DreamPharm Products:
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13681-6. Epub 2002 Sep 23.
Macrophage migration inhibitory factor (MIF) plays a pivotal role in immunity against Salmonella typhimurium.
Koebernick H, Grode L, David JR, Rohde W, Rolph MS, Mittrucker HW, Kaufmann SH.
Max Planck Institute for Infection Biology, Department of Immunology, Schumannstrasse 20/21, 10117 Berlin, Germany.
The cytokine macrophage migration inhibitory factor (MIF) exerts a multitude of biological functions. Notably, it induces inflammation at the interface between the immune system and the hypothalamus-pituitary-adrenal stress axis. The role of MIF in infectious diseases is not understood completely. Here, we show that MIF-deficient (MIF(-/-)) knockout mice fail to control an infection with wild-type Salmonella typhimurium. Increased susceptibility was accompanied by a reduced Th1 response, demonstrated by decreased levels of IL-12, IFNgamma, and tumor necrosis factor alpha. In Salmonella-infected MIF(-/-) mice, levels of IL-1beta were markedly increased. Additionally, infected MIF(-/-) mice showed elevated serum levels of nitric oxide and corticosterone as compared with control mice. Our results point to MIF as a key mediator in the host response to S. typhimurium. MIF not only promotes development of a protective Th1 response but ameliorates disease by altering levels of reactive nitrogen intermediates and corticosteroid hormones, which both exert immunosuppressive functions.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12271144&dopt=Abstract
Histochem Cell Biol. 2002 Sep;118(3):231-9. Epub 2002 Jul 04.
Expression of peroxisome proliferator-activated receptors in zebrafish (Danio rerio).
Ibabe A, Grabenbauer M, Baumgart E, Fahimi HD, Cajaraville MP.
Biologia Zelularra eta Histologia Laborategia, Zoologia eta Animali Zelulen Dinamika Saila, Euskal Herriko Unibertsitatea/Universidad del Pais Vasco, 644 PK, Bilbao 48080, Basque Country, Spain.
Peroxisomes increase in size and number in responsive animals ranging from mammals to marine mussels and fish species when treated with certain compounds named peroxisome proliferators. This phenomenon, known as peroxisome proliferation, is mediated by nuclear receptors termed peroxisome proliferator-activated receptors (PPARs). Three PPAR subtypes have been described (alpha, beta, and gamma) and in mammals PPARalpha is mainly expressed in tissues that catabolize fatty acids, PPARbeta is ubiquitously distributed, and PPARgamma is mainly expressed in the adipose tissue and immune system. The aim of this study was to analyze the tissue distribution of different PPAR subtypes in zebrafish Danio rerio using commercially available antibodies against PPARalpha, PPARbeta, and PPARgamma. In western blots, specific bands were detected at about 58 kDa for PPARalpha and PPARbeta. For PPARgamma the band was detected at 56 kDa. Similar results were obtained in mouse liver homogenates used as positive control, indicating the specificity of the antibodies. Immunohistochemistry was performed in paraformaldehyde-fixed tissue using either microwave or microwave plus trypsin pretreatment for antigen retrieval. In zebrafish, PPARalpha was expressed mainly in liver parenchymal cells, proximal tubules of kidney, enterocytes, and pancreas. PPARbeta showed a widespread distribution and was expressed in the liver, proximal and distal tubules and glomeruli of the kidney, pancreas, enterocytes and smooth muscle of the intestine, skin epithelium, lymphocytes, and male and female gonads. PPARgamma expression was weak in pancreatic cells, intestine, and gonads for both pretreatments. Most of the signal detected was cytoplasmic; only in the cases of PPARalpha and PPARbeta was some nuclear labeling detected in the liver. In mouse tissues, the distribution of PPAR subtypes was similar to that described previously for rats. Our results demonstrate that all three distinct PPAR subtypes are present in zebrafish. The tissue and cellular distribution of PPAR subtypes in zebrafish resembled partly that described before in mammals. Further studies are needed to decipher the functions of PPAR subtypes in zebrafish and other aquatic organisms and particularly their role in regulation of metabolic responses to xenobiotic exposure.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12271359&dopt=Abstract
IDRC Rep. 1985 Jan;13(4):4-6.
Malaria: the king is threatened.
Smith NJ.
