSS. DATA SOURCE: Literature is from Medline database and experience from gastroenterology clinics. Our own experience has been blended on top. STUDY SELECTION AND DATA EXTRACTION: We have selected material, which have been verified and can be applicable in resource poor-countries, where this problem is a major health threat. DATA SYNTHESIS: Based on published studies and meta-analyses and our own experience we have been able to draw conclusions on the current understanding of the subject. CONCLUSION: Hepatosplenic schistosomiasis is a deadly complication and occurs mainly in poor countries. Regular reviews and updates of our knowledge is important to enable stakeholders of health sector understand the problem and develop strategies on its management.

Age Factors↗

[Technology of extract improving the immune system].

The article deals with the production of the extract of Echinacea purpurea herbs when selecting an extractant concentration, the size of particles in a raw material and the method of extraction. Using 60% (v/v) ethanol for production of the immune system enhancing extract, the extract becomes green due to pigmental substances; therefore, 60% (v/v), 70% (v/v), and 96% (v/v) ethanol was not used for extraction. It is recommended to use 50% (v/v) ethanol for extraction. Using 40% (v/v) ethanol not all active substances are extracted and resistance of the extract to microbial contamination is weaker. It was determined that the method of repercolation should be used to yield the largest amount of active substances. The largest amount of active substances in the immune system enhancing extract was obtained when the flow speed of extract was 0.2 ml/min. The quality of extract was tested within the period of 26 months by the monitoring of following parameters: appearance of the extract, refraction index, relative density, ethanol concentration, the amounts of dry residue and chicoric acid. The analysis was carried out every three months. The samples of the extract remained stable during storage: no alterations of color, smell or taste were observed. Some of the samples had deposits, which is quite natural in the production of drugs from herbal material, as they have no influence on the quality of the drug (the amounts of active substances were found to be within acceptable limits). On the basis of the obtained results, the period of expiry of the immune system enhancing tincture was confirmed to be 2 years.

Caffeic Acids↗

[Operative and diagnostic set-up for dysfunctional patients].

The application of the set-up for treatment planning and prognosis can be extended to the stimulation of the orthodontic teeth movements in the patients with TMJ dysfunctions, already repositioned, and with very severe dentoalveolar discrepancy in order to decide the indication for extractions and selection of the teeth to be extracted. The limits of this simulation always remain the function of the masticatory system. The sequences of the procedures on the articulator and the different steps on the upper and lower models are described. A patient with TMJ disorders and dento-alveolar discrepancy is presented with the different procedures of treatment as for the dysfunction as for the orthodontic problems.

Adult↗

Problems in diagnosing nosocomial pneumonia in mechanically ventilated patients: a review.

OBJECTIVE: To review the available information about diagnosing nosocomial pneumonia in mechanically ventilated intensive care unit patients. DATA SOURCES: The National Library of Medicine MEDLINE database and bibliographies of the reviewed articles. STUDY SELECTION AND DATA EXTRACTION: Studies were selected from the English literature, with an emphasis on recent studies. Studies were selected on the basis of their historical value and originality. A total of 82 articles was considered relevant. DATA SYNTHESIS: Many efforts have been made to diagnose nosocomial pneumonia with more accuracy. Two promising new diagnostic modalities are the protected specimen brush and bronchoalveolar lavage, both performed via flexible bronchoscopy. Depending on the study design and patient selection, sensitivity and specificity of bronchoalveolar lavage and protected specimen brush differ widely, ranging from 50% to 100%. However, interpretation of study results is seriously hampered because a standardized diagnostic threshold is not available, the influence of previous antimicrobial therapy on culture results remains unclear, and, most importantly, a well-defined gold standard to study the value of both methods is lacking. CONCLUSIONS: Because studies of bronchoalveolar lavage and protected specimen brush are seriously hampered by several pitfalls, these studies as well as clinical results must be interpreted with caution.

