Hyperbaric oxygen therapy in BKV-associated hemorrhagic cystitis refractory to intravenous and intravesical cidofovir: case report and review of literature.

PubMed

Focosi, Daniele; Maggi, Fabrizio; Pistolesi, Donatella; Benedetti, Edoardo; Papineschi, Federico; Galimberti, Sara; Ceccherini-Nelli, Luca; Petrini, Mario

2009-04-01

Hemorrhagic cystitis is a common complication in hematopoietic stem cell transplant recipients. We report here a case of severe BKV-associated hemorrhagic cystitis who did not respond to intravenous cidofovir. Overt hematuria successfully resolved after a few days on hyperbaric oxygen and intravesical instillations of cidofovir, while BK viruria dropped after a few weeks and remained low. We review the literature for therapeutic options in hemorrhagic cystitis and try to explain how hyperbaric oxygen stimulates mucosal repair in the urinary bladder.

Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type

PubMed Central

de Padua Silva, Leandro; Patah, Poliana A.; Saliba, Rima M.; Szewczyk, Nicholas A.; Gilman, Lisa; Neumann, Joyce; Han, Xiang-Yang; Tarrand, Jeffrey; Ribeiro, Rachel; Gulbis, Alison; Shpall, Elizabeth J.; Jones, Roy; Popat, Uday; Walker, Julia A.; Petropoulos, Demetrios; Chiattone, Alexandre; Stewart, John; El-Zimaity, Maha; Anderlini, Paolo; Giralt, Sergio; Champlin, Richard E; de Lima, Marcos

2010-01-01

Background Hemorrhagic cystitis is a common cause of morbidity after allogeneic stem cell transplantation, frequently associated with BK virus infection. We hypothesized that patients with positive BK viruria before unrelated or mismatched related donor allogeneic hematopoietic stem cell transplantation have a higher incidence of hemorrhagic cystitis. Design and Methods To test this hypothesis, we prospectively studied 209 patients (median age 49 years, range 19–71) with hematologic malignancies who received bone marrow (n=78), peripheral blood (n=108) or umbilical cord blood (n=23) allogeneic hematopoietic stem cell transplantation after myeloablative (n=110) or reduced intensity conditioning (n=99). Donors were unrelated (n=201) or haploidentical related (n=8). Results Twenty-five patients developed hemorrhagic cystitis. Pre-transplant BK viruria detected by quantitative PCR was positive in 96 patients. The one-year cumulative incidence of hemorrhagic cystitis was 16% in the PCR-positive group versus 9% in the PCR-negative group (P=0.1). The use of umbilical cord blood or a haploidentical donor was the only significant predictor of the incidence of hemorrhagic cystitis on univariate analysis. There was also a trend for a higher incidence after myeloablative conditioning. Multivariate analysis showed that patients who had a positive PCR pre-transplant and received haploidentical or cord blood grafts with myeloablative conditioning had a significantly higher risk of developing hemorrhagic cystitis (58%) than all other recipients (7%, P<0.001). Conclusions Hemorrhagic cystitis is the result of a complex interaction of donor type, preparative regimen intensity, and BK viruria. PMID:20410183

Ultrasonography in the diagnosis of hemorrhagic cystitis – a complication of bone marrow transplantation in pediatric oncology patients

PubMed Central

Biel, Anna; Sokołowska-Dąbek, Dąbrówka; Olchowy, Cyprian; Łasecki, Mateusz

2014-01-01

Objective The aim of this study was to evaluate the usefulness of ultrasonography in the diagnosis of hemorrhagic cystitis following bone marrow transplantation in children. Material and methods The study involved an analysis of clinical material and the results of imaging tests performed in 334 patients who underwent hematopoietic cell transplantation. Ultrasonographic findings in 42 patients with hemorrhagic cystitis were analyzed in detail. The ultrasound images served to assess the severity of hemorrhagic cystitis and the results were compared with the clinical assessment of the disease on the Droller scale, as well as the laboratory and endoscopic tests. Results In the studied group of patients hemorrhagic cystitis following allogeneic transplantation was diagnosed in 12.5% cases. 73.8% patients received transplants from unrelated donors, 26.2% – from compatible siblings. The study revealed a higher incidence of hemorrhagic cystitis in children above 10 years of age. Grade 3 according to the Droller was diagnosed in 42.9%, grade 2 – in 30.9%, grade 4 – in 14.3%, and grade 1 – in 11.9% patients. The number of ultrasound examinations depended on the clinical symptoms, severity, duration and co-occurrence of other complications following the transplantation and was within the 1–15 range (average: 4.6). Grades 3 and 4 were related to the poor clinical condition of the patients and to their longer hospitalization. During this period there was an increased risk of renal malfunction and acute renal failure, post-inflammatory narrowing of the ureters, hydronephrosis, and in grade 4 the fibrosis of the bladder with reduced bladder capacity. Analyses demonstrated a significant correlation between the ultrasound image of the bladder wall and the clinical severity. Conclusions Ultrasound with Doppler options remains the primary diagnostic tool in the evaluation of hemorrhagic cystitis, and is useful in terms of its diagnosis, determination of the severity, and

Hemorrhagic cystitis in a patient receiving conventional doses of dacarbazine for metastatic malignant melanoma: case report and review of the literature.

PubMed

Mohammadianpanah, Mohammad; Shirazi, Mehdi; Mosalaei, Ahmad; Omidvari, Shapour; Ahmadloo, Niloofar

2007-06-01

Hemorrhagic cystitis is a potentially life-threatening complication in patients receiving cancer therapy. This urologic emergency is commonly associated with the chemotherapeutic use of oxazaphosphorine alkylating agents. This report describes a case of hemorrhagic cystitis associated with dacarbazine treatment. A 63-year-old man with asymptomatic metastatic malignant melanoma received 3 cycles of dacarbazine (600-850 mg/m2) monochemotherapy, each 3 weeks apart. Two weeks after the third cycle, he presented with gross hematuria and mild dysuria. Physical examination revealed no significant finding. Hematuria was confirmed by urinalysis, and urinary infection was excluded by repeated urine cultures. Ultrasonography revealed diffuse bladder wall thickening with no discrete mass or ulceration. Cystoscopy findings revealed generalized inflammation and edema of the mucosa of the bladder, confirming the diagnosis of hemorrhagic cystitis. The patient's gross hematuria continued for 2 weeks and then completely resolved with supportive care. Two weeks after complete resolution, the patient experienced 2 transient episodes of gross hematuria that lasted a few hours and subsided spontaneously. Dacarbazine is currently considered the standard first-line treatment in patients with advanced malignant melanoma. At standard prescribed doses (a single dose of 850-1000 mg/m2 or 250 mg/m2 for 5 days per cycle), dacarbazine is a reasonably well tolerated chemotherapeutic drug; nausea, vomiting, and myelosuppression are the most common adverse effects. Association of dacarbazine with hemorrhagic cystitis has not been reported previously (in a PubMed literature search from 1950-2006), and only 1 case report associates temozolomide (an analog of dacarbazine) with hemorrhagic cystitis. Based on the Naranjo adverse drug reactions probability scale, an objective assessment revealed dacarbazine to be a probable cause of hemorrhagic cystitis in this case. This case report suggests that

Treatment of radiation cystitis with hyperbaric oxygen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenrock, G.J.; Cianci, P.

A patient with severe radiation cystitis resistant to current therapy was treated with hyperbaric oxygen to facilitate closure of a vesicocutaneous fistula. In addition to the fistula healing, her symptoms of radiation cystitis have not recurred for over a year and a half.

Radiation-induced cystitis following intracavitary irradiation for superficial bladder cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maatman, T.J.; Novick, A.C.; Montague, D.K.

Intracavitary irradiation is effective in the treatment of noninvasive papillary transitional cell carcinoma and carcinoma in situ of the bladder. Mortality has not been associated with this form of therapy. The morbidity associated with intracavitary irradiation consists of mild to severe radiation cystitis and we report 2 such cases. One patient is from a series of 65 patients with noninvasive bladder tumors treated with intracavitary irradiation at this clinic since 1965. The second patient had noninvasive bladder tumors and was treated with intracavitary irradiation elsewhere. In both patients severe radiation cystitis subsequently developed, requiring simple cystectomy and urinary diversion. Themore » potential for this serious side effect must be considered when choosing a form of therapy for patients with noninvasive papillary transitional cell carcinoma and carcinoma in situ of the bladder.« less

Hyperbaric Oxygen Treatment in Radiation-Induced Cystitis and Proctitis: A Prospective Cohort Study on Patient-Perceived Quality of Recovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oscarsson, Nicklas, E-mail: nicklas.oscarsson@vgregion.se; Arnell, Per; Lodding, Pär

Purpose: In this prospective cohort study, the effects of hyperbaric oxygen treatment (HBOT) were evaluated concerning patient-perceived symptoms of late radiation-induced cystitis and proctitis secondary to radiation therapy for pelvic cancer. Methods and Materials: Thirty-nine patients, 35 men and 4 women with a mean age of 71 (range, 35-84) years were included after informed consent and institutional ethics approval. They had all been treated with radiation therapy for prostate (n=34), cervix (n=2), or rectal (n=3) cancer using external beam radiation at a dose of 25 to 75 Gy. Patients with hematuria requiring blood transfusion were excluded. The HBOT was deliveredmore » with 100% oxygen for 90 minutes at 2.0 to 2.4 atmospheres (ATA). Mean number of treatments was 36 (28-40). Symptoms were prospectively assessed using the Expanded Prostate Index Composite score before, during, and 6 to 12 months after HBOT. Results: The HBOT was successfully conducted, and symptoms were alleviated in 76% for patients with radiation cystitis, 89% for patients with radiation proctitis, and 88% of patients with combined cystitis and proctitis. Symptom reduction was demonstrated by an increased Expanded Prostate Index Composite score in the urinary domain from 50 ± 16 to 66 ± 20 after treatment (P<.001) and in the bowel domain from 48 ± 18 to 68 ± 18 after treatment (P<.001). For 31% of the patients with cystitis and 22% with proctitis, there were only trivial symptoms after HBOT. The improvement was sustained at follow-up in both domains 6 to 12 months after HBOT. No severe side effects were observed related to HBOT, and treatment compliance was high. Conclusions: HBOT can be an effective and safe treatment modality for late radiation therapy-induced soft tissue injuries in the pelvic region.« less

Cystitis - noninfectious

MedlinePlus

Abacterial cystitis; Radiation cystitis; Chemical cystitis; Urethral syndrome - acute; Bladder pain syndrome; Painful bladder disease complex; Dysuria - noninfectious cystitis; Frequent urination - noninfectious cystitis; Painful urination - noninfectious

Successful Treatment of BK Virus Hemorrhagic Cystitis (HC) Post Allogenic Hematopoietic Stem Cell Transplantation with Low Dose Cidofovir.

PubMed

Arora, R; Jasmita; Singh, M; Garg, A; Gupta, M; Gupta, N

2017-05-01

BK virus (BKV) hemorrhagic cystitis (HC) is a serious cause of morbidity and mortality after allogeneic hematopoietic SCT (allo-HSCT) in patients with hematological malignancies. Around half of allogenic HSCT patients present with BKV viruria at some point after HSCT; about 5-40% of these patients subsequently develop active HC. Supportive care including bladder irrigation, blood transfusions and symptomatic pain management remains the mainstay of therapy; the acyclic nucleoside analogue cidofovir is currently the front-line drug for BKV-HC treatment. Here we report the first case of severe hemorrhagic cystitis from India who was successfully treated with low dose cidofovir therapy. © Journal of the Association of Physicians of India 2011.

Extracorporeal shock wave markedly alleviates radiation-induced chronic cystitis in rat

PubMed Central

Chen, Yen-Ta; Chen, Kuan-Hung; Sung, Pei-Hsun; Yang, Chih-Chao; Cheng, Ben-Chung; Chen, Chih-Hung; Chang, Chia-Lo; Sheu, Jiunn-Jye; Lee, Fan-Yen; Shao, Pei-Lin; Sun, Cheuk-Kwan; Yip, Hon-Kan

2018-01-01

This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can effectively inhibit radiation-induced chronic cystitis (CC). Adult male Sprague-Dawley (SD) rats (n = 24) were randomly divided into group 1 (normal control), group 2 (CC induced by radiation with 300 cGy twice with a four-hour interval to the urinary bladder), group 3 [CC with ECSW treatment (0.2 mJ/mm2/120 impulses/at days 1, 7, and 14 after radiation)]. Bladder specimens were harvested by day 28 after radiation. By day 28 after radiation, the degree of detrusor contraction impairment was significantly higher in group 2 than that in groups 1 and 3, and significantly higher in group 3 than that in group 1 (P<0.0001). The urine albumin concentration expressed an opposite pattern compared to that of detrusor function among the three groups (P<0.0001). The bladder protein expressions of inflammatory (TLR-2/TLR-4/IL-6/IL-12/MMP-9/TNF-α/NF-κB/RANTES/iNOS) and oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers exhibited a pattern identical to that of urine albumin in all groups (all P<0.0001). The cellular expressions of inflammatory (CD14+/CD68+/CD74+/COX-2/MIF+/substance P+) and cytokeratin (CK13+/HMW CK+/CK+17/CK+18/CK+19) biomarkers, and collagen-deposition/fibrotic areas as well as epithelial-damaged score displayed an identical pattern compared to that of urine albumin among the three groups (all P<0.0001). In conclusion, ECSW treatment effectively protected urinary bladder from radiation-induced CC. PMID:29636892

Mucosa-sparing, KTP laser coagulation of submucosal telangiectatic vessels in patients with radiation-induced cystitis: a novel approach.

PubMed

Talab, Saman Shafaat; McDougal, W Scott; Wu, Chin-Lee; Tabatabaei, Shahin

2014-08-01

This study aimed evaluate the safety and feasibility of endoscopic potassium titanyl phosphate (KTP) laser application in the management of patients with radiation-induced hemorrhagic cystitis (RHC). We retrospectively reviewed the records of 20 patients with RHC who underwent endoscopic KTP laser ablation of telangiectatic bladder vessels between October 2005 and January 2013. After initial cystoscopy, KTP laser was used to ablate the submucosal vasculature while preserving the overlying mucosa. The surgical outcome was evaluated by duration of hematuria-free interval, number of episodes of hematuria, and number of required medical and/or surgical interventions after initial treatment. Overall, 20 patients underwent 26 sessions of KTP laser ablation of bladder vessels. The procedure was able to stop bleeding 92% of the time and the average hematuria-free interval after ablation was 11.8 months, with a range of 1-37 months. In 13 patients (65%) hematuria resolved after 1 session of KTP laser treatment, whereas 5 patients (25%) required multiple sessions. Two patients (10%) with severe hematuria continued to have bleeding after laser treatment, which necessitated proximal diversion of urine with percutaneous nephrostomy tubes to control bleeding. This study suggests that KTP laser, with its unique photoselectivity property, is a safe, effective, and durable treatment with minimal side effects for ablation of submucosal bladder vessels in patients with RHC. Copyright © 2014 Elsevier Inc. All rights reserved.

Polyomavirus BK: possibly associated skin eruption in a patient with hemorrhagic cystitis.

PubMed

Medeiros, Patricia V; Abagge, Kerstin T; Carvalho, Vânia O; Bonfim, Carmem M; Raboni, Sonia M

2011-01-01

A 14-year-old girl with Fanconi anemia was submitted to allogeneic hematopoietic stem cell transplantation. After 17 days she developed hemorrhagic cystitis due to polyoma BK virus (BKV), confirmed by PCR (polymerase chain reaction). Two weeks after the appearance of the urinary symptoms the patient presented numerous papules and vesicles on both hands and feet. PCR of the skin lesions and plasma was positive for BKV. The relationship of BKV with frequent infections in immunocompromised patients is well established. The positive PCR of vesicular fluid suggests that this was the causative agent of the skin lesion in this case. There are no reports of skin lesions with positive PCR for BKV. © 2011 Wiley Periodicals, Inc.

Computed tomography findings of human polyomavirus BK (BKV)-associated cystitis in allogeneic hematopoietic stem cell transplant recipients.

PubMed

Schulze, M; Beck, R; Igney, A; Vogel, M; Maksimovic, O; Claussen, C D; Faul, C; Horger, M

2008-12-01

Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and increased mucosal enhancement. These findings are not specific for

Early urinary diversion with ileal conduit and vesicovaginostomy in the treatment of radiation cystitis due to carcinoma cervix: a study from a tertiary care hospital in South India.

