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Current status of malaria control.

Malaria caused by Plasmodium parasites kills approximately 1-3 million people and causes disease in 300-500 million people annually throughout the world. The current approaches to curtail this disease include vector control, vaccination, immunotherapy and chemotherapy. The vector control is achieved by reducing vector density, interrupting their life cycle, and creating a barrier between the human host and mosquitoes. A number of vaccine candidates are being clinically tried and R&D effort in this direction is coming in a big way. Currently there are only limited safe drugs for the treatment of this disease, however, reports of emerging resistance against existing drugs warrant the introduction of new drugs, which are unlikely to come from pharmaceutical industries because of limited commercial opportunities. One of the most important current approaches to develop new drugs involves the synthesis of chemical libraries and evaluate them against most validated biochemical targets of malarial parasite. Although a number of such targets in antimalarial drug development are known today, yet only validated and selective biochemical targets including mitochondrial transport, glycolic pathway, folate pathway, proteases and heme metabolism, apicoplast metabolism, glycophospatidyl inositol, lipid metabolism (glycerophospholipids), peptidyl deformylase and oxidative stress in parasite-infected erythrocytes have been discussed here. The well known antimalarial drugs and different drug combinations for the treatment of malaria are also briefly reviewed. A survey of the recently discovered new molecules active against malaria has also been narrated. Lastly, the future of malaria chemotherapy and new directions emerging from literature has been elucidated.

Animals↗

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: I. Criteria for starting and discontinuing and the pharmacological bases of antiepileptic treatment].

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

Anticonvulsants↗

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: II. Chronic therapy with antiepileptic drugs in adults and in children].

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

Adult↗

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: III. Antiepileptic therapy in special situations].

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

Abnormalities, Drug-Induced↗

[The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: IV. General principles of antiepileptic polytherapy and therapeutic strategies in refractory epilepsy].

AIMS: The objective of this work was to produce a scientific evidence-based guide to clinical practice dealing with the basic questions concerning the treatment of epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia Epilepsy Society, made up of six neurologists, three neuropaediatricians, one neurosurgeon and a pharmacologist, all of whom were deeply involved and experienced in epilepsy, conducted a thorough review of the literature in search of all the evidence available on the proposed subject matter. The following databases were used: MEDLINE, Cochrane Library and the databases of several clinical practice guidelines (National Guideline Clearinghouse, National Institute of Clinical Excellence and the American Academy of Neurology's Clinical Guidelines). The Guide was set out in seven sections and was published in four parts. From a total number of 187 relevant documents, the committee found 63 examples of scientific evidence and 91 therapeutic recommendations. These were tabulated and classified according to the European Federation of Neurological Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The results of this survey provide scientific evidence-based clinical guidelines that are useful, simple and applicable at different levels of health care.

Anticonvulsants↗

Circulation versus photocopy: Quid pro Quo?

Information thought necessary for assessing the potential impact of a limited journal circulation policy at the University of California, San Francisco, included the effects on seating, on in-house photocopying, and on circulation. An initial survey during a "typical circulation" week showed journal circulation to be 71% of the total, with journals issued during the past five years comprising 45% of the total. A survey of user photocopying practice suggested that circulation limited to journals more than five years old might result in a 90% increase in photocopying, and results of the circulation survey were used to predict a 45% decrease in circulation. Results of implementing a limited circulation policy were a 41% decrease in circulation and a 136% increase in photocopy. Differences between prediction and results may be accounted for by the effect of duplicate copy subscriptions and by provision of convenient photocopy facilities.

Copying Processes↗

A comparative map of the porcine and human genomes demonstrates ZOO-FISH and gene mapping-based chromosomal homologies.

ZOO-FISH with chromosome-specific DNA libraries (CSLs) from individual flow-sorted human chromosomes was applied on porcine metaphase chromosomes to establish segment homology between the pig and human karyotypes. Forty-seven porcine chromosomal segments corresponding to all human chromosomes except the Y were delineated, resulting in a nearly complete coverage of the porcine karyotype. The syntenic segments detected were further confirmed by the gene mapping information available in the two species. A map demarcating physical boundaries of human homologies on individual pig chromosomes is complemented with a detail survey of the physical and genetic linkage mapping data in the two species. The resultant map, thus, provides a comprehensive and updated comparative status of the human and porcine genomes.

