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Sample records for isoniazid preventive therapy

  1. Isoniazid

    MedlinePlus

    Isoniazid is used alone or with other drugs to treat tuberculosis (TB) and to prevent it in ... resting (nongrowing) state for long periods, therapy with isoniazid (and other antituberculosis drugs) must be continued for ...

  2. The prevention and treatment of isoniazid toxicity in the therapy of pulmonary tuberculosis

    PubMed Central

    1963-01-01

    A recent report from the Tuberculosis Chemotherapy Centre, Madras, showed that a vitamin-B-complex preparation containing a small amount of pyridoxine (as well as aneurine hydrochloride, riboflavine, nicotinamide, panthenol and cyanocobalamin) was effective in the treatment of peripheral neuropathy caused by daily high-dosage (12.5-15.2 mg/kg body-weight) isoniazid therapy of pulmonary tuberculosis. The present report gives results which show that the B-complex preparation is fully effective in preventing peripheral neuropathy in patients receiving the same high dosage of isoniazid, and that this is due to the small pyridoxine content of only 6 mg daily, and not to any of its other constituents. The low cost of this small dose of pyridoxine makes high-dosage isoniazid therapy, given in combination with other drugs or alone, a possible proposition in developing countries. Studies in the Centre have produced clear evidence that there is an increase in the frequency of peripheral neuropathy when the dosage of isoniazid is increased from 7.8-9.6 mg/kg body-weight to 12.5-15.6 mg/kg daily, and that its incidence is higher among slow than among rapid inactivators of isoniazid. The studies also show that increasing the dosage of isoniazid when given alone from a moderate daily dosage of 7.8-9.6 mg/kg to the high daily dosage of 12.5-15.6 mg/kg has not materially altered the radiographic or the bacteriological response to treatment. PMID:14099673

  3. The prevention and treatment of isoniazid toxicity in the therapy of pulmonary tuberculosis

    PubMed Central

    1963-01-01

    This paper from the Tuberculosis Chemotherapy Centre, Madras, presents the results of a study designed primarily (a) to assess the efficacy of two preparations—Tab. Aneurin. Co. (a vitamin B compound not containing pyridoxine) and glutamic acid—in preventing the development of peripheral neuropathy during high-dosage (12.5-15.2 mg/kg) isoniazid therapy for pulmonary tuberculosis, and (b) to compare the therapeutic efficacy, once isoniazid neuropathy has developed, of Tab. Aneurin. Co., administered at twice the prophylactic dosage, and a vitamin-B-complex preparation containing a small amount of pyridoxine (amounting to 6 mg daily). Tab. Aneurin. Co. was found to be ineffective in preventing peripheral neuropathy, which occurred in five of the 18 patients receiving this preparation, as compared with six of the 18 who received a placebo, calcium gluconate. Glutamic acid appeared to have some prophylactic effect, since only two of the 19 patients receiving it developed the neuropathy, but the difference between the frequency in the glutamic series and that in the placebo series did not attain statistical significance. As to the therapeutic efficacy of the two vitamin B preparations, Tab. Aneurin. Co., at twice the prophylactic dosage, did not prevent the progression of the neuropathy in five out of seven patients, whereas improvement occurred in eight of the nine patients who received the vitamin-B-complex preparation containing the small amount of pyridoxine. This study has confirmed that the frequency of peripheral neuropathy is significantly higher among slow than among rapid inactivators of isoniazid and has indicated that the therapeutic response of the tuberculosis is not materially affected by increasing the dosage of isoniazid from 7.8-9.6 mg/kg (the dosage used in a previous study) to 12.5-15.2 mg/kg. PMID:20604148

  4. Interventions to improve delivery of isoniazid preventive therapy: an overview of systematic reviews

    PubMed Central

    2014-01-01

    Background Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals. Methods We searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), and MEDLINE up to August 15, 2012. Two authors used a standardized data extraction form and the AMSTAR instrument to independently assess each review. Results Six reviews met inclusion criteria. Interventions included changes in the setting/site of IPT delivery, use of quality monitoring mechanisms (e.g., directly observed therapy), IPT delivery integration into other healthcare services, and use of lay health workers. Most reviews reported a combination of outcomes related to IPT adherence and treatment completion rate but without a baseline or comparison rate. Generally, we found limited evidence to demonstrate that the studied interventions improved treatment completion. Conclusions While most of the interventions were not shown to improve IPT completion, integration of tuberculosis and HIV services yielded high treatment completion rates in some settings. The lack of data from high burden TB settings limits applicability. Further research to assess different IPT delivery interventions, including those that address barriers to care in at-risk populations, is urgently needed to identify the most effective practices for IPT delivery and TB control in high TB burden settings. PMID:24886159

  5. Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind placebo-controlled trial

    PubMed Central

    Rangaka, Molebogeng X; Wilkinson, Robert J; Boulle, Andrew; Glynn, Judith R; Fielding, Katherine; van Cutsem, Gilles; Wilkinson, Katalin A; Goliath, Rene; Mathee, Shaheed; Goemaere, Eric; Maartens, Gary

    2014-01-01

    Background Antiretroviral therapy (ART) reduces the risk of tuberculosis, but the incidence still exceeds that in HIV-uninfected people. Isoniazid preventive therapy (IPT), which decreases the risk of tuberculosis in people not on ART, may offer additional protection. Methods Pragmatic randomized double-blind placebo-controlled trial to evaluate the effect of 12 months IPT among participants established on or newly starting ART, in Khayelitsha, South Africa (NCT00463086, Lancet D-09-02885). Tuberculosis was excluded at screening by sputum culture. Incident tuberculosis was the primary endpoint. Findings 1,329 participants contributed 3,227 person-years (PY) of follow up in the modified intention-to-treat analysis; 662 on IPT and 667 on placebo. There were 95 incident tuberculosis cases: 2.3 (95%CI 1.6-3.1) versus 3.6 (95%CI 2.8-4.7) per 100 PY in the IPT and placebo arms respectively (hazard ratio 0.63, 95%CI 0.41-0.94). Study drug was discontinued due to grade 3 or 4 raised ALT in 19/662 in the IPT and 10/667 in the placebo arm, risk ratio=1.9 (95%CI 0.90-4.09). In secondary analyses, there was no evidence that the effect of IPT was restricted to those who were positive on tuberculin skin test (TST) or interferon gamma release assay (IGRA): adjusted hazard ratio for those with negative tests 0.43 (95%CI 0.21-0.86) and 0.43 (95%CI 0.20-0.96); for positive tests 0.86 (95%CI 0.37-2.00) and 0.55 (95%CI 0.26-1.24) respectively. No all cause mortality benefit of IPT was demonstrated Interpretation IPT reduced the incidence of tuberculosis in HIV-infected individuals on ART. In this high incidence setting, individuals on ART who have TST or IGRA negative results may also benefit from IPT. IPT can easily be implemented in ART clinics. PMID:24835842

  6. THE PREVENTION AND TREATMENT OF ISONIAZID TOXICITY IN THE THERAPY OF PULMONARY TUBERCULOSIS. 2. AN ASSESSMENT OF THE PROPHYLACTIC EFFECT OF PYRIDOXINE IN LOW DOSAGE.

    PubMed

    ZILBER, L A; BAJDAKOVA, Z L; GARDASJAN, A N; KONOVALOV, N V; BUNINA, T L; BARABADZE, E M

    1963-01-01

    A recent report from the Tuberculosis Chemotherapy Centre, Madras, showed that a vitamin-B-complex preparation containing a small amount of pyridoxine (as well as aneurine hydrochloride, riboflavine, nicotinamide, panthenol and cyanocobalamin) was effective in the treatment of peripheral neuropathy caused by daily high-dosage (12.5-15.2 mg/kg body-weight) isoniazid therapy of pulmonary tuberculosis. The present report gives results which show that the B-complex preparation is fully effective in preventing peripheral neuropathy in patients receiving the same high dosage of isoniazid, and that this is due to the small pyridoxine content of only 6 mg daily, and not to any of its other constituents. The low cost of this small dose of pyridoxine makes high-dosage isoniazid therapy, given in combination with other drugs or alone, a possible proposition in developing countries.Studies in the Centre have produced clear evidence that there is an increase in the frequency of peripheral neuropathy when the dosage of isoniazid is increased from 7.8-9.6 mg/kg body-weight to 12.5-15.6 mg/kg daily, and that its incidence is higher among slow than among rapid inactivators of isoniazid.The studies also show that increasing the dosage of isoniazid when given alone from a moderate daily dosage of 7.8-9.6 mg/kg to the high daily dosage of 12.5-15.6 mg/kg has not materially altered the radiographic or the bacteriological response to treatment. PMID:14099673

  7. Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point.

    PubMed

    Tadesse, Yared; Gebre, Nigussie; Daba, Shallo; Gashu, Zewdu; Habte, Dereje; Hiruy, Nebiyu; Negash, Solomon; Melkieneh, Kassahun; Jerene, Degu; K Haile, Yared; Kassie, Yewulsew; Melese, Muluken; G Suarez, Pedro

    2016-01-01

    A child's risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76-4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges. PMID:27196627

  8. Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point

    PubMed Central

    Gebre, Nigussie; Daba, Shallo; Gashu, Zewdu; Habte, Dereje; Hiruy, Nebiyu; Negash, Solomon; Melkieneh, Kassahun; Jerene, Degu; K. Haile, Yared; Kassie, Yewulsew; Melese, Muluken; G. Suarez, Pedro

    2016-01-01

    A child’s risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76–4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges. PMID:27196627

  9. Benefits of combined preventive therapy with co-trimoxazole and isoniazid in adults living with HIV: time to consider a fixed-dose, single tablet coformulation.

    PubMed

    Harries, Anthony D; Lawn, Stephen D; Suthar, Amitabh B; Granich, Reuben

    2015-12-01

    Antiretroviral therapy (ART) is the main intervention needed to reduce morbidity and mortality and to prevent tuberculosis in adults living with HIV. However, in most resource-limited countries, especially in sub-Saharan Africa, ART is started too late to have an effect with substantial early morbidity and mortality, and in high tuberculosis burden settings ART does not reduce the tuberculosis risk to that reported in individuals not infected with HIV. Co-trimoxazole preventive therapy started before or with ART, irrespective of CD4 cell count, reduces morbidity and mortality with benefits that continue indefinitely. Isoniazid preventive therapy as an adjunct to ART prevents tuberculosis in high-exposure settings, with long-term treatment likely to be needed to sustain this benefit. Unfortunately, both preventive therapies are underused in low-income and high-burden settings. ART development has benefited from patient-centred simplification with several effective regimens now available as a one per day pill. We argue that co-trimoxazole and isoniazid should also be combined into a single fixed-dose pill, along with pyridoxine (vitamin B6), that would be taken once per day to help with individual uptake and national scale-up of therapies. PMID:26515525

  10. Systematic Review of TST Responses in People Living with HIV in Under-Resourced Settings: Implications for Isoniazid Preventive Therapy

    PubMed Central

    Kerkhoff, Andrew D.; Kranzer, Katharina; Samandari, Taraz; Nakiyingi-Miiro, Jessica; Whalen, Christopher C.; Harries, Anthony D.; Lawn, Stephen D.

    2012-01-01

    Background People living with HIV (PLWH) who have positive tuberculin skin tests (TST) benefit from isoniazid preventive therapy (IPT) whereas those testing TST-negative do not. Revised World Health Organization guidelines explicitly state that assessment of TST is not a requirement for initiation of IPT. However, it is not known what proportions of patients will benefit from IPT if implemented without targeting according to TST status. We therefore determined the proportions of PLWH who test TST-positive. Methodology/Principal Findings We systematically reviewed the literature published between January 1990 and February 2012 to determine the proportions of patients without active tuberculosis attending HIV care services in low and middle-income countries who tested TST-positive (≥5 mm induration). Proportions were also determined for different CD4 count strata. Data from 19 studies with 9,478 PLWH from sub-Saharan Africa, Asia and Central and South America were summarized. The vast majority were not receiving antiretroviral therapy (ART). A sub-analysis was conducted of 5 studies (5,567 subjects) from high TB prevalence countries of PLWH with negative TB screens attending HIV care and treatment settings for whom CD4 stratified data were available. The median proportion of PLWH testing TST-positive overall was 22.8% (range, 19.5–32.6%). The median (range) proportions with CD4 cell counts of <200, 200–499 or ≥500 cells/µL who tested positive were 12.4% (8.2–15.3%), 28.4% (20.1–36.9%) and 37.4% (31.3–56.3%), respectively. Heterogeneity in the data precluded calculation of pooled summary estimates. Conclusions/Significance In most settings, if IPT is administered to PLWH pre-ART without assessment of TST status, only a minority of those treated are likely to benefit, especially among those with the lowest CD4 cell counts. This may be inefficient use of resources and cost-effectiveness analyses should take this into account. Local knowledge of TST

  11. High Incidence of Tuberculosis in the Absence of Isoniazid and Cotrimoxazole Preventive Therapy in Children Living with HIV in Northern Ethiopia: A Retrospective Follow-Up Study

    PubMed Central

    Alemu, Yihun Mulugeta; Andargie, Gashaw; Gebeye, Ejigu

    2016-01-01

    Objective To identify the incidence of and predictors for tuberculosis in children living with HIV in Northern Ethiopia. Design Observational, retrospective follow-up study. Methods A total of 645 HIV-infected children were observed between September 2009 and September 2014. Cox regression analysis was used to identify predictors for developing TB. Results The incidence rate of tuberculosis was 4.2 per 100 child-years. Incidence of tuberculosis was higher for subjects who were not on cotrimoxazole preventive therapy, were not on isoniazid preventive therapy, had delayed motor development, had a CD4 cell count below the threshold, had hemoglobin level less than 10 mg/dl and were assessed as World Health Organization (WHO) clinical stage III or IV. Conclusion Incidence of TB in children living with HIV was high. This study reaffirmed that isoniazid preventive therapy is one of the best strategy to reduce incidence of TB in children living with HIV. All children living with HIV should be screened for TB but for children with delayed motor development, advanced WHO clinical stage, anemia or immune suppression, intensified screening is highly recommended. PMID:27070435

  12. Tuberculin Skin Test Reversion following Isoniazid Preventive Therapy Reflects Diversity of Immune Response to Primary Mycobacterium tuberculosis Infection

    PubMed Central

    Johnson, Denise F.; Malone, LaShaunda L.; Zalwango, Sarah; Mukisa Oketcho, Joy; Chervenak, Keith A.; Thiel, Bonnie; Mayanja-Kizza, Harriet; Stein, Catherine M.; Boom, W. Henry; Lancioni, Christina L.

    2014-01-01

    Rationale Healthy household contacts (HHC) of individuals with Tuberculosis (TB) with Tuberculin Skin Test (TST) conversions are considered to harbor latent Mycobacterium tuberculosis (Mtb), and at risk for TB. The immunologic, clinical, and public health implications of TST reversions that occur following Isoniazid preventive therapy (IPT) remain controversial. Objectives To measure frequency of TST reversion following IPT, and variation in interferon-gamma (IFN-γ) responses to Mtb, in healthy Ugandan TB HHC with primary Mtb infection evidenced by TST conversion. Methods Prospective cohort study of healthy, HIV-uninfected, TST-negative TB HHC with TST conversions. Repeat TST was performed 12 months following conversion (3 months following completion of 9 month IPT course) to assess for stable conversion vs. reversion. Whole blood IFN-γ responses to Mtb antigen 85B (MtbA85B) and whole Mtb bacilli (wMtb) were measured in a subset (n = 27 and n = 42, respectively) at enrollment and TST conversion, prior to initiation of IPT. Results Of 122 subjects, TST reversion was noted in 25 (20.5%). There were no significant differences in demographic, clinical, or exposure variables between reverters and stable converters. At conversion, reverters had significantly smaller TST compared to stable converters (13.7 mm vs 16.4 mm, respectively; p = 0.003). At enrollment, there were no significant differences in IFN-γ responses to MtbA85B or wMTB between groups. At conversion, stable converters demonstrated significant increases in IFN-γ responses to Ag85B and wMtb compared to enrollment (p = 0.001, p<0.001, respectively), while there were no significant changes among reverters. Conclusions TST reversion following IPT is common following primary Mtb infection and associated with unique patterns of Mtb-induced IFN-γ production. We have demonstrated that immune responses to primary Mtb infection are heterogeneous, and submit that prospective longitudinal studies

  13. Risk of Disease After Isoniazid Preventive Therapy for Mycobacterium tuberculosis Exposure in Young HIV-uninfected Children

    PubMed Central

    Tameris, Michele D.; Geldenhuys, Hennie D.; Mulenga, Humphrey; Van Schalkwyk, Amaryl; Hughes, Elizabeth J.; Toefey, Asma; Scriba, Thomas J.; Hussey, Gregory; Mahomed, Hassan; McShane, Helen; Landry, Bernard; Hanekom, Willem A.; Hatherill, Mark

    2015-01-01

    Background: The risk of developing tuberculosis (TB) disease in HIV-uninfected children after isoniazid preventive therapy (IPT) for a positive QuantiFERON-TB Gold In-Tube test (QFT-GIT) is unknown. The aim of this study was to evaluate risk of TB disease after IPT in young HIV-uninfected children with a positive QFT-GIT result, or household TB contact. Methods: HIV-uninfected South African infants aged 4–6 months were screened for enrolment in a TB vaccine trial. Baseline household TB contact and positive QFT-GIT result were exclusion criteria, and these infants were referred for IPT. Outcome data are reported for 36 months after IPT referral. Results: Four thousand seven hundred forty-nine infants were screened. Household TB contact was reported in 131 (2.8%) infants; 279 (6.0%) were QFT-GIT positive, and 138 of these 410 infants (34.0%) started IPT. Forty-four cases of TB disease (11.0%) were recorded within 991 child years of observation. TB disease incidence was 4.8 versus 3.6 per 100 child years in household exposed versus QFT-GIT-positive children [incidence rate ratio: 1.35; 95% confidence interval (CI): 0.67–2.88] and 2.4 versus 5.5 per 100 child years in children who received versus did not receive IPT, respectively (incidence rate ratio: 0.44; 95% CI: 0.17–0.96). Adjusted hazard ratio (Cox regression) for TB disease was 0.48 (95% CI: 0.21–1.05) for those who received IPT. Conclusion: In young HIV-uninfected children, the effect of IPT on risk of TB disease is similar, whether TB exposure was defined by household contact history or by positive QFT-GIT result. International IPT guidelines for HIV-uninfected children with a positive QFT-GIT result should be updated. PMID:26252568

  14. Implementation of Tuberculosis Intensive Case Finding, Isoniazid Preventive Therapy, and Infection Control ("Three I's") and HIV-Tuberculosis Service Integration in Lower Income Countries

    PubMed Central

    Charles, M. Katherine; Lindegren, Mary Lou; Wester, C. William; Blevins, Meridith; Sterling, Timothy R.; Dung, Nguyen Thi; Dusingize, Jean Claude; Avit-Edi, Divine; Durier, Nicolas; Castelnuovo, Barbara; Nakigozi, Gertrude; Cortes, Claudia P.; Ballif, Marie; Fenner, Lukas

    2016-01-01

    Setting World Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control (“Three I’s”) for TB prevention and control among persons living with HIV. Objective To assess the implementation of the “Three I’s” of TB-control at HIV treatment sites in lower income countries. Design Survey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa. Results ICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03). Conclusions Implementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status. PMID:27073928

  15. Isoniazid

    MedlinePlus

    (eye soe nye' a zid)Isoniazid may cause severe and sometimes fatal liver damage. Tell your doctor if you have or have ever had liver disease or a history of alcoholism or injection drug use. Keep all appointments with ...

  16. Isoniazid prevents Nrf2 translocation by inhibiting ERK1 phosphorylation and induces oxidative stress and apoptosis

    PubMed Central

    Verma, Ajeet Kumar; Yadav, Arti; Dewangan, Jayant; Singh, Sarvendra Vikram; Mishra, Manisha; Singh, Pradhyumna Kumar; Rath, Srikanta Kumar

    2015-01-01

    Isoniazid is used either alone or in combination with other drugs for the treatment of tuberculosis. It is also used for the prevention of tuberculosis. Chronic treatment of Isoniazid may cause severe liver damage leading to acute liver failure. The mechanism through which Isoniazid causes liver damage is investigated. Isoniazid treatment generates reactive oxygen species and induces apoptosis in Hep3B cells. It induces antioxidative and apoptotic genes leading to increase in mRNA expression and protein levels in Hep3B cells. Whole genome expression analysis of Hep3B cells treated with Isoniazid has resulted in differential expression of various genes playing prime role in regulation of apoptotic, antioxidative, DNA damage, cell signaling, cell proliferation and differentiation pathways. Isoniazid increased cytosolic Nrf2 protein level while decreased nuclear Nrf2 protein level. It also decreased ERK1 phosphorylation and treatment of Hep3B cells with ERK inhibitor followed by Isoniazid resulting in increased apoptosis in these cells. Two dimensional gel electrophoresis results have also shown differential expression of various protein species including heat shock proteins, proteins playing important role in oxidative stress, DNA damage, apoptosis, cell proliferation and differentiation. Results suggest that Isoniazid induces apoptosis through oxidative stress and also prevents Nrf2 translocation into the nucleus by reducing ERK1 phosphorylation thus preventing cytoprotective effect. PMID:26202867

  17. Preventive therapy for tuberculosis in Maryland.

    PubMed

    Rabindran, E; Matuszak, D L; Israel, E; Woodall, H; Highsmith, H; Flynn, J

    1991-09-01

    Maryland data substantiate the safety of isoniazid therapy in preventing tuberculosis. To eradicate tuberculosis in the U.S., private physicians must play an active role by offering preventive therapy to patients at high risk of developing the disease. PMID:1921656

  18. The pharmacokinetics of nevirapine when given with isoniazid in South African HIV-infected individuals

    PubMed Central

    DECLOEDT, Eric H; MWANSA-KAMBAFWILE, Judith; VAN DER WALT, Jan-Stefan; MCILLERON, Helen; DENTI, Paolo; SMITH, Peter; WIESNER, Lubbe; RANGAKA, Molebogeng; WILKINSON, Robert J; MAARTENS, Gary

    2014-01-01

    Summary Isoniazid preventive therapy is recommended in patients on antiretroviral therapy. Isoniazid inhibits CYP3A4, which metabolizes nevirapine. Administration of isoniazid may cause higher nevirapine concentrations and toxicity. We studied the effect of isoniazid on nevirapine concentrations in 21 patients randomized to either placebo (n=13) or isoniazid (n=8) in an ongoing trial of IPT in patients on ART. Isoniazid was associated with a 24% increase in median nevirapine AUC0-12, which was not statistically significant (p=0.66). PMID:23407222

  19. Isoniazid toxicity and TB development during biological therapy of patients with psoriasis in Colombia.

    PubMed

    Cataño, Juan; Morales, Milena

    2016-10-01

    Background The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. Objective The aim of this study was to present the follow-up results for Isoniazid (INH) chemoprophylaxis in patients with psoriasis receiving different biological therapies. Methods In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between two and nine months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. Results A total of 101 patients, 44.5% females, with a mean age of 46.9 ± 11.5 years (20-73) were enrolled. LTBI was identified in 100 patients (99%), of whom 81.2% completed nine months of chemoprophylaxis. Three patients (2.9%) developed active TB and 17 patients (16.8%) developed intolerance or toxicity related to INH. Conclusions Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivations in individuals with LTBI receiving biological therapy, but toxicity must be monitored during follow-up. PMID:27003177

  20. Follow-up results of isoniazid chemoprophylaxis during biological therapy in Colombia.

    PubMed

    Cataño, Juan Carlos; Morales, Milena

    2015-09-01

    The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. The aim of this study was to present the follow-up results for isoniazid (INH) chemoprophylaxis in patients receiving different biological therapies. In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between 2 and 9 months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. A total of 221 patients, 122 females (55.2 %), with a mean age of 46.8 ± 11.3 years (16-74) were enrolled. LTBI was identified in 218 patients (98.7 %), all of whom received INH chemoprophylaxis. Seven patients (3.2 %) developed active tuberculosis, and 32 (17.2 %) patients developed intolerance or toxicity related to INH. Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivation in individuals with LTBI, but toxicity must be monitored during follow-up. PMID:25763992

  1. Alopecia caused by isoniazid

    PubMed Central

    Dixit, Ramakant; Qureshi, Danish; Mathur, Sunil

    2014-01-01

    Drug-induced alopecia is a known clinical entity and mainly seen with anti-mitotic drug therapy. Alopecia during anti-tuberculosis therapy is very uncommon and previously observed with isoniazid, thiacetazone, and ethionamide. Present communication describes an additional case of isoniazid-induced alopecia in a 10-year-old male child, which was reversible after isoniazid withdrawal. Possible mechanisms of drug-induced alopecia are also briefly discussed. PMID:24799819

  2. Isoniazid preventive treatment in children in two districts of South India: does practice follow policy?

    PubMed Central

    Shivaramakrishna, H. R.; Frederick, A.; Shazia, A.; Murali, L.; Satyanarayana, S.; Nair, S. A.; Kumar, A. M.; Moonan, P. K.

    2015-01-01

    SUMMARY SETTING Two districts of Tamil Nadu, India OBJECTIVES To determine the proportion of household contacts aged <6 years of patients with tuberculosis (TB) with positive sputum microscopy results who initiated and completed isoniazid preventive treatment (IPT), and to determine reasons for non-initiation and non-completion of IPT. DESIGN Household visits were conducted on a random sample of adult patients registered during January–June 2012 to identify household contacts aged <6 years. RESULTS Among 271 children living with 691 index patients, 218 (80%) were evaluated and 9 (4%) were diagnosed with TB. Of 209 remaining contacts, 70 (33%) started IPT and 16 (22.9%) completed a full course of IPT. Of 139 contacts who did not start IPT, five developed TB disease. Reasons for non-initiation of IPT included no home visit by the field staff (19%) and no education about IPT (61%). Reasons for non-completion included isoniazid not provided (52%) and long duration of treatment (28%). CONCLUSION This study shows that Revised National TB Programme guidance was not being followed and IPT implementation was poor. Poor IPT uptake represents a missed opportunity to prevent future TB cases. Provision of IPT may be improved through training, improved logistics and enhanced supervision and monitoring. PMID:25199005

  3. Peripheral neuritis due to isoniazid*

    PubMed Central

    Devadatta, S.; Gangadharam, P. R. J.; Andrews, R. H.; Fox, Wallace; Ramakrishnan, C. V.; Selkon, J. B.; Velu, S.

    1960-01-01

    It is well known that in the treatment of tuberculosis with isoniazid the complication of peripheral neuritis may arise. This complication is normally rare when small dosages of the drug are used, but a high incidence of the neuropathy has recently been observed in East Africa in a group of malnourished tuberculous patients receiving isoniazid in comparatively low dosage (4-6 mg/kg body-weight daily). The present paper reports on 20 cases of peripheral neuritis encountered in Madras, India, among 338 poorly nourished tuberculous patients during a trial of four isoniazid regimens, two of low and two of high dosage (3.9-5.5 and 7.8-9.6 mg/kg body-weight daily, respectively). Nineteen of the 20 cases occurred in the two groups of patients receiving the high dosage and these 19 patients were found to have a higher mean serum level of free isoniazid than the patients in the same groups who did not develop the complication. The authors consider that dosages of 7.8-9.6 mg/kg body-weight daily should not be used for the mass therapy of poorly nourished patients unless steps are taken to prevent the development of peripheral neuritis. Pyridoxine has been reported to be an effective preventive, but is too expensive for use on a large scale. This study indicates, however, that administration of the cheaper vitamin B complex might give satisfactory results and warrants further investigation. PMID:13722334

  4. Successful desensitization therapy for a patient with isoniazid-induced hypersensitivity pneumonia.

    PubMed

    Chihara, Yuichi; Takahashi, Ken-Ichi; Sakai, Naoki; Sato, Atsuo; Tsuboi, Tomomasa

    2016-01-01

    A 57-year-old male was diagnosed with mycobacterium tuberculoma and was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Three weeks after initiation of treatment, he presented with fever and appetite loss. Chest radiograph showed diffuse micronodular shadows on both lung fields. High-resolution chest computed tomography findings were diffuse parenchymal micronodules in both lungs, which was consistent with hypersensitivity pneumonia. Because drug-induced pneumonia was suspected, the antituberculous regimen was discontinued. The symptoms and diffuse micronodular shadows improved. A drug lymphocyte stimulation test was only positive for isoniazid, so we suspected that the pneumonia was induced by isoniazid. Rifampicin and ethambutol were reintroduced without any recurrence of the abnormal shadows. Next, we tried desensitization to isoniazid over a period of two weeks, which was successful without any adverse events. Although isoniazid-induced pneumonia is extremely rare, it is important to recognize that isoniazid can cause such an adverse reaction. In addition, drug desensitization may be useful in drug-induced pneumonia. PMID:27330958

  5. Isoniazid induced convulsions at therapeutic dose in an alcoholic and smoker patient.

    PubMed

    Aiwale, Amol S; Patel, Utkarsh A; Barvaliya, Manish J; Jha, Pramod R; Tripathi, Chandrabhanu

    2015-01-01

    We report a case of isoniazid induced convulsions in 35 years old male alcoholic and smoker patient receiving intensive phase therapy for pulmonary tuberculosis. A case was confirmed by accidental positive de-challenge and rechallenge as well as ruled out other conditions. Use of isoniazid in alcoholic and smoker patient required a caution for prevention of neurological adverse reactions. Pyridoxine should always be prescribed to such patients for the prevention of such adverse reaction. PMID:25859682

  6. Different Risk of Tuberculosis and Efficacy of Isoniazid Prophylaxis in Rheumatoid Arthritis Patients with Biologic Therapy: A Nationwide Retrospective Cohort Study in Taiwan

    PubMed Central

    Chen, Yi-Ming; Chang, Chia-Li; Chen, Hsin-Hua; Chen, Der-Yuan

    2016-01-01

    Increasing evidence indicates an increased risk of tuberculosis (TB) for rheumatoid arthritis (RA) patients receiving biologic therapy, and the effectiveness of isoniazid prophylaxis (INHP) in TB prevention. We aimed to examine 1) the incidence rate (IR) and risk factors for TB among RA patients receiving different therapies; 2) INHP effectiveness for TB prevention; 3) mortality rates after TB diagnosis in patients receiving different therapies. This retrospective study was conducted using a nationwide database: 168,720 non-RA subjects and a total of 42,180 RA patients including 36,162 csDMARDs-exposed, 3,577 etanercept-exposed, 1,678 adalimumab-exposed and 763 rituximab-exposed patients. TB risk was 2.7-fold higher in RA cohort compared with non-RA group, with an adjusted hazard ratio (aHR) of 2.58. Advanced age, male, the use of corticosteroids≧5mg/day, and the presence of diabetes mellitus (DM), chronic obstructive pulmonary disease and chronic kidney disease were risk factors for developing TB. Using csDMARDs-exposed group as reference, aHR of TB was the highest with adalimumab treatment (1.52), followed by etanercept (1.16), and the lowest with rituximab (0.08). INHP could effectively reduce TB risk in biologics-exposed patients. Mortality rates after TB diagnosis were higher in RA patients, particularly the elderly and those with DM, with lower rates in adalimumab-exposed patients compared with csDMARDs-exposed patients. In conclusion, TB risk was increased in patients receiving TNF-α inhibitors, but the risk associated with rituximab therapy was relatively low. With the effectiveness of INHP shown in the prevention of biologics-associated TB, stricter implementation of INHP should be beneficial. The mortality from biologics–associated TB may be efficiently reduced through increased awareness. PMID:27064275

  7. Different Risk of Tuberculosis and Efficacy of Isoniazid Prophylaxis in Rheumatoid Arthritis Patients with Biologic Therapy: A Nationwide Retrospective Cohort Study in Taiwan.

    PubMed

    Liao, Tsai-Ling; Lin, Ching-Heng; Chen, Yi-Ming; Chang, Chia-Li; Chen, Hsin-Hua; Chen, Der-Yuan

    2016-01-01

    Increasing evidence indicates an increased risk of tuberculosis (TB) for rheumatoid arthritis (RA) patients receiving biologic therapy, and the effectiveness of isoniazid prophylaxis (INHP) in TB prevention. We aimed to examine 1) the incidence rate (IR) and risk factors for TB among RA patients receiving different therapies; 2) INHP effectiveness for TB prevention; 3) mortality rates after TB diagnosis in patients receiving different therapies. This retrospective study was conducted using a nationwide database: 168,720 non-RA subjects and a total of 42,180 RA patients including 36,162 csDMARDs-exposed, 3,577 etanercept-exposed, 1,678 adalimumab-exposed and 763 rituximab-exposed patients. TB risk was 2.7-fold higher in RA cohort compared with non-RA group, with an adjusted hazard ratio (aHR) of 2.58. Advanced age, male, the use of corticosteroids ≧ 5 mg/day, and the presence of diabetes mellitus (DM), chronic obstructive pulmonary disease and chronic kidney disease were risk factors for developing TB. Using csDMARDs-exposed group as reference, aHR of TB was the highest with adalimumab treatment (1.52), followed by etanercept (1.16), and the lowest with rituximab (0.08). INHP could effectively reduce TB risk in biologics-exposed patients. Mortality rates after TB diagnosis were higher in RA patients, particularly the elderly and those with DM, with lower rates in adalimumab-exposed patients compared with csDMARDs-exposed patients. In conclusion, TB risk was increased in patients receiving TNF-α inhibitors, but the risk associated with rituximab therapy was relatively low. With the effectiveness of INHP shown in the prevention of biologics-associated TB, stricter implementation of INHP should be beneficial. The mortality from biologics-associated TB may be efficiently reduced through increased awareness. PMID:27064275

  8. 3D-printed hierarchical scaffold for localized isoniazid/rifampin drug delivery and osteoarticular tuberculosis therapy.

    PubMed

    Zhu, Min; Li, Kun; Zhu, Yufang; Zhang, Jianhua; Ye, Xiaojian

    2015-04-01

    After surgical treatment of osteoarticular tuberculosis (TB), it is necessary to fill the surgical defect with an implant, which combines the merits of osseous regeneration and local multi-drug therapy so as to avoid drug resistance and side effects. In this study, a 3D-printed macro/meso-porous composite scaffold is fabricated. High dosages of isoniazid (INH)/rifampin (RFP) anti-TB drugs are loaded into chemically modified mesoporous bioactive ceramics in advance, which are then bound with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) through a 3D printing procedure. The composite scaffolds show greatly prolonged drug release time compared to commercial calcium phosphate scaffolds either in vitro or in vivo. In addition, the drug concentrations on the periphery tissues of defect are maintained above INH/RFP minimal inhibitory concentrations even up to 12 weeks post-surgery, while they are extremely low in blood. Examinations of certain serum enzymes suggest no harm to hepatic or renal functions. Micro-CT evaluations and histology results also indicate partly degradation of the composite scaffolds and new bone growth in the cavity. These results suggest promising applications of our hierarchical composite scaffold in bone regeneration and local anti-TB therapy after osteoarticular TB debridement surgery. PMID:25653217

  9. In vitro evaluation of inhalable isoniazid-loaded surfactant liposomes as an adjunct therapy in pulmonary tuberculosis.

    PubMed

    Chimote, G; Banerjee, R

    2010-07-01

    In this study, exogenous pulmonary surfactant was evaluated as an inhalable drug carrier for antitubercular drug isoniazid (INH). Isoniazid-entrapped liposomes of dipalmitoylphosphatidylcholine (DPPC) (the most abundant lipid of lung surfactant and exogenous surfactant) were developed and evaluated for size, drug entrapment, release, in vitro alveolar deposition, biocompatibility, antimycobacterial activity, and pulmonary surfactant action. Isoniazid-entrapped DPPC liposomes were about 750 nm in diameter and had entrapment efficiency of 36.7% +/- 1.8%. Sustained release of INH from DPPC liposomes was observed over 24 h. In vitro alveolar deposition efficiency using the twin impinger exhibited approximately 25-27% INH deposition in the alveolar chamber upon one minute nebulization using a jet nebulizer. At 37 degrees C, the formulation had better pulmonary surfactant function with quicker reduction of surface tension on adsorption (36.7 +/- 0.4 mN/m) than DPPC liposomes (44.7 +/- 0.6 mN/m) and 87% airway patency was exhibited by the formulation in a capillary surfactometer. The formulation was biocompatible and had antimycobacterial activity. The isoniazid-entrapped DPPC liposomes could fulfill the dual purpose of pulmonary drug delivery and alveolar stabilization due to antiatelectatic effect of the surfactant action which can improve the reach of antitubercular drug INH to the alveoli. PMID:20524179

  10. Acute Psychosis after Recent Isoniazid Initiation.

    PubMed

    Arya, Sidharth; Sukhija, Gagandeep; Singh, Harpreet

    2015-06-01

    Isoniazid as part of Directly Observed Treatment-Short course (DOTS) regimen is universally used. Although, associated psychosis in certain cases is documented earlier, type of symptoms and onset of symptoms remains highly variable. We describe a case of 54-year-old female on anti-tubercular therapy with onset of psychosis within three days of Isoniazid initiation characterised by agitation, loosening of association, echolalia with spontaneous remission after drug stoppage. This case highlights the importance of remaining vigilant and considering isoniazid as possible causative agent for psychosis even within days of its intiation and avoiding delay in management. PMID:26266198

  11. Isoniazid-induced alopecia

    PubMed Central

    Gupta, K. B.; Kumar, V.; Vishvkarma, S.; Shandily, R.

    2011-01-01

    Isoniazid is a safe and very effective antituberculosis drug. Antimitotic agents routinely cause alopecia. Drug-induced alopecia is usually reversible upon withdrawal of the drug. Isoniazid, thiacetazone and ethionamide are the antituberculosis drugs which have been associated with alopecia. Isoniazid-induced alopecia was observed in one case and confirmed by the finding that hair growth resumed when drug removed from the regimen. PMID:21654989

  12. Isoniazid-resistant Mycobacterium kansasii in an HIV-positive patient, and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy: case report.

    PubMed

    Despotovic, A; Savic, B; Salemovic, D; Ranin, J; Jevtovic, Dj

    2016-01-01

    Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB) was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn. Highly active antiretroviral therapy (HAART) was initiated soon after, consisting of abacavir/lamivudine and efavirenz. The patient's general condition deteriorated 2 weeks after HAART initiation, which could have been due to the development of immune reconstitution inflammatory syndrome (IRIS). The patient recovered and was discharged in good condition. However, the results of resistance testing of the isolated organism arrived after discharge, and showed isoniazid and streptomycin resistance. This is the first case report of M. kansasii infection from Serbia and shows the difficulties encountered during the course of treatment. PMID:26603644

  13. Transmission of Mycobacterium tuberculosis in a High School and School-Based Supervision of an Isoniazid-Rifapentine Regimen for Preventing Tuberculosis - Colorado, 2011-2012.

    PubMed

    2013-10-01

    Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), is spread from person to person by the airborne route. It can be transmitted extensively in congregate settings, making investigating exposures and treating infected contacts challenging. In December 2011, a student at a Colorado high school with 1,381 students and school personnel received a diagnosis of pulmonary TB disease. One of five household contacts had TB disease, and the other four had latent M. tuberculosis infection (LTBI). Screening of 1,249 school contacts (90%) found one person with pulmonary TB disease, who was fully treated, and 162 with LTBI, of whom 159 started an LTBI treatment regimen for preventing progression to TB disease and 153 completed a regimen. Only the index patient required inpatient care for TB, and TB caused no deaths. Use of short-course treatment regimens, either 12-dose weekly isoniazid and rifapentine directly observed at school or 4 months of self-supervised rifampin daily, facilitated treatment completion. State and county incident command structures led by county TB control authorities guided a response team from multiple jurisdictions. News media reports brought public scrutiny, but meetings with the community addressed the concerns and enhanced public participation. Two contacts of the index patient outside of the school had TB disease diagnosed after the school investigation. As of July 2013, no additional TB disease associated with in-school exposure had been found. An emergency plan for focusing widespread resources, an integral public communications strategy, and new, efficient interventions should be considered in other large TB contact investigations. PMID:24080593

  14. How could preventive therapy affect the prevalence of drug resistance? Causes and consequences.

    PubMed

    Kunkel, Amber; Colijn, Caroline; Lipsitch, Marc; Cohen, Ted

    2015-06-01

    Various forms of preventive and prophylactic antimicrobial therapies have been proposed to combat HIV (e.g. pre-exposure prophylaxis), tuberculosis (e.g. isoniazid preventive therapy) and malaria (e.g. intermittent preventive treatment). However, the potential population-level effects of preventative therapy (PT) on the prevalence of drug resistance are not well understood. PT can directly affect the rate at which resistance is acquired among those receiving PT. It can also indirectly affect resistance by altering the rate at which resistance is acquired through treatment for active disease and by modifying the level of competition between transmission of drug-resistant and drug-sensitive pathogens. We propose a general mathematical model to explore the ways in which PT can affect the long-term prevalence of drug resistance. Depending on the relative contributions of these three mechanisms, we find that increasing the level of coverage of PT may result in increases, decreases or non-monotonic changes in the overall prevalence of drug resistance. These results demonstrate the complexity of the relationship between PT and drug resistance in the population. Care should be taken when predicting population-level changes in drug resistance from small pilot studies of PT or estimates based solely on its direct effects. PMID:25918446

  15. Preventive therapy in children exposed to Mycobacterium tuberculosis: problems and solutions.

    PubMed

    Rutherford, Merrin E; Hill, Philip C; Triasih, Rina; Sinfield, Rebecca; van Crevel, Reinout; Graham, Stephen M

    2012-10-01

    Young children living with a tuberculosis patient are at high risk of Mycobacterium tuberculosis infection and disease. WHO guidelines promote active screening and isoniazid (INH) preventive therapy (PT) for such children under 5 years, yet this well-established intervention is seldom used in endemic countries. We review the literature regarding barriers to implementation of PT and find that they are multifactorial, including difficulties in screening, poor adherence, fear of increasing INH resistance and poor acceptability among primary caregivers and healthcare workers. These barriers are largely resolvable, and proposed solutions such as the adoption of symptom-based screening and shorter drug regimens are discussed. Integrated multicomponent and site-specific solutions need to be developed and evaluated within a public health framework to overcome the policy-practice gap and provide functional PT programmes for children in endemic settings. PMID:22862994

  16. Emerging Therapies for Scar Prevention

    PubMed Central

    Block, Lisa; Gosain, Ankush; King, Timothy W.

    2015-01-01

    Significance: There are ∼12 million traumatic lacerations treated in the United States emergency rooms each year, 250 million surgical incisions created worldwide every year, and 11 million burns severe enough to warrant medical treatment worldwide. In the United States, over $20 billion dollars per year are spent on the treatment and management of scars. Recent Advances: Investigations into the management of scar therapies over the last decade have advanced our understanding related to the care of cutaneous scars. Scar treatment methods are presented including topical, intralesional, and mechanical therapies in addition to cryotherapy, radiotherapy, and laser therapy. Critical Issues: Current treatment options for scars have significant limitations. This review presents the current and emerging therapies available for scar management and the scientific evidence for scar management is discussed. Future Directions: Based upon our new understanding of scar formation, innovative scar therapies are being developed. Additional research on the basic science of scar formation will lead to additional advances and novel therapies for the treatment of cutaneous scars. PMID:26487979

  17. Interactions of isoniazid with foods.

    PubMed

    Hauser, M J; Baier, H

    1982-01-01

    We reviewed reactions previously reported in patients treated with isoniazid, who ate certain fish and cheeses. We observed similar reactions in two patients after they ingested cheese and wine. Isoniazid is an inhibitor of both monoamine and diamine oxidases, which contribute to the metabolism of histamine that may be present in some fish and cheeses. Monoamine oxidase also acts in the metabolism of tyramine, present in some cheeses and wines. Reactions reported after eating fish or cheese, in patients treated with isoniazid, are similar in that both are characterized by headache, palpitations, skin flushing, nausea, vomiting, and pruritus. Reactions after fish have not been associated with increased blood pressure, whereas those following cheese ingestion frequently result in modest increases in blood pressure. Patients treated with isoniazid should be alerted to the possibility of reactions after eating certain foods. PMID:7105982

  18. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    SciTech Connect

    Cheng, Jie; Krausz, Kristopher W.; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J.

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  19. Magnesium in Prevention and Therapy

    PubMed Central

    Gröber, Uwe; Schmidt, Joachim; Kisters, Klaus

    2015-01-01

    Magnesium is the fourth most abundant mineral in the body. It has been recognized as a cofactor for more than 300 enzymatic reactions, where it is crucial for adenosine triphosphate (ATP) metabolism. Magnesium is required for DNA and RNA synthesis, reproduction, and protein synthesis. Moreover, magnesium is essential for the regulation of muscular contraction, blood pressure, insulin metabolism, cardiac excitability, vasomotor tone, nerve transmission and neuromuscular conduction. Imbalances in magnesium status—primarily hypomagnesemia as it is seen more common than hypermagnesemia—might result in unwanted neuromuscular, cardiac or nervous disorders. Based on magnesium’s many functions within the human body, it plays an important role in prevention and treatment of many diseases. Low levels of magnesium have been associated with a number of chronic diseases, such as Alzheimer’s disease, insulin resistance and type-2 diabetes mellitus, hypertension, cardiovascular disease (e.g., stroke), migraine headaches, and attention deficit hyperactivity disorder (ADHD). PMID:26404370

  20. Dance as a therapy for cancer prevention.

    PubMed

    Aktas, Gurbuz; Ogce, Filiz

    2005-01-01

    Even though the field of medicine has developed tremendously, the wide variety of cancer is still among chronic and life threatening disease today. Therefore, the specialists constantly research and try every possible way to find cure or preventive ways to stop its further development. For this reason, studies concerning the chronic disease such as cancer have been spread to many different fields. In this regard, many other alternative ways besides medicine, are used in prevention of cancer. Nutritional therapy, herbal therapy, sportive activities, art therapy, music therapy, dance therapy, imagery, yoga and acupuncture can be given as examples. Among these, dance/movement therapy which deals with individuals physical, emotional, cognitive as well as social integration is widely used as a popular form of physical activity. The physical benefits of dance therapy as exercise are well documented. Studies have shown that physical activity is known to increase special neurotransmitter substances in the brain (endorphins), which create a state of well-being. And total body movement such as dance enhances the functions of other body systems, such as circulatory, respiratory, skeletal, and muscular systems. Regarding its unique connection to the field of medicine, many researches have been undertaken on the effects of dance/movement therapy in special settings with physical problems such as amputations, traumatic brain injury, and stroke, chronic illnesses such as anorexia, bulimia, cancer, Alzheimer's disease, cystic fibrosis, heart disease, diabetes, asthma, AIDS, and arthritis. Today dance/movement therapy is a well recognized form of complementary therapy used in hospitals as well as at the comprehensive clinical cancer centres. PMID:16236009

  1. Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis

    PubMed Central

    Gerona, Roy; Wen, Anita; Chin, Aaron T.; Koss, Catherine A.; Bacchetti, Peter; Metcalfe, John; Gandhi, Monica

    2016-01-01

    Background Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV. Methods A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay’s suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested. Results Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10–25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05–50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range. Conclusions An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to

  2. Nanotechnology in dentistry: prevention, diagnosis, and therapy

    PubMed Central

    Abou Neel, Ensanya Ali; Bozec, Laurent; Perez, Roman A; Kim, Hae-Won; Knowles, Jonathan C

    2015-01-01

    Nanotechnology has rapidly expanded into all areas of science; it offers significant alternative ways to solve scientific and medical questions and problems. In dentistry, nanotechnology has been exploited in the development of restorative materials with some significant success. This review discusses nanointerfaces that could compromise the longevity of dental restorations, and how nanotechnolgy has been employed to modify them for providing long-term successful restorations. It also focuses on some challenging areas in dentistry, eg, oral biofilm and cancers, and how nanotechnology overcomes these challenges. The recent advances in nanodentistry and innovations in oral health-related diagnostic, preventive, and therapeutic methods required to maintain and obtain perfect oral health, have been discussed. The recent advances in nanotechnology could hold promise in bringing a paradigm shift in dental field. Although there are numerous complex therapies being developed to treat many diseases, their clinical use requires careful consideration of the expense of synthesis and implementation. PMID:26504385

  3. Therapy and prevention of cryptosporidiosis in animals.

    PubMed

    Shahiduzzaman, Md; Daugschies, Arwid

    2012-09-10

    Cryptosporidiosis is a common gastro-intestinal illness in animals and man worldwide. The disease is devastating in immune-suppressed individuals but self-limiting in competent hosts. The infectious stages of the organism (oocysts) are shed in the faeces of affected individuals, survive in adverse environmental conditions and spread by direct contact or through contaminants (food, water). Due to the robustness of the oocysts, their tenacity, tiny size, and resistance to common disinfectants, the parasite is difficult to eradicate from contaminated environments. To obtain sufficient control both treatment of infected hosts and inactivation of oocysts are necessary. Several drugs are commonly used to treat cryptosporidiosis in man and very few in animals but none of them are completely effective in terms of both clinical and parasitological response. Only a few chemical agents are able to inactivate oocysts in the environment including water treatment plants but their application has certain limitations. Therefore, control of cryptosporidiosis remains a global challenge in both veterinary and human medicine. Extensive research has been performed on suitable drugs and disinfectants. Thousands of agents have been tested both in vivo and in vitro. Some are excitingly active in vitro but exhibit poor or no response in clinical trials. Currently, no single or combined drug therapy has proven to be completely effective against this disease. This article will focus on therapy and prevention of cryptosporidiosis in animals including perspectives for new drugs. PMID:22521978

  4. Immunosuppressants in cancer prevention and therapy

    PubMed Central

    Blagosklonny, Mikhail V

    2013-01-01

    Rapalogs such as rapamycin (sirolimus), everolimus, temserolimus, and deforolimus are indicated for the treatment of some malignancies. Rapamycin is the most effective cancer-preventive agent currently known, at least in mice, dramatically delaying carcinogenesis in both normal and cancer-prone murine strains. In addition, rapamycin and everolimus decrease the risk of cancer in patients receiving these drugs in the context of immunosuppressive regimens. In general, the main concern about the use of immunosuppressants in humans is an increased risk of cancer. Given that rapalogs are useful in cancer prevention and therapy, should they be viewed as immunosuppressants or immunostimulators? Or should we reconsider the role of immunity in cancer altogether? In addition to its anti-viral, anti-inflammatory, anti-angiogenic and anti-proliferative effects, rapamycin operates as a gerosuppressant, meaning that it inhibits the cellular conversion to a senescent state (the so-called geroconversion), a fundamental process involved in aging and age-related pathologies including cancer. PMID:24575379

  5. Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions

    MedlinePlus

    ... recommendations summarize what the Task Force learned: The harms of hormone therapy, when used to prevent chronic ... Primary Prevention of Chronic Conditions Potential Benefits and Harms The Task Force found that taking both estrogen ...

  6. High Incidence of Tuberculosis Infection in Rheumatic Diseases and Impact for Chemoprophylactic Prevention of Tuberculosis Activation during Biologics Therapy

    PubMed Central

    Bai, Fengmin; Zhang, Shu; Jiang, Ting; Shen, Jie; Zhu, Qi; Yue, Tao; Shao, Lingyun; Gao, Yan; Feng, Yun; Weng, Xinhua; Zou, Hejian; Zhang, Ying

    2013-01-01

    We conducted a long-term follow-up study in patients with rheumatic diseases who were candidates for biologics treatment to evaluate the effects of biologic agents on the risk of tuberculosis infection and the effect of prophylactic treatment on tuberculosis activation. One hundred one patients with rheumatic diseases who were candidates for biologics treatment were recruited, and 57 healthy subjects were recruited as controls. Tuberculin skin test (TST) and the T-SPOT.TB test were performed for all subjects at baseline. Follow-up testing by the T-SPOT.TB assay was performed every 6 months in patients with rheumatic diseases and at 2 years of recruitment in the healthy controls. In patients with rheumatic diseases and healthy controls, the TST-positive (induration, ≥10 mm) rates were 37.6% (38/101) and 34.0% (18/53), respectively (P > 0.05), while the T-SPOT.TB-positive rates were 46.5% (47/101) and 21.1 (12/57), respectively (P = 0.0019). Fifty-two patients were followed up at month 6 with a T-SPOT.TB-positive rate of 40.4%, and 49 were followed up for ≥12 months with a T-SPOT.TB-positive rate of 36.7%, with no significant difference in the positive rate at different time points including baseline (P > 0.05). Long-term follow-up revealed that conversion to T-SPOT.TB positivity occurred only in the biologics treatment group, with a positive conversion rate of 11.2% (4/38). Most importantly, no latent tuberculosis developed into active tuberculosis during follow-up with T-SPOT.TB screening and preemptive treatment with isoniazid. Biologics treatment appears to increase the risk of tuberculosis infection. However, tuberculosis activation could be prevented by preemptive isoniazid treatment in patients with latent tuberculosis infection while receiving biologics therapy. PMID:23554465

  7. Completion Rate and Side-Effect Profile of Three-Month Isoniazid and Rifapentine Treatment for Latent Tuberculosis Infection in an Urban County Jail

    PubMed Central

    Juarez-Reyes, Maria; Gallivan, Mark; Chyorny, Alexander; O'Keeffe, Linda; Shah, Neha S.

    2016-01-01

    In an urban jail population, 3 months of isoniazid and rifapentine (3HP) was associated with an 85% latent tuberculosis infection treatment completion rate compared with 18% in a standard 9-month isoniazid treatment group. Among the 91 patients who started 3HP therapy, there were 2 treatment discontinuations from adverse drug reactions. PMID:26885547

  8. Primary Isoniazid Prophylaxis against Tuberculosis in HIV-Exposed Children

    PubMed Central

    Madhi, Shabir A.; Nachman, Sharon; Violari, Avy; Kim, Soyeon; Cotton, Mark F.; Bobat, Raziya; Jean-Philippe, Patrick; McSherry, George; Mitchell, Charles

    2011-01-01

    Background The dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period. Methods We randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette–Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization. Results Antiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P = 0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P = 0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups. Conclusions Primary isoniazid prophylaxis did not improve tuberculosis-disease–free survival among HIV-infected children or tuberculosis-infection–free survival among HIV

  9. [Extravasation of chemotherapeutic agents: prevention and therapy].

    PubMed

    Jordan, K; Grothe, W; Schmoll, H-J

    2005-01-01

    Based on the potential to cause local tissue injury drugs are classified as vesicant, irritant and non-irritant. The frequency of extravasation is considered to be between 0.6 % and 6 %. More frequently an inflammatory reaction is caused by thrombophlebitis or a local hypersensitivity reaction following chemotherapy administration rather than by an extravasation. A number of factors are known to increase the risk of extravasation. By the consideration of these risk factors preventive guidelines for the safe administration of chemotherapeutic agents have been published. Central venous devices significantly reduce the risk of extravasation. To date there are no generally approved treatment guidelines for the management of extravasations. Treatment is mostly empirical. Nevertheless some general measures are to be recommended: Firstly, aspiration of the extravasated fluids should be attempted. Furthermore local supportive care such as intermittent topical warming or cooling is at least palliative and to a certain degree reduces the extent of the injury. Beside these non pharmacological therapies the beneficial effects of Dimethylsulfoxid (DMSO) -- or Hyaluronidase-administration dependent on the type of paravasation have been proven. The use of sodium bicarbonate, sodium thiosulfate or corticosteroids is no longer recommended. In the case of extravasation rapid and correct management is crucial for the benefit of any treatment. Therefore, written guidelines for both the handling of cytotoxic agents and also the management of an extravasation should be present in all Departments where cytotoxic agents are administered. In addition to these guidelines an extravasation kit including all necessary materials and drugs to treat extravasations should be available. PMID:15619172

  10. Isoniazid induced motor-dominant neuropathy.

    PubMed

    Arsalan, Rabeeya; Sabzwari, Saniya

    2015-10-01

    Isoniazid though a very effective treatment for tuberculosis can cause severe motor-dominant neuropathy which can be reversible with pyridoxine supplementation. A 45-year-old female diagnosed with psoas abscess, culture positive for mycobacterium tuberculosis, was started on anti- tuberculous treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three months later she developed severe motor weakness of lower limbs with loss of ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid treatment was continued. Her motor weakness gradually improved in a few months, but mild sensory impairment persisted even after two years. There is need for vigilance regarding neurological effects of isoniazid in seemingly low-risk individuals in whom development of symptoms should raise the suspicion about slow acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can reduce the long-term morbidity associated with this easily reversible condition. PMID:26440850

  11. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study

    PubMed Central

    Vinnard, Christopher; Gopal, Anand; Linkin, Darren R.; Maslow, Joel

    2013-01-01

    Background: our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI) and determine whether advancing age was a risk factor for toxicity. Methods: we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. Results: 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%). Among 18/219 patients (8%) that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1–5 months). In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07). In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52). Conclusions: cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population. PMID:23365735

  12. Antiplatelet therapy to prevent recurrent stroke: Three good options.

    PubMed

    Mansoor, Atizazul H; Mujtaba, Mohammad T; Silver, Brian

    2013-12-01

    Drugs that prevent platelets from sticking together-ie, aspirin, dipyridamole, and clopidogrel-are an important part of therapy to prevent recurrence of ischemic stroke of atherosclerotic origin. We discuss current indications for these drugs and review the evidence behind our current use of aspirin, dipyridamole, and clopidogrel. PMID:24307163

  13. A rare case of unilateral gynecomastia during antituberculous chemotherapy with isoniazid

    PubMed Central

    Goud, B. K. Manjunatha; Devi, Oinam Sarsina; Nayal, Bhavna; Devaki, R. N.

    2012-01-01

    Gynecomastia refers to enlargement of male breast (s) due to benign proliferation of glandular tissue and is caused by excessive estrogen. The etiology may be pathological, pharmacological, or idiopathic reasons. The present report describes a case of gynecomastia due to isoniazid therapy. PMID:23087519

  14. Three cases of intentional isoniazid overdose - a life-threatening condition.

    PubMed

    Stead, David Francis; Mason, Carolyn Ruth

    2016-09-01

    Currently, isoniazid (INH) overdose seems to be a growing and life-threatening problem, partly due to the recent national roll-out of INHpreventive therapy (IPT) for HIV-positive adults. We present three cases, two of which were fatal, seen at Frere and Cecilia Makiwanehospitals, East London, South Africa over the past 16 months. PMID:27601114

  15. Role of hydrazine in isoniazid-induced hepatotoxicity in a hepatocyte inflammation model

    SciTech Connect

    Tafazoli, Shahrzad; Mashregi, Mariam; O'Brien, Peter J.

    2008-05-15

    Isoniazid is an anti-tuberculosis drug that can cause hepatotoxicity in 20% of patients that is usually associated with an inflammatory response. Hepatocytes when exposed to non-toxic levels of H{sub 2}O{sub 2}, to simulate H{sub 2}O{sub 2} formation by inflammatory cells, became twice as sensitive to isoniazid toxicity. Isoniazid cytotoxicity was prevented by 1-aminobenzotriazole, a non-selective P450 inhibitor or by bis-p-nitrophenyl phosphate (BNPP), an esterase inhibitor. Moreover, the cytotoxicity of hydrazine, the metabolite formed by amidase-catalyzed hydrolysis of isoniazid, was increased 16-fold by a non-toxic H{sub 2}O{sub 2}-generating system. The acetylhydrazine metabolite was found to be much less cytotoxic than hydrazine in this hepatocyte inflammation model. Hydrazine, therefore, seems to be the isoniazid reactive metabolite in this inflammation model. The molecular mechanism of hydrazine-induced cytotoxicity was attributed to oxidative stress as reactive oxygen species (ROS) and protein carbonyl formation occurred before the onset of hepatocyte toxicity. Hydrazine toxicity also involved significant production of endogenous H{sub 2}O{sub 2} which resulted in lysosomal membrane damage and leads to a collapse in mitochondrial membrane potential. These results implicated H{sub 2}O{sub 2}, a cellular mediator of inflammation, as a potential risk factor for the manifestation of adverse drug reactions, particularly those caused by hydrazine containing drugs.

  16. Hepatoprotective Activity of Heptoplus on Isoniazid and Rifampicin Induced Liver Damage in Rats

    PubMed Central

    Sankar, M.; Rajkumar, Johanna; Sridhar, Dorai

    2015-01-01

    The present study is designed to evaluate the efficacy of heptoplus a polyherbal formulation as an oral supplementary agent for isoniazid and rifampicin induced hepatotoxicity in rats. 50 and 100 mg/kg of heptoplus supplement were fed orally to the rats along with isoniazid and rifampicin and compared to rats treated with 100 mg/kg Liv 52 standard drug. Rats treated with isoniazid and rifampicin suffered from severe oxidative stress by the virtue of free radicals induced lipid per oxidation. As a result abnormal index of serum biochemical markers for liver function and increased liver lysosomal enzymes activity was observed. However rats nourished with 100 mg/kg of heptoplus and Liv 52 protected the liver from oxidative damage by maintaining normal antioxidant profile status and restored normal serum liver biochemical markers. Increased liver lysosomal enzymes activity is prevented in the rats supplemented with heptoplus and Liv 52. Histopathological analysis also revealed severe vascular changes and lobular necrosis in the treatment of isoniazid and rifampicin. Heptoplus (100 mg/kg) and Liv 52 supplemented rats liver apparently revealed normal architecture of liver. This study confirms that heptoplus has liver protective activity against Isoniazid and Rifampicin induced liver injury in rats, in par with Liv 52. PMID:26798170

  17. Isoniazid Inhibits the Heme-Based Reactivity of Mycobacterium tuberculosis Truncated Hemoglobin N

    PubMed Central

    Ascenzi, Paolo; Coletta, Andrea; Cao, Yu; Trezza, Viviana; Leboffe, Loris; Fanali, Gabriella; Fasano, Mauro; Pesce, Alessandra; Ciaccio, Chiara; Marini, Stefano; Coletta, Massimo

    2013-01-01

    Isoniazid represents a first-line anti-tuberculosis medication in prevention and treatment. This prodrug is activated by a mycobacterial catalase-peroxidase enzyme called KatG in Mycobacterium tuberculosis), thereby inhibiting the synthesis of mycolic acid, required for the mycobacterial cell wall. Moreover, isoniazid activation by KatG produces some radical species (e.g., nitrogen monoxide), that display anti-mycobacterial activity. Remarkably, the ability of mycobacteria to persist in vivo in the presence of reactive nitrogen and oxygen species implies the presence in these bacteria of (pseudo-)enzymatic detoxification systems, including truncated hemoglobins (trHbs). Here, we report that isoniazid binds reversibly to ferric and ferrous M. tuberculosis trHb type N (or group I; Mt-trHbN(III) and Mt-trHbN(II), respectively) with a simple bimolecular process, which perturbs the heme-based spectroscopic properties. Values of thermodynamic and kinetic parameters for isoniazid binding to Mt-trHbN(III) and Mt-trHbN(II) are K = (1.1±0.1)×10−4 M, kon = (5.3±0.6)×103 M−1 s−1 and koff = (4.6±0.5)×10−1 s−1; and D = (1.2±0.2)×10−3 M, don = (1.3±0.4)×103 M−1 s−1, and doff = 1.5±0.4 s−1, respectively, at pH 7.0 and 20.0°C. Accordingly, isoniazid inhibits competitively azide binding to Mt-trHbN(III) and Mt-trHbN(III)-catalyzed peroxynitrite isomerization. Moreover, isoniazid inhibits Mt-trHbN(II) oxygenation and carbonylation. Although the structure of the Mt-trHbN-isoniazid complex is not available, here we show by docking simulation that isoniazid binding to the heme-Fe atom indeed may take place. These data suggest a direct role of isoniazid to impair fundamental functions of mycobacteria, e.g. scavenging of reactive nitrogen and oxygen species, and metabolism. PMID:23936350

  18. [Therapy and prevention of infectious endocarditis].

    PubMed

    Horstkotte, D; Rosin, H

    1984-11-10

    Only 40 years ago infectious endocarditis (IE) was lethal in most cases. Due to the development of numerous antibiotics and continuous improvements in heart valve surgery, a wide range of possibilities for therapy and prophylaxis of IE are available. The prognosis depends essentially on rapid and relevant diagnosis, which should be followed by immediate and adequate therapy consisting of general measures for treatment of septicaemic disease and specific antibiotic therapy. As multiple complications may develop during IE, careful follow-up by clinical, laboratory and mechanical examinations is necessary to decide whether surgical intervention is urgently indicated or not. In case of complications such as myocardial failure, septicaemic embolism or acute renal failure, as well as septicaemia persisting for more than 72 hours in spite of antibiotic treatment, immediate valve replacement is usually indispensable. Furthermore, large vegetations found by echocardiography, or infections caused by staphylococci, gramnegative bacteria or fungi are arguments for early surgery. For most of the IE pathogens the antibiotic treatment concept is nowadays widely acknowledged. Penicillin-sensitive streptococci are treated with a combination of penicillin S and an amino-glycoside (streptomycin). If the penicillin-MBK is very low, combined treatment can usually be abandoned. In patients allergic to penicillin, treatment with lincomycin has advantages over vancomycin or cephalosporins. In enterococcal IE, ampicillin plus aminoglycoside is the combination of choice. Streptomycin has preference over gentamicin here only if the enterococci are not streptomycin-resistant. If penicillin allergy is evident, the new beta-lactam antibiotic imipenem offers a way out of the present therapy dilemma. For penicillin-sensitive staphylococci a combination of penicillin-G with gentamicin given over 6 weeks is recommended. In case of penicillin allergy, cefazolin or vancomycin may provide a substitute

  19. Medical and dietary therapy for kidney stone prevention.

    PubMed

    Gul, Zeynep; Monga, Manoj

    2014-12-01

    The prevalence of kidney stone disease is increasing, and newer research is finding that stones are associated with several serious morbidities. These facts suggest that emphasis needs to be placed not only on stone treatment but also stone prevention. However, there is a relative dearth of information on dietary and medical therapies to treat and avoid nephrolithiasis. In addition, studies have shown that there are many misconceptions among both the general community and physicians about how stones should be managed. This article is meant to serve as a review of the current literature on dietary and drug therapies for stone prevention. PMID:25512810

  20. Medical and Dietary Therapy for Kidney Stone Prevention

    PubMed Central

    Gul, Zeynep

    2014-01-01

    The prevalence of kidney stone disease is increasing, and newer research is finding that stones are associated with several serious morbidities. These facts suggest that emphasis needs to be placed not only on stone treatment but also stone prevention. However, there is a relative dearth of information on dietary and medical therapies to treat and avoid nephrolithiasis. In addition, studies have shown that there are many misconceptions among both the general community and physicians about how stones should be managed. This article is meant to serve as a review of the current literature on dietary and drug therapies for stone prevention. PMID:25512810

  1. Chemiluminescence detection of isoniazid using Ru(phen)3(2+)-isoniazid-Ce(IV) system.

    PubMed

    Xi, Juan; Shi, Bo'an; Ai, Xinping; He, Zhike

    2004-09-21

    In our experiment, it was observed that isoniazid could enhance the chemiluminescence (CL) emission of tris-(1,10-phenanthroline)ruthenium(II) (Ru(phen)3(2+))-cerium(IV) (Ce(IV)) system and this enhancement effect was dependent on the concentration of isoniazid, based on which, a novel CL system was established for the detection of isoniazid. Under the optimum experimental conditions, the dynamic range and detection limit are 7.0 x 10(-2) to 6.5 microg ml(-1) and 2.5 x 10(-2) microg ml(-1), respectively. The R.S.D. is 3.4% (n = 11). The proposed method has been applied to detect the content of isoniazid in the injection solution with satisfactory results. The possible mechanism of the CL reaction was studied. PMID:15351072

  2. Gene therapy for the prevention of vein graft disease

    PubMed Central

    Southerland, Kevin W.; Frazier, Sarah B.; Bowles, Dawn E.; Milano, Carmelo A.; Kontos, Christopher D.

    2013-01-01

    Ischemic cardiovascular disease remains the leading cause of death worldwide. Despite advances in the medical management of atherosclerosis over the past several decades, many patients require arterial revascularization to reduce mortality and alleviate ischemic symptoms. Technological advancements have led to dramatic increases in the use of percutaneous and endovascular approaches, yet surgical revascularization (bypass surgery) with autologous vein grafts remains a mainstay of therapy for both coronary and peripheral artery disease. Although bypass surgery is highly efficacious in the short-term, long-term outcomes are limited by relatively high failure rates as a result of intimal hyperplasia, which is a common feature of vein graft disease. The supply of native veins is limited, and many individuals require multiple grafts and repeat procedures. The need to prevent vein graft failure has led to great interest in gene therapy approaches to this problem. Bypass grafting presents an ideal opportunity for gene therapy, as surgically harvested vein grafts can be treated with gene delivery vectors ex vivo, thereby maximizing gene delivery while minimizing the potential for systemic toxicity and targeting the pathogenesis of vein graft disease at its onset. Here we will review the pathogenesis of vein graft disease and discuss vector delivery strategies and potential molecular targets for its prevention. We will summarize the preclinical and clinical literature on gene therapy in vein grafting and discuss additional considerations for future therapies to prevent vein graft disease. PMID:23274305

  3. Global and Regional Burden of Isoniazid-Resistant Tuberculosis

    PubMed Central

    Yuen, Courtney M.; Jenkins, Helen E.; Rodriguez, Carly A.; Keshavjee, Salmaan

    2015-01-01

    BACKGROUND: Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and infection. To inform policies around treatment of tuberculosis disease and infection in children, we sought to estimate both the proportion of child tuberculosis cases with isoniazid resistance and the number of incident isoniazid-resistant tuberculosis cases in children, by region. METHODS: We determined the relationship between rates of isoniazid resistance among child cases and among treatment-naive adult cases through a systematic literature review. We applied this relationship to regional isoniazid resistance estimates to estimate proportions of childhood tuberculosis cases with isoniazid resistance. We applied these proportions to childhood tuberculosis incidence estimates to estimate numbers of children with isoniazid-resistant tuberculosis. RESULTS: We estimated 12.1% (95% confidence interval [CI] 9.8% to 14.8%) of all children with tuberculosis had isoniazid-resistant disease, representing 120 872 (95% CI 96 628 to 149 059) incident cases of isoniazid-resistant tuberculosis in children in 2010. The majority of these occurred in the Western Pacific and Southeast Asia regions; the European region had the highest proportion of child tuberculosis cases with isoniazid resistance, 26.1% (95% CI: 20.0% to 33.6%). CONCLUSIONS: The burden of isoniazid-resistant tuberculosis in children is substantial, and risk varies considerably by setting. The large number of child cases signals extensive ongoing transmission from adults with isoniazid-resistant tuberculosis. The risk of isoniazid resistance must be considered when evaluating treatment options for children with disease or latent infection to avoid inadequate treatment and consequent poor outcomes. PMID:26034243

  4. Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy.