Bronchoalveolar Lavage Fluid↗

Determination of important odor-active aldehydes of wine through gas chromatography-mass spectrometry of their O-(2,3,4,5,6-pentafluorobenzyl)oximes formed directly in the solid phase extraction cartridge used for selective isolation.

A method for the quantitative determination of octanal, nonanal, decanal, (E)-2-nonenal and (E, Z)-2,6-nonadienal in wine has been developed. In the proposed method, 200 ml of wine percolate through a solid phase extraction (SPE) cartridge packed with 200 mg of LiChrolut EN resins. The interferences are eluted with 60 ml of an aqueous solution containing 40% of methanol and 1% of NaHCO3. In the same SPE cartridge, the corresponding O-(2,3,4,5,6-pentafluorobenzyl)oximes are formed by letting percolate 2 ml of the reagent solution (5 mg ml(-1)). At room temperature the derivatization goes to completion in 15 min. The derivatives are eluted with 2 ml of dichloromethane, and the extract is concentrated and then analyzed by gas chromatography-mass spectrometry (GC-MS). The percentage of recovery in the isolation process is better than 90% in all cases with the exception of octanal, and is independent of the wine studied. In the cases of octanal, nonanal and decanal, the detection limits of the method are determined by the contamination levels of the reagent itself, and vary between 160 and 380 ng l(-1). For (E)-2-nonenal and (E, Z)-2,6-nonadienal, the detection limits were 12 and 20 and ng l(-1), respectively. The linearity of the method upheld until 10 microg l(-1) and was satisfactory in all cases. The reproducibility of the method is independent of the concentration and ranges from 30 to 190 ng (l(-1). The method has been applied to the analysis of these components in several wine samples. With the exception of (E, Z)-2,6-nonadienal, all the components can reach concentrations above their corresponding odor threshold values.

Aldehydes↗

The contact system.

OBJECTIVES: To review the literature for conditions, diseases, and disorders that affect activity of the contact factors, and further to review the literature for evidence that less than normal activity of any of the contact factors may be associated with thrombophilia. DATA SOURCES: MEDLINE search for English-language articles published from 1988 to 2001 and pertinent references contained therein, as well as search of references in recent relevant articles and reviews. STUDY SELECTION: Relevant clinical and laboratory information was extracted from selected articles. Meta-analysis was not feasible because of heterogeneity of reports. DATA EXTRACTION AND SYNTHESIS: Evidence for association of altered levels of the contact factors and thrombophilia was sought. A wide variety of disorders is associated with decreased activity of the contact factors; chief among these disorders are liver disease, hepatic immaturity of newborns, the antiphospholipid syndrome, and, for factor XII, being of Asian descent. These disorders are more common than homozygous deficiency. The few series and case reports of thrombophilic events in patients homozygous for deficiency of contact factors are not persuasive enough to support causality. The apparent association between levels consistent with heterozygosity (40%-60% of normal) of any of the contact factors (but especially factor XII) in persons with antiphospholipid antibodies appears to be due to falsely decreased in vitro activity levels of these factors, which are normal on antigenic testing. The apparent association with thrombosis is better explained by the antiphospholipid syndrome than by the modest reduction of the levels of contact factors. CONCLUSIONS: Presently, it is not recommended to measure activity of contact factors during routine evaluation of patients who have suffered venous or arterial thromboembolism or acute coronary syndromes.

Blood Coagulation↗

In vitro antiprotozoal activities and cytotoxicity of some selected Cameroonian medicinal plants.

