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Microbes Infect. 2003 Apr;5(4):275-83.
Characterization of a locus encoding four paralogous outer membrane lipoproteins of Brachyspira hyodysenteriae.

Cullen PA, Coutts SA, Cordwell SJ, Bulach DM, Adler B.

Bacterial Pathogenesis Research Group, Department of Microbiology, Monash University, Melbourne, Vic. 3800, Australia.

The identification of Brachyspira hyodysenteriae outer membrane proteins (OMPs) that may stimulate immunity to swine dysentery is important for vaccine development. We report here the analysis of a novel locus, blpGFEA, encoding four tandem paralogous proteins of approximately 30 kDa from B. hyodysenteriae. The four proteins share 31-39% sequence identity with lipoproteins from several species of bacterial pathogens, but the locus possesses a unique genetic organization. Using antisera raised to recombinant versions of each of these proteins, only BlpA and BlpE were found to be immunologically cross-reactive with the other proteins encoded by the locus. Northern hybridization indicated that only blpA was expressed under in vitro growth conditions. In addition, convalescent swine serum recognized recombinant BlpA in immunoblotting experiments, demonstrating that it is also expressed during infection. Analysis of the translated sequences of each of the genes revealed atypical spirochetal signal peptidase II recognition sites, and BlpA was shown to be a lipoprotein by incorporation of tritiated palmitic acid. Native BlpA was completely extracted by Triton X-114 (TX-114) and partitioned exclusively into the detergent phase during extraction of whole B. hyodysenteriae cells, implicating it as a component of the brachyspiral outer membrane. Consistent with the transcriptional and immunological data, analysis of the brachyspiral outer membrane proteome also revealed expression of only BlpA. Notably, inactivation of blpA homologs in Haemophilus influenzae and Salmonella enteritidis resulted in attenuation of virulence.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12706440&dopt=Abstract

Kidney Int. 2000 Nov;58(5):2215-20.
CD28 knockout mice as a useful clue to examine the pathogenesis of chronic graft-versus-host reaction.

Ogawa S, Nitta K, Hara Y, Horita S, Nihei H, Abe R.

The Research Institutes for Biological Sciences, Science University of Tokyo, Chiba, Japan.

BACKGROUND: Injection of BALB/c or DBA/2 spleen cells into F1 C57BL/6 (B6) hybrids induces a graft-versus-host reaction (GVHR) of a chronic stimulatory type that results in clinical and pathologic manifestations that resemble the human systemic lupus erythematosus (SLE). The aim of the present study was to examine the role of a major T-cell costimulatory signal receptor, CD28, in the production of autoantibody and the development of an immune complex glomerulonephritis, which are common in SLE pathology. METHODS: For this purpose, CD28-deficient (CD28KO) mice were used for the source of donor lymphocytes. Chronic GVHR was induced by an injection of BALB/c or BALB. CD28KO donor cells into normal BCF1 mice. Serum titers of anti-dsDNA antibodies were assessed by enzyme-linked immunosorbent assay (ELISA) and major histocompatibility complex (MHC) class II antigen expression on B cells were tested by flow cytometry. In addition, depositions of immunoglobulin (Ig) were examined by direct immunofluorescence staining on frozen kidney sections. RESULTS: When (BALB/c x B6)F1 mice were injected with parental BALB/c lymphocytes, serum anti-dsDNA titer was significantly increased in association with nonspecific B-cell activation and IgG deposition in the glomerular basement membrane. In sharp contrast, none of these signs were observed in F1 mice, which were injected with CD28KO spleen cells. CONCLUSION: The CD28-mediated T-cell costimulatory pathway plays a pivotal role in the development of polyclonal B-cell activation, autoantibody production, and an immune complex glomerulonephritis. We propose that CD28KO mice are useful clues in examining the pathogenesis of experimental lupus nephritis.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11044244&dopt=Abstract

Trop Med Int Health. 2000 Oct;5(10):711-21.
Antibiotic medication and bacterial resistance to antibiotics: a survey of children in a Vietnamese community.

Larsson M, Kronvall G, Chuc NT, Karlsson I, Lager F, Hanh HD, Tomson G, Falkenberg T.

Department of Public Health, Karolinska Institutet, Stockholm, Sweden. mattias.larssohs.ki.se

OBJECTIVE: To investigate antibiotic use and antibiotic susceptibility of respiratory tract pathogens in children aged 1-5 years in Bavi, Vietnam. METHOD: Nasopharynx and throat specimens were collected from 200 children from randomly selected households in a demographically defined population. Respiratory isolates were tested for antibiotic susceptibility according to the standard disk diffusion method. A questionnaire survey of carers elicited information on type of antibiotic used, duration of treatment, where the antibiotics had been purchased, type of treatment information retained by carers and episodes of illness preceding the study. RESULTS: 82% of the children had at least one symptom of acute respiratory tract infection (ARI) in the 4 weeks prior to the study, and of these 91% were treated with antibiotics. The most commonly used antibiotics were ampicillin (74%), penicillin (12%), amoxicillin (11%), erythromycin (5%), tetracycline (4%) and streptomycin (2%). Ampicillin was used for 3.3 days on average (SD:1.8) and penicillin for 2.6 days (SD:0.7). When deciding which antibiotic to use, 67% of the carers consulted the pharmacy seller, 11% decided themselves and 22% followed the doctor's prescription. The carrier rate of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis was 50%, 39% and 17%, respectively. Isolates from 145 children were susceptibility tested, and 74% were found to carry resistant pathogens. Of the tested isolates, 90% of S. pneumoniae, 68% of H. influenzae and 74% of M. catarrhalis were resistant to at least one antibiotic. The mean number of antibiotics (susceptible strains excluded) to which resistance was found was 2.0 (SD:1.2), 2.5 (SD:1.8) and 2.1 (SD:0.9), respectively. S. pneumoniae and H. influenzae showed high resistance to tetracycline (88% and 32%, respectively), trimethoprim/sulphonamide (32% and 44%), and chloramphenicol (25% and 24%). 23% of S. pneumoniae were erythromycin-resistant and 18% of H. influenzae isolates were resistant to ampicillin. There was a significant difference in ampicillin and penicillin resistance between the group of children previously treated with beta lactam antibiotics and the group of children who did not receive antibiotics. CONCLUSION: As reported by the carers, children in Bavi are treated with antibiotics frequently. Most antibiotics were obtained without consulting a doctor. High levels of antibiotic resistance and high prevalence of multidrug-resistant strains were found among respiratory pathogens. The existence of a large reservoir of resistance genes among children in low-income countries represents a threat to the success of antibiotic therapy throughout the world. Multi-faceted programmes to improve rational use of antibiotics in Vietnam are urgently needed.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11044266&dopt=Abstract