Animals↗

Information needs and information seeking behaviour in primary health care.

A questionnaire survey of 186 general practitioners in Sweden showed that 67% saw the overall supply of medical information as less satisfactory or unsatisfactory, and that 80% experienced major hindrances in seeking relevant information. The most frequent need for information concerned general medicine, with respect to both diagnosis and choice of therapy. Of situations which required additional information, only every second was completely resolved. These results imply a need for a reorganization of the supply of information to general practitioners. As they cannot depend on conventional medical libraries for day-to-day information, personal libraries should be improved and updated regularly, and be readily to hand. Computer technology should be considered for communication between health care providers, and as support for differential diagnosis in general medicine.

Consumer Behavior↗

Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death.

BACKGROUND: Surveys have documented the continued popularity of low-dose dopamine to influence renal dysfunction even though few data support it and editorials and reviews have discouraged its use. PURPOSE: To evaluate the effects of low-dose dopamine (< or =5 microg/kg of body weight per minute) compared with placebo or no therapy in patients with or at risk for acute renal failure. DATA SOURCES: MEDLINE (1966-January 2005), EMBASE (1980-week 5, 2005), CANCERLIT (1975-2002), CINAHL (1982-January 2005), and CENTRAL (The Cochrane Library, fourth quarter, 2004); bibliographies of retrieved publications; and additional information from 50 trials. STUDY SELECTION: Two reviewers independently selected parallel-group randomized and quasi-randomized controlled trials of low-dose dopamine versus control. DATA EXTRACTION: Study methods, clinical and renal physiologic outcomes, and adverse events (arrhythmias and myocardial, limb, and cutaneous ischemia) were extracted. DATA SYNTHESIS: 61 trials that randomly assigned 3359 patients were identified. Meta-analyses using random-effects models showed no effect of low-dose dopamine on mortality (relative risk, 0.96 [95% CI, 0.78 to 1.19]), need for renal replacement therapy (relative risk, 0.93 [CI, 0.76 to 1.15]), or adverse events (relative risk, 1.13 [CI, 0.90 to 1.41]). Low-dose dopamine increased urine output by 24% (CI, 14% to 35%) on day 1. Improvements in serum creatinine level (4% relative decrease [CI, 1% to 7%]) and measured creatinine clearance (6% relative increase [CI, 1% to 11%]) on day 1 were clinically insignificant. There were no significant changes on days 2 and 3 of therapy. LIMITATIONS: Statistically significant between-study heterogeneity in physiologic but not clinical outcomes was unexplained by prespecified hypotheses. CONCLUSION: Low-dose dopamine offers transient improvements in renal physiology, but no good evidence shows that it offers important clinical benefits to patients with or at risk for acute renal failure.

Acute Kidney Injury↗

Survey of transcript expression in rainbow trout leukocytes reveals a major contribution of interferon-responsive genes in the early response to a rhabdovirus infection.

Virus infections induce changes in the expression of host cell genes. A global knowledge of these modifications should help to better understand the virus/host cell interactions. To obtain a more comprehensive view of the rainbow trout response to a viral infection, we used the subtractive suppressive hybridization methodology in the viral hemorrhagic septicemia model of infection. We infected rainbow trout leukocytes with viral hemorrhagic septicemia virus (VHSV), and total RNA from infected and mock-infected cells was compared at 40 h postinfection. Twenty-four virus-induced genes were ultimately retrieved from the subtracted cDNA library, and their differential expression was further confirmed by semiquantitative reverse transcription-PCR and Northern blot analysis. Among these sequences, three were already described as VHSV-induced genes. Eight sequences with known homologs were extended to full-length cDNA using 5' and 3' rapid amplification of cDNA ends, and they were subsequently divided into three functional subsets. Four genes were homologous to mammalian interferon responsive genes, three were similar to chemo-attractant molecules (CXC chemokine, galectin), and two had nucleic acid binding domains. All of the virus-induced genes were also induced by rainbow trout interferon, indicating that the interferon pathway is the predominant component of the anti-VHSV response. They were also expressed in vivo in experimentally infected fish, indicating their biological relevance in natural infection.

Amino Acid Sequence↗

Characterization of a novel human T cell receptor beta chain variable region family by transspecies DNA hybridization.