PubMed

Banerji, John Samuel; Devasia, Antony; Kekre, Nitin Sudhakar; Chacko, Ninan

2015-10-01

To study the magnitude of radiation cystitis following radiation therapy for carcinoma cervix, and propose an algorithm to decide on early diversion, with or without vesicovaginostomy. Women who developed radiation cystitis following radiotherapy for carcinoma cervix from January 1998 to December 2011 were included in this retrospective study. Electronic hospital records were analysed to document the presence of radiation cystitis. All women who developed evidence of radiation-induced cystitis, according to the common toxicity and Radiation Therapy Oncology Group criteria, were included in the study. We looked at transfusion requirements, number of hospital admissions, quality of life and cost involved. Chi-square tests were done where applicable. SPSS version 16 was used for analysis. Of the 902 patients who received radiation for carcinoma cervix in the 13-year period, 62 (6.87%) developed grade 3/4 cystitis. Twenty-eight of them underwent ileal conduit diversion, with 18 undergoing concomitant vesicovaginostomy. When compared with the patients who did not have diversion, the transfusion requirements, number of hospital admissions and quality of life had a statistically significant difference. Cost analysis of early diversion too showed a marginal benefit with early diversion. The limitation of the study was that it was retrospective in nature. In radiation cystitis, multiple hospital admissions and consequential increase in cost is the norm. In severe disease, early diversion is a prudent, cost-effective approach with good quality of life and early return to normal activity. © 2014 Royal Australasian College of Surgeons.

Hyperbaric oxygen therapy (HBOT) in case of hemorrhagic cystitis after radiotherapy

PubMed Central

Klejnotowska, Alicja; Matuszewski, Marcin; Sicko, Zdzislaw; Markuszewski, Marcin; Krajka, Kazimierz

2012-01-01

Introduction We present the effect of hyperbaric oxygen therapy (HBOT) after radiotherapy for cancer in the pelvic cavity resulting in hematuria. Increasing the pressure of oxygen (PO2) in ischemic tissues favors the formation of new blood vessels and increases the secretion of collagen. Material and methods We evaluated 10 patients who were treated with HBOT from October 2006 to December 2010 due to persistent radiation damage to the lining of the bladder leading to recurrent hematuria. The study group was comprised of seven men and three women. In the case of cervical and endometrial cancers, 30 Gy of brachytherapy with 45-50 Gy of teleradiotherapy were used. In prostate cancer (PCa), we applied 50 Gy of teleradiotherapy with an additional dose of 20-24 Gy, and in the case of bladder cancer (BCa), 50 Gy of teleradiotherapy was applied with an additional dose of 16 Gy. HBOT consisted of 60 HBO2 treatments, in which patients were administered 100% oxygen at a pressure of 2.5 atm. Results The group effect of total or partial resolution was observed in six patients. In one case, treatment was discontinued due to an increase in hematuria and the consequent suspicion of bladder tumor recurrence. While in and additional three cases, the treatment did not produce the desired result. Conclusions Treatment of hemorrhagic cystitis is a difficult therapeutic challenge. One possible method is the implementation of HBOT. In very difficult cases, HBO2 treatment appears to be effective in giving more than half of patients a chance of getting better. PMID:24578962

Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation.

PubMed

Gorczynska, Ewa; Turkiewicz, Dominik; Rybka, Katarzyna; Toporski, Jacek; Kalwak, Krzysztof; Dyla, Agnieszka; Szczyra, Zofia; Chybicka, Alicja

2005-10-01

We analyzed the incidence, etiology, risk factors, and clinical management of hemorrhagic cystitis (HC) in 102 children who underwent allogeneic stem cell transplantation: 28 from matched siblings, 57 from unrelated donors, and 17 from mismatched relatives. Conditioning regimens consisted of high-dose chemotherapy (n=83) or total body irradiation (n=19). In all children, urine and plasma were prospectively screened for human polyomavirus (HPV; BK virus [BKV] and JC virus [JCV]) or adenovirus (AdV) DNA with a polymerase chain reaction-based assay. Viral DNA was detected in the urine of 56 children (54.9%): BKV in 48 (47%), JCV in 4 (3.9%), and AdV in 4 (3.9%). HC occurred in 26 children (25.5%), and viruria was detected in all of them: BKV in 21 (80.8%), AdV in 4 (14.4%), and JCV in 1 (3.8%). All patients with AdV viruria developed HC. The cumulative incidence of HC in patients with HPV viruria was 0.43. The only significant risk factor for HC in patients with HPV-positive urine was conditioning with high-dose chemotherapy. Twenty-two children were treated with cidofovir, with no significant toxicity. In all treated patients but 1, the clinical symptoms were moderate, and no HC-related death was observed. We conclude that virus-induced HC is a frequent complication after allogeneic hematopoietic cell transplantation. Treatment with cidofovir is feasible, and further studies are warranted to evaluate its activity in HC mediated by BKV or JCV.

A retrospective study of treatment and prophylaxis of ifosfamide-induced hemorrhagic cystitis in pediatric and adolescent and young adult (AYA) patients with solid tumors.

PubMed

Saito, Yoshimasa; Kumamoto, Tadashi; Makino, Yoshinori; Tamai, Ikumi; Ogawa, Chitose; Terakado, Hiroyuki

2016-09-01

Ifosfamide (IFO) is considered an essential drug for the treatment of pediatric, adolescent and young adult patients with solid tumors. Hemorrhagic cystitis (HC) is one of the dose-limiting toxicity of IFO. However, there are insufficient evidence for risk factor and supportive care of IFO-induced HC. In this retrospective study, patients (<30-year-old) with malignant solid tumors who had been treated with IFO-based chemotherapy, were categorized according to the presence or absence of HC, and were analyzed possible risk factors for IFO-induced HC. In our institution, continuous hydration to increase urine output and intravenous 2-mercaptethane sulfonate (mesna) are used for prophylaxis of IFO-induced HC. Increased hydration and dosage of mesna are administered to patients who develop IFO-induced HC; they also receive 24-h continuous infusion of mesna in subsequent treatment cycles. Nine treatment regimens were used in the 70 study patients. The range of daily IFO dosage was 1.2-3.0 g/m(2). HC occurred in 14/425 IFO-based chemotherapy cycles (3.3%). The daily IFO dosages (mean ± SD) in patients with or without HC were 2.23 ± 0.58 g/m(2) and 1.85 ± 0.50 g/m(2), respectively (P = 0.006). Only one of the nine patients who developed IFO-induced HC had experienced this complication in a subsequent cycle of treatment. The incidence of IFO-induced HC may be associated with the dosage of IFO. When administering IFO higher than 2.0 g/m(2)/day, the volume of hydration, dosage of mesna and duration of mesna infusion should be increased to prevent HC. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

BKV infection and hemorrhagic cystitis after allogeneic bone marrow transplant.

PubMed

Fioriti, D; Degener, A M; Mischitelli, M; Videtta, M; Arancio, A; Sica, S; Sora, F; Pietropaolo, V

2005-01-01

Hemorrhagic cystitis (HC) is a well-known complication after allogeneic bone marrow transplant (BMT) and can be related to adenovirus or human polyomavirus BK (BKV) infections. In this study a group of 20 patients after allogeneic BMT has been examined. BMT urine samples were analysed for the presence of Adenovirus and BKV DNAby means of polymerase chain reaction (PCR). 5/20 BMT patients developed HC after BMT. The presence of BKV DNA in urine samples was evident in 3/15 patients without HC and in 5/5 patients with HC. In 2/5 HC-patients the BKV DNA was not found after therapy with Cidofovir and Ribavirin. The search for adenovirus DNA in all samples was negative. The analysis of BKV non-coding control region (NCCR) isolated from urine samples revealed a structure very similar to the archetype in all samples. The RFLP (Restriction Fragment Length Polymorphism assay) showed the presence of BKV subtypes I and IV, with the prevalence of subtype I (4/5). This study supports the hypothesis that HC is mainly related to BKV rather than to adenovirus infection in BMT patients. Moreover, since BKV subtype I was predominant, it is reasonable to hypothesize that a specific BKV subtype could be associated with the development of HC.

Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation.

PubMed

Bogdanovic, G; Priftakis, P; Giraud, G; Kuzniar, M; Ferraldeschi, R; Kokhaei, P; Mellstedt, H; Remberger, M; Ljungman, P; Winiarski, J; Dalianis, T

2004-11-01

BK virus (BKV) load in urine alone or in combination with acute graft-versus-host disease (GVHD) was correlated to development of hemorrhagic cystitis (HC). BKV load in combination with acute GVHD discriminated the best, while BKV and viral load alone, but not GVHD, still showed predictive ability for HC.

The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide-Induced Cystitis in Rats

PubMed Central

Moraes, Janaína P.; Pereira, Denyson S.; Matos, Alexandre S.; Santana, Danielle G.; Santos, Cliomar A.; Estevam, Charles S.; Fakhouri, Ricardo; de Lucca Junior, Waldecy; Camargo, Enilton A.

2013-01-01

Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400 mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx − were also evaluated. Treatment with EECp (100–400 mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx − induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100 mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats. PMID:24348180

Association between a High BK Virus Load in Urine Samples of Patients with Graft-Versus-Host Disease and Development of Hemorrhagic Cystitis after Hematopoietic Stem Cell Transplantation

PubMed Central

Bogdanovic, G.; Priftakis, P.; Giraud, G.; Kuzniar, M.; Ferraldeschi, R.; Kokhaei, P.; Mellstedt, H.; Remberger, M.; Ljungman, P.; Winiarski, J.; Dalianis, T.

2004-01-01

BK virus (BKV) load in urine alone or in combination with acute graft-versus-host disease (GVHD) was correlated to development of hemorrhagic cystitis (HC). BKV load in combination with acute GVHD discriminated the best, while BKV and viral load alone, but not GVHD, still showed predictive ability for HC. PMID:15528753

BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation.

PubMed

Iwamoto, Shotaro; Azuma, Eiichi; Hori, Hiroki; Hirayama, Masahiro; Kobayashi, Michihiro; Komada, Yoshihiro; Nishimori, Hisashi; Miyahara, Masazumi

2002-06-01

The human polyomavirus BK (BKV)-associated hemorrhagic cystitis (HC) has been a frequent and, seldom life-threatening complication after bone marrow transplantation (BMT). The authors report a male with melodysplastic syndrome, who developed BKV-associated late-onset HC 12 days after HLA-matched unrelated BMT. His urine contained epithelial cells with intranuclear inclusion bodies suggestive of BKV infection and was positive for BKV in polymerase chain reaction. He did not respond to any treatment for HC. In addition, he developed BKV-associated acute renal failure on day 26, followed by hepatic veno-occlusive disease on day 42. This is the first case in which BKV may be associated with fatal progressive renal failure.

Low-dose cidofovir treatment of BK virus-associated hemorrhagic cystitis in recipients of hematopoietic stem cell transplant.

PubMed

Savona, M R; Newton, D; Frame, D; Levine, J E; Mineishi, S; Kaul, D R

2007-06-01

In recipients of hematopoietic stem cell transplants (HSCTs), BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC). In our institution, HSCT recipients with BKV-associated HC are treated with 1 mg/kg of cidofovir weekly. We identified HSCT recipients with BKV-associated HC, treated with weekly cidofovir. Microbiological response was defined as at least a one log reduction in urinary BKV viral load; clinical response was defined as improvement in symptoms and stability or reduction in the grade of cystitis. Nineteen allogeneic HSCT patients received a mean of 4.5 weekly doses of cidofovir. HC occurred at a mean of 68.7 days after transplant. A clinical response was detected in 16/19 (84%) patients, and 9/19 (47%) had a measurable microbiological response (8/10 nonresponders had a BKV viral load above the upper limit of the assay before treatment). Fourteen out of nineteen (74%) patients had no significant increase in serum creatinine. Five patients with renal dysfunction resolved after completion of the therapy and removal of other nephrotoxic agents. We conclude that weekly low-dose cidofovir appears to be a safe treatment option for BKV-associated HC. Although the efficacy of low-dose cidofovir is not proven, a prospective trial is warranted.

BK virus-hemorrhagic cystitis following allogeneic stem cell transplantation: Clinical characteristics and utility of leflunomide treatment.

PubMed

Park, Young Hoon; Lim, Joo Han; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo

2016-04-18

BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. From January 2005 to June 2014, among the 69 patients underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Hemorrhagic cystitis (HC) was observed in 30 patients (43.5%), and among them, 18 patients (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (range, 13-63). Patients received Allo-SCT from acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1).The donor types were a HLA-matched sibling donor for 6 patients, HLA-matched unrelated donor for 9, and a haploidentical familial donor for 2. The median onset and duration of BKV-HC was on day 21 (range, 7-97) after transplantation and 22 days (range, 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response (CR), one partial response (PR), and five no response (NR). Among the five non-responders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, with achieving CR (n=2) and PR (n=2). The median duration from the start of leflunomide therapy to response was 13 days (range, 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who fail supportive care, leflunomide may be a feasible option without significant toxicity.

Presence of human polyomavirus DNA in the peripheral circulation of bone marrow transplant patients with and without hemorrhagic cystitis.

PubMed

Bogdanovic, G; Ljungman, P; Wang, F; Dalianis, T

1996-04-01

In BMT patients, shedding of BK virus (BKV) in the urine has been strongly but not absolutely correlated to hemorrhagic cystitis (HC). The possible presence of human polyomaviruses in peripheral blood leukocytes (PBLs), plasma, serum and urine in BMT patients and an association with HC was investigated by a nested PCR assay. Samples from allogeneic BMT patients with and without HC as well as from autologous BMT patients were analyzed. Human polyomaviruses were detected in urine and blood samples of both allogeneic and autologous BMT patients with and without HC. An association between the presence of a specific human polyomavirus in blood and HC was thus not observed.

BK virus-associated hemorrhagic cystitis in pediatric cancer patients receiving high-dose cyclophosphamide.

PubMed

Cheerva, Alexandra C; Raj, Ashok; Bertolone, Salvatore J; Bertolone, Kathy; Silverman, Craig L

2007-09-01

Hemorrhagic cystitis (HC) is a known complication of oxazophosphorine chemotherapy. BK virus (BKV) has been commonly found to be associated with hematuria in stem cell transplant patients; however, it has rarely been reported after cyclophosphamide chemotherapy alone. The authors present 3 cases of BK viruria with HC in nontransplant pediatric oncology patients. The 3 patients with BKV had more prolonged hematuria (14 to 16 wk) compared with 1 patient with BKV-negative HC (10 wk). The HC necessitated chemotherapy delays and also prolonged supportive care. One patient was treated with intravenous cidofovir with resolution of BK viruria and hematuria. BKV may have an association with the development of HC in nonstem cell transplant patients receiving high-dose oxazophosphorine chemotherapy. HC may present early and be more prolonged in patients with BK viruria. Patients with HC after cyclophosphamide or ifosfamide with negative bacterial cultures should be studied for BKV. Cidofovir may be beneficial in certain patients with BK viruria and HC; however, definitive data will require a clinical trial.

Successful hyperbaric oxygen therapy for refractory BK virus-associated hemorrhagic cystitis after cord blood transplantation.

PubMed

Hosokawa, K; Yamazaki, H; Nakamura, T; Yoroidaka, T; Imi, T; Shima, Y; Ohata, K; Takamatsu, H; Kotani, T; Kondo, Y; Takami, A; Nakao, S

2014-10-01

BK virus-associated hemorrhagic cystitis (BKV-HC) is a common and major cause of morbidity in recipients of allogeneic hematopoietic stem cell transplantation. A 32-year-old woman developed severe BKV-HC on day 24 after cord blood transplantation (CBT). Despite supportive therapies - such as hyperhydration, forced diuresis, and urinary catheterization - macroscopic hematuria and bladder irritation persisted for over a month. Hyperbaric oxygen (HBO) therapy at 2.1 atmospheres for 90 min per day was started on day 64 after CBT. Macroscopic hematuria resolved within a week, and microscopic hematuria was no longer detectable within 2 weeks. Hematuria did not recur after 11 sessions of HBO therapy, and no significant side effects were observed during or after treatment. HBO therapy could thus be useful in controlling refractory BKV-HC after CBT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ketamine-snorting associated cystitis.

PubMed

Chen, Chung-Hsien; Lee, Ming-Huei; Chen, Yi-Chang; Lin, Ming-Fong

2011-12-01

Ketamine hydrochloride, commonly used as a pediatric anesthetic agent, is an N-methyl-D-aspartic (NMDA) acid receptor antagonist with rapid onset and short duration of action. It produces a cataleptic-like state where the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. It has emerged as an increasingly popular choice among young drug users, especially within dance club venues. Cases of bladder dysfunction among recreational ketamine users were reported since Shahani et al first reported nine cases of ketamine-associated ulcerative cystitis in 2007. We report on four patients who had history of ketamine abuse, presenting with dysuria, fluctuating lower urinary tract symptoms (LUTS), lower abdominal or perineal pain, and impaired functional bladder capacities. Urinalysis showed pyuria and microhematuria. Urine culture was sterile. Bladder ulceration with severe diffuse hemorrhage and low bladder capacity were noted under anesthetized cystoscopic examination. Transurethral bladder mucosa biopsy was consistent with chronic cystitis. Cessation of ketamine abuse was the milestone of treatment, followed by the administration of mucosal protective agents, such as pentosan polysulphate or hyaluronic acid. Suprapubic pain was improved in three patients during follow-up. However, the outcome of treatment depends on the severity of the disease process, similar to that of interstitial cystitis (IC). Copyright © 2011. Published by Elsevier B.V.

BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: treatment response and evidence for nosocomial transmission.

PubMed

Koskenvuo, Minna; Dumoulin, Alexis; Lautenschlager, Irmeli; Auvinen, Eeva; Mannonen, Laura; Anttila, Veli-Jukka; Jahnukainen, Kirsi; Saarinen-Pihkala, Ulla M; Hirsch, Hans H

2013-01-01

BK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads. Characterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment. By prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments). Decreasing BKV viremia of>2log(10)copies/mL and clinical resolution was seen in 4 patients over 5-12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patients The data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir. Copyright © 2012 Elsevier B.V. All rights reserved.

Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation

PubMed Central

Lee, Seung-Shin; Jung, Sung-Hoon; Ahn, Seo-Yeon; Kim, Jae-Yong; Jang, Hee-Chang; Kang, Seung-Ji; Jang, Mi-Ok; Yang, Deok-Hwan; Kim, Yeo-Kyeoung; Lee, Je-Jung; Kim, Hyeoung-Joon

2015-01-01

Background/Aims BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. Methods Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. Results Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. Conclusions Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC. PMID:25750563

Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation.

PubMed

Lee, Seung-Shin; Ahn, Jae-Sook; Jung, Sung-Hoon; Ahn, Seo-Yeon; Kim, Jae-Yong; Jang, Hee-Chang; Kang, Seung-Ji; Jang, Mi-Ok; Yang, Deok-Hwan; Kim, Yeo-Kyeoung; Lee, Je-Jung; Kim, Hyeoung-Joon

2015-03-01

BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.

Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

PubMed

Savva-Bordalo, J; Pinho Vaz, C; Sousa, M; Branca, R; Campilho, F; Resende, R; Baldaque, I; Camacho, O; Campos, A

2012-08-01

Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90 min, 5 days per week, with a median 13 treatments (range, 4-84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition.

Photoselective Vaporisation of the Bladder for the Management of Radiation Cystitis - Technique and Initial Outcomes.

PubMed

Pascoe, Claire; Christidis, Daniel; Manning, Todd; Lamb, Benjamin W; Murphy, Declan G; Lawrentschuk, Nathan

2018-05-16

Objective To describe our technique utilising photoselective vaporisation of the bladder (PVB) for the management of haemorrhagic cystitis and initial results of 12 patients. Materials and Method An audit of theatre records of a single surgeon was performed to identify patients who had undergone PVB for management of radiation-cystitis. Rigid cystoscopy was performed. Ureteric catheters were placed and active bleeding sites targeted to optimise vision. Ablation was commenced using the vaporize function. When lasering around delicate structures the coagulation function was used. Ureteric catheters remained in situ for 24h. An 18Fr Foley catheter was placed. When urine output was clear continuous bladder irrigation was ceased. Both uretetric catheters and Foley catheter were removed prior to the 24hour mark. Results 12 patients were identified. 8 had previously required blood transfusion secondary to bladder haemorrhage. 9 were successfully treated and 2 saw improvement in haematuria but required a repeat procedure at 3 weeks post operatively. 4 went on to receive hyperbaric oxygenation as consolidative therapy. 1 patient was unsuccessfully treated and went on to cystectomy. There were no mortalities. No patients sustained bladder perforation or damage to surrounding structures. Conclusion Radiation cystitis can be life threatening and remains a challenge for the urologist with traditional intra-vescical treatments such as aluminium or formalin having variable results. We present an alternate technique using PVB to ablate the bladder mucosa, with good results. Consolidation with hyperbaric oxygen therapy may be considered. Our study is limited by small sample size and the presence of bilateral ureteric catheters leaving the bladder free from urine may impact immediate post operative outcomes. These initial results are promising however further prospective evaluation with a larger cohort and pre and post operative cystograms would enable better evaluation of this

Cidofovir for BK virus-associated hemorrhagic cystitis: a retrospective study.

PubMed

Cesaro, Simone; Hirsch, Hans H; Faraci, Maura; Owoc-Lempach, Joanna; Beltrame, Angela; Tendas, Andrea; Baltadakis, Ioannis; Dalle, Jean-Hughes; Koc, Yener; Toporski, Jacek; Styczynski, Jan; Yesilipek, M Akif; Heinz, Werner; Caniglia, Maurizio; Rascon, Jelena; Fauser, Axel A; Michallet, Mauricette; Lopez-Corral, Lucia; Neuburger, Stefan; Tridello, Gloria; Einsele, Herman

2009-07-15

BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P = .01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P = .001 and P = .001, respectively). Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.

HEMORRHAGIC CYSTITIS AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION: RISK FACTORS, GRAFT SOURCE, AND SURVIVAL

PubMed Central

Lunde, Laura E.; Dasaraju, Sandhyarani; Cao, Qing; Cohn, Claudia S.; Reding, Mark; Bejanyan, Nelli; Trottier, Bryan; Rogosheske, John; Brunstein, Claudio; Warlick, Erica; Young, Jo Anne H.; Weisdorf, Daniel J.; Ustun, Celalettin

2017-01-01

Although hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic cell transplantation (alloHCT), its risk factors and effects on survival are not well-known. We evaluated HC in a large cohort (n=1321, 2003 – 2012) receiving alloHCT from all graft sources, including umbilical cord blood (UCB). We compared HC patients with non-HC (control) patients and examined clinical variables at HC onset and resolution. Of these 1321 patients, 219 (16.6%) developed HC at a median of 22 days after alloHCT. BK viruria was detected in 90% of 109 tested HC patients. Median duration of HC was 27 days. At the time of HC diagnosis, acute graft-versus-host disease (GVHD), fever, severe thrombocytopenia, and steroid use were more frequent than at the time of HC resolution. In univariate analysis, male sex, age <20 years, myeloablative conditioning with cyclophosphamide and acute GVHD were associated with HC. In multivariate analysis, HC was significantly more common in males and HLA-mismatched UCB graft recipients. Severe grade HC (grade III–IV) was associated with increased treatment-related mortality (TRM) but not with overall survival at 1 year. HC remains hazardous and therefore better prophylaxis and early interventions to limit its severity are still needed. PMID:26168069

Expression and function of transforming growth factor-β isoforms and cognate receptors in the rat urinary bladder following cyclophosphamide-induced cystitis

PubMed Central

Gonzalez, Eric J.; Girard, Beatrice M.

2013-01-01

Numerous proinflammatory cytokines have been implicated in the reorganization of lower urinary tract function following cyclophosphamide (CYP)-induced cystitis. The present study investigated the functional profile of three pleiotropic transforming growth factor-β (TGF-β) isoforms and receptor (TβR) variants in the normal and inflamed (CYP-induced cystitis) rat urinary bladder. Our findings indicate that TGF-β (1, 2, and 3) and TβR (1, 2, and 3) transcript and protein expression were regulated to varying degrees in the urothelium or detrusor smooth muscle following intermediate (48 h; 150 mg/kg ip) or chronic (75 mg/kg ip; once every 3 days for 10 days), but not acute (4 h; 150 mg/kg ip), CYP-induced cystitis. Conscious, open-outlet cystometry was performed to determine whether aberrant TGF-β signaling contributes to urinary bladder dysfunction following intermediate (48 h) CYP-induced cystitis. TβR-1 inhibition with SB505124 (5 μM) significantly (p ≤ 0.001) decreased voiding frequency and increased bladder capacity (2.5-fold), void volume (2.6-fold), and intercontraction intervals (2.5-fold) in CYP-treated (48 h) rats. Taken together, these results provide evidence for 1) the involvement of TGF-β in lower urinary tract neuroplasticity following urinary bladder inflammation, 2) a functional role of TGF-β signaling in the afferent limb of the micturition reflex, and 3) urinary bladder TβR-1 as a viable target to reduce voiding frequency with cystitis. PMID:23926183

Adenovirus is a key pathogen in hemorrhagic cystitis associated with bone marrow transplantation.

PubMed

Akiyama, H; Kurosu, T; Sakashita, C; Inoue, T; Mori Si; Ohashi, K; Tanikawa, S; Sakamaki, H; Onozawa, Y; Chen, Q; Zheng, H; Kitamura, T

2001-05-01

Late-onset hemorrhagic cystitis (HC) is a well-known complication of bone marrow transplantation (BMT) that is mainly attributed to infection with BK virus (BKV) and adenovirus (AdV). From 1986 through 1998, 282 patients underwent BMT, and 45 of them developed HC. Urine samples tested positive for AdV in 26 patients, of which 22 showed virus type 11. Among patients who underwent allogeneic BMT, logistic regression analysis revealed acute graft-versus-host disease (grade, > or = 2) to be the most significant predictive factor for HC (P < .0001). In addition, a total of 193 urine samples regularly obtained from 26 consecutive patients who underwent allogeneic BMT were examined for BKV, JC virus (JCV), and AdV by means of polymerase chain reaction. Of patients without HC, approximately 30% of the specimens tested positive for BKV (58 samples) and JCV (55 samples), whereas 5 (3%) tested positive for AdV. Of the 3 samples obtained from patients with HC, the numbers of positive results for BKV, JCV, and AdV were 3, 1, and 1, respectively; the numbers of positive results increased to 14 of 17, 9 of 17, and 10 of 17, respectively, when we added another 14 samples obtained from 14 patients with HC (P < .0001, P = .026, and P < .0001, respectively). In conclusion, there was significant correlation between AdV and HC in the patients we studied.

Interstitial cystitis - resources

MedlinePlus

Resources - interstitial cystitis ... The following organizations are good resources for information on interstitial cystitis : Interstitial Cystitis Association -- www.ichelp.org National Institute of Diabetes and Digestive and Kidney Diseases -- www. ...

Delayed hemorrhage after surgery and radiation in suprasellar pilocytic astrocytomas

PubMed Central

Turel, Mazda K.; Kiehl, Tim-Rasmus; Gentili, Fred

2016-01-01

Delayed intracranial hemorrhage is a rare complication of treatment for central nervous system tumors. This may be secondary to malignant transformation of the tumor or vasculopathy related to radiation therapy (RT). While most reports on radiation-induced vasculopathy in children with optic pathway gliomas are associated with ischemic complications, there are only two reports of hemorrhagic complications in these patients. In both cases, the hemorrhage was asymptomatic and remote from the site of the original tumor but within the field of irradiation. We describe a female patient who underwent surgery for an optico-chiasmatic pilocytic astrocytoma (PA) at the age of 12 followed by RT at the age of 17 for tumor progression. The patient was followed with serial magnetic resonance imaging (MRI) scans showing marginal regression and no subsequent evidence of tumor recurrence, including the most recent MRI done only 6 months before the latest presentation. She then developed a symptomatic intratumoral hemorrhage at the age of 32 for which she underwent emergent surgery. To our knowledge, this is the first report of a nonaneurysmal-delayed hemorrhage within the site of previous surgery, several years after RT for a suprasellar PA. We review literature on delayed vasculopathy following the treatment of pediatric optic pathway gliomas and discuss the possible mechanisms of hemorrhage in our case. These long-term follow-up outcomes add significant insight and have implications in patient management. PMID:27857781

Levofloxacin for the treatment of severe refractory BK virus-associated hemorrhagic cystitis in hematopoietic stem cell transplantation recipients: A report of three cases.

PubMed

Toptas, Tayfur; Kaygusuz-Atagunduz, Isik; Kani, Haluk Tarik; Adiguzel, Cafer; Firatli-Tuglular, Tulin

2014-10-01

BK-virus (BKV) is an important etiological agent for late-onset hemorrhagic cystitis (HC) in patients undergoing hematopoietic stem cell transplantation. Late-onset HC causes significant morbidity among these patients. Therapeutic approaches remain predominantly symptomatic. Several treatment options have been used with variable success rates. Cidofovir has the highest specificity against BKV; however, its lack of availability in the majority of countries, high costs and potential nephrotoxic effects limit its use. The present study reports three cases of severe and prolonged BKV-associated HC (BKHC). HC was resolved in all three of the patients using oral levofloxacin. Thus, levofloxacin may be an effective treatment modality for achieving complete clinical and molecular response in patients with refractory, severe BKHC.

Effects of CYP-Induced Cystitis on Growth Factors and Associated Receptor Expression in Micturition Pathways in Mice with Chronic Overexpression of NGF in Urothelium.

PubMed

Girard, Beatrice M; Malley, Susan; May, Victor; Vizzard, Margaret A

2016-08-01

We have determined if cyclophosphamide (CYP)-induced cystitis produces additional changes in growth factor/receptors expression in the urinary bladder (urothelium, detrusor) and lumbosacral (L6-S1) dorsal root ganglia (DRG) in a transgenic mouse model with chronic urothelial overexpression of NGF (NGF-OE). Functionally, NGF-OE mice treated with CYP exhibit significant increases in voiding frequency above that observed in control NGF-OE mice (no CYP). Quantitative PCR was used to determine NGF, BDNF, VEGF, and receptors (TrkA, TrkB, p75(NTR)) transcripts expression in tissues from NGF-OE and wild-type (WT) mice with CYP-induced cystitis of varying duration (4 h, 48 h, 8 days). In urothelium of control NGF-OE mice, NGF mRNA was significantly (p ≤ 0.001) increased. Urothelial expression of NGF mRNA in NGF-OE mice treated with CYP (4 h, 48 h, 8 days) was not further increased but maintained with all durations of CYP treatment evaluated. In contrast, CYP-induced cystitis (4 h, 48 h, 8 days) in NGF-OE mice demonstrated significant (p ≤ 0.05) regulation in BDNF, VEGF, TrkA, TrkB, and P75(NTR) mRNA in urothelium and detrusor smooth muscle. Similarly, CYP-induced cystitis (4 h, 48 h, 8 days) in NGF-OE mice resulted in significant (p ≤ 0.05), differential changes in transcript expression for NGF, BDNF, and receptors (TrkA, TrkB, p75(NTR)) in S1 DRG that was dependent on the duration-of CYP-induced cystitis. In general, NGF, BDNF, TrkA, and TrkB protein content in the urinary bladder increased in WT and NGF-OE mice with CYP-induced cystitis (4 h). Changes in NGF, TrkA and TrkB expression in the urinary bladder were significantly (p ≤ 0.05) greater in NGF-OE mice with CYP-induced cystitis (4 h) compared to WT mice with cystitis (4 h). However, the magnitude of change between WT and NGF-OE mice was only significantly (p ≤ 0.05) different for TrkB expression in urinary bladder of NGF-OE mice treated with CYP. These studies are

EFFECTS OF CYP-INDUCED CYSTITIS ON GROWTH FACTORS AND ASSOCIATED RECEPTORS EXPRESSION IN MICTURITION PATHWAYS IN MICE WITH CHRONIC OVEREXPRESSION OF NGF IN UROTHELIUM

PubMed Central

Girard, Beatrice M.; Malley, Susan; May, Victor; Vizzard, Margaret A.

2016-01-01

We have determined if cyclophosphamide (CYP)-induced cystitis produces additional changes in growth factor/receptors expression in the urinary bladder (urothelium, detrusor) and lumbosacral (L6-S1) dorsal root ganglia (DRG) in a transgenic mouse model with chronic urothelial overexpression of NGF (NGF-OE). Functionally, NGF-OE mice treated with CYP exhibit significant increases in voiding frequency above that observed in control NGF-OE mice (no CYP). Quantitative PCR was used to determine NGF, BDNF, VEGF and receptors (TrkA, TrkB, p75NTR) transcripts expression in tissues from NGF-OE and wildtype (WT) mice with CYP-induced cystitis of varying duration (4 h, 48 h, 8 d). In urothelium of control NGF-OE mice, NGF mRNA was significantly (p ≤ 0.001) increased. Urothelial expression of NGF mRNA in NGF-OE mice treated with CYP (4 h, 48 h, 8 d) was not further increased but maintained with all durations of CYP treatment evaluated. In contrast, CYP-induced cystitis (4 h, 48 h, 8 d) in NGF-OE mice demonstrated significant (p ≤ 0.05) regulation in BDNF, VEGF, TrkA, TrkB and P75NTR mRNA in urothelium and detrusor smooth muscle. Similarly, CYP-induced cystitis (4 h, 48 h, 8 d) in NGF-OE mice resulted in significant (p ≤ 0.05), differential changes in transcript expression for NGF, BDNF and receptors (TrkA, TrkB, p75NTR) in S1 DRG that was dependent on the duration-of CYP-induced cystitis. In general, NGF, BDNF, TrkA and TrkB protein content in the urinary bladder increased in WT and NGF-OE mice with CYP-induced cystitis (4 h). Changes in NGF, TrkA and TrkB expression in the urinary bladder were significantly (p ≤ 0.05) greater in NGF-OE mice with CYP-induced cystitis (4 h) compared to WT mice with cystitis (4 h). However, the magnitude of change between WT and NGF-OE mice was only significantly (p ≤ 0.05) different for TrkB expression in urinary bladder of NGF-OE mice treated with CYP. These studies are consistent with target-derived NGF and other inflammatory

Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation.