    PubMed

    Miyanishi, Koji; Hoki, Toshifumi; Tanaka, Shingo; Kato, Junji

    2015-03-27

    Oxidative stress has been investigated in the context of alcoholic liver injury for many years and shown to be a causal factor of chronic hepatitis C (CHC), nonalcoholic steatohepatitis (NASH), drug-induced liver injury, Wilson's disease, and hemochromatosis. In CHC, it has been demonstrated that oxidative stress plays an important role in hepatocarcinogenesis. In cases with persistent hepatitis due to failure of hepatitis C virus eradication, or chronic liver disease, such as NASH, the treatment of which remains unestablished, it is important to reduce serum alanine aminotransferase levels and prevent liver fibrosis and development of hepatocellular carcinoma. This also suggests the importance of antioxidant therapy. Among treatment options where it would be expected that anti-inflammatory activity plays a role in their confirmed efficacy for chronic hepatitis, iron depletion therapy, glycyrrhizin, ursodeoxycholic acid, Sho-Saiko-To, and vitamin E can all be considered antioxidant therapies. To date, however, the ability of these treatments to prevent cancer has been confirmed only in CHC. Nevertheless, anti-inflammatory and anti-fibrotic effects have been demonstrated in other liver diseases and these therapies may potentially be effective for cancer prevention. PMID:25848483

  5. Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy

    PubMed Central

    Miyanishi, Koji; Hoki, Toshifumi; Tanaka, Shingo; Kato, Junji

    2015-01-01

    Oxidative stress has been investigated in the context of alcoholic liver injury for many years and shown to be a causal factor of chronic hepatitis C (CHC), nonalcoholic steatohepatitis (NASH), drug-induced liver injury, Wilson’s disease, and hemochromatosis. In CHC, it has been demonstrated that oxidative stress plays an important role in hepatocarcinogenesis. In cases with persistent hepatitis due to failure of hepatitis C virus eradication, or chronic liver disease, such as NASH, the treatment of which remains unestablished, it is important to reduce serum alanine aminotransferase levels and prevent liver fibrosis and development of hepatocellular carcinoma. This also suggests the importance of antioxidant therapy. Among treatment options where it would be expected that anti-inflammatory activity plays a role in their confirmed efficacy for chronic hepatitis, iron depletion therapy, glycyrrhizin, ursodeoxycholic acid, Sho-Saiko-To, and vitamin E can all be considered antioxidant therapies. To date, however, the ability of these treatments to prevent cancer has been confirmed only in CHC. Nevertheless, anti-inflammatory and anti-fibrotic effects have been demonstrated in other liver diseases and these therapies may potentially be effective for cancer prevention. PMID:25848483

  6. Update on Antithrombotic Therapy for Stroke Prevention in Atrial Fibrillation

    PubMed Central

    Ovbiagele, Bruce

    2010-01-01

    Opinion statement Atrial fibrillation (AF) is the most common cardiac arrhythmia in the elderly, affecting 1 in 20 adults over the age of 70 years. Stroke is a major yet highly preventable complication of AF, and the strokes related to AF often are disabling and fatal. Warfarin is the treatment of choice in high-risk patients with AF, and its superior efficacy over aspirin for preventing stroke in these patients is widely recognized. However, several eligible patients with AF are not being treated with warfarin or are being treated inadequately, largely because of concerns regarding the attendant strict monitoring, drug interactions, and risk of major bleeding. As such, alternative antithrombotic therapies that can rival or exceed the efficacy of warfarin, yet compare favorably with its administration and side effect profile, are being sought. One such strategy, the use of a combination antiplatelet regimen, for stroke prevention in high-risk patients with nonvalvular AF was investigated recently in two clinical trials. This article reviews the role of combination antiplatelet regimens in stroke prevention for patients with AF. Other therapies discussed include oral anticoagulation, single antiplatelet therapies, oral anticoagulation plus antiplatelet treatment, direct thrombin inhibitors, and factor Xa inhibitors. PMID:20461116

  7. Therapy of Chagas Disease: Implications for Levels of Prevention

    PubMed Central

    Sosa-Estani, Sergio; Colantonio, Lisandro; Segura, Elsa Leonor

    2012-01-01

    This paper reviews the evidence supporting the use of etiological treatment for Chagas disease that has changed the standard of care for patients with Trypanosoma cruzi infection in the last decades. Implications of this evidence on different levels of prevention as well as gaps in current knowledge are also discussed. In this regard, etiological treatment has shown to be beneficial as an intervention for secondary prevention to successfully cure the infection or to delay, reduce, or prevent the progression to disease, and as primary disease prevention by breaking the chain of transmission. Timely diagnosis during initial stages would allow for the prescription of appropriate therapies mainly in the primary health care system thus improving chances for a better quality of life. Based on current evidence, etiological treatment has to be considered as an essential public health strategy useful to reduce disease burden and to eliminate Chagas disease altogether. PMID:22523499

  8. Eating disorder therapy concepts with a preventive goal.

    PubMed

    Gerlinghoff, M; Gross, G; Backmund, H

    2003-01-01

    In this paper, we describe our 4-phase-therapy program for eating disorders at a specialized unit. Core of the treatment is a 4-month day patient phase. Our approach, which implies a fixed structure in terms of time and content, is based on cognitive-behavioral group therapy. It follows the principle of self-management developed by Kanfer and involves patients in organizational and therapeutic activities. Patients' participation in our extensive efforts aiming at the prevention of eating disorders is invaluable for therapists and serves patients as an important protective factor. PMID:12567218

  9. The Pharmacogenetics of NAT2 Enzyme Maturation in Perinatally HIV Exposed Infants Receiving Isoniazid

    PubMed Central

    Zhu, Rui; Kiser, Jennifer J.; Seifart, Heiner I.; Werely, Cedric J.; Mitchell, Charles D.; D’Argenio, David Z.; Fletcher, Courtney V.

    2011-01-01

    The roles of the NAT2 genotype and enzyme maturation on isoniazid pharmacokinetics were investigated in South African infants with perinatal HIV exposure enrolled in a randomized, double-blind, controlled trial of isoniazid for prevention of tuberculosis disease and latent infection. Plasma concentration-time measurements of isoniazid from 151 infants (starting at 3-4 months of age) receiving isoniazid 10 to 20 mg/kg/d orally during the course of the 24-month study were incorporated in a population analysis along with NAT2 genotype, body weight, age, and sex. The results showed a different NAT2 enzyme maturation profile for each of the 3 acetylation groups, with the 70-kg body weight–normalized typical apparent clearance for the fast and intermediate acetylators increasing from 14.25 L/h and 10.88 L/h at 3 months of age to 22.84 L/h and 15.58 L/h at 24 months of age, respectively, with no significant change in the apparent clearance of the slow group during this period. A hypothesis is proposed to explain the genotype-dependent enzyme maturation processes for the NAT2 enzyme. PMID:21558457

  10. Antiretroviral Therapy for Prevention of Human Immunodeficiency Virus Infection.

    PubMed

    Kalapila, Aley G; Marrazzo, Jeanne

    2016-07-01

    Human immunodeficiency virus (HIV) infection is considered a chronic medical condition. Several new drugs are available, including fixed-dose combination tablets, that have greatly simplified combination antiretroviral therapy (ART) regimens to treat HIV, while increasing the life-expectancy of infected individuals. In the last decade, multiple well-regarded studies have established the benefits of using ART in high-risk, HIV-negative persons to prevent HIV acquisition. The primary care provider must not only understand commonly encountered issues pertaining to ART, such as toxicities and drug interactions, but also needs to be aware of using ART for HIV prevention. PMID:27235622

  11. Synthesis, characterization, solubility and stability studies of hydrate cocrystal of antitubercular Isoniazid with antioxidant and anti-bacterial Protocatechuic acid

    NASA Astrophysics Data System (ADS)

    Mashhadi, Syed Muddassir Ali; Yunus, Uzma; Bhatti, Moazzam Hussain; Ahmed, Imtiaz; Tahir, Muhammad Nawaz

    2016-08-01

    Isoniazid is an important component used in "triple therapy" to combat tuberculosis. It has reduced Tabletting formulations stability. Anti-oxidants are obligatory to counter oxidative stress, pulmonary inflammation, and free radical burst from macrophages caused in tuberculosis and other diseases. In the present study a hydrate cocrystal of Isoniazid with anti-oxidant and anti-inflammatory and anti-bacterial Protocatechuic acid (3,4-dihydroxybenzoic acid) in 1:1 is reported. This Cocrystal may have improved tabletting stability and anti-oxidant properties. Cocrystal structure analysis confirmed the existence of pyridine-carboxylic acid synthon in the Cocrystal. Other synthons of different graph sets involving Nsbnd H···O and Osbnd H···N bonds are formed between hydrazide group of isoniazid and coformer. Solubility studies revealed that cocrystal is less soluble as compared to isoniazid in buffer at pH 7.4 at 22 °C while stability studies at 80 °C for 24 h period disclosed the fact that cocrystal has higher stability than that of isoniazid.

  12. Hydrophobic ion pairing of isoniazid using a prodrug approach.

    PubMed

    Zhou, Huiyu; Lengsfeld, Corinne; Claffey, David J; Ruth, James A; Hybertson, Brooks; Randolph, Theodore W; Ng, Ka-Yun; Manning, Mark C

    2002-06-01

    Inhalation therapy for infectious lung diseases, such as tuberculosis, is currently being explored, with microspheres being used to target alveolar macrophages. One method of drug encapsulation into polymeric microspheres to form hydrophobic ion-paired (HIP) complexes, and then coprecipitate the complex and polymer using supercritical fluid methodology. For the potent antituberculosis drug, isoniazid (isonicotinic acid hydrazide, INH), to be used in this fashion, it was modified into an ionizable form suitable for HIP. The charged prodrug, sodium isoniazid methanesulfonate (Na-INHMS), was then ion paired with hydrophobic cations, such as alkyltrimethylammonium or tetraalkylammonium. The logarithms of the apparent partition coefficients (log P') of various HIP complexes of INHMS display a roughly linear relationship with the numbers of carbon atoms in the organic counterions. The water solubility of the tetraheptylammonium-INHMS complex is about 220-fold lower than that of Na-INHMS, while the solubility in dichloromethane exceeds 10 mg/mL, which is sufficient for microencapsulation of the drug into poly(lactide) microspheres. The actual logarithm of the dichloromethane/water partition coefficient (log P) for tetraheptylammonium-INHMS is 1.55, compared to a value of - 1.8 for the sodium salt of INHMS. The dissolution kinetics of the tetraheptylammonium-INHMS complex in 0.9% aqueous solutions of NaCl was also investigated. Dissolution of tetraheptylammonium-INHMS exhibited a first-order time constant of about 0.28 min(-1), followed by a slower reverse ion exchange process to form Na-INHMS. The half-life of this HIP complex is on the order of 30 min, making the enhanced transport of the drug across biological barriers possible. This work represents the first use of a prodrug approach to introduce functionality that would allow HIP complex formation for a neutral molecule. PMID:12115849

  13. A Review of Probiotic Therapy in Preventive Dental Practice.

    PubMed

    Cannon, Mark L

    2011-06-01

    Probiotics have been widely publicized in the general press and the consumer media. Knowledge of the existence of "probiotics" is commonplace, and the effectiveness of probiotic therapy has been well reported in the medical literature. However, even though most published dental studies have reported positive results, the dental profession has not yet accepted the use of probiotic therapy as an adjunct for preventive dental care. This review article discusses published and current research into the applications of probiotics along with diagnostic testing of the oral biofilm. Probiotic therapy appears to be generally safe and effective in modifying with beneficial bacteria the oral biofilm and thereby reducing the effects of pathogenic oral bacteria. In this review, some examples of current oral probiotic research are discussed along with reference to the potential application of diagnostic testing of the oral biofilm for the presence of oral pathogens as a precursor to initiation of specific probiotic therapy. Dental professionals should be actively investigating this potentially very useful therapeutic measure for the benefit of their patients. PMID:26781571

  14. Antidiuretic hormone replacement therapy to prevent or ameliorate vasodilatory shock.

    PubMed

    Singh Ranger, Gurpreet

    2002-09-01

    Vasodilatory shock is a syndrome with high mortality. It is becoming evident that depletion of antidiuretic hormone (ADH) after cardiac surgery or during sepsis plays an important role in the pathogenesis of this condition. Established vasodilatory shock responds well to exogenous ADH infusion. It is possible that preventing ADH depletion at an earlier stage may abrogate the onset of vasodilatory shock, or at least reduce its severity. This paper examines the evidence supporting this concept, and the potential areas of concern in considering this particular type of hormone replacement therapy. PMID:12208165

  15. [Diet therapy and life guidance to prevent calcium stones].

    PubMed

    Moriyama, Manabu T

    2011-10-01

    Urolithiasis patients have a low continuation rate with regard to visiting the hospital and undergoing periodic check-ups following therapy. The increased Westernization of diets has played a major role in its onset, and it is believed to be a lifestyle disease. Therefore, the prevention of relapse is difficult without improving the patients' lifestyle and eating habits, and it has been defined as a disease with an extremely high relapse rate. On the other hand, it is believed that the opportunity for periodic visits to the hospital and check-ups can be assured by continuously performing careful dietary interventions appropriate for each patient and by educating patients about the disease, thereby contributing to the prevention of relapses of urolithiasis. PMID:21960239

  16. Hormone replacement therapy and the prevention of postmenopausal osteoporosis

    PubMed Central

    Levancini, Marco

    2014-01-01

    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR), is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC), is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence. PMID:26327857

  17. Cost-Effectiveness of Antiretroviral Therapy for Prevention

    PubMed Central

    Kahn, James G; Marseille, Elliot A; Bennett, Rod; Williams, Brian G; Granich, Reuben

    2011-01-01

    Recent empirical studies and analyses have heightened interest in the use of expanded antiretroviral therapy (ART) for prevention of HIV transmission. However, ART is expensive, approximately $600 per person per year, raising issues of the cost and cost-effectiveness of ambitious ART expansion. The goal of this review is to equip the reader with the conceptual tools and substantive background needed to understand and evaluate the policy and programmatic implications of cost-effectiveness assessments of ART for prevention. We provide this review in six sections. We start by introducing and explaining basic concepts of health economics as they relate to this issue, including resources, costs, health metrics (such as Disability-Adjusted Life Years), and different types of economic analysis. We then review research on the cost and cost-effectiveness of ART as treatment, and on the cost-effectiveness of traditional HIV prevention. We describe critical issues in the epidemic impact of ART, such as suppression of transmission and the role of the acute phase of infection. We then present a conceptual model for conducting and interpreting cost-effectiveness analyses of ART as prevention, and review the existing preliminary estimates in this area. We end with a discussion of future directions for programmatic demonstrations and evaluation. PMID:21999776

  18. Effect of isoniazid on antigen-specific interferon-γ secretion in latent tuberculosis

    PubMed Central

    Torres, Martha; Cruz-Hervert, Pablo; Guio, Heinner; Carranza, Claudia; Ferreyra-Reyes, Leticia; Canizales, Sergio; Molina, Susana; Ferreira-Guerrero, Elizabeth; Téllez, Norma; Montero-Campos, Rogelio; Delgado-Sánchez, Guadalupe; Mongua-Rodriguez, Norma; Sifuentes-Osornio, Jose; Ponce-de Leon, Alfredo; Sada, Eduardo; Young, Douglas B.; Wilkinson, Robert J.

    2015-01-01

    Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes. We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays of in vitro interferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed. During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy. The in vitro IFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection. PMID:25359354

  19. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    PubMed Central

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S.; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy. PMID:24467530

  20. Neurotransmission and cancer: implications for prevention and therapy.

    PubMed

    Schuller, Hildegard M

    2008-08-01

    Published evidence compiled in this review supports the hypothesis that the development, progression, and responsiveness to prevention and therapy of the most common human cancers is strongly influenced, if not entirely orchestrated, by an imbalance in stimulatory and inhibitory neurotransmission. The neurotransmitters acetylcholine, adrenaline, and noradrenaline of the autonomic nervous system act as powerful upstream regulators that orchestrate numerous cell and tissue functions, by releasing growth factors, angiogenesis factors and metastasis factors, arachidonic acid, proinflammatory cytokines, and local neurotransmitters from cancer cells and their microenvironment. In addition, they modulate proliferation, apoptosis, angiogenesis, and metastasis of cancer directly by intracellular signaling downstream of neurotransmitter receptors. Nicotine and the tobacco-specific nitrosamines have the documented ability to hyperstimulate neurotransmission by both branches of the autonomic nervous system. The expression and function of these neurotransmitter pathways are cell type specific. Lifestyle, diet, diseases, stress, and pharmacological treatments modulate the expression and responsiveness of neurotransmitter pathways. Current preclinical testing systems fail to incorporate the modulating effects of neurotransmission on the responsiveness to anticancer agents and should be amended accordingly. The neurotransmitter gamma-aminobutyric acid has a strong inhibitory function on sympathicus-driven cancers whereas stimulators of cyclic adenosine monophosphate/protein kinase A signaling have strong inhibitory function on parasympathicus-driven cancers. Marker-guided restoration of the physiological balance in stimulatory and inhibitory neurotransmission represents a promising and hitherto neglected strategy for the prevention and therapy of neurotransmitter-responsive cancers. PMID:18594207

  1. Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

    PubMed

    Cohen, Myron S; Chen, Ying Q; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; Santos, Breno R; Mayer, Kenneth H; Hoffman, Irving F; Eshleman, Susan H; Piwowar-Manning, Estelle; Cottle, Leslie; Zhang, Xinyi C; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Faesen, Sharlaa; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Elharrar, Vanessa; Burns, David; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David D; Essex, Max; Hudelson, Sarah E; Redd, Andrew D; Fleming, Thomas R

    2016-09-01

    Background An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. Methods We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. Results Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. Conclusions The early initiation of ART led to a sustained

  2. [Anticoagulant therapy in secondary prevention of coronary events].

    PubMed

    Bultas, Jan

    2014-12-01

    Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban). PMID:25692828

  3. [Relapse prevention group therapy for paedophiles: French adaptation].

    PubMed

    Smith, J; Petibon, C

    2005-01-01

    Psychotherapy for sex offenders has only very recently started to develop in France. The French law on compulsory treatment for sex offenders was voted in 1998, and many mental health practitioners are not trained to treat such patients yet. In our ambulatory forensic consultation, sex offenders have been treated since 1992 and group psychotherapy has been offered to them since 1994. Our first therapeutic models were the North-American behavioural-cognitive therapy and Pithers' relapse prevention model. Behavioural-cognitive theory describes paedophilia as an acquired sexual preference maintained by positive reinforcement. Pithers (1990) considered that relapse only occurs in high-risk situations, and that high-risk situations always come after offence precursors. In North America, relapse prevention consists in helping paedophiles spot their high-risk situations and offence precursors, and enhance their skills to cope with such situations or to prevent them. Therapy programs were developed according to these models, aiming to help offenders develop such skills, ie empathy, social skills, cognitive restructuring, self-esteem, etc. Trying to apply these therapy programs in France, our team quickly realised that we would have to adapt them to French culture. On the one hand, behavioural-cognitive theory did not seem satisfactory enough in explaining paedophilic behaviour and paedophilic preference. On the other hand, behavioural-cognitive therapy made patients into children too much and increased resistance. Therapy based on programs seemed too rigid for French patients and therapists, and we often felt we were working on an issue that would have been much more accurate to work on a few sessions earlier, when this issue was spontaneously brought up by a patient. We believe change occurs all the more as issues are worked on at the right moment for the patient. Moreover, on a cultural point of view, we also realised the use of programs in psychotherapy was difficult to

  4. The role of Fc receptors in HIV prevention and therapy.

    PubMed

    Boesch, Austin W; Brown, Eric P; Ackerman, Margaret E

    2015-11-01

    Over the past decade, a wealth of experimental evidence has accumulated supporting the importance of Fc receptor (FcR) ligation in antibody-mediated pathology and protection in many disease states. Here we present the diverse evidence base that has accumulated as to the importance of antibody effector functions in the setting of HIV prevention and therapy, including clinical correlates, genetic associations, viral evasion strategies, and a rapidly growing number of compelling animal model experiments. Collectively, this work identifies antibody interactions with FcR as important to both therapeutic and prophylactic strategies involving both passive and active immunity. These findings mirror those in other fields as investigators continue to work toward identifying the right antibodies and the right effectors to be present at the right sites at the right time. PMID:26497529

  5. Boron neutron capture therapy for the prevention of restenosis

    SciTech Connect

    Yanch, J.C.; Delfaus, M.L.

    1997-12-01

    The potential application of boron neutron capture therapy (BNCT) for the prevention of restenosis following angioplasty is under investigation at Massachusetts Institute of Technology`s Laboratory for Accelerator Beam Applications. The process of Percutaneous transluminal coronary angioplasty involves the insertion of a balloon dilation catheter into the occluded artery. The balloon is then inflated for several minutes to dilate the artery. The blockage is decreased, and blood flow through the artery is improved. This procedure is, initially, very successful. However, 30 to 60% of patients treated also show restenosis within 6 months. Although many physiological processes may contribute to restenosis, the primary mechanism is thought to be abnormal proliferation of the smooth muscle cells in the treated artery.

  6. [Child sexual abuse. Epidemiology, clinical diagnostics, therapy, and prevention].

    PubMed

    Fegert, J M; Hoffmann, U; Spröber, N; Liebhardt, H

    2013-02-01

    The article provides an overview of the research on sexual abuse and the current political developments in Germany. First, the terminology of sexual child abuse is discussed, followed by the presentation of epidemiological data. The section on diagnostics and therapy shows that--because of mostly nonspecific indicators--the diagnosis of child sexual abuse is very difficult to define. Child sexual abuse is discussed as a traumatic experience for children and adolescents with different psychiatric and physical diseases. Current studies have shown that especially cognitive behavioral therapeutic-oriented approaches are effective in curing posttraumatic stress disorders. Based on the new German Child Protection Act, the focus lies on the clarification of confidentiality for medical professionals and their right to consulting services for child protection. In conclusion, guidelines and minimum standards for a child prevention and protection model are presented as well as institutional recommendations addressed to all institutions (also clinical) that take care of or treat children and adolescents. PMID:23361204

  7. Therapies for Prevention and Treatment of Alzheimer's Disease.

    PubMed

    Mendiola-Precoma, J; Berumen, L C; Padilla, K; Garcia-Alcocer, G

    2016-01-01

    Alzheimer's disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-β peptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists and etiology-based treatments such as secretase inhibitors, amyloid binders, and tau therapies. Strategies for prevention of AD through nonpharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. AD is an important health issue on which all people should be informed so that prevention strategies that minimize the risk of its development may be implemented. PMID:27547756

  8. Therapies for Prevention and Treatment of Alzheimer's Disease

    PubMed Central

    2016-01-01

    Alzheimer's disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-β peptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists and etiology-based treatments such as secretase inhibitors, amyloid binders, and tau therapies. Strategies for prevention of AD through nonpharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. AD is an important health issue on which all people should be informed so that prevention strategies that minimize the risk of its development may be implemented. PMID:27547756

  9. Porcine Neonatal Coccidiosis: Evaluation of Monensin as Preventive Therapy

    PubMed Central

    Doré, Monique; Morin, Michel

    1987-01-01

    In this study, we evaluated the efficacy of monensin as a preventive therapy for porcine neonatal coccidiosis. Fifteen three-day-old piglets were given 50,000 sporulated oocysts of Isospora suis and eight of them received 15 mg/kg of monensin orally every other day. Seven piglets served as normal controls. Fecal samples were collected and checked for oocyst shedding. At 18 days of age, piglets were euthanized and necropsied. The onset of clinical signs was delayed in the treated group, but all inoculated piglets displayed anorexia, soft stool, or diarrheic feces. Treated piglets shed large numbers of oocysts in their feces (up to 201,200 oocysts per gram of feces). All infected piglets had lesions of villous atrophy in the jejunum and most of them were in the late atrophic or villous regrowth stages. The results of this study suggest that monensin does not prevent clinical signs, oocyst shedding, and intestinal lesions caused by I. suis in neonatal piglets. PMID:17422909

  10. Hepatoprotective activity of Ficus religiosa leaves against isoniazid+rifampicin and paracetamol induced hepatotoxicity

    PubMed Central

    Parameswari, Sundaramoorthi Angala; Chetty, Challa Madhusudhana; Chandrasekhar, Kothapalli Bannoth

    2013-01-01

    Background: The present study was designed to investigate the hepato protective effect of methanolic extract of Ficus religisoa L., Moraceae, on isoniazid-rifampicin and paracetamol induced hepatotoxicity in rats. Materials and Methods: Male Wistar albino rats were divided into six groups; group 1 served as a control received vehicle (Distilled water), group 2 served as a toxic control, received isoniazid-rifampicin (100 mg/ kg, i.p.) or paracetamol 200mg/kg, p.o in sterile water, groups 3, 4 and 5 received 100, 200 and 300mg/kg bw, p.o. methanolic extract of F. religisoa along with INH+RIF or paracetamol and group 6 received Liv 52 as reference standard. All the treatment protocols followed 21 days for INH+RIF model and seven days for paracetamol model, after treatment rats were sacrificed and blood was used for biochemical and liver was used for histological studies. Results: Administration of INH+RIF and paracetamol caused a significant elevation in the levels of liver marker enzymes (P < 0.05 and P < 0.01) and thiobarbituric acid reactive substances (P < 0.001) in experimental rats. Administration of methanolic extracts of F. religisoa significantly prevented isoniazid-rifampicin and paracetamol induced elevation in the levels of serum diagnostic liver marker enzymes and TBARS level in experimental groups of rats. Moreover, total protein and reduced glutathione levels were significantly (P < 0.001) increased in treatment group. The effect of extract was compared with a standard drug, Liv 52. The changes in biochemical parameters were supported by histological profile. Conclusion: The methanolic extract of F. religisoa protects against isoniazid- rifampicin and paracetamol induced oxidative liver injury in rats. PMID:24174821

  11. Molecular Analysis of Isoniazid-Resistant Mycobacterium tuberculosis Isolates from England and Wales Reveals the Phylogenetic Significance of the ahpC −46A Polymorphism

    PubMed Central

    Baker, L. V.; Brown, T. J.; Maxwell, O.; Gibson, A. L.; Fang, Z.; Yates, M. D.; Drobniewski, F. A.

    2005-01-01

    The present study investigated the prevalence and diagnostic potential of the most commonly reported mutations associated with isoniazid resistance, katG 315Thr, katG 315Asn, inhA −15T, inhA −8A, and the oxyR-ahpC intergenic region, in a population sample of 202 isoniazid-resistant Mycobacterium tuberculosis isolates and 176 randomly selected fully sensitive isolates from England and Wales identified by using a directed oligonucleotide array and limited DNA sequencing. The strains were recovered from patients originating from 29 countries; 41 isolates were multidrug resistant. Mutations affecting katG 315, the inhA promoter, and the oxyR-ahpC intergenic region were found in 62.7, 21.9, and 30% of 169 genotypically distinct isoniazid-resistant isolates, respectively, whereas they were found in 0, 0, and 8% of susceptible strains, respectively. The frequency of mutation at each locus was unrelated to the resistance profile or previous antituberculous drug therapy. The commonest mutation in the oxyR-ahpC intergenic region, ahpC −46A, was present in 23.7% of isoniazid-resistant isolates and 7.5% of susceptible isolates. This proved to be a phylogenetic marker for a subgroup of M. tuberculosis strains originating on the Indian subcontinent, which shared IS6110-based restriction fragment length polymorphism and spoligotype features with the Delhi strain and Central Asian strain CAS1; and this marker is strongly associated with isoniazid resistance and the katG 315Thr mutation. In total, 82.8% of unrelated isoniazid-resistant isolates could be identified by analysis of just two loci: katG 315 and the inhA promoter. Analysis of the oxyR-ahpC intergenic region, although phylogenetically interesting, does not contribute significantly to further identification of isoniazid-resistant isolates. PMID:15793126

  12. Migraine preventive therapy: current and emerging treatment options.

    PubMed

    Rapoport, A M; Bigal, M E

    2005-05-01

    In this paper we review new treatment options for migraine prevention. We start with an overview about migraine and then briefly discuss current indications for migraine prevention and new and emerging preventive medications. PMID:15926007

  13. Role of medication therapy management in preexposure prophylaxis therapy for HIV prevention.

    PubMed

    Ferrell, Kelli W; Woodard, Laresa M; Woodard, Todd J

    2015-02-01

    Patient medication adherence is a long-standing problem and is one that raises serious issues for patient health, public health, and health care quality. Medication nonadherence costs the US economy an estimated US$290 billion in avoidable medical spending every year. One of the most costly health conditions is HIV disease, which continues to be a serious health issue for parts of the world. About 34 million people are living with HIV around the world. With the emerging preventative treatment against HIV, known as preexposure prophylaxis (PrEP), come concerns surrounding the potential impact of nonadherence to this newly approved medication therapy. Nonadherence to antiretroviral treatments are commonly the root cause for patients not reaching their treatment goals, putting them at risk of progression and worsening of their disease and complications, such as increased risk of opportunistic infections. Therefore, it is essential to improve antiretroviral medication adherence. By identifying members who are nonadherent to their prescribed antiretroviral medications and working collaboratively with patients, physicians, and pharmacists, Medication Therapy Management (MTM) can potentially increase medication adherence by helping patients identify, resolve, and prevent issues that may affect their decision not to take a medication as intended. PMID:25500557

  14. Alternative Therapies for the Prevention of Postoperative Nausea and Vomiting.

    PubMed

    Stoicea, Nicoleta; Gan, Tong J; Joseph, Nicholas; Uribe, Alberto; Pandya, Jyoti; Dalal, Rohan; Bergese, Sergio D

    2015-01-01

    Postoperative nausea and vomiting (PONV) is a complication affecting between 20 and 40% of all surgery patients, with high-risk patients experiencing rates of up to 80%. Recent studies and publications have shed light on the uses of alternative treatment for PONV through their modulation of endogenous opioid neuropeptides and neurokinin ligands. In addition to reducing PONV, hypnosis was reported to be useful in attenuating postoperative pain and anxiety, and contributing to hemodynamic stability. Music therapy has been utilized to deepen the sedation level and decrease patient anxiety, antiemetic and analgesic requirements, hospital length of stay, and fatigue. Isopropyl alcohol and peppermint oil aromatherapy have both been used to reduce postoperative nausea. With correct training in traditional Chinese healing techniques, acupuncture (APu) at the P6 acupoint has also been shown to be useful in preventing early PONV, postdischarge nausea and vomiting, and alleviating of pain. Electro-acupuncture (EAPu), as with APu, provided analgesic and antiemetic effects through release and modulation of opioid neuropeptides. These non-pharmacological modalities of treatment contribute to an overall patient wellbeing, assisting in physical and emotional healing. PMID:26734609

  15. Alternative Therapies for the Prevention of Postoperative Nausea and Vomiting

    PubMed Central

    Stoicea, Nicoleta; Gan, Tong J.; Joseph, Nicholas; Uribe, Alberto; Pandya, Jyoti; Dalal, Rohan; Bergese, Sergio D.

    2015-01-01

    Postoperative nausea and vomiting (PONV) is a complication affecting between 20 and 40% of all surgery patients, with high-risk patients experiencing rates of up to 80%. Recent studies and publications have shed light on the uses of alternative treatment for PONV through their modulation of endogenous opioid neuropeptides and neurokinin ligands. In addition to reducing PONV, hypnosis was reported to be useful in attenuating postoperative pain and anxiety, and contributing to hemodynamic stability. Music therapy has been utilized to deepen the sedation level and decrease patient anxiety, antiemetic and analgesic requirements, hospital length of stay, and fatigue. Isopropyl alcohol and peppermint oil aromatherapy have both been used to reduce postoperative nausea. With correct training in traditional Chinese healing techniques, acupuncture (APu) at the P6 acupoint has also been shown to be useful in preventing early PONV, postdischarge nausea and vomiting, and alleviating of pain. Electro-acupuncture (EAPu), as with APu, provided analgesic and antiemetic effects through release and modulation of opioid neuropeptides. These non-pharmacological modalities of treatment contribute to an overall patient wellbeing, assisting in physical and emotional healing. PMID:26734609

  16. Isoniazid@Fe2 O3 Nanocontainers and Their Antibacterial Effect on Tuberculosis Mycobacteria.

    PubMed

    Leidinger, Peter; Treptow, Jens; Hagens, Kristine; Eich, Jacqueline; Zehethofer, Nicole; Schwudke, Dominik; Oehlmann, Wulf; Lünsdorf, Heinrich; Goldmann, Oliver; Schaible, Ulrich E; Dittmar, Kurt E J; Feldmann, Claus

    2015-10-19

    Isoniazid-filled Fe2 O3 hollow nanospheres (INH@Fe2 O3 , diameter <30 nm, 48 wt % INH-load) are prepared for the first time and suggested for tuberculosis therapy. After dextran-functionalization, the INH@Fe2 O3 @DEX nanocontainers show strong activity against Mycobacterium tuberculosis (M.tb.) and M.tb.-infected macrophages. The nanocontainers can be considered as "Trojan horses" and show efficient, active uptake into both M.tb.-infected macrophages and even into mycobacterial cells. PMID:26332072

  17. New Regimens to Prevent Tuberculosis in Adults with HIV Infection

    PubMed Central

    Martinson, Neil A.; Barnes, Grace L.; Moulton, Lawrence H.; Msandiwa, Reginah; Hausler, Harry; Ram, Malathi; McIntyre, James A.; Gray, Glenda E.; Chaisson, Richard E.

    2012-01-01

    BACKGROUND Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment. METHODS We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival. RESULTS The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine–isoniazid group, 2.9 per 100 person-years in the rifampin–isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance. CONCLUSIONS On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid. PMID:21732833

  18. Zidovudine and isoniazid induced liver toxicity and oxidative stress: Evaluation of mitigating properties of silibinin.

    PubMed

    Raghu, Ramanathan; Karthikeyan, Sivanesan

    2016-09-01

    HIV/AIDS patients are more prone for opportunistic TB infections and they are administered the combined regimen of anti-retroviral drug zidovudine (AZT) and isoniazid (INH) for therapy. However, AZT+INH treatment has been documented to induce injury and remedial measures to prevent this adversity are not clearly defined. Silibinin (SBN) is a natural hepatoprotective principle isolated from medicinal plant Silybum marianum and is currently used for therapy of various liver diseases. This study investigate the hepatotoxic potentials of AZT alone, INH alone and AZT+INH treatments and the mitigating potentials of SBN against these drugs induced toxic insults of liver in rats. Separate groups of rats (n=6 in each group) were administered AZT alone (50mg/kg b.w.), INH alone (25mg/kg, b.w.), AZT+INH (50mg/kg, b.w. and 25mg/kg, b.w.), SBN alone (100mg/kg, b.w.) and SBN+AZT+INH daily for sub-chronic period of 45days orally. The control rats received saline/propylene glycol. INH alone and AZT+INH-induced parenchymal cell injury and cholestasis of liver was evidenced by highly significant increase in the activities of marker enzymes (aspartate and alanine transaminase, alkaline phosphatase, argino succinic acid lyase), bilirubin, protein, oxidative stress parameters (lipid peroxidation, superoxide dismutase, catalase, reduced glutathione, vitamins C and E) and membrane bound ATPases were evaluated in serum/liver tissue homogenates. Histopathological studies show ballooning degradation, inflammatory lesions, lipid deposition and hydropic changes in the liver tissue. All the above biochemical and pathological changes induced by AZT+INH treatments were mitigated in rats receiving SBN simultaneously with these hepatotoxins, indicating its hepatoprotective and antioxidant potentials against AZT+INH-induced hepatotoxicity. The moderate hepatoprotective and oxidant potentials of SBN could be due to its low bioavailability and this deficiency could be prevented by supplementation of

  19. Increased urinary excretion of toxic hydrazino metabolites of isoniazid by slow acetylators. Effect of a slow-release preparation of isoniazid.

    PubMed

    Peretti, E; Karlaganis, G; Lauterburg, B H

    1987-01-01

    To test the hypothesis that slow acetylators, who may have a greater risk of developing isoniazid hepatitis than rapid acetylators, are exposed to more acetylhydrazine and hydrazine, two toxic metabolites of isoniazid, the urinary excretion of hydrazino metabolites of isoniazid was measured following the ingestion of 300 mg isoniazid. Slow acetylators (n = 7) excreted significantly more isoniazid (32.4 vs 9.2% dose), acetylhydrazine (3.1 vs 1.6% dose), and hydrazine (1.0 vs 0.4% dose) in 24 h than rapid acetylators (n = 5), whereas the excretion of acetylisoniazid and diacetylhydrazine was significantly lower. As the acetylation (i.e. detoxification) of acetylhydrazine is inhibited in the presence of high concentrations of isoniazid, a study was also made of the effect of a slow-release preparation that results in lower plasma concentrations of isoniazid on the production of hydrazino metabolites. The ratio of acetylisoniazid to isoniazid in urine was significantly increased in slow acetylators from 0.84 to 1.02 following administration of the slow release preparation, indicating increased acetylation of isoniazid. However, the excretion of diacetylhydrazine relative to the excretion of acetylhydrazine and hydrazine did not change. It is concluded that exposure to toxic metabolites of isoniazid is increased in slow acetylators. Detoxification of the toxic metabolites was not enhanced by a slow-release preparation of isoniazid. PMID:3691615

  20. Reagent Precoated Targets for Rapid In-Tissue Derivatization of the Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Manier, M. Lisa; Reyzer, Michelle L.; Goh, Anne; Dartois, Veronique; Via, Laura E.; Barry, Clifton E.; Caprioli, Richard M.

    2011-08-01

    Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS.

  1. Cognitive-Behavioral Therapy for Suicide Prevention (CBT-SP): Treatment Model, Feasibility, and Acceptability

    ERIC Educational Resources Information Center

    Stanley, Barbara; Brown, Gregory; Brent, David A.; Wells, Karen; Poling, Kim; Curry, John; Kennard, Betsy D.; Wagner, Ann; Cwik, Mary F.; Klomek, Anat Brunstein; Goldstein, Tina; Vitiello, Benedetto; Barnett, Shannon; Daniel, Stephanie; Hughes, Jennifer

    2009-01-01

    Objective: To describe the elements of a manual-based cognitive-behavioral therapy for suicide prevention (CBT-SP) and to report its feasibility in preventing the recurrence of suicidal behavior in adolescents who have recently attempted suicide. Method: The CBT-SP was developed using a risk reduction and relapse prevention approach and…

  2. Broad targeting of angiogenesis for cancer prevention and therapy.

    PubMed

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M; Arreola, Alexandra; Rathmell, W Kimryn; Generali, Daniele; Nagaraju, Ganji P; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I; Azmi, Asfar S; Bilsland, Alan; Keith, W Nicol; Jensen, Lasse D

    2015-12-01

    pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleanolic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies. PMID:25600295

  3. Broad targeting of angiogenesis for cancer prevention and therapy

    PubMed Central

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M.; Arreola, Alexandra; Rathmell, W. Kimryn; Generali, Daniele; Nagaraju, Ganji P.; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I.; Azmi, Asfar S.; Bilsland, Alan; Keith, W. Nicol; Jensen, Lasse D.

    2015-01-01

    angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleanolic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the “hallmarks” of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies. PMID:25600295

  4. Isoniazid cocrystals with anti-oxidant hydroxy benzoic acids

    NASA Astrophysics Data System (ADS)

    Mashhadi, Syed Muddassir Ali; Yunus, Uzma; Bhatti, Moazzam Hussain; Tahir, Muhammad Nawaz

    2014-11-01

    Isoniazid is the primary constituent of “triple therapy” used to effectively treat tuberculosis. In tuberculosis and other diseases, tissue inflammation and free radical burst from macrophages results in oxidative stress. These free radicals cause pulmonary inflammation if not countered by anti-oxidants. Therefore, in the present study cocrystals of isoniazid with four anti-oxidant hydroxy benzoic acids have been reported. Gallic acid, 2,3-dihydroxybenzoic acid, 3,5-dihydroxybenzoic acid, and 3-hydroxybenzoic acid resulted in the formation of cocrystals when reacted with isoniazid. Cocrystal structure analysis confirmed the existence of pyridine-carboxylic acid synthon in the cocrystals of isoniazid with Gallic acid, 2,3-dihydroxybenzoic acid and 3-hydroxybenzoic acid. While cocrystal of 3,5-dihydroxybenzoic acid formed the pyridine-hydroxy group synthon. Other synthons of different graph sets are formed between hydrazide group of isoniazid and coformers involving Nsbnd H⋯O and Osbnd H⋯N bonds. All the cocrystals were in 1:1 stoichiometric ratio.

  5. Differentiated thyroid cancer-personalized therapies to prevent overtreatment.

    PubMed

    Luster, Markus; Weber, Theresia; Verburg, Frederik A

    2014-09-01

    The concept of individualized therapy is rapidly gaining recognition in the management of patients with differentiated thyroid cancer (DTC). This Review provides an overview of the most important elements of this paradigm shift in DTC management and discusses the implications for clinical practice. In the majority of patients with DTC who have an inherently good prognosis, the extent of surgery, the dosage of (131)I therapy and the use of levothyroxine therapy are all aspects suitable for individualization, on the basis of both the stage of disease and the response to treatment. In individuals with advanced disease, newer imaging techniques, advances in (131)I therapy and the use of targeted molecular therapies (such as multitargeted kinase inhibitors) have provided new options for the personalized care of patients, for whom until recently no effective therapies were available. Individualized therapies could reduce adverse effects, including the sometimes debilitating hypothyroidism that used to be required before initiation of (131)I treatment, and major salivary gland damage, a common and unpleasant side effect of (131)I therapy. Highly individualized interdisciplinary treatment of patients with DTC might lead to improved outcomes with reduced severity and frequency of complications and adverse effects. However, in spite of ongoing research, personalized therapies remain in their infancy. PMID:24981455

  6. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis.

    PubMed

    Hazbón, Manzour Hernando; Brimacombe, Michael; Bobadilla del Valle, Miriam; Cavatore, Magali; Guerrero, Marta Inírida; Varma-Basil, Mandira; Billman-Jacobe, Helen; Lavender, Caroline; Fyfe, Janet; García-García, Lourdes; León, Clara Inés; Bose, Mridula; Chaves, Fernando; Murray, Megan; Eisenach, Kathleen D; Sifuentes-Osornio, José; Cave, M Donald; Ponce de León, Alfredo; Alland, David

    2006-08-01

    The molecular basis for isoniazid resistance in Mycobacterium tuberculosis is complex. Putative isoniazid resistance mutations have been identified in katG, ahpC, inhA, kasA, and ndh. However, small sample sizes and related potential biases in sample selection have precluded the development of statistically valid and significant population genetic analyses of clinical isoniazid resistance. We present the first large-scale analysis of 240 alleles previously associated with isoniazid resistance in a diverse set of 608 isoniazid-susceptible and 403 isoniazid-resistant clinical M. tuberculosis isolates. We detected 12 mutant alleles in isoniazid-susceptible isolates, suggesting that these alleles are not involved in isoniazid resistance. However, mutations in katG, ahpC, and inhA were strongly associated with isoniazid resistance, while kasA mutations were associated with isoniazid susceptibility. Remarkably, the distribution of isoniazid resistance-associated mutations was different in isoniazid-monoresistant isolates from that in multidrug-resistant isolates, with significantly fewer isoniazid resistance mutations in the isoniazid-monoresistant group. Mutations in katG315 were significantly more common in the multidrug-resistant isolates. Conversely, mutations in the inhA promoter were significantly more common in isoniazid-monoresistant isolates. We tested for interactions among mutations and resistance to different drugs. Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance. There was also a significant inverse association between katG315 mutations and mutations in ahpC or inhA and between mutations in kasA and mutations in ahpC. Our results suggest that isoniazid resistance and the evolution of multidrug-resistant strains are complex dynamic processes that may be influenced by interactions between genes and drug-resistant phenotypes. PMID:16870753

  7. Isoniazid interaction with phosphatidylcholine-based membranes

    NASA Astrophysics Data System (ADS)

    Marques, Amanda Vicente; Marengo Trindade, Paulo; Marques, Sheylla; Brum, Tainá; Harte, Etienne; Rodrigues, Marieli Oliveira; D'Oca, Marcelo Gonçalves Montes; da Silva, Pedro Almeida; Pohlmann, Adriana R.; Alves, Isabel Dantas; de Lima, Vânia Rodrigues

    2013-11-01

    Interaction between the anti-tuberculosis drug isoniazid (INH) and phosphatidylcholine membranes was investigated in terms of: (i) drug affinity to a lipid bilayer and (ii) drug-induced changes in the dynamic properties of liposomes, such as membrane hydration state, polar head and non-polar acyl chain order and lipid phase transition behavior. These parameters were studied by plasmon waveguide resonance spectroscopy (PWR), UV-visible, horizontal attenuated total reflectance-Fourier transform infrared (HATR-FTIR), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques. PWR measurements showed an INH membrane dissociation constant value of 0.031 μM to phosphatidylcholine bilayers. INH induced higher membrane perturbation in the plane which is perpendicular to the membrane plane. The INH saturation concentration in phosphatidylcholine liposomes was 170 μM. At this concentration, HATR-FTIR and NMR findings showed that INH may interact with the lipid polar head, increasing the number of hydrogen bonds in the phosphate region and enhancing the choline motional freedom. DSC measurements showed that, at 115 μM, INH was responsible for a decrease in lipid phase transition temperature of approximately 2 °C and had no influence in the lipid enthalpy variation (ΔH). However, at 170 μM, INH induced the reduction of the ΔH by approximately 52%, suggesting that the drug may increase the distance among lipid molecules and enhance the freedom of the lipid acyl chains methylene groups. This paper provides information on the effects of INH on membrane dynamics which is important to understand liposome targeting of the drug and for the development of anti-TB pharmacologic systems that not only are less susceptible to resistance but also have low toxicity.

  8. Antiretroviral Therapy as HIV Prevention: Status and Prospects

    PubMed Central

    Venkatesh, Kartik K.

    2010-01-01

    As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682

  9. The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

    SciTech Connect

    Epstein, J.B.; Wong, F.L.W. )

    1994-02-01

    The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed using a quantitative scale and symptoms were assessed using visual analogue scales. The statistical model was developed to detect a 40% reduction in mucositis. No statistically significant reduction in mucositis was seen. Early during radiation therapy less oral pain was reported in the sucralfate group, but as treatment progressed all patients experienced pain. Patients in the sucralfate group were prescribed topical and systemic analgesics later in the course of radiation therapy. Prophylactic oral rinsing with sucralfate did not prevent oral ulcerative mucositis. Sucralfate may reduce the experience of pain during radiation therapy. 32 refs., 3 tabs.

  10. Heart failure therapy and sudden cardiac death prevention.

    PubMed

    Morgan, J M

    2004-12-01

    Primary prophylaxis of sudden cardiac death by implantable defibrillators is an accepted therapeutic strategy because sudden cardiac death is reduced by their use. However, many patients at risk of sudden cardiac death due to left ventricular systolic dysfunction also suffer heart failure symptoms. There is increasing evidence that the morbidity of heart failure can be alleviated by device therapy in which ventricular dysynchrony is improved by biventricular pacing. Both therapies in the same device can reduce both morbidity and mortality. Device therapy is an important new aspect in the field of heart failure management. PMID:15729212

  11. Gene and Cell Therapies for the Failing Heart to Prevent Sudden Arrhythmic Death

    PubMed Central

    Sovari, Ali A.; Dudley, Samuel C.

    2013-01-01

    Current therapies for treatment and prevention of sudden cardiac death have certain limitations, and a search for new therapeutic approaches is desirable to reduce the burden of sudden arrhythmic death. Gene therapy and stem cell therapy have been investigated as new, valuable tools in treating cardiac diseases such as arrhythmias. In this review, the basics of each modality, important related experimental and clinical studies, and potential advantages and limitations of these treatments will be discussed. The future success of gene and cell therapy to become practical clinical tools greatly depends on our understanding of the mechanisms of ventricular arrhythmia and the mechanisms of action of gene and cell therapy. PMID:22858914

  12. Cognitive-Behavioral Therapy to Prevent Relapse in Pediatric Responders to Pharmacotherapy for Major Depressive Disorder

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Emslie, Graham J.; Mayes, Taryn L.; Nightingale-Teresi, Jeanne; Nakonezny, Paul A.; Hughes, Jennifer L.; Jones, Jessica M.; Tao, Rongrong; Stewart, Sunita M.; Jarrett, Robin B.

    2008-01-01

    The outcome of a sequential treatment strategy that included cognitive behavioral therapy (CBT) in the prevention of major depressive disorder relapse among 46 youths is examined. Results show that youths under the antidepressant medication management plus relapse prevention CBT treatment was at lower risk for relapse than those under the…

  13. Isoniazid: metabolic aspects and toxicological correlates.

    PubMed

    Preziosi, Paolo

    2007-12-01

    For over half a century, pyridine-4-carboxy hydrazide (isonicotinyl hydrazide; isoniazid - INH) has been a front-line weapon in the battle against tuberculosis. Its metabolism has been the subject of important research, much of which has focused on the pharmacodynamic and toxicological aspects of certain INH metabolites. Since 1952, when the drug was first introduced, multiple INH metabolites have been identified, including hydrazine (HZ), isonicotinic acid (INA), ammonia, the acetylated derivative N(1)-acetyl-N(2)-isonicotinylhydrazide (AcINH), hydrazones with pyruvic and ketoglutaric acids (INH-PA and INH-KA, respectively), monoacetylhydrazine (AcHZ), diacetylhydrazine (DiAcHZ), and oxidizing free radicals. Their formation is the result of hydrolysis (INA, HZ), cytochrome P450 (CYP)-dependent oxidation (HZ, NH(3), oxidizing free radicals), and N-acetyltransferase (NAT) activity (AcINH, AcHZ, DiAcHZ). Doubts remain about isonicotinamide (INAAM) as an INH metabolite in mammals. Quantitatively speaking, one of the major metabolites is AcINH, which is produced by the enzyme NAT. It has virtually no antitubercular activity and is far less toxic than INH. Its formation and elimination are genetically controlled, and its elimination profile is trimodal (rapid, intermediate, and slow acetylation). Slow acetylation, which is transmitted as an autosomal recessive trait, increases the risk for peripheral neurotoxicity and hepatotoxicity in INH users. Thus far, there is no conclusive pharmacogenetic evidence that the formation of HZ and oxidizing radicals are linked to CYP polymorphisms. This article examines INH, HZ and its mono- and diacetylated metabolites, and ammonia (which in vitro and in vivo studies indicate as another derivative of HZ) in terms of their potential to cause neurotoxic and hepatotoxic effects (the two major forms of INH toxicity observed in animals and humans). INH hepatotoxicity seems to be related mainly to HZ, AcHZ, and other HZ metabolites that are

  14. Effect of pyridoxine on vitamin B6 concentrations and glutamic-oxaloacetic transaminase activity in whole blood of tuberculous patients receiving high-dosage isoniazid, *†

    PubMed Central

    Krishnamurthy, D. V.; Selkon, J. B.; Ramachandran, K.; Devadatta, S.; Mitchison, D. A.; Radhakrishna, S.; Stott, H.

    1967-01-01

    An earlier report from the Tuberculosis Chemotherapy Centre, Madras, showed that, in tuberculous patients receiving high-dosage isoniazid (12.5-15.6 mg/kg body-weight), the concomitant administration of 6 mg of pyridoxine prevented peripheral neuropathy. In that study, biochemical determinations of B6 concentrations and GOT activity in whole blood had been routinely undertaken on all patients on admission to treatment, and at 6, 12, 24 and 52 weeks thereafter; in addition, extra determinations were undertaken for patients who developed peripheral neuropathy. The present paper reports the findings of these investigations, which are: (a) peripheral neuropathy developed predominantly among slow inactivators of isoniazid, and was associated with a substantial reduction in GOT activity but no apparent change in B6 concentration; (b) the reduction in GOT activity appeared to be due to deficiency of both the coenzyme (pyridoxal phosphate) and the apoenzyme; (c) the concomitant administration of pyridoxine (6 mg or 48 mg) with high-dosage isoniazid to 3 patients with peripheral neuropathy, 1 of whom had convulsions also, resulted in increased B6 concentrations and GOT activity, and no further convulsions; and (d) the concomitant administration of pyridoxine 6 mg daily, as a prophylactic, resulted in a significant increase in B6 concentrations and GOT activity and prevention of the neuropathy. These findings establish the existence of a definite association between the occurrence of isoniazid-induced toxicity and diminished pyridoxine function. PMID:4866185

  15. Primary Prevention of Variceal Bleeding: Pharmacological Therapy Versus Endoscopic Banding

    PubMed Central

    Karadsheh, Zeid; Allison, Harmony

    2013-01-01

    Variceal bleeding is one of the most feared complications in patients with liver cirrhosis. It continues to be a leading cause of death among patients with liver cirrhosis. Although its prognosis has improved over the last several decades, it still carries substantial mortality. Preventing variceal bleeding has been extensively studied and evaluated in several studies in the recent years and the comparison between the different modalities available to prevent variceal bleeding has been an area of discussion. Currently the two most widely used modalities to prevent variceal bleeding are pharmacologic (non-selective beta-blockers [NSBB]) and endoscopic (variceal band ligation [VBL]) which have replaced sclerotherapy in the recent years. In addition to NSBB and recent carvedilol, different other medications have been evaluated including isosorbide mononitrates, spironolactone and angiotensin blocking agents. Comparing the outcomes and adverse effects of these two modalities has been evaluated in different studies. Some studies have showed superiority of VBL until recently, when carvedilol has been included, however; overall mortality has been similar in most trials. Despite that, NSBB remain the first line treatment, as they are cheaper and relatively effective in preventing both esophageal and gastric bleeding. The following sections discuss the primary prevention of variceal bleeding with a focus on NSBB, carvedilol and VBL. PMID:24350068

  16. Can Molecular Methods Detect 1% Isoniazid Resistance in Mycobacterium tuberculosis?

    PubMed Central

    Folkvardsen, Dorte Bek; Thomsen, Vibeke Ø.; Rasmussen, Erik Michael; Bang, Didi; Werngren, Jim; Hoffner, Sven; Hillemann, Doris; Rigouts, Leen

    2013-01-01

    Patients may harbor both drug-susceptible and -resistant bacteria, representing heteroresistance. We studied mixtures of isoniazid-resistant and -susceptible Mycobacterium tuberculosis strains. Conventional drug susceptibility testing was the most sensitive method of detection, whereas the line probe assay and sequencing were not able to detect the clinically relevant 1% proportion of resistant bacteria. PMID:23447641

  17. A vertical diffusion method for the microbiological assay of isoniazid

    PubMed Central

    Lloyd, Janet; Mitchison, D. A.

    1964-01-01

    A method is described for the assay of isoniazid in serum and other fluids by diffusion along slopes of Löwenstein-Jensen medium inoculated with tubercle bacilli. The method is convenient, rapid and robust, but is less accurate than diffusion systems for the assay of some other substances. PMID:14227431

  18. The Wilderness Therapy Prevention Program: A Prevention Model for At-Risk Children and Adolescents

    ERIC Educational Resources Information Center

    Butler, Meghan

    2008-01-01

    Wilderness Therapy Programs have recently become a formal alternative treatment for adolescents with emotional and behavioral disorders (Hinkle, 1999; Russell & Hendee, 1999; Russell, Hendee, & Phillips-Miller, 2000; Russell, 2003a, 2003b). Adolescent populations are unique in that traditional forms of psychotherapy, including "talk-therapies,"…

  19. [Pressure ulcer prevention and therapy: results of a descriptive study].

    PubMed

    Schlüer, Anna-Barbara; Cignacco, Eva; Halfens, Ruud J

    2008-03-01

    Pressure ulcers are a common nursing care issue in hospitals. Sick children, premature infants and toddlers, but also disabled and impaired children are at a high risk of developing pressure ulcers. The aim of this descriptive cross-sectional study was to describe the patients at risk as well as to identify the preventive and therapeutic interventions in a pediatric care setting. Of 213 hospitalised children, 155 (82 percent) from the age of 0 to 18 years could be included in the study. Altogether, preventive actions of any kind were performed with 92 percent of the patients. These were repositioning (84 percent), mobilisation of the patients (75 percent), followed by skin inspection (61 percent) and the application of lotions (56 percent). The high risk rate of pediatric patients considered at risk according to the Braden Scale is disconcerting and requires further exploration in terms of effective preventive and therapeutic interventions to improve the outcome for this patient group. PMID:18450264

  20. Does hyperbaric oxygen therapy prevent airway anastomosis from breakdown?

    PubMed

    Dickhoff, Chris; Daniels, Johannes M A; van den Brink, Ad; Paul, Marinus A; Verhagen, Ad F T M

    2015-02-01

    Ischemia with subsequent necrosis of anastomoses, after central airway resection and reconstruction, remains a feared complication for thoracic surgeons and their patients. To date, there is no evidence to support the use of hyperbaric oxygen in the prevention of necrosis of airway reconstructions in humans. We present a patient who underwent central airway surgery with postoperative ischemia of an end-to-side anastomosis. Repeat visit to a hyperbaric oxygen chamber seemed to prevent the anastomosis from subsequent necrosis and dehiscence with complete healing as a result. In conclusion, hyperbaric oxygen treatment can be considered when ischemia or necrosis is observed in central airway anastomoses during postoperative bronchoscopic surveillance. PMID:25639406

  1. Selected Micronutrients in Cognitive Decline Prevention and Therapy.

    PubMed

    Visioli, Francesco; Burgos-Ramos, Emma

    2016-08-01

    Population aging is a worldwide demographic trend. Consequently, the prevalence of chronic age-related conditions such as clinically diagnosed neurological diseases, cognitive decline, and dementia will significantly increase in the near future. The important role of diets and healthy lifestyle as preventative of neurodegenerative diseases is widely accepted nowadays, and it may provide preventive strategies in very early, non-symptomatic phases of dementia well, especially because there are still no effective treatments for it. In this article, we review the known effects of selected micronutrients on the aging brain and we propose strategies for dietary improvements. PMID:26198569

  2. Developing Cognitive Behavioral Therapy to Prevent Depressive Relapse in Youth

    ERIC Educational Resources Information Center

    Kennard, Betsy D.; Stewart, Sunita M.; Hughes, Jennifer L.; Jarrett, Robin B.; Emslie, Graham J.

    2008-01-01

    Relapse rates for children and adolescents with major depressive disorder (MDD) range from 30% to 40% within 1 to 2 years after acute treatment. Although relapse rates are high, there have been relatively few studies on the prevention of relapse in youth. While acute phase pharmacotherapy has been shown to reduce symptoms rapidly in depressed…

  3. Making family therapy easier for the therapist: burnout prevention.

    PubMed

    Friedman, R

    1985-12-01

    Burnout prevention for family therapists can be enhanced by careful consideration of the degree of responsibility taken by the therapist contrasted with responsibility placed on the family. Attention to issues of expectations, role definition, sharing of feelings, and therapeutic ambition can ease the strain on the therapist. PMID:4085618

  4. Migraine preventive therapy: selection of appropriate patients and general principles of management.

    PubMed

    D'Amico, Domenico; Lanteri-Minet, Michel

    2006-08-01

    The goal of this review is to communicate the rationale and the possible benefits of migraine preventive treatments to clinicians and patients, and to address the many problematic issues created by missed diagnosis or misdiagnoses and inadequate migraine management. Successful implementation of migraine preventive treatment requires appropriate patient selection based on several factors, including the frequency of migraine attacks (> or =2-3 attacks/month), the level of disability incurred and the frequency of acute medication usage. Unfortunately, several epidemiologic surveys indicate that preventive therapies are significantly underutilized, which supports the need for greater dialog concerning migraine prevention between consumers and physicians. Effective migraine preventive therapy should reduce the frequency, duration, and severity of migraine, and also improve function, reduce disability, and possibly reduce the risk of worsening the headache syndrome, through acute medication overuse. PMID:16893343

  5. Prevention of electrical shock hazards in physical therapy.

    PubMed

    Arledge, R L

    1978-10-01

    Basic electrical safety information for the physical therapist is presented, and the most hazardous areas in a physical therapy clinic are identified. Physical therapy modalities are no safer than the power receptacle (wall outlet) into which they are plugged. High frequency physical therapy equipment should never be operated without a three-prong polarized plug and a matching polarized wall receptacle. Three-to-two prong adapters must never be used. Hydrotherapy is an especially dangerous area and should be equipped with ground fault detector receptacles with ground fault interrupters that cut the current when the electrical ground is lost. Ultrasound leakage current measurements on many older ultrasound units may now exceed today's acceptable standards. An external isolation transformer may be required to modify older ultrasonic units before they meet present standards. Physical therapists must never assume that rountine electrical safety inspections are being conducted by hospital maintenance personnel. The physical therapist is responsible for ensuring that all hazardous areas are rountinely checked for electrical safety. PMID:693580

  6. Engineering broadly neutralizing antibodies for HIV prevention and therapy.

    PubMed

    Hua, Casey K; Ackerman, Margaret E

    2016-08-01

    A combination of advances spanning from isolation to delivery of potent HIV-specific antibodies has begun to revolutionize understandings of antibody-mediated antiviral activity. As a result, the set of broadly neutralizing and highly protective antibodies has grown in number, diversity, potency, and breadth of viral recognition and neutralization. These antibodies are now being further enhanced by rational engineering of their anti-HIV activities and coupled to cutting edge gene delivery and strategies to optimize their pharmacokinetics and biodistribution. As a result, the prospects for clinical use of HIV-specific antibodies to treat, clear, and prevent HIV infection are gaining momentum. Here we discuss the diverse methods whereby antibodies are being optimized for neutralization potency and breadth, biodistribution, pharmacokinetics, and effector function with the aim of revolutionizing HIV treatment and prevention options. PMID:26827912

  7. Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

    Cancer.gov

    This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. |

  8. Targeting transcription factor STAT3 for cancer prevention and therapy.

    PubMed

    Chai, Edna Zhi Pei; Shanmugam, Muthu K; Arfuso, Frank; Dharmarajan, Arunasalam; Wang, Chao; Kumar, Alan Prem; Samy, Ramar Perumal; Lim, Lina H K; Wang, Lingzhi; Goh, Boon Cher; Ahn, Kwang Seok; Hui, Kam Man; Sethi, Gautam

    2016-06-01

    Signal Transducers and Activators of Transcription (STATs) comprise an important class of transcription factors that have been implicated in a wide variety of essential cellular functions related to proliferation, survival, and angiogenesis. Among various STAT members, STAT3 is frequently overexpressed in tumor cells as well as tissue samples, and regulates the expression of numerous oncogenic genes controlling the growth and metastasis of tumor cells. The current review briefly discusses the importance of STAT3 as a potential target for cancer therapy and also provides novel insights into various classes of existing pharmacological inhibitors of this transcription factor that can be potentially developed as anti-cancer drugs. PMID:26478441

  9. Barriers to preventive therapy for breast and other major cancers and strategies to improve uptake.

    PubMed

    DeCensi, Andrea; Thorat, Mangesh A; Bonanni, Bernardo; Smith, Samuel G; Cuzick, Jack

    2015-01-01

    The global cancer burden continues to rise and the war on cancer can only be won if improvements in treatment go hand in hand with therapeutic cancer prevention. Despite the availability of several efficacious agents, utilisation of preventive therapy has been poor due to various barriers, such as the lack of physician and patient awareness, fear of side effects, and licensing and indemnity issues. In this review, we discuss these barriers in detail and propose strategies to overcome them. These strategies include improving physician awareness and countering prejudices by highlighting the important differences between preventive therapy and cancer treatment. The importance of the agent-biomarker-cohort (ABC) paradigm to improve effectiveness of preventive therapy cannot be overemphasised. Future research to improve therapeutic cancer prevention needs to include improvements in the prediction of benefits and harms, and improvements in the safety profile of existing agents by experimentation with dose. We also highlight the role of drug repurposing for providing new agents as well as to address the current imbalance between therapeutic and preventive research. In order to move the field of therapeutic cancer prevention forwards, engagement with policymakers to correct research imbalance as well as to remove practical obstacles to implementation is also urgently needed. PMID:26635899

  10. Barriers to preventive therapy for breast and other major cancers and strategies to improve uptake

    PubMed Central

    DeCensi, Andrea; Thorat, Mangesh A; Bonanni, Bernardo; Smith, Samuel G; Cuzick, Jack

    2015-01-01

    The global cancer burden continues to rise and the war on cancer can only be won if improvements in treatment go hand in hand with therapeutic cancer prevention. Despite the availability of several efficacious agents, utilisation of preventive therapy has been poor due to various barriers, such as the lack of physician and patient awareness, fear of side effects, and licensing and indemnity issues. In this review, we discuss these barriers in detail and propose strategies to overcome them. These strategies include improving physician awareness and countering prejudices by highlighting the important differences between preventive therapy and cancer treatment. The importance of the agent–biomarker–cohort (ABC) paradigm to improve effectiveness of preventive therapy cannot be overemphasised. Future research to improve therapeutic cancer prevention needs to include improvements in the prediction of benefits and harms, and improvements in the safety profile of existing agents by experimentation with dose. We also highlight the role of drug repurposing for providing new agents as well as to address the current imbalance between therapeutic and preventive research. In order to move the field of therapeutic cancer prevention forwards, engagement with policymakers to correct research imbalance as well as to remove practical obstacles to implementation is also urgently needed. PMID:26635899

  11. Late-onset sepsis in preterm infants: update on strategies for therapy and prevention.

    PubMed

    Pammi, Mohan; Weisman, Leonard E

    2015-04-01

    Late-onset sepsis occurs in 15-25% of very low birth weight neonates. Early diagnosis and therapy optimize patient outcomes. Despite these efforts, mortality remains high (18-36%) and survivors suffer significant neurological and pulmonary morbidity. Although rapid diagnostics are improving, more are needed. Current therapy remains antibiotics and supportive care. Adjunctive therapies have either limited data (e.g., pentoxifylline) or have been found ineffective (e.g., granulocyte transfusions, granulocyte macrophage colony-stimulating factor/granulocyte colony-stimulating factor, and intravenous immunoglobulin). Preventive strategies that have proven beneficial include infection control measures (e.g., hand hygiene and universal precautions), early enteral feeds with human milk, early removal of central lines, catheter infection prevention bundles, antibiotic stewardship and focused quality improvement measures. Promising strategies to prevent late-onset sepsis include oral lactoferrin, and pathogen-specific monoclonal antibodies but more evidence is required to make practice recommendations. PMID:25661566

  12. Trimetazidine therapy prevents obesity-induced cardiomyopathy in mice.

    PubMed

    Ussher, John R; Fillmore, Natasha; Keung, Wendy; Mori, Jun; Beker, Donna L; Wagg, Cory S; Jaswal, Jagdip S; Lopaschuk, Gary D

    2014-08-01

    Obesity is a significant risk factor for the development of cardiovascular disease. Inhibiting fatty acid oxidation has emerged as a novel approach for the treatment of ischemic heart disease. Our aim was to determine whether pharmacologic inhibition of 3-ketoacyl-coenzyme A thiolase (3-KAT), which catalyzes the final step of fatty acid oxidation, could improve obesity-induced cardiomyopathy. A 3-week treatment with the 3-KAT inhibitor trimetazidine prevented obesity-induced reduction in both systolic and diastolic function. Therefore, targeting cardiac fatty acid oxidation may be a novel therapeutic approach to alleviate the growing burden of obesity-related cardiomyopathy. PMID:25064584

  13. [Suicidality in mental illness – prevention and therapy].

    PubMed

    Röcker, Sabine; Bachmann, Silke

    2015-10-01

    The great majority of suicides and suicide attempts are related to mental illness. Special risk has been attributed to depression, psychosis, substance use, personality, and trauma-related disorders. Many affected persons seek medical attention prior to taking action. Primary care therefor plays an outstanding role in suicide prevention. Doctors should pay attention to potential risk constellations and actively address the issue. This paper presents possibly helpful models and instruments for everyday use. Most importantly, however, professionals’ empathy and time are required as well as appropriate decisions concerning a referral to a psychiatrist or psychiatric inpatient treatment. PMID:26423879

  14. Approaches to caries prevention and therapy in the elderly.

    PubMed

    Walls, A W G; Meurman, J H

    2012-09-01

    The population of the world is aging. A greater proportion of older people are retaining increasing numbers of natural teeth. Aging is associated with changes in oral architecture and muscle weakness, making personal oral hygiene more difficult, particularly for the oldest and most frail individuals. Furthermore, there is exposure of root dentin with its higher pH for demineralization in addition to enamel as a substrate for caries. Aging is also associated, for many in the developed world, with taking multiple medications, with the associated risk of dry mouth. These variables combine to increase caries risk in older vulnerable populations. Caries occurs on both the crowns of teeth (predominantly around existing restorations) and the exposed roots. Prevention needs to be aggressive to control disease in this combination of circumstances, with multiple strategies for limiting the damage associated with caries in this population. This paper explores the evidence that is available supporting preventive strategies, including fluorides in various forms, chlorhexidine, and calcium phosphate supplementation. PMID:22899677

  15. Antioxidants and Coronary Artery Disease: From Pathophysiology to Preventive Therapy

    PubMed Central

    Leopold, Jane A.

    2014-01-01

    Oxidant stress in the cardiovascular system may occur when antioxidant capacity is insufficient to reduce reactive oxygen species and other free radicals. Oxidant stress has been linked to the pathogenesis of atherosclerosis and incident coronary artery disease. As a result of this connection, early observational studies focused on dietary antioxidants, such as β-carotene, α-tocopherol, and ascorbic acid, and demonstrated an inverse relationship between intake of these antioxidants and major adverse cardiovascular events. These findings supported a number of randomized trials of selected antioxidants as primary and secondary prevention to decrease cardiac risk; however, many of these studies reported disappointing results with little or no observed risk reduction in antioxidant treated patients. Several plausible explanations for these findings have been suggested, including incorrect antioxidant choice or dose, synthetic versus dietary antioxidant as the intervention, and patient selection, all of which will be important to consider when designing future clinical trials. This review will focus on the contemporary evidence that is the basis for our current understanding of the role of antioxidants in cardiovascular disease prevention. PMID:25369999

  16. A virtual simulator designed for collision prevention in proton therapy

    SciTech Connect

    Jung, Hyunuk; Kum, Oyeon; Han, Youngyih Park, Hee Chul; Kim, Jin Sung; Choi, Doo Ho

    2015-10-15

    Purpose: In proton therapy, collisions between the patient and nozzle potentially occur because of the large nozzle structure and efforts to minimize the air gap. Thus, software was developed to predict such collisions between the nozzle and patient using treatment virtual simulation. Methods: Three-dimensional (3D) modeling of a gantry inner-floor, nozzle, and robotic-couch was performed using SolidWorks based on the manufacturer’s machine data. To obtain patient body information, a 3D-scanner was utilized right before CT scanning. Using the acquired images, a 3D-image of the patient’s body contour was reconstructed. The accuracy of the image was confirmed against the CT image of a humanoid phantom. The machine components and the virtual patient were combined on the treatment-room coordinate system, resulting in a virtual simulator. The simulator simulated the motion of its components such as rotation and translation of the gantry, nozzle, and couch in real scale. A collision, if any, was examined both in static and dynamic modes. The static mode assessed collisions only at fixed positions of the machine’s components, while the dynamic mode operated any time a component was in motion. A collision was identified if any voxels of two components, e.g., the nozzle and the patient or couch, overlapped when calculating volume locations. The event and collision point were visualized, and collision volumes were reported. Results: All components were successfully assembled, and the motions were accurately controlled. The 3D-shape of the phantom agreed with CT images within a deviation of 2 mm. Collision situations were simulated within minutes, and the results were displayed and reported. Conclusions: The developed software will be useful in improving patient safety and clinical efficiency of proton therapy.

