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Arthritis Rheum. 2000 Nov;43(11):2598-605.
Increased numbers of microchimeric cells of fetal origin are associated with dermal fibrosis in mice following injection of vinyl chloride.
Christner PJ, Artlett CM, Conway RF, Jimenez SA.
Division of Rheumatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5541, USA.
OBJECTIVE: To develop a murine model for use in examining the role of microchimeric cells and certain chemical exposures in the pathogenesis of systemic sclerosis (SSc). METHODS: Female BALB/cJ retired breeder mice were bled before and after vinyl chloride injection. The DNA from their white blood cells was obtained, and the number of microchimeric cell equivalents was determined by quantitative polymerase chain reaction using DNA primers specific for the H-2Kb gene, a sequence not found in BALB/cJ mice. Skin was obtained at autopsy, embedded in paraffin, sectioned, and stained with Masson's trichrome. Hydroxyproline analyses were performed on 4-mm skin biopsy samples. RESULTS: Microchimeric cells were identified and quantitated before and after 20 daily intraperitoneal injections of vinyl chloride. The number of microchimeric cells in the peripheral blood increased an average of 48-fold after treatment with vinyl chloride. Histologic examination of the skin of these same mice (which had an increased number of microchimeric cells) showed inflammation, with abundant fibroblasts and a heavy mononuclear infiltration in the dermis. The collagen fibers appeared densely packed and disorganized. Histologic examination of the skin of untreated retired breeder mice and treated virgin mice appeared normal. Quantitative assays to determine the collagen content of skin biopsy samples obtained from treated microchimeric mice compared with nontreated microchimeric or with treated nonmicrochimeric mice showed a 2-3-fold increase in collagen content in the treated microchimeric mice. Extraordinary splenomegaly was present in the vinyl chloride-treated microchimeric mice, accompanied by cellular infiltration and fibrosis. CONCLUSION: The results suggest that vinyl chloride injections into BALB/cJ retired breeder mice lead to activation of microchimeric cells, which causes the cells to divide and multiply. The correlation between the 48-fold increase in microchimeric cells and the appearance of dermal inflammation and fibrosis similar to that of graft-versus-host disease suggests that activated microchimeric cells may be a necessary factor in the pathogenesis of autoimmune diseases such as SSc.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11083286&dopt=Abstract
Platelets. 2000 Sep;11(6):320-4.
Diurnal variation in platelet aggregation iwth the PFA-100 platelet function analyser.
Dalby MC, Davidson SJ, Burman JF, Davies SW.
Department of Cardiology, Royal Brompton and Harefield NHS Trust, London, UK. milesdalbotmail.com
BACKGROUND: Myocardial infarction is commoner in the morning, and previous small studies suggesting diurnal variation in platelet aggregation have been limited to optical aggregometry with platelet-rich plasma and low shear. This phenomenon was studied using whole blood at high shear rates. METHOD: Fifteen healthy volunteers were venesected at 0800 hrs supine in bed immediately before rising, at 0830 hrs 30 min after rising, at 1200 hrs and 1700 hrs. Samples underwent the high shear method of PFA-100 using additional chemical agonists of collagen with ADP or collagen with epinephrine. PFA-100 results are reported as closure time of the experimental aperture in seconds, a longer time indicating less platelet aggregation. RESULTS: With both epinephrine and ADP, a non-significant shortening of closure time was seen on rising. Subsequently, with both agonists the closure time lengthened through the day. With ADP the difference was small (medians 0830 hrs: 85 s, 1700 hrs: 87.5 s) but statistically significant (p = 0.03). With epinephrine it was much more marked (medians 0830 hrs: 114.3 s, 1700 hrs: 140.5 s) and highly significant (p = 0.002). CONCLUSIONS: These findings demonstrate a diurnal rhythm in platelet function using whole blood at high shear rates. This is likely to be more applicable to the in vivo situation than previously reported optical aggregometry studies.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11083456&dopt=Abstract
Biochem Biophys Res Commun. 2002 Nov 29;299(2):208-15.
Immunoselection and adenoviral genetic modulation of human osteoprogenitors: in vivo bone formation on PLA scaffold.
Howard D, Partridge K, Yang X, Clarke NM, Okubo Y, Bessho K, Howdle SM, Shakesheff KM, Oreffo RO.
University Orthopaedics, University of Southampton, SO16 6YD, Southampton, UK.