PubMed

Leung, A Y; Suen, C K; Lie, A K; Liang, R H; Yuen, K Y; Kwong, Y L

2001-09-15

Polyoma BK virus (BKV) is frequently identified in the urine of bone marrow transplantation (BMT) patients with hemorrhagic cystitis (HC). However, viruria is common even in asymptomatic patients, making a direct causative role of BKV difficult to establish. This study prospectively quantified BK viruria and viremia in 50 BMT patients to define the quantitative relationship of BKV reactivation with HC. Adenovirus (ADV) was similarly quantified as a control. More than 800 patient samples were quantified for BKV VP1 gene with a real-time quantitative polymerase chain reaction. Twenty patients (40%) developed HC, 6 with gross hematuria (HC grade 2 or higher) and 14 with microscopic hematuria (HC grade 1). When compared with asymptomatic patients, patients with HC had significantly higher peak BK viruria (6 x 10(12) versus 5.7 x 10(7) genome copies/d, P <.001) and larger total amounts of BKV excreted during BMT (4.9 x 10(13) versus 7.7 x 10(8) genome copies, P <.001). There was no detectable increase in BK viremia. Binary logistic regression analysis showed that BK viruria was the only risk factor, with HC not related to age, conditioning regimen, type of BMT, and graft-versus-host disease. Furthermore, the levels of ADV viruria in patients with or without HC were similar and comparable with those of BK viruria in patients without HC, suggesting that the significant increase in BK viruria in HC patients was not due to background viral reactivation or damage to the urothelium. BK viruria was quantitatively related to the occurrence of HC after BMT.

Risk factors for hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplant recipients.

PubMed

Hayden, R T; Gu, Z; Liu, W; Lovins, R; Kasow, K; Woodard, P; Srivastava, K; Leung, W

2015-04-01

Hemorrhagic cystitis (HC) results in significant morbidity among hematopoietic stem cell transplant (HSCT) recipients. Several potential causes for HC have been postulated, including viral infection, but definitive evidence is lacking, particularly in pediatric HSCT patients. Ninety pediatric HSCT recipients were prospectively tested on a weekly basis for adenovirus (ADV) and BK virus (BKV) by quantitative real-time polymerase chain reaction in blood and urine samples. Results were correlated with the occurrence of grade II-IV HC. The odds ratio (OR) of HC (95% confidence interval) for BKV ≥1 × 10(9) copies/mL of urine was 7.39 (1.52, 35.99), with a P-value of 0.013. Those with acute graft-versus-host disease (aGVHD) also had higher odds of developing HC, with an OR of 5.34. Given a 20% prevalence rate of HC, positive and negative predictive values of 29% and 95% were seen with a cutoff of 10(9) copies/mL. BK viremia did not reach significance as a risk factor for development of HC (P = 0.06). Only 8 patients showed ADV viruria and 7 showed ADV viremia; all had low viral loads and 4 had no evidence of HC. HC in pediatric HSCT is correlated most strongly to elevated urinary viral load of BKV and to aGVHD, but less strongly to BK viremia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Suppression of the PI3K pathway in vivo reduces cystitis-induced bladder hypertrophy and restores bladder capacity examined by magnetic resonance imaging.

PubMed

Qiao, Zhongwei; Xia, Chunmei; Shen, Shanwei; Corwin, Frank D; Liu, Miao; Guan, Ruijuan; Grider, John R; Qiao, Li-Ya

2014-01-01

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.

Choreito formula for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

PubMed

Kawashima, Nozomu; Ito, Yoshinori; Sekiya, Yuko; Narita, Atsushi; Okuno, Yusuke; Muramatsu, Hideki; Irie, Masahiro; Hama, Asahito; Takahashi, Yoshiyuki; Kojima, Seiji

2015-02-01

Therapy for BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is limited after hematopoietic stem cell transplantation (HSCT). We examined whether choreito, a formula from Japanese traditional Kampo medicine, is effective for treating BKV-HC. Among children who underwent allogeneic HSCT between October 2006 and March 2014, 14 were diagnosed with BKV-HC (median, 36 days; range, 14 to 330 days) after HSCT, and 6 consecutive children received pharmaceutical-grade choreito extract granules. The hematuria grade before treatment was significantly higher in the choreito group than in the nonchoreito group (P = .018). The duration from therapy to complete resolution was significantly shorter in the choreito group (median, 9 days; range, 4 to 17 days) than in the nonchoreito group (median, 17 days; range, 15 to 66 days; P = .037). In 11 children with macroscopic hematuria, the duration from treatment to resolution of macroscopic hematuria was significantly shorter in the choreito group than in the nonchoreito group (median, 2 days versus 11 days; P = .0043). The BKV load in urine was significantly decreased 1 month after choreito administration. No adverse effects related to choreito administration were observed. Choreito may be a safe and considerably promising therapy for the hemostasis of BKV-HC after HSCT. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Levofloxacin for the treatment of severe refractory BK virus-associated hemorrhagic cystitis in hematopoietic stem cell transplantation recipients: A report of three cases

PubMed Central

TOPTAS, TAYFUR; KAYGUSUZ-ATAGUNDUZ, ISIK; KANI, HALUK TARIK; ADIGUZEL, CAFER; FIRATLI-TUGLULAR, TULIN

2014-01-01

BK-virus (BKV) is an important etiological agent for late-onset hemorrhagic cystitis (HC) in patients undergoing hematopoietic stem cell transplantation. Late-onset HC causes significant morbidity among these patients. Therapeutic approaches remain predominantly symptomatic. Several treatment options have been used with variable success rates. Cidofovir has the highest specificity against BKV; however, its lack of availability in the majority of countries, high costs and potential nephrotoxic effects limit its use. The present study reports three cases of severe and prolonged BKV-associated HC (BKHC). HC was resolved in all three of the patients using oral levofloxacin. Thus, levofloxacin may be an effective treatment modality for achieving complete clinical and molecular response in patients with refractory, severe BKHC. PMID:25202408

Treating acute cystitis with biodegradable micelle-encapsulated quercetin

PubMed Central

Wang, Bi Lan; Gao, Xiang; Men, Ke; Qiu, Jinfeng; Yang, Bowen; Gou, Ma Ling; Huang, Mei Juan; Huang, Ning; Qian, Zhi Yong; Zhao, Xia; Wei, Yu Quan

2012-01-01

Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy. PMID:22661886

Quantification of BK polyoma viruria in Japanese children and adults with hemorrhagic cystitis complicating stem cell transplantation.

PubMed

Tanaka, Kaori; Hori, Tsukasa; Hatakeyama, Naoki; Yamamoto, Masaki; Takayama, Rumiko; Yoto, Yuko; Suzuki, Nobuhiro; Hayashi, Toshiaki; Ikeda, Yukiho; Ikeda, Hiroshi; Ishida, Tadao; Tsutsumi, Hiroyuki

2008-12-01

Polyoma BK virus (BKV) is frequently found in the urine of stem cell transplantation (SCT) patients with hemorrhagic cystitis (HC), but also occurs in SCT patients without HC. How BK viruria relates to the development of HC in SCT patients, especially in children, has not yet been fully evaluated. In the present study, we analyzed the relationship of several factors including urinary BKV load to HC development in children and adults undergoing SCT. We employed a quantitative PCR assay and evaluated 37 patients (aged 9 months-62 years) of whom 12 developed HC and 25 did not. Older age was a risk factor for the development of HC; however, other factors such as sex, primary disease, type of SCT, conditioning regimen and aGVHD were not. Peak urinary BKV values in HC patients were not higher than those in non-HC patients. Severity of HC also did not correlate with urinary BKV loads. However, in some patients who secreted higher urinary BKV loads, the peak loads were closely related with the onset of HC. Higher BKV loads may be a risk factor for the development of HC in conjunction with other coexisting factors.

Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation.

PubMed

Mori, Yasuo; Miyamoto, Toshihiro; Kato, Koji; Kamezaki, Kenjiro; Kuriyama, Takuro; Oku, Seido; Takenaka, Katsuto; Iwasaki, Hiromi; Harada, Naoki; Shiratsuchi, Motoaki; Abe, Yasunobu; Nagafuji, Koji; Teshima, Takanori; Akashi, Koichi

2012-03-01

Virus-associated hemorrhagic cystitis (HC) is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Although numerous studies have attempted to identify factors that predispose patients to viral HC, its causes remain controversial. We analyzed retrospectively the results of 266 allogeneic HSCTs to identify factors associated with HC. Of this group, 42 patients (15.8%) were diagnosed with viral HC, because of either adenovirus (ADV; n = 26; 9.8%) or BK virus (BKV; n = 16; 6.0%). ADV-HC was frequently associated with T cell purging, and was less common in patients with acute graft-versus-host-disease (GVHD). Conversely, BKV-HC was more frequently observed in patients with excessive immune reactions such as GVHD, preengraftment immune reaction, and hemophagocytic syndrome. These observations indicate that ADV- and BKV-HC may differ significantly in their risk factors and pathogenesis. Profound immune deficiency is more likely to be associated with ADV-HC, whereas immune hyperactivity might play a key role in BKV-HC. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease

PubMed Central

Le Calloch, R.; Ianotto, J. C.; Berthou, C.; Tempescul, A.

2011-01-01

Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy. PMID:22937308

Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease.

PubMed

Le Calloch, R; Ianotto, J C; Berthou, C; Tempescul, A

2011-01-01

Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy.

Hemorrhagic cystitis in children undergoing bone marrow transplantation: a putative role for simian virus 40.

PubMed

Comar, Manola; D'Agaro, Pierlanfranco; Andolina, Marino; Maximova, Natasha; Martini, Fernanda; Tognon, Mauro; Campello, Cesare

2004-08-27

Late-onset hemorrhagic cystitis (HC) is a well-known severe complication of bone marrow transplantation (BMT), both in adults and in children. Protracted postengraftment HC is associated with graft-versus-host disease and viral infections, mainly caused by BK virus (BKV) or adenovirus (AV). This study investigated whether simian virus 40 (SV40) DNA sequences can be detected in specimens from pediatric patients affected by severe postengraftment HC. The clinical diagnosis of HC was made in 7 of 28 BMT children. DNA from peripheral blood mononuclear cells (PBMC) and urine sediment cells and supernatants was analyzed by polymerase chain reaction (PCR) for human cytomegalovirus (HCMV), AV, BKV, JC virus (JCV), and SV40. DNA filter hybridization and sequencing was carried out in SV40-positive samples. SV40 footprints were detected in two of seven cases of HC. Specific SV40 DNA sequences were detected by PCR and by filter hybridization both in urine and in PBMC samples at the HC onset and during the follow-up. The DNA sequencing proved that the amplicons belonged to the SV40 wild-type. Urine samples of the two HC cases tested negative by cell cultures, PCR, or both for HCMV, BKV, JCV, and AV. The detection of SV40 DNA sequences suggest that this simian polyomavirus could be involved, at least in some cases, in the HC occurring in children after BMT.

BK Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplantation in the Pediatric Population.

PubMed

Pérez-Huertas, Pablo; Cueto-Sola, Margarita; Escobar-Cava, Paloma; Fernández-Navarro, José María; Borrell-García, Carmela; Albert-Marí, Asunción; López-Briz, Eduardo; Poveda-Andrés, José Luis

2016-02-22

To study the incidence, risk factors, and treatment of hemorrhagic cystitis secondary to BK-virus reactivation (HC-BKV) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the pediatric population. Case-control study in which all pediatric patients (0-18 years) who underwent allo-HSCT from September 2009 to January 2014 were followed. Twenty-nine patients underwent an allo-HSCT. The median age was 9 years (range = 6 months to 15 years), 61% male. The primary diagnosis was acute lymphoblastic leukemia (72.4%). Six (20.7%) developed HC-BKV. In a multivariate analysis of risk factors, it was observed that the reactivation of BK virus was associated with age more than 10 years (P = .098) and those with positive serology for Epstein-Barr virus (P = .06). Five of the 6 patients with HC-BKV received cidofovir (CDV) at doses of 3 to 5 mg/kg/week. The treatment lasted a median of 3 cycles (range = 2-5). One of the patients (20%) developed nephrotoxicity. Of the 5 patients treated with CDV, 3 (60%) had a complete response, 1 (20%) partial response, and 1 (20%) no response. We conclude that HC-BKV is a frequent complication after allo-HSCT. CDV therapy can be effective but controlled clinical trials are needed. © 2016 by Association of Pediatric Hematology/Oncology Nurses.

Overview of ultrasound-induced lung hemorrhage

NASA Astrophysics Data System (ADS)

O'Brien, William D.; Simpson, Douglas G.; Frizzell, Leon A.; Oelze, Michael L.; Zachary, James F.

2003-10-01

It is well documented that ultrasound-induced lung hemorrhage can occur in mice, rats, rabbits, pigs, and monkeys. Our own experimental studies have focused on mice, rats, and pigs as animal models. The characteristics of the lesions produced in mice, rats and pigs were similar to those described in studies by our research group and others, suggesting a common pathogenesis for the initiation and propagation of the lesions at the macroscopic and microscopic levels. Five experimental in vivo studies have been conducted to evaluate whether cavitation is responsible for ultrasound-induced lung hemorrhage. The studies evaluated the dependencies of hydrostatic pressure, frequency, pulse polarity, contrast agents and lung inflation, and the results of each study appeared inconsistent with the hypothesis that the mechanism for the production of a lung hemorrhage was inertial cavitation. Other dependencies evaluated included beam width, pulse repetition frequency, pulse duration, exposure duration, and animal species and age. The thresholds for producing ultrasound-induced lung hemorrhage, in general, were less than the FDA's regulatory limit of a Mechanical Index (MI) of 1.9. Further, the MI does not appear to provide a risk-based index for lung hemorrhage. [Work supported by NIH Grant No. R01EB02641.

Effects of CYP-induced cystitis on PACAP/VIP and receptor expression in micturition pathways and bladder function in mice with overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Tompkins, John D; Parsons, Rodney L; May, Victor; Vizzard, Margaret A

2012-11-01

We have previously demonstrated nerve growth factor (NGF) regulation of pituitary adenylate cyclase-activating polypeptide (PACAP)/receptors in bladder reflex pathways using a transgenic mouse model of chronic NGF overexpression in the bladder using the urothelial-specific uroplakin II promoter. We have now explored the contribution of target-derived NGF in combination with cyclophosphamide (CYP)-induced cystitis to determine whether additional changes in neuropeptides/receptors are observed in micturition reflex pathways due to the presence of additional inflammatory mediators in the urinary bladder. Quantitative PCR was used to determine PACAP/vasoactive intestinal polypeptide (VIP), substance P, galanin, and receptor transcript expression in the urinary bladder (urothelium, detrusor) in mice with overexpression of NGF in the urothelium (NGF-OE) and wild-type (WT) mice with CYP-induced cystitis (4 h, 48 h, and chronic). With CYP-induced cystitis (4 h), WT and NGF-OE mice exhibited similar changes in galanin transcript expression in the urothelium (30-fold increase) and detrusor (threefold increase). In contrast, PACAP, VIP, and substance P transcripts exhibited differential changes in WT and NGF-OE with CYP-induced cystitis. PAC1, VPAC1, and VPAC2 transcript expression also exhibited differential responses in NGF-OE mice that were tissue (urothelium vs. detrusor) and CYP-induced cystitis duration-dependent. Using conscious cystometry, NGF-OE mice treated with CYP exhibited significant (p ≤ 0.01) increases in voiding frequency above that observed in control NGF-OE mice. In addition, no changes in the electrical properties of the major pelvic ganglia neurons of NGF-OE mice were detected using intracellular recording, suggesting that the urinary bladder phenotype in NGF-OE mice is not influenced by changes in the efferent limb of the micturition reflex. These studies are consistent with target-derived NGF and other inflammatory mediators affecting

Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in urinary bladder biopsies.