Eight extracts from seven selected Cameroonian medicinal plants, traditionally used to treat malaria and other protozoal diseases, were tested in vitro for their antiprotozoal activities against Plasmodium falciparum K1 chloroquine-resistant strain, Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei rhodesiense, protozoa responsible for malaria, visceral leishmaniasis, Chagas disease and African trypanosomiasis, respectively. The most active extract against Plasmodium falciparum K1 strain and Trypanosoma brucei rhodesiense was the methanolic extract of Albizia zygia (Fabaceae) stem bark with IC(50) values of 1.0 microg/ml and 0.2 microg/ml, respectively. Five extracts showed IC(50) values below 5mug/ml against Leishmania donovani, with the methanolic seed extract of Harungana madagascarensis showing the highest activity, but only the methanolic extract of Albizia zygia showed activity against Trypanosoma cruzi. Cytotoxicity and selectivity indexes were estimated for the most active extracts. The best ratio of cytotoxicity to antiplasmodial activity (SI(a)=14) was established for the methanolic leaf extract of Symphonia globulifera (Clusiaceae), while the methanolic stem bark extract of Albizia zygia showed the best ratio of cytotoxicity to antitrypanosomal activity (SI(b)=22.5).

Albizzia↗

Lectin extracts of champedak seeds demonstrate selective stimulation of T lymphocyte proliferation.

The effect of extracts of champedak (Artocarpus integer) seed lectin on the proliferation of normal human lymphocyte was investigated. The IgA1 binding lectin was demonstrated to stimulate the proliferation of human peripheral blood mononuclear cells. Action of the lectin on enriched T and B cell populations demonstrated T lymphocyte specificity. The lectin was not mitogenic to B lymphocytes. Optimal stimulation of proliferative response was achieved when cells were subjected to 5 days exposure to the crude lectin at 20 micrograms/ml.

Adult↗

Focused microwave-assisted extraction combined with solid-phase microextraction and gas chromatography-mass spectrometry for the selective analysis of cocaine from coca leaves.

An effective combination of focused microwave-assisted extraction (FMAE) with solid-phase microextraction (SPME) prior to gas chromatography (GC) is described for the selective extraction and quantitative analysis of cocaine from coca leaves (Erythroxylum coca). This approach required switching from an organic extraction solvent to an aqueous medium more compatible with SPME liquid sampling. SPME was performed in the direct immersion mode with a universal 100 microm polydimethylsiloxane (PDMS) coated fibre. Parameters influencing this extraction step, such as solution pH, sampling time and temperature are discussed. Furthermore, the overall extraction process takes into account the stability of cocaine in alkaline aqueous solutions at different temperatures. Cocaine degradation rate was determined by capillary electrophoresis using the short end injection procedure. In the selected extraction conditions, less than 5% of cocaine was degraded after 60 min. From a qualitative point of view, a significant gain in selectivity was obtained with the incorporation of SPME in the extraction procedure. As a consequence of SPME clean-up, shorter columns could be used and analysis time was reduced to 6 min compared to 35 min with conventional GC. Quantitative results led to a cocaine content of 0.70 +/- 0.04% in dry leaves (RSD <5%) which agreed with previous investigations.

Chemical Fractionation↗

What is the most effective adhesive for attaching orthodontic bands?

DATA SOURCES: The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase were used and a search of the internet also undertaken. There was no restriction with regard to publication status or language of publication. STUDY SELECTION: Randomised controlled trials (RCT) and controlled clinical trials (CCT), including split-mouth studies, of adhesives used to attach orthodontic bands to molar teeth were selected. DATA EXTRACTION AND SYNTHESIS: All review authors were involved in study selection, validity assessment and data extraction without blinding to the authors, adhesives used or results obtained. All disagreements were resolved by discussion. RESULTS: Five RCT and three CCT were identified as meeting the review's inclusion criteria. All the included trials were of split-mouth design. Four trials compared chemically cured zinc phosphate and chemically cured glass ionomer; three trials compared chemically cured glass ionomer cement with light-cured compomer; one trial compared chemically cured glass ionomer with a chemically cured glass phosphonate. Data analysis was often inappropriate within the studies that did meet the inclusion criteria. CONCLUSIONS: There is insufficient evidence to determine the most effective adhesive for attaching orthodontic bands to molar teeth in patients with full-arch fixed orthodontic appliances.

