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Sample records for bcg live intravesical

  1. Investigation of granulomatous prostatitis incidence following intravesical BCG therapy

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    Balasar, Mehmet; Doğan, Metin; Kandemir, Abdulkadir; Taskapu, Hakan Hakki; Cicekci, Faruk; Toy, Hatice; Gurbuz, Recai

    2014-01-01

    In the present manuscript, we studied the incidence of granulomatous prostatitis in the prostatectomy specimen of the patients who underwent transurethral resection of the prostate (TURP) after superficial bladder cancer treatment with intravesical Bacillus Calmette-Guerin (BCG) and were diagnosed with benign prostate hyperplasia (BPH). The clinical data and histopathological specimen records of 472 patients who underwent TUR-P due to BPH diagnosis, obtained over a period of 6 years in the urology department of Private Konya Hospital, Konya, Turkey, were studied retrospectively. The cases were divided into two groups as (Group I) who did not undergo any treatment and as (Group II) who underwent BCG treatment. The frequency and the clinical course of the cases with granulomatous prostatitis were studied histopathologically. There were in total 472 patients who underwent TUR-P. Out of the 459 patients who did not undergo BCG treatment (Group I), the histopathological specimen records of 262 (57%) was BPH, of 197 (43%) BPH + chronic prostatitis. Of the second group, 13 cases underwent intravesical BCG treatment before surgical intervention due to superficial bladder CA diagnosis. In this group 4 of the cases were diagnosed as (30%) BPH, 9 as (70%) chronic prostatitis + BPH. 6 out of the 9 chronic prostatitis cases were chronic prostatitis, 2 caseous granulomatous prostatitis, 1 non-caseous granulomatous prostatitis. Granulomatous prostatitis cases should require no specific therapy. Conclusion: In patients with obstruction complaints following intravesical BCG treatment, granulomatous prostatitis should also be considered and treatment plans should be made accordingly. PMID:25035779

  2. Prosthetic Joint Infection due to Mycobacterium bovis after Intravesical Instillation of Bacillus Calmette-Guerin (BCG

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    Eric Gomez

    2009-01-01

    Full Text Available Intravesical instillation of Bacillus Calmette-Guerin (BCG is a treatment to prevent recurrence of superficial urothelial bladder carcinoma. Complications after bladder instillation of BCG have been reported including locally invasive and systemic infections due to dissemination of Mycobacterium bovis from the bladder. We present an uncommon case and literature review of prosthetic joint infection due to M. bovis after intravesical BCG treatment of bladder cancer.

  3. Novel intravesical therapies for non-muscle-invasive bladder cancer refractory to BCG.

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    Barlow, Lamont J; Seager, Catherine M; Benson, Mitchell C; McKiernan, James M

    2010-01-01

    The definitive treatment for patients with non-muscle-invasive bladder cancer (NMIBC) who fail to respond to intravesical BCG is cystectomy. When a patient is deemed BCG-refractory and cannot or will not undergo cystectomy, alternative intravesical therapy may be the most effective way to minimize recurrence and progression. A number of immunotherapeutic and chemotherapeutic agents have been given intravesically over the years, and several recently and currently investigated novel agents appear to be particularly promising for the management of BCG-refractory NMIBC. The most effective treatments in the future will likely utilize targeted therapies based on the underlying genetic mutations associated with each individual diagnosis of NMIBC.

  4. BCG pneumonitis with a miliary radiological pattern complicating intravesical BCG immunotherapy

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    Evangelia Fouka

    2010-01-01

    Full Text Available SUMMARY. The case is described of a 42 year-old male who presented with fever, haematuria, hypoxaemia, impaired liver function and a miliary pattern on chest X-ray while receiving intravesical BCG treatment for superficial bladder cancer. Initiation of antituberculous therapy resulted in rapid amelioration of the symptoms and the X-ray findings, and the patient left hospital in a good general state of health. Although M. bovis was not isolated from samples of sputum, bronchioalveolar lavage fluid (BALF or bronchial biopsy tissue, the prompt response to antituberculous therapy suggests an infectious aetiology due to microbial dissemination. Pneumon 2010, 23(4:388-391.

  5. Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

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    S. Lukacs

    2013-01-01

    Full Text Available Intravesical Bacilli Calmette-Guérin (BCG immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin, he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

  6. Role of fibronectin in intravesical BCG therapy for superficial bladder cancer.

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    Ratliff, T L; Kavoussi, L R; Catalona, W J

    1988-02-01

    Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both for prophylaxis and treatment of superficial bladder cancer. In order to identify the progression of events that result in BCG-mediated antitumor activity, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix proteins to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified fibronectin (FN) but not to other purified proteins including laminin, collagen or fibrinogen. The attachment of BCG to purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine.

  7. Discriminators of mouse bladder response to intravesical Bacillus Calmette-Guerin (BCG

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    Centola Michael

    2007-05-01

    Full Text Available Abstract Background Intravesical Bacillus Calmette-Guerin (BCG is an effective treatment for bladder superficial carcinoma and it is being tested in interstitial cystitis patients, but its precise mechanism of action remains poorly understood. It is not clear whether BCG induces the release of a unique set of cytokines apart from its pro-inflammatory effects. Therefore, we quantified bladder inflammatory responses and alterations in urinary cytokine protein induced by intravesical BCG and compared the results to non-specific pro-inflammatory stimuli (LPS and TNF-α. We went further to determine whether BCG treatment alters cytokine gene expression in the urinary bladder. Methods C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Morphometric analyses were conducted in bladders isolated from all groups and urine was collected for multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation combined with real-time polymerase chain reaction assay (CHIP/Q-PCR was used to test whether intravesical BCG would alter bladder cytokine gene expression. Results Acute BCG instillation induced edema which was progressively replaced by an inflammatory infiltrate, composed primarily of neutrophils, in response to weekly administrations. Our morphological analysis suggests that these polymorphonuclear neutrophils are of prime importance for the bladder responses to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-α treatment but the major difference observed was the unique granuloma formation in response to BCG. Among the cytokines measured, this study highlighted the importance of IL-1β, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and Rantes as discriminators between generalized inflammation and BCG-specific inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL-17B, IL-17RA, and

  8. Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer.

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    Kathrin Buffen

    2014-10-01

    Full Text Available The anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens. It has been recently proposed that the non-specific effects of BCG are mediated through epigenetic reprogramming of monocytes, a process called trained immunity. In the present study we demonstrate that autophagy contributes to trained immunity induced by BCG. Pharmacologic inhibition of autophagy blocked trained immunity induced in vitro by stimuli such as β-glucans or BCG. Single nucleotide polymorphisms (SNPs in the autophagy genes ATG2B (rs3759601 and ATG5 (rs2245214 influenced both the in vitro and in vivo training effect of BCG upon restimulation with unrelated bacterial or fungal stimuli. Furthermore, pharmacologic or genetic inhibition of autophagy blocked epigenetic reprogramming of monocytes at the level of H3K4 trimethylation. Finally, we demonstrate that rs3759601 in ATG2B correlates with progression and recurrence of bladder cancer after BCG intravesical instillation therapy. These findings identify a key role of autophagy for the nonspecific protective effects of BCG.

  9. [Generalized BCG infection after intravesical instillations of Calmette-Guerin bacillus].

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    de Saint Martin, L; Boiron, C; Poveda, J D; Herreman, G

    1993-10-02

    BCG has been disappointing as immunotherapy of numerous cancers, but it has been clinically successful in the intravesical treatment of bladder carcinomas sparing the muscle coat; it has indeed become the reference treatment for this type of cancer. However, complications are repeatedly reported, including generalized BCGitis. We report such a case with positive BCG culture. From the cases already published there emerges a homogeneous and often subacute clinical presentation suggestive of an ordinary pathogen. Bacteriology is not very helpful, even when recent techniques are used, and therefore the diagnosis rests on the context and, when samples are taken, on suggestive histological findings. To discuss the physiopathology of BCGitis--generalized immune reaction or multifocal BCG proliferation--is not useless since treatment depends on it. It is probable that these 2 mechanisms working together can be incriminated justifying the prescription of both antibiotics and corticosteroids. When this is done, the prognosis seems to be favourable in most patients. Yet a strict respect of contra-indications and a very careful subsequent radiotherapy should reduce the risks.

  10. Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG, LPS, and TNF-α

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    Dozmorov Igor

    2008-02-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression in the bladder target organ beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following chronic intravesical BCG therapy and to compare the results to non-specific pro inflammatory stimuli (LPS and TNF-α. For this purpose, C57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-α. Seven days after the last instillation, the urothelium along with the submucosa was removed from detrusor muscle and the RNA was extracted from both layers for cDNA array experiments. Microarray results were normalized by a robust regression analysis and only genes with an expression above a conditional threshold of 0.001 (3SD above background were selected for analysis. Next, genes presenting a 3-fold ratio in regard to the control group were entered in Ingenuity Pathway Analysis (IPA for a comparative analysis in order to determine genes specifically regulated by BCG, TNF-α, and LPS. In addition, the transcriptome was precipitated with an antibody against RNA polymerase II and real-time polymerase chain reaction assay (Q-PCR was used to confirm some of the BCG-specific transcripts. Results Molecular networks of treatment-specific genes generated several hypotheses regarding the mode of action of BCG. BCG-specific genes involved small GTPases and BCG-specific networks overlapped with the following canonical signaling pathways: axonal guidance, B cell receptor, aryl hydrocarbon receptor, IL-6, PPAR, Wnt/β-catenin, and cAMP. In addition, a specific detrusor network expressed a high degree of overlap with the

  11. Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer

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    Buffen, Kathrin; Oosting, Marije; Quintin, Jessica; Ng, Aylwin; Kleinnijenhuis, Johanneke; Magadi Gopalaiah, Vinod Kumar; van de Vosse, Esther; Wijmenga, Cisca; van Crevel, Reinout; Oosterwijk, Egbert; Grotenhuis, Anne J.; Vermeulen, Sita H.; Kiemeney, Lambertus A.; van de Veerdonk, Frank L.; Chamilos, Georgios; Xavier, Ramnik J.; van der Meer, Jos W. M.; Netea, Mihai G.; Joosten, Leo A. B.

    2014-01-01

    The anti-tuberculosis-vaccine Bacillus Calmette-Guerin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malignancy and against infections with unrelated pathogens

  12. Mycotic aneurysm of the popliteal artery as a complication of intravesical BCG therapy for superficial bladder cancer. Case report and literature review.

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    Witjes, J.A.; Vriesema, J.L.J.; Brinkman, K.; Bootsma, G.P.; Barentsz, J.O.

    2003-01-01

    A 67-year-old man was treated with maintenance intravesical BCG for superficial bladder cancer. As a culture-proven complication of this therapy, he developed general malaise, high fever, granulomatous hepatitis and a mycotic aneurysm in his left knee. All complications were treated successfully wit

  13. BCG-THERAPIE ET CANCER DE LA VESSIE : LA CARACTERISATION ET LA MODELISATION DE LA REPONSE IMMUNE AU BCG DANS LA VESSIE REVELENT DES STRATEGIES POUR L'AMELIORATION DE LA REPONSE ANTI-TUMORALE

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    Biot, Claire

    2012-01-01

    Intravesical instillation of bacillus Calmette-Guérin (BCG) for non-muscle invasive bladder cancer is one of the few examples of successful immunotherapy in the clinic, with 50-70% treatment response. While success of therapy is known to rely on repeated instillations of live BCG, administered as adjuvant therapy shortly after tumor resection, its precise mechanisms of action remain unclear. I established an experimental mouse model to study the dynamics of the immune response following intra...

  14. Oral vaccination with lipid-formulated BCG induces a long-lived, multifunctional CD4(+ T cell memory immune response.

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    Lindsay R Ancelet

    Full Text Available Oral delivery of BCG in a lipid formulation (Liporale™-BCG targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4(+ T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4(+ T cell response, evident by the detection of effector CD4(+ T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4(+ T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4(+ T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4(+ T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines.

  15. Emerging intravesical therapies for management of nonmuscle invasive bladder cancer

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    Jeffrey J Tomaszewski

    2010-05-01

    Full Text Available Jeffrey J Tomaszewski, Marc C SmaldoneDepartment of Urology, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Transitional cell carcinoma (TCC is the second most common urologic malignancy, and 70% of patients present with superficial or nonmuscle invasive bladder cancer (NMIBC. Intravesical bacillus Calmette-Guerin (BCG is the most effective agent for preventing disease recurrence, and the only therapy able to inhibit disease progression. However, recurrence rates as high as 30% and significant local and systemic toxicity have led to increased interest in alternative intravesical therapies. In patients refractory or intolerant to BCG, BCG-interferon α2b, gemcitabine, and anthracyclines (doxorubicin, epirubicin, valrubicin have demonstrated durable clinical responses. Phase I trials investigating alternative cytotoxic agents, such as apaziquone, taxanes (docetaxel, paclitaxel, and suramin are reporting promising data. Novel immunomodulating agents have demonstrated promise as efficacious alternatives in patients refractory to BCG. Optimization of existing chemotherapeutic regimens using hyperthermia, photodynamic therapy, magnetically-targeted carriers, and liposomes remains an area of active investigation. Despite enthusiasm for new intravesical agents, radical cystectomy remains the treatment of choice for patients with NMIBC who have failed intravesical therapy and selected patients with naïve T1 tumors and aggressive features. This report provides a comprehensive review of contemporary intravesical therapy for NMIBC and refractory NMIBC, with an emphasis on emerging agents and novel treatment modalities.Keywords: transitional cell carcinoma, nonmuscle, invasive, intravesical therapy, BCG

  16. BCG induced granulomatous prostatitis ; a case report

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    Moon, Min Hoan; Seong, Chang Kyu; Lee, Kyoung Ho; Kim, Seung Hyup [College of Medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of)

    2000-04-01

    Granulomatous prostatitis was relatively uncommon until the introduction of intravesical BCG for the treament of bladder cancer. Since that time, there has been an increase in the number of cases of granulomatous prostatitis, but the domestic literature contains no report. We recently encountered a classic case of BCG induced granulomatous prostatitis and describe this case, including its radiologic findings. (author)=20.

  17. Nanoparticulation of BCG-CWS for application to bladder cancer therapy.

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    Nakamura, Takashi; Fukiage, Masafumi; Higuchi, Megumi; Nakaya, Akihiro; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Ito, Toshihiro; Hosokawa, Hiroyuki; Nakayama, Toshinori; Harashima, Hideyoshi

    2014-02-28

    The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor (MBT-2) cells in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.

  18. Intravesical electro-osmotic administration of mitomycin C.

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    Di Stasi, Savino M; Verri, Cristian; Celestino, Francesco; De Carlo, Francesco; Pagliarulo, Vincenzo

    2016-10-04

    Bladder cancer is very common and most cases are diagnosed as nonmuscle invasive disease, which is characterized by its propensity to recur and progress. Intravesical therapy is used to delay recurrence and progression, while cystectomy is reserved for patients who are refractory to transurethral resection and intravesical therapy. There is an increasing interest in methods to enhance the delivery of intravesical chemotherapeutic agents to improve efficacy. In vitro and in vivo studies demonstrated that electro-osmosis of mitomycin C (MMC) is more effective in delivering this drug into the urothelium, lamina propria, and superficial muscle layers of the bladder wall than is passive transport. Higher MMC tissue concentrations might have a clinical impact in the treatment of nonmuscle invasive bladder cancer (NMIBC). In randomized trials, intravesical electro-osmotic MMC was associated with superior response rate in high-risk NMIBC cancer, compared with passive diffusion MMC transport. New strategies such as intravesical Bacillus Calmette-Guerin (BCG) combined with electro-osmotic MMC as well as intravesical pre-operative electro-osmotic MMC provided promising results in terms of higher remission rates and longer remission times.Device-assisted intravesical chemotherapy may be a useful ancillary procedure in the treatment of NMIBC. Its evaluation must be planned with respect to the technical functioning of equipment and their use for a clear purpose to avoid the financial and human costs associated with incorrect therapies.

  19. Bladder Cancer Immunotherapy: BCG and Beyond

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    Eric J. Askeland

    2012-01-01

    Full Text Available Mycobacterium bovis bacillus Calmette-Guérin (BCG has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1 immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10.

  20. Bladder Cancer Immunotherapy: BCG and Beyond.

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    Askeland, Eric J; Newton, Mark R; O'Donnell, Michael A; Luo, Yi

    2012-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) has become the predominant conservative treatment for nonmuscle invasive bladder cancer. Its mechanism of action continues to be defined but has been shown to involve a T helper type 1 (Th1) immunomodulatory response. While BCG treatment is the current standard of care, a significant proportion of patients fails or do not tolerate treatment. Therefore, many efforts have been made to identify other intravesical and immunomodulating therapeutics to use alone or in conjunction with BCG. This paper reviews the progress of basic science and clinical experience with several immunotherapeutic agents including IFN-α, IL-2, IL-12, and IL-10.

  1. Urinary fibronectin levels in patients treated with intravesical bacillus Calmette-Guérin for superficial bladder cancer.

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    Danişman, A; Bulut, K; Kukul, E; Ozen, I; Sevük, M

    2000-01-01

    Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p 0. 05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy.

  2. BCG LYMPHADENITIS

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    Vijayakumar

    2014-08-01

    Full Text Available Background: The World Health Organization (WHO has recommended Bacillus Calmette-Guerin (BCG vaccination as a part of the global expanded program for immunization. Although the BCG vaccine is usually a safe vaccine, a number of complications with lymphadenitis being the most common complication, can occur. AIM: The aim of the present study was to evaluate the clinical presentation and the histomorphological features of BCG adenitis in children. RESULTS: A total of 60 patients with BCG lymphadenitis presented between June 2010 and December 2013. The most common age of presentation was 3 months. In the majority (50 of the cases, the lymphadenitis involved ipsilateral left axillary nodes. Other sites of involvement included the left supraclavicular lymph nodes in 5 (8.3% patients, and both the left axillary and supraclavicular lymph nodes were involved in 5 cases (8.3%. All the patients had history of BCG vaccination prior to the onset of lymphadenitis. CONCLUSION: Diagnosis of BCG lymphadenitis is clinical. Parental education and awareness among paramedical personnel, including general practitioners, is essential so that prompt recognition and management of BCG adenitis can be ensured.

  3. Re: Sequential Combination of Mitomycin C Plus Bacillus Calmette-Guerin (BCG Is More Effective but More Toxic Than BCG Alone in Patients with Non–Muscle-Invasive Bladder Cancer in Intermediate-and High-Risk Patients: Final Outcome of CUETO 93009, A Randomized Prospective Trial

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    Eduardo Solsona

    2015-03-01

    Full Text Available EAU Guideline recommendation in non-muscle invasive bladder cancer (NMIBC is that patients who have intermediate or high risk for recurrence and intermediate risk for progression should receive early single dose intravesical chemotherapy followed by maintenance or a minimum of 1 year of BCG. Intravesical Mitomycin C (MMC plus Bacillus Calmette-Guerin (BCG treatment schemes were studied. However, MMC+BCG were not found to be superior to BCG alone (1,2. In the present study, authors conducted a randomized prospective trial on combination of MMC+BCG (n=192 or BCG alone (n=190. EORTC definition of NMIBC intermediate and high-risk patientswere included in the study. Unlike previous reported studies, disease-free interval at 5 years for MMC+BCG was found to be significantly better (HR: 0.57; 95% CI, 0.39 -0,83; p=0.003 than BCG alone. In an interim analysis, excessive toxicity was observed in MMC+BCG than BCG alone group. Consequently MMC dose was reduced from 30 mg to 10 mg. However, toxicity remained higher in the MMC+BCG group. Especially in EORTC highrisk NMIBCs, MMC+BCG is better than BCG alone, but with worse toxicity. In conclusion, despite some limitations, the results of Solsona et al. provided a new potential bladder-sparing management alternative, but it has higher toxicity. Additional studies are required to confirm these findings and availability of a less toxic intravesical chemotherapeutic agent.

  4. [Intravesical therapy with mitomycin through electromotive drug administration].

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    Verri, Cristian; Liberati, Emanuele; Celestino, Francesco; De Carlo, Francesco; Torelli, Fiammetta; Di Stasi, Savino M

    2013-01-01

    In the management of non-muscle invasive bladder cancer (NMIBC), high-level evidence supports the widespread practice of intravesical therapy with mitomycin-C (MMC). Randomized trials showed a significant reduction in short-term recurrence compared with transurethral resection of bladder tumor (TURBT) alone, but little effect on long-term and no impact at all in preventing progression. Electromotive drug administration (EMDA®) offers a means of controlling and enhancing the tissue transport of certain drugs, in order to increase their efficacy. In both laboratory and clinical studies, intravesical electromotive drug administration (EMDA) increases MMC bladder uptake, resulting in an improved clinical efficacy in NMIBC without systemic side effects. New frameworks for treatment of NMIBC - e.g., sequential intravesical BCG and EMDA/MMC, as well as intravesical EMDA/MMC immediately before TURBT - have provided promising preliminary results with higher remission rates and longer remission times, and they are a priority to minimise the costs of disease management. These findings suggest EMDA-enhanced MMC efficacy against urothelial cancer could be a major therapeutic breakthrough in the treatment of NMIBC.

  5. Bladder Contracture – A Rare and Serious Side Effect of Intravesical Bacillus Calmette-Guérin Therapy

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    Cindy Garcia

    2016-01-01

    Full Text Available Instillation of intravesical bacillus Calmette-Guérin (BCG is an effective treatment for non-muscle invasive bladder cancer (NMIBC. The high incidence of side effects may limit its tolerability in patients. Local side effects including cystitis and hematuria are common but generally self-limiting. Bladder contractures are a rare but serious consequence of BCG treatment. In this case, an 82 year-old male developed BCG reactivation and subsequent bladder contractures following transurethral resection of the prostate (TURP three years post-BCG. To our knowledge, this is the first reported case of BCG reactivation post-TURP leading to the rare but serious effect of bladder contractures.

  6. Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

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    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2010-02-01

    Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either.

  7. BCG and the treatment of superficial bladder cancer.

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    Moss, J T; Kadmon, D

    1991-12-01

    In this report, we review the evolution of bacillus Calmette-Guérin (BCG) immunotherapy as a legitimate form of treatment in superficial, nonmuscle-invasive bladder cancer. In the US, an estimated 45,000 new cases of bladder cancer are diagnosed each year and the annual death rate approaches 11,000. Approximately 70 percent of these cancers are superficial at the time of initial presentation. The treatment of superficial bladder cancer has three objectives: (1) eradication of existing disease, (2) prophylaxis against tumor recurrence, and (3) prevention of tumor progression (either muscular invasion, metastatic spread, or both). Cystectomy generally is reserved for muscle-invasive disease. Transurethral resection of the bladder tumor is the preferred initial therapy. Intravesical instillations of various chemotherapeutic agents following transurethral resection have been extensively investigated. Some of the common agents used include thiotepa, mitomycin, and doxorubicin. Despite such treatment efforts, however, over 40 percent of patients with superficial bladder cancer experience a recurrence of their tumor within three years. Approximately half of these recurrences either present as less-well-differentiated tumors or have already penetrated into the bladder musculature, metastasized, or both. Since Morales et al. first introduced intravesical BCG vaccine for prophylaxis as well as for treatment of superficial bladder tumors in 1976, support has grown rapidly for its use as an alternative to chemotherapy. When used with prophylactic intent following transurethral resection, recurrence rates are lower than those achieved with other agents. In addition, BCG is emerging as the consensus drug of choice for treating carcinoma in situ of the bladder. The mechanisms by which BCG exerts its antitumor activity remain largely unknown. BCG is thought to stimulate a localized, nonspecific inflammatory response that leads to subsequent shedding of tumor cells. A large body

  8. Intravesical Bacillus Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guérin.

    Science.gov (United States)

    Ratliff, T L; Palmer, J O; McGarr, J A; Brown, E J

    1987-04-01

    Intravesical Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial bladder cancer. Although the mechanisms by which BCG inhibits tumor growth are not known, previous studies have shown that systemic immunization to BCG and the local expression of the immune response in the bladder are associated with a favorable response to BCG therapy. We have investigated the conditions required for the initiation of an immunological response after the intravesical instillation of BCG. Initial histological studies showed that BCG attached to the bladder wall only in areas where the urothelium was damaged by electrocautery and suggested that attachment was associated with the fibrin clot. Quantitative studies verified the histological observations. Minimal BCG attachment (mean less than 10(2) colony forming units) was observed in normal bladders in contrast with a mean of 1.42 X 10(4) colony forming units/bladder in bladders damaged by electrocautery (10 separate experiments). BCG attachment to the bladder wall was durable since organisms were observed in bladders 48 h after instillation. To investigate the proteins to which BCG attached, we tested the binding of BCG to extracellular matrix and inflammatory proteins which comprise a significant portion of the fibrin clot. BCG bound in vitro to coverslips coated in vivo with extracellular matrix proteins but did not bind to control albumin-coated coverslips. BCG also bound to coverslips coated with purified plasma fibronectin but not to coverslips coated with other purified extracellular matrix proteins including laminin, fibrinogen, and type IV collagen. BCG attachment to coverslips coated with either extracellular matrix proteins or purified fibronectin was inhibited by antibodies specific for fibronectin. Moreover, BCG attachment to cauterized bladders in vivo was inhibited by antifibronectin antibodies. These results demonstrate that fibronectin mediates the attachment of BCG

  9. A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Yuan, Xuefeng; Teng, Xindong; Jing, Yukai; Ma, Jilei; Tian, Maopeng; Yu, Qi; Zhou, Lei; Wang, Ruibo; Wang, Weihua; Li, Li; Fan, Xionglin

    2015-12-01

    Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4(+)Th1-biased immune responses and specific polyfunctional CD4(+)T cells but also augmented the CD8(+) CTL effects against Ag85B in vivo. In particular, higher levels of CD4(+) TEM and CD8(+) TCM cells, dominated by IL2(+) CD4(+) and CD8(+) TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG.

  10. Active Mycobacterium Infection Due to Intramuscular BCG Administration Following Multi-Steps Medication Errors

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    MohammadReza Rafati

    2015-10-01

    Full Text Available Bacillus Calmette-Guérin (BCG is indicated for treatment of primary or relapsing flat urothelial cell carcinoma in situ (CIS of the urinary bladder. Disseminated infectious complications occasionally occur due to BCG as a vaccine and intravesical therapy.  Intramuscular (IM or Intravenous (IV administrations of BCG are rare medication errors which are more probable to produce systemic infections. This report presents 13 years old case that several steps medication errors occurred consequently from physician handwriting, pharmacy dispensing, nursing administration and patient family. The physician wrote βHCG instead of HCG in the prescription. βHCG was read as BCG by the pharmacy staff and 6 vials of intravesical BCG were administered IM twice a week for 3 consecutive weeks. The patient experienced fever and chills after each injection, but he was admitted 2 months after first IM administration of BCG with fever and pancytopenia. Unfortunately four month after using drug, during second admission duo to cellulitis at the sites of BCG injection the physicians diagnosed the medication error. Using handwritten prescription and inappropriate abbreviations, spending inadequate time for taking a brief medical history in pharmacy, lack of verifying name, dose and wrote before medication administration and lack of considering medication error as an important differential diagnosis had roles to occur this multi-steps medication error.

  11. Giant intravesical calculus during pregnancy.

    Science.gov (United States)

    Escobar-del Barco, Laura; Rodriguez-Colorado, Silvia; Dueñas-Garcia, Omar Felipe; Avilez-Cevasco, Juan Carlos

    2008-10-01

    Urolithiasis is commonly found during pregnancy; but the presence of a giant vesical calculus during pregnancy is a very rare entity, associated with several potential obstetric complications. A 25-year-old primigravida at 25 weeks of gestational age was referred to our tertiary care unit because she presented a giant hyperechoic intravesical mass and inability to pass urine with suprapubic pain since 2 days. An open cystolithotomy revealed a huge intravesical calculus. The patient continued with her pregnancy until full term without adverse perinatal outcomes.

  12. Changes observed in multiparametric prostate magnetic resonance imaging characteristics correlate with histopathological development of chronic granulomatous prostatitis after intravesical Bacillus Calmette-Guerin therapy.

    Science.gov (United States)

    Logan, Jennifer K; Walton-Diaz, Annerleim; Rais-Bahrami, Soroush; Merino, Maria J; Turkbey, Baris; Choyke, Peter L; Pinto, Peter A

    2014-01-01

    Administration of Bacillus Calmette-Guerin (BCG) has been shown to cause granulomatous prostatitis, a rare inflammatory process that can be mistaken for prostate cancer. We present a case of a 78-year-old man on active surveillance for prostate cancer with a subsequent diagnosis of high-grade urothelial carcinoma. After intravesical BCG therapy, he developed chronic granulomatous prostatitis. We present serial magnetic resonance imaging and biopsy data demonstrating the time interval between BCG administration and the manifestation of chronic granulomatous prostatitis.

  13. Tuberculous Spondylitis following Intravesical Bacillus Calmette-Guerin for Bladder Cancer

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    Masashi Miyazaki

    2016-01-01

    Full Text Available We present a rare case of tuberculous spondylitis following intravesical Bacillus Calmette-Guerin (BCG therapy for bladder cancer. An 82-year-old man presented with low back pain. Past medical history revealed bladder cancer diagnosed and treated 16 months previously by intravesical BCG. Magnetic resonance imaging of the thoracic spine showed destruction of the T5 and T6 vertebrae and an epidural soft tissue mass with anterior dural sac compression. Due to the progression of vertebral destruction, posterior spinal segmental fusion was performed. Mycobacterium bovis (M. bovis was identified using multiplex polymerase chain reaction of surgical tissue specimens. The patient was started on an antituberculosis treatment regimen including isoniazid, rifampicin, and ethambutol. After surgery, his back pain resolved completely. At the latest examination, the patient was pain-free with no functional limitations or recurrent infection in clinical or imaging findings. Patients undergoing BCG therapy should be monitored for possible hematogenous spread of mycobacteria to the spine for months or even years after treatment.

  14. Nonclinical Development of BCG Replacement Vaccine Candidates

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    Bernd Eisele

    2013-04-01

    Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  15. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Science.gov (United States)

    Rentsch, Cyrill A; Biot, Claire; Gsponer, Joël R; Bachmann, Alexander; Albert, Matthew L; Breban, Romulus

    2013-01-01

    Intravesical Bacillus Calmette Guérin (BCG) immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1) duration between resection and the first instillation; (2) BCG dose; (3) indwelling time; and (4) treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

  16. Intravesical explosion during transurethral electrosurgery.

    Science.gov (United States)

    Georgios, Kallinikas; Evangelos, Boulinakis; Helai, Habib; Ioannis, Gerzelis

    2015-05-01

    Intravesical explosion is a very rare complication of transurethral resection of prostate and transurethral resection of bladder tumour operations. In vitro studies have shown that the gases produced during the procedure could result in a blast once they are mixed with air from the atmosphere. A 79-year-old male experienced an explosion in his bladder while undergoing a transurethral resection of bladder tumour. The case is presented as well as the way that it was treated as an emergency. Precautions of such events are finally suggested.

  17. Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with p - mapa and systemic administration of cisplatin and doxorubicin.

    Science.gov (United States)

    Dias, Queila Cristina; Nunes, Iseu da Silva; Garcia, Patrick Vianna; Favaro, Wagner Jose

    2016-01-01

    The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.

  18. Role of a bacillus Calmette-Guérin fibronectin attachment protein in BCG-induced antitumor activity.

    Science.gov (United States)

    Zhao, W; Schorey, J S; Bong-Mastek, M; Ritchey, J; Brown, E J; Ratliff, T L

    2000-04-01

    Intravesical Mycobacterium bovis bacillus Calmette-Gu*erin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity.

  19. Disseminated Bacille Calmette-Guerin (BCG) disease in an infant with severe combined immunodeficiency.

    Science.gov (United States)

    Sohail, Shagufta; Afzal, Muhammad; Anwar, Vaqas; Shama, Quratulain

    2014-11-01

    Bacille Calmette-Guerin (BCG) vaccine is administered to all newborns in countries where tuberculosis is still endemic. It is a live attenuated vaccine and considered quite safe in immunocompetent children. Disseminated BCG disease is the most serious complication seen only in individuals with underlying primary or secondary immunodeficiencies. We report a case of disseminated BCG disease in an infant with Severe Combined Immunodeficiency (SCID) who received BCG administration prior to diagnosis of SCID.

  20. Intravesical therapy for urothelial carcinoma of the urinary bladder: a critical review

    Directory of Open Access Journals (Sweden)

    Daher C. Chade

    2009-12-01

    Full Text Available The management of non-muscle-invasive urothelial carcinoma of the bladder (UCB is a challenge for physicians and patients alike. This is largely due to the heterogeneous natural history of this disease, in which tumors range from indolent to rapidly progressive and eventually fatal. Moreover, the high rate of recurrence and progression cause significant morbidity, expense, and detriment to quality of life. The advent of effective and safe intravesical therapies has improved the management of non-muscle-invasive UCB. Nevertheless, despite over 30 years of research and clinical experience, the mechanism, risks, benefits, and optimal regimens and treatment algorithms remain unclear. Although immunotherapy with bacillus Calmette-Guerin (BCG has been the mainstay of intravesical treatment and represents a significant advance in the interaction of immunology and oncology, its clinical effectiveness is accompanied by a wide range of adverse events. Here, we review the literature on intravesical immunotherapy and chemotherapy with the aim of evaluating the clinical utility of the different treatments and providing recommendations. Many studies over the years have compared efficacy and toxicities of different agents and regimens, and certain conclusions are now well supported by high-level evidence. Future perspectives and promising advances in drug development are discussed and areas of improvement are identified in order to promote better cancer control and decrease the rate and severity of side-effects.

  1. The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette-Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder.

    Science.gov (United States)

    Rosevear, Henry M; Lightfoot, Andrew J; O'Donnell, Michael A; Griffith, Thomas S

    2009-12-01

    Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy's mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research.

  2. The clinical use of BCG-CWS and IL-2 for preventing recurrence of superficial bladder cancer%BCG-CWS联合IL-2预防浅表性膀胱癌术后复发

    Institute of Scientific and Technical Information of China (English)

    秦自科; 林奕中; 周志伟; 梅骅; 戴宇平

    2001-01-01

    Objective To study the therapeutic effects of intravesical instillation of cell wall skeleton of bacillus Calmett-Guerin ( BCG-CWS ) and interleukin 2 (IL-2 ) in preventing bladder cancers from recurring after local ablation.Methods 56 patients with superficial bladder cancers were randomized in using BCG-CWS and IL-2 or MMC for preventing bladder cancers from recurring after local ablation.Results The patients have been followed up for 12~30 months (mean 22.9 months).One patient had tumor recurrence in the group using BCG-CWS and IL-2 and five in the MMC group,the rates of tumor recurrence were 3.6%(1/28)and 18.0%(5/28) respectively, and the difference was statistically significant(P<0.05). There were obviously more side effects in intravesical instillation with MMC than BCG-CWS and IL-2.Conclusions Intravesical instillation of BCG-CWS and IL-2 is effective in preventing superficial bladder cancer from recurring after local ablation with fewer adverse effects.The ragimen is not only reliable but also safe.%目的 探讨卡介苗细胞壁骨架(BCG-CWS)+白细胞介素2(IL-2)膀胱灌注预防浅表性膀胱癌术后复发的临床效果。方法 56例浅表性膀胱癌局部手术后随机分为两组,每组28例。分别采用BCG-CWS加IL-2和单用丝裂霉素C(MMC)进行膀胱灌注。结果 56例随访12~30个月,平均22.9个月。BCG-CWS+IL-2组有1例肿瘤复发,MMC组有5例肿瘤复发,两组肿瘤复发率差别有显著性意义(P<0.05);MMC灌注组的毒副反应较BCG-CWS+IL-2组多。结论 BCG-CWS联合IL-2预防浅表性膀胱癌术后复发疗效较好,副反应少,临床使用安全可靠。

  3. BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis

    Directory of Open Access Journals (Sweden)

    Hermann Inge-Marie

    2010-06-01

    Full Text Available Abstract Background Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC. We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines. Results In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip. Conclusions S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC.

  4. Nanoparticulation of BCG-CWS for application to bladder cancer therapy

    OpenAIRE

    Nakamura, Takashi; Fukiage, Masafumi; Higuchi, Megumi; NAKAYA, Akihiro; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Ito, Toshihiro; Hosokawa, Hiroyuki; Nakayama, Toshinori; Harashima, Hideyoshi

    2014-01-01

    The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of mu m, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166 nm-sized lipid particles. The BCG-CWS encapsulated nano parti...

  5. Primary tuberculosis of glans penis after intravesical Bacillus Calmette Guerin immunotherapy

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    V K Sharma

    2011-01-01

    Full Text Available A 55-year-old male with carcinoma in situ of urinary bladder was treated with weekly intravesical injections of Bacillus Calmette Guerin (BCG vaccine. Three days after the sixth injection, he developed low grade fever and multiple grouped punched out, 2-3 mm ulcers around meatus and corona glandis. In addition, multiple, firm, indurated, nontender papules and few deeper nodules were present on the proximal part of glans penis, along with bilateral enlarged, matted and nontender inguinal lymph nodes. There was no history suggestive of sexually transmitted diseases and high risk behavior. Chest X-ray was within normal limits, and Mantoux, Venereal Disease Research Laboratory (VDRL and HIV antibody tests were negative. The biopsy from the penile ulcer revealed epithelioid cell granuloma with Langhans giant cells. Fine needle aspiration cytology from the lymph node also revealed epithelioid cell granuloma and acid fast bacilli on Ziehl Neelsen′s stain. The tissue biopsy grew Mycobacterium tuberculosis. The BCG immunotherapy was stopped and patient was treated with four drug antitubercular therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide in standard daily doses along with pyridoxine. The edema resolved and the ulcers started healing within 2 weeks, and at 6 weeks after starting antitubercular therapy almost complete healing occurred. To the best of our knowledge, we describe the first case of an Indian patient with BCG induced primary tuberculosis of penis after immunotherapy for carcinoma urinary bladder and review the previously described cases to increase awareness of this condition in dermatologists and venereologists.

  6. Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity

    DEFF Research Database (Denmark)

    Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter

    2015-01-01

    were less strong than those induced by live BCG. γBCG vaccination in volunteers had only minimal effects on innate immunity, whereas a significant increase in heterologous Th1/Th17 immunity was observed. Our results indicate that γBCG induces long-term training of innate immunity in vitro. In vivo, γ...

  7. Intravesical Instillation in Pure Line LEW Rats and Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jie; XIE Shusheng; GUO Xiaoyun; MO Zengnan

    2007-01-01

    In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and angle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activities of animals weren't influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

  8. Outcomes of Extravesical Versus Intravesical Ureteral Reimplantation

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    Leah P. McMann

    2004-01-01

    Full Text Available Purpose: The purpose of our study was to examine outcomes and compare length of stay after extravesical and intravesical ureteral reimplantation at our institution. Materials and Methods: Retrospective review was performed of 30 patients (55 ureters with vesicoureteral reflux who underwent either the Cohen (intravesical cross-trigonal procedure or the extravesical (detrusorrhaphy approach. Each patient had documented follow-up consisting of a postoperative renal ultrasound and/or a voiding cystourethrogram (VCUG. Inclusion criteria was the presence of primary vesicoureteral reflux. Exclusion criteria were patients who had undergone a previous repair and patients in whom results of neither the renal ultrasound nor the VCUG were available. Results: There were no significant cases of obstruction or wound infection with either approach. Two patients who underwent the extravesical approach had persistent reflux on VCUG three months postoperatively, but both resolved by fifteen months. Average length of stay was only 3.00 ± 1.33 days for the extravesical approach, compared to 5.36 ± 1.75 days for the intravesical approach ( P = .0003 . Conclusions: Given that by fifteen months success rates were the same with either approach, the extravesical approach is comparable to the intravesical technique and is a viable option in terms of outcome and economics given the shorter length of hospital stay.

  9. Repeated BCG treatment of mouse bladder selectively stimulates small GTPases and HLA antigens and inhibits single-spanning uroplakins

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    O'Donnell Michael A

    2007-11-01

    Full Text Available Abstract Background Despite being a mainstay for treating superficial bladder carcinoma and a promising agent for interstitial cystitis, the precise mechanism of Bacillus Calmette-Guerin (BCG remains poorly understood. It is particularly unclear whether BCG is capable of altering gene expression beyond its well-recognized pro-inflammatory effects and how this relates to its therapeutic efficacy. The objective of this study was to determine differentially expressed genes in the mouse bladder following repeated intravesical BCG therapy. Methods Mice were transurethrally instilled with BCG or pyrogen-free on days 1, 7, 14, and 21. Seven days after the last instillation, urothelia along with the submucosa was removed and amplified ds-DNA was prepared from control- and BCG-treated bladder mucosa and used to generate suppression subtractive hybridization (SSH. Plasmids from control- and BCG-specific differentially expressed clones and confirmed by Virtual Northern were then purified and the inserts were sequenced and annotated. Finally, chromatin immune precipitation combined with real-time polymerase chain reaction assay (ChIP/Q-PCR was used to validate SSH-selected transcripts. Results Repeated intravesical BCG treatment induced an up regulation of genes associated with antigen presentation (B2M, HLA-A, HLA-DQA1, HLA-DQB2, HLA-E, HLA-G, IGHG, and IGH and representatives of two IFNγ-induced small GTPase families: the GBPs (GBP1, GBP2, and GBP5 and the p47GTPases (IIGTP1, IIGTP2, and TGTP. Genes expressed in saline-treated bladders but down-regulated by BCG included: the single-spanning uroplakins (UPK3a and UPK2, SPRR2G, GSTM5, and RSP 19. Conclusion Here we introduced a hypothesis-generator approach to determine key genes involved in the urothelium/sumbmucosa responses to BCG therapy. Urinary bladder responds to repeated BCG treatment by up-regulating not only antigen presentation-related genes, but also GBP and p47 small GTPases, both potentially

  10. High-Risk Non-Muscle-Invasive Bladder Cancer-Therapy Options During Intravesical BCG Shortage.

    Science.gov (United States)

    Veeratterapillay, Rajan; Heer, Rakesh; Johnson, Mark I; Persad, Raj; Bach, Christian

    2016-09-01

    Bladder cancer is the second commonest urinary tract malignancy with 70-80 % being non-muscle invasive (NMIBC) at diagnosis. Patients with high-risk NMIBC (T1/Tis, with high grade/G3, or CIS) represent a challenging group as they are at greater risk of recurrence and progression. Intravesical Bacilli Calmette-Guerin (BCG) is commonly used as first line therapy in this patient group but there is a current worldwide shortage. BCG has been shown to reduce recurrence in high-risk NMIBC and is more effective that other intravesical agents including mitomycin C, epirubicin, interferon-alpha and gemcitabine. Primary cystectomy offers a high change of cure in this cohort (80-90 %) and is a more radical treatment option which patients need to be counselled carefully about. Bladder thermotherapy and electromotive drug administration with mitomycin C are alternative therapies with promising short-term results although long-term follow-up data are lacking.

  11. Chest wall granuloma associated with BCG vaccination presenting as hot abscess in an immunocompetent infant

    OpenAIRE

    Lee, Hyun Seung; Seo, Kyung Jin; Kim, Jae Jun

    2015-01-01

    Bacillus-Calmette-Gue´rin (BCG) vaccine is a live attenuated vaccine to prevent tuberculosis by cell mediated immune response and is routinely administered early after birth. Although it is considered to be a very safe vaccine, sometimes a variety of complications may develop. Herein we describe a clinically unusual case of chest wall granuloma considered to be induced by BCG, presenting as hot abscess, and developed 7 months after BCG vaccination in an immunocompetent infant. The diagnosis w...

  12. Bilateral symmetrical corneal melting following intravesical Bacille Calmette-Guerin therapy for bladder carcinoma

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    Chandana Chakraborty

    2012-01-01

    Full Text Available A 63-year-old man with unremarkable previous ocular history presented with bilateral symmetrical corneal ulceration along with mucopurulent conjunctivitis and dry eye 10 days after the fourth dose of intravesical Bacille Calmette-Guerin (BCG instillation for treatment of bladder carcinoma. Slit lamp examination revealed thinning of the cornea at the base of the ulcer in both eyes. Conjunctival swab and scraping from ulcer sent for Gram and acid fast bacilli stain and culture were negative. On the basis of history, clinical examination, and laboratory investigations, we diagnosed it as bilateral immune mediated sterile corneal ulceration along with mucopurulent conjunctivitis and dry eye. He was treated with topical antibiotics, cycloplegics, cyclosporine, lubricant gel, and bandage contact lens. There was progressive stromal melting, descemetocele formation, and perforation in the inferior part of cornea in both the eyes. He was treated with pulse steroid and paramedian tarsorraphy in both eyes. The patient was subsequently lost to follow-up. We report this case to highlight this rare complication of BCG therapy, in order to improve their management protocol in patients with similar clinical profile. We could not find a similar case after thorough PubMed search.

  13. The response of variant histology bladder cancer to intravesical immunotherapy compared to conventional cancer

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    Ofer Nathan Gofrit

    2016-03-01

    Full Text Available Background: High-grade urothelial carcinomas (UC often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with Bacillus Calmette Guerin (BCG. We compared the response to treatment with BCG of UC containing glandular, squamous, nested and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade urothelial carcinoma. Methods: A total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. 41 patients with Ta or T1, confirmed by 2nd look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation 13 patients with squamous differentiation, in 9 patients glandular differentiation was seen and in 7 patients nested variant. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly. Findings: Patients with variant tumors had similar clinical features to patients with conventional disease including: age, males to female ratio, stage, presence of Tis and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC including: 5-year recurrence-free survival (63.5% Vs. 71.5%, p=0.05, 5-year progression to≥T2 -free survival (60% Vs. 82.5%, p=0.002, 5-year disease-specific survival (73% Vs. 92.5%, p=0.0004 and overall survival (66% Vs. 89.5%, 0.05. Interpretation: A patient with variant bladder cancer treated with intra-vesical immunotherapy has a 27% chance of dying from this disease within 5-years compared to 7.5% for a patient with conventional high-grade UC.

  14. Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

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    Shanmugalakshmi Sadagopal

    Full Text Available BACKGROUND: In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB. Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli. CONCLUSIONS/SIGNIFICANCE: We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

  15. Tuberculin reaction and BCG scar

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Biering-Sørensen, Sofie; Aaby, Peter;

    2015-01-01

    Abstract Objective To test the hypothesis that having a scar and a positive tuberculin skin test (TST) response after vaccination with Bacille Calmette–Guérin (BCG) is associated with reduced infant mortality. Methods We studied cohorts of 2709 normal-birthweight (NBW) and 1102 low-birthweight (LBW......) infants in Guinea-Bissau. Children were enrolled in randomised trials between year 2002 and 2008 and received BCG vaccination at birth. BCG scars and TST responses were assessed at 2 and 6 months of age. The infants were followed for mortality to 12 months of age, and survival was analysed using Cox...... regression. Results At age 2 months, 88% of NBW children and 91% of LBW children had a BCG scar, and 36% and 17% had a TST response, respectively. The LBW infants had nearly twofold higher mortality (4.5%) than the NBW infants (2.8%) between 2 and 12 months of age. In the LBW cohort, the adjusted mortality...

  16. Ultrasonographic features of BCG lymphadenitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Youn; Lee, Sun Wha; Hwang, Ji Young [College of Medicine, Ewha Womans University, Seoul (Korea, Republic of)

    2005-07-15

    To evaluate the ultrasonographic findings of BCG lymphadenitis complicated by BCG vaccination in children. Ultrasonography was performed for 22 cases of BCG lymphadenitis in 21 patients who were diagnosed by clinical (n=10) or pathological (n=11) examinations. Their age ranged from 4 months to 3 years (mean age; 14 months). We retrospectively analyzed the ultrasonographic findings for location, multiplicity, size, shape, margin, echogenecity, posterior enhancement, calcifications, inner anechoic portion and Doppler pattern of the BCG lymphadenitis. The BCG lymphadenitis was found at the axillary area in 15 cases (68%) and at the supraclavicular area in 7 cases (32%). There were ten cases (45%) of solitary lesion and 12 cases (55%) of multiple conglomerated lesions. The maximum diameter ranged from about 0.9 cm to 3.2 cm. The BCG lymphadenitis showed as round (82%), well defined (86%), or heterogeneous hypoechoic (68%) lesions with posterior enhancement (78%). Calcifications were found in 6 cases (27%) and 5 cases (83%) had been vaccinated more than 5 months ago. There were eccentric inner anechoic portions in 16 cases (73%), which were pathologically confirmed as having caseating necrosis. There were increased Doppler flow patterns in 15 cases (68%); 4 cases (18%) were of the central type, 6 cases (27%) were of the peripheral type and 5 cases (23%) were of mixed type. BCG lymphadenitis is frequently located at the axillary area adjacent to a vaccination site. The ultrasonographic findings of BCG lymphadenitis are well-defined, round, heterogeneously hypoechoic lesions with posterior enhancement, calcifications and inner eccentric anechoic portion.

  17. Chest wall granuloma associated with BCG vaccination presenting as hot abscess in an immunocompetent infant.

    Science.gov (United States)

    Lee, Hyun Seung; Seo, Kyung Jin; Kim, Jae Jun

    2015-03-04

    Bacillus-Calmette-Gue´rin (BCG) vaccine is a live attenuated vaccine to prevent tuberculosis by cell mediated immune response and is routinely administered early after birth. Although it is considered to be a very safe vaccine, sometimes a variety of complications may develop. Herein we describe a clinically unusual case of chest wall granuloma considered to be induced by BCG, presenting as hot abscess, and developed 7 months after BCG vaccination in an immunocompetent infant. The diagnosis was made based on the history, histopathology and virological studies. We suggest, although very rare, a BCG disease should be considered as a differential diagnosis in case of chest wall abscess, even if this is presenting as a hot abscess and even in immunocompetent infants if their age is related to BCG vaccination complications.

  18. BCG vaccines: their mechanisms of attenuation and impact on safety and protective efficacy.

    Science.gov (United States)

    Liu, Jun; Tran, Vanessa; Leung, Andrea S; Alexander, David C; Zhu, Baoli

    2009-02-01

    Mycobacterium bovis Bacille Calmette-Guérin (BCG) was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, the mechanisms of attenuation of BCG remain poorly understood. BCG is not a single organism, but comprises a number of substrains that differ in genotypes and phenotypes. The impacts of these differences on BCG vaccine properties are largely unknown. Nevertheless, in the past decade, the development of sophisticated genome analysis techniques, coupled with advances in knowledge of the virulence mechanisms of Mycobacterium tuberculosis, have provided greater insights into the attenuation and evolution of BCG. This review article discusses these new developments, focusing on molecular mechanisms that contribute to the attenuation of BCG substrains. It is evident that BCG strains comprise natural mutants of major virulence factors of M. tb, including ESX-1, PDIM/PGL and PhoP, and that BCG substrains differ markedly in virulence level. The impacts of these findings on vaccine properties including adverse reaction effect, tuberculin reactivity and protective efficacy are discussed. These new insights have extremely important implications for national immunization programs and the development of future vaccines.

  19. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

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    Kiss Tamas

    2010-06-01

    Full Text Available Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG is effective in non-muscle-invasive bladder cancer (BC, adverse events (AEs are considerable. Monocyte-derived activated killer cells (MAK are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM® to BCG in patients after transurethral resection (TURB of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM. Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint and prophylactic effects (secondary endpoint were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE, respectively (p Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

  20. Combined immunochemotherapy (CEP, M-VEP + BCG) in the treatment of invasive bladder tumors.

    Science.gov (United States)

    Damianov, C; Terziev, T; Koleva, P; Chuchkova, M

    1994-06-01

    Forty patients with invasive bladder tumors were consecutively treated and followed between June 1986 and February 1993. The treatment included systemic chemotherapy combining cyclophosphamide, epirubicin and cisplatin (CEP) or methotrexate, vinblastine, epirubicin and cisplatin (M-VEP) along with intravesically applied BCG vaccine. The treatment was well tolerated by the patients. No relevant toxic effects requiring hospitalization or fatalities due to the treatment were observed. Toxic manifestations of a hematologic nature were considerably less frequent than usual, nausea and vomiting being among the most frequently observed toxic signs on the second day of application of cisplatin. The side effects resulting from intravesically applied BCG vaccine showed no significant difference in terms of severity and variety from those due to its application in superficial tumors. A median follow-up of 50.3 months (range 6-80 months) showed an objective response to the treatment as follows: complete and partial response in 27 out of 40 (67.5%) and a complete clinical response in eight out of 40 (20%). Ten patients with partial response and stabilization had complete surgical response after operative treatment. The recurrence rate in patients with a complete response and a complete surgical response was 33% (six out of 18). The survival rate was 78% at 1 year, 70% at 2 years and 68% at 4 years. A complete response to the treatment of concomitant carcinoma in situ was observed in three patients. The lack of comparative and randomized studies and insufficient clinical experience did not allow an overall assessment of the therapeutic opportunities that our combined immunochemotherapy offers.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. The clinical course of non-muscle invasive bladder cancer after transuretral resection of the tumor with or without subsequent intravesical application of bacillus Calmette-Guérin: The influence of patients gender and age

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    Milošević Radovan

    2015-01-01

    Full Text Available Bacground/Aim. The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG after transurethral resection (TUR of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC. The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. Methods. This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using χ2 test and the Kolmogorov-Smirnov test. Results. This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. Conclusions. Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years.

  2. Outcomes of BCG Induction in High-Risk Non-Muscle-Invasive Bladder Cancer Patients (NMIBC): A Retrospective Cohort Study

    Science.gov (United States)

    Ghauri, Rashid; Ahmed, Monis J; Shah, Muhammad F; Nasir, Irfan ul Islam; Siddiqui, Jasim; Ahmed, Irfan; Mir, Khurram

    2017-01-01

    Non-muscle-invasive bladder cancer (NMIBC) is categorized into high-risk and low-risk groups. Although, bacillus Calmette-Guerin (BCG) is the recommended adjuvant therapy of high-risk bladder tumor, optimal schedule (induction versus maintenance) of this therapy is a subject of debate. The objective was to evaluate outcomes of induction BCG in high-risk NMIBC patients at Shaukat Khanum Memorial Cancer Hospital & Research Centre, Pakistan and retrospective cohort study conducted in the department of urology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Pakistan. Three-year disease-free survival and progression-free survival was the main outcome measure. Data of 68 high-risk (Ta and T1 with G3 or high-grade subtype) bladder cancer patients who underwent transurethral resection followed by six-weekly intravesical BCG instillation was included in the study. Recurrence was described as biopsy-proven bladder cancer; whereas the presence of muscle invasion was considered as progression. Disease-free survival and progression-free survival were defined as time intervals elapsed between the starting date of BCG instillation and recurrence or progression, respectively. Kaplan-Meier curve was employed to estimate the three-year study end-points. Disease-free survival at three years was observed to be 66.2% and progression-free survival at 86.8%. The use of induction BCG alone for high-risk patients of NMIBC is a viable option both in terms of effective disease-free and progression-free survival rates. PMID:28168135

  3. Tuberculous prostatic abscess following intravesical bacillus Calmette-Guérin immu-notherapy:a case report%卡介苗膀胱灌注治疗致结核性前列腺脓肿1例

    Institute of Scientific and Technical Information of China (English)

    叶海云; 许清泉; 黄晓波; 马凯; 王晓峰

    2015-01-01

    SUMMARY Intravesical bacillus Calmette-Guérin ( BCG) was a common treatment for non-muscle inva-sive urothelial carcinoma of the bladder. The complication of prostatic abscess was rare. We reported a case of tuberculous prostatic abscess after BCG therapy. A 65-year-old man was diagnosed as bladder cancer and accepted transurethral resection of bladder tumor ( TURBT) treatment. He received a 6-week induction course without any infection complication. Following the second BCG maintenance instillation, he complained of fever and dysuria. Transrectal ultrasound ( TRUS) demonstrated a well-defined complex mass in the right lobe of his prostate. The diagnosis of tuberculous prostatic abscess was considered after excluding other bacterial infection. The patient was treated with an anti-tuberculous regimen of isoniazid, rifampicin, and ethambutol. The symptoms were relieved after 4 weeks of anti-tuberculous therapy. Be-cause of the good response to the medicine, no further aspiration or drainage of prostatic abscess was car-ried out. The anti-tuberculous therapy had to be stopped for serious drug induced liver injury after 6 weeks of anti-tuberculous therapy. Eight weeks later of stopping anti-tuberculous therapy, the follow-up TRUS showed the disappearance of the prostatic abscess and the test of his liver function was normal. Considering the virulence of BCG is weaker than that of common tuberclebacillus, the shorter course of anti-tuberculous therapy maybe an alternative choice, and surgical drainage is not always necessary.

  4. BCG vaccination: a role for vitamin D?

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    Maeve K Lalor

    Full Text Available BACKGROUND: BCG vaccination is administered in infancy in most countries with the aim of providing protection against tuberculosis. There is increasing interest in the role of vitamin D in immunity to tuberculosis. This study objective was to determine if there was an association between circulating 25(OHD concentrations and BCG vaccination status and cytokine responses following BCG vaccination in infants. METHODS: Blood samples were collected from UK infants who were vaccinated with BCG at 3 (n = 47 and 12 (n = 37 months post BCG vaccination. These two time-points are denoted as time-point 1 and time-point 2. Two blood samples were also collected from age-matched unvaccinated infants (n = 32 and 28 respectively, as a control group. Plasma vitamin D concentrations (25(OHD were measured by radio-immunoassay. The cytokine IFNγ was measured in supernatants from diluted whole blood stimulated with M.tuberculosis (M.tb PPD for 6 days. RESULTS: 58% of infants had some level of hypovitaminosis (25(OHD <30 ng/ml at time-point 1, and this increased to 97% 9 months later. BCG vaccinated infants were almost 6 times (CI: 1.8-18.6 more likely to have sufficient vitamin D concentrations than unvaccinated infants at time-point 1, and the association remained strong after controlling for season of blood collection, ethnic group and sex. Among vaccinees, there was also a strong inverse association between IFNγ response to M.tb PPD and vitamin D concentration, with infants with higher vitamin D concentrations having lower IFNγ responses. CONCLUSIONS: Vitamin D may play an immuno-regulatory role following BCG vaccination. The increased vitamin D concentrations in BCG vaccinated infants could have important implications: vitamin D may play a role in immunity induced by BCG vaccination and may contribute to non-specific effects observed following BCG vaccination.

  5. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis.

    Science.gov (United States)

    Pym, Alexander S; Brodin, Priscille; Majlessi, Laleh; Brosch, Roland; Demangel, Caroline; Williams, Ann; Griffiths, Karen E; Marchal, Gilles; Leclerc, Claude; Cole, Stewart T

    2003-05-01

    The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (RD1) locus, which is intact in virulent members of the Mycobacterium tuberculosis complex. To increase their immunogenicity and protective capacity, we complemented both vaccines with different constructs containing the esxA and esxB genes, which encode ESAT-6 and CFP-10 respectively, as well as a variable number of flanking genes. Only reintroduction of the complete locus, comprising at least 11 genes, led to full secretion of the antigens and resulted in specific ESAT-6-dependent immune responses; this suggests that the flanking genes encode a secretory apparatus. Mice and guinea pigs vaccinated with the recombinant strain BCG::RD1-2F9 were better protected against challenge with M. tuberculosis, showing less severe pathology and reduced dissemination of the pathogen, as compared with control animals immunized with BCG alone.

  6. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer.

    Science.gov (United States)

    Białek, Waldemar; Rudzki, Sławomir; Iberszer, Paweł; Wronecki, Lech

    2016-12-01

    Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

  7. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies.

    Science.gov (United States)

    Jin, Xun; Zhang, Peilan; Luo, Li; Cheng, Hao; Li, Yunzu; Du, Ting; Zou, Bingwen; Gou, Maling

    Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer.

  8. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies

    Directory of Open Access Journals (Sweden)

    Jin X

    2016-09-01

    Full Text Available Xun Jin,1 Peilan Zhang,1 Li Luo,1 Hao Cheng,1 Yunzu Li,1 Ting Du,1 Bingwen Zou,2 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China; 2Department of Thoracic Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China Abstract: Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol (DPP nanoparticles to deliver doxorubicin (Dox for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. Keywords: bladder cancer, drug delivery, nanoparticles, intravesical therapy

  9. Intravesical oxybutinin chloride in children with intermittent catheterization: sonographic findings.

    Science.gov (United States)

    Zerin, J M; DiPietro, M A; Ritchey, M L; Bloom, D A

    1994-01-01

    The sonographic findings in the bladder are presented in four children with myelomeningocele and neurogenic dysfunction of the bladder, who were treated with intermittent self-catheterization and intravesical oxybutinin chloride. All were referred for routine sonography of the urinary tract. Each had infused a crushed tablet of oxybutinin chloride intravesically 30-120 min before the examination. In two children, brightly echogenic, non-shadowing particles were suspended in the bladder urine. In one of these, the particles swirled giving the impression of a "snowstorm"; in the other, most of the particles gradually settled forming an irregular clump on the bladder base. In the remaining two children, the urine appeared diffusely hazy with innumerable tiny particles giving the impression of a fine mist filling the bladder. The sonographic appearance of the urine in the bladder after intravesical instillation of crushed tablets can be dramatic and can simulate pus, blood, fungus, or other debris in the bladder lumen. In the absence of clinical symptoms or hematuria, a history of recent infusion of medication into the bladder should be sought.

  10. Mitsuda's reactions: induced by BCG in the normal Rhesus ("Macacca mulatta"

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    M. J. Pereira Filho

    1955-12-01

    the repetition of the tests, even though the intensity of the reaction always remains the same. This precocious reaction (Fernandez type occurs both shortly and long time after the application of the BCG. Its precocity depends not of the antigen only because the first Mitsuda's reaction after the BCG application occurs after some time and seems not influenced by the control lepromin test effected on the Rhesus before the BCG. 5 On the control group, the animals which received a.a.f. bacilli suspensions (Mycobacterium sp.; M. avium, and M. smegmatis, did not show reverseals of the Mitsuda's reaction. Two Rhesus, however, which received dead BCG (120ºC autoclave 1 hour, one intradermically (0.006 g and the other orally (1.2 g, did both present reversals of the Mitsuda's reaction, with weak positivity (+. In all animals of the control-group, the allergic reactions were found negative. 6 Strong local inflammatory reactions were observed in the Rhesus that had received living BCG by intradermal via, and in the one submitted to multipunctures, there occurred the formation of a large caseous abcess. 7 The allergic tuberculinic and infratuberculinic reactions appeared dissociated from the Mitsuda's reactions: sometimes they are more precocious, occurring before of the lepromin test; on other occasions they disappear, when the Mitsuda's reactions still persist; and finally, they may be absent, when the latter occur, especially after the oral application of the BCG. 8 In Rhesus which received BCG by testicular and peritonela via, in the infratuberculinic test (0.1 ml of total BCG extract, besides the classic answer, which occurs between 48 and 96 hours, one could observe a delayed answer (15 to 20 days, represented by a non-erythematous nodule, which persists for 11-14 days.