One essential component in the generation of diversity of T cell receptor (TcR) alpha and beta chains is the existence of multiple tandemly arranged variable regions in the germ line which are subsequently rearranged to form functional units. In attempting to establish the extent of the human TcR alpha and beta chain repertoire an approach of randomly sequencing cDNA for rearranged receptors has been generally pursued. So far, 24 human V beta families have been characterized and they encompass some 51 transcriptionally active gene segments. Recently, surveys of several hundred TcR beta cDNA clones have failed to establish further V beta families which suggests that if they exist, they are likely to be poorly represented in the peripheral blood repertoire. It is likely, therefore, that the majority of human V beta regions which are rearranged conventionally and are transcriptionally active have already been described. To investigate whether additional V beta families characterize the human TcR repertoire we have examined V beta sequences from an inverse polymerase chain reaction (PCR) TcR beta cDNA library of the chimpanzee, the most closely related creature to man. One clone which could not be assigned to any human V beta family cross-hybridized with human TcR beta chain cDNA. This new human family has been called V beta 25. Comparison of chimpanzee and human V beta 25 sequences using the Lipman-Pearson method gives a similarity index of 94.6% over a consensus length of 112 amino acids. On the evidence of Southern blotting with cDNA probes, V beta 25 segments in human and chimpanzee appear to represent single member gene families and no restriction fragment length polymorphism was evident with the restriction enzymes used. Equalization of TcR beta cDNA followed by family-specific quantitative PCR showed that the gene is expressed at similar levels in the chimpanzee and the human. The actual level of expression in the human is less that 0.5% of the total TcR beta repertoire. Transspecies DNA hybridization using novel sequences from closely related species may be a powerful tool for establishing the full extent of TcR alpha and beta and immunoglobulin repertoires.

Amino Acid Sequence↗

Microsatellite marker polymorphism and mapping in pea (Pisum sativum L.).

This paper aims at providing reliable and cost effective genotyping conditions, level of polymorphism in a range of genotypes and map position of newly developed microsatellite markers in order to promote broad application of these markers as a common set for genetic studies in pea. Optimal PCR conditions were determined for 340 microsatellite markers based on amplification in eight genotypes. Levels of polymorphism were determined for 309 of these markers. Compared to data obtained for other species, levels of polymorphism detected in a panel of eight genotypes were high with a mean number of 3.8 alleles per polymorphic locus and an average PIC value of 0.62, indicating that pea represents a rather polymorphic autogamous species. One of our main objectives was to locate a maximum number of microsatellite markers on the pea genetic map. Data obtained from three different crosses were used to build a composite genetic map of 1,430 cM (Haldane) comprising 239 microsatellite markers. These include 216 anonymous SSRs developed from enriched genomic libraries and 13 SSRs located in genes. The markers are quite evenly distributed throughout the seven linkage groups of the map, with 85% of intervals between the adjacent SSR markers being smaller than 10 cM. There was a good conservation of marker order and linkage group assignment across the three populations. In conclusion, we hope this report will promote wide application of these markers and will allow information obtained by different laboratories worldwide in diverse fields of pea genetics, such as QTL mapping studies and genetic resource surveys, to be easily aligned.

Chromosome Mapping↗

Genes galore: a summary of methods for accessing results from large-scale partial sequencing of anonymous Arabidopsis cDNA clones.

High-throughput automated partial sequencing of anonymous cDNA clones provides a method to survey the repertoire of expressed genes from an organism. Comparison of the coding capacity of these expressed sequence tags (ESTs) with the sequences in the public data bases results in assignment of putative function to a significant proportion of the ESTs. Thus, the more than 13,400 plant ESTs that are currently available provide a new resource that will facilitate progress in many areas of plant biology. These opportunities are illustrated by a description of the results obtained from analysis of 1500 Arabidopsis ESTs from a cDNA library prepared from equal portions of poly(A+) mRNA from etiolated seedlings, roots, leaves, and flowering inflorescences. More than 900 different sequences were represented, 32% of which showed significant nucleotide or deduced amino acid sequences similarity to previously characterized genes or proteins from a wide range of organisms. At least 165 of the clones had significant deduced amino acid sequence homology to proteins or gene products that have not been previously characterized from higher plants. A summary of methods for accessing the information and materials generated by the Arabidopsis cDNA sequencing project is provided.