Comment↗

Molecularly imprinted polymer membranes for substance-selective solid-phase extraction from water by surface photo-grafting polymerization.

Hydrophilized polyvinylidene fluoride microfiltration membranes were surface-modified in the presence of a template (terbumeton) in methanol with a graft copolymer of a functional monomer (2-acrylamido-2-methyl-1-propane sulfonic acid, AMPS, methacrylic acid, MAA, or acrylic acid, AA) and a cross-linker (N,N'-methylene-bis-acrylamide) using UV irradiation and benzophenone as photoinitiator. As result, membranes covered with a thin layer of imprinted polymer selective to terbumeton were obtained. Blank membranes were prepared with the same monomer composition, but in the absence of the template. The membranes' capacity to adsorb terbumetone from aqueous solution was evaluated yielding information regarding the effect of polymer synthesis (type and concentration of functional monomer, concentration of cross-linker) on the resulting membranes' recognition properties. UV spectroscopic studies of the interactions with terbumetone revealed that AMPS forms a stronger complex than MAA and AA. In agreement with that finding, imprinting with AMPS gave higher affinities than with MAA and AA. The terbumeton-imprinted membranes showed significantly higher sorption capability to this herbicide than to similar compounds (atrazine, desmetryn, metribuzine). With the novel surface modification technology, the low non-specific binding properties of the hydrophilized microfiltration membrane could successfully be combined with the receptor properties of molecular imprints, yielding substance-specific molecularly imprinted polymer composite membranes. The high affinity of these synthetic affinity membranes to triazine herbicides together with their straightforward and inexpensive preparation provides a good basis for the development of applications of imprinted polymers in separation processes such as solid-phase extraction.

Membranes, Artificial↗

Antibody to immunoselected L-cell antigens mimics stimulating activity of antibody to whole L cells.

A heterogeneous IgG antibody raised in rabbits in response to injections of whole L cells was used to identify and select relevant antigens in a nonionic detergent extract of L cells prelabeled with [35S]methionine by means of immunoprecipitation and immunoaffinity chromatography. When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the immunoprecipitate and immunoeluate contained far fewer protein bands than the whole cell extract but selectively retained a 42,000-MW protein species. In response to injections of the immunoprecipitate, rabbits produced a new antiserum which reacted predominantly with the 42,000-MW protein when reacted with L-cell proteins separated by sodium dodecyl sulfate-gel electrophoresis and transferred to nitrocellulose paper by the Western blot technique. The new antiserum (raised to the immunoprecipitate) and the original antiserum (raised to whole cells) were equipotent in stimulating calcium transport, phospholipid metabolism, and DNA synthesis in L cells. Binding of the IgG fractions of the two antisera displayed identical high affinity binding to L-cell surface antigens, with the same average association constant of 1.5 X 10(6) M-1. These studies have shown that an antiserum raised to whole L cells has a much narrower reactive spectrum with L-cell membrane antigens than might be imagined and has identified a 42,000-MW membrane protein as an important immunogen which itself elicits a potent immune response resulting in an antibody capable of mimicking the cell stimulatory properties of the original antiserum.

Animals↗

Optimization and comparison of three methods for extraction of volatile compounds from Cyperus rotundus evaluated by gas chromatography-mass spectrometry.

The essential oil of Cyperus rotundus has multiple pharmacological activities. Therefore, the extraction with high yield and quality is very important for preparation of essential oil of C. rotundus. In this paper, three methods, namely hydrodistillation (HD), pressurized liquid extraction (PLE) and supercritical fluid extraction (SFE), for extraction of volatile compounds from C. rotundus were optimized and compared by gas chromatography-mass spectrometry. Among eight identified compounds in C. rotundus, five components including alpha-copaene, cyperene, beta-selinene, beta-cyperone and alpha-cyperone were quantitatively determined or estimated using alpha-cyperone as standard, which showed that PLE had the highest extraction efficiency, while SFE had the best selectivity for extraction of beta-cyperone and alpha-cyperone. The contents of ingredients from C. rotundus extracted with HD, PLE and SFE are significantly different, which suggest that comparison of chemical components and pharmacological activities of different extracts is helpful to elucidate the active components in C. rotundus and control its quality.