  11. Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation

    Science.gov (United States)

    Caetano, Liliana A.; Almeida, António J.; Gonçalves, Lídia M.D.

    2016-01-01

    The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID:27187418

  12. [Assessment of BCG vaccine practices].

    Science.gov (United States)

    Lechiche, C; Charpille, M; Saissi, G; Sotto, A

    2016-01-01

    Tuberculosis is a major public health problem. In France, the vaccine against tuberculosis (Bacillus Calmette-Guerin, BCG) is in decline. This decline is firstly due to changes in BGG administration that were implemented in 2006 and secondly because of new recommandations in 2007 that ended compulsory vaccination. To determine their position on this vaccine, in 2013-2014 we asked general practitioners, pediatricians, and Maternal and Infantile Protection Center physicians in the Gard and Herault departments (in Southern France) why this vaccine was not administered and their suggestions for improvement. Most of these doctors (73.9%) stated that they did not oppose this vaccination for children. They expressed concern about potential side effects, technical problems (intradermic injection, multi-dose bottles) and parents' refusal. One quarter of these physicians would have preferred that this vaccine remains compulsory and one third that this vaccine be administered in the maternity hospital. They also requested simplified criteria for patient eligibility, technical improvements (training for intradermal injection, single-dose vaccine) and more information for the public concerning this vaccination.

  13. BCG skin reaction in Mantoux-negative healthy children

    Directory of Open Access Journals (Sweden)

    Sodhi Sukhbir

    2005-03-01

    Full Text Available Abstract Background Tuberculosis poses a great challenge, especially in children. The response of BCG Test may be different in previously vaccinated children and needs to be considered before interpreting positivity for TB. This study has been carried out to determine the pattern of BCG reaction comparing previously vaccinated with non-vaccinated children. Methods The study was conducted in the healthy school children aged 4–6 years. The BCG skin reaction in Mantoux-negative children was compared between children with and without previous BCG scar. After the Mantoux and BCG Test, the analysis of variance was done as per protocol. Results Out of 50 children previously BCG vaccinated, 39(78% showed exaggerated BCG test responses while out of another 50 children who were not vaccinated for TB, only 9(18% showed exaggerated BCG Test response (p-value Conclusion The present study indicates that normal healthy children may have a mild exaggerated BCG Test response i.e. induration up to 8 mm because of prior BCG vaccination. Therefore, BCG Test, though important should not be the only criteria for start of chemotherapy for TB in children as the side effects of drugs may cause much morbidity. An induration up to 8 mm after the BCG Test can be normal in Indian settings due to exposure to Mycobacterium in environment and/or BCG vaccine.

  14. Effectiveness of BCG vaccination to aged mice

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    Ito Tsukasa

    2010-09-01

    Full Text Available Abstract Background The tuberculosis (TB still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice. Results The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old were comparable to those of young mice (4- to 6-week-old. The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice. Conclusion These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.

  15. Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

    Directory of Open Access Journals (Sweden)

    Degrave Wim M

    2011-04-01

    Full Text Available Abstract Background Bacille Calmette-Guerin (BCG is currently the only available vaccine against tuberculosis (TB and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. Results The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa, Rv1926c (BCG1965c, Mpb63 and Rv1886c (BCG1923c, Ag85B in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2 and Rv0350 (BCG0389, DnaK, show the opposite pattern. Conclusions Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.

  16. Non-specific immunity of BCG vaccine: A perspective of BCG immunotherapy

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    Najeeha Talat Iqbal

    2014-01-01

    Full Text Available BCG is a widely used vaccine worldwide for neonates including Pakistan. BCG has more than 90% coverage through the EPI program which was introduced in 1965 in Pakistan. BCG has limited efficacy against the transmissible form of pulmonary tuberculosis in high TB endemic countries. However, BCG vaccination continues in these countries because BCG confers protection against the disseminated form of TB in children. BCG has also shown some protection against leprosy and certain forms of cancers. One reason for such nonspecific protection may be that BCG activates APCs via PAMPS that interacts with TLRs (2, 4 & 8, which initiate the inflammatory cascade thereby recruiting inflammatory cells to the site of infection and providing maturation signals for neutrophils, macrophages and dendritic cells. Such activation may be crucial for restricting the infection at the initial site. Furthermore, activation of the pro-inflammatory cascade also results in expression of adhesion molecules, co-stimulatory molecules as well as MHC class II molecule. MHC class II molecules engage CD4+ cells via the TCR receptor while the adhesion and costimulatory molecules bind to their respective receptors on CD4+ T cells for additional high affinity binding for T cell activation. Although activation of the innate arm may not provide subsequent memory, activation of T cells may introduce a certain level of memory response and therefore, may form a rational basis for BCG immunotherapy. This review, therefore, focuses on the immune activation related to both the innate and adaptive arm of the immune response that has been reported and further explores the utility of BCG immunotherapy related to non TB conditions.

  17. BCG protects toddlers during a tuberculosis outbreak.

    LENUS (Irish Health Repository)

    Gaensbauer, J T

    2009-05-01

    In 2007, an outbreak of tuberculosis occurred in a toddler population attending two child care centres in Cork, Ireland. Of 268 children exposed, 18 were eventually diagnosed with active tuberculosis. We present the initial clinical and radiographic characteristics of the active disease group. Mantoux testing was positive in only 66% of cases. All cases were either pulmonary or involved hilar adenopathy on chest radiograph; there were no cases of disseminated disease or meningitis. 24% of the exposed children had been previously vaccinated with BCG, and no case of active disease was found in this group (p = 0.016), suggesting a profound protective effect of BCG in this population. Our experience provides evidence supporting a protective effect of BCG against pulmonary disease in young children.

  18. BCG protects against tuberculosis irrespective of HIV status

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Daniel; Range, Nyagosya; PrayGod, George

    2013-01-01

    While BCG vaccine protects against severe tuberculosis (TB) in children, its effect against adult TB is questionable. Furthermore, it is not known if HIV co-infection modifies the effect of BCG. Among 352 pairs of Tanzanian TB cases and matched controls, the BCG scar was associated with a reduced...

  19. Randomized trial of BCG vaccination at birth to low-birth-weight children

    DEFF Research Database (Denmark)

    Aaby, Peter; Roth, Adam Anders Edvin; Ravn, Henrik

    2011-01-01

    Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG.......Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG....

  20. Effectiveness of routine BCG vaccination on buruli ulcer disease: a case-control study in the Democratic Republic of Congo, Ghana and Togo.

    Directory of Open Access Journals (Sweden)

    Richard Odame Phillips

    2015-01-01

    Full Text Available The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis also called Bacillus Calmette-Guérin (BCG. Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD. The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD.The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors.After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31, sex (p = 0.24, age (p = 0.96, and presence of a BCG scar (p = 0.07 did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions.In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD.

  1. BCG coverage and barriers to BCG vaccination in Guinea-Bissau

    DEFF Research Database (Denmark)

    Thysen, Sanne Marie; Byberg, Stine; Pedersen, Marie;

    2014-01-01

    in selected intervention regions. Factors associated with delayed BCG vaccination were evaluated using logistic regression models. Coverage between intervention and control regions were evaluated in log-binomial regression models providing prevalence ratios. RESULTS: Among 3951 children born in 2010...

  2. Auxotrophic complementation as a selectable marker for stable expression of foreign antigens in Mycobacterium bovis BCG.

    Science.gov (United States)

    Borsuk, Sibele; Mendum, Tom A; Fagundes, Michel Quevedo; Michelon, Marcelo; Cunha, Cristina Wetzel; McFadden, Johnjoe; Dellagostin, Odir Antônio

    2007-11-01

    Mycobacterium bovis BCG has the potential to be an effective live vector for multivalent vaccines. However, most mycobacterial cloning vectors rely on antibiotic resistance genes as selectable markers, which would be undesirable in any practical vaccine. Here we report the use of auxotrophic complementation as a selectable marker that would be suitable for use in a recombinant vaccine. A BCG auxotrophic for the amino acid leucine was constructed by knocking out the leuD gene by unmarked homologous recombination. Expression of leuD on a plasmid not only allowed complementation, but also acted as a selectable marker. Removal of the kanamycin resistance gene, which remained necessary for plasmid manipulations in Escherichia coli, was accomplished by two different methods: restriction enzyme digestion followed by re-ligation before BCG transformation, or by Cre-loxP in vitro recombination mediated by the bacteriophage P1 Cre Recombinase. Stability of the plasmid was evaluated during in vitro and in vivo growth of the recombinant BCG in comparison to selection by antibiotic resistance. The new system was highly stable even during in vivo growth, as the selective pressure is maintained, whereas the conventional vector was unstable in the absence of selective pressure. This new system will now allow the construction of potential recombinante vaccine strains using stable multicopy plasmid vectors without the inclusion of antibiotic resistance markers.

  3. The Cyclic Di-GMP Phosphodiesterase Gene Rv1357c/BCG1419c Affects BCG Pellicle Production and In Vivo Maintenance.

    Science.gov (United States)

    Flores-Valdez, Mario Alberto; Aceves-Sánchez, Michel de Jesús; Pedroza-Roldán, César; Vega-Domínguez, Perla Jazmín; Prado-Montes de Oca, Ernesto; Bravo-Madrigal, Jorge; Laval, Françoise; Daffé, Mamadou; Koestler, Ben; Waters, Christopher M

    2015-02-01

    Bacteria living in a surface-attached community that contains a heterogeneous population, coated with an extracellular matrix, and showing drug tolerance (biofilms) are often linked to chronic infections. In mycobacteria, the pellicle mode of growth has been equated to an in vitro biofilm and meets several of the criteria mentioned above, while tuberculosis infection presents a chronic (latent) phase of infection. As mycobacteria lack most genes required to control biofilm production by other microorganisms, we deleted or expressed from the hsp60 strong promoter the only known c-di-GMP phosphodiesterase (PDE) gene in Mycobacterium bovis BCG. We found changes in pellicle production, cellular protein profiles, lipid production, resistance to nitrosative stress and maintenance in lungs and spleens of immunocompetent BALB/mice. Our results show that pellicle production and capacity to remain within the host are linked in BCG.

  4. Decoding intravesical pressure from local field potentials in rat lumbosacral spinal cord

    Science.gov (United States)

    Im, Changkyun; Park, Hae Yong; Koh, Chin Su; Ryu, Sang Baek; Seo, In Seok; Kim, Yong Jung; Kim, Kyung Hwan; Shin, Hyung-Cheul

    2016-10-01

    Chronic monitoring of intravesical pressure is required to detect the onset of intravesical hypertension and the progression of a more severe condition. Recent reports demonstrate the bladder state can be monitored from the spiking activity of the dorsal root ganglia or lumbosacral spinal cord. However, one of the most serious challenges for these methods is the difficulty of sustained spike signal acquisition due to the high-electrode-location-sensitivity of spikes or neuro-degeneration. Alternatively, it has been demonstrated that local field potential recordings are less affected by encapsulation reactions or electrode location changes. Here, we hypothesized that local field potential (LFP) from the lumbosacral dorsal horn may provide information concerning the intravesical pressure. LFP and spike activities were simultaneously recorded from the lumbosacral spinal cord of anesthetized rats during bladder filling. The results show that the LFP activities carry significant information about intravesical pressure along with spiking activities. Importantly, the intravesical pressure is decoded from the power in high-frequency bands (83.9-256 Hz) with a substantial performance similar to that of the spike train decoding. These findings demonstrate that high-frequency LFP activity can be an alternative intravesical pressure monitoring signal, which could lead to a proper closed loop system for urinary control.

  5. Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

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    Joan Joseph

    2010-01-01

    Full Text Available Mycobacterium bovis Bacillus Calmette-Guérin (BCG as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261 and Mycobacteria spp. α-antigen promoter (in plasmid pJH222. Among 14 rBCG:HIV-1gp120 (pMV261 colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222 colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

  6. Descendant of daughter Brazilian BCG Moreau substrain in Poland.

    Science.gov (United States)

    Krysztopa-Grzybowska, Katarzyna; Brzezińska, Sylwia; Augustynowicz-Kopeć, Ewa; Polak, Maciej; Augustynowicz, Ewa; Lutyńska, Anna

    2012-08-10

    In this study we assessed the genomic stability of Mycobacterium bovis BCG Moreau seed lots used in Poland for BCG vaccine production since 1955 by pulsed field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) and random amplification of polymorphic DNA (RAPD). BCG vaccine lots were more closely related the original lot -M. bovis BCG Rio de Janeiro Moreau compared with seeds used before 1980, which is consistent with seed lot distribution recorded in the archives. We confirmed the presence of RD8, RD2, senX3-regX3, RD14, DU2-I, whiB3, trcR, the second copy of IS6110 inserted in the promoter region of phoP, mutation D322G in phoR, ΔRD1, and ΔfadD26-ppsA in M. bovis BCG Moreau used for BCG production in Poland. However, unlike the Rio de Janeiro parent BCG, the BCG Moreau substrain used in Poland does not harbour a deletion in Rv3887c, a region that is involved in the membrane transport protein that is part of the ESX-2 type VII secretion system. Differences in the distribution of BCG Moreau for its subsequent use for manufacturing influenced the microevolution of BCG Moreau used in Brazil and Poland.

  7. Osteíte por BCG

    OpenAIRE

    Yamada,André Fukunishi; Pellegrini,Juliana Barbosa; Cunha,Luciana Menezes; Fernandes, Artur da Rocha Corrêa

    2009-01-01

    Os autores relatam o caso de um menino de 1 ano e 9 meses que apresentou lesão osteolítica na região proximal do úmero direito. Com base na história clínica e em achados histológicos, os autores suspeitaram de osteíte pósvacina BCG. Após o início do tratamento antituberculose, os sintomas desapareceram e o paciente apresentou melhora radiológica. Os autores descrevem esta entidade incomum na prática pediátrica e alertam para possíveis complicações da vacina BCG.

  8. BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro

    DEFF Research Database (Denmark)

    Madura Larsen, Jeppe; Benn, Christine Stabell; Fillie, Yvonne;

    2007-01-01

    enhanced IL-10 and diminished IL-12 production. These DCs primed naive T cells to develop into IL-10-producing T cells, with no T helper 1 or T helper 2 bias. These results suggest that BCG vaccination might result in the development of IL-10-producing DCs as well as IL-10-producing T cells that could......Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been associated with beneficial effects on overall childhood mortality in low-income countries; this cannot be explained merely by the prevention of tuberculosis (TB) deaths. The beneficial effects of BCG vaccine could be the result...... of either strengthening of pro-inflammatory mechanisms, helping neonates to fight infections, or the induction of an immune-regulatory network restricting overt inflammation and intense pathology. We aimed to study the effect of live BCG on the ability of dendritic cells (DCs) to polarize T-cell responses...

  9. Arthritis and iritis after BCG therapy for bladder cancer.

    Science.gov (United States)

    Price, G E

    1994-03-01

    A patient with preexisting inactive ankylosing spondylitis experienced a recurrence of back pain and his first episode of acute peripheral arthritis and iritis after a second course of treatment with BCG for bladder cancer. The occurrence of iritis after BCG therapy has not been reported. The recurrence of spondyloarthropathy and the new appearance of iritis may have been part of a generalized enhancement of immunological reactivity produced by the BCG.

  10. CLINICAL MANAGEMENT OF LOCALIZED BCG ADVERSE EVENTS IN CHILDREN

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    Thais das Neves Fraga MOREIRA

    Full Text Available SUMMARY BCG adverse events (BCG-AE are rare conditions with no well-established treatment. This study aims to describe clinical characteristics and outcome of localized BCG-AE. Children with BCG-AEs who were treated at the Reference Center for Special Immunobiologicals of the Federal University of São Paulo from 2009 to 2011 were included. Patients were followed monthly until 3 months after healing. One hundred and twenty-seven patients with localized BCG-AE were followed: 67 (52.7% had suppurative lymphadenitis; 30 (23.6% injection-site abscess; five (3.9% had enlarged lymph node > 3 cm; four (3.1% had ulcer > 1 cm; and one (0.8% had a local bacterial infection. Five patients (3.9% had more than one BCG-AE simultaneously. Fifteen patients (11.8% had atypical manifestations: seven wart-like lesions; five BCG reactivations; two other dermatologic lesions and one with vasomotor phenomenon. Isoniazid was used in 96 patients with typical BCG-AE (85.7% until lesion resolution which took place 3.1 months later (in median; the healing rate was 90.6%. Patients with atypical manifestations had an individual approach. Regarding the outcome, 105/112 patients with typical AE and 13/15 patients with atypical AE had resolution of BCG-AE. Localized BCG-AE caused by BCG Moreau RJ had positive outcome when treated with a short course of isoniazid. Atypical BCG-AE are not infrequent.

  11. Genome sequencing and analysis of BCG vaccine strains.

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    Wen Zhang

    Full Text Available BACKGROUND: Although the Bacillus Calmette-Guérin (BCG vaccine against tuberculosis (TB has been available for more than 75 years, one third of the world's population is still infected with Mycobacterium tuberculosis and approximately 2 million people die of TB every year. To reduce this immense TB burden, a clearer understanding of the functional genes underlying the action of BCG and the development of new vaccines are urgently needed. METHODS AND FINDINGS: Comparative genomic analysis of 19 M. tuberculosis complex strains showed that BCG strains underwent repeated human manipulation, had higher region of deletion rates than those of natural M. tuberculosis strains, and lost several essential components such as T-cell epitopes. A total of 188 BCG strain T-cell epitopes were lost to various degrees. The non-virulent BCG Tokyo strain, which has the largest number of T-cell epitopes (359, lost 124. Here we propose that BCG strain protection variability results from different epitopes. This study is the first to present BCG as a model organism for genetics research. BCG strains have a very well-documented history and now detailed genome information. Genome comparison revealed the selection process of BCG strains under human manipulation (1908-1966. CONCLUSIONS: Our results revealed the cause of BCG vaccine strain protection variability at the genome level and supported the hypothesis that the restoration of lost BCG Tokyo epitopes is a useful future vaccine development strategy. Furthermore, these detailed BCG vaccine genome investigation results will be useful in microbial genetics, microbial engineering and other research fields.

  12. Tuberculin reaction, BCG scar, and lower female mortality

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik;

    2006-01-01

    Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in respo......Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar...

  13. Kinetic model of drug distribution in the urinary bladder wall following intravesical instillation.

    Science.gov (United States)

    Grabnar, I; Bogataj, M; Belic, A; Logar, V; Karba, R; Mrhar, A

    2006-09-28

    Intravesical administration of cytotoxic agents is commonly used in urological practice for treatment of superficial bladder cancer. The leading motive is optimisation of drug delivery near the site of action and reduction of systemic toxicity. Bladder pharmacokinetics is complicated by several mechanisms. The objectives of this work were to develop a kinetic model of drug distribution in the bladder wall following intravesical instillation and to study the effect of various parameters on tissue and systemic drug exposure and explore the potential benefits of permeability enhancing effects of chitosan (CH) and polycarbophil (PC) through simulation. Key elements of the model are variable urinary drug concentration due to urine formation and voiding, biphasic diffusion in the bladder tissue and systemic absorption. Model parameters were estimated from bladder-tissue concentration profiles obtained in previous in vitro experiments with pipemidic acid (PPA) as a model drug. The results support further investigations on application of CH and PC in intravesical drug delivery. Both polymers increase permeability of the bladder wall by diffusion enhancement in the urothelium and presumably by improving the contact with the bladder surface. The developed mathematical model could serve for optimisation of intravesical drug delivery and future development of intravesical drug delivery systems.

  14. BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

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    Sofia Fernanda Gonçalves Zorzella-Pezavento

    2013-01-01

    Full Text Available A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65 after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

  15. Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg

    2011-01-01

    A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell) Bordetella pertussis (DTwP). In contrast, similar studies suggest that many African...... females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG) vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium...... phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence...

  16. Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

    Directory of Open Access Journals (Sweden)

    Mogens Helweg Claesson

    2011-01-01

    Full Text Available A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell Bordetella pertussis (DTwP. In contrast, similar studies suggest that many African females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence both the deleterious and beneficial nonspecific effects of immunisation.

  17. Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.

    Directory of Open Access Journals (Sweden)

    Gillian S Dean

    Full Text Available The incidence of bovine tuberculosis (bTB in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission.

  18. Invitro immune responses in children following BCG vaccination

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi V

    2006-01-01

    Full Text Available Introduction: There is still no consensus on the efficacy of BCG vaccine in the prevention of tuberculosis. This study therefore addressed the question of the magnitude of immunity afforded by BCG, by studying the effector mechanisms of protection in children. The main objectives were to assess the degree of immunity conferred by BCG vaccine in children and to identify the most immunogenic antigen(s of BCG by conducting in-vitro studies. Materials and methods: Children in the age-group of 1 to 10 years, were categorized: (A normal, and vaccinated with BCG during the first year, n=45, (B normal, without scar and with no evident history of vaccination, n=31: and (C children admitted in the hospital with a confirmed diagnosis of tuberculosis, n=31. Fractions of BCG were obtained by lysis, sonication, separation by gel chromatography, HPLC and confirmed by SDS-PAGE. In lymphoproliferative assays PBMC were cultured and stimulated with either Concanavalin-A or Tuberculin or the fractions of BCG. Stimulation indices (SI in lymphoproliferation, CD4/CD8 cells, levels of Interferon-γ (IFN- γ in the culture supernatants were measured by ELISA. Results: The vaccinated children displayed significantly high (P< 0.05 mean values of SI in LTT, CD4/CD8 cell ratio against the unfractionated, 67kDa fraction and BCG-CF Ags. While 100% of the vaccinated children had positive lymphoproliferation indices to BCG-CF, only 8.3% of the unvaccinated children were positive. Conclusion: Some of the components of BCG induced a strong Thl cell response in children. These immunogenic antigens were present in the whole cell lysate. The use of BCG vaccine for tuberculosis is worthwhile till a new vaccine is developed.

  19. TO ESTIMATE SERUM ADA LEVELS IN BCG VACCINATED CHILDREN

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    Manjunatha Babu

    2015-04-01

    Full Text Available BACKGROUND: Tuberculosis is an important cause of morbidity and mortality in both adults and children, especially in developing countries. For prevention of childhood tuberculosis, BCG vaccination is advocated. Protection is attained 4 - 6 weeks after BCG vaccination a nd is mainly due to cell mediated immunity. After BCG vaccination almost 12 to 15% of neonates do not develop scar but have positive cell mediated immune response. ADA estimation is simple and inexpensive method to assess the cell mediated immunity. OBJECT IVE: To estimate serum ADA levels in children with and without BCG scar, after receiving BCG vaccination. MATERIAL AND METHODS: This prospective observational study was conducted at a tertiary care hospital for a period of 2 years. Babies in post natal ward and infants up to the age of 12 weeks attending well baby clinic for BCG vaccination were included in the study. Serum ADA lev els were estimated before BCG vaccination and 12 - 14 weeks after the vaccination. ADA levels were estimated by colorimetric method. Presence or absence of BCG scar was noted at 12 - 14 weeks of age. RESULTS: A total of 75 babies followed up, of which only 60 babies noted to have scar and in rest 15 babies there was no scar noticed. Twenty unvaccinated babies at 12 weeks of age were included as controls. The Mean ADA levels are significantly elevated after BCG vaccination (34 . 12 ± 3 . 28 U/L in comparison to le vels before vaccination (12 . 55± 2 . 64 U/L with p value 0. 06. CONCLUSION: After BCG vaccination, there is increase in serum ADA levels indicating adequ ate immunity. Increase in ADA levels in children without scar after BCG vaccination may indicate the probability of adequate immunity.

  20. Bladder uptake of liposomes after intravesical administration occurs by endocytosis.

    Directory of Open Access Journals (Sweden)

    Bharathi Raja Rajaganapathy

    Full Text Available Liposomes have been used therapeutically and as a local drug delivery system in the bladder. However, the exact mechanism for the uptake of liposomes by bladder cells is unclear. In the present study, we investigated the role of endocytosis in the uptake of liposomes by cultured human UROtsa cells of urothelium and rat bladder. UROtsa cells were incubated in serum-free media with liposomes containing colloidal gold particles for 2 h either at 37°C or at 4°C. Transmission Electron Microscopy (TEM images of cells incubated at 37°C found endocytic vesicles containing gold inside the cells. In contrast, only extracellular binding was noticed in cells incubated with liposomes at 4°C. Absence of liposome internalization at 4°C indicates the need of energy dependent endocytosis as the primary mechanism of entry of liposomes into the urothelium. Flow cytometry analysis revealed that the uptake of liposomes at 37°C occurs via clathrin mediated endocytosis. Based on these observations, we propose that clathrin mediated endocytosis is the main route of entry for liposomes into the urothelial layer of the bladder and the findings here support the usefulness of liposomes in intravesical drug delivery.

  1. BCG vaccination at birth and early childhood hospitalization

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Sørup, Signe; Aaby, Peter

    2017-01-01

    vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. METHODS: Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age......-protocol analyses. RESULTS: 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child......BACKGROUND: The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG...

  2. Distinct effector memory CD4+ T cell signatures in latent Mycobacterium tuberculosis infection, BCG vaccination and clinically resolved tuberculosis.

    Science.gov (United States)

    Adekambi, Toidi; Ibegbu, Chris C; Kalokhe, Ameeta S; Yu, Tianwei; Ray, Susan M; Rengarajan, Jyothi

    2012-01-01

    Two billion people worldwide are estimated to be latently infected with Mycobacterium tuberculosis (Mtb) and are at risk for developing active tuberculosis since Mtb can reactivate to cause TB disease in immune-compromised hosts. Individuals with latent Mtb infection (LTBI) and BCG-vaccinated individuals who are uninfected with Mtb, harbor antigen-specific memory CD4(+) T cells. However, the differences between long-lived memory CD4(+) T cells induced by latent Mtb infection (LTBI) versus BCG vaccination are unclear. In this study, we characterized the immune phenotype and functionality of antigen-specific memory CD4(+) T cells in healthy BCG-vaccinated individuals who were either infected (LTBI) or uninfected (BCG) with Mtb. Individuals were classified into LTBI and BCG groups based on IFN-γ ELISPOT using cell wall antigens and ESAT-6/CFP-10 peptides. We show that LTBI individuals harbored high frequencies of late-stage differentiated (CD45RA(-)CD27(-)) antigen-specific effector memory CD4(+) T cells that expressed PD-1. In contrast, BCG individuals had primarily early-stage (CD45RA(-)CD27(+)) cells with low PD-1 expression. CD27(+) and CD27(-) as well as PD-1(+) and PD-1(-) antigen-specific subsets were polyfunctional, suggesting that loss of CD27 expression and up-regulation of PD-1 did not compromise their capacity to produce IFN-γ, TNF-α and IL-2. PD-1 was preferentially expressed on CD27(-) antigen-specific CD4(+) T cells, indicating that PD-1 is associated with the stage of differentiation. Using statistical models, we determined that CD27 and PD-1 predicted LTBI versus BCG status in healthy individuals and distinguished LTBI individuals from those who had clinically resolved Mtb infection after anti-tuberculosis treatment. This study shows that CD4(+) memory responses induced by latent Mtb infection, BCG vaccination and clinically resolved Mtb infection are immunologically distinct. Our data suggest that differentiation into CD27(-)PD-1(+) subsets in

  3. Distinct effector memory CD4+ T cell signatures in latent Mycobacterium tuberculosis infection, BCG vaccination and clinically resolved tuberculosis.

    Directory of Open Access Journals (Sweden)

    Toidi Adekambi

    Full Text Available Two billion people worldwide are estimated to be latently infected with Mycobacterium tuberculosis (Mtb and are at risk for developing active tuberculosis since Mtb can reactivate to cause TB disease in immune-compromised hosts. Individuals with latent Mtb infection (LTBI and BCG-vaccinated individuals who are uninfected with Mtb, harbor antigen-specific memory CD4(+ T cells. However, the differences between long-lived memory CD4(+ T cells induced by latent Mtb infection (LTBI versus BCG vaccination are unclear. In this study, we characterized the immune phenotype and functionality of antigen-specific memory CD4(+ T cells in healthy BCG-vaccinated individuals who were either infected (LTBI or uninfected (BCG with Mtb. Individuals were classified into LTBI and BCG groups based on IFN-γ ELISPOT using cell wall antigens and ESAT-6/CFP-10 peptides. We show that LTBI individuals harbored high frequencies of late-stage differentiated (CD45RA(-CD27(- antigen-specific effector memory CD4(+ T cells that expressed PD-1. In contrast, BCG individuals had primarily early-stage (CD45RA(-CD27(+ cells with low PD-1 expression. CD27(+ and CD27(- as well as PD-1(+ and PD-1(- antigen-specific subsets were polyfunctional, suggesting that loss of CD27 expression and up-regulation of PD-1 did not compromise their capacity to produce IFN-γ, TNF-α and IL-2. PD-1 was preferentially expressed on CD27(- antigen-specific CD4(+ T cells, indicating that PD-1 is associated with the stage of differentiation. Using statistical models, we determined that CD27 and PD-1 predicted LTBI versus BCG status in healthy individuals and distinguished LTBI individuals from those who had clinically resolved Mtb infection after anti-tuberculosis treatment. This study shows that CD4(+ memory responses induced by latent Mtb infection, BCG vaccination and clinically resolved Mtb infection are immunologically distinct. Our data suggest that differentiation into CD27(-PD-1(+ subsets in LTBI is

  4. Effect of oral cephalexin in the treatment of BCG lymphadenitis.

    Science.gov (United States)

    Ayazi, Parviz; Mahyar, Abolfazl; Taremiha, Alireza; Ghorani, Najmeh; Esmailzadehha, Neda

    2014-06-01

    Lymphadenitis and abscess formation are the most common side effects of vaccination with Bacille Calmette Guerin (BCG). The lower the child's age at the time of vaccination, the higher the incidence of BCG lymphadenitis tends to be. Although various therapeutic approaches are in use for the treatment of BCG lymphadenitis, there is no consensus on which of them is optimal. This study aimed to determine whether oral cephalexin treatment hastens recovery from BCG lymphadenitis. The study involved 40 children (24 boys and 16 girls) with BCG lymphadenitis who were referred to Qazvin Children's Hospital, Qazvin University of Medical Sciences between December 2008 and the end of September 2009. The patients were randomly assigned to two groups of 20 patients each (12 boys and 8 girls in each group): group A patients did not receive any treatment and served as controls, and group B patients were treated with 50 mg/kg/day cephalexin syrup, administered in four doses, for 10 days. In all patients, clinical examination was normal, except for lymphadenitis. In all patients, BCG vaccination had been performed at birth, and polymerase chain reaction tests were positive for tuberculous bacilli. The recovery period and requirement of fine needle aspiration did not significantly differ between the two groups (P 0.05). This study showed that treatment with cephalexin does not hasten recovery from BCG lymphadenitis.

  5. Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+CD56(bright cells.

    Directory of Open Access Journals (Sweden)

    Damien Portevin

    Full Text Available Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.

  6. Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

    Directory of Open Access Journals (Sweden)

    JoĂŤl Pestel

    2008-06-01

    Full Text Available Mycobacterium bovis bacillus Calmette-GuĂŠrin (BCG is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

  7. High efficacy of intravesical treatment of metformin on bladder cancer in preclinical model.

    Science.gov (United States)

    Peng, Mei; Su, Qiongli; Zeng, Qing; Li, Le; Liu, Zhihong; Xue, Lei; Cheng, Yan; Huang, Yanjun; Tao, Ting; Lv, Hongwei; Li, Xiaohui; Tao, Xiaojun; Guo, Peng; Chen, Alex F; Yang, Xiaoping

    2016-02-23

    Anticancer potential of metformin has been extensively studied. However, its anticancer clinical use remains yet to be approved since sufficient concentration on target organs could not be achieved via conventional administration. To overcome this drawback, we aim to examine the efficiency of novel intravesical treatment of metformin on syngeneic orthotopic preclinical model. Three human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. AMPK pathway including AKT, Erk and S6K was examined by western blot and further explored by regulating activated levels using specific inhibitors. In vivo efficacy was determined by Kaplan-Meier survival curves and measurements of body and bladder weights plus tumor biomarkers. Lactic acid and metformin levels of plasma were measured by standard procedures. The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk. Furthermore, combinations of metformin with either Akt or Erk inhibitors synergistically diminished cancer proliferation, suggesting the involvement of Akt- and Erk- related pathways. Intravesical metformin 26 and 104 mg/kg, twice per week demonstrated a rapid elimination of the implanted tumor without any evidence of toxicity. In contrast, oral treatment at a dose of 800mg/kg/d exhibited little efficacy whereas severe toxicity existed if the dosage is higher. Collectively, intravesical metformin displays potent inhibition on bladder cancer in vitro and this preclinical study reveals the profound therapeutic application of metformin with durable tolerance via intravesical administration route.

  8. Visualized intravesical floating hydrogel encapsulating vaporized perfluoropentane for controlled drug release.

    Science.gov (United States)

    Zhu, Guanchen; Zhang, Yifan; Wang, Kaikai; Zhao, Xiaozhi; Lian, Huibo; Wang, Wei; Wang, Haoran; Wu, Jinhui; Hu, Yiqiao; Guo, Hongqian

    2016-10-01

    Intravesical drug delivery is the main strategy for the treatment of bladder disorders. To reduce the relief arising from frequent intravesical instillation, mucoadhesive hydrogel was used for the controlled release of the drug. However, the viscosity of mucoadhesive gel might cause severe urinary obstruction and bladder irritation. To solve all these problems, a floating hydrogel delivery system was developed using perfluoropentane (PFP) as the floating agent. After intravesical instillation of the floating hydrogel, the increased temperature in bladder vaporized PFP, resulting in the generation of microbubbles in the hydrogel. Then, it can float in urine to avoid the urinary obstruction and bladder irritation. In this study, systematic experiments were conducted to investigate the influences of PFP vaporization on the morphology and floating ability of hydrogels. The floating process is much milder and safer than other floating methods published before. In addition, PFP had been used as contrast agent, which affiliated the monitoring of gels during the operation. Therefore, this new drug delivery system addresses the problems of conventional intravesical instillation and is promising for clinic use.

  9. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis

    NARCIS (Netherlands)

    Bade, JJ; Nieuwenburg, A; vanderWeele, LT; Mensink, HJA

    1997-01-01

    Objective To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC). Patients and methods Twenty patients who fullfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study; 10

  10. BCG Induced Necrosis of the Entire Bladder Urothelium

    Directory of Open Access Journals (Sweden)

    Malte Krönig

    2015-09-01

    Full Text Available Instillation therapy with attenuated tuberculosis bacteria (BCG can significantly reduce rates of recurrence of non-muscle invasive bladder cancer. Local and systemic side effects such as dysuria, irritative voiding symptoms or partial bladder contracture and systemic inflammation were reported. A 75 year-old male patient with recurrent non muscle invasive bladder cancer developed necrosis of the entire bladder urothelium more than six years after BCG instillation immunotherapy. The resulting irritative voiding symptoms and low bladder capacity required radical cystectomy. BCG instillation can cause severe side effects, which develop gradually and eventually need radical surgical therapy such as cystectomy without tumor recurrence.

  11. Hubungan antara Pembentukan Scar Vaksin BCG dan Kejadian Infeksi Tuberkulosis

    Directory of Open Access Journals (Sweden)

    Fajriah Rosandali

    2016-08-01

    Full Text Available AbstrakTuberkulosis adalah penyakit menular yang disebabkan oleh kuman Mycobacterium tuberculosis. Orang dewasa yang menderita tuberkulosis sangat mudah menularkan kuman TB kepada orang disekitarnya terutama pada anak-anak. Salah satu cara pencegahan penyakit tuberkulosis adalah pemberian imunisasi BCG pada saat bayi baru lahir. Scar vaksin BCG dapat terbentuk setelah penyuntikan, kadang Scar tidak terbentuk setelah penyuntikan. Tujuan penelitian ini adalah menentukan hubungan antara pembentukan Scar vaksin BCG dan kejadian infeksi tuberkulosis. Penelitian ini menggunakan desain cross sectional dengan jumlah subjek sebanyak 80 orang. Pengambilan data berupa melakukan pengamatan terhadap Scar pada lengan atas serta wawancara kepada responden dengan menggunakan pedoman wawancara. Kemudian data ditabulasi dalam bentuk persentase dan dianalisis dengan uji chi-square . Hasil penelitian menunjukan bahwa responden yang terbanyak adalah perempuan dan usia yang terbanyak 35-44 tahun. Terdapat hubungan yang bermakna antara pembentukan Scar  vaksin BCG dengan kejadian infeksi tuberkulosis (p < 0,05. Disimpulkan bahwa terdapat pengaruh antara pembentukan Scar vaksin BCG terhadap kejadian infeksi tuberkulosis.Kata kunci: tuberkulosis, vaksin BCG, Scar. AbstractTuberculosis is an infectious disease caused by Mycobacterium tuberculosis with the number of sufferers tend to increase every years. Adults who suffer  tuberculosis is very easy to spread it to around, especially to children. One of the way to prevent tuberculosis is immunization of BCG vaccine which given since infant. The Scar of BCG vaccine can formed after injection or not. The objective of this study was to determine the relation of BCG vaccine Scar formation on  the incidence of tuberculosis infection.This research used a cross sectional design with 80 total subjects. The data was collected by observations of the scar on the upper arm while interviewed  respondents using interview guide

  12. [Modifications by BCG of the mortality of the irradiated mouse].

    Science.gov (United States)

    Allain, P; Chaleil, D; Maingot, D; Larra, F

    1976-01-01

    Freeze-dried Bacillus Calmette Guerin (B.C.G.) of Institut Pasteur was given by intravenous route to mice at 1,2 and 4 mg/kg before and after gamma irradiation of animals by 1 000 rad. B.C.G. 1 mg/kg injected the day or the day after irradiation has a protective effect (mortality reduced from 77% for controls to 58% and 50% for treated mice). B.C.G. given before irradiation in single or double doses increased mortality.

  13. Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: a contemporary evaluation

    Directory of Open Access Journals (Sweden)

    Mary E. Westerman

    Full Text Available ABSTRACT Introduction: Hemorrhagic cystitis (HC represents a challenging clinical entity. While various intravesical agents have been utilized in this setting, limited data exist regarding safety or efficacy. Herein, then, we evaluated the effectiveness and complications associated with intravesical alum instillation for HC in a contemporary cohort. Materials and Methods: We identified 40 patients treated with intravesical alum for HC between 1997-2014. All patients had failed previous continuous bladder irrigation with normal saline and clot evacuation. Treatment success was defined as requiring no additional therapy beyond normal saline irrigation after alum instillation. Results: Median patient age was 76.5 years (IQR 69, 83. Pelvic radiation was the most common etiology for HC (n=38, 95%. Alum use decreased patient's transfusion requirement, with 82% (32/39 receiving a transfusion within 30 days before alum instillation (median 4 units versus 59% (23/39 within 30 days after completing alum (median 3 units (p=0.05. In total, 24 patients (60% required no additional therapy prior to hospital discharge. Moreover, at a median follow-up of 17 months (IQR 5, 38.5, 13 patients (32.5% remained without additional treatment for HC. Adverse effects were reported in 15 patients (38%, with bladder spasms representing the most common event (14/40; 35%. No clinical evidence of clinically significant systemic absorption was detected. Conclusion: Intravesical alum therapy is well-tolerated, with resolution of HC in approximately 60% of patients, and a durable response in approximately one-third. Given its favorable safety/efficacy profile, intravesical alum may be considered as a first-line treatment option for patients with HC.

  14. The Abell 85 BCG: a nucleated, core-less galaxy

    CERN Document Server

    Madrid, Juan P

    2016-01-01

    New high-resolution r band imaging of the brightest cluster galaxy (BCG) in Abell 85 (Holm 15A) was obtained using the Gemini Multi Object Spectrograph. These data were taken with the aim of deriving an accurate surface brightness profile of the BCG of Abell 85, in particular its central region. The new Gemini data show clear evidence of a previously unreported nuclear emission that is evident as a distinct light excess in the central kiloparsec of the surface brightness profile. We find that the light profile is never flat nor does it present a downward trend towards the center of the galaxy. That is, the new Gemini data show a different physical reality from the featureless, "evacuated core" recently claimed for the Abell 85 BCG. After trying different models, we find that the surface brightness profile of the BCG of Abell 85 is best fit by a double Sersic model.

  15. Attrition of T-cell functions and simultaneous upregulation of inhibitory markers correspond with the waning of BCG-induced protection against tuberculosis in mice.

    Directory of Open Access Journals (Sweden)

    Subhadra Nandakumar

    Full Text Available Mycobacterium bovis bacille Calmette-Guérin (BCG is the most widely used live attenuated vaccine. However, the correlates of protection and waning of its immunity against tuberculosis is poorly understood. In this study, we correlated the longitudinal changes in the magnitude and functional quality of CD4(+ and CD8(+ T-cell response over a period of two years after mucosal or parenteral BCG vaccination with the strength of protection against Mycobacterium tuberculosis in mice. The BCG vaccination-induced CD4(+ and CD8(+ T cells exhibited comparable response kinetics but distinct functional attributes in-terms of IFN-γ, IL-2 and TNF-α co-production and CD62L memory marker expression. Despite a near life-long BCG persistence and the induction of enduring CD4(+ T-cell responses characterized by IFN-γ and/or TNF-α production with comparable protection, the protective efficacy waned regardless of the route of vaccination. The progressive decline in the multifactorial functional abilities of CD4(+ and CD8(+ T cells in-terms of type-1 cytokine production, proliferation and cytolytic potential corresponded with the waning of protection against M. tuberculosis infection. In addition, simultaneous increase in the dysfunctional and terminally-differentiated T cells expressing CTLA-4, KLRG-1 and IL-10 during the contraction phase of BCG-induced response coincided with the loss of protection. Our results question the empirical development of BCG-booster vaccines and emphasize the pursuit of strategies that maintain superior T-cell functional capacity. Furthermore, our results underscore the importance of understanding the comprehensive functional dynamics of antigen-specific T-cell responses in addition to cytokine polyfunctionality in BCG-vaccinated hosts while optimizing novel vaccination strategies against tuberculosis.

  16. Attrition of T-cell functions and simultaneous upregulation of inhibitory markers correspond with the waning of BCG-induced protection against tuberculosis in mice.

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Posey, James E; Amara, Rama Rao; Sable, Suraj B

    2014-01-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most widely used live attenuated vaccine. However, the correlates of protection and waning of its immunity against tuberculosis is poorly understood. In this study, we correlated the longitudinal changes in the magnitude and functional quality of CD4(+) and CD8(+) T-cell response over a period of two years after mucosal or parenteral BCG vaccination with the strength of protection against Mycobacterium tuberculosis in mice. The BCG vaccination-induced CD4(+) and CD8(+) T cells exhibited comparable response kinetics but distinct functional attributes in-terms of IFN-γ, IL-2 and TNF-α co-production and CD62L memory marker expression. Despite a near life-long BCG persistence and the induction of enduring CD4(+) T-cell responses characterized by IFN-γ and/or TNF-α production with comparable protection, the protective efficacy waned regardless of the route of vaccination. The progressive decline in the multifactorial functional abilities of CD4(+) and CD8(+) T cells in-terms of type-1 cytokine production, proliferation and cytolytic potential corresponded with the waning of protection against M. tuberculosis infection. In addition, simultaneous increase in the dysfunctional and terminally-differentiated T cells expressing CTLA-4, KLRG-1 and IL-10 during the contraction phase of BCG-induced response coincided with the loss of protection. Our results question the empirical development of BCG-booster vaccines and emphasize the pursuit of strategies that maintain superior T-cell functional capacity. Furthermore, our results underscore the importance of understanding the comprehensive functional dynamics of antigen-specific T-cell responses in addition to cytokine polyfunctionality in BCG-vaccinated hosts while optimizing novel vaccination strategies against tuberculosis.

  17. Intravesical cidofovir to treat BK virus-associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Rascon, Jelena; Verkauskas, Gilvydas; Pasauliene, Ramune; Zubka, Vytautas; Bilius, Vytautas; Rageliene, Lina

    2015-06-01

    HC related to BK virus replication might be a severe complication following allogeneic HSCT. There are no clearly defined treatment guidelines in pediatric population. The data on the effectiveness of ICI to manage severe bleeding in children are very limited. We report our experience of intravesical cidofovir in four children, 6-15 yr of age, to manage grade III-IV BK virus-associated HC. Three of four children had high CSA serum level prior to developing cystitis. Intravesical instillations of cidofovir resulted only in temporal relief of bleeding. After immune suppression was withdrawn or tapered, intravesical instillations of formalin solution had to be undertaken to abort severe bleeding. We concluded that intravesical cidofovir alone did not appear to be sufficiently effective in case of severe HC, necessitating complimentary procedures to stop macrohematuria.

  18. SIMULTANEOUS SMALLPOX AND B.C.G. VACCINATION IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Nyoman Kumara Rai

    2012-09-01

    Full Text Available Vaksinasi cacar dan BCG mulai diberikan secara simultan di Jawa dan Bali pada bulan April 1972 vaksinasi cacar diberikan pada lengan kiri dan BCG pada lengan kanan. Secara berangsur-angsur prograi ini kemudian diperluas kedaerah luar Jawa-Bali, sehingga pada akhir tahun 1973 sudah mencakup seluruh Indonesia. Tenaga yang digunakan adalah para juru cacar yang sudah ada dalam rangka proyek pembasmian penyakit cacar yang dimulai tahun 1968, dan terdapat hampir disemua kecamatan diseluru Indonesia. Ide untuk menggabungkan kedua jenis vaksinasi ini yang kebetulan mempunyai target sam (anak2 0 - 14 thn  timbul setelah penderita cacar tidak dilaporkan lagi dibulan September 1971 (ternyata kemudian letusan cacar terakhir adalah dibulan Desember 1971. Sampai saat itu vaksina BCG dilakukan oleh petugas Puskesmas dan tenaga part timer. Ternyata target tidak pernah tercapa hal ini mungkin disebabkan oleh terbatasnya waktu yang tersedia untuk melakukan vaksinasi BCC sehingga para tenaga part timer tsb. hanya mampu mencakup daerah disekitar Puskesmas dan sekolah dasar. Sebelumnya telah diadakan dua trial; yang pertama diadakan di Bandung untuk melihat at tidaknya saling pengaruh mempengaruhi antara kedua jenis vaksin cacar dan BCG bila diberikan pat saat yang bersamaan, sedangkain trial kedua dilakukan untuk menilai kemampuan juru cacar dala melaksanakan vaksinasi BCG serta kesukaran! yang dijumpai dilapangan (masing2 didua kabupaten (Jawa Tengah, Timur dan Yogyakarta. Disamping keuntungan yang diperoleh dari penggabungan kedua jenis vaksinasi ini yakni penghematan tenaga, biaya dan waktu, dijumpai juga beberapa kesukaran antara lain pengumpulan anak2, supply vaksin BCG yang tidak teratur dll. Walaupun demikian, di Jawa dan Bali hasil vaksinasi BCG antara April 1972 sampai dengan April 1973 menunjukkan kenaikan out-put leb dari 4 kali lipat bila dibandingkan dengan out-put sebelum penggabungan, meskipun out-put prin vaksinasi cacar mempunyai tendensi menurun

  19. Disseminated BCG infection in a patient with severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Han, Tae Il [Eulji University School of Medicine, Taejon (Korea, Republic of); Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2000-06-01

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.

  20. Disseminated BCG Infection in a patient with Severe Combined Immunodeficiency

    OpenAIRE

    Han, Tae Il; Kim, In-One; Kim, Woo Sun; Yeon, Kyung Mo

    2000-01-01

    Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) vaccination is a very rare disorder, occurring mostly in patients with immunologic deficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.

  1. [Pulmonal bacillus Calmette-Guérin infection two years after intravesical bacillus Calmette-Guérin installation].

    Science.gov (United States)

    Harbjerg, Julie Lykke; Bjerre, Cathrine Collin; Lillebæk, Troels; Weinreich, Ulla Møller

    2014-12-15

    Major complications following installation of bacillus Calmette Guérin (BCG) in the bladder as treatment for early stage cancer are rare and there are only few reports of BCG isolated from patients with suspected "BCGitis". We report a case where sputum culture yielded a BCG strain identical to one used two years earlier to treat the patient's bladder cancer. Some aspects were challenging in differential diagnosis: the patient's prior history of pulmonary tuberculosis ten years earlier and a two-year interval since BCG installation. PCR analysis and culture finally provided the diagnosis disseminated BCG infection.

  2. SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

    Directory of Open Access Journals (Sweden)

    Abdul Rivai

    2012-09-01

    Full Text Available Telah dikemukakan anggapan-anggapan yang terdapat dewasa ini tentang vaksinasi BCG dan cacar secara simultan. Telah dilakukan vaksinasi BCG dan cacar secara simultan pada 729 neonati dengan freeze dried Smallpox vaccine buatan dari Bio Farma dan freeze dried BCG vaccine Tokyo. Pencacaran dilakukan secara multiple puncture dan bifurcated needle dengan suntikan BCG dengan jarum dan spuit khusus intracutan dengan dosis 0,1 ml. Tuberkulin test dilakukan dengan PPD dari Kopenhagen dengan kekuatan 2 TU 9 minggu setelah vaksinasi. Dari 741 bayi yang diikut sertakan dalam survey, 12 menolak, 3 bayi tidak dapat dilakukan pemeriksaan pertama, 35 bayi belum diperiksa, pemeriksaan pertama telah dilakukan pada 691 bayi. Dari 406 bayi yang seharusnya sudah diperiksa untuk pemeriksaan kedua, 23 dapat dilakukan karena tidak dapat dijumpai atau meninggal. Telah dikemukakan bahwa pencatatan alamat yang jelas dan lengkap serta kesungguhan dalam melakukan home visits sangat penting untuk berhasilnya penyelidikan semacam ini. Dari hasil-hasil yang didapatkan sampai sekarang telah dapat diambil kesimpulan sementara, bahwa vaksinasi BCG dan cacar secara simultan memberikan hasil yang memuaskan, juga bila dibandingkan dengan hasil-hasil penyelidikan diluar negeri take pada pencacaran 99.4 percent, test tuberkulin dengan PPD 2 TU 9 minggu setelah vaksinasi memberikan indurasi lebih dari 5 mm pada 99.75 percent dan tidak menimbulkan komplikasi-komplikasi. Pelaksanaan vaksinasi BCG dan cacar dapat dilakukan oleh tenaga paramedis yang telah mendapat latihan khusus dan diawasi oleh dokter yang kompeten. Dianjurkan untuk melakukan follow up pada bayi-bayi yang diikut sertakan dalam survey ini.

  3. Fatal complication of intravesical formalin during control of intractable hemorrhage from radiation cystitis

    Energy Technology Data Exchange (ETDEWEB)

    Rao, M.S.; Singhal, P.C.; Bapna, B.C.; Vaidyanathan, S.; Chugh, K.S.; Bhat, V.N.; Dutta, T.K.; Gupta, C.L.

    1978-06-01

    Fatal acute tubular necrosis occurred in 1 patient in whom intravesical formalin was used to control massive persistent hemorrhage from radiation cystitis. A suggestion is made to monitor blood formic acid levels and institute prompt dialysis whenever these exceed 80 mg per 100 ml to avert such a catastrophe. Intravenous sodium bicarbonate appears to be indicated prophylactically in combating the associated metabolic acidosis due to absorbed formic acid.

  4. Intravesical instillation of pentosan polysulfate encapsulated in a liposome nanocarrier for interstitial cystitis.

    Science.gov (United States)

    Lander, Elliot B; See, Jackie R

    2014-01-01

    We determined the effect of intravesical instillation of pentosan polysulfate encapsulated in liposomes for refractory interstitial cystitis patients. This was an open label uncontrolled study. Subjects were recruited from a private urology practice. Inclusion criteria included patients who met NIDDK criteria for Interstitial Cystitis (IC) and who were responding poorly to conventional treatments. Exclusion criteria included evidence of a urinary tract infection, bladder cancer, or other forms of chronic cystitis. Patients received 400 mg of Pentosan Polysulfate (PP) encapsulated into liposomes as an intravesical instillation performed every 2 weeks for 3 months. Baseline and post treatment outcome measures were obtained that included the O'Leary-Sant Interstitial Cystitis Symptom and Problem Questionnaire and the Pelvic Pain and Urgency/Frequency Patient symptom Scale tests. A total of 37 instillations were used and no adverse events occurred. Clinically significant decreases in symptom scores greater than 50% were seen in virtually all outcome measures at 3 month follow up. All subjects reported remarkable subjective improvement in pain symptoms marked by decreased use of narcotics and increased enjoyment of daily activities. No patients developed systemic symptoms or poor tolerance of the instillations. Intravesical Pentosan Polysulfate encapsulated into liposomes can significantly decrease frequency, urgency, pain and improve quality of life for two months after deployment. Additional studies are needed to determine cellular effects of glycosaminoglycan restoration, ideal doses, dosing intervals, safety and cost-effectiveness of this therapy.

  5. Intravesical Botulinum Toxin for Persistent Autonomic Dysreflexia in a Pediatric Patient

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    Gina Lockwood

    2016-01-01

    Full Text Available Introduction. We present a novel case of persistent autonomic dysreflexia in a pediatric spinal cord injury patient treated successfully with intravesical botulinum toxin. Study Design. A retrospective chart review of one patient seen at the Children’s Hospital of Wisconsin from 2006 to 2012 was performed. Results. A pediatric spinal cord injury patient with known neurogenic bladder presented with severe hypertension consistent with autonomic dysreflexia. His symptoms and hypertension did not improve with conservative measures, and he necessitated ICU admission and antihypertensive drips. He was taken to the operating room for intravesical botulinum toxin for refractory bladder spasms. Following this, his symptoms abated, and he was weaned off IV antihypertensives and returned to his baseline state. His symptoms were improved for greater than six months. Conclusions. There are few treatment options for the management of refractory autonomic dysreflexia. Intravesical botulinum toxin has never been reported for this use. Dedicated research is warranted to assess its efficacy, as it was used successfully to abort autonomic dysreflexia in this patient.

  6. Intravesical Dimethyl Sulfoxide Inhibits Acute and Chronic Bladder Inflammation in Transgenic Experimental Autoimmune Cystitis Models

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    Ronald Kim

    2011-01-01

    Full Text Available New animal models are greatly needed in interstitial cystitis/painful bladder syndrome (IC/PBS research. We recently developed a novel transgenic cystitis model (URO-OVA mice that mimics certain key aspects of IC/PBS pathophysiology. This paper aimed to determine whether URO-OVA cystitis model was responsive to intravesical dimethyl sulfoxide (DMSO and if so identify the mechanisms of DMSO action. URO-OVA mice developed acute cystitis upon adoptive transfer of OVA-specific OT-I splenocytes. Compared to PBS-treated bladders, the bladders treated with 50% DMSO exhibited markedly reduced bladder histopathology and expression of various inflammatory factor mRNAs. Intravesical DMSO treatment also effectively inhibited bladder inflammation in a spontaneous chronic cystitis model (URO-OVA/OT-I mice. Studies further revealed that DMSO could impair effector T cells in a dose-dependent manner in vitro. Taken together, our results suggest that intravesical DMSO improves the bladder histopathology of IC/PBS patients because of its ability to interfere with multiple inflammatory and bladder cell types.

  7. A Pilot Study on Intravesical Administration of Curcumin for Cystitis Glandularis

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    Qiong Lu

    2013-01-01

    Full Text Available Cystitis glandularis (CG is a proliferative disorder in the urinary bladder. The outcome of current treatments in some patients is not satisfactory. Curcumin, a herbal medicine that has been used for centuries, has shown great potential in treating various diseases. Our pilot study aimed to explore the feasibility of an intravesical treatment for CG using curcumin. 14 patients diagnosed with CG that remained symptomatic after primary treatments were enrolled, underwent a 3-month curcumin intravesical treatment (50 mg/50 mL, 1 hour, once per week for first 4 weeks and once per month for next 2 months and were followed up for 3 months. Efficacy of the treatment was evaluated using core lower urinary tract symptom score (CLSS questionnaire. 10 patients demonstrated persistent improvement in symptoms up to the end of the 6-month study. Their CLSS decreased significantly after the 3-month treatment (6.0±0.8; P<0.01 from the baseline (10.5±1.6 and maintained decreasing till the end of the study (6.2±0.7; P<0.01. 4 patients were classified as nonresponders. Our study suggests the feasibility of further randomized controlled trials on curcumin intravesical treatment in CG patients who remain symptomatic after primary treatments.

  8. Evaluating the need for transurethral bladder biopsy at first follow up after intravesical BCG therapy for superficial bladder cancer: Preliminary data

    Directory of Open Access Journals (Sweden)

    K. Mursi

    2012-03-01

    Conclusion: Until more studies on larger numbers of patients are done, a routine biopsy from the site of previously resected tumor at the time of check cystoscopy may improve the detection of tumor recurrence.

  9. Comparative Proteomic Profiling of Mycobacterium bovis and BCG Vaccine Strains

    KAUST Repository

    Gao, Ge

    2013-09-01

    BCG is the only licensed human vaccine currently available against TB. Derived from a virulent strain of M. bovis, the vaccine was thought to have struck a balance between reduced virulence and preserved immunogenicity. Nowadays, BCG vaccine strains used in different countries and vaccination programs show clear variations in their genomes and immune protective properties. The aim of this study was to characterize the proteomic profile on Mycobacterium bovis and five BCG strains Pasteur, Tokyo, Danish, Phipps and Birkhaug by Tandem Mass Tag® (TMT®)-labeling quantitative proteomic approach. In total, 420 proteins were identified and 377 of them were quantitated for their relative abundance. We reported the number and relationship of differential expressed proteins in BCG strains compared to M. bovis and investigated their functions by bioinformatics analysis. Several interesting up-regulated and down-regulated protein targets were found. The identified proteins and their quantitative expression profiles provide a basis for further understanding of the cellular biology of M. bovis and BCG vaccine strains, and hopefully would assist in the design of better anti-TB vaccine and drugs.

  10. BCG vaccination reduces risk of tuberculosis infection in vaccinated badgers and unvaccinated badger cubs.

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    Stephen P Carter

    Full Text Available Wildlife is a global source of endemic and emerging infectious diseases. The control of tuberculosis (TB in cattle in Britain and Ireland is hindered by persistent infection in wild badgers (Meles meles. Vaccination with Bacillus Calmette-Guérin (BCG has been shown to reduce the severity and progression of experimentally induced TB in captive badgers. Analysis of data from a four-year clinical field study, conducted at the social group level, suggested a similar, direct protective effect of BCG in a wild badger population. Here we present new evidence from the same study identifying both a direct beneficial effect of vaccination in individual badgers and an indirect protective effect in unvaccinated cubs. We show that intramuscular injection of BCG reduced by 76% (Odds ratio = 0.24, 95% confidence interval (CI 0.11-0.52 the risk of free-living vaccinated individuals testing positive to a diagnostic test combination to detect progressive infection. A more sensitive panel of tests for the detection of infection per se identified a reduction of 54% (Odds ratio = 0.46, 95% CI 0.26-0.88 in the risk of a positive result following vaccination. In addition, we show the risk of unvaccinated badger cubs, but not adults, testing positive to an even more sensitive panel of diagnostic tests decreased significantly as the proportion of vaccinated individuals in their social group increased (Odds ratio = 0.08, 95% CI 0.01-0.76; P = 0.03. When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79% (Odds ratio = 0.21, 95% CI 0.05-0.81; P = 0.02.

  11. Enhancement of Leishmania amazonensis infection in BCG non-responder mice by BCG-antigen specific vaccine

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    Kátia da Silva Calabrese

    1992-01-01

    Full Text Available Different patterns of cutaneous leishmaniasis can be induced when a challenge of alike dose of Leishmania amazonensis amastigotes in various inbred strains was applied. Two strains of mice, the Balb/c and C57 BL/10J, showed exceptional suscepbility, and 10(elevado a sexta potência amastigotes infective dose lead, to ulcerative progressive lesions with cutaneous metastasis and loss by necrosis of leg on wich the footpad primary lesion occured. Lesions were also progressive but in a lower degree when C3H/HeN and C57BL/6 were infected. Lesions progress slowly in DBA/2 mice presenting lesions wich reach a discreet peack after 12 weeks, do not heal but do not uncerate. DBA/2 mice is, therefore, a good model for immunomodualtion. In attempt to determine the influence of BCG in vaccination schedule using microsomal fraction, DBA/2 became an excellent model, since it is also a non-responder to BCG. Vaccination of DBA/2 mice, receiving the same 10(elevado a sexta potência BCG viable dose and 10 *g or 50 *g of protein content of microsomal fraction, lead to a progressive disease with time course similar to those observed in susceptible non-vaccinated C57BL/10J mice after 6 months of observation. An enhancement of infection in BCG non-responder mice suggests that use of BCG as immunostimulant in humans could be critical for both vaccination and immunoprophylactic strategies.

  12. Different effects of BCG strains - A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau

    DEFF Research Database (Denmark)

    Frankel, H; Byberg, S; Andersen, Morten Bjerregaard;

    2016-01-01

    models. Scar prevalence and size were compared using binomial regression and ranksum tests. RESULTS: Among 1206 children, 18% received Danish BCG (n=215) and 82% Russian BCG (n=991). The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60-1.46) for Danish BCG compared with Russian BCG......BACKGROUND: Different Bacillus Calmette-Guerin (BCG) vaccine strains may have different non-specific effects. We assessed the effect of two BCG strains (Danish and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau. METHODS: During 2011-2013, infants in the Bandim Health Project....... Girls vaccinated with Danish BCG tended to have lower consultation rates compared with girls vaccinated with Russian BCG (aHR 0.56 (0.25-1.24)), whereas the effect was opposite for boys (aHR 1.24 (0.74-2.11)), p=0.09. Children vaccinated with Danish BCG were more likely to develop a scar (97%) than...

  13. BCG vaccination scar associated with better childhood survival in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Gustafson, Per; Nhaga, Alexandro

    2005-01-01

    Recent studies have suggested that Bacille Calmette-Guerin (BCG) vaccination may have a non-specific beneficial effect on infant survival and that a BCG scar may be associated with lower child mortality. No study has previously examined the influence of BCG vaccination on cause of death....