PubMed

Hukkanen, V; Haarala, M; Nurmi, M; Klemi, P; Kiilholma, P

1996-01-01

Microbes may be involved in the pathogenesis of interstitial cystitis (IC). Adenoviruses and BK virus (BKV) can infect epithelial cells in urinary bladder and they are causative agents for hemorrhagic cystitis. We therefore studied the presence of adenovirus and BKV genomes in urinary bladder tissue specimens of patients with IC using polymerase chain reaction (PCR) and in situ hybridization (ISH). Controls were specimens from cases with transitional cell carcinoma of the bladder. Nucleic acids were extracted from paraffin sections of the bladder tissue for PCR. Primers detecting all adenovirus types were used. In situ hybridization was carried out for the paraffin sections using digoxigenin-labeled DNA probes for adenovirus and BKV. The adenovirus DNA PCR was able to detect one to two infected cells/specimen. All the seven IC cases studied and six controls were negative for adenovirus DNA by PCR and ISH. The ISH test for BKV genomes was also considered negative in IC cases and controls. The specimens which were negative in PCR tests yielded a signal with beta-globin primers, thus being amplifiable. We conclude that adenovirus and BKV do not play a major pathogenetic role in interstitial cystitis.

[Hemorrhagic cystitis due to adenovirus in a renal transplant recipient: the first reported case in black Africa in a setting of a very beginning of a kidney transplantation program and review of the literature].

PubMed

Ackoundou-N'Guessan, Clément; Coulibaly, Noël; Guei, Cyr Monley; Aye, Denis; N'guessan, Francis Yapi; N'Dah, Justin Kouame; Lagou, Delphine Amélie; Tia, Mélanie Weu; Coulibaly, Pessa Albert; Nzoue, Sita; Konan, Serges; Gnionsahe, Daze Apollinaire

2015-04-01

Viral infections are an important complication of transplantation. Polyomavirus are the commonest viruses that infect the renal allograft. Herpes virus nephropathy has also been described. In the past 15 years, adenovirus nephritis has emerged as a potentially life-threatening disease in renal transplant patients in developed countries. Most of the papers devoted to adenovirus nephritis are reported cases. The fate of such patients in resources-limited countries is not known. Herein, we describe the clinical, biological and prognostic findings of a black African transplanted patient with adenoviral hemorrhagic cystitis. This case is the very first of its kind reported in black Africa in a setting of a start of a renal transplantation pilot project. The patient is a 54-year-old man admitted at the nephrology service for gross haematuria and fever occurred 1 month after kidney transplantation. The diagnosis of adenoviral hemorrhagic cystitis has been suspected because the patient has displayed recurrent conjunctivitis and gastroenteritis well before transplantation, which was then confirmed by the real-time polymerase chain reaction performed on the blood. Conservatory measures associated with immunosuppression reduction have permitted the discontinuation of haematuria. This case has been discussed in regard of the epidemiology, the diagnosis, the treatment, the evolution and the prognosis of the adenoviral infection in the renal transplant patient. A review of the literature has been performed subsequently. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Growth hormone used to control intractable bleeding caused by radiation-induced gastritis.

PubMed

Zhang, Liang; Xia, Wen-Jie; Zhang, Zheng-Sen; Lu, Xin-Liang

2015-08-21

Intractable bleeding caused by radiation-induced gastritis is rare. We describe a 69-year-old man with intractable hemorrhagic gastritis induced by postoperative radiotherapy for the treatment of esophageal carcinoma. Although anti-secretory therapy with or without octreotide was initiated for hemostasis over three months, melena still occurred off and on, and the patient required blood transfusions to maintain stable hemoglobin. Finally growth hormone was used in the treatment of hemorrhage for two weeks, and hemostasis was successfully achieved. This is the first report that growth hormone has been used to control intractable bleeding caused by radiation-induced gastritis.

The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation

PubMed Central

Uppugunduri, Chakradhara Rao S.; Storelli, Flavia; Mlakar, Vid; Huezo-Diaz Curtis, Patricia; Rezgui, Aziz; Théorêt, Yves; Marino, Denis; Doffey-Lazeyras, Fabienne; Chalandon, Yves; Bader, Peter; Daali, Youssef; Bittencourt, Henrique; Krajinovic, Maja; Ansari, Marc

2017-01-01

Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen. The cytotoxic effects of Su and acrolein (Ac, water soluble metabolite of CY) were tested on human urothelial cells (HUCs). The effect of Su was also tested on cytochrome P 450 (CYP) function in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were estimated using Kaplan–Meier curves and log-rank test was used to compare the difference between groups in a univariate analysis. Multivariate Cox regression was used to estimate hazard ratios with 95% confidence intervals (CIs). Multivariate analysis included co-variables that were significantly associated with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the univariate analysis, HC incidence was significantly (p < 0.05) higher in children older than 10 years (28.6 vs. 6.8%) or in children with higher Su levels (>40 vs. <11%) or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3%) compared to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9 genotype status was associated with HC occurrence with a hazards ratio of 4.8 (95% CI: 1.3–18.4; p = 0.02). Ac was found to be toxic to HUC cells at lower concentrations (33 μM), Su was not toxic to HUC cells at concentrations below 1 mM and did not affect CYP function in HepaRG cells. Our observations suggest that pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective prophylaxis to reduce HC

The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Uppugunduri, Chakradhara Rao S; Storelli, Flavia; Mlakar, Vid; Huezo-Diaz Curtis, Patricia; Rezgui, Aziz; Théorêt, Yves; Marino, Denis; Doffey-Lazeyras, Fabienne; Chalandon, Yves; Bader, Peter; Daali, Youssef; Bittencourt, Henrique; Krajinovic, Maja; Ansari, Marc

2017-01-01

Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen. The cytotoxic effects of Su and acrolein (Ac, water soluble metabolite of CY) were tested on human urothelial cells (HUCs). The effect of Su was also tested on cytochrome P 450 (CYP) function in HepaRG hepatic cells. Cumulative incidences of HC before day 30 post HSCT were estimated using Kaplan-Meier curves and log-rank test was used to compare the difference between groups in a univariate analysis. Multivariate Cox regression was used to estimate hazard ratios with 95% confidence intervals (CIs). Multivariate analysis included co-variables that were significantly associated with HC in a univariate analysis. Cumulative incidence of HC was 15.3%. In the univariate analysis, HC incidence was significantly ( p < 0.05) higher in children older than 10 years (28.6 vs. 6.8%) or in children with higher Su levels (>40 vs. <11%) or in carriers of both functional GSTM1 and CYP2C9 (33.3 vs. 6.3%) compared to the other group. In a multivariate analysis, combined GSTM1 and CYP2C9 genotype status was associated with HC occurrence with a hazards ratio of 4.8 (95% CI: 1.3-18.4; p = 0.02). Ac was found to be toxic to HUC cells at lower concentrations (33 μM), Su was not toxic to HUC cells at concentrations below 1 mM and did not affect CYP function in HepaRG cells. Our observations suggest that pre-emptive genotyping of CYP2C9 and GSTM1 may aid in selection of more effective prophylaxis to reduce HC

Kidney and bladder outcomes in children with hemorrhagic cystitis and BK virus infection after allogeneic hematopoietic stem cell transplantation

PubMed Central

Oshrine, Benjamin; Bunin, Nancy; Li, Yimei; Furth, Susan; Laskin, Benjamin L

2015-01-01

BK virus (BKV) infection is associated with hemorrhagic cystitis (HC) in hematopoietic stem cell transplant (HSCT) recipients and nephropathy after kidney transplant. We assessed the association between BKV and kidney and bladder complications in children developing HC by retrospectively reviewing 221 consecutive pediatric allogeneic HSCT recipients at the Children’s Hospital of Philadelphia from 2005–2011. We included all patients with BKV PCR testing performed for clinical indication from day 0 until 1 year post-HSCT (N=68). We assessed the association of any BKV infection (urine and/or blood) or peak BK viremia ≥10,000 copies/ml (high viremia) with severe HC (defined as grade IV—bladder catheterization or surgical intervention), the need for dialysis, serum creatinine-estimated glomerular filtration rate (eGFR) at the time of BKV testing, day 100, and day 365, and death. Children with high viremia more likely developed severe HC compared to those with peak viremia <10,000 copies/mL (21% versus 2%; p=0.02). BKV infection of the blood or urine was not associated with the need for dialysis, change in eGFR, or mortality. BKV infection is common after pediatric allogeneic HSCT and plasma testing in those with HC may predict patients who will develop severe bladder injury. PMID:24060406

Urologic Outcomes of Children With Hemorrhagic Cystitis After Bone Marrow Transplant at a Single Institution.

PubMed

Au, Jason K; Graziano, Christopher; Elizondo, Rodolfo A; Ryan, Sheila; Roth, David R; Koh, Chester J; Gonzales, Edmond T; Tu, Duong T; Janzen, Nicolette; Naik, Swati; Seth, Abhishek

2017-03-01

To analyze clinical outcomes and the risk factors associated with genitourinary (GU) morbidity and mortality in children who present with hemorrhagic cystitis (HC) after bone marrow transplant (BMT). A retrospective chart review of patients with HC who had undergone BMT at a single pediatric hospital from 2008 to 2015 was conducted. Demographic data, severity of hematuria, HC management, and mortality were analyzed. Bivariate analysis and binary logistic regression were performed to identify risk factors. Out of 43 patients who met inclusion criteria, 67.4% were male with a median age at BMT of 10.2 years (interquartile range 5.8-14.6). Percutaneous nephrostomy catheters were inserted in 5 patients for urinary diversion. All-cause mortality was 32.6% (N = 14). Intravesical retroviral therapy (P <.001), HC grade (P <.001), total Foley time (P <.001), total gross hematuria time (P <.001), total days hospitalized (P = .012), and days to most improved hematuria (P = .032) were associated with significant GU morbidity on bivariate analysis. On multivariable analysis, days to most improved hematuria was associated with significant GU morbidity odds ratio of 1.177 (1.006-1.376) (P = .042). Status of percutaneous nephrostomy was not associated with increased mortality (P = .472); however, in the multivariate model, BK viremia (P = .023), need for renal dialysis (P = .003), and presence of Foley catheter (P = .005) were associated with increased mortality. Children with HC after BMT fall in a very high-risk category with high mortality and significant GU morbidity. The presence of a Foley catheter, need for dialysis, and BK viremia are associated with increased mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of tramadol on pain-related behaviors and bladder overactivity in rodent cystitis models.

PubMed

Oyama, Tatsuya; Homan, Takashi; Kyotani, Junko; Oka, Michiko

2012-02-15

Tramadol is a widely used analgesic that stimulates the μ opioid receptor and inhibits serotonin and noradrenalin reuptake. There have been studies on the analgesic effects of tramadol based on the tail-flick test, the formalin test, and the induction of allodynia by sciatic-nerve ligation. However, the effects of tramadol on behaviors related to bladder pain and bladder overactivity induced by cystitis have not been reported. To investigate the usefulness of tramadol for patients with cystitis, we investigated these effects of tramadol in rodent cystitis models. Intraperitoneal injection of cyclophosphamide caused bladder-specific inflammation and increases in pain-related behaviors, the number of voids and bladder weight in mice. Tramadol suppressed the cyclophosphamide-induced pain-related behaviors but did not affect the number of voids or the bladder weight. During continuous-infusion cystometrograms in anesthetized rats, cyclophosphamide shortened the intercontraction interval, indicating bladder overactivity. Tramadol significantly prolonged the intercontraction interval, and the effect was partially blocked by the opioid antagonist naloxone. This finding indicates that μ opioid receptors may be involved in the action of tramadol. In conclusion, tramadol ameliorated cyclophosphamide-induced bladder-pain-related behaviors and bladder overactivity in rodents. These findings suggest that tramadol might be a treatment option for cystitis-induced bladder pain and bladder overactivity. Copyright © 2011 Elsevier B.V. All rights reserved.

Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat.

PubMed

Hidalgo-Lucas, Sophie; Rozan, Pascale; Guérin-Deremaux, Laetitia; Baert, Blandine; Violle, Nicolas; Saniez-Degrave, Marie-Hélène; Bisson, Jean-François

2016-05-01

Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1-16 (250 and 500 mg/kg body weight). Six hours after an intraperitoneal injection of 200 mg/kg body weight of CYP, body temperature, general behavior, food intake, and body weight were recorded. Twenty-four hours after CYP injection, rats were tested in two behavioral tests, an open field and the aversive light stimulus avoidance conditioning test, to evaluate the influence of pain on general activity and learning ability of rats. After euthanasia, bladders were weighed, their thickness was scored, and the urinary hemoglobin was measured. RCs orally administered at the two dosages significantly reduced visceral pain and associated inflammatory parameters related to cystitis both induced by CYP injection, and improved rat behavior. To conclude, RCs demonstrated beneficial effects against visceral pain and cystitis.

Hemorrhage-induced intestinal damage is complement independent in Helicobacter-hepaticus infected mice

PubMed Central

Hylton, Diana J.; Phillips, Lauren M.; Hoffman, Sara M.; Fleming, Sherry D.

2010-01-01

With over half of the world population infected, Helicobacter infection is an important public health issue associated with gastrointestinal cancers and inflammatory bowel disease. Animal studies indicate that complement and oxidative stress play a role in Helicobacter infections. Hemorrhage induces tissue damage which is attenuated by blockade of either complement activation or oxidative stress products. Therefore, we hypothesized that chronic Helicobacter hepaticus infection would modulate hemorrhage-induced intestinal damage and inflammation. To test this hypothesis, we examined hemorrhage-induced jejunal damage and inflammation in uninfected and H. hepaticus infected mice. H. hepaticus infection increased hemorrhage-induced mid-jejunal mucosal damage despite attenuating complement activation. In addition, infection alone increased chemokine secretion, changing the hemorrhage-induced neutrophil infiltration to a macrophage-mediated inflammatory response. The hemorrhage-induced macrophage infiltration correlated with increased secretion of tumor necrosis factor-α (TNF-α3) and nitric oxide (NO) in the infected mice. Together these data indicate that Helicobacter infection modulates the mechanism of hemorrhage-induced intestinal damage and inflammation from a complement-mediated response to a macrophage response with elevated TNF-α and NO. These data indicate that chronic, low level infections change the response to trauma and should be considered when designing and administering therapeutics. PMID:20220569

BK virus associated pronounced hemorrhagic cystoureteritis after bone marrow transplantation.

PubMed

Haab, Alexander C; Keller, Isabelle S; Padevit, Christian; John, Hubert

2015-10-01

Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of immunodeficiency is very rare. More common is the appearance of a hemorrhagic cystitis. This report not only shows bilateral ureteral stenosis after bone marrow transplantation, but also presents severe complications as chronic pelvic pain and impaired kidney function as well as irreparable damage to the whole urinary tract leading to nephroureterectomy, subtrigonal cystectomy and orthotopic ileal neobladder. Finally renal transplantation was required. To our knowledge this is the first case in the literature where such a severe course of BKV associated hemorrhagic cystoureteritis is described.

Evaluation of the impact of the urinary symptoms on quality of life of patients with painful bladder syndrome/chronic pelvic pain and radiation cystitis: EURCIS study.

PubMed

Rapariz-González, M; Castro-Díaz, D; Mejía-Rendón, D

2014-05-01

To evaluate the impact of urinary symptoms of Painful Bladder/Pelvic Pain Syndrome and Radiation Cystitis (PBCPPS) on the Quality of Life, and self-esteem of the patient. An observational, multicenter, epidemiological and cross-sectional study was performed on patients with Painful Bladder/Chronic Pelvic Pain Syndrome and Radiation Cystitis. Data was recorded on severity of urinary symptoms and QoL impairment using the PUF Score. The patients evaluated the QoL deterioration grade through the King's Health Questionnaire (KHQ), and the level of their anxiety and self-esteem with the Goldberg's Anxiety Scale (GAS) and Rosenberg's Self-Esteem Scale (RSES), respectively. Post-hoc comparisons were performed between the results of the KHQ of this study and a sample of patients with urinary incontinence (UI). Results on RSES were analyzed with data from the general population and from patients with erectile dysfunction. A total of 530 cases, mostly female patients, who had been diagnosed with PBCPPS, were analyzed. High levels of deterioration in QoL were described: KHQ scores were significantly higher when compared with patients with UI (P<.01). Involvement of self-esteem was higher in patients with RC and men, who obtained scores similar to those of patients with erectile dysfunction. Patients with Painful Bladder Syndrome/Chronic Pelvic Pain Syndrome and Radiation Cystitis present high levels of anxiety, and significant reductions in both quality of life and self-esteem. Especially for men, this affectation is similar to that caused by erectile dysfunction. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Kidney and bladder outcomes in children with hemorrhagic cystitis and BK virus infection after allogeneic hematopoietic stem cell transplantation.