Amino Acid Sequence↗

The Social Transition in the North: collection and data access protocols.

OBJECTIVE: These protocols were designed to provide access to the Social Transition in the North (STN) collection and data set. METHOD: Staff at the (UAA) Institute for Circumpolar Health Studies (ICHS) reviewed, organized, inventoried, and cataloged the STN collection. RESULTS: Most of the materials in the collection are available from the UAA Archives and Manuscripts Department, Consortium Library. Documents and data containing sensitive information are maintained by ICHS to assure confidentiality of research participants. CONCLUSION: These access protocols allow researchers to obtain access to this valuable data set consistent with US research policy while protecting the integrity of the data and the confidentiality of the participants.

Alaska↗

A comparison of health information on Florida's free-nets.

In the popular rush to provide electronic consumer health information, particularly via the Internet, one system has been largely overlooked-the free-net. Free-nets are often text-based systems from which users choose topics from "menus." While the World Wide Web can be more graphically appealing, it can also be overwhelming. Medical information resources are available to diverse populations through free-nets, which are convenient, free services. The amount of information and range of topics they offer are vast. A study of Florida's free-nets during a six-month period involved five free-net systems. Survey items included user demographics, interlibrary loan services, attitudes toward providing medical advice, and availability of medical librarian expertise. Comparisons include the number of user queries on medical and health-related free-net menus, user-friendliness, and the type of health information provided.

Computer Communication Networks↗

Detection of autoantibodies to ribosomal P protein using recombinant autoantigen in a quantitative immunoassay.

Antibodies to ribosomal P proteins are markers for systemic lupus erythematosus (SLE) but are often missed by assays utilizing routine immunofluorescence or immunoprecipitation. Expression of autoantigenic sites encoded by complementary DNA (cDNA) clones offers an inexpensive source of antigen for use in quantitative immunoassays. Using a monospecific ribosomal P positive serum to screen a human placental lambda gt11 expression library, a cDNA clone was isolated which reacted with all anti-P human sera tested. Autoantibodies which were affinity purified from the expressed cDNA reacted with the 38 kDa ribosomal Po protein and reactivity was blocked by absorption with recombinant fusion protein. A stable beta-galactosidase fusion protein of 150 kDa was partially purified by a simple differential centrifugation method and used in an enzyme-linked immunoabsorbent assay to reliably quantitate anti-P responses, with a sensitivity and specificity equal to Western blotting. A survey of 84 normals and 151 patients with autoimmune diseases confirmed the high specificity of anti-P antibodies for SLE. The availability of cloned autoantigen will facilitate more detailed clinico-serologic correlations for anti-P antibodies.

Autoantibodies↗

Molecular cloning of a major cockroach (Blattella germanica) allergen, Bla g 2. Sequence homology to the aspartic proteases.

Inhalation of allergens produced by the German cockroach (Blattella germanica) elicits IgE antibody formation and the development of asthma in genetically predisposed individuals. We compared the allergenic importance of two cockroach (CR) allergens, Bla g 1 and Bla g 2, and determined the complete amino acid sequence of the major 36-kDa allergen, Bla g2. A survey of 106 sera from CR allergic patients showed the prevalence of IgE antibodies to Bla g 1 and Bla g 2 to be 30.2% and 57.6%, respectively. Immediate skin tests on 7 selected patients gave positive reactions using 10(-3) micrograms/ml either allergen, whereas controls showed no response to 10 micrograms/ml. Natural Bla g 2 was purified and the sequence of the NH2 terminus and tryptic peptides, comprising 36% of the molecule, was determined. The cDNA for Bla g 2 was cloned from a B. germanica expression library and encoded a 24-amino acid signal peptide and a 328-amino acid mature protein, which showed the highest degree of identity to mosquito (Aedes aegypti) lysosomal aspartic protease (30.8%), with similar identity to pepsin, cathepsins D and E, renin, and chymosin. Bla g 2 mRNA and protein were detected in B. germanica, but not in Periplaneta americana, the other principal domiciliary CR species in the U.S. High concentrations of Bla g 2 were found in CR digestive organs (esophagus, gut, and proventriculus). The results show that Bla g 2 is a major species-specific allergen of B. germanica and suggest that the allergen functions as a digestive enzyme in the cockroach.

Allergens↗