  14. ROLE OF ADJUVANT INTRAVESICAL CHEMOTHERAPY IN THE COMBINED ORGAN-SPARING TREATMENT OF NON-MUSCLE-INVASIVE BLADDER CANCER

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    A. Yu. Zubko

    2014-01-01

    Full Text Available Objective: to enhance the efficiency of combined treatment for non-muscle-invasive bladder cancer ((NMIBC and to assess the results of its treatment using transurethral resection (TUR as monotherapy and in combination with intravesical adjuvant chemotherapy (CT.Subjects and methods. The results of treatment were analyzed in 59 patients with NMIBC. Twenty-two patients underwent TUR in Group 1; TUR and single intravesical injection of drugs were performed in 19 patients in Group 2; 18 patients had TUR and long-term intravesical CT.Results and discussion. The recurrence rates were 59.1, 57.9, and 38.89 % in Groups 1, 2, and 3, respectively. Intravesical CT was found to appreciably affect the prevention of recurrence in the area of resection. The rate of this recurrence was 31.81, 26.32, and 5.56 % in Groups 1, 2, and 3, respectively. Conclusion. Adjuvant intravesical chemotherapy CT is an effective method to prevent recurrent bladder cancer.

  15. UPEC biomimickry at the urothelial barrier: lectin-functionalized PLGA microparticles for improved intravesical chemotherapy.

    Science.gov (United States)

    Neutsch, Lukas; Wambacher, Michael; Wirth, Eva-Maria; Spijker, Sylvia; Kählig, Hanspeter; Wirth, Michael; Gabor, Franz

    2013-06-25

    The urgent demand for more potent treatment schedules in bladder cancer (BCa) therapy calls for a refinement of the intravesical administration modalities. However, progress on drug delivery systems tailored to the penetration-hostile urothelial barrier lags behind the advancements in comparable fields. This study reports on a multimodal, carrier-based delivery concept that combines biorecognitive targeting with modified release strategies for improved intravesical chemotherapy. The plant lectin wheat germ agglutinin (WGA) was immobilized on poly(lactide-co-glycolide) (PLGA) microparticles (MP) to induce stable cytoadhesion via cellular carbohydrate chains, similar to the specific attachment mechanism utilized by uropathogenic bacteria. A panel of DNA-selective chemotherapeutics with established track record in uro-oncology was screened for physicochemical compatibility with the polymeric carrier formulation. Critical limitations in encapsulation efficiency were found for mitomycin C (MMC), doxorubicin (DOX), and gemcitabine hydrochloride (GEM), despite multiparametric optimization of the preparation conditions. In contrast, the amphiphilic 4-(N)-stearoyl prodrug of gemcitabine (GEM-C18) exhibited excellent processability with PLGA. In vitro bioassays on 5637 human BCa cells showed that the enhanced cytoadhesion of WGA-GEM-C18-PGLA-MP traces back to the specific lectin/carbohydrate interaction, and is not easily disrupted by adverse environmental factors. Owing to several synergistic effects, the combined prodrug/targeting approach resulted in strong cytostatic response even when adjusting the exposure scheme to the confined temporal conditions of instillative treatment. Our results highlight the importance of fine-tuning both pharmacokinetic and pharmacologic parameters to gain adequate impact on urothelial cancer cells, and assign promising potential to glycan-targeted delivery concepts for the intravesical route.

  16. Immunological mechanisms of intravesical chitosan/interleukin-12 immunotherapy against murine bladder cancer

    Science.gov (United States)

    2017-01-01

    ABSTRACT There is a critical unmet clinical need for bladder cancer immunotherapies capable of inducing durable antitumor immunity. We have shown that four intravesical treatments with a simple co-formulation of interleukin-12 and the biopolymer chitosan not only destroy orthotopic bladder tumors, but also promote a potent long-lasting systemic immune response as evidenced through tumor-specific in vitro killing assays, complete protection from rechallenge, and abscopal antitumor responses at distant non-treated tumors. This study investigates the immunological kinetics underlying these results. We show through depletion studies that CD8+ T cells are required for initial tumor rejection, but CD4+ T cells protect against rechallenge. We also show that even a single intravesical treatment can eliminate tumors in 50% of mice with 6/9 and 7/8 mice eliminating tumors after three or four treatments respectively. We then performed immunophenotyping studies to analyze shifts in immune cell populations after each treatment within the tumor itself as well as in secondary lymphoid organs. These studies demonstrated an initial infiltration of macrophages and granulocytes followed by increased CD4+ and CD8+ effector-memory cells. This was coupled with a decreased level of regulatory T cells in peripheral lymph nodes as well as decreased myeloid-derived suppressor cell infiltration in the bladder. Taken together, these data demonstrate the ability of properly delivered interleukin-12-based therapies to engage adaptive immunity within the tumor itself as well as throughout the body and strengthen the case for clinical translation of chitosan/interleukin-12 as an intravesical treatment for bladder cancer.

  17. Factors Associated with Therapeutic Efficacy of Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Syndrome.

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    Sheng-Mou Hsiao

    Full Text Available To analyze the predictors of therapeutic efficacy after intravesical botulinum toxin A injection for overactive bladder syndrome (OAB refractory to antimuscarinic therapy.All consecutively OAB patients, who visited the urologic outpatient clinics of a medical center and refractory to antimuscarinic treatment, were prospectively enrolled. All enrolled patients received intravesical injection of 100 U onabotulinumtoxinA (Botox. The Global Response Assessment (GRA score ≥ 2 at 3 months after Botox injection was defined as a successful treatment, otherwise failed.Overall, 89 patients received intravesical injection. Eighty patients, including 42 men and 38 women, had received follow-up at 3 months. The overall success rate was 63.8%. The global response assessment, urgency severity score, urgency, urgency urinary incontinence and frequency episodes, and functional bladder capacity improved after treatment. However, post-void residual volume (PVR increased, and voiding efficiency (VE decreased after treatment. Female gender (odds ratio = 3.75 was the only independent factor associated with the success. Female gender (coefficient = 0.74, low baseline overactive bladder symptoms score (coefficient = -0.12 and the presence of OAB-wet (coefficient = 0.79 were independent factors associated with therapeutic efficacy (i.e., GRA score. VE (odds ratio = 0.062 was the only predictor for a large PVR at 3 months. The optimum cutoff value of VE was <87% with the area under the ROC curve being 0.64 (sensitivity = 63.8%, specificity = 57.1%.The therapeutic effects of Botox can persist till 6 months after treatment. Female gender, low overactive bladder symptoms score and OAB-wet are associated better therapeutic efficacy, and low baseline VE is associated with large PVR. These findings can serve as an initial guide or assist in consultation regarding the treatment of OAB patients with Botox injection.ClinicalTrials.gov NCT01657409.

  18. EFFECT OF INTRAVESICAL PROSTATIC PROTRUSION (IVPP ON LOWER URINARY TRACT FUNCTION AND MANAGEMENT

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    Rajaraman T

    2016-07-01

    Full Text Available AIMS AND OBJECTIVES To correlate Intravesical Prostatic Protrusion (IVPP with International Prostate Symptoms Score (IPSS, Quality of Life Index (QOL, Uroflowmetry, Post Void Urine (PVR and Pressure Flow Study (PFS and to assess whether the presence and increasing grades of Intravesical prostatic protrusion are directly correlated with the severity of Bladder outlet obstruction due to Benign prostatic hypertrophy. MATERIALS AND METHODS Non-randomized prospective cohort study, conducted in Department of Urology, Govt. Stanley Hospital, from June 2012 to June 2015, on a sample of 100 patients with IVPP. IVPP was correlated with IPSS, Quality of life index, Uroflowmetry, Effects of drug therapy, Response to surgical therapy. Response of patients with Intravesical prostatic protrusion of same grade to surgical therapy and drug therapy are compared to decide which modality of management is best. RESULTS The incidence of IVPP in patients presenting with LUTS due to BPH is 1 in 5. Majority present with grade 2 IVPP. The increasing grades of IVPP are significantly directly correlated with IPSS score, Q-max and Post void residual. Statistical analysis showed IVPP to correlate significantly with BOO. TURP showed a very good and significant mean decrease of IPSS and Q-max, whereas those who had medical treatment showed only a mean decrease of 2 in IPSS score and 1 in Q-max. CONCLUSION The increasing grades of IVPP are significantly directly correlated with IPSS score max and Post void residual. IVPP have a very good positive and negative predictive value and also a good accuracy rate in comparison with all other parameters in predicting the BOO. The surgical intervention statistically proved to be superior to medical treatment in IVPP patients.

  19. Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter.

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    Vítor S Fernandes

    Full Text Available According to previous observations nitric oxide (NO, as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE and cystathionine β-synthase (CBS, measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS and the H2S donor P-(4-methoxyphenyl-P-4-morpholinylphosphinodithioic acid (GYY4137 evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS with, respectively, PPG and NG-nitro-L-arginine (L-NOARG, greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA desensitization with capsaicin and blockade of ATP-dependent K+ (KATP channels, transient receptor potential A1 (TRPA1, transient receptor potential vanilloid 1 (TRPV1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP and calcitonin gene-related peptide (CGRP receptors with glibenclamide, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission

  20. Inhibitory effect of BCG cell-wall skeletons (BCG-CWS) emulsified in squalane on tumor growth and metastasis in mice.

    Science.gov (United States)

    Yoo, Yung Choon; Hata, Katsusuke; Lee, Kyung Bok; Azuma, Ichiro

    2002-08-01

    The antimetastatic effect of BCG-CWS, which was emulsified in an oil-in-water form with either Drakeol 6VR mineral oil (BCG-CWS/DK) or squalane (BCG-CWS/SQA), on lung metastasis produced by highly metastatic murine tumor cells, Colon26-M3.1 carcinoma cells and B16-BL6 melanoma cells, was investigated in syngeneic mice. An intravenous (i.v.) administration of BCG-CWS (100 mg/mouse) 1 day after tumor inoculation significantly inhibited tumor metastasis of both Colon26-M3.1 carcinoma and B16-BL6 melanoma cells in experimental lung metastasis models. No differences in the antitumor activity of the two oil-based formulations (BCG-CWS/DK and BCG-CWS/SQA) were obverved. However, BCG-CWS/SQA administered through subcutaneous (s.c.) route was shown to be effective only when it was consecutively injected (3 times) after tumor inoculation. An in vivo analysis for tumor-induced angiogenesis showed that a single i.v. administration of BCG-CWS/SQA inhibited the number of tumor-induced blood vessels and suppressed tumor growth. Furthermore, the multiple administration of BCG-CWS/SQA given at on week intervals led to a significant reduction in spontaneous lung metastasis of B16-BL6 melanoma cells in a spontaneous metastasis model. These results suggest that BCG-CWS emulsified with squalane is a potent inhibitory agent of lung metastasis, and that the antimetastatic effect of BCG-CWS is related to the suppression of tumor growth and the inhibition of tumor-induced angiogenesis.

  1. Oral delivery of BCG Moreau Rio de Janeiro gives equivalent protection against tuberculosis but with reduced pathology compared to parenteral BCG Danish vaccination.

    Science.gov (United States)

    Clark, Simon O; Kelly, Dominic L F; Badell, Edgar; Castello-Branco, Luiz Roberto; Aldwell, Frank; Winter, Nathalie; Lewis, David J M; Marsh, Philip D

    2010-10-08

    There is a need for an improved vaccine to better control human tuberculosis (TB), as the only currently available TB vaccine, bacillus Calmette-Guerin (BCG) delivered parenterally, offers variable levels of efficacy. Therefore, recombinant strains expressing additional antigens are being developed alongside alternative routes to parenteral delivery. There is strong evidence that BCG Moreau (RdJ) is a safe and effective vaccine in humans when given by the oral route. This study compared the efficacy of a single oral dose of wild type BCG Moreau Rio de Janeiro (RdJ), or a recombinant RdJ strain expressing Ag85B-ESAT6 fusion protein, formulated with and without lipid to enhance oral delivery, with subcutaneous BCG Danish 1331 and saline control groups in a guinea pig aerosol infection model of pulmonary tuberculosis. Protection was measured as survival at 30 weeks post-challenge and reduced bacterial load and histopathology in lungs and spleen. Results showed that a single oral dose of BCG Moreau (RdJ) or recombinant BCG Moreau (RdJ)-Ag85B-ESAT6, formulated with or without lipid, gave protection equivalent to subcutaneously delivered BCG Danish in the 30 weeks post-challenge survival study. The orally delivered vaccines gave reduced pathology scores in the lungs (three of the four formulations) and spleens (all four formulations) compared to subcutaneously delivered BCG Danish. The oral wild type BCG Moreau (RdJ) in lipid and the unformulated oral wild type BCG Moreau (RdJ) vaccine also gave statistically lower bacterial loads in the lungs and spleens, respectively, compared to subcutaneously delivered BCG Danish. This study provides further evidence to show that lipid formulation does not impair vaccine efficacy and may enhance the delivery and stability of oral vaccines intended for use in countries with poor health infrastructure. Oral delivery also avoids needles (and associated cross-infection risks) and immunisation without the need for specially trained

  2. Local skin reaction following an accidental injection from a BCG vaccine in a healthcare worker

    Directory of Open Access Journals (Sweden)

    Kundan Mittal

    2011-02-01

    Full Text Available Exposure to blood-borne pathogens from sharp injuriescontinue to pose a significant risk to healthcare workers(HCW. The number of sharps injuries sustained by HCW is stillunclear, primarily due to under-reporting of events.Healthcare professionals are at risk of sustaining such injuriesfrom hollow-bore needles. Sharps injuries are associated withrisk of infection with blood-borne pathogens such as humanimmunodeficiency virus (HIV, hepatitis B virus (HBV hepatitisC virus (HCV and other live organisms. Here we are reportinga case of an adverse reaction in a HCW due to an accidentalsharps injury by a needle used to administer the BacillusCalmittee Gurien (BCG vaccine.

  3. Effectiveness of BCG Vaccination in Prevention of Childhood Tuberculosis: A Prospective Study from Kishanganj, Bihar

    Directory of Open Access Journals (Sweden)

    Kashif Shahnawaz, Goutam Sarkar, Palash Das, Mausumi Basu, Biman Roy

    2013-01-01

    Full Text Available Introduction: BCG vaccine has shown consistently high efficacy against childhood tubercular meningitis and miliary tuberculosis and other mycobacterial diseases. It is considered to be a safe vaccine with a low incidence of adverse effects. Efficacy of BCG vaccine found in different clinical trials is variable in different geography. Objectives: Study was done to assess the efficacy of BCG vac-cine. Materials and Methods: All the children who were less than three years of age and were previously BCG vaccinated and not-vaccinated, were included in this study. A total of sixty (60 vaccinated children and sixty non-vaccinated children were selected. These children were followed up prospectively for 24 months, at the end of which, it was seen whether they developed tuberculosis or not. Results: Out of these 60 children in both the cases and control groups, total number of BCG vaccinated children who developed TB were 4 (i.e. 6.6% and total number of Non-BCG vaccinated children who developed TB were 12 (i.e. 20%. Thus, the efficacy of BCG vaccine calculated in our study was 67%. Conclusion: Most studies in different parts of the world have shown that the efficacy of BCG vaccine varies from zero to eigh-ty percent. This study favors the efficacy of BCG vaccine. This vaccination strategy will be favorable for our children. Creation of awareness among the parents and family members for an early administration of BCG vaccine after child birth can be recom-mended.

  4. Late-onset granulomatous prostatitis following intravesical bacille Calmette-Guerin therapy: case report

    Directory of Open Access Journals (Sweden)

    Octavio Castillo Cádiz

    2016-06-01

    Full Text Available Resumen El bacilo de Calmette-Guerin es el tratamiento intravesical más efectivo para disminuir la recurrencia de los carcinomas uroteliales no-músculo-invasivos. La aplicación de este tratamiento en ocasiones puede presentar efectos secundarios y, excepcionalmente, complicaciones graves. La prostatitis granulomatosa es un hallazgo histológico frecuente pero una entidad rara desde el punto de vista clínico. Se presenta el caso de un paciente de 75 años, diabético tipo 2, que fue diagnosticado de carcinoma in situ vesical, para lo cual inició tratamiento con bacilo de Calmette-Guerin intravesical. El paciente consultó cinco años después por presentar cuadro de nicturia, frecuencia miccional aumentada, urgencia miccional grave y dolor perineal intenso y recurrente asociado a una curva de antígeno prostático específico con marcada elevación. Se le realizó biopsia prostática que mostró una prostatitis crónica granulomatosa de grado moderado a grave relacionada a bacilo de Calmette-Guerin. El paciente recibió esquema antituberculoso completo con buena respuesta clínica.

  5. Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection in Patients with Detrusor Hyperactivity and Impaired Contractility

    Directory of Open Access Journals (Sweden)

    Chung-Cheng Wang

    2016-03-01

    Full Text Available We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with detrusor hyperactivity and impaired contractility (DHIC. Twenty-one patients with urodynamically proven DHIC and 21 age-matched patients with overactive bladder (OAB with urodynamic detrusor overactivity were treated with intravesical injections of 100 U of onabotulinumtoxinA. The overactive bladder symptom score, urgency severity score, patient perception of bladder condition, global response assessment, voiding diary, and procedure-related adverse events (AE at baseline, two weeks, one, three, and six months after treatment were assessed. The results showed that the subjective symptom scores improved significantly in both groups, and the scores did not differ between the groups. The decrease in urgency episodes and urgency urinary incontinence were noted in OAB patients but not in DHIC patients. Although the incidence of AEs was comparable between the groups, the therapeutic efficacy lasted for a mean of 4.9 ± 4.8 months in DHIC patients and 7.2 ± 3.3 months in OAB patients (p = 0.03. We concluded that the efficacy of intravesical onabotulinumtoxinA injection for DHIC patients was limited and short-term. Nevertheless, AEs did not increase in DHIC. Intravesical onabotulinumtoxinA might not be a good indication in patients with DHIC and high post-voiding residual urine. Physicians should inform patients of the potential benefits and risks of onabotulinumtoxinA injection for treatment of DHIC.

  6. Cytokines as effectors and predictors of responses in the treatment of bladder cancer by bacillus Calmette-Guérin.

    Science.gov (United States)

    Liu, Xiaoxuan; Dowell, Alexander C; Patel, Prashant; Viney, Richard P; Foster, Michael C; Porfiri, Emilio; James, Nicholas D; Bryan, Richard T

    2014-06-01

    The most effective intravesical treatment of non-muscle-invasive bladder cancer is instillation of live Mycobacterium bovis bacillus Calmette-Guérin (BCG). BCG stimulates the release of cytokines, contributing directly or indirectly to its effectiveness. However, the function of specific cytokines is not well understood. We have undertaken a nonsystematic review of primary evidence regarding cytokine detection, activation and response in BCG patients. Cytokines IL-2, IL-8 and TNF-α appear to be essential for effective BCG therapy and nonrecurrence, while IL-10 may have an inhibitory effect on BCG responses. IL-2, IL-8, TRAIL and TNF-α are potentially predictive of response to BCG. Alterations in genes encoding cytokines may also affect responses. There are significant data showing the association of certain cytokines with successful BCG treatment, and which may be useful predictive markers. Isolating those cytokines mediating efficacy may hold the key to ameliorating BCG's side effects and improving efficacy and patient compliance.

  7. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    Science.gov (United States)

    Bacalhau, Sílvia; Freitas, Cristina; Valente, Rosalina; Barata, Deolinda; Neves, Conceição; Schäfer, Katrin; Lubatschofski, Annelie; Schulz, Ansgar; Neves, João Farela

    2011-01-01

    In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highlighting the specific strategies adopted. PMID:22110512

  8. Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Sílvia Bacalhau

    2011-01-01

    Full Text Available In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID who developed disseminated BCG disease, highlighting the specific strategies adopted.

  9. Low Dose BCG Infection as a Model for Macrophage Activation Maintaining Cell Viability

    Directory of Open Access Journals (Sweden)

    Leslie Chávez-Galán

    2016-01-01

    Full Text Available Mycobacterium bovis BCG, the current vaccine against tuberculosis, is ingested by macrophages promoting the development of effector functions including cell death and microbicidal mechanisms. Despite accumulating reports on M. tuberculosis, mechanisms of BCG/macrophage interaction remain relatively undefined. In vivo, few bacilli are sufficient to establish a mycobacterial infection; however, in vitro studies systematically use high mycobacterium doses. In this study, we analyze macrophage/BCG interactions and microenvironment upon infection with low BCG doses and propose an in vitro model to study cell activation without affecting viability. We show that RAW macrophages infected with BCG at MOI 1 activated higher and sustained levels of proinflammatory cytokines and transcription factors while MOI 0.1 was more efficient for early stimulation of IL-1β, MCP-1, and KC. Both BCG infection doses induced iNOS and NO in a dose-dependent manner and maintained nuclear and mitochondrial structures. Microenvironment generated by MOI 1 induced macrophage proliferation but not MOI 0.1 infection. In conclusion, BCG infection at low dose is an efficient in vitro model to study macrophage/BCG interactions that maintains macrophage viability and mitochondrial structures. This represents a novel model that can be applied to BCG research fields including mycobacterial infections, cancer immunotherapy, and prevention of autoimmunity and allergies.

  10. The immunological effects of oral polio vaccine provided with BCG vaccine at birth

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Karkov, Hanne Sophie; Lund, Najaaraq

    2014-01-01

    BACKGROUND: Vaccines may have non-specific effects. An observational study from Guinea-Bissau suggested that oral polio vaccine at birth (OPV0) provided with Bacillus Calmette-Guérin (BCG) vaccine was associated with down-regulation of the immune response to BCG vaccine 6 weeks later. Based...... BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen...

  11. Protective capacity of proteoliposomes from Mycobacterium bovis BCG in a mouse model of tuberculosis

    Science.gov (United States)

    Tirado, Yanely; Puig, Alina; Alvarez, Nadine; Borrero, Reinier; Aguilar, Alicia; Camacho, Frank; Reyes, Fatima; Fernández, Sonsire; Pérez, José Luis; Espinoza, Dulce Mata; Payán, Jorge Alberto Barrios; Sarmiento, María Elena; Norazmi, Mohd-Nor; Hernández-Pando, Rogelio; Acosta, Armando

    2015-01-01

    Tuberculosis (TB) is one of the most important causes of mortality and morbidity due to infectious diseases. BCG, the vaccine in use, is not fully protective against TB. In a previous study, we have shown that proteoliposomes (outer membrane extracts), obtained from BCG (PLBCG) were able to induce humoral immune responses against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLBCG alone or as a booster with BCG, a murine model of progressive pulmonary TB was used. Animals immunized with PLBCG adjuvanted with alum (PLBCG-Al) showed similar protection to that conferred by BCG. The group immunized with PLBCG-Al as a booster to BCG gave superior protection than BCG as evidenced by a reduction of bacterial load in lungs 2 months after infection with Mtb. Animals immunized with BCG, PLBCG-Al and this formulation as a booster of BCG, showed a significant decrease of tissue damage (percentage of pneumonic area/lung) compared with non-immunized animals. These results demonstrate that immunization with PLBCG-Al alone or as a booster to BCG induce appropriate protection against challenge with Mtb in mice and support the future evaluation of PLBCG as a promising vaccine candidate against Mtb. PMID:25671612

  12. Protective capacity of proteoliposomes from Mycobacterium bovis BCG in a mouse model of tuberculosis.

    Science.gov (United States)

    Tirado, Yanely; Puig, Alina; Alvarez, Nadine; Borrero, Reinier; Aguilar, Alicia; Camacho, Frank; Reyes, Fatima; Fernández, Sonsire; Pérez, José Luis; Espinoza, Dulce Mata; Payán, Jorge Alberto Barrios; Sarmiento, María Elena; Norazmi, Mohd-Nor; Hernández-Pando, Rogelio; Acosta, Armando

    2015-01-01

    Tuberculosis (TB) is one of the most important causes of mortality and morbidity due to infectious diseases. BCG, the vaccine in use, is not fully protective against TB. In a previous study, we have shown that proteoliposomes (outer membrane extracts), obtained from BCG (PLBCG) were able to induce humoral immune responses against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLBCG alone or as a booster with BCG, a murine model of progressive pulmonary TB was used. Animals immunized with PLBCG adjuvanted with alum (PLBCG-Al) showed similar protection to that conferred by BCG. The group immunized with PLBCG-Al as a booster to BCG gave superior protection than BCG as evidenced by a reduction of bacterial load in lungs 2 months after infection with Mtb. Animals immunized with BCG, PLBCG-Al and this formulation as a booster of BCG, showed a significant decrease of tissue damage (percentage of pneumonic area/lung) compared with non-immunized animals. These results demonstrate that immunization with PLBCG-Al alone or as a booster to BCG induce appropriate protection against challenge with Mtb in mice and support the future evaluation of PLBCG as a promising vaccine candidate against Mtb.

  13. Clostridium perfringens enterotoxin as a potential drug for intravesical treatment of bladder cancer.

    Science.gov (United States)

    Gabig, Theodore G; Waltzer, Wayne C; Whyard, Terry; Romanov, Victor

    2016-09-16

    The current intravesical treatment of bladder cancer (BC) is limited to a few chemotherapeutics that show imperfect effectiveness and are associated with some serious complications. Thus, there is an urgent need for alternative therapies, especially for patients with high-risk non-muscle invasive (NMIBC). Clostridium perfringens enterotoxin (CPE), cytolytic protein binds to its receptors: claudin 3 and 4 that are expressed in epithelial cells. This binding is followed by rapid cell death. Claudin 4 is present in several epithelial tissue including bladder urothelium and its expression is elevated in some forms of BC. In addition to directly targeting BC cells, binding of CPE to claudins increases urothelium permeability that creates conditions for better accession of the tumor. Therefore, we evaluated CPE as a candidate for intravesical treatment of BC using a cellular model. We examined cytotoxicity of CPE against BC cells lines and 3D cultures of cells derived from surgical samples. To better elucidate cellular mechanisms, activated by CPE and to consider the use of CPE non-toxic fragment (C-CPE) for combination treatment with other drugs we synthesized C-CPE, compared its cytotoxic activity with CPE and examined claudin 4 expression and intracellular localization after C-CPE treatment. CPE induced cell death after 1 h in low aggressive RT4 cells, in moderately aggressive 5637 cells and in the primary 3D cultures of BC cells derived from NMIBC. Conversely, non-transformed urothelial cells and cells derived from highly aggressive tumor (T24) survived this treatment. The reason for this resistance to CPE might be the lower expression of CLDNs or their inaccessibility for CPE in these cells. C-CPE treatment for 48 h did not affect cell viability in tested cells, but declined expression of CLDN4 in RT4 cells. C-CPE increased sensitivity of RT4 cells to Mitommycin C and Dasatinib. To better understand mechanisms of this effect we examined expression and

  14. Vacina BCG contra tuberculose: efeito protetor e políticas de vacinação BCG vaccine against tuberculosis: its protective effect and vaccination policies

    Directory of Open Access Journals (Sweden)

    Susan M Pereira

    2007-09-01

    Full Text Available OBJETIVO: A vacina BCG é utilizada desde 1921, embora ainda apresente controvérsias e aspectos não esclarecidos. O objetivo do artigo foi analisar aspectos relacionados ao efeito protetor da primeira e segunda doses da vacina BCG e as políticas de vacinação adotadas. MÉTODOS: Foi realizada revisão sistemática da literatura publicada em inglês e espanhol, abrangendo o período compreendido entre 1948 e 2006, na base PubMed. Os principais descritores utilizados foram BCG vaccine, BCG efficacy, BCG e tuberculosis. Os estudos foram agrupados por tipo de desenho, apresentando-se separadamente os principais resultados de ensaios clínicos, estudos de caso-controle e metanálises. RESULTADOS: O efeito protetor da primeira dose da vacina BCG contra a tuberculose na forma miliar ou na meningite é elevado. No entanto, os resultados são discordantes em relação à forma pulmonar, variando de ausência de efeito a níveis próximos a 80%. Estão sendo conduzidas pesquisas sobre novas vacinas candidatas a substituir a BCG ou serem utilizadas como reforço. CONCLUSÕES: Há evidências de que a segunda dose da BCG não aumenta o seu efeito protetor. Apesar de seus limites e da expectativa futura de nova vacina para tuberculose, a vacina BCG mantém-se como importante instrumento no controle dos efeitos danosos da doença, sobretudo em países com taxas de incidência médias e elevadas.OBJECTIVE: The BCG vaccine has been in use since 1921, but still arouses controversy and uncertainties. The objective was to analyze the protective effect of the BCG vaccine in its first and second doses and the accompanying vaccination policies. METHODS: A systematic review of the literature in both English and Spanish was carried out, covering the period 1948 to 2006, using the PubMed database. The main search terms used included BCG vaccine, BCG efficacy, BCG and tuberculosis. The studies were grouped by design, with the main results from the clinic tests, case

  15. Production of BCG alginate-PLL microcapsules by emulsification/internal gelation.

    Science.gov (United States)

    Esquisabel, A; Hernández, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

    1997-01-01

    A biocompatible emulsification method for microencapsulation of live cells and enzymes within a calcium alginate matrix applied to Bacillus Calmette-Guérin (BCG) has been developed. Small-diameter alginate beads (microcapsules) were formed via internal gelation of an alginate solution emulsified within vegetable oil. Five different oils (sesame, sweet almond, perhydrosqualene, camomile and jojoba) were used. The rheological analysis of the oils showed a Newtonian behaviour, with viscosities = 30.0, 37.7, 51.2, 59.3 and 67.1 mPa.s for perhydrosqualene, jojoba, camomile, sesame and sweet almond oil respectively. The particle size of the microcapsules obtained ranged from 30.3 microns for the microcapsules prepared with sweet almond oil to 57.0 microns for those made with perhydrosqualene. The mean particle diameter obtained was found to be dependent on the viscosity of the oil employed, according to the equation: phi (micron) = 76.6-0.628 eta (mPa.s) (r2 = 0.943). The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Freeze-drying of the microcapsules was carried out to ensure their stability during storage. Two batches of microcapsules (those prepared with sesame and jojoba oil) and four types of cryoprotectors (glucose, trehalose, mannitol and sorbitol), at three concentration levels (5, 10 and 20% w/v) were studied. The parameters evaluated were particle size, physical appearance, reconstitution of lyophilizates and microscopical evaluation. For both batches of microcapsules the best results were obtained with trehalose 5%, showing particle sizes of 42.1 microns in the case of the microcapsules prepared with sesame oil, and of 45.3 microns for those prepared with jojoba.

  16. Measurement of intravesical and rectal pressures simultaneously with electromyography of anal sphincter in children with myelomeningocele.

    Science.gov (United States)

    van Gool, J D; de Ridder, A L; Kuijten, R H; Donckerwolcke, R A; Tiddens, H A

    1976-06-01

    This paper reports a technique for simultaneous measurement of intravesical pressure, intra-abdominal pressure, electromyographic activity of the external and sphincter and urinary flow. Using this technique during filling of the bladder and during micturition in 38 children with myelomeningocele and neurogenic bladder disturbance, it was possible to identify four main types of bladder dysfunction in these children. Once the type of bladder dysfunction is established for each child, adequate management can be planned far in advance of the detection of inherent upper urinary tract damage. This is particularly important in children with upper somatomotor lesions of bladder innervation in which detrusor-spincter dyssynergia may be present; this dyssynergia always causes some degree of obstruction at the level of the external urethral sphincter and is a constant threat to renal function.

  17. Late-onset granulomatous prostatitis following intravesical bacille Calmette-Guerin therapy: case report.

    Science.gov (United States)

    Castillo Cádiz, Octavio; Villasenín Parrado, Lorena; Borgna Christie, Vincenzo; Gallegos Méndez, Iván; Martínez Corta, Virginia

    2016-06-20

    Bacille Calmette-Guerin intravesical treatment is the most effective treatment for reducing the recurrence of non-muscle-invasive urothelial carcinomas. This treatment can sometimes have side effects and serious complications. Granulomatous prostatitis is a common histological finding but it rarely has a clinical presentation. We report a case of a 75-year-old, type 2 diabetic, male patient who was diagnosed with urothelial in situ carcinoma, for which he began treatment with Bacille Calmette-Guerin instillations. Five years later the patient presented nocturia, pollakiuria, severe urgency, and intense and recurrent perineal pain associated with marked elevation of prostatic specific antigen. A prostatic biopsy was performed that showed a moderate to severe granulomatous prostatitis related to bacille Calmette-Guerin. The patient received full antituberculosis combination drugs with a favorable clinical response.

  18. Photodynamic diagnosis following intravesical instillation of aminolevulinic acid (ALA): first clinical experiences in urology

    Science.gov (United States)

    Baumgartner, Reinhold; Kriegmair, M.; Stepp, Herbert G.; Lumper, W.; Heil, Peter; Riesenberg, Rainer; Stocker, Susanne; Hofstetter, Alfons G.

    1993-06-01

    Delta Aminolevulinic acid (ALA), a precursor of Protoporphyrin IX (PP IX) in hem biosynthesis has been topically applied in urinary bladders in order to study its potential as fluorescent tumor marker. Preclinical experiments have been performed on chemically induced tumors in rats, revealing a ratio of PP IX-fluorescence intensity up to 20:1 in tumors as compared to healthy urothelium. Synthesis of PP IX has been stimulated in 56 patients by intravesical instillation of a pH-neutral ALA-solution. After an incubation time of two to four hours strong red fluorescence was endoscopically observed even in tiny superficial tumors. Brightness and contrast allows visualization of early stage urothelial diseases with naked eyes and without the necessity suppressing background fluorescence or violet excitation light.

  19. Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

    Science.gov (United States)

    Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

    2008-11-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation.

  20. Uptake of newly introduced universal BCG vaccination in newborns.

    LENUS (Irish Health Repository)

    Braima, O

    2010-06-01

    Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

  1. Uptake of newly introduced universal BCG vaccination in newborns.

    LENUS (Irish Health Repository)

    Braima, O

    2012-01-31

    Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

  2. Cutaneous complication after BCG vaccination: Case report and review of the literature

    NARCIS (Netherlands)

    Keijsers, R.R.M.C.; Bovenschen, H.J.; Seijger, M.M.B.

    2011-01-01

    Abstract The bacille Calmette-Gu?rin (BCG) vaccination protects against tuberculosis (TB)-related meningitis and disseminated tuberculosis. While severe complications after BCG vaccination are relatively rare, different cutaneous reactions have been reported. We report a patient with a 7-mm erythema

  3. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2016-01-01

    Full Text Available Yu Zhang,1,* Linguo Xie,1,* Tao Chen,1,* Wanqin Xie,2 Zhouliang Wu,1 Hao Xu,1 Chen Xing,1 Nan Sha,1 Zhonghua Shen,1 Yunkai Qie,1 Xiaoteng Liu,1 Hailong Hu,1 Changli Wu1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 2Key Laboratory of Genetics and Birth Health of Hunan Province, The Family Planning Research Institute of Hunan Province, Changsha, People’s Republic of China *These authors contributed equally to this work Objective: The management of stage 1 and grade 3 (T1G3 bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after

  4. Construction of EGFP-tagged rBCG of E.tenella and distribution in chickens

    Institute of Scientific and Technical Information of China (English)

    WANG QiuYue; LI JianHua; ZHANG XiChen; LIU ChengWu; CAO LiLi; REN KeYan; GONG PengTao; CAI YaNan

    2009-01-01

    Chicken coccidiosis is a major parasitic disease with substantial economic burden to the poultry in-dustry. Enhanced green fluorescent protein (EGFP) tagged recombinant Bacille Calmette-Guerin (rBCG), as a fusion protein with coccidian rhomboid antigen was constructed to track rBCG in vivo in chickens in this study. Immunization of chickens with one dose of rBCG pMV361-Rho/EGFP induced humoral immune response. The colonization of rBCG in liver, spleen, lung, kidney and caecum was observed by laser confocal microscopy. Real-time quantitative RT-PCR showed s rise expression level of rhomboid protein on the 7th day and a peak on the 14th day and disappearance on the 28th day after immunization. These results have significant implications for the development of rBCG vaccines against avian coccidiosis.

  5. Nonspecific effect of BCG vaccination at birth on early childhood infections

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Birk, Nina Marie; Nørrelykke Nissen, Thomas

    2016-01-01

    BackgroundChildhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via non-specific effects.MethodsA randomized, clinical multicenter trial. All women planning to give birth (n = 16521) at the three study sites were invited during the recruitment...... vaccinated. From 3 to 13 months there were 7028 vs. 6791 events, IRR = 1.02 (0.97 to 1.07).ConclusionsThis study did not find a non-specific public health benefit of BCG on parent reported infections. BCG may have reduced the incidence of infections in children of BCG vaccinated mothers during the first 3...... period. Participating children were randomized to receive BCG within seven days of birth or to a no intervention control group. Parent reported infections (events) were collected using telephone interviews at 3 and 13 months. Data collectors were blinded to allocation.ResultsThe analyses included 4224...

  6. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960.

    Science.gov (United States)

    Brimnes, Niels

    2011-02-01

    Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.

  7. Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Saied Mostaan

    2016-01-01

    Full Text Available Although in the last two decades the World Health Organization (WHO has introduced tuberculosis as “a threat to global”, the vaccination with the Mycobacterium bovis Bacillus Calmette-Guerin (BCG is the only way for the prevention of this fatal infectious disease. Despite of the efficacy of BCG vaccine especially against infants' meningitis, it has still some limitations due to a variety of adverse effects. Many studies have evaluated the side effects of different strains of BCG vaccines in different countries. In Iran, some studies have been done so far to evaluate the adverse effects of 1173 P2 strain which is used for BCG vaccination. Each of these studies have used different standardization and sampling methods. This review will survey all studies that have been published about adverse effects of 1173 P2 strain of BCG vaccine in Iran using data mining methods.

  8. Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis

    Science.gov (United States)

    Mostaan, Saied; Yazdanpanah, Bahador; Moukhah, Rasool; Hozouri, Hamid Reza; Rostami, Manouchehr; Khorashadizadeh, Mohsen; Zerehsaz, Javad; Mahabadi, Ramin Pirhajati; Saadi, Arya; Khanahmad, Hossein; Pooya, Mohammad

    2016-01-01

    Although in the last two decades the World Health Organization (WHO) has introduced tuberculosis as “a threat to global”, the vaccination with the Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the only way for the prevention of this fatal infectious disease. Despite of the efficacy of BCG vaccine especially against infants’ meningitis, it has still some limitations due to a variety of adverse effects. Many studies have evaluated the side effects of different strains of BCG vaccines in different countries. In Iran, some studies have been done so far to evaluate the adverse effects of 1173 P2 strain which is used for BCG vaccination. Each of these studies have used different standardization and sampling methods. This review will survey all studies that have been published about adverse effects of 1173 P2 strain of BCG vaccine in Iran using data mining methods. PMID:27376038

  9. Construction of EGFP-tagged rBCG of E.tenella and distribution in chickens

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Chicken coccidiosis is a major parasitic disease with substantial economic burden to the poultry industry.Enhanced green fluorescent protein(EGFP) tagged recombinant Bacille Calmette-Guerin(rBCG),as a fusion protein with coccidian rhomboid antigen was constructed to track rBCG in vivo in chickens in this study.Immunization of chickens with one dose of rBCG pMV361-Rho/EGFP induced humoral immune response.The colonization of rBCG in liver,spleen,lung,kidney and caecum was observed by laser confocal microscopy.Real-time quantitative RT-PCR showed a rise expression level of rhomboid protein on the 7th day and a peak on the 14th day and disappearance on the 28th day after immunization.These results have significant implications for the development of rBCG vaccines against avian coccidiosis.

  10. Pre-clinical development of BCG.HIVA(CAT, an antibiotic-free selection strain, for HIV-TB pediatric vaccine vectored by lysine auxotroph of BCG.

    Directory of Open Access Journals (Sweden)

    Narcís Saubi

    Full Text Available In the past, we proposed to develop a heterologous recombinant BCG prime-recombinant modified vaccinia virus Ankara (MVA boost dual pediatric vaccine platform against transmission of breast milk HIV-1 and Mycobacterium tuberculosis (Mtb. In this study, we assembled an E. coli-mycobacterial shuttle plasmid pJH222.HIVA(CAT expressing HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism based on Operator-Repressor Titration (ORT system for plasmid selection and maintenance in E. coli and lysine complementation in mycobacteria. This shuttle plasmid was electroporated into parental lysine auxotroph (safer strain of BCG to generate vaccine BCG.HIVA(CAT. All procedures complied with Good Laboratory Practices (GLPs. We demonstrated that the episomal plasmid pJH222.HIVA(CAT was stable in vivo over a 20-week period, and genetically and phenotypically characterized the BCG.HIVA(CAT vaccine strain. The BCG.HIVA(CAT vaccine in combination with MVA.HIVA induced HIV-1- and Mtb-specific interferon γ-producing T-cell responses in newborn and adult BALB/c mice. On the other hand, when adult mice were primed with BCG.HIVA(CAT and boosted with MVA.HIVA.85A, HIV-1-specific CD8(+ T-cells producing IFN-γ, TNF-α, IL-2 and CD107a were induced. To assess the biosafety profile of BCG.HIVA(CAT-MVA.HIVA regimen, body mass loss of newborn mice was monitored regularly throughout the vaccination experiment and no difference was observed between the vaccinated and naïve groups of animals. Thus, we demonstrated T-cell immunogenicity of a novel, safer, GLP-compatible BCG-vectored vaccine using prototype immunogen HIVA. Second generation immunogens derived from HIV-1 as well as other major pediatric pathogens can be constructed in a similar fashion to prime protective responses soon after birth.

  11. Significant intravesical prostatic protrusion and prostatic calcification predict unfavorable outcomes of medical treatment for male lower urinary tract symptoms

    OpenAIRE

    Chia-Hao Kuei; Chun-Hou Liao; Bing-Juin Chiang

    2016-01-01

    Objective: To evaluate the impact of intravesical prostatic protrusion (IPP) and prostatic calcification on medical treatment for male lower urinary tract symptoms (LUTS). Materials and methods: Men over the age of 40 years with total International Prostate Symptom Score (IPSS) ≥ 8 were recruited from January to August 2013. The maximal flow rate, postvoiding residual (PVR) urine volume, total prostate volume (TPV), transitional zone volume (TZV), transitional zone index (TZI), and grades ...

  12. BCG Infection to Human B Cells Induce Cell Apoptosis%卡介苗感染人B细胞诱导细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    朱旗; 冯国栋; 杨毅宁; 赵青; 王文菁; 张敏; 刘扬; 赵钢

    2015-01-01

    目的 探究卡介苗( BCG)是否能感染人B细胞及观察感染后对细胞的影响. 方法 人B细胞系Raji细胞与BCG共培养, 4、12和24h后分别用共聚焦及透射电镜观察Raji细胞对BCG的结合和摄取情况,用CCK-8法检测细胞毒性,流式An-nexin Ⅴ-PI双标法检测细胞凋亡和坏死情况. 结果 培养4、12和24h后,感染了BCG的细胞比例分别为12. 4%±2. 0%, 23. 8%±5. 1%, 25. 2%±4. 8%.BCG感染可引起细胞毒性,4h后Raji细胞存活率为75. 5%±8. 8%,12h后细胞存活率降至51. 0%± 5. 3%,24h后细胞存活率仅为21. 6%±4. 2%,而感染灭活BCG的细胞存活率均在95%以上. 进一步用流式检测凋亡坏死发现,与未感染细胞相比,Raji细胞感染BCG后凋亡,坏死均有所增加,以凋亡增加为主. 结论 BCG可以感染人B细胞并诱导细胞凋亡.%Objective To explore whether Bacillus Calmette-Guérin ( BCG) can infect human B cells and observe the effects of the infection on B cells. Methods Human B cell line Raji cells were incubated with BCG. After incubation for 4h, 12h and 24h, the direct interaction of Raji cells with BCG was observed under confocal microscopy and transmission electronic microscopy. Cytotoxity was detected by cell counting kit (CCK-8). Cell apoptosis and necrosis were assayed by flow cytometry. Results After 4h, 12h and 24h of incuba-tion, the percentage of Raji cells that were infected by BCG was 12. 4%±2. 0%, 23. 8%±5. 1%, 25. 2%±4. 8%, respectively. Live BCG infection induced cytotoxicity. The cell survival rates at 4h, 12h, 24h were 75. 5%±8. 8%, 51. 0%±5. 3%, 21. 6%±4. 2% re-spectively, while the cells infected with inactivated BCG showed a high survival rate of 95% at any time. Further analysis by flow cytome-try showed that cell apoptosis and necrosis, predominantly cell apoptosis of Raji cells were increased by BCG infection. Conclusion BCG can infect human B cells and induce cell apoptosis.

  13. Comparison between prostate volume and intravesical prostatic protrusion in detecting bladder outlet obstruction due to benign prostatic hyperplasia.

    Science.gov (United States)

    Hossain, A K M S; Alam, A K M K; Habib, A K M K; Rashid, M M; Rahman, H; Islam, A K M A; Jahan, M U

    2012-04-01

    The objectives of this study were to determine and compare the correlation of intravesical prostatic protrusion (IPP) and prostate volume (PV) with bladder outlet obstruction (BOO). This study was conducted in the department of urology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, between July 2009 to September 2010. Fifty benign prostatic hyperplasia (BPH) patients were included in the study. Their evaluation consisted of history along with International Prostate Symptoms Score (IPSS), digital rectal examination (DRE), transabdominal ultrasonography to measure prostate volume, intravesical prostatic protrusion & post voidal residual (PVR) urine and pressure-flow studies to detect bladder outflow obstruction (BOO). Statistical analysis included Unpaired 't' test, Chi-square test and Spearman's Rank correlation test. Receiver Operator Characteristic (ROC) curves were used to compare the correlation of PV and IPP with BOO. Mean prostate volume was significantly larger in bladder outlet obstructed patients (PProstate volume & intravesical prostatic protrusion measured through transabdominal ultrasonography are noninvasive and accessible method that significantly correlates with bladder outlet obstruction in patients with benign prostatic hyperplasia and the correlation of IPP is much more stronger than that of prostate volume.

  14. Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Mossberg, Ann-Kristin; Wullt, Björn; Gustafsson, Lotta; Månsson, Wiking; Ljunggren, Eva; Svanborg, Catharina

    2007-09-15

    We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers.

  15. Intravesical capsaicin in patients with detrusor hyper-reflexia--a placebo-controlled cross-over study

    DEFF Research Database (Denmark)

    Petersen, T; Nielsen, J B; Schrøder, H D

    1999-01-01

    The aim of this study was to determine whether intravesical treatment with capsaicin could block detrusor hyper-reflexia (DH) and alter the substance P content, nerve fibres and mucosa of the bladder. Twelve patients with spinal cord disease with DH and urinary incontinence resistant to anticholi......The aim of this study was to determine whether intravesical treatment with capsaicin could block detrusor hyper-reflexia (DH) and alter the substance P content, nerve fibres and mucosa of the bladder. Twelve patients with spinal cord disease with DH and urinary incontinence resistant...... to anticholinergic treatment underwent intravesical administration of 50 ml 2% lignocaine. followed by either 100 ml 1 mmol/l capsaicin or 100 ml physiological saline for 30 min. Cross-over to the alternative treatment took place after 4 weeks. Varying degrees of burning sensation were experienced by all but one...... patient during the capsaicin treatment and precluded the possibility of conducting studies of this type in a blind manner. No preference for capsaicin treatment was found, and micturition and VAS scores were unchanged after treatment with capsaicin. The mean volume of the contents of the bladder at which...

  16. Preparation and stability of agarose microcapsules containing BCG.

    Science.gov (United States)

    Esquisabel, A; Hernandez, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

    2002-01-01

    An emulsification/internal gelation method of preparing small-sized agarose microcapsules containing Bacillus Calmette-Guerin (BCG) is reported. Agarose microcapsules have been prepared by the emulsification of the hydrogel within a vegetable oil followed by its gelation due to the cooling of the system. Four different oils (sesame, sweet almonds, camomile and jojoba) were assayed. The rheological analysis of the oils showed a Newtonian behaviour, with viscosity values of 37.7, 51.2, 59.3 and 67.1 mPa s for jojoba, camomile, sesame and sweet almonds oil, respectively. The particle size of the microcapsules obtained ranged from 23.1 microm for the microcapsules prepared with sweet almonds oil to 42.6 microm for those prepared with jojoba. The microcapsule particle size was found to be dependent on the viscosity of the oil used in the emulsification step. The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Once prepared, microcapsules were freeze-dried using 5% trehalose as cryoprotectant and the stability of the microcapsules was assayed during 12 months storage at room temperature, observing that agarose microcapsules were stable after 12 months storage, since there was no evidence of alteration in the freeze-dried appearance, resuspension rate, observation under microscope, or particle size.

  17. Cosmological Constraints from the SDSS maxBCG Cluster Catalog

    Energy Technology Data Exchange (ETDEWEB)

    Rozo, Eduardo; /CCAPP; Wechsler, Risa H.; /KIPAC, Menlo Park /SLAC; Rykoff, Eli S.; /UC, Santa Barbara; Annis, James T.; /Fermilab; Becker, Matthew R.; /Chicago U. /KICP, Chicago; Evrard, August E.; /Michigan U. /Michigan U., MCTP; Frieman, Joshua A.; /Fermilab /KICP, Chicago /Chicago U.; Hansen, Sarah M.; /UC, Santa Cruz; Hao, Jia; /Michigan U.; Johnston, David E.; /Northwestern U.; Koester, Benjamin P.; /KICP, Chicago /Chicago U.; McKay, Timothy A.; /Michigan U. /Michigan U., MCTP; Sheldon, Erin S.; /Brookhaven; Weinberg, David H.; /CCAPP /Ohio State U.

    2009-08-03

    We use the abundance and weak lensing mass measurements of the SDSS maxBCG cluster catalog to simultaneously constrain cosmology and the richness-mass relation of the clusters. Assuming a flat {Lambda}CDM cosmology, we find {sigma}{sub 8}({Omega}{sub m}/0.25){sup 0.41} = 0.832 {+-} 0.033 after marginalization over all systematics. In common with previous studies, our error budget is dominated by systematic uncertainties, the primary two being the absolute mass scale of the weak lensing masses of the maxBCG clusters, and uncertainty in the scatter of the richness-mass relation. Our constraints are fully consistent with the WMAP five-year data, and in a joint analysis we find {sigma}{sub 8} = 0.807 {+-} 0.020 and {Omega}{sub m} = 0.265 {+-} 0.016, an improvement of nearly a factor of two relative to WMAP5 alone. Our results are also in excellent agreement with and comparable in precision to the latest cosmological constraints from X-ray cluster abundances. The remarkable consistency among these results demonstrates that cluster abundance constraints are not only tight but also robust, and highlight the power of optically-selected cluster samples to produce precision constraints on cosmological parameters.

  18. Cosmological Constraints From SDSS MaxBCG Cluster Abundances

    Energy Technology Data Exchange (ETDEWEB)

    Rozo, Eduardo; /Ohio State U. /Chicago U. /KICP, Chicago; Wechsler, Risa H.; /KICP, Chicago /KIPAC, Menlo Park; Koester, Benjamin P.; /Chicago U., Astron. Astrophys. Ctr.; McKay, Timothy A.; Evrard, August E.; /Michigan U.; Johnston, David; /Caltech, JPL; Sheldon, Erin S.; /CCPP, New York; Annis, James; /Fermilab; Frieman, Joshua A.; /KICP,

    2007-03-26

    We perform a maximum likelihood analysis of the cluster abundance measured in the SDSS using the maxBCG cluster finding algorithm. Our analysis is aimed at constraining the power spectrum normalization {sigma}{sub 8}, and assumes flat cosmologies with a scale invariant spectrum, massless neutrinos, and CMB and supernova priors {Omega}{sub m}h{sup 2} = 0.128 {+-} 0.01 and h = 0.72 {+-} 0.05 respectively. Following the method described in the companion paper Rozo et al. (2007), we derive {sigma}{sub 8} = 0.92 {+-} 0.10 (1{sigma}) after marginalizing over all major systematic uncertainties. We place strong lower limits on the normalization, {sigma}{sub 8} > 0.76 (95% CL) (> 0.68 at 99% CL). We also find that our analysis favors relatively low values for the slope of the Halo Occupation Distribution (HOD), {alpha} = 0.83 {+-} 0.06. The uncertainties of these determinations will substantially improve upon completion of an ongoing campaign to estimate dynamical, weak lensing, and X-ray cluster masses in the SDSS maxBCG cluster sample.

  19. Vaccine-associated paralytic poliomyelitis and BCG-osis in an immigrant child with severe combined immunodeficiency syndrome - Texas, 2013.

    Science.gov (United States)

    Trimble, Robert; Atkins, Jane; Quigg, Troy C; Burns, Cara C; Wallace, Gregory S; Thomas, Mary; Mangla, Anil T; Infante, Anthony J

    2014-08-22

    Poliovirus transmission has been eliminated in most of the world through the use of inactivated poliovirus vaccine (IPV) and live, attenuated oral poliovirus vaccine (OPV). In the United States, use of OPV was discontinued by the year 2000 because of the potential for vaccine-associated paralytic polio (VAPP); an average of eight cases were reported each year in the United States during 1980-2000. Polio eradication efforts in other parts of the world continue to rely on OPV to take advantage of transmission of poliovirus vaccine strains to unvaccinated persons in the population, lower cost, and ease of administration. In 2013, an infant aged 7 months who recently immigrated to the United States from India was referred to a hospital in San Antonio, Texas. The infant had fever, an enlarging skin lesion in the deltoid region with axillary lymphadenopathy, decreased activity, and inability to bear weight on the left leg, progressing to paralysis of the left leg over a 6-week period. Recognition of lymphopenia on complete blood count led to immune evaluation, which revealed the presence of severe combined immunodeficiency syndrome (SCIDS), an inherited disorder. A history of OPV and bacille Calmette-Guérin (BCG) vaccination in India led to the diagnoses of VAPP and BCG-osis, which were confirmed microbiologically. This report demonstrates the importance of obtaining a comprehensive clinical history in a child who has recently immigrated to the United States, with recognition that differing vaccine practices in other countries might require additional consideration of potential etiologies.

  20. Hepatoprotective role of ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Guo-Liang Zhang; Ye-Hong Wang; Wei Ni; Hui-Ling Teng; Zhi-Bin Lin

    2002-01-01

    AIM: To examine the effect of ganoderma lucidumpolysaccharide (GLP) on the immune liver injuryinduced by BCG infection, and investigate therelationship between degrees of hepatic damage andNO production in mice.METHODS: Immune hepatic injury was markedlyinduced by BCG-pretreatment (125 mg.kg-1, 2-week, iv)or by BCG-pretreatment plus lipopolysaccharide (LPS,125 μg.kg-1, 12-hour, iv) in mice in vivo.Hepatocellulardamage induced by BCG-pretreated plus inflammatorycytokines mixture (CM), which was included TNF-α, IL1β, IFN-γ and LPS in culture medium in vitro.Administration of GLP was performed by oral orincubating with culture medium at immune stimulisimultaneity. Liver damage was determined by activityof alanine aminotransferase (ALT) in serum and inhepatocytes cultured supernatant, by liver weightchanges and histopathological examination. NOproduction in the cultured supematant was determinedby the Griess reaction. Moreover, inducible nitric oxidesynthase (iNOS) protein expression was alsoexaminated by immunohistochemi1cal method.RESULTS: Immune hepatic injury was markedly inducedby BCG or BCG plus inflammatory cytokines in BALB/cmice in vivoand in vitro. Under BCG-stimulated condition,augment of the liver weight and increase of the serum/supernatant ALT level were observed, as well asgranuloma forming and inflammatory cells soakage wereobserved by microscopic analysis within liver tissues.Moreover, NO production was also increased by BCG or/and CH stimuli in the culture supernatant, and a lot ofiNOS positive staining was observed in BCG-prestimulated hepatic sections. Application of GLPsignificantly mitigated hepatic tumefaction, decreasedALT enzyme release and NO production in serum/supernatant, improved the pathological changes ofchronic and acute inflammation induced by BCG-stimuliin mice. Moreover, the immunohistochemical resultshowed that GLP inhibited iNOS protein expression inBCG-immune hepatic damage model.CONCLUSION: The present study indicates that

  1. Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial

    DEFF Research Database (Denmark)

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby

    2017-01-01

    INTRODUCTION: BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG......) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. METHODS: Within 7days after birth, children were randomised 1:1 to BCG vaccination...... children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis...

  2. Early BCG vaccine to low-birth-weight infants and the effects on growth in the first year of life

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Andersen, Andreas; Ravn, Henrik

    2015-01-01

    BACKGROUND: Randomised trials have shown that early Bacille Calmette-Guérin (BCG) vaccine reduces overall neonatal and infant mortality. However, no study has examined how BCG affects growth. We investigated the effect on infant growth of early BCG vaccine given to low-birth-weight (LBW) infants....... METHODS: Two-thousand three hundred forty-three LBW infants were randomly allocated 1:1 to "early BCG" (intervention group) or "late BCG" (current practice). Furthermore, a subgroup (N = 1717) were included in a two-by-two randomised trial in which they were additionally randomised 1:1 to vitamin...... but not among boys (interaction between "early BCG" and sex: weight p = 0.03 and MUAC p = 0.04). This beneficial effect among girls was particularly seen among the largest infants weighing 2.0 kg or more at inclusion. CONCLUSION: Though BCG vaccination is not recommended to be given to LBW infants at birth...

  3. Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

    DEFF Research Database (Denmark)

    Sartono, E.; Lisse, I.M.; Terveer, E.M.

    2010-01-01

    Background: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did...... not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. Methods and Findings: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG...... scar (0.95 (0.91-1.00), p = 0.057)). Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05), p = 0.012. Conclusions: This study is the first to address the consequences for the immune response to BCG of simultaneous administration...

  4. The BCG Moreau RD16 deletion inactivates a repressor reshaping transcription of an adjacent gene.

    Science.gov (United States)

    Galvão, Teca Calcagno; Lima, Cristiane Rodrigues; Gomes, Leonardo Henrique Ferreira; Pagani, Talita Duarte; Ferreira, Marcelo Alves; Gonçalves, Antonio S; Correa, Paloma Rezende; Degrave, Wim Maurits; Mendonça-Lima, Leila

    2014-01-01

    The Brazilian anti-tuberculosis vaccine strain Mycobacterium bovis bacillus Calmette-Guérin (BCG) BCG Moreau is unique in having a deletion of 7608 bp (RD16) that results in the truncation of a putative TetR transcriptional regulator, the ortholog of Mycobacterium tuberculosis rv3405c, BCG_M3439c. We investigated the effect of this truncation on the expression of the rv3406 ortholog (BCG_M3440), lying 81 bp downstream in the opposite orientation. RT-PCR and western blot experiments show that rv3406 mRNA and Rv3406 accumulate in BCG Moreau but not in BCG Pasteur (strain that bears an intact rv3405c), suggesting this to be a result of rv3405c truncation. Recombinant Rv3405c forms a complex with the rv3405c-rv3406 intergenic region, which contains a characteristic transcription factor binding site, showing it to have DNA binding activity. Complementation of M. bovis BCG Moreau with an intact copy of rv3405c abolishes Rv3406 accumulation. These results show that Rv3405c is a DNA binding protein that acts as a transcriptional repressor of rv3406.

  5. Urovysion™ testing can lead to early identification of intravesical therapy failure in patients with high risk non-muscle invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    Jared M. Whitson

    2009-12-01

    Full Text Available Purpose: In this study, we investigated the ability of UroVysion™ to assess response to intravesical therapy in patients with high risk superficial bladder tumors. Materials and methods: We performed a retrospective review of patients undergoing intravesical therapy for high risk superficial bladder tumors. Urine specimens were collected for UroVysion™ analysis before and immediately after a course of intravesical therapy. Cytology and cystoscopy were performed six weeks after treatment, using either a positive cytology or visible abnormality on cystoscopy as a prompt for biopsy. The operating characteristics of the UroVysion™ test were then determined. Results: 41 patients were identified in whom 47 cycles of induction and 41 cycles of maintenance intravesical therapy were given during the study period. This yielded a total of 88 treatment and evaluation cycles. Median follow-up was 9 months per induction (range 1-21 months and 13 months per patient (range 1-25 months. A total of 133 urine samples were collected for UroVysion™ of which 40 were positive. Based upon standard clinical evaluation, 41 biopsies were performed which detected 20 recurrences. UroVysion™ testing performed immediately upon completion of therapy for the 41 patients undergoing biopsy yielded a sensitivity, specificity, and accuracy of 85%, 61%, and 71%. Conclusions: The use of UroVysion™ following intravesical therapy for high-risk superficial bladder tumors helps to identify patients at high risk of refractory or recurrent disease who should undergo immediate biopsy under anesthesia.

  6. Evaluation of BCG Vaccination in Neonatal%新生儿卡介苗接种效果评价

    Institute of Scientific and Technical Information of China (English)

    段俊霞

    2012-01-01

    Objective:o investigate the situation of neonatal BCG vaccination in our city,evaluate the vaccination quality and results,and analysis its impact factor.Methods:Analysis the the number of BCG vaccination cases in April 2006 to April 2010 and the number of live births over the same period,analysis vaccination rates in different demographic. And investigation neonatal BCG vaccination after 12 weeks of PPD positive rate,analysis of different kinds of time in early seroconversion rate differences.Results:The total of live births in the city in April 2006 to April 2010 was 10421 cases and neonatal BCG early species of 10059 cases,the total rate of 96.56% in early types.Among them,the early species of the city' s population rate (96.75%) was higher than the initial species field population rate (95.74%).PPD test 3433 cases,the positive rate 95.66%,of which the baby' s positive rate (95.65%) and girls (95.10%) showed no significant difference.The cards scar group PPD test positive rate (96.40%) was significantly higher than non-card scar group (92.67%),the relative odds ratio was 2.121.Kinds of time in early January and the PPD test positive rate (97.02%) was significantly higher than the first time kind of positive rates greater than 1 month (52%),the relative odds ratio was 30.014.Conclusion:The city' s overall neonatal BCG vaccination rate was higher, reaching the state level,but should strengthen the floating population of foreign publicity and vaccination. And care to emphasize the importance of early vaccination.%目的:调查我市新生儿卡介苗接种情况,评价接种质量及效果,并分析其影响因素.方法:收集2006~2010年在我市接种卡介苗例数及同期活产数,分析不同人口构成的接种率差异.并调查12周后卡介苗接种新生儿的PPD阳转率,分析不同初种时间的阳转率差异.结果:2006年4月~2010年4月我市共有活产新生儿10421例,卡介苗初种10059例,总初种率96.56%.

  7. "A Study of Relation between BCG Scar and Atopy in Schoolchildren of Zanjan City "

    Directory of Open Access Journals (Sweden)

    Akefeh Ahmadiafshar

    2005-12-01

    Three hundred and three subjects had at least one of these disorders, which were diagnosed as atopy. There was reverse correlation between BCG scar and asthma (P=0.013, atopic dermatitis (P<0.01, and atopy (P<0.01. We did not find any association between the diameter of BCG scar and allergic rhinitis. Reverse correlation of asthma, atopic dermatitis and atopy with BCG scar are significant. This relied on history and symptoms of patients. Further studies with skin tests, measurements of total and specific IgE levels and spirometery are recommended.