PubMed

Oshrine, Benjamin; Bunin, Nancy; Li, Yimei; Furth, Susan; Laskin, Benjamin L

2013-12-01

BK virus (BKV) infection is associated with hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HSCT) recipients and nephropathy after kidney transplantation. We assessed the association between BKV and kidney and bladder complications in children developing HC by retrospectively reviewing 221 consecutive pediatric allogeneic HSCT recipients at the Children's Hospital of Philadelphia from 2005 to 2011. We included all patients with BKV PCR testing performed for clinical indication from day 0 until 1 year post-HSCT (N = 68). We assessed the association of any BKV infection (urine and/or blood) or peak BK viremia ≥ 10,000 copies/mL (high viremia) with severe HC (defined as grade IV-bladder catheterization or surgical intervention); the need for dialysis; serum creatinine-estimated glomerular filtration rate at the time of BKV testing, day 100, and day 365; and death. Children with high viremia more likely developed severe HC compared with those with peak viremia < 10,000 copies/mL (21% versus 2%; P = .02). BKV infection of the blood or urine was not associated with the need for dialysis, change in estimated glomerular filtration rate, or mortality. BKV infection is common after pediatric allogeneic HSCT, and plasma testing in those with HC may predict patients who will develop severe bladder injury. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Risk factors for recurrent cystitis following acute cystitis in female patients.

PubMed

Yoon, Byung Il; Kim, Sun Wook; Ha, U-Syn; Sohn, Dong Wan; Cho, Yong-Hyun

2013-08-01

We conducted a retrospective analysis of acute cystitis (AC) patients to evaluate the risk factors of recurrent cystitis (RC) patients following AC. The clinical records of 254 subjects with a confirmed diagnosis of AC and 90 healthy subjects who visited the Health Promotion Center between 2008 and 2012 were reviewed. A patient was diagnosed with RC if she was treated for three or more symptomatic episodes of cystitis over a 12-month period. Results were analyzed according to three groups: normal control (group A, n = 90), AC (group B, n = 121), and RC (group C, n = 133). Women in the cystitis groups (groups B and C) were more likely to have diabetes, be menopausal, have a history of catheterization or sexually transmitted infections (STI), have a low daily water intake, have frequent sexual intercourse, and to use contraception more frequently than the normal control group (P < 0.05). In groups B and C, Escherichia coli was the most common uropathogen, followed by Staphylococcus saprophyticus, Enterococcus species, and Klebsiella species. There were no differences between groups in the detection rates of these uropathogens. Factors that affected progression to RC were diabetes, catheterization history, STI history, sexual intercourse more than four times per month, sexual intercourse in the last month, and the use of contraceptives (P < 0.05). The identification of these factors may help develop preventive, diagnostic, and therapeutic strategies for treating RC that has progressed from AC.

Control of Postpartum Hemorrhage Using Vacuum-Induced Uterine Tamponade.

PubMed

Purwosunu, Yuditiya; Sarkoen, Widyastuti; Arulkumaran, Sabaratnam; Segnitz, Jan

2016-07-01

Postpartum hemorrhage is the leading cause of maternal mortality worldwide. Vacuum-induced uterine tamponade is a possible alternative approach to balloon tamponade systems for the treatment of postpartum hemorrhage resulting from atony. In a prospective proof-of-concept investigation of 10 women with vaginal deliveries in a hospital setting who failed first-line therapies for postpartum hemorrhage, tamponade was used. Vacuum-induced uterine tamponade was created through a device inserted transvaginally into the uterine cavity. An occlusion balloon built into the device shaft was inflated at the level of the external cervical os to create a uterine seal. Negative pressure was created by attaching a self-contained, mobile, electrically powered, pressure-regulated vacuum pump with a sterile graduated canister. In all 10 cases, the suction created an immediate seal at the cervical os, 50-250 mL of residual blood was evacuated from the uterine cavity, the uterus collapsed and regained tone within minutes, and hemorrhaging was controlled. The device remained in place for a minimum of 1 hour and up to 6.5 hours in one case while vaginal and perineal lacerations were easily repaired. This preliminary investigation suggests that a device designed to create vacuum-induced uterine tamponade may be a reasonable alternative to other devices used to treat atonic postpartum hemorrhage.

Clinical utility of hyperbaric oxygen therapy in genitourinary medicine

PubMed Central

Gandhi, Jason; Seyam, Omar; Smith, Noel L.; Joshi, Gunjan; Vatsia, Sohrab; Khan, Sardar Ali

2018-01-01

Hyperbaric oxygen therapy (HBOT) is a medical technique which delivers oxygen at ambient pressures to increase the amount of dissolved oxygen in the blood and oxygen distribution to tissues. There are several beneficial properties of HBOT concomitant with elevated oxygen distribution in tissue including anti-inflammation, angiogenesis through vascular endothelial growth factor proliferation, augmented fibroblast activity through fibroblast growth factor proliferation, tissue and wound repair, enhancement of lymphocyte and macrophage activity, increased male testosterone secretion, and bactericidal activity. Given its renown in treating conditions such as decompression sickness and carbon monoxide poisoning, HBOT is making gradual strides for use in genitourinary medicine due to its low risk and likeliness to achieve favorable results. Early success has been observed in the treatment of Fournier's gangrene, radiation cystitis, and interstitial cystitis via the elimination of clinical symptoms such as pain. Further indications that have exhibited positive outcomes despite HBOT's ambiguous mechanism of action include cyclophosphamide hemorrhagic cystitis, emphysematous cystitis, pelvic radiation disease, radiation-induced proctopathy, dystrophic calcification of the prostate, erectile dysfunction secondary to urethroplasty, priapism, abnormal renal morphology, blood testosterone, calcific uremic arteriolopathy, and hidradenitis suppurativa. For other indications, multicenter studies must be conducted to determine HBOT's true efficacy, mechanism of action, risks, and advantages over conventional treatments.

Interstitial Cystitis

MedlinePlus

... the bladder. Doctors are not sure exactly why distension helps. It may make your bladder better able ... cystitis may have painful spasms of pelvic floor muscles. If you have muscle spasms, you can learn ...

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

PubMed

Gilis, L; Morisset, S; Billaud, G; Ducastelle-Leprêtre, S; Labussière-Wallet, H; Nicolini, F-E; Barraco, F; Detrait, M; Thomas, X; Tedone, N; Sobh, M; Chidiac, C; Ferry, T; Salles, G; Michallet, M; Ader, F

2014-05-01

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \\[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Comparison of voiding function and nociceptive behavior in two rat models of cystitis induced by cyclophosphamide or acetone

PubMed Central

Saitoh, Chikashi; Yokoyama, Hitoshi; Chancellor, Michael B.; de Groat, William C.; Yoshimura, Naoki

2009-01-01

Aims Nociceptive behavior and its relationship with bladder dysfunction were investigated in two cystitis models, which were induced by intraperitoneal (ip) injection of cyclophosphamide (CYP) or intravesical instillation of acetone, using freely moving, non-catheterized conscious rats. Methods Female Sprague-Dawley rats were used. Cystitis was induced by ip injection of CYP (100 and 200mg/kg) or intravesical instillation of acetone (10, 30 and 50%) via a polyethylene catheter temporarily inserted into the bladder through the urethra. Then the incidence of nociceptive behavior (immobility with decreased breathing rates) was scored. Voided urine was collected simultaneously and continuously to measure bladder capacity. The plasma extravasation in the bladder was quantified by an evans blue (EB) dye leakage technique. Results CYP (100mg/kg, ip) induced nociceptive behavior without affecting bladder capacity or EB concentration in the bladder. A higher dose of CYP (200mg/kg, ip) decreased bladder capacity and increased EB levels as well as nociceptive behavior. In contrast, intravesical instillation of acetone (30%) decreased bladder capacity and increased EB levels, but evoked nociceptive behavior less frequently compared with CYP-treated animals. In capsaicin pretreated rats, nociceptive behavior induced by CYP or acetone was reduced; however, the overall effects of CYP or acetone on bladder capacity and bladder EB levels were unaffected. Conclusions These results suggest that there is a difference in the induction process of nociceptive behavior and small bladder capacity after two different types of bladder irritation and that C-fiber sensitization is more directly involved in pain sensation than reduced bladder capacity. PMID:19618450

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury.

PubMed

Kan, Wen-Hong; Hsu, Jun-Te; Schwacha, Martin G; Choudhry, Mashkoor A; Raju, Raghavan; Bland, Kirby I; Chaudry, Irshad H

2008-10-01

Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of protein expression following trauma-hemorrhage. To investigate this, male Sprague-Dawley rats were subjected to midline laparotomy and hemorrhagic shock (mean blood pressure 35-40 mmHg for approximately 90 min) followed by fluid resuscitation. Animals were treated with either vehicle (DMSO) or 1400W (10 mg/kg body wt ip), or L-NAME (30 mg/kg iv), 30 min before resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation induced a marked hypotension and increase in markers of hepatic injury (i.e., plasma alpha-glutathione S-transferase, tissue myeloperoxidase activity, and nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor-1alpha, ICAM-1, IL-6, TNF-alpha, and neutrophil chemoattractant (cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein levels were also markedly increased following trauma-hemorrhage/resuscitation. Administration of the iNOS inhibitor 1400W significantly attenuated hypotension and expression of these mediators of hepatic injury induced by trauma-hemorrhage/resuscitation. However, administration of L-NAME could not attenuate hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it improved mean blood pressure as did 1400W. These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions.

Emphysematous cystitis: a rare cause of gross hematuria.

PubMed

Chang, Chirn-Bin; Chang, Chia-Chu

2011-05-01

Emphysematous cystitis is a relatively rare infectious condition of the urinary bladder. The mortality rate is high if the diagnosis is delayed or if the treatment is inadequate. We present an uncommon case of emphysematous cystitis and highlight the risk factors for this disease. An 81-year-old man with a past medical history of type 2 diabetes and a central pontine infarction presented to the Emergency Department due to gross hematuria. Computed tomography (CT) and plain radiography revealed localized gas within the bladder that was compatible with the diagnosis of emphysematous cystitis. A Foley catheter was inserted. Urine culture grew Klebsiella pneumoniae; 2 g cefotaxime daily was initiated. Subsequent plain radiography and CT scan showed regression of intraluminal gas. We recommend CT for the definitive diagnosis of emphysematous cystitis. Adequate antibiotic therapy, strict blood glucose control, adequate drainage of urine, and early goal-directed therapy for suspected sepsis are suggested to prevent the complications of emphysematous cystitis. Copyright © 2011 Elsevier Inc. All rights reserved.

Cytomegalovirus is a potential risk factor for late-onset hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation.

PubMed

Han, Ting-Ting; Xu, Lan-Ping; Liu, Dai-Hong; Liu, Kai-Yan; Fu, Hai-Xia; Zhao, Xiang-Yu; Zhao, Xiao-Su; Huang, Xiao-Jun

2014-01-01

Late-onset hemorrhagic cystitis (LOHC) is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is primarily associated with viral infection. We prospectively quantified cytomegalovirus (CMV), BK virus (BKV), and adenovirus in urine and plasma using Q-RT-PCR in 50 consecutive patients to define the relationship between virus and LOHC. Of the 50 patients, 21 developed LOHC at a median of 29 days (range 4-64 days), with a cumulative incidence of 42% (±7.1%). The cumulative incidence of LOHC on day 100 in patients with and without CMV viremia (prior to or at the onset of LOHC) were 56.3% (±8.9%) and 16.7% (±9.1%) (P = 0.018), respectively, and it was 59.3% (±9.8%) and 21.7% (±8.8%) in patients with and without CMV viruria (prior to or at the onset of LOHC) (P = 0.021), respectively. The cumulative incidence of LOHC was also higher in patients with a plasma BKV load increased ≥3 log10 or with a urine BKV load increased ≥4 log10 than those without the increase (P < 0.001). Only one patient with LOHC was tested positive for ADV. Both the univariate and multivariate analyses showed that CMV viremia (HR = 3.461, 95% CI: 1.005-11.922, P = 0.049) and a plasma BKV load that was increased ≥3 log10 (HR = 10.705, 95%CI: 2.469-46.420, P = 0.002) were independent risk factors for the development of LOHC. We conclude that both CMV viremia and an increase of plasma BKV are independent risk factors for LOHC. And the role of CMV viremia was firstly demonstrated. Copyright © 2013 Wiley Periodicals, Inc.

[Alternative treatments for interstitial cystitis].

PubMed

Gamé, X; Bart, S; Castel-Lacanal, E; De Sèze, M; Karsenty, G; Labat, J-J; Rigaud, J; Scheiber-Nogueira, M C; Ruffion, A

2009-06-01

Interstitial cystitis is the first cause of bladder pain. In case of failure of the usual treatments, several other modalities have been proposed. These therapeutic modalities are posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, intradetrusor botulinum toxin injections and surgery. A certain efficiency of each of these treatments in the interstitial cystitis has been reported. However, the evaluation of these treatments is limited and the level of evidence is too low to propose these treatments in routine.

BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment

PubMed Central

Park, Young Hoon; Lim, Joo Han; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo

2016-01-01

Objective: BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. Materials and Methods: From January 2005 to June 2014, among the 69 patients that underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Results: HC was observed in 30 patients (43.5%), and among them, 18 of the cases (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (minimum-maximum: 13-63). Patients received Allo-SCT for acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1). The donor types were human leukocyte antigen (HLA)-matched sibling donor for six patients, HLA-matched unrelated donor for nine, and haploidentical familial donor for two. The median onset and duration of BKV-HC was on day 21 after transplantation (minimum-maximum: 7-97) and 22 days (minimum-maximum: 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response, one had partial response, and five had no response. Among the five nonresponders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, achieving complete response (n=2) and partial response (n=2). The median duration from the start of leflunomide therapy to response was 13 days (minimum-maximum: 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. Conclusion: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who do not respond to supportive

Heat Shock Protein-70 Inducers and iNOS Inhibitors as Therapeutics to Ameliorate Hemorrhagic Shock

DTIC Science & Technology

2004-09-01

downregulation of iNOS can limit tissue injury caused by ischemia / reperfusion or hemorrhage/resuscitation. In our laboratory, geldanamycin, a member of... ischemia / reperfusion [Charier 1999]. Mice deficient in inducible NO synthase (iNOS) also demonstrate limited hemorrhage/resuscitation-induced injury ...tissues and leukotriene B4 (LTB4) generation increases. In a hemorrhage/resuscitation-induced injury model, iNOS, cyclooxygenase- 2 , and CD14 are all

Intravesical NGF Antisense Therapy Using Lipid Nanoparticle for Interstitial Cystitis

DTIC Science & Technology

2015-10-01

intravesical botulinum toxin type A injec- tions plus hydrodistention with hydrodis- tention alone for the treatment of refractory interstitial cystitis/ painful ...SUPPLEMENTARY NOTES 14. ABSTRACT Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating disorder characterized by persistent pelvic pain ...from an animal efficacy experiment conducted during the previous period. The project is ongoing. 15. SUBJECT TERMS Interstitial cystitis/ painful

Elevated Urine Levels of Macrophage Migration Inhibitory Factor in Inflammatory Bladder Conditions: A Potential Biomarker for a Subgroup of Interstitial Cystitis/Bladder Pain Syndrome Patients.

PubMed

Vera, Pedro L; Preston, David M; Moldwin, Robert M; Erickson, Deborah R; Mowlazadeh, Behzad; Ma, Fei; Kouzoukas, Dimitrios E; Meyer-Siegler, Katherine L; Fall, Magnus

2018-06-01

To investigate whether urinary levels of macrophage migration inhibitory factor (MIF) are elevated in interstitial cystitis/bladder pain syndrome (IC/BPS) patients with Hunner lesions and also whether urine MIF is elevated in other forms of inflammatory cystitis. Urine samples were assayed for MIF by enzyme-linked immunosorbent assay. Urine samples from 3 female groups were examined: IC/BPS patients without (N = 55) and with Hunner lesions (N = 43), and non-IC/BPS patients (N = 100; control group; no history of IC/BPS; cancer or recent bacterial cystitis). Urine samples from 3 male groups were examined: patients with bacterial cystitis (N = 50), radiation cystitis (N = 18) and noncystitis patients (N = 119; control group; negative for bacterial cystitis). Urine MIF (mean MIF pg/mL ±  standard error of the mean) was increased in female IC/BPS patients with Hunner lesions (2159 ± 435.3) compared with IC/BPS patients without Hunner lesions (460 ± 114.5) or non-IC/BPS patients (414 ± 47.6). Receiver operating curve analyses showed that urine MIF levels discriminated between the 2 IC groups (area under the curve = 72%; confidence interval 61%-82%). Male patients with bacterial and radiation cystitis had elevated urine MIF levels (2839 ± 757.1 and 4404 ± 1548.1, respectively) compared with noncystitis patients (681 ± 75.2). Urine MIF is elevated in IC/BPS patients with Hunner lesions and also in patients with other bladder inflammatory and painful conditions. MIF may also serve as a noninvasive biomarker to select IC/BPS patients more accurately for endoscopic evaluation and possible anti-inflammatory treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T-cell depleted peripheral blood and cord blood stem cell transplants

PubMed Central

Lee, Yeon Joo; Zheng, Junting; Kolitsopoulos, Yovanna; Chung, Dick; Amigues, Isabelle; Son, Tammy; Choo, Kathleen; Hester, Jeff; Giralt, Sergio A.; Glezerman, Ilya G.; Jakubowski, Ann A.; Papanicolaou, Genovefa A.