  17. Human papillomavirus as a target for management, prevention and therapy.

    PubMed

    Crosbie, Emma J; Kitchener, Henry C

    2012-01-01

    The discovery that human papillomavirus (HPV) is the necessary causal factor in cervical carcinogenesis has made it a target for prophylactic and therapeutic vaccines, as well as a diagnostic tool in cervical screening. Whilst prophylactic vaccination has proven very effective in terms of preventing cervical cancer precursor lesions, therapeutic strategies have presented far greater challenges. HPV testing has shown itself to be extremely valuable in the triage of low grade cytological abnormalities, test of cure following treatment of cervical intraepithelial neoplasia (CIN), and will, over the next 10 years, gradually replace cytology as the mainstay of primary cervical screening. In this review, the latest evidence supporting HPV as both a biomarker of risk for cervical cancer and a target for prophylactic and therapeutic vaccination is presented. PMID:22690976

  18. Extracorporeal shock wave therapy effectively prevented diabetic neuropathy

    PubMed Central

    Chen, Yi-Ling; Chen, Kuan-Hung; Yin, Tsung-Cheng; Huang, Tien-Hung; Yuen, Chun-Man; Chung, Sheng-Ying; Sung, Pei-Hsun; Tong, Meng-Shen; Chen, Chih-Hung; Chang, Hsueh-Wen; Lin, Kun-Chen; Ko, Sheung-Fat; Yip, Hon-Kan

    2015-01-01

    Background: We tested the hypothesis that extracorporeal shock wave (ECSW) therapy can effectively protect sciatic nerve (SN) from diabetes mellitus (DM)-induced neuropathy in leptin-deficient (ob/ob) mice. Methods and results: Eighteen-week C57BL/6 mice (n=8) served as age-matched controls (group 1) and ob/ob mice (n=16) were categorized into DM (group 2) and DM + ECSW (0.12 mJ/mm2 for 4 times of 200 impulses at 3-week intervals) (group 3). The animals were sacrificed two weeks post-ECSW. In vitro results showed that the protein expressions of oxidative stress (NOX-1, NOX-2, oxidized protein), inflammation (MMP-9, TNF-α, iNOS), apoptosis (Bax, cleaved caspase-3, & PARP), and DNA-damage marker (γ-H2AX) were significantly higher in RT4-D6P2T (schwannoma cell line) treated by menadione (25 µM) compared with control group and were significantly reversed after ECSW (0.12 mJ/mm2, 200 impulses) (all p<0.001). mRNA expressions of inflammation (MMP-9, TNF-α, iNOS), oxidative stress (NOX-1, NOX-2) and apoptosis (Bax, caspase-3) in SN were significantly higher in group 2 than in group 1 and were significantly reversed in group 3, whereas the mRNA expressions of anti-oxidants (HO-1, NQO1) progressively increased from group 1 to group 3 (all p<0.001). Cellular expressions of F4/80+, CD14+, γ-H2AX+ cells, and number of vacuolar formation in SN showed a pattern identical to that of inflammation markers among all groups (all p<0.001). Microscopic findings of Schwann cells and myelin-sheath scores, and number of eNOS+ cells in SN showed a reversed pattern compared to that of inflammation among all groups (all p<0.001). Conclusions: ECSW therapy protected SN against DM-induced neuropathy. PMID:26885256

  19. [From case formulation to relapse prevention : a systematic cognitive therapy of schizophrenia.].

    PubMed

    Siddle, R; Turkington, D

    1999-01-01

    This paper discusses the current status of cognitive therapy research in schizophrenia. After reviewing the extent of the evidence base indicating the efficacy of CT in this disorder, the typical process of therapy is outlined. The key techniques of CT in schizophrenia are described along with typical case examples and caveats concerning possible blocks in therapy. The key techniques described are engaging, developing explanations, introducing doubt, peripheral questioning, behavioural homework experiments, schema focussed approaches and relapse prevention. CT for schizophrenia is proposed as an acceptable, effective and safe adjunct to neuroleptic and other psychosocial interventions. PMID:18253540

  20. C-peptide replacement therapy as an emerging strategy for preventing diabetic vasculopathy.

    PubMed

    Bhatt, Mahendra Prasad; Lim, Young-Cheol; Ha, Kwon-Soo

    2014-11-01

    Lack of C-peptide, along with insulin, is the main feature of Type 1 diabetes mellitus (DM) and is also observed in progressive β-cell loss in later stage of Type 2 DM. Therapeutic approaches to hyperglycaemic control have been ineffective in preventing diabetic vasculopathy, and alternative therapeutic strategies are necessary to target both hyperglycaemia and diabetic complications. End-stage organ failure in DM seems to develop primarily due to vascular dysfunction and damage, leading to two types of organ-specific diseases, such as micro- and macrovascular complications. Numerous studies in diabetic patients and animals demonstrate that C-peptide treatment alone or in combination with insulin has physiological functions and might be beneficial in preventing diabetic complications. Current evidence suggests that C-peptide replacement therapy might prevent and ameliorate diabetic vasculopathy and organ-specific complications through conservation of vascular function, as well as prevention of endothelial cell death, microvascular permeability, vascular inflammation, and neointima formation. In this review, we describe recent advances on the beneficial role of C-peptide replacement therapy for preventing diabetic complications, such as retinopathy, nephropathy, neuropathy, impaired wound healing, and inflammation, and further discuss potential beneficial effects of combined C-peptide and insulin supplement therapy to control hyperglycaemia and to prevent organ-specific complications. PMID:25239825

  1. Ultrastructural characteristics of type A epithelioid cells during BCG-granulomatosis and treatment with lysosomotropic isoniazid.

    PubMed

    Shkurupii, V A; Kozyaev, M A; Nadeev, A P

    2006-04-01

    We studied BCG-granulomas, their cellular composition, and ultrastructure of type A epithelioid cells in the liver of male BALB/c mice with spontaneous granulomatous inflammation. The animals received free isoniazid or isoniazid conjugated with lysosomotropic intracellularly prolonged matrix (dialdehyde dextran, molecular weight 65-75 kDa). Lysosomotropic isoniazid was accumulated in the vacuolar apparatus of epithelioid cells and produced a stimulatory effect on plastic processes in these cells. PMID:17152378

  2. Coresistance to isoniazid and ethionamide maps to mycothiol biosynthetic genes in Mycobacterium bovis.

    PubMed

    Vilchèze, Catherine; Av-Gay, Yossef; Barnes, S Whitney; Larsen, Michelle H; Walker, John R; Glynne, Richard J; Jacobs, William R

    2011-09-01

    A search to identify new mechanisms of isoniazid resistance in Mycobacterium bovis led to the isolation of mutants defective in mycothiol biosynthesis due to mutations in genes coding for the glycosyltransferase (mshA) or the cysteine ligase (mshC). These mutants showed low-level resistance to isoniazid but were highly resistant to ethionamide. This study further illustrates that mutations in mycothiol biosynthesis genes may contribute to isoniazid or ethionamide resistance across mycobacterial species. PMID:21709101

  3. Molecular Characterization of Isoniazid-Resistant Mycobacterium tuberculosis Clinical Isolates in Lithuania

    PubMed Central

    Bakonyte, Daiva; Baranauskaite, Aurelija; Cicenaite, Jurate; Sosnovskaja, Anaida; Stakenas, Petras

    2003-01-01

    Mutations at codon 315 of the katG gene were detected in 312 of 364 (85.7%) isoniazid-resistant Mycobacterium tuberculosis isolates. Seven of 52 (13.5%) isoniazid-resistant isolates with the wild-type Ser315 codon and 10 of 52 (19.2%) isoniazid-resistant isolates with a mutated katG allele had mutation −15C→T in the promoter of the mabA-inhA operon. PMID:12760887

  4. Incretin-Based Therapy for Prevention of Diabetic Vascular Complications

    PubMed Central

    Mima, Akira

    2016-01-01

    Diabetic vascular complications are the most common cause of mortality and morbidity worldwide, with numbers of affected individuals steadily increasing. Diabetic vascular complications can be divided into two categories: macrovascular andmicrovascular complications. Macrovascular complications include coronary artery diseaseand cerebrovascular disease, while microvascular complications include retinopathy and chronic kidney disease. These complications result from metabolic abnormalities, including hyperglycemia, elevated levels of free fatty acids, and insulin resistance. Multiple mechanisms have been proposed to mediate the adverse effects of these metabolic disorders on vascular tissues, including stimulation of protein kinase C signaling and activation of the polyol pathway by oxidative stress and inflammation. Additionally, the loss of tissue-specific insulin signaling induced by hyperglycemia and toxic metabolites can induce cellular dysfunction and both macro- and microvascular complications characteristic of diabetes. Despite these insights, few therapeutic methods are available for the management of diabetic complications. Recently, incretin-based therapeutic agents, such as glucagon-like peptide-1 and dipeptidyl peptidase-4 inhibitors, have been reported to elicit vasotropic actions, suggesting a potential for effecting an actual reduction in diabetic vascular complications. The present review will summarize the relationship between multiple adverse biological mechanisms in diabetes and putative incretin-based therapeutic interventions intended to prevent diabetic vascular complications. PMID:26881236

  5. Prevention is the Best Therapy: The Geneticist's Approach.

    PubMed

    Altarescu, Gheona

    2016-06-01

    Abstract During the last two decades prenatal genetic screening and diagnosis has become the cornerstone of medical care for family planning to prevent genetic disease. Carrier screening programs for genetic disorders that are prevalent in various populations identify couples and pregnancies at risk of having an affected child. These couples can proceed with a choice of invasive prenatal diagnosis tests of the fetus (chorionic villous sampling and amniocentesis), or non-invasive prenatal testing of free fetal DNA circulation in the maternal blood which has emerged within the last few years and is currently available for fetal sexing for X Linked disorders. Despite the advances in prenatal diagnosis, couples found to have a fetus affected with a genetic disorder may need to face the dilemma of pregnancy termination. Preimplantation genetic diagnosis (PGD) is an alternative to preempt risk of having a child affected with a life-altering genetic disorder. This technique allows biopsy and genetic diagnosis of embryos obtained from in vitro fertilization by analysis of the genetic material from one or a few embryonic cells. Only unaffected embryos are returned to the mother to establish the pregnancy. We present our experience using PGD for four Lysosomal storage disorders: Tay Sachs, Gaucher type 1, Hunter and Fabry disease with some of the couples being carriers of more than one genetic disorder. PGD is applicable to most disorders for which the gene and the familial mutation are known and should be presented to couples as an alternative to invasive prenatal testing. PMID:27491212

  6. Synthesis and bioevaluation of some new isoniazid derivatives.

    PubMed

    Matei, Lilia; Bleotu, Coralia; Baciu, Ion; Draghici, Constantin; Ionita, Petre; Paun, Anca; Chifiriuc, Mariana Carmen; Sbarcea, Adriana; Zarafu, Irina

    2013-09-01

    The aim of the study was to synthesize some new compounds with potential anti-tuberculosis activity, containing isoniazid and α,β-unsaturated thiocinnamamide-like thioamides as precursors. The obtained derivatives were evaluated regarding their biological activity (antioxidant and antibacterial), as well as their influence on the eukaryotic cell cycle. The results suggested that the newly obtained derivatives of isoniazid exhibited different biological activities, depending on their structure; thus, the most active compound in terms of anti-oxidant and anti-Mycobacterium tuberculosis effects proved to be the isonicotinic acid N'-(1-amino-1-mercapto-3-phenyl-propen-1-yl)-hydrazide. This compound also increased the expression of NAT1 and NAT2 genes, which are implicated in the metabolism of the isoniazid, demonstrating that it could be rapidly metabolized, and thus well tolerated. The largest spectrum of antibacterial activity (excluding M. tuberculosis) was noticed for the isonicotinic acid N'-[1-amino-1-mercapto-3-(p-chloro-phenyl)-propen-1-yl]-hydrazide, which was also the most cytotoxic, especially at high concentrations, although not significantly affecting the cellular cycle phases. The obtained results showed that the new derivatives could represent potential candidates for the treatment of M. tuberculosis infections, but further research is needed in order to improve their pharmacological properties, by increasing their antimicrobial activity and reducing the risk of side-effects. PMID:23823011

  7. Integrating Motivational Interviewing and Self-Determination Theory with Cognitive Behavioral Therapy to Prevent Suicide

    ERIC Educational Resources Information Center

    Britton, Peter C.; Patrick, Heather; Wenzel, Amy; Williams, Geoffrey C.

    2011-01-01

    Cognitive behavioral therapy (CBT) has been found to be effective in preventing suicide-related behavior. However, it is often difficult to engage patients who are at-risk in treatment. Motivational Interviewing (MI) has been shown to increase treatment engagement and improve treatment outcomes when it is used to complement other treatments. As a…

  8. Feasibility of a Prototype Web-Based Acceptance and Commitment Therapy Prevention Program for College Students

    ERIC Educational Resources Information Center

    Levin, Michael E.; Pistorello, Jacqueline; Seeley, John R.; Hayes, Steven C.

    2014-01-01

    Objective: This study examined the feasibility of a prototype Web-based acceptance and commitment therapy (ACT) program for preventing mental health problems among college students. Participants: Undergraduate first-year students ("N" = 76) participated between May and November 2011. Methods: Participants were randomized to ACT or a…

  9. Endocrine therapy for breast cancer prevention in high-risk women: clinical and economic considerations.

    PubMed

    Groom, Amy G; Younis, Tallal

    2016-04-01

    The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their "value for money" in various health care jurisdictions. PMID:26923683

  10. Thyroxine administration during radiation therapy to the neck does not prevent subsequent thyroid dysfunction

    SciTech Connect

    Bantle, J.P.; Lee, C.K.; Levitt, S.H.

    1985-11-01

    In an attempt to reduce the incidence of hypothyroidism following irradiation of the neck, we administered oral L-thyroxine in doses sufficient to suppress serum TSH to 20 patients receiving radiation therapy for Hodgkin's disease or other lymphomas. L-thyroxine was discontinued when radiation therapy was completed. Twenty similar patients who did not receive L-thyroxine during radiation therapy served as a control group. After a mean follow-up period of 33 months, seven patients (35%) in the L-thyroxine group developed elevation of serum TSH and were started on chronic L-thyroxine therapy. In the control group, after mean follow-up of 19 months, five patients (25%) developed elevation of TSH and were started on chronic L-thyroxine. We conclude that suppression of serum TSH during neck irradiation does not prevent subsequent thyroid dysfunction.

  11. Review article: Medical decision models of Helicobacter pylori therapy to prevent gastric cancer.

    PubMed

    Sonnenberg, A; Inadomi, J M

    1998-02-01

    The aim of the present article is to study the utility of Helicobacter pylori eradication programmes in decreasing the incidence of gastric cancer. Three types of decision models are employed to pursue this aim, i.e. decision tree, present value, and declining exponential approximation of life expectancy (DEALE). 1) A decision tree allows one to model the interaction of multiple variables in great detail and to calculate the marginal cost, as well as the marginal cost-benefit ratio, of a preventive strategy. The cost of gastric cancer, the efficacy of H. pylori therapy in preventing cancer, and the cumulative probability of developing gastric cancer exert the largest influence on the marginal cost of cancer prevention. The high cost of future gastric cancer and a high efficacy of therapy make screening for H. pylori and its eradication the preferred strategy. 2) The present value is an economic method to adjust future costs or benefits to their current value using a discount rate and the length of time between now and a given time point in the future. It accounts for the depreciation of money and all material values over time. During childhood, the present value of future gastric cancer is very low. Vaccination of children to prevent gastric cancer would need to be very inexpensive to be practicable. Cancer prevention becomes a feasible option, only if the time period between the preventive measures and the occurrence of gastric cancer can be made relatively short. 3) The DEALE provides a means to calculate the increase in life expectancy that would occur, if death from a particular disease became preventable. Life expectancy of the general population is hardly affected by gastric cancer. For life expectancy to increase appreciably by vaccination or antibiotic therapy directed against H. pylori infection, these interventions would need to be focused towards a sub-population with an a priori high risk for gastric cancer. PMID:9701008

  12. Barriers Prevent Patient Access to Personalized Therapies Identified by Molecular Tumor Profiling of Gynecologic Malignancies

    PubMed Central

    Hillman, R. Tyler; Ward, Kristy; Saenz, Cheryl; McHale, Michael; Plaxe, Steven

    2015-01-01

    Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics. Results. Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%). Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13). A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%). Six patients sought insurance approval for a targeted therapy and two were declined (33%). One patient (4%) received a targeted therapy and this was discontinued due to tumor progression. Conclusions. There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials. PMID:26011384

  13. Cognitive Behavior Therapy for Suicide Prevention (CBT-SP): Treatment Model, Feasibility and Acceptability

    PubMed Central

    Stanley, Barbara; Brown, Gregory; Brent, David; Wells, Karen; Poling, Kim; Curry, John; Kennard, Betsy D.; Wagner, Ann; Cwik, Mary; Klomek, Anat Brunstein; Goldstein, Tina; Vitiello, Benedetto; Barnett, Shannon; Daniel, Stephanie; Hughes, Jennifer

    2009-01-01

    Objective To describe the elements of a manualized cognitive behavior psychotherapy for suicide prevention (CBT-SP) and to report its feasibility in preventing the recurrence of suicidal behavior in adolescents who have recently attempted suicide. Method CBT-SP was developed using a risk reduction, relapse prevention approach and theoretically grounded in principles of cognitive behavior therapy, dialectical behavioral therapy and targeted therapies for suicidal, depressed youth. CBT-SP consists of acute and continuation phases, each lasting about 12 sessions, and includes a chain analysis of the suicidal event, safety plan development, skill building, psychoeducation, family intervention, and relapse prevention. Results CBT-SP was administered to 110 depressed, recent suicide attempters aged 13–19 years (mean 15.8±1.6) across five academic sites. Twelve or more sessions were completed by 72.4% of the sample. Conclusions A specific intervention for adolescents at high risk for repeated suicide attempts has been developed and manualized, and further testing of its efficacy appears feasible. PMID:19730273

  14. The Mechanism of and Preventive Therapy for Stroke in Patients with Atrial Fibrillation

    PubMed Central

    Kim, Young-Hoon; Roh, Seung-Young

    2016-01-01

    Atrial fibrillation is a major cardiac cause of stroke, and a pathogenesis involving thrombus formation in patients with atrial fibrillation is well established. A strategy for rhythm control that involves catheter ablation and anticoagulation therapy is evolving. A strategy for rhythm control that restores and maintains sinus rhythm should reduce the risk of ischemic stroke that is associated with atrial fibrillation; however, this is yet to be proven in large-scale randomized controlled trials. This paper reviews the emerging role of rhythm control therapy for atrial fibrillation to prevent stroke. PMID:27283277

  15. Fixed-dose combination therapy for the prevention of cardiovascular disease

    PubMed Central

    de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark

    2014-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903

  16. FEMALE SEX AND DISCONTINUATION OF ISONIAZID DUE TO ADVERSE EFFECTS DURING THE TREATMENT OF LATENT TUBERCULOSIS

    PubMed Central

    Pettit, April C.; Bethel, James; Hirsch-Moverman, Yael; Colson, Paul W.; Sterling, Timothy R.

    2013-01-01

    SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects. PMID:23845828

  17. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders

    PubMed Central

    Kelesidis, Theodoros

    2012-01-01

    Several clinical trials and experimental studies strongly suggest a place for Saccharomyces boulardii as a biotherapeutic agent for the prevention and treatment of several gastrointestinal diseases. S. boulardii mediates responses resembling the protective effects of the normal healthy gut flora. The multiple mechanisms of action of S. boulardii and its properties may explain its efficacy and beneficial effects in acute and chronic gastrointestinal diseases that have been confirmed by clinical trials. Caution should be taken in patients with risk factors for adverse events. This review discusses the evidence for efficacy and safety of S. boulardii as a probiotic for the prevention and therapy of gastrointestinal disorders in humans. PMID:22423260

  18. Prevention of Distant Lung Metastasis After Photodynamic Therapy Application in a Breast Cancer Tumor Model.

    PubMed

    Longo, João Paulo Figueiró; Muehlmann, Luis Alexandre; Miranda-Vilela, Ana Luisa; Portilho, Flávia Arruda; de Souza, Ludmilla Regina; Silva, Jaqueline Rodrigues; Lacava, Zulmira Guerrero Marques; Bocca, Anamelia Lorenzetti; Chaves, Sacha Braun; Azevedo, Ricardo Bentes

    2016-04-01

    The objective of this study was to investigate the activity of photodynamic therapy mediated by aluminum-chlorophthalocyanine contained in a polymeric nanostructured carrier composed by methyl vinyl ether-co-maleic anhydride (PVM/MA) against local subcutaneous breast cancer tumors and its effects against distant metastasis in a mouse tumor model. In our results, we observed a decrease in breast cancer tumor growth, prevention of distant lung metastases, and a significant increased survival in mice treated with photodynamic therapy. In addition to these results, we observed that tumor-bearing mice without treatment developed a significant extension of liver hematopoiesis that was significantly reduced in mice treated with photodynamic therapy. We hypothesized and showed that this reduction in (1) metastasis and (2) liver hematopoiesis may be related to the systemic activity of immature hematopoietic cells, specifically the myeloid-derived suppressor cells, which were suppressed in mice treated with photodynamic therapy. These cells produce a tolerogenic tumor environment that protects tumor tissues from immunological surveillance. Therefore, we suggest that photodynamic therapy could be employed in combination with other conventional therapies; such as surgery and radiotherapy, to improve the overall survival of patients diagnosed with breast cancer, as observed in our experimental resuIts. PMID:27301195

  19. [Detoxication in opiate addiction and prevention of recurrence: administration of naltrexone and cognitive behavior therapy].

    PubMed

    Roozen, H G; Deden, A L; Kerkhof, A J; Vorsteveld, J P; van den Brink, W

    1997-12-01

    Rapid opiate withdrawal and relapse prevention in opiate addicts are made possible by naltrexone, clonidine and diazepam in combination with cognitive behavioural therapy according to the Community Reinforcement Approach. In an open pilot experiment 12 addicted patients achieved initial detoxification. At follow-up after a minimum of 6 months, 10 of these had not relapsed. Good results with this detoxification method could be booked by selecting highly motivated opiate addicts. PMID:9554156

  20. A concurrent comparison of isoniazid plus PAS with three regimens of isoniazid alone in the domiciliary treatment of pulmonary tuberculosis in South India

    PubMed Central

    1960-01-01

    Recent studies have shown that treatment of pulmonary tuberculosis with isoniazid plus p-aminosalicylic acid (PAS) at home is, in the majority of cases, as satisfactory as treatment with the same combination of drugs in sanatorium and does not appear to expose the patient's contacts to any special risk. Before mass domiciliary chemotherapy can be introduced, however, a question that has to be decided is what drug or drugs and what dosage and rhythm of administration will be most effective. This paper presents the results of a controlled comparison of four chemotherapeutic regimens: (a) 3.9-5.5 mg/kg body-weight of isoniazid plus 0.2-0.3 g/kg body-weight of PAS (sodium salt) daily in two doses (the standard combined chemotherapy); (b) 7.8-9.6 mg/kg body-weight of isoniazid alone daily in one dose; (c) 7.8-9.6 mg/kg body-weight of isoniazid alone daily in two doses; (d) 3.9-5.5 mg/kg body-weight of isoniazid alone daily in two doses. Isoniazid plus PAS proved to be the most satisfactory regimen; it was clinically effective and there were very few toxic manifestations. PMID:14447270

  1. Hypnotically facilitated exposure response prevention therapy for an OIF veteran with OCD.

    PubMed

    Proescher, Eric J

    2010-07-01

    The highly stressful conditions of a war zone may exacerbate or trigger a wide variety of symptoms including Obsessive Compulsive Disorder (OCD) once a service member returns home. Service members and new veterans of the Iraq and Afghanistan wars present to treatment with multiple psychosocial concerns and co-morbid psychiatric conditions. Evidence-based treatments including exposure based therapies are commonly recommended for use with returning veterans. Although studies support the efficacy of Exposure Response Prevention (ERP) therapy for treating OCD, eligibility for these studies limits participation to subjects who self-report a well-defined, circumscribed complaint. This approach is not typical of clinic clients who, more often than not, report multiple psychological issues. The following individual case study demonstrates how integrating hypnosis facilitated the cognitive-behavioral ERP therapy and treatment for a patient suffering from OCD. PMID:20718240

  2. Manualization of Occupational Therapy Interventions: Illustrations from the Pressure Ulcer Prevention Research Program

    PubMed Central

    Blanche, Erna Imperatore; Fogelberg, Donald; Diaz, Jesus; Carlson, Mike; Clark, Florence

    2011-01-01

    The manualization of a complex occupational therapy intervention is a crucial step in ensuring treatment fidelity for both clinical application and research purposes. Towards this latter end, intervention manuals are essential for assuring trustworthiness and replicability of randomized controlled trials (RCT’s) that aim to provide evidence of the effectiveness of occupational therapy. In this paper, literature on the process of intervention manualization is reviewed. The prescribed steps are then illustrated through our experience in implementing the University of Southern California/Rancho Los Amigos National Rehabilitation Center’s collaborative Pressure Ulcer Prevention Project (PUPP). In this research program, qualitative research provided the initial foundation for manualization of a multifaceted occupational therapy intervention designed to reduce incidence of medically serious pressure ulcers in people with SCI. PMID:22214116

  3. Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function.

    PubMed

    Takami, Taro; Yamasaki, Takahiro; Saeki, Issei; Matsumoto, Toshihiko; Suehiro, Yutaka; Sakaida, Isao

    2016-08-28

    Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis. PMID:27621572

  4. Targeting the TGF-β1 Pathway to Prevent Normal Tissue Injury After Cancer Therapy

    PubMed Central

    2010-01-01

    With >10,000,000 cancer survivors in the U.S. alone, the late effects of cancer treatment are a significant public health issue. Over the past 15 years, much work has been done that has led to an improvement in our understanding of the molecular mechanisms underlying the development of normal tissue injury after cancer therapy. In many cases, these injuries are characterized at the histologic level by loss of parenchymal cells, excessive fibrosis, and tissue atrophy. Among the many cytokines involved in this process, transforming growth factor (TGF)-β1 is thought to play a pivotal role. TGF-β1 has a multitude of functions, including both promoting the formation and inhibiting the breakdown of connective tissue. It also inhibits epithelial cell proliferation. TGF-β1 is overexpressed at sites of injury after radiation and chemotherapy. Thus, TGF-β1 represents a logical target for molecular therapies designed to prevent or reduce normal tissue injury after cancer therapy. Herein, the evidence supporting the critical role of TGF-ß1 in the development of normal tissue injury after cancer therapy is reviewed and the results of recent research aimed at preventing normal tissue injury by targeting the TGF-ß1 pathway are presented. PMID:20413640

  5. Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function

    PubMed Central

    Takami, Taro; Yamasaki, Takahiro; Saeki, Issei; Matsumoto, Toshihiko; Suehiro, Yutaka; Sakaida, Isao

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis. PMID:27621572

  6. Adjunctive Therapies to Cerclage for the Prevention of Preterm Birth: A Systematic Review

    PubMed Central

    DeFranco, Emily A.; Valent, Amy Miyoshi; Newman, Tondra; Regan, Jodi; Smith, Jessica; Muglia, Louis J.

    2013-01-01

    The aim of this paper is to provide a thorough summary of published studies that have assessed the efficacy of adjunctive therapies used in addition to cervical cerclage as a preventive measure for preterm birth. We limited our paper to patients treated with cerclage plus an additional prophylactic therapy compared to a reference group of women with cerclage alone. The specific adjunctive therapies included in this systematic review are progesterone, reinforcing or second cerclage placement, tocolytics, antibiotics, bedrest, and pessary. We searched PubMed and Cochrane databases without date criteria with restriction to English language and human studies and performed additional bibliographic review of selected articles and identified 305 total studies for review. Of those, only 12 studies compared the use of an adjunctive therapy with cerclage to a reference group of cerclage alone. None of the 12 were prospective randomized clinical trials. No comparative studies were identified addressing the issues of antibiotics, bedrest, or pessary as adjunctive treatments to cerclage. None of the 12 studies included in this paper demonstrated a clear benefit of any adjunctive therapy used in addition to cerclage over and above cerclage used alone; however, few studies with small numbers limited the strength of the conclusions. PMID:23606847

  7. Omeprazole maintenance therapy prevents recurrent ulcer bleeding after surgery for duodenal ulcer

    PubMed Central

    Demertzis, Konstantinos; Polymeros, Dimitrios; Emmanuel, Theodoros; Triantafyllou, Konstantinos; Tassios, Pericles; Ladas, Spiros D

    2006-01-01

    AIM: To evaluate the omeprazole maintenance therapy in patients with recurrent ulcer bleeding after surgery for duodenal ulcer. METHODS: We studied 15 consecutive patients with recurrent ulcer bleeding after surgery for duodenal ulcer. Omeprazole (20 mg/d) maintenance therapy was given after ulcer healing. In addition to clinical follow-up, ambulatory 24-h gastric pH assay was performed before and during omeprazole therapy in those patients and controls with previous duodenal ulcer surgery but no ulcer recurrence. RESULTS: All the 15 ulcers were healed after being treated with omeprazole (40 mg/d) for 2 mo. Eleven patients with two (1-9) episodes of recurrent ulcer bleeding completed the follow-up (43, 12-72 mo). None of them had a bleeding episode while on omeprazole. One patient discontinued the therapy and had recurrent bleeding. The median 24-h fraction time of gastric pH <4 in patients was 80, 46-95%, and was reduced to 32, 13-70% by omeprazole (P = 0.002). CONCLUSION: Long-term maintenance therapy with omeprazole (20 mg/day) is effective in preventing recurrent ulcer bleeding. PMID:16521197

  8. Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis

    PubMed Central

    Subbian, Selvakumar; Koo, Mi-Sun; Tsenova, Liana; Khetani, Vikram; Zeldis, Jerome B.; Fallows, Dorothy; Kaplan, Gilla

    2016-01-01

    The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment. PMID:27379099

  9. Pharmacologic Inhibition of Host Phosphodiesterase-4 Improves Isoniazid-Mediated Clearance of Mycobacterium tuberculosis.

    PubMed

    Subbian, Selvakumar; Koo, Mi-Sun; Tsenova, Liana; Khetani, Vikram; Zeldis, Jerome B; Fallows, Dorothy; Kaplan, Gilla

    2016-01-01

    The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment. Previously, we showed that the administration of CC-3052, a phosphodiesterase-4 inhibitor (PDE4i), reduced the host inflammatory response during Mycobacterium tuberculosis (Mtb) infection and improved the antimicrobial efficacy of isoniazid (INH) in both the mouse and rabbit models. In the present study, we evaluated the pharmacokinetics and explored the mechanism underlying the efficacy of a more potent PDE4i, CC-11050, as adjunct to INH treatment in a mouse model of pulmonary Mtb infection. Genome-wide lung transcriptome analysis confirmed the dampening of inflammation and associated network genes that we previously reported with CC-3052. Consistent with the reduction in inflammation, a significant improvement in Mtb control and pathology was observed in the lungs of mice treated with CC-11050 plus INH, compared to INH alone. This important confirmatory study will be used to help design upcoming human clinical trials with CC-11050 as an HDT for TB treatment. PMID:27379099

  10. Development of a three component complex to increase isoniazid efficacy against isoniazid resistant and nonresistant Mycobacterium tuberculosis.

    PubMed

    Manning, Thomas; Plummer, Sydney; Baker, Tess; Wylie, Greg; Clingenpeel, Amy C; Phillips, Dennis

    2015-10-15

    The bacterium responsible for causing tuberculosis has evolved resistance to antibiotics used to treat the disease, resulting in new multidrug resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug resistant M. tuberculosis (XDR-TB) strains. Analytical techniques (1)H and (13)C Nuclear Magnetic Resonance (NMR), Fourier Transform-Ion Cyclotron Resonance with Electrospray Ionization (FT-ICR/ESI), and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-TOF-MS) were used to study different aspects of the Cu(II)-polyethylene glycol (PEG-3350)-sucrose-isoniazid and Cu(II)-polyethylene glycol (PEG3350)-glucose-isoniazid complexes. The Cu(II) cation, sucrose or glucose, and the aggregate formed by PEG primarily serve as a composite drug delivery agent for the frontline antibiotic, however the improvement in MIC values produced with the CU-PEG-SUC-INH complex suggest an additional effect. Several Cu-PEG-SUC-INH complex variations were tested against INH resistant and nonresistant strains of M. tuberculosis. PMID:26341133

  11. Reagent Precoated Targets for Rapid In-Tissue Derivatization of the Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass Spectrometry

    PubMed Central

    Manier, M. Lisa; Reyzer, Michelle L.; Goh, Anne; Dartois, Veronique; Via, Laura E.; Barry, Clifton E.; Caprioli, Richard M.

    2012-01-01

    Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS. PMID:21953196

  12. Music therapy as an early intervention to prevent chronification of tinnitus

    PubMed Central

    Grapp, Miriam; Hutter, Elisabeth; Argstatter, Heike; Plinkert, Peter K; Bolay, Hans V

    2013-01-01

    In the present study a music therapeutic intervention according to the ‘Heidelberg Model’ was evaluated as a complementary treatment option for patients with acute tinnitus whom medical treatment only brought minimal or no improvement. The central question was if music therapy in an early phase of tinnitus was able to reduce tinnitus symptoms and to prevent them from becoming chronical. 23 patients with acute tinnitus (6-12 weeks) were included in this study and took part in our manualized short term music therapeutic treatment which lasted ten consecutive 50-minutes sessions of individualized therapy. Tinnitus severity and individual tinnitus related distress were assessed by the Tinnitus Beeinträchtigungs-Fragebogen (i.e. Tinnitus Impairment Questionnaire, TBF-12) at baseline, start of treatment, and end of treatment. Score changes in TBF-12 from start to end of the treatment showed significant improvements in tinnitus impairment. This indicates that this music therapy approach applied in an initial stage of tinnitus can make an important contribution towards preventing tinnitus from becoming a chronic condition. PMID:23936599

  13. Music therapy as an early intervention to prevent chronification of tinnitus.

    PubMed

    Grapp, Miriam; Hutter, Elisabeth; Argstatter, Heike; Plinkert, Peter K; Bolay, Hans V

    2013-01-01

    In the present study a music therapeutic intervention according to the 'Heidelberg Model' was evaluated as a complementary treatment option for patients with acute tinnitus whom medical treatment only brought minimal or no improvement. The central question was if music therapy in an early phase of tinnitus was able to reduce tinnitus symptoms and to prevent them from becoming chronical. 23 patients with acute tinnitus (6-12 weeks) were included in this study and took part in our manualized short term music therapeutic treatment which lasted ten consecutive 50-minutes sessions of individualized therapy. Tinnitus severity and individual tinnitus related distress were assessed by the Tinnitus Beeinträchtigungs-Fragebogen (i.e. Tinnitus Impairment Questionnaire, TBF-12) at baseline, start of treatment, and end of treatment. Score changes in TBF-12 from start to end of the treatment showed significant improvements in tinnitus impairment. This indicates that this music therapy approach applied in an initial stage of tinnitus can make an important contribution towards preventing tinnitus from becoming a chronic condition. PMID:23936599

  14. Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats.

    PubMed

    Dominguez, James M; Yorek, Mark A; Grant, Maria B

    2015-02-01

    We previously showed that peripheral neuropathy of the bone marrow was associated with loss of circadian rhythmicity of stem/progenitor cell release into the circulation. Bone marrow neuropathy results in dramatic changes in hematopoiesis that lead to microvascular complications, inflammation, and reduced endothelial repair. This series of events represents early pathogenesis before development of diabetic retinopathy. In this study we characterized early alterations within the bone marrow of streptozotocin (STZ)-induced diabetic rats following treatments that prevent experimental peripheral neuropathy. We asked whether bone marrow neuropathy and the associated bone marrow pathology were reversed with treatments that prevent peripheral neuropathy. Three strategies were tested: inhibition of neutral endopeptidase, inhibition of aldose reductase plus lipoic acid supplementation, and insulin therapy with antioxidants. All strategies prevented loss of nerve conduction velocity resulting from STZ-induced diabetes and corrected the STZ-induced diabetes-associated increase of immunoreactivity of neuropeptide Y, tyrosine hydroxylase, and somatostatin. The treatments also reduced concentrations of interleukin-1β, granulocyte colony-stimulating factor, and matrix metalloproteinase 2 in STZ-induced diabetic bone marrow supernatant and decreased the expression of NADPH oxidase 2, nitric oxide synthase 2, and nuclear factor-κB1 mRNA in bone marrow progenitor cells. These therapies represent novel approaches to attenuate the diabetic phenotype within the bone marrow and may constitute an important therapeutic strategy for diabetic microvascular complications. PMID:25204979

  15. Determination of rifampicin and its main metabolite in plasma and urine in presence of pyrazinamide and isoniazid by HPLC method.

    PubMed

    Panchagnula, R; Sood, A; Sharda, N; Kaur, K; Kaul, C L

    1999-01-01

    A reversed phase HPLC method is described for the simultaneous estimation of rifampicin and its major metabolite desacetyl rifampicin, in the presence of isoniazid and pyrazinamide, in human plasma and urine. The assay involves simple liquid extraction of drug, metabolite and internal standard (rifapentine) from biological specimens and their subsequent separation on a C18 reversed phase column and single wavelength UV detection. In plasma as well as in urine samples, all the three compounds of interest eluted within 17 min. Using methanol-sodium phosphate buffer (pH 5.2; 0.01 M) (65:35, v/v) as mobile phase under isocratic conditions, it was established that isoniazid, pyrazinamide and ascorbic acid (added to prevent oxidative degradation of analytes) did not interfere with the analyte peaks. Recoveries (extraction efficiency) for drug were greater than 90% in both plasma and urine, whereas for metabolite the values were found to be 79 and 86% in plasma and urine, respectively. The plasma and urine methods were precise (total coefficient of variation ranged from 5 to 23%) and accurate (-7 to 5% of the nominal values) for both the analytes. Individual variance components, their estimates and their contribution to the total variance were also determined. Using the same method, unknown samples supplied by WHO were assayed and good correlations were obtained between the found and intended values. The method developed proved to be suitable for simultaneous estimation of rifampicin and desacetyl rifampicin in plasma and urine samples. PMID:9925337

  16. Impact of the Increased Recommended Dosage of Isoniazid on Pyridoxine Levels in Children and Adolescents.

    PubMed

    Rodà, Diana; Rozas, Librada; Fortuny, Clàudia; Sierra, Cristina; Noguera-Julian, Antoni

    2016-05-01

    Isoniazid exposure causes dose-dependent pyridoxine deficiency. Recently, the recommended dosage of isoniazid in children was increased from 5 (4-6) to 10 (10-15) mg/kg/day. We aimed to analyze longitudinally pyridoxine levels in a cohort of previously healthy children and adolescents treated with isoniazid. Mild symptom-free pyridoxine deficiency was observed in 4/75 (5.6%) and 3/40 (7.5%) at baseline and at 3-month follow-up, respectively. Classical age-related risk factors identified patients at risk of pyridoxine deficiency. Our preliminary results support current recommendations regarding pyridoxine supplementation in healthy children. PMID:26862674

  17. Immunomodulatory Gene Therapy Prevents Antibody Formation and Lethal Hypersensitivity Reactions in Murine Pompe Disease

    PubMed Central

    Sun, Baodong; Kulis, Michael D; Young, Sarah P; Hobeika, Amy C; Li, Songtao; Bird, Andrew; Zhang, Haoyue; Li, Yifan; Clay, Timothy M; Burks, Wesley; Kishnani, Priya S; Koeberl, Dwight D

    2009-01-01

    Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was reduced by high-titer antibody responses. Immunomodulatory gene therapy with a low dose adeno-associated virus (AAV) vector (2 × 1010 particles) containing a liver-specific regulatory cassette significantly lowered immunoglobin G (IgG), IgG1, and IgE antibodies to GAA in Pompe disease mice, when compared with mock-treated mice (P < 0.05). AAV-LSPhGAApA had the same effect on GAA-antibody production whether it was given prior to, following, or simultaneously with the initial GAA injection. Mice given AAV-LSPhGAApA had significantly less decrease in body temperature (P < 0.001) and lower anaphylactic scores (P < 0.01) following the GAA challenge. Mouse mast cell protease-1 (MMCP-1) followed the pattern associated with hypersensitivity reactions (P < 0.05). Regulatory T cells (Treg) were demonstrated to play a role in the tolerance induced by gene therapy as depletion of Treg led to an increase in GAA-specific IgG (P < 0.001). Treg depleted mice were challenged with GAA and had significantly stronger allergic reactions than mice given gene therapy without subsequent Treg depletion (temperature: P < 0.01; symptoms: P < 0.05). Ubiquitous GAA expression failed to prevent antibody formation. Thus, immunomodulatory gene therapy could provide adjunctive therapy in lysosomal storage disorders treated by enzyme replacement. PMID:19690517

  18. Immunomodulatory gene therapy prevents antibody formation and lethal hypersensitivity reactions in murine pompe disease.

    PubMed

    Sun, Baodong; Kulis, Michael D; Young, Sarah P; Hobeika, Amy C; Li, Songtao; Bird, Andrew; Zhang, Haoyue; Li, Yifan; Clay, Timothy M; Burks, Wesley; Kishnani, Priya S; Koeberl, Dwight D

    2010-02-01

    Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was reduced by high-titer antibody responses. Immunomodulatory gene therapy with a low dose adeno-associated virus (AAV) vector (2 x 10(10) particles) containing a liver-specific regulatory cassette significantly lowered immunoglobin G (IgG), IgG1, and IgE antibodies to GAA in Pompe disease mice, when compared with mock-treated mice (P < 0.05). AAV-LSPhGAApA had the same effect on GAA-antibody production whether it was given prior to, following, or simultaneously with the initial GAA injection. Mice given AAV-LSPhGAApA had significantly less decrease in body temperature (P < 0.001) and lower anaphylactic scores (P < 0.01) following the GAA challenge. Mouse mast cell protease-1 (MMCP-1) followed the pattern associated with hypersensitivity reactions (P < 0.05). Regulatory T cells (Treg) were demonstrated to play a role in the tolerance induced by gene therapy as depletion of Treg led to an increase in GAA-specific IgG (P < 0.001). Treg depleted mice were challenged with GAA and had significantly stronger allergic reactions than mice given gene therapy without subsequent Treg depletion (temperature: P < 0.01; symptoms: P < 0.05). Ubiquitous GAA expression failed to prevent antibody formation. Thus, immunomodulatory gene therapy could provide adjunctive therapy in lysosomal storage disorders treated by enzyme replacement. PMID:19690517

  19. Familial Breast Cancer – Targeted Therapy in Secondary and Tertiary Prevention

    PubMed Central

    Kast, Karin; Rhiem, Kerstin

    2015-01-01

    Summary The introduction of an increasing number of individualized molecular targeted therapies into clinical routine mirrors their importance in modern cancer prevention and treatment. Well-known examples for targeted agents are the monoclonal antibody trastuzumab and the selective estrogen receptor modulator tamoxifen. The identification of an unaltered gene in tumor tissue in colon cancer (KRAS) is a predictor for the patient's response to targeted therapy with a monoclonal antibody (cetuximab). Targeted therapy for hereditary breast and ovarian cancer has become a reality with the approval of olaparib for platin-sensitive late relapsed BRCA-associated ovarian cancer in December 2014. This manuscript reviews the status quo of poly-ADP-ribose polymerase inhibitors (PARPi) in the therapy of breast and ovarian cancer as well as the struggle for carboplatin as a potential standard of care for triple-negative and, in particular, BRCA-associated breast cancer. Details of the mechanism of action with information on tumor development are provided, and an outlook for further relevant research is given. The efficacy of agents against molecular targets together with the identification of an increasing number of cancer-associated genes will open the floodgates to a new era of treatment decision-making based on molecular tumor profiles. Current clinical trials involving patients with BRCA-associated cancer explore the efficacy of the molecular targeted therapeutics platinum and PARPi. PMID:25960722

  20. The Development of Drug-free Therapy for Prevention of Dental Caries

    PubMed Central

    Chen, Fu; Jia, Zhenshan; Rice, Kelly C.; Reinhardt, Richard A.; Bayles, Kenneth W.; Wang, Dong

    2015-01-01

    Purpose The purpose of this study was to develop a novel, drug-free therapy that can reduce the over-accumulation of cariogenic bacteria on dental surfaces. Method We designed and synthesized a polyethylene glycol (PEG)-based hydrophilic copolymer functionalized with a pyrophosphate (PPi) tooth-binding anchor using “click” chemistry. The polymer was then evaluated for hydroxyapatite (HA) binding kinetics and capability of reducing bacteria adhesion to artificial tooth surface. Results The PPi-PEG copolymer can effectively inhibit salivary protein adsorption after rapid binding to an artificial tooth surface. As a result, thein vitro S. mutans adhesion study showed that the PPi-PEG copolymer can inhibit saliva protein-promotedS. mutans adhesion through the creation of a neutral, hydrophilic layer on the artificial tooth surface. Conclusion The results suggested the potential application of a PPi-PEG copolymer as a drug-free alternative to current antimicrobial therapy for caries prevention. PMID:24831311

  1. Efficacy and safety of combination therapy for preventing bone damage in rheumatoid arthritis.

    PubMed

    Iannone, Florenzo; Lopalco, Giuseppe; Cantarini, Luca; Galeazzi, Mauro; Lapadula, Giovanni

    2016-01-01

    The main outcomes of the therapies for rheumatoid arthritis (RA) must be preventing, or at least lessening, the development of structural damage. Biological disease-modifying anti-rheumatic drugs (bDMARDs), targeting tumour necrosis factor-α (TNF-α) or other key steps (IL-1, IL-6, T cells, B cells) in the pathogenesis of RA, have given clues to be effective and safe as treatments for RA, being capable of improving disease activity, ameliorating functional ability and halting joint damage. A large body of evidence, stemming from randomized clinical trials, observational studies, and registries, has shown that the beneficial effects of the bDMARDs become optimal when combined with synthetic (s)-DMARDs, mainly methotrexate (MTX). Despite combination therapy is advocated by the international guidelines for the management of RA, data from the daily standard of care indicate that almost one third of RA patients are treated with bDMARDs as monotherapy. Many reasons may be taken into account to explain this gap from official recommendations, among which the fact that in real-life settings, the assessment of clinical outcomes is exclusively based on clinical indices, disregarding the evolution of bone damage. Furthermore, some bDMARDs have been launched in the market with the official approval to be used as monotherapy. But even for the latter, there is no conclusive proof that monotherapy regimen is comparable to co-therapy with MTX in preventing articular damage. In conclusion, the most recent published data show that combination therapy with bDMARDs and MTX represents the best therapeutic option for the treatment of RA since it can stop or at least slow the progression of disabling structural damage. PMID:26581205

  2. Preventing stem cell transplantation-associated viral infections using T-cell therapy

    PubMed Central

    Tzannou, Ifigeneia; Leen, Ann M

    2015-01-01

    Hematopoietic stem cell transplantation is the treatment of choice for many hematologic malignancies and genetic diseases. However, viral infections continue to account for substantial post-transplant morbidity and mortality. While antiviral drugs are available against some viruses, they are associated with significant side effects and are frequently ineffective. This review focuses on the immunotherapeutic strategies that have been used to prevent and treat infections over the past 20 years and outlines different refinements that have been introduced with the goal of moving this therapy beyond specialized academic centers. PMID:26250410

  3. Non-thermal plasmas: novel preventive and curative therapy against melanomas?

    PubMed

    Gesbert, Franck; Larue, Lionel

    2014-10-01

    Malignant melanoma is a very aggressive cancer with a very poor short-term prognosis once metastatic. For years, there was no efficient adjuvant therapy after surgery. Chemotherapy and immunotherapy provided hope, but not victory. Further efforts are therefore required, to find new ways to cure this disease. Physics has, once again, opened up new possibilities for treatment, through the use of non-equilibrium atmospheric pressure plasma (NEAPP). The curative potential of this technique was initially assessed on cancer cells, among which melanoma. In a recent issue, Yajima et al. use NEAPP on benign nevi, as a preventive treatment. PMID:24980188

  4. Laser-triggered intraocular implant to induce photodynamic therapy for posterior capsule opacification prevention.

    PubMed

    Zhang, Zhaoguo; Huang, Wenyong; Lei, Ming; He, Yuanfeng; Yan, Mina; Zhang, Xuefei; Zhao, Chunshun

    2016-02-10

    Posterior capsule opacification (PCO) is one of the main reasons for loss of vision again after cataract surgery. In this study, intraocular lenses were modified with indocyanine green (ICG) and sealed up with PLGA to form long-term intraocular implants (ICG-IOL). When triggered by laser, ICG-IOL would induce photodynamic therapy (PDT). In-vitro cell viability assay and scratch wound healing assay demonstrated that ICG-IOL could effectively inhibit HLEpiC proliferation and migration without causing damage to the cells far away from it. Laser attenuation test indicated that ICG-IOL could be applied in vivo. In-vivo pharmacodynamics and safety study showed that ICG-IOL could significantly prevent the occurrence of PCO and was safe for intraocular normal tissue. All these results suggested that ICG-IOL would be a very promising candidate for PCO prevention. PMID:26456263

  5. Oral silicon supplementation: an effective therapy for preventing oral aluminum absorption and retention in mammals.

    PubMed

    Domingo, José L; Gómez, Mercedes; Colomina, M Teresa

    2011-01-01

    Silicon is an essential element for some lower forms of life. However, it is not generally considered an essential nutrient for mammals and the mechanisms underlying its potential essentiality remain partially unknown. In recent years, a possible association between the aluminum and silicon levels in drinking water and Alzheimer's disease (AD) has been suggested. It has been reported that silicon might have a protective effect for limiting oral aluminum absorption. This review is focused primarily on the potential role of silicon in preventing oral aluminum absorption and retention in mammals. The results of a number of studies suggest that dietary silicon supplementation could be of therapeutic value for preventing chronic aluminum accumulation in the brain, and hence, be a potential therapy for AD. However, it must be noted that controversy remains about whether aluminum accumulation in the brain is a cause or a consequence of AD. It is suggested that further investigation of this issue is warranted. PMID:21198634

  6. Acetylator phenotyping of tuberculosis patients using matrix isoniazid or sulphadimidine and its prognostic significance for treatment with several intermittent isoniazid-containing regimens.

    PubMed Central

    Ellard, G A; Gammon, P T

    1977-01-01

    1. The acetylator phenotype of over 600 pulmonary tuberculosis patients treated with intermittent isoniazid-containing regimens in two controlled clinical trials was determined using either sulphadimidine or a slow-release isoniazid formulation. 2. Both methods unequivocally classified over 99% of the patients as being either slow or rapid acetylators. 3. Rapid and slow acetylation did not differ in their ability of hydrolyse acetylisoniazid to isonicotonic acid plus monoacetylhydrazine, or to conjugate isonicotinic acid with glycine. 4. Rapid acetylators acetylated the monoacetylhydrazine liberated in vivo more rapidly than slow acetylators, demonstrating that this compound is also polymorphologically acetylated in man. 5. The acetylator phenotype of the patients was without prognostic significance when they were treated on a twice-weekly basis with isoniazid plus streptomycin plus pyraziniamide, or with isoniazid plus rifampicin. However, when patients were treated once every week for 12 months with isoniazid plus rifampicin, 5% of the rapid acetylators had an unsatisfactory response as contrasted to the complete success of the treatment in the slow acetylators. PMID:843424

  7. Biological Evaluation of Isoniazid Derivatives as an Anticancer Class

    PubMed Central

    Rodrigues, Felipe A. R.; Oliveira, Augusto C. A.; Cavalcanti, Bruno C.; Pessoa, Claudia; Pinheiro, Alessandra C.; de Souza, Marcus V. N.

    2014-01-01

    A series of thirty-two isoniazid derivatives have been evaluated for their activity against four human cancer cell lines with potent cytotoxicity (IC50 ranging from 0.61 to 3.36 μg/mL). The structure-activity relationship (SAR) analysis indicated the number, the positions, and the types of substituents attached to the aromatic ring as being critical factors for the biological activity. Briefly, we observed that the presence of a hydroxyl group on the benzene ring plays an important role in the anticancer activity of this series, especially when it is located in ortho-position. Among the thirty-two compounds, three displayed good cytotoxic activity when compared to the reference drug doxorubicin and are thus being considered leading compounds of this new class. PMID:24634839

  8. Mechanism of isoniazid-induced hepatotoxicity: then and now.

    PubMed

    Metushi, Imir; Uetrecht, Jack; Phillips, Elizabeth

    2016-06-01

    Isoniazid (INH) remains a mainstay for the treatment of tuberculosis despite the fact that it can cause liver failure. Previous mechanistic hypotheses have classified this type of drug-induced liver injury (DILI) as 'metabolic idiosyncrasy' which was thought not to involve an immune response and was mainly due to the bioactivation of the acetylhydrazine metabolite. However, more recent studies support an alternative hypothesis, specifically, that INH itself is directly bioactivated to a reactive metabolite, which in some patients leads to an immune response and liver injury. Furthermore, there appear to be two phenotypes of INH-induced liver injury. Most cases involve mild liver injury, which resolves with immune tolerance, while other cases appear to have a more severe phenotype that is associated with the production of anti-drug/anti-CYP P450 antibodies and can progress to liver failure. PMID:26773235

  9. [Primary and secondary prevention of cardiovascular events through hormone replacement therapy (HRT)].

    PubMed

    Pilz, Heidemarie

    2005-09-01

    A recently (2002) published, randomised, double blind placebo controlled trial of hormone replace ment therapy (HRT), the Women's Health Initiative (WHI), is not consistent with the decrease in cardiovascular disease under CEE/HPA seen in observational primary prevention studies like the Nurses' Health Study. Baseline characteristics of participants like age, body mass index, years since menopause and preexistent cardiovascular diseases may be responsible for the lack of benefit seen in this trial. Clinical outcome data of HRT from randomised trials in secondary prevention of cardiovasular diseases are limited. The first prospective, randomised placebo controlled trial, the Heart and Estrogen/Progestin Replacement Study (HERS) in secondary prevention did not show any difference in CHD events between treatment groups and placebo during a follow up of 4.1 years. However, an increased risk of CHD was seen especially during the first year on HRT, subsequent years showed a decrease in event rate compared with never-users. One explanation for this lack of benefit may be a bi-directional effect of estrogen - early risk and late benefit - especially in an elderly study population with established atherosclerotic lesions. In postmenopausal women, estrogen replacement therapy affects LDL- and HDL-cholesterol levels favorably, causes vasodilatation by activating NOS, inhibits platelet aggregation and proinflammatory cell adhesion on endothelial cells of vascular wall. Estrogen can affect the cardiovascular system adversely by increasing triglycerid levels, CPR and proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha). Alternatives to HRT like phytoestrogens act via estrogen alpha and beta receptor modulation. Phytoestrogens may lower LDL-cholesterol levels without increasing triglyceride levels, they have shown antioxidannt properties as well as favorable effects on vascular reactivity. The importance of HRT and phytoestrogens in primary and secondary

  10. Antiretroviral Therapy in Prevention of HIV and TB: Update on Current Research Efforts

    PubMed Central

    Granich, Reuben; Gupta, Somya; Sutha, Amitabh B; Smyth, Caoimhe; Hoos, David; Vitoria, Marco; Simao, Mariangela; Hankins, Catherine; Schwartlander, Bernard; Ridzon, Renee; Bazin, Brigitte; Williams, Brian; Lo, Ying-Ru; McClure, Craig; Montaner, Julio; Hirnschall, Gottfried

    2011-01-01

    There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies. PMID:21999779

  11. A Pilot Study of Emollient Therapy for the Primary Prevention of Atopic Dermatitis

    PubMed Central

    Simpson, Eric L.; Berry, Trista M.; Brown, Peter A.; Hanifin, Jon M.

    2011-01-01

    Background Prevention strategies in atopic dermatitis (AD) using allergen avoidance have not been consistently effective. New research reveals the importance of the skin barrier in the development of AD and possibly food allergy and asthma. Correcting skin barrier defects from birth may prevent AD onset or moderate disease severity. Objective We sought to determine the feasibility of skin barrier protection as a novel AD prevention strategy. Methods We enrolled 22 neonates at high risk for developing AD in a feasibility pilot study using emollient therapy from birth. Results No intervention-related adverse events occurred in our cohort followed up for a mean time of 547 days. Of the 20 subjects who remained in the study, 3 (15.0%) developed AD, suggesting a protective effect when compared with historical controls. Skin barrier measurements remained within ranges seen in normal-appearing skin. Limitations No conclusions regarding efficacy can be made without a control group. Conclusions Skin barrier repair from birth represents a novel and feasible approach to AD prevention. Further studies are warranted to determine the efficacy of this approach. PMID:20692725

  12. Physical Therapy for Metabolic Syndrome Prevention in Workers: Novel Role of Physical Therapist.

    PubMed

    Satoh, Tomonori; Nemoto, Yuki; Utumi, Takako; Munakata, Masanori

    2016-01-01

    In Japan, physical therapists have usually been involved in physical therapy for patients with functional disorders associated with cerebrovascular or orthopedic diseases in hospitals. With the aging of Japanese society, the number of diseased people will progressively increase; thus, it is important to pay much more attention to disease prevention. In this regard, physical therapists are expected to play a new role in the field of preventive medicine. Metabolic syndrome or central obesity with multiple cardiometabolic risks is associated with a high risk of type 2 diabetes or cardiovascular diseases and is now a central target for early detection and intervention for disease prevention. The incidence of metabolic syndrome increases with age, and men showed a higher incidence of metabolic syndrome than women in all generations. We have been involved in the guidance of workers with metabolic syndrome for a long time, and we conducted a multicenter study to establish effective guidance for these worker. In this paper, we will use our evidence to discuss the role of physical therapists in providing guidance for preventing metabolic syndrome. We are now conducting worksite supporting exercise intervention for workers who were resistant to conventional lifestyle guidance. In addition, the unique role of physical therapists in this new trial will be introduced. PMID:27246150

  13. Retrospective evaluation of cotrimoxazole use as preventive therapy in people living with HIV/AIDS in Boru Meda Hospital

    PubMed Central

    2014-01-01

    Background Drug use evaluation is a performance improvement method that focuses on evaluating and improving drug use process to achieve optimal patient outcomes. Drug use evaluation helps in identifying, preventing or resolving actual and potential drug related problems. The objective of the study was to evaluate the use of cotrimoxazole as preventive therapy in people living with HIV/AIDS in Boru Meda Hospital, Northeast Ethiopia. Methods A retrospective drug use evaluation was conducted on patients’ medical history records based on a validated drug use evaluation criteria according to the national guideline. Medical history records of 248 patients were selected using systematic sampling method. Results The result showed that 49.6% of the patients were at WHO clinical stage III at the start of cotrimoxazole preventive therapy. In this study, the use of cotrimoxazole preventive therapy was consistent with the guideline in the rationale for indication (97.98%), dose (96.77%), and its use despite the presence of contraindications (91.93%). Problems regarding drug-drug interaction were identified in 49.59% of cases, and 20.97% of patients discontinued cotrimoxazole preventive therapy due to different reasons. Conclusions In most patients cotrimoxazole preventive therapy was consistent with the national guideline regarding the rationale for indication, dose, discontinuation and its use in the presence of contraindications. PMID:24507658

  14. Preventing cerebral oedema in acute liver failure: the case for quadruple-H therapy.

    PubMed

    Warrillow, S J; Bellomo, R

    2014-01-01

    Severe cerebral oedema is a life-threatening complication of acute liver failure. Hyperammonaemia and cerebral hyperaemia are major contributing factors. A multimodal approach, which incorporates hyperventilation, haemodiafiltration, hypernatraemia and hypothermia (quadruple-H therapy), may prevent or attenuate severe cerebral oedema. This approach is readily administered by critical care clinicians and is likely to be more effective than the use of single therapies. Targeting of PaCO2 in the mild hyperventilation range, as seen in acute liver failure patients before intubation, aims to minimise hyperaemic cerebral oedema. Haemodiafiltration aims to achieve the rapid control of elevated blood ammonia concentrations by its removal and to reduce production via the lowering of core temperature. The administration of concentrated saline increases serum tonicity and further reduces cerebral swelling. In addition, the pathologically increased cerebral blood-flow is further attenuated by therapeutic hypothermia. The combination of all four treatments in a multimodal approach may be a safe and effective means of attenuating or treating the cerebral oedema of acute liver failure and preventing death from neurological complications. PMID:24471667

  15. Secondary prevention after PCI: the cost-effectiveness of statin therapy in the Netherlands

    PubMed Central

    Chaplin, S.; Scuffham, P.A.; Alon, M.; van den Boom, G.

    2004-01-01

    Background Little is known about the cost-effectiveness of secondary prevention after percutaneous coronary intervention (PCI). The aim of this study was to estimate the cost-effectiveness of statin therapy. Methods A cost-effectiveness analysis was performed using data from the Lescol Intervention Prevention Study (LIPS). In the LIPS trial, patients with normal-to-moderate hypercholesterolaemia who had undergone a first PCI were randomised to receive either fluvastatin 40 mg twice-daily plus dietary counselling or dietary counselling alone. A Markov model was used to estimate the incremental costs per quality-adjusted life year (QALY) and life year gained (LYG). Costs were based on prices and reimbursed charges, utility data were drawn from literature. Monte Carlo simulations and multivariate analysis were used to assess uncertainty. Results Routine statin treatment costs an additional €734 (SD €686) per patient over ten years compared with controls. It resulted in an additional 0.078 (0.047) QALYs or 0.082 (0.041) LYG. The incremental costs per QALY and LYG were €9312 (€14,648) and €8954 (€16,617) respectively. Anticipating a willingness to pay of €20,000 per QALY, there is a 75.1% chance that fluvastatin treatment is cost-effective. Conclusion Statin therapy with fluvastatin is economically efficient with regard to reducing heart disease in the Netherlands when given routinely to all patients following PCI. PMID:25696357

  16. Primary prevention of skin dysplasia in renal transplant recipients with photodynamic therapy: a randomized controlled trial.

    PubMed

    Togsverd-Bo, K; Omland, S H; Wulf, H C; Sørensen, S S; Haedersdal, M

    2015-11-01

    Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were randomized to split-side PDT of the face, forearm and hand, the contralateral side serving as untreated control. Patients received PDT on inclusion and at 6-monthly intervals for 5 years. Blinded evaluation was performed at each visit. We found that prophylactic PDT significantly delayed onset of AK compared with untreated skin, p = 0.020. At 3-year follow-up, we observed AK in 63% of patients in untreated skin areas compared with 28% of patients in PDT-treated skin, with a total number of cumulated AKs in untreated skin (n = 43) compared with PDT-treated skin (n = 8), p = 0.005. These preliminary data indicate a novel approach to early prevention of skin dysplasia that may reduce morbidity from multiple AKs and SCCs in OTR. PMID:26018207

  17. Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

    PubMed

    Barton, Matthias; Husmann, Marc; Meyer, Matthias R

    2016-05-01

    Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease. PMID:27118295

  18. Impact of nanotechnology on the delivery of natural products for cancer prevention and therapy.

    PubMed

    Siddiqui, Imtiaz A; Sanna, Vanna

    2016-06-01

    Chemoprevention of human cancer by dietary products is a practical approach of cancer control, especially when chemoprevention is involved during the early stages of the carcinogenesis process. Research over the last few decades has clearly demonstrated the efficacy of dietary products for chemoprevention in cell culture and preclinical animal model systems. However, these in vitro and in vivo effects have not been able to be translated to bedside for clinical use. Among many reasons, inefficient systemic delivery and bioavailability of promising chemopreventive agents are considered to significantly contribute to such a disconnection. Since its advent in the field of cancer, nanotechnology has provided researchers with expertise to explore new avenues for diagnosis, prevention, and therapy of the disease. In a similar trait, we introduced a novel concept in which nanotechnology was utilized for enhancing the outcome of chemoprevention (Cancer Res. 2009; 69:1712-1716). This idea, which we termed as 'nanochemoprevention', was exploited by several laboratories and has now become an advancing field in chemoprevention research. This review summarizes some of these applications of nanotechnology in medicine, particularly focused on controlled and sustained release of bioactive compounds with emphasis on current and future utilization of nanochemoprevention for prevention and therapy of cancer. PMID:26935239

  19. Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer

    PubMed Central

    Saylor, Philip J

    2014-01-01

    Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-κ-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed. PMID:24435057

  20. Protective Effects of Metallothionein on Isoniazid and Rifampicin-Induced Hepatotoxicity in Mice

    PubMed Central

    Xu, Peiyu; Wang, Yimei; Zhao, Jun; Jia, Li; Fu, Ze; Jing, Li; Liu, Gang; Peng, Shuangqing

    2013-01-01

    Isoniazid (INH) and Rifampicin (RFP) are widely used in the world for the treatment of tuberculosis, but the hepatotoxicity is a major concern during clinical therapy. Previous studies showed that these drugs induced oxidative stress in liver, and several antioxidants abated this effect. Metallothionein (MT), a member of cysteine-rich protein, has been proposed as a potent antioxidant. This study attempts to determine whether endogenous expression of MT protects against INH and RFP-induced hepatic oxidative stress in mice. Wild type (MT+/+) and MT-null (MT−/−) mice were treated intragastrically with INH (150 mg/kg), RFP (300 mg/kg), or the combination (150 mg/kg INH +300 mg/kg RFP) for 21 days. The results showed that MT−/− mice were more sensitive than MT+/+ mice to INH and RFP-induced hepatic injuries as evidenced by hepatic histopathological alterations, increased serum AST levels and liver index, and hepatic oxidative stress as evidenced by the increase of MDA production and the change of liver antioxidant status. Furthermore, INH increased the protein expression of hepatic CYP2E1 and INH/RFP (alone or in combination) decreased the expression of hepatic CYP1A2. These findings clearly demonstrate that basal MT provides protection against INH and RFP-induced toxicity in hepatocytes. The CYP2E1 and CYP1A2 were involved in the pathogenesis of INH and RFP-induced hepatotoxicity. PMID:23967274

  1. Mathematical modeling and systems pharmacology of tuberculosis: Isoniazid as a case study.

    PubMed

    Lalande, Laure; Bourguignon, Laurent; Maire, Pascal; Goutelle, Sylvain

    2016-06-21

    Tuberculosis (TB) treatment needs to be optimized as it is currently long and associated with increasing drug resistance. The antimycobacterial effect of isoniazid (INH) is characterized by a biphasic kill curve, whose causes are still debated. In this work, we developed a complete mathematical model describing the time-course of TB infection and its treatment by INH in human lung. This model was based on a pharmacokinetic model, a pharmacodynamic model and a pathophysiological model. It was used to simulate the antibacterial effect of INH during the first days of therapy. This full model adequately reproduced some qualitative and quantitative properties of the early bactericidal activity of INH observed in TB patients. The kill curves simulated with the model reproduced the biphasic killing effect of INH and the predicted declines in extracellular bacteria were comparable to clinical data. A sensitivity analysis provided interesting insights regarding the biphasic kill curve. The first phase appeared to be essentially driven by the drug effect. In the second phase, while drug pharmacology was the major determinant of the antibacterial effect, a slight influence of the dynamics of infected macrophages was also observed. This work permits to formulate hypotheses for optimizing the efficacy of TB drug candidates and confirms the utility of mathematical modeling to generate new assumptions for TB research. PMID:27059890

  2. Novel perspectives in the tuberculosis treatment: Administration of isoniazid through the skin.

    PubMed

    Caon, Thiago; Campos, Carlos Eduardo Maduro; Simões, Cláudia Maria Oliveira; Silva, Marcos Antônio Segatto

    2015-10-15

    Despite its high efficacy in anti-tuberculosis therapy, the oral administration of isoniazid (INH) may lead to poor patient compliance due to hepatotoxicity events. In this context, the transdermal administration of INH was evaluated, for the first time, since this route avoids hepatic first pass effect. INH was applied to porcine skin in Franz diffusion chambers alone and with 5% menthol, limonene or Transcutol(®). Infrared and DSC analyses were selected for mechanistic studies. The transdermal absorption of INH was sufficient to ensure a systemic therapeutic effect. Menthol was not able to improve the absorption of INH, but it increased the drug accumulation in skin compared to the control (1.4-fold). Transcutol(®) reduced permeation flux of INH (2.2-fold) and also increased the amount of drug retained in skin (1.7-fold). Limonene was the most effective excipient since it increased permeation flux of INH (1.5-fold) and lag time was greatly shortened (2.8-fold). DSC and FTIR analyses of limonene-treated skin suggest higher degree of disorder in lipid bilayers. Transdermal delivery of INH was positively correlated with logP of chemical enhancers. INH can be efficiently delivered by skin route and specific excipients may be selected depending on intended use. PMID:26319631

  3. Cognitive-behavioral therapy vs. light therapy for preventing winter depression recurrence: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Seasonal affective disorder (SAD) is a subtype of recurrent depression involving major depressive episodes during the fall and/or winter months that remit in the spring. The central public health challenge in the management of SAD is prevention of winter depression recurrence. Light therapy (LT) is the established and best available acute SAD treatment. However, long-term compliance with daily LT from first symptom through spontaneous springtime remission every fall/winter season is poor. Time-limited alternative treatments with effects that endure beyond the cessation of acute treatment are needed to prevent the annual recurrence of SAD. Methods/design This is an NIMH-funded R01-level randomized clinical trial to test the efficacy of a novel, SAD-tailored cognitive-behavioral group therapy (CBT) against LT in a head-to-head comparison on next winter outcomes. This project is designed to test for a clinically meaningful difference between CBT and LT on depression recurrence in the next winter (the primary outcome). This is a concurrent two-arm study that will randomize 160 currently symptomatic community adults with major depression, recurrent with seasonal pattern, to CBT or LT. After 6 weeks of treatment in the initial winter, participants are followed in the subsequent summer, the next winter, and two winters later. Key methodological issues surround timing study procedures for a predictably recurrent and time-limited disorder with a focus on long-term outcomes. Discussion The chosen design answers the primary question of whether prior exposure to CBT is associated with a substantially lower likelihood of depression recurrence the next winter than LT. This design does not test the relative contributions of the cognitive-behavioral treatment components vs. nonspecific factors to CBT’s outcomes and is not adequately powered to test for differences or equivalence between cells at treatment endpoint. Alternative designs addressing these limitations

  4. Is it possible to prevent morbidity on post cardiovascular surgery applying low level laser therapy?

    NASA Astrophysics Data System (ADS)

    Pinto, Nathali C.; Baptista, Ivany Machado d. C.; Pereira, Mara Helena C.; Serrão, Nelson F.; Pomerantzeff, Pablo M. A.; Chavantes, Maria Cristina

    2014-03-01

    Background and Objective: Complications following cardiovascular surgery incision are common in mediastinitis and wound dehiscence form, a 47% mortality rate remaining. Low Level Laser Therapy (LLLT) has been employed mainly to its effectiveness analgesic and anti-inflammatory actions, aiding the tissue repair process. The aim of this study was to evaluate infrared LLLT onto surgical incision in patients submitted to cardiovascular surgery. Materials and Methods: 40 patients were divided in two groups: Placebo Group (G1) - conventional therapy + "Laser pointer" and Laser Group (G2) - conventional therapy + Infrared Laser irradiation on surgical incision. Diode Laser was employed, C.W. mode, around the surgical wound bed, on immediate Post Operative (PO), 1st PO and 3rd PO with the following parameters: wavelength (λ): 830nm, P=35mW, E=0,75J. Results: G2 didn't present any complication and 5% of patients in G1 developed incision dehiscence and infection. On 7thPO, still a large amount of G1 patients showed pain and unquestionable inflammatory signs surrounding the surgical wound, when compared to G2. Besides, hospital stay in Laser Group was 2 times shorter than in Placebo Group (p-value=0.001). Conclusion: Infrared Laser denoted to be safe and exceptionally valuable tools in preventing morbidities on post cardiovascular surgeries.

  5. Cell-based therapy for prevention and reversal of myocardial remodeling

    PubMed Central

    Karantalis, Vasileios; Balkan, Wayne; Schulman, Ivonne H.; Hatzistergos, Konstantinos E.

    2012-01-01

    Although pharmacological and interventional advances have reduced the morbidity and mortality of ischemic heart disease, there is an ongoing need for novel therapeutic strategies that prevent or reverse progressive ventricular remodeling following myocardial infarction, the process that forms the substrate for ventricular failure. The development of cell-based therapy as a strategy to repair or regenerate injured tissue offers extraordinary promise for a powerful anti-remodeling therapy. In this regard, the field of cell therapy has made major advancements in the past decade. Accumulating data from preclinical studies have provided novel insights into stem cell engraftment, differentiation, and interactions with host cellular elements, as well as the effectiveness of various methods of cell delivery and accuracy of diverse imaging modalities to assess therapeutic efficacy. These findings have in turn guided rationally designed translational clinical investigations. Collectively, there is a growing understanding of the parameters that underlie successful cell-based approaches for improving heart structure and function in ischemic and other cardiomyopathies. PMID:22636682

  6. Systems Pharmacology Approach Toward the Design of Inhaled Formulations of Rifampicin and Isoniazid for Treatment of Tuberculosis

    PubMed Central

    Cilfone, NA; Pienaar, E; Thurber, GM; Kirschner, DE; Linderman, JJ

    2015-01-01

    Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy treatment regimens and inadequate bacterial sterilization. Inhaled formulations are a promising strategy to increase antibiotic efficacy and reduce dose frequency. We develop a multiscale computational approach that accounts for simultaneous dynamics of a lung granuloma, carrier release kinetics, pharmacokinetics, and pharmacodynamics. Using this computational platform, we predict that a rationally designed inhaled formulation of isoniazid given at a significantly reduced dose frequency has better sterilizing capabilities and reduced toxicity than the current oral regimen. Furthermore, we predict that inhaled formulations of rifampicin require unrealistic carrier antibiotic loadings that lead to early toxicity concerns. Lastly, we predict that targeting carriers to macrophages has limited effects on treatment efficacy. Our platform can be extended to account for additional antibiotics and provides a new tool for rapidly prototyping the efficacy of inhaled formulations. PMID:26225241

  7. Cancers in Australia in 2010 attributable to and prevented by the use of menopausal hormone therapy

    PubMed Central

    Jordan, Susan J; Wilson, Louise F; Nagle, Christina M; Green, Adele C; Olsen, Catherine M; Bain, Christopher J; Pandeya, Nirmala; Whiteman, David C; Webb, Penelope M

    2015-01-01

    Objectives To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to menopausal hormone therapy (MHT) use. Methods We estimated the population attributable fraction for cancers causally associated with MHT (breast, endometrium, ovary), and the proportion of colorectal cancers prevented by MHT. We used standard formulae incorporating Australian prevalence data, relative risks of cancer associated with MHT and cancer incidence. We also estimated potential change in cancer incidence under two hypothetical scenarios whereby 25% fewer Australian women used MHT, or women exclusively used oestrogen-only MHT. Results An estimated 539 cancers in Australia in 2010 were attributable to MHT: 453 breast, 67 endometrial and 19 ovarian cancers equating to 3.4%, 3.1% and 1.6% of each cancer type, respectively. In contrast, MHT may have prevented 52 colorectal cancers. If 25% fewer women used MHT, then 141 cancers may have been avoided. If women exclusively used oestrogen-only MHT then 240 cancers may have been avoided. Conclusions MHT use caused more than 500 cancers in Australian women in 2010 and prevented ∼50 colorectal cancers. Implications MHT use continues to cause an excess of cancers. The risks, benefits, regimen and treatment duration should be carefully considered for each woman before MHT is commenced. PMID:26437728

  8. Controversies and future perspectives of antiplatelet therapy in secondary stroke prevention

    PubMed Central

    Weber, Ralph; Diener, Hans-Christoph

    2010-01-01

    Abstract Antiplatelet agents are a cornerstone in the treatment of acute arterial thrombotic events and in the prevention of thrombus formation. However, existing antiplatelet agents (mainly aspirin, the combination of aspirin and dipyridamole and clopidogrel) reduce the risk of vascular events only by about one quarter compared with placebo. As a consequence, more efficacious antiplatelet therapies with a reduced bleeding risk are needed. We give an overview of several new antiplatelet agents that are currently investigated in secondary stroke prevention: adenosine 5′-diphosphonate receptor antagonists, cilostazol, sarpogrelate, terutroban and SCH 530348. There are unique features in secondary stroke prevention that have to be taken into account: ischaemic stroke is a heterogeneous disease caused by multiple aetiologies and the blood–brain barrier is disturbed after stroke which may result in a higher intracerebral bleeding risk. Several small randomized trials indicated that the combination of aspirin and clopidogrel might be superior to antiplatelet monotherapy in the acute and early post-ischaemic phase. There is an ongoing debate about antiplatelet resistance. Decreasing response to aspirin is correlated independently with an increased risk of cardiovascular events. However, there is still no evidence from randomized trials linking aspirin resistance and recurrent ischaemic events. Similarly, randomized trials have not demonstrated a clinical significantly decreased antiplatelet effect by the concomitant use of clopidogrel and proton pump inhibitors. Nevertheless, a routine use of this drug combination is not recommended. PMID:20738445

  9. Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia.

    PubMed

    McKee, M D; Nakano, Y; Masica, D L; Gray, J J; Lemire, I; Heft, R; Whyte, M P; Crine, P; Millán, J L

    2011-04-01

    Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2(-/-)) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B(6)-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2(-/-) mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD(10)). sALP-FcD(10) prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin--a marker of acellular cementum--was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2(-/-) mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life--where the majority of tooth root development occurs, including acellular cementum formation--could prevent the accelerated tooth loss seen in individuals with HPP. PMID:21212313

  10. Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

    SciTech Connect

    Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A. )

    1990-12-01

    Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy.

  11. Metabolism of isoniazid by neutrophil myeloperoxidase leads to isoniazid-NAD(+) adduct formation: A comparison of the reactivity of isoniazid with its known human metabolites.

    PubMed

    Khan, Saifur R; Morgan, Andrew G M; Michail, Karim; Srivastava, Nutan; Whittal, Randy M; Aljuhani, Naif; Siraki, Arno G

    2016-04-15

    The formation of isonicotinyl-nicotinamide adenine dinucleotide (INH-NAD(+)) via the mycobacterial catalase-peroxidase enzyme, KatG, has been described as the major component of the mode of action of isoniazid (INH). However, there are numerous human peroxidases that may catalyze this reaction. The role of neutrophil myeloperoxidase (MPO) in INH-NAD(+) adduct formation has never been explored; this is important, as neutrophils are recruited at the site of tuberculosis infection (granuloma) through infected macrophages' cell death signals. In our studies, we showed that neutrophil MPO is capable of INH metabolism using electron paramagnetic resonance (EPR) spin-trapping and UV-Vis spectroscopy. MPO or activated human neutrophils (by phorbol myristate acetate) catalyzed the oxidation of INH and formed several free radical intermediates; the inclusion of superoxide dismutase revealed a carbon-centered radical which is considered to be the reactive metabolite that binds with NAD(+). Other human metabolites, including N-acetyl-INH, N-acetylhydrazine, and hydrazine did not show formation of carbon-centered radicals, and either produced no detectable free radicals, N-centered free radicals, or superoxide, respectively. A comparison of these free radical products indicated that only the carbon-centered radical from INH is reducing in nature, based on UV-Vis measurement of nitroblue tetrazolium reduction. Furthermore, only INH oxidation by MPO led to a new product (λmax=326nm) in the presence of NAD(+). This adduct was confirmed to be isonicotinyl-NAD(+) using LC-MS analysis where the intact adduct was detected (m/z=769). The findings of this study suggest that neutrophil MPO may also play a role in INH pharmacological activity. PMID:26867495

  12. [Non-antiarrhythmic drug therapy for the prevention of atrial fibrillation?].

    PubMed

    Fauchier, L; Zannad, N; Clementy, N; Pierre, B; Cosnay, P; Babuty, D

    2010-12-01

    In atrial fibrillation (AF), the absence of a clear benefit of a rhythm-control strategy over a rate-control strategy seen in recent trials may be due to the fact that many of the usual antiarrhythmic strategy have significant weaknesses. Besides research efforts to improve the efficacy and safety of conventional antiarrhythmic agents, therapies directed 'upstream'of the electrical aspects of AF, towards the underlying anatomical substrate and atrial remodelling, have been proposed as new pharmacological therapeutic approaches. Potential upstream therapies for AF comprise a variety of agents such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), statins, N-3 polyunsaturated fatty acids and steroids. On the basis of experimental data, clinical studies have provided information on the potential of upstream therapy for the prevention of AF across a broad spectrum of cardiovascular patient groups. In patients with heart failure or hypertension, data are sufficient to support the use of ACEI or ARB as treatment that may decrease the risk of AF beyond their other beneficial effects. Similarly, it is highly possible that the use of statin in patients with a recognized indication may be associated with a benefit against AF. However, in most clinical settings, the evidence appears to be insufficient to drive changes in therapy management per se, and large-scale, randomized controlled trials with adequately defined endpoints are still needed. The results from these trials may help to understand the complex mechanisms that lead to AF, and may clarify the benefit-to-risk ratio of these new therapeutic approaches. PMID:21211623

  13. Neonatal Thymulin Gene Therapy Prevents Ovarian Dysgenesis and Attenuates Reproductive Derangements in Nude Female Mice

    PubMed Central

    Reggiani, Paula C.; Barbeito, Claudio G.; Zuccolilli, Gustavo O.; Cónsole, Gloria M.; Flamini, Alicia M.; Dardenne, Mireille

    2012-01-01

    Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70–71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis. PMID:22700775

  14. Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice.

    PubMed

    Reggiani, Paula C; Barbeito, Claudio G; Zuccolilli, Gustavo O; Cónsole, Gloria M; Flamini, Alicia M; Dardenne, Mireille; Goya, Rodolfo G

    2012-08-01

    Congenitally athymic (nude) female mice show severe ovarian dysgenesis after puberty, which seems to be consequential to a number of neuroendocrine derangements described in these mutants. Thus, considerable evidence suggests that thymulin, a thymic peptide, may be involved in thymus-pituitary communication. In order to clarify the relevance of thymulin for the maturation of the female reproductive system, we assessed at hypothalamic, pituitary, ovarian, and uterine level the preventive action of neonatal thymulin gene therapy (NTGT) on the changes that typically occur after puberty in congenitally athymic female mice. We injected (im) an adenoviral vector harboring a synthetic DNA sequence encoding a biologically active analog of thymulin, methionine-serum thymic factor, in newborn nude mice (which are thymulin deficient) and killed the animals at 70-71 d of age. NTGT in the athymic mice restored the serum thymulin levels. Morphometric analysis revealed that athymic nudes have reduced numbers of brain GnRH neurons and pituitary gonadotropic cells as compared with heterozygous controls. NTGT prevented these changes and also rescued the premature ovarian failure phenotype typically observed in athymic nude mice (marked reduction in the number of antral follicles and corpora lutea, increase in atretic follicles). Serum estrogen, but not progesterone, levels were low in athymic nudes, a reduction that was partially prevented by NTGT. Little to no morphological changes were observed in the endometrium of female nudes. The delay in the age of vaginal opening that occurs in athymic nudes was significantly prevented by NTGT. Our results suggest that thymulin plays a relevant physiologic role in the thymus-hypothalamo-pituitary-gonadal axis. PMID:22700775

  15. Harnessing the Prevention Benefits of Antiretroviral Therapy to Address HIV and Tuberculosis

    PubMed Central

    Granich, Reuben; Lo, Ying-Ru; Suthar, Amitabh B; Vitoria, Marco; Baggaley, Rachel; Obermeyer, Carla Makhlouf; McClure, Craig; Souteyrand, Yves; Perriens, Jos; Kahn, James G; Bennett, Rod; Smyth, Caoimhe; Williams, Brian; Montaner, Julio; Hirnschall, Gottfried

    2011-01-01

    After 30 years we are still struggling to address a devastating HIV pandemic in which over 25 million people have died. In 2010, an estimated 34 million people were living with HIV, around 70% of whom live in sub-Saharan Africa. Furthermore, in 2009 there were an estimated 1.2 million new HIV-associated TB cases, and tuberculosis (TB) accounted for 24% of HIV-related deaths. By the end of 2010, 6.6 million people were taking antiretroviral therapy (ART), around 42% of those in need as defined by the 2010 World Health Organization (WHO) guidelines. Despite this achievement, around 9 million people were eligible and still in need of treatment, and new infections (approximately 2.6 million in 2010 alone) continue to add to the future caseload. This combined with the international fiscal crisis has led to a growing concern regarding weakening of the international commitment to universal access and delivery of the Millennium Development Goals by 2015. The recently launched UNAIDS/WHO Treatment 2.0 platform calls for accelerated simplification of ART, in line with a public health approach, to achieve and sustain universal access to ART, including maximizing the HIV and TB preventive benefit of ART by treating people earlier, in line with WHO 2010 normative guidance. The potential individual and public health prevention benefits of using treatment in the prevention of HIV and TB enhance the value of the universal access pledge from a life-saving initiative, to a strategic investment aimed at ending the HIV epidemic. This review analyzes the gaps and summarizes the evidence regarding ART in the prevention of HIV and TB. PMID:21999771

  16. Functionalized single-walled carbon nanotube (5, 0) as a carrier for isoniazid — A tuberculosis drug

    NASA Astrophysics Data System (ADS)

    Rajarajeswari, M.; Iyakutti, K.; Lakshmi, I.; Rajeswarapalanichamy, R.; Kawazoe, Y.

    2015-06-01

    Nanostructures functionalized with amino acid are able to penetrate the cell wall. In this first principle study, we have demonstrated that the amino acid alanine functionalized carbon nanotubes (CNTs) (5, 0) can be a drug carrier for the tuberculosis drug isoniazid. Isoniazid is binding with both the non-covalently and covalently functionalized CNTs through the π-π stacking and NH⋯π interactions. The planar structure of isoniazid and hydrophobic nature of CNT promote the π-π stacking interactions. The amine group present in the isoniazid enables the NH⋯π interaction with the delocalized π electron cloud of CNT.

  17. Prevention

    MedlinePlus

    ... our e-newsletter! Aging & Health A to Z Prevention Basic Facts & Information Some factors that affect your ... control of the things that you can change. Preventive Recommendations for Adults Aged 65 and Older The ...

  18. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy.

    PubMed

    Law, Man Fai; Ho, Rita; Cheung, Carmen K M; Tam, Lydia H P; Ma, Karen; So, Kent C Y; Ip, Bonaventure; So, Jacqueline; Lai, Jennifer; Ng, Joyce; Tam, Tommy H C

    2016-07-28

    Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although

  19. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

    PubMed Central

    Law, Man Fai; Ho, Rita; Cheung, Carmen K M; Tam, Lydia H P; Ma, Karen; So, Kent C Y; Ip, Bonaventure; So, Jacqueline; Lai, Jennifer; Ng, Joyce; Tam, Tommy H C

    2016-01-01

    Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although

  20. Fixed-dose combination therapy for the prevention of cardiovascular disease

    PubMed Central

    de Cates, Angharad N; Farr, Matthew RB; Wright, Nicola; Jarvis, Morag C; Rees, Karen; Ebrahim, Shah; Huffman, Mark D

    2014-01-01

    Background Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, yet CVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of CVD by up to 80% given its potential for better adherence and lower costs. Objectives To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD. We also aimed to determine discontinuation rates, adverse events, health-related quality of life, and costs of fixed-dose combination therapy. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library(2013, Issue 6), MEDLINE Ovid (1946 to week 2 July 2013), EMBASE Ovid (1980 to Week 28 2013), ISI Web of Science (1970 to 19 July 2013), and the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), and Health Economics Evaluations Database (HEED) (2011, Issue 4) in The Cochrane Library. We used no language restrictions. Selection criteria We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care, placebo, or a single drug active component for any treatment duration in adults ≥ 18 years old with no restrictions on presence or absence of pre-existing cardiovascular disease. Data collection and analysis Three review authors independently selected studies for inclusion and extracted the data. We evaluated risk of bias using the Cochrane risk of bias assessment tool. We sought to include outcome data on all-cause mortality, fatal and non-fatal CVD events, adverse events, changes in systolic and diastolic blood

  1. Quantifying and Qualifying the Preventive Effects of Acute-Phase Cognitive Therapy: Pathways to Personalizing Care

    PubMed Central

    Jarrett, Robin B.; Minhajuddin, Abu; Vittengl, Jeffrey R.; Clark, Lee Anna; Thase, Michael E.

    2016-01-01

    Objective To determine the extent to which prospectively identified responders to cognitive therapy (CT) for recurrent major depressive disorder (MDD) hypothesized to be lower risk show significantly less relapse/recurrence than treated higher risk counterparts across 32 months. Method Outpatients (N = 523), aged 18–70, with recurrent MDD received 12–14 weeks of CT. The last seven consecutive scores from the Hamilton Rating Scale for Depression (HRSD-17), were used to stratify/define responders (n = 290) into lower (seven HRSD-17 scores of ≤ 6; n = 49; 17%) and higher risk (n = 241; 83%). The lower risk entered the 32-month follow-up. Higher risk patients were randomized to 8 months of continuation-phase CT or clinical management plus double-blind fluoxetine or pill placebo, with a 24-month follow-up. Results Lower risk patients were significantly less likely to relapse over the first 8 months compared to higher risk (Kaplan-Meier [KM] estimates (i.e., 4.9%=lower risk; 22.1%= higher risk; log-rank χ2 = 6.83, p = .009). This increased risk was attenuated, but not completely neutralized, by active continuation-phase therapy. Over the subsequent 24 months, the lower and higher risk groups did not differ in relapse/recurrence risk. Conclusions Rapid and sustained acute-phase CT remission identifies responders who do not require continuation-phase treatment to prevent relapse (i.e., return of an index episode). To prevent recurrence (i.e., new episodes), however, strategic allocation and more frequent “dosing” of CT and/or targeted maintenance-phase treatments may be required. Longitudinal follow-up is recommended. PMID:26654211

  2. Partial prevention of hepatic lipid alterations in nude mice by neonatal thymulin gene therapy.

    PubMed

    García de Bravo, Margarita M; Polo, Mónica P; Reggiani, Paula C; Rimoldi, Omar J; Dardenne, Mireille; Goya, Rodolfo G

    2006-08-01

    During adult life athymic (nude) male mice display not only a severe T-cell-related immunodeficiency but also endocrine imbalances and a moderate hyperglycemia. We studied the impact of congenital athymia on hepatic lipid composition and also assessed the ability of neonatal thymulin gene therapy to prevent the effects of athymia. We constructed a recombinant adenoviral vector, RAd-metFTS, expressing a synthetic DNA sequence encoding met-FTS, an analog of the thymic peptide facteur thymique sérique (FTS), whose Zn-bound biologically active form is known as thymulin. On postnatal day 1-2 homozygous (nu/nu) nude and heterozygous (nu/+) mice were injected with 10(8) pfu of RAd-metFTS or RAd-betagal (control vector) intramuscularly. The animals were processed at 52 d of age. Serum thymulin, glycemia, hepatic phospholipid FA composition and free and esterified cholesterol were determined. Adult homozygous male nudes were significantly (P < 0.01) hyperglycemic when compared with their heterozygous counterparts (2.04 vs. 1.40 g/L, respectively). The relative percentage of 16:0, 18:1 n-9, and 18:1n-7 FA was lower, whereas that of 18:0, 20:4n-6, and 22:6n-3 FA was higher, in hepatic phospholipid (PL) of nu/nu animals as compared with their nu/+ counterparts. Some of these alterations, such as that in the relative content of 22:6n-3 in liver PL and the unsaturation index, were completely or partially prevented by neonatal thymulin gene therapy. We conclude that the thymus influences lipid metabolism and that thymulin is involved in this modulatory activity. PMID:17120928

  3. Escitalopram and Problem-Solving Therapy for Prevention of Poststroke Depression: A Randomized Controlled Trial

    PubMed Central

    Robinson, Robert G.; Jorge, Ricardo E.; Moser, David J.; Acion, Laura; Solodkin, Ana; Small, Steven L.; Fonzetti, Pasquale; Hegel, Mark; Arndt, Stephan

    2009-01-01

    Context Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal. Objective To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication. Design, Setting, and Participants A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n=59) with placebo (n=58), and a nonblinded problem-solving therapy group (n=59). Main Outcome Measures The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressivelike episode or minor depression (ie, research criteria). Results Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 min or cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4–8.2; P<.001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4–3.5; P<.001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site

  4. Bone targeted therapy for preventing skeletal-related events in metastatic breast cancer.

    PubMed

    Irelli, Azzurra; Cocciolone, Valentina; Cannita, Katia; Zugaro, Luigi; Di Staso, Mario; Lanfiuti Baldi, Paola; Paradisi, Stefania; Sidoni, Tina; Ricevuto, Enrico; Ficorella, Corrado

    2016-06-01

    Cancer cells can alter physiological mechanisms within bone resulting in high bone turnover, and consequently in skeletal-related events (SREs), causing severe morbidity in affected patients. The goals of bone targeted therapy, as bisphosphonates and denosumab, are the reduction of incidence and the delay in occurrence of the SREs, to improve quality of life and pain control. The toxicity profile is similar between bisphosphonates and denosumab, even if pyrexia, bone pain, arthralgia, renal failure and hypercalcemia are more common with bisphosphonates, while hypocalcemia and toothache are more frequently reported with denosumab. Osteonecrosis of the jaw (ONJ) occurred infrequently without statistically significant difference. The present review aims to provide an assessment on bone targeted therapies for preventing the occurrence of SREs in bone metastatic breast cancer patients, critically analyzing the evidence available so far on their effectiveness, in light of the different mechanisms of action. Thus, we try to provide tools for the most fitting treatment of bone metastatic breast cancer patients. We also provide an overview on the usefulness of bone turnover markers in clinical practice and new molecules currently under study for the treatment of bone metastatic disease. PMID:27091227

  5. Home infusion therapy. First things first: the patient and the prevention of central catheter infections.

    PubMed

    Polzien, Gladys

    2006-01-01

    During the past seventeen years, I've had the privilege of working as a home healthcare nurse in two rural counties in the Upper Peninsula of Michigan. In the early 1990s, it was rare that our agency received referrals for IV antibiotics, opiate infusions for pain management or for total parenteral infusion (TPN) to be administered at home. Most patients stayed in the hospital for infusion therapy. Today, as more healthcare treatments are being shifted from hospital to outpatient or home care settings, referrals for home infusion have become more common in our area as well as across the nation (Jarvis, 2001). I'll never forget my first patient whom I cared for with home infusion therapy for pain management. I learned a great deal from Sally, and to this day I always remember that I can make a real difference in patient outcomes when I keep--"First Things First": the patient and infection prevention--when caring for any of my patients. PMID:17135849

  6. Centering prayer as an alternative to mindfulness-based cognitive therapy for depression relapse prevention.

    PubMed

    Knabb, Joshua J

    2012-09-01

    In the last two decades, mindfulness has made a significant impact on Western secular psychology, as evidenced by several new treatment approaches that utilize mindfulness practices to ameliorate mental illness. Based on Buddhist teachings, mindfulness offers individuals the ability to, among other things, decenter from their thoughts and live in the present moment. As an example, mindfulness-based cognitive therapy (MBCT) teaches decentering and mindfulness techniques to adults in an eight-session group therapy format so as to reduce the likelihood of depression relapse. Yet, some Christian adults may prefer to turn to their own religious heritage, rather than the Buddhist tradition, in order to stave off depression relapse. Thus, the purpose of this article is to present centering prayer, a form of Christian meditation that is rooted in Catholic mysticism, as an alternative treatment for preventing depression relapse in adults. I argue that centering prayer overlaps considerably with MBCT, which makes it a suitable treatment alternative for many Christians in remission from depressive episodes. PMID:20924682

  7. Microenvironmental acidosis in carcinogenesis and metastases: new strategies in prevention and therapy.

    PubMed

    Fais, Stefano; Venturi, Giulietta; Gatenby, Bob

    2014-12-01

    Much effort is currently devoted to developing patient-specific cancer therapy based on molecular characterization of tumors. In particular, this approach seeks to identify driver mutations that can be blocked through small molecular inhibitors. However, this approach is limited by extensive intratumoral genetic heterogeneity, and, not surprisingly, even dramatic initial responses are typically of limited duration as resistant tumor clones rapidly emerge and proliferate. We propose an alternative approach based on observations that while tumor evolution produces genetic divergence, it is also associated with striking phenotypic convergence that loosely correspond to the well-known cancer "hallmarks". These convergent properties can be described as driver phenotypes and may be more consistently and robustly expressed than genetic targets. To this purpose, it is necessary to identify strategies that are critical for cancer progression and metastases, and it is likely that these driver phenotypes will be closely related to cancer "hallmarks". It appears that an antiacidic approach, by targetting a driver phenotype in tumors, may be thought as a future strategy against tumors in either preventing the occurrence of cancer or treating tumor patients with multiple aims, including the improvement of efficacy of existing therapies, possibly reducing their systemic side effects, and controlling tumor growth, progression, and metastasis. This may be achieved with existing molecules such as proton pump inhibitors (PPIs) and buffers such as sodium bicarbonate, citrate, or TRIS. PMID:25376898

  8. Role of the pharmacist in pre-exposure chemoprophylaxis (PrEP) therapy for HIV prevention

    PubMed Central

    Clauson, Kevin A.; Polen, Hyla H.; Joseph, Shine A.; Zapantis, Antonia

    2008-01-01

    With a global estimate of 2.5 million new infections of HIV occurring yearly, discovering novel methods to help stem the spread of the virus is critical. The use of antiretroviral chemoprophylaxis for preventing HIV after accidental or occupational exposure and in maternal to fetal transmission has become a widely accepted method to combat HIV. Based on this success, pre-exposure chemoprophylaxis (PrEP) is being explored in at-risk patient populations such as injecting drug users, female sex workers and men who have sex with men. This off-label and unmonitored use has created a need for education and intervention by pharmacists and other healthcare professionals. Pharmacists should educate themselves on PrEP and be prepared to counsel patients about their means of obtaining it (e.g. borrowing or sharing medications and ordering from disreputable Internet pharmacies). They should also be proactive about medication therapy management in these patients due to clinically important drug interactions with PrEP medications. Only one trial exploring the safety and efficacy of tenofovir as PrEP has been completed thus far. However, five ongoing trials are in various stages and two additional studies are scheduled for the near future. Unfortunately, studies in this arena have met with many challenges that have threatened to derail progress. Ethical controversy surrounding post-trial care of participants who seroconvert during studies, as well as concerns over emerging viral resistance and logistical site problems, have already halted several PrEP trials. Information about these early trials has already filtered down to affected individuals who are experimenting with this unproven therapy as an “evening before pill”. The potential for PrEP is promising; however, more extensive trials are necessary to establish its safety and efficacy. Pharmacists are well-positioned to play a key role in helping patients make choices about PrEP, managing their therapy, and developing

  9. Role of the pharmacist in pre-exposure chemoprophylaxis (PrEP) therapy for HIV prevention.

    PubMed

    Clauson, Kevin A; Polen, Hyla H; Joseph, Shine A; Zapantis, Antonia

    2009-01-01

    With a global estimate of 2.5 million new infections of HIV occurring yearly, discovering novel methods to help stem the spread of the virus is critical. The use of antiretroviral chemoprophylaxis for preventing HIV after accidental or occupational exposure and in maternal to fetal transmission has become a widely accepted method to combat HIV. Based on this success, pre-exposure chemoprophylaxis (PrEP) is being explored in at-risk patient populations such as injecting drug users, female sex workers and men who have sex with men. This off-label and unmonitored use has created a need for education and intervention by pharmacists and other healthcare professionals. Pharmacists should educate themselves on PrEP and be prepared to counsel patients about their means of obtaining it (e.g. borrowing or sharing medications and ordering from disreputable Internet pharmacies). They should also be proactive about medication therapy management in these patients due to clinically important drug interactions with PrEP medications. Only one trial exploring the safety and efficacy of tenofovir as PrEP has been completed thus far. However, five ongoing trials are in various stages and two additional studies are scheduled for the near future. Unfortunately, studies in this arena have met with many challenges that have threatened to derail progress. Ethical controversy surrounding post-trial care of participants who seroconvert during studies, as well as concerns over emerging viral resistance and logistical site problems, have already halted several PrEP trials. Information about these early trials has already filtered down to affected individuals who are experimenting with this unproven therapy as an "evening before pill". The potential for PrEP is promising; however, more extensive trials are necessary to establish its safety and efficacy. Pharmacists are well-positioned to play a key role in helping patients make choices about PrEP, managing their therapy, and developing policy

  10. Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism

    SciTech Connect

    Bartalena, L.; Marcocci, C.; Bogazzi, F.; Panicucci, M.; Lepri, A.; Pinchera, A. )

    1989-11-16

    We studied the effects of radioiodine treatment of hyperthyroidism due to Graves' disease on Graves' ophthalmopathy and the possible protective role of corticosteroids. Between June 1985 and June 1988, 26 patients were randomly assigned to treatment with radioiodine alone (group 1) and 26 to treatment with this agent and concomitant administration of systemic prednisone for four months (group 2). The initial dose of prednisone was 0.4 to 0.5 mg per kilogram of body weight for one month; the drug was gradually withdrawn over the next three months. All patients were evaluated at 3-month intervals for 18 months after they underwent radioiodine therapy. Ocular changes were assessed with the ophthalmopathy index; patients with moderate-to-severe changes (scores greater than or equal to 4) were excluded from the study. Before treatment, 10 patients in group 1 and 5 in group 2 had no evidence of ophthalmopathy: in none of them did ocular symptoms appear after radioiodine therapy. Among the patients in group 1 with an initial ophthalmopathy index greater than or equal to 1, ocular disease worsened in 56 percent (mostly involving soft-tissue changes and extraocular-muscle function) and did not change in 44 percent. In contrast, ophthalmopathy improved in 52 percent and did not change in 48 percent of group 2. The mean ophthalmopathy index increased from 1.5 to 3.0 in group 1 (P less than 0.005) and decreased from 2.2 to 1.3 in group 2 (P less than 0.05). We conclude that systemic corticosteroid treatment prevents the exacerbations of Graves' ophthalmopathy that occur after radioiodine therapy in a substantial proportion of patients with hyperthyroidism who have some degree of ocular involvement before treatment.

  11. Severe sporotrichoid fish tank granuloma following infliximab therapy.

    PubMed

    Rallis, Efstathios; Koumantaki-Mathioudaki, Elma; Frangoulis, Effie; Chatziolou, Eftihia; Katsambas, Andreas

    2007-01-01

    Mycobacterium marinum is an atypical mycobacterium usually found in non-chlorinated water. It rarely disseminates, except in the setting of a severely immunosuppressed patient, and usually follows a sporotrichotic type of distribution. We report the case of a 45-year-old man who had ankylosing spondylitis and was receiving infliximab and isoniazid for latent tuberculosis. The patient presented with a 5-month history of painful erythematous and suppurative nodules and abscesses on the right upper extremity. M. marinum was not isolated in cultures and histologic findings together with clinical examination provided evidence of sporotrichoid-like fish tank granuloma. The patient was treated with rifampin (rifampicin) and ethambutol for 8 months and responded satisfactorily while continuing to receive infliximab. In accordance with data in the published literature, isoniazid proved ineffective in preventing M. marinum infection in this patient. While mycobacterial complications of tumor necrosis factor-alpha (TNFalpha) inhibitor therapy are well established, our case appears to be the first reported instance of M. marinum infection in a patient taking infliximab. As anti-TNFalpha agents become increasingly used for a variety of conditions, awareness of the potential infectious complications associated with use of these agents will be vital for clinicians. PMID:18039022

  12. Haemodynamic effects of negative pressure wound therapy when using a rigid barrier to prevent heart rupture.

    PubMed

    Lindstedt, Sandra; Ingemansson, Richard; Malmsjo, Malin

    2011-08-01

    Right ventricular heart rupture is a devastating complication associated with negative pressure wound therapy (NPWT) in cardiac surgery. The use of a rigid barrier has been suggested to offer protection against this lethal complication by preventing the heart from being drawn up and damaged by the sharp sternum bone edges. The aim of this study was to investigate the haemodynamic effects of placing a rigid barrier over the heart to protect it from rupture during NPWT. Eight pigs underwent median sternotomy followed by NPWT at --70 and --120 mmHg, using foam, with or without a rigid plastic disc between the heart and the sternal edges. The heart frequency, cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, central venous pressure and left atrial pressure were recorded. Cardiac output was not affected by NPWT, regardless of whether a rigid barrier was used. Heart frequency decreased during NPWT without a disc, and showed a tendency towards a decrease when using a rigid disc. The blood pressure decreased during NPWT without a disc, and showed only a tendency towards a decrease when a disc was inserted between the heart and the sternum. In conclusion, the results of this haemodynamic study show that a rigid disc can safely be placed over the heart during NPWT, to prevent heart rupture. The haemodynamic effects of NPWT in sternotomy wounds are slightly reduced by the presence of the rigid disc. PMID:21585658

  13. Cancer prevention and therapy through the modulation of the tumor microenvironment.

    PubMed

    Casey, Stephanie C; Amedei, Amedeo; Aquilano, Katia; Azmi, Asfar S; Benencia, Fabian; Bhakta, Dipita; Bilsland, Alan E; Boosani, Chandra S; Chen, Sophie; Ciriolo, Maria Rosa; Crawford, Sarah; Fujii, Hiromasa; Georgakilas, Alexandros G; Guha, Gunjan; Halicka, Dorota; Helferich, William G; Heneberg, Petr; Honoki, Kanya; Keith, W Nicol; Kerkar, Sid P; Mohammed, Sulma I; Niccolai, Elena; Nowsheen, Somaira; Vasantha Rupasinghe, H P; Samadi, Abbas; Singh, Neetu; Talib, Wamidh H; Venkateswaran, Vasundara; Whelan, Richard L; Yang, Xujuan; Felsher, Dean W

    2015-12-01

    Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2,3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer. PMID:25865775

  14. Probiotics to prevent gastrointestinal toxicity from cancer therapy: An interpretive review and call to action

    PubMed Central

    Ciorba, Matthew A; Hallemeier, Christopher L; Stenson, William F; Parikh, Parag J

    2016-01-01

    Purpose of Review There is currently an unmet need for agents that can prevent the gastrointestinal toxicity (mucositis, enteritis) associated with chemotherapy and radiation therapy of abdominal and pelvic cancers. Herein we provide an overview of how manipulation of the gut microbiota by probiotic administration affects these gastrointestinal symptoms. We focus this review on published human trials and also provide suggestions on how the field can move forward. Recent Findings Several clinical trials of varying design, patient populations and probiotic product have been reported. Lactobacillus probiotics of adequate dosage demonstrate a potential to reduce gastrointestinal toxicity when administered prophylactically. Common study limitations prevent the widespread adoption of this practice at this point, but are informative for rational design of future trials. Summary No single probiotic strain or product has emerged from human clinical trials for this indication. Further human studies are required to address limitations in the current literature. Preclinical model data should be used to inform the rational design of these new clinical trials to adequately address this important question. PMID:25872116

  15. Prevention of Nausea and Vomiting in Patients Undergoing Oral Anticancer Therapies for Solid Tumors

    PubMed Central

    Costa, Ana Lúcia; Abreu, Catarina; Pacheco, Teresa Raquel; Macedo, Daniela; Sousa, Ana Rita; Pulido, Catarina; Quintela, António; Costa, Luís

    2015-01-01

    Chemotherapy-induced nausea and vomiting (CINV) is still a common and debilitating side effect despite recent advances in its prevention and treatment. The intrinsic emetogenicity of chemotherapy agents allowed grouping into four risk groups (high, moderate, low, and minimal risk of emetogenicity). The prevention of acute and delayed CINV for intravenous agents and one day regimens is well studied, although, there are few data about management of CINV induced by oral cytotoxic agents and targeted therapies, usually administered in extended regimens of daily oral use. Until now treatment of nausea and vomiting caused by oral antineoplastic agents remains largely empirical. The level of evidence of prophylactic antiemetics recommended for these agents is low. There are differences in the classification of emetogenic potential of oral antineoplastic agents between the international guidelines and different recommendations for prophylactic antiemetic regimens. Herein we review the evidence for antiemetic regimens for the most used oral antineoplastic agents for solid tumors and propose antiemetic regimens for high to moderate risk and low to minimal risk of emetogenicity. PMID:26421283

  16. Fasting therapy for treating and preventing disease - current state of evidence.

    PubMed

    Michalsen, Andreas; Li, Chenying

    2013-01-01

    Periods of deliberate fasting with restriction of solid food intake are practiced worldwide, mostly based on traditional, cultural or religious reasons. There is large empirical and observational evidence that medically supervised modified fasting (fasting cure, 200-500 kcal nutritional intake per day) with periods of 7-21 days is efficacious in the treatment of rheumatic diseases, chronic pain syndromes, hypertension, and metabolic syndrome. The beneficial effects of fasting followed by vegetarian diet in rheumatoid arthritis are confirmed by randomized controlled trials. Further beneficial effects of fasting are supported by observational data and abundant evidence from experimental research which found caloric restriction and intermittent fasting being associated with deceleration or prevention of most chronic degenerative and chronic inflammatory diseases. Intermittent fasting may also be useful as an accompanying treatment during chemotherapy of cancer. A further beneficial effect of fasting relates to improvements in sustainable lifestyle modification and adoption of a healthy diet, possibly mediated by fasting-induced mood enhancement. Various identified mechanisms of fasting point to its potential health-promoting effects, e.g., fasting-induced neuroendocrine activation and hormetic stress response, increased production of neurotrophic factors, reduced mitochondrial oxidative stress, general decrease of signals associated with aging, and promotion of autophagy. Fasting therapy might contribute to the prevention and treatment of chronic diseases and should be further evaluated in controlled clinical trials and observational studies. PMID:24434759

  17. Warfarin versus aspirin: using CHADS2 to guide therapy for stroke prevention in nonvalvular atrial fibrillation.

    PubMed

    Hopps, Sarah; Marcy, Todd R

    2009-11-01

    Atrial fibrillation (AF) results in nearly a quarter of the strokes suffered in patients 80 to 89 years of age. Aspirin and warfarin are primary choices for preventing these ischemic strokes. CHADS2 (Congestive heart failure, Hypertention, Age, Diabetes, Stroke) is a validated assessment tool for cardioembolic stroke in AF. Ischemic stroke rates increase from 1.9 to 18.2 events per 100 patient-years with CHADS2 scores of 0 and 6, respectively. Warfarin is more effective than aspirin at preventing stroke in AF, but is associated with more hemorrhagic events. The American College of Chest Physicians recommends the use of warfarin in patients with a CHADS2 score of 2 or higher and suggests warfarin be used in patients with a score of 1. We recommend a patient-specific approach to therapy in which warfarin is offered to patients with a CHADS2 score of 1 or higher unless the patient is at high risk for a hemorrhagic event or cannot attain regular warfarin monitoring. PMID:20092222

  18. [Strengthening parenting competences through primary prevention: one ounce of prevention weighs more than one pound of therapy].

    PubMed

    Schneewind, Klaus A; Berkic, Julia

    2007-01-01

    Upon a clarification of the term and main components of parenting competences, the present contribution first delineates research-focused aspects and various target groups for primary familial prevention. Then, an overview of a selection of preventive measures for German speaking countries aiming at strengthening parental competences is provided for universal prevention programs including available information on the effectiveness of the corresponding programs. Next, an account of some meta-analytic findings and cost-benefit analyses concerning the relevance of parenting programs is presented. Finally, some desiderata concerning the development and evaluation of preventive approaches to strengthening parenting competences are briefly addressed. PMID:18051614

  19. Melatonin as a preventive and curative therapy against pulmonary hypertension.

    PubMed

    Maarman, Gerald; Blackhurst, Dee; Thienemann, Friedrich; Blauwet, Lori; Butrous, Ghazwan; Davies, Neil; Sliwa, Karen; Lecour, Sandrine

    2015-10-01

    Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure, which leads to right ventricular (RV) hypertrophy and failure. The pathophysiological mechanisms of PH remain unclear but oxidative stress is believed to contribute to RV dysfunction. Melatonin is a powerful antioxidant and is cardioprotective against ischemia-reperfusion injury and hypertension. Therefore, we hypothesized that a chronic treatment with melatonin, given as a curative or preventive therapy, may confer cardiovascular benefits in PH. PH was induced in Long Evans rats (n ≥ 6 per group), with a single subcutaneous injection of monocrotaline (MCT, 80 mg/kg). Melatonin was given daily in the drinking water, with the treatment starting either on the day of the injection of MCT (dose testing: melatonin 75 ng/L and 6 mg/kg), 14 days after the injection of MCT (curative treatment: 6 mg/kg), or 5 days before the injection (preventive treatment: 6 mg/kg). The development of PH was assessed by measuring RV hypertrophy, RV function, cardiac interstitial fibrosis, and plasma oxidative stress. Compared with controls, MCT-treated rats displayed RV hypertrophy and dysfunction, increased interstitial fibrosis, and elevated plasma oxidative stress. A chronic melatonin treatment (75 ng/L or 6 mg/kg) reduced RV hypertrophy, improved RV function and reduced plasma oxidative stress. Curative and preventive treatment improved RV functional and plasma oxidative stress parameters and reduced cardiac interstitial fibrosis. Our data demonstrate that melatonin confers cardioprotection in this model of PH. As melatonin is an inexpensive and safe drug, we propose that clinical investigation of the effects of melatonin on RV function in patients with PH should be considered. PMID:26201290

  20. Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives.

    PubMed

    Parikh, Nisha R; Mandal, Animesh; Bhatia, Deepak; Siveen, Kodappully Sivaraman; Sethi, Gautam; Bishayee, Anupam

    2014-12-01

    Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented. PMID:25395898

  1. Molecular targets of dietary agents for prevention and therapy of cancer.

    PubMed

    Aggarwal, Bharat B; Shishodia, Shishir

    2006-05-14

    While fruits and vegetables are recommended for prevention of cancer and other diseases, their active ingredients (at the molecular level) and their mechanisms of action less well understood. Extensive research during the last half century has identified various molecular targets that can potentially be used not only for the prevention of cancer but also for treatment. However, lack of success with targeted monotherapy resulting from bypass mechanisms has forced researchers to employ either combination therapy or agents that interfere with multiple cell-signaling pathways. In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food. PMID:16563357

  2. Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives

    PubMed Central

    Parikh, Nisha R.; Mandal, Animesh; Bhatia, Deepak; Siveen, Kodappully Sivaraman; Sethi, Gautam

    2014-01-01

    Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented. PMID:25395898

  3. Adenosine Deaminase Enzyme Therapy Prevents and Reverses the Heightened Cavernosal Relaxation in Priapism

    PubMed Central

    Wen, Jiaming; Jiang, Xianzhen; Dai, Yingbo; Zhang, Yujin; Tang, Yuxin; Sun, Hong; Mi, Tiejuan; Kellems, Rodney E.; Blackburn, Michael R.; Xia, Yang

    2010-01-01

    Introduction Priapism featured with painful prolonged penile erection is dangerous and commonly seen in sickle cell disease (SCD). The preventive approaches or effective treatment options for the disorder are limited because of poor understanding of its pathogenesis. Recent studies have revealed a novel role of excess adenosine in priapism caused by heightened cavernosal relaxation, and therefore present an intriguing mechanism-based therapeutic possibility. Aim The aim of this study was to determine the therapeutic effects of adenosine deaminase (ADA) enzyme therapy to lower adenosine in priapism. Methods Both ADA-deficient mice and SCD transgenic (Tg) mice display priapism caused by excessive adenosine. Thus, we used these two distinct lines of mouse models of priapism as our investigative tools. Specifically, we treated both of these mice with different dosages of polyethylene glycol–modified ADA (PEG–ADA) to reduce adenosine levels in vivo. At the end points of the experiments, we evaluated the therapeutic effects of PEG–ADA treatment by measuring adenosine levels and monitoring the cavernosal relaxation. Main Outcome Measures Adenosine levels in penile tissues were measured by high-performance liquid chromatography, and cavernosal relaxation was quantified by electrical field stimulation (EFS)-induced corporal cavernosal strip (CCS) assays. Results We found that lowering adenosine levels in penile tissues by PEG–ADA treatment from birth in ADA-deficient mice prevented the increased EFS-induced CCS relaxation associated with priapism. Intriguingly, in both ADA-deficient mice and SCD Tg mice with established priapism, we found that normalization of adenosine levels in penile tissues by PEG–ADA treatment relieved the heightened EFS-induced cavernosal relaxation in priapism. Conclusions Our studies have identified that PEG–ADA is a novel, safe, and mechanism-based drug to prevent and correct excess adenosine-mediated increased cavernosal relaxation

  4. Flow-injection determination of isoniazid using sodium dichloroisocyanurate- and trichloroisocyanuric acid-luminol chemiluminescence systems.

    PubMed

    Safavi, A; Karimi, M A; Hormozi Nezhad, M R

    2004-06-01

    A chemiluminescent (CL) method for the determination of isoniazid is described. The method is based on the CL generated during the oxidation of luminol by sodium dichloroisocyanurate (SDCC) and trichloroisocyanuric acid (TCCA) in alkaline medium. It was found that isoniazid greatly enhances this CL intensity when present in the luminol solution. Based on this observation, a new flow-injection CL method for the determination of isoniazid has been proposed in this paper. The detection limits were 2 and 3 ng ml(-1) isoniazid for the SDCC-luminol and TCCA-luminol CL systems, respectively. The relative CL intensity was linear with the isoniazid concentration in the range of 4-100 and 100-200 ng ml(-1) for the SDCC-luminol CL system, and 6-200 and 200-1000 ng ml(-1) for the TCCA-luminol CL system. The results obtained for the assay of pharmaceutical preparations compared well with those obtained by the official methods and demonstrated good accuracy and precision. PMID:15178311

  5. Antibodies to nucleoprotein and to hydrazide-altered soluble nucleoprotein in tuberculous patients receiving isoniazid

    PubMed Central

    Alarcón-Segovia, D.; Fishbein, Eugenia; Betancourt, V. M.

    1969-01-01

    Antibodies to calf thymus nuclei, nucleoprotein, DNA, soluble nucleoprotein and hydrazide (hydrallazine and isoniazid)-altered nucleoprotein were investigated by a standard complement-fixation method in 214 tuberculous patients receiving isoniazid. Findings were compared to those on thirty-seven sera from lupus patients receiving neither steroids nor immunosuppressants and on sixty-six sera from normal controls. The incidence of antibodies to all antigens studied except DNA was significantly higher in isoniazid-treated tuberculous patients than in the normal controls, but lower than in the lupus patients. Unlike lupus there were no detectable DNA antibodies in the tuberculous or in the control sera. Antibodies to nucleoprotein (soluble and insoluble) and particularly to hydrazide-altered nucleoprotein were the most frequently found in the isoniazid-treated tuberculous patients. In general, antinuclear antibodies were more frequent in the isoniazid-treated tuberculous female than in the male; in the adult than in the child. It is suggested that hydrazides may cause in vivo similar alteration of nucleoprotein to that which they cause in vitro. Hydrazide-altered nucleoprotein probably elicits the production of antinuclear antibodies which in turn may activate systemic lupus erythematosus in otherwise predisposed individuals. PMID:5359961

  6. Detection of Anti-Isoniazid and Anti-CYP Antibodies in Patients with Isoniazid-Induced Liver Failure

    PubMed Central

    Metushi, Imir G; Sanders, Corron; Lee, William M.; Uetrecht, Jack

    2016-01-01

    Isoniazid (INH)-induced hepatotoxicity remains one of the most common causes of drug-induced idiosyncratic liver injury and liver failure. This form of liver injury is not believed to be immune-mediated because it is not usually associated with fever or rash, does not recur more rapidly on rechallenge, and previous studies have failed to identify anti-INH antibodies. In this paper we found antibodies present in the sera of 15/19 cases of INH-induced liver failure. Anti-INH antibodies were present in 8; 11 sera had anti-CYP2E1 antibodies, 14 sera had antibodies against CYP2E1 modified by INH, 14 sera had anti-CYP3A4 antibodies, and 10 sera had anti-CYP2C9 antibodies. INH was found to form covalent adducts with CYP2E1, CYP3A4, and CYP2C9. None of these antibodies were detected in sera from INH-treated controls without significant liver injury. The presence of a range of anti-drug and autoantibodies has been observed in other drug-induced liver injury that is presumed to be immune-mediated. Conclusion These data provide strong evidence that INH induces an immune response that causes INH-induced liver injury. PMID:23775837

  7. Successful prevention of scedosporiosis after lung transplantation in a cystic fibrosis patient by combined local and systemic triazole therapy.

    PubMed

    Hartmann, Carolin; Müller, Carsten; Weißbrodt, Hartmut; Suerbaum, Sebastian; Tintelnot, Kathrin; Stolle, Stefan; Hansen, Gesine; Sedlacek, Ludwig

    2013-05-23

    A persistent colonization with Scedosporium apiospermum (S. apiospermum) often results in disseminated infection with a high mortality rate in immunosuppressed patients. We present the first case of successful prevention of scedosporiosis in an adolescent female cystic fibrosis patient post double lung transplant, with a combination of local and systemic voriconazole therapy and surgical intervention. PMID:24432232

  8. Computerised Cognitive Behavioural Therapy for the Prevention and Treatment of Depression and Anxiety in Children and Adolescents: A Systematic Review

    ERIC Educational Resources Information Center

    Richardson, Thomas; Stallard, Paul; Velleman, Sophie

    2010-01-01

    Research has shown that computerised cognitive behaviour therapy (cCBT) can be effective in the treatment of depression and anxiety in adults, although the outcomes with children and adolescents are unclear. The aim of the study is to systematically review the literature on the effectiveness of cCBT for the prevention and treatment of depression…

  9. E-therapy in the treatment and prevention of eating disorders: A systematic review and meta-analysis.

    PubMed

    Loucas, Christina E; Fairburn, Christopher G; Whittington, Craig; Pennant, Mary E; Stockton, Sarah; Kendall, Tim

    2014-12-01

    The widespread availability of the Internet and mobile-device applications (apps) is changing the treatment of mental health problems. The aim of the present study was to review the research on the effectiveness of e-therapy for eating disorders, using the methodology employed by the UK's National Institute for Health and Care Excellence (NICE). Electronic databases were searched for published randomised controlled trials of e-therapies, designed to prevent or treat any eating disorder in all age groups. Studies were meta-analysed where possible, and effect sizes with confidence intervals were calculated. The GRADE approach was used to determine the confidence in the effect estimates. Twenty trials met the inclusion criteria. For prevention, a CBT-based e-intervention was associated with small reductions in eating disorder psychopathology, weight concern and drive for thinness, with moderate confidence in the effect estimates. For treatment and relapse prevention, various e-therapies showed some beneficial effects, but for most outcomes, evidence came from single studies and confidence in the effect estimates was low. Overall, although some positive findings were identified, the value of e-therapy for eating disorders must be viewed as uncertain. Further research, with improved methods, is needed to establish the effectiveness of e-therapy for people with eating disorders. PMID:25461787

  10. Does hormone therapy affect blood pressure changes in the Diabetes Prevention Program?

    PubMed Central

    Kim, Catherine; Golden, Sherita H.; Kong, Shengchun; Nan, Bin; Mather, Kieren J.; Barrett-Connor, Elizabeth

    2013-01-01

    Objectives To examine whether blood pressure reductions differ by estrogen use among overweight glucose-intolerant women. Methods We conducted a secondary analysis of postmenopausal Diabetes Prevention Program participants who used oral estrogen with or without progestogen at baseline and at 1-year follow-up (n=324) vs. those who did not use at either time point (n=382). Systolic (SBP) and diastolic blood pressure (DBP) changes were examined by randomization arm (intensive lifestyle change (ILS), metformin 850 mg twice daily, or placebo). Associations between changes in blood pressure with changes in sex hormone binding globulin, estradiol, testosterone, and dehydroepiandrosterone were also examined. Results Estrogen users and non-users had similar prevalences of baseline hypertension (33% vs. 34%, p=0.82) and use of blood pressure medications at baseline (p=0.25) and follow-up (p=0.10). Estrogen users and non-users randomized to ILS had similar decreases in SBP (-3.3 vs. -4.7 mmHg, p=0.45) and DBP (-3.1 vs. -4.7 mmHg, p=0.16). Among estrogen users, women randomized to ILS had significant declines in SBP (p=0.016) and DBP (p=0.009) vs. placebo. Among non-users, women randomized to ILS had significant declines in DBP (p=0.001) vs. placebo, but declines in SBP were not significant (p=0.11). Metformin was not associated with blood pressure reductions vs. placebo regardless of estrogen therapy. Blood pressure changes were not associated with changes in sex hormones regardless of estrogen therapy. Conclusions Among overweight women with dysglycemia, the magnitude of blood pressure reductions after ILS was unrelated to postmenopausal estrogen use. PMID:23942251

  11. Nitrite impacts the survival of Mycobacterium tuberculosis in response to isoniazid and hydrogen peroxide

    PubMed Central

    Cunningham-Bussel, Amy; Bange, Franz C; Nathan, Carl F

    2013-01-01

    When access to molecular oxygen is restricted, Mycobacterium tuberculosis (Mtb) can respire an alternative electron acceptor, nitrate. We found that Mtb within infected primary human macrophages in vitro at physiologic tissue oxygen tensions respired nitrate, generating copious nitrite. A strain of Mtb lacking a functioning nitrate reductase was more susceptible than wild-type Mtb to treatment with isoniazid during infection of macrophages. Likewise, nitrate reductase-deficient Mtb was more susceptible to isoniazid than wild-type Mtb in axenic culture, and more resistant to hydrogen peroxide. These phenotypes were reversed by the addition of exogenous nitrite. Further investigation suggested that nitrite might inhibit the bacterial catalase. To the extent that Mtb itself is the most relevant source of nitrite acting within Mtb, these findings suggest that inhibitors of Mtb's nitrate transporter or nitrate reductase could enhance the efficacy of isoniazid. PMID:24019302

  12. Isoniazid-resistant tuberculosis in Iran: A systematic review.

    PubMed

    Javad Nasiri, Mohammad; Chirani, Alireza Salimi; Amin, Mohsen; Halabian, Raheleh; Imani Fooladi, Abbas Ali

    2016-05-01

    Isoniazid (INH) is one of the most potent anti-tuberculosis (TB) agents. INH resistance is an obstacle to the treatment of TB disease and the National TB control Program (NTP). We aimed to determine the true prevalence of INH-resistant TB in Iran. Several databases including Embase, Medline, Cochrane library and Iranian databases were searched to identify studies addressing INH-resistant tuberculosis in Iran. We identified 156 articles, of which 129 records were excluded based on their titles and abstracts. In a secondary screening, we assessed the eligibility of 27 full-text articles of which, 6 did not report usage data. Finally, 21 studies published from different regions of Iran from March 1999 until July 2015 were included in this study. Comprehensive meta-analysis (V2.2, Biostat) software was used to analyze the data. The meta-analysis showed that 12.8% (95% CI 9.4-15.8; I(2) = 87.8; P < 0.001 test for heterogeneity) of new TB cases and 40.1% (95% CI 28.5-53.0; I(2) = 88.2; P < 0.001 test for heterogeneity) of previously treated cases were resistant to INH. High prevalence of INH resistance among TB patients has been reported in many health-care settings, suggesting that better management of such cases, use of effective treatment regimens and establishing advanced diagnostic facilities are needed to avoid further emergence of INH-resistant TB. PMID:27156625

  13. Statin Therapy for Primary Prevention of Atrial Fibrillation: Guided by CHADS2/CHA2DS2VASc Score

    PubMed Central

    Hung, Chen-Ying; Hsieh, Yu-Cheng; Huang, Jin-Long; Lin, Ching-Heng

    2014-01-01

    Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased cardiovascular morbidity and mortality. The anti-arrhythmic effect of statins on AF prevention appears to be highly significant in most clinical studies. However, some discrepancies do exist among different clinical studies. Different clinical settings and types of stains used may explain these differences between trials. The CHADS2 and CHA2DS2VASc scoring systems have been used for stroke risk stratification in AF patients. The recent study suggested that these scores can also be used to guide statin therapy for AF prevention. Patients with higher scores had a higher risk of developing AF and gained more benefits from statins therapy than those with lower scores. This review article focused on the ability of these scores to predict AF prevention by statins. PMID:25089130

  14. Rifampicin/Cotrimoxazole/Isoniazid Versus Mefloquine or Quinine + Sulfadoxine- Pyrimethamine for Malaria: A Randomized Trial

    PubMed Central

    Genton, Blaise; Mueller, Ivo; Betuela, Inoni; Casey, Gerard; Ginny, Meza; Alpers, Michael P; Reeder, John C

    2006-01-01

    Objectives: Previous studies of a fixed combination including cotrimoxazole, rifampicin, and isoniazid (Cotrifazid) showed efficacy against resistant strains of Plasmodium falciparum in animal models and in small-scale human studies. We conducted a multicentric noninferiority trial to assess the safety and efficacy of Cotrifazid against drug-resistant malaria in Papua New Guinea. Design: The trial design was open-label, block-randomised, comparative, and multicentric. Setting: The trial was conducted in four primary care health facilities, two in urban and two in rural areas of Madang and East Sepik Province, Papua New Guinea. Participants: Patients of all ages with recurrent uncomplicated malaria were included. Interventions: Patients were randomly assigned to receive Cotrifazid, mefloquine, or the standard treatment of quinine with sulfadoxine–pyrimethamine (SP). Outcome Measures: Incidence of clinical and laboratory adverse events and rate of clinical and/or parasitological failure at day 14 were recorded. Results: The safety analysis population included 123 patients assigned to Cotrifazid, 123 to mefloquine, and 123 to quinine + SP. The Cotrifazid group experienced lower overall incidence of adverse events than the other groups. Among the efficacy analysis population (72 Cotrifazid, 71 mefloquine, and 75 quinine + SP), clinical failure rate (symptoms and parasite load) on day 14 was equivalent for the three groups (0% for Cotrifazid and mefloquine; 1% for quinine + SP), but parasitological failure rate (P. falciparum asexual blood-stage) was higher for Cotrifazid than for mefloquine or quinine + SP (9% [PCR corrected 8%] versus 0% and 3%, respectively [p = 0.02]). Conclusion: Despite what appears to be short-term clinical equivalence, the notable parasitological failure at day 14 in both P. falciparum and P. vivax makes Cotrifazid in its current formulation and regimen a poor alternative combination therapy for malaria. PMID:17192794

  15. Topical management of striae distensae (stretch marks): prevention and therapy of striae rubrae and albae.

    PubMed

    Ud-Din, S; McGeorge, D; Bayat, A

    2016-02-01

    Striae distensae (SD) are common dermal lesions, with significant physical and psychological impact. Many therapeutic modalities are available but none can completely eradicate SD. The most common therapy is the application of topicals used both therapeutically and prophylactically. Even though there are many commercially available topical products, not all have sufficient level of evidence to support their continued use in SD. The aim here was to assess the evidence for the use of topicals in SD and to propose a structured approach in managing SD. A systematic search of published literature and manufacturer website information for topicals in SD was carried out. The results showed that there are few studies (n = 11) which investigate the efficacy of topicals in management of SD. Trofolastin and Alphastria creams demonstrated level-2 evidence of positive results for their prophylactic use in SD. Additionally, tretinoin used therapeutically showed varying results whilst cocoa butter and olive oil did not demonstrate any effect. Overall, there is a distinct lack of evidence for each topical formulation. The majority of topicals failed to mention their effect on early vs. later stages of SD (striae rubrae compared to striae albae) and their role in both prevention and treatment. In conclusion, there is no topical formulation, which is shown to be most effective in eradicating or improving SD. A structured approach in identification and targeted management of symptoms and signs with the appropriate topical is required. Randomized controlled trials are necessary to assess the efficacy of topical products for treatment and prevention of different stages of SD. PMID:26486318

  16. Relapse Prevention in Major Depressive Disorder: Mindfulness-Based Cognitive Therapy Versus an Active Control Condition

    PubMed Central

    Shallcross, Amanda J.; Gross, James J.; Visvanathan, Pallavi D.; Kumar, Niketa; Palfrey, Amy; Ford, Brett Q.; Dimidjian, Sona; Shirk, Stephen; Holm-Denoma, Jill; Goode, Kari M.; Cox, Erica; Chaplin, William; Mauss, Iris B.

    2015-01-01

    Objective We evaluated the comparative effectiveness of Mindfulness-based cognitive therapy (MBCT) versus an active control condition (ACC) for depression relapse prevention, depressive symptom reduction, and improvement in life satisfaction. Method Ninety-two participants in remission from Major Depressive Disorder with residual depressive symptoms were randomized to either an 8-week MBCT or a validated ACC that is structurally equivalent to MBCT and controls for non-specific effects (e.g., interaction with a facilitator, perceived social support, treatment outcome expectations). Both interventions were delivered according to their published manuals. Results Intention-to-treat analyses indicated no differences between MBCT and ACC in depression relapse rates or time to relapse over a 60-week follow-up. Both groups experienced significant and equal reductions in depressive symptoms and improvements in life satisfaction. A significant quadratic interaction (group x time) indicated that the pattern of depressive symptom reduction differed between groups. The ACC experienced immediate symptom reduction post-intervention and then a gradual increase over the 60-week follow-up. The MBCT group experienced a gradual linear symptom reduction. The pattern for life satisfaction was identical but only marginally significant. Conclusions MBCT did not differ from an ACC on rates of depression relapse, symptom reduction, or life satisfaction, suggesting that MBCT is no more effective for preventing depression relapse and reducing depressive symptoms than the active components of the ACC. Differences in trajectory of depressive symptom improvement suggest that the intervention-specific skills acquired may be associated with differential rates of therapeutic benefit. This study demonstrates the importance of comparing psychotherapeutic interventions to active control conditions. PMID:26371618

  17. Determination of the acute toxicity of isoniazid to three invasive carp species and rainbow trout in static exposures

    USGS Publications Warehouse

    Schreier, Theresa M.; Hubert, Terrance D.

    2015-01-01

    Three invasive fishes of considerable concern to aquatic resource managers are the Hypophthalmichthys nobilis (bighead carp),Hypophthalmichthys molitrix (silver carp), and Ctenopharyngodon idella (grass carp), collectively known as Asian carps. There is a need for an effective chemical control agent for Asian carps. Isoniazid was identified as a potential toxicant for grass carp. The selective toxicity of isoniazid to grass carp was verified as a response to an anecdotal report received in 2013. In addition, the toxicity of isoniazid to bighead carp, silver carp, and Oncorhynchus mykiss (rainbow trout) was evaluated. Isoniazid was not toxic to grass carp at the reported anecdotal concentration, which was 13 milligrams per liter. Isoniazid (130 milligrams per liter) was not selectively toxic to bighead carp, silver carp, or grass carp when compared to rainbow trout.

  18. Antimicrobial therapy of pulmonary tuberculosis*

    PubMed Central

    McDermott, Walsh

    1960-01-01

    The discovery, some nine years ago, of the highly specific antituberculous drug, isoniazid, marked an important advance in the antimicrobial therapy of tuberculosis, first practised successfully with streptomycin and p-aminosalicylic acid (PAS) in the late 'forties. Isoniazid is relatively non-toxic and, unlike streptomycin, can be administered orally, so that it is eminently suitable for use, either alone or in combination with PAS, in the domiciliary treatment of tuberculous patients. The wisdom of employing it on a large scale in home-treatment programmes, however, has been questioned on the ground that such wide-spread use might result in a spread of tubercle bacilli resistant to the drug. This controversial subject is discussed in some detail in this general review of the chemotherapy of tuberculosis. The author is convinced that, so far, the benefits of isoniazid therapy have outweighed the disadvantages and, though well aware of the possible consequences in terms of isoniazid-resistance, sees no reason at the present time for not making full use of this valuable weapon in the antituberculosis armamentarium. PMID:20604078

  19. Prevention

    MedlinePlus

    ... Prevention Treatment 2003 U.S. Outbreak African Rodent Importation Ban For Clinicians Clinical Recognition Specimen Collection Treatment Smallpox ... Examining Animals with Suspected Monkeypox African Rodent Importation Ban Resources Related Links Poxvirus Molluscum Contagiosum Orf Virus ( ...

  20. Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates.

    PubMed

    Lee, A S; Teo, A S; Wong, S Y

    2001-07-01

    Novel mutations in NADH dehydrogenase (ndh) were detected in 8 of 84 (9.5%) isoniazid (INH)-resistant isolates (T110A [n = 1], R268H [n = 7]), but not in 22 INH-susceptible isolates of Mycobacterium tuberculosis. Significantly, all eight isolates with mutations at ndh did not have mutations at katG, kasA, or the promoter regions of inhA or ahpC, except for one isolate. Mutations in ndh appear to be an additional molecular mechanism for isoniazid resistance in M. tuberculosis. PMID:11408244

  1. Phage Therapy as an Approach to Prevent Vibrio anguillarum Infections in Fish Larvae Production

    PubMed Central

    Silva, Yolanda J.; Costa, Liliana; Pereira, Carla; Mateus, Cristiana; Cunha, Ângela; Calado, Ricardo; Gomes, Newton C. M.; Pardo, Miguel A.; Hernandez, Igor; Almeida, Adelaide

    2014-01-01

    Fish larvae in aquaculture have high mortality rates due to pathogenic bacteria, especially the Vibrio species, and ineffective prophylactic strategies. Vaccination is not feasible in larvae and antibiotics have reduced efficacy against multidrug resistant bacteria. A novel approach to controlling Vibrio infections in aquaculture is needed. The potential of phage therapy to combat vibriosis in fish larvae production has not yet been examined. We describe the isolation and characterization of two bacteriophages capable of infecting pathogenic Vibrio and their application to prevent bacterial infection in fish larvae. Two groups of zebrafish larvae were infected with V. anguillarum (∼106 CFU mL−1) and one was later treated with a phage lysate (∼108 PFU mL−1). A third group was only added with phages. A fourth group received neither bacteria nor phages (fish control). Larvae mortality, after 72 h, in the infected and treated group was similar to normal levels and significantly lower than that of the infected but not treated group, indicating that phage treatment was effective. Thus, directly supplying phages to the culture water could be an effective and inexpensive approach toward reducing the negative impact of vibriosis in larviculture. PMID:25464504

  2. Antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke: a critical review.

    PubMed

    O'Donnell, Martin J; Hankey, Graeme J; Eikelboom, John W

    2008-05-01

    For patients with ischemic stroke or transient ischemic attack caused by atherothromboembolism, immediate and long-term aspirin reduces the relative risk of recurrent stroke, MI, and death attributable to vascular causes. Oral anticoagulation is not more effective than aspirin. Long-term clopidogrel reduces the relative risk of stroke, MI, or vascular death by about 9% (0.3% to 16.5%) compared with aspirin. Any long-term benefits of clopidogrel combined with aspirin, compared with aspirin or clopidogrel alone, appear to be offset by increased major bleeding. The combination of aspirin and extended-release dipyridamole reduces the relative odds of stroke, MI, or vascular death by about 18% (odds ratio 0.82, 0.74 to 0.91) compared with aspirin alone without causing more bleeding. Cilostazole reduces the risk of stroke, MI, or vascular death by 39% compared to placebo. A large clinical trial comparing clopidogrel with the combination of aspirin and dipyridamole, in >20 000 patients with recent (<120 days) atherothrombotic ischemic stroke, is expected to report in 2008. Emerging antiplatelet therapies presently being evaluated for secondary prevention of atherothromboembolism include other P(2)Y(12) ADP receptor antagonists (prasugrel, cangrelor, AZD 6140), thromboxane receptor antagonists (eg, S18886 - terutroban), and thrombin receptor (PAR-1) antagonists (eg, SCH530348). PMID:18369175

  3. The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders

    PubMed Central

    Działo, Magdalena; Mierziak, Justyna; Korzun, Urszula; Preisner, Marta; Szopa, Jan; Kulma, Anna

    2016-01-01

    Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract. PMID:26901191

  4. Molecular-based screening for perinatal group B streptococcal infection: implications for prevention and therapy.

    PubMed

    Emonet, Stéphane; Schrenzel, Jacques; Martinez de Tejada, Begoña

    2013-12-01

    Group B streptococci (GBS) are a leading cause of infectious neonatal morbidity and mortality. Timely and accurate identification of colonized pregnant women is imperative to implement intrapartum antibioprophylaxis (IAP) to reduce the risk of early neonatal sepsis. Current guidelines recommend screening for GBS carriage with vaginal-rectal cultures. However, cultures require 24-72 h, thus precluding their use for intrapartum screening and these are only performed at 35-37 weeks gestation. New rapid molecular-based tests can detect GBS within hours. They have the potential to be used intrapartum and to allow for selective IAP in women carrying GBS. An advantage is that they can sometimes be performed by non-laboratory staff in the labor suite, thus avoiding delays in sample transfers to the microbiology laboratory. Another possible use of molecular-based assays is for the diagnosis of neonatal sepsis, where tests with a short turnaround time and high sensitivity and specificity are crucial. In this situation, the detection of microorganisms once antibiotic therapy has already been started is important, as treatment is started immediately once sepsis is suspected without waiting for microbiological confirmation. In this article, we discuss the state-of-the-art molecular-based tests available for GBS screening during pregnancy, as well as their implications for IAP for the diagnosis and prevention of neonatal sepsis. PMID:23832874

  5. The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders.

    PubMed

    Działo, Magdalena; Mierziak, Justyna; Korzun, Urszula; Preisner, Marta; Szopa, Jan; Kulma, Anna

    2016-01-01

    Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract. PMID:26901191

  6. Treatment as prevention: are Argentinean HIV care providers willing to adopt earlier antiretroviral therapy?

    PubMed

    Socías, María Eugenia; Sued, Omar; Pryluka, Daniel; Patterson, Patricia; Fink, Valeria; Cesar, Carina; Cahn, Pedro

    2014-01-01

    HIV guidelines increasingly recommend antiretroviral therapy (ART) initiation at a higher CD4 levels. The extent to which these evolving standards are translated into routine clinical care has not been evaluated in Argentina. During October 2012, we conducted an online survey among Argentinean HIV clinicians to assess their attitudes and practices toward ART initiation and its potential use for HIV prevention. Of the 280 physicians included, 61% would prescribe ART at CD4 ≤ 500 cells/µL for asymptomatic patients. Although, only 11% would recommend ART irrespective of CD4 cell count, 72% would do it for serodiscordant couples, and 75% for sex workers. Most participants agreed that they would consider earlier initiation of ART if transmission risk exists, and that expansion of ART could help decrease HIV incidence. These results suggest that a large proportion of Argentinean HIV care providers are willing to adopt the recently updated Argentinean guidelines recommending earlier ART, especially when high HIV transmission risk exists. PMID:24773142

  7. Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention.