  8. BCG plus levamisole following irradiation of advanced squamous bronchial carcinoma. [Hard X Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pines, A.

    1980-08-01

    Fifty patients with inoperable squamous cell carcinoma of the bronchus were treated with radical radiotherapy. Afterwards, 16 patients received levamisole on 2 days per week and bacillus calmette guerin (B.C.G.) skin innoculations every two weeks;another 16 received the same dosage of levamisole but B.C.G. every 4 weeks; 18 patients were controls. Survival was better in the first group of patients only during the first two years of study (P = 0.02) but not later: metastases were fewer. Both B.C.G. and levamisole gave little discomfort when the dose was adjusted for each patient.

  9. A COMBINED FULL-WAVE BCG-FFT METHOD FOR RADIATION OF MICROSTRIP ANTENNA ARRAYS

    Institute of Scientific and Technical Information of China (English)

    Zhang Hou; Peng Hongli; Liu Qizhong; Yin Yingzeng; Gong Shuxi

    2001-01-01

    A method of combining BiConjugate Gradient(BCG) with Fast Fourier Transform(FFT) to analyze the radiation of microstrip antenna arrays is presented, where the spatially discrete BCG-FFT for analyzing microstrip structure is used and the del operators on Green's functions are transferred from the singular kernel to the expansion and testing functions. The resultant equations are solved by using BCG method in which the matrix-vector product is evaluated efficiently with FFT. The calculated patterns are in good agreement with the measured data.

  10. A Single Dose of Oral BCG Moreau Fails to Boost Systemic IFN-γ Responses to Tuberculin in Children in the Rural Tropics: Evidence for a Barrier to Mucosal Immunization.

    Science.gov (United States)

    Vaca, Maritza; Moncayo, Ana-Lucia; Cosgrove, Catherine A; Chico, Martha E; Castello-Branco, Luiz R; Lewis, David J; Cooper, Philip J

    2012-01-01

    Immune responses to oral vaccines are impaired in populations living in conditions of poverty in developing countries, and there is evidence that concurrent geohelminth infections may contribute to this effect. We vaccinated 48 children living in rural communities in Ecuador with a single oral dose of 100 mg of BCG Moreau RDJ and measured the frequencies of tuberculin-stimulated peripheral blood mononuclear cells expressing IFN-γ before and after vaccination. Vaccinated children had active ascariasis (n = 20) or had been infected but received short- (n = 13) or long-term (n = 15) repeated treatments with albendazole prior to vaccination to treat ascariasis. All children had a BCG scar from neonatal vaccination. There was no evidence of a boosting of postvaccination IFN-γ responses in any of the 3 study groups. Our data provide support for the presence of a barrier to oral vaccination among children from the rural tropics that appeared to be independent of concurrent ascariasis.

  11. rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

    Science.gov (United States)

    Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

    2014-09-01

    Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy.

  12. Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood

    DEFF Research Database (Denmark)

    Kiraly, N; Benn, Christine Stabell; Biering-Sørensen, S

    2013-01-01

    Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood....

  13. How do parents make their decision about letting their child get a BCG vaccination?

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte; Ammentorp, Jette; Schmidt Jensen, Jane

    Introduction: In a large prospective randomised clinical trial in Denmark we are testing the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood. My...... focus for this project is parents decision making and risk evaluation. I want to investigate how parents make their decision about letting their child get a BCG vaccination and how they evaluate the risk of side effects. Method: Before the clinical trial was started, we conducted 5 focus groups...... with expectant mothers and fathers to discuss considerations for and against letting their newborn child vaccinate with BCG in order to achieve a non-specific stimulation of the immune system and to discuss their concerns about side effects. The focus groups were analysed qualitatively. Results: The pre...

  14. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.;

    2010-01-01

    children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrolment (hazard...... inhabitants. Participants 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrolment. Intervention BCG vaccination or no vaccination (control). Main outcome measure Hazard ratios for mortality. Results 77 children died during follow...... controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated...

  15. Comparison of BCG vaccination at birth and at third month of life.

    Science.gov (United States)

    Ildirim, I; Sapan, N; Cavuşoğlu, B

    1992-01-01

    Tuberculosis is an important health problem in developing countries and the BCG vaccine plays an important part in preventing the disease. There are different reports about the preventive value of BCG. Some of them claim that it is satisfactory while others suggest that it provides little protection. There are also varying ideas about the optimum time to vaccinate babies, some studies suggesting that late vaccination confers a high degree of protection. This prospective controlled study has been undertaken to evaluate the value of BCG vaccine given to babies during their first three days of life versus its value when given in their third month of life. Evaluation was measured by the results of tests with purified protein derivative (PPD), by vaccine scars, that by the complications of the vaccine. It was found that BCG given at the end of the third month provides a higher rate of response and fewer complications than when given during the first three days of life.

  16. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Fisker, Ane Baerent; Napirna, Bitiguida Mutna

    2010-01-01

    OBJECTIVE: To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. DESIGN: Randomised, placebo controlled, two by two factorial trial. SETTING: Bissau, Guinea-Bissau. PARTICIPANTS: 1717 low birthweight neonates born at the national hospital....... INTERVENTION: Neonates who weighed less than 2.5 kg were randomly assigned to 25 000 IU vitamin A or placebo, as well as to early BCG vaccine or the usual late BCG vaccine, and were followed until age 12 months. MAIN OUTCOME MEASURE: Mortality, calculated as mortality rate ratios (MRRs), after follow-up to 12...... months of age for infants who received vitamin A supplementation compared with those who received placebo. RESULTS: No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality...

  17. Drug Treatment Combined with BCG Vaccination Reduces Disease Reactivation in Guinea Pigs Infected with Mycobacterium tuberculosis

    Science.gov (United States)

    Shang, Shaobin; Shanley, Crystal A.; Caraway, Megan L.; Orme, Eileen A.; Henao-Tamayo, Marcela; Hascall-Dove, Laurel; Ackart, David; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

    2012-01-01

    Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease. PMID:22244979

  18. The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Marcela Henao-Tamayo

    Full Text Available To date, most new vaccines against Mycobacterium tuberculosis, including new recombinant versions of the current BCG vaccine, have usually been screened against the laboratory strains H37Rv or Erdman. In this study we took advantage of our recent work in characterizing an increasingly large panel of newly emerging clinical isolates [from the United States or from the Western Cape region of South Africa], to determine to what extent vaccines would protect against these [mostly high virulence] strains. We show here that both BCG Pasteur and recombinant BCG Aeras-422 [used here as a good example of the new generation BCG vaccines] protected well in both mouse and guinea pig low dose aerosol infection models against the majority of clinical isolates tested. However, Aeras-422 was not effective in a long term survival assay compared to BCG Pasteur. Protection was very strongly expressed against all of the Western Cape strains tested, reinforcing our viewpoint that any attempt at boosting BCG would be very difficult to achieve statistically. This observation is discussed in the context of the growing argument made by others that the failure of a recent vaccine trial disqualifies the further use of animal models to predict vaccine efficacy. This viewpoint is in our opinion completely erroneous, and that it is the fitness of prevalent strains in the trial site area that is the centrally important factor, an issue that is not being addressed by the field.

  19. Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000-2002

    DEFF Research Database (Denmark)

    Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik

    2005-01-01

    The rates of positive tuberculin skin test (TST) reactions and BCG scarring after BCG vaccination vary between studies and populations. Tuberculin reactivity and BCG scarring may be related to better child survival in low-income countries. We therefore studied determinants for TST reaction......=2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD.......66 (1.24-2.21)). In the multivariable analyses of BCG-vaccinated children assessed at 6 months of age, monitoring of vaccination technique and type of BCG vaccine were important. This was not changed by control for other determinants, including sex, season, vaccination place, birthplace, ethnic group...

  20. [Increase in the production of oncovirus type C by an L929 cell culture as a result of BCG infection].

    Science.gov (United States)

    Klitsunova, N V; Gosteva, V V; Kim, A A; Bykovskiĭ, A F

    1984-01-01

    The effect of BCG infection of L929 cells on replication of oncovirus type C was studied. Ultrathin sections of the BCG-infected culture were examined electron microscopically 1, 3, 6, 8, and 10 days postinfection. Most microorganisms with the morphology typical of mycobacteria were found inside phagosomes. The number of extracellular virions as well as budding and abnormal forms per one cell contour was counted. BCG-infected cells were found to produce significantly more virus than the controls. The difference was maximal 3 days postinoculation. Possible reasons for the increased oncovirus production by continuous cell lines after infection with BCG are discussed.

  1. Successful treatment with intravesical cidofovir for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A case report and a review of the literature.

    Science.gov (United States)

    Sakurada, Maki; Kondo, Tadakazu; Umeda, Masayuki; Kawabata, Hiroshi; Yamashita, Kouhei; Takaori-Kondo, Akifum

    2016-07-01

    Virus-associated hemorrhagic cystitis (VAHC) is a formidable complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The standard management of severe VAHC after allo-HSCT has not been established. Intravenous administration of cidofovir (CDV), an acyclic nucleoside analogue with broad-spectrum activity against DNA viruses, has been reported to be effective for VAHC, but it can cause severe renal toxicity. Here we report four cases who achieved clinical responses with intravesical instillation of CDV for severe VAHC after allo-HSCT. Median age was 57 years (40-63), and all were male. The underlying diseases were hematological malignancies. Three had received bone marrow transplantation, and one received cord blood transplantation twice. Conditioning regimen was myeloablative for one, and reduced-intensity for three. The viral types were BK virus and/or adenovirus. Two patients had received CDV intravenously prior to the intravesical therapy. A dose of intravesical CDV was 2-5 mg/kg. In all cases, symptoms of cystitis improved dramatically within a few days without showing any systemic adverse effects. The virological response was observed in two cases. This local therapy was effective even in the cases refractory to the intravenous CDV and a case with severe renal failure. Along with the review of literature, we propose that the intravesical instillation of CDV can be a therapeutic option for severe VAHC after allo-HSCT.

  2. Maternal BCG scar is associated with increased infant proinflammatory immune responses

    Science.gov (United States)

    Mawa, Patrice Akusa; Webb, Emily L.; Filali-Mouhim, Abdelali; Nkurunungi, Gyaviira; Sekaly, Rafick-Pierre; Lule, Swaib Abubaker; Prentice, Sarah; Nash, Stephen; Dockrell, Hazel M.; Elliott, Alison M.; Cose, Stephen

    2017-01-01

    Introduction Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants. Material and methods Maternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24 h and cytokines and chemokines in supernatants were measured using the Luminex® assay. The associations between maternal latent Mycobacterium tuberculosis infection (LTBI), maternal BCG scar (adjusted for each other’s effect) and infant responses were examined using linear regression. Principal Component Analysis (PCA) was used to assess patterns of cytokine and chemokine responses. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n = 42) and six (n = 51) weeks after BCG immunisation using microarray. Results Maternal LTBI was positively associated with infant IP-10 responses with an adjusted geometric mean ratio (aGMR) [95% confidence interval (CI)] of 5.10 [1.21, 21.48]. Maternal BCG scar showed strong and consistent associations with IFN-γ (aGMR 2.69 [1.15, 6.17]), IL-12p70 (1.95 [1.10, 3.55]), IL-10 (1.82 [1.07, 3.09]), VEGF (3.55 [1.07, 11.48]) and IP-10 (6.76 [1.17, 38.02]). Further assessment of the associations using PCA showed no differences for maternal LTBI, but maternal BCG scar was associated with higher scores for principal component (PC) 1 (median level of scores: 1.44 in scar-positive versus −0.94 in scar-negative, p = 0.020) in the infants. PC1 represented a controlled proinflammatory response. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation. Conclusions

  3. Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Roth, A.E.; Benn, Christine Stabell; Ravn, H.;

    2010-01-01

    controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated...... children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrolment (hazard...... ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrolment (1.78, 1.04 to 3.04). Conclusions There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions...

  4. [Immune reconstitution syndrome due to BCG in HIV-treated children].

    Science.gov (United States)

    Miranda-Choque, Edwin; Candela-Herrera, Jorge; R Segura, Eddy; Farfán-Ramos, Sonia; Barriga, Aldo

    2012-01-01

    The objective of this study is to describe the clinical profile of the immune reconstitution syndrome due to Mycobacterium bovis Bacillus Calmette-Guérin (IRS-BCG) in children with HIV infection who receive highly active antiretroviral treatment (HAART) at Instituto Nacional de Salud del Niño de Lima (National Children's Health Institute of Lima), Peru. A case study was conducted, including 8 children with IRS-BCG, defined as the presence of regional lymphadenopathy or inflammation on the BCG vaccination site with at least one less logarithm in the viral load or immune improvement. All patients had AIDS (C3). The starting median age in HAART was 7.2 months and the event occurred 3 to 11 weeks after the treatment was started. 7 cases showed axillary adenitis. When compared with the Non IRS-BCG group, a significant association between the age at which HAART was started at one year, severe immunodepression, and increased viral load was found. It is concluded that IRS-BCG was related to a rapid clinical progression of the mother-to-child transmitted HIV/AIDS infection, severe immunosuppression and high viral load when the HAART began.

  5. Living in Living Cities

    CERN Document Server

    Gershenson, Carlos

    2011-01-01

    This paper presents and overview of current and potential applications of living technology to urban problems. Living technology can be described as technology that exhibits the core features of living systems. These features can be useful to solve dynamic problems. In particular, urban problems concerning mobility, logistics, telecommunications, governance, safety, sustainability, and society and culture are presented, while solutions involving living technology are reviewed. Finally, the usefulness of describing cities as living systems is discussed.

  6. A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence.

    Science.gov (United States)

    Shoen, Carolyn M; DeStefano, Michelle S; Hager, Cynthia C; Tham, Kyi-Toe; Braunstein, Miriam; Allen, Alexandria D; Gates, Hiriam O; Cynamon, Michael H; Kernodle, Douglas S

    2013-01-11

    Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  7. A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

    Directory of Open Access Journals (Sweden)

    Douglas S. Kernodle

    2013-01-01

    Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  8. Mechanism responsible for the antitumor effect of BCG-CWS using the LEEL method in a mouse bladder cancer model.

    Science.gov (United States)

    Nakamura, Takashi; Fukiage, Masafumi; Suzuki, Yoshiteru; Yano, Ikuya; Miyazaki, Jun; Nishiyama, Hiroyuki; Akaza, Hideyuki; Harashima, Hideyoshi

    2014-12-28

    We previously reported on the development of a water soluble formulation of the cell wall skeleton of BCG (BCG-CWS), a major immune active center of BCG, by encapsulating it into a nanoparticle (CWS-NP). The CWS-NP allowed us to clarify the machinery associated with the BCG mediated anti-bladder tumor effect, especially the roles of bladder cancer cells and dendritic cells (DCs) in the initial step, which remains poorly understood. We show herein that the internalization of BCG-CWS by bladder cancer cells, but not DCs, is indispensable for the induction of an antitumor effect against bladder cancer. Tumor growth was significantly inhibited in mice that had been inoculated with mouse bladder cancer (MBT-2) cells containing internalized BCG-CWS. On the other hand, the internalization of BCG-CWS by DCs had only a minor effect on inducing an antitumor effect against MBT-2 tumors. This was clarified for the first time by using the CWS-NP. This finding provides insights into our understanding of the role of bladder cancer cells and DCs in BCG therapy against bladder cancer.

  9. Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Larsen, Nanna; Biering-Sørensen, Sofie

    2015-01-01

    BACKGROUND:  Bacillus Calmette-Guérin (BCG) seems to have beneficial nonspecific effects; early BCG vaccination of low-birth-weight (LBW) newborns reduces neonatal mortality by >40% due to prevention of primarily septicemia and pneumonia. METHODS:  Within a randomized trial in LBW infants in Guin...

  10. Optimal control on bladder cancer growth model with BCG immunotherapy and chemotherapy

    Science.gov (United States)

    Dewi, C.; Trisilowati

    2015-03-01

    In this paper, an optimal control model of the growth of bladder cancer with BCG (Basil Calmate Guerin) immunotherapy and chemotherapy is discussed. The purpose of this optimal control is to determine the number of BCG vaccine and drug should be given during treatment such that the growth of bladder cancer cells can be suppressed. Optimal control is obtained by applying Pontryagin principle. Furthermore, the optimal control problem is solved numerically using Forward-Backward Sweep method. Numerical simulations show the effectiveness of the vaccine and drug in controlling the growth of cancer cells. Hence, it can reduce the number of cancer cells that is not infected with BCG as well as minimize the cost of the treatment.

  11. Lupus vulgaris at the site of BCG vaccination: report of three cases.

    Science.gov (United States)

    Farsinejad, K; Daneshpazhooh, M; Sairafi, H; Barzegar, M; Mortazavizadeh, M

    2009-07-01

    Lupus vulgaris (LV) is a rare complication of the bacille Calmette-Guérin (BCG) vaccination, and about 65 cases of inoculation tuberculosis resembling LV have been reported in the literature. We report three cases of LV, developing many years later at the inoculation site of BCG vaccine. All three cases had a single BCG vaccination, with a LV lesion at or in the vicinity of the vaccination site, a strong positive Mantoux test, noncaseating granuloma histologically, and two of the patients had a positive PCR result for mycobacterial complex. One of the patients had an unusually delayed appearance of the LV lesion, after an interval of about 17 years, and another case was remarkable because of the large size of the lesion (210 x 110 mm).

  12. A Trend Analysis of Competition Positioning in Chinese Seaports by Using DEA Model and BCG Matrix

    Institute of Scientific and Technical Information of China (English)

    Hoki Nam

    2007-01-01

    <正>This paper has shown the trend of competition positioning of ten critical Chinese seaports from 2003 to 2006 by using DEA model for the performance efficiency analysis and BCG matrix,which consists of relative market share and growth rate as well as the scores of both BCC and CCR in the vertical and horizontal axis of BCG matrix.The expected results will include the total economic efficiency ranking of each Chinese seaport,and the relative competitive positioning in terms of growth rate and efficiency scores.The main policy implication of this paper is to emphasize the DEA model and BCG matrix method can support the seaport managers the basic information for planning the future port management for enhancing the competitive positioning among Chinese seaports.

  13. SAPHO syndrome with bacillus Calmette-Guerin (BCG) immunotherapy for bladder cancer.

    Science.gov (United States)

    Matsumaru, Katsuhiko; Nagai, Kazuki; Murakami, Takayuki; Andoh, Kazuo

    2010-08-31

    The authors describe a case of SAPHO syndrome with bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer. The patient had undergone transurethral resection (TUR) and was treated with BCG immunotherapy following TUR. Two years after treatment for bladder cancer, the patient had palmoplantar pustulosis, and in the past 1 month suffered from pain localised to the anterior chest wall. The bone scintigraphy showed a strong focal enrichment in the right chest wall, suggesting spondyloarthropathy rather than malignant disease. On the basis of clinical and scintigraphy findings, SAPHO syndrome was diagnosed. The patient was treated with topical therapy and non-steroidal anti-inflammatory drugs and symptoms improved. The authors suggest that SAPHO syndrome might be caused by an association with BCG immunotherapy.

  14. Granulomas do pênis: uma complicação rara da terapia intravesical com Bacilo Calmette-Guérin Granulomas of the penis: a rare complication of intravesical therapy with Bacillus Calmette-Guerin

    Directory of Open Access Journals (Sweden)

    Sara Isabel Alcântara Lestre

    2011-08-01

    Full Text Available A imunoterapia com o Bacilo Calmette-Guérin é amplamente usada no tratamento e profilaxia da neoplasia urotelial superficial. As complicações associadas ao tratamento são comuns. Os autores relatam um caso de inflamação granulomatosa do pênis, associada à terapia intravesical com Bacilo Calmette-Guérin, com múltiplos nódulos eritematosos indolores localizados na glande. É também efetuada uma revisão da literatura. A balanopostite granulomatosa é uma complicação rara associada à imunoterapia com Bacilo Calmette-Guérin, com uma apresentação clinicamente heterogênea que pode dificultar o diagnóstico. O seu reconhecimento clínico é essencial para o início precoce de tuberculostáticos e interrupção de Bacilo Calmette-GuérinImmunotherapy with Bacillus Calmette-Guérin is widely used for treatment and prophylaxis of superficial urothelial cancer. Complications associated with Bacillus Calmette-Guérin treatment are common. The authors describe a case of granulomatous inflammation of the penis associated with intravesical Bacillus Calmette-Guérin therapy, presenting with multiple erythematous and painless nodules located on the glans. A review of the literature is also performed. Granulomatous balanoposthitis is a rare complication of Bacillus Calmette-Guérin immunotherapy, with heterogeneous clinical presentation, which can make the diagnosis difficult. Its clinical recognition is essential for early start of therapy with antitubercular agents and interruption of Bacillus Calmette-Guérin

  15. Stable Expression of Lentiviral Antigens by Quality-Controlled Recombinant Mycobacterium bovis BCG Vectors.

    Science.gov (United States)

    Hart, Bryan E; Asrican, Rose; Lim, So-Yon; Sixsmith, Jaimie D; Lukose, Regy; Souther, Sommer J R; Rayasam, Swati D G; Saelens, Joseph W; Chen, Ching-Ju; Seay, Sarah A; Berney-Meyer, Linda; Magtanong, Leslie; Vermeul, Kim; Pajanirassa, Priyadharshini; Jimenez, Amanda E; Ng, Tony W; Tobin, David M; Porcelli, Steven A; Larsen, Michelle H; Schmitz, Joern E; Haynes, Barton F; Jacobs, William R; Lee, Sunhee; Frothingham, Richard

    2015-07-01

    The well-established safety profile of the tuberculosis vaccine strain, Mycobacterium bovis bacille Calmette-Guérin (BCG), makes it an attractive vehicle for heterologous expression of antigens from clinically relevant pathogens. However, successful generation of recombinant BCG strains possessing consistent insert expression has encountered challenges in stability. Here, we describe a method for the development of large recombinant BCG accession lots which stably express the lentiviral antigens, human immunodeficiency virus (HIV) gp120 and simian immunodeficiency virus (SIV) Gag, using selectable leucine auxotrophic complementation. Successful establishment of vaccine stability stems from stringent quality control criteria which not only screen for highly stable complemented BCG ΔleuCD transformants but also thoroughly characterize postproduction quality. These parameters include consistent production of correctly sized antigen, retention of sequence-pure plasmid DNA, freeze-thaw recovery, enumeration of CFU, and assessment of cellular aggregates. Importantly, these quality assurance procedures were indicative of overall vaccine stability, were predictive for successful antigen expression in subsequent passaging both in vitro and in vivo, and correlated with induction of immune responses in murine models. This study has yielded a quality-controlled BCG ΔleuCD vaccine expressing HIV gp120 that retained stable full-length expression after 10(24)-fold amplification in vitro and following 60 days of growth in mice. A second vaccine lot expressed full-length SIV Gag for >10(68)-fold amplification in vitro and induced potent antigen-specific T cell populations in vaccinated mice. Production of large, well-defined recombinant BCG ΔleuCD lots can allow confidence that vaccine materials for immunogenicity and protection studies are not negatively affected by instability or differences between freshly grown production batches.

  16. Intratumoral injection of BCG-CWS-pretreated dendritic cells following tumor cryoablation.

    Science.gov (United States)

    Kawamura, Naoshi; Udagawa, Masaru; Fujita, Tomonobu; Sakurai, Toshiharu; Yaguchi, Tomonori; Kawakami, Yutaka

    2014-01-01

    Intratumoral administration of dendritic cells (DC) following cryoablation of tumor is one of the personalized cancer immunotherapies which is able to induce immune responses to multiple endogenous tumor antigens, including shared and unique antigens. Here we describe protocols of cryoablation of tumors, generation of cultured DC, pretreatment of DC with a Toll-like receptor (TLR)-stimulating purified component of Bacillus Calmette-Guerin cell wall fraction (BCG-CWS) and highly immunogenic keyhole limpet hemocyanin (KLH) antigen, and combined use of tumor cryoablation and intratumoral administration of BCG-CWS-pretreated DC in both a murine model and cancer patients.

  17. A Complication of BCG Vaccine: A Case of Localized Cutaneous Abscess due to Mycobacterium bovis

    Directory of Open Access Journals (Sweden)

    Nathalie Lussier

    1999-01-01

    Full Text Available The attenuated bacille Calmette-Guérin (BCG vaccine is administered to prevent tuberculosis. Complications of vaccination are uncommon. A case of cutaneous abscess due to BCG is presented in a 24-year-old woman. The abscess developed at the inoculation site four weeks after vaccination. Routine Gram stain and bacterial cultures of the pus were negative. The auramine stain was positive. Mycobacterial cultures were positive after 14 and 18 days, using the BACTEC 12B bottle and Löwenstein-Jensen media, respectively. The mycobacteria were identified as Mycobacterium bovis, vaccinal strain by high-performance liquid chromatography and DNA probe assays.

  18. Avaliação da resposta inflamatória hematológica em cascavéis (Crotalus durissus Linnaeus, 1758 inoculadas com BCG Assessment of blood inflammatory response in BCG stimulated rattlesnakes (Crotalus durissus Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Wellington Bandeira da Silva

    2009-12-01

    grandes vacúolos. De forma geral, a inoculação de BCG em cascavéis desencadeia respostas inflamatórias hematológicas caracterizadas pela participação de trombócitos, granulócitos e azurófilos.The high demand for anti-venom production in response to the increased number of cases of snakebite envenomation highlights the importance of raising and breeding venomous snakes in captivity. Knowledge of types of venoms and anti-venoms is of great interest to public health. The maintenance of venomous serpents in captivity started in the early twentieth century, but still nowadays it is a challenge to manage and prevent diseases in captive fauna. Hematology is commonly used for general health assessment and illness detection. However, data on serpent blood analysis are still scarce. Alterations in hematological parameters were experimentally induced in rattlesnakes by the inoculation of BCG. Based on this, hemograms can be used as a health auxiliary diagnosis method for bacterial diseases in this species. In this study, blood samples were taken from 10 healthy specimens of rattlesnakes (Crotalus durissus born and bred in captivity in the Herpetological Division of Vital Brazil Institute. Animals were divided into two groups (group 1 and 2 with similar live weight and sex proportion, and were then inoculated subcutaneously with BCG (Bacillus Calmette-Guérin. Blood samples were taken before and after inoculation at three experimental times (days 3, 5 and 7 for group 1 and days 11, 17 and 21 for group 2. Hematological analysis was performed through semi-direct technique, blood samples were diluted in Natt and Herrick solution and smears were stained by Giemsa. Serpents from group 1 developed discrete anemia due to the inflammatory syndrome, and showed significant decrease of MCH and MCHC. Granulocytes were characterized by the presence of rough granules. The azurophils varied in shape and size and showed large amount of cytoplasmic vacuoles. The thrombocytopenia observed

  19. Cystectomy with orthotopic ileal neobladder reconstruction for treatment of bladder contracture after intravesical bacillus Calmette-Guerin therapy.

    Science.gov (United States)

    Vetorazzo Filho, José Eduardo; Bahia, Leandro Augusto Costa; Vedovato, Bruno César; Maron, Paulo Eduardo Goulart; Esteves, Paulo Ebert; Fernandes, Roni de Carvalho; Perez, Marjo Deninson Cardenuto

    2014-01-01

    Bladder cancer is an important health problem worldwide due to high prevalence rates and costs related to treatment. A reduction in recurrence rates has been observed since the introduction of adjuvant intravesical immunotherapy with bacillus Calmette-Guerin. There are mild complications that are easily solved by local measures and orientations. Bladder contracture, a rare and severe local complication, in some cases leading to disability, is observed primarily in patients in a maintenance program. In this article we reported the case of a male patient who underwent transurethral resection of the bladder because of a high-grade T1 urothelial carcinoma and developed this complication during treatment with bacillus Calmette-Guerin. For this reason he was submitted to cystoprostatectomy with orthotopic ileal neobladder reconstruction.

  20. Toxicogenomic response of Mycobacterium bovis BCG to peracetic acid and a comparative analysis of the M. bovis BCG response to three oxidative disinfectants.

    Science.gov (United States)

    Nde, Chantal W; Toghrol, Freshteh; Jang, Hyeung-Jin; Bentley, William E

    2011-04-01

    Tuberculosis is a leading cause of death worldwide and infects thousands of Americans annually. Mycobacterium bovis causes tuberculosis in humans and several animal species. Peracetic acid is an approved tuberculocide in hospital and domestic environments. This study presents for the first time the transcriptomic changes in M. bovis BCG after treatment with 0.1 mM peracetic acid for 10 and 20 min. This study also presents for the first time a comparison among the transcriptomic responses of M. bovis BCG to three oxidative disinfectants: peracetic acid, sodium hypochlorite, and hydrogen peroxide after 10 min of treatment. Results indicate that arginine biosynthesis, virulence, and oxidative stress response genes were upregulated after both peracetic acid treatment times. Three DNA repair genes were downregulated after 10 and 20 min and cell wall component genes were upregulated after 20 min. The devR-devS signal transduction system was upregulated after 10 min, suggesting a role in the protection against peracetic acid treatment. Results also suggest that peracetic acid and sodium hypochlorite both induce the expression of the ctpF gene which is upregulated in hypoxic environments. Further, this study reveals that in M. bovis BCG, hydrogen peroxide and peracetic acid both induce the expression of katG involved in oxidative stress response and the mbtD and mbtI genes involved in iron regulation/virulence.

  1. Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

    2016-05-13

    Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

  2. Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment

    DEFF Research Database (Denmark)

    Sartono, Erliyani; Lisse, Ida M; Terveer, Elisabeth M;

    2010-01-01

    BACKGROUND: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did...

  3. BCG vaccine-induced neuroprotection in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Yong, Jing; Lacan, Goran; Dang, Hoa; Hsieh, Terry; Middleton, Blake; Wasserfall, Clive; Tian, Jide; Melega, William P; Kaufman, Daniel L

    2011-01-31

    There is a growing interest in using vaccination with CNS antigens to induce autoreactive T cell responses that home to damaged areas in the CNS and ameliorate neurodegenerative disease. Neuroprotective vaccine studies have focused on administering oligodendrocyte antigens or Copaxone® in complete Freund's adjuvant (CFA). Theoretical considerations, however, suggest that vaccination with a neuronal antigen may induce more robust neuroprotective immune responses. We assessed the neuroprotective potential of vaccines containing tyrosine hydroxylase (a neuronal protein involved in dopamine synthesis) or Copaxone® in CFA in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Surprisingly, we observed that the main beneficial factor in these vaccines was the CFA. Since the major immunogenic component in CFA is Mycobacterium tuberculosis, which closely related to the bacille Calmette-Guérin (BCG) that is used in human vaccines, we tested BCG vaccination in the MPTP mouse model. We observed that BCG vaccination partially preserved markers of striatal dopamine system integrity and prevented an increase in activated microglia in the substantia nigra of MPTP-treated mice. These results support a new neuroprotective vaccine paradigm in which general (nonself-reactive) immune stimulation in the periphery can limit potentially deleterious microglial responses to a neuronal insult and exert a neurorestorative effect in the CNS. Accordingly, BCG vaccination may provide a new strategy to augment current treatments for a wide range of neuropathological conditions.

  4. Construction, Expression and Identification of a Recombinant BCG Vaccine Encoding Human Mycobacterium Tuberculosis Heat Shock Protein 65

    Institute of Scientific and Technical Information of China (English)

    戴五星; 梁靓; 高红; 黄海浪; 陈智浩; 程继忠; 皇甫永穆

    2004-01-01

    Heat shock protein 65 (HSP65) is one of the most important protective immunogens against the tuberculosis infection. The signal sequence of antigen 85B and the whole HSP65 DNA sequence of human Mycobacterium tuberculosis (M. tuberculosis) were amplified from BCG genome and plasmid pCMV-MTHSP65 respectively by polymerase chain reactions (PCR). These two sequences were cloned into the plasmid pBCG-2100 under the control of the promoter of heat shock protein 70 (HSP70) from human M. tuberculosis, yielding the prokaryotic shuttle expression plasmid pBCG-SP-HSP65. Results of restriction endonuclease analysis, PCR detection and DNA sequencing analysis showed that the two cloned DNA sequences were consistent with those previously reported, and the direction of their inserting into the recombinant was correct and the reading frame had been maintained. The recombinants were electroporated into BCG to construct the recombinant BCG vaccine and induced by heating. The induced expression detected by SDS-PAGE showed that the content of 65 kD protein expressed in recombinant BCG was 35.69 % in total bacterial protein and 74.09 % in the cell lysate supernatants, suggesting that the recombinant HSP65 gene could express in BCG with high efficiency and the expressed proteins were mainly soluble. Western-blot showed that the secretive recombinant proteins could specifically combine with antibody against M.tuberculosis HSP65, indicating that the recombinant proteins possess the biological activity of HSP65.

  5. Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

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    Daniel H. Libraty

    2014-01-01

    Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

  6. Pattern and determinants of BCG immunisation delays in a sub-Saharan African community

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    Olusanya Bolajoko O

    2010-01-01

    Full Text Available Abstract Background Childhood immunisation is recognised worldwide as an essential component of health systems and an indispensable indicator of quality of care for vaccine-preventable diseases. While performance of immunisation programmes is more commonly measured by coverage, ensuring that every child is immunised at the earliest/appropriate age is an important public health goal. This study therefore set out to determine the pattern and predictors of Bacille de Calmette-Guérin (BCG immunisation delays in the first three months of life in a Sub-Saharan African community where BCG is scheduled at birth in order to facilitate necessary changes in current policy and practices for improved services. Methods A cross-sectional study in which immunisation delays among infants aged 0-3 months attending community-based BCG clinics in Lagos, Nigeria over a 2-year period from July 2005 to June 2007 were assessed by survival analysis and associated factors determined by multivariable logistic regression. Population attributable risk (PAR was computed for the predictors of delays. Results BCG was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants enrolled, 3380 (65.4% were immunised within two weeks and a further 1265 (24.5% by six weeks. A significantly higher proportion of infants born in hospitals were vaccinated in the first six weeks compared to those born outside hospitals. Undernourishment was predictive of delays beyond 2 and 6 weeks while treated hyperbilirubinaemia was associated with decreased odds for any delays. Lack of antenatal care and multiple gestations were also predictive of delays beyond 6 weeks. Undernourishment was associated with the highest PAR for delays beyond 2 weeks (18.7% and 6 weeks (20.8%. Conclusions BCG immunisation is associated with significant delays in this setting and infants at increased risk of delays can be identified and supported early possibly through improved maternal uptake of

  7. 斑马鱼模型评价BCG-CpG-DNA的安全性%Evaluation of safety of BCG-CpG-DNA by using zebrafish model

    Institute of Scientific and Technical Information of China (English)

    王勇; 赵爱华; 陈将飞; 陈保文; 陈元红; 王国治

    2012-01-01

    目的 用斑马鱼模型对BCG-CpG-DNA进行安全性评价.方法 以斑马鱼胚胎为实验材料,将BCG-CpG-DNA设置4个浓度组(0.15、1.5、15、75 mg/L),暴露斑马鱼,以胚胎培养液暴露为空白对照组,以三甲基氯化锡(TMT)和全氟辛烷磺酸盐(PFOS)暴露为阳性对照组,胚胎期6 hpf(受精后6h)脱膜,8 hpf进行暴露毒性实验,研究其对斑马鱼发育、遗传、免疫以及行为的毒性影响.每组做3个重复,试验重复3次.结果 未观察到BCG-CpG-DNA各浓度组的斑马鱼胚胎明显的畸形和孵化死亡情况,其自主运动、触摸运动、行为检测、免疫强度检测与空白对照组相比,差异均无统计学意义(P>0.05).TMT对照组暴露对斑马鱼生长、发育、免疫及其神经等均有不同程度的影响,导致心胞肿大,对光暗刺激反应敏感,相对荧光强度明显增强,嗜中性粒细胞数量增多,对炎症的敏感性增强,与空白对照组相比,差异有统计学意义(P<0.05).结论 BCG-CpG-DNA暴露对斑马鱼生长、发育、免疫及其神经均无明显的急性毒性作用,在斑马鱼的胚胎暴露中具有较好的安全性.%Objective To evaluate the safety of BCG-CpG-DNA by using zebrafish model. Methods The embryos of ze-brafish were exposed to BCG-CpG-DNA at concentrations of 0. 15, 1. 5, 15 and 75 mg/L respectively, using those exposed to cul-ture liquid as blank control, and those exposed to TMT and PFOS as positive controls. Membrane shedding test was performed 6 h, while exposure toxicity test 8 h post fertilization to investigate the toxic effect on development, genetics, immune status and behavior of zebrafish. Each test was performed for 3 times in triplicate. Results No obvious monstrosities or deaths during incubation were ob-served in various test groups, while the autonomous movement, touch movement, behavior and immune level showed no significant difference with those in blank control group (P > 0. 05). However, TMT exposure showed

  8. Intravesical Toll-like receptor 7 agonist R-837: Optimization of its formulation in an orthotopic mouse model of bladder cancer

    Science.gov (United States)

    Hayashi, Tomoko; Crain, Brian; Corr, Maripat; Chan, Michael; Cottam, Howard B; Maj, Roberto; Barberis, Alcide; Leoni, Lorenzo; Carson, Dennis A

    2013-01-01

    Objective To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer. Methods Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy. The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-β-cyclodextrin (HPβCD). Induction of tumor necrosis factor α (TNFα) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay. The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells. Results Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFα and KC in a dose-dependent manner. Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC. Addition of HPβCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFα and KC. Histological examination showed that poloxamer-HPβCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria. In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice. Conclusion The optimized poloxamer-HPβCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects. PMID:20337728

  9. Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells.

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    Taweewun Hunsawong

    2015-09-01

    Full Text Available Dengue viruses (DENVs are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world's population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV composed of UV-inactivated DENV-2 (UVI-DENV and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs loaded into chitosan nanoparticles (CS-NPs. CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines.

  10. Glutamate Dehydrogenase Is Required by Mycobacterium bovis BCG for Resistance to Cellular Stress.

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    James L Gallant

    Full Text Available We recently reported on our success to generate deletion mutants of the genes encoding glutamate dehydrogenase (GDH and glutamine oxoglutarate aminotransferase (GOGAT in M. bovis BCG, despite their in vitro essentiality in M. tuberculosis. We could use these mutants to delineate the roles of GDH and GOGAT in mycobacterial nitrogen metabolism by using M. bovis BCG as a model for M. tuberculosis specifically. Here, we extended our investigation towards the involvement of GDH and GOGAT in other aspects of M. bovis BCG physiology, including the use of glutamate as a carbon source and resistance to known phagosomal stresses, as well as in survival inside macrophages. We find that gdh is indispensable for the utilization of glutamate as a major carbon source, in low pH environments and when challenged with nitric oxide. On the other hand, the gltBD mutant had increased viability under low pH conditions and was unaffected by a challenge with nitric oxide. Strikingly, GDH was required to sustain M. bovis BCG during infection of both murine RAW 264.7 and bone-marrow derived and macrophages, while GOGAT was not. We conclude that the catabolism of glutamate in slow growing mycobacteria may be a crucial function during infection of macrophage cells and demonstrate a novel requirement for M. bovis BCG GDH in the protection against acidic and nitrosative stress. These results provide strong clues on the role of GDH in intracellular survival of M. tuberculosis, in which the essentiality of the gdh gene complicates knock out studies making the study of the role of this enzyme in pathogenesis difficult.

  11. Tuberculin skin test distribution following a change in BCG vaccination policy.

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    Sei Won Lee

    Full Text Available BACKGROUND: Epidemiologic data regarding tuberculin skin test (TST responses are an important basis for TB control strategies. This study analyzed TST responses in Korea, which experienced a rapid change in BCG vaccination status. METHODS: TST responses in young adults were examined over 5 years. Participants with active TB lesions were excluded. RESULTS: A total of 5,552 participants were enrolled with median age of 21 years. When an induration diameter ≥10 mm was used as the criterion for a positive test, TST positivity fell (from 28.0% in 2005 to 15.3% in 2009; however, they remained steady when the criterion was ≥15-20 mm. A positive TST was associated with a personal or family of TB, the presence of a Bacille Calmette-Guérin (BCG scar, and age (odds ratio [95% confidence interval] = 4.03 [2.61-6.22], 2.91 [1.80-4.71], 1.50 [1.31-1.72], and 1.15 [1.09-1.20], respectively. Among these factors, the decrease of participants with BCG scars was the most prominent change, which appeared to be associated with the change of TST positivity rate. CONCLUSION: Overall, the rate of TST positivity in Korea decreased. However, this trend seems associated with the change of BCG vaccination strategy rather than successful control of LTBI. This study showed that change in BCG vaccination strategy can have great impact on TB epidemiologic survey based on TST.

  12. The Effect of BCG-PSN on T-cell Subsets and Cytokines in Vernal Conjunctivitis

    Institute of Scientific and Technical Information of China (English)

    胡军; 陈欢

    2002-01-01

    The effects of BCG-PSN on T-cell subsets and cytokines in vernal conjunctivitis were observed. The level of total IgE was quantitatively determined before and after treatment with BCGPSN by allergen diagnostic instrument in vitro. The content of T-cell subsets of peripheral blood and cytokine were determined by using indirect immune fluorescence method, and IL-4 and INF-γ were quantified by ELISA. The results showed that the level of total IgE was substantially reduced (P<0.01) after treatment in the BCG-PSN group. Meanwhile, CD8+ was decreased, CD4+ and CD4+/CD8+ratio elevated with significant differences (P<0. 05) as compared with pre-treatment results. The changes in total IgE, CD+8 ,CD4+ and CD4+/CD+8 ratio after treatment also presented significant differences (P<0. 05) between BCG-PSN group and routine treatment group. The level of IL-4 in serum declined (P<0. 05) after treatment in the BCG-PSN group, and INF-γ went up (P<0.05). IL-4and INF-γ in serum showed significant differences (P<0. 05) between two groups after treatment.It is concluded that BCG-PSN has a bi-directional immunoregulating effect. It can bring CD4+ and CD+8- into homeostasis, thereby preventing the occurrence of anaphylaxis. At the same time, BCGPSN can restrain Th2, decrease the synthesis of IL-4, switch the balance of Th1/Th2 to Th1 side,boost up the predominance of Th1 relatively, which is propitious to perennial stabilization and recov cry of vernal conjunctivitis.

  13. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

    DEFF Research Database (Denmark)

    Benn, Christine S; Fisker, Ane B; Whittle, Hilton C

    2016-01-01

    BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi......BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore....... In a quasi-experimental study two doses before and after 9months compared with one dose of MV after 9months of age reduced mortality by 59% (25-81%). BCG-revaccination significantly enhanced BCG's effect against overall child mortality in two RCTs. In a natural experiment study of OPV campaigns over a 13......-year-period in Guinea-Bissau, each additional dose of OPV was associated with a 13% (4-21%) reduction in mortality rate. The beneficial NSEs of smallpox vaccination for survival increased significantly with the number of smallpox vaccination scars. INTERPRETATION: Revaccination with live vaccines led...

  14. The glycosylated Rv1860 protein of Mycobacterium tuberculosis inhibits dendritic cell mediated TH1 and TH17 polarization of T cells and abrogates protective immunity conferred by BCG.

    Science.gov (United States)

    Satchidanandam, Vijaya; Kumar, Naveen; Jumani, Rajiv S; Challu, Vijay; Elangovan, Shobha; Khan, Naseem A

    2014-06-01

    We previously reported interferon gamma secretion by human CD4⁺ and CD8⁺ T cells in response to recombinant E. coli-expressed Rv1860 protein of Mycobacterium tuberculosis (MTB) as well as protection of guinea pigs against a challenge with virulent MTB following prime-boost immunization with DNA vaccine and poxvirus expressing Rv1860. In contrast, a Statens Serum Institute Mycobacterium bovis BCG (BCG-SSI) recombinant expressing MTB Rv1860 (BCG-TB1860) showed loss of protective ability compared to the parent BCG strain expressing the control GFP protein (BCG-GFP). Since Rv1860 is a secreted mannosylated protein of MTB and BCG, we investigated the effect of BCG-TB1860 on innate immunity. Relative to BCG-GFP, BCG-TB1860 effected a significant near total reduction both in secretion of cytokines IL-2, IL-12p40, IL-12p70, TNF-α, IL-6 and IL-10, and up regulation of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone marrow derived dendritic cells (BMDC), while leaving secreted levels of TGF-β unchanged. These effects were mimicked by BCG-TB1860His which carried a 6-Histidine tag at the C-terminus of Rv1860, killed sonicated preparations of BCG-TB1860 and purified H37Rv-derived Rv1860 glycoprotein added to BCG-GFP, but not by E. coli-expressed recombinant Rv1860. Most importantly, BMDC exposed to BCG-TB1860 failed to polarize allogeneic as well as syngeneic T cells to secrete IFN-γ and IL-17 relative to BCG-GFP. Splenocytes from mice infected with BCG-SSI showed significantly less proliferation and secretion of IL-2, IFN-γ and IL-17, but secreted higher levels of IL-10 in response to in vitro restimulation with BCG-TB1860 compared to BCG-GFP. Spleens from mice infected with BCG-TB1860 also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF-α compared to mice infected with BCG-GFP. Glycoproteins of MTB, through their deleterious effects on DC may thus contribute to suppress the generation of a TH1- and TH17-dominated

  15. The glycosylated Rv1860 protein of Mycobacterium tuberculosis inhibits dendritic cell mediated TH1 and TH17 polarization of T cells and abrogates protective immunity conferred by BCG.

    Directory of Open Access Journals (Sweden)

    Vijaya Satchidanandam

    2014-06-01

    Full Text Available We previously reported interferon gamma secretion by human CD4⁺ and CD8⁺ T cells in response to recombinant E. coli-expressed Rv1860 protein of Mycobacterium tuberculosis (MTB as well as protection of guinea pigs against a challenge with virulent MTB following prime-boost immunization with DNA vaccine and poxvirus expressing Rv1860. In contrast, a Statens Serum Institute Mycobacterium bovis BCG (BCG-SSI recombinant expressing MTB Rv1860 (BCG-TB1860 showed loss of protective ability compared to the parent BCG strain expressing the control GFP protein (BCG-GFP. Since Rv1860 is a secreted mannosylated protein of MTB and BCG, we investigated the effect of BCG-TB1860 on innate immunity. Relative to BCG-GFP, BCG-TB1860 effected a significant near total reduction both in secretion of cytokines IL-2, IL-12p40, IL-12p70, TNF-α, IL-6 and IL-10, and up regulation of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone marrow derived dendritic cells (BMDC, while leaving secreted levels of TGF-β unchanged. These effects were mimicked by BCG-TB1860His which carried a 6-Histidine tag at the C-terminus of Rv1860, killed sonicated preparations of BCG-TB1860 and purified H37Rv-derived Rv1860 glycoprotein added to BCG-GFP, but not by E. coli-expressed recombinant Rv1860. Most importantly, BMDC exposed to BCG-TB1860 failed to polarize allogeneic as well as syngeneic T cells to secrete IFN-γ and IL-17 relative to BCG-GFP. Splenocytes from mice infected with BCG-SSI showed significantly less proliferation and secretion of IL-2, IFN-γ and IL-17, but secreted higher levels of IL-10 in response to in vitro restimulation with BCG-TB1860 compared to BCG-GFP. Spleens from mice infected with BCG-TB1860 also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF-α compared to mice infected with BCG-GFP. Glycoproteins of MTB, through their deleterious effects on DC may thus contribute to suppress the generation of a TH1- and TH

  16. Analysis of Japanese Patients Treated with or without Long-Term Epirubicin Plus Ara-C Intravesical Instillation Therapy for Low-Grade Superficial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Tomonori Kato

    2015-01-01

    Full Text Available The high incidence of tumor recurrence following transurethral resection (TUR represents a major problem encountered in the management of bladder cancer. This study examined the efficacy of intravesical chemotherapy in superficial bladder cancer. We retrospectively analyzed 90 Japanese cases with low-grade superficial transitional cell carcinoma (stage T1, grades 1 and 2 who were rendered tumor-free by TURBT (TUR of bladder tumor and who thereafter were treated with or without intravesical chemotherapy. Among them, instillation was terminated in 2 patients due to adverse effects (severe but reversible chemical cystitis. Remaining 88 patients were divided into 2 groups according to therapy: the TURBT-only group (n=46, defined as patients treated with TURBT alone, and the Instillation group (n=42, defined as patients treated with weekly intravesical instillation therapies using epirubicin plus Ara-C. Recurrence-free rate was significantly higher in the Instillation group than in the TURBT-only group (p=0.02, HR = 0.457. The 5-year recurrence-free rate was 58.5% for the Instillation group and 38.6% for the TURBT-only group. Our instillation schedule represents the most intensive regimen among previously reported therapies and resulted in a 54.3% decrease in incidence of tumor recurrence. We believe that the results of this study could provide useful information on management of bladder cancer.

  17. Evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall obtained by transurethral intravesical echotomography

    Directory of Open Access Journals (Sweden)

    Milošević Radovan

    2007-01-01

    Full Text Available Background/Aim. Transitional cell carcinoma (TCC is the most frequent tumor of the bladder and represents 95−98% of blader neoplasams and 2−3% of all carcinomas in the body. In urogenital oncology more frequent is only prostatic cancer. Evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall represents the clinical base in treatment planning and prognosis. Clinical investigation and convential radiological procedures have a low level of accuracy in estimating the local growth of the tumor. The aims of our investigation were to determine the depth of infiltration of urothelial carcinoma in the vesical wall in the investigated group of patients by transurethral intravesical echotomography (TIE and computerised tomography (CT scan and to compare results obtained by both methods with pathohistological (PH results, and, based on the difference of the results determine which method was more accurate in the evaluation of the depth of infiltration of urothelial carcinoma in the vesical wall. Methods. Thirty patients with TCC of the bladder both genders, aged 51−81 years were involved in our investigation. In all of these patients, radical cystectomy (RC was performed. This was neccessary to provide the defintive PH result. Transurethral intravesical echotomography was performed by ultrasound scanner type 1846 Bruel and Kjaer, sond type 1850, and the CT scan was perfomed by Pace plus, General Electric, U.S.A. The specimen for the definitive PH result obtained by RC includes all standards of the TNM classification. Results. Using CT scan, the most frequent was T1 stage (17 patients or 56.68%. Using TIE, the most frequent was T2 stage (22 patients or 73.33%. After RC the most frequent was T2 stage (21 patients or 70%. The Kolmogorov-Smirnov test, showed a high significant difference between the results obtained using CT and definitive PH results after RC. The same test showed no statistically significant difference between

  18. Enhanced and durable protective immune responses induced by a cocktail of recombinant BCG strains expressing antigens of multistage of Mycobacterium tuberculosis.

    Science.gov (United States)

    Liang, Jinping; Teng, Xindong; Yuan, Xuefeng; Zhang, Ying; Shi, Chunwei; Yue, Tingting; Zhou, Lei; Li, Jianrong; Fan, Xionglin

    2015-08-01

    Although Bacillus Calmette-Guérin (BCG) vaccine confers protection from Mycobacterium tuberculosis infection in children, its immune protection gradually wanes over time, and consequently leads to an inability to prevent the reactivation of latent infection of M. tuberculosis. Therefore, improving BCG for better control of tuberculosis (TB) is urgently needed. We thus hypothesized that recombinant BCG overexpressing immunodominant antigens expressed at different growth stages of M. tuberculosis could provide a more comprehensive protection against primary and latent M. tuberculosis infection. Here, a novel cocktail of recombinant BCG (rBCG) strains, namely ABX, was produced by combining rBCG::85A, rBCG::85B, and rBCG::X, which overexpressed respective multistage antigens Ag85A, Ag85B, and HspX of M. tuberculosis. Our results showed that ABX was able to induce a stronger immune protection than individual rBCGs or BCG against primary TB infection in C57BL/6 mice. Mechanistically, the immune protection was attributed to stronger antigen-specific CD4(+) Th1 responses, higher numbers of IFN-γ(+) CD4(+) TEM and IL-2(+) CD8(+) TCM cells elicited by ABX. These findings thus provide a novel strategy for the improvement of BCG efficacy and potentially a promising prophylactic TB vaccine candidate, warranting further investigation.

  19. Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection.

    Science.gov (United States)

    Xu, Zheng Zhong; Chen, Xiang; Hu, Ting; Meng, Chuang; Wang, Xiao Bo; Rao, Yan; Zhang, Xiao Ming; Yin, Yue Lan; Pan, Zhi Ming; Jiao, Xin An

    2016-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide-MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG::Ag85A were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN-γ) responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that rBCG::Ag85A can enhance protection against Mycobacterium tuberculosis (M. tuberculosis) H37Rv infection compared to the BCG vaccine alone. Our results demonstrate the potential of rBCG::Ag85A as a candidate vaccine against TB.

  20. Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection.

    Science.gov (United States)

    Ma, Xiumin; Zhao, Hui; Zhang, Fengbo; Zhu, Yuejie; Peng, Shanshan; Ma, Haimei; Cao, Chunbao; Xin, Yan; Yimiti, Delixiati; Wen, Hao; Ding, Jianbing

    2016-01-01

    Cystic hydatid disease is a zoonotic parasitic disease caused by Echinococcus granulosus which is distributed worldwide. The disease is difficult to treat with surgery removal is the only cure treatment. In the high endemic areas, vaccination of humans is believed a way to protect communities from the disease. In this study we vaccinated BALB/c mice with rBCG-EgG1Y162, and then detected the level of IgG and IgE specifically against the recombinant protein by ELISA, rBCG-EgG1Y162 induced strong and specific cellular and humoral immune responses. In vitro study showed that rBCG-EgG1Y162 vaccine not only promote splenocytes proliferation but also active T cell. In addition, the rBCG-EgG1Y162 induced a protection in the mice against secondary infection of Echinococcus granulosus.

  1. Factors determining whether the parents accept BCG immunization of the new-born child in a high-income country

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte; Ammentorp, Jette; Kofoed, Poul-Erik

    Introduction: A large prospective randomised clinical trial in Denmark is planned to test the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood........ My focus for this project is decision making. Method: During the next year all parents planning to give birth at Kolding Hospital will be offered inclusion in the study . In the 2nd/3rd trimester they will receive a letter with information on the study and afterward the local Ph......' Connors 'Decisional Conflict scale' to compare decisional conflicts for the parents that accept BCG vaccination and parents who do not accept the BCG vaccination of their newborn child....

  2. Enhanced protective efficacy against tuberculosis provided by a recombinant urease deficient BCG expressing heat shock protein 70-major membrane protein-II having PEST sequence.

    Science.gov (United States)

    Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Mukai, Tetsu; Mitarai, Satoshi; Yamamoto, Saburo; Makino, Masahiko

    2016-12-07

    Enhancement of the T cell-stimulating ability of Mycobacterium bovis BCG (BCG) is necessary to develop an effective tuberculosis vaccine. For this purpose, we introduced the PEST-HSP70-major membrane protein-II (MMPII)-PEST fusion gene into ureC-gene depleted recombinant (r) BCG to produce BCG-PEST. The PEST sequence is involved in the proteasomal processing of antigens. BCG-PEST secreted the PEST-HSP70-MMPII-PEST fusion protein and more efficiently activated human monocyte-derived dendritic cells (DCs) in terms of phenotypic changes and cytokine productions than an empty-vector-introduced BCG or HSP70-MMPII gene-introduced ureC gene-depleted BCG (BCG-DHTM). Autologous human naïve CD8(+) T cells and naïve CD4(+) T cells were effectively activated by BCG-PEST and produced IFN-γ in an antigen-specific manner through DCs. These T cell activations were closely associated with phagosomal maturation and intraproteasomal protein degradation in antigen-presenting cells. Furthermore, BCG-PEST produced long-lasting memory-type T cells in C57BL/6 mice more efficiently than control rBCGs. Moreover, a single subcutaneous injection of BCG-PEST more effectively reduced the multiplication of subsequent aerosol-challenged Mycobacterium tuberculosis of the standard H37Rv strain and clinically isolated Beijing strain in the lungs than control rBCGs. The vaccination effect of BCG-PEST lasted for at least 6months. These results indicate that BCG-PEST may be able to efficiently control the spread of tuberculosis in human.

  3. The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles)

    Science.gov (United States)

    Chambers, Mark A.; Aldwell, Frank; Williams, Gareth A.; Palmer, Si; Gowtage, Sonya; Ashford, Roland; Dalley, Deanna J.; Davé, Dipesh; Weyer, Ute; Salguero, Francisco J.; Nunez, Alejandro; Nadian, Allan K.; Crawshaw, Timothy; Corner, Leigh A. L.; Lesellier, Sandrine

    2017-01-01

    The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 108 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or

  4. Vacina BCG: eficácia e indicações da vacinação e da revacinação BCG vaccine: efficacy and indications for vaccination and revaccination

    Directory of Open Access Journals (Sweden)

    Mauricio L. Barreto

    2006-07-01

    Full Text Available OBJETIVOS: Revisar aspectos relacionados ao efeito protetor da primeira e segunda doses da vacina BCG e discutir as suas principais indicações e contra-indicações. FONTES DOS DADOS: Utilizando o PubMed, foi realizada uma revisão sistemática da literatura abrangendo um período de, aproximadamente, 50 anos. Os estudos foram agrupados por tipo de desenho, apresentando-se separadamente os principais resultados de ensaios clínicos, estudos de caso-controle e meta-análises. Outros tópicos relevantes, como a BCG e HIV/AIDS, o uso do teste tuberculínico, aspectos relacionados à cicatriz vacinal e ao desenvolvimento de novas vacinas, dentre outros, foram também revistos. SÍNTESE DOS DADOS: A vacina BCG é utilizada desde 1921. Apesar disso, ainda apresenta controvérsias e aspectos não esclarecidos. O efeito protetor da primeira dose da vacina BCG contra a tuberculose na forma miliar ou na meningite é bastante significativa. No entanto, em relação à forma pulmonar, os resultados são discordantes, variando de ausência de efeito a níveis próximos a 80%. Há evidências de que uma segunda dose da BCG não aumenta o seu efeito protetor. Estudos demonstram proteção da vacina contra a hanseníase. Pesquisas sobre novas vacinas que, no futuro, poderão vir a substituir a BCG estão sendo realizadas. CONCLUSÕES:Apesar da expectativa de que, no futuro, venhamos a ter uma nova vacina para a tuberculose, no presente e ainda por muitos anos, a vacina BCG, apesar de suas deficiências, mantém-se como um importante instrumento nos esforços para controle dos efeitos danosos da tuberculose, sobretudo em países em que essa doença ocorre em médias e elevadas taxas de incidência.OBJECTIVES: To review the protective efficacy of the first and second doses of BCG vaccine and to assess its major indications and contraindications. SOURCES OF DATA: A systematic review of the literature was made by searching PubMed and selecting studies carried out

  5. PD-L2 induction on dendritic cells exposed to Mycobacterium avium downregulates BCG-specific T cell response.

    Science.gov (United States)

    Mendoza-Coronel, Elizabeth; Camacho-Sandoval, Rosa; Bonifaz, Laura C; López-Vidal, Yolanda

    2011-01-01

    The exposure to certain species of Nontuberculous Mycobacteria (NTM) can modulate the immune response induced by Mycobacterium bovis BCG. Mycobacterium avium has been postulated as a weak inducer of dendritic cell (DC) maturation. However, how the DC exposure to M. avium could contribute to the modulation of a BCG-specific CD4+ T cell response and the molecules involved remain unknown. Here, we exposed bone marrow-derived DCs (BMDCs) to M. avium either prior to exposure to BCG or as a unique stimulus. We found that M. avium induces high expression of PD-L2 (B7-DC) in BMDCs. This was dependent on IL-10 production through the TLR2-p38 MAPK signaling pathway. Exposure to M. avium prior to BCG results in BMDCs that do not express co-stimulatory molecules and pro-inflammatory cytokines, while the expression of PD-L2 and IL-10 was maintained. BMDCs exposed to M. avium impaired the activation of BCG-specific T cells through the PD-1: PD-L interaction. This suggests that a M. avium-induced phenotype in DCs might be implicated in the induction of mechanisms of tolerance that could impact the T cell response induced by BCG vaccination.

  6. Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

    Science.gov (United States)

    Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

    2016-02-10

    Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible.

  7. Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice.

    Science.gov (United States)

    Yang, Enzhuo; Gu, Jin; Wang, Feifei; Wang, Honghai; Shen, Hongbo; Chen, Zheng W

    2016-04-01

    Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425. Results showed that the prime-boost strategy could significantly increase the protective efficiency against Mtb infection, characterized by reduction of bacterial load in lung and spleen, attenuation of tuberculosis lesions in lung tissues. Importantly, we found that Rv3425 boost, superior to Ag85B boost, provided better protection against Mtb infection. Further research proved that rBCG prime-Rv3425 boost could obviously increase the expansion of lymphocytes, significantly induce IL-2 production by lymphocytes upon PPD stimulation, and inhibit IL-6 production at an early stage. It implied that rBCG prime-Rv3425 boost opted to induce Th1 immune response and provided a long-term protection against TB. These results implicated that rBCG prime-Rv3425 boost is a potent and promising strategy to prevent acute Mtb infection.

  8. Efeito do Mycobacterium bovis BCG, lipopolissacarideo bacteriano e hidrocortisona no desenvolvimento de imunidade ao Plasmodium berghei em camundongos

    Directory of Open Access Journals (Sweden)

    José J. Ferraroni

    1986-02-01

    Full Text Available Mycobacterium bovis (BCG aumenta significantemente o desenvolvimento da imunidade nos camundongos CFW, C57BL/6, C57BL/l0ScN e BALB/c (Nu/+ para os estágios eritrocitos do Plasmodium berghei. Camundongos tratados com BCG requerem menos ciclos de infecção com P. berghei e cura pelo Fansidar (pirimetamina + sulfadoxina para desenvolverem imunidade sólida a este parasita do que os controles. Contudo, os animais que receberam BCG 30 dias antes do início da imunização evidenciaram uma perda precoce da imunidade adquirida para o P. berghei, quando comparado com os animais que receberam BCG 14 dias antes ou que não receberam BCG. Assim, sendo, o BCG aumentada a indução na resposta imune do hospedeiro ao P. berghei no curso de infecções subseqüentes. O tratamento de camundongos CFW, BALB/c e C57BL/6 com lipopolissacarídeo bacteriano ou hidrocortisona faz com que os animais requeiram um número maior de ciclos de infecção e cura para tornarem-se imunes ao P. berghei que os controles. O tratamento dos camundongos C57BL/10ScN com hidrocortisona aboliu completamente a sua habilidade de sobrevida subseqüentes a ciclos de infecção com P. berghei e cura pelo Fansidar.

  9. Characterization of different carbon nanotubes for the development of a mucoadhesive drug delivery system for intravesical treatment of bladder cancer.

    Science.gov (United States)

    Rieger, Christiane; Kunhardt, David; Kaufmann, Anika; Schendel, Darja; Huebner, Doreen; Erdmann, Kati; Propping, Stefan; Wirth, Manfred P; Schwenzer, Bernd; Fuessel, Susanne; Hampel, Silke

    2015-02-20

    In order to increase the effectiveness of therapeutics for bladder carcinoma (BCa) treatment, alternative strategies for intravesical applications are needed. The use of carbon nanotubes (CNTs) as basis for a multifunctional drug transporter is a promising possibility to combine traditional chemotherapeutics with innovative therapeutic agents such as antisense oligodeoxynucleotides or small interfering RNA. In the current study four CNT types varying in length and diameter (CNT-1, CNT-2, CNT-3, CNT-4) were synthesized and then characterized with different spectroscopic techniques. Compared to the pristine CNT-1 and CNT-3, the shortened CNT-2 and CNT-4 exhibited more defects and lower aspect ratios. To analyze their mucoadhesive properties, CNTs were exposed to mouse bladders ex vivo by using Franz diffusion cells. All four tested CNT types were able to adhere to the urothelium with a mean covering area of 5-10%. In vitro studies on UM-UC-3 and EJ28 BCa cells were conducted to evaluate the toxic potential of these CNTs. Viability and cytotoxicity assays revealed that the shortened CNT-2 and CNT-4 induced stronger inhibitory effects on BCa cells than CNT-1 and CNT-3. In conclusion, CNT-1 and CNT-3 showed the most promising properties for further optimization of a multifunctional drug transporter.

  10. Potential therapeutic effect of intravesical botulinum toxin type A on bladder pain syndrome/interstitial cystitis.

    Science.gov (United States)

    Jhang, Jia-Fong; Jiang, Yuan-Hong; Kuo, Hann-Chorng

    2014-04-01

    Bladder pain syndrome/interstitial cystitis is characterized by bladder pain associated with urgency, frequency, nocturia, dysuria and sterile urine. Recent studies have shown that these bladder dysfunctions could originate from chronic inflammation or urothelial insult and proceed to a cascade of tissue reactions, which finally ascends to the central nervous system. Pilot studies of intravesical injection of botulinum toxin type A for bladder pain syndrome/interstitial cystitis had been introduced since 2005 with a promising result. Recent evidence suggests that botulinum toxin type A could significantly improve symptoms such as daytime frequency, nocturia, pain, quality of life and bladder capacity in bladder pain syndrome/interstitial cystitis patients. Single injection of botulinum toxin could not achieve long-term successful therapeutic result, and repeat injections could provide a better long-term success rate. However, patients with ulcer type bladder pain syndrome/interstitial cystitis might not gain a benefit from botulinum toxin type A injection. Laboratory evidence showed that botulinum toxin type A for bladder pain syndrome/interstitial cystitis injection could induce peripheral desensitization, reduces bladder chronic inflammation and decreases apoptotic signal molecules in the urothelium. The present article reviewed the recent advances of botulinum toxin type A on bladder pain syndrome/interstitial cystitis.

  11. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie;

    2016-01-01

    MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age Developmental assessment was available for 3453/4262 (81%). RESULTS......OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

  12. Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

    LENUS (Irish Health Repository)

    Forde, J C

    2012-03-01

    Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

  13. "PRESUMED SYSTEMIC BACILLE CALMETTE-GUÉRIN DISEASE AFTER BCG VACCINATION: REPORT OF A CLINICAL CASE "

    Directory of Open Access Journals (Sweden)

    P. Tabatabaie

    2006-08-01

    Full Text Available BCG (bacille Calmette–Guérin vaccine is administered worldwide to prevent severe forms of tuberculosis. It is considered to be safe; however, occasional complications are seen. The most serious complication is BCGosis. We report a case of BCGosis with granulomatous hepatitis and acid-fast bacilli in liver and spleen. We treated the patient with antituberculosis drugs without any response to treatment.

  14. Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, Ernest J.; Poston, Ted M.; Tiller, Brett L.; Patton, Gene W.

    2003-07-01

    Abstract. In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy’s Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwest National Laboratory’s Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel® spreadsheet and Visual Basic® software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator’s site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program’s kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.

  15. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

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

    Science.gov (United States)

    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.

  17. bcgTree: automatized phylogenetic tree building from bacterial core genomes.

    Science.gov (United States)

    Ankenbrand, Markus J; Keller, Alexander

    2016-10-01

    The need for multi-gene analyses in scientific fields such as phylogenetics and DNA barcoding has increased in recent years. In particular, these approaches are increasingly important for differentiating bacterial species, where reliance on the standard 16S rDNA marker can result in poor resolution. Additionally, the assembly of bacterial genomes has become a standard task due to advances in next-generation sequencing technologies. We created a bioinformatic pipeline, bcgTree, which uses assembled bacterial genomes either from databases or own sequencing results from the user to reconstruct their phylogenetic history. The pipeline automatically extracts 107 essential single-copy core genes, found in a majority of bacteria, using hidden Markov models and performs a partitioned maximum-likelihood analysis. Here, we describe the workflow of bcgTree and, as a proof-of-concept, its usefulness in resolving the phylogeny of 293 publically available bacterial strains of the genus Lactobacillus. We also evaluate its performance in both low- and high-level taxonomy test sets. The tool is freely available at github ( https://github.com/iimog/bcgTree ) and our institutional homepage ( http://www.dna-analytics.biozentrum.uni-wuerzburg.de ).

  18. New Recombinant Mycobacterium bovis BCG Expression Vectors: Improving Genetic Control over Mycobacterial Promoters

    Science.gov (United States)

    Kanno, Alex I.; Goulart, Cibelly; Rofatto, Henrique K.; Oliveira, Sergio C.; Leite, Luciana C. C.

    2016-01-01

    The expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such as Mycobacterium bovis BCG or M. smegmatis was made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. However, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. To establish a systematic selection of promoters with a range of strengths, we generated a library of mutagenized promoters through error-prone PCR of the strong PL5 promoter, originally from mycobacteriophage L5. These promoters were cloned upstream of the enhanced green fluorescent protein reporter gene, and recombinant M. smegmatis bacteria exhibiting a wide range of fluorescence levels were identified. A set of promoters was selected and identified as having high (pJK-F8), intermediate (pJK-B7, pJK-E6, pJK-D6), or low (pJK-C1) promoter strengths in both M. smegmatis and M. bovis BCG. The sequencing of the promoter region demonstrated that it was extensively modified (6 to 11%) in all of the plasmids selected. To test the functionality of the system, two different expression vectors were demonstrated to allow corresponding expression levels of the Schistosoma mansoni antigen Sm29 in BCG. The approach used here can be used to adjust expression levels for synthetic and/or systems biology studies or for vaccine development to maximize the immune response. PMID:26850295

  19. Is tuberculin testing before BCG vaccination necessary for children over three months of age?

    LENUS (Irish Health Repository)

    Hennessy, B

    2008-03-01

    In July 2007 Irish national policy changed such that children aged 3 months to 6 years no longer routinely require tuberculin (Mantoux) skin testing prior to BCG vaccination. Previous to that a tuberculin test was required in all children in this age group pre vaccination. While the previous policy was in place this study was conducted to assess the value of this test. The observation that children are frightened by the test (an injection into the skin) prompted the study. The author conducted a retrospective study of the results of 1,854 tuberculin tests performed as a prerequisite to BCG vaccination and found that only 0.7% of children had a positive test result (induration > 5mm). None of 107 children < 6 years of age tested positive. Those > 12 years were more likely to test positive than younger children (1.09% vs 0.4% respectively, p < 0.05). This study suggests that testing young children before BCG vaccination has a low yield of positive results and adds little to the detection of latent or active TB.

  20. Effects of berberine hydrochloride on CYP450 total content and expression in BCG-induced immune hepatic injury in mice and its possible mechanism

    Institute of Scientific and Technical Information of China (English)

    XinWANG; DanLI; Jun-jieZHANG; Xiu-yunBU; Guo-liangZHANG

    2004-01-01

    AIM:To investigate effects of berberine hydrochloride on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice and its possible mechanism. METHODS: Immunological liver injury was induced by intravenous injection of Mycobacterium bovis bacillus Calmette-Guerin (BCG, 125 mg/kg) in BALB/c mice. After one week stimulated by BCG,berberine hydrochloride (10, 25, 50, 75, and 100 mg/kg,respectively, qid 7 d) was administrated by intragastric

  1. The inhibitory effect of intravesical fisetin against bladder cancer by induction of p53 and down-regulation of NF-kappa B pathways in a rat bladder carcinogenesis model.

    Science.gov (United States)

    Li, Jing; Qu, Weixing; Cheng, Yongyi; Sun, Yi; Jiang, Yazhuo; Zou, Tiejun; Wang, Zhiping; Xu, Yonggang; Zhao, Huacai

    2014-10-01

    Intravesical chemotherapy after transurethral resection has been widely used as an adjuvant therapy to prevent recurrence and progression of superficial bladder cancer. Due to the insufficiency of the current chemotherapeutics, there is an urgent need to search for more novel, effective and safe intravesical agents. Previously, we have proved the in vitro apoptotic effects of fisetin, a dietary flavonoid, on bladder carcinoma cells. In the present study, we have further explored its intravesical efficacy and investigated the underlying mechanisms of its inhibitory effect of bladder cancer through an autochthonous rat model of bladder cancer induced by intravesical N-methyl-N-nitrosourea (MNU). We found that fisetin-induced apoptosis in bladder cancer is mediated via modulation of two related pathways: up-regulation of p53 and down-regulation of NF-κB pathway activity, causing changes in the ratio of pro- and antiapoptotic proteins. Meanwhile, administration of fisetin significantly reduced the incidence of MNU-induced bladder tumours by suppressing NF-κB activation and modulating the expression of NF-κB target genes that regulate cell proliferation and cell apoptosis. Our study suggests that the activation of p53 and inhibition of the NF-κB pathway may play important roles in the fisetin-induced apoptosis in bladder cancer. Furthermore, intravesical fisetin effectively inhibited, without any toxicity, the carcinogenesis of bladder cancer in MNU-initiated rats. These findings identify the in vivo chemopreventive efficacy of fisetin and suggest that fisetin could be used as a novel, effective and safe intravesical agent for bladder cancer.

  2. Rabbits immunised with recombinant BCG expressing the cottontail rabbit papillomavirus (CRPV) L2E7E2 genes induces regression of established papillomas.

    Science.gov (United States)

    Govan, V A; Williamson, A-L

    2007-07-01

    We previously demonstrated in a cottontail rabbit papillomavirus (CRPV) challenge model that recombinant Bacille Calmette-Guerin (rBCG) could potentially be used as a prophylactic vaccine vehicle to deliver papillomavirus proteins. In this study we investigated whether regression of CRPV-induced papillomas could be achieved following immunisation of out-bred New Zealand White rabbits with rBCG expressing CRPVL2, CRPVE2, CRPVE7 or CRPVL2E7E2 proteins. Rabbits immunised with rBCG/CRPVL2E7E2 had papillomas that were largely suppressed and were significantly smaller compared to the rBCG negative control group (Prabbits immunised with rBCG/CRPVL2E7E2 had papillomas that completely regressed 1.5 weeks post third immunisation. Rabbits immunised with rBCG/CRPVL2, rBCG/CRPVE7, or rBCG/CRPVE2 had papillomas that were significantly smaller than the negative control rabbits (PBCG could probably be used as a vaccine delivery vehicle for human papillomavirus proteins as a possible therapeutic vaccine.

  3. Studies of monocytopoiesis in patients with malignant disease and after imunostimulation with BCG, using /sup 3/H-thymidine as a DNA-label

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, E.; Meuret, G.; Waldermann, F.; Hoffmann, G.

    1982-04-01

    Monocytopoiesis and blood monocytes were investigated in patients with Hodgkin's disease, non-Hodgkin lymphomas, mycosis fungoides, breast cancer or melanoma. The investigation was carried out before surgery and just before each application of BCG. Monocyte production was increased in untreated patients. Postoperative prophylactic BCG-vaccination gave rise to increased proliferation activity. However monocyte production returned to normal between the 4th and 6th month of BCG immunotherapy. These results indicate that monocytopoiesis is stimulated by human tumors. BCG immunostimulation is able to increase proliferation activity during the first month of treatment only.

  4. A New Recombinant BCG Vaccine Induces Specific Th17 and Th1 Effector Cells with Higher Protective Efficacy against Tuberculosis

    Science.gov (United States)

    da Costa, Adeliane Castro; Costa-Júnior, Abadio de Oliveira; de Oliveira, Fábio Muniz; Nogueira, Sarah Veloso; Rosa, Joseane Damaceno; Resende, Danilo Pires; Kipnis, André; Junqueira-Kipnis, Ana Paula

    2014-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. PMID:25398087

  5. A booster vaccine expressing a latency-associated antigen augments BCG induced immunity and confers enhanced protection against tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bappaditya Dey

    Full Text Available BACKGROUND: In spite of a consistent protection against tuberculosis (TB in children, Mycobacterium bovis Bacille Calmette-Guerin (BCG fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA vaccine expressing α-crystallin--a key latency antigen of M. tuberculosis to boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log(10 and 1.96 log(10 fewer bacilli in lungs and spleen, respectively; p<0.01. In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice results in a heightened frequency of PPD and antigen specific multi-functional CD4 T cells (3(+ simultaneously producing interferon (IFNγ, tumor necrosis factor (TNFα and interleukin (IL2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based B/D regimen over BCG. Our study, also demonstrates that protection against TB is predictable by an increased frequency of 3(+ Th1 cells with superior effector functions. We anticipate that this study would significantly contribute towards the development of superior booster vaccines for BCG vaccinated individuals. In addition, this regimen can also be expected to reduce the risk of developing active TB due to reactivation of latent infection.

  6. Is there a correlation between the size of the BCG scar and renal scar of urinary tract infections in children?

    Directory of Open Access Journals (Sweden)

    Salih Kavukçu

    2013-03-01

    Full Text Available Objective: Pyelonephritis cause cellular death, and developmentof scars in kidneys. The aim of this study is todemonstrate a correlation (if any between renal scar, andsize of the scar induced by BCG vaccine in children whohad experienced urinary tract infections. In case of detectionof any correlation, BCG scar formation can be usedas a determinative marker of renal scars, which developfollowing urinary tract infection.Methods: Patients with a history of urinary tract infectionat least 4 months old who had undergone 99mTcDMSAscanning were included in this study. Vertical and horizontaldiameters of BCG scars of the patients in the studygroup were measured. For statistical analysis the greatestdiameter was taken into consideration, and the patientswere divided into 2 subgroups based on the greatest diameterof their BCG scars (Subgroups 1, ≤5 mm, and 2,>5 mm. The patients were also evaluated in 2 groupsas those with (Group 1 or without (Group 2 scars. Bothgroups were compared with subgroups with the largestscar diameters of ≤ 5mm or >5 mmResults: Study population included 108 (82 girls patients.DMSA detected scars in a total of 51 patients.Mean ages of the patients with and without scars were notdifferent (p=0.414. No significant difference was found insize of the BCG scars between renal scar positive andnegative groups (p>0.05.Conclusion: No correlation was found between developmentof renal scar and the size of BCG scar in childrenafter urinary tract infection. J Clin Exp Invest 2013; 4 (1:8-12Key words: BCG scar, renal scar, urinary tract infection,children

  7. Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case–control study

    Science.gov (United States)

    Ciani, Oriana; Arendsen, Erik; Romancik, Martin; Lunik, Richard; Costantini, Elisabetta; Di Biase, Manuel; Morgia, Giuseppe; Fragalà, Eugenia; Roman, Tomaskin; Bernat, Marian; Guazzoni, Giorgio; Tarricone, Rosanna; Lazzeri, Massimo

    2016-01-01

    Objectives To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs). Setting A European Union-based multicentre, retrospective nested case–control study. Participants 276 adult women treated for RUTIs starting from 2009 to 2013. Interventions Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). Primary and secondary outcome measures The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented. Results 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥5. Conclusions Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time. Trial registration number NCT02016118. PMID:27033958

  8. A Single Dose of Oral BCG Moreau Fails to Boost Systemic IFN-γ Responses to Tuberculin in Children in the Rural Tropics: Evidence for a Barrier to Mucosal Immunization

    Directory of Open Access Journals (Sweden)

    Maritza Vaca

    2012-01-01

    Full Text Available Immune responses to oral vaccines are impaired in populations living in conditions of poverty in developing countries, and there is evidence that concurrent geohelminth infections may contribute to this effect. We vaccinated 48 children living in rural communities in Ecuador with a single oral dose of 100 mg of BCG Moreau RDJ and measured the frequencies of tuberculin-stimulated peripheral blood mononuclear cells expressing IFN-γ before and after vaccination. Vaccinated children had active ascariasis (n=20 or had been infected but received short- (n=13 or long-term (n=15 repeated treatments with albendazole prior to vaccination to treat ascariasis. All children had a BCG scar from neonatal vaccination. There was no evidence of a boosting of postvaccination IFN-γ responses in any of the 3 study groups. Our data provide support for the presence of a barrier to oral vaccination among children from the rural tropics that appeared to be independent of concurrent ascariasis.

  9. Clinical and immunological evaluation after BCG-id vaccine in leprosy patients in a 5-year follow-up study

    Directory of Open Access Journals (Sweden)

    Zenha EM

    2012-12-01

    Full Text Available Erika Muller Ramalho Zenha, Carlos Gustavo Wambier, Ana Lúcia Novelino, Thiago Antônio Moretti de Andrade, Maria Aparecida Nunes Ferreira, Marco Andrey Cipriani Frade, Norma Tiraboschi FossDivision of Dermatology, Ribeirão Preto Medical School, São Paulo University, São Paulo, BrazilIntroduction: The use of bacillus Calmette–Guérin (BCG has long been considered a stimulus for immune reactivity in leprosy household contacts. Probably, the combination of multidrug therapy with BCG could facilitate the clearance of leprosy bacilli in the host, reduce relapse rates, and shorten the duration of skin-smear positivity.Methods: To investigate the mechanism of action of BCG, a study involving 19 leprosy patients, eleven multibacillary (MB and eight paucibacillary, was performed to assess the in vitro production of interleukin (IL-10, interferon (IFN-γ, tumor necrosis factor (TNF-α, IL-6, and IL-17 in the supernatant of peripheral blood mononuclear cells, before and 30 days after inoculation with BCG intradermally (BCG-id. Peripheral blood mononuclear cells isolated by Ficoll–Hypaque gradient were cultivated with Concanavalin-A (Con-A, lipopolysccharides (LPS, or BCG. The supernatant was collected for ELISA quantification of cytokines. The immunohistochemistry of IFN-γ, IL-1, IL-10, IL-12, transforming growth factor (TGF-β, and TNF-α was carried out in biopsies of skin lesions of leprosy patients before and 30 days after inoculation of BCG-id. These patients were followed up for 5 years to assess the therapeutic response to multidrug therapy, the occurrence of leprosy reactions, and the results of bacterial index and anti-PGL-1 serology after the end of treatment. Results: The results showed increased production of cytokines after BCG-id administration in MB and paucibacillary leprosy patients. There was statistically higher levels of TNF-α (P = 0.017 in MB patients and of IL-17 (P = 0.008 and IFN-γ (P = 0.037 in paucibacillary patients

  10. Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

    Science.gov (United States)

    Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2011-12-15

    Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

  11. Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

    Directory of Open Access Journals (Sweden)

    Ting-Yu Angela Liao

    Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

  12. Screening and Assessing 11 Mycobacterium tuberculosis Proteins as Potential Serodiagnostical Markers for Discriminating TB Patients from BCG Vaccinees

    Institute of Scientific and Technical Information of China (English)

    Guoqiang Zhang; Lingxia Zhang; Mingcheng Zhang; Linlin Pan; Fengyu Wang; Jun Huang; Guoli Li; Jun Yu; Songnian Hu

    2009-01-01

    Purified protein derivative(PPD)skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tu-berculosis infection and Bacille Calmette-Guerin(BCG)vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames(ORFs)based on the genome sequences of M. tu-berculosis H37Rv and M. bovis BCG, as well as their functions and differences of expression under different stimulus. The candidate ORFs were cloned from H37Rv sequences and expressed as recombinant proteins in Escherichia coll. We studied the serodiagnostic potential of 11 purified recombinants by using enzyme-linked immunosorbent assay(ELISA)and involving a cohort composed of 58 TB patients (34 males and 24 females), 8 healthy volunteers and 50 PPD-negative individuals before and after BCG vaccination. For all the 11 antigens, the median OD val-ues for the sera from TB patients were statistically significantly higher than those for PPD-negative individuals before or after BCG vaccination(P<0.01). They had at least 92% specificity in healthy controls and six seroantigens(Rv0251c, Rv1973, Rv2376c, Rv2537c, Rv2785c and Rv3873A)were never reported with seroantigenicities previously. Thus the approach combining comparative genomies, bioinformatics and ELISA techniques can be employed to identify new seroantigens distinguishing M. tuberculosis infection from BCG vaccination.

  13. The preparation of HL-60 cells vaccine expressing BCG heat shock protein 70 and detection of its immunogenicity in vitro.

    Science.gov (United States)

    Li, Xiao-Ling; Zhao, Yan-Xia; Sun, Li-Rong; Yang, Jing; Xu, Hui-Juan

    2012-10-01

    Gene-modified cell vaccines are the best way to achieve the immunotherapy for all types of acute leukemia. In this study, the recombinant eukaryotic expression vector (pDisplay-HSP70) of heat shock protein 70 (HSP70) of Bacille Calmette-Guérin (BCG) was constructed by amplifying the whole BCG HSP70 gene using polymerase chain reaction (PCR) and sub-cloning into the polyclone endonuclease sites in pDisplay. Then the HL-60 cell vaccine expressing the protein onto the cell surface was prepared by lipofectamine transfection and its anti-tumor effect and mechanism were further studied. Results showed that the fragment of BCG HSP70 was consistent with Mycobacterium tuberculosis HSP70 gene published in GeneBank. DNA sequencing showed that the recombinant vector was correctly constructed and named pDisplay-HSP70. After BCG HSP70 gene transfection, the yellow-green fluorescence on the HL-60 cells surface was observed under a fluorescence microscope. The immunogenicity of HSP70-transfected HL-60 cells exhibited upregulated proliferation of lymphocytes, increased cytokine secretion (IFN-γ) and enhanced killing activity. These results suggested that gene transfection of BCG HSP70 could significantly enhance the immunogenicity of HL-60 cells. It may be used as a suitable candidate gene-modified cell vaccine for cancer immunotherapy.

  14. Assessment of an oral Mycobacterium bovis BCG vaccine and an inactivated M. bovis preparation for wild boar in terms of adverse reactions, vaccine strain survival, and uptake by nontarget species

    OpenAIRE

    Beltrán-Beck, Beatriz; Romero, Beatriz; Sevilla, Iker A; Barasona, José A.; Garrido, Joseba M; González-Barrio, David; Díez-Delgado, Iratxe; Minguijón, Esmeralda; Casal, Carmen; Vicente, Joaquín; Gortázar, Christian; Aranaz, Alicia

    2014-01-01

    Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or i...

  15. Systematic Review and Meta-Analysis of Intravesical Hyaluronic Acid and Hyaluronic Acid/Chondroitin Sulfate Instillation for Interstitial Cystitis/Painful Bladder Syndrome

    Directory of Open Access Journals (Sweden)

    Jung-Soo Pyo

    2016-09-01

    Full Text Available Background/Aims: To assess the efficacy of intravesical hyaluronic acid (HA and HA/chondroitin sulfate (CS instillation in patients with interstitial cystitis/painful bladder syndrome by systematic review and meta-analysis. Methods: A systematic literature search was performed using the keywords: ‘interstitial cystitis' or ‘painful bladder syndrome' or ‘bladder pain syndrome' and ‘hyaluronic acid', up to March 31, 2016. The primary outcome was visual analogue scale related pain symptom (VAS. Secondary outcomes were the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI and Problem Index (ICPI, frequency, nocturia, bladder volume, and voided urine volume. Results: Ten articles involving 390 patients were retrieved and assessed in analysis. A significant improvement in mean VAS on fixed-effect and random-effect models (mean difference [MD] -3.654, 95% confidence interval [CI] -3.814 to -3.495, and MD -3.206, 95% CI -4.156 to -2.257, respectively was found. Significant improvements were found in the ICSI (MD -3.223, 95% CI -4.132 to -2.315 and ICPI (MD -2.941, 95% CI -3.767 to -2.116. Similarly, the other outcomes were significantly improved. Conclusion: Intravesical HA and HA/CS instillation improved pain symptom, quality of life, and other outcomes and could be included as therapeutic modality of interstitial cystitis/painful bladder syndrome.

  16. The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921-1933.

    Science.gov (United States)

    Bonah, Christian

    2005-12-01

    The anti-tuberculosis BCG (Bacille Calmette-Guérin) vaccine was conceived and developed between 1905 and 1921 at Pasteur Institutes in France. Between 1921 and A. Calmette's death in 1933, the vaccine went through a first period of national and international production and distribution for its use in humans. In France these activities were exclusively carried out by Calmette and his collaborators at the Pasteur Institute in Paris. Initially improvised production in a small room in the cellar gave way in 1931 to the construction of the spacious and magnificent 'New laboratories for research on tuberculosis and the preparation of the BCG' within the premises of the Pasteur Institute. Presentation and image-building of the vaccine in France insisted on the fact that the BCG was not a commercial specialty but distributed free of charge. The technical monopoly of its production nevertheless lay with the Paris Pasteur Institute and standardization of scientific proof of safety, efficacy and stability was dominated by that Institute in France. In contrast, the international production and distribution of the vaccine was entrusted and transferred, free of charge, to trustworthy laboratories outside France. Multiplication of producers and users led to an increased need for standardization. For this process the analysis distinguishes between the standardization of scientific proof concerning safety, efficacy and stability of the vaccine and standardization of its medical uses. Whereas standardization was rather successful in the inter-war period in France, the international efforts remained rather unsuccessful. Only after world war II under Scandinavian leadership and in the context of mass vaccination programs supported by the WHO and UNICEF was the international standardization effectively implemented and succeeded at least to some extend.

  17. BCG vaccine combined with dipyridamole in the treatment of HBV infection

    Institute of Scientific and Technical Information of China (English)

    Xu Wen Gao; Shi Ying Jia; Xue Mei Liu

    2000-01-01

    AIM To investigate the effect of BCG vaccine and dipyridamole in treating hepatitis B due to their anti-virus effects.METHODS Among 602 patients with positive HBeAg, 512 were allocated to the treatment group and 90patients to the control group. There was no significant difference in disease and age between the two groups.All the patients in the treatment group with no abnormal findings by chest X-ray fluoroscopy, whose localskin scleromata diameters were less than 7 mm after the 1:2000 OT test, were given BCG vaccine 0.1 mlintracutaneously at the deltoid once a month, and simultaneously took dipyridamole 50 mg twice a day forfour to eight months. The hepatic function, B-mode ultrasound and the five markers of hepatitis B wereroutinely examined before each injection. The results at one month after the last injection in the treatmentgroup were compared with those of the control group.RESULTS The recovery rates of hepatic functions and the rates of improvement of the symptoms and signsin the treatment group were better than those in the control group. The negative transformation rates ofHBeAg and the positive transformation rates of HBeAb were 60.3% and 31.6% in the treatment group vs.13.3% and 13.0% in the control group (P0.05. Test x2, x2=1.11, 0.22).CONCLUSION The application of BCG vaccine in combination with dipyridamole increased the negativetransformation rate of HBeAg and the positive transformation rate of HBeAb, improved the clinicalsymptoms, signs and hepatic function of the patients. These two drugs had significant anti-HBV effect andshowed good efficacy in the treatment of HBV infection.

  18. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

    KAUST Repository

    Abdallah, Abdallah M.

    2015-10-21

    Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

  19. Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage

    DEFF Research Database (Denmark)

    Aaby, Peter; Nielsen, Jens; Benn, Christine S;

    2016-01-01

    and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. RESULTS: BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person...

  20. Effect of milk fermentation by kefir grains and selected single strains of lactic acid bacteria on the survival of Mycobacterium bovis BCG.

    Science.gov (United States)

    Macuamule, C L S; Wiid, I J; van Helden, P D; Tanner, M; Witthuhn, R C

    2016-01-18

    Mycobacterium bovis that causes Bovine tuberculosis (BTB) can be transmitted to humans thought consumption of raw and raw fermented milk products from diseased animals. Lactic acid bacteria (LAB) used in popular traditional milk products in Africa produce anti-microbial compounds that inhibit some pathogenic and spoilage bacteria. M. bovis BCG is an attenuated non-pathogenic vaccine strain of M. bovis and the aim of the study was to determine the effect of the fermentation process on the survival of M. bovis BCG in milk. M. bovis BCG at concentrations of 6 log CFU/ml was added to products of kefir fermentation. The survival of M. bovis BCG was monitored at 12-h intervals for 72 h by enumerating viable cells on Middlebrook 7H10 agar plates enriched with 2% BD BACTEC PANTA™. M. bovis BCG was increasingly reduced in sterile kefir that was fermented for a period of 24h and longer. In the milk fermented with kefir grains, Lactobacillus paracasei subsp. paracasei or Lactobacillus casei, the viability of M. bovis BCG was reduced by 0.4 logs after 24h and by 2 logs after 48 h of fermentation. No viable M. bovis BCG was detected after 60 h of fermentation. Results from this study show that long term fermentation under certain conditions may have the potential to inactivate M. bovis BCG present in the milk. However, to ensure safety of fermented milk in Africa, fermentation should be combined with other hurdle technologies such as boiling and milk pasteurisation.

  1. Adverse events following immunisation with bacille Calmette-Guérin vaccination: baseline data to inform monitoring in Australia following introduction of new unregistered BCG vaccine.

    Science.gov (United States)

    Hendry, Alexandra J; Dey, Aditi; Beard, Frank H; Khandaker, Gulam; Hill, Richard; Macartney, Kristine K

    2016-12-24

    In recent years there has been a global shortage of bacille Calmette-Guérin (BCG) vaccine and, from September 2012, unregistered vaccines have needed to be used in Australia (a Danish product initially until the end of 2015, and a Polish product used in some jurisdictions from early 2016). We examined rates and types of adverse events following immunisation (AEFI) with BCG vaccine reported to the Therapeutic Goods Administration between 2009 and 2014 in children aged less than 7 years. Reporting rates of AEFI with BCG vaccine increased from 87 per 100,000 doses (registered Sanofi Pasteur product) in 2009 to 201 per 100,000 doses (unregistered Danish Statens Serum Institute product) in 2014, with Victoria having the highest rate each year. Substantial variation between jurisdictions exists, suggesting differential reporting of BCG vaccine doses administered and/or BCG vaccine-related AEFI. The most commonly reported reactions were abscess (31%), injection site reaction (27%) and lymphadenopathy/lymphadenitis (17%). This study provides baseline data on BCG vaccine safety to inform surveillance. Given the current use of unregistered vaccines in the context of vaccine supply issues, improved recording of both administered BCG vaccine doses and the reporting of BCG vaccine-related AEFI are required to facilitate close monitoring of vaccine safety.

  2. PERBANDINGAN PENGGUNAAN MEDIA OGAWA PUSAT PENELITIAN PENYAKIT MENULAR DAN PERUM. BIO FARMA DALAM TES JUMLAH KUMAN VAKSIN BCG DI JAKARTA

    Directory of Open Access Journals (Sweden)

    Dyah W. Isbagio

    2012-09-01

    Full Text Available The aim of the study was to elaborate factors those might have played a role in the interlaboratory results discrepancies of the quality control for BCG vaccine. One hundred and nineteen samples of commercial BCG vaccine, produced by Bio Farma, had been put into extensive viability tests at Communicable Diseases Research Centre. The tests were done in a pair using Ogawa media prepared both by Bio Farma and by Communicable Diseases Research Centre. The Bio Farma's Ogawa medium revealed an average colony-count values of 1,529 x 106 particles/ ml^ while the Communicable Diseases Research Centre's Ogawa medium gave average figure of 1,504 x 10 particles/ml. As judged by student's paired t test, these results were not statistically significant. Apparently, the media used in the test were not responsible for the discrepancies of results of quality control for BCG vaccine.

  3. Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

    DEFF Research Database (Denmark)

    Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank

    2013-01-01

    '. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months...... in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained...... changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses. © 2013 S. Karger AG, Basel....

  4. Design and evaluation of an intravesical delivery system for superficial bladder cancer: preparation of gemcitabine HCl-loaded chitosan-thioglycolic acid nanoparticles and comparison of chitosan/poloxamer gels as carriers.

    Science.gov (United States)

    Şenyiğit, Zeynep Ay; Karavana, Sinem Yaprak; İlem-Özdemir, Derya; Çalışkan, Çağrı; Waldner, Claudia; Şen, Sait; Bernkop-Schnürch, Andreas; Baloğlu, Esra

    2015-01-01

    This study aimed to develop an intravesical delivery system of gemcitabine HCl for superficial bladder cancer in order to provide a controlled release profile, to prolong the residence time, and to avoid drug elimination via urination. For this aim, bioadhesive nanoparticles were prepared with thiolated chitosan (chitosan-thioglycolic acid conjugate) and were dispersed in bioadhesive chitosan gel or in an in situ gelling poloxamer formulation in order to improve intravesical residence time. In addition, nanoparticle-loaded gels were diluted with artificial urine to mimic in vivo conditions in the bladder and were characterized regarding changes in gel structure. The obtained results showed that chitosanthioglycolic acid nanoparticles with a mean diameter of 174.5±3.762 nm and zeta potential of 32.100±0.575 mV were successfully developed via ionotropic gelation and that the encapsulation efficiency of gemcitabine HCl was nearly 20%. In vitro/ex vivo characterization studies demonstrated that both nanoparticles and nanoparticle-loaded chitosan and poloxamer gels might be alternative carriers for intravesical administration of gemcitabine HCl, prolonging its residence time in the bladder and hence improving treatment efficacy. However, when the gel formulations were diluted with artificial urine, poloxamer gels lost their in situ gelling properties at body temperature, which is in conflict with the aimed formulation property. Therefore, 2% chitosan gel formulation was found to be a more promising carrier system for intravesical administration of nanoparticles.

  5. Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung.

    Directory of Open Access Journals (Sweden)

    Ruchi Jain

    Full Text Available BACKGROUND: The variable efficacy (0-80% of Mycobacterium bovis Bacille Calmette Guréin (BCG vaccine against adult tuberculosis (TB necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. METHODS/PRINCIPAL FINDINGS: A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immuno-dominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log(10, p<0.01 and spleen (2.36 log(10, p<0.001 bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL-12, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF-beta along with up-regulation of inducible nitric oxide synthase (iNOS. In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all

  6. Comparative genomics of the Mycobacterium signaling architecture and implications for a novel live attenuated Tuberculosis vaccine.

    Science.gov (United States)

    Zhou, Peifu; Xie, Jianping

    2014-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a major threat to global public health. A new TB vaccine affording superior immune protection to M. bovis Bacillus Calmette-Guérin (BCG) is imperative. The advantage of a live attenuated vaccine is that it can mimic the bona fide pathogen, elicit immune responses similar to natural infection, and potentially provide more protection than other vaccines. BCG, the only vaccine and a live attenuated vaccine that is the result of cumulative mutations by serial passage of M. bovis, has provided clues for the construction of novel improved vaccines. A strategy is put forward for identifying a new live attenuated TB vaccine generated by cumulative mutation based on M.tb. Given the important role of the M.tb signaling network consisting of a two-component system, eukaryotic-like Ser/Thr protein kinase system and sigma factor system based on comparisons among M.tb H37Rv, M. bovis, and BCG, we have put a premium on this signaling circuit as the starting point for the generation of an attenuated TB vaccine.

  7. The maxBCG technique for finding galaxy clusters in SDSS data

    Science.gov (United States)

    Annis, J.; Kent, S.; Castander, F.; Eisenstein, D.; Gunn, J.; Kim, R.; Lupton, R.; Nichol, R.; Postman, M.; Voges, W.; SDSS Collaboration

    1999-12-01

    We present a new technique for finding galaxy clusters based on looking for a core of red, early type galaxies in the cluster center. These galaxies are known to have a small dispersion in color out to at least z=0.5. Further, the brightest of the ellipticals have near constant luminosity. In the maxBCG technique, one looks for objects whose appararent magnitudes and colors are consistent with their being brightest cluster galaxies (BCGs). If one presumes that any such object is a BCG, one can estimate a redshift and then search an area a half megaparsec around the galaxy for other galaxies that have the colors of the E/S0 ridgeline. One obtains a good estimate of the redshift by jointly minimizing the difference from the mean restframe brightest cluster galaxy properties while maximizing the number of galaxies in the E/S0 ridgeline. We have run this algoritm on the Abell clusters in the Sloan Digital Sky Survey commisioning data area with known redshifts, and find that the error in the estimated redshift z is only 0.02. This work was supported by the U.S. Department of Energy under contract No. DE-AC02-76CH03000.

  8. Mycobacterium leprae phenolglycolipid-1 expressed by engineered M. bovis BCG modulates early interaction with human phagocytes.

    Directory of Open Access Journals (Sweden)

    Guillaume Tabouret

    Full Text Available The species-specific phenolic glycolipid 1 (PGL-1 is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. Based on studies using the purified compound, PGL-1 was proposed to mediate the tropism of M. leprae for the nervous system and to modulate host immune responses. However, deciphering the biological function of this glycolipid has been hampered by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Here, we identified the M. leprae genes required for the biosynthesis of the species-specific saccharidic domain of PGL-1 and reprogrammed seven enzymatic steps in M. bovis BCG to make it synthesize and display PGL-1 in the context of an M. leprae-like cell envelope. This recombinant strain provides us with a unique tool to address the key questions of the contribution of PGL-1 in the infection process and to study the underlying molecular mechanisms. We found that PGL-1 production endowed recombinant BCG with an increased capacity to exploit complement receptor 3 (CR3 for efficient invasion of human macrophages and evasion of inflammatory responses. PGL-1 production also promoted bacterial uptake by human dendritic cells and dampened their infection-induced maturation. Our results therefore suggest that M. leprae produces PGL-1 for immune-silent invasion of host phagocytic cells.

  9. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review

    Science.gov (United States)

    Soares-Weiser, Karla; López-López, José A; Kakourou, Artemisia; Chaplin, Katherine; Christensen, Hannah; Martin, Natasha K; Sterne, Jonathan A C; Reingold, Arthur L

    2016-01-01

    Objectives To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. Design Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. Study eligibility criteria Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. Data sources Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. Results Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies

  10. Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960 Outra vacina, outra história: a vacinação de BCG contra tuberculose na Índia, 1948 a 1960

    Directory of Open Access Journals (Sweden)

    Niels Brimnes

    2011-02-01

    Full Text Available Through an examination of mass BCG vaccination against tuberculosis in India between 1948 and 1960 this article draws attention to the diversity of the history of vaccination. The features of vaccination campaigns often differed from those of the celebrated campaign to eradicate smallpox. Due to differences between smallpox and tuberculosis as well as between the vaccines developed against them, an analysis of BCG mass vaccination against tuberculosis seems particularly well suited for this purpose. Three points of difference are identified. First, in non-Western contexts BCG vaccination procedures were modified to a greater extent than vaccination against smallpox. Second, tuberculosis lacked the drama and urgency of smallpox and BCG vaccination campaigns suffered more from recruitment problems than did the more "heroic" smallpox eradication campaign. Third, the BCG vaccine was contested in medical circles and was much better suited than the vaccine against smallpox as a vehicle for the articulation of concerns about post-colonial modernization.Através da observação da vacinação em massa de BCG contra a tuberculose na Índia durante os anos de 1948 a 1960, este artigo chama a atenção para a diversidade da história da vacinação. As características das campanhas de vacinação geralmente diferem daquelas celebradas nas campanhas para erradicação da varíola. Devido às diferenças entre a varíola e a turberculose, assim como entre as vacinas desenvolvidas para combater essas doenças, uma análise da vacinação em massa de BCG contra a turberculose parece especialmente bem situada para essa proposta. Três pontos de diferença foram identificados. O primeiro é que em contextos não ocidentais os procedimentos da vacinação de BCG foram modificados em uma extensão maior do que a vacinação contra a varíola. Em segundo lugar, a tuberculose não tinha o drama e a urgência da varíola, e as campanhas de vacinação de BCG

  11. Prova tuberculínica, BCG oral e infecção tuberculosa em crianças menores de 5 anos Tuberculin test, oral BCG vaccine, and tuberculosis infection among children under five years of age

    Directory of Open Access Journals (Sweden)

    Marialda Höfling de Pádua Dias

    1978-12-01

    Full Text Available São relatados os resultados das provas tuberculínicas com PPD Rt23, 2 UT, em crianças menores de um ano e de um a 4 anos, matriculadas na Clínica Pediátrica do Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brasil, no período de 1971 a 1975. Em 665 crianças menores de um ano encontrou-se 3,15% de reatores fracos e 6,62% de reatores fortes e em 1.298 crianças de um a 4 anos, 0,69% de reatores fracos e 5,5% de reatores fortes. Nas mesmas crianças, foram estudadas as relações entre vacinação BCG oral prévia e positividade à prova tuberculínica nos 2 grupos etários considerados e nos quais se obteve a informação de vacinação anterior com BCG oral. Em 575 crianças menores de um ano e 1.113 de um a 4 anos encontrou-se associação positiva entre vacinação BCG oral prévia e positividade à prova tuberculínica. Analisando a relação entre o número de doses de BCG oral prévio e o resultado das provas tuberculínicas pelo método de Goodman, verificou-se que a proporção de crianças que tinham tomado 3 doses e mais de BCG oral e que apresentaram reação forte à prova tuberculínica é significantemente maior que a observada para os não reatores, fato esse não verificado para o grupo de um a 4 anos. Nas crianças que tomaram uma ou duas doses não foram encontradas diferenças estatisticamente significantes.Results of tuberculin reaction from PPD Rt 23, 2UT are reported on children under one year of age and children from one to four years of age who were registered in the Pediatric Clinics of the Hospital das Clinicas of the College of Medicine of the State University of São Paulo. The study was carried out from 1971 through 1975. In a group of 665 children under one year of age, 3.15% were weak reactors while 6.62% were strong reactors, and, in a group of 1298 children between one to four years of age, 0.69% were weak reactors while 5.5% were strong reactors. The relationship between prior BCG oral

  12. Isolation and identification of arabinose mycolates of Cell Wall Skeleton (CWS) derived from Mycobacterium bovis BCG Tokyo 172 (SMP-105).

    Science.gov (United States)

    Uenishi, Yuko; Kusunose, Naoto; Yano, Ikuya; Sunagawa, Makoto

    2010-03-01

    A unique hydrolysis method using a two-layer solution, consisting of diluted hydrochloric acid and toluene was developed to isolate whole arabinose mycolates from the cell wall skeleton of Mycobacterium bovis BCG Tokyo 172 (SMP-105) in order to reveal its pivotal role in enhancing immune responses against tumors.

  13. Developing the Biological Condition Gradient (BCG), as a Tool for Describing the Condition of US Coral Reefs

    Science.gov (United States)

    Understanding effects of human activity on coral reefs requires knowing what characteristics constitute a high quality coral reef and identifying measurable criteria. The BCG is a conceptual model that describes how biological attributes of coral reefs change along a gradient of ...

  14. The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.

    Directory of Open Access Journals (Sweden)

    Rolf Billeskov

    Full Text Available BACKGROUND: The current vaccine against tuberculosis (TB, BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4, consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb. Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.

  15. A Comparative Study on the Effect of BCG-PSN and Thymopeptides on T-lymphocyte Subsets of Normal and Immunosuppressed Mice

    Institute of Scientific and Technical Information of China (English)

    邓云华; 陈映玲; 陈兴平; 李永喜; 周礼义

    2003-01-01

    To compare the effects of polysaccharide nucleic acid fraction of bacillus calmette guerin (BCG-PSN) and thymopeptides on T-lymphocytes of normal and immunosuppressed mice, CD4+ and CD8+ T-lymphocyte subsets of single nucleic cell in thymus, spleen and peripheral blood were detected successively by flow cytometry after application of BCG-PSN and thymopeptides. Meanwhile, CD4+/CD8+ ratio was also calculated. The results showed that both BCG-PSN and thymopeptides could decrease the proportion of CD4+ CD8+ T-lymphocyte subsets in the thymus, at the same time increase CD4+ T-lymphocyte, CD8+ T-lymphocyte proportion in the three tissues.The fluctuation in amplitude was greater in thymopeptides group than that in BCG-PSN group. It is concluded that acting location of thymopeptides is in thymus, its stimulating action is stronger than that of BCG-PSN, while BCG-PSN not only accelerates the differentiation in thymus, but also has some direct stimulation to peripheral CD4+ T-lymphocytes, and can maintain CD4+/CD8+ ratio within normal range. So, BCG-PSN is safer.

  16. Histopathological, immunohistochemical and ultraestructural evaluation of inflammatory response in Arius genus fish under experimental inoculation of BCG

    Directory of Open Access Journals (Sweden)

    Ricardo Yuji Sado

    2008-10-01

    Full Text Available The aim of this study was to evaluate the inflammatory response kinetics after experimental inoculation with BCG in the primitive Arius sp. fish. The BCG was applied through the intramuscular injection in the caudal peduncular region, and the samples were collected for the analyses at days 1, 3, 7, 14, 21, and 33 post-injection. Acute phase inflammatory infiltrate was characterized by the predominant mononuclear cells, intersticial edema, and muscular tissue necrosis. As the inflammatory response evolved, a large number of multinuclear giant cells were formed containing the BCG. These giant cells were positive for the S100 protein at the histochemical analysis, which demonstrate the macrofage activity, confirmed by the ultra-structural analysis showing the lack of the cytoplasmic membrane enveloping the many nuclei within the giant cell. These results led to the conclusion that Arius sp. fish injected with the BCG showed a difuse inflammatory response characterized by a large number of mononuclear cells, absence of granuloma formation, and predominant giant cells.Avaliou-se a cinética da resposta inflamatória induzida experimentalmente com BCG em peixes primitivos pertencentes ao gênero Arius. Os animais foram inoculados com BCG por via intramuscular na região do pedúnculo caudal, sendo realizada a coleta do material nos tempos experimentais de 1, 3, 7, 14, 21 e 33 dias pós-inoculação. A fase aguda da resposta inflamatória se mostrou na forma de infiltrado inflamatório composto predominantemente por células mononucleares, edema intersticial e necrose de tecido muscular. À medida que o processo se desenvolveu, houve formação e aumento no número de células gigantes multinucleadas envolvendo o inóculo. Essas células gigantes, ao exame imunohistoquímico, apresentaram positividade à proteína S100 indicando ação de células macrofágicas, além da ultraestrutura apontar a ausência de membrana citoplasmática entre os in

  17. The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection

    Science.gov (United States)

    Seddon, James A; Paton, James; Nademi, Zohreh; Keane, Denis; Williams, Bhanu; Williams, Amanda; Welch, Steven B; Liebeschutz, Sue; Riddell, Anna; Bernatoniene, Jolanta; Patel, Sanjay; Martinez-Alier, Nuria; McMaster, Paddy; Kampmann, Beate

    2016-01-01

    Background Following exposure to TB, contacts are screened to target preventive treatment at those at high risk of developing TB. The UK has recently revised its recommendations for screening and now advises a 5 mm tuberculin skin test (TST) cut-off irrespective of age or BCG status. We sought to evaluate the impact of BCG on TST responses in UK children exposed to TB and the performance of different TST cut-offs to predict interferon γ release assay (IGRA) positivity. Methods Children vaccination on TST positivity was evaluated in IGRA-negative children, as was the performance of different TST cut-offs to predict IGRA positivity. Results Of 422 children recruited (median age 69 months; IQR: 32–113 months), 300 (71%) had been vaccinated with BCG. BCG vaccination affected the TST response in IGRA-negative children less than 5 years old but not in older children. A 5 mm TST cut-off demonstrated good sensitivity and specificity in BCG-unvaccinated children, and an excellent negative predictive value but was associated with low specificity (62.7%; 95% CI 56.1% to 69.0%) in BCG-vaccinated children. For BCG-vaccinated children, a 10 mm cut-off provided a high negative predictive value (97.7%; 95% CI 94.2% to 99.4%) with the positive predictive value increasing with increasing age of the child. Discussion BCG vaccination had little impact on TST size in children over 5 years of age. The revised TST cut-off recommended in the recent revision to the UK TB guidelines demonstrates good sensitivity but is associated with impaired specificity in BCG-vaccinated children. PMID:27335104

  18. Cellular immunity confers transient protection in experimental Buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination.

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    Alexandra G Fraga

    Full Text Available BACKGROUND: Buruli ulcer (BU is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-γ T cell response in the draining lymph node (DLN. BCG vaccination also resulted in cell-mediated immunity (CMI in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-γ and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE: The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised.

  19. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

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    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  20. The mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG influences various growth characteristics

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    Maurischat Sven

    2008-06-01

    Full Text Available Abstract Background Pathogenic mycobacteria such as M. tuberculosis, M. bovis or M. leprae are characterised by their extremely slow growth rate which plays an important role in mycobacterial virulence and eradication of the bacteria. Various limiting factors influence the generation time of mycobacteria, and the mycobacterial DNA-binding protein 1 (MDP1 has also been implicated in growth regulation. Our strategy to investigate the role of MDP1 in mycobacterial growth consisted in the generation and characterisation of a M. bovis BCG derivative expressing a MDP1-antisense gene. Results The expression rate of the MDP1 protein in the recombinant M. bovis BCG containing the MDP1-antisense plasmid was reduced by about 50% compared to the reference strain M. bovis BCG containing the empty vector. In comparison to this reference strain, the recombinant M. bovis BCG grew faster in broth culture and reached higher cell masses in stationary phase. Likewise its intracellular growth in mouse and human macrophages was ameliorated. Bacterial clumping in broth culture was reduced by the antisense plasmid. The antisense plasmid increased the susceptibility of the bacteria towards Ampicillin. 2-D protein gels of bacteria maintained under oxygen-poor conditions demonstrated a reduction in the number and the intensity of many protein spots in the antisense strain compared to the reference strain. Conclusion The MDP1 protein has a major impact on various growth characteristics of M. bovis BCG. It plays an important role in virulence-related traits such as aggregate formation and intracellular multiplication. Its impact on the protein expression in a low-oxygen atmosphere indicates a role in the adaptation to the hypoxic conditions present in the granuloma.

  1. Living Technology

    DEFF Research Database (Denmark)

    2010-01-01

    This book is aimed at anyone who is interested in learning more about living technology, whether coming from business, the government, policy centers, academia, or anywhere else. Its purpose is to help people to learn what living technology is, what it might develop into, and how it might impact...... our lives. The phrase 'living technology' was coined to refer to technology that is alive as well as technology that is useful because it shares the fundamental properties of living systems. In particular, the invention of this phrase was called for to describe the trend of our technology becoming...... increasingly life-like or literally alive. Still, the phrase has different interpretations depending on how one views what life is. This book presents nineteen perspectives on living technology. Taken together, the interviews convey the collective wisdom on living technology's power and promise, as well as its...

  2. Curative effect of BCG-polysaccharide nuceic acid on atopic dermatitis in mice

    Institute of Scientific and Technical Information of China (English)

    Liu-Hui Wang; Ying Ye; Yi-Qun Zhang; Tao Xiao

    2014-01-01

    Objective:To explore the effect of bacilli Galmette-Gurin (BCG)-polysaccharide nuceic acid on atopic dermatitis in mice and its mechanism. Methods: Forty NC/Nga mice were selected and randomly divided into Group A (model group), Group B (dexamethasone treatment group), Group C (BCG polysaccharide nucleic acid treatment group) and Group D (control group) with 10 mice in each group. Atopic dermatitis model were constructed by applying 2, 4-dinitrochlorobenzene on the skin of the mice. Mice in Group D were treated with acetone solution (100μL) on the foot pad and abdomen after hair removal at the age of 7 weeks, then on ear skin at the age of 8-13 weeks. For mice in A, B and C groups, 100μL of acetone solution containing 2, 4-dinitrochlorobenzene was applied to the foot pad and the abdomen at the age of 7 weeks, then on ear skins at the age of 8 to 13 weeks. At the age of 7-13 weeks, mice in Group A and Group D were treated with 100μL saline (i.p.);mice were given dexamethasone (0.1 mL/kg, i.p.) every other day for 7 weeks in Group B;mice were treated with BCG polysaccharide nucleic acid (0.5 mg/kg, i.p.) every other day for 7 weeks in Group C. The ear thickness was measured every week and the scratching frequency was recorded 1 times for 10 min a week. The mice were sacrificed after the last administration of drugs. IgE, IL-4, IL-10, IL-12 and IFN-γin the plasma were detected using ELISA, and RT-PCR method was employed to detect the concentrations of IL-4, IL-10, IL-12 and IFN-γproteins. After HE staining, the lesion degree of inflammation in ear tissue was observed microscopically. Results:The ear thickness and scratching frequency of Group A were significantly higher than those in group B, C and D (P0.05);the concentrations of IgE, IL-4 and IL-10 in the plasma and the expression of IL-4, IL-10 mRNA in the spleen tissues of Group A, B and C were all significantly higher than those of Group D (P<0.05);the concentrations of plasma IL-12 and IFN-γ, and spleen

  3. The role of glutamine oxoglutarate aminotransferase and glutamate dehydrogenase in nitrogen metabolism in Mycobacterium bovis BCG.

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    Albertus J Viljoen

    Full Text Available Recent evidence suggests that the regulation of intracellular glutamate levels could play an important role in the ability of pathogenic slow-growing mycobacteria to grow in vivo. However, little is known about the in vitro requirement for the enzymes which catalyse glutamate production and degradation in the slow-growing mycobacteria, namely; glutamine oxoglutarate aminotransferase (GOGAT and glutamate dehydrogenase (GDH, respectively. We report that allelic replacement of the Mycobacterium bovis BCG gltBD-operon encoding for the large (gltB and small (gltD subunits of GOGAT with a hygromycin resistance cassette resulted in glutamate auxotrophy and that deletion of the GDH encoding-gene (gdh led to a marked growth deficiency in the presence of L-glutamate as a sole nitrogen source as well as reduction in growth when cultured in an excess of L-asparagine.

  4. EFISIENSI PERSAINGAN BANK UMUM SYARIAH: PENDEKATAN DATA ENVELOPMENT ANALYSIS (DEA DAN BOSTON CONSULTING GROUP (BCG

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    Rizqon Halal Syah Aji

    2015-10-01

    Full Text Available Islamic Banking industry in Indonesia has begun dynamic. Product availability and standardization of Islamic banking products, the level of understanding by the public of products of Islamic banks and human resources. Market share of Islamic Banking in Indonesia to lock everything. Recent data Directorate of Islamic Banking in 2011 reached Rp 127,19 T, assets of BPRS amounting to Rp 3.35 T, can be calculated total Islamic banking assets as of October 2011 reached Rp 130,5 T. Financing very important factor, Data Envelopment Analisys (DEA is a measuring instrument of financing. Map of the Bank's performance in the competition between banks can be analyzed by matrix BCG (Boston Consulting Group. This matrix is used to describe the difference between the position of the relative market share of the Bank.DOI: 10.15408/sjie.v3i1.2059

  5. BCG-vaccination of newborns – a descriptive study about shared decision making and decisional conflicts

    DEFF Research Database (Denmark)

    Thybo Pihl, Gitte

    mothers, 662 (67 %) had a score single parent status. To investigate the extent to which the decisional conflicts reflected inadequate knowledge......BCG-vaccination of newborns – a descriptive study about shared decision making and decisional conflicts Objective: To evaluate the use of shared decision making to support the parent in a low-evidence decision about a vaccine when using telephone consultations. The present study was conducted.......9 % of the mothers felt that they had inadequate support. Almost half of the mothers (43.7 %) were uncertain about the best choice, indicating that they were not confident that they had made the right decision. Discussion: Because all parents received both written information and were offered personal counselling...

  6. A family history of serious complications due to BCG vaccination is a tool for the early diagnosis of severe primary immunodeficiency.

    Science.gov (United States)

    Roxo-Junior, Pérsio; Silva, Jorgete; Andrea, Mauro; Oliveira, Larissa; Ramalho, Fernando; Bezerra, Thiago; Nunes, Altacílio A

    2013-09-10

    Severe Combined Immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency (PID). Complications of BCG vaccination, especially disseminated infection and its most severe forms, are known to occur in immunodeficient patients, particularly in SCID. A carefully taken family history before BCG injection as well as delaying vaccination if PID is suspected could be a simple and effective method to avoid inappropriate vaccination of an immunodeficient child in some cases until the prospect of newborn screening for SCID has been fully developed. We describe a patient with a very early diagnosis of SCID, which was suspected on the basis of the previous death of two siblings younger than one year due to severe complications secondary to the BCG vaccine. We suggest that a family history of severe or fatal reactions to BCG should be included as a warning sign for an early diagnosis of SCID.

  7. Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants.

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    April Kaur Randhawa

    2011-08-01

    Full Text Available The development of effective immunoprophylaxis against tuberculosis (TB remains a global priority, but is hampered by a partially protective Bacillus Calmette-Guérin (BCG vaccine and an incomplete understanding of the mechanisms of immunity to Mycobacterium tuberculosis. Although host genetic factors may be a primary reason for BCG's variable and inadequate efficacy, this possibility has not been intensively examined. We hypothesized that Toll-like receptor (TLR variation is associated with altered in vivo immune responses to BCG. We examined whether functionally defined TLR pathway polymorphisms were associated with T cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after newborn BCG vaccination of South African infants. In the primary analysis, polymorphism TLR6_C745T (P249S was associated with increased BCG-induced IFN-γ in both discovery (n = 240 and validation (n = 240 cohorts. In secondary analyses of the combined cohort, TLR1_T1805G (I602S and TLR6_G1083C (synonymous were associated with increased IFN-γ, TLR6_G1083C and TLR6_C745T were associated with increased IL-2, and TLR1_A1188T was associated with increased IFN-γ and IL-2. For each of these polymorphisms, the hypo-responsive allele, as defined by innate immunity signaling assays, was associated with increased production of TH1-type T cell cytokines (IFN-γ or IL-2. After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12. These studies provide evidence that functionally defined innate immune gene variants are associated with the

  8. Granulomatous prostatitis after intravesical bacillus Calmette-Guérin instillation therapy: A potential cause of incidental F-18 FDG uptke in the prostate gland on F-18 FDG PET/CT in patients with bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Choon Young; Lee, Sang Woo; Choi, Seock Hwan; Son, Seung Hyun; Jung, Ji Hoon; Lee, Chang Hee; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae [Kyungpook National University Medical Center and School of Medicine, Daegu (Korea, Republic of)

    2016-03-15

    This study aimed to evaluate the possibility that Bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake. A total of 395 bladder cancer patients who underwent F-18 FDG PET/CT (PET/CT) were retrospectively evaluated. Patients were divided into two groups according to BCG therapy status. Elapsed time after BCG therapy, serum PSA level, results of prostate biopsy, and the SUV{sub max} and uptake pattern in the prostate gland were reviewed. For patients who underwent follow-up PET/CT, the changes in SUV{sub max} were calculated. While 35 % of patients showed prostate uptake in the BCG therapy group, only 1 % showed prostate uptake in the non-BCG therapy group (p < 0.001). Among 49 patients with FDG-avid prostate lesions, none had suspected malignancy during the follow-up period (median: 16 months). Five patients revealed granulomatous prostatitis on biopsy. The incidence of FDG-avid prostate lesions was significantly higher if the elapsed time after BCG therapy was less than 1 year compared to more than 1 year (p < 0.001). Serum PSA was normal in 88 % of patients. All patients with incidental F-18 FDG uptake in the prostate gland showed focal or multifocal prostate uptake, and median SUV{sub max} was 4.7. In 16 patients who underwent follow-up PET/CT, SUV{sub max} was decreased in 14 patients (88 %) without treatment, and no patients demonstrated further increased prostate uptake (p < 0.001). BCG-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake, especially in those with a history of bladder cancer treated with BCG. In BCG-induced granulomatous prostatitis, focal or multifocal prostate uptake is frequently seen within 1 year after BCG therapy, and the intensity of prostate uptake is decreased on the follow-up PET/CT without any treatment.

  9. Effects of Ganoderma sterols (GS) on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    XinWANG; DanLI; Guo-liangZHANG; Zhi-binLIN

    2004-01-01

    AIM: To investigate effects of Ganoderma sterols (GS) isolated from Ganoderma lucidum (Leyss ex fr) Karst on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice and its possible mechanism. METHODS: Immunological liver injury was induced by one intravenous injection of BCG (125 mg/kg) in BALB/c mice. One week later, successiveintragastric administration of GS (20, 40, 80 mg/kg, per day) and

  10. The tuberculin skin test (TST is affected by recent BCG vaccination but not by exposure to non-tuberculosis mycobacteria (NTM during early life.

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    Sarah Burl

    Full Text Available The tuberculin skin test (TST is widely used in TB clinics to aid Mycobacterium tuberculosis (M.tb diagnosis, but the definition and the significance of a positive test in very young children is still unclear. This study compared the TST in Gambian children at 4(1/2 months of age who either received BCG vaccination at birth (Group 1 or were BCG naïve (Group 2 in order to examine the role of BCG vaccination and/or exposure to environmental mycobacteria in TST reactivity at this age. Nearly half of the BCG vaccinated children had a positive TST (>or=5 mm whereas all the BCG naïve children were non-reactive, confirming that recent BCG vaccination affects TST reactivity. The BCG naïve children demonstrated in vitro PPD responses in peripheral blood in the absence of TST reactivity, supporting exposure to and priming by environmental mycobacterial antigens. Group 2 were then vaccinated at 4(1/2 months of age and a repeat TST was performed at 20-28 months of age. Positive reactivity (>or=5 mm was evident in 11.1% and 12.5% infants from Group 1 and Group 2 respectively suggesting that the timing of BCG vaccination had little effect by this age. We further assessed for immune correlates in peripheral blood at 4(1/2 months of age. Mycobacterial specific IFNgamma responses were greater in TST responders than in non-responders, although the size of induration did not correlate with IFNgamma. However the IFNgamma: IL-10 ratio positively correlated with TST induration suggesting that the relationship between PPD induced IFNgamma and IL-10 in the peripheral blood may be important in controlling TST reactivity. Collectively these data provide further insights into how the TST is regulated in early life, and how a positive response might be interpreted.