2014-01-01

Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BKV reactivation, hemorrhagic cystitis (HC) and renal dysfunction. We prospectively monitored 98 HSCT by serial BKV PCR in the urine through Day (D) +100 to analyze the relationship between BKV viruria and HC, serum creatinine (Cr) and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years, range 20-73, received T-cell depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BKV viruria ≥ 107 copies/mL. By D +100, 53 (54%) patients had BKV viruria. BKV viral load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7/10 with BKV viruria. In competing risk analyses, BKV viruria ≥ 107 copies/mL, older age, CMV reactivation and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3 and 6 months post-HSCT were similar between patients with and without BKV viruria. PMID:24769326

Full myeloablative conditioning and an unrelated HLA mismatched donor increase the risk for BK virus-positive hemorrhagic cystitis in allogeneic hematopoetic stem cell transplanted patients.

PubMed

Dalianis, Tina; Ljungman, Per

2011-03-01

BK virus (BKV)-associated hemorrhagic cystitis (HC), varying from mild hematuria with or without dysuria to life-threating bleeding and clots that may cause urinary obstruction and renal failure, causes significant morbidity and mortality in haematopoetic stem cell transplanted (HSCT) patients. Unfortunately, its development is difficult to predict since BK viruria is very common after HSCT and can be present in patients with and without HC. There is therefore the need to identify risk factors that may increase the risk of developing HC after HSCT. The viral load of BK-viruria, as well as BK viremia, has been monitored for this purpose. Moreover, having full myeoblative conditioning (MC) versus reduced intensity conditioning (RIC) prior to HSCT and an HLA-matched or -mismatched graft from an unrelated donor in contrast to an HLA-matched graft from a related donor have been studied as risk factors for HC. In addition, graft versus host disease has been examined, but has not been defined as a definite risk factor for HC. We conclude that the present evidence suggests that HSCT patients with BK viruria, receiving MC and an unrelated donor graft that is HLA-mismatched have an increased risk for developing HC in comparison to patients receiving RIC and an HLA-matched related donor graft.

BK virus (BKV) plasma dynamics in patients with BKV-associated hemorrhagic cystitis following allogeneic stem cell transplantation.

PubMed

Drew, R J; Walsh, A; Ní Laoi, B; Conneally, E; Crowley, B

2013-06-01

The use of real-time polymerase chain reaction testing in the investigation of BK virus (BKV)-associated disease has been widely studied in renal transplant recipients; however, far less research has been done in this area with respect to the plasma BK viral load dynamics of BKV hemorrhagic cystitis (BKV-HC) in hematopoietic stem cell transplant recipients. The aim of this study was to examine the BK viral load dynamics in plasma samples collected from patients post transplant who had laboratory-confirmed BKV-HC. Patients who developed BK viremia were compared with patients who did not develop viremia, and a statistical comparison of risk factors for viremia was performed. Seventeen patients were included in this study. Urine samples from the day of BKV diagnosis were available in 13 of the 17 cases. In total, 154 archived plasma samples from around the time of the BKV-HC event were also included in the study from these 17 patients. The median time from transplantation to the onset of detectable viremia was 68 days. The median viral load in the 13 urine samples was 1.8 × 10(8) copies/mL, which was significantly higher than the median viral load in the 38 positive plasma samples of 6.6 × 10(2) copies/mL (Mann-Whitney test, U = 16, P < 0.001). The lymphocyte count on the day of the positive BKV test was significantly lower in patients with BKV viremia than in patients with no viremia (P = 0.02) and also the white cell and platelet counts were lower on the day of the first positive BKV test. Although there is not inter-patient consistency as regards correlation between urinary BK viral loads and severity of clinical BKV-HC, in individual patients the decline in viral load in plasma did correlate with clinical recovery. © 2013 John Wiley & Sons A/S.

Severe emphysematous cystitis: Outcome after seven days of antibiotics

PubMed Central

Sereno, Maria; Gómez-Raposo, César; Gutiérrez- Gutiérrez, Gerardo; López-Gómez, Miriam; Casado, Enrique

2011-01-01

We present the case of a 70-year-old woman with emphysematous cystitis. She was a diabetic patient and she was on chemotherapy treatment for a breast cancer. She complaint of severe asthenia and pain in her right lower extremity, but no fever or urinary symptoms. A computed tomography (CT) scan was suggestive of severe emphysematous cystitis. Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients. A conservative treatment approach using antibiotics and bladder catheterization is typically successful, with a complication rate less than 20%. PMID:22363178

Aging exacerbates intracerebral hemorrhage-induced brain injury.

PubMed

Lee, Jae-Chul; Cho, Geum-Sil; Choi, Byung-Ok; Kim, Hyoung Chun; Kim, Won-Ki

2009-09-01

Aging may be an important factor affecting brain injury by intracerebral hemorrhage (ICH). In the present study, we investigated the responses of glial cells and monocytes to intracerebral hemorrhage in normal and aged rats. ICH was induced by microinjecting autologous whole blood (15 microL) into the striatum of young (4 month old) and aged (24 month old) Sprague-Dawley rats. Age-dependent relations of brain tissue damage with glial and macrophageal responses were evaluated. Three days after ICH, activated microglia/macrophages with OX42-positive processes and swollen cytoplasm were more abundantly distributed around and inside the hemorrhagic lesions. These were more dramatic in aged versus the young rats. Western blot and immunohistochemistry analyses showed that the expression of interleukin-1beta protein after ICH was greater in aged rats, whereas the expression of GFAP and ciliary neurotrophic factor protein after ICH was significantly lower in aged rats. These results suggest that ICH causes more severe brain injury in aged rats most likely due to overactivation of microglia/macrophages and concomitant repression of reactive astrocytes.

Efficacy and safety of leflunomide for the treatment of BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients.

PubMed

Chen, Xin-Chuan; Liu, Ting; Li, Jian-Jun; He, Chuan; Meng, Weng-Tong; Huang, Rui

2013-01-01

BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation. So far, no specific antiviral drug with proven efficacy has been approved for treating BKV-HC. Leflunomide is an immunosuppressive drug with antiviral activity and has been used in treating BKV-associated nephropathy after renal transplantation. This is the first report on the efficacy and safety of leflunomide in the treatment of BKV-HC. From January 2006 to January 2009, 89 patients received allogeneic hematopoietic stem cell transplantation, and among them, 18 patients were identified as having BKV-HC, with a 20% cumulative incidence. Fourteen patients were treated with oral leflunomide. Three days of 100 mg/day leflunomide was used as loading doses and followed by maintenance doses of 20 mg/day. The urinary BKV-DNA load was monitored weekly by real-time quantitative PCR. The efficacy was evaluated on day 20 after leflunomide treatment. Seven patients (50%) achieved complete remission, 5 patients (35.7%) achieved partial remission, and 2 patients (14.3%) had more than a 1-log reduction in urinary BKV-DNA loads after treatment. During the leflunomide treatment, the graft-versus-host disease of the patients did not progress, and the dosages of the immunosuppressant were reduced simultaneously. One patient discontinued treatment because of intolerable gastrointestinal symptoms. Neutropenia occurred in 2 cases. These preliminary data suggest that leflunomide may be a potentially effective medication for treating BKV-HC without significant toxicity, but evidence supporting its use requires randomized controlled trials. Copyright © 2013 S. Karger AG, Basel.

[The BK virus load in urine in association with the development of hemorrhagic cystitis after hematopoietic stem cell transplantation].

PubMed

Xie, Ying; Han, Yue; Wu, De-pei; Sun, Ai-ning; Cen, Jian-nong; Yao, Li; Ruan, Chang-geng

2009-08-01

To analyze the relationship between BK viruria and the late onset hemorrhagic cystitis (LOHC) after hematopoietic stem cell transplantation (HSCT), and investigate the role of BK virus load in the development of LOHC. From August 2006 to April 2008, urine samples were collected weekly from 113 patients undergoing HSCT. Virus DNA were extracted from the urine samples and amplified by qualitative PCR. Real-time quantitative PCR was used to quantify BKV DNA in the urine samples of all BK viruria patients. LOHC occurred in 22 patients (19.5%), including grade 1 in 7, grade 2 in 11, grade 3 in 3, and grade 4 in one. The median onset time was 44 (13 - 114) days after transplantation. Twenty-one of which (95.5%) were BK virus positive, being significantly higher than that in non-LOHC patients (31.9%) (P = 0.000). No BK virus was detected in the healthy control group at the same time. Quantitative PCR detection showed that the mean BK virus DNA copies in LOHC patients at a week before occurring HC was higher than that at the first positive samples (10(5) copies/microl versus 10(4) copies/microl, P = 0.025), and it was no significant change at the onset and a week after HC. Meanwhile, there was no statistical difference in the mean level of BK virus DNA copies among the LOHC patients with different grades. The mean level of BK virus DNA copies in non-HC patients was 10(3) to 10(4) copies/microl, being lower than that in LOHC patients. BK viruria is an important pathogenic cause of the LOHC after HSCT. The occurrence of BKV viruria in HSCT patients, together with the increasing of BK virus DNA copies in urine, over the level of 10(5) copies/microl may indicate a possible development of LOHC.

Treatment of BK virus-associated hemorrhagic cystitis in pediatric hematopoietic stem cell transplant recipients with cidofovir: a single-center experience.

PubMed

Kwon, H J; Kang, J H; Lee, J W; Chung, N-G; Kim, H-K; Cho, B

2013-12-01

BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is a severe complication after hematopoietic stem cell transplantation (HSCT). Cidofovir (CDV) has emerged as an effective agent for the treatment of BKV nephropathy, but its use for BKV-HC in pediatric HSCT recipients has not yet been established as a standard therapy. We retrospectively investigated the efficacy and safety of CDV therapy for patients with BKV-HC at a single institution and analyzed the clinical management outcomes. From April 2009 to July 2011, 12 patients developed BKV-HC at a median of 37 days after transplant (range 15-59 days). The cumulative incidence was 9% and the median peak of the urine BKV load was 2.5 × 10(10) copies/mL (range 1.4 × 10(9) -1.2 × 10(11) copies/mL). Eleven patients received intravenous CDV (5 mg/kg/dose, with probenecid), whereas 1 patient received CDV (5 mg/kg/dose, without probenecid) intravesically. The median duration of therapy was 25 days (range 9-73 days), and a median of 2 doses was given (range 1-4). A reduction of ≥ 1 log in the BKV load was found in 11 patients, while 1 patient did not have any significant change in BKV load. Clinical improvement was observed in all cases, and no HC-related death was observed. CDV-related toxicity occurred in 1 patient (8%) and spontaneously resolved. CDV appears to be an effective and safe treatment for BKV-HC in pediatric HSCT recipients, but prospective trials are warranted to support its use. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of the Human Polyomavirus, BKV, in Prostate Cancer

DTIC Science & Technology

2004-08-01

can be reactivated upon immunosuppression, often leading to hemorrhagic cystitis or nephritis. Previous studies have found BKV to be tumorigenic in...reactivated upon immunosuppression of the host and is The BKV genome is divided into regulatory, early, associated with hemorrhagic cystitis and...life cycle is replication of its urinary tract, which can lead to hemorrhagic cystitis and DNA. To assess this step, we isolated low molecular weight

EXERCISE-INDUCED PULMONARY HEMORRHAGE AFTER RUNNING A MARATHON

EPA Science Inventory

We report on a healthy 26-year-old male who had an exercise-induced pulmonary hemorrhage (EIPH) within 24 hours of running a marathon. There were no symptoms, abnormalities on exam, or radiographic infiltrates. He routinely participated in bronchoscopy research and the EIPH was e...

Lupus cystitis in Korean patients with systemic lupus erythematosus: risk factors and clinical outcomes.

PubMed

Koh, J H; Lee, J; Jung, S M; Ju, J H; Park, S-H; Kim, H-Y; Kwok, S-K

2015-10-01

This study was performed to investigate the clinical characteristics of lupus cystitis and determine the risk factors and clinical outcomes of lupus cystitis in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed 1064 patients at Seoul St. Mary's Hospital in Seoul, Korea, from 1998 to 2013. Twenty-four patients had lupus cystitis. Lupus cystitis was defined as unexplained ureteritis and/or cystitis as detected by imaging studies, cystoscopy, or bladder histopathology without urinary microorganisms or stones. Three-fourths of patients with lupus cystitis had concurrent lupus mesenteric vasculitis (LMV). The initial symptoms were gastrointestinal in nature for most patients (79.2%). High-dose methylprednisolone was initially administered to most patients (91.7%) with lupus cystitis. Two patients (8.3%) died of urinary tract infections. Sixty-five age- and sex-matched patients with SLE who were admitted with other manifestations were included as the control group. Patients with lupus cystitis showed a lower C3 level (p = 0.031), higher SLE Disease Activity Index score (p = 0.006), and higher ESR (p = 0.05) upon admission; more frequently had a history of LMV prior to admission (p < 0.001); and less frequently had a history of neuropsychiatric lupus (p = 0.031) than did patients with SLE but without lupus cystitis. The occurrence of lupus cystitis was associated with a history of LMV (OR, 21.794; 95% CI, 4.061-116.963). The median follow-up period was 3.4 years, and the cumulative one-year mortality rate was 20%. Complications developed in 33.3% of patients with lupus cystitis and were related to survival (log-rank p = 0.021). Our results suggest that the possibility of lupus cystitis should be considered when a patient with SLE and history of LMV presents with gastrointestinal symptoms or lower urinary tract symptoms. Development of complications in patients with lupus cystitis can be fatal. Thus, intensive treatment

Neonatal cystitis-induced colonic hypersensitivity in adult rats: a model of viscero-visceral convergence.

PubMed

Miranda, A; Mickle, A; Schmidt, J; Zhang, Z; Shaker, R; Banerjee, B; Sengupta, J N

2011-07-01

The objective of this study was to determine if neonatal cystitis alters colonic sensitivity later in life and to investigate the role of peripheral mechanisms. Neonatal rats received intravesical zymosan, normal saline, or anesthesia only for three consecutive days [(postnatal (PN) days 14-16)]. The estrous cycle phase was determined prior to recording the visceromotor response (VMR) to colorectal distension (CRD) in adult rats. Eosinophils and mast cells were examined from colon and bladder tissues. CRD- or urinary bladder distension (UBD)-sensitive pelvic nerve afferents (PNAs) were identified and their responses to distension were examined. The relative expression of N-methyl-d-aspartic acid (NMDA)-NR1 subunit in the lumbo-sacral (L6-S1) spinal cord was examined using Western blot. The VMR to CRD (≥10mmHg) in the neonatal zymosan group was significantly higher than control in both the diestrus, estrus phase and in all phases combined. There was no difference in the total number of eosinophils, mast cells or number of degranulated mast cells between groups. The spontaneous firing of UBD, but not CRD-sensitive PNAs from the zymosan-treated rats was significantly higher than the saline-treated control. However, the mechanosensitive properties of PNAs to CRD or UBD were no different between groups (P>0.05). The expression of spinal NR1 subunit was significantly higher in zymosan-treated rats compared with saline-treated rats (P<0.05). Neonatal cystitis results in colonic hypersensitivity in adult rats without changing tissue histology or the mechanosensitive properties of CRD-sensitive PNAs. Neonatal cystitis does result in overexpression of spinal NR1 subunit in adult rats. © 2011 Blackwell Publishing Ltd.

Prolonged hydrocephalus induced by intraventricular hemorrhage in rats is reduced by curcumin therapy.

PubMed

Qi, Zhihua; Zhang, Huiqin; Fu, Chuhua; Liu, Xiao; Chen, Bo; Dang, Yanwei; Chen, Huayun; Liu, Lijun

2017-01-10

Prolonged hydrocephalus is a major cause of severe disability and death of intraventricular hemorrhage (IVH) patients. However, the therapeutic options to minimize the detrimental effects of post-hemorrhagic hydrocephalus are limited. Curcumin has been reported to confer neuroprotective effects in numerous neurological diseases and injuries, but its role in IVH-induced hydrocephalus has not been determined. The aim of present study was to determine whether curcumin treatment ameliorates blood brain barrier (BBB) damage and reduces the incidence of post-hemorrhagic hydrocephalus in IVH rat model. Autologous blood intraventricular injection was used to establish the IVH model. Our results revealed that repeated intraperitoneal injection of curcumin ameliorated IVH-induced learning and memory deficits as determined by Morris water maze and reduced the incidence of post-hemorrhagic hydrocephalus in a dose-dependent manner at 28 d post-IVH induction. Further, the increased BBB permeability and brain edema induced by IVH were significantly reduced by curcumin administration. In summary, these findings highlighted the important role of curcumin in improving neurological function deficits and protecting against BBB disruption via promoting the neurovascular unit restoration, and thus it reduced the severity of post-hemorrhagic hydrocephalus in the long term. It is believed that curcumin might prove to be an effective therapeutic component in prevent the post-IVH hydrocephalus in the near future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Involvement of the cystathionine-γ-lyase/Cav3.2 pathway in substance P-induced bladder pain in the mouse, a model for nonulcerative bladder pain syndrome.