    PubMed

    Joya, Xavier; Garcia-Algar, Oscar; Salat-Batlle, Judith; Pujades, Cristina; Vall, Oriol

    2015-03-01

    Ethanol is the most common human teratogen, and its consumption during pregnancy can produce a wide range of abnormalities in infants known as fetal alcohol spectrum disorder (FASD). The major characteristics of FASD can be divided into: (i) growth retardation, (ii) craniofacial abnormalities, and (iii) central nervous system (CNS) dysfunction. FASD is the most common cause of nongenetic mental retardation in Western countries. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, the induction of oxidative stress is believed to be one central process linked to the development of the disease. Currently, there is no known effective strategy for prevention (other than alcohol avoidance) or treatment. In the present review we will provide the state of art in the evidence for the use of antioxidants as a potential therapeutic strategy for the treatment using whole-embryo and culture cells models of FASD. We conclude that the imbalance of the intracellular redox state contributes to the pathogenesis observed in FASD models, and we suggest that antioxidant therapy can be considered a new efficient strategy to mitigate the effects of prenatal ethanol exposure. PMID:25131946

  8. Prevalence and early attack rate of tuberculosis among close family contacts of tuberculous patients in South India under domiciliary treatment with isoniazid plus PAS or isoniazid alone*

    PubMed Central

    Ramakrishnan, C. V.; Andrews, R. H.; Devadatta, S.; Fox, Wallace; Radhakrishna, S.; Somasundaram, P. R.; Velu, S.

    1961-01-01

    The authors present a report from the Tuberculosis Chemotherapy Centre, Madras, on the prevalence and attack rate of tuberculosis among close family contacts of tuberculous patients in South India undergoing domiciliary chemotherapy either with isoniazid plus PAS or with one of three regimens of isoniazid alone. The report gives (a) the prevalence of tuberculosis among the contacts at the time of diagnosis of the disease in the patients and (b) the incidence of tuberculosis in the contacts during the first year of treatment of the patients. The contacts were divided into four series, corresponding to the four chemotherapeutic regimens of the patients. The prevalence of active tuberculosis was found to be particularly high among children under five years of age, being 12.0% as compared with 7.6% for all age-groups combined. The incidence of active tuberculosis during the year of treatment of the patients was also found to be highest in the under five years' age-group—a further indication that child contacts are especially vulnerable to infection. The incidence was considerably higher in the first quarter of the year than in the other quarters, and it was lowest in the last quarter. This finding, together with the fact that the attack rates in the four contact series were not related either to the duration of bacteriological positivity in the patients or to the period of excretion of isoniazid-resistant organisms by the patients, suggests that the major risk to contacts in the first year results from exposure to the patient before treatment rather than from exposure during treatment. These results thus confirm the findings in an earlier study by the Centre of the contacts of patients in a controlled comparison of chemotherapy with isoniazid plus PAS at home and in sanatorium. PMID:14038589

  9. Understanding Concerns About Treatment-as-Prevention Among People with HIV who are not Using Antiretroviral Therapy.

    PubMed

    Newman, C E; de Wit, J; Persson, A; Holt, M; Slavin, S; Kidd, M R; Post, J J; Wright, E; Mao, L

    2015-05-01

    The use of antiretroviral therapy to prevent HIV transmission is now advocated in many settings, yet little research has documented the views of people with HIV. Semi-structured interviews were conducted in Australia between 2012 and 2014 with 27 HIV-positive people not using treatment at the time of interview. Thematic analysis of views on treatment-as-prevention found that while many participants recognised potential prevention benefits, only a minority was in support of initiating treatment solely to achieve those benefits. A range of uncertain or critical views were expressed regarding who would benefit, risk reduction, and changing treatment norms. Participants resisted responsibility narratives that implied treatment should be used for the public good, in favour of making considered decisions about their preferred approach to managing HIV. Engaging communities in dialogue and debate regarding the risks and benefits of treatment will be critical if this new prevention strategy is to engender public trust. PMID:25432878

  10. Pharmacogenetics of apolipoprotein E gene during lipid-lowering therapy: lipid levels and prevention of coronary heart disease.

    PubMed

    Nieminen, Tuomo; Kähönen, Mika; Viiri, Leena E; Grönroos, Paula; Lehtimäki, Terho

    2008-10-01

    A non-optimal plasma concentration of lipids is among the major modifiable risk factors of atherosclerosis. Therefore, the prevention of cardiovascular disease by means of lipid-lowering therapy with statins and other agents is of great importance for patient groups where a lifestyle change, for example, diet modification, does not lead to adequately reduced lipid levels. The response of low-density-lipoprotein cholesterol (LDL-C) levels to statin therapy is highly variable. This is partly attributed to hereditary variation in genes involved in pharmacokinetics, pharmacodynamics and lipid metabolism. The pharmacogenetics of lipid-lowering therapy have been investigated for more than 40 different genes. The gene for apolipoprotein E (APOE) has been the most frequently studied, particularly regarding the epsilon2/epsilon3/epsilon4 polymorphism. Those with the epsilon4 allele seem to have the poorest and those with the epsilon2 allele the strongest response to statins with regards to LDL-C levels. In addition, the epsilon2 carriers may reach the LDL-C treatment goals more frequently than epsilon4 carriers. Few studies have investigated the interaction of the APOE epsilon2/epsilon3/epsilon4 polymorphism and lipid-lowering therapy in relation to the course of coronary heart disease; the results are contradictory and so far inconclusive. This review summarizes the pharmacogenetic findings related to the influence of APOE gene variation on lipid responses and the prevention of coronary heart disease during lipid-lowering therapy. PMID:18855536

  11. Isoniazid pharmacokinetics, pharmacodynamics and dosing in South African infants

    PubMed Central

    Kiser, Jennifer J.; Zhu, Rui; D’Argenio, David Z.; Cotton, Mark F.; Bobat, Raziya; McSherry, George D.; Madhi, Shabir A; Carey, Vincent J.; Seifart, Heiner I.; Werely, Cedric J.; Fletcher, Courtney V.

    2012-01-01

    Aims There are limited data on isoniazid (INH) pharmacokinetics in infants and young children and, therefore, uncertainty on appropriate dosing. Methods Pharmacokinetic data were obtained from perinatally HIV-exposed South African infants ages 3–24 months receiving INH 10–20 mg/kg/day orally for Mycobacterium tuberculosis (TB) prophylaxis. INH pharmacokinetic parameters were characterized with a population pharmacokinetic approach. Dosing simulations were performed to evaluate weight-based INH doses in children based on N-acetyltransferase 2 enzyme (NAT2) genotype, age, maximum concentrations (Cmax) ≥ 3mg/L, and area under the curve (AUC0-24) ≥ 10.52 mg*hr/L. Results In 151 infants (53% female, 48% HIV positive) receiving a mean INH dose of 14.5 mg/kg/day, mean (±SD) Cmax at 3, 6, and 23 months of age were 10.0 (3.5), 8.6 (2.6), and 9.3 (3.8) mg/L, respectively, mean (±SD) AUC0-24 were 53.6 (26.8), 42 (19.9), and 44 (30.7) mg*hr/L, respectively, and mean (±SD) half-life were 2.1 (0.7), 1.9 (0.6), and 1.8 (0.9) hours, respectively. A trimodal apparent oral clearance of INH as a function of NAT2 genotype was apparent as early as 3 months. INH was well tolerated. At an average INH dose of 14.5 mg/kg/day, 99% of infants ages 3–24 months have an INH Cmax ≥ 3 mg/L and 98% have an INH AUC0-24 ≥ 10.52 mg*hr/L. Conclusions INH at an average dose of 14.5 mg/kg once daily was well tolerated in infants and achieved INH Cmax values ≥ 3 mg/L and AUC0-24 values ≥ 10.52 mg*hr/L. PMID:22695364

  12. Adherence to Antiretroviral Therapy for the Success of Emerging Interventions to Prevent HIV Transmission: A Wake up Call

    PubMed Central

    Nachega, Jean B; Uthman, Olalekan A; Mills, Edward J; Quinn, Thomas C

    2012-01-01

    Despite recent successes in several HIV prevention trials, the epidemic continues to increase in many countries. The most successful biomedical interventions to prevent HIV have been the use of Antiretroviral Therapy (ART) to Prevent Mother-To-Child Transmission (PMTCT), and sexual transmission via microbicides, PreExposure Prophylaxis (PrEP), and treatment of the infected person within discordant couples. In addition medical male circumcision has also been shown to be highly effective in prevention of HIV acquisition. However, emerging data demonstrate that adherence to several of these prevention interventions is critical. ART adherence during and after pregnancy has been shown to be significantly below that recommended for adequate virologic suppression, particularly during the postpartum period. Five recent PrEP trials also demonstrate that the success of PrEP as a public health intervention will necessitate monitoring ART adherence and will include additional interventions to improve or maintain adherence to optimal levels. New successes in HIV prevention research have been tempered by suboptimal adherence. There is a critical need to define practical and effective adherence monitoring strategies as well as controlled trials of adherence interventions in the era of PrEP, Treatment as Prevention (TasP), and PMTCT to maximize their benefit. PMID:24032088

  13. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

    PubMed Central

    Anglemyer, Andrew; Rutherford, George W; Horvath, Tara; Baggaley, Rachel C; Egger, Matthias; Siegfried, Nandi

    2014-01-01

    subgroup analyses among the observational studies to see if the effect of ART on prevention of HIV differed by the index partner’s CD4 cell count. Among couples in which the infected partner had ≥350 CD4 cells/µL, we estimated a rate ratio of 0.12 [95% CI 0.01, 1.99]. In this subgroup, there were 247 transmissions in untreated couples and 30 in treated couples. Authors’ conclusions ART is a potent intervention for prevention of HIV in discordant couples in which the index partner has ≤550 CD4 cells/µL. A recent multicentre RCT confirms the suspected benefit seen in earlier observational studies and reported in more recent ones. Questions remain about durability of protection, the balance of benefits and adverse events associated with earlier therapy, long-term adherence and transmission of ART-resistant strains to partners. Resource limitations and implementation challenges must also be addressed. Counselling, support, and follow up, as well as mutual disclosure, may have a role in supporting adherence, so programmes should be designed with these components. In addition to ART provision, the operational aspects of delivering such programmes must be considered. PMID:23633367

  14. Rapid genotypic detection of rifampin- and isoniazid-resistant Mycobacterium tuberculosis directly in clinical specimens.

    PubMed

    Bang, Didi; Bengård Andersen, Ase; Thomsen, Vibeke Østergaard

    2006-07-01

    A multiplex PCR DNA strip assay (Genotype MTBDR) designed to detect rifampin (rpoB) and high-level isoniazid (katG) resistance mutations in Mycobacterium tuberculosis isolates was optimized for clinical specimens. Successful genotypic results were achieved with 36 of 38 (95%) smear-positive respiratory specimens, allowing rapid therapeutic adjustments in transmittable drug-resistant tuberculosis. PMID:16825393

  15. Isoniazid poisoning: Pharmacokinetics and effect of hemodialysis in a massive ingestion.

    PubMed

    Skinner, Kirsty; Saiao, Ana; Mostafa, Ahmed; Soderstrom, Jessamine; Medley, Gregory; Roberts, Michael S; Isbister, Geoffrey K

    2015-10-01

    Isoniazid is a rare overdose that causes seizures and there is limited evidence to guide treatment. We report a 20-year-old female migrant who presented with recurrent seizures after ingesting 25 g of isoniazid. She was treated with activated charcoal, repeated doses of midazolam for the seizures, and given multiple doses of pyridoxine (14 mg), limited by availability. She was admitted to intensive care, and 5.5 hours post-ingestion, she was commenced on continuous veno-venous hemodiafiltration (CVVHDF). She was extubated after 24 hours and CVVHDF was ceased 6 hours later (30 hours post-overdose). Her renal function remained normal and her initial lactate was the highest at 2.3. She made a full recovery. Five plasma samples were collected before, during, and after CVVHDF, and isoniazid was quantified with liquid chromatography-tandem mass spectrometry. A pharmacokinetic analysis of time-isoniazid concentration data was fitted to a two-compartment model with first-order input (with fixed ka ) with the effect of CVVHDF modeled as a time-dependent covariate. This suggested that there was initially good clearance with CVVHDF (4 times endogenous clearance), which rapidly declined within hours. PMID:25779481

  16. Non-Drug Therapy and Prevention of Diabetes Mellitus by Dalk (Massage)

    PubMed Central

    Bayat, Davood; Vakilinia, Seyed Reza; Asghari, Majid

    2016-01-01

    Background: According to WHO estimation, the number of diabetic patients would reach about 591.9 million people in 2035. The tendency towards other kinds of treatment is increasing because of the high therapeutic expenditures and current medical complications. Positive results of massage in recent articles and the prominent role of dalk in Iranian traditional medicine led us to the present study review. Methods: Studying Iranian traditional medicine textbooks, such as Canon of Ibn Sina, Kholasat Al Hekma of Aghili, Zakhireh-ye Khwarazm shahi of Jorjani, Alhavi of Razes and Kamel-al-sanaat of Ibn Abas were done on the topic of dalk discussion. Additionally, a search on “massage and diabetes mellitus” articles was done in motor search engines of PubMed, Google Scholars and the site of “Farhangestane Oloume Pezeshki”. The data were eventually compared and evaluated. Results: In Iranian traditional medicine, dalk means kneading or massage of the body. Depending on the quality and quantity of the performance, it was divided into different kinds. The mechanism of dalk is to increase the blood supply in organs and subsequently increasing organ’s warmness and metabolism that lead to increased residues expulsion. Therefore, it could be advised to healthcare system as a means of treatment. On the other hand, for different diseases such as asthma, arthritis, insomnia, paralysis, DM, and constipation the effect of massage was evaluated and its positive results were confirmed. For example, in DM, its effects in decreasing FBS and HBA1C are shown. Conclusion: According to Iranian traditional medicine and latest articles, dalk as a non-drug therapy and prevention manner is recommended. PMID:27516677

  17. [Osteoporosis in rheumatoid arthritis--significance of alfacalcidol in prevention and therapy].

    PubMed

    Schacht, E

    2000-01-01

    production of Th2 helper cells which produce bone protective cytokines like IL-4 and IL-10. It is important to know that D-hormone protects osteoblasts against TNF-alpha-induced cell death. After conversion to D-hormone in the liver and bone, alfacalcidol antagonises the above described pathogenetic factors of the corticosteroids. D-hormone is one of the body's own immunoregulators, which is produced in macrophages in cases of need to reduce immunological overreactions in a feed-back loop. Improved understanding of the pathogenesis of corticosteroid-induced osteoporosis and of the pharmacological effects of alfacalcidol in this type of iatrogenic bone loss as well as the results of specific animal models simulating bone loss in inflammatory diseases explain the favourable effects of alfacalcidol in this indication. Various clinical studies have demonstrated clearly that alfacalcidol retards corticosteroid-induced bone loss in contrast to plain vitamin D. Due to its immunomodulating properties, alfacalcidol is particularly suitable for RA-induced bone loss and for the prevention of transplantation osteoporosis, and an adjuvant contribution to the disease-modifying therapy of RA and to the immunosuppressive therapy after transplantation can not be excluded. PMID:10769429

  18. The role of statin therapy in the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials

    PubMed Central

    Fang, Wen-tong; Li, Hong-jian; Zhang, Haibo; Jiang, Su

    2012-01-01

    AIMS The use of statins has been suggested to protect against atrial fibrillation (AF) in some clinical observational and experimental studies but has remained inadequately explored. This study was designed to examine whether statins can reduce the risk of AF. METHODS Meta-analysis of randomized, controlled trials with use of statins on incidence or recurrence of AF was performed. RESULTS Twenty studies with 23 577 patients were included in the analysis. Seven studies investigated the use of statins in patients with AF, 11 studies investigated the primary prevention of statins in patients without AF, and two studies investigated mixed populations of patients. The incidence or recurrence of AF occurred in 1543 patients. Overall, statin therapy was significantly associated with a decreased risk of AF compared with control (odds ratio 0.49, 95% confidence interval 0.37–0.65; P < 0.00001). A beneficial effect was found in the atorvastatin subgroup and the simvastatin subgroup, but not in the pravastatin subgroup or the rosuvastatin subgroup. The benefit of statin therapy appeared to be more pronounced in secondary prevention (odds ratio 0.34, 95% confidence interval 0.18–0.64; P < 0.0008) than in primary prevention (odds ratio 0.54, 95% confidence interval 0.40–0.74; P < 0.0001). CONCLUSIONS Statin therapy was significantly associated with a decreased risk of incidence or recurrence of AF. Heterogeneity was explained by differences in statin types, patient populations and surgery types. The benefit of statin therapy seemed more pronounced in secondary than in primary prevention. PMID:22376147

  19. Supporting our military families: a case for a larger role for occupational therapy in prevention and mental health care.

    PubMed

    Cogan, Alison M

    2014-01-01

    More than 2 million U.S. military servicemembers have deployed to Afghanistan or Iraq since September 11, 2001. Unlike during prior conflicts, many servicemembers leave spouses and children behind. Long, multiple deployments cause strain on family at home, with new challenges arising when servicemembers return from combat and reintegrate into family and civilian life. In World Wars I and II, occupational therapy practitioners played a significant role in supporting servicemember reintegration. However, their presence in program delivery in this practice area is limited. Occupational therapy researchers and practitioners can make a valuable contribution by helping families tailor daily activities and routines to address challenges and optimize health and wellness. However, barriers such as reimbursement for services, workforce availability, and access to military families have limited the profession's full engagement. Advocacy is needed to help establish occupational therapy as a key component of the mental and preventive health care teams serving military servicemembers. PMID:25005512

  20. [Influence of isoniazid complex with A-I apolipoprotein on activity of lysosomal enzymes in mice with tuberculous inflammation model].

    PubMed

    Sumenkova, D V; Poliakov, L M; Panin, L E

    2012-01-01

    It is established that isoniazid (isonicotinic acid hydrazide) can interact with A-I apolipoprotein to form a complex, which can be considered as the transport form of the preparation. The use of this complex for the treatment of mice with BCG-induced tuberculous inflammation led to an increase in the free activities of acid phosphatase and cathepsin D in the liver, which was decreased under the action of mycobacteria and the free form of isoniazid. The isoniazid complex with A-I apolipoprotein exhibited more expressed anti-inflammatory effect (estimated by the activity of chitotriosidase in blood serum) as compared to the free drug. PMID:23323330

  1. A descriptive study of a manual therapy intervention within a randomised controlled trial for hamstring and lower limb injury prevention

    PubMed Central

    2010-01-01

    Background There is little literature describing the use of manual therapy performed on athletes. It was our purpose to document the usage of a sports chiropractic manual therapy intervention within a RCT by identifying the type, amount, frequency, location and reason for treatment provided. This information is useful for the uptake of the intervention into clinical settings and to allow clinicians to better understand a role that sports chiropractors offer. Methods All treatment rendered to 29 semi-elite Australian Rules footballers in the sports chiropractic intervention group of an 8 month RCT investigating hamstring and lower-limb injury prevention was recorded. Treatment was pragmatically and individually determined and could consist of high-velocity, low-amplitude (HVLA) manipulation, mobilization and/or supporting soft tissue therapies. Descriptive statistics recorded the treatment rendered for symptomatic or asymptomatic benefit, delivered to joint or soft tissue structures and categorized into body regions. For the joint therapy, it was recorded whether treatment consisted of HVLA manipulation, HVLA manipulation and mobilization, or mobilization only. Breakdown of the HVLA technique was performed. Results A total of 487 treatments were provided (mean 16.8 consultations/player) with 64% of treatment for asymptomatic benefit (73% joint therapies, 57% soft tissue therapies). Treatment was delivered to approximately 4 soft tissue and 4 joint regions each consultation. The most common asymptomatic regions treated with joint therapies were thoracic (22%), knee (20%), hip (19%), sacroiliac joint (13%) and lumbar (11%). For soft tissue therapies it was gluteal (22%), hip flexor (14%), knee (12%) and lumbar (11%). The most common symptomatic regions treated with joint therapies were lumbar (25%), thoracic (15%) and hip (14%). For soft tissue therapies it was gluteal (22%), lumbar (15%) and posterior thigh (8%). Of the joint therapy, 56% was HVLA manipulation only

  2. Combination therapy for hypertension in patients with CKD: a subanalysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events trial.

    PubMed

    Rakugi, Hiromi; Ogihara, Toshio; Umemoto, Seiji; Matsuzaki, Masunori; Matsuoka, Hiroaki; Shimada, Kazuyuki; Higaki, Jitsuo; Ito, Sadayoshi; Kamiya, Akira; Suzuki, Hiromichi; Ohashi, Yasuo; Shimamoto, Kazuaki; Saruta, Takao

    2013-11-01

    The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was a multicenter, randomized, three-arm comparative study (N=3293) undertaken to determine the optimal combination therapy, based on the occurrence of cardiovascular events in patients treated with an angiotensin II receptor blocker (ARB), a β-blocker (BB) or a thiazide diuretic (TD) in addition to the calcium antagonist benidipine as baseline medication. This subanalysis was conducted to compare the efficacy of three combination therapies in a subset of 834 patients with chronic kidney disease (CKD) (287 patients treated with benidpine-ARB, 283 patients treated with benidipine-BB and 264 patients treated with benidipine-TD). The incidence of composite cardiovascular events as the primary end point did not differ among these three groups. The incidence of hard end points and cerebrovascular events among these groups did not differ either, although the incidence among all patients in the COPE trial was lower in the benidipine-TD group than in the benidipine-BB group. The incidence of new-onset diabetes mellitus was higher in the benidipine-TD group than in the benidipine-ARB group among patients with CKD. The estimated glomerular filtration rate (eGFR) was maintained even after 12 months of treatment in patients with a baseline eGFR <60 ml min(-1) per 1.73 m(2) regardless of the treatment group, although the eGFR decreased over time in all patients in the three groups. In conclusion, in patients with CKD, all of the tested combination therapies demonstrated comparable efficacy in terms of prevention of cardiovascular events as well as maintenance of eGFR. PMID:23864054

  3. Lack of benefits for prevention of cardiovascular disease with aspirin therapy in type 2 diabetic patients - a longitudinal observational study

    PubMed Central

    Leung, Wilson Y; So, Wing-yee; Stewart, Derek; Lui, Augustine; Tong, Peter C; Ko, Gary T; Kong, Alice P; Ma, Ronald C; Chan, Francis K; Yang, Xilin; Chiang, Sau-chu; Chan, Juliana C

    2009-01-01

    Background The risk-benefit ratio of aspirin therapy in prevention of cardiovascular disease (CVD) remains contentious, especially in type 2 diabetes. This study examined the benefit and harm of low-dose aspirin (daily dose < 300 mg) in patients with type 2 diabetes. Methods This is a longitudinal observational study with primary and secondary prevention cohorts based on history of CVD at enrolment. We compared the occurrence of primary composite (non-fatal myocardial infarction or stroke and vascular death) and secondary endpoints (upper GI bleeding and haemorrhagic stroke) between aspirin users and non-users between January 1995 and July 2005. Results Of the 6,454 patients (mean follow-up: median [IQR]: 4.7 [4.4] years), usage of aspirin was 18% (n = 1,034) in the primary prevention cohort (n = 5731) and 81% (n = 585) in the secondary prevention cohort (n = 723). After adjustment for covariates, in the primary prevention cohort, aspirin use was associated with a hazard-ratio of 2.07 (95% CI: 1.66, 2.59, p < 0.001) for primary endpoint. There was no difference in CVD event rate in the secondary prevention cohort. Overall, aspirin use was associated with a hazard-ratio of 2.2 (1.53, 3.15, p < 0.001) of GI bleeding and 1.71 (1.00, 2.95, p = 0.051) of haemorrhagic stroke. The absolute risk of aspirin-related GI bleeding was 10.7 events per 1,000 person-years of treatment. Conclusion In Chinese type 2 diabetic patients, low dose aspirin was associated with a paradoxical increase in CVD risk in primary prevention and did not confer benefits in secondary prevention. In addition, the risk of GI bleeding in aspirin users was rather high. PMID:19878541

  4. Computer-aided study of the relationship between structure and antituberculosis activity of a series of isoniazid derivatives

    NASA Astrophysics Data System (ADS)

    Klopman, Gilles; Fercu, Dan; Jacob, Jason

    1996-04-01

    The Multiple Computer Automated Structure Evaluation (MultiCASE) program was used to analyze the relationship between the structure and antituberculous activity of a series of 136 hydrazides, most of them isoniazid related. The structural features revealed by this analysis are discussed. The most significant one seemed to be the distance between the pyridinic nitrogen and the terminal nitrogen of the hydrazido group. Given the affiliation of these two heteroatoms with a planar conjugated system, we suggest that Schiff base chemistry similar to that of vitamin B 6 may be involved in the mode of action of isoniazid and its related compounds. A mechanism of action of isoniazid is proposed and suggestions for the design of new isoniazid-type drugs are made.

  5. PCR-Restriction Fragment Length Polymorphism for Rapid, Low-Cost Identification of Isoniazid-Resistant Mycobacterium tuberculosis▿

    PubMed Central

    Caws, Maxine; Tho, Dau Quang; Duy, Phan Minh; Lan, Nguyen Thi Ngoc; Hoa, Dai Viet; Torok, Mili Estee; Chau, Tran Thi Hong; Van Vinh Chau, Nguyen; Chinh, Nguyen Tran; Farrar, Jeremy

    2007-01-01

    PCR-restriction fragment length poymorphism (PCR-RFLP) is a simple, robust technique for the rapid identification of isoniazid-resistant Mycobacterium tuberculosis. One hundred consecutive isolates from a Vietnamese tuberculosis hospital were tested by MspA1I PCR-RFLP for the detection of isoniazid-resistant katG_315 mutants. The test had a sensitivity of 80% and a specificity of 100% against conventional phenotypic drug susceptibility testing. The positive and negative predictive values were 1 and 0.86, respectively. None of the discrepant isolates had mutant katG_315 codons by sequencing. The test is cheap (less than $1.50 per test), specific, and suitable for the rapid identification of isoniazid resistance in regions with a high prevalence of katG_315 mutants among isoniazid-resistant M. tuberculosis isolates. PMID:17428939

  6. Risk Factors for Acquired Rifamycin and Isoniazid Resistance: A Systematic Review and Meta-Analysis

    PubMed Central

    Rockwood, Neesha; Abdullahi, Leila H.; Wilkinson, Robert J.; Meintjes, Graeme

    2015-01-01

    Background Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies. Methods Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies. Results Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I2 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I2 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5th to 95th percentile 0.07 to 3.2%). Conclusion Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with

  7. The effects of isoniazid on the carbohydrates of Mycobacterium tuberculosis BCG

    PubMed Central

    Winder, F. G.; Rooney, S. A.

    1970-01-01

    1. Mycobacterium tuberculosis BCG was usually grown in glycerol–asparagine–casein hydrolysate medium. A soluble fraction was obtained from the cells with aq. 50% ethanol; unbound lipids were then removed and the cells were treated with dilute alkali to give, after acidification, an alkali-extractable fraction and an insoluble fraction. On occasion, lipopolysaccharides were obtained by extracting with phenol or dimethyl sulphoxide instead of alkali. The soluble fraction contained, particularly after long extraction, polysaccharide containing mainly glucose, in addition to trehalose and monosaccharides and their derivatives. The alkali-extractable fraction contained polysaccharides containing mannose, glucose, arabinose, galactose and 6-O-methylglucose. These could be resolved into three fractions of markedly different molecular size. It is argued that the high-molecular-weight materials originated from the outside of the cell envelope and the medium-molecular-weight materials from a middle layer of the envelope. 2. Exposure of the growing cells to isoniazid, usually at 1 or 10μg/ml for 6–12h, increased the total cell carbohydrate, mainly due to an increase in trehalose and in insoluble glucan. It also facilitated the extraction of polysaccharide into the medium and the soluble fraction. This produced about a 25% decrease in the amount of carbohydrate in the alkaline-extractable fraction, mainly due to a fall in glucose, arabinose and 6-O-methylglucose. The decrease was confined to polysaccharides of large and medium molecular weight. When intact lipopolysaccharides were extracted, their amount was also decreased by isoniazid. 3. Substitution of ammonium sulphate for asparagine and casein hydrolysate in the medium, so that glycerol was the sole carbon source, decreased the carbohydrate accumulation brought about by isoniazid but did not alter its effect on polysaccharide extraction. 4. Growth with 14C-labelled substrates showed that glycerol provided two to

  8. Preamputation mirror therapy may prevent development of phantom limb pain: a case series.

    PubMed

    Hanling, Steven R; Wallace, Scott C; Hollenbeck, Kerry J; Belnap, Brian D; Tulis, Matthew R

    2010-02-01

    We report the cases of 4 patients who performed daily mirror therapy for 2 wk before undergoing elective limb amputation. One patient experienced no phantom limb pain (PLP). Two patients experienced rare episodes of mild PLP without effect on their participation in physical therapy (PT) or their quality of life. One patient reported daily, brief episodes of moderate PLP without effect on his participation in PT or his stated quality of life. These results indicate that preoperative mirror therapy may improve postamputation PT compliance and decrease the incidence of PLP. Future prospective studies are needed to confirm the results of this case series. PMID:19917622

  9. Localized surface plasmon resonance of gold nanoparticles as colorimetric probes for determination of Isoniazid in pharmacological formulation

    NASA Astrophysics Data System (ADS)

    Zargar, Behrooz; Hatamie, Amir

    2013-04-01

    Isoniazid is an important antibiotic, which is widely used to treat tuberculosis. This study presents a colorimetric method for the determination of Isoniazid based on localized surface plasmon resonance (LSPR) property of gold nanoparticles. An LSPR band is produced by reducing gold ions in solution using Isoniazid as the reducing agent. Influences of the following relevant variables were examined and optimized in the experiment, formation time of gold nanoparticles, pH, buffer and stabilizer. These tests demonstrated that under optimum conditions the absorbance of Au nanoparticles at 530 nm related linearly to the concentration of Isoniazid in the range of 1.0-8.0 μg mL-1 with a detection limit of 0.98 μg mL-1. This colorimetric method has been successfully applied to the determine Isoniazid in tablets and spiked serum samples. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for analysis of Isoniazid.

  10. Benzydamine hydrochloride in prevention and management of pain in oral mucositis associated with radiation therapy

    SciTech Connect

    Epstein, J.B.; Stevenson-Moore, P.

    1986-08-01

    Benzydamine hydrochloride rinse reduced pain associated with radiation mucositis when it was used during the course of radiation therapy. Fewer patients using benzydamine rinse required systemic analgesics. All patients using benzydamine tolerated the rinse well and continued with regular rinsing throughout the course of radiation therapy. Benzydamine hydrochloride is currently undergoing clinical trials in the United States for application for approval from the Food and Drug Administration.

  11. Development and Validation of an HPLC Method for Simultaneous Determination of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol Hydrochloride in Pharmaceutical Formulations.

    PubMed

    Chellini, Paula R; Lages, Eduardo B; Franco, Pedro H C; Nogueira, Fernando H A; César, Isabela C; Pianetti, Gerson A

    2015-01-01

    Tuberculosis treatment consists of a fixed dose combination of rifampicin (RIF), isoniazid (INH), pyrazinamide (PYZ), and ethambutol hydrochloride (EMB). The combined treatment using various drugs is necessary for patient curing, without recrudescence, and for prevention of drug-resistant mutants, which may occur during treatment. An HPLC-diode array detector (DAD) method for the simultaneous determination of RIF, INH, PYZ, and EMB in fixed dose combination tablets was developed and validated. Chromatographic experiments were performed on an Agilent 1200 HPLC system, and the separation was carried out on a Purospher STAR RP18e (250×4.6 mm id, 5 μm, Merck) analytical column. Gradient elution was carried out with a mobile phase of 20 mM monobasic sodium phosphate buffer with 0.2% triethylamine (pH 7.0) and acetonitrile at a flow rate of 1.5 mL/min. The total run time was 12 min, and the re-equilibration time was 5 min. EMB detection was performed at 210 nm, and RIF, INH, and PYZ were detected at 238 nm, using a DAD. The method proved to be specific, linear (r2>0.99), precise (RSD<2%), accurate, and robust and may be applied to the QC analysis of pharmaceutical formulations. PMID:26525241

  12. Electrochemical sensor for Isoniazid based on the glassy carbon electrode modified with reduced graphene oxide-Au nanomaterials.

    PubMed

    Guo, Zhuo; Wang, Ze-Yu; Wang, Hui-Hua; Huang, Guo-Qing; Li, Meng-Meng

    2015-12-01

    A sensitive electrochemical sensor has been fabricated to detect Isoniazid (INZ) using reduced graphene oxide (RGO) and Au nanocomposites (RGO-Au). RGO-Au nanocomposites were synthesized by a solution-based approach of chemical co-reduction of Au(III) and graphene oxide (GO), and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, and Fourier transform infrared (FT-IR). The Au nanoparticles separate the RGO sheets in the precipitate and prevent RGO sheets from aggregation upon π-π stacking interactions. RGO-Au nanocomposites were used to modify the glassy carbon electrode (GCE). The electrochemical properties of RGO-Au/GCE were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and the RGO-Au/GCE exhibited remarkably strong electrocatalytic activities towards INZ. Under the optimized conditions, there was linear relationships between the peak currents and the concentrations in the range of 1.0×10(-7)M to 1.0×10(-3)M for INZ, with the limit of detection (LOD) (based on S/N=3) of 1.0×10(-8)M for INZ. PMID:26354255

  13. Hepatitis C virus in the new era: Perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy

    PubMed Central

    Ansaldi, Filippo; Orsi, Andrea; Sticchi, Laura; Bruzzone, Bianca; Icardi, Giancarlo

    2014-01-01

    Despite the great successes achieved in the fields of virology and diagnostics, several difficulties affect improvements in hepatitis C virus (HCV) infection control and eradication in the new era. New HCV infections still occur, especially in some of the poorest regions of the world, where HCV is endemic and long-term sequelae have a growing economic and health burden. An HCV vaccine is still no available, despite years of researches and discoveries about the natural history of infection and host-virus interactions: several HCV vaccine candidates have been developed in the last years, targeting different HCV antigens or using alternative delivery systems, but viral variability and adaption ability constitute major challenges for vaccine development. Many new antiviral drugs for HCV therapy are in preclinical or early clinical development, but different limitations affect treatment validity. Treatment predictors are important tools, as they provide some guidance for the management of therapy in patients with chronic HCV infection: in particular, the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets, representing a chance for modulated and personalized treatment management, when also very potent therapies will be available. In the present review we discuss the most recent data about HCV epidemiology, the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis, therapy and predictors of response to it. PMID:25110404

  14. Alzheimer’s disease: review of hormone therapy trials and implications for treatment and prevention after menopause

    PubMed Central

    Henderson, Victor W.

    2013-01-01

    Hormonal changes associated with the menopausal transition and postmenopause have the potential to influence processes linked to Alzheimer’s disease symptoms and pathogenesis, but effects of menopause on Alzheimer risk can be addressed only indirectly. Nine randomized clinical trials of estrogen-containing hormone therapy in Alzheimer’s disease patients were identified by a systematic literature search. Findings suggest that hormone therapy does not improve cognitive symptoms of women with Alzheimer’s disease. No clinical trials of hormone therapy address Alzheimer prevention, but one clinical trial provides moderate evidence that continuous, combined estrogen plus progestogen initiated at age 65 years or older increases the risk of dementia. The timing, or critical window, hypothesis suggests that hormone therapy initiated at a younger age in closer temporal proximity to menopause may reduce the risk of Alzheimer’s disease. This hypothesis is supported by observational research but is not addressed by clinical trial data. Unrecognized confounding is of concern in interpreting observational results, and research that helps resolve this issue will have important public health implications. Well-designed cohort studies, convergent evidence from appropriate laboratory models, and long-term clinical trials using surrogate biomarkers of brain function and neural pathology could provide relevant answers. Other estrogenic compounds are of theoretical interest with respect to Alzheimer treatment and risk. Effects of selective estrogen receptor modulators such as raloxifene may differ from those of estrogens; potential effects of phytoestrogens are not well studied. PMID:23727128

  15. Spectroscopic and theoretical study of the o-vanillin hydrazone of the mycobactericidal drug isoniazid

    NASA Astrophysics Data System (ADS)

    González-Baró, Ana C.; Pis-Diez, Reinaldo; Parajón-Costa, Beatriz S.; Rey, Nicolás A.

    2012-01-01

    A complete and detailed study of the hydrazone obtained from condensation of antituberculous isoniazid (hydrazide of the isonicotinic acid, INH) and o-vanillin (2-hydroxy-3-methoxybenzaldehyde, o-HVa) is performed. It includes structural and spectroscopic analyses, comparing experimental and theoretical results. The compound was obtained as a chloride of the pyridinic salt (INHOVA +Cl -) but it will be referred as INHOVA for the sake of simplicity. The conformational space was searched and optimized geometries were determined both in gas phase and including solvent effects. Vibrational (IR and Raman), electronic and NMR spectra were registered and assigned with the help of computational methods based on the Density Functional Theory. Isoniazid hydrazones are good candidates for therapeutic agents against tuberculosis with conserved efficiency and lower toxicity and resistance than parent INH.

  16. Analysis of the role of Mycobacterium tuberculosis kasA gene mutations in isoniazid resistance.

    PubMed

    Sun, Y-J; Lee, A S G; Wong, S-Y; Paton, N I

    2007-08-01

    Previous studies have suggested that Mycobacterium tuberculosis kasA G312S and G269S gene mutations may represent sequence polymorphisms of the M. tuberculosis East-African-Indian (EAI) and T families, respectively, rather than relating to isoniazid resistance. The present study examined polymorphisms of these two codons in 98 drug-susceptible M. tuberculosis isolates (68 EAI and 30 T isolates). Twenty-eight isolates belonging to a sub-lineage of the EAI family had the kasA G312S mutation, but none of the 30 T isolates had the G269S mutation. The data suggest that the kasA G312S mutation is not related to isoniazid resistance, but represents a sequence polymorphism in a sub-lineage of the EAI family. PMID:17501974

  17. Potassium permanganate-acridine yellow chemiluminescence system for the determination of fluvoxamine, isoniazid and ceftriaxone.

    PubMed

    Abolhasani, Jafar; Hassanzadeh, Javad

    2014-12-01

    Based on the oxidation of acridine yellow by permanganate in basic medium, a new chemiluminescence system was developed for the sensitive determination of some important drugs. The remarkable inhibiting effect of fluvoxamine, ceftriaxone and isoniazid on this reaction was applied to their detection. A possible mechanism was proposed for this system based on chemiluminescence emission wavelengths and experimental observations. Under optimum conditions, calibration graphs were obtained for 1 × 10(-9) to 1 × 10(-6) mol/L of fluvoxamine; 2 × 10(-8) to 8 × 10(-6) mol/L of ceftriaxone and 5 × 10(-8) to 4 × 10(-5) mol/L of isoniazid. This proposed method was satisfactorily used in the determination of these drugs in pharmaceutical samples and human urine and serum. PMID:24753178

  18. The Effect of Cognitive Behavioral Therapy and Cognitive Behavioral Therapy Plus Media on the Reduction of Bullying and Victimization and the Increase of Empathy and Bystander Response in a Bully Prevention Program for Urban Sixth-Grade Students

    ERIC Educational Resources Information Center

    McLaughlin, Laura Pierce

    2009-01-01

    The purpose of this study was to investigate the effect of cognitive behavioral therapy and cognitive behavioral therapy plus media on the reduction of bullying and victimization and the increase in empathy and bystander response in a bully prevention program for urban sixth-graders. Sixty-eight students participated. Because one of the…

  19. Antithrombotic therapy in the primary and secondary prevention of coronary-related death and infarction: focus on gender differences.

    PubMed

    Clyne, C A

    1990-01-01

    Much of our understanding of the role of antithrombotic therapy for postmyocardial infarction patients comes from studies which often included few or no women. Despite this shortcoming there are data available which identify gender differences in risk factors, presentation, natural history and treatment results for myocardial infarction. The use of anticoagulants and antiplatelet agents in the prevention and management of myocardial infarction has evolved over 30 years of investigation. The major randomized, controlled and blinded studies of antithrombotics and myocardial infarction are reviewed, with special emphasis on the female population. PMID:2198101

  20. RELATIONSHIP OF COGNITIVE BEHAVIORAL THERAPY EFFECTS AND HOMEWORK IN AN INDICATED PREVENTION OF DEPRESSION INTERVENTION FOR NON-PROFESSIONAL CAREGIVERS (.).

    PubMed

    Otero, Patricia; Vázquez, Fernando L; Hermida, Elisabet; Díaz, Olga; Torres, Ángela

    2015-06-01

    Activities designed to be performed outside of the intervention are considered an essential aspect of the effectiveness of cognitive-behavioral therapy. However, these have received little attention in interventions aimed at individuals with subclinical depressive symptoms who do not yet meet diagnostic criteria for depression (indicated prevention). In this study, the completion of tasks given as homework and their relationship with post-treatment depressive symptoms was with relation to an indicated prevention of depression intervention. Eighty-nine female non-professional caregivers recruited from an official registry completed an intervention involving 11 homework tasks. Tasks performed were recorded and depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D). Among caregivers, 80.9% completed 9-11 tasks. The number of tasks performed was associated with post-treatment depressive symptoms, with 9 being optimal for clinically significant improvement. These findings highlight the relationship between homework and post-treatment depressive symptoms. PMID:25799123

  1. Induction of protective effector immunity to prevent pathogenesis caused by the respiratory syncytial virus. Implications on therapy and vaccine design

    PubMed Central

    Espinoza, Janyra A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2014-01-01

    Human respiratory syncytial virus (hRSV) is the leading cause of respiratory illness in infants and young children around the globe. This pathogen, which was discovered in 1956, continues to cause a huge number of hospitalizations due to respiratory disease and it is considered a health and economic burden worldwide, especially in developing countries. The immune response elicited by hRSV infection leads to lung and systemic inflammation, which results in lung damage but is not efficient at preventing viral replication. Indeed, natural hRSV infection induces a poor immune memory that allows recurrent infections. Here, we review the most recent knowledge about the lifecycle of hRSV, the immune response elicited by this virus and the subsequent pathology induced in response to infection in the airways. Novel findings about the alterations that this virus causes in the central nervous system and potential therapies and vaccines designed to treat or prevent hRSV infection are discussed. PMID:24801878

  2. Catalase-peroxidase (Mycobacterium tuberculosis KatG) catalysis and isoniazid activation.

    PubMed

    Chouchane, S; Lippai, I; Magliozzo, R S

    2000-08-15

    Resonance Raman spectra of native, overexpressed M. tuberculosis catalase-peroxidase (KatG), the enzyme responsible for activation of the antituberculosis antibiotic isoniazid (isonicotinic acid hydrazide), have confirmed that the heme iron in the resting (ferric) enzyme is high-spin five-coordinate. Difference Raman spectra did not reveal a change in coordination number upon binding of isoniazid to KatG. Stopped-flow spectrophotometric studies of the reaction of KatG with stoichiometric equivalents or small excesses of hydrogen peroxide revealed only the optical spectrum of the ferric enzyme with no hypervalent iron intermediates detected. Large excesses of hydrogen peroxide generated oxyferrous KatG, which was unstable and rapidly decayed to the ferric enzyme. Formation of a pseudo-stable intermediate sharing optical characteristics with the porphyrin pi-cation radical-ferryl iron species (Compound I) of horseradish peroxidase was observed upon reaction of KatG with excess 3-chloroperoxybenzoic acid, peroxyacetic acid, or tert-butylhydroperoxide (apparent second-order rate constants of 3.1 x 10(4), 1.2 x 10(4), and 25 M(-1) s(-1), respectively). Identification of the intermediate as KatG Compound I was confirmed using low-temperature electron paramagnetic resonance spectroscopy. Isoniazid, as well as ascorbate and potassium ferrocyanide, reduced KatG Compound I to the ferric enzyme without detectable formation of Compound II in stopped-flow measurements. This result differed from the reaction of horseradish peroxidase Compound I with isoniazid, during which Compound II was stably generated. These results demonstrate important mechanistic differences between a bacterial catalase-peroxidase and the homologous plant peroxidases and yeast cytochrome c peroxidase, in its reactions with peroxides as well as substrates. PMID:10933818

  3. An Altered Mycobacterium tuberculosis Metabolome Induced by katG Mutations Resulting in Isoniazid Resistance

    PubMed Central

    2014-01-01

    The most common form of drug resistance found in tuberculosis (TB)-positive clinical samples is monoresistance to isoniazid. Various genomics and proteomics studies to date have investigated this phenomenon; however, the exact mechanisms relating to how this occurs, as well as the implications of this on the TB-causing organisms function and structure, are only partly understood. Considering this, we followed a metabolomics research approach to identify potential new metabolic pathways and metabolite markers, which when interpreted in context would give a holistic explanation for many of the phenotypic characteristics associated with a katG mutation and the resulting isoniazid resistance in Mycobacterium tuberculosis. In order to achieve these objectives, gas chromatography-time of flight mass spectrometry (GCxGC-TOFMS)-generated metabolite profiles from two isoniazid-resistant strains were compared to a wild-type parent strain. Principal component analyses showed clear differentiation between the groups, and the metabolites best describing the separation between these groups were identified. It is clear from the data that due to a mutation in the katG gene encoding catalase, the isoniazid-resistant strains experience increased susceptibility to oxidative stress and have consequently adapted to this by upregulating the synthesis of a number of compounds involved in (i) increased uptake and use of alkanes and fatty acids as a source of carbon and energy and (ii) the synthesis of a number of compounds directly involved in reducing oxidative stress, including an ascorbic acid degradation pathway, which to date hasn't been proposed to exist in these organisms. PMID:24468786

  4. Polymorphisms in isoniazid and prothionamide resistance genes of the Mycobacterium tuberculosis complex.

    PubMed

    Projahn, Michaela; Köser, Claudio U; Homolka, Susanne; Summers, David K; Archer, John A C; Niemann, Stefan

    2011-09-01

    Sequence analyses of 74 strains that encompassed major phylogenetic lineages of the Mycobacterium tuberculosis complex revealed 10 polymorphisms in mshA (Rv0486) and four polymorphisms in inhA (Rv1484) that were not responsible for isoniazid or prothionamide resistance. Instead, some of these mutations were phylogenetically informative. This genetic diversity must be taken into consideration for drug development and for the design of molecular tests for drug resistance. PMID:21709103

  5. Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes

    SciTech Connect

    Chen, Yanyan; Xue, Peng; Hou, Yongyong; Zhang, Hao; Zheng, Hongzhi; Zhou, Tong; Qu, Weidong; Teng, Weiping; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2013-12-15

    Transcriptional signaling through the antioxidant response element (ARE), orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major cellular defense mechanism against oxidative or electrophilic stress. Here, we reported that isoniazid (INH), a widely used antitubercular drug, displays a substantial inhibitory property against ARE activities in diverse mouse and human cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE-luciferase reporter activity and mRNA expression of various ARE-dependent antioxidant genes under basal and oxidative stressed conditions. In keeping with our previous findings that Nrf2-ARE plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein β (C/EBPβ) and peroxisome proliferator-activated receptor γ (PPARγ), suppression of ARE signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced levels of lipid accumulation and attenuated expression of C/EBPα and PPARγ. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by INH occurred in the early stage of terminal adipogenic differentiation, where reduced expression of C/EBPβ and C/EBPδ was observed. To our knowledge, the present study is the first to demonstrate that INH suppresses ARE signaling and interrupts with the transcriptional network of adipogenesis, leading to impaired adipogenic differentiation. The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. - Highlights: • Isoniazid suppresses ARE-mediated transcriptional activity. • Isoniazid inhibits adipogenesis in preadipocytes. • Isoniazid suppresses adipogenic gene expression during adipogenesis.

  6. Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Newly Diagnosed Pulmonary TB Patients in Tanzania

    PubMed Central

    Chigutsa, Emmanuel; Faurholt-Jepsen, Daniel; PrayGod, George; Range, Nyagosya; Castel, Sandra; Wiesner, Lubbe; Hagen, Christian Munch; Christiansen, Michael; Changalucha, John; McIlleron, Helen; Friis, Henrik; Andersen, Aase Bengaard

    2015-01-01

    Exposure to lower-than-therapeutic levels of anti-tuberculosis drugs is likely to cause selection of resistant strains of Mycobacterium tuberculosis and treatment failure. The first-line anti-tuberculosis (TB) regimen consists of rifampicin, isoniazid, pyrazinamide, and ethambutol, and correct management reduces risk of TB relapse and development of drug resistance. In this study we aimed to investigate the effect of standard of care plus nutritional supplementation versus standard care on the pharmacokinetics of isoniazid, pyrazinamide and ethambutol among sputum smear positive TB patients with and without HIV. In a clinical trial in 100 Tanzanian TB patients, with or without HIV infection, drug concentrations were determined at 1 week and 2 months post initiation of anti-TB medication. Data was analysed using population pharmacokinetic modelling. The effect of body size was described using allometric scaling, and the effects of nutritional supplementation, HIV, age, sex, CD4+ count, weight-adjusted dose, NAT2 genotype, and time on TB treatment were investigated. The kinetics of all drugs was well characterised using first-order elimination and transit compartment absorption, with isoniazid and ethambutol described by two-compartment disposition models, and pyrazinamide by a one-compartment model. Patients with a slow NAT2 genotype had higher isoniazid exposure and a lower estimate of oral clearance (15.5 L/h) than rapid/intermediate NAT2 genotype (26.1 L/h). Pyrazinamide clearance had an estimated typical value of 3.32 L/h, and it was found to increase with time on treatment, with a 16.3% increase after the first 2 months of anti-TB treatment. The typical clearance of ethambutol was estimated to be 40.7 L/h, and was found to decrease with age, at a rate of 1.41% per year. Neither HIV status nor nutritional supplementations were found to affect the pharmacokinetics of these drugs in our cohort of patients. PMID:26501782

  7. Signature gene expression profiles discriminate between isoniazid-, thiolactomycin-, and triclosan-treated Mycobacterium tuberculosis.

    PubMed

    Betts, Joanna C; McLaren, Alistair; Lennon, Mark G; Kelly, Fiona M; Lukey, Pauline T; Blakemore, Steve J; Duncan, Ken

    2003-09-01

    Genomic technologies have the potential to greatly increase the efficiency of the drug development process. As part of our tuberculosis drug discovery program, we used DNA microarray technology to profile drug-induced effects in Mycobacterium tuberculosis. Expression profiles of M. tuberculosis treated with compounds that inhibit key metabolic pathways are required as references for the assessment of novel antimycobacterial agents. We have studied the response of M. tuberculosis to treatment with the mycolic acid biosynthesis inhibitors isoniazid, thiolactomycin, and triclosan. Thiolactomycin targets the beta-ketoacyl-acyl carrier protein (ACP) synthases KasA and KasB, while triclosan inhibits the enoyl-ACP reductase InhA. However, controversy surrounds the precise mode of action of isoniazid, with both InhA and KasA having been proposed as the primary target. We have shown that although the global response profiles of isoniazid and thiolactomycin are more closely related to each other than to that of triclosan, there are differences that distinguish the mode of action of these two drugs. In addition, we have identified two groups of genes, possibly forming efflux and detoxification systems, through which M. tuberculosis may limit the effects of triclosan. We have developed a mathematical model, based on the expression of 21 genes, which is able to perfectly discriminate between isoniazid-, thiolactomycin-, or triclosan-treated M. tuberculosis. This model is likely to prove invaluable as a tool to improve the efficiency of our drug development programs by providing a means to rapidly confirm the mode of action of thiolactomycin analogues or novel InhA inhibitors as well as helping to translate enzyme activity into whole-cell activity. PMID:12936993

  8. Preventive measures to prevent loss to follow-up in highly active antiretroviral therapy (HAART): implementing a strategy in Ziguinchor (Casamance, Senegal) in 2014.

    PubMed

    Randé, H; Rouffy, D

    2016-05-01

    Since 2010, the Pharmacie et Aide Humanitaire (PAH) in Casamance (Senegal) has been maintaining a software package (Tacojo) that allows monthly monitoring of the distribution of treatment to every patient with HIV infection receiving highly active antiretroviral therapy (HAART). We used this program to set up measures to prevent the loss to follow-up of patients receiving HAART. Our involvement focused on two main areas. First, each patient is routinely contacted after inclusion, to help us to understand the patient's experience of the disease and the treatment. This process aims to improve adherence to the treatment. Then, all patients who miss an appointment are routinely contacted by telephone within seven days of that appointment. The goal is to understand the reasons for the absence and to encourage patients to continue their treatment. Despite the lack of distance due to the relative newness of this program, these preventive measures have shown hopeful results (80% of the patients came back after a call). It would be interesting to apply it in a sustainable manner and in more medical facilities. PMID:27412981

  9. New concepts and challenges in the clinical translation of cancer preventive therapies: the role of pharmacodynamic biomarkers.

    PubMed

    Brown, Karen; Rufini, Alessandro

    2015-01-01

    Implementation of therapeutic cancer prevention strategies has enormous potential for reducing cancer incidence and related mortality. Trials of drugs including tamoxifen and aspirin have led the way in demonstrating proof-of-principle that prevention of breast and colorectal cancer is feasible. Many other compounds ranging from drugs in widespread use for various indications, including metformin, bisphosphonates, and vitamin D, to dietary agents such as the phytochemicals resveratrol and curcumin, show preventive activity against several cancers in preclinical models. Notwithstanding the wealth of opportunities, major challenges have hindered the development process and only a handful of therapies are currently approved for cancer risk reduction. One of the major obstacles to successful clinical translation of promising preventive agents is a lack of pharmacodynamic biomarkers to provide an early read out of biological activity in humans and for optimising doses to take into large scale randomised clinical trials. A further confounding factor is a lack of consideration of clinical pharmacokinetics in the design of preclinical experiments, meaning results are frequently reported from studies that use irrelevant or unachievable concentrations. This article focuses on recent findings from investigations with dietary-derived agents to illustrate how a thorough understanding of the mechanisms of action, using models that mimic the clinical scenario, together with the development of compound-specific accompanying pharmacodynamic biomarkers could accelerate the developmental pipeline for preventive agents and maximise the chances of success in future clinical trials. Moreover, the concept of a bell-shaped dose-response curve for therapeutic cancer prevention is discussed, along with the need to rethink the traditional 'more is better' approach for dose selection. PMID:26635905

  10. An open trial of mindfulness-based cognitive therapy for the prevention of perinatal depressive relapse/recurrence.

    PubMed

    Dimidjian, Sona; Goodman, Sherryl H; Felder, Jennifer N; Gallop, Robert; Brown, Amanda P; Beck, Arne

    2015-02-01

    Pregnant women with histories of depression are at high risk of depressive relapse/recurrence during the perinatal period, and options for relapse/recurrence prevention are limited. Mindfulness-based cognitive therapy (MBCT) has strong evidence among general populations but has not been studied among at-risk pregnant women to prevent depression. We examined the feasibility, acceptability, and clinical outcomes of depression symptom severity and relapse/recurrence associated with MBCT adapted for perinatal women (MBCT-PD). Pregnant women with depression histories were recruited from obstetrics clinics in a large health maintenance organization at two sites and enrolled in MBCT-PD (N = 49). Self-reported depressive symptoms and interview-based assessments of depression relapse/recurrence status were measured at baseline, during MBCT-PD, and through 6-months postpartum. Pregnant women reported interest, engagement, and satisfaction with the program. Retention rates were high, as were rates of completion of daily homework practices. Intent to treat analyses indicated a significant improvement in depression symptom levels and an 18 % rate of relapse/recurrence through 6 months postpartum. MBCT-PD shows promise as an acceptable, feasible, and clinically beneficial brief psychosocial prevention option for pregnant women with histories of depression. Randomized controlled trials are needed to examine the efficacy of MBCT-PD for the prevention of depressive relapse/recurrence during pregnancy and postpartum. PMID:25298253

  11. Early, But Not Late Onset Estrogen Replacement Therapy Prevents Oxidative Stress and Metabolic Alterations Caused by Ovariectomy

    PubMed Central

    López-Grueso, Raúl; Gambini, Juan; Abdelaziz, Kheira M.; Monleón, Daniel; Díaz, Ana; El Alami, Marya; Bonet-Costa, Vicent; Borrás, Consuelo

    2014-01-01

    Abstract Aims: The usefulness of estrogen replacement therapy (ERT) in preventing oxidative stress associated with menopause is controversial. We aimed to study if there is a critical time window for effective treatment of the effects of ovariectomy with estrogens at the molecular, metabolic, and cellular level. Results: Our main finding is that early, but not late onset of ERT prevents an ovariectomy-associated increase in mitochondrial hydrogen peroxide levels, oxidative damage to lipids and proteins, and a decrease in glutathione peroxidase and catalase activity in rats. This may be due to a change in the estrogen receptor (ER) expression profile: ovariectomy increases the ER α/β ratio and immediate estrogen replacement prevents it. Positron emission tomography analysis shows that ovariectomy decreases the brain glucose uptake in vivo and that estrogen administration is beneficial, but only if administered immediately after deprivation. Ovariectomy decreases GLUT-1 and 3 glucose transporters in the brain, and only early onset estrogen administration prevents it. Plasma from rats treated with estrogens immediately after ovariectomy show similar metabolomics profiles as controls. Innovation: We provide molecular basis for the recommendation of early onset ERT and explain its lack of effectiveness if a significant time period elapses after ovariectomy and probably after the onset of menopause. Conclusion: Only early, but not late onset administration of estrogens after ovariectomy has beneficial effects at molecular levels on oxidative stress, brain glucose uptake, and metabolomic profiles. Antioxid. Redox Signal. 20, 236–246. PMID:23725100

  12. Felbamate antagonizes isoniazid- and FG 7142-induced reduction of GABAA receptor function in mouse brain.

    PubMed

    Serra, M; Ghiani, C A; Spano, S; Biggio, G

    1994-11-24

    Injection of the antiepileptic drug, felbamate (2-phenyl-1,3-propanediol dicarbamate), into mice reduced in a dose-dependent manner (150-300 mg/kg i.p.) the isoniazid (200 mg/kg s.c.)-induced increase in ex vivo binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) to cerebral cortical and hippocampal membranes. The same doses of felbamate reduced significantly the number of mice exhibiting isoniazid-induced seizures. A dose of felbamate (50 mg/kg) ineffective in isoniazid-treated mice completely antagonized the increase of [35S]TBPS binding elicited by FG 7142 (N-methyl-beta-carboline-3-carboxamide), a benzodiazepine receptor inverse agonist. The above effects of felbamate resembled those of diazepam. Accordingly, the combination of ineffective doses of felbamate (50 mg/kg) and diazepam (0.2 mg/kg) elicited a marked decrease of [35S]TBPS binding. The results indicate that facilitation of gamma-aminobutyric acid type A (GABAA) receptor function may play a role in the anticonvulsant action of felbamate. PMID:7875235

  13. Expert position paper on prolonged dual antiplatelet therapy in secondary prevention following myocardial infarction.

    PubMed

    Weiss, Thomas W; Aichinger, Josef; Huber, Kurt; Speidl, Walter S; Watzinger, Norbert; Zweiker, Robert; Alber, Hannes F

    2016-06-01

    The protective effect of dual antiplatelet therapy (DAPT) following acute coronary syndrome is undisputed, but its duration is subject of debate. Several studies show that prolonged therapy provides a clinical benefit in patients following acute coronary syndrome. The aim of this position paper authored by Austrian experts is to outline the current evidence and provide an overview of recent studies. It is also intended to serve as a practical guide to identify those patients who may benefit from prolonged DAPT. PMID:27278134

  14. Mindfulness-Based Cognitive Therapy to Prevent Relapse in Recurrent Depression

    ERIC Educational Resources Information Center

    Kuyken, Willem; Byford, Sarah; Taylor, Rod S.; Watkins, Ed; Holden, Emily; White, Kat; Barrett, Barbara; Byng, Richard; Evans, Alison; Mullan, Eugene; Teasdale, John D.

    2008-01-01

    For people at risk of depressive relapse, mindfulness-based cognitive therapy (MBCT) has an additive benefit to usual care (H. F. Coelho, P. H. Canter, & E. Ernst, 2007). This study asked if, among patients with recurrent depression who are treated with antidepressant medication (ADM), MBCT is comparable to treatment with maintenance ADM (m-ADM)…

  15. Accumulating Evidence for Parent-Child Interaction Therapy in the Prevention of Child Maltreatment

    ERIC Educational Resources Information Center

    Thomas, Rae; Zimmer-Gembeck, Melanie J.

    2011-01-01

    In a randomized controlled trial, the effectiveness of Parent-Child Interaction Therapy (PCIT) and correlates of maltreatment outcomes were examined. Mothers (N = 150) had a history or were at high risk of maltreating their children. After 12 weeks and compared to waitlist, PCIT mothers were observed to have improved parent-child interactions and…

  16. Prevention of postoperative pulmonary complications with CPAP, incentive spirometry, and conservative therapy.

    PubMed

    Stock, M C; Downs, J B; Gauer, P K; Alster, J M; Imrey, P B

    1985-02-01

    Continuous positive airway pressure (CPAP) administered at intervals with a mask and incentive spirometry (IS) were compared with a regimen of coughing and deep breathing (CDB) to determine which promoted the most rapid recovery of pulmonary function after upper abdominal operations in 65 adults. Postoperatively, FRC of patients in all groups was similar relative to preoperative values. However, mean FRC of patients who received CPAP increased more rapidly than did mean FRC of those receiving CDB when compared to the values obtained following operation (p less than 0.05). Incentive spirometry did not increase FRC to a greater extent than did CDB. Roentgenographic evidence of atelectasis 72 hours postoperatively was observed in 23 percent of CPAP patients (five of 22) and 42 percent and 41 percent of patients who received CDB (eight of 19) and IS (nine of 22). Two patients (3 percent) developed pneumonia. The low incidence of pneumonia regardless of the type of therapy may be attributable to vigorous, vigilant respiratory care in a population at high risk for developing pneumonia. Frequency and supervision of respiratory therapy may be more important than the type of therapy delivered after upper abdominal operations. Mask CPAP offers advantages because it requires no effort from the patient, and therapy is not painful. PMID:3881226

  17. A Reappraisal of the Safety and Cost-Effectiveness of Statin Therapy in Primary Prevention.

    PubMed

    Bleakley, Caroline; Pumb, Richard; Harbinson, Mark; McVeigh, Gary Eugene

    2015-12-01

    Statins are among the most investigated drugs of all time. There is now a wealth of evidence supporting their use in the primary and secondary prevention arenas. The reduction in event recurrence has since been demonstrated across all levels of risk and in elderly patients. As a result, it is now accepted practice for statins to be prescribed universally in secondary prevention unless contraindicated. The extension of this policy into the primary prevention setting is more problematic, with moral and financial issues arising from the long-term treatment of many young apparently healthy individuals. For these reasons it is necessary to prove not only the financial sustainability of such a strategy but also the long-term safety of statins and the degree of benefit that might be expected. PMID:26386731

  18. [Cardiovascular risk assessment and risk stratification- guided therapy: predict, prevent and individualize].

    PubMed

    Ural, Dilek

    2011-09-01

    Modern concept in primary prevention of cardiovascular diseases (CVD) entails assessing the person's global risk and making the right management in accordance with these results. Correspondingly, 3 steps recommended for the prevention of CVD under risk guidance are: (a) risk assessment via a proper system like Framingham Risk Score, SCORE, QRISK, PROCAM; (b) decision-making in the proper management in terms of informing the patient about lifestyle changes that he or she can cope and drug selection; and (c) evaluation of treatment decision in terms of cost effectiveness. Although, a significant decline is observed in CVD morbidity and mortality, particularly in the western countries, we still are trying to approach to competent quality measures about management under CV risk guidance. This review summarizes the main challenges regarding risk stratification-guided management strategy in primary prevention of CVD. PMID:21821497

  19. Prevention or amelioration of morphologic lesions in LD100 E coli-shocked baboons with steroid/antibiotic therapy.

    PubMed

    Archer, L T; Kosanke, S D; Beller, B K; Passey, R B; Hinshaw, L B

    1983-01-01

    We have documented the effectiveness of methylprednisolone sodium succinate (MPSS) and gentamicin sulfate (GS) therapy for LD100 E coli-induced shock in the baboon. We sequentially delayed initiation of MPSS infusion from 30 to 120 min and then to 240 min after onset of a 2-h E coli infusion. Treatment resulted in 100%, 85%, and 65% survival respectively. In this study we evaluated tissue taken at autopsy in the three MPSS/GS treatment studies including untreated baboons and those treated with GS only. When animals died (3-49 h) or were sacrificed (7-71 days), tissues were removed, coded, and prepared for histopathologic evaluation by light microscopy. On the basis of morphologic changes animals split into two groups: baboons with little or no tissue alterations (survivors), and those with multiple organ damage (nonsurvivors). Combinations of mild to massive congestion, edema, hemorrhage, fibrin thrombi, increased numbers of polymorphonuclear leukocytes (PMNs), and necrosis of the adrenal glands, liver, kidneys, lungs, and spleen of nonsurvivors were prevented or ameliorated in the MPSS/GS-treated surviving baboons. Data demonstrate the MPSS/GS therapy prevents or reverses the multiple organ damage and increases survival in lethal septic shock. PMID:6349298

  20. AAV8-mediated Gene Therapy Prevents Induced Biochemical Attacks of Acute Intermittent Porphyria and Improves Neuromotor Function

    PubMed Central

    Yasuda, Makiko; Bishop, David F; Fowkes, Mary; Cheng, Seng H; Gan, Lin; Desnick, Robert J

    2009-01-01

    Acute intermittent porphyria (AIP), an autosomal dominant hepatic porphyria due to half-normal hydroxymethylbilane synthase (HMB-synthase) activity, is manifested by life-threatening acute neurological attacks that are precipitated by factors that induce heme biosynthesis. The acute attacks are currently treated with intravenous hemin, but a more continuous therapy is needed, particularly for patients experiencing frequent attacks. Thus, a recombinant AAV8-based serotype vector expressing murine HMB-synthase driven by liver-specific regulatory elements was generated and its effectiveness to prevent the biochemical induction of an acute attack was evaluated in an AIP mouse model. Intraperitoneal administration of the adeno-associated viral (AAV) vector resulted in a rapid and dose-dependent increase of HMB-synthase activity that was restricted to the liver. Stable expression of hepatic HMB-synthase was achieved and wild-type or greater levels were sustained for 36 weeks. When heme synthesis was periodically induced by a series of phenobarbital injections, the treated mice did not accumulate urinary δ-aminolevulinic acid (ALA) or porphobilinogen (PBG), indicating that the expressed enzyme was functional in vivo and prevented induction of the acute attack. Further, rotarod performance and footprint analyses improved significantly. Thus, liver-directed gene therapy provided successful long-term correction of the hepatic metabolic abnormalities and improved neuromotor function in the murine model of human AIP. PMID:19861948

  1. Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

    PubMed Central

    Suthar, Amitabh B.; Lawn, Stephen D.; del Amo, Julia; Getahun, Haileyesus; Dye, Christopher; Sculier, Delphine; Sterling, Timothy R.; Chaisson, Richard E.; Williams, Brian G.; Harries, Anthony D.; Granich, Reuben M.