  11. T-Cell mRNA Expression in Response to Mycobacterium bovis BCG Vaccination and Mycobacterium bovis Infection of White-Tailed Deer▿

    OpenAIRE

    Tyler C Thacker; Palmer, Mitchell V.; Waters, W. Ray

    2009-01-01

    Understanding immune responses of white-tailed deer (WTD) to infection with Mycobacterium bovis provides insight into mechanisms of pathogen control and may provide clues to development of effective vaccine strategies. WTD were vaccinated with either M. bovis BCG strain Pasteur or BCG strain Danish. Both vaccinees and unvaccinated controls were subsequently inoculated with virulent M. bovis via the intratonsillar route. Real-time PCR was used to assess T-cell mRNA expression in peripheral blo...

  12. Valor preditivo do teste tuberculínico padronizado em crianças vacinadas com BCG The predictive value of the standard tuberculin test in BCG-vaccinated children

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    Gilberto Ribeiro Arantes

    1992-08-01

    Full Text Available A aplicabilidade do teste tuberculínico em crianças menores de 5 anos vacinadas com BCG é assunto controvertido. Visando contribuir para esclarecê-lo foi analisado o valor preditivo positivo do teste tuberculínico padronizado em população sob elevada cobertura vacinal e baixa prevalência de infecção tuberculosa. A partir da proporção de reatores fortes em lactentes e escolares vacinados e não vacinados, foram calculadas a razão de declínio da alergia tuberculínica nos vacinados e a razão de crescimento nos não vacinados, o que possibilitou a estimativa dos respectivos valores nas idades intermediárias. A expectativa de falsos-positivos (FP foi então calculada por diferença. Conhecidas a sensibilidade e a especificidade do teste (E=1-FP, a cobertura BCG e a prevalência de infecção, os valores preditivos (para a infecção tuberculosa foram: 1,52%, 4,22%, 8,26%, 14,86% e 23,00%, do primeiro ao quinto ano de vida. Nessas condições, a probabilidade de uma reação forte ser devida ao BCG é grande, especialmente nos dois primeiros anos, o que reduz a aplicabilidade clínica e epidemiológica do teste.The applicability of tuberculin test in children under five years of age, BCG-vaccinated during their first year of life, is a controversial matter. With a view to clarifying the subject the predictive positive value of the test in a region of high BCG coverage and low prevalence of tuberculous infection was analysed. From the proportion of strong reactors among infants and school-age children, vaccinated and not unvaccinated, the declining rate of BCG induced allergy and the increment rate of naturally acquired tuberculin sensitivity between the first and the seventh years of life were calculated. Those calculations allowed for the estimation of the respective values for the intermediate ages. The numbers of false positives to be expected were calculated by difference. Knowing the sensibility and the especificity (1 - FP of

  13. La Matriz BCG (Boston Consulting Group para la Gestión de Publicaciones Periádicas The BCG (Boston Consulting Group matrix for management of periodic publications

    Directory of Open Access Journals (Sweden)

    Mª del Pilar Serrano Gallardo

    2005-11-01

    Full Text Available El marketing documental se ha de encargar de satisfacer las necesidades informativas de los usuarios de forma rentable para ellos y para el centro; para ello se ha de partir de un conjunto de herramientas técnicas que se conocen como el Marketing - Mix, y que abarcan el Producto, el Precio, la Distribución y la Comunicación. Dentro de las herramientas destinadas al producto se encuentra la matriz BCG (Boston Consulting Group, que está orientada a gestión, sobre la base de la situación del producto en el mercado. El objetivo del presente artículo es proponer una matriz BCG para la gestión de una publicación periódica enfermera en nuestro mercado.La matriz BCG se construye con dos variables: el Crecimiento del Mercado y la Tasa Relativa del Mercado, las cuales se han operacionalizado como Media de Crecimiento Anual en el número de suscripciones de tres revistas enfermeras (Rol de Enfermería, Metas de Enfermería y Nursing durante el último quinquenio y Media de Tirada Actual de las tres publicaciones. Se han utilizado datos ofrecidos por la Oficina para el Control de la Difusión (OJD. La matriz BCG puede constituirse como herramienta básica en la gestión de publicaciones, dado que tras determinar la situación del producto, se pueden establecer estrategias que ayuden o favorezcan el mejor posicionamiento posible del producto en el mercado.Documentary marketing has to address the information needs of the users in a manner that is cost-effective not only for them but also for the institution. To do this, a set of technical tools, known as Marketing- Mix, need to be used. These tools include the Product, Price, Distribution and Communication. Within the set of tools used for the Product, we find the BCG matrix (Boston Consulting Group, a tool aimed at the management of the product on the basis of where it is positioned in the market. The objective of this paper is to propose a BCG matrix for the management of a nursing periodic

  14. Hepatitis in Disseminated Bacillus Calmette-Guérin Infection

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    Markus U Göttke

    2000-01-01

    Full Text Available Local immunotherapy with an attenuated live strain of Mycobacterium bovis, bacillus Calmette-Guérin (BCG, is an effective and frequently used treatment for in situ transitional cell carcinoma (TCC of the bladder. Success rates are high, and serious side effects are infrequent but can affect every organ system. A 79-year-old patient with recently diagnosed TCC who was treated with intravesical BCG for a recurrence after initial surgical treatment is reported. After unsuccessful attempts at bladder catheterization with the creation of a false passage for his third treatment, BCG was instilled via a suprapubic catheter the same day and again a week later. Two weeks after the third BCG instillation, the patient presented with profound lethargy and weakness to the point of not being able to get up out of a chair. He was febrile, anorexic, icteric and had hepatosplenomegaly. Disseminated BCG infection was suspected on the basis of history, clinical examination and a liver biopsy that showed noncaseating granulomatous hepatitis. Empirical treatment was started with antituberculous combination therapy. A short course of an oral corticosteroid was given. Clinical improvement was marked and sustained so that the patient could be discharged home for the full six-month course of his treatment. Disseminated BCG infection with granulomatous hepatitis can be severe and life-threatening in cases where a large intravascular inoculum of BCG may have been given inadvertently.

  15. Identification of Botrytis cinerea genes up-regulated during infection and controlled by the Galpha subunit BCG1 using suppression subtractive hybridization (SSH).

    Science.gov (United States)

    Schulze Gronover, Christian; Schorn, Corinna; Tudzynski, Bettina

    2004-05-01

    The Galpha subunit BCG1 plays an important role during the infection of host plants by Botrytis cinerea. Delta bcg1 mutants are able to conidiate, penetrate host leaves, and produce small primary lesions. However, in contrast to the wild type, the mutants completely stop invasion of plant tissue at this stage; secondary lesions have never been observed. Suppression subtractive hybridization (SSH) was used to identify fungal genes whose expression on the host plant is specifically affected in bcg1 mutants. Among the 22 differentially expressed genes, we found those which were predicted to encode proteases, enzymes involved in secondary metabolism, and others encoding cell wall-degrading enzymes. All these genes are highly expressed during infection in the wild type but not in the mutant. However, the genes are expressed in both the wild type and the mutant under certain conditions in vitro. Most of the BCG1-controlled genes are still expressed in adenylate cyclase (bac) mutants in planta, suggesting that BCG1 is involved in at least one additional signaling cascade in addition to the cAMP-depending pathway. In a second SSH approach, 1,500 clones were screened for those that are specifically induced by the wild type during the infection of bean leaves. Of the 22 BCG1-controlled genes, 11 also were found in the in planta SSH library. Therefore, SSH technology can be successfully applied to identify target genes of signaling pathways and differentially expressed genes in planta.

  16. Construction and Expression of the Echinococcus granulosus Recombinant BCG-EgG1Y162%细粒棘球绦虫重组BCG-EgG1Y162菌株的构建和表达

    Institute of Scientific and Technical Information of China (English)

    祖力皮也·吐尔逊; 德力夏提·依米提; 曹春宝; 马海梅; 李玉娇; 周晓涛; 朱明; 马秀敏; 温浩

    2013-01-01

    Objective To construct and express Echinococcus granulosus recombinant bacille Calmette-Guerin (BCG) strain rBCG-EgG1Y162. Methods The encoding gene of the antigen EgG1Y162 of E. granulosus was recombined with E. coli-Mycobacterium shuttle expression plasmid vector pMV361 by genetic engineering technique, and transformed into E. coll for amplification. The recombinant plasmid rpMV-EgG1Y162 was identified by PCR, double digestion with restriction enzymes, and sequence analysis. The confirmed rpMV-EgG1Y162 was transformed into BCG strain via electroporation technique to construct the recombinant rBCG-EgG1Y162. After identification by PCR and double digestion with restriction enzymes, the recombinant strain was cultured for about 2 weeks. In order to induce the expression of target protein, the rBCG was placed in 45℃ for 30 min. SDS-PAGE and Western blotting were used to analyze the expressive protein. Results The product of recombinant plasmid rpMV-EgG1Y162 was approximately 360 bp by PCR amplification and double digestion with restriction enzymes, consistent with the expected fragment length. Sequencing results showed that the inserted sequence was correct. The rBCG-EgG1Y162 grew well and the identification of PCR and enzyme digestion revealed accuracy. The results of SDS-PAGE and Western blotting showed that the relative molecular weight (Mr) of the protein was about 71 000. Conclusion The E. granulosus rBCG-EgG1Y162 strain is constructed and expressed.%目的 构建和表达细粒棘球绦虫重组卡介苗(BCG)菌株rBCG-EgG1Y162.方法 通过基因工程技术将细粒棘球绦虫抗原EgG1Y162的编码基因与大肠埃希菌(E.coli)-分枝杆菌穿梭表达质粒载体pMV361重组,并转化E.coli后进行扩增.重组质粒pMV-EgG1Y162经PCR和双酶切鉴定后,进行测序.将鉴定正确的rpMV-EgG1Y162通过电穿孔技术转化至感受态BCG菌株中,构建rBCG-EgG1Y162.经PCR和双酶切鉴定正确后,扩增培养2周,并于45℃放置30 min,诱导

  17. Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2017-01-01

    Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

  18. An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

    Science.gov (United States)

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2009-09-01

    Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products.

  19. [Ag85B and BCG enhance immune activity of dendritic cells in patients with initially treated tuberculosis].

    Science.gov (United States)

    Guo, Yun; Su, Yuanyuan; Sun, Yang; Guan, Weiwei; Yang, Li; Zhang, Zhi; Wang, Yuling; Dai, Erhei

    2016-06-01

    Objective To investigate the regulatory effects of Mycobacterium tuberculosis major secreted protein Ag85B and Bacillus Calmette-Guerin (BCG) on the immune function of dendritic cells (DCs) in the patients with tuberculosis who have received an initial treatment. Methods The peripheral blood mononuclear cells were collected and separated in 26 healthy subjects and 31 patients with tuberculosis who had been treated initially. Every specimen was divided into 4 groups and DCs were induced and cultured. On the 6th day, the DCs in the three experimental groups were treated by lipopolysaccharide (LPS), BCG, Ag85B, respectively and no-treated DCs served as a control group. After 24-hour treatment, DCs were collected and examined for the levels of CD83, CD86, HLA-DR and CD11c using flow cytometry. Moreover, the levels of interleukin 12 (IL-12), IL-10 and interferon γ (IFN-γ) in the supernatants were measured by ELISA. Results The expression levels of CD83 and IL-10 in the patient control group were significantly lower than those in healthy subject control group. The levels of CD83, CD86 and IFN-γ in the Ag85B treated group were obviously high than those in the control group. The level of IFN-γ in the BCG treated group was significantly high than that in the control group. The levels of CD83, CD86, HLA-DR and IL-10 in the LPS treated group were remarkably higher than those in the control group. The levels of CD83, CD86 and IL-10 in the healthy subject LPS treated group were significantly higher than those in the healthy subject control group. Conclusion The immune-enhancing effect of Ag85B on DCs is superior to that of BCG in the patients with initially treated tuberculosis.

  20. The role of the mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG in host cell interaction

    Directory of Open Access Journals (Sweden)

    Kunisch Ralph

    2012-08-01

    Full Text Available Abstract Background Mycobacterium tuberculosis differs from most pathogens in its ability to multiply inside monocytes and to persist during long periods of time within granuloma in a status of latency. A class of proteins called mycobacterial histone-like proteins has been associated with regulation of replication and latency, but their precise role in the infection process has yet to be uncovered. Our study aimed at defining the impact of the histone-like protein MDP1 from M. bovis BCG (mycobacterial DNA-binding protein 1, corresponding to Rv2986c from M. tuberculosis on early steps of infection. Results Previously, a BCG (Bacillus Calmette Guérin strain had been generated by antisense-technique exhibiting reduced MDP1 expression. This strain was now used to analyse the impact of reduced amount of MDP1 on the interaction with human blood monocytes, macrophage lines and PBMC (peripheral blood mononuclear cells. MDP1 was revealed to be required for growth at acidic pH and for intracellular replication in human blood monocytes. Down-regulation of MDP1 resulted in reduced secretion of the cytokine IL-1β by infected human PBMC. In addition, a reduction of MDP1 expression had a major impact on the formation of fused multi-nucleated macrophages. In monocyte preparations from human blood as well as in human and mouse macrophage cell lines, both the percentage of multi-nucleated cells and the number of nuclei per cell were much enhanced when the monocytes were infected with BCG expressing less MDP1. Conclusion MDP1 from M. bovis BCG affects the growth at acidic pH and the intracellular replication in human monocytes. It furthermore affects cytokine secretion by host cells, and the formation of fused multi-nucleated macrophages. Our results suggest an important role of MDP1 in persistent infection.

  1. Assisted Living

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    ... term care and institutional living. Sheltered Housing Sheltered housing is often in a home that offers personal-care support, housekeeping services, and meals. Social work services and coordination for activities can be ...

  2. Live Well

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    ... message, please visit this page: About CDC.gov . HIV Treatment Works Get In Care HIV 101 Locate a ... Sharing Your Status Stay In Care Understanding Care HIV Treatment Cost of HIV Treatment Related Health Conditions Live ...

  3. The toxicity of rifampicin polylactic acid nanoparticles against Mycobacterium bovis BCG and human macrophage THP-1 cell line

    Science.gov (United States)

    Erokhina, M.; Rybalkina, E.; Barsegyan, G.; Onishchenko, G.; Lepekha, L.

    2015-11-01

    Tuberculosis is rapidly becoming a major health problem. The rise in tuberculosis incidence stimulates efforts to develop more effective delivery systems for the existing antituberculous drugs while decreasing the side effects. The nanotechnology may provide novel drug delivery tools allowing controlled drug release. Rifampicin is one of the main antituberculous drugs, characterized by high toxicity, and Poly (L-lactic acid) (PLLA) is a biodegradable polymer used for the preparation of encapsulated drugs. The aim of our work was to evaluate the toxicity of rifampicin-PLLA nanoparticles against Mycobacterium bovis BCG using human macrophage THP-1 cell line. Our data demonstrate that rifampicin-PLLA is effective against M. bovis BCG in the infected macrophages. The drug is inducing the dysfunction of mitochondria and apoptosis in the macrophages and is acting as a potential substrate of Pgp thereby modulating cell chemosensitivity. The severity of the toxic effects of the rifampicin-PLLA nanoparticles is increasing in a dose-dependent manner. We suggest that free rifampicin induces death of M. bovis BCG after PLLA degradation and diffusion from phago-lysosomes to cytoplasm causing mitochondria dysfunction and affecting the Pgp activity.

  4. 75 cases of BCG (BCG) after vaccination with abnormal response of curative effect observation and nursing%75例卡介苗(BCG)接种后异常反应的疗效观察及护理

    Institute of Scientific and Technical Information of China (English)

    秦曼玲

    2013-01-01

    Objective:Study of BCG after vaccination with abnormal response of curative effect observation and nursing. Methods:To BCG after inoculation of common abnormal reaction were summarized and analyzed and appropriate nursing measures. Results:BCG after vaccination abnormal reactions occurred in the left side of vaccination vaccine, it is the most in axil ary lymphadenopathy. Lymph nodes found in the after inoculation of 2-7month , it’s Most in 3-4month, Lymph node enlargement of diameter in 1~3 cm, Al were cured after comprehensive treatment, the cure rate is 100%. Conclusions:In BCG vaccination, we want to do good conduct propaganda and In order to reduce the abnormal reactions after inoculation of BCG vaccination, we should strengthen professional training and take treatment and nursing measures to abnormal response and ensure children Physical and mental health.%目的:探讨卡介苗(BCG)接种后异常反应的疗效观察及护理。方法:对卡介苗(BCG)接种后的常见异常反应进行总结分析,并采取适当的护理措施。结果:卡介苗(BCG)接种后异常反应均发生在左侧接种菌苗侧,以腋下淋巴结肿大为最多,淋巴结肿大发现于接种后2~7个月,大部分为3~4个月。淋巴结肿大直径以1~3 cm多见。经综合治疗后,全部治愈,治愈率达100%。结论:在进行卡介苗接种时,要做好宣传,为减少接种后异常反应的发生,应加强卡介苗接种人员的业务培训,发现异常反应要及时采取有效的治疗及护理措施,确保儿童的身心健康。

  5. Design and evaluation of an intravesical delivery system for superficial bladder cancer: preparation of gemcitabine HCl-loaded chitosan–thioglycolic acid nanoparticles and comparison of chitosan/poloxamer gels as carriers

    Directory of Open Access Journals (Sweden)

    Ay Şenyiğit Z

    2015-10-01

    Full Text Available Zeynep Ay Şenyiğit,1 Sinem Yaprak Karavana,1 Derya İlem-Özdemir,2 Çağrı Çalışkan,2 Claudia Waldner,3 Sait Şen,4 Andreas Bernkop-Schnürch,5 Esra Baloğlu1 1Faculty of Pharmacy, Department of Pharmaceutical Technology, Ege University, Bornova, İzmir, Turkey; 2Faculty of Pharmacy, Department of Radiopharmacy, Ege University, Bornova, İzmir, Turkey; 3ThioMatrix, Forschungs-Beratungs GmbH, Innsbruck, Austria; 4Faculty of Medicine, Department of Pathology, Ege University, Bornova, İzmir, Turkey; 5Institute of Pharmacy, Department of Pharmaceutical Technology, University of Innsbruck, Innsbruck, AustriaAbstract: This study aimed to develop an intravesical delivery system of gemcitabine HCl for superficial bladder cancer in order to provide a controlled release profile, to prolong the residence time, and to avoid drug elimination via urination. For this aim, bioadhesive nanoparticles were prepared with thiolated chitosan (chitosan–thioglycolic acid conjugate and were dispersed in bioadhesive chitosan gel or in an in situ gelling poloxamer formulation in order to improve intravesical residence time. In addition, nanoparticle-loaded gels were diluted with artificial urine to mimic in vivo conditions in the bladder and were characterized regarding changes in gel structure. The obtained results showed that chitosan-thioglycolic acid nanoparticles with a mean diameter of 174.5±3.762 nm and zeta potential of 32.100±0.575 mV were successfully developed via ionotropic gelation and that the encapsulation efficiency of gemcitabine HCl was nearly 20%. In vitro/ex vivo characterization studies demonstrated that both nanoparticles and nanoparticle-loaded chitosan and poloxamer gels might be alternative carriers for intravesical administration of gemcitabine HCl, prolonging its residence time in the bladder and hence improving treatment efficacy. However, when the gel formulations were diluted with artificial urine, poloxamer gels lost their in

  6. Efficient activation of human T cells of both CD4 and CD8 subsets by urease-deficient recombinant Mycobacterium bovis BCG that produced a heat shock protein 70-M. tuberculosis-derived major membrane protein II fusion protein.

    Science.gov (United States)

    Mukai, Tetsu; Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Makino, Masahiko

    2014-01-01

    For the purpose of obtaining Mycobacterium bovis bacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8(+) T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8(+) T cells and perforin-producing effector CD8(+) T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive to in vitro secondary stimulation with HSP70, MMP-II, and M. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challenged M. tuberculosis more efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.

  7. Intravesical resiniferatoxin for the treatment of storage lower urinary tract symptoms in patients with either interstitial cystitis or detrusor overactivity: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Changcheng Guo

    Full Text Available BACKGROUND: While Resin-iferatoxin (RTX has been widely used for patients with storage lower urinary tract symptoms (LUTS, its clinical efficiency hasn't yet been well evaluated. A meta-analysis was performed to evaluate the exact roles of intravesical RTX for the treatment of storage LUTS in patients with either interstitial cystitis (IC or detrusor overactivity (DO. METHODS: A meta-analysis of RTX treatment was performed through a comprehensive search of the literature. In total, 2,332 records were initially recruited, 1,907 from Elsevier, 207 from Medline and 218 from the Web of Science. No records were retrieved from the Embase or Cochrane Library. Seven trials with 355 patients were included and one trial was excluded because of the lack of extractable data. The analyses were all performed using RevMan 5.1 and MIX 2.0. RESULTS: Bladder pain was significantly reduced after RTX therapy in patients with either IC or DO. The average decrease of the visual an alogue pain scale was 0.42 after RTX treatment (p = 0.02. The maximum cystometric capacity (MCC was significantly increased in patients with DO (MCC increase, 53.36 ml, p = 0.006 but not in those with IC (MCC increase, -19.1 ml, p = 0.35. No significant improvement in urinary frequency, nocturia, incontinence or the first involuntary detrusor contraction (FDC was noted after RTX therapy (p = 0.06, p = 0.52, p = 0.19 and p = 0.41, respectively. CONCLUSIONS: RTX could significantly reduce bladder pain in patients with either IC or DO, and increase MCC in patients with DO; however, no significant improvement was observed in frequency, nocturia, incontinence or FDC. Given the limitations in the small patient size and risk of bias in the included trials, great caution should be taken when intravesical RTX is used before a large, multicenter, well-designed random control trial with a long-term follow-up is carried out to further assess the clinical efficacy of RTX in in patients with storage LUTS.

  8. Impact of surgery and epirubicin intravesical chemotherapy on peripheral blood dendritic cell subsets in patients with superficial urothelial carcinoma of the bladder

    Institute of Scientific and Technical Information of China (English)

    FENG Lang; MA Lin-lin; ZHANG Yu-hai; TIAN Ye; QU Chen-xue; WANG Yang

    2012-01-01

    Background Superficial urothelial carcinoma (SUC) of the bladder is a common urinary tract tumor in China.There is a high recurrence rate of this tumor even after surgery and intravesical instillation.Previous reports have described a suppression of the immune system in cancer patients.Dendritic cells (DCs) play a pivotal role in the induction of an effective antitumor immune response.The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy (IC) on peripheral blood DCs in subsets of patients with bladder SUC.@@Methods A total of 66 SUC patients and 38 healthy controls were enrolled in this study.All the patients had undergone transurethral resection (TUR) of their cancer and adjunctive IC after tumor removal.The patients were divided into a non-recurrence group (n=40) and a recurrence group (n=26) based on the presence or absence of tumor recurrence.Blood samples were taken preoperatively (PreOP),on postoperative days (POD) 1 and 7,and at postoperative month (POM) 3.Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets.@@Results The preoperative percentages of myeloid dendritic cells (mDCs) and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls (P <0.05).The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7,remaining higher than the preoperative values in POM 3 (P <0.05).The percentages of mDCs,and CD80 and CD86 in the non-recurrence group on PreOP,POD 7,and POM 3 were higher than those in recurrence group.@@Conclusions Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function.Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.

  9. First data on Eurasian wild boar response to oral immunization with BCG and challenge with a Mycobacterium bovis field strain.

    Science.gov (United States)

    Ballesteros, C; Garrido, J M; Vicente, J; Romero, B; Galindo, R C; Minguijón, E; Villar, M; Martín-Hernando, M P; Sevilla, I; Juste, R; Aranaz, A; de la Fuente, J; Gortázar, C

    2009-11-12

    The Eurasian wild boar (Sus scrofa) is considered a reservoir for bovine tuberculosis (bTB) caused by Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex in south-central Spain. The vaccination of wildlife with BCG offers an alternative to culling and to movement restriction for the control of bTB among wildlife reservoirs. In this study, we hypothesized that oral BCG immunization of wild boar would affect the expression of immunoregulatory genes and confer protection against M. bovis. Three groups were used to describe the infection, pathological findings and gene expression profiles in wild boar: BCG-vaccinated and M. bovis-challenged (vaccinated challenged group; N=6), non-vaccinated and M. bovis-challenged (non-vaccinated challenged group; N=4), and non-vaccinated and mock-infected (control group; N=2) animals. M. bovis was isolated from 50% (3/6) and 75% (3/4) of vaccinated challenged and non-vaccinated challenged animals, respectively. All four wild boar from the non-vaccinated challenged group developed bTB-compatible lesions 114 days after challenge. In contrast, only 50% of vaccinated challenged wild boar developed lesions. The PBMC mRNA levels of IL4, RANTES, C3, IFN-gamma and methylmalonyl-CoA mutase (MUT) were analyzed at several days post-vaccination (dpi). When vaccinated challenged animals were compared to controls, all five genes were significantly upregulated at the time of M. bovis infection at 186dpi but IFN-gamma levels were also upregulated at 11 and 46dpi. The C3 and MUT mRNA levels were higher at 46dpi, and 11 and 186dpi, respectively, in vaccinated protected wild boar when compared to non-vaccinated challenged animals. At the end of the experiment (300dpi), the mRNA levels of selected genes were lower in non-vaccinated challenged animals when compared to control wild boar. Exposing wild boar to a dose of 10(4)cfu of M. bovis by the oropharyngeal route is an adequate protocol to produce an infection model

  10. Improving Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer by adding interleukin 2 (IL-2): a mathematical model.

    Science.gov (United States)

    Bunimovich-Mendrazitsky, Svetlana; Halachmi, Sarel; Kronik, Natalie

    2016-06-01

    One of the treatments offered to non-invasive bladder cancer patients is BCG instillations, using a well-established, time-honoured protocol. Some of the patients, however, do not respond to this protocol. To examine possible changes in the protocol, we provide a platform for in silico testing of alternative protocols for BCG instillations and combinations with IL-2, to be used by urologists in planning new treatment strategies for subpopulations of bladder cancer patients who may benefit from a personalized protocol. We use a systems biology approach to describe the BCG-tumour-immune interplay and translate it into a set of mathematical differential equations. The variables of the equation set are the number of tumour cells, bacteria cells, immune cells, and cytokines participating in the tumour-immune response. Relevant parameters that describe the system's dynamics are taken from a variety of independent literature, unrelated to the clinical trial results assessed by the model predictions. Model simulations use a clinically relevant range of initial tumour sizes (tumour volume) and tumour growth rates (tumour grade), representative of a virtual population of fifty patients. Our model successfully retrieved previous clinical results for BCG induction treatment and BCG maintenance therapy with a complete response (CR) rate of 82%. Furthermore, we designed alternative maintenance protocols, using IL-2 combinations with BCG, which improved success rates up to 86% and 100% of the patients, albeit without considering possible side effects. We have shown our simulation platform to be reliable by demonstrating its ability to retrieve published clinical trial results. We used this platform to predict the outcome of treatment combinations. Our results suggest that the subpopulation of non-responsive patients may benefit from an intensified combined BCG IL-2 maintenance treatment.

  11. Immunomodulation of Homeopathic Thymulin 5CH in a BCG-Induced Granuloma Model

    Directory of Open Access Journals (Sweden)

    Leoni Villano Bonamin

    2013-01-01

    Full Text Available The present study analyzed the immune modulation mechanisms of thymulin 5CH in a granuloma experimental model. Male adult Balb/c mice were inoculated with BCG into the footpad to induce granuloma, which was quantitatively evaluated. The phenotypic characterization of phagocyte, T- and B-lymphocyte populations in the peritoneum, and local lymph node was done by flow cytometry. During all experimental periods, thymulin 5CH and vehicle (control were given ad libitum to mice, diluted into the drinking water (1.6×10−17 M. After 7 days from inoculation, thymulin-treated mice presented reduction in the number of epithelioid cytokeratine-positive cells (P=0.0001 in the lesion, in relation to young phagocytes. After 21 days, the differentiation of B1 peritoneal stem cells into phagocytes reached the peak, being higher in thymulin-treated mice (P=0.0001. Simultaneously, the score of infected phagocytes in the lesion decreased (P=0.001, and the number of B1-derived phagocytes, CD4+ and CD8+ T lymphocytes in the local lymph node increased in relation to control (P=0.0001. No difference was seen on the CD25+ Treg cells. The results show that thymulin 5CH treatment is able to improve the granuloma inflammatory process and the infection remission, by modulating local and systemic phagocyte differentiation.

  12. Contrary to BCG, MLM fails to induce the production of TNF alpha and NO by macrophages.

    Science.gov (United States)

    Rojas-Espinosa, Oscar; Wek-Rodríguez, Kendy; Arce-Paredes, Patricia; Aguilar-Torrentera, Fabiola; Truyens, Carine; Carlier, Yves

    2002-06-01

    Pathogenic mycobacteria must possess efficient survival mechanisms to resist the harsh conditions of the intraphagosomal milieu. In this sense, Mycobacterium lepraemurium (MLM) is one of the most evolved intracellular parasites of murine macrophages; this microorganism has developed a series of properties that allows it not only to resist, but also to multiply within the inhospitable environment of the phagolysosome. Inside the macrophages, MLM appears surrounded by a thick lipid-envelope that protects the microorganism from the digestive effect of the phagosomal hydrolases and the acid pH. MLM produces a disease in which the loss of specific cell-mediated immunity ensues, thus preventing activation of macrophages. In vitro, and possibly also in vivo, MLM infects macrophages without triggering the oxidative (respiratory burst) response of these cells, thus preventing the production of the toxic reactive oxygen intermediaries (ROI). Supporting the idea that MLM is within the most evolved pathogenic microorganisms, in the present study we found, that contrary to BCG, M. lepraemurium infects macrophages without stimulating these cells to produce meaningful levels of tumor necrosis factor alpha (TNF alpha) or nitric oxide (NO). Thus, the ability of the microorganisms to stimulate in their cellular hosts, the production of ROI and RNI (reactive nitrogen intermediates), seems to be an inverse correlate of their pathogenicity; the lesser their ability, the greater their pathogenicity.

  13. Living language

    CERN Document Server

    Shuttleworth, John

    2008-01-01

    Living Language 3rd edition' has been devised to meet all the new specifications for AS and A level English Language. The best-selling previous edition has been comprehensively revised to ensure full assessment objectives coverage and fulfilment, and delivery of the new four-unit courses from 2008 onwards. 'Living Language 3rd edition' provides linguistic theory, information and ideas which are easily accessed via supported activities and investigations. The text will actively develop students' skills in reading, listening and responding to an extensive range of text genres and data. Building

  14. Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line: a potential improvement of intravesical chemotherapy in bladder cancer.

    Science.gov (United States)

    Vásquez, Juan L; Gehl, Julie; Hermann, Gregers G

    2012-12-01

    Intravesical mitomycin instillation combined with electric pulses is being used experimentally for the treatment of T1 bladder tumors, in patients unfit for surgery. Electroporation may enhance the uptake of chemotherapeutics by permeabilization of cell membranes. We investigated if electroporation improves the cytotoxicity of mitomycin. In two cell lines, T24 (bladder cancer cell line) and DC3F (Chinese hamster fibroblast), exposure to different concentrations of mitomycin (0.01-2000μM) was tested with and without electroporation (6 pulses of 1kV/cm, duration: 99μs, frequency: 1Hz). Cell viability was assessed by colorimetric assay (MTT). For both cell lines, mitomycin's IC_50 was approximately 1000μM in both pulsed and unpulsed cells. On T24 cells, electroporation and mitomycin caused (relative reduction) RR of survival of: 25%, 31% and 29%, by concentrations 0μM, 500μM and 1000μM respectively. For DC3F cells, the RRs of survival were: 28%, 29%, and 33%, by concentrations 0μM, 500μM and 1000μM respectively. In conclusion, electroporation and mitomycin together are about 30% more effective than mitomycin alone. The results help to elucidate the additive effect of mitomycin and electric pulses and support the use of this combination in the treatment of bladder cancer.

  15. Enhancement of BCG-induced Th1 immune response through Vgamma9Vdelta2 T cell activation with non-peptidic drugs.

    Science.gov (United States)

    Martino, Angelo; Casetti, Rita; Poccia, Fabrizio

    2007-01-22

    Since drug-activated gammadelta T cells promote dendritic cell (DC) maturation, we analyzed the effect of combining gammadelta T cell specific drugs with BCG in vitro. BCG-induced DC maturation was increased by bromohydrin-pirophosphate (BrHPP) or zoledronate (Zol)-activated gammadelta T cells. Specifically, the co-culture with activated Vgamma9Vdelta2 T cells with BCG-infected DC resulted in a significant increase of the expression of CD80, CD86, CD40 and CD25 molecules on DC. Moreover, DC were able to produce increased levels of TNF-alpha and synthesize ex novo IL-15 without altering the IL-10/IL-12 immunoregulatory pathway. Finally, the Th1 immunity induced by BCG-infected DC on naïve CD4 T cells was increased by gammadelta T cell activation with BrHpp or Zol. These data indicate that gammadelta T cell triggering drugs could be used to enhance the BCG induced Th1 immunity.

  16. Detection of a Putative TetR-Like Gene Related to Mycobacterium bovis BCG Growth in Cholesterol Using a gfp-Transposon Mutagenesis System

    Science.gov (United States)

    Otal, Isabel; Pérez-Herrán, Esther; Garcia-Morales, Lazaro; Menéndez, María C.; Gonzalez-y-Merchand, Jorge A.; Martín, Carlos; García, María J.

    2017-01-01

    In vitro transposition is a powerful genetic tool for identifying mycobacterial virulence genes and studying virulence factors in relation to the host. Transposon shuttle mutagenesis is a method for constructing stable insertions in the genome of different microorganisms including mycobacteria. Using an IS1096 derivative, we have constructed the Tngfp, a transposon containing a promoterless green fluorescent protein (gfp) gene. This transposon was able to transpose randomly in Mycobacterium bovis BCG. Bacteria with a single copy of the gfp gene per chromosome from an M. bovis BCG::Tngfp library were analyzed and cells exhibiting high levels of fluorescence were detected by flow cytometry. Application of this approach allowed for the selection of a mutant, BCG_2177c::Tngfp (BCG-Tn), on the basis of high level of long-standing fluorescence at stationary phase. This BCG-Tn mutant showed some particular phenotypic features compared to the wild type strain, mainly during stationary phase, when cholesterol was used as a sole carbon source, thus supporting the relationships of the targeted gene with the regulation of cholesterol metabolism in this bacteria. This approach showed that Tngfp is a potentially useful tool for studying the involvement of the targeted loci in metabolic pathways of mycobacteria. PMID:28321208

  17. Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components.

    Science.gov (United States)

    Rhoades, Elizabeth R; Geisel, Rachel E; Butcher, Barbara A; McDonough, Sean; Russell, David G

    2005-05-01

    The chronic inflammatory response to Mycobacterium generates complex granulomatous lesions that balance containment with destruction of infected tissues. To study the contributing factors from host and pathogen, we developed a model wherein defined mycobacterial components and leukocytes are delivered in a gel, eliciting a localized response that can be retrieved and analysed. We validated the model by comparing responses to the cell wall lipids from Mycobacterium bovis bacillus Calmette-Guerin (BCG) to reported activities in other models. BCG lipid-coated beads and bone marrow-derived macrophages (input macrophages) were injected intraperitoneally into BALB/c mice. Input macrophages and recruited peritoneal exudate cells took up fluorescently tagged BCG lipids, and matrix-associated macrophages and neutrophils produced tumor necrosis factor, interleukin-1alpha, and interleukin-6. Leukocyte numbers and cytokine levels were greater in BCG lipid-bearing matrices than matrices containing non-coated or phosphatidylglycerol-coated beads. Leukocytes arrived in successive waves of neutrophils, macrophages and eosinophils, followed by NK and T cells (CD4(+), CD8(+), or gammadelta) at 7 days and B cells within 12 days. BCG lipids also predisposed matrices for adherence and vascularization, enhancing cellular recruitment. We submit that the matrix model presents pertinent features of the murine granulomatous response that will prove to be an adaptable method for study of this complex response.

  18. Treatment Options Available for Bacillus Calmette-Guerin Failure in Non-muscle-invasive Bladder Cancer

    NARCIS (Netherlands)

    Yates, D.R.; Brausi, M.A.; Catto, J.W.; Dalbagni, G.; Roupret, M.; Shariat, S.F.; Sylvester, R.J.; Witjes, J.A.; Zlotta, A.R.; Palou-Redorta, J.

    2012-01-01

    CONTEXT: Intravesical bacillus Calmette-Guerin (BCG) is a standard conservative treatment for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Many patients will experience recurrence or progression following BCG and are termed BCG failures. OBJECTIVE: To summarise the current tre

  19. Composition and immunoreactivity of the A60 complex and other cell fractions from Mycobacterium bovis BCG.

    Science.gov (United States)

    Cocito, C; Vanlinden, F

    1995-02-01

    Surface static cultures of Mycobacterium bovis BCG contained cells embedded in an extracellular matrix, whose mechanical removal yielded free cells that were pressure disrupted and fractionated into cytoplasm and walls. Cell envelopes were either mechanically disrupted or extracted with detergents. Intracellular and extracellular fractions were analysed for proteins, polysaccharides, and antigen 6O (A60), a major complex immunodominant in tuberculosis. A60 was present in extracellular matrix, cytoplasm and walls: it represented a substantial portion of the proteins and polysaccharides of these fractions. While the protein/polysaccharide ratio varied according to the origin of A60 preparations, the electrophoretic patterns of A60 proteins (which accounted for the immunogenicity of the complex) remained unchanged. Western blots pointed to the proteins present within the 29-45 kDa range as the A60 components endowed with the highest immunogenicity level. Since the most heavily stained protein bands in SDS-PAGE patterns were located outside the region best recognized by antisera, a striking discordance was found between concentration and immunogenicity patterns of A60 proteins. The electrophoretic patterns of A60- and non-A60-proteins from cytoplasm were also different. A60 complexes in dot blots and some electrophoresed A60 proteins reacted with monoclonal antibodies directed against lipoarabinomannan (LAM), a highly immunogenic polymer of cell envelope. This contaminating compound was removed from A60 with organic solvents and detergents. SDS-PAGE and Western blot patterns of proteins from delipidated A60 were similar to those of native A60 proteins.

  20. Living Lands

    DEFF Research Database (Denmark)

    Christensen, Suna Møller

    2014-01-01

    , hunters attended to questions like safe-journeying on ice or the role of natural surroundings in children’s education, in ways revealing a relational perception of ‘nature’ and dissolving culture-nature dualisms. Hunters’ experiences in living the land afforded children a dwelling position from which...... of the social world pushes questions about education and life, disregarding being educated as human control of nature....

  1. Valor preditivo do teste tuberculínico padronizado em crianças vacinadas com BCG

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-08-01

    Full Text Available A aplicabilidade do teste tuberculínico em crianças menores de 5 anos vacinadas com BCG é assunto controvertido. Visando contribuir para esclarecê-lo foi analisado o valor preditivo positivo do teste tuberculínico padronizado em população sob elevada cobertura vacinal e baixa prevalência de infecção tuberculosa. A partir da proporção de reatores fortes em lactentes e escolares vacinados e não vacinados, foram calculadas a razão de declínio da alergia tuberculínica nos vacinados e a razão de crescimento nos não vacinados, o que possibilitou a estimativa dos respectivos valores nas idades intermediárias. A expectativa de falsos-positivos (FP foi então calculada por diferença. Conhecidas a sensibilidade e a especificidade do teste (E=1-FP, a cobertura BCG e a prevalência de infecção, os valores preditivos (para a infecção tuberculosa foram: 1,52%, 4,22%, 8,26%, 14,86% e 23,00%, do primeiro ao quinto ano de vida. Nessas condições, a probabilidade de uma reação forte ser devida ao BCG é grande, especialmente nos dois primeiros anos, o que reduz a aplicabilidade clínica e epidemiológica do teste.

  2. Multivalent TB vaccines targeting the esx gene family generate potent and broad cell-mediated immune responses superior to BCG.

    Science.gov (United States)

    Villarreal, Daniel O; Walters, Jewell; Laddy, Dominick J; Yan, Jian; Weiner, David B

    2014-01-01

    Development of a broad-spectrum synthetic vaccine against TB would represent an important advance to the limited vaccine armamentarium against TB. It is believed that the esx family of TB antigens may represent important vaccine candidates. However, only 4 esx antigens have been studied as potential vaccine antigens. The challenge remains to develop a vaccine that simultaneously targets all 23 members of the esx family to induce enhanced broad-spectrum cell-mediated immunity. We sought to investigate if broader cellular immune responses could be induced using a multivalent DNA vaccine representing the esx family protein members delivered via electroporation. In this study, 15 designed esx antigens were created to cross target all members of the esx family. They were distributed into groups of 3 self-processing antigens each, resulting in 5 trivalent highly optimized DNA plasmids. Vaccination with all 5 constructs elicited robust antigen-specific IFN-γ responses to all encoded esx antigens and induced multifunctional CD4 Th1 and CD8 T cell responses. Importantly, we show that when all constructs are combined into a cocktail, the RSQ-15 vaccine, elicited substantial broad Ag-specific T cell responses to all esx antigens as compared with vaccination with BCG. Moreover, these vaccine-induced responses were highly cross-reactive with BCG encoded esx family members and were highly immune effective in a BCG DNA prime-boost format. Furthermore, we demonstrate the vaccine potential and immunopotent profile of several novel esx antigens never previously studied. These data highlight the likely importance of these novel immunogens for study as preventative or therapeutic synthetic TB vaccines in combination or as stand alone antigens.

  3. Complement factor H interferes with Mycobacterium bovis BCG entry into macrophages and modulates the pro-inflammatory cytokine response.

    Science.gov (United States)

    Abdul-Aziz, Munirah; Tsolaki, Anthony G; Kouser, Lubna; Carroll, Maria V; Al-Ahdal, Mohammed N; Sim, Robert B; Kishore, Uday

    2016-09-01

    Mycobacterium tuberculosis is an accomplished intracellular pathogen, particularly within the macrophage and this is of the utmost importance in the host-pathogen stand-off observed in the granuloma during latent tuberculosis. Contact with innate immune molecules is one of the primary interactions that can occur with the pathogen M. tuberculosis once inhaled. Complement proteins may play a role in facilitating M. tuberculosis interactions with macrophages. Here, we demonstrate that factor H, a complement regulatory protein that down-regulates complement alternative pathway activation, binds directly to the model organism M. bovis BCG. Binding of factor H reaches saturation at 5-10μg of factor H/ml, well below the plasma level. C4 binding protein (C4BP) competed with factor H for binding to mycobacteria. Factor H was also found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Real-time qPCR analysis showed stark differential responses of pro- and anti-inflammatory cytokines during the early stages of phagocytosis, as evident from elevated levels of TNF-α, IL-1β and IL-6, and a concomitant decrease in IL-10, TGF-β and IL-12 levels, when THP-1:BCG interaction took place in the presence of factor H. Our results suggest that factor H can interfere with mycobacterial entry into macrophages and modulate inflammatory cytokine responses, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. Our results offer novel insights into complement activation-independent functions of factor H during the host-pathogen interaction in tuberculosis.

  4. Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry.

    Science.gov (United States)

    Venisse, A; Berjeaud, J M; Chaurand, P; Gilleron, M; Puzo, G

    1993-06-15

    It was recently shown that mycobacterial lipoarabinomannan (LAM) can be classified into two types (Chatterjee, D., Lowell, K., Rivoire B., McNeil M. R., and Brennan, P. J. (1992) J. Biol. Chem. 267, 6234-6239) according to the presence or absence of mannosyl residues (Manp) located at the nonreducing end of the oligoarabinosyl side chains. These two types of LAM were found in a pathogenic Mycobacterium tuberculosis strain and in an avirulent M. tuberculosis strain, respectively, suggesting that LAM with Manp characterizes virulent and "disease-inducing strains." We now report the structure of the LAM from Mycobacterium bovis Bacille Calmette-Guérin (BCG) strain Pasteur, largely used throughout the world as vaccine against tuberculosis. Using an up-to-date analytical approach, we found that the LAM of M. bovis BCG belongs to the class of LAMs capped with Manp. By means of two-dimensional homonuclear and heteronuclear scalar coupling NMR analysis and methylation data, the sugar spin system assignments were partially established, revealing that the LAM contained two types of terminal Manp and 2-O-linked Manp. From the following four-step process: (i) partial hydrolysis of deacylated LAM (dLAM), (ii) oligosaccharide derivatization with aminobenzoic ethyl ester, (iii) HPLC purification, (iv) FAB/MS-MS analysis; it was shown that the dimannosyl unit alpha-D-Manp-(1-->2)-alpha-D-Manp is the major residue capping the termini of the arabinan of the LAM. In this report, LAM molecular mass determination was established using matrix-assisted UV-laser desorption/ionization mass spectrometry which reveals that the LAM molecular mass is around 17.4 kDa. The similarity of the LAM structures between M. bovis BCG and M. tuberculosis H37Rv is discussed in regard to their function in the immunopathology of mycobacterial infection.

  5. The Mean and Scatter of the Velocity Dispersion-Optical Richness Relation for MaxBCG Galaxy Clusters

    Energy Technology Data Exchange (ETDEWEB)

    Becker, M.R.; McKay, T.A.; /Michigan U.; Koester, B.; /Chicago U., Astron. Astrophys. Ctr.; Wechsler, R.H.; /KIPAC, Menlo Park /SLAC /Stanford U., Phys. Dept.; Rozo, E.; /Ohio State U.; Evrard, A.; /Michigan U. /Michigan U., MCTP; Johnston, D.; /Caltech, JPL; Sheldon, E.; /New York U.; Annis, J.; /Fermilab; Lau, E.; /Chicago U., Astron. Astrophys. Ctr.; Nichol, R.; /Portsmouth U., ICG; Miller, C.; /Michigan U.

    2007-06-05

    The distribution of galaxies in position and velocity around the centers of galaxy clusters encodes important information about cluster mass and structure. Using the maxBCG galaxy cluster catalog identified from imaging data obtained in the Sloan Digital Sky Survey, we study the BCG--galaxy velocity correlation function. By modeling its non-Gaussianity, we measure the mean and scatter in velocity dispersion at fixed richness. The mean velocity dispersion increases from 202 {+-} 10 km s{sup -1} for small groups to more than 854 {+-} 102 km s{sup -1} for large clusters. We show the scatter to be at most 40.5{+-}3.5%, declining to 14.9{+-}9.4% in the richest bins. We test our methods in the C4 cluster catalog, a spectroscopic cluster catalog produced from the Sloan Digital Sky Survey DR2 spectroscopic sample, and in mock galaxy catalogs constructed from N-body simulations. Our methods are robust, measuring the scatter to well within one-sigma of the true value, and the mean to within 10%, in the mock catalogs. By convolving the scatter in velocity dispersion at fixed richness with the observed richness space density function, we measure the velocity dispersion function of the maxBCG galaxy clusters. Although velocity dispersion and richness do not form a true mass--observable relation, the relationship between velocity dispersion and mass is theoretically well characterized and has low scatter. Thus our results provide a key link between theory and observations up to the velocity bias between dark matter and galaxies.

  6. Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

    DEFF Research Database (Denmark)

    Nørrelykke Nissen, Thomas; Birk, Nina Marie; Kjærgaard, Jesper;

    2016-01-01

    OBJECTIVE: To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. DESIGN: A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no inter...

  7. Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

    DEFF Research Database (Denmark)

    Diness, B.R.; Roth, A.; Nante, E.;

    2008-01-01

    Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Design Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering...... approximately 90 000 inhabitants. Participants 4345 infants due to receive BCG. Intervention Infants were randomised to 50 000 IU vitamin A or placebo and followed until age 12 months. Main outcome measure Mortality rate ratios. Results 174 children died during follow-up (mortality=47/ 1000 person.......84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African...

  8. The results of treatments and complications of immunotherapy (BCG and alpha-interferon in superficial TCC of bladder

    Directory of Open Access Journals (Sweden)

    Jabalameli P

    1994-04-01

    Full Text Available The treatment of choice for bladder tumors is TUR, but because of high incidence of recurrence in these tumors, various treatments are suggested. In one study, 32 patients involved with superficial T.C.C. of bladder selected and divided in two equal groups. In the first group, after T.U.R, 10 million IU of a alpha-interferon was injected into the bladder through a catheter and in the other group, after TUR, they treated with injection of BCG into bladders. The results of these two drugs in prevention of recurrence and their side effects were studied and compaired

  9. Impact of PGL-I seropositivity on the protective effect of BCG vaccination among leprosy contacts: a cohort study.

    Directory of Open Access Journals (Sweden)

    Nádia C Düppre

    Full Text Available BACKGROUND: Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG vaccination after index case diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135 leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR = 4.1; 95% CI: 1.8-8.2 compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2-8.1. The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6 occurred in PGL-I-positive unvaccinated contacts. CONCLUSION: Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index

  10. Strategic analysis of PKM Duda SA. on Polish meat market with the application of BCG growth-share matrix

    OpenAIRE

    Anna Zielińska-Chmielewska

    2012-01-01

    The main goal of this paper was to examine the market position of one leading meat processing enterprise PKM Duda SA. on the domestic meat market. The assessment of the activity portfolio on its three strategic units was undertaken with the usage of BCG matrix. The PKM Duda SA. was chosen for the study because: a) processes more than 20 tons of slaughter per week, b) is located in the country of origin, c) exists on Warsaw Stock Exchange Market, d) preserves continuity of its database in Moni...

  11. Living edge

    DEFF Research Database (Denmark)

    Earon, Ofri

    2014-01-01

    of the involved actors at the border. By doing so, the study underlines a forgotten, yet important, role of this edge zone – being a zone of commonality between the house and city, between indoors and outdoors, between the man at home and the man at the street. The city of Copenhagen promotes porous borders...... is a collection of material from the case study of an ongoing PhD study titled: LIVING EDGE - The Architectural and Urban Prospect of Domestic Borders. The paper includes a description of the problem analysis, research question, method, discussion and conclusion....

  12. Successive Intramuscular Boosting with IFN-Alpha Protects Mycobacterium bovis BCG-Vaccinated Mice against M. lepraemurium Infection

    Directory of Open Access Journals (Sweden)

    G. G. Guerrero

    2015-01-01

    Full Text Available Leprosy caused by Mycobacterium leprae primarily affects the skin and peripheral nerves. As a human infectious disease, it is still a significant health and economic burden on developing countries. Although multidrug therapy is reducing the number of active cases to approximately 0.5 million, the number of cases per year is not declining. Therefore, alternative host-directed strategies should be addressed to improve treatment efficacy and outcome. In this work, using murine leprosy as a model, a very similar granulomatous skin lesion to human leprosy, we have found that successive IFN-alpha boosting protects BCG-vaccinated mice against M. lepraemurium infection. No difference in the seric isotype and all IgG subclasses measured, neither in the TH1 nor in the TH2 type cytokine production, was seen. However, an enhanced iNOS/NO production in BCG-vaccinated/i.m. IFN-alpha boosted mice was observed. The data provided in this study suggest a promising use for IFN-alpha boosting as a new prophylactic alternative to be explored in human leprosy by targeting host innate cell response.

  13. The XXL survey XV: Evidence for dry merger driven BCG growth in XXL-100-GC X-ray clusters

    CERN Document Server

    Lavoie, S; Democles, J; Eckert, D; Gastaldello, F; Smith, G P; Lidman, C; Adami, C; Pacaud, F; Pierre, M; Clerc, N; Giles, P; Lieu, M; Chiappetti, L; Altieri, B; Ardila, F; Baldry, I; Bongiorno, A; Desai, S; Elyiv, A; Faccioli, L; Gardner, B; Garilli, B; Groote, M W; Guennou, L; Guzzo, L; Hopkins, A M; Liske, J; McGee, S; Melnyk, O; Owers, M S; Poggianti, B; Ponman, T J; Scodeggio, M; Spitler, L; Tuffs, R J

    2016-01-01

    The growth of brightest cluster galaxies is closely related to the properties of their host cluster. We present evidence for dry mergers as the dominant source of BCG mass growth at $z\\lesssim1$ in the XXL 100 brightest cluster sample. We use the global red sequence, H$\\alpha$ emission and mean star formation history to show that BCGs in the sample possess star formation levels comparable to field ellipticals of similar stellar mass and redshift. XXL 100 brightest clusters are less massive on average than those in other X-ray selected samples such as LoCuSS or HIFLUGCS. Few clusters in the sample display high central gas concentration, rendering inefficient the growth of BCGs via star formation resulting from the accretion of cool gas. Using measures of the relaxation state of their host clusters, we show that BCGs grow as relaxation proceeds. We find that the BCG stellar mass corresponds to a relatively constant fraction 1\\%\\ of the total cluster mass in relaxed systems. We also show that, following a cluste...

  14. Strategic analysis of PKM Duda SA. on Polish meat market with the application of BCG growth-share matrix

    Directory of Open Access Journals (Sweden)

    Anna Zielińska-Chmielewska

    2012-01-01

    Full Text Available The main goal of this paper was to examine the market position of one leading meat processing enterprise PKM Duda SA. on the domestic meat market. The assessment of the activity portfolio on its three strategic units was undertaken with the usage of BCG matrix. The PKM Duda SA. was chosen for the study because: a processes more than 20 tons of slaughter per week, b is located in the country of origin, c exists on Warsaw Stock Exchange Market, d preserves continuity of its database in Monitor Polski „B”. The analysis proved that all three examined strategic units have different market shares and operate on markets of a different acceleration. The highest income rate brings the meat processing unit (B, the lowest slaughter unit (A. The market position of PKM Duda SA. can be improved when a retail trade unit (B moves away from question marks into stars. Although BCG matrix draws a fast and a complex strategic situation, is not free from disadvantages. That is the reason why further, also portfolio, analysis should be im-plemented.

  15. Live CMS

    CERN Document Server

    2017-01-01

    CMS live from Facebook. The Pixel Tracker (or Pixel Detector) is the innermost instrument in the very heart of the CMS apparatus, installed around the LHC beampipe. This is the very point where new particles, such as the Higgs boson, are produced by the energy of the proton proton collisions, and so the Pixel detector receives the largest particle-flux of any sub-component of CMS. The new component is made up of two “parts”: a central barrel region (called BPIX), made of two cylindrical halves, and forward discs on either side of the collision point (FPIX). The new BPIX was manufactured by a consortium of European institutes from Switzerland, Italy and Germany, supported by CERN. The new FPIX was manufactured by 14 institutes in the USA.

  16. Serviced Living

    Institute of Scientific and Technical Information of China (English)

    LIU BO

    2006-01-01

    @@ As recently as ten years ago,the term serviced apartment made no sense to most people living in Beijing and residing in hotels was the only options for foreign visitors. But since then, serviced apartments have begun to appear in big cities all around China. In Beijing alone, it is estimated that there are more than 30,000service apartments spread across dozens of properties occupying a space of more than I million square meters. Concentrating in the Financial Street, the Central Business District and Zhongguancun, also known as China's Silicon Valley, the explosion in service apartments in the city continues to be fueled by the influx of overseas and domestic business people.

  17. Construction and expression of a recombinant BCG-TSOL18 vaccine of Taenia solium%猪带绦虫重组 BCG-TSOL18疫苗构建及其表达

    Institute of Scientific and Technical Information of China (English)

    杨凤娇; 周必英

    2015-01-01

    We constructed a recombinant Bacillus Calmette‐Guerin(BCG)‐TSOL18 vaccine of Taenia solium and observed the expression of the TSOL18 gene in BCG .The TSOL18 gene of Taenia solium was obtained from the recombinant plasmid pGEX‐TSOL18 by digestion method and cloned into Escherichia coli (E .coli)‐mycobacterium shuttle plasmid pMV261 to con‐struct the recombinant plasmid pMV261‐TSOL18 of Taenia solium ,and the recombinant plasmid was identified by restriction enzyme digestion ,PCR and DNA sequencing .Then ,the recombinant plasmid was transformed into BCG by electroporation to construct the recombinant BCG‐TSOL18 vaccine of Taenia solium ,and the vaccine was identified by PCR .The expression of the TSOL18 gene in BCG was identified by SDS‐PAGE and Western blot .The 393 bp TSOL18 gene fragment was successfully obtained by restriction enzyme digestion .Restriction enzyme digestion ,PCR and DNA sequencing suggested that the recombi‐nant plasmid pMV261‐TSOL18 of Taenia solium was successfully constructed .PCR confirmed that the recombinant plasmid pMV261‐TSOL18 of Taenia solium was successfully transformed into BCG ,suggesting that the recombinant BCG‐TSOL18 vaccine of Taenia solium was successfully constructed .SDS‐PAGE showed that the relative molecular mass (Mr) of TSOL18 target protein was approximately 14 .7 kD .Results of western blot showed the TSOL18 target protein could be recognized by rabbit antiserum or cysticercosis swine serum .The recombinant BCG‐TSOL18 vaccine of Taenia solium was successfully con‐structed .The TSOL18 gene of Taeniasolium was successfully expressed in BCG and the expressed TSOL18 recombinant pro‐tein had specific antigenicity .This result would lay a foundation for further study of the vaccine .%目的:构建猪带绦虫重组BCG‐TSOL18疫苗,研究TSOL18基因在BCG中的表达情况。方法通过酶切的方法从重组质粒pGEX‐TSOL18获取猪带绦虫TSOL18基因,将其定向克隆到大肠

  18. Fatal Renal Failure in a Spinal Cord Injury Patient with Vesicoureteric Reflux Who Underwent Repeated Ureteric Reimplantations Unsuccessfully: Treatment Should Focus on Abolition of High Intravesical Pressures rather than Surgical Correction of Reflux

    Directory of Open Access Journals (Sweden)

    Subramanian Vaidyanathan

    2012-01-01

    Full Text Available A 29-year-old man developed paraplegia at T-10 level due to road traffic accident in 1972. Both kidneys were normal and showed good function on intravenous urography. Division of external urethral sphincter was performed in 1973. In 1974, cystogram showed retrograde filling of left renal tract, which was hydronephrotic. Left ureteric reimplantation was performed. Following surgery, cystogram revealed marked retrograde filling of left renal tract as before. Penile sheath drainage was continued. In 1981, intravenous urography revealed bilateral severe hydronephrosis. Left ureteric reimplantation was performed again in 1983. Blood pressure was 220/140 mm Hg; this patient was prescribed atenolol. Cystogram showed gross left vesicoureteral reflux. Intermittent catheterisation was commenced in 2001. In 2007, proteinuria was 860 mg/day. This patient developed progressive renal failure and expired in 2012. In a spinal cord injury patient with vesicoureteral reflux, the treatment should focus on abolition of high intravesical pressures rather than surgical correction of vesicoureteric reflux. Detrusor hyperactivity and high intravesical pressures are the basic causes for vesicoureteral reflux in spinal cord injury patients. Therefore, it is important to manage spinal cord injury patients with neuropathic bladder by intermittent catheterisations along with antimuscarinic drug therapy in order to abolish high detrusor pressures and prevent vesicoureteral reflux. Angiotensin-converting enzyme inhibitors or angiotensin-receptor-blocking agents should be prescribed even in the absence of hypertension when a spinal cord injury patient develops vesicoureteral reflux and proteinuria.

  19. Family history of immigration from a tuberculosis endemic country and low family income are associated with a higher BCG vaccination coverage in Ile-de-France region, France.

    Science.gov (United States)

    Guthmann, Jean-Paul; Chauvin, Pierre; Le Strat, Yann; Soler, Marion; Fonteneau, Laure; Lévy-Bruhl, Daniel

    2013-11-19

    After withdrawal of multipuncture BCG device from the French market in January 2006, vaccination coverage (VC) with the intradermal device has dropped and since remained sub-optimal in Ile-de-France, the only region of mainland France where BCG is recommended to all children. We conducted a cross-sectional study to identify socio-economic factors associated with BCG VC in children of Paris metropolitan area born after January 2006. Two-stage random sampling was used to include 425 children up to 5 years old from Paris and its suburbs. Information was collected through face-to-face interviews and vaccination status confirmed by a vaccination document. Poisson regression analyzed the association between VC and potential determinants. VC of children from families with the lowest incomes (first quartile of family income/consumption unit (CU) (history of immigration, regardless of family income, are correctly identified as being at high risk of tuberculosis and properly vaccinated with BCG in this area.

  20. Sex-differential effect on infant mortality of oral polio vaccine administered with BCG at birth in Guinea-Bissau. A natural experiment

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Fisker, Ane Baerent; Rodrigues, Amabelia;

    2008-01-01

    was not available during several periods. We took advantage of this "natural experiment" to test the effect on mortality of receiving OPV at birth. METHODOLOGY: Between 2002 and 2004, the VAS trial randomised normal-birth-weight infants to 50,000 IU VAS or placebo administered with BCG. Provision of OPV at birth...

  1. Synthetic oligonucleotides with particular base sequences from the cDNA encoding proteins of Mycobacterium bovis BCG induce interferons and activate natural killer cells.

    Science.gov (United States)

    Tokunaga, T; Yano, O; Kuramoto, E; Kimura, Y; Yamamoto, T; Kataoka, T; Yamamoto, S

    1992-01-01

    Thirteen kinds of 45-mer single-stranded oligonucleotide, having sequence randomly selected from the known cDNA encoding BCG proteins, were tested for their capability to augment natural killer (NK) cell activity of mouse spleen cells in vitro. Six out of the 13 oligonucleotides showed the activity, while the others did not. In order to know the minimal and essential sequence(s) responsible for the biological activity, 2 kinds of 30-mer and 5 kinds of 15-mer oligonucleotide fragments of an active 45-mer nucleotide were tested for their activity. One of the 30-mer oligonucleotides, designated BCG-A4a, was active, but the other 30-mer was inactive. All of the 15-mer oligonucleotide fragments were inactive. The BCG-A4a also stimulated the spleen cells to produce interferon (IFN)-alpha and -gamma. An experiment using anti-IFN antisera showed that the NK cell activation by the oligonucleotide was ascribed to the IFN-alpha produced. It was noticed that all of the biologically active oligonucleotides possessed one or more palindrome sequence(s), and the inactive ones did not, with an exception of a 45-mer inactive oligonucleotide containing overlapping palindrome sequences (GGGCCCGGG). These findings strongly suggest that certain palindrome sequences, like GACGTC, GGCGCC and TGCGCA, are essential for 30-mer oligonucleotides, like BCG-A4a, to induce IFNs.

  2. [Bacillus Calmette-Guérin (BCG) disease and interleukin 12 receptor β1 deficiency: clinical experience of two familial and one sporadic case].

    Science.gov (United States)

    Strickler, Alexis; Pérez, Amir; Risco, Migdy; Gallo, Silvanna

    2014-08-01

    BCG disease has been reported in primary and secondary immunodeficiency and as Mendelian Susceptibility to Mycobacterial Diseases (MSMD). Investigation of this syndrome has led to the identifications of a series of genetic, inherited defects in the IL-12/IFN-γ axis. MSMD-causing mutations have been found in seven autosomal and two X-linked genes. In these patients, local or disseminated vaccine BCG infections are common. We report a clinical series including two infants with left axillary adenitis ipsilateral to the site of neonatal BCG immunization; one of them member of a family with two previously reported cases and a single sporadic case. All of them were diagnosed sequentially in Puerto Montt, Chile. The aim of this report is to notify the first Chilean disseminated BCG patients without previous immunodeficiency, in whom it was possible to identify an underlying immunodeficiency, although specific tests for IL-12/IFN-γ axis was no performed in our country. Clinical suspicion and international collaboration permitted to confirm IL12-Rβ1 deficiency in 2 of 3 familial cases and a sporadic case.

  3. Inhibitory effect of intravesical instillation of trichostatin A in rats with bladder cancer%曲古抑菌素A膀胱灌注对大鼠膀胱癌生长的抑制作用

    Institute of Scientific and Technical Information of China (English)

    李功成; 潘铁军; 田雨冬; 叶章群

    2013-01-01

    目的:探讨曲古抑菌素A(TSA)膀胱灌注对大鼠膀胱肿瘤生长的抑制作用和机制.方法:将42只雌性Wistar大鼠,随机分为对照组和TSA组,制作MNU诱导大鼠原位膀胱癌模型,在第10周分别行生理盐水和TSA连续膀胱灌注,每周1次,共7次.分别在灌注的第12周和17周进行病理观察、测量膀胱总重量、凋亡指数及western blot检测.结果:与对照组相比,TSA组大鼠膀胱肿瘤小且单发较多.TSA组大鼠膀胱的重量小于对照组(P<0.05);TSA组大鼠膀胱肿瘤的凋亡指数大于对照组(P<0.01),TSA组大鼠膀胱肿瘤组织XIAP的表达较对照组明显降低.结论:TSA膀胱灌注可抑制大鼠膀胱肿瘤生长,延缓肿瘤进展,其机制与诱导肿瘤细胞凋亡有关,并可能涉及相关基因XIAP表达的调控.%Objective: To investigate the effect and mechanism of intravesical instillation of trichostatin A in bladder cancer of rats. Method:Forty-two female Wistar rats were randomized into control group and trichostatin A group. Orthotopic bladder tumors were established in rats by intravesical administration of N-mmethyl-noitro-sourea. Rats of control and trichostatin A group received a total of seven times(every week) intravesical instillation of physiologic saline and trichostatin A respectively from the tenth week. Rats were executed in the twelfth and seventeenth week and their weights of bladder,pathologic characters,apoptotic indexes were surveyed. The expression of XIAP protein was detected by Western blot. Result:Compared with control group, the bladder tumors of trichostatin A group were small and more single. The bladder weights of trichostatin A group were significantly lower than those in control group(P<0. 05) , but the apoptotic indexes of control group were significantly lower than those in trichostatin A group(P<0. 01). It was showed by Western blot that the XIAP protein level dropped after Intravesical instillation of trichostatin A. Conclusion

  4. Comparative Study on the Immunogenicity between Recombinant MS-Sj26GST Vaccine and Recombinant BCG-Sj26GST Vaccine in Schistosoma japonicum

    Institute of Scientific and Technical Information of China (English)

    戴五星; 高红; 黄海浪; 袁野; 胡佳杰; 皇甫永穆

    2003-01-01

    The BALB/c mice were immunized with rMS-Sj26GST and rBCG-Sj26GST vaccine inSchistosoma japonicum by subcutaneous injection. After they were immunized for 8 weeks, the eye-balls were removed to get blood and macrophages of abdominal cavity and spleen cells were harves-ted. The lymphocytic stimulating index (SI) was used to measure the cellular proliferating abilityand NO release was used to measure the phagocytic activity of the macrophages. By using ELISAkit, the levels of interleukin-2 (IL-2) and interferon-γ(IFN-γ) in serum and the splenic lymphocyt-ic cultured supernatant were detected. The results showed that after the mice were immunized with106 CFU of rMS-Sj26GST and rBCG-Sj26GST vaccine separately by subcutaneous injection, prolif-erating ability of splenic lymphocytes in the mice showed no difference (P>0.05), but both weresignificantly increased as compared with that in the control group(P<0.05); The contents of NOin the intraperitoneal macrophages of rMS-Sj26GST vaccine group were significantly lower than inthe control group (P<0. 001) and rBCG-Sj26GST vaccine group (P<0. 01); The levels of serumIL-2 in the rMS-Sj26GST vaccine group were significantly increased as compared with that in thecontrol group (P<0. 001), vector group (P<0.01) and rBCG-Sj26GST vaccine group (P<0.05);The contents of serum IFN-γ in the rMS-Sj26GST vaccine group were significantly increased ascompared with that in the control group (P<0.01) and rBCG-Sj26GST vaccine group (P<0.05).The contents of IFN-γ in the cultured supernatant were significantly lower than those of rBCG-Sj26GST vaccine group (P<0. 001), but were significantly increased as compared with that in thecontrol group (P<0.01). It was indicated that both vaccines could enhance the immune response ofthe mice, but rMS-Sj26GST vaccine had stronger immunogenicity than rBCG-Sj26GST vaccine.

  5. Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials.

    Science.gov (United States)

    Arbues, Ainhoa; Aguilo, Juan I; Gonzalo-Asensio, Jesus; Marinova, Dessislava; Uranga, Santiago; Puentes, Eugenia; Fernandez, Conchita; Parra, Alberto; Cardona, Pere Joan; Vilaplana, Cristina; Ausina, Vicente; Williams, Ann; Clark, Simon; Malaga, Wladimir; Guilhot, Christophe; Gicquel, Brigitte; Martin, Carlos

    2013-10-01

    The development of a new tuberculosis vaccine is an urgent need due to the failure of the current vaccine, BCG, to protect against the respiratory form of the disease. MTBVAC is an attenuated Mycobacterium tuberculosis vaccine candidate genetically engineered to fulfil the Geneva consensus requirements to enter human clinical trials. We selected a M. tuberculosis clinical isolate to generate two independent deletions without antibiotic-resistance markers in the genes phoP, coding for a transcription factor key for the regulation of M. tuberculosis virulence, and fadD26, essential for the synthesis of the complex lipids phthiocerol dimycocerosates (DIM), one of the major mycobacterial virulence factors. The resultant strain MTBVAC exhibits safety and biodistribution profiles similar to BCG and confers superior protection in preclinical studies. These features have enabled MTBVAC to be the first live attenuated M. tuberculosis vaccine to enter clinical evaluation.

  6. Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy.

    Science.gov (United States)

    Ishii, Kazuo; Kurita-Taniguchi, Mitsue; Aoki, Mikio; Kimura, Toru; Kashiwazaki, Yasuo; Matsumoto, Misako; Seya, Tsukasa

    2005-05-15

    Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in association with TLRs and recently discovered TLR adapters.

  7. HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

    Directory of Open Access Journals (Sweden)

    Tsungai Ivai Jongwe

    Full Text Available Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA vaccines expressing HIV-1C mosaic Gag (GagM were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C.

  8. Polyclonal activation of naïve T cells by urease deficient-recombinant BCG that produced protein complex composed of heat shock protein 70, CysO and major membrane protein-II

    OpenAIRE

    Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Mukai, Tetsu; Makino, Masahiko

    2014-01-01

    Background Mycobacterium bovis bacillus Calmette-Guérin (BCG) is known to be only partially effective in inhibiting M. tuberculosis (MTB) multiplication in human. A new recombinant (r) urease-deficient BCG (BCG-dHCM) that secretes protein composed of heat shock protein (HSP)70, MTB-derived CysO and major membrane protein (MMP)-II was produced for the efficient production of interferon gamma (IFN-γ) which is an essential element for mycobacteriocidal action and inhibition of neutrophil accumul...

  9. Living Nanomachines

    Science.gov (United States)

    Carlier, M.-F.; Helfer, E.; Wade, R.; Haraux, F.

    The living cell is a kind of factory on the microscopic scale, in which an assembly of modular machines carries out, in a spatially and temporally coordinated way, a whole range of activities internal to the cell, including the synthesis of substances essential to its survival, intracellular traffic, waste disposal, and cell division, but also activities related to intercellular communication and exchanges with the outside world, i.e., the ability of the cell to change shape, to move within a tissue, or to organise its own defence against attack by pathogens, injury, and so on. These nanomachines are made up of macromolecular assemblies with varying degrees of complexity, forged by evolution, within which work is done as a result of changes in interactions between proteins, or between proteins and nucleic acids, or between proteins and membrane components. All these cell components measure a few nanometers across, so the mechanical activity of these nanomachines all happens on the nanometric scale. The directional nature of the work carried out by biological nanomachines is associated with a dissipation of energy. As examples of protein assemblies, one could mention the proteasome, which is responsible for the degradation of proteins, and linear molecular motors such as actomyosin, responsible for muscle contraction, the dynein-microtubule system, responsible for flagellar motility, and the kinesin-microtubule system, responsible for transport of vesicles, which transform chemical energy into motion. Nucleic acid-protein assemblies include the ribosome, responsible for synthesising proteins, polymerases, helicases, elongation factors, and the machinery of DNA replication and repair; the mitotic spindle is an integrated system involving several of these activities which drive chromosome segregation. The machinery coupling membranes and proteins includes systems involved in the energy metabolism, such as the ATP synthase rotary motor, signalling cascades, endocytosis

  10. Compostos indutores e genes regulando a expressão da bomba de efluxo Tap em Mycobacterium bovis BCG

    OpenAIRE

    Felix, Carolina Rodrigues

    2013-01-01

    Proteínas transportadoras relacionada ao efluxo de drogas desempenham um papel importante não só na aquisição de fenótipos resistentes aos fármacos, mas também na virulência de M. tuberculosis. O principal objetivo deste estudo foi analisar a regulação do gene Rv1258c codificador da proteína Tap considerando a expressão dos genes Rv1255c e Rv1257c. RNA foi extraído a partir de culturas de M. bovis BCG superexpressando Rv1255c e Rv1257c, bem como de uma cepa controle contendo o vector pVV16 re...

  11. Infección diseminada por BCG en la Región de Los Lagos, Chile: Reporte de cinco casos clínicos Disseminated infection by BCG in Región de Los Lagos, Chile: Five cases report

    Directory of Open Access Journals (Sweden)

    ALEXIS STRICKLER P

    2009-01-01

    Full Text Available El bacilo Calmette-Guérin (BCG, es la cepa atenuada de Mycobacterium bovis utilizada en países en vías de desarrollo para la prevención de formas graves de tuberculosis. La vacuna BCG neonatal se administra en países con alta prevalencia de la enfermedad. La mayoría de los vacunados no presenta reacciones adversas, algunos evidencian reacciones secundarias a una inmunidad alterada del huésped. Dichas reacciones varían desde una simple adenomegalia ipsilateral a la inoculación de BCG, hasta una infección diseminada, a menudo mortal. La infección diseminada se ha descrito en pacientes inmuno deficientes secundarios, primarios y en pacientes con defectos genéticos del eje interleuquina 12-23 (IL12/23-interferón gama (IFN-γ denominados "Síndrome de predisposición mendeliana a infecciones micobacterianas" (PMIM. Describimos cinco pacientes con infección por M. bovis-BCG diagnosticados entre 1995-2008, en el Hospital Base de Puerto Montt, Región de Los Lagos, Chile que cumplen con los criterios del PMIM.The bacillus Calmette-Guérin (BCG is the attenuated strain of Mycobacterium bovis used in developing countries for preventing serious forms of tuberculosis. The neonatal BCG vaccine is applied in countries with high prevalence of tuberculosis. Most of the vaccinated individuáis develop no adverse reactions; although, some subjects show side effects due to a host altered immunity. These reactions range from a simple adenomegaly in the same side of BCG vaccine inoculation, to a spread infection, often fatal. A regional or systemic spread has been described in patients with secondary or primary immunodeficiencies and partial or total genetic defects of interleukin IL-12/23 and IFN-γ called as a whole "Mendelian susceptibility to mycobacterial infections" (MSMD. We describe five patients infected with M. bovis BCG-diagnosed between 1995-2008, at the base hospital in the city of Puerto Montt, Región de Los Lagos, Chile. These patients

  12. [Commemorative lecture of receiving Imamura Memorial Prize. II. Mode of action of oligonucleotide fraction extracted from Mycobacterium bovis BCG].

    Science.gov (United States)

    Yamamoto, S

    1994-09-01

    A fraction extracted from Mycobacterium bovis BCG was found to exhibit strong antitumor activity. This fraction, which was designated MY-1, caused some animal tumors to regress and/or prevent metastasis very effectively. MY-1 after digestion with DNase had almost completely reduced activity, while MY-1 digested with RNase did not. MY-1 also augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factors which showed anti-viral activity and rendered macrophages cytotoxic towards tumor cells. The function of the factor to activate macrophages was destroyed by treatment with anti-interferon (IFN)-gamma antibody, while the anti-viral activity was destroyed by treatment with anti-INF alpha/beta antibody. The oligonucleotides contained in MY-1 distributed in a broad range of molecular size, and peaked at 45 nucleotides. We synthesized 13 kinds of 45-mer nucleotides with sequence present in the known cDNA encoding various BCG proteins. Six out of these oligonucleotides, which contained one or more hexameric palindromic structures, showed strong antitumor activity, while the other without palindrome did not. These active oligonucleotides possessed the capability to induce IFN and to augment NK cell activity of mouse spleen cells by coincubation in vitro. When a portion of the sequence of the inactive oligonucleotides was substituted with either palindromic sequence of GACGTC, AGCGCT or AACGTT, the oligonucleotide acquired the ability to augment NK activity. In contrast, the oligonucleotides substituted with another palindromic sequence such as ACCGGT was without effect. Furthermore, exchange of two neighboring mononucleotides within, but not outside, the active palindromic sequence destroyed the ability of the oligonucleotide to augment NK activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Intravesical instillation with povidone-iodine for treatment of fungal urinary tract infections%聚维酮碘膀胱灌注治疗真菌性尿路感染7例报道

    Institute of Scientific and Technical Information of China (English)

    刘奔; 盛玉文; 高凡; 韩立维; 张春阳

    2012-01-01

    目的 探讨真菌性尿路感染的临床特点及聚维酮碘膀胱灌注治疗真菌性尿路感染的有效性和安全性.方法 7例真菌性尿路感染均长期留置导尿管或膀胱造瘘管;对7例真菌性尿路感染采用0.25%聚维碘酮溶液膀胱灌注,保留5~8 min,观察尿中真菌清除情况.结果 7例尿路真菌感染均得到控制,尿液真菌培养阴性,尿中白细胞消失;1例灌注3d后出现下腹部针刺样疼痛,但可耐受.结论 长期留置尿管和机体抵抗力下降,是引起真菌性尿路感染的重要因素,聚维酮碘膀胱灌注治疗真菌性尿路感染安全、有效.%OBJECTIVE To explore the clinical features of fungal urinary tract infection and the efficacy and safety of intravesical instillation with povidone- iodine for the treatment of fungal urinary tract infections. METHODS A total of 7 patients with indwelling catheter or bladder fistula for long term suffering fungal urinary tract infections were enrolled in the study. All the patients were irrigated bladder with 0. 25% povidone-iodine solution for 5 to 8 min, then the clearance of fungi in the urine was observed, RESULTS All the 7 patients with urinary tract infections were under control, the urine culture for fungi showed negative, WBC in the urine disappeared; there was only one patient who felt slight lower abdominal pain 3d after the intravesical instillation and can be tolerated. CONCLUSION Long-term indwelling catheter and the decline in body immunity are the main factors for fungal . urinary tract infections. Intravesical instillation with povidone-iodine for the treatment of iungai urinary tract infections is safe and effective.

  14. Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

    Directory of Open Access Journals (Sweden)

    Meywald-Walter K

    2006-05-01

    Full Text Available Abstract Background BCG-vaccination can confound tuberculin skin test (TST reactions in the diagnosis of latent tuberculosis infection. Methods We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON®-TB-Gold In Tube; QFT-G during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. Results During a 6-month period, 309 contacts (mean age 28.5 ± 10.5 years from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8% had received BCG vaccination and 84 (27.2% had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000. For the TST, the positive response rate was 44.3% (137/309, whilst only 31 (10% showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (κ = 0.2, with 95% CI 0.14.-0.23, and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7–52.5. In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (κ = 0.58, with 95% CI 0.4–0.68, increasing to 0.68 (95% CI 0.46–0.81, if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. Conclusion The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.

  15. Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG Determining the risk of tuberculosis infection in BCG-vaccinated populations

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1992-04-01

    Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.The revaccination of schoolchildren can restore the residual allergy induced by vaccination in the first years of life but can not modify the allergy resulting from a

  16. Immunization with Bacillus Calmette-Guérin (BCG) alleviates neuroinflammation and cognitive deficits in APP/PS1 mice via the recruitment of inflammation-resolving monocytes to the brain.

    Science.gov (United States)

    Zuo, Zejie; Qi, Fangfang; Yang, Junhua; Wang, Xiao; Wu, Yingying; Wen, Yaru; Yuan, Qunfang; Zou, Juntao; Guo, Kaihua; Yao, Zhi Bin

    2017-05-01

    The immune system plays a crucial role in the progression of Alzheimer's disease (AD). Recently, immune-dependent cascade induced by systemic immune activation has been verified to play a beneficial role in AD mouse models. Here, we tested whether Bacillus Calmette-Guérin (BCG) immunization alters AD pathology and cognitive dysfunction in APP/PS1 AD mouse model, and with 4Aβ1-15 vaccination as positive control. It was found that BCG treatment reversed the cognitive decline to the extent observed in 4Aβ1-15 group, but did not reduce the β-amyloid (Aβ) burden in the brain. Then, we demonstrated the enhanced recruitment of inflammation-resolving monocytes across the choroid plexus and perivascular spaces to cerebral sites of plaque pathology in APP/PS1 mice immunized with BCG. Furthermore, elevated splenocyte Foxp3(+) regulatory T cell levels in the control APP/PS1 mice were down-regulated back to the wild-type (WT) levels by BCG treatment but not 4Aβ1-15 vaccination. In addition, BCG treatment induced the production of more circulating interferon (IFN)-γ than the controls and 4Aβ1-15 vaccination. Though the similar reductions in brain levels of pro-inflammatory cytokines were observed in the BCG and 4Aβ1-15 groups compared to the controls, only BCG had the great effect in upregulating cerebral anti-inflammatory cytokine levels as well as elevating the expression of neurotrophic factors in the brain of APP/PS1 mice. Thus, it is suggested that BCG exerts a beneficial immunomodulatory effect in APP/PS1 mice through mitigation of systemic immune suppression, induction of IFN-γ response and alleviation of the neuroinflammatory response.

  17. Assessment of an oral Mycobacterium bovis BCG vaccine and an inactivated M. bovis preparation for wild boar in terms of adverse reactions, vaccine strain survival, and uptake by nontarget species.

    Science.gov (United States)

    Beltrán-Beck, Beatriz; Romero, Beatriz; Sevilla, Iker A; Barasona, Jose A; Garrido, Joseba M; González-Barrio, David; Díez-Delgado, Iratxe; Minguijón, Esmeralda; Casal, Carmen; Vicente, Joaquín; Gortázar, Christian; Aranaz, Alicia

    2014-01-01

    Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or inactivated M. bovis (n = 21). BCG was not found at necropsy (175 to 300 days postvaccination [n = 27]). No BCG excretion was detected in fecal samples (n = 162) or in urine or nasal, oral, or fecal swab samples at 258 days postvaccination (n = 29). In the field, we found no evidence of loss of BCG viability in baits collected after 36 h (temperature range, 11°C to 41°C). Camera trapping showed that wild boar (39%) and birds (56%) were the most frequent visitors to bait stations (selective feeders). Wild boar activity patterns were nocturnal, while diurnal activities were recorded for all bird species. We found large proportions of chewed capsules (29%) (likely ingestion of the vaccine) and lost baits (39%) (presumably consumed), and the proportion of chewed capsules showed a positive correlation with the presence of wild boar. Both results suggest proper bait consumption (68%). These results indicate that BCG vaccination in wild boar is safe and that, while bait consumption by other species is possible, this can be minimized by using selective cages and strict timing of bait deployment.

  18. Transdifferentiation of Small Cell Carcinoma of the Urinary Bladder from Urothelial Carcinoma after Transurethral Resection of a Bladder Tumor, Intravesical Bacillus Calmette-Guerin Instillation, and Chemotherapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Kento Morozumi

    2016-11-01

    Full Text Available A 73-year-old male underwent transurethral resection of a bladder tumor in August 2010 and April 2011. Pathological examination revealed urothelial carcinoma. After the surgery, chemotherapy and intravesical Bacillus Calmette-Guerin instillation were performed. In September 2014, he once again underwent transurethral resection of the bladder tumor for recurrence, and was again diagnosed with urothelial carcinoma, pT2, by pathological examination. After neoadjuvant chemotherapy, radical cystectomy for tumor recurrence was performed. Pathological examination at this time revealed small cell carcinoma, pT3N0. It is rare for urothelial carcinoma to change to small cell carcinoma, and the mechanism and cause of this change are still unknown. In this case report, we discuss what causes small cell carcinoma of the urinary bladder and review the literature regarding its origin.

  19. A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.

    Science.gov (United States)

    Carlétti, Dyego; Morais da Fonseca, Denise; Gembre, Ana Flávia; Masson, Ana Paula; Weijenborg Campos, Lívia; Leite, Luciana C C; Rodrigues Pires, Andréa; Lannes-Vieira, Joseli; Lopes Silva, Célio; Bonato, Vânia Luiza Deperon; Horn, Cynthia

    2013-08-01

    Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

  20. Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development: Results from the Danish Calmette Study - A Randomised Clinical Trial

    DEFF Research Database (Denmark)

    Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie;

    2016-01-01

    MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age Developmental assessment was available for 3453/4262 (81%). RESULTS......OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

  1. Living with an Arrhythmia

    Science.gov (United States)

    ... from the NHLBI on Twitter. Living With an Arrhythmia Many arrhythmias are harmless. It's common to have an occasional ... heartbeat or mild palpitations . People who have harmless arrhythmias can live healthy lives. They usually don't ...

  2. Living with endometriosis

    Science.gov (United States)

    Pelvic pain - living with endometriosis; Endometrial implant - living with endometriosis; Endometrioma - living with endometriosis ... counter pain relievers can reduce the pain of endometriosis. These include: Ibuprofen (Advil) Naproxen (Aleve) Acetaminophen (Tylenol) ...

  3. Living Gluten Free

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Celiac Disease Living Gluten Free Past Issues / Spring 2015 Table of Contents ... Learning to Live Well with Celiac Disease / Living Gluten-Free Spring 2015 Issue: Volume 10 Number 1 ...

  4. WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradication than WT1 peptide vaccination alone.

    Science.gov (United States)

    Nakajima, Hiroko; Kawasaki, Kotomi; Oka, Yoshihiro; Tsuboi, Akihiro; Kawakami, Manabu; Ikegame, Kazuhiro; Hoshida, Yoshihiko; Fujiki, Fumihiro; Nakano, Akiko; Masuda, Tomoki; Wu, Fei; Taniguchi, Yuki; Yoshihara, Satoshi; Elisseeva, Olga A; Oji, Yusuke; Ogawa, Hiroyasu; Azuma, Ichiro; Kawase, Ichiro; Aozasa, Katsuyuki; Sugiyama, Haruo

    2004-07-01

    A Wilms' tumor gene WT1 is expressed at high levels not only in most types of leukemia but also in various types of solid tumors, including lung and breast cancer. WT1 protein has been reported to serve as a target antigen for tumor-specific immunotherapy both in vitro in human systems and in vivo in murine models. We have shown that mice immunized with WT1 peptide or WT1 cDNA could reject a challenge from WT1-expressing tumor cells (a "prophylactic" model). However, it was not examined whether WT1 peptide vaccination had the potency to reject tumor cells in a "therapeutic" setting. In the present study, we demonstrated for the first time that WT1 peptide vaccination combined with Mycobacterium bovis bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) was more effective for eradication of WT1-expressing tumor cells that had been implanted into mice before vaccination (a "therapeutic" model) compared with WT1 peptide vaccination alone. An intradermal injection of BCG-CWS into mice, followed by that of WT1 peptide at the same site on the next day, generated WT1-specific cytotoxic T lymphocytes (CTLs) and led to rejection of WT1-expressing leukemia or lung cancer cells. These results showed that BCG-CWS, which was well known to enhance innate immunity, could enhance WT1-specific immune responses (acquired immunity) in combination with WT1 peptide vaccination. Therefore, WT1 peptide vaccination combined with BCG-CWS may be applied to cancer immunotherapy in clinical settings.

  5. Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

    DEFF Research Database (Denmark)

    Biering-Sørensen, Sofie; Jensen, Kristoffer Jarlov; Aamand, Susanne Havn

    2015-01-01

    reaction (geometric mean ratio: 1.40 (1.20-1.63)) at 2 months. In response to secondary heterologous stimulation, monocytes primed with Slow growth batches induced higher IL-6 (p=0.03) and TNF-α responses (p=0.03) compared with Normal growth batches. CONCLUSION: The study indicates that variations...... in the production of BCG vaccine may influence important immunological effects of the vaccine. TRIAL REGISTRATION: clinicaltrials.gov (NCT00625482)....

  6. Optimization of cell-wall skeleton derived from Mycobacterium bovis BCG Tokyo 172 (SMP-105) emulsion in delayed-type hypersensitivity and antitumor models.

    Science.gov (United States)

    Miyauchi, M; Murata, M; Fukushima, A; Sato, T; Nakagawa, M; Fujii, T; Koseki, N; Chiba, N; Kashiwazaki, Y

    2012-08-01

    Cell-wall skeleton prepared from Mycobacterium bovis BCG (BCG-CWS) is known as a potent adjuvant and has been shown to possess antitumor activity in many non-clinical and clinical studies. As there are no approved BCG-CWS formulations for cancer therapy, we investigated the potential for cancer immunotherapy of SMP-105, our originally produced BCG-CWS. For optimizing SMP-105 emulsion, we compared the effects of drakeoland squalane-based SMP-105 emulsions on IFN-γ production in rats and evaluated their ability to induce skin reaction in guinea pigs. Both emulsions had the same activity in both experiments. We selected squalane as base material and produced two types of squalane-based formulations (vialed emulsion and pumped emulsion) that can easily be prepared as oil-in-water emulsions. Although the vialed emulsion showed the same pattern of distribution as a usual homogenized emulsion, the pumped emulsion showed more uniform distribution than the other two emulsions. Whereas both emulsions enhanced strong delayed type hypersensitivity (DTH) reaction in a mouse model, the pumped emulsion induced slightly smaller edema. Data on oil droplet size distribution suggest that few micrometer oil droplet size might be appropriate for oil-in-water microemulsion of SMP-105. The antitumor potency of SMP-105 emulsion was stronger than that of some of the launched toll-like receptor (TLR) agonists (Aldara cream, Picibanil, and Immunobladder). Aldara and Picibanil showed limited antitumor effectiveness, while Immunobladder had almost the same effect as SMP-105 at the highest dose, but needed about 10 times the amount of SMP-105. These findings first indicate that SMP-105 has great potential in cancer immunotherapy.

  7. Boosting BCG-primed mice with chimeric DNA vaccine HG856A induces potent multifunctional T cell responses and enhanced protection against Mycobacterium tuberculosis.

    Science.gov (United States)

    Ji, Ping; Hu, Zhi-Dong; Kang, Han; Yuan, Qin; Ma, Hui; Wen, Han-Li; Wu, Juan; Li, Zhong-Ming; Lowrie, Douglas B; Fan, Xiao-Yong

    2016-02-01

    The tuberculosis pandemic continues to rampage despite widespread use of the current Bacillus Calmette-Guerin (BCG) vaccine. Because DNA vaccines can elicit effective antigen-specific immune responses, including potent T cell-mediated immunity, they are promising vehicles for antigen delivery. In a prime-boost approach, they can supplement the inadequate anti-TB immunological memory induced by BCG. Based on this, a chimeric DNA vaccine HG856A encoding Mycobacterium tuberculosis (M. tuberculosis) immunodominant antigen Ag85A plus two copies of ESAT-6 was constructed. Potent humoral immune responses, as well as therapeutic effects induced by this DNA vaccine, were observed previously in M. tuberculosis-infected mice. In this study, we further evaluated the antigen-specific T cell immune responses and showed that repeated immunization with HG856A gave modest protection against M. tuberculosis challenge infection and significantly boosted the immune protection primed by BCG vaccination. Enhanced protection was accompanied by increased multifunctional Th1 CD4(+) T cell responses, most notably by an elevated frequency of M. tuberculosis antigen-specific IL-2-producing CD4(+) T cells post-vaccination. These data confirm the potential of chimeric DNA vaccine HG856A as an anti-TB vaccine candidate.

  8. Impact of the BCG vaccination policy on tuberculous meningitis in children under 6 years in metropolitan France between 2000 and 2011.

    Science.gov (United States)

    Van Bui, T; Lévy-Bruhl, D; Che, D; Antoine, D; Jarlier, V; Robert, J

    2015-03-19

    In France, Bacillus Calmette–Guérin (BCG) vaccination by multipuncture device was withdrawn in 2006. In 2007, universal mandatory BCG vaccination was replaced by vaccination of high-risk children. To evaluate the impact of these changes on tuberculous meningitis (TBM) epidemiology, data on culture-positive and culture-negative (or unknown microbiological result) TBM in ≤5 years olds were collected from 2000–2011. Ten culture-positive and 17 culture-negative TBM cases were identified, with an annual incidence rate ranging from 0.16 to 0.66 cases per 10 million inhabitants. The average annual numbers of TBM cases were 2.7 and 1.8 from 2000–2005 and 2006–2011, respectively. In Ile-de-France where all children are considered at risk, the overall incidence rates were 1.14 and 0.29 per million for the two periods. In other regions where only at-risk children are vaccinated since 2007, rates were 0.30 and 0.47, respectively. None of these differences were significant. Annual incidence rates for each one year age group cohort were comparable before and after changes. Childhood TBM remains rare in France. No increase in incidence was observed after changes in BCG vaccination strategy. Ongoing surveillance should be maintained, as a slight increase in TBM in the coming years remains possible, in the context of suboptimal vaccination coverage of high-risk children.

  9. Constraining the Scatter in the Mass-Richness Relation of maxBCG Clusters With Weak Lensing and X-ray Data

    Energy Technology Data Exchange (ETDEWEB)

    Rozo, Eduardo; /Ohio State U.; Rykoff, Eli S.; /UC, Santa Barbara; Evrard, August; /Michigan U.; Becker, Matthew R.; /Chicago U.; McKay, Timothy; /Michigan U.; Wechsler, Risa H.; /SLAC; Koester, Benjamin P.; /Chicago U. /KICP, Chicago; Hao, Jiangang; /Michigan U.; Hansen, Sarah; /Chicago U. /KICP, Chicago; Sheldon, Erin; /New York U.; Johnston, David; /Houston U.; Annis, James T.; /Fermilab; Frieman, Joshua A.; /Chicago U. /KICP, Chicago /Fermilab

    2009-08-03

    We measure the logarithmic scatter in mass at fixed richness for clusters in the maxBCG cluster catalog, an optically selected cluster sample drawn from SDSS imaging data. Our measurement is achieved by demanding consistency between available weak lensing and X-ray measurements of the maxBCG clusters, and the X-ray luminosity-mass relation inferred from the 400d X-ray cluster survey, a flux limited X-ray cluster survey. We find {sigma}{sub lnM|N{sub 200}} = 0.45{sub -0.18}{sup +0.20} (95%CL) at N{sub 200} {approx} 40, where N{sub 200} is the number of red sequence galaxies in a cluster. As a byproduct of our analysis, we also obtain a constraint on the correlation coefficient between lnL{sub X} and lnM at fixed richness, which is best expressed as a lower limit, r{sub L,M|N} {ge} 0.85 (95% CL). This is the first observational constraint placed on a correlation coefficient involving two different cluster mass tracers. We use our results to produce a state of the art estimate of the halo mass function at z = 0.23 - the median redshift of the maxBCG cluster sample - and find that it is consistent with the WMAP5 cosmology. Both the mass function data and its covariance matrix are presented.

  10. Dynamic observation of immune responses induced in mice by immunization with a recombinant BCG-TSOL18 vaccine of Taenia solium%猪带绦虫重组BCG-TSOL18疫苗诱导小鼠免疫应答的动态观察

    Institute of Scientific and Technical Information of China (English)

    杨凤娇; 江楠; 周泠; 刘晖; 王灵军; 周必英

    2015-01-01

    Objective To dynamically observe humoral and cellular immune responses induced in mice by immunization with a recombinant BCG-TSOL18 vaccine of Taenia solium.Methods Totally 80 Kunming mice were divided into 4 groups by using random number table according to body mass, 20 mice in each group: rBCG-TSOL18 intraperitoneal injection group [mice were vaccinated with 5 × 106 colony forming units (CFU) recombinant BCG-TSOL18 vaccine of Taenia solium through intraperitoneal injection], rBCG-TSOL18 intragastric administration group(mice were vaccinated with 4 × 108 CFU recombinant BCG-TSOL18 vaccine of Taenia solium through intragastric administration), BCG control (mice were vaccinated with 5 × 106 CFU BCG through intraperitoneal injection), PBS control (mice were vaccinated with PBS through intraperitoneal injection).Zero, 2, 4, 6 and 8 weeks after immunization, eye blood was collected and serum w as separated.Levels of specific IgG and IgG2a were detected by enzyme linked immunosorbent assay (ELISA).Proliferation level of spleen lymphocytes was detected by CCK-8.Levels of interleukin-2 (IL-2) and IL-4 were determined by ELISA.Results The level of specific IgG in rBCG-TSOL18 intraperitoneal injection group and rBCG-TSOL18 intragastric administration group increased from 2 to 8 weeks, and reached the highest level by the 6th week (0.310 ± 0.022, 0.356 ± 0.026).Compared with 0 week in the same group, BCG and PBS control group of the same time periods (0.054 ± 0.005, 0.057 ± 0.006, 0.093 ± 0.014, 0.085 ± 0.010), there were statistically significant differences (all P < 0.05).The level of specific IgG2a increased from 2 to 8 weeks, and reached the highest level by the 6th week (0.965 ± 0.031, 1.144 ± 0.049).Compared with 0 week in the same group, BCG and PBS control group of the same time periods (0.102 ± 0.014, 0.093 ± 0.012, 0.115 ± 0.012, 0.103 ± 0.013), there were statistically significant differences (all P < 0.05).The proliferation level of spleen

  11. Allergy, living and learning

    DEFF Research Database (Denmark)

    Chivato, T; Valovirta, E; Dahl, R;

    2012-01-01

    Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care.......Allergy Living and Learning (ALL) is a European initiative designed to increase knowledge and understanding of people living with allergies in order to improve respiratory allergy care....

  12. Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

    Science.gov (United States)

    Clark, Simon; Cross, Martin L; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R Glyn; Batchelor, Hannah K; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E; Chambers, Mark A

    2008-10-29

    Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery

  13. A derivation of masses and total luminosities of galaxy groups and clusters in the maxBCG catalogue

    CERN Document Server

    Proctor, Robert N; Azanha, Luiz; Dupke, Renato; Overzier, Roderik

    2015-01-01

    We report the results of a multi-waveband analysis of the masses and luminosities of $\\sim$600 galaxy groups and clusters identified in the maxBCG catalogue. These data are intended to form the basis of future work on the formation of the "$m_{12}$ gap" in galaxy groups and clusters. We use SDSS spectroscopy and $g$, $r$ and $i$ band photometry to estimate galaxy group/cluster virial radii, masses and total luminosities. In order to establish the robustness of our results, we compare them with literature studies that utilize a variety of mass determinations techniques (dynamical, X-ray, weak lensing) and total luminosities estimated in the $B$, $r$, $i$, and $K$ wavebands. We also compare our results to predictions derived from the Millennium Simulation. We find that, once selection effects are properly accounted for, excellent agreement exists between our results and the literature with the exception of a single observational study. We also find that the Millennium Simulation does an excellent job of predict...

  14. Effectiveness of transurethral resection under the control of photodynamic diagnosis and intravesical instillation of bacillus Calmette–Guérin in case of poorly differentiated non-muscle-invasive bladder cancer

    Directory of Open Access Journals (Sweden)

    A. I. Rolevich

    2016-01-01

    Full Text Available Background. High-grade non-muscle-invasive bladder cancer (NMIBC is characterized by a high rate of recurrence, progression, and mortality associated with this disease. Organ-preserving treatment by transurethral resection and immunotherapy with bacillus Calmette-Guerin (BCG is an initial approach to therapy in these patients. However, the efficacy of such therapy is limited. This justifies the use of other methods of treatment, such as TUR under the control of photodynamic diagnosis (PDD. Aim of this study was to evaluate the effectiveness of therapeutic interventions in patients with high-grade NMIBC.Materials and methods. We have retrospectively analyzed results of follow-up of patients with primary or recurrent high-grade transitional cell NMIBC, treatment by TUR in conjunction with BCG or without it N.N. Alexandrov National Cancer Centre in the period from 2004 to 2013. In total, the study included 113 patients (27 women and 86 men, in the median age of 72 years. We have evaluated 5-year recurrence- and progression-free survival, analyzed an influence of prognostic factors and methods of treatment on the risk of recurrence and progression with Cox model and Kaplan–Meier method.Results. With a median of follow up of 59 (12–116 months the rates of 5-year recurrence- and progression-free survival were respectively 42.5 and 71.6 %. Statistically significant association with the risk of recurrence was observed in multivariate Cox regression analysis for recurrent tumors (hazard ratio (HR 2.73; 95 % confidence interval (CI 1.61–4.62 and immunotherapy with BCG (HR 0.56; 95 % CI 0.31–0.99. BCG significantly increased recurrence-free survival in patients with both primary tumors, and with recurrent ones. Significant factors in the multivariate analysis with regard to the risk of progression were suspicion for muscle-invasive tumors according to the cystoscopic picture (HR 3.36; 95 % CI 1.09–10.4, abnormal tumor-free bladder mucosa

  15. 膀胱内注射肉毒毒素对膀胱疼痛综合征疼痛程度影响的Meta分析%Effect of Intravesical Botulinum Toxin Injection on Pain of Bladder Pain Syndrome:A Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    张杰; 王强; 王增春; 任自刚; 熊巍; 刘海泉; 王俊杰; 范婷婷

    2016-01-01

    Objective To systemically evaluate the effect of intravesical Botulinum toxin on pain of patientspain syndrom. Methods The following databases as Cochrane Library, PubMed, Web of Science, Embase, Springer, Wiley, Science Direct, OVID were searched to col-lect the randomized controlled trials (RCTs) with the treatment of intravesical Botulinum toxin vs. 0.9%sodium chloride for patients with bladder pain syndrome. Two reviewers screened the trials according to the inclusion and exclusion criterias, extracted the data, assessed the quality, and the changes of Visual Analogue Scales (VAS) before and after treatment were used to conduct Meta analysis with RevMan5.2 software. Results Five studies were included with a total of 218 patients, there were 127 cases in intravesical Botulinum toxin group and 91 cases in 0.9%sodium chloride group. Meta analysis showed that the pain relief effect of intravesical Botulinum toxin was better than that of 0.9%sodium chloride. Conclusion Intravesical Botulinum toxin can relieve the pain of patients with bladder pain syndrome.%目的:系统评价膀胱内注射肉毒毒素对膀胱疼痛综合征疼痛程度的影响。方法检索Cochrane图书馆、PubMed、Web of Science、Embase、Springer、Wiley、Science Direct、OVID数据库,搜集膀胱内注射肉毒毒素治疗膀胱疼痛综合征的随机对照试验。由两位研究者根据纳入与排除标准筛选试验,提取资料并进行质量评价后,取治疗前、后视觉模拟评分值,利用Rev-Man 5.2软件进行Meta分析。结果最终筛选出5篇符合条件的文献,共纳入218例患者,其中对照组91例,膀胱内注射肉毒毒素组127例。Meta分析结果显示膀胱内注射肉毒毒素组对疼痛的缓解程度优于对照组。结论膀胱内注射肉毒毒素能够缓解膀胱疼痛综合征的疼痛程度。

  16. Living with Hemophilia

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Living With Hemophilia If you or your child has hemophilia, you ... today is likely to live a normal lifespan. Hemophilia Treatment Centers The Federal Government funds a nationwide ...

  17. Living with Chronic Bronchitis

    Science.gov (United States)

    ... Health Topics » Bronchitis » Living With Chronic Bronchitis Explore Bronchitis What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics ...

  18. Living with Parkinson's

    Science.gov (United States)

    ... PD. Strategies for living well may include: Managing nutrition and medications – to maintain the highest quality of daily living with Parkinson's disease. Performing activities that may benefit you and your ...

  19. Living with hearing loss

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000360.htm Living with hearing loss To use the sharing features on this page, please enable JavaScript. If you are living with hearing loss, you know that it takes extra effort to ...

  20. Infeccão tuberculosa natural e o uso do BCG oral e intradérmico em escolares de Laranjal Paulista, SP, Brasil Tuberculosis infections and the use of oral and intradermic BCG in school children from Laranjal Paulista, S. Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Eurivaldo Sampaio de Almeida

    1973-09-01

    Full Text Available Foi pesquisado no 2.° semestre de 1969, o índice de infecção tuberculosa nos escolares de nível primário da sede municipal de Laranjal Paulista, SP, com faixa etária de 7 a 15 anos. Utilizou-se PPD RT23 com 2UT (0,04 mcg de acordo com a 2.ª recomendação do Serviço Nacional de Tuberculose, sendo encontrado nível de 8% de reatores fortes o que sugere necessidade de intensificação local do controle da tuberculose. Houve diferenças significativas a 5% quanto à cor e grupo etário, predominando nos "não brancos" e nos de 11 a 15 anos, o mesmo não ocorrendo, entretanto, quanto ao sexo. Os reatores e seus conviventes foram encaminhados ao Dispensário de Tuberculose. Foi também pesquisada a viragem tuberculínica pelo BCG oral e intradérmico, comparados com grupo controle, encontrando-se resultados significantes. O resultado verificado no grupo que tomou BCG por via intradérmica foi quase duas vezes maior que os observados no grupo de BCG oral. Não houve diferenças quanto ao sexo e grupo etário, mas o grupo "não branco" mostrou-se mais reativo. Não foram definidas estatisticamente as reações pós-vacinais e a expectativa populacional foi considerada dentro da esperada para atividades desse tipo.The rate of tuberculosis infections was studied in 92.1% of all the 7 to 15 years old school children from the District of Laranjal Paulista, Sp. Tests were made with PPd-RT23 with 2UP (0.04mcg, as recomended by the "Serviço Nacional de Tuberculose". Strong positive reactions (10 or more mm in diameter were obtained in 8% of the tested children, an indication of the necessity of improvement in the local efforts to control tuberculosis. Positive results were significantly (P 0,05 more frequent in non whites as well as in the 11 - 15 years old group; no significant differences were observed related to sex. Samples of PPd negatives received oral or intradermic BCG; positives PPd's atfer intradermic BCG were almost two times more

  1. Living Planet Report 2004

    OpenAIRE

    Loh, J; Wackernagel, M. (ed.)

    2004-01-01

    The Living Planet Report is WWF's periodic update on the state of the world's ecosystems. This is measured using 2 main indicators. The first indicator is the fact that the Living Planet Index is derived from trends over the past 30 years in populations of hundreds of species of birds, mammals, reptiles, amphibians and fish. The Living Planet Index (LPI) is an indicator of the state of the world's biodiversity: it measures trends in populations of vertebrate species living in terrestrial, fre...

  2. Removal of BCG artifacts from EEG recordings inside the MR scanner: a comparison of methodological and validation-related aspects.

    Science.gov (United States)

    Vanderperren, Katrien; De Vos, Maarten; Ramautar, Jennifer R; Novitskiy, Nikolay; Mennes, Maarten; Assecondi, Sara; Vanrumste, Bart; Stiers, Peter; Van den Bergh, Bea R H; Wagemans, Johan; Lagae, Lieven; Sunaert, Stefan; Van Huffel, Sabine

    2010-04-15

    Multimodal approaches are of growing interest in the study of neural processes. To this end much attention has been paid to the integration of electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data because of their complementary properties. However, the simultaneous acquisition of both types of data causes serious artifacts in the EEG, with amplitudes that may be much larger than those of EEG signals themselves. The most challenging of these artifacts is the ballistocardiogram (BCG) artifact, caused by pulse-related electrode movements inside the magnetic field. Despite numerous efforts to find a suitable approach to remove this artifact, still a considerable discrepancy exists between current EEG-fMRI studies. This paper attempts to clarify several methodological issues regarding the different approaches with an extensive validation based on event-related potentials (ERPs). More specifically, Optimal Basis Set (OBS) and Independent Component Analysis (ICA) based methods were investigated. Their validation was not only performed with measures known from previous studies on the average ERPs, but most attention was focused on task-related measures, including their use on trial-to-trial information. These more detailed validation criteria enabled us to find a clearer distinction between the most widely used cleaning methods. Both OBS and ICA proved to be able to yield equally good results. However, ICA methods needed more parameter tuning, thereby making OBS more robust and easy to use. Moreover, applying OBS prior to ICA can optimize the data quality even more, but caution is recommended since the effect of the additional ICA step may be strongly subject-dependent.

  3. Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

    Science.gov (United States)

    Cross, Martin L; Henderson, Ray J; Lambeth, Matthew R; Buddle, Bryce M; Aldwell, Frank E

    2009-07-01

    Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife.

  4. Mycobacterium tuberculosis PPD-induced immune biomarkers measurable in vitro following BCG vaccination of UK adolescents by multiplex bead array and intracellular cytokine staining

    Directory of Open Access Journals (Sweden)

    Worth Andrew

    2010-07-01

    Full Text Available Abstract Background The vaccine efficacy reported following Mycobacterium bovis Bacillus Calmette Guerin (BCG administration to UK adolescents is 77% and defining the cellular immune response in this group can inform us as to the nature of effective immunity against tuberculosis. The aim of this study was to identify which cytokines and lymphocyte populations characterise the peripheral blood cellular immune response following BCG vaccination. Results Diluted blood from before and after vaccination was stimulated with Mycobacterium tuberculosis purified protein derivative for 6 days, after which soluble biomarkers in supernatants were assayed by multiplex bead array. Ten out of twenty biomarkers measured were significantly increased (p Mycobacterium tuberculosis purified protein derivative stimulation of PBMC samples from the 12 month group revealed that IFNγ expression was detectable in CD4 and CD8 T-cells and natural killer cells. Polyfunctional flow cytometry analysis demonstrated that cells expressing IFNγ alone formed the majority in each subpopulation of cells. Only in CD4 T-cells and NK cells were there a notable proportion of responding cells of a different phenotype and these were single positive, TNFα producers. No significant expression of the cytokines IL-2, IL-17 or IL-10 was seen in any population of cells. Conclusions The broad array of biomarker responses detected by multiplex bead array suggests that BCG vaccination is capable, in this setting, of inducing a complex immune phenotype. Although polyfunctional T-cells have been proposed to play a role in protective immunity, they were not present in vaccinated adolescents who, based on earlier epidemiological studies, should have developed protection against pulmonary tuberculosis. This may be due to the later sampling time point available for testing or on the kinetics of the assays used.

  5. Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination

    DEFF Research Database (Denmark)

    Elias, D; Wolday, D; Akuffo, H;

    2001-01-01

    -vaccinated humans. The study population was assessed for helminthic infection and those found to be positive were randomly assigned to either an albendazole treatment group or a control group who received a placebo. The immune response to PPD was compared between the two groups. In addition, subjects who were...... tuberculin skin test-negative in both groups were BCG vaccinated and later on tested for PPD-specific responses. Albendazole induced elimination/or reduction in intestinal worms resulting in a significant improvement in T cell proliferation and in interferon-gamma production by peripheral blood mononuclear...

  6. Analisis Matriks Boston Consulting Group (BCG untuk Memenangkan Strategi Organisasi (Studi Kasus Perguruan Tinggi Di Kopertis Wilayah III – DKI Jakarta

    Directory of Open Access Journals (Sweden)

    Haryadi Sarjono

    2013-05-01

    Full Text Available This research intends to know position of market growth in higher education, especially Sekolah Tinggi, based on market share, using BCG metrics. Unit analysis is all private higher educations in Kopertis III – DKI Jakarta, consisting of University, Sekolah Tinggi, Institute, and Academics. The object of analysis is the numberof new student admission. Method of data collection in this paper is field research including observation and literature research method. The secondary data used in this study is data from Kopertis region III. Based on the results of the study, it is obtained Sekolah Tinggi for the academic year 2008 and 2009 is in quadrant III (Cash Cow.

  7. Avaluació de la qualitat de vida dels pacients amb tumor vesical sotmesos a tractament amb BCG o Mitomicina endovesical

    OpenAIRE

    2011-01-01

    El tumor vesical superficial és la neoplàsia més comuna de l'aparell genitourinari. El tractament d'elecció és la RTU vesical, però moltes vegades precisa d'adjuvància posterior, com les instil·lacions de BCG o Mitomicina C endovesicals. Aquests tractaments no estan exempts d'efectes adversos, que poden afectar la qualitat de vida dels pacients als quals se'ls administra. La qualitat de vida relacionada amb la salut és una eina important per valorar l'impacte que tenen alguns procediments ter...

  8. Study on pre-immunization with Bacillus Calmette-Guerin (BCG) on Candida albicans infection in mice%卡介苗免疫预防小鼠白色念珠菌感染的实验研究

    Institute of Scientific and Technical Information of China (English)

    李丽波; 王玉祥

    2009-01-01

    目的 探讨卡介苗(BCG)预先免疫对小鼠白色念珠菌感染的影响.方法 采用BCG或灭菌生理盐水皮内注射预先免疫2周,然后由尾静脉注射白色念珠菌进行攻击,观察小鼠死亡率及计算存活小鼠肾组织带菌量.结果 BCG免疫组存活时间长于生理盐水免疫组(P<0.01);存活小鼠肾组织菌落计数:BCG免疫组远少于省里盐水免疫组(P<0.01).结论 BCG对小鼠白色念珠菌感染具有很好的保护作用.%Objective To investigate the effect of preimmunization with Bacillus Calmette-Guerin (BCG) on Candida albicans infection in mice. Methods BCG or 0.9% sterile saline was injected intracutaneously to ICR mice for preimmunization for two weeks before inoculation of Candida albicans by vena caudalis injection, then mortality rate of mice was observed and Candida albicans in mice kidney was examined. Results Survival time in BCG preimmunization group was longer than that in 0.9% sterile saline group (P<0.01); colony count of Candida albicans in mice kidney in BCG preimmunization group was less than that in saline group (P < 0.01). Conclusions BCG pre-immunization has protective effect from Candida albicans infection in mice.

  9. Efeitos do reiki na evolução do granuloma induzido através da inoculação do BCG em hamsters e do tumor ascítico de Ehrlich induzido em camundongos

    OpenAIRE

    2008-01-01

    Estudaram-se os efeitos da influência do Reiki na evolução do granuloma induzido experimentalmente pela inoculação do BCG no coxim plantar de hamsters, assim como os efeitos da mesma terapia em camundongos portadores do tumor ascítico de Ehrlich in vivo e in vitro. No modelo de inflamação granulomatosa crônica, utilizou-se 40 hamsters machos, os quais após serem inoculados com BCG no dia 0 no coxim da pata posterior direita, foram separados em dois grupos contendo 20 animais em cada. Um grupo...

  10. Effect of BCG on prevention of tubercular meningitis in children: a case - control study%卡介苗预防儿童结核性脑膜炎效果病例对照研究

    Institute of Scientific and Technical Information of China (English)

    熊昌辉; 周义生; 王华庆; 梁晓峰; 廖征; 陈海婴; 邓爱花; 付军; 赵萍萍; 文海蓉

    2012-01-01

    目的:讨论卡介苗保护儿童结核性脑膜炎(结脑)的效果,探讨儿童现行卡介苗(BCG)免疫策略.方法:严格采用病例对照研究方法,对入选结脑病例和对照进行调查,以EpiInfo流行病学软件建立数据库,进行相应分析,据此测算疫苗效力(VE).结果:入选42例病例及126例对照.接种BCG(x2=25.4873,P=0.0000)与儿童结脑发病有统计学关联,BCG的VE=89.42%,95%可信区间(CI)为(69%,97%).结论:接种BCG是儿童结脑保护因素,保护率89.24%.建议继续推行卡介苗免疫策略,以保护儿童免受结脑等重症结核的侵袭.%Objective: To discuss the protective effect of BCG on tubercular meningitis in children, explore the immune strategy of current BCG in children. Methods: A case - control study method was used to survey the children with tubercular meningitis (case group) and the children in control group, Epi Info epidemical software was used to establish database, corresponding analysis was performed to calculate vaccine efficacy (VE). Results:A total of 42 children in case group and 126 children in control group were included into the study. There was a correlation between BCG inoculation and the incidence of tubercular meningitis in children (χ2 = 25. 487 3, P = 0. 000 0), VE of BCG was 89.42% , 95% confidence interval (Cl) was 69% -97%. Conclusion: BCG inoculation is a protective factor of tubercular meningitis in children, the protective rate was 89. 24%. It is recommended to carry out BCG immune strategy to avoid children from invasion of severe tuberculosis, such as tubercular meningitis.

  11. Early BCG and pertussis vaccination and atopic diseases in 5- to 7-year-old preschool children from Augsburg, Germany: results from the MIRIAM study.

    Science.gov (United States)

    Möhrenschlager, Matthias; Haberl, Victoria M; Krämer, Ursula; Behrendt, Heidrun; Ring, Johannnes

    2007-02-01

    The role of immunization in the development of atopic disorders is still under debate. One reason might be, that because of high vaccination coverage in most countries only few and selected children are not immunized, leading to unstable and often biased effect estimates. In Germany, the situation was different between 1985 and 1991: bacillus Calmette-Guérin (BCG) and pertussis vaccination were not officially recommended leading to high numbers of non-vaccinated children in the 1990s. We report on a cross-sectional study with 1673 participants among 5- to 7-year-old preschool children conducted in 1996. We found no hint that BCG vaccination or whole-cell pertussis (WCP) vaccination may lead to higher prevalences of asthma, allergic rhinitis, eczema or allergic sensitization at preschool age. None of the associations was significantly positive. WCP vaccination may be protective against asthma OR 0.55 (95% CI: 0.31-0.98) and against symptoms of eczema in boys.

  12. Exosomes derived from M. Bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Pramod K Giri

    Full Text Available Activation of both CD4(+ and CD8(+ T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma. Our previous studies showed that infected macrophages release from cells small membrane-bound vesicles called exosomes which contain mycobacterial lipid components and showed that these exosomes could stimulate a pro-inflammatory response in naïve macrophages. In the present study we demonstrate that exosomes stimulate both CD4(+ and CD8(+ splenic T cells isolated from mycobacteria-sensitized mice. Although the exosomes contain MHC I and II as well as costimulatory molecules, maximum stimulation of T cells required prior incubation of exosomes with antigen presenting cells. Exosomes isolated from M. bovis and M. tuberculosis infected macrophages also stimulated activation and maturation of mouse bone marrow-derived dendritic cells. Interestingly, intranasal administration of mice with exosomes isolated from M. bovis BCG infected macrophages induce the generation of memory CD4(+ and CD8(+ T cells. The isolated T cells also produced IFN-gamma upon restimulation with BCG antigens. The release of exosomes from infected macrophages may overcome some of the defects in antigen presentation associated with mycobacterial infections and we suggest that exosomes may be a promising M. tuberculosis vaccine candidate.

  13. The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Rodrigues, Amabelia; Yazdanbakhsh, Maria;

    2009-01-01

    Unexpectedly, we found no overall beneficial effect on mortality in a randomised trial of vitamin A supplementation (VAS) or placebo administered with BCG vaccine at birth in Guinea-Bissau. We conducted an explorative analysis to examine whether subsequent diphtheria-tetanus-pertussis (DTP......) vaccinations had modified the effect of VAS at birth. VAS was associated with a weak tendency for decreased mortality as long as BCG was the most recent vaccination, the mortality rate ratio being 0.86 (0.48-1.54); 0.82 (0.32-2.08) in girls and 0.89 (0.43-1.88) in boys. However, after DTP vaccination VAS...... at birth was associated with increased mortality in girls (2.19 (1.09-4.38)), whereas no difference was seen for boys (0.90 (0.44-1.82)) (p=0.08 for equal effect of VAS in the two sexes if DTP is the last vaccine). The explanation for the lack of beneficial effect in our setting may have been that VAS...

  14. [Support in living].

    Science.gov (United States)

    Krebs, H

    1993-06-01

    "Lebenshilfe" (help in living) is of crucial importance for the organization of live of persons with a handicap. This help in living, training and social integration, however, requires an image of the handicapped person that unrestrictedly recognizes her right to live and to be a human being with a handicap. But todays hedonistic and preference-utilitarian social trends make other, selecting value judgements. This article comments on these dubious ethical positions critically and develops a paradigmatic, positive point of view. This statement is partly based on the principles of 2 self-help organizations of the same name ("Lebenshilfe für geistig Behinderte") in Germany and in Austria.

  15. Living with Hepatitis

    Science.gov (United States)

    ... HFI Summits Newsletter Our Stories Calendar of Events Advertise RESOURCES Health Savings Card Links Webinars YOUR LIVER Overview Adults Children & Adolescents Nutrition & Health Lifestyle RESEARCH DVDs Overview Live- ...

  16. Hand Hygiene Saves Lives

    Medline Plus

    Full Text Available ... Center (EOC) 101 Emergency Operations Center CDC Laboratory Science: Mission Critical Saving Lives, Protecting People Environmental Health CDC Tracking Network Health Begins at Home Smoke- ...

  17. Probably safe or live

    NARCIS (Netherlands)

    Katoen, Joost-Pieter; Song, Lei; Zhang, Lijun

    2014-01-01

    This paper presents a formal characterisation of safety and liveness properties for fully probabilistic systems. As for the classical setting, it is established that any (probabilistic tree) property is equivalent to a conjunction of a safety and liveness property. A simple algorithm is provided to

  18. Our Urban Living Room

    DEFF Research Database (Denmark)

    Hjortshøj, Rasmus

    2016-01-01

    the boundaries between private and public space become fluid. Based on specific Cobe projects, Our Urban Living Room tells stories about the architectural development of Copenhagen, while exploring the progression of the Danish Capital - from an industrial city into an urban living room, known as one...

  19. Animals that Live Longest

    Institute of Scientific and Technical Information of China (English)

    饶扬志

    2000-01-01

    Reptiles(爬行类) are animals that live longest. The turtle's(海龟)long life is legendary(传奇的), no one has ever been able to calculate the exact age of the turtle, and for good reason, tortoises live a lot longer than humans do.

  20. Living Willow Huts

    Science.gov (United States)

    Keeler, Rusty

    2007-01-01

    Living Willow Huts are inexpensive to make, fun to plant, easy to grow, and make beautiful spaces for children. They involve planting dormant willow shoots in the ground and weaving them into shapes that will sprout and grow over time. People have been creating similar living architecture throughout the world for centuries in the forms of living…

  1. The governmentalization of living

    DEFF Research Database (Denmark)

    Wahlberg, Ayo; Rose, Nikolas

    2015-01-01

    and scales (e.g. the QALY and DALY) has contributed to a governmentalization of living, in the course of which the social and personal consequences of living with disease come to be an object of political concern, and made knowable, calculable and thereby amenable to various strategies of intervention. We...

  2. Living the Utopia

    DEFF Research Database (Denmark)

    Davis, John; Warring, Anette Elisabeth

    2011-01-01

    This article examines experiments in communal living in Britain and Denmark in the early 1970s, using life-story interviews from seventeen members of two British and two Danish communes. It examines communal living as a fusion of radical political principles with the practice of experimental coll...

  3. Live and Dead Nodes

    DEFF Research Database (Denmark)

    Jørgensen, Sune Lehman; Jackson, A. D.

    2005-01-01

    In this paper, we explore the consequences of a distinction between `live' and `dead' network nodes; `live' nodes are able to acquire new links whereas `dead' nodes are static. We develop an analytically soluble growing network model incorporating this distinction and show that it can provide a q...

  4. 经尿道钬激光联合大剂量丝裂霉素灌注治疗腺性膀胱炎%Effect of transurethral Holmium laser therapy combined with high dose mitomycin intravesical instillation on cystitis glandularis

    Institute of Scientific and Technical Information of China (English)

    刘向伟

    2011-01-01

    目的 探讨经尿道钬激光联合大剂量丝裂霉素灌注治疗腺性膀胱炎的方法及疗效.方法 经膀胱镜检查及活检确诊58例腺性膀胱炎患者,均行经尿道钬激光切除术,术后给予大剂量丝裂霉素膀胱灌注治疗.结果 58例分别随访6~36个月,37例治愈,16例好转,5例复发.结论 经尿道钬激光切除术后应用大剂量丝裂霉素膀胱灌注能减少腺性膀胱炎术后复发,且副作用少,疗效满意.%Objective To evaluate the method and resultassess the effect of intravesical instillation of high dose mitomycin at high dose combined with transurethral Holmium laser therapy in the treatment of on cystitis glandularis. Methods Fifty-eight patients with cystitis glandularis diagnosed through cystoscope biopsy were treated with intravesical instillation of mitomycin at high dose after transurethral Holmium laser therapy. Results All patients were all followed up in 6 - 36 months. The clinical symptom of Thirty-seven patients disappeared were cured, and 16 patients were alleviated, and 5 patients recurred. Conclusion Combining the transurethral Holmium laser therapy with high dose mitomycin intravesical instillation is effective and safe against local recurrence of cystitis glandularis.

  5. Evaluating Living Standard Indicators

    Directory of Open Access Journals (Sweden)

    Birčiaková Naďa

    2015-09-01

    Full Text Available This paper deals with the evaluation of selected available indicators of living standards, divided into three groups, namely economic, environmental, and social. We have selected six countries of the European Union for analysis: Bulgaria, the Czech Republic, Hungary, Luxembourg, France, and Great Britain. The aim of this paper is to evaluate indicators measuring living standards and suggest the most important factors which should be included in the final measurement. We have tried to determine what factors influence each indicator and what factors affect living standards. We have chosen regression analysis as our main method. From the study of factors, we can deduce their impact on living standards, and thus the value of indicators of living standards. Indicators with a high degree of reliability include the following factors: size and density of population, health care and spending on education. Emissions of carbon dioxide in the atmosphere also have a certain lower degree of reliability.