PIP: Malaria received high priority at the XI international Congress for Tropical Medicine held in the fall of 1984. 30 of the sessions focused on the malarial parasite and its "Anopheles" mosquito vector. Topics covered included genetics, epidemiology, chemotherapy, health care delivery, training, and vaccine development. Dr. (Sir) Gustav Nossal, Director of the Walter and Eliza Hall Medical Research Institute, Victoria, Australia, set the theme with his statement: "Vaccines are history's most cost-effective public health tool." He went on to add that the importance of a malaria vaccine is equivalent to that of the Salk vaccine. Some progress has been made towards the development of malaria vaccines. Most advanced is the antisporozoite vaccine being developed by Drs. Ruth and Victor Nussensweig of New York University Medical Hospital and groups at the National Institutes of Health and Walter Reed Army Institute of Research in Washington. In several papers, Dr. Ruth Nussensweig and members of her research team presented biotechnical details of their work that has led to the identification of the main antigen involved in stimulating the body's immune system to produce protective antibodies against sporozoites of "Plasmodium falciparum," the most deadly of the human malarial parasites. Due to the fact that the sporozoite vaccine may not be totally effective, a 2nd vaccine -- a merozoite vaccine -- is being developed. Field testing for this 2nd vaccine most likely will begin in about 2 years. Dr. Geoffrey Targett of the University of London's School of Hygiene and Tropical Medicine reported progress on the development of a 3rd "altruistic" vaccine, which would work against the sexual stage of malaria, transmitted to a mosquito when it feasts on an infected person. Both scientists and health worker participants at the congress were cautious in their assessment of the potential vaccines. No one knows as yet their final properties, e.g., stability, mode of administration, or length of time they will provide immunity. Reports on the geographical distribution of drug resistance showed that chloroquine-resistant "P. falciparum" strains have spread to all continents in the tropics. From Thailand there also were reports of Mefloquine resistance. In discussion, Dr. W. H. Wernsdorfer, Chief of the World Health Organization's Malaria Research Unit, advised that the poorer nations will be hit the hardest if drug resistance is permitted to spread unchecked.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12281239&dopt=Abstract
Fertil Contracept Sex. 1989 Feb;17(2):133-8.
[Cigarette smoking: male and female infertility]
[Article in French]
Zavos PM.
PIP: Despite problems of methodology, epidemiologic studies of women who smoke have clearly indicated that they suffer a lowering of fertility. Harmful effects are particularly noted in the periodicity of the menstrual cycle, tubal function and embryo transfer, development and viability of the ovocyte, age at menopause, and bone metabolism. Several epidemiologic studies have shown that the rate of infertility among women smoking is 21% vs. 14% among nonsmokers. Fertility declines significantly with daily cigarette consumption among women smoking 16 cigarettes a day or more. Nevertheless, in some cases such as tubal infertility, further research is needed to determine clearly whether there is a true causal mechanism or whether there is simply an association related to differences in the lifestyle of smoking women. In general, studies in women and animals confirm the possible alteration of physiological characteristics of the tubes in smokers, resulting in a disturbance of intratubal transport of the embryo, a premature or delayed arrival of the blastocyst in the uterus, and alterations of the immune system that could explain the epidemiologic association of smoking and lowered fertility. Studies in mice and rats have shown that smoking can destroy ovocytes, but observations in women have not been completely convincing. It has been concluded however that smoking can decrease the number of viability of ovocytes, ending in premature extinction of reproductive function and early menopause. Results of a small number of studies tend to demonstrate that compared to nonsmokers, smokers experience a greater frequency of secondary amenorrhea, increased vaginal bleeding, and a significant lowering of urinary estrogens in the luteal phase. Taken together, clinical reports on women and animal studies demonstrate the effect of nicotine and smoke on the basic hormonal homeostasis of women, an effect which can change the timing of cycles and reduce fertility. The risk of osteoporosis after menopause is known to be greater among smokers than nonsmokers, probably because of hormonal modifications caused by elements in cigarette smoke. Available data on effects of smoking on male fertility are inconclusive, but a certain number of studies have shown an increased incidence of morphologic anomalies and a lowering of mobility and density in the sperm of smokers. Fluctuations in the levels of androgens and gonadotropins have also been observed in men who smoke. The evidence suggests that all persons wishing to reproduce but especially those with fertility impairments should avoid smoking.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12281878&dopt=Abstract
New Egypt J Med. 1988 Oct 15;2(3):691-2.
A review of AIDS (the evaluation of individuals-suspected of having an infection with the AIDS).
El-ayat A, Sheir M.
PIP: At this time, the evaluation of individuals suspected of having an injection with the Acquired Immune Deficiency Syndrome (AIDS) virus is a rapidly evolving area of science. As the testing procedures for detecting antibodies to the virus become more routine, it will become more important to understand the impact the infection has had on the host's immune system. Currently, the enzyme-linked immunosorbent assay (ELISA) is the standard method for sensitive screening for antibodies to the AIDS virus. This test lacks specificity, and, in view of the impact of a positive antibody test, confirmation of the result with Western blot analysis or radio-immunoprecipitation assay is essential a positive ELISA test occurs in the absence of an appropriate clinical setting. Viral isolation also may be helpful in individuals who are seronegative for the virus but who have the clinical diseases. The ELISA is the most commonly used test for screening sera for the presence of antibodies to HTLV-III/LAV. All the available kits take advantage of the fact that certain cell lines have been developed which allow for the growth of the virus without killing the cell. Supernatants or purified virus from these infected cells then are used as the material adhered to the solid phase for the ELISA. Consequently, in addition to placing viral proteins and nucleic acids on the plate, one also is adhering cell antigens. The sensitivity of such tests is good, ranging from 92-95%, whereas, depending upon the test population, the specificity may be as low as 30%. One common formula used for presenting data generated from such ELISA tests and for making the cutoff between negative and positive is to develop a ratio between the sample and the negative control and use that ratio to score samples as negative, borderline, or positive. The specificity of the Western blot technique stems from the fact that it takes the entire virus, reduces it to a variety of protein fragments electrophoretically, and then looks for antibodies directed toward any or all fragments.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12281981&dopt=Abstract
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