    2012-01-01

    Background Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection. Methods and Findings PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count. Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). Conclusions Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis

  2. Hepatitis B Reactivation During Immunosuppressive Therapy or Cancer Chemotherapy, Management, and Prevention: A Comprehensive Review-Screened

    PubMed Central

    Tavakolpour, Soheil; Alavian, Seyed Moayed; Sali, Shahnaz

    2016-01-01

    Context Due to the close relationship between the immune system and the hepatitis B virus (HBV) replication, it is essential to monitor patients with current or past HBV infection under any type of immunosuppression. Cancer chemotherapy, immunosuppressive therapies in autoimmune diseases, and immunosuppression in solid organ and stem cell transplant recipients are the major reasons for hepatitis B virus reactivation (HBVr). In this review, the challenges associated with HBVr are discussed according to the latest studies and guidelines. We also discuss the role of treatments with different risks, including anti-CD20 agents, tumor necrosis factor-alpha (TNF-α) inhibitors, and other common immunosuppressive agents in various conditions. Evidence Acquisition Through an electronic search of the PubMed, Google Scholar, and Scopus databases, we selected the studies associated with HBVr in different conditions. The most recent recommendations were collected in order to reach a consensus on how to manage patients at risk of HBVr. Results It was found that the positive hepatitis B surface antigen (HBsAg), the high baseline HBV DNA level, the positive hepatitis B virus e antigen (HBeAg), and an absent or low hepatitis B surface antibody (HBsAb) titer prior to starting treatment are the most important viral risk factors. Furthermore, rituximab, anthracycline, and different types of TNF-α inhibitors were identified as the high-risk therapies. By analyzing the efficiency of prophylaxis on the prevention of HBVr, it was concluded that those with a high risk of antiviral resistance should not be used in long-term immunosuppressants. Receiving HBV antiviral agents at the commencement of immunosuppressant therapy or chemotherapy was demonstrated to be effective in decreasing the risk of HBVr. Prophylaxis could also be initiated before the start of therapy. For most immune suppressive regimes, antiviral therapy should be kept up for at least 6 months after the cessation of

  3. Radioprotective agents for the prevention of side effects induced by radioiodine-131 therapy.

    PubMed

    Noaparast, Zohreh; Hosseinimehr, Seyed Jalal

    2013-08-01

    Radioiodine 131 ((131)I) has been used worldwide for the ablation of remnant thyroidal tissue after surgery or as the first-line treatment for Graves' disease. Although the use of (131)I is becoming increasingly prevalent, there is evidence suggesting that this treatment is associated with side effects such as salivary gland dysfunction and an increased risk of leukemia. This article aims to review the potential use of radioprotective agents and the side effects induced by (131)I therapy. Several synthetic and natural compounds have been investigated in preclinical and clinical studies. The protective agents reduced the toxicity of (131)I, mainly in the salivary glands, and mitigated the genetic damage through different mechanisms. There are limited clinical studies evaluating the use of radioprotective agents in patients undergoing radioiodine therapy. However, lemon candies, lemon juice and sugarless chewing gum have been proposed to be beneficial for minimizing the side effects of radioiodine within the salivary glands. PMID:23902246

  4. Menopausal Estrogen Therapy Benefits and Risks Vary by Age, WHI Analysis Suggests | Division of Cancer Prevention

    Cancer.gov

    Long-term follow-up data from the Women’s Health Initiative (WHI) provide important new information about the potential risks and benefits of hormone therapy to treat symptoms or conditions related to menopause, including its effect on breast cancer risk. The results were published April 5 in the Journal of the American Medical Association. |

  5. [Non-invasive cerclage using supportive pessaries for prevention and therapy of premature birth].

    PubMed

    Seyffarth, K

    1978-01-01

    It was told about a pessary, with the help of which could be done an excellent therapy and prophylaxis of the threatening of a partus prämaturus imminens in cervixinsufficiency. To make use of it is very simple. With the help of this method one could lower the rate of miscarriages to 3,6% in comparison to a period without cerclage or pessary, when the rate of premature children was 6,6%. PMID:570333

  6. Cytokine and anti-cytokine therapies in prevention or treatment of fibrosis in IBD.

    PubMed

    Jacob, Noam; Targan, Stephan R; Shih, David Q

    2016-08-01

    The frequency of fibrosing Crohn's disease (CD) is significant, with approximately 40% of CD patients with ileal disease developing clinically apparent strictures throughout their lifetime. Although strictures may be subdivided into fibrotic, inflammatory, or mixed forms, despite immunosuppressive therapy in CD patients in the form of steroids or immunomodulators, the frequency of fibrostenosing complications has still remained significant. A vast number of genetic and epigenetic variables are thought to contribute to fibrostenosing disease, including those that affect cytokine biology, and therefore highlight the complexity of disease, but also shed light on targetable pathways. Exclusively targeting fibrosis may be difficult, however, because of the relatively slow evolution of fibrosis in CD, and the potential adverse effects of inhibiting pathways involved in tissue repair and mucosal healing. Acknowledging these caveats, cytokine-targeted therapy has become the mainstay of treatment for many inflammatory conditions and is being evaluated for fibrotic disorders. The question of whether anti-cytokine therapy will prove useful for intestinal fibrosis is, therefore, acutely relevant. This review will highlight some of the current therapeutics targeting cytokines involved in fibrosis. PMID:27536363

  7. Cytokine and anti-cytokine therapies in prevention or treatment of fibrosis in IBD

    PubMed Central

    Jacob, Noam; Targan, Stephan R

    2016-01-01

    The frequency of fibrosing Crohn’s disease (CD) is significant, with approximately 40% of CD patients with ileal disease developing clinically apparent strictures throughout their lifetime. Although strictures may be subdivided into fibrotic, inflammatory, or mixed forms, despite immunosuppressive therapy in CD patients in the form of steroids or immunomodulators, the frequency of fibrostenosing complications has still remained significant. A vast number of genetic and epigenetic variables are thought to contribute to fibrostenosing disease, including those that affect cytokine biology, and therefore highlight the complexity of disease, but also shed light on targetable pathways. Exclusively targeting fibrosis may be difficult, however, because of the relatively slow evolution of fibrosis in CD, and the potential adverse effects of inhibiting pathways involved in tissue repair and mucosal healing. Acknowledging these caveats, cytokine-targeted therapy has become the mainstay of treatment for many inflammatory conditions and is being evaluated for fibrotic disorders. The question of whether anti-cytokine therapy will prove useful for intestinal fibrosis is, therefore, acutely relevant. This review will highlight some of the current therapeutics targeting cytokines involved in fibrosis.

  8. Endoscopic injection therapy to prevent rebleeding from peptic ulcers with a protruding vessel: a controlled comparative trial.

    PubMed Central

    Rutgeerts, P; Gevers, A M; Hiele, M; Broeckaert, L; Vantrappen, G

    1993-01-01

    Seventy five patients with severely bleeding peptic ulcer were included in a controlled comparative trial to assess the efficacy and safety of endoscopic injection therapy in preventing rebleeding from peptic ulcers that presented at endoscopy with a protruding vessel. Twenty five patients were treated with injection of epinephrine followed by polidocanol, 25 were treated with injection of absolute alcohol, and 25 with sham injection. Rebleeding occurred in 44% of patients in the sham group, 40% of those treated with epinephrine and polidocanol, and in 20% of those treated with absolute ethanol. The difference in the haemostasis rate between the control and ethanol treated subjects nearly reached significance (p = 0.07). A second therapy session resulted in haemostasis rates of 68% in the epinephrine-polidocanol group and of 88% in the absolute ethanol group. These rates after two treatments as well as the emergency surgery rates (32% in the epinephrine-polidocanol group and 8% in the absolute ethanol group; p = 0.07) were not significantly different. In eight of the 11 patients with rebleeding in the sham treatment group, definitive haemostasis was achieved by elective injection therapy. Overall transfusion requirements were mean (SD) 6.0 (0.7) units in the sham group, 6.0 (0.9) in the epinephrine-polidocanol group, and 3.9 (0.5) in the absolute ethanol group. Only the difference between ethanol and sham was significant (p = 0.02). This study shows that injection with absolute ethanol reduces rebleeding in these patients and significantly lowers transfusion requirements. Absolute ethanol was superior to epinephrine-polidocanol, which was not significantly better than sham therapy. PMID:8472981

  9. Treatment with lithium prevents serum thyroid hormone increase after thionamide withdrawal and radioiodine therapy in patients with Graves' disease.

    PubMed

    Bogazzi, Fausto; Bartalena, Luigi; Campomori, Alberto; Brogioni, Sandra; Traino, Claudio; De Martino, Fabio; Rossi, Giuseppe; Lippi, Francesco; Pinchera, Aldo; Martino, Enio

    2002-10-01

    concentrations are prevented by lithium; and 4) the increased effectiveness of RAI therapy in lithium-treated patients is related to the increased RAI retention in the thyroid gland. Accordingly, a short course of lithium therapy can be considered a useful adjunct to RAI therapy to obtain a prompter control of thyrotoxicosis and avoid its transient exacerbation because of MMI withdrawal and RAI administration. PMID:12364424

  10. Post reperfusion syndrome during liver transplantation: From pathophysiology to therapy and preventive strategies

    PubMed Central

    Siniscalchi, Antonio; Gamberini, Lorenzo; Laici, Cristiana; Bardi, Tommaso; Ercolani, Giorgio; Lorenzini, Laura; Faenza, Stefano

    2016-01-01

    This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A PubMed search was conducted using the MeSH database, “Reperfusion” AND “liver transplantation” were the combined MeSH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies. PMID:26819522

  11. Post reperfusion syndrome during liver transplantation: From pathophysiology to therapy and preventive strategies.

    PubMed

    Siniscalchi, Antonio; Gamberini, Lorenzo; Laici, Cristiana; Bardi, Tommaso; Ercolani, Giorgio; Lorenzini, Laura; Faenza, Stefano

    2016-01-28

    This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A PubMed search was conducted using the MeSH database, "Reperfusion" AND "liver transplantation" were the combined MeSH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies. PMID:26819522

  12. Impact of preventive therapy on the risk of breast cancer among women with benign breast disease.

    PubMed

    Cuzick, Jack; Sestak, Ivana; Thorat, Mangesh A

    2015-11-01

    There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4-5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer. Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts. Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts. PMID:26255741

  13. Induction of CYP2E1 in testes of isoniazid-treated rats as possible cause of testicular disorders.

    PubMed

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Voronina, Alla K; Anisimova, Svitlana I; Matvienko, Anatoliy V; Kovalenko, Valentina M

    2015-04-16

    Isoniazid is reported to be the most reliable and cost-effective remedy for tuberculosis treatment and prophylaxis among first line anti-tuberculosis drugs. Conventionally, the most common and best studied adverse effect of isoniazid is hepatotoxicity, but as for testicular toxicity the problem has not yet explored extensively. The aim of the study was to identify in vivo influence of isoniazid on induction of testicular cytochrome Р-450 2Е1 (CYP2E1) mRNA expression and enzymatic activity, testes DNA fragmentation, serum total testosterone level, and spermatogenesis indices. The significant induction of CYP2E1 was demonstrated in rat's testes following isoniazid administration, specifically CYP2E1 mRNA expression and p-nitrophenolhydroxylase activity was increased in 28 and 7 times as compared with control, respectively. These changes were accompanied by activating of testicular GST in 32%, changing in levels and character of DNA fragmentation, as well as damaging of the spermatogenic epithelium, decreasing in serum testosterone content (1.62 fold), sperm count (19%), and losing of fertility in comparison with untreated males. We assume that in testes of isoniazid-treated rats CYP2E1 may act as a trigger in generating of reactive oxygen species and other toxic metabolites which subsequently mediates DNA damage, spermatogenesis disturbances, and altered male fertilizing capacity. PMID:25683034

  14. Prevention and treatment of nephrolithiasis: a review on the role of spa therapy.

    PubMed

    Mennuni, G; Serio, A; Fontana, M; Nocchi, S; Costantino, C; Tanzi, G; Stornelli, G; Fraioli, A

    2015-01-01

    The prevalence and incidence of nephrolithiasis is reported to be increasing across the world. It is a disease of increased urinary concentration of stone-forming salts. The physicochemical mechanism of stone formation includes precipitation, homogenous/heterogeneous nucleation, growth, aggregation and concretion of various modulators in urine. Necessary condition to develop stones is urinary supersaturation, due to reduced urinary volume or to an excesses solutes. Fluid intake is the main determinant of urine volume. Urine dilution can significantly decrease both the crystallization rate of the urinary salts and the aggregation of the crystals. A correct fluid intake can act on different effects: urinary tract washing, urinary volume increasing and dilution of solutes. In addition mineral waters have other particular features: greater diuretic effect, more important urinary dilution with solutes and microbial concentration reduction, urinary pH changes, superior washout effect due to mechanical effects and ureteral contractions. Adequate water intake is the most important conservative strategy in urolithiasis prevention; particularly hydropinotherapy with oligomineral water should be considered as an important instrument to prevent stones in subjects predisposed to the disease (family members of people suffering from kidney stones), to reduce relapses, and can help to eliminate residual fragments also after extracorporeal shock wave lithotripsy. It is recommended a management with increased mineral water intake to promote urine volume of at least 2.5L each day to prevent stone formation. Obviously water intake shall be varied in relation to the presence of contraindications or any diseases. PMID:26550821

  15. Early-initiated zidovudine therapy prevents disease but not low levels of persistent retrovirus in mice.

    PubMed

    Morrey, J D; Okleberry, K M; Sidwell, R W

    1991-01-01

    An F1 hybrid mouse strain containing the Rfv-3r/s genotype was inoculated with Friend virus complex (FV) and treated with zidovudine (ZDV) intraperitoneally three times daily for 20 days beginning as early as 10 min after initial viral exposure. This strain of mice develops FV-specific neutralizing antibodies that aid in reducing viremia and splenic virus titers but do not prevent splenomegaly and eventual FV-associated death. The virally exposed mice treated with ZDV did not develop splenomegaly or have detectable viremia after the last drug treatment. On day 21, a single animal had demonstrable virus in the spleen as determined by a focal immunoenzyme assay; 57% had detectable virus at 5 weeks, but non displayed splenic virus after 35 weeks. None of the animals died after the 35-week holding period, compared to 38% dying in placebo-treated mice. To detect low levels of the virus, or potentially latent virus, splenocytes were cocultivated with a cell line known to readily propagate FV, and the cells were subsequently passaged four times to amplify replication of the virus. After amplification, a significant increase was seen in the number of mice testing positive for virus. Thus, ZDV treatment initiated early after virus exposure was effective in preventing FV-induced splenomegaly and death, but did not prevent low levels of persistent retrovirus in the mice. PMID:2016687

  16. Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS.

    PubMed

    Swamy, Manjunath N; Wu, Haoquan; Shankar, Premlata

    2016-08-01

    RNA interference (RNAi) provides a powerful tool to silence specific gene expression and has been widely used to suppress host factors such as CCR5 and/or viral genes involved in HIV-1 replication. Newer nuclease-based gene-editing technologies, such as zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, also provide powerful tools to ablate specific genes. Because of differences in co-receptor usage and the high mutability of the HIV-1 genome, a combination of host factors and viral genes needs to be suppressed for effective prevention and treatment of HIV-1 infection. Whereas the continued presence of small interfering/short hairpin RNA (si/shRNA) mediators is needed for RNAi to be effective, the continued expression of nucleases in the gene-editing systems is undesirable. Thus, RNAi provides the only practical way for expression of multiple silencers in infected and uninfected cells, which is needed for effective prevention/treatment of infection. There have been several advances in the RNAi field in terms of si/shRNA design, targeted delivery to HIV-1 susceptible cells, and testing for efficacy in preclinical humanized mouse models. Here, we comprehensively review the latest advances in RNAi technology towards prevention and treatment of HIV-1. PMID:27013255

  17. Longitudinal persistence with secondary prevention therapies relative to patient risk after myocardial infarction

    PubMed Central

    Shore, Supriya; Jones, Philip G.; Maddox, Thomas M.; Bradley, Steven M.; Stolker, Joshua M.; Arnold, Suzanne V.; Parashar, Susmita; Peterson, Pamela; Bhatt, Deepak L.; Spertus, John; Ho, P. Michael

    2016-01-01

    Background Prior studies have demonstrated that high-risk AMI patients are less likely to receive guideline-directed medications during hospitalization. It is unknown if this paradox persists following discharge. We aimed to assess if persistence with guideline-directed medications post-discharge varies by patients’ risk following acute myocardial infarction (AMI). Methods Data were analyzed from two prospective, multicenter U.S. AMI registries. The primary outcome was persistence with all prescribed guideline-directed medications (aspirin, beta-blockers, statins, angiotensin-antagonists) at 1, 6, and 12-months post-discharge. The association between risk and medication persistence post-discharge was assessed using multivariable mixed-effect models. Results Among 6434 AMI patients discharged home, 2824 were considered low-risk, 2014 intermediate-risk and 1596 high-risk for death based upon their GRACE 6-month risk score. High-risk was associated with a lower likelihood of receiving all appropriate therapies at discharge compared with low-risk patients (RR 0.90; 95% CI 0.87–0.94). At 12-months, the rate of persistence with all prescribed therapies was 61.5%, 57.9% and 45.9% among low-, intermediate- and high-risk patients respectively. After multivariable adjustment, high-risk was associated with lower persistence with all prescribed medications (RR 0.87; 95% CI 0.82–0.92) over follow-up. Similar associations were seen for individual medications. Over the 5 years of the study, persistence with prescribed therapies post-discharge improved modestly among high-risk patients (RR 1.05; 95% CI 1.03–1.08 per year). Conclusion High-risk AMI patients have a lower likelihood of persistently taking prescribed medications post-discharge as compared with low-risk patients. Continued efforts are needed to improve the use of guideline-directed medications in high-risk patients. PMID:25801001

  18. Cardiotoxicity of cancer therapeutics: current issues in screening, prevention, and therapy.

    PubMed

    Sheppard, Richard J; Berger, Jenna; Sebag, Igal A

    2013-01-01

    In the context of modern cancer chemotherapeutics, cancer survivors are living longer and being exposed to potential comorbidities related to non-cancer side effects of such treatments. With close monitoring of cancer patients receiving potentially cardiotoxic medical therapies, oncologists, and cardiologists alike are identifying patients in both clinical and subclinical phases of cardiovascular disease related to such chemotherapies. Specifically, cardiotoxicity at the level of the myocardium and potential for the development of heart failure are becoming a growing concern with increasing survival of cancer patients. Traditional chemotherapeutic agents used commonly in the treatment of breast cancer and hematologic malignancies, such as anthracyclines and HER-2 antagonists, are well known to be associated with cardiovascular sequelae. Patients often present without symptoms and an abnormal cardiac imaging study performed as part of routine evaluation of patients receiving cardiotoxic therapies. Additionally, patients can present with signs and symptoms of cardiovascular disease months to years after receiving the chemotherapies. As the understanding of the physiology underlying the various cancers has grown, therapies have been developed that target specific molecules that represent key aspects of physiologic pathways responsible for cancer growth. Inhibition of these pathways, such as those involving tyrosine kinases, has lead to the potential for cardiotoxicity as well. In view of the potential cardiotoxicity of specific chemotherapies, there is a growing interest in identifying patients who are at risk of cardiotoxicity prior to becoming symptomatic or developing cardiotoxicity that may limit the use of potentially life-saving chemotherapy agents. Serological markers and novel cardiac imaging techniques have become the source of many investigations with the goal of screening patients for pre-clinical cardiotoxicity. Additionally, studies have been performed

  19. [Relapse prevention program consisting of coping skills training, cue exposure treatment, and letter therapy for Japanese alcoholic men who relapsed after standard cognitive-behavioral therapy].

    PubMed

    Yokoyama, Akira; Matsushita, Sachio; Toyama, Tomomi; Nakayama, Hideki; Takimura, Tsuyoshi; Kimura, Mitsuru; Yoneda, Junichi; Maesato, Hitoshi; Mizukami, Takeshi; Higuchi, Susumu; Yokoyama, Tetsuji

    2015-04-01

    Coping skills training (CST) and cue exposure treatment (CET) have yielded favorable outcomes when used to treat alcoholics. We conducted 6-week inpatient programs that consisted of 9 CST group sessions (n = 117) during 2005-2009 and 9 CST group sessions plus 4 CET group sessions (n = 49) during 2009-2011 and subsequent 1-year letter therapy for Japanese alcoholic men who had relapsed and been readmitted after standard cognitive-behavioral inpatient therapy. When patients received a letter containing encouraging words every 2 weeks, they were asked to reread their CST and CET records and to respond to the letter by marking drinking days on a calendar and naming the skills on a list of the 9 CST themes and CET that were useful for maintaining abstinence during that 2-week period. The estimated percentages of achievement of 30 or fewer drinking days during the one year of letter therapy were 36.1 - 45.8%. 'Non-smoking', '2nd admission', and 'After age-limit job retirement' were significant factors in achieving good outcomes. The 'usefulness' responses for 'Increasing pleasant activities', 'CET', 'Anger management', ' Managing negative thinking', 'Problem solving', and ' Seemingly irrelevant decisions' as percentages of overall responses to the letters were significantly higher, in order of decreasing percentages, in the achiever group than in the non-achiever group, but the differences between the groups in ' Managing urges to drink', ' Drink refusal skills', ' Planning for emergencies', and ' Receiving criticism about drinking' were not significant. The odds ratios for achievement of 30 or fewer drinking days during the 1-year period increased significantly by 1.15 -1.31 fold per 10% increment in the 'usefulness' ratio for 'Increasing pleasant activities'. The difference in percentage achievement between the group treated by CST alone and the group treated by CST plus CET was not significant. In conclusion, some coping skills were more useful for relapse prevention

  20. DIMETHPYRINDENE—Use in High Dosage Hyposensitization Therapy; Prevention of Constitutional and Excessive Local Reactions

    PubMed Central

    Hartman, Milton M.

    1962-01-01

    To give larger doses of antigen for hyposensitization, yet hold down constitutional reactions and excessive local reactions, the antigen was mixed with epinephrine, ephedrine and dimethpyrindene, the latter a new antihistamine, just before subcutaneous injection. Dimethpyrindene, a potent antihistamine with minimal side effects, was also administered orally. The incidence of constitutional reactions and excessive local reactions was considerably diminished. Larger doses of antigens were tolerated and longer intervals between treatments were possible, a point of particular significance in maintenance therapy. There was less pain and discomfort at the site of injection and clinical results were improved. PMID:13905021

  1. [Clinical efficacy instant goat milk in the complex therapy and prevention of osteoporosis in patients with rheumatoid arthritis].

    PubMed

    Shostak, N A; Muradiants, A A; Kondrashov, A A; Denisova, S N

    2014-01-01

    Osteoporosis (OP) in rheumatoid arthritis (RA) refers to a secondary immune-mediated metabolic osteopathy characterized by periarticular and systemic decreased bone mass, impaired bone strength and increased risk of fractures. According to some studies, adding milk in the diet helps to increase bone mineral density and to reduce the risk of osteoporosis and maintain normal levels of vitamin D. To study the state of mineral and bone metabolism in RA patients zeith osteopenic syndrome and to evaluate the effectiveness of treatment and prevention of OP by adding dry goat milk "Amalteya" in the diet. The study included 42 patients with a documented diagnosis of RA (ACR, 1987) - 23 men (mean age 59 years) and 19 postmenopausal women (mean age 62 years) with the presence of osteoporosis and osteopenia according to the dual-energy X-ray absorptiometry. 21 (50%) RA patients (main group) received standard antiosteoporotichesky (alendronate 70 mg/week + calcium 1000 mg/day + Vitamin D3 800 IU/day) therapy and milk powder Amalteya® (400 ml/day). The control group (21 patients with RA) received only standard antiosteoporotic therapy. Follow-up lasted for 6 months. The concentration of total calcium in the blood of RA patients was on average 2.33 mmol/l, ionized Ca - 1,18 mmol/l and inorganic P - 1,09 mmol/l, which corresponds to normal values. Vitamin D deficiency was found in 17,5% of patients, and failure - in 32,5% of patients with RA. After 6 months of the treatment it was found that b-CrossLaps levels tend to be reducing in both of the groups and with reduction of bone formation marker osteocalcin in the group not receiving goat milk. Also, due to the background of ongoing combinative therapy it was clear that concentrations of 1,25(OH)2D and 25(OH)D in the blood serum are increasing (by 18,5-28,2% at the main group and by 8,0-17,9% at the control group), however, inter-group differences was below the level of the reliable importance. It was strongly marked in the group

  2. Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial

    PubMed Central

    Hovi, Sirpa-Liisa; Veerus, Piret; Rahu, Mati; Hemminki, Elina

    2008-01-01

    Background Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment. Methods The Estonian Postmenopausal Hormone Therapy trial (EPHT), originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM) in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT) on health services utilization. Results After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI) in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT. Conclusion Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials. The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old) drug for a new preventive indication? In preventive drug trials companies may donate drugs but they take a

  3. Recent advances in the prevention and treatment of skin cancer using photodynamic therapy

    PubMed Central

    Zhao, Baozhong; He, Yu-Ying

    2011-01-01

    Photodynamic therapy (PDT) is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to produce reactive oxygen species that specifically destroy target cells. Recently, PDT has been widely used in treating non-melanoma skin malignancies, the most common cancer in the USA, with superior cosmetic outcomes compared with conventional therapies. The topical ‘photosensitizers’ commonly used are 5-aminolevulinic acid (ALA) and its esterified derivative methyl 5-aminolevulinate, which are precursors of the endogenous photosensitizer protoporphyrin IX. After treatment with ALA or methyl 5-aminolevulinate, protoporphyrin IX preferentially accumulates in the lesion area of various skin diseases, which allows not only PDT treatment but also fluorescence diagnosis with ALA-induced porphyrins. Susceptible lesions include various forms of non-melanoma skin cancer such as actinic keratosis, basal cell carcinoma and squamous cell carcinoma. The most recent and promising developments in PDT include the discovery of new photosensitizers, the exploitation of new drug delivery systems and the combination of other modalities, which will all contribute to increasing PDT therapeutic efficacy and improving outcome. This article summarizes the main principles of PDT and its current clinical use in the management of non-melanoma skin cancers, as well as recent developments and possible future research directions. PMID:21080805

  4. A medicated polycarboxylate cement to prevent complications in composite resin therapy

    SciTech Connect

    Okamoto, Y.; Shintani, H.; Yamaki, M. )

    1990-01-01

    Preparative treatment is the preferred method to protect the dentin and pulp from complications in composite resin therapy. This study investigated the in vivo effects of the polycarboxylate cement containing zinc fluoride and tannic acid in composite resin restorations. Scanning electron micrographs established that the composite resin failed to contact the axial wall. The gaps varied from 10 to 60 microns. However, this polycarboxylate cement was shown to provide excellent adaptation to dentin when used as a base and its chemical adhesion allowed it to make close contact with the unetched dentin. The newly developed electron probe x-ray microanalyzer revealed that the in vivo penetration of fluoride and zinc occurred through the dentinal tubules. When this polycarboxylate cement was used, the orifices of dentinal tubules were partially occluded, possibly with the smear layer fixed by tannic acid. In addition, by releasing the components, this polycarboxylate cement adds acid resistance to dentin and increases the resistance of dentin collagen to proteolytic enzymes. As such this polycarboxylate cement offers advantages as a base to composite resin therapy.

  5. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

    PubMed Central

    Hütter, Gero; Bodor, Josef; Ledger, Scott; Boyd, Maureen; Millington, Michelle; Tsie, Marlene; Symonds, Geoff

    2015-01-01

    Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape. PMID:26225991

  6. Tumor microenvironment, a dangerous society leading to cancer metastasis. From mechanisms to therapy and prevention.

    PubMed

    Albini, Adriana

    2008-03-01

    Cancer is no longer considered by scientists just a jumble of mutated cells. To grow, invade and metastasize, a treacherous society between cancer and host cells must be formed, and this association provides novel and effective clinical targets for cancer control and prevention. This collection of reviews at the front-edge of scientific knowledge focuses on host-tumor cell interactions, the disastrous consequences they can produce and approaches the ways to break up these cellular conspiracies, to leave the tumor cells unattended and vulnerable. PMID:18043872

  7. Sporadic colorectal cancer: microbial contributors to disease prevention, development and therapy.

    PubMed

    Drewes, Julia L; Housseau, Franck; Sears, Cynthia L

    2016-07-26

    The gut microbiota has been hailed as an accessory organ, with functions critical to the host including dietary metabolic activities and assistance in the development of a proper functioning immune system. However, an aberrant microbiota (dysbiosis) may influence disease processes such as colorectal cancer. In this review, we discuss recent advances in our understanding of the contributions of the microbiota to prevention, initiation/progression, and treatment of colorectal cancer, with a major focus on biofilms and the antimicrobial and antitumoural immune response. PMID:27380134

  8. Sporadic colorectal cancer: microbial contributors to disease prevention, development and therapy

    PubMed Central

    Drewes, Julia L; Housseau, Franck; Sears, Cynthia L

    2016-01-01

    The gut microbiota has been hailed as an accessory organ, with functions critical to the host including dietary metabolic activities and assistance in the development of a proper functioning immune system. However, an aberrant microbiota (dysbiosis) may influence disease processes such as colorectal cancer. In this review, we discuss recent advances in our understanding of the contributions of the microbiota to prevention, initiation/progression, and treatment of colorectal cancer, with a major focus on biofilms and the antimicrobial and antitumoural immune response. PMID:27380134

  9. Anti-prostglandin therapy in prevention of side-effects of intrauterine contraceptive devices.

    PubMed

    Ylikorkala, O; Kauppila, A; Siljander, M

    1978-08-19

    The efficacy of an anti-prostaglandin, tolfenamic acid (T.A.), in the prevention of side-effects after insertion of a copper-T200 intrauterine contraceptive device (I.U.D.) was evaluated in a double-blind trial in 160 women. T.A. relieved pain and reduced bleeding after insertion and during three subsequent menstruations without serious side-effects. A scoring system for the assessment of I.U.D. side-effects showed that the acceptability of I.U.D. was significantly better in women treated with T.A. than in those given placebo. PMID:79760

  10. [Is primary or secondary prevention of diabetes mellitus in hyperliporoteinemia possible under long-term clofibrate therapy?].

    PubMed

    Haller, H; Michaelis, D; Hanefeld, M; Leonhardt, W; Schulze, J

    1976-07-01

    The investigations of metabolism explained speak for an improved condition of the carbohydrate metabolism during the first months of the therapy. However, they are not sufficient to prove a preventive effect of clofibrat per se during long-term treatment. Our examinations by means of the glucose infusion test show that on certain defined conditions with intensive general treatment positive effects may be registered, which, however, cannot be reproduced in a large collective during outpatient care. On the contrary, it is to be assumed that the whole therapeutic regime has an influence. Nevertheless, one may establish that the incidence portion of the diabetes manifestation in patients with hyperlipoproteinaemia treated with regadrin corresponds nearly to that one of the average population of Dresden. It is puzzling that the death rate in patients with hyperlipoproteinaemia and diabetic condition of metabolism is significantly higher than in hyperlipoproteinaemia without disturbance of the carbohydrate metabolism. PMID:822610

  11. Combined therapy for migraine prevention? Clinical experience with a beta-blocker plus sodium valproate in 52 resistant migraine patients.

    PubMed

    Pascual, J; Leira, R; Láinez, J M

    2003-12-01

    The aim was to explore whether combining a beta-blocker and sodium valproate could lead to an advantage in efficacy in patients with migraine previously resistant to the two medications in monotherapy. Fifty-two patients (43 women) with a history of episodic migraine with or without aura, and previously unresponsive to beta-blockers and sodium valproate in monotherapy, were treated with a combination of propranolol or nadolol and sodium valproate in an open-label fashion. Eight patients (15%) discontinued due to adverse events. Fifteen (29%) did not respond. The remaining 29 cases (56%) showed response (> 50% reduction in migraine days). The response was excellent in nine (17%). From this open trial, combination therapy with a beta-blocker and sodium valproate appears to be a good migraine preventative in some previously resistant migraine cases. Controlled trials are now necessary to determine the true advantage in efficacy of this combination in difficult to treat migraineurs. PMID:14984228

  12. Hydroxytyrosol-Derived Compounds: A Basis for the Creation of New Pharmacological Agents for Cancer Prevention and Therapy.

    PubMed

    Bernini, Roberta; Gilardini Montani, Maria Saveria; Merendino, Nicolò; Romani, Annalisa; Velotti, Francesca

    2015-12-10

    Hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol, HTyr] is a phenolic compound found in olive leaves and fruits and extra-virgin olive oil, which has well-known strong antioxidant and radical-scavenging properties. Recently, it has received particular attention for its antiproliferative and apoptotic activities and its anti-inflammatory properties. During the past few years, more efforts have been focused on synthesizing HTyr-derived compounds with enhanced biological activities for their potential use in different chronic degenerative diseases. In this paper, we report a dissertation on the current knowledge of selected synthetic HTyr derivatives and analogues and their potential use in cancer prevention and therapy, which are related to their antioxidant, antiproliferative/apoptotic, and anti-inflammatory properties. On the basis of the perspective of using HTyr-derived compounds as anticancer agents, we have taken into account only studies that were performed in experimental cell-based models. PMID:26225717

  13. Scheie syndrome: enzyme replacement therapy does not prevent progression of cervical myelopathy due to spinal cord compression.

    PubMed

    Illsinger, S; Lücke, T; Hartmann, H; Mengel, E; Müller-Forell, W; Donnerstag, F; Das, A M

    2009-12-01

    Hurler-Scheie syndrome is caused by alpha-l-iduronidase deficiency. Enzyme replacement therapy (ERT) can improve physical capacity and reduces organomegaly. However, the effect on bradytrophic connective tissue is limited. As intravenously administered enzyme cannot cross the blood-brain barrier, the therapy of choice for the more severe Hurler syndrome is haematopoietic stem cell transplantation (HCT). In the more attenuated Scheie syndrome, neurological impairment is less severe; therefore, ERT may be appropriate to treat these patients. Information on long-term outcome in Scheie patients undergoing ERT is scarce. We report a 38-year-old female Scheie patient who has been on ERT for 8 years. While non-neurological symptoms improved, she developed paresthesias in her hands and feet and progressive pain in her legs. Somatosensory evoked potentials were abnormal, suggesting dysfunction of the dorsal funiculus and lemniscus medialis. After 6 years of ERT, a spinal MRI showed dural thickening at the upper cervical spine. These soft-tissue deposits are presumably due to the accumulation of mucopolysaccharides. Intramedullary hyperintensities at the level of C1/2 revealed cervical myelopathy. An MRI before the start of ERT had shown milder spinal lesions. Cystic lesions in the white matter of the centrum semiovale due to dilated Virchow-Robin spaces were essentially unchanged compared with the MRI scan before ERT. Decompression of the spinal cord resulted in clinical improvement. In an adult patient with Scheie syndrome, ERT failed to prevent progression of cervical myelopathy. Clinical significance of cerebral changes is unclear. Whether early HCT or intrathecal ERT could have prevented these lesions remains speculative. PMID:19894140

  14. A new method of estimating cost effectiveness of cholesterol reduction therapy for prevention of heart disease.

    PubMed

    Kinlay, S; O'Connell, D; Evans, D; Halliday, J

    1994-03-01

    The purpose of this study was to demonstrate a new method of estimating the cost effectiveness of interventions that lower blood cholesterol levels in the prevention of coronary heart disease (CHD) at the community level. The participants in the study were 67 651 men aged 35 to 64 years in the Lower Hunter region of New South Wales, Australia. Census data, risk factor profiles and CHD event rates from community surveillance, plus costs in 1988-1989 Australian dollars, were used as inputs to a computer program that used a logistic equation. The output estimated the CHD events avoided and the cost effectiveness of an intervention that identified and treated men with cholesterol levels greater than 6.5 mmol/L with dietary modification and cholestyramine. The cost of implementation of the intervention was $A50.1 million to prevent 104 CHD events. The cost-effectiveness ratio was $A482 224 per CHD event avoided (SD = $A24 761) and the direct medical costs avoided were approximately $A500 000 over a 5-year period ($A4535.07 per CHD event avoided). Drug acquisition costs contributed substantially (88%) to the total costs of interventions that rely on screening to identify individuals with high cholesterol for intensive treatment. PMID:10146898

  15. Development of a biocompatible nanodelivery system for tuberculosis drugs based on isoniazid-Mg/Al layered double hydroxide

    PubMed Central

    Saifullah, Bullo; Arulselvan, Palanisamy; El Zowalaty, Mohamed Ezzat; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin M; Hussein, Mohd Zobir

    2014-01-01

    The primary challenge in finding a treatment for tuberculosis (TB) is patient non-compliance to treatment due to long treatment duration, high dosing frequency, and adverse effects of anti-TB drugs. This study reports on the development of a nanodelivery system that intercalates the anti-TB drug isoniazid into Mg/Al layered double hydroxides (LDHs). Isoniazid was found to be released in a sustained manner from the novel nanodelivery system in humans in simulated phosphate buffer solutions at pH 4.8 and pH 7.4. The nanodelivery formulation was highly biocompatible compared to free isoniazid against human normal lung and 3T3 mouse fibroblast cells. The formulation was active against Mycobacterium tuberculosis and gram-positive bacteria and gram-negative bacteria. Thus results show significant promise for the further study of these nanocomposites for the treatment of TB. PMID:25336952

  16. [Epidural abscess due to a Mycobacterium tuberculosis strain with primary resistance to isoniazid and ethambutol].

    PubMed

    Sener, Alper; Akçalı, Alper; Karatağ, Ozan; Koşar, Sule; Değirmenci, Yıldız; Akman, Tarık

    2012-10-01

    Tuberculosis is primarily characterized by pulmonary involvement, however, one third of the cases exhibit extrapulmonary tuberculosis. In this report, a case of epidural abscess due to Mycobacterium tuberculosis with primary resistance to isoniazid and ethambutol was presented. A 57-year-old male patient was admitted to emergency service with ten days history of weakness in legs, disability of walking and fever. Neurological examination revealed paraplegia of lower extremities, numbness distal to T2 disc level and hyperactivity of deep tendon reflexes indicating transverse myelitis. Laboratory findings were as follows; ESR: 74 mm/hour, CRP: 22 g/L, ALT: 42 IU/L, AST: 45 IU/L and white blood cell count 23.000/mm3 (45% polymorphonuclear leukocyte, 45% lymphocyte, 10% monocyte). Spinal magnetic resonance imaging showed a fusiform abscess localized at anterior epidural space and extending along levels of C5-6 and C6-7. The longitudinal dimension of the abscess was 3 cm. The lesion was hypointense on T1 and hyperintense on T2 weighted MRI images with prominent rim shaped contrast enhancement on contrast-enhanced T1-weighted images. At fourth day of hospitalization the patient underwent neurosurgical management. M.tuberculosis was isolated from the cultures of operation material by Mycobacteria Growth Incubator Tube system (MGIT, BBL; BD, USA) on the 12th day. The isolate was found susceptible to streptomycin and rifampisin, but resistant to isoniazid and ethambutol. The treatment was initiated with rifampicin 600 mg/day, pyrazinamid 2 g/day, ethambutol 1.5 g/day and levofloxacin 500 mg/day. At the end of second month levofloxacin 500 mg/day and rifampisin 600 mg/day combination was sustained and total treatment period was planned as nine months. As far as the national literature was considered, this was the first case of extrapulmonary tuberculosis with primary resistance to isoniazid and ethambutol. PMID:23188583

  17. [Indication for exercise therapy in infancy in the prevention of childhood cerebral palsy].

    PubMed

    Weber, S

    1983-01-01

    As in physiotherapy of cerebral palsy early therapy is desired, if possible even in early infancy, a period, when a safe diagnosis does not yet exist, infants at risk have to be identified. The resulting difficulties in early diagnosis and inevitability of treating a considerable number of not affected infants are discussed. The most common methods of physiotherapy are briefly described and evaluated critically concerning possible side effects as well. Superiority in effectivity improving motor efficiency of one method over another cannot be proven. It is shown, however, that in the Vojta method adverse psychological side effects cannot be excluded. Therefore, physiotherapy being a purely prophylactic and not a therapeutic procedure in the multitude of cases should be considered in ordering and selecting a particular method and the one according to Bobath should be favoured. PMID:6632714

  18. Lipid-Lowering Drug Therapy for CVD Prevention: Looking into the Future.

    PubMed

    Stein, Evan A; Raal, Frederick J

    2015-11-01

    Over the past three decades, statins have become first-line treatment for reducing LDL cholesterol (LDL-C) and cardiovascular disease (CVD). They have provided a clear, robust, and reproducible relationship between the absolute LDL-C reduction and the decrease in CVD; every 1 mmol/L (~40 mg/dL) in LDL-C reduction results in a 22 % decrease in CVD events. This relationship has recently been extended to reduction in LDL-C with a non-statin, ezetimibe, on top of statin therapy, further consolidating LDL-C as the cornerstone in CVD risk reduction. Despite these two effective and safe LDL-C-lowering drugs, there remains a need for additional drugs to reduce LDL-C, the focus of this review which covers agents which produce sufficient LDL-C reduction to potentially help address this unmet need and are either recently approved or currently in clinical trials. PMID:26385394

  19. Cow's milk allergy: from allergens to new forms of diagnosis, therapy and prevention.

    PubMed

    Hochwallner, Heidrun; Schulmeister, Ulrike; Swoboda, Ines; Spitzauer, Susanne; Valenta, Rudolf

    2014-03-01

    The first adverse reactions to cow's milk were already described 2,000 years ago. However, it was only 50 years ago that several groups started with the analysis of cow's milk allergens. Meanwhile the spectrum of allergy eliciting proteins within cow's milk is identified and several cow's milk allergens have been characterized regarding their biochemical properties, fold and IgE binding epitopes. The diagnosis of cow's milk allergy is diverse ranging from fast and cheap in vitro assays to elaborate in vivo assays. Considerable effort was spent to improve the diagnosis from an extract-based into a component resolved concept. There is still no suitable therapy available against cow's milk allergy except avoidance. Therefore research needs to focus on the development of suitable and safe immunotherapies that do not elicit severe side effect. PMID:23954566

  20. Effectiveness of probiotic therapy for the prevention of relapse in patients with inactive ulcerative colitis

    PubMed Central

    Yoshimatsu, Yasushi; Yamada, Akihiro; Furukawa, Ryuichi; Sono, Koji; Osamura, Aisaku; Nakamura, Kentaro; Aoki, Hiroshi; Tsuda, Yukiko; Hosoe, Nobuo; Takada, Nobuo; Suzuki, Yasuo

    2015-01-01

    AIM: To evaluate the effectiveness of probiotic therapy for suppressing relapse in patients with inactive ulcerative colitis (UC). METHODS: Bio-Three tablets, each containing 2 mg of lactomin (Streptococcus faecalis T-110), 10 mg of Clostridium butyricum TO-A, and 10 mg of Bacillus mesentericus TO-A, were used as probiotic therapy. Sixty outpatients with UC in remission were randomly assigned to receive 9 Bio-Three tablets/day (Bio-Three group) or 9 placebo tablets/day (placebo group) for 12 mo in addition to their ongoing medications. Clinical symptoms were evaluated monthly or on the exacerbation of symptoms or need for additional medication. Fecal samples were collected to analyze bacterial DNA at baseline and 3-mo intervals. Terminal restriction fragment length polymorphism and cluster analyses were done to examine bacterial components of the fecal microflora. RESULTS: Forty-six patients, 23 in each group, completed the study, and 14 were excluded. The relapse rates in the Bio-Three and placebo groups were respectively 0.0% vs 17.4% at 3 mo (P = 0.036), 8.7% vs 26.1% at 6 mo (P = 0.119), and 21.7% vs 34.8% (P = 0.326) at 9 mo. At 12 mo, the remission rate was 69.5% in the Bio-Three group and 56.6% in the placebo group (P = 0.248). On cluster analysis of fecal flora, 7 patients belonged to cluster I, 32 to cluster II, and 7 to cluster III. CONCLUSION: Probiotics may be effective for maintaining clinical remission in patients with quiescent UC, especially those who belong to cluster I on fecal bacterial analysis. PMID:26019464

  1. Nitric oxide release combined with nonsteroidal antiinflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy

    PubMed Central

    Brunelli, Silvia; Sciorati, Clara; D'Antona, Giuseppe; Innocenzi, Anna; Covarello, Diego; Galvez, Beatriz G.; Perrotta, Cristiana; Monopoli, Angela; Sanvito, Francesca; Bottinelli, Roberto; Ongini, Ennio; Cossu, Giulio; Clementi, Emilio

    2007-01-01

    Duchenne muscular dystrophy is a relatively common disease that affects skeletal muscle, leading to progressive paralysis and death. There is currently no resolutive therapy. We have developed a treatment in which we combined the effects of nitric oxide with nonsteroidal antiinflammatory activity by using HCT 1026, a nitric oxide-releasing derivative of flurbiprofen. Here, we report the results of long-term (1-year) oral treatment with HCT 1026 of two murine models for limb girdle and Duchenne muscular dystrophies (α-sarcoglycan-null and mdx mice). In both models, HCT 1026 significantly ameliorated the morphological, biochemical, and functional phenotype in the absence of secondary effects, efficiently slowing down disease progression. HCT 1026 acted by reducing inflammation, preventing muscle damage, and preserving the number and function of satellite cells. HCT 1026 was significantly more effective than the corticosteroid prednisolone, which was analyzed in parallel. As an additional beneficial effect, HCT 1026 enhanced the therapeutic efficacy of arterially delivered donor stem cells, by increasing 4-fold their ability to migrate and reconstitute muscle fibers. The therapeutic strategy we propose is not selective for a subset of mutations; it provides ground for immediate clinical experimentation with HCT 1026 alone, which is approved for use in humans; and it sets the stage for combined therapies with donor or autologous, genetically corrected stem cells. PMID:17182743

  2. Fullerene isoniazid conjugate--a tuberculostat with increased lipophilicity: synthesis and evaluation of antimycobacterial activity.

    PubMed

    Kumar, Anish; Patel, Gaurang; Menon, Shobhana Karuveettil

    2009-05-01

    A fullerene-isoniazid conjugate has been synthesized by 1, 3 dipolar cycloaddition reaction of fullerene (C(60)) with isonicotinic acid (4-formyl-benzylidene) hydrazide and N-methylglycine. The identity and purity of the compound was confirmed by elemental analysis, (1)H NMR, (13)C NMR and MALDI-TOF mass spectral analysis. Stable water suspension, in which the particles of the synthesized conjugate were made to aggregate in nanosize, was successfully tested for antimycobacterial activity against Mycobacterium avium and strains of Mycobacterium tuberculosis- H(37)Rv & H6/99 at concentration as low as 0.50 microg/mL. PMID:19366360

  3. Genetic Mutations Associated with Isoniazid Resistance in Mycobacterium tuberculosis: A Systematic Review

    PubMed Central

    Seifert, Marva; Catanzaro, Donald; Catanzaro, Antonino; Rodwell, Timothy C.

    2015-01-01

    Background Tuberculosis (TB) incidence and mortality are declining worldwide; however, poor detection of drug-resistant disease threatens to reverse current progress toward global TB control. Multiple, rapid molecular diagnostic tests have recently been developed to detect genetic mutations in Mycobacterium tuberculosis (Mtb) genes known to confer first-line drug resistance. Their utility, though, depends on the frequency and distribution of the resistance associated mutations in the pathogen population. Mutations associated with rifampicin resistance, one of the two first-line drugs, are well understood and appear to occur in a single gene region in >95% of phenotypically resistant isolates. Mutations associated with isoniazid, the other first-line drug, are more complex and occur in multiple Mtb genes. Objectives/Methodology A systematic review of all published studies from January 2000 through August 2013 was conducted to quantify the frequency of the most common mutations associated with isoniazid resistance, to describe the frequency at which these mutations co-occur, and to identify the regional differences in the distribution of these mutations. Mutation data from 118 publications were extracted and analyzed for 11,411 Mtb isolates from 49 countries. Principal Findings/Conclusions Globally, 64% of all observed phenotypic isoniazid resistance was associated with the katG315 mutation. The second most frequently observed mutation, inhA-15, was reported among 19% of phenotypically resistant isolates. These two mutations, katG315 and inhA-15, combined with ten of the most commonly occurring mutations in the inhA promoter and the ahpC-oxyR intergenic region explain 84% of global phenotypic isoniazid resistance. Regional variation in the frequency of individual mutations may limit the sensitivity of molecular diagnostic tests. Well-designed systematic surveys and whole genome sequencing are needed to identify mutation frequencies in geographic regions where rapid

  4. Contribution of kasA analysis to detection of isoniazid-resistant Mycobacterium tuberculosis in Singapore.

    PubMed

    Lee, A S; Lim, I H; Tang, L L; Telenti, A; Wong, S Y

    1999-08-01

    Genotypic analysis of resistance to isoniazid (INH) in Mycobacterium tuberculosis is complex due to the various genes potentially involved. Mutations in ketoacyl acyl carrier protein synthase (encoded by kasA) were present in 16 of 160 (10%) INH-resistant isolates (R121K [n = 1], G269S [n = 3], G312S [n = 11], G387D [n = 1]). However, G312S was also present in 6 of 32 (19%) susceptible strains. kasA analysis contributed marginally to the performance of INH genotypic testing in Singapore. The significance of kasA polymorphisms in INH resistance should be carefully established. PMID:10428945

  5. Pentecostalism and AIDS treatment in Mozambique: creating new approaches to HIV prevention through anti-retroviral therapy.

    PubMed

    Pfeiffer, James

    2011-01-01

    Pentecostal fervor has rapidly spread throughout central and southern Mozambique since the end of its protracted civil war in the early 1990s. In the peri-urban bairros and septic fringes of Mozambican cities African Independent Churches (AICs) with Pentecostal roots and mainstream Pentecostals can now claim over half the population as adherents. Over this same period another important phenomenon has coincided with this church expansion: the AIDS epidemic. Pentecostalism and HIV have travelled along similar vectors and been propelled by deepening inequality. Recognising this relationship has important implications for HIV/AIDS prevention and treatment strategies. The striking overlap between high HIV prevalence in peri-urban populations and high Pentecostal participation suggests that creative strategies, to include these movements in HIV/AIDS programming, may influence the long-term success of HIV care and the scale-up of anti-retroviral treatment (ART) across the region. The provision of ART has opened up new possibilities for engaging with local communities, especially Pentecostals and AICS, who are witnessing the immediate benefits of ARV therapy. Expanded treatment may be the key to successful prevention as advocates of a comprehensive approach to the epidemic have long argued. PMID:21892893

  6. [Achillodynia in athletes and dancers--recommendations for prevention and therapy].

    PubMed

    Paul, B; von Frankenberg, E

    1990-02-01

    Based on a disproportion between individual exercise tolerance and actual physical strain a multicausal tender swelling of achilles tendon with concomitant impaired function due to oedematous swelling, cellular proliferation and degeneration in tendon and paratenon is developing especially in motion engaged professionals like dancers artists and sportsmen. Consistent prevention of paratenonitis exist in selection of favourable bottom or mal conditions, maintenance of muscular balances, correction of ligamentous laxities and foot deformities, fitting chuck absorbing footwear and every time dosed increase of physical strain. While in acute stage after elimination of causative factors the conservative treatment is indicated, the treatment resistant chronic achillodynia with anamnesis of 4 month and more is an indication for operative treatment. PMID:2360888

  7. [Recommendations for the prevention and therapy of hypertrophic scars and keloids].

    PubMed

    Gauglitz, G G; Kunte, C

    2011-05-01

    Hypertrophic scars and keloids form due to aberrations in the physiologic wound healing cascade characterized by greater and more sustained ECM deposition. Both entities are frequently associated with pain, pruritus and contractures, and are thus significantly affecting the patient's quality of life. Genetic susceptibility, specific anatomic locations, prolonged inflammation and delayed epithelialization significantly contribute to excessive scar formation. However, despite intensive scientific work in this field the complex mechanisms underlying the processes of scarring and wound contraction remain poorly understood and most therapeutic approaches are clinically unsatisfactory. Nevertheless, based on a rising number of clinical studies next to well-known therapeutic concepts including cryotherapy and intralesional triamcinolone, recent techniques extend the spectrum for treating excessive scars. Nonetheless, prevention of pathologic scarring is undoubtedly more effective than to later attempts to treat it. PMID:21468729

  8. Concise Review: Next-Generation Cell Therapies to Prevent Infections in Neutropenic Patients

    PubMed Central

    Brunck, Marion E. G.

    2014-01-01

    High-dose chemotherapy is accompanied by an obligate period of neutropenia. Resulting bacterial and fungal infections are the leading cause of morbidity and mortality in neutropenic patients despite prophylactic antimicrobials and hematopoietic growth factor supplements. Replacing neutrophils in the patient through transfusion of donor cells is a logical solution to prevent fulminant infections. In the past, this strategy has been hampered by poor yield, inability to store collected cells, and possible donor morbidity caused by granulocyte colony-stimulating factor injections and apheresis. Today, neutrophil-like cells can be manufactured in the laboratory at the clinical scale from hematopoietic stem and progenitor cells enriched from umbilical cord blood. This article reviews the rationale for focusing research efforts toward ex vivo neutrophil production and explores clinical settings for future trials. PMID:24598780

  9. Prevention and treatment of oropharyngeal mucositis following cancer therapy: are there new approaches?

    PubMed

    Kwong, Karis K F

    2004-01-01

    Oropharyngeal mucositis is an acute and distressing toxic effect of chemotherapy and head and neck irradiation. This oral sequela significantly impairs the daily functioning and quality of life of patients. The biological basis of mucositis is quite complex, involving sequential interaction of chemotherapeutic drugs or irradiation on mitosis of proliferating epithelium, a number of cytokines, and elements of oral microbial environment. Various interventions based on biological attenuation have been tested for mucositis. Such interventions have been reviewed elsewhere; however, most reviews focus on biomedical outcomes. Little attention has been paid to mucositis outcomes with oral morbidity or psychosocial aspects. The purpose of this article is to review the current research studies on the prevention and treatment of oropharyngeal mucositis following chemotherapy, radiotherapy, and bone marrow transplantation with an emphasis on biomedical, oral symptomatic, and functional impairment outcomes. In addition, further avenues of mucositis management, including psychotherapeutic intervention and integrated and stage-based treatment approaches are discussed. PMID:15238805

  10. Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy.

    PubMed

    Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

    2013-10-15

    Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n = 8; 0.5, 0.3, 0.1 μg g(-1)) or D with vitamins C and E (DCE; n = 8; 200 and 100 mg kg(-1), respectively) on postnatal days 1-3 (P1-3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n = 8). A fourth group received vitamins alone (CCE; n = 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μM), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (cardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min(-1)) or afterload (cardiac output: -5.3 ± 2.0 vs.1.4 ± 1.2 ml min(-1)); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes cardiac

  11. Model-guided therapy for hepatocellular carcinoma: a role for information technology in predictive, preventive and personalized medicine

    PubMed Central

    2014-01-01

    Predictive, preventive and personalized medicine (PPPM) may have the potential to eventually improve the nature of health care delivery. However, the tools required for a practical and comprehensive form of PPPM that is capable of handling the vast amounts of medical information that is currently available are currently lacking. This article reviews a rationale and method for combining and integrating diagnostic and therapeutic management with information technology (IT), in a manner that supports patients through their continuum of care. It is imperative that any program devised to explore and develop personalized health care delivery must be firmly rooted in clinically confirmed and accepted principles and technologies. Therefore, a use case, relating to hepatocellular carcinoma (HCC), was developed. The approach to the management of medical information we have taken is based on model theory and seeks to implement a form of model-guided therapy (MGT) that can be used as a decision support system in the treatment of patients with HCC. The IT structures to be utilized in MGT include a therapy imaging and model management system (TIMMS) and a digital patient model (DPM). The system that we propose will utilize patient modeling techniques to generate valid DPMs (which factor in age, physiologic condition, disease and co-morbidities, genetics, biomarkers and responses to previous treatments). We may, then, be able to develop a statistically valid methodology, on an individual basis, to predict certain diseases or conditions, to predict certain treatment outcomes, to prevent certain diseases or complications and to develop treatment regimens that are personalized for that particular patient. An IT system for predictive, preventive and personalized medicine (ITS-PM) for HCC is presented to provide a comprehensive system to provide unified access to general medical and patient-specific information for medical researchers and health care providers from different

  12. Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention

    PubMed Central

    Jia, Shidong; Gao, Xueliang; Lee, Sang Hyun; Maira, Sauveur-Michel; Wu, Xiaoqiu; Stack, Edward C.; Signoretti, Sabina; Loda, Massimo; Zhao, Jean J; Roberts, Thomas M.

    2012-01-01

    Prostate cancer is an ideal target for chemoprevention. To date, chemoprevention clinical trials with 5α-reductase inhibitors (5-ARI) have yielded encouraging yet ultimately confounding results. Using a pre-clinical mouse model of high-grade prostatic intraepithelial neoplasia (HG-PIN) induced by PTEN loss, we observed unprecedented deteriorating effects of androgen deprivation, where surgical castration or MDV3100 treatment accelerated disease progression of the otherwise stable HG-PIN to invasive castration-resistant prostate cancer (CRPC). As an alternative, targeting the PI3K signaling pathway via either genetic ablation of PI3K components or pharmacological inhibition of PI3K pathway reversed the PTEN loss-induced HG-PIN phenotype. Finally, concurrent inhibition of PI3K and MAPK pathways was effective in blocking the growth of PTEN-null CRPC. Together, these data have revealed the potential adverse effects of anti-androgen chemoprevention in certain genetic contexts (such as PTEN loss) while demonstrating the promise of targeted therapy in the clinical management of this complex and prevalent disease. PMID:23258246

  13. Prevention of bladder tumor implantion after fluorescence-guided TUR with photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Berrahmoune, Saoussen; Bezdetnaya, Lina; de Witte, Peter; Leroux, Agnès; Dumas, Dominique; Guillemin, François; D'Hallewin, Marie Ange

    2009-06-01

    The prevalence of bladder cancer is very high, due to its high recurrence rate in superficial bladder cancer (30 to 85%), which is the staging of approximately 80% of the patients at first diagnosis. Risk of recurrence and progression is associated with grade, stage, presence of concomitant carcinoma in situ, size and number of lesions, as well as time to first recurrence. Recurrences can be partly attributed to new occurrences but also to residual tumors after resection. Incomplete tumor removal has been observed in 30 to 50% of TUR's, especially when dealing with T1 or poorly visible malignant or pre-malignant disease1. Fluorescence guided resection with 5 amino levulinic acid (ALA) or its hexyl ester derivative (Hexvix, has now unequivocally been demonstrated to increase detection rate and a growing number of studies indicate this has a positive impact on recurrence and progression ratesImplantation of viable tumor cells, dispersed during resection, is a third factor influencing bladder cancer recurrence. The aim of early intravesical therapy is to interfere with cell viability and thus reduce implantation risks.

  14. Photodynamic Therapy: Occupational Hazards and Preventative Recommendations for Clinical Administration by Healthcare Providers

    PubMed Central

    Lacey, Steven E.; Vesper, Benjamin J.; Paradise, William A.; Radosevich, James A.; Colvard, Michael D.

    2013-01-01

    Abstract Objective: Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these treatment devices and photosensitizing agents administered to patients. Materials and methods: Here we outline and identify pertinent health and safety considerations to be taken by healthcare staff during PDT procedures. Results: Physical hazards (for example, non-ionizing radiation generated by the light-emitting device, with potential for skin and eye exposure) and chemical hazards (including the photosensitizing agents administered to patients that have the potential for exposure via skin, subcutaneous, ingestion, or inhalation routes) must be considered for safe use of PDT by the healthcare professional. Conclusions: Engineering, administrative, and personal protective equipment controls are recommendations for the safe use and handling of PDT agents and light-emitting technologies. PMID:23859750

  15. Prevention of comorbidity and acute attack of gout by uric acid lowering therapy.

    PubMed

    Joo, Kowoon; Kwon, Seong-Ryul; Lim, Mie-Jin; Jung, Kyong-Hee; Joo, Hoyeon; Park, Won

    2014-05-01

    The object of this study was to evaluate the effect of uric acid lowering therapy in reducing the new development of comorbidities and the frequency of acute attacks in gout patients. We retrospectively reviewed patients who were diagnosed to have gout with at least 3 yr of follow up. They were divided into 2 groups; 53 patients with mean serum uric acid level (sUA)<6 mg/dL and 147 patients with mean sUA≥6 mg/dL. Comorbidities of gout such as hypertension (HTN), type II diabetes mellitus (DM), chronic kidney disease, cardiovascular disease (CVD) and urolithiasis were compared in each group at baseline and at last follow-up visit. Frequency of acute gout attacks were also compared between the groups. During the mean follow up period of 7.6 yr, the yearly rate of acute attack and the new development of HTN, DM, CVD and urolithiasis was lower in the adequately treated group compared to the inadequately treated group. Tight control of uric acid decreases the incidence of acute gout attacks and comorbidities of gout such as HTN, DM, CVD and urolithiasis. PMID:24851021

  16. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration

    PubMed Central

    Rouver, Wender Nascimento; Delgado, Nathalie Tristão Banhos; Menezes, Jussara Bezerra; Santos, Roger Lyrio; Moyses, Margareth Ribeiro

    2015-01-01

    The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium–dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose–response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium–dependent, BK–induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium–dependent vasodilator without increasing SBP. PMID:26322637

  17. Creosote bush lignans for human disease treatment and prevention: Perspectives on combination therapy

    PubMed Central

    Gnabre, John; Bates, Robert; Huang, Ru Chih

    2015-01-01

    The medicinal properties of the most successful plant in the deserts of the western hemisphere, the creosote bush (Larrea tridentata), are evidenced by the long traditional usage of the plants by the Native Americans Indian tribes in Southwestern North America and the Amerindians from South America. The plant is rich in simple bisphenyl lignans and tricyclic lignans known as cyclolignans. These compounds are responsible for many of the pharmacological activities of extracts of the plants. Some of these activities, namely antiherpes, antioxidant, antifungal, and anti-inflammatory, were known a century ago. Only recently have further studies revealed other crucial activities of the same plant molecules as powerful agents against human immunodeficiency virus, human papillomavirus, cancer, neurodegenerative diseases, and symptoms of aging. Molecular mechanisms underlying the antiviral and anticancer activities have been elucidated and involve the inhibition of SP1 dependent gene transcription. This review summarizes the recent findings on creosote bush lignans. We introduce the concept of a cocktail of safe well-characterized natural products from the creosote bush that would represent a bridge between oriental herbal medicines and Western drug-based therapies. PMID:26151022

  18. Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance

    PubMed Central

    Nichol, Daniel; Jeavons, Peter; Fletcher, Alexander G.; Bonomo, Robert A.; Maini, Philip K.; Paul, Jerome L.; Gatenby, Robert A.; Anderson, Alexander R.A.; Scott, Jacob G.

    2015-01-01

    The increasing rate of antibiotic resistance and slowing discovery of novel antibiotic treatments presents a growing threat to public health. Here, we consider a simple model of evolution in asexually reproducing populations which considers adaptation as a biased random walk on a fitness landscape. This model associates the global properties of the fitness landscape with the algebraic properties of a Markov chain transition matrix and allows us to derive general results on the non-commutativity and irreversibility of natural selection as well as antibiotic cycling strategies. Using this formalism, we analyze 15 empirical fitness landscapes of E. coli under selection by different β-lactam antibiotics and demonstrate that the emergence of resistance to a given antibiotic can be either hindered or promoted by different sequences of drug application. Specifically, we demonstrate that the majority, approximately 70%, of sequential drug treatments with 2–4 drugs promote resistance to the final antibiotic. Further, we derive optimal drug application sequences with which we can probabilistically ‘steer’ the population through genotype space to avoid the emergence of resistance. This suggests a new strategy in the war against antibiotic–resistant organisms: drug sequencing to shepherd evolution through genotype space to states from which resistance cannot emerge and by which to maximize the chance of successful therapy. PMID:26360300

  19. Creosote bush lignans for human disease treatment and prevention: Perspectives on combination therapy.

    PubMed

    Gnabre, John; Bates, Robert; Huang, Ru Chih

    2015-07-01

    The medicinal properties of the most successful plant in the deserts of the western hemisphere, the creosote bush (Larrea tridentata), are evidenced by the long traditional usage of the plants by the Native Americans Indian tribes in Southwestern North America and the Amerindians from South America. The plant is rich in simple bisphenyl lignans and tricyclic lignans known as cyclolignans. These compounds are responsible for many of the pharmacological activities of extracts of the plants. Some of these activities, namely antiherpes, antioxidant, antifungal, and anti-inflammatory, were known a century ago. Only recently have further studies revealed other crucial activities of the same plant molecules as powerful agents against human immunodeficiency virus, human papillomavirus, cancer, neurodegenerative diseases, and symptoms of aging. Molecular mechanisms underlying the antiviral and anticancer activities have been elucidated and involve the inhibition of SP1 dependent gene transcription. This review summarizes the recent findings on creosote bush lignans. We introduce the concept of a cocktail of safe well-characterized natural products from the creosote bush that would represent a bridge between oriental herbal medicines and Western drug-based therapies. PMID:26151022

  20. Testosterone Replacement Therapy Prevents Alterations of Coronary Vascular Reactivity Caused by Hormone Deficiency Induced by Castration.

    PubMed

    Rouver, Wender Nascimento; Delgado, Nathalie Tristão Banhos; Menezes, Jussara Bezerra; Santos, Roger Lyrio; Moyses, Margareth Ribeiro

    2015-01-01

    The present study aimed to determine the effects of chronic treatment with different doses of testosterone on endothelium-dependent coronary vascular reactivity in male rats. Adult male rats were divided into four experimental groups: control (SHAM), castrated (CAST), castrated and immediately treated subcutaneously with a physiological dose (0.5 mg/kg/day, PHYSIO group) or supraphysiological dose (2.5 mg/kg/day, SUPRA group) of testosterone for 15 days. Systolic blood pressure (SBP) was assessed at the end of treatment through tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed using the Langendorff retrograde perfusion technique. A dose-response curve for bradykinin (BK) was constructed, followed by inhibition with 100 μM L-NAME, 2.8 μM indomethacin (INDO), L-NAME + INDO, or L-NAME + INDO + 0.75 μM clotrimazole (CLOT). We observed significant endothelium-dependent, BK-induced coronary vasodilation, which was abolished in the castrated group and restored in the PHYSIO and SUPRA groups. Furthermore, castration modulated the lipid and hormonal profiles and decreased body weight, and testosterone therapy restored all of these parameters. Our results revealed an increase in SBP in the SUPRA group. In addition, our data led us to conclude that physiological concentrations of testosterone may play a beneficial role in the cardiovascular system by maintaining an environment that is favourable for the activity of an endothelium-dependent vasodilator without increasing SBP. PMID:26322637

  1. A Mechanism-Based Approach to Prevention of and Therapy for Fibromyalgia

    PubMed Central

    Vierck, Charles J.

    2012-01-01

    Fibromyalgia syndrome (FMS) is characterized by pain referred to deep tissues. Diagnosis and treatment of FMS are complicated by a variable coexistence with regional pain, fatigue, sleep disruption, difficulty with mentation, and depression. The widespread, deep pain of FMS can be a consequence of chronic psychological stress with autonomic dysregulation. Stress acts centrally to facilitate pain and acts peripherally, via sympathetic vasoconstriction, to establish painful muscular ischemia. FMS pain, with or without a coexistent regional pain condition, is stressful, setting up a vicious circle of reciprocal interaction. Also, stress interacts reciprocally with systems of control over depression, mentation, and sleep, establishing FMS as a multiple-system disorder. Thus, stress and the ischemic pain it generates are fundamental to the multiple disorders of FMS, and a therapeutic procedure that attenuates stress and peripheral vasoconstriction should be highly beneficial for FMS. Physical exercise has been shown to counteract peripheral vasoconstriction and to attenuate stress, depression, and fatigue and improve mentation and sleep quality. Thus, exercise can interrupt the reciprocal interactions between psychological stress and each of the multiple-system disorders of FMS. The large literature supporting these conclusions indicates that exercise should be considered strongly as a first-line approach to FMS therapy. PMID:22110947

  2. Benefits & risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians – A population with the highest risk of premature coronary artery disease & diabetes

    PubMed Central

    Enas, Enas A.; Kuruvila, Arun; Khanna, Pravien; Pitchumoni, C.S.; Mohan, Viswanathan

    2013-01-01

    Several reviews and meta-analyses have demonstrated the incontrovertible benefits of statin therapy in patients with cardiovascular disease (CVD). But the role for statins in primary prevention remained unclear. The updated 2013 Cochrane review has put to rest all lingering doubts about the overwhelming benefits of long-term statin therapy in primary prevention by conclusively demonstrating highly significant reductions in all-cause mortality, major adverse cardiovascular events (MACE) and the need for coronary artery revascularization procedures (CARPs). More importantly, these benefits of statin therapy are similar at all levels of CVD risk, including subjects at low (<1% per year) risk of a MACE. In addition to preventing myocardial infarction (MI), stroke, and death, primary prevention with statins is also highly effective in delaying and avoiding expensive CARPs such as angioplasties, stents, and bypass surgeries. There is no evidence of any serious harm or threat to life caused by statin therapy, though several adverse effects that affect the quality of life, especially diabetes mellitus (DM) have been reported. Asian Indians have the highest risk of premature coronary artery disease (CAD) and diabetes. When compared with Whites, Asian Indians have double the risk of CAD and triple the risk of DM, when adjusted for traditional risk factors for these diseases. Available evidence supports the use of statin therapy for primary prevention in Asian Indians at a younger age and with lower targets for low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein (non-HDL-C), than those currently recommended for Americans and Europeans. Early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of CAD among Indians. PMID:24434254

  3. The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae.

    PubMed

    Tsapanos, Vassilios S; Stathopoulou, Lavinia P; Papathanassopoulou, Vassiliki S; Tzingounis, Vassilios A

    2002-01-01

    This randomized controlled blind prospective study is undertaken to evaluate the safety and efficacy of Seprafilm--a novel bioresorbable membrane of chemically modified hyaluronic acid and carboxymethylcellulose--in prevention and reduction of postoperative endometrial and endocervical synechiae formation after general suction evacuation or curettage for incomplete, missed, and recurrent abortion. In total, 150 patients with incomplete or missed abortion participated in the clinical study. The study population was divided into two main groups. In the treatment (Seprafilm) group (n=50), application of Seprafilm membrane in the endometrial cavity and the cervical canal was used after the suction evacuation and/or the curettage. In the control group (n=100), nothing was inserted in the uterus. Both groups were divided into two subgroups: patients who had no previous suction or curettage, (with no previous D&C) (n=88), and patients who had at least one previous suction or curettage (with one or more previous D&C) (n=62). In the treatment (Seprafilm) group, 32 patients had no previous D&C and 18 patients had one or more previous D&C. In the control group, 56 patients had no previous D&C and 44 patients had one or more previous D&C. Further fertility was estimated by pregnancy success in all groups. Endometrial synechiae formation was evaluated with the use of hysterosalpingography (HSG) in patients of all groups without pregnancy success 8 months after the intervention. Registering any adverse reaction and performing ultrasound controls assessed the safety of Seprafilm use. From the subgroup with no previous D&C, all 32 patients (100%) who received Seprafilm had a pregnancy in the following 8 months; in the controls, pregnancy occurred only in 54%. It was also demonstrated with hysterosalpingography (HSG) that patients with one or more previous interventions and no pregnancy 8 months later were adhesion free in 90% of the patients where Seprafilm was used, and only 50

  4. Venous thromboembolism prevention during asparaginase-based therapy for acute lymphoblastic leukemia

    PubMed Central

    Sibai, H.; Seki, J.T.; Wang, T.Q.; Sakurai, N.; Atenafu, E.G.; Yee, K.W.L.; Schuh, A.C.; Gupta, V.; Minden, M.D.; Schimmer, A.D.; Brandwein, J.M.