Circulation. 2000 Oct 24;102(17):2105-10.
Adriamycin-induced early changes in myocardial antioxidant enzymes and their modulation by probucol.

Li T, Singal PK.

Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.

BACKGROUND: The clinical usefulness of adriamycin is restricted by the development of congestive heart failure. It has been suggested that probucol, a strong antioxidant, completely prevents adriamycin-induced cardiomyopathy without interfering with its antitumor properties. The present study investigated the effects of adriamycin and probucol on myocardial antioxidant enzyme activities and immunoreactive protein levels in rats. METHODS AND RESULTS: Activities and protein levels of glutathione peroxidase (GSHPx) were significantly decreased from 2 to 24 hours, and those of manganese superoxide dismutase were decreased at 1 and 2 hours after adriamycin treatment. These changes were prevented by probucol. Catalase activity was increased from 2 to 24 hours after adriamycin treatment, but its protein levels were not significantly changed. Copper zinc superoxide dismutase activity and protein level were not changed at any time. Myocardial lipid peroxidation was found to be significantly higher at all time points, and this change was also prevented by probucol. Treatment with probucol alone increased GSHPx activity at 2 weeks, and in these hearts, lipid peroxidation was lower than the control value. Within 24 hours, there was no mortality in any of the groups. CONCLUSIONS: It is suggested that an early and persistent decrease in GSHPx activity and protein may play an important role in the pathogenesis of adriamycin-induced cardiomyopathy, worsening heart failure and mortality.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11044428&dopt=Abstract

Circulation. 2000 Oct 24;102(17):2131-6.
Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure.

Yano M, Ono K, Ohkusa T, Suetsugu M, Kohno M, Hisaoka T, Kobayashi S, Hisamatsu Y, Yamamoto T, Kohno M, Noguchi N, Takasawa S, Okamoto H, Matsuzaki M.

Second Department of Internal Medicine, Yamaguchi University School of Medicine, Yamaguchi, Japan. yanomo.cc.yamaguchi-u.ac.jp

BACKGROUND: In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase is believed to be a major determinant. Here, we report a novel mechanism of cardiac dysfunction revealed by assessing the functional interaction of FK506-binding protein (FKBP12.6) with the cardiac ryanodine receptor (RyR) in a canine model of pacing-induced heart failure. METHODS AND RESULTS: SR vesicles were isolated from left ventricular muscles (normal and heart failure). The stoichiometry of FKBP12.6 per RyR was significantly decreased in failing SR, as assessed by the ratio of the B(max) values for [(3)H]dihydro-FK506 to those for [(3)H]ryanodine binding. In normal SR, the molar ratio was 3.6 ( approximately 1 FKBP12.6 for each RyR monomer), whereas it was 1.6 in failing SR. In normal SR, FK506 caused a dose-dependent Ca(2+) leak that showed a close parallelism with the conformational change in RyR. In failing SR, a prominent Ca(2+) leak was observed even in the absence of FK506, and FK506 produced little or no further increase in Ca(2+) leak and only a slight conformational change in RyR. The level of protein expression of FKBP12.6 was indeed found to be significantly decreased in failing SR. CONCLUSIONS: An abnormal Ca(2+) leak through the RyR is present in heart failure, and this leak is presumably caused by a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR. This abnormal Ca(2+) leak might possibly cause Ca(2+) overload and consequent diastolic dysfunction, as well as systolic dysfunction.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11044432&dopt=Abstract

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Hair Loss, or alopecia is a concern for increasing number of folks in aging society. Loss of hair is a visible problem, and affects the appearance and changes identity of a person.
The phenomenon of hair thinning and hair loss is most commonly associated with natural aging, although there are many other causes of hair loss, which include inherited or genetic conditions, illnesses, malnutrition, stress, hormonal problems, chemotherapy, and use of some drugs.
Hair growth is a sophisticated biological process, which has not yet been completely understood. A multitude of therapeutic measures, including drugs, surgery, and suppelements have been made available, and used. However, due to the heterogeneity in the underlying cause, there is no perfect cure for all hair loss cases. Most of chemical drugs and hair transplantation surgeries are not free from varying degrees of undesirable side effects on health.

Hair Million is an alternative solution to hair loss problems. Anecdotally, it shows prositive results and improvement for age-related hair thinning and hair loss for a fraction of people who take it. We do not know the mechanisms of action as to how Hair Million works to help stop hair loss, and promote hair growth. We only know by anecdotal observations. There has been no clinical trials nor placebo controlled statistical analysis on the efficacy of Hair Million on hair loss and hair growth. However, there are two merits in this hair restoration herbal formula:
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