PubMed

Tsubota, Maho; Okawa, Yasumasa; Irie, Yuhei; Maeda, Mariko; Ozaki, Tomoka; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Kawabata, Atsufumi

2018-05-01

Hydrogen sulfide (H 2 S) formed by cystathionine-γ-lyase (CSE) enhances the activity of Ca v 3.2 T-type Ca 2+ channels, contributing to the bladder pain accompanying hemorrhagic cystitis caused by systemic administration of cyclophosphamide (CPA) in mice. Given clinical and fundamental evidence for the involvement of the substance P/NK 1 receptor systems in bladder pain syndrome (BPS)/interstitial cystitis (IC), we created an intravesical substance P-induced bladder pain model in mice and analyzed the possible involvement of the CSE/Ca v 3.2 pathway. Bladder pain/cystitis was induced by i.p. CPA or intravesical substance P in female mice. Bladder pain was evaluated by counting nociceptive behavior and by detecting referred hyperalgesia in the lower abdomen and hindpaw. The isolated bladder tissue was weighed to estimate bladder swelling and subjected to histological observation and Western blotting. Intravesical substance P caused profound referred hyperalgesia accompanied by little bladder swelling or edema 6-24 h after the administration, in contrast to i.p. CPA-induced nociceptive behavior/referred hyperalgesia with remarkable bladder swelling/edema and urothelial damage. The bladder pain and/or cystitis symptoms caused by substance P or CPA were prevented by the NK 1 receptor antagonist. CSE in the bladder was upregulated by substance P or CPA, and the NK 1 antagonist prevented the CPA-induced CSE upregulation. A CSE inhibitor, a T-type Ca 2+ channel blocker and gene silencing of Ca v 3.2 abolished the intravesical substance P-induced referred hyperalgesia. The intravesical substance P-induced pain in mice is useful as a model for nonulcerative BPS, and involves the activation of the NK 1 receptor/CSE/H 2 S/Ca v 3.2 cascade. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prevention of Cystitis: Travelling between the Imaginary and Reality.

PubMed

Vecchio, Mariacristina; Iroz, A; Seksek, I

2018-01-01

As a preventive strategy, increased water intake is often recommended to women affected by recurrent cystitis; however, clinical data are sparse and conflicting. This review evaluates the preventive approaches used as alternatives to obtain relief from the burden of cystitis and focuses on the effect of fluid intake on urinary tract infection. © 2018 The Author(s) Published by S. Karger AG, Basel.

Complement component C5a mediates hemorrhage-induced intestinal damage

PubMed Central

Fleming, Sherry D.; Phillips, Lauren M.; Lambris, John D.; Tsokos, George C.

2008-01-01

Background Complement has been implicated in the pathogenesis of intestinal damage and inflammation in multiple animal models. Although the exact mechanism is unknown, inhibition of complement prevents hemodynamic alterations in hemorrhage. Materials/Methods C57Bl/6, complement 5 deficient (C5−/−) and sufficient (C5+/+) mice were subjected to 25% blood loss. In some cases, C57Bl/6 mice were treated with C5a receptor antagonist (C5aRa) post-hemorrhage. Intestinal injury, leukotriene B4, and myeloperoxidase production were assessed for each treatment group of mice. Results Mice subjected to significant blood loss without major trauma develop intestinal inflammation and tissue damage within two hours. We report here that complement 5 (C5) deficient mice are protected from intestinal tissue damage when subjected to hemorrhage (Injury score = 0.36 compared to wildtype hemorrhaged animal injury score = 2.89; p<0.05). We present evidence that C5a represents the effector molecule because C57Bl/6 mice treated with a C5a receptor antagonist displayed limited intestinal injury (Injury score = 0.88), leukotriene B4 (13.16 pg/mg tissue) and myeloperoxidase (115.6 pg/mg tissue) production compared to hemorrhaged C57Bl/6 mice (p<0.05). Conclusion Complement activation is important in the development of hemorrhage-induced tissue injury and C5a generation is critical for tissue inflammation and damage. Thus, therapeutics targeting C5a may be useful therapeutics for hemorrhage-associated injury. PMID:18639891

A Prospective Study on the Predictive Value of Plasma BK Virus-DNA Load for Hemorrhagic Cystitis in Pediatric Patients After Stem Cell Transplantation.

PubMed

Cesaro, Simone; Tridello, Gloria; Pillon, Marta; Calore, Elisabetta; Abate, Davide; Tumino, Manuela; Carucci, Nicolina; Varotto, Stefania; Cannata, Elisa; Pegoraro, Anna; Barzon, Luisa; Palù, Giorgio; Messina, Chiara

2015-06-01

In hematopoietic stem cell transplantation (HSCT), late hemorrhagic cystitis (HC) has been associated with BK virus (BKV) infection. We assessed the value of plasma BKV load in predicting HC. Plasma and urine BKV-DNA load were assessed prospectively in 107 pediatric patients. Twenty patients developed grade II and III HC, with 100-day cumulative incidence of 18.8%. At diagnosis of HC, the median load of BKV DNA was 2.3 × 10(3) copies/mL. A plasma BKV-DNA load of 10(3) copies/mL had a sensitivity of 100% and a specificity of 86% with a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 39% for HC. A urine BKV-DNA load of >10(7) copies/mL had a sensitivity of 86% and a specificity of 60% with a NPV of 98% and a PPV of 14% for HC. A BKV load of 10(3) copies/mL on plasma was significantly associated with HC in multivariate analysis (hazard ratio [HR], 6.1; P = .0006). Patients with HC had a significantly higher risk of mortality than patients who did not have HC (HR, 2.6; P = .018). The above values were used to monitor plasma BKV-DNA load, and they provided a better prediction of patients at risk of HC than urine BKV-DNA load. © The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study.

PubMed

Suskind, Anne M; Berry, Sandra H; Ewing, Brett A; Elliott, Marc N; Suttorp, Marika J; Clemens, J Quentin

2013-01-01

As part of the RICE (RAND Interstitial Cystitis Epidemiology) study, we developed validated case definitions to identify interstitial cystitis/bladder pain syndrome in women and chronic prostatitis/chronic pelvic pain syndrome in men. Using population based screening methods, we applied these case definitions to determine the prevalence of these conditions in men. A total of 6,072 households were contacted by telephone to screen for men who had symptoms of interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome. An initial 296 men screened positive, of whom 149 met the inclusionary criteria and completed the telephone interview. For interstitial cystitis/bladder pain syndrome 2 case definitions were applied (1 with high sensitivity and 1 with high specificity), while for chronic prostatitis/chronic pelvic pain syndrome a single case definition (with high sensitivity and specificity) was used. These case definitions were used to classify subjects into groups based on diagnosis. The interstitial cystitis/bladder pain syndrome weighted prevalence estimates for the high sensitivity and high specificity definitions were 4.2% (3.1-5.3) and 1.9% (1.1-2.7), respectively. The chronic prostatitis/chronic pelvic pain syndrome weighted prevalence estimate was 1.8% (0.9-2.7). These values equate to 1,986,972 (95% CI 966,042-2,996,924) men with chronic prostatitis/chronic pelvic pain syndrome and 2,107,727 (95% CI 1,240,485-2,974,969) men with the high specificity definition of interstitial cystitis/bladder pain syndrome in the United States. The overlap between men who met the high specificity interstitial cystitis/bladder pain syndrome case definition or the chronic prostatitis/chronic pelvic pain syndrome case definition was 17%. Symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome are widespread among men in the United States. The prevalence of interstitial cystitis/bladder pain

Cystitis glandularis in a cat.

PubMed

Agut, Amalia; Carrillo, Juana D; Soler, Marta; García, Juan D; Belda, Eliseo; Gómez, Miguel A; Bernabe, Antonio

2014-04-01

An 8-year-old intact male Persian cat was presented for investigation of chronic haematuria. The cat had episodes of haematuria on several occasions that were non-responsive to antimicrobial therapy. Abdominal ultrasound examination revealed dilation of the renal pelvis and ureters of both kidneys. The urinary bladder wall was thickened, a mass of heterogeneous echogenicity filled the lumen of the bladder, and two parallel thin hyperechoic lines were identified within the lumen, which suggested a urethral catheter. Differential diagnoses for the urinary bladder mass included cystitis and neoplasia. The mass was surgically removed from the urinary bladder, and a urethral catheter was found embedded in the mass. Histopathological findings were consistent with cystitis glandularis of a typical type. Periodic bladder ultrasonographic studies were performed; at the time of writing, over 2 years later, recurrence had not been detected.

Use of Hypoprothrombinemia-Inducing Cephalosporins and the Risk of Hemorrhagic Events: A Nationwide Nested Case-Control Study

PubMed Central

Shen, Li-Jiuan; Wu, Fe-Lin Lin; Tsay, Woei; Hung, Chien-Ching; Lin, Shu-Wen

2016-01-01

Objective Existing data regarding the risk of hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins are limited by the small sample size. This population-based study aimed to examine the association between exposure to hypoprothrombinemia-inducing cephalosporins and hemorrhagic events using National Health Insurance Research Database in Taiwan. Design A nationwide nested case-control study. Setting National Health Insurance Research database. Participants We conducted a nested case-control study within a cohort of 6191 patients who received hypoprothrombinemia-inducing cephalosporins and other antibiotics for more than 48 hours. Multivariable conditional logistic regressions were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins (overall, cumulative dose measured as defined daily dose (DDD), and individual cephalosporins). Results Within the cohort, we identified 704 patients with hemorrhagic events and 2816 matched controls. Use of hypoprothrombinemia-inducing cephalosporins was associated with increased risk of hemorrhagic events (aOR, 1.71; 95% CI, 1.42–2.06), which increased with higher cumulative doses (<3 DDDs, aOR 1.62; 3–5 DDDs, aOR 1.78; and >5 DDDs, aOR 1.89). The aOR for individual cephalosporin was 2.88 (95% CI, 2.08–4.00), 1.35 (1.09–1.67) and 4.57 (2.63–7.95) for cefmetazole, flomoxef, and cefoperazone, respectively. Other risk factors included use of anticoagulants (aOR 2.08 [95% CI, 1.64–2.63]), liver failure (aOR 1.69 [1.30–2.18]), poor nutritional status (aOR 1.41 [1.15–1.73]), and history of hemorrhagic events (aOR 2.57 [1.94–3.41]) 6 months prior to the index date. Conclusions Use of hypoprothrombinemia-inducing cephalosporins increases risk of hemorrhagic events. Close watch for hemorrhagic events is recommended when prescribing these cephalosporins, especially in

[Experience in the treatment of interstitial cystitis: review of 17 cases].

PubMed

Flores-Carreras, Oscar; Martínez-Espinoza, Claudia J; González-Ruiz, María Isabel

2011-03-01

The Interstitial Cystitis (IC) has been considered in the past an uncommon pathology, however it has received a special attention during the last 20 years, (1678 scientific articles published since 1984 to 2009). There are many therapeutic options not at all satisfactory because there isn't consensus about diagnostic and treatment. To share our experiences in the treatment of interstitial cystitis, additionally, to comment on the therapeutic response of treatment used. Observational, retrospective an analytic study of 17 treated patients from 22 with diagnosis of IC and Bladder Painful Syndrome (IC/BPS) were managed in Urodifem de Occidente, S.C. a private Urogynecologic unit between January 2001 and April 2010. The diagnosis was done in agreement with the concepts of Interstitial Cystitis group from clinical and cystoscopic characteristics. The treatment was: Dimethyl sulfoxide (DIMSO) and Pentosan Polysulfate. The evaluation was measured by Interstitial Cystitis Symptomatic Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) both validated evaluation instruments, 82% of the patients had a significative improvement of symptomatology and quality of live The ICSI pre and post treatment was of 17.0 and 4.5 and the ICPI was of 14.8 and 4.1 respectively. We recommend the use of combine treatment of DIMSO and PPS in cases of I.C.

Bladder pain syndrome/interstitial cystitis as a functional somatic syndrome.

PubMed

Warren, John W

2014-12-01

To determine whether bladder pain syndrome/interstitial cystitis (BPS/IC) has the characteristics of a functional somatic syndrome (FSS). There is no accepted definition of an FSS. Consequently, this paper reviewed the literature for common FSS characteristics and for reports that BPS/IC has these characteristics. Eleven articles met inclusion and exclusion criteria and yielded 18 FSS characteristics. BPS/IC patients manifest all but two: the exceptions were normal light microscopic anatomy (after hydrodistention under anesthesia, some BPS/IC bladders have Hunner's lesions and most have petechial hemorrhages) and normal laboratory tests (many BPS/IC patients have hematuria). Petechial hemorrhages and hematuria are probably related and may appear during naturally-occurring bladder distention. Without such distention, then, the 90% of BPS/IC patients without a Hunner's lesion have all the characteristics of an FSS. Comparisons in the opposite direction were consistent: several additional features of BPS/IC were found in FSSs. This systematic but untested method is consistent with but does not test the hypothesis that BPS/IC in some patients might best be understood as an FSS. Like most conditions, BPS/IC is probably heterogeneous; hence only a proportion of BPS/IC cases are likely to be manifestations of an FSS. This hypothesis has several implications. Explorations of processes that connect the FSSs might contribute to understanding the pathogenesis of BPS/IC. Patients with FSSs are at risk for BPS/IC and may benefit from future preventive strategies. Therapies that are useful in FSSs also may be useful in some cases of BPS/IC. Copyright © 2014 Elsevier Inc. All rights reserved.

Monitoring of polyomavirus BK viruria in bone marrow transplantation patients by DNA hybridization assay and by polymerase chain reaction: an approach to assess the relationship between BK viruria and hemorrhagic cystitis.

PubMed

Azzi, A; Fanci, R; Bosi, A; Ciappi, S; Zakrzewska, K; de Santis, R; Laszlo, D; Guidi, S; Saccardi, R; Vannucchi, A M

1994-08-01

An association between long-lasting hemorrhagic cystitis (HC) in bone marrow transplantation (BMT) patients and viral infections, mostly with reactivation of the human polyomavirus BK (BKV), is suggested by several previous reports. We have carried out a prospective study in 55 (30 allogeneic, 24 autologous, 1 syngeneic) BMT recipients with the aim of evaluating the role of BKV in this frequent complication after BMT. To overcome the well known difficulties in BK virus isolation in cell cultures, a DNA hybridization assay and the polymerase chain reaction (PCR) were used for the detection and monitoring of viral urinary shedding, respectively. The presence of human polyomavirus JC and adenovirus DNA was also sought in urine specimens. BK viruria was demonstrated in 52.7% of patients (in 53.3% allogeneic and in 54.1% autologous BMT), whereas JCV and adenovirus were seldom present. Seven cases of HC (20% in allogeneic and 4% in autologous BMT) occurred and in all cases the clinical event was associated with BKV urinary shedding. This study suggests that BKV infection alone does not invariably lead to HC in BMT patients; for HC to occur the presence of other, at present unidentified, factors seems to be necessary.

Randomized study of whole-abdomen irradiation versus pelvic irradiation plus cyclophosphamide in treatment of early ovarian cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sell, A.; Bertelsen, K.; Andersen, J.E.

From 1 September 1981 to 1 January 1987, 118 patients with FIGO Stage IB, IC, IIA, IIB, and IIC epithelial ovarian cancer were randomized to abdominal irradiation or pelvic irradiation + cyclophosphamide. There was no difference between the regimens with respect to recurrence-free survival (55%) and 4-year overall survival (63%). At routine second-look laparotomy, 16% of patients without clinical detectable tumor showed recurrence. Twenty-five percent of the patients treated with pelvic irradiation + cyclophosphamide had hemorrhagic cystitis, probably caused by radiation damage and cyclophosphamide cystitis. Eight percent had late gastrointestinal symptoms requiring surgery.

Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T Cell-depleted peripheral blood and cord blood stem cell transplantations.

PubMed

Lee, Yeon Joo; Zheng, Junting; Kolitsopoulos, Yovanna; Chung, Dick; Amigues, Isabelle; Son, Tammy; Choo, Kathleen; Hester, Jeff; Giralt, Sergio A; Glezerman, Ilya G; Jakubowski, Ann A; Papanicolaou, Genovefa A

2014-08-01

Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BK virus (BKV) reactivation, hemorrhagic cystitis (HC), and renal dysfunction. We prospectively monitored 98 patients who had received HSCT by serial BKV PