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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

    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

  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 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

  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. 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

  16. 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.

  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 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

  5. 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

  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. 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

  13. 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

  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 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

  8. 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

  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. 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…

  1. 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.

  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. 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

  8. 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.

  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. 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

  1. 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

  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. [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

  13. 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

  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. 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

  2. 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

  3. 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

  4. 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

  5. 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

  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. 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

  1. 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

  2. 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

  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. 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

  5. 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

  6. 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

  7. 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

  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. 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

  11. 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

  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

    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

  18. 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

  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. 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

  5. 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

  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. [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

  8. 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

  9. 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

  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. 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

  15. 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

  16. 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

  17. 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

  18. 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

  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. 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

  2. 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

  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. 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.

  8. 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

  9. 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

  10. 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

  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. 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

  2. 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

  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. 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

  6. 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

  7. 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

  8. 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

  9. 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

  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. 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

  13. 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

  14. 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

  15. 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

  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. 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

  5. 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

  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. 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…

  8. 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

  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