Chromatography, Supercritical Fluid↗

[Red cell substitutes: perfluorocarbon emulsions and hemoglobin solutions].

OBJECTIVE: To review the current data on perfluorocarbon (PFC) emulsions and haemoglobin (Hb) solutions. DATA SOURCES: For this paper we analysed the literature using Medline search along with major review articles. DATA SELECTION AND EXTRACTION: The collected articles were reviewed and selected according to their quality and originality. DATA SYNTHESIS: PFCs are synthetic fluorinated hydrocarbons capable of dissolving, at increased FIO2, large amounts of oxygen. They deliver oxygen at tissular level, and are administered as emulsions containing particles of around 0.1 micron, reaching the smallest vessels. They are exhaled unchanged by the lungs within 7 days. The first clinically used PFC was Fluosol-DA 20%. Currently, Oxyfluor 40% and Oxygent 60% are under evaluation. PFCs are not true blood substitutes, but rather a means to support tissue oxygenation during extreme haemodilution. Solutions of free Hb do not require compatibility testing and are fully saturated with oxygen at ambient FIO2. Hb is either human, bovine or recombinant Hb. In order to maintain adequate intravascular half-life and affinity for oxygen, the Hb molecules are modified by internal cross-linking, polymerisation and encapsulation. After promising results using animal models, some of these modified Hb solutions are now undergoing phase III clinical trials. Among these, diaspirin cross-linked haemoglobin (DCLHb) has been tested in cardiac and orthopaedic surgery, as well as in trauma patients. The initial results of these multicentre trials are currently being analysed.

Animals↗

Management of insomnia: a place for traditional herbal remedies.

(1) Insomnia should be treated first with non drug measures; this has traditionally involved the use of herbal remedies. (2) About 20 plants are approved in France in the production of medications 'traditionally used' for minor sleep disturbances. Virtually nothing is known of their efficacy or potential dangers. (3) Most of these plants are suspected of toxicity and should therefore be avoided, especially in view of their unproven efficacy. (4) Littleleaf linden, vervain, melissa and orange flower have no demonstrated efficacy but are safe and can therefore be used. Similarly, there are no scientific grounds for rejecting preparations based on hawthorn or passiflora. (5) Available data suggest that valerian extracts have a modest impact on subjective sleep quality; they are nevertheless more effective than a placebo. Valerian products that do not contain valepotriates have no apparent adverse effects. It is best to avoid high-titre alcoholic extracts and powdered valerian root, and to select aqueous extracts and low-titre hydro-alcoholic preparations.

Anemone↗

Independent component analysis of fMRI group studies by self-organizing clustering.

Independent component analysis (ICA) is a valuable technique for the multivariate data-driven analysis of functional magnetic resonance imaging (fMRI) data sets. Applications of ICA have been developed mainly for single subject studies, although different solutions for group studies have been proposed. These approaches combine data sets from multiple subjects into a single aggregate data set before ICA estimation and, thus, require some additional assumptions about the separability across subjects of group independent components. Here, we exploit the application of similarity measures and a related visual tool to study the natural self-organizing clustering of many independent components from multiple individual data sets in the subject space. Our proposed framework flexibly enables multiple criteria for the generation of group independent components and their random-effects evaluation. We present real visual activation fMRI data from two experiments, with different spatiotemporal structures, and demonstrate the validity of this framework for a blind extraction and selection of meaningful activity and functional connectivity group patterns. Our approach is either alternative or complementary to the group ICA of aggregated data sets in that it exploits commonalities across multiple subject-specific patterns, while addressing as much as possible of the intersubject variability of the measured responses. This property is particularly of interest for a blind group and subgroup pattern extraction and selection.

Adult↗