    2016-01-01

    Background Venous thromboembolism (vte) is a recognized complication in patients treated with asparaginase-containing chemotherapy regimens; the optimal preventive strategy is unclear. We assessed the safety and efficacy of prophylaxis using low-dose low molecular weight heparin in adult patients with acute lymphoblastic leukemia in complete remission treated with an asparaginase-based post-remission chemotherapy regimen. Methods As part of the intensification phase of the Dana-Farber Cancer Institute 91-01 regimen, asparaginase was administered weekly to 41 consecutive patients for 21–30 weeks; these patients also received prophylaxis with enoxaparin 40 mg daily (60 mg for patients ≥80 kg). Outcomes were assessed against outcomes in a comparable cohort of 99 patients who received the same chemotherapy regimen without anticoagulation prophylaxis. Results The overall rate of symptomatic venous thrombosis was not significantly different in the prophylaxis and non-prophylaxis cohorts (18.92% and 21.74% respectively). Among patients receiving prophylaxis, vte occurred in higher proportion in those who weighed at least 80 kg (42.86% vs. 4.35%, p = 0.0070). No major bleeding complications occurred in the prophylaxis group (minor bleeding: 8.1%). Conclusions Prophylaxis with low-dose enoxaparin during the intensification phase was safe, but was not associated with a lower overall proportion of vte. PMID:27536184

  5. [Development of Preventive Therapy by Clarification of Mechanisms of Environmental-Factor-Mediated Diseases].

    PubMed

    Kato, Masashi; Omata, Yasuhiro; Iida, Machiko; Kumasaka, Mayuko Y; Ohgami, Nobutaka; Li, Xiang; Zou, Cunchao; Nakano, Chihiro; Kato, Yoko; Ohgami, Kyoko; Ohnuma, Shoko; Yajima, Ichiro

    2015-01-01

    Environmental factors affecting human health are generally classified into physical, chemical and biological factors. In this review article, we focus on ultraviolet (UV) as a physical factor, heavy metals as a chemical factor and Japanese cedar pollens as a biological factor. Since we believe that progress based on both fieldwork research and experimental research is essential in hygiene study, we included the results of both the research approached. We first introduced the mechanism of development of and prevention of UV-mediated skin melanoma in our experimental research after showing our epidemiological research on UV-mediated DNA damage in humans. We then introduced our evaluation of toxicity and development of a remediation system in our experimental research on heavy metals after showing our fieldwork research for the monitoring of drinking water from wells in Asian countries. We finally introduced the results of pathogenic analysis of pollinosis in our clinical study. We would be very happy if young researchers would re-realize the importance of experimental research as well as epidemiological research in hygiene study. PMID:26411934

  6. Systematic review of occupational therapy and mental health promotion, prevention, and intervention for children and youth.

    PubMed

    Arbesman, Marian; Bazyk, Susan; Nochajski, Susan M

    2013-01-01

    We describe the results of a systematic review of the literature on children's mental health using a public health model consisting of three levels of mental health service: universal, targeted, and intensive. At the universal level, strong evidence exists for the effectiveness of occupation- and activity-based interventions in many areas, including programs that focus on social-emotional learning; schoolwide bullying prevention; and after-school, performing arts, and stress management activities. At the targeted level, strong evidence indicates that social and life skills programs are effective for children who are aggressive, have been rejected, and are teenage mothers. The evidence also is strong that children with intellectual impairments, developmental delays, and learning disabilities benefit from social skills programming and play, leisure, and recreational activities. Additionally, evidence of the effectiveness of social skills programs is strong for children requiring services at the intensive level (e.g., those with autism spectrum disorder, diagnosed mental illness, serious behavior disorders) to improve social behavior and self-management. PMID:24195907

  7. Stroke and atrial fibrillation: risks, prevention and therapy in the elderly.

    PubMed

    Raffaeli, S; Paciaroni, E

    1995-01-01

    Atrial fibrillation (AF) represents a high risk of systemic embolism, particularly of stroke (S). This is true not only when AF is associated with an organic cardiopathy, but also in the so-called nonvalvular AF (NVAF). Not all cases of AF are of the same S-risk; such risk is higher for rheumatic AF and lower for NVAF. Therefore, a risk stratification is important in order to decide long-term antithrombotic prophylaxis. Five major trials have recently examined the thromboembolic prophylaxis in this group of patients. These randomised prospective open studies showed a significant reduction of S and systematic embolism in patients receiving low dose of warfarin (W), even in the elderly, as compared to placebo, and the incidence of hemorrhagic complications was also very low. Significant benefits of aspirin (ASA) were observed only in one trial in patients, except those older than 75 years. In a double blind, randomised trial indobufene was found effective resulting in 67% reduction of S and systematic embolism in patients with various cardiac diseases in AF or sinus rhythm. Consequently, a reasonable policy would be to treat patients with NVAF (also old ones) with anticoagulants unless contraindications or lone atrial fibrillations are present; in the latter cases ASA and indobufene should be considered. In the secondary prevention of ischemic S, W has given good results, whereas ASA and indobufene seem to be promising. PMID:15374252

  8. Neuroglobin Gene Therapy Prevents Optic Atrophy and Preserves Durably Visual Function in Harlequin Mice

    PubMed Central

    Lechauve, Christophe; Augustin, Sébastien; Cwerman-Thibault, Hélène; Reboussin, Élodie; Roussel, Delphine; Lai-Kuen, René; Saubamea, Bruno; Sahel, José-Alain; Debeir, Thomas; Corral-Debrinski, Marisol

    2014-01-01

    Neuroglobin (NGB) is considered as an endogenous neuroprotective molecule against stroke, since the protein alleviates the adverse effects of hypoxic and ischemic insults. We previously demonstrated the functional link between NGB and mitochondria since it is required for respiratory chain function. Thus, here, we evaluated the relevance of this effect in the Harlequin (Hq) mouse strain, which exhibits retinal ganglion cell (RGC) loss and optic atrophy due to a respiratory chain complex I (CI) defect. A twofold decrease of NGB amounts was observed in Hq retinas. We constructed a recombinant adeno-associated virus which combines to the mouse NGB open reading frame, its 5′ and 3′UTR, for guarantying mRNA stability and translation capacity. The vector was administrated intravitreally to Hq mice and NGB expression was stable for up to 7 months without negative effect on retinal architecture or function. On the contrary, RGCs and their axons were substantially preserved from degeneration; consequently, CI activity in optic nerves was protected conferring improvements in vision. Hence, we established that NGB prevents respiratory chain impairment, therefore, protecting visual function otherwise compromised by mitochondrial energetic failure. PMID:24622090

  9. Prevention and Treatment of Venous Thromboembolism in Patients with Cancer: Focus on Drug Therapy.

    PubMed

    van Es, Nick; Bleker, Suzanne M; Wilts, Ineke T; Porreca, Ettore; Di Nisio, Marcello

    2016-03-01

    Venous thromboembolism (VTE) is a frequent complication in patients with cancer and is associated with significant morbidity and mortality. The use of anticoagulants for the prevention and treatment of VTE in this population is challenging given the high risk of both recurrent VTE and bleeding complications. Thromboprophylaxis with subcutaneous low-molecular-weight heparin (LMWH) is recommended in cancer patients hospitalized for an acute medical illness and in those undergoing major surgery. In ambulatory cancer patients with or without central venous catheters, routine thromboprophylaxis is not recommended because of the relatively low benefit-to-risk ratio. To identify cancer outpatients at very high risk of VTE who may benefit from thromboprophylaxis, VTE risk stratification tools based on tumour type, clinical parameters, or coagulation biomarkers have been proposed, but their clinical utility needs validation. The mainstay of treatment for cancer-associated VTE is LMWH for at least 6 months or longer in case of active disease. The same initial and long-term treatment for incidental VTE as for symptomatic VTE can be suggested while awaiting additional studies in this area. PMID:26729187

  10. Preparation and characterization of magnetic Fe3O4-chitosan nanoparticles loaded with isoniazid

    NASA Astrophysics Data System (ADS)

    Qin, H.; Wang, C. M.; Dong, Q. Q.; Zhang, L.; Zhang, X.; Ma, Z. Y.; Han, Q. R.

    2015-05-01

    A novel and simple method has been proposed to prepare magnetic Fe3O4-chitosan nanoparticles loaded with isoniazid (Fe3O4/CS/INH nanocomposites). Efforts have been made to develop isoniazid (INH) loaded chitosan (CS) nanoparticles by ionic gelation of chitosan with tripolyphosphate (TPP). The factors that influence the preparation of chitosan nanoparticles, including the TPP concentration, the chitosan/TPP weight ratio and the chitosan concentration on loading capacity and encapsulation efficiency of chitosan nanoparticles were studied. The magnetic Fe3O4 nanoparticles were prepared by co-precipitation method of Fe2+ and Fe3+. Then the magnetic Fe3O4/CS/INH nanocomposites were prepared by ionic gelation method. The magnetic Fe3O4 nanoparticles and magnetic Fe3O4/CS/INH nanocomposites were characterized by XRD, TEM, FTIR and SQUID magnetometry. The in vitro release of Fe3O4/CS/INH nanocomposites showed an initial burst release in the first 10 h, followed by a more gradual and sustained release for 48 h. It is suggested that the magnetic Fe3O4/CS/INH nanocomposites may be exploited as potential drug carriers for controlled-release applications in magnetic targeted drugs delivery system.

  11. Simultaneous chemometric determination of pyridoxine hydrochloride and isoniazid in tablets by multivariate regression methods.

    PubMed

    Dinç, Erdal; Ustündağ, Ozgür; Baleanu, Dumitru

    2010-08-01

    The sole use of pyridoxine hydrochloride during treatment of tuberculosis gives rise to pyridoxine deficiency. Therefore, a combination of pyridoxine hydrochloride and isoniazid is used in pharmaceutical dosage form in tuberculosis treatment to reduce this side effect. In this study, two chemometric methods, partial least squares (PLS) and principal component regression (PCR), were applied to the simultaneous determination of pyridoxine (PYR) and isoniazid (ISO) in their tablets. A concentration training set comprising binary mixtures of PYR and ISO consisting of 20 different combinations were randomly prepared in 0.1 M HCl. Both multivariate calibration models were constructed using the relationships between the concentration data set (concentration data matrix) and absorbance data matrix in the spectral region 200-330 nm. The accuracy and the precision of the proposed chemometric methods were validated by analyzing synthetic mixtures containing the investigated drugs. The recovery results obtained by applying PCR and PLS calibrations to the artificial mixtures were found between 100.0 and 100.7%. Satisfactory results obtained by applying the PLS and PCR methods to both artificial and commercial samples were obtained. The results obtained in this manuscript strongly encourage us to use them for the quality control and the routine analysis of the marketing tablets containing PYR and ISO drugs. PMID:20645279

  12. Molecular Dynamics Assisted Mechanistic Study of Isoniazid-Resistance against Mycobacterium tuberculosis InhA

    PubMed Central

    Kumar, Vivek; Sobhia, M. Elizabeth

    2015-01-01

    Examination of InhA mutants I16T, I21V, I47T, S94A, and I95P showed that direct and water mediated H-bond interactions between NADH and binding site residues reduced drastically. It allowed conformational flexibility to NADH, particularly at the pyrophosphate region, leading to weakening of its binding at dinucleotide binding site. The highly scattered distribution of pyrophosphate dihedral angles and chi1 side chain dihedral angles of corresponding active site residues therein confirmed weak bonding between InhA and NADH. The average direct and water mediated bridged H-bond interactions between NADH and mutants were observed weaker as compared to wild type. Further, estimated NADH binding free energy in mutants supported the observed weakening of InhA-NADH interactions. Similarly, per residue contribution to NADH binding was also found little less as compared to corresponding residues in wild type. This investigation clearly depicted and supported the effect of mutations on NADH binding and can be accounted for isoniazid resistance as suggested by previous biochemical and mutagenic studies. Further, structural analysis of InhA provided the crucial points to enhance the NADH binding affinity towards InhA mutants in the presence of direct InhA inhibitors to combat isoniazid drug resistance. This combination could be a potential alternative for treatment of drug resistant tuberculosis. PMID:26658674

  13. Vitamin D3 in cancer prevention and therapy: the nutritional issue.

    PubMed

    Chirumbolo, Salvatore

    2015-09-01

    The action of vitamin D3, in its biological form 1α,25(OH)2vitD3 or calcitriol, may be summarized as a steroid-like hormone able to modulate basic functions of cell encompassing energy balance, stress response, mitochondria biogenesis, intracellular calcium oscillations, and replication/apoptosis mechanisms leading to cell survival. Moreover, calcitriol exerts a potent role as an innate and adaptive immune cytokine as immunity is closely related to self-maintenance through its energetic/metabolic balance and homeostasis of cell turnover. Therefore, vitamin D might be the ancestral form of survival hormones developed with calcified vertebrate bearing skeleton in order to survive far from water. This characteristic may suggest that the role of dietary vitamin D in preventing cancer is simply ancillary to the many factors playing a major role in contrasting impairment in energy balance and cell survival. Most probably, the immune role of calcitriol might be included in the maintenance, mostly by adipose tissue, of an anti-inflammatory, tolerant immune status, depending on the immune tolerance and modulation from the gut. A balance closely modulated by the leptin axis, which when impairments in metabolism occur, such as in insulin resistance or obesity, calcitriol is unable to face at this imbalance, while leptin plays a major role and cancer progression may be promoted. Furthermore, this mechanism promotes epithelial/mesenchymal transition-mediated fibrosis, leading to cancer resistance to immune control and drug action. Interestingly, this pathologic picture is triggered by deficiency in vitamin D from the diet. Therefore, a dietary habit including vitamin D sources, besides flavonoids, may ameliorate lifestyle and health span in most individuals, depending on their genetic background. PMID:26057218

  14. Statin Therapy for the Prevention of Atrial Fibrillation Trial (SToP AF trial)

    PubMed Central

    Negi, Smita; Shukrullah, Irfan; Veledar, Emir; Bloom, Heather L.; Jones, Dean P.; Dudley, Samuel C.

    2010-01-01

    Background Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation. (NCT00252967) Methods and Results In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n=33) or placebo (n=31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers [ high sensitivity C- reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α (TNFα)] were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (p=0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, p=0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median (IR): 29 (2-145) days vs. 22 (7-70) days, p=0.9). While no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, p= 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, p=0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (p=0.03). Conclusions High dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress. PMID:20946227

  15. Potential of tocotrienols in the prevention and therapy of Alzheimer's disease.

    PubMed

    Xia, Weiming; Mo, Huanbiao

    2016-05-01

    Currently there is no cure for Alzheimer's disease (AD); clinical trials are underway to reduce amyloid generation and deposition, a neuropathological hallmark in brains of AD patients. While genetic factors and neuroinflammation contribute significantly to AD pathogenesis, whether increased cholesterol level is a causative factor or a result of AD is equivocal. Prenylation of proteins regulating neuronal functions requires mevalonate-derived farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). The observation that the levels of FPP and GGPP, but not that of cholesterol, are elevated in AD patients is consistent with the finding that statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, reduce FPP and GGPP levels and amyloid β protein production in preclinical studies. Retrospective studies show inverse correlations between incidence of AD and the intake and serum levels of the HMG CoA reductase-suppressive tocotrienols; tocopherols show mixed results. Tocotrienols, but not tocopherols, block the processing and nuclear localization of sterol regulatory element binding protein-2, the transcriptional factor for HMG CoA reductase and FPP synthase, and enhance the degradation of HMG CoA reductase. Consequently, tocotrienols deplete the pool of FPP and GGPP and potentially blunt prenylation-dependent AD pathogenesis. The antiinflammatory activity of tocotrienols further contributes to their protection against AD. The mevalonate- and inflammation-suppressive activities of tocotrienols may represent those of an estimated 23,000 mevalonate-derived plant secondary metabolites called isoprenoids, many of which are neuroprotective. Tocotrienol-containing plant foods and tocotrienol derivatives and formulations with enhanced bioavailability may offer a novel approach in AD prevention and treatment. PMID:27133418

  16. Apolipoprotein A-V gene therapy for disease prevention / treatment: a critical analysis

    PubMed Central

    Forte, Trudy M.; Sharma, Vineeta; Ryan, Robert O.

    2016-01-01

    Abstract Apolipoprotein (apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol (TG) homeostasis. Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipo­protein lipase-mediated TG hydrolysis, another portion is recovered intracellularly, in association with cytosolic lipid droplets. Loss of apoA-V function is positively correlated with elevated plasma TG and increased risk of car­diovascular disease. Single nucleotide polymorphisms (SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions. Likewise, rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction. Genetically engineered mouse mod­els and human population studies suggest that, in certain instances, supplementation with wild type (WT) apoA-V may have therapeutic benefit. It is hypothesized that individuals that manifest elevated plasma TG owing to deleter­ious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance. On the other hand, subjects with hypertriglyceridemia of independent origin (unrelated to apoA-V func­tion) may not respond to apoA-V augmentation in this manner. Improvement in the ability to identify individuals predicted to benefit, advances in gene transfer technology and the strong connection between HTG and heart disease, point to apoA-V supplementation as a viable disease prevention / therapeutic strategy. Candidates would include individuals that manifest chronic TG elevation, have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels. PMID:26679785

  17. Key Pathways to Prevent Posttraumatic Arthritis for Future Molecule-Based Therapy

    PubMed Central

    Wimmer, Markus A.

    2013-01-01

    Joint injuries are common, especially among young adults aged 18 to 44 years. They are accompanied by a cascade of events that increase the risk of posttraumatic osteoarthritis (PTOA). Therefore, understanding of biological responses that predispose to PTOA should help in determining treatment modalities to delay and/or prevent the onset and progression of the disease. The vast majority of the literature pointed to chondrocyte death and apoptosis, inflammation and matrix damage/fragmentation being the earliest events that follow joint trauma. Together these events lead to the development of osteoarthritis-like focal cartilage lesions that if untreated have a tendency to expand and progress to fully developed disease. Currently, the only treatments available for joint trauma are surgical interventions. Experimental biologic approaches involve engineering of cartilage with the use of cells (stem cells or chondrocytes), juvenile or adult cartilage pieces, scaffolds, and various polymeric matrices. The major challenge for all of them is regeneration of normal functional mature hyaline cartilage that can sustain the load, resist compression, and most important, integrate with the host tissue. If the tissue is spontaneously repaired it fails to reproduce original structure and function and thus, may be more susceptible to re-injury. Thus, there is a critical need to develop novel molecular mechanism-based therapeutic approaches to biologic chondral and/or osteochondral repair. The focus of this review is on the earliest molecular and cellular manifestations of injury that can be grouped based on the following therapeutic options for PTOA: chondroprotection, anti-inflammatory, matrix protection, and matrix remodeling/matrix synthesis. PMID:26069661

  18. Guidelines of Care for the Management of Atopic Dermatitis Part 4: Prevention of Disease Flares and Use of Adjunctive Therapies and Approaches

    PubMed Central

    Sidbury, Robert; Tom, Wynnis L.; Bergman, James N.; Cooper, Kevin D.; Silverman, Robert A.; Berger, Timothy G.; Chamlin, Sarah L.; Cohen, David E.; Cordoro, Kelly M.; Davis, Dawn M.; Feldman, Steven R.; Hanifin, Jon M.; Krol, Alfons; Margolis, David J.; Paller, Amy S.; Schwarzenberger, Kathryn; Simpson, Eric L.; Williams, Hywel C.; Elmets, Craig A.; Block, Julie; Harrod, Christopher G.; Begolka, Wendy Smith; Eichenfield, Lawrence F.

    2015-01-01

    Atopic dermatitis (AD) is a common, chronic inflammatory dermatosis that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this final section, treatments for flare prevention and adjunctive and complementary therapies and approaches are reviewed. Suggestions on utilization are given based on available evidence. PMID:25264237

  19. Treatment-Specific Changes in Decentering Following Mindfulness-Based Cognitive Therapy versus Antidepressant Medication or Placebo for Prevention of Depressive Relapse

    ERIC Educational Resources Information Center

    Bieling, Peter J.; Hawley, Lance L.; Bloch, Richard T.; Corcoran, Kathleen M.; Levitan, Robert D.; Young, L. Trevor; MacQueen, Glenda M.; Segal, Zindel V.

    2012-01-01

    Objective: To examine whether metacognitive psychological skills, acquired in mindfulness-based cognitive therapy (MBCT), are also present in patients receiving medication treatments for prevention of depressive relapse and whether these skills mediate MBCT's effectiveness. Method: This study, embedded within a randomized efficacy trial of MBCT,…

  20. Vitamin D: considerations in the continued development as an agent for cancer prevention and therapy.

    PubMed

    Trump, Donald L; Deeb, Kristin K; Johnson, Candace S

    2010-01-01

    Considerable preclinical and epidemiologic data suggest that vitamin D may play a role in the pathogenesis, progression, and therapy for cancer. Numerous epidemiologic studies support the hypothesis that individuals with lower serum vitamin D levels have a higher risk of a number of cancers. Measures of vitamin D level in such studies include both surrogate estimates of vitamin D level (residence in more northern latitudes, history of activity, and sun exposure) as well as measured serum 25(OH) cholecalciferol levels. Perhaps, the most robust of these epidemiologic studies is that of Giovannucci et al, who developed and validated an estimate of serum 25(OH) cholecalciferol level and reported that among >40,000 individuals in the Health Professionals Study, an increase in 25(OH) cholecalciferol level of 62.5 ng/mL was associated with a reduction in the risk of head/neck, esophagus, pancreas cancers, and acute leukemia by >50%. Unfortunately, very limited data are available to indicate whether or not giving vitamin D supplements reduces the risk of cancer. Many preclinical studies indicate that exposing cancer cells, as well as vascular endothelial cells derived from tumors, to high concentrations of active metabolites of vitamin D halts progression through cell cycle, induces apoptosis and will slow or stop the growth of tumors in vivo. There are no data that one type of cancer is more or less susceptible to the effects of vitamin D. Vitamin D also potentiates the antitumor activity of a number of types of cytotoxic anticancer agents in in vivo preclinical models. Vitamin D analogues initiate signaling through a number of important pathways, but the pathway(s) essential to the antitumor activities of vitamin D are unclear. Clinical studies of vitamin D as an antitumor agent have been hampered by the lack of a suitable pharmaceutical preparation for clinical study. All commercially available formulations are inadequate because of the necessity to administer large

  1. Vitamin D: Considerations in the Continued Development as an Agent for Cancer Prevention and Therapy

    PubMed Central

    Trump, Donald L.; Deeb, Kristen; Johnson, Candace S.

    2010-01-01

    Considerable preclinical and epidemiologic data suggest that vitamin D may play a role in the pathogenesis, progression and therapy of cancer. Numerous epidemiologic studies support the hypothesis that individuals with lower serum vitamin D levels have a higher risk of a number of cancers. Measures of vitamin D level in such studies include both surrogate estimates of vitamin D level (residence in more northern latitudes, history of activity and sun exposure) as well as measured serum 25(OH) cholecalciferol levels. Perhaps the most robust of these epidemiologic studies is that of Giovannucci and colleagues who developed and validated an estimate of serum 25(OH) cholecalciferol level and reported that among more than 40,000 individuals in the Health professionals Study an increase in 25(OH) cholecalciferol level of 62.5ng/mL was associated with a reduction in the risk of head/neck, esophagus, pancreas cancers and acute leukemia by >50%. Unfortunately very limited data are available to indicate whether or not giving vitamin D supplements reduces the risk of cancer. Many preclinical studies indicate that exposing cancer cells – as well as vascular endothelial cells derived from tumors - to high concentrations of active metabolites of vitamin D halts progression through cell cycle, induces apoptosis and will slow or stop the growth of tumors in vivo. There are no data that one type of cancer is more or less susceptible to the effects of vitamin D. Vitamin D also potentiates the antitumor activity of a number of types of cytotoxic anticancer agents in in vivo preclinical models. Vitamin D analogues initiate signaling through a number of important pathways, but the pathway(s) essential to the antitumor activities of vitamin D are unclear. Clinical studies of vitamin D as an antitumor agent have been hampered by the lack of a suitable pharmaceutical preparation for clinical study. All commercially available formulations are inadequate because of the necessity to

  2. Impact of Maintenance Therapy for the Prevention of Peri-implant Diseases: A Systematic Review and Meta-analysis.

    PubMed

    Monje, A; Aranda, L; Diaz, K T; Alarcón, M A; Bagramian, R A; Wang, H L; Catena, A

    2016-04-01

    At the present time, peri-implantitis has become a global burden that occurs with a frequency from 1% to 47% at implant level. Therefore, we aimed herein at assessing the impact of peri-implant maintenance therapy (PIMT) on the prevention of peri-implant diseases. Electronic and manual literature searches were conducted by 3 independent reviewers using several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register, for articles up to June 2015 without language restriction. Articles were included if they were clinical trials aimed at demonstrating the incidence of peri-implant diseases under a strict regime or not of PIMT. Implant survival and failure rate were studied as secondary outcomes. A meta-analysis was conducted to evaluate the influence of PIMT and other reported variables upon peri-implant diseases. Thirteen and 10 clinical trials were included in the qualitative and quantitative analysis, respectively. Mucositis was affected by history of periodontitis and mean PIMT at implant and patient levels, respectively. Similarly, significant effects of history of periodontal disease were obtained for peri-implantitis for both implant and patient levels. Furthermore, mean PIMT interval was demonstrated to influence the incidence of peri-implantitis at implant but not patient level. PIMT interval showed significance at both levels. For implant survival, implants under PIMT have 0.958 the incident event than those with no PIMT. Within the limitations of the present systematic review, it can be concluded that implant therapy must not be limited to the placement and restoration of dental implants but to the implementation of PIMT to potentially prevent biologic complications and hence to heighten the long-term success rate. Although it must be tailored to a patient's risk profiling, our findings suggest reason to claim a minimum recall PIMT interval of 5 to 6 mo. Additionally, it must be

  3. Cost-effectiveness of rifampin for 4 months and isoniazid for 9 months in the treatment of tuberculosis infection.

    PubMed

    Pina, J M; Clotet, L; Ferrer, A; Sala, M R; Garrido, P; Salleras, L; Domínguez, A

    2013-05-01

    The purpose of this study was to evaluate the cost-effectiveness of the strategy of controlling the contacts of tuberculosis patients with latent tuberculosis infection by means of treatment with rifampin for 4 months or isoniazid for 9 months. The cost was the sum of the cost of treating latent tuberculosis infection in all contacts plus the cost of treating tuberculosis in whom the disease was not avoided. The effectiveness was expressed as cases avoided. The efficacy adopted was 90 % for rifampin for 4 months and 93 % for isoniazid for 9 months. We carried out a sensitivity analysis for efficacies of rifampin for 4 months of 80 %, 75 %, 69 % and 65 %. Of the 1,002 patients studied, 139 were treated with rifampin for 4 months and 863 were treated with isoniazid for 9 months. The cost-effectiveness was 436,842.83/50 cases avoided with rifampin for 4 months and 692,164.42/40 cases avoided with isoniazid for 9 months. Rifampin for 4 months was dominant. In the sensitivity analysis, rifampin for 4 months was dominant for efficacies of 75 % or greater. The cost-effectiveness analysis favoured the use of rifampin for 4 months when its efficacy was 75 % or greater. PMID:23238684

  4. Lupus érythémateux systémique induit par l'isoniazide: une complication rare à craindre

    PubMed Central

    Jguirim, Mahbouba; Jbeli, Amna; Brahim, Hajer Ben; Mhenni, Amira; Youssef, Monia; Touzi, Mongi; Zrour, Sawssen; Bejia, Ismail; Bergaoui, Naceur

    2015-01-01

    Le lupus induit est défini comme un syndrome lupique généralement cutanéo-articulaire secondaire à une exposition continue à un traitement et qui disparaît après arrêt de celle-ci. Nous rapportons deux cas de lupus induit par l'isoniazide. Il s'agissait de deux femmes âgées respectivement de 30 et 35 ans. Elles présentaient un lupus induit par l'isoniazide après un et deux mois de traitement d'une tuberculose ganglionnaire. La maladie s'est manifestée par des signes articulaires, une éruption cutanée, une leucopénie et une anémie. Les anticorps antinucléaires et les anticorps antihistone étaient présents dans le sérum des deux malades. L’évolution était favorable après arrêt de l'isoniazide et une corticothérapie per os. Les médicaments antituberculeux notamment l'isoniazide sont responsables d'effets indésirables fréquents. Le lupus induit doit être évoqué lorsqu'un patient présente un tableau clinico-biologique évocateur. PMID:26430478

  5. Prevalence, Risk Factors, and Treatment Outcomes of Isoniazid- and Rifampicin- Mono-Resistant Pulmonary Tuberculosis in Lima, Peru

    PubMed Central

    Villegas, Leonela; Huaman, Moises A.; Van der Stuyft, Patrick; Gotuzzo, Eduardo; Seas, Carlos

    2016-01-01

    Background Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes. Methods A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment. Results Of 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1–4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9–47.8). Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01). Conclusion A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes. PMID:27045684

  6. Web-Based Cognitive Behavioral Therapy Intervention for the Prevention of Suicidal Ideation in Medical Interns: A Randomized Controlled Trial

    PubMed Central

    Guille, Constance; Zhao, Zhuo; Krystal, John; Nichols, Breck; Brady, Kathleen; Sen, Srijan

    2016-01-01

    Importance In the United States, approximately one physician dies by suicide every day. Training physicians are at particularly high risk, with suicidal ideation increasing over four-fold during the first three months of internship year. Despite this dramatic increase, very few efforts have been made to prevent the escalation of suicidal thoughts among training physicians. Objective To assess the effectiveness of a Web-based Cognitive Behavioral Therapy (wCBT) program delivered prior to the start of internship year in the prevention of suicidal ideation in medical interns. Design, Setting and Participants A randomized controlled trial conducted at two university hospitals with 199 interns from multiple specialties during academic years 2009-10 or 2011-12. Interventions Interns were randomly assigned to study groups (wCBT, n=100; attention-control group (ACG), n=99), and completed study activities lasting 30-minutes each week for four weeks prior to starting internship year. Subjects assigned to wCBT completed online-CBT modules and subjects assigned to ACG received emails with general information about depression, suicidal thinking and local mental health providers. Main Outcome Measure The Patient Health Questionnaire (PHQ-9) was employed to assess suicidal ideation (i.e., “thoughts that you would be better off dead, or hurting yourself in some way”) prior to the start of intern year and at 3-month intervals throughout the year. Results 62.2% (199/320) of individuals agreed to take part in the study. During at least one time point over the course of internship year 12% (12/100) of interns assigned to wCBT endorsed suicidal ideation, compared to 21%(21/99) of interns assigned to ACG. After adjusting for covariates identified a priori that have previously shown to increase the risk for suicidal ideation, interns assigned to wCBT were 60% less likely to endorse suicidal ideation during internship year (RR: 0.40, 95% CI 0.17-0.91; p=0.03), compared to those

  7. Antiretroviral Therapy to Prevent HIV Acquisition in Serodiscordant Couples in a Hyperendemic Community in Rural South Africa

    PubMed Central

    Oldenburg, Catherine E.; Bärnighausen, Till; Tanser, Frank; Iwuji, Collins C.; De Gruttola, Victor; Seage, George R.; Mimiaga, Matthew J.; Mayer, Kenneth H.; Pillay, Deenan; Harling, Guy

    2016-01-01

    Background. Antiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in “real-life” population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other. Methods. Data arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships. Results. We observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3–5.6), 1.4/100 PY (.4–3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5–8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI, .07–.80). Conclusions. ART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this “real-life” effect was substantially lower than the effect observed in the HPTN-052

  8. Isoniazid-resistance conferring mutations in Mycobacterium tuberculosis KatG: Catalase, peroxidase, and INH-NADH adduct formation activities

    PubMed Central

    Cade, Christine E; Dlouhy, Adrienne C; Medzihradszky, Katalin F; Salas-Castillo, Saida Patricia; Ghiladi, Reza A

    2010-01-01

    Mycobacterium tuberculosis catalase-peroxidase (KatG) is a bifunctional hemoprotein that has been shown to activate isoniazid (INH), a pro-drug that is integral to frontline antituberculosis treatments. The activated species, presumed to be an isonicotinoyl radical, couples to NAD+/NADH forming an isoniazid-NADH adduct that ultimately confers anti-tubercular activity. To better understand the mechanisms of isoniazid activation as well as the origins of KatG-derived INH-resistance, we have compared the catalytic properties (including the ability to form the INH-NADH adduct) of the wild-type enzyme to 23 KatG mutants which have been associated with isoniazid resistance in clinical M. tuberculosis isolates. Neither catalase nor peroxidase activities, the two inherent enzymatic functions of KatG, were found to correlate with isoniazid resistance. Furthermore, catalase function was lost in mutants which lacked the Met-Tyr-Trp crosslink, the biogenic cofactor in KatG which has been previously shown to be integral to this activity. The presence or absence of the crosslink itself, however, was also found to not correlate with INH resistance. The KatG resistance-conferring mutants were then assayed for their ability to generate the INH-NADH adduct in the presence of peroxide (t-BuOOH and H2O2), superoxide, and no exogenous oxidant (air-only background control). The results demonstrate that residue location plays a critical role in determining INH-resistance mechanisms associated with INH activation; however, different mutations at the same location can produce vastly different reactivities that are oxidant-specific. Furthermore, the data can be interpreted to suggest the presence of a second mechanism of INH-resistance that is not correlated with the formation of the INH-NADH adduct. PMID:20054829

  9. Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses

    PubMed Central

    Zvada, Simbarashe P.; Denti, Paolo; Donald, Peter R.; Schaaf, H. Simon; Thee, Stephanie; Seddon, James A.; Seifart, Heiner I.; Smith, Peter J.; McIlleron, Helen M.; Simonsson, Ulrika S. H.

    2014-01-01

    Objectives To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. Patients and methods We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. Results The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. Conclusions Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing. PMID:24486870

  10. AAV-based Gene Therapy Prevents Neuropathology and Results in Normal Cognitive Development in the Hyperargininemic Mouse

    PubMed Central

    Lee, Eun K.; Hu, Chuhong; Bhargava, Ragini; Ponnusamy, Ravi; Park, Hana; Novicoff, Sarah; Rozengurt, Nora; Marescau, Bart; De Deyn, Pater; Stout, David; Schlichting, Lisa; Grody, Wayne W.; Cederbaum, Stephen D.; Lipshutz, Gerald S.

    2013-01-01

    Complete arginase I deficiency is the least severe urea cycle disorder, characterized by hyperargininemia and infrequent episodes of hyperammonemia. Patients suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation, and seizures, and is associated with intellectual disability. In mice, onset is heralded by weight loss beginning around day 15; gait instability follows progressing to inability to stand and development of tail tremor with seizure-like activity and death. Here we report that hyperargininemic mice treated neonatally with an adeno-associated virus expressing arginase and followed long-term lack any presentation consistent with brain dysfunction. Behavioral and histopathological evaluation demonstrated that treated mice are indistinguishable from littermates and that putative compounds associated with neurotoxicity are diminished. In addition, treatment results in near complete resolution of metabolic abnormalities early in life; however there is the development of some derangement later with decline in transgene expression. Ammonium challenging revealed that treated mice are affected by exogenous loading much greater than littermates. These results demonstrate that AAV-based therapy for hyperargininemia is effective and prevents development of neurological abnormalities and cognitive dysfunction in a mouse model of hyperargininemia; however nitrogen challenging reveals that these mice remain impaired in the handling of waste nitrogen. PMID:23388701

  11. NF-kappaB, a mediator for lung carcinogenesis and a target for lung cancer prevention and therapy

    PubMed Central

    Chen, Wenshu; Li, Zi; Bai, Lang; Lin, Yong

    2011-01-01

    Lung cancer ranks as the first malignant tumor killer worldwide. Despite the knowledge that carcinogens from tobacco smoke and the environment constitute the main causes of lung cancer, the mechanisms for lung carcinogenesis are still elusive. Cancer development and progression depend on the balance between cell survival and death signals. Common cell survival signaling pathways are activated by carcinogens as well as by inflammatory cytokines, which contribute substantially to cancer development. As a major cell survival signal, nuclear factor-kappaB (NF-kappaB) is involved in multiple steps in carcinogenesis and in cancer cell’s resistance to chemo- and radiotherapy. Recent studies with animal models and cell culture systems have established the links between NF-kappaB and lung carcinogenesis, highlighting the significance of targeting the NF-kappaB signaling pathway for lung cancer treatment and chemoprevention. In this review, we summarize progresses in understanding the NF-kappaB pathway in lung cancer development as well as in modulating NF-kappaB for lung cancer prevention and therapy. PMID:21196225

  12. Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs

    PubMed Central

    Adhvaryu, Meghna R; Reddy, Narsimha; Parabia, Minoo H

    2007-01-01

    AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression induced by Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA). METHODS: Duncan Hartley guinea pigs, weighing 700-1050 g, were treated orally with 50 mg/kg of INH, 100 mg/kg of RIF and 300 mg/Kg of PZA for 21-d. 200 mg/kg (bw) of each herb crude extract was administered to the herb control group and 2-h previous to INH + RIF + PZA (AKT) doses to the Herb + AKT groups. Serum alanine aminotransferase (ALT), aspertate aminotransferase (AST) bilirubin and Alkaline Phosphatase (ALP) were assessed on d 0 and 21 in all the groups. Phagocytic % (P%), Phagocytic Index (PI) and Chemotactic Index (CI) were also measured as immunologic parameters. Histological analysis was carried out to assess injury to the liver. RESULTS: The AKT treated control group showed hepatotoxicity as judged by elevated serum AST 5-fold, AST/ALT ratio 4-fold, ALP 2-fold and hepatological changes, such as focal necrosis, portal triaditis and steatosis. Immune function was suppressed as judged by decreased P% (51.67 ± 1.68 vs 40.61 ± 1.28, P < 0.01), PI (2.0725 ± 0.05 vs 0.61 ± 0.05, P < 0.001) and CI (1.8525 ± 0.04 vs 0.695 ± 0.07, P < 0.001). All four herb treated groups showed normal liver histology, enzyme levels and increased P%, while PI and CI were enhanced in the TC and ZM treated groups, respectively. CL + AKT, TC + AKT and ZM + AKT showed nearly normal histology with minimal inflammation and microvesicular steatosis, while OS + AKT showed partial protection. Hepatotoxicity was prevented by restricting the rise of AST by 2-fold in CL + AKT and TC + AKT groups and by 3-fold in OS + AKT and ZM + AKT groups, AST/ALT by 2-fold and ALP to normal levels in all four groups. All four herb + AKT groups showed normal to enhanced neutrophil function. CONCLUSION: All four herbs

  13. Roles and indications for use of implantable defibrillator and resynchronization therapy in the prevention of sudden cardiac death in heart failure.

    PubMed

    Biton, Yitschak; Baman, Jayson R; Polonsky, Bronislava

    2016-07-01

    Implantable devices are indicated in the primary and secondary prevention of potentially life-threatening ventricular tachyarrhythmias in patients with heart failure. Early studies, including the landmark MADIT trials, showed that implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices can play a significant role in aborting and preventing ventricular arrhythmias, respectively, that can cause sudden cardiac death. To this day, there have been a number of randomized controlled trials, with respective substudy analyses, that have attempted to better understand the indications for these interventions in patient care. Here, we summarize the major results of these studies, and we discuss the role of ICD therapy for both ischemic and non-ischemic cardiomyopathy, emerging evidence in support of wearable defibrillators, and the impact of modified ICD programming strategies on patient outcomes. Regarding CRT therapy, the phenomenon of ventricular reverse remodeling is an important prognostic indicator in preventing future ventricular tachyarrhythmia episodes. In summation, we provide an overview of the possible selection criteria that can be used in identifying appropriate patients for ICD and/or CRT therapy, as supported by the data. PMID:26910804

  14. Isolated ocular Jarisch-Herxheimer reaction after initiating tuberculostatic therapy in a child.

    PubMed

    Neunhöffer, Henrike; Gold, Annika; Hoerauf, Hans; Herbort, Carl; Heiligenhaus, Arnd; Zimmermann, Ortrud; Feltgen, Nicolas

    2014-06-01

    After being exposed to a kindergarten teacher with infectious pulmonary tuberculosis, a7-year-old girl with a positive tuberculin skin test was treated with isoniazid. 3 days after initiation of the tuberculostatic therapy, the girl was referred to our hospital with an acute onset of blurred vision. Visual acuity (VA) was 20/200 in both eyes. Examination revealed mild anterior chamber inflammation, optic disc swelling, cystoid macular edema and periphlebitis in both eyes. However, although active tuberculosis was ruled out, the interferon-gamma release assay was positive. The anti-tuberculosis therapy was intensified with pyrazinamide, isoniazid, rifampicin and methylprednisolone. Within 10 days we saw a resolution of the macular edema and VA was 20/25. The paradoxical worsening of the patient’s condition after initiation of tuberculostatic therapy with isoniazid and the prompt response to systemic steroids are typical for Jarisch-Herxheimer reaction (JHR). Our patient presented no symptoms before the isoniazid therapy was started and the reaction was ocular without any generalized symptoms. This is unique among all other reported cases of ocular JHR. PMID:24022644

  15. Optimization of SABRE for polarization of the tuberculosis drugs pyrazinamide and isoniazid

    NASA Astrophysics Data System (ADS)

    Zeng, Haifeng; Xu, Jiadi; Gillen, Joseph; McMahon, Michael T.; Artemov, Dmitri; Tyburn, Jean-Max; Lohman, Joost A. B.; Mewis, Ryan E.; Atkinson, Kevin D.; Green, Gary G. R.; Duckett, Simon B.; van Zijl, Peter C. M.

    2013-12-01

    Hyperpolarization produces nuclear spin polarization that is several orders of magnitude larger than that achieved at thermal equilibrium thus providing extraordinary contrast and sensitivity. As a parahydrogen induced polarization (PHIP) technique that does not require chemical modification of the substrate to polarize, Signal Amplification by Reversible Exchange (SABRE) has attracted a lot of attention. Using a prototype parahydrogen polarizer, we polarize two drugs used in the treatment of tuberculosis, namely pyrazinamide and isoniazid. We examine this approach in four solvents, methanol-d4, methanol, ethanol and DMSO and optimize the polarization transfer magnetic field strength, the temperature as well as intensity and duration of hydrogen bubbling to achieve the best overall signal enhancement and hence hyperpolarization level.

  16. Synthesis and in vitro antimicrobial and antitumoral screening of novel lipophilic isoniazid analogues. VI.

    PubMed

    Vigorita, M G; Ottanà, R; Maccari, R; Monforte, F; Bisignano, G; Pizzimenti, F C

    1998-01-01

    Various kinds of lipophilic analogues of isonicotinic acid hydrazide (Isoniazid) were synthesized and in vitro explored in a search for antimycobacterial agents with extended activity spectrum against pathogens responsible for the AIDS-associated diseases. The primary in vitro screening showed that a) isonicotinoylhydrazones 1a, 1b, 1d, 1e are more active than the parent drug against non-tubercular mycobacteria (MIC ranging between 0.5 and 4 micrograms/ml), b) isonicotinohydrazides 6b and 6e display interesting antibacterial activity on some Gram + and Gram-strains, and c) trifluoromethyl-containing compounds 1a and 2c inhibit the growth of several human tumor cell lines at doses between 10(-5) and 10(-6) M. On the contrary, none of the tested analogues significantly counteracts the cytopathogenicity induced by HIV and HSV viruses. PMID:9795482

  17. An Isoniazid Analogue Promotes Mycobacterium tuberculosis-Nanoparticle Interactions and Enhances Bacterial Killing by Macrophages

    PubMed Central

    de Faria, Tatiany J.; Roman, Mariane; de Souza, Nicole M.; De Vecchi, Rodrigo; de Assis, João Vitor; dos Santos, Ana Lúcia Gomes; Bechtold, Ivan H.; Winter, Nathalie; Soares, Maurilio José; Silva, Luciano Paulino; De Almeida, Mauro V.

    2012-01-01

    Nanoenabled drug delivery systems against tuberculosis (TB) are thought to control pathogen replication by targeting antibiotics to infected tissues and phagocytes. However, whether nanoparticle (NP)-based carriers directly interact with Mycobacterium tuberculosis and how such drug delivery systems induce intracellular bacterial killing by macrophages is not defined. In the present study, we demonstrated that a highly hydrophobic citral-derived isoniazid analogue, termed JVA, significantly increases nanoencapsulation and inhibits M. tuberculosis growth by enhancing intracellular drug bioavailability. Importantly, confocal and atomic force microscopy analyses revealed that JVA-NPs associate with both intracellular M. tuberculosis and cell-free bacteria, indicating that NPs directly interact with the bacterium. Taken together, these data reveal a nanotechnology-based strategy that promotes antibiotic targeting into replicating extra- and intracellular mycobacteria, which could actively enhance chemotherapy during active TB. PMID:22330919

  18. Rv3080c regulates the rate of inhibition of mycobacteria by isoniazid through FabD.

    PubMed

    Kumari, Ruma; Saxena, Richa; Tiwari, Sameer; Tripathi, Dinesh K; Srivastava, Kishore K

    2013-02-01

    The mycobacterial FASII multi-enzyme complex has been identified to be a target of Ser/Thr protein kinases (STPKs) of Mycobacterium tuberculosis (MTB), with substrates, including the malonyl-CoA:ACP transacylase (FabD) and the β-ketoacyl-ACP synthases KasA and KasB. These proteins are phosphorylated by various kinases in vitro. The present study links the correlation of FASII pathway with serine threonine protein kinase of MTB. In the preliminary finding, we have shown that mycobacterial protein Rv3080c (PknK) phosphorylates FabD and the knockdown of PknK protein in mycobacteria down regulates FabD expression. This event leads to the differential inhibition of mycobacteria in the presence of isoniazid (INH), as the inhibition of growth of mycobacteria in the presence of INH is enhanced in PknK deficient mycobacteria. PMID:23180244

  19. Inhibition of a Mycobacterium tuberculosis beta-ketoacyl ACP synthase by isoniazid.

    PubMed

    Mdluli, K; Slayden, R A; Zhu, Y; Ramaswamy, S; Pan, X; Mead, D; Crane, D D; Musser, J M; Barry, C E

    1998-06-01

    Although isoniazid (isonicotinic acid hydrazide, INH) is widely used for the treatment of tuberculosis, its molecular target has remained elusive. In response to INH treatment, saturated hexacosanoic acid (C26:0) accumulated on a 12-kilodalton acyl carrier protein (AcpM) that normally carried mycolic acid precursors as long as C50. A protein species purified from INH-treated Mycobacterium tuberculosis was shown to consist of a covalent complex of INH, AcpM, and a beta-ketoacyl acyl carrier protein synthase, KasA. Amino acid-altering mutations in the KasA protein were identified in INH-resistant patient isolates that lacked other mutations associated with resistance to this drug. PMID:9616124

  20. An Atypical and Resistant Case of Obsessive Compulsive Disorder Responding Satisfactorily with an Unusual way of Exposure and Response Prevention Therapy.

    PubMed

    Nath, Kamal; Victor, Robin; Naskar, Subrata

    2016-03-01

    It is well established fact that a combination of pharmacological therapy plus cognitive behaviour therapy (CBT) - exposure and response prevention (ERP) is considered first line for the treatment of obsessive compulsive disorder (OCD). This case presented here supports this point in unusual way of ERP administration in an atypical and resistant case of OCD proved to be beneficial over pharmacotherapy. The case was atypical in the sense that it had many overvalued ideas, superstitions and religious beliefs playing major role in its aetiology. Also, misconstruction of chance associations, intense stimulus generalization and invivo exposure proving the best modality of treatment made it atypical. PMID:27134980

  1. An Atypical and Resistant Case of Obsessive Compulsive Disorder Responding Satisfactorily with an Unusual way of Exposure and Response Prevention Therapy

    PubMed Central

    Nath, Kamal; Victor, Robin

    2016-01-01

    It is well established fact that a combination of pharmacological therapy plus cognitive behaviour therapy (CBT) - exposure and response prevention (ERP) is considered first line for the treatment of obsessive compulsive disorder (OCD). This case presented here supports this point in unusual way of ERP administration in an atypical and resistant case of OCD proved to be beneficial over pharmacotherapy. The case was atypical in the sense that it had many overvalued ideas, superstitions and religious beliefs playing major role in its aetiology. Also, misconstruction of chance associations, intense stimulus generalization and invivo exposure proving the best modality of treatment made it atypical. PMID:27134980

  2. Chitosan-isoniazid conjugates: Synthesis, evaluation of tuberculostatic activity, biodegradability and toxicity.

    PubMed

    Berezin, Alexander S; Skorik, Yury A

    2015-08-20

    Novel water-soluble chitosan-isoniazid conjugates were synthesized by two methods: (1) the carbodiimide method using isoniazid (INH) and N-(2-carboxyethyl)chitosan (CEC), and (2) the reaction between INH and N-(3-chloro-2-hydroxypropyl)chitosan (CHPC). The solubility of the conjugates under physiological conditions was enhanced by phosphorylation. Method (1) is preferable in terms of obtaining conjugates with a high content of active substance; depending on reaction conditions, the degree of substitution in the INH-CEC conjugates varies from 0.08 to 0.39. Ultrasound treatment increased the reaction rate by a factor of 1.3-1.5, but caused partial degradation of the polymer. Consecutive modification led to a considerable decrease in polymer biodegradability in the following order: chitosan>CEC or CHPC>conjugate. In vitro screening of the antimicrobial activity against Mycobacterium tuberculosis H37Rv demonstrated a comparable or slightly higher minimum inhibitory concentration for conjugates than for INH itself (0.20, 0.25, and 1.05 μg INH/mL for INH, CEC-INH, and CHPC-INH, respectively). A slug mucosal irritation test employing Limax flavus revealed a lower toxicity for the conjugates than for INH by a factor of 3-4; the most noticeable toxicity decrease was observed for the conjugates obtained by method (1). Studies of acute toxicity in mice revealed a 3-4-fold increase in median lethal dose for the conjugates compared with INH (LD50 210, 850, and 650 mg INH/kg for INH, CEC-INH, and CHPC-INH, respectively). PMID:25965488

  3. Cost-effectiveness of antiviral therapy during late pregnancy to prevent perinatal transmission of hepatitis B virus.

    PubMed

    Wang, Wenjun; Wang, Jingjing; Dang, Shuangsuo; Zhuang, Guihua

    2016-01-01

    Background. Hepatitis B virus (HBV) infections are perinatally transmitted from chronically infected mothers. Supplemental antiviral therapy during late pregnancy with lamivudine (LAM), telbivudine (LdT), or tenofovir (TDF) can substantially reduce perinatal HBV transmission compared to postnatal immunoprophylaxis (IP) alone. However, the cost-effectiveness of these measures is not clear. Aim. This study evaluated the cost-effectiveness from a societal perspective of supplemental antiviral agents for preventing perinatal HBV transmission in mothers with high viral load (>6 log10 copies/mL). Methods. A systematic review and network meta-analysis were performed for the risk of perinatal HBV transmission with antiviral therapies. A decision analysis was conducted to evaluate the clinical and economic outcomes in China of four competing strategies: postnatal IP alone (strategy IP), or in combination with perinatal LAM (strategy LAM + IP), LdT (strategy LdT + IP), or TDF (strategy TDF + IP). Antiviral treatments were administered from week 28 of gestation to 4 weeks after birth. Outcomes included treatment-related costs, number of infections, and quality-adjusted life years (QALYs). One- and two-way sensitivity analyses were performed to identify influential clinical and cost-related variables. Probabilistic sensitivity analyses were used to estimate the probabilities of being cost-effective for each strategy. Results. LdT + IP and TDF + IP averted the most infections and HBV-related deaths, and gained the most QALYs. IP and TDF + IP were dominated as they resulted in less or equal QALYs with higher associated costs. LdT + IP had an incremental $2,891 per QALY gained (95% CI [$932-$20,372]) compared to LAM + IP (GDP per capita for China in 2013 was $6,800). One-way sensitivity analyses showed that the cost-effectiveness of LdT + IP was only sensitive to the relative risk of HBV transmission comparing LdT + IP with LAM + IP. Probabilistic sensitivity analyses

  4. Cost-effectiveness of antiviral therapy during late pregnancy to prevent perinatal transmission of hepatitis B virus

    PubMed Central

    Wang, Wenjun; Wang, Jingjing; Zhuang, Guihua

    2016-01-01

    Background. Hepatitis B virus (HBV) infections are perinatally transmitted from chronically infected mothers. Supplemental antiviral therapy during late pregnancy with lamivudine (LAM), telbivudine (LdT), or tenofovir (TDF) can substantially reduce perinatal HBV transmission compared to postnatal immunoprophylaxis (IP) alone. However, the cost-effectiveness of these measures is not clear. Aim. This study evaluated the cost-effectiveness from a societal perspective of supplemental antiviral agents for preventing perinatal HBV transmission in mothers with high viral load (>6 log10 copies/mL). Methods. A systematic review and network meta-analysis were performed for the risk of perinatal HBV transmission with antiviral therapies. A decision analysis was conducted to evaluate the clinical and economic outcomes in China of four competing strategies: postnatal IP alone (strategy IP), or in combination with perinatal LAM (strategy LAM + IP), LdT (strategy LdT + IP), or TDF (strategy TDF + IP). Antiviral treatments were administered from week 28 of gestation to 4 weeks after birth. Outcomes included treatment-related costs, number of infections, and quality-adjusted life years (QALYs). One- and two-way sensitivity analyses were performed to identify influential clinical and cost-related variables. Probabilistic sensitivity analyses were used to estimate the probabilities of being cost-effective for each strategy. Results. LdT + IP and TDF + IP averted the most infections and HBV-related deaths, and gained the most QALYs. IP and TDF + IP were dominated as they resulted in less or equal QALYs with higher associated costs. LdT + IP had an incremental $2,891 per QALY gained (95% CI [$932–$20,372]) compared to LAM + IP (GDP per capita for China in 2013 was $6,800). One-way sensitivity analyses showed that the cost-effectiveness of LdT + IP was only sensitive to the relative risk of HBV transmission comparing LdT + IP with LAM + IP. Probabilistic sensitivity analyses

  5. Acupuncture in Treating Dry Mouth Caused By Radiation Therapy in Patients With Head and Neck Cancer | Division of Cancer Prevention

    Cancer.gov

    RATIONALE: Acupuncture may help relieve dry mouth caused by radiation therapy. PURPOSE: This randomized phase III trial is studying to see how well one set of acupuncture points work in comparison to a different set of acupuncture points or standard therapy in treating dry mouth caused by radiation therapy in patients with head and neck cancer. |

  6. Prevention of Gynecomastia and Breast Pain Caused by Androgen Deprivation Therapy in Prostate Cancer: Tamoxifen or Radiotherapy?

    SciTech Connect

    Arruda Viani, Gustavo; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

    2012-07-15

    Purpose: To determine, in a meta-analysis, whether gynecomastia and breast pain rates in men with prostate cancer treated with androgen deprivation therapy (ADT) are reduced if treated with prophylactic radiotherapy (RT) or tamoxifen (TMX). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing RT or TMX with observation for men with prostate cancer using ADT. Results: Six RCTs (three RT trials and three TMX trials, N = 777 patients total) were identified that met the study criteria. Pooled results from these RCTs comparing RT vs. observation showed a significant reduction in the incidence of gynecomastia and breast pain rates in patients treated with RT (odds ratio [OR] = 0.21, 95% confidence interval [CI] = 0.12-0.37, p < 0.0001, and OR = 0.34, 95% CI 0.20-0.57, p < 0.0001, respectively). Use of RT resulted in an absolute risk reduction (ARR) of 29.4% and 19.9%, with a number needed to treat (NNT) of 3.4 and 5 to avoid one case of gynecomastia and breast pain, respectively. Pooled results from trials comparing TMX vs. observation showed a statistical benefit for breast pain and gynecomastia in favor of TMX arms (OR = 0.04, 95% CI = 0.02-0.08, p < 0.0001 and OR = 0.07, 95% CI = 0.0-0.14, p < 0.00001). TMX resulted in an ARR = 64.1% and 47.6%, with an NNT of 1.56 and 2.1 to avoid one case of gynecomastia and breast pain, respectively. Considering adverse effects, TMX was 6 times more adverse effects than RT. Conclusions: Our data have shown that both TMX and RT prevented gynecomastia and breast pain in patients with prostate cancer receiving ADT for prostate cancer. Although TMX was two times more effective in preventing gynecomastia, RT should represent an effective and safe treatment option, to take into account mainly in patients with cardiovascular risk factors or thrombotic diathesis.

  7. Year-long antihypertensive therapy with candesartan completely prevents development of cardiovascular organ injuries in spontaneously hypertensive rats.

    PubMed

    Ishimitsu, Toshihiko; Honda, Takeaki; Ohno, Eri; Furukata, Satoshi; Sudo, Yasuyo; Nakano, Nobuyuki; Takahashi, Toshiaki; Ono, Hidehiko; Matsuoka, Hiroaki

    2010-01-01

    Most previous studies have examined the effects of antihypertensive drugs in hypertensive animals for only a few months, and little information has been provided as to the protective effects of lifetime antihypertensive medication against cardiovascular organ injury. In this study, spontaneously hypertensive rats (SHR) were treated for 1 year with an angiotensin-II receptor antagonist (ARB) and the development of hypertensive organ injury was evaluated. Male 15-week-old SHR (n = 9) were given 25 mg/L candesartan (CS) in their drinking water for 1 year. Twelve SHR and 9 normotensive Wistar-Kyoto rats (WKY) were given normal tap water. Tail-cuff blood pressure was almost normalized by CS throughout 1 year (at 12-months: WKY 132 ± 3, SHR 229 ± 3, CS 137 ± 4 mmHg). After 1 year, cardiac ventricular weight (SHR +33%, CS -2% versus WKY) and aortic thickness (SHR +34%, CS +4% versus WKY) in the CS-treated SHR rats were not different than those of WKY. Echocardiographic midwall fractional shortening (SHR -18%, CS -1% versus WKY) and left ventricular hydroxyproline content (SHR +47%, CS +11% versus WKY) were also improved by CS to the WKY level. With respect to kidney function, GFR (SHR -24%, CS +9% versus WKY) was preserved, proteinuria (SHR +312%, CS +12% versus WKY) was reduced, and the histological glomerular injury rate (SHR +186%, CS +6% versus WKY) was reduced by CS. These results suggest that long-term antihypertensive therapy with CS can completely prevent hypertensive cardiovascular and renal injuries in SHR. PMID:20966610

  8. Oral Gentamicin Gut Decontamination for Prevention of KPC-Producing Klebsiella pneumoniae Infections: Relevance of Concomitant Systemic Antibiotic Therapy

    PubMed Central

    Tascini, Carlo; Sbrana, Francesco; Flammini, Sarah; Tagliaferri, Enrico; Arena, Fabio; Leonildi, Alessandro; Ciullo, Ilaria; Amadori, Francesco; Di Paolo, Antonello; Ripoli, Andrea; Lewis, Russell; Rossolini, Gian Maria

    2014-01-01

    Gut colonization represents the main source for KPC-producing Klebsiella pneumoniae (KPC-Kp) epidemic dissemination. Oral gentamicin, 80 mg four times daily, was administered to 50 consecutive patients with gut colonization by gentamicin-susceptible KPC-Kp in cases of planned surgery, major medical intervention, or need for patient transfer. The overall decontamination rate was 68% (34/50). The median duration of gentamicin treatment was 9 days (interquartile range, 7 to 15 days) in decontaminated patients compared to 24 days (interquartile range, 20 to 30 days) in those with persistent colonization (P < 0.001). In the six-month period of follow-up, KPC-Kp infections were documented in 5/34 (15%) successfully decontaminated patients compared to 12/16 (73%) persistent carriers (P < 0.001). The decontamination rate was 96% (22/23) in patients receiving oral gentamicin only, compared to 44% (12/27) of those treated with oral gentamicin and concomitant systemic antibiotic therapy (CSAT) (P < 0.001). The multivariate analysis confirmed CSAT and KPC-Kp infection as the variables associated with gut decontamination. In the follow-up period, KPC-Kp infections were documented in 2/23 (9%) of patients treated with oral gentamicin only and in 15/27 (56%) of those also receiving CSAT (P = 0.003). No difference in overall death rate between different groups was documented. Gentamicin-resistant KPC-Kp strains were isolated from stools of 4/16 persistent carriers. Peak gentamicin blood levels were below 1 mg/liter in 12/14 tested patients. Oral gentamicin was shown to be potentially useful for gut decontamination and prevention of infection due to KPC-Kp, especially in patients not receiving CSAT. The risk of emergence of gentamicin-resistant KPC-Kp should be considered. PMID:24419337

  9. The Association of Elective Hormone Therapy with Changes in Lipids Among Glucose Intolerant Postmenopausal Women in the Diabetes Prevention Program

    PubMed Central

    Golden, Sherita H.; Kim, Catherine; Barrett-Connor, Elizabeth; Nan, Bin; Kong, Shengchun; Goldberg, Ronald

    2013-01-01

    Objective It is unclear how lipids change in response to lifestyle modification or metformin among postmenopausal glucose intolerant women using and not using hormone therapy (HT). We examined the one-year changes in lipids among postmenopausal, prediabetic women in the Diabetes Prevention Program (DPP), and whether changes were mediated by sex hormones. Materials/Methods We performed a secondary analysis of a randomized controlled trial of 342 women who used HT at baseline and year 1 and 382 women who did not use HT at either time point. Interventions included intensive lifestyle (ILS) with goals of weight reduction of at least 7% of initial weight and 150 minutes per week of moderate intensity exercise, or metformin or placebo administered 850 mg up to twice a day. Women were not randomized to HT. Main outcome measures were changes between baseline and study year 1 in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Results Compared to placebo, both ILS and metformin significantly reduced LDL-C and raised HDL-C among HT users, changes partially explained by change in estradiol and testosterone but independent of changes in waist circumference and 1/fasting insulin. In contrast, DPP interventions had no effect on LDL-C and HDL-C among non-HT users. ILS significantly lowered triglycerides among non-users but did not significantly change triglycerides among HT users. Metformin did not significantly change triglycerides among non-users but increased triglycerides among HT users. Conclusions The beneficial effects of ILS and metformin on lowering LDL-C and raising HDL-C differ depending upon concurrent HT use. PMID:23660512

  10. Comprehensive Suppression of All Apoptosis-Induced Proliferation Pathways as a Proposed Approach to Colorectal Cancer Prevention and Therapy

    PubMed Central

    Bordonaro, Michael; Drago, Eric; Atamna, Wafa; Lazarova, Darina L.

    2014-01-01

    Mutations in the WNT/beta-catenin pathway are present in the majority of all sporadic colorectal cancers (CRCs), and histone deacetylase inhibitors induce apoptosis in CRC cells with such mutations. This apoptosis is counteracted by (1) the signaling heterogeneity of CRC cell populations, and (2) the survival pathways induced by mitogens secreted from apoptotic cells. The phenomena of signaling heterogeneity and apoptosis-induced survival constitute the immediate mechanisms of resistance to histone deacetylase inhibitors, and probably other chemotherapeutic agents. We explored the strategy of augmenting CRC cell death by inhibiting all survival pathways induced by the pro-apoptotic agent LBH589, a histone deacetylase inhibitor: AKT, JAK/STAT, and ERK signaling. The apoptosis-enhancing ability of a cocktail of synthetic inhibitors of proliferation was compared to the effects of the natural product propolis. We utilized colorectal adenoma, drug-sensitive and drug-resistant colorectal carcinoma cells to evaluate the apoptotic potential of the combination treatments. The results suggest that an effective approach to CRC combination therapy is to combine apoptosis-inducing drugs (e.g., histone deacetylase inhibitors, such as LBH589) with agents that suppress all compensatory survival pathways induced during apoptosis (such as the cocktail of inhibitors of apoptosis-associated proliferation). The same paradigm can be applied to a CRC prevention approach, as the apoptotic effect of butyrate, a diet-derived histone deacetylase inhibitor, is augmented by other dietary agents that modulate survival pathways (e.g., propolis and coffee extract). Thus, dietary supplements composed by fermentable fiber, propolis, and coffee extract may effectively counteract neoplastic growth in the colon. PMID:25500581

  11. Oral gentamicin gut decontamination for prevention of KPC-producing Klebsiella pneumoniae infections: relevance of concomitant systemic antibiotic therapy.

    PubMed

    Tascini, Carlo; Sbrana, Francesco; Flammini, Sarah; Tagliaferri, Enrico; Arena, Fabio; Leonildi, Alessandro; Ciullo, Ilaria; Amadori, Francesco; Di Paolo, Antonello; Ripoli, Andrea; Lewis, Russell; Rossolini, Gian Maria; Menichetti, Francesco

    2014-01-01

    Gut colonization represents the main source for KPC-producing Klebsiella pneumoniae (KPC-Kp) epidemic dissemination. Oral gentamicin, 80 mg four times daily, was administered to 50 consecutive patients with gut colonization by gentamicin-susceptible KPC-Kp in cases of planned surgery, major medical intervention, or need for patient transfer. The overall decontamination rate was 68% (34/50). The median duration of gentamicin treatment was 9 days (interquartile range, 7 to 15 days) in decontaminated patients compared to 24 days (interquartile range, 20 to 30 days) in those with persistent colonization (P<0.001). In the six-month period of follow-up, KPC-Kp infections were documented in 5/34 (15%) successfully decontaminated patients compared to 12/16 (73%) persistent carriers (P<0.001). The decontamination rate was 96% (22/23) in patients receiving oral gentamicin only, compared to 44% (12/27) of those treated with oral gentamicin and concomitant systemic antibiotic therapy (CSAT) (P<0.001). The multivariate analysis confirmed CSAT and KPC-Kp infection as the variables associated with gut decontamination. In the follow-up period, KPC-Kp infections were documented in 2/23 (9%) of patients treated with oral gentamicin only and in 15/27 (56%) of those also receiving CSAT (P=0.003). No difference in overall death rate between different groups was documented. Gentamicin-resistant KPC-Kp strains were isolated from stools of 4/16 persistent carriers. Peak gentamicin blood levels were below 1 mg/liter in 12/14 tested patients. Oral gentamicin was shown to be potentially useful for gut decontamination and prevention of infection due to KPC-Kp, especially in patients not receiving CSAT. The risk of emergence of gentamicin-resistant KPC-Kp should be considered. PMID:24419337

  12. Lymphadenitis caused by infection with an isoniazid- and rifampin-resistant strain of Mycobacterium bovis BCG in an infant with IFN-γ/IL-12 pathway defect*

    PubMed Central

    Diniz, Lilian Martins Oliveira; Guimarães, Tiago; de Oliveira, Maria das Graças Rodrigues; Pinto, Jorge Andrade; de Miranda, Silvana Spindola

    2014-01-01

    We report a rare case in a female infant (age, 3.5 months) with primary immunodeficiency (IFN-γ/IL-12 pathway defect) who presented with suppurative lymphadenitis after Mycobacterium bovis BCG vaccination. The strain of M. bovis BCG identified was found to be resistant to isoniazid and rifampin. The patient was treated with a special pharmacological regimen involving isoniazid (in a limited, strategic manner), ethambutol, streptomycin, and IFN-γ, after which there was complete resolution of the lesions. PMID:24831405

  13. The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis.

    PubMed

    Slayden, R A; Barry, C E

    2002-01-01

    Mycobacterium tuberculosis has two discrete beta-ketoacyl synthases encoded by kasA and kasB that are located in tandem within a five-gene operon that has been implicated in isoniazid-sensitivity and mycolic acid synthesis. We have developed an in vitro meromycolic acid synthase assay to elucidate the anabolic role of these enzymes. Overproduction of KasA and KasB individually and together in M. smegmatis enabled cell-free incorporation of [(14)C]malonyl-CoA into lipids whose chain length was dependent upon the M. tuberculosis elongating enzyme used. KasA specifically elongated palmitoyl-CoA to monounsaturated fatty acids that averaged 40 carbons in length. KasB hyperproduction in the presence of KasA produced longer chain multiunsaturated hydrocarbons averaging 54 carbons in length. These products comigrated with a synthetic standard of meromycolic acid and their production was sensitive to isoniazid, thiolactomycin, and triclosan. KasA mutations associated with isoniazid resistance produced an enzyme that had a diminished overall catalytic activity but conferred enhanced resistance to isoniazid. In vivo analysis confirmed that overexpression of each of the four mutant KasAs enhanced isoniazid resistance when compared to overexpression of wild-type KasA. These results suggest discrete anabolic roles for both KasA and KasB in mycolic acid synthesis and substantiate the involvement of KasA mutations in isoniazid resistance. PMID:12464486

  14. Costimulation-Adhesion Blockade is Superior to Cyclosporine A and Prednisone Immunosuppressive Therapy for Preventing Rejection of Differentiated Human Embryonic Stem Cells Following Transplantation

    PubMed Central

    Huber, Bruno C.; Ransohoff, Julia D.; Ransohoff, Katherine J.; Riegler, Johannes; Ebert, Antje; Kodo, Kazuki; Gong, Yongquan; Sanchez-Freire, Veronica; Dey, Devaveena; Kooreman, Nigel G.; Diecke, Sebastian; Zhang, Wendy Y.; Odegaard, Justin; Hu, Shijun; Gold, Joseph D.; Robbins, Robert C.; Wu, Joseph C.

    2014-01-01

    Rationale Human embryonic stem cell (hESC) derivatives are attractive candidates for therapeutic use. The engraftment and survival of hESC derivatives as xenografts or allografts require effective immunosuppression to prevent immune cell infiltration and graft destruction. Objective To test the hypothesis that a short-course, dual-agent regimen of two costimulation-adhesion blockade agents can induce better engraftment of hESC derivatives compared to current immunosuppressive agents. Methods and Results We transduced hESCs with a double fusion reporter gene construct expressing firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP), and differentiated these cells to endothelial cells (hESC-ECs). Reporter gene expression enabled longitudinal assessment of cell engraftment by bioluminescence imaging (BLI). Costimulation-adhesion therapy resulted in superior hESC-EC and mouse EC engraftment compared to cyclosporine therapy in a hindlimb model. Costimulation-adhesion therapy also promoted robust hESC-EC and hESC-derived cardiomyocyte (hESC-CM) survival in an ischemic myocardial injury model. Improved hESC-EC engraftment had a cardioprotective effect after myocardial injury, as assessed by magnetic resonance imaging (MRI). Mechanistically, costimulation-adhesion therapy is associated with systemic and intra-graft upregulation of T cell immunoglobulin and mucin domain 3 (TIM3) and a reduced pro-inflammatory cytokine profile. Conclusions Costimulation-adhesion therapy is a superior alternative to current clinical immunosuppressive strategies for preventing the post-transplant rejection of hESC derivatives. By extending the window for cellular engraftment, costimulation-adhesion therapy enhances functional preservation following ischemic injury. This regimen may function through a TIM3-dependent mechanism. PMID:24038578

  15. Biomedical HIV prevention including pre-exposure prophylaxis and opiate agonist therapy for women who inject drugs: State of research and future directions

    PubMed Central

    Page, Kimberly; Tsui, Judith; Maher, Lisa; Choopanya, Kachit; Vanichseni, Suphak; Mock, Philip A.; Celum, Connie; Martin, Michael

    2015-01-01

    Women who inject drugs are at higher risk of HIV compared to their male counterparts as a result of multiple factors including biological, behavioral and socio-structural, yet comparatively little effort has been invested in testing and delivering prevention methods that directly target this group. In this paper, we discuss the need for expanded prevention interventions for women who inject drugs, focusing on two safe, effective, and approved, yet underutilized biomedical prevention methods: opiate agonist therapy (OAT) and oral pre-exposure prophylaxis (PrEP). While both interventions are well researched they have not been well examined in the context of gender. We discuss the drivers of women injectors’ higher HIV risk, review the effectiveness of OAT and PrEP interventions among women, and explain why these new HIV prevention tools should be prioritized for women who inject drugs. There is substantial potential for impact of OAT and PrEP programs for women who inject drugs in the context of broader gender-responsive HIV prevention initiatives. While awaiting efficacy data on other biomedical approaches in the HIV prevention research ‘pipeline’, we propose that the scale up and implementation of these proven, safe, and effective interventions are needed now. PMID:25978484

  16. Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research

    PubMed Central

    2011-01-01

    Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research-related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes’ performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders. PMID:21967874

  17. Adipose tissue-derived stem cell therapy for prevention and treatment of erectile dysfunction in a rat model of Peyronie's disease.

    PubMed

    Gokce, A; Abd Elmageed, Z Y; Lasker, G F; Bouljihad, M; Kim, H; Trost, L W; Kadowitz, P J; Abdel-Mageed, A B; Sikka, S C; Hellstrom, W J

    2014-03-01

    Peyronie's disease (PD) is a localized connective tissue disorder that involves the tunica albuginea (TA) of the penis. While surgical correction remains the gold standard, the search for an effective and less invasive therapy continues. The objective of this study was to evaluate the effects of intratunical injection of adipose tissue-derived stem cells (ADSCs) for the prevention and treatment of erectile dysfunction in a rat model of PD. Twenty-four male Sprague-Dawley rats (300-350 g) were randomly divided into four groups: sham, PD, PD + ADSC (prevention) and PD + ADSC (treatment). All rats underwent penile injections into the TA with 50 μL vehicle (sham) or 0.5 μg transforming growth factor (TGF)-β1 (remaining groups). The ADSC groups received intratunical injections with 0.5 million rat-labelled ADSCs on day 0 (prevention) or day 30 (treatment). Forty-five days following TGF-β1 injection, rats underwent cavernous nerve stimulation (CNS) with total intracavernous-to-mean arterial pressure ratio (ICP/MAP) and total ICP recorded to measure response to therapy. Tissues were evaluated histologically and for mRNA expression of tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs) and zymographic activity of MMPs. Statistical analysis was performed by analysis of variance followed by the Tukey test for post hoc comparisons. In both prevention and treatment groups, intratunical injection of ADSCs resulted in significantly higher ICP/MAP and total ICP in response to CNS compared with the PD group. Local injection of ADSCs prevented and/or reduced Peyronie's-like changes by decreasing the expression of TIMPs, and stimulating expression and activity of MMPs. This study documents the preventive and therapeutic benefits of ADSC on penile fibrosis and erectile function in an animal model of PD. PMID:24574095

  18. Evaluation of GenoFlow DR-MTB Array Test for Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis.

    PubMed

    Molina-Moya, B; Kazdaglis, G; Lacoma, A; Prat, C; Gómez, A; Villar-Hernández, R; García-García, E; Haba, L; Maldonado, J; Samper, S; Ruiz-Manzano, J; Ausina, V; Domínguez, J

    2016-04-01

    The aim of this study was to evaluate the GenoFlow DR-MTB array test (DiagCor Bioscience, Hong Kong) on 70 cultured isolates and 50 sputum specimens. The GenoFlow array test showed good sensitivity and specificity compared to the phenotypic Bactec 460TB. This array accurately detected mutations inrpoB,katG, andinhAassociated with resistance to rifampin and isoniazid. PMID:26865688

  19. The use of antiretroviral therapy for the prevention of new HIV infection in populations at high risk for HIV sero-conversion in Nigeria.

    PubMed

    Idoko, John; Folayan, Morenike O

    2014-09-01

    The last few years have witnessed a renewed commitment to HIV prevention. The evidence to support the use of antiretroviral therapy (ART) for prevention of new HIV infection in the form of Pre-exposure prophylaxis (PrEP) among men who have sex with men, transgender, people who inject drugs, heterosexual men and women and HIV-1 serodiscordant couples, or treatment as prevention (TasP) for serodiscordant couples have also grown. The need to explore the possible use of ART for HIV prevention in Nigeria has become imperative in view of its high HIV burden and the current slow pace of effort to achieve the universal target of reducing its HIV incidence by 50%. While PrEP and TasP are welcome addendum to the existing HIV prevention armamentarium, it is still important to conduct a demonstration project to identify strategies that can facilitate access to PrEP and TasP taking cognizance of the peculiar local challenges with respect to ART and HIV prevention commodity access. The country has therefore drawn a roadmap for itself on how to introduce ART for use for HIV prevention as either PrEP or TasP. This paper discusses the three year national roadmap that would enable the country generated the needed scientific evidence as well as extensive community support for use of ART for HIV prevention in Nigeria. This process includes the conduct of modeling and formative studies, and the implementation of a 24 months demonstration project. The outcome of the demonstration project would inform plans for the scale up of pre-exposure prophylaxis (PrEP) access for population(s) at high risk for HIV infection in Nigeria. PMID:26050385

  20. A review of cilostazol, a phosphodiesterase inhibitor, and its role in preventing both coronary and peripheral arterial restenosis following endovascular therapy.

    PubMed

    Dindyal, Shiva; Kyriakides, Constantinos

    2009-01-01

    Systemic vascular disease is the greatest cause of mortality in the western world. Treatment options have been preventative with medical therapy or curative with surgical bypass. Recently, there has been an increase in the use and popularity of minimally invasive endovascular techniques, particularly angioplasty and stent insertions. The short-term results of these techniques have been demonstrated to be superior in a number of studies when compared with conventional surgery, which itself carries high mortality and morbidity. The long-term outcomes of endovascular treatments have not been as impressive, due to vascular restenosis caused mainly by intimal hyperplasia. There have been a large number of studies and therapeutic trials to discover a solution to restenosis, but to date success has not been reached. Cilostazol is a phosphodiesterase inhibitor licensed for treating patients suffering from intermittent claudication. Recent clinical trials have shown the effects of cilostazol in also preventing coronary artery restenosis post-endovascular treatments. These results have recently been repeated for peripheral vascular stents. This review discusses the pharmacology of cilostazol, peripheral vascular disease, mechanisms of intimal hyperplasia causing vascular restenosis. We also discuss the use of cilostazol and other current patents of novel targets and therapeutics, for preventing restenosis of both coronary and peripheral arterial disease following endovascular therapies. PMID:19149700

  1. Multidimensional infrared spectroscopy reveals the vibrational and solvation dynamics of isoniazid

    NASA Astrophysics Data System (ADS)

    Shaw, Daniel J.; Adamczyk, Katrin; Frederix, Pim W. J. M.; Simpson, Niall; Robb, Kirsty; Greetham, Gregory M.; Towrie, Michael; Parker, Anthony W.; Hoskisson, Paul A.; Hunt, Neil T.

    2015-06-01

    The results of infrared spectroscopic investigations into the band assignments, vibrational relaxation, and solvation dynamics of the common anti-tuberculosis treatment Isoniazid (INH) are reported. INH is known to inhibit InhA, a 2-trans-enoyl-acyl carrier protein reductase enzyme responsible for the maintenance of cell walls in Mycobacterium tuberculosis but as new drug-resistant strains of the bacterium appear, next-generation therapeutics will be essential to combat the rise of the disease. Small molecules such as INH offer the potential for use as a biomolecular marker through which ultrafast multidimensional spectroscopies can probe drug binding and so inform design strategies but a complete characterization of the spectroscopy and dynamics of INH in solution is required to inform such activity. Infrared absorption spectroscopy, in combination with density functional theory calculations, is used to assign the vibrational modes of INH in the 1400-1700 cm-1 region of the infrared spectrum while ultrafast multidimensional spectroscopy measurements determine the vibrational relaxation dynamics and the effects of solvation via spectral diffusion of the carbonyl stretching vibrational mode. These results are discussed in the context of previous linear spectroscopy studies on solid-phase INH and its usefulness as a biomolecular probe.

  2. Radiosynthesis and bioimaging of the tuberculosis chemotherapeutics isoniazid, rifampicin and pyrazinamide in baboons

    SciTech Connect

    Liu, L.; Hooker, J.; Liu, L.; Xu, Y.; Shea, C.; Fowler, J.S.; Hooker, J.M.; Tonge, P.J.

    2010-03-03

    The front-line tuberculosis (TB) chemotherapeutics isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA) have been labeled with carbon-11 and the biodistribution of each labeled drug has been determined in baboons using positron emission tomography (PET). Each radiosynthesis and formulation has been accomplished in 1 h, using [{sup 11}C]CH{sub 3}I to label RIF and [{sup 11}C]HCN to label INH and PZA. Following iv administration, INH, PZA, RIF, and/or their radiolabeled metabolites clear rapidly from many tissues; however, INH, PZA, and/or their radiolabeled metabolites accumulate in the bladder while RIF and/or its radiolabeled metabolites accumulates in the liver and gall bladder, consistent with the known routes of excretion of the drugs. In addition, the biodistribution data demonstrate that the ability of the three drugs and their radiolabeled metabolites to cross the blood-brain barrier decreases in the order PZA > INH > RIF, although in all cases the estimated drug concentrations are greater than the minimum inhibitory concentration (MIC) values for inhibiting bacterial growth of Mycobacterium tuberculosis (MTB). The pharmacokinetic (PK) and drug distribution data have important implications for treatment of disseminated TB in the brain and pave the way for imaging the distribution of the pathogen in vivo.

  3. A Novel Mechanism of Growth Phase-dependent Tolerance to Isoniazid in Mycobacteria*

    PubMed Central

    Niki, Makoto; Niki, Mamiko; Tateishi, Yoshitaka; Ozeki, Yuriko; Kirikae, Teruo; Lewin, Astrid; Inoue, Yusuke; Matsumoto, Makoto; Dahl, John L.; Ogura, Hisashi; Kobayashi, Kazuo; Matsumoto, Sohkichi

    2012-01-01

    Tuberculosis remains one of the most deadly infectious diseases worldwide and is a leading public health problem. Although isoniazid (INH) is a key drug for the treatment of tuberculosis, tolerance to INH necessitates prolonged treatment, which is a concern for effective tuberculosis chemotherapy. INH is a prodrug that is activated by the mycobacterial enzyme, KatG. Here, we show that mycobacterial DNA-binding protein 1 (MDP1), which is a histone-like protein conserved in mycobacteria, negatively regulates katG transcription and leads to phenotypic tolerance to INH in mycobacteria. Mycobacterium smegmatis deficient for MDP1 exhibited increased expression of KatG and showed enhanced INH activation compared with the wild-type strain. Expression of MDP1 was increased in the stationary phase and conferred growth phase-dependent tolerance to INH in M. smegmatis. Regulation of KatG expression is conserved between M. smegmatis and Mycobacterium tuberculosis complex. Artificial reduction of MDP1 in Mycobacterium bovis BCG was shown to lead to increased KatG expression and susceptibility to INH. These data suggest a mechanism by which phenotypic tolerance to INH is acquired in mycobacteria. PMID:22648414

  4. Participation of P450-dependent oxidation of isoniazid in isonicotinic acid formation in rat liver.

    PubMed

    Ono, Y; Wu, X; Noda, A; Noda, H; Yoshitani, T

    1998-04-01

    By determining the formation amount of isonicotinic acid (INA) from isonicotinic acid hydrazide (isoniazid:INH) in isolated rat hepatocytes, we were able to identify the involvement of the oxidative cleavage of the acid hydrazide. INA formation from INH increased significantly using the isolated hepatocytes prepared from rats pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), dexamethazone (DEX) and rifampicin (RIF), respectively, in comparison to the control group. On the other hand, a remarkable decrease in INA formation from INH was observed by the addition of such P450 inhibitor as metyrapone or cimetidine as well as an amidase inhibitor bis(p-nitrophenyl)phosphate (BNPP) to the isolated hepatocytes prepared from PB-pretreated rats. By further experiments using rat hepatic microsomes, the oxidative pathway of INA formation in INH metabolism was determined to be P450-dependent, since NADPH and oxygen were both essential for the oxidative pathway of INH to INA and the amount of INA formation was also significantly increased by P450 inducers. Regarding acetylisoniazid (AcINH) and isonicotinic acid amide (INAA), however, INA formation by P450 was little observed in the microsomal experiments. PMID:9586587

  5. Isoniazid-induced polyneuropathy in a tuberculosis patient – implication for individual risk stratification with genotyping?

    PubMed Central

    Stettner, Mark; Steinberger, Daniela; Hartmann, Christian J; Pabst, Tatjana; Konta, Lidija; Hartung, Hans Peter; Kieseier, Bernd C

    2015-01-01

    Background Development of polyneuropathy (PNP) under treatment for tuberculosis (TB), including isoniazid (INH), is a highly relevant adverse drug effect. The NAT2 acetylation status is a predictor of potential toxic effects of INH. The question as to whether individual risk stratification by genotyping is useful to avoid suffering of patients and to lower costs for the health care system is of considerable clinical importance. Case Presentation After drug treatment for TB, including INH, a 23-year-old man developed severe PNP. During the treatment, laboratory results have been indicating incipient liver and renal injury. Later, molecular genetic analyses were performed and revealed a variation in the NAT2 gene and the c1/c2 genotype of the CYP2E1 gene, both described to contribute to an elevated risk for anti-tuberculostatic-induced liver damages (ATIL). Conclusion The combination of metabolizer genotypes should be taken into account as a cause for toxic effects and the development of PNP. Individual genotyping, performed before medication or at least if an elevation of liver parameters is observed, may reduce the risk of severe cases of PNP by early adjustment of treatment. Our case study indicates that evaluation of individual risk stratification with systematic pharmacogenetic genotyping of metabolizer gene combinations in the context of TB treatment should be addressed in clinical studies with larger cohorts. PMID:26355945

  6. Synthesis, characterization, and efficacy of antituberculosis isoniazid zinc aluminum-layered double hydroxide based nanocomposites

    PubMed Central

    Saifullah, Bullo; El Zowalaty, Mohamed Ezzat; Arulselvan, Palanisamy; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin Mahler; Hussein, Mohd Zobir

    2016-01-01

    The chemotherapy for tuberculosis (TB) is complicated by its long-term treatment, its frequent drug dosing, and the adverse effects of anti-TB drugs. In this study, we have developed two nanocomposites (A and B) by intercalating the anti-TB drug isoniazid (INH) into Zn/Al-layered double hydroxides. The average size of the nanocomposites was found to bê164 nm. The efficacy of the Zn/Al-layered double hydroxides intercalated INH against Mycobacterium tuberculosis was increased by approximately three times more than free INH. The nanocomposites were also found to be active against Gram-positive and -negative bacteria. Compared to the free INH, the nanodelivery formulation was determined to be three times more biocompatible with human normal lung fibroblast MRC-5 cells and 3T3 fibroblast cells at a very high concentration of 50 µg/mL for up to 72 hours. The in vitro release of INH from the Zn/Al-layered double hydroxides was found to be sustained in human body-simulated buffer solutions of pH 4.8 and 7.4. This research is a step forward in making the TB chemotherapy patient friendly. PMID:27486322

  7. Cytoprotective effect of isoniazid against H2O2 derived injury in HL-60 cells.

    PubMed

    Khan, Saifur R; Aljuhani, Naif; Morgan, Andrew G M; Baghdasarian, Argishti; Fahlman, Richard P; Siraki, Arno G

    2016-01-25

    To combat tuberculosis (TB), host phagocytic cells need to survive against self-generating oxidative stress-induced necrosis. However, the effect of isoniazid (INH) in protecting cells from oxidative stress-induced necrosis has not been previously investigated. In this in vitro study, the cytotoxic effect of H2O2 generation using glucose oxidase (a model of oxidative stress) was found to be abrogated by INH in a concentration-dependent manner in HL-60 cells (a human promyelocytic leukemia cell). In cells treated with glucose oxidase, both ATP and mitochondrial membrane potential were found to be decreased. However, treatment with INH demonstrated small but significant attenuation in decreasing ATP levels, and complete reversal for the decrease in mitochondrial membrane potential. Quantitative proteomics analysis identified up-regulation of 15 proteins and down-regulation of 14 proteins which all together suggest that these proteomic changes signal for increasing cellular replication, structural integrity, ATP synthesis, and inhibiting cell death. In addition, studies demonstrated that myeloperoxidase (MPO) was involved in catalyzing INH-protein adduct formation. Unexpectedly, these covalent protein adducts were correlated with INH-induced cytoprotection in HL-60 cells. Further studies are needed to determine whether the INH-protein adducts were causative in the mechanism of cytoprotection. PMID:26658028

  8. Design and evaluation of enteric-coated tablets for rifampicin and isoniazid combinations.

    PubMed

    Wang, Yongjun; Liu, Hongzhuo; Liu, Kai; Sun, Jin; He, Zhonggui

    2013-01-01

    In order to improve the bioavailability of rifampicin (RIF) from rifampicin and isoniazid (INH) combination formulations, the physicochemical characteristics of RIF, stability of RIF in different pH buffers in the presence of INH, as well as the effect of particle size of RIF materials on the dissolution rate were investigated. On the basis of the above examinations, enteric-coated tablets for RIF and INH combinations were designed and prepared. RIF showed low solubility and high apparent distribution coefficient in the intestinal pH (pH 4.0-7.4). With the decrease in pH, the degradation of RIF increase and the presence of INH deepen the degradation. Enteric-coated tablets were prepared after grinding the RIF materials by dry granulation technique. The pharmacokinetics of RIF and INH of self-made enteric-coated tablets in dogs were studied by comparing with the reference tablets. The AUC(0-48) of RIF in both reference and test tablets were 304.77 ± 42.27 and 353.79 ± 31.63 µg·h·mL(-1), respectively. The AUC(0-48) of INH in both reference and test tablets were 17.14 ± 8.59 and 19.62 ± 10.57 µg·h·mL(-1), respectively. Enteric-coated tablets may minimize the decomposition of RIF in gastrointestinal tract and improve the bioavailability. PMID:22339279

  9. Multidimensional infrared spectroscopy reveals the vibrational and solvation dynamics of isoniazid.

    PubMed

    Shaw, Daniel J; Adamczyk, Katrin; Frederix, Pim W J M; Simpson, Niall; Robb, Kirsty; Greetham, Gregory M; Towrie, Michael; Parker, Anthony W; Hoskisson, Paul A; Hunt, Neil T

    2015-06-01

    The results of infrared spectroscopic investigations into the band assignments, vibrational relaxation, and solvation dynamics of the common anti-tuberculosis treatment Isoniazid (INH) are reported. INH is known to inhibit InhA, a 2-trans-enoyl-acyl carrier protein reductase enzyme responsible for the maintenance of cell walls in Mycobacterium tuberculosis but as new drug-resistant strains of the bacterium appear, next-generation therapeutics will be essential to combat the rise of the disease. Small molecules such as INH offer the potential for use as a biomolecular marker through which ultrafast multidimensional spectroscopies can probe drug binding and so inform design strategies but a complete characterization of the spectroscopy and dynamics of INH in solution is required to inform such activity. Infrared absorption spectroscopy, in combination with density functional theory calculations, is used to assign the vibrational modes of INH in the 1400-1700 cm(-1) region of the infrared spectrum while ultrafast multidimensional spectroscopy measurements determine the vibrational relaxation dynamics and the effects of solvation via spectral diffusion of the carbonyl stretching vibrational mode. These results are discussed in the context of previous linear spectroscopy studies on solid-phase INH and its usefulness as a biomolecular probe. PMID:26049421

  10. Rapid Detection of Rifampicin- and Isoniazid-Resistant Mycobacterium tuberculosis using TaqMan Allelic Discrimination

    PubMed Central

    Darban-Sarokhalil, Davood; Nasiri, Mohammad J.; Fooladi, Abbas A.I.; Heidarieh, Parvin; Feizabadi, Mohammad M.

    2016-01-01

    Objectives Multidrug-resistant tuberculosis (MDR-TB) is a global problem that many countries are challenged with. Rapid and accurate detection of MDR-TB is critical for appropriate treatment and controlling of TB. The aim of the present study was to evaluate the TaqMan allelic discrimination without minor groove binder (MGB) as a rapid, efficient, and low-cost method for detection of drug resistant strains of Mycobacterium tuberculosis. Methods A total of 112 M. tuberculosis isolates from cases with diagnosed TB were subjected to drug susceptibility testing (DST), using the proportion method. Resistant isolates were tested for characterization of mutations in the rpoB and KatG genes by TaqMan genotyping. Results Of 112 M. tuberculosis isolates for which DST was performed, three, one, and two isolates were MDR, rifampin (RIF) resistant, and isoniazid (INH) resistant, respectively. According to the threshold cycle (Ct) and curve pattern of mutants, TaqMan probes detect all of the mutations in the analyzed genes (katG 315, AGC→ACC, rpoB 531, TCG→TTG, and rpoB 531, TCG→TGG). Conclusion The present study suggests that drug-resistant strains of M. tuberculosis can be detected by pattern’s curve or Ct with TaqMan probes without MGB in real-time polymerase chain reaction (PCR). PMID:27169012

  11. Genomic Stability over 9 Years of an Isoniazid Resistant Mycobacterium tuberculosis Outbreak Strain in Sweden

    PubMed Central

    Sandegren, Linus; Groenheit, Ramona; Koivula, Tuija; Ghebremichael, Solomon; Advani, Abdolreza; Castro, Elsie; Pennhag, Alexandra; Hoffner, Sven; Mazurek, Jolanta; Pawlowski, Andrzej; Kan, Boris; Bruchfeld, Judith; Melefors, Öjar; Källenius, Gunilla

    2011-01-01

    In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e.g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance. PMID:21304944

  12. Molecular analysis of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from India.

    PubMed

    Nusrath Unissa, A; Selvakumar, N; Narayanan, Sujatha; Narayanan, P R

    2008-01-01

    The presence of mutations in specific regions of katG, inhA, oxyR-ahpC and kasA associated with isoniazid (INH)-resistant clinical isolates of Mycobacterium tuberculosis from India were analysed by DNA sequencing. Point mutations in the katG gene at codon 315 and a mutation at codon 138 were detected in 64.3% (45/70) and 4% (1/25) of isolates, respectively. Polymorphisms at codon 463 of the katG gene were found both in resistant and sensitive isolates. Mutation at the inhA and oxyR-ahpC promoter regions occurred in 11.4% (8/70) and 35.0% (14/40) of the isolates, respectively. No mutation was found to occur in kasA and inhA structural gene regions. Of the 70 resistant isolates studied, 55 (78.6%) showed mutation in the regions sequenced. This is the first comprehensive molecular analysis of INH resistance in India, which suggests that point mutation rather than deletion and insertion is the major cause of INH resistance. PMID:18006278

  13. Detection of mutations associated with isoniazid resistance in Mycobacterium tuberculosis isolates from China.

    PubMed

    Zhang, Min; Yue, Jun; Yang, Yan-Ping; Zhang, Hong-Mei; Lei, Jian-Qiang; Jin, Rui-Liang; Zhang, Xue-Lian; Wang, Hong-Hai

    2005-11-01

    Nine structural genes (furA, katG, inhA, kasA, Rv0340, iniB, iniA, iniC, and efpA) and two regulatory regions (the oxyR-ahpC intergenic region and the promoter of mabA-inhA) in 87 isoniazid (INH)-monoresistant and 50 INH-susceptible Mycobacterium tuberculosis isolates collected from five provinces of China were analyzed by sequencing. Eighty-two (94.3%) INH-resistant isolates had mutations in the katG gene, with the katG Ser315Thr mutation predominant (55.2%). No mutation at codon 463 of katG was detected among the 50 INH-susceptible isolates with different IS6110 fingerprints. In addition, there were 35 (40.2%) INH-resistant isolates that had a mutation at codon 463 of katG. Of the INH-resistant strains, 20 (23.0%) isolates harbored double mutations at two separate loci of katG. Mutations in the inhA promoter region occurred in 13 (14.9%) isolates; 4.6% of the isolates had inhA structural gene mutations, and 11.5% harbored mutations in the oxyR-ahpC intergenic region. Drug resistance-associated mutations were detected in the iniBAC region and efpA. PMID:16272473

  14. Differential effects of isoniazid and oral contraceptive steroids on antipyrine oxidation and acetaminophen conjugation.

    PubMed

    Ochs, H R; Greenblatt, D J; Verburg-Ochs, B; Abernethy, D R; Knüchel, M

    1984-01-01

    Factors influencing hepatic oxidation of antipyrine and conjugation of acetaminophen were evaluated in volunteers who received 1.0 g of antipyrine intravenously and on a different occasion a 650 mg intravenous dose of acetaminophen. In study one, subjects received both drugs in the control state and at another time during coadministration of isoniazid (INH), 180 mg daily. In control versus INH conditions, mean clearance of antipyrine was reduced from 0.67 to 0.60 ml/min/kg as was clearance of acetaminophen from 4.97 to 4.23 ml/min/kg, but these differences were not statistically significant. In study two, females on low-dose estrogen oral contraceptives (OC) and drug-free controls matched for age received both drugs. Compared to controls, OC users had reduced total clearance of antipyrine (0.71 vs. 0.50 ml/min/kg; p less than 0.005) and prolonged antipyrine t1/2 (9.6 vs. 13.3 h; p less than 0.005). For acetaminophen, however, OC users had higher clearance (5.2 vs. 6.1 ml/min/kg) and shorter t1/2 (2.2 vs. 1.9 h) although differences did not attain statistical significance. Clearance of antipyrine and acetaminophen across both studies was not statistically significantly correlated within individuals (r = 0.22). The capacities for drug oxidation and conjugation appear to be controlled by different mechanisms. PMID:6728897

  15. Synthesis, characterization, and efficacy of antituberculosis isoniazid zinc aluminum-layered double hydroxide based nanocomposites.

    PubMed

    Saifullah, Bullo; El Zowalaty, Mohamed Ezzat; Arulselvan, Palanisamy; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin Mahler; Hussein, Mohd Zobir

    2016-01-01

    The chemotherapy for tuberculosis (TB) is complicated by its long-term treatment, its frequent drug dosing, and the adverse effects of anti-TB drugs. In this study, we have developed two nanocomposites (A and B) by intercalating the anti-TB drug isoniazid (INH) into Zn/Al-layered double hydroxides. The average size of the nanocomposites was found to bê164 nm. The efficacy of the Zn/Al-layered double hydroxides intercalated INH against Mycobacterium tuberculosis was increased by approximately three times more than free INH. The nanocomposites were also found to be active against Gram-positive and -negative bacteria. Compared to the free INH, the nanodelivery formulation was determined to be three times more biocompatible with human normal lung fibroblast MRC-5 cells and 3T3 fibroblast cells at a very high concentration of 50 µg/mL for up to 72 hours. The in vitro release of INH from the Zn/Al-layered double hydroxides was found to be sustained in human body-simulated buffer solutions of pH 4.8 and 7.4. This research is a step forward in making the TB chemotherapy patient friendly. PMID:27486322

  16. A Note on Derivatives of Isoniazid, Rifampicin, and Pyrazinamide Showing Activity Against Resistant Mycobacterium tuberculosis.

    PubMed

    Nusrath Unissa, Ameeruddin; Hanna, Luke Elizabeth; Swaminathan, Soumya

    2016-04-01

    Drug-resistant tuberculosis (DR-TB) is a serious problem that impedes the success of the TB control program. Of note, multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB have certainly complicated the scenario. One of the possible strategies to overcome drug resistance in an economic and simple manner would involve modification of existing anti-TB drugs to obtain derivatives that can work on resistant TB bacilli. These may have improved half-life and increased bioavailability, be more efficacious, and serve as cost-effective alternatives, as compared to new drugs identified through conventional methods of drug discovery and development. Although extensive literature is available on the activity of various derivatives of first-line drugs (isoniazid, rifampicin and pyrazinamide) on drug-susceptible Mycobacterium tuberculosis (MTB), reports on the activity of derivatives on resistant MTB are very limited, to our knowledge. In light of this, the present review aims to provide a concise report on the derivatives of first-line drugs that have the potential to overcome the resistance to the parental drug and could thus serve as effective alternatives. PMID:26613382

  17. PROPOSAL OF ANTI-TUBERCULOSIS REGIMENS BASED ON SUSCEPTIBILITY TO ISONIAZID AND RIFAMPICIN

    PubMed Central

    Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos

    2014-01-01

    Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502

  18. Mutations Prevalent among Rifampin- and Isoniazid-Resistant Mycobacterium tuberculosis Isolates from a Hospital in Vietnam

    PubMed Central

    Caws, M.; Duy, Phan Minh; Tho, Dau Quang; Lan, Nguyen Thi Ngoc; Hoa, Dai Viet; Farrar, Jeremy

    2006-01-01

    Vietnam is ranked 13th among the WHO list of 22 high-burden countries, based upon estimated total number of tuberculosis cases. Despite having a model national tuberculosis program, consistently achieving and exceeding WHO targets for detection and cure, drug-resistant and multidrug-resistant tuberculosis cases continue to rise. Rapid multidrug-resistant tests applicable in this setting, coupled with effective treatment regimens, would be a useful tool in reversing this trend, allowing early identification of patients with multidrug-resistant tuberculosis and avoiding resistance-amplifying regimens. Sequencing of consecutive isolates identified by the National Tuberculosis Program showed 89% of isoniazid-resistant isolates could be detected by targeting just 2 codons, katG 315 and −15C→T in the inhA promoter, while rifampin resistance will be more complex to detect, with many different mutation and insertion events in rpoB. The most prevalent rifampin resistance-conferring mutations, as in other countries, were in rpoB codons 531 (43%), 526 (31%), and 516 (15%). However, a hybridization-based resistance test with probes targeting the 5 most common mutations would only detect 78% of rifampin-resistant isolates. Overall, these data suggest that rifampin resistance may be used as a surrogate marker for multidrug-resistant tuberculosis and that a sensitivity of between 70 to 80% may be possible for rapid molecular detection of multidrug-resistant tuberculosis in this setting. PMID:16825345

  19. [Bilateral Granulomatous Renal Masses after Intravesical BCG Therapy for Non-muscle-invasive Bladder Cancer and Carcinoma in Situ of the Upper Urinary Tract: A Case Study].

    PubMed

    Higashioka, Kazuhiko; Miyake, Noriko; Nishida, Ruriko; Chong, Yong; Shimoda, Shinji; Shimono, Nobuyuki

    2015-07-01

    Bacillus Calmette-Guèrin (BCG) is commonly used not only as an infant vaccination, but also as a treatment of and prophylaxis to prevent recurrence in the management of non-muscle-invasive bladder cancer. However, the use of "live" BCG is sometimes complicated by associated infection. We present a case study of a 77-year-old man who developed bilateral renal masses after intravesical BCG therapy was initiated in November 2013, following transurethral resection of non-muscle-invasive bladder cancer. After four courses of BCG (Japan strain, 80 mg per treatment) instillations, a computed tomography examination for febrile episodes showed multiple bilateral renal masses, accompanied by a histological finding of a granulomatous reaction. An acid fast bacterium was cultured from only urine among blood, urine, and microscopic samples. Using the cultured strain, BCG infection was confirmed by the specific gene deletion pattern based on allele-specific polymerase chain reaction analysis. Anti-tuberculosis treatment, including isoniazid (300 mg/day), rifampicin (600 mg/day), and ethambutol (1,000 mg/day), was started for the BCG-related renal granuloma in February 2014. After 3 months, antibiotic therapy was discontinued owing to severe appetite loss, though the masses remained solid. No rapid growth has been detected after anti-BCG therapy. Intravesical BCG therapy is recommended worldwide as one of standard treatments for non-muscle-invasive bladder cancer. We should closely observe patients undergoing this approach for emerging BCG complications. PMID:26554225

  20. Low-level laser therapy for the prevention of low salivary flow rate after radiotherapy and chemotherapy in patients with head and neck cancer*

    PubMed Central

    Gonnelli, Fernanda Aurora Stabile; Palma, Luiz Felipe; Giordani, Adelmo José; Deboni, Aline Lima Silva; Dias, Rodrigo Souza; Segreto, Roberto Araújo; Segreto, Helena Regina Comodo

    2016-01-01

    Objective To determine whether low-level laser therapy can prevent salivary hypofunction after radiotherapy and chemotherapy in head and neck cancer patients. Materials and Methods We evaluated 23 head and neck cancer patients, of whom 13 received laser therapy and 10 received clinical care only. An InGaAlP laser was used intra-orally (at 660 nm and 40 mW) at a mean dose of 10.0 J/cm2 and extra-orally (at 780 nm and 15 mW) at a mean dose of 3.7 J/cm2, three times per week, on alternate days. Stimulated and unstimulated sialometry tests were performed before the first radiotherapy and chemotherapy sessions (N0) and at 30 days after the end of treatment (N30). Results At N30, the mean salivary flow rates were significantly higher among the laser therapy patients than among the patients who received clinical care only, in the stimulated and unstimulated sialometry tests (p = 0.0131 and p = 0.0143, respectively). Conclusion Low-level laser therapy, administered concomitantly with radiotherapy and chemotherapy, appears to mitigate treatment-induced salivary hypofunction in patients with head and neck cancer. PMID:27141130

  1. Relationship Between Nonprescribed Therapy Use for Illness Prevention and Health Promotion and Health-Related Quality of Life

    PubMed Central

    Altizer, Kathryn P.; Nguyen, Ha T.; Neiberg, Rebecca H.; Quandt, Sara A.; Grzywacz, Joseph G.; Lang, Wei; Bell, Ronny A.; Arcury, Thomas A.

    2014-01-01

    Objectives This study describes the nonprescribed therapy use (prayer, over-the-counter medications [OTC's], home remedies, vitamins, herbs and supplements, and exercise) for health promotion among rural elders. It also delineates the association of such therapy use with physical and mental health-related quality of life (HRQoL). Method The sample (N = 200) consisted of African American and White elders from south-central North Carolina. Participants completed baseline interviews and repeated measures of nonprescribed therapy use over a 6-month follow-up. Results Prayer had the highest percentage (80.7%) of use for health promotion followed by OTC (54.3%); vitamins only (49.3%); herbs and supplements (40.5%); exercise (31.9%); and home remedies (5.2%). Exercise was significantly associated with better physical HRQoL (p < .05). However, elders who used nonprescribed therapies had poorer mental HRQoL than nonusers, adjusting for potential confounders. Conclusion This analysis suggests that use of some nonprescribed therapies for health promotion is associated with poorer mental HRQoL. PMID:24781966

  2. Early application of negative pressure wound therapy to acute wounds contaminated with Staphylococcus aureus: An effective approach to preventing biofilm formation

    PubMed Central

    LI, TONGTONG; ZHANG, LIHAI; HAN, LI; WANG, GUOQI; YIN, PENG; LI, ZHIRUI; ZHANG, LICHENG; GUO, QI; LIU, DAOHONG; TANG, PEIFU

    2016-01-01

    Negative pressure wound therapy (NPWT) has been demonstrated to be effective at preventing biofilm-associated infections; however, its role in biofilm prevention is unknown. The present study evaluated the effect of NPWT on biofilm prevention when rapidly initiated following wound contamination. Full-thickness dermal wounds (8 mm) were created in rabbit ears and inoculated with green fluorescent protein-labeled Staphylococcus aureus (S. aureus). At 6 h following inoculation, continuous NPWT at −125 mmHg was initiated, with the wounds on the contralateral ear left untreated in order to serve as self-controls. S. aureus rapidly formed mature biofilms in the wound beds post-inoculation, with a persistent bacterial burden of ~105−107 colony-forming units (CFUs)/wound and impaired wound healing. Compared with the untreated group, NPWT resulted in a significant reduction in biofilm matrix, which was verified by scanning electron microscopy and epifluorescence. A reduction in bacterial counts followed (P<0.05) with ~103 CFUs/wound on postoperative day 13 and improvement in all healing parameters (P<0.05) relative to control wounds. The results of the present investigation suggest that NPWT is an effective strategy to impeding the formation of S. aureus wound biofilms when initiated rapidly following bacterial contamination. The early application of NPWT, aimed at biofilm prevention, may improve wound care. PMID:26997991

  3. Oral Mucositis Prevention By Low-Level Laser Therapy in Head-and-Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy: A Phase III Randomized Study

    SciTech Connect

    Gouvea de Lima, Aline; Villar, Rosangela Correa; Castro, Gilberto de; Antequera, Reynaldo; Gil, Erlon; Rosalmeida, Mauro Cabral; Federico, Miriam Hatsue Honda; Snitcovsky, Igor Moises Longo

    2012-01-01

    Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm{sup 2} or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might

  4. A Pound of Cure Requires An Ounce (or More) of Prevention: Survivorship and Complications of Therapy for Hematologic Malignancies.

    PubMed

    Luskin, Marlise R; Banerjee, Rahul; Del Percio, Sarah; Loren, Alison W

    2015-09-01

    Patients treated for a hematologic malignancy are at risk for treatment-related complications. As the goal of therapy is frequently curative, treatments are especially intensive and long-term toxicity is common. Chemotherapy and radiation are associated with increased risk for cardiac and pulmonary disease, endocrine disorders, infertility, sexual dysfunction, second cancers, and psychosocial distress. The risk for each complication is dictated by patient characteristics including age, co-morbidities, and genetic predispositions, as well as the specifics of therapy. Survivors of pediatric cancers and allogeneic hematopoietic stem cell transplantation have unique risks due to vulnerable age at time of toxic exposure and ongoing immune dysfunction, respectively. PMID:26162948

  5. Role of tacrolimus combination therapy with mycophenolate mofetil in the prevention of organ rejection in kidney transplant patients

    PubMed Central

    Dalal, P; Shah, G; Chhabra, D; Gallon, Lorenzo

    2010-01-01

    Introduction: Several new medications are now available for immunosuppression in the kidney transplant field. Tacrolimus and mycophenolate mofetil were first introduced for immunosuppression in renal transplantation in the mid 1990s. Since then, the combination of tacrolimus and mycophenolate mofetil has been evaluated in numerous clinical trials. The outcomes of these trials have varied due to differences in induction and/or maintenance therapy, drug dosing and monitoring protocols, and study design. The aim of this review is to analyze the literature critically and to provide an overview of tacrolimus and mycophenolate mofetil combination therapy in renal transplantation. PMID:21694936

  6. Promoting Positive Interactions in the Classroom: Adapting Parent-Child Interaction Therapy as a Universal Prevention Program

    ERIC Educational Resources Information Center

    Gershenson, Rachel A.; Lyon, Aaron R.; Budd, Karen S.

    2010-01-01

    The adaptation of Parent-Child Interaction Therapy (PCIT), an empirically-supported dyadic parent training intervention, to a preschool setting may provide an opportunity to enhance the well-being of both teachers and children by improving the teacher-child relationship and supplying teachers with effective tools for behavior management. The…

  7. BET 1: Safety and efficacy of colchicine as stand-alone therapy for the prevention of recurrent pericarditis.

    PubMed

    Manspeaker, Andrew; Andrews-Dickert, Rebecca

    2016-08-01

    A short cut review was carried out looking for evidence of the benefits of using colchicine as a single therapy for acute pericarditis. A literature search was performed but no papers were found to provide evidence of the efficacy of colchicine without the concurrent use of Non-steriodal anti-inflammatory drugs (NSAIDs) for this condition. PMID:27440768

  8. Randomized Trial of Behavioral Activation, Cognitive Therapy, and Antidepressant Medication in the Prevention of Relapse and Recurrence in Major Depression

    ERIC Educational Resources Information Center

    Dobson, Keith S.; Hollon, Steven D.; Dimidjian, Sona; Schmaling, Karen B.; Kohlenberg, Robert J.; Gallop, Robert J.; Rizvi, Shireen L.; Gollan, Jackie K.; Dunner, David L.; Jacobson, Neil S.

    2008-01-01

    This study followed treatment responders from a randomized controlled trial of adults with major depression. Patients treated with medication but withdrawn onto pill-placebo had more relapse through 1 year of follow-up compared to patients who received prior behavioral activation, prior cognitive therapy, or continued medication. Prior…

  9. Systematic review and meta-analysis: Multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events

    PubMed Central

    Huang, Ying; Wang, Lin; Malfertheiner, Peter

    2015-01-01

    Background Eradication rates with triple therapy for Helicobacter pylori infections have currently declined to unacceptable levels worldwide. Newer quadruple therapies are burdened with a high rate of adverse events. Whether multi-strain probiotics can improve eradication rates or diminish adverse events remains uncertain. Methods Relevant publications in which patients with H. pylori infections were randomized to a multi-strain probiotic or control were identified in PubMed, Cochrane Databases, and other sources from 1 January 1960–3 June 2015. Primary outcomes included eradication rates, incidence of any adverse event and the incidence of antibiotic-associated diarrhea. As probiotic efficacy is strain-specific, pooled relative risks and 95% confidence intervals were calculated using meta-analysis stratified by similar multi-strain probiotic mixtures. Results A total of 19 randomized controlled trials (20 treatment arms, n = 2730) assessing one of six mixtures of strains of probiotics were included. Four multi-strain probiotics significantly improved H. pylori eradication rates, five significantly prevented any adverse reactions and three significantly reduced antibiotic-associated diarrhea. Only two probiotic mixtures (Lactobacillus acidophilus/Bifidobacterium animalis and an eight-strain mixture) had significant efficacy for all three outcomes. Conclusions Our meta-analysis found adjunctive use of some multi-strain probiotics may improve H. pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea, but not all mixtures were effective. PMID:27536365

  10. Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

    PubMed Central

    Bourguignon, L.; Bihari, S.; Maire, P.; Neely, M.; Jelliffe, R.

    2015-01-01

    Among first-line antituberculosis drugs, isoniazid (INH) displays the greatest early bactericidal activity (EBA) and is key to reducing contagiousness in treated patients. The pulmonary pharmacokinetics and pharmacodynamics of INH have not been fully characterized with modeling and simulation approaches. INH concentrations measured in plasma, epithelial lining fluid, and alveolar cells for 89 patients, including fast acetylators (FAs) and slow acetylators (SAs), were modeled by use of population pharmacokinetic modeling. Then the model was used to simulate the EBA of INH in lungs and to investigate the influences of INH dose, acetylator status, and M. tuberculosis MIC on this effect. A three-compartment model adequately described INH concentrations in plasma and lungs. With an MIC of 0.0625 mg/liter, simulations showed that the mean bactericidal effect of a standard 300-mg daily dose of INH was only 11% lower for FA subjects than for SA subjects and that dose increases had little influence on the effects in either FA or SA subjects. With an MIC value of 1 mg/liter, the mean bactericidal effect associated with a 300-mg daily dose of INH in SA subjects was 41% greater than that in FA subjects. With the same MIC, increasing the daily INH dose from 300 mg to 450 mg resulted in a 22% increase in FA subjects. These results suggest that patients infected with M. tuberculosis with low-level resistance, especially FA patients, may benefit from higher INH doses, while dose adjustment for acetylator status has no significant impact on the EBA in patients with low-MIC strains. PMID:26077251

  11. Isoniazid-induced cell death is precipitated by underlying mitochondrial complex I dysfunction in mouse hepatocytes.

    PubMed

    Lee, Kang Kwang; Fujimoto, Kazunori; Zhang, Carmen; Schwall, Christine T; Alder, Nathan N; Pinkert, Carl A; Krueger, Winfried; Rasmussen, Theodore; Boelsterli, Urs A

    2013-12-01

    Isoniazid (INH) is an antituberculosis drug that has been associated with idiosyncratic liver injury in susceptible patients. The underlying mechanisms are still unclear, but there is growing evidence that INH and/or its major metabolite, hydrazine, may interfere with mitochondrial function. However, hepatic mitochondria have a large reserve capacity, and minor disruption of energy homeostasis does not necessarily induce cell death. We explored whether pharmacologic or genetic impairment of mitochondrial complex I may amplify mitochondrial dysfunction and precipitate INH-induced hepatocellular injury. We found that INH (≤ 3000 μM) did not induce cell injury in cultured mouse hepatocytes, although it decreased hepatocellular respiration and ATP levels in a concentration-dependent fashion. However, coexposure of hepatocytes to INH and nontoxic concentrations of the complex I inhibitors rotenone (3 μM) or piericidin A (30 nM) resulted in massive ATP depletion and cell death. Although both rotenone and piericidin A increased MitoSox-reactive fluorescence, Mito-TEMPO or N-acetylcysteine did not attenuate the extent of cytotoxicity. However, preincubation of cells with the acylamidase inhibitor bis-p-nitrophenol phosphate provided protection from hepatocyte injury induced by rotenone/INH (but not rotenone/hydrazine), suggesting that hydrazine was the cell-damaging species. Indeed, we found that hydrazine directly inhibited the activity of solubilized complex II. Hepatocytes isolated from mutant Ndufs4(+/-) mice, although featuring moderately lower protein expression levels of this complex I subunit in liver mitochondria, exhibited unchanged hepatic complex I activity and were therefore not sensitized to INH. These data indicate that underlying inhibition of complex I, which alone is not acutely toxic, can trigger INH-induced hepatocellular injury. PMID:23911619

  12. Characterization of the binding of isoniazid and analogues to Mycobacterium tuberculosis catalase-peroxidase.

    PubMed

    Zhao, Xiangbo; Yu, Shengwei; Magliozzo, Richard S

    2007-03-20

    The first-line antituberculosis drug isonicotinic hydrazide (INH) is a prodrug whose bactericidal function requires activation by Mycobacterium tuberculosis catalase-peroxidase (KatG) to produce an acyl-NAD adduct. Peroxidation of INH is considered a required catalytic process for drug action. The binding of INH and a series of hydrazide analogues to resting KatG was examined using optical and calorimetric techniques to provide thermodynamic parameters, binding stoichiometries, and kinetic constants (on and off rates). This work revealed high-affinity binding of these substrates to a small fraction of ferric enzyme in a six-coordinate heme iron form, a species most likely containing a weakly bound water molecule, which accumulates during storage of the enzyme. The binding of hydrazides is associated with a large enthalpy loss (>100 kcal/mol); dissociation constants are in the range of 0.05-1.6 microM, and optical stopped-flow measurements demonstrated kon values in the range of 0.5-27 x 10(3) M-1 s-1 with very small koff rates. Binding parameters did not depend on pH in the range 5-8. High-affinity binding of INH is disrupted in two mutant enzymes bearing replacements of key distal side residues, KatG[W107F] and KatG[Y229F]. The rates of reduction of KatG Compound I by hydrazides parallel the on rates for association with the resting enzyme. In a KatG-mediated biomimetic activation assay, only isoniazid generated in good yield the acyl-NAD adduct which is considered a key molecule in INH action, providing a better understanding of the action mechanism of INH. PMID:17309235

  13. Protein Targets of Isoniazid-Reactive Metabolites in Mouse Liver in Vivo.

    PubMed

    Koen, Yakov M; Galeva, Nadezhda A; Metushi, Imir G; Uetrecht, Jack; Hanzlik, Robert P

    2016-06-20

    Isoniazid (INH) has been a first-line drug for the treatment of tuberculosis for more than 40 years. INH is well-tolerated by most patients, but some patients develop hepatitis that can be severe in rare cases or after overdose. The mechanisms underlying the hepatotoxicity of INH are not known, but covalent binding of reactive metabolites is known to occur in animals and is suspected in human cases. A major unresolved question is the identity of the liver proteins that are modified by INH metabolites. Treating mice with INH leads to accumulation of isonicotinoyl-lysine residues on numerous proteins in the hepatic S9 fraction. Analysis of this fraction by SDS-PAGE followed by tryptic digestion of bands and LC-MS/MS revealed a single adducted peptide derived from d-dopachrome decarboxylase. When a tryptic digest of whole S9 was applied to anti-INH antibody immobilized on beads, only 12 peptides were retained, 5 of which clearly contained isonicotinoyl-lysine adducts and could be confidently assigned to 5 liver proteins. In another experiment, undigested S9 fractions from INA-treated and untreated (UT) mice were adsorbed in parallel on anti-INA beads and the retained proteins were digested and analyzed by LC-MS/MS. The INA-S9 digest showed 1 adducted peptide that was associated with a unique protein whose identity was corroborated by numerous nonadducted peptides in the digest and 13 other proteins identified only by multiple nonadducted peptides. None of these 14 proteins was associated with any peptides present in the UT-S9 fraction. Overall, we identified 7 mouse liver proteins that became adducted by INH metabolites in vivo. Of these 7 INH target proteins, only 2 have been previously reported as targets of any reactive metabolite in vivo. PMID:27097313

  14. Population pharmacokinetic analysis of isoniazid, acetylisoniazid, and isonicotinic acid in healthy volunteers.

    PubMed

    Seng, Kok-Yong; Hee, Kim-Hor; Soon, Gaik-Hong; Chew, Nicholas; Khoo, Saye H; Lee, Lawrence Soon-U

    2015-11-01

    In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one-compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤ Cmax ≤ 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH. PMID:26282412

  15. Population Pharmacokinetic Analysis of Isoniazid, Acetylisoniazid, and Isonicotinic Acid in Healthy Volunteers

    PubMed Central

    Seng, Kok-Yong; Hee, Kim-Hor; Soon, Gaik-Hong; Chew, Nicholas; Khoo, Saye H.

    2015-01-01

    In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one-compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤ Cmax ≤ 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH. PMID:26282412

  16. Detecting Novel Genetic Variants Associated with Isoniazid-Resistant Mycobacterium tuberculosis

    PubMed Central

    Chan, Maurice K. L.; Ong, Danny C. T.; Tongyoo, Pumipat; Wong, Sin-Yew; Lee, Ann S. G.

    2014-01-01

    Background Isoniazid (INH) is a highly effective antibiotic central for the treatment of Mycobacterium tuberculosis (MTB). INH-resistant MTB clinical isolates are frequently mutated in the katG gene and the inhA promoter region, but 10 to 37% of INH-resistant clinical isolates have no detectable alterations in currently known gene targets associated with INH-resistance. We aimed to identify novel genes associated with INH-resistance in these latter isolates. Methodology/Principal Findings INH-resistant clinical isolates of MTB were pre-screened for mutations in the katG, inhA, kasA and ndh genes and the regulatory regions of inhA and ahpC. Twelve INH-resistant isolates with no mutations, and 17 INH-susceptible MTB isolates were subjected to whole genome sequencing. Phylogenetically related variants and synonymous mutations were excluded and further analysis revealed mutations in 60 genes and 4 intergenic regions associated with INH-resistance. Sanger sequencing verification of 45 genes confirmed that mutations in 40 genes were observed only in INH-resistant isolates and not in INH-susceptible isolates. The ratios of non-synonymous to synonymous mutations (dN/dS ratio) for the INH-resistance associated mutations identified in this study were 1.234 for INH-resistant and 0.654 for INH-susceptible isolates, strongly suggesting that these mutations are indeed associated with INH-resistance. Conclusion The discovery of novel targets associated with INH-resistance described in this study may potentially be important for the development of improved molecular detection strategies. PMID:25025225

  17. Novel katG mutations causing isoniazid resistance in clinical M. tuberculosis isolates

    PubMed Central

    Torres, Jessica N; Paul, Lynthia V; Rodwell, Timothy C; Victor, Thomas C; Amallraja, Anu M; Elghraoui, Afif; Goodmanson, Amy P; Ramirez-Busby, Sarah M; Chawla, Ashu; Zadorozhny, Victoria; Streicher, Elizabeth M; Sirgel, Frederick A; Catanzaro, Donald; Rodrigues, Camilla; Gler, Maria Tarcela; Crudu, Valeru; Catanzaro, Antonino; Valafar, Faramarz

    2015-01-01

    We report the discovery and confirmation of 23 novel mutations with previously undocumented role in isoniazid (INH) drug resistance, in catalase-peroxidase (katG) gene of Mycobacterium tuberculosis (Mtb) isolates. With these mutations, a synonymous mutation in fabG1g609a, and two canonical mutations, we were able to explain 98% of the phenotypic resistance observed in 366 clinical Mtb isolates collected from four high tuberculosis (TB)-burden countries: India, Moldova, Philippines, and South Africa. We conducted overlapping targeted and whole-genome sequencing for variant discovery in all clinical isolates with a variety of INH-resistant phenotypes. Our analysis showed that just two canonical mutations (katG 315AGC-ACC and inhA promoter-15C-T) identified 89.5% of resistance phenotypes in our collection. Inclusion of the 23 novel mutations reported here, and the previously documented point mutation in fabG1, increased the sensitivity of these mutations as markers of INH resistance to 98%. Only six (2%) of the 332 resistant isolates in our collection did not harbor one or more of these mutations. The third most prevalent substitution, at inhA promoter position -8, present in 39 resistant isolates, was of no diagnostic significance since it always co-occurred with katG 315. 79% of our isolates harboring novel mutations belong to genetic group 1 indicating a higher tendency for this group to go down an uncommon evolutionary path and evade molecular diagnostics. The results of this study contribute to our understanding of the mechanisms of INH resistance in Mtb isolates that lack the canonical mutations and could improve the sensitivity of next generation molecular diagnostics. PMID:26251830

  18. Screening and characterization of mutations in isoniazid-resistant Mycobacterium tuberculosis isolates obtained in Brazil.

    PubMed

    Cardoso, Rosilene Fressatti; Cooksey, Robert C; Morlock, Glenn P; Barco, Patricia; Cecon, Leticia; Forestiero, Francisco; Leite, Clarice Q F; Sato, Daisy N; Shikama, Maria de Lourdes; Mamizuka, Elsa M; Hirata, Rosario D C; Hirata, Mario H

    2004-09-01

    We investigated mutations in the genes katG, inhA (regulatory and structural regions), and kasA and the oxyR-ahpC intergenic region of 97 isoniazid (INH)-resistant and 60 INH-susceptible Mycobacterium tuberculosis isolates obtained in two states in Brazil: São Paulo and Paraná. PCR-single-strand conformational polymorphism (PCR-SSCP) was evaluated for screening mutations in regions of prevalence, including codons 315 and 463 of katG, the regulatory region and codons 16 and 94 of inhA, kasA, and the oxyR-ahpC intergenic region. DNA sequencing of PCR amplicons was performed for all isolates with altered PCR-SSCP profiles. Mutations in katG were found in 83 (85.6%) of the 97 INH-resistant isolates, including mutations in codon 315 that occurred in 60 (61.9%) of the INH-resistant isolates and 23 previously unreported katG mutations. Mutations in the inhA promoter region occurred in 25 (25.8%) of the INH-resistant isolates; 6.2% of the isolates had inhA structural gene mutations, and 10.3% had mutations in the oxyR-ahpC intergenic region (one, nucleotide -48, previously unreported). Polymorphisms in the kasA gene occurred in both INH-resistant and INH-susceptible isolates. The most frequent polymorphism encoded a G(269)A substitution. Although KatG(315) substitutions are predominant, novel mutations also appear to be responsible for INH resistance in the two states in Brazil. Since ca. 90.7% of the INH-resistant isolates had mutations identified by SSCP electrophoresis, this method may be a useful genotypic screen for INH resistance. PMID:15328099

  19. Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis.

    PubMed

    Slayden, R A; Lee, R E; Barry, C E

    2000-11-01

    Genetic and biochemical evidence has implicated two different target enzymes for isoniazid (INH) within the unique type II fatty acid synthase (FAS) system involved in the production of mycolic acids. These two components are an enoyl acyl carrier protein (ACP) reductase, InhA, and a beta-ketoacyl-ACP synthase, KasA. We compared the consequences of INH treatment of Mycobacterium tuberculosis (MTB) with two inhibitors having well-defined targets: triclosan (TRC), which inhibits InhA; and thiolactomycin (TLM), which inhibits KasA. INH and TLM, but not TRC, upregulate the expression of an operon containing five FAS II components, including kasA and acpM. Although all three compounds inhibit mycolic acid synthesis, treatment with INH and TLM, but not with TRC, results in the accumulation of ACP-bound lipid precursors to mycolic acids that were 26 carbons long and fully saturated. TLM-resistant mutants of MTB were more cross-resistant to INH than TRC-resistant mutants. Overexpression of KasA conferred more resistance to TLM and INH than to TRC. Overexpression of InhA conferred more resistance to TRC than to INH and TLM. Co-overexpression of both InhA and KasA resulted in strongly enhanced levels of INH resistance, in addition to cross-resistance to both TLM and TRC. These results suggest that these components of the FAS II complex are not independently regulated and that alterations in the expression level of InhA affect expression levels of KasA. Nonetheless, INH appeared to resemble TLM more closely in overall mode of action, and KasA levels appeared to be tightly correlated with INH sensitivity. PMID:11069675

  20. Screening and Characterization of Mutations in Isoniazid-Resistant Mycobacterium tuberculosis Isolates Obtained in Brazil

    PubMed Central

    Cardoso, Rosilene Fressatti; Cooksey, Robert C.; Morlock, Glenn P.; Barco, Patricia; Cecon, Leticia; Forestiero, Francisco; Leite, Clarice Q. F.; Sato, Daisy N.; Shikama, Maria de Lourdes; Mamizuka, Elsa M.; Hirata, Rosario D. C.; Hirata, Mario H.

    2004-01-01

    We investigated mutations in the genes katG, inhA (regulatory and structural regions), and kasA and the oxyR-ahpC intergenic region of 97 isoniazid (INH)-resistant and 60 INH-susceptible Mycobacterium tuberculosis isolates obtained in two states in Brazil: São Paulo and Paraná. PCR-single-strand conformational polymorphism (PCR-SSCP) was evaluated for screening mutations in regions of prevalence, including codons 315 and 463 of katG, the regulatory region and codons 16 and 94 of inhA, kasA, and the oxyR-ahpC intergenic region. DNA sequencing of PCR amplicons was performed for all isolates with altered PCR-SSCP profiles. Mutations in katG were found in 83 (85.6%) of the 97 INH-resistant isolates, including mutations in codon 315 that occurred in 60 (61.9%) of the INH-resistant isolates and 23 previously unreported katG mutations. Mutations in the inhA promoter region occurred in 25 (25.8%) of the INH-resistant isolates; 6.2% of the isolates had inhA structural gene mutations, and 10.3% had mutations in the oxyR-ahpC intergenic region (one, nucleotide −48, previously unreported). Polymorphisms in the kasA gene occurred in both INH-resistant and INH-susceptible isolates. The most frequent polymorphism encoded a G269A substitution. Although KatG315 substitutions are predominant, novel mutations also appear to be responsible for INH resistance in the two states in Brazil. Since ca. 90.7% of the INH-resistant isolates had mutations identified by SSCP electrophoresis, this method may be a useful genotypic screen for INH resistance. PMID:15328099

  1. Multivariate optimization of formulation and process variables influencing physico-mechanical characteristics of site-specific release isoniazid pellets.

    PubMed

    Pund, Swati; Joshi, Amita; Vasu, Kamala; Nivsarkar, Manish; Shishoo, Chamanlal

    2010-03-30

    In the present study, isoniazid was formulated as site-specific release pellets with high drug loading (65%, w/w) using extrusion-spheronization followed by aqueous coating of Sureteric (35% weight gain). A statistical experimental strategy was developed to optimize simultaneously the effect of the two formulation variables and one process variable on the critical physico-mechanical properties of the core pellets of isoniazid. Amount of granulating fluid and amount of binder were selected as formulation variables and spheronization speed as a process variable. A 2(3) full factorial experimental design was employed for the present study. Pellets were characterized for physico-mechanical properties viz. usable yield, pellet size, pellips, porosity, abrasion resistance, mechanical crushing force, residual moisture and dissolution efficiency. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation and process variables active on the selected responses. A polynomial equation fitted to the data was used to predict the responses in the optimal region. The optimum formulation and process parameters were found to be 44.24% (w/w) of granulating fluid, 2.13% (w/w) of binder and spheronization speed of 1000rpm. Optimized formulation showed usable yield 84.95%, particle size 1021.32microm, pellips 0.945, porosity 46.11%, and abrasion resistance 0.485%. However, mechanical crushing force, residual moisture and dissolution efficiency were not significantly affected by the selected independent variables. These results demonstrate the importance of, amount of water, binder and spheronization speed, on physico-mechanical characteristics of the isoniazid core pellets with high drug loading. PMID:20035851

  2. Contribution of dfrA and inhA mutations to the detection of isoniazid-resistant Mycobacterium tuberculosis isolates.

    PubMed

    Ho, Yu Min; Sun, Yong-Jiang; Wong, Sin-Yew; Lee, Ann S G

    2009-09-01

    Screening of 127 isoniazid (INH)-resistant Mycobacterium tuberculosis isolates from Singapore for mutations within the dfrA and inhA genes revealed mutations in 0 and 5 (3.9%) isolates respectively, implying that mutations in dfrA do not contribute to the detection of INH-resistant M. tuberculosis and that mutations within inhA are rare. Thirty-seven (29%) of the 127 isolates had no mutations in any of the genes implicated in INH resistance (katG, kasA, and ndh; inhA and ahpC promoters), suggesting that there are new INH targets yet to be discovered. PMID:19581462

  3. Contribution of dfrA and inhA Mutations to the Detection of Isoniazid-Resistant Mycobacterium tuberculosis Isolates▿

    PubMed Central

    Ho, Yu Min; Sun, Yong-Jiang; Wong, Sin-Yew; Lee, Ann S. G.

    2009-01-01

    Screening of 127 isoniazid (INH)-resistant Mycobacterium tuberculosis isolates from Singapore for mutations within the dfrA and inhA genes revealed mutations in 0 and 5 (3.9%) isolates respectively, implying that mutations in dfrA do not contribute to the detection of INH-resistant M. tuberculosis and that mutations within inhA are rare. Thirty-seven (29%) of the 127 isolates had no mutations in any of the genes implicated in INH resistance (katG, kasA, and ndh; inhA and ahpC promoters), suggesting that there are new INH targets yet to be discovered. PMID:19581462

  4. Rationale and Baseline Characteristics of PREVENT: A Second-Generation Intervention Trial in Subjects At-Risk (Prodromal) of Developing First-Episode Psychosis Evaluating Cognitive Behavior Therapy, Aripiprazole, and Placebo for the Prevention of Psychosis

    PubMed Central

    Bechdolf, Andreas; Müller, Hendrik; Stützer, Hartmut; Wagner, Michael; Maier, Wolfgang; Lautenschlager, Marion; Heinz, Andreas; de Millas, Walter; Janssen, Birgit; Gaebel, Wolfgang; Michel, Tanja Maria; Schneider, Frank; Lambert, Martin; Naber, Dieter; Brüne, Martin; Krüger-Özgürdal, Seza; Wobrock, Thomas; Riedel, Michael; Klosterkötter, Joachim

    2011-01-01

    Antipsychotics, cognitive behavioral therapy (CBT), and omega-3-fatty acids have been found superior to control conditions as regards prevention of psychosis in people at-risk of first-episode psychosis. However, no large-scale trial evaluating the differential efficacy of CBT and antipsychotics has been performed yet. In PREVENT, we evaluate CBT, aripiprazole, and clinical management (CM) as well as placebo and CM for the prevention of psychosis in a randomized, double-blind, placebo-controlled trial with regard to the antipsychotic intervention and a randomized controlled trial with regard to the CBT intervention with blinded ratings. The hypotheses are first that CBT and aripiprazole and CM are superior to placebo and CM and second that CBT is not inferior to aripiprazole and CM combined. The primary outcome is transition to psychosis. By November 2010, 156 patients were recruited into the trial. The subjects were substantially functionally compromised (Social and Occupational Functioning Assessment Scale mean score 52.5) and 78.3% presented with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition axis I comorbid diagnosis. Prior to randomization, 51.5% of the participants preferred to be randomized into the CBT arm, whereas only 12.9% preferred pharmacological treatment. First, assessments of audiotaped treatment sessions confirmed the application of CBT-specific skills in the CBT condition and the absence of those in CM. The overall quality rating of the CBT techniques applied in the CBT condition was good. When the final results of the trial are available, PREVENT will substantially expand the current limited evidence base for best clinical practice in people at-risk (prodromal) of first-episode psychosis. PMID:21860040

  5. Psycho-Pedagogical Interventions in the Prevention and the Therapy of Learning Difficulties in the Field of Mathematics

    ERIC Educational Resources Information Center

    Anca, Maria; Hategan, Carolina

    2009-01-01

    In the given study dyscalculia is approached in the context of learning difficulties, but also in relation with damaged psychic processes and functions. The practical part of the study describes intervention models from the perspective of dyscalculia prevention and therapymaterialized in personalized intervention programs.

  6. Multi-constituent cardiovascular pills (MCCP)--challenges and promises of population-based prophylactic drug therapy for prevention of heart attack.

    PubMed

    Jamieson, Michael J; Naghavi, Morteza

    2007-01-01

    Risk factors for atherosclerotic cardiovascular disease (CVD) are highly co-prevalent but poorly identified and treated. The Screening for Heart Attack Prevention and Education (SHAPE) Task Force from the Association for Eradication of Heart Attack (AEHA) has recently proposed a new strategy that recommends screening for subclinical atherosclerosis and implementing aggressive treatment of "vulnerable patients". The Task Force has also envisioned future developments that may shift mass screening strategies to mass prophylactic therapy. The "Polypill" concept, introduced by Wald and Law suggests a combination of statin, low-dose antihypertensives, aspirin and folic acid, in a single pill, taken prophylactically by high risk population can cut CVD event rates by as much as 80%. In this communication, we review the challenges and promises of such a strategy. "Polypill" is but one of an astronomical number of possible multiconstituent pills (MCCP). Attractive as the MCCP concept is, it lacks evidence from randomized controlled trials, and begs numerous questions about the credibility of the concept, the design and synthesis of such complex pills, pharmacokinetics, pharmacodynamics, bioequivalence, "class" vs. unique properties, interactions, evidence of clinical efficacy and safety, regulatory approval, post-marketing surveillance, prescription vs. over-the-counter use, responsibility for initiating and monitoring therapy, patient education, counterfeiting and importation, reimbursement, advertisement, patent protection, commercial viability, etc. If these issues are favorably addressed, MCCP stand to dramatically change the manner in which CVD is prevented particularly in developing societies. Notwithstanding, assuming low commercial interests, realizing the promises of MCCP will demand serious attention from national public health policymakers. The clinical and regulatory implications of population-based secondary prevention (which rely on a different evidence base

  7. Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice

    PubMed Central

    Shih, Yao-Ming; Sun, Cheng-Pu; Chou, Hui-Hsien; Wu, Tzu-Hui; Chen, Chun-Chi; Wu, Ping-Yi; Enya Chen, Yu-Chen; Bissig, Karl-Dimiter; Tao, Mi-Hua

    2015-01-01

    Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the “PICKY” software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients. PMID:26482836

  8. Integrative approach in prevention and therapy of basal cellular carcinoma by association of three actives loaded into lipid nanocarriers.

    PubMed

    Badea, Gabriela; Lacatusu, Ioana; Ott, Cristina; Badea, Nicoleta; Grafu, Iulia; Meghea, Aurelia

    2015-06-01

    Basal cell carcinoma (BCC) is one of the commonest malignancies occurred on sun-exposed skin, mainly by UV-B radiation, of lighter-skinned individuals. The aim of the present study was to develop advanced drug delivery formulations used in BCC therapy that overcomes chemotherapy-induced side-effects of skin photosensitivity by an integrative approach of nanoencapsulation in conjunction with combination therapy that uses chemotherapeutic, chemoprotective and sunscreen agents. The combination of anticancer drug together with sunscreen agent is very useful in therapy, especially for individuals who are more exposed to the sun without using a sunscreen. Nanostructured lipid carriers (NLCs) employed as drug delivery systems were co-loaded with 5-fluorouracil (5-FU), a hydrophilic chemotherapeutic drug, and ethylhexyl salicylate (EHS), a lipophilic UV-B sunscreen agent. The NLCs were developed using bioactive squalene (50.8% w/w) from amaranth seed oil as chemoprotective agent. By varying the concentrations of 5-FU and EHS, the co-loaded NLCs presented particle sizes of about 100nm, acceptable physical stability with values smaller than -25mV and appropriate entrapment efficiency that reaches values over 65% for both types of drugs. The UV-B blocking ability of EHS loaded into NLCs were influenced by the concentration of 5-FU. The amaranth oil offered a capacity of 70% in scavenging the free radicals. In vitro drug release showed that NLCs presented sustained release of 5-FU that followed the Fick's law of diffusion. PMID:25828466

  9. Preventive fluid and dietary therapy for urolithiasis: An appraisal of strength, controversies and lacunae of current literature.

    PubMed

    Agarwal, Mayank Mohan; Singh, Shwaran K; Mavuduru, Ravimohan; Mandal, Arup K

    2011-07-01

    Regulation of fluid and dietary intake habits is essential in comprehensive preventive management of urolithiasis. However, despite large body of epidemiological database, there is dearth of good quality prospective interventional studies in this regard. Often there is conflict in pathophysiological basis and actual clinical outcome. We describe conflicts, controversies and lacunae in current literature in fluid and dietary modifications in prevention of urolithiasis. Adequate fluid intake is the most important conservative strategy in urolithiasis-prevention; its positive effects are seen even at low volumes. Of the citrus, orange provides the most favorable pH changes in the urine, equivalent to therapeutic alkaline citrates. Despite being richest source of citrate, lemon does not increase pH significant due to its acidic nature. Fructose, animal proteins and fats are implicated in contributing to obesity, which is an established risk factor for urolithiasis. Fructose and proteins also contribute to lithogenecity of urine directly. Sodium restriction is commonly advised since natriuresis is associated with calciuresis. Calcium restriction is not advisable for urolithiasis prevention. Adequate calcium intake is ben