The aim of this study was to examine the potential of immunoselected genetically modified human osteoprogenitors to form bone in vivo on porous PLA scaffolds. Human osteoprogenitors from bone marrow were selected using the antibody STRO-1 utilising a magnetically activated cell separation system. The STRO-1(+) fraction isolated 7% of nucleated marrow cells and increased fibroblastic colony formation by 300% and alkaline phosphatase activity by 190% over unselected marrow cell cultures. To engineer bone tissue, STRO-1(+) culture-expanded cells were transduced with AxCAOBMP-2, an adenovirus carrying the human BMP-2 gene, injected into diffusion chambers containing porous PLA scaffolds, and implanted in vivo. After 11 weeks the presence of bone mineral was observed by X-ray analysis and confirmed for mineral by von Kossa, as well as bone matrix composition by Sirius red staining, birefringence, and type I collagen immunohistochemistry. Bone formation in vivo indicates the potential of using immunoselected progenitor cells and ex vivo gene transfer with biodegradable scaffolds, for the development of protocols for the treatment of a wide variety of musculo-skeletal disorders.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12437971&dopt=Abstract
Gene Ther. 2000 Oct;7(19):1631-9.
Tissue-specific expression and long-term deposition of human collagen VII in the skin of transgenic mice: implications for gene therapy.
Sat E, Leung KH, Bruckner-Tuderman L, Cheah KS.
Department of Biochemistry, The University of Hong Kong, China.
We report the isolation of a cosmid clone containing the entire human COL7A1 gene in one piece. The ability of the genomic sequences within this clone to direct tissue-specific expression of human collagen VII in transgenic mice was tested. The data show that the gene construct is capable of directing expression of collagen VII in the skin of fetal and neonatal transgenic mice. Expression of COL7A1 in these mice was widespread, in a pattern consistent with that found in human tissues and was in parallel with that of the endogenous mouse gene. Immunostaining, using human-specific antibodies, showed that human collagen VII protein was present at the skin basement membrane zone of the transgenic mice. Dermal extracts from 19-month-old transgenic mice contained mature human collagen VII protein, and fibroblasts derived from skin biopsies of these mice actively synthesized human collagen VII. The demonstration of successful and stable expression of human collagen VII in in vivo gene transfer is the first step towards the future development of therapeutic protocols for the rescue of keratinocyte function in severe blistering diseases such as dystrophic epidermolysis bullosa.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11083471&dopt=Abstract
Antimicrob Agents Chemother. 2000 Dec;44(12):3306-9.
Polycationic peptides as prophylactic agents against methicillin-susceptible or methicillin-resistant Staphylococcus epidermidis vascular graft infection.
Giacometti A, Cirioni O, Ghiselli R, Goffi L, Mocchegiani F, Riva A, Scalise G, Saba V.
Institute of Infectious Diseases and Public Health, National Institute for Research and Therapy in the Elderly, University of Ancona, Ancona, Italy. cmalinopcsi.unian.it
Several polycationic peptides isolated from animals, plants, and bacterial species possess a broad spectrum of antimicrobial activity. A rat model was used to investigate the efficacies of two peptides, ranalexin and buforin II, in the prevention of vascular prosthetic graft infections. The effect of peptide-soaked collagen-sealed Dacron was compared to that of rifampin-soaked collagen-sealed Dacron in the rat model of graft infection caused by methicillin-susceptible rifampin-susceptible Staphylococcus epidermidis and methicillin-resistant rifampin-susceptible S. epidermidis. Graft infections were established in the back subcutaneous tissue of 240 adult male Wistar rats by implantation of 1-cm(2) Dacron prostheses, followed by topical inoculation with 2 x 10(7) CFU of S. epidermidis. The study included a control group (no graft contamination), two contaminated groups that did not receive any antibiotic prophylaxis, two contaminated groups to which perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg of body weight) was administered, six contaminated groups that received a peptide- or rifampin-soaked graft, and six contaminated groups that received a peptide- or rifampin-soaked graft and perioperative intraperitoneal cefazolin prophylaxis (30 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Overall, the efficacies of the polycationic peptides against the methicillin-susceptible and methicillin-resistant strains were not significantly different from that of rifampin. Nevertheless, the combinations of ranalexin- and buforin II-coated grafts with cefazolin treatment demonstrated efficacies significantly higher than that of the combination of rifampin-coated grafts and cefazolin treatment against the methicillin-resistant strain.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11083632&dopt=Abstract
While the hair loss and resulting baldness in general have not been proven to be related to underlying health problems, there are certain correlations between hair loss and health problems. For instance, premature hair loss could suggest premature aging or nutritional and hormonal imbalances, stressful life, use of drugs that cause hair loss as a side effect, skin disease, or heart disease. The balding appearance could also impart a subdued impression of integrity in bodily health and youthfulness. Fortunately, in many cases, hair loss is reversible by change in lifestyle and/or nutritional supplementation. Herbal hair growth formula and other nutritional supplements have been shown to be effective in warding off hair loss and resuming hair growth. Certain prescription drugs such as Propecia may also reverse hair loss by blocking the formation of DHT, a hormonal byproduct produced inceasingly as a person age.
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