  6. Interventions in everyday lives

    DEFF Research Database (Denmark)

    Dreier, Ole

    2015-01-01

    The purpose of psychotherapy is to help clients address and overcome problems troubling them in their everyday lives. Therapy can therefore only work if clients include it in their ongoing lives to deal with their problems. Detailed, systematic research is needed on how clients do so in their eve......The purpose of psychotherapy is to help clients address and overcome problems troubling them in their everyday lives. Therapy can therefore only work if clients include it in their ongoing lives to deal with their problems. Detailed, systematic research is needed on how clients do so...... clients change their everyday lives to overcome their troubles. They also highlight what it involves for clients to accomplish this. It is concluded that we need more research on how to understand intervention; on the interaction between interventions and clients’ conduct of their everyday life...

  7. Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS)

    NARCIS (Netherlands)

    Witjes, J.A.; Palou, J.; Soloway, M.; Lamm, D.; Kamat, A.M.; Brausi, M.; Persad, R.; Buckley, R.; Colombel, M.; Bohle, A.

    2013-01-01

    OBJECTIVES: To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guerin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU)

  8. ANALYSIS OF THE QUALITY OF NEONATAL BCG VACCINATION FROM 2006 TO 2009 IN SUZHOU%苏州市2006~2009年新生儿卡介苗接种质量分析

    Institute of Scientific and Technical Information of China (English)

    黄桥梁; 穆卫明; 颜建荣; 吴美芳; 孙明丽

    2012-01-01

    [Objective] To evaluate the completion and the effectiveness of BCC vaccination in Suzhou city during the year of 2006 to 2009, and analyze and resolve the problem in BCG vaccination, so as to.provide scientific evidence for tuberculosis control. [Methods] We conduct a analysis on BCG revaecination between Suzhou Center For Disease Prevention and Control and the effectiveness of BCG vaccination in the hospital of the district area in Suzhou, and compared with the PPD positive rate after 12 weeks' BCG vaccination among them. [Results] There were significant difference in BCG vaccination among the CDC and hospitals {P 0.05) in the PPD positive rate after 12 weeks' BCG vaccination. [Conclusion] It should improve the indications of BCG vaccination rate on the hospital in Suzhou, find out the potential tuberculosis as soon as possible, and avoid the newly infection.%[目的]了解苏州市2006~2009年新生儿卡介苗接种效果,为预时结核病提供科学依据.[方法]对在2006~2009年间市辖区医院出生时接种卡介苗和市疾控门诊补种卡介苗新生儿,进行结核菌素实验(PPD)观察比较.[结果]卡介苗接种市辖区医院、市疾控以及两者之间差异均有统计学意义(P<0.05);而在按种卡介苗3个月后PPD测试结果,市疾控与市辖区医院之间差异无统计学意义(P>0.05).[结论]进一步提高医院接种率水平,尽早发现患结核可能性患者,避免产生新的感染者.

  9. Complete genome sequencing and sequence analysis of BCG Tice%卡介苗美国株全基因组测序缺口修补及序列

    Institute of Scientific and Technical Information of China (English)

    王志明; 潘元龙; 吴俊; 朱宝利

    2012-01-01

    [目的]对卡介苗( Bacillus Calmette-Guerin,BCG)美国株(BCG Tice)进行基因组补缺口(补洞)工作,以得到它的基因组完整序列.[方法]首先对BCG Tice进行高通量测序,使用SOAPdenovo软件对得到的数据进行拼接.由于在高通量测序的过程中基因组某些区域测序覆盖度低,测序质量差会使测序结果经拼接后形成众多的重叠群(contig),相邻的位置关系确定的contig形成一个scaffold,contig之间未测到的区域为缺口序列( gap),在contig末端设计引物进行PCR扩增,得到连接相邻contig的PCR产物,对PCR产物进行测序.通过优化PCR引物设计策略,尝试不同的聚合酶进行聚合反应,调整PCR反应条件并结合PCR产物构建克隆测序等方法,补齐contig之间的缺口序列.[结果]完成了BCG Tice的全基因组测序,得到了它的基因组完整序列,序列已提交到美国国立生物技术信息中心(NCBI)的GenBank数据库.[结论]BCG属于高GC含量的革兰氏阳性细菌,其基因组GC含量高达65.65%.本文以BCG Tice基因组补洞为例,对高GC含量基因组补缺口过程中遇到的问题与采取的策略给予概述,望给相关高GC含量基因组的物种全基因组测序补缺口工作提供一些借鉴.%[Objective ] The objective of this study is to obtain the complete genome sequence of Bacillus Calmette-Guerin Tice ( BCG Tice) , in order to provide more information about the molecular biology of BCG Tice and design more reasonable vaccines to prevent tuberculosis. [Methods] We assembled the data from high-throughput sequencing with SOAPdenovo software, with many contigs and scaffolds obtained. There are many sequence gaps and physical gaps remained as a result of regional low coverage and low quality. We designed primers at the end of contigs and performed PCR amplification in order to link these contigs and scaffolds. With various enzymes to perform PCR amplification, adjustment of PCR reaction conditions, and combined

  10. 泌尿外科膀胱灌注化疗操作护理人员职业防护知识及行为调查%Survey of urology nurses on occupation protection from intravesical chemotherapy

    Institute of Scientific and Technical Information of China (English)

    丁娥; 徐秀莲; 菅向东

    2015-01-01

    Objective To investigate the awareness of self protection and practice of nurses from urology department when giving intravesical chemotherapy to patients with urinary bladder cancer.Methods One survey via a self-designed questionnaire and an on-the-spot examination of anticancer drugs preparing were done and compared among 42 nurses from urology department and 48 nurses from oncology department.Results All nurses from oncology department were trained with anticancer drugs-associated knowledge and 83.3% nurses from urology department had received some training (P<0.05).Over 64.6% nurses from department of medical oncology were familiar with all the five parts of chemotherapy drugs protection protocol,while only 40.5% nurses from department of urology were aware of them.During the on-the-spot examination,50.0% and 21.4% nurses respectively from oncology department and urology department could complete seven anticancer drugs preparation procedure correctly (P<0.05).Conclusions The nurses from urology department had weak awareness of self protection and were lack of chemotherapy associated training and standard practice when giving intravesical chemotherapy.It is imperative to work out a protection plan to educate the nurses and establish the protocols for preparing anticancer drugs to reduce the occurrence of occupational hazard.%目的 了解泌尿外科护理人员膀胱灌注化疗操作时的自我防护知识的知晓情况及行为.方法 采用自行设计调查问卷对接触化疗药物的42名泌尿外科护士和48名化疗科护士进行问卷调查及药物配制操作流程现场考核,并对结果进行比较分析.结果 化疗科护士均接受过化疗药物相关知识培训,只有83.3%的泌尿外科护士接受过培训,培训率明显低于化疗科护士(100%),差异有统计学意义(P<0.05);化疗科护士和泌尿外科护士5项调查的配制化疗药物防护相关知识全部知晓率分别为64.6%和40.5%,泌尿

  11. Diagnostic potentialities of enzyme-linked immunosorbent assay for polycolonal anti-BCG IgM antibodies in tuberculous pleurisy%多克隆抗BCG IgM抗体在结核性胸膜炎的诊断价值

    Institute of Scientific and Technical Information of China (English)

    郑晓滨; 洪海裕; 邬伟明; 黄瑾

    2014-01-01

    Objective To evaluate the diagnostic value of the levels of anti-BCG IgM antibodies in tubercu-lous pleurisy. Methods 102 patients were consequently included in this research, and the pleural effusion samples were collected from each subject in the first thoracocentesis procedure. Individuals historically diagnosed as having tu-berculosis were defined as tuberculous pleurisy (40 cases). Subjects clinically diagnosed with other well defined dis-eased were included in the control group (24 cases). We developed an indirect whole bacterial cell ELISA test to de-tect polycolonal anti-BCG IgM antibodies of pleural effusion in the tuberculous pleurisy group and the control group. And then ROC analysis was performed to evaluate the value of the test for the diagnosis of tuberculous pleurisy. Re-sults Compared with the control group, the levels of polycolonal anti-BCG IgM antibodies of pleural effusion in the tuberculous pleurisy group statically significantly increased (P<0. 001). The average of antibody levels in the con-trol group plus 2SD as diagnostic cutoff point was appropriate. Conclusion Pleural effusion polycolonal anti-BCG IgM antibodies can be proposed as a diagnostic marker of tuberculous pleurisy.%目的:研究胸水多克隆抗卡介苗( BCG) IgM抗体的浓度是否有助于结核性胸膜炎的诊断。方法序贯纳入胸腔积液患者102例,进入研究的患者于第一次胸穿时留取胸水待检,以胸膜活检病理检查为金标准,综合其他临床资料,剔除诊断未明者,分为结核性胸膜炎组( n=40)及对照组( n=24)。建立以BCG全菌细胞包被作为固相载体的间接法ELISA反应体系,检测胸水多克隆抗BCG抗体的浓度。评价其在结核性胸膜炎诊断方面的效能。结果病例组胸水抗BCGIgM抗体浓度显著高于对照组( P<0.001)。以对照组抗体水平平均值加2倍标准差为诊断界值,阳性预测值可高达96.0%。结论胸水多克隆抗卡介苗( BCG) IgM抗体

  12. A functional whole blood assay to measure viability of mycobacteria, using reporter-gene tagged BCG or M.Tb (BCGlux/M.Tb lux).

    Science.gov (United States)

    Newton, Sandra; Martineau, Adrian; Kampmann, Beate

    2011-09-14

    employed in studies of adults and children in TB-endemic settings. We have shown immunogenicity of the BCG vaccine, increased growth of mycobacteria in HIV-positive patients, as well as the effect of anti-retroviral therapy and Vitamin D on mycobacterial survival in vitro. Here we summarise the methodology, and present our reproducibility data using this relatively simple, low-cost and field-friendly model. Note: Definitions/Abbreviations BCG lux = M. bovis BCG, Montreal strain, transformed with shuttle plasmid pSMT1 carrying the luxAB genes from Vibrio harveyi, under the control of the mycobacterial GroEL (hsp60) promoter. CFU = Colony Forming Unit (a measure of mycobacterial viability).

  13. Revacinação BCG em escolares: evolução da lesão vacinal entre 48 horas e 10 semanas

    Directory of Open Access Journals (Sweden)

    Ferreira Arlan A.

    2002-01-01

    Full Text Available Objetivo: a reação cutânea na revacinação BCG tem sido motivo de questionamentos dado à sua magnitude. Seria ela intensa o suficiente para desencorajar seu uso na idade escolar? O objetivo deste estudo é descrever o aspecto evolutivo da lesão vacinal entre 48 horas e a décima semana pós-revacinação. Métodos: estudo de coorte descritivo em que foram revacinadas 484 crianças entre seis e 11 anos de idade, com 0,1ml da vacina BCG Moreau, e aferidos eritema, enduração, pústula, úlcera, crosta e cicatriz em 48h, 72h e, semanalmente, até a décima semana de evolução, acompanhadas no período de julho a dezembro de 1997. Os dados foram informatizados em programa Epi-Info 6.0, avaliando-se freqüências, médias, medianas e desvios-padrões. Resultados: enduração estava presente em 99,1%, e eritema em 91,6% das 438 crianças avaliadas com 48h. Pústulas foram observadas na primeira semana em 26,1% de 479 crianças. Na segunda semana, já apareceram as primeiras úlceras. Na décima semana, 69,8% das 463 crianças presentes exibiam crostas, mas apenas 29,2% havia completado o processo de cicatrização. Conclusão: a revacinação BCG em escolares produz intensa e precoce reação, que pode ser atribuível ao fenômeno de Koch, mas sem a esperada redução no tempo de cicatrização. Se por um lado a magnitude da reação não chega a comprometer sua indicação na idade escolar, a pronta resposta inflamatória aponta para a ativa resposta imune possivelmente remanescente da primo-vacinação.

  14. Living with Worms

    DEFF Research Database (Denmark)

    Bertoni, Filippo

    2016-01-01

    The thesis explores what living together can offer in rethinking political theory and in creating a space in which "politics" is not just a matter between people, but also with nature. These lessons about living together emerge from fieldwork around practices in which worms are central. Thus......, the work focuses on ecologists who, in turn, examine worms; and worms amateurs who learn to collect and identify them in the field. Composting, and the waste-eating of earthworms are also experimented with. The "living together " that worms unearth is about eating and being eaten - a set of relations...

  15. Digital Living at Home

    DEFF Research Database (Denmark)

    Andersen, Pernille Viktoria Kathja; Christiansen, Ellen Tove

    2013-01-01

    Does living with digital technology inevitably lead to digital living? Users talking about a digital home control system, they have had in their homes for eight years, indicate that there is more to living with digital technology than a functional-operational grip on regulation. Our analysis...... of these user voices has directed us towards a ‘home-keeping’ design discourse, which opens new horizons for design of digital home control systems by allowing users to perform as self-determined controllers and groomers of their habitat. The paper concludes by outlining the implications of a ‘home...

  16. Living with psoriasis

    DEFF Research Database (Denmark)

    Bak, Kirsten Tarri

    2004-01-01

    Living with psoriasis is a considerable burden and quality of life in patients is deeply affected, yet compliance with therapy is a major problem. The literature is abundant in quantitative studies stating the incidence of decrease in quality of life and related, measurable terms, and in efforts...... of energy. They described their lives as a tightrope walking of taking into account the disease yet having a life worth living. The personal significance of the disease showed to be the most important factor in respect to the patients’ deliberations and actions regarding treatment and care. The patients...

  17. 家兔膀胱体表肌电和膀胱内压关系的实验研究%Experimental study on the relationship of vesical detrusor surface electromyogram and intravesical pressure in rabbit

    Institute of Scientific and Technical Information of China (English)

    俞小梅; 李承晏; 袁天琪

    2011-01-01

    Objective To study the change of vesical detrusor electromyogram(D-sEMG) from abdominal surface and intravesical pressure during storage and elimination of urine in rabbit and the relationship between both,and evaluate the value of D-sEMG. Methods There was 3 male rahbits in the study. Infusion of normal saline into one of ear veins of rabbits was performed at a speed of 40-50 drips/min. A pair of recording electrodes were sticked vertically on the midline body surface of urinary bladder and one reference electrode was on the body surface of one thigh end. The wires of the three electrodes were connected to channel 1 of RM6240 biological signal acquisition system to detect D-sEMG; One single-lumen 8Fr catheter was inserted into bladder through urethra,the out lumen of which was connected to channel 2 of RM6240 system via a pressure transducer for detecting intravesical pressure. Bladder EMG and the pressure were recorded simultaneously during the normal storage and micturition of rabbits. 4 experiements were performed repeatedly in every rabbit. 10 micturating periods were recorded in every experiement. Results During filling peirod, bladder pressure was maintained basically at a certain level and no electromyographic activity was recorded from the surface electrodes. With the increasing of urine in bladder, the bladder pressure ascended slowly at first and rapidly to peak when it is beyond (36. 4 ± 5. 9) cmH2O, and subsequently decreased fast to baseline level: Meanwhile, the rabbits micturated and obvious surface EMG like twophase bursts with different amplitudes was detected.Correlation coefficients between the pressure peak and the EMG average amplitude and frequency was r1 =0. 803(P<0.05) and r2 = 0. 254(P<0.05)respectively;The pressure peak lagged behind the EMG amplitude peak and the delay time was (0. 12 ± 0. 10 s. Correlation coefficient between both was r= 1 (P<0. 05) : there was no significant difference between the pressure rising duration and

  18. Writing lives in sport

    DEFF Research Database (Denmark)

    Christensen, Mette Krogh

    Writing lives in sport is a book of stories about sports-persons. The people concerned include sports stars, sports people who are not quite so famous, and relatively unknown physical education teachers and sports scientists.Writing lives in sport raises questions about writing biographies...... in the academis world of sport studies. It does not set out to be a methodological treatise but through the writing of lives in sports does raise questions of method. Each essay in this collection deals with problems of writing sports-people's lives. These essays could be said to fall along a spectrum from those...... of the essays fails to recognise problems of sport-biography. Indeed, several focus explicitly on exemplifications of these problems and as such the book raises important questions for writing in a variety of sporting and educational disciplines....

  19. Living with others

    DEFF Research Database (Denmark)

    Zabiliute, Emilija

    Living with Others’ is an ethnographic study of everyday lives and health-seeking practices among urban poor living in a settlement in the margins of Delhi, India.By exploring subjectivities, lived experiences of poverty, and relations through a prism ofhealth, the inquiry aims to move beyond...... the explorations of precarity embedded in political economies and urban governance that dominate discussions on urban poor neighbourhoods in India.Empirically, the study draws on long-term ethnographic fieldwork and interviews among urban poor,mostly women;and formal and informal health practitioners, abundant...... community belonging and relatedness among neighbours and families.Concurrently, the study showshowthe knowledge of relatedness informsgovernmental health interventionswhichproblematizefamilial relations through evaluations of care in the families amidst poverty; and which functioned to sustain familial...

  20. Hand Hygiene Saves Lives

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    Full Text Available ... Corner Stores Healthy Snacking in Philadelphia, PA Hidden Sodium Salt Matters Salt Matters: Preserving Choice, Protecting Health ( ... Health Easier: Active Living in Philadelphia, PA Hidden Sodium Hidden Sodium Me? Have a baby? Preconception Health ...

  1. Living with Fanconi Anemia

    Science.gov (United States)

    ... from the NHLBI on Twitter. Living With Fanconi Anemia Improvements in blood and marrow stem cell transplants ... November 1, 2011 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA NO FEAR ACT OIG ...

  2. Hand Hygiene Saves Lives

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    Full Text Available ... Lives shows how patients can play an active role in reminding healthcare providers to practice hand hygiene ... Director for Communication, Division of News and Electronic Media Email Recommend Tweet YouTube Instagram Listen Watch RSS ...

  3. Living with Thalassemias

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    ... page from the NHLBI on Twitter. Living With Thalassemias Survival and quality of life have improved for people who have moderate or severe thalassemias. This is because: More people are able to ...

  4. Hand Hygiene Saves Lives

    Medline Plus

    Full Text Available ... Health (4:17) Vital Signs High Blood Pressure Spanish Diseases & Conditions Hablemos de la Influenza Influenza Influenza (: ... 2010 Source: Healthcare-associated Infections (HAI) Other versions: Spanish (5:10) Healthy Living Featured Videos Fight Germs. ...

  5. Administration for Community Living

    Science.gov (United States)

    ... Grantees About ACL Organization Why Community Living? Authorizing Statutes Budget Mandatory Grant Allocations Strategic Plan Federal Initiatives Career Opportunities Contact Us Home FEATURES #InclusionWorks IL Final Rule Get ACL ...

  6. Living with Heart Failure

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Living With Heart Failure Currently, heart failure has no cure. You'll ... avoid harmful side effects. Take Steps To Prevent Heart Failure From Getting Worse Certain actions can worsen your ...

  7. Living With Lupus

    Science.gov (United States)

    ... Information Lupus Find a Clinical Trial Journal Articles Lupus July 2014 Living With Lupus: Health Information Basics for You and Your Family ... If You Have Lupus? Symptom Checklist What Is Lupus? Lupus is an autoimmune (AW-toe-ih-MYOON) ...

  8. Influenza Vaccine, Live Intranasal

    Science.gov (United States)

    ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.

  9. Living Better with Osteoarthritis

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Osteoarthritis Living Better with Osteoarthritis Past Issues / Winter 2013 Table of Contents What Is Osteoarthritis? Osteoarthritis is the most common type of arthritis. ...

  10. Living with Low Vision

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    ... Life TIPS To Its Fullest LIVING WITH LOW VISION Savings Medical Bills A VARIETY OF EYE CONDITIONS, ... which occupational therapy practitioners help people with low vision to function at the highest possible level. • Prevent ...

  11. Hand Hygiene Saves Lives

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    Full Text Available ... Saving Lives, Protecting People Environmental Health CDC Tracking Network Health Begins at Home Smoke-free Multiunit Housing ... maintained by: Office of the Associate Director for Communication, Division of News and Electronic Media Email Recommend ...

  12. Living with Atherosclerosis

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    ... page from the NHLBI on Twitter. Living With Atherosclerosis Improved treatments have reduced the number of deaths ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  13. Healthy Living after Stroke

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    ... Stories Stroke Heroes Among Us Healthy Living After Stroke Nutrition Good nutrition is one way to reduce ... look to maintain health and wellness. Subscribe to Stroke Connection Get quarterly digital issues plus our monthly ...

  14. Hand Hygiene Saves Lives

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    Full Text Available ... Saving Lives, Protecting People Environmental Health CDC Tracking Network Health Begins at Home Smoke-free Multiunit Housing ... Email CDC-INFO U.S. Department of Health & Human Services HHS/Open USA.gov Top

  15. Living with VHL

    Science.gov (United States)

    ... effectively manage the VHL and lead full and productive lives. Early diagnosis, regularly surveillance, appropriate ... Sign Up VHLA Login Sitemap © 2017 by The VHL Alliance. All Rights Reserved. The VHL Alliance is a ...

  16. The Effect of 50 000 IU Vitamin A with BCG Vaccine at Birth on Growth in the First Year of Life

    DEFF Research Database (Denmark)

    Fisker, Ane Bærent; Benn, Christine Stabell; Diness, Birgitte Rode;

    2011-01-01

    interaction between VAS and DTP in girls would be reflected in growth. Length and weight were measured at 6 weekly visits and WHO-growth-reference z-scores derived. Neonatal VAS had no effect on anthropometric measures at 12 months, but may interact sex differentially with routine vaccines. While BCG...... was the most recent vaccine, neonatal VAS benefitted growth (difference in weight-for-length z-score (dWFL: 0.31(95% CI: 0.03-0.59)). While DTP was the most recent vaccine, VAS tended to affect growth adversely in girls (dWFL = -0.21 (-0.48-0.06)). After measles vaccine (MV) there was no overall effect...

  17. Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age

    DEFF Research Database (Denmark)

    Fisker, Ane B; Lisse, Ida M; Aaby, Peter;

    2007-01-01

    with higher (9%; 95% CI: 2, 17%) RBP concentrations in children of noneducated mothers but not in children of educated mothers. Overall, RBP concentrations increased between 6 wk and 4 mo of age. The increase correlated inversely with the number of diphtheria-tetanus-pertussis (DTP) vaccines received......BACKGROUND: The effect of vitamin A supplementation (VAS) at birth on subsequent vitamin A status has not been studied. OBJECTIVE: The objective was to study the effect of 50,000 IU vitamin A administered with BCG vaccine at birth on vitamin A status in both sexes. DESIGN: Within a randomized...... A recipients, subsequent DTP vaccines affected vitamin A status negatively. The main trial was registered at clinicaltrials.gov as NCT00168597....

  18. Effect of vitamin A supplementation with BCG vaccine at birth on vitamin A status at 6 wk and 4 mo of age

    DEFF Research Database (Denmark)

    Fisker, Ane B; Lisse, Ida M; Aaby, Peter;

    2007-01-01

    with higher (9%; 95% CI: 2, 17%) RBP concentrations in children of noneducated mothers but not in children of educated mothers. Overall, RBP concentrations increased between 6 wk and 4 mo of age. The increase correlated inversely with the number of diphtheria-tetanus-pertussis (DTP) vaccines received......BACKGROUND: The effect of vitamin A supplementation (VAS) at birth on subsequent vitamin A status has not been studied. OBJECTIVE: The objective was to study the effect of 50,000 IU vitamin A administered with BCG vaccine at birth on vitamin A status in both sexes. DESIGN: Within a randomized...... A recipients, subsequent DTP vaccines affected vitamin A status negatively. The main trial was registered at clinicaltrials.gov as NCT00168597. Udgivelsesdato: 2007-Oct...

  19. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  20. High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area

    Directory of Open Access Journals (Sweden)

    Jiang Weimin

    2009-05-01

    Full Text Available Abstract Background An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST was performed for all recruited subjects. Results The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32, group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46 and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22. In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST P 85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells Conclusion ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.

  1. Routine Transurethral Biopsy of the Bladder is not Necessary to Evaluate the Response to Bacillus Calmette-guerin Therapy

    Directory of Open Access Journals (Sweden)

    Manabe,Daisuke

    2007-12-01

    Full Text Available We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy results. Fifty-three of 54 patients (98.1% with no visible recurrent tumor and negative urinary cytology demonstrated negative pathological results on bladder biopsy. When not found in conjunction with positive urinary cytology, erythematous mucosa on cystoscopy was not an indicator of tumor recurrence or residual cancer. In conclusion, routine transurethral biopsy of the bladder for evaluating the response to BCG intravesical therapy is not necessary in patients who have no visible tumor on cystoscopy and negative urinary cytology./

  2. Estimativa da prevalência de infecção tuberculosa em escolares vacinados com BCG, por meio de método de Bhattacharya The determination of the prevalence of tuberculosis infection among school-children vaccinated by Bhattacharya's method

    Directory of Open Access Journals (Sweden)

    Gilberto Ribeiro Arantes

    1991-04-01

    Full Text Available Em populações muito afetadas por reações tuberculínicas inespecíficas, o teste tuberculínico padronizado, via de regra, superestima a infecção tuberculosa. A bem sucedida aplicação do método de Bhattacharya (método gráfico para a decomposição de uma distribuição de freqüências em componentes normais na análise de resultados do teste em população contaminada por infecçõcs atípicas sugeriu seu uso nos resultados obtidos cm populações vacinadas com BCG. Assim, na análise dos resultados de dois inquéritos tuberculínicos realizados na cidade de São Paulo, SP (Brasil, em 1982 (escolares vacinados entre o segundo e o sexto ano de vida, e em 1988 (escolares vacinados no primeiro ano de vida, foi possível a caracterização e quantificação da componente normal devida à infecção natural em cada uma das misturas. Na população de 1982 o diâmetro médio das reações foi de 17,40 mm com desvio padrão 3,72 mm, e a proporção de infectados foi de 7,71% contra 4,85% nos não vacinados; na população de 1988, o diâmetro médio foi 17,00 mm com desvio padrão 4,67 mm, e a proporção de infectados foi de 4,14% contra 4,48% nos não vacinados. Concluiu-se que o método permite estimar a prevalência da infecção tuberculosa em populações com alta cobertura vacinal, desde que a vacina tenha sido aplicada no primeiro ano de vida.The sucessful application of Bhattacharya's method ( decomposition of frequency distribution into normal components by a grafic method in the analysis of the results of tuberculin test performed on a population sensitized by "anonymous" strains of mycobacteria, suggested the possibility of its application to two samples of BCG vacinated school-children, living in the city of S. Paulo (Brazil. One of the sample groups, vaccinated between the second and seventh years of life, was surveyed in 1982 and the other, vaccinated during the first year of life, was surveyed in 1988. In both populations it

  3. Are we following the guidelines on non-muscle invasive bladder cancer?

    Directory of Open Access Journals (Sweden)

    Leonardo Oliveira Reis

    2016-02-01

    Full Text Available ABSTRACT Objectives To evaluate the clinical practice of non-muscle invasive bladder cancer (NMIBC treatment in Brazil in relation to international guidelines: Sociedade Brasileira de Urologia (SBU, European Association of Urology (EAU and American Urological Association (AUA. Materials and Methods Cross-sectional study using questionnaires about urological practice on treatment of NMIBC during the 32nd Brazilian Congress of Urology. A total of 650 question forms were answered. Results There were 73% of complete answers (total of 476 question forms. In total, 246 urologists (51.68% lived in the southeast region and 310 (65.13% treat 1 to 3 cases of NMIBC per month. Low risk cancer: Only 35 urologists (7.5% apply the single intravesical dose of immediate chemotherapy with Mitomicin C recommended by the above guidelines. Adjuvant therapy with BCG 2 to 4 weeks after TUR is used by 167 participants (35.1% and 271 urologists (56.9% use only TUR. High risk tumors: 397 urologists (83.4% use adjuvant therapy, 375 (78.8% use BCG 2 to 4 weeks after TUR, of which 306 (64.3% referred the use for at least one year. Intravesical chemotherapy with Mitomicin C (a controversial recommendation was used by 22 urologists (4.6%. BCG dose raised a lot of discrepancies. Induction doses of 40, 80 and 120mg were referred by 105 (22%, 193 (40.4% and 54 (11.3% respectively. Maintenance doses of 40, 80 and 120mg were referred by 190 (48.7%, 144 (37.0% and 32 (8.2% urologists, respectively. Schemes of administration were also varied and the one cited by SWOG protocol was the most used: 142 (29.8%. Conclusion SBU, EAU and AUA guidelines are partially respected by Brazilian urologists, particularly in low risk tumors. In high risk tumors, concordance rates are comparable to international data. Further studies are necessary to fully understand the reasons of such disagreement.

  4. Are we following the guidelines on non-muscle invasive bladder cancer?

    Science.gov (United States)

    Reis, Leonardo Oliveira; Moro, Juliano Cesar; Ribeiro, Luis Fernando Bastos; Voris, Brunno Raphael Iamashita; Sadi, Marcos Vinicius

    2016-01-01

    ABSTRACT Objectives To evaluate the clinical practice of non-muscle invasive bladder cancer (NMIBC) treatment in Brazil in relation to international guidelines: Sociedade Brasileira de Urologia (SBU), European Association of Urology (EAU) and American Urological Association (AUA). Materials and Methods Cross-sectional study using questionnaires about urological practice on treatment of NMIBC during the 32nd Brazilian Congress of Urology. A total of 650 question forms were answered. Results There were 73% of complete answers (total of 476 question forms). In total, 246 urologists (51.68%) lived in the southeast region and 310 (65.13%) treat 1 to 3 cases of NMIBC per month. Low risk cancer: Only 35 urologists (7.5%) apply the single intravesical dose of immediate chemotherapy with Mitomicin C recommended by the above guidelines. Adjuvant therapy with BCG 2 to 4 weeks after TUR is used by 167 participants (35.1%) and 271 urologists (56.9%) use only TUR. High risk tumors: 397 urologists (83.4%) use adjuvant therapy, 375 (78.8%) use BCG 2 to 4 weeks after TUR, of which 306 (64.3%) referred the use for at least one year. Intravesical chemotherapy with Mitomicin C (a controversial recommendation) was used by 22 urologists (4.6%). BCG dose raised a lot of discrepancies. Induction doses of 40, 80 and 120mg were referred by 105 (22%), 193 (40.4%) and 54 (11.3%) respectively. Maintenance doses of 40, 80 and 120mg were referred by 190 (48.7%), 144 (37.0%) and 32 (8.2%) urologists, respectively. Schemes of administration were also varied and the one cited by SWOG protocol was the most used: 142 (29.8%). Conclusion SBU, EAU and AUA guidelines are partially respected by Brazilian urologists, particularly in low risk tumors. In high risk tumors, concordance rates are comparable to international data. Further studies are necessary to fully understand the reasons of such disagreement. PMID:27136464

  5. Tuberculous meningitis in children: a review of clinical, laboratory, epidemiological, and therapeutic aspects and of the usefulness of BCG vaccination Meningitis tuberculosa en niños: una revisión de aspectos clínicos, de laboratorio, epidemiológicos y terapéuticos y de la utilidad de la vacunación con BCG

    Directory of Open Access Journals (Sweden)

    José William Cornejo Ochoa

    2010-08-01

    Full Text Available

    Tuberculous meningitis is the most frequent extrapulmonary form of tuberculosis in underdeveloped countries, among them Colombia. It is associated with high rates of morbidity and mortality. In this article a review is presented of the following aspects of the disease: clinical, epidemiological, therapeutic, prophylactic by means of BCG vaccination, laboratory diagnosis, and tomographic findings.

    La tuberculosis meníngea (MTB es la enfermedad tuberculosa extrapulmonar más frecuente en los países del tercer mundo, incluida Colombia, y tiene tasas altas de morbilidad y mortalidad. En este artículo se presenta una revisión de la literatura sobre los siguientes aspectos de la enfermedad: clínicos, epidemiológicos, de laboratorio, tomográficos, terapéuticos y de prevención con la vacuna BCG.

  6. Intraurethraland Intracystal Electrocoagulation and Sodium Hyaluronate Intravesical Instillation in Treatment of Hemorrhagic Radiation Cystitis%经尿道膀胱内电灼止血及透明质酸钠膀胱灌注治疗放射性膀胱炎出血的临床研究

    Institute of Scientific and Technical Information of China (English)

    李强; 王大亚

    2015-01-01

    Objective To study clinical effect of electrocoagulation and sodium hyaluronate intravesical in⁃stillation in the treatment of hemorrhagic radiation cystitis. Methods Sixty patients with acute hemorrhage of bladder radiotherapy after surgery were randomly divided into 3 groups, 20 cases in each group; the conservative treatment group, transurethral resection of intra-bladder electrocoagulation+hyperbaric oxygen treatment group and electrocoagulation+sodium hyaluronate bladder reperfusion group. Urethral syndrome symptom score was used on the score sheet and related symptoms in patients with curative effect of the patients after treatment were observed. Results The total efficiency of transurethral hemostatic+sodium hyaluronate intravesical therapy of hemorrhagic radiation cystitis was 95%, significantly higher than those of the conservative treatment group (70%) and transurethral resection of the bladder in hemostatic+hyperbaric oxygen treatment group (80%), with statisti⁃cal significant difference, P<0.05;and transurethral hemostatic+sodium hyaluronate intravesical therapy of hem⁃orrhagic radiation cystitis FUSS scores were significantly higher than those in the conservative treatment group and transurethral resection of the bladder in hemostatic+hyperbaric oxygen treatment group, with statistically sig⁃nificant differences, P<0.05. And the use of transurethral resection of the bladder within the electrocoagulation and sodium hyaluronate intravesical therapy, patients in daytime and nighttime urination, urination urgency and urge incontinence were significantly better than those before treatment, with statistically significant differences, P<0.05. Conclusions Transurethral electrocoagulation+sodium hyaluronate intravesical therapy for hemor⁃rhagic radiation cystitis is a simple effective and practical operation, worthy for clinical promotion.%目的:探讨经尿道膀胱内电灼止血及透明质酸钠膀胱灌注治疗放射性膀胱炎出血的效

  7. Old men living alone

    DEFF Research Database (Denmark)

    Hansen, Kristian Frausing; Munk, Karen Pallesgaard

    2014-01-01

    Background: Even in the Danish welfare state inequality in health proves hard to overcome. According to the literature elderly men living alone seem to be a vulnerable group in several respects: they lead shorter lives; are at increased risk of committing suicide; and some are found to have...... dysfunctional coping patterns in relation to stress, which could indicate difficulties adapting to the challenges of old age. Moreover, as to treatment and prevention men in general do not seem to profit from the offers from the health care system as much as women do. Improving singular elderly men’s health...

  8. Living with Heart Disease

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Living With Heart Disease If you have coronary heart disease (CHD), you can take steps to control its ... the section of this article titled "How Is Heart Disease Treated?" You also can visit the Health Topics ...

  9. Living with HIV

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Syndicated Content Website Feedback HIV/AIDS Living With HIV Language: English Spanish Recommend on Facebook Tweet Share ...

  10. Living Systems Energy Module

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-26

    The Living Systems Energy Module, renamed Voyage from the Sun, is a twenty-lesson curriculum designed to introduce students to the major ways in which energy is important in living systems. Voyage from the Sun tells the story of energy, describing its solar origins, how it is incorporated into living terrestrial systems through photosynthesis, how it flows from plants to herbivorous animals, and from herbivores to carnivores. A significant part of the unit is devoted to examining how humans use energy, and how human impact on natural habitats affects ecosystems. As students proceed through the unit, they read chapters of Voyage from the Sun, a comic book that describes the flow of energy in story form (Appendix A). During the course of the unit, an ``Energy Pyramid`` is erected in the classroom. This three-dimensional structure serves as a classroom exhibit, reminding students daily of the importance of energy and of the fragile nature of our living planet. Interactive activities teach students about adaptations that allow plants and animals to acquire, to use and to conserve energy. A complete list of curricular materials and copies of all activity sheets appear in Appendix B.

  11. Thalassemia: Healthy Living

    Science.gov (United States)

    ... Thalassemia” More What can a person living with thalassemia do to stay healthy? A healthy lifestyle is ... disorder”, as well as making healthy choices. Managing Thalassemia Thalassemia is a treatable disorder that can be ...

  12. The Living Periodic Table

    Science.gov (United States)

    Nahlik, Mary Schrodt

    2005-01-01

    To help make the abstract world of chemistry more concrete eighth-grade students, the author has them create a living periodic table that can be displayed in the classroom or hallway. This display includes information about the elements arranged in the traditional periodic table format, but also includes visual real-world representations of the…

  13. Cave Dwellers’ Lives Improved

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    IN the Loess Plateau of northern Shaanxi. there are many gullies but little rain, which has deeply affected the growth of crops there. People have been living under hard conditions for generations until very recently. The State government has encouraged rural economic policies which has enabled the people of this area to develop a diversified economy that has greatly improved life.

  14. Living with Rh Incompatibility

    Science.gov (United States)

    ... Living With Rh Incompatibility If you have Rh-negative blood, injections of Rh immune globulin can reduce your ... baby or come in contact with Rh-positive blood. If you're Rh-negative, your risk of problems from Rh incompatibility is ...

  15. Learning from Live Theater

    Science.gov (United States)

    Greene, Jay P.; Hitt, Collin; Kraybill, Anne; Bogulski, Cari A.

    2015-01-01

    Culturally enriching field trips matter. They produce significant benefits for students on a variety of educational outcomes that schools and communities care about. This experiment on the effects of field trips to see live theater demonstrates that seeing plays is an effective way to teach academic content; increases student tolerance by…

  16. A "Living" Machine

    Institute of Scientific and Technical Information of China (English)

    N.R.Bogatyrev

    2004-01-01

    Biomimetics (or bionics) is the engineering discipline that constructs artificial systems using biological principles. The ideal final result in biomimetics is to create a living machine. But what are the desirable and non-desirable properties of biomimetic product? Where can natural prototypes be found? How can technical solutions be transferred from nature to technology? Can we use living nature like LEGO bricks for construction our machines? How can biology help us? What is a living machine? In biomimetic practice only some "part" (organ, part of organ, tissue) of the observed whole organism is utilized. A possible template for future super-organism extension for biomimetic methods might be drawn from experiments in holistic ecological agriculture (ecological design, permaculture, ecological engineering, etc. ). The necessary translation of these rules to practical action can be achieved with the Russian Theory of Inventive Problem Solving (TRIZ), specifically adjusted to biology. Thus, permaculture, reinforced by a TRIZ conceptual framework, might provide the basis for Super-Organismic Bionics, which is hypothesized as necessary for effective ecological engineering. This hypothesis is supported by a case study-the design of a sustainable artificial nature reserve for wild pollinators as a living machine.

  17. Moab's Living Room

    Science.gov (United States)

    Berry, John N., III

    2007-01-01

    This article describes the Grand County Public Library (GCPL) which was awarded the 2007 Best Small Library in America, an award sponsored by "Library Journal" and the Bill & Melinda Gates Foundation. Some 4800 of Grand County, Utah's 8,826 people live in Moab and the rest in the adjacent Spanish Valley and environs. The locals are a…

  18. Mitomycin C from birth to adulthood.

    Science.gov (United States)

    Serretta, Vincenzo; Scalici Gesolfo, Cristina; Alonge, Vincenza; Di Maida, Fabrizio; Caruana, Giovanni

    2016-10-04

    Mitomycin C (MMC) intravesical therapy for "superficial" papillary bladder tumors was firstly introduced in the early seventies with promising results. In the following years, several pharmacokinetic studies investigated its mechanism of action to optimize the intravesical administration. Numerous studies confirmed thereafter both the ablative and the prophylactic efficacy and the low toxicity of MMC when intravesically given. In 1984, a complete response rate of 42% in 60 patients not responsive to thiotepa was reported with intravesical MMC at the dose of 40 mg diluted in 40 ml for 8 weeks. In the following decades, many large randomized studies showed the benefit of intravesical prophylaxis with MMC versus transurethral resection (TUR) alone. Since 2002, the role of adjuvant intravesical chemotherapy and of an early MMC instillation in preventing recurrence compared with TUR alone has been confirmed by large meta-analyses and stated by the European Association of Urology (EAU) guidelines. The need for further intravesical chemotherapy after the early instillation in patients at intermediate-high risk of recurrence has been proved by several trials. Although intravesical Bacillus Calmette-Guerìn (BCG) is considered the best choice for high-risk patients and MMC for the low-risk group, both MMC and BCG can be given to prevent recurrence in intermediate-risk patients. However, the higher efficacy of BCG over MMC is evident only if maintenance regimen is administered. Despite its proven efficacy, immediate intravesical MMC is not yet fully entered in common clinical practice and efforts should be made by the urologists to optimize its adoption.

  19. A modified agar pad method for mycobacterial live-cell imaging

    Directory of Open Access Journals (Sweden)

    Robertson Brian D

    2011-03-01

    Full Text Available Abstract Background Two general approaches to prokaryotic live-cell imaging have been employed to date, growing bacteria on thin agar pads or growing bacteria in micro-channels. The methods using agar pads 'sandwich' the cells between the agar pad on the bottom and a glass cover slip on top, before sealing the cover slip. The advantages of this technique are that it is simple and relatively inexpensive to set up. However, once the cover slip is sealed, the environmental conditions cannot be manipulated. Furthermore, desiccation of the agar pad, and the growth of cells in a sealed environment where the oxygen concentration will be in gradual decline, may not permit longer term studies such as those required for the slower growing mycobacteria. Findings We report here a modified agar pad method where the cells are sandwiched between a cover slip on the bottom and an agar pad on top of the cover slip (rather than the reverse and the cells viewed from below using an inverted microscope. This critical modification overcomes some of the current limitations with agar pad methods and was used to produce time-lapse images and movies of cell growth for Mycobacterium smegmatis and Mycobacterium bovis BCG. Conclusions This method offers improvement on the current agar pad methods in that long term live cell imaging studies can be performed and modification of the media during the experiment is permitted.

  20. Observation on the Treatment Effect of Chronic Urticaria with BCG-polysaccharide Nucleic Acid Injection%卡介菌多糖核酸注射液治疗慢性荨麻疹疗效观察

    Institute of Scientific and Technical Information of China (English)

    马跃民

    2000-01-01

    目的:观察卡介菌多糖核酸注射液治疗慢性荨麻疹的疗效。方法:将门诊慢性荨麻疹患者85例分为对照组40例(男23例,女17例),给抗组胺药物及外用止痒剂等常规治疗。治疗组45例(男26例,女19例),在给抗组胺药物及外用止痒剂等常规治疗基础上加用卡介菌多糖核酸注射液。结果:治疗组有效率93.3%,对照组有效率72.5%,无副作用。结论:用卡介菌多糖核酸注射液治疗慢性荨麻疹有效、安全。%Objective: To investigate the effect of BCG-polysaccharide nucleic acid injection (BCG-PSN)on chronic urticaria. Methods: 85 cases of chronic urticaria were treated at the outpatient department. Among them 40Patients(male 23, female 17)were chosen as control. They were given routine treatment shch as antihistamine drugs and topical agents. The othet 45 patients (male 26, female 19)were included in the treatment group. In addition to the routine treatment, they received intramuscular injection of BCG-PSN. ResuIts:Toal cure rate was 93.3% in the treatment group and 72.5% in the control group. No adverse effect was observed. ConcIusion: BCG-PSN was both safe and effective in treating chronic urticaria.

  1. Effect Analysis of BCG Vaccination among Children in Hangu District of Tianjin%天津市汉沽区儿童卡介苗免疫接种效果分析

    Institute of Scientific and Technical Information of China (English)

    窦俊娟

    2011-01-01

    [Objective]To learn the immune effect of BCC vaccination among children in Hangu district of Tianjin in the past 3 years. [Methods]The PPD test results of 4281 children who have received the initial BCG vaccination were analyzed. [Results]The positive rates of PPD test of children aged 3~36 months old, 4 -5 years old and 6 ~7 years old in 2008, 2009 and 2010 were 97. 3% - 85.7% , 97.1 % ~ 83.3% and 97.2% ~90.0% respectively. [ Conclusion] The immune effect and vaccination quality of BCG vaccination among children in Hangu district of Tianjin is good in the past 3 years. The key to success of BCG vaccination is the quality of initial BCG vaccination in newboms.%目的 了解天津市汉沽辖区近3年内结核菌素儿童卡介苗接种的免疫效果.方法 对4 281名已初种卡介苗儿童结核菌素( PPD)试验结果进行分析.结果 3个月~3岁、4~5岁和6~7岁3个年龄组PPD试验阳性率,2008、2009和2010年分析为97.3%~85.7%、97.1% ~83.3%和97.2%~90.0%.结论汉沽近3年儿童卡介苗接种免疫效果较好,接种质量较高.抓好新生儿卡介苗初种质量,是提高卡介苗接种成功率的关键.

  2. Increased TNF-alpha/IFN-gamma/IL-2 and decreased TNF-alpha/IFN-gamma production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination

    Directory of Open Access Journals (Sweden)

    Mayara Fernanda Maggioli

    2016-10-01

    Full Text Available Central memory T cells (Tcm and polyfunctional CD4 T cell responses contribute to vaccine-elicited protection with both human and bovine tuberculosis (TB; however, their combined role in protective immunity to TB is unclear. To address this question, we evaluated polyfunctional cytokine responses by CD4 T cell effector / memory populations from bacille Calmette Guerin (BCG vaccinated and non-vaccinated calves prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves; only differing in magnitude (i.e., infected > vaccinated. BCG vaccination, however, did alter the kinetics of the ensuing response to virulent M. bovis infection. Early after challenge (three weeks post-infection, non-vaccinates had greater antigen-specific IFN-γ/TNF-α and lesser IFN-γ/TNF-α/IL-2 responses by Tcm cells than did vaccinated animals. Importantly, these differences were also associated with mycobacterial burden upon necropsy. Polyfunctional responses to ESAT-6:CFP10 (antigens not synthesized by BCG strains were detected in memory subsets, as well as in effector cells, as early as three weeks after challenge. These findings suggest that cell fate divergence may occur early after antigen priming in the response to bovine TB and that memory and effector T cells may expand concurrently during the initial phase of the immune response. In summary, robust IFN-γ/TNF-α response by Tcm cells is associated with greater mycobacterial burden while IFN-γ/TNF-α/IL-2 response by Tcm cells are indicative of a protective response to bovine TB.

  3. 基于波士顿矩阵法的医疗设备安全模型的建立%Research on the building of the medical equipment safety model based on BCG Matrix

    Institute of Scientific and Technical Information of China (English)

    樊廷玖; 王维红; 李婷; 周晓辉

    2013-01-01

    目的:全面、客观和真实地对在用医疗设备安全做出整体评价,从中找出设备安全管理方面的薄弱环节,为医疗设备的科学管理提供合理化方案。方法:对设备安全性指标分解、优化,从安全性和重要性两方面进行量化处理,利用波士顿矩阵(BCG Matrix)法建立设备的安全模型,对其分析并找出薄弱环节,加以重点关注与整改。结果:建立医疗设备的安全模型,能够较为客观、真实地反映在用医疗设备阶段性安全状况。结论:利用BCG Matrix法建立的医疗设备安全模型,可以用于对医疗设备安全性的量化分析。%Objective: To provide reasonable proposals for hospital administration, one whole evaluation was made in comprehensively, objectively and truthfully on the medical equipment. Methods:To optimize safety indexes of the medical equipment, the safety model was build using BCG Matrix, analyse it and find out weak link to focus on and rehabilitation it. Results: The safety of the medical equipment can be reflected in comprehensively and truthfully by means of building its safety model. Conclusion:The safety model of using BCG Matrix can be quantize and analyze the safety of the medical equipment.

  4. A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG immunisation [ISRCTN32849447

    Directory of Open Access Journals (Sweden)

    Nampijja Margaret

    2005-12-01

    Full Text Available Abstract Background Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown. Methods In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ and interleukin (IL-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP of Mycobacterium tuberculosis were measured in a whole blood assay. We analysed results for binary variables using χ2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests. Results Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021. Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013. Maternal albendazole tended to reduce these effects. Conclusion Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.

  5. Transcription analysis of the dnaA gene and oriC region of the chromosome of Mycobacterium smegmatis and Mycobacterium bovis BCG, and its regulation by the DnaA protein.

    Science.gov (United States)

    Salazar, Leiria; Guerrero, Elba; Casart, Yveth; Turcios, Lilia; Bartoli, Fulvia

    2003-03-01

    The regions flanking the Mycobacterium dnaA gene have extensive sequence conservation, and comprise various DnaA boxes. Comparative analysis of the dnaA promoter and oriC region from several mycobacterial species revealed that the localization, spacing and orientation of the DnaA boxes are conserved. Detailed transcriptional analysis in M. smegmatis and M. bovis BCG shows that the dnaN gene of both species and the dnaA gene of M. bovis BCG are transcribed from two promoters, whereas the dnaA gene of M. smegmatis is transcribed from a single promoter. RT-PCR with total RNA showed that dnaA and dnaN were expressed in both species at all growth stages. Analysis of the promoter activity using dnaA-gfp fusion plasmids and DnaA expression plasmids indicates that the dnaA gene is autoregulated, although the degree of transcriptional autorepression was moderate. Transcription was also detected in the vicinity of oriC of M. bovis BCG, but not of M. smegmatis. These results suggest that a more complex transcriptional mechanism may be involved in the slow-growing mycobacteria, which regulates the expression of dnaA and initiation of chromosomal DNA replication.

  6. Leishmania donovani-derived lipophosphoglycan plus BCG induces a Th1 type immune response but does not protect Syrian golden hamsters (Mesocricetus auratus and BALB/c mice against Leishmania donovani

    Directory of Open Access Journals (Sweden)

    W.K. Tonui

    2003-11-01

    Full Text Available The efficacy of Leishmania donovani-derived lipophosphoglycan (LPG plus Mycobacterium bovis Bacille Calmette-Guérin (BCG as a vaccine candidate against visceral leishmaniosis in susceptible BALB/c mouse and Syrian golden hamster (Mesocricetus auratus models was investigated. Following a triple vaccination with a total dose of 150 µl BCG plus 60 µg or 30 µg of LPG for hamsters and BALB/c mice respectively, there were no noticeable side effects both locally and systemically; implying that the molecule was safe at this dosage level. Vaccinated animals demonstrated an activation of both the humoral as well as cell-mediated responses to LPG, which correlated with resistance against the disease. Protection by LPG plus BCG, was however, poor as the remaining immunized animals showed disease progression leading to severity of the disease as illustrated by emaciation, mass loss and heavy splenic parasitaemia in hamsters. These data nevertheless suggest that it may be rewarding to further evaluate the potential of LPG as a vaccine candidate in leishmaniosis using other adjuvants, which may enhance its immunogenicity.

  7. 经膀胱内腹腔镜手术治疗膀胱输尿管连接处疾病%Intravesical laparoscopic procedure for patients with vesicoureteral malformations under pneumovesicum

    Institute of Scientific and Technical Information of China (English)

    何大维; 林涛; 魏光辉; 李旭良; 刘俊宏; 华燚; 刘丰

    2009-01-01

    目的 探讨经膀胱内腹腔镜治疗膀胱输尿管连接处疾病的手术技巧及适应证.方法 回顾分析30例患儿,男19例,女11例.年龄4个月~7岁.单侧输尿管末端狭窄18例(其中输尿管囊肿3例、伴发结石2例),原发性膀胱输尿管反流12例(双侧4例).在膀胱镜引导下,经膀胱顶置入5 mm目镜鞘管并固定,建立CO2气膀胱,两侧放置3~5 mm操作鞘管.术式同开放手术,术后留置导尿5~7 d.结果 29例在CO2气膀胱下完成手术,1例中转开放手术.所有病例手术时间57~260min.术后轻度血尿6例,均在2d内消失.术后随访3~26个月,21根恢复正常,9根较术前明显缩小,3根输尿管直径大于2.0 cm者,术后未裁剪部分输尿管扩张无缓解.无输尿管反流.结论 CO2>气膀胱下经膀胱内腹腔镜治疗膀胱输尿管连接处疾病是一种安全有效的手术,容易学习,具有微创优势,但是,输尿管末端结石或扩张直径大于2.0 cm者,不宜首选该术式,术中注意避免输精管损伤.%Objective To report our experience on intravesical laparoscopic Cohen ureteral reim-plantation under pneumovesicum for patients with vesicoureteral malformations. Methods Thirty cases with vesicoureteral malformations were analyzed retrospectively, including 19 boys and 11 girls aging from 4 months to 7 years. Of all the patients, 18 were diagnosed with the unilateral vesicoureteral junction obstruction (3 complicated with ureterocele and 2 with calculus), and 12 were diagnosed with primary vesicoureteral reflux (VUR, 4 in bilateral sides). The operative procedure was as follows, a 5ram port was inserted into the bladder under cystoscopic guidance. After the bladder was insufflated with CO2, 2 more working ports were inserted on both sides of the lateral bladder wall The following laparoscopic procedures were similar as the open technique, followed by bladder drainage with a ure-thral catheter for five to seven days postoperatively. Results Of all the

  8. PPD-induced monocyte mitochondrial damage is associated with a protective effect to develop tuberculosis in BCG vaccinated individuals: A cohort study

    Science.gov (United States)

    Marín, Diana; Marín, Nancy; del Corral, Helena; López, Lucelly; Ramirez-Agudelo, María Elena; Rojas, Carlos A.; Arbeláez, María P.; García, Luis F.; Rojas, Mauricio

    2017-01-01

    Introduction The mechanisms of mononuclear phagocyte death have been associated with the permissiveness and resistance to mycobacterial replication, but it remains unknown whether or not they help predict the risk of developing TB. Objective To describe the factors associated with the induction of monocyte mitochondrial and membrane damage in response to PPD as well as determine if this type of damage might predict the susceptibility of developing active tuberculosis in a cohort of household contacts (HHCs) from Medellin, Colombia from 2005 to 2008. Methods The prospective cohort study contains 2060 HHCs patients with pulmonary tuberculosis who were meticulously followed for two years. A survey of the socio-demographic, clinical, epidemiological factors and blood samples were collected. Mononuclear cell cultures were stimulated with or without PPD and the type of monocyte death was determined by the flow of cytometry, an indicator was also used for its analysis. Logistic regression was adjusted by the Generalized Estimations Equations and the survival was estimated with the Kaplan-Meier and Cox regression. Confidence intervals were used for estimating the association. Results 1,859 out of 2,060 blood samples of the HHCs patients analyzed showed monocyte death. In response to PPD, 83.4% underwent mitochondrial damage while 50.9% had membrane damage. The membrane damage in response to PPD was higher in children under 4 years (OR: 1.57; (95% CI: 1.1 to 2.4) and the HHCs who slept regularly in the same household has an index case of (OR: 1.54; 95% CI: 1.0 to 2.3). After adjustment by age, comorbidities, nutritional status, proximity to index case and overcrowding, the risk of developing active TB among BCG vaccinated HHCs individuals with induction of mitochondrial damage was HR = 0.19 (95% CI: 0.1 to 0.5). Conclusions The induction of monocytes mitochondrial damage by PPD stimulation correlates with protection of TB disease development in BCG-vaccinated HHCs. This

  9. Living in history

    DEFF Research Database (Denmark)

    Brown, Norman R.; Lee, Peter J.; Krslak, Mirna

    2009-01-01

    Foreslår et paradigme - "Living in history" - til undersøgelse af forholdet mellem samtidshistorie og selvbiografisk hukommelse. Metoden spørger ikke direkte og altså ikke til den anknytning, man bevidst ville vælge at fremhæve, men undersøger indirekte, om der spontant associeres til samtidsbegi......Foreslår et paradigme - "Living in history" - til undersøgelse af forholdet mellem samtidshistorie og selvbiografisk hukommelse. Metoden spørger ikke direkte og altså ikke til den anknytning, man bevidst ville vælge at fremhæve, men undersøger indirekte, om der spontant associeres til...

  10. Learning, Working and Living

    DEFF Research Database (Denmark)

    Andersen, Vibeke

    In the recent years, learning and knowing have emerged as key issues in understanding work organizations. Identifying ways in which learning can be supported in the workplace has been a long standing concern for organization studies and education. The book presents new ways of thinking about...... learning at work. Moreover it paves the way for the repositioning of learning, working and living in the context of organizationel complexity....

  11. Improving assisted living care.

    Science.gov (United States)

    Gregory, Nancy; Gesell, Sabina B; Widmer, Tom

    2007-01-01

    In the absence of a national measurement system, private vendors of satisfaction measurement and improvement services have played a crucial role in the quality movement in the assisted living industry. Survey responses from 175 resident-family dyads at 20 facilities were analyzed to identify priorities for service improvement from the customers' perspective. They include improving care provided by aides and management, meal service, and activities. Practical solutions for addressing these issues are presented.

  12. Readiness for Living Technology

    DEFF Research Database (Denmark)

    Peronard, Jean-Paul

    2013-01-01

    This paper is a comparative analysis between workers in healthcare with high and low degree of readiness for living technology such as robotics. To explore the differences among workers’ readiness for robotics in healthcare, statistical analysis was conducted in the data set obtained from 200...... respondents. The results showed important differences between high and low readiness types on issues such as staff security, documentation and autonomy and future challenges....

  13. Living the (codesign) lab

    DEFF Research Database (Denmark)

    Binder, Thomas; Brandt, Eva; Halse, Joachim;

    2011-01-01

    Design research environments are becoming visible in many places, in universities, in design schools, in companies and in public organizations. What most of them have in common is a commitment to the exploration of the possible rather than the factual. In this paper we will discuss what define su...... that the laboratories of design research must have a consistent portfolio yet design researchers still have to mobilize and join forces with the many “living labs” of the everyday....

  14. Live feeds in aquaculture

    OpenAIRE

    Dhert, Ph.; Sorgeloos, P

    1995-01-01

    Over the past two decades intensive larviculture of several fish and shellfish species has expanded into a multimillion dollar industry. Although much progress has been made in identifying the dietary requirements of the larvae of various aquaculture species, the mass culture of their early larval stages still requires the use of live feeds. Selected either through trial and error approaches or because of their convenience in mass production and use, hatcheries are relying today on three grou...

  15. 应用四唑鎓盐法快速检测卡介苗活菌含量%Tetrazolium salt assay for rapid determination of viable count of BCG vaccine

    Institute of Scientific and Technical Information of China (English)

    赵爱华; 贾淑珍; 寇丽杰; 乔来艳; 王国治

    2009-01-01

    目的 通过四唑鎓盐(XTT)方法 快速检测卡介苗样品中的活菌含量,结果 与传统培养法菌落形成单位计数结果 进行相关性分析,探讨应用XTT 方法 快速检测卡介苗(BCG)制品中的活菌含量的可行性.方法 活菌含量是BCG 疫苗重要的质控指标,它决定疫苗的效力.传统活菌含量的检测采用固体培养法计数菌落形成单位,但耗时长,重复性差.因此快速检测卡介苗活菌含量的方法 急需建立和应用.四唑鎓盐(XTT)由于其水溶性的显色反应能够反映细胞的活力,同样也能应用于细菌的活力检测.其原理是细菌在代谢过程中,通过氧化-还原反应将XTT 还原为可溶性的高色产物甲臢(formazan),甲臢含量反应了细菌的活菌数量.将该方法 应用于卡介苗活菌含量的快速检测中,通过已知活菌含量BCG 参考品制备活菌含量和XTT 有色产物吸光度值的参比曲线,根据未知样品的吸光度值,在此参比曲线上读出未知样品的活菌含量.同时将该快速检测方法 得到的结果 和传统培养法活菌含量结果 进行相关性分析.结果 XTT 法能反应BCG 制品中活菌的含量差异,在一定的浓度范围内,活菌含量和有色产物吸光度值间有线性关系,相关系数R2 达到0.99 以上,应用该方法 对10 批BCG 样品活菌含量进行快速检测,结果 和培养法菌落形成单位(CFU)结果 的相关系数r = 0.834,实验可在24 h 左右完成.结论XTT 法能够快速检测BCG 制品中的活菌含量,结果 与培养法菌落形成单位计数结果 有较好的相关性,实验耗时由4 周减少到24 h,该法可以用于BCG 活菌含量快速检测.

  16. 2μm激光联合丝裂霉素治疗表浅性膀胱癌的疗效分析%Study on 2μ m laser in combination with intravesical Instillation of mitomycin for treatment of superficial bladder cancer

    Institute of Scientific and Technical Information of China (English)

    王延东; 罗光恒; 杨秀书; 刘军; 陈卫红; 孙兆林

    2013-01-01

    Objectives To evaluate the safety and efficacy of 2μm laser resection in combination with intravesical instillation of mitomycin for treatment of superficial bladder cancer.Methods From June.2009 to June.2012,116 patients with superficial bladder cancer,18 cases of high grade urothelial papillary carcinoma,93 low grade urothelial papillary carcinoma and 5 papillary urothelial neoplasm with low malignant potential,were enrolled in our institute.Imaging methods including CT scan and intravenous pyelography,were performed to exclude extravesical invasion,involvement of lymph nodes and tumor in upper urinary tract.Tumors were resected successfully in patients with 2μm laser under epidural anesthesia.Immediate intravesical instillation of mitomycin was applied in all patients followed with 8 weekly and 10 monthly doses of mitomycin maintenance therapy.Results Total 201 tumors in 106 patients were resected successfully and mean operation time of every patient was 28 minutes.No obturator nerve reflex and severe perforation occurred.All patients underwent 12 months of intravesical mitomycin and tumor recurrence was found in 9.5% patients.Conclusions 2μ m laser in combination with mitomycin intravesical instillation was safe and effective for treatment of superficial bladder cancer.%目的 探讨2μm激光联合丝裂霉素治疗表浅性膀胱癌的安全性和有效性.方法 自2009年6月至2012年6月共116例表浅性膀胱癌患者入选研究,平均年龄58.3岁.其中,高级别泌尿上皮乳头状癌18例,低级别泌尿上皮乳头状癌93例,低度恶性倾向泌尿上皮乳头状瘤5例.影像学检查包括盆腔CT和排泄性尿路造影均显示没有膀胱外侵犯,淋巴结转移以及上尿路肿瘤性病变.所有患者在连续硬膜外麻醉下行2μm激光肿瘤切除,术后24h内即刻灌注撕裂霉素一次,然后1周后开始连续8周每周膀胱灌注丝裂霉素一次,然后改为每月一次维持治疗12个月.结果 116

  17. Live and let die

    DEFF Research Database (Denmark)

    Næss, Petter

    2004-01-01

    and globally solidary development appears to have declined significantly. Instead a cynicism or hostility against ?the Others? seems to gain momentum. Within the environmental discourse, such cynicism is rooted in particular in the writings of the influential American biologist Garrett Hardin, notably his 1974...... article ?Living on a Lifeboat?. Below, Hardin`s ?Lifeboat ethic? is reviewed and critically discussed, focusing on the hidden premises embedded in Hardin`s position. In the final part of the paper, the environmental consequences of economic growth and increasing consumption levels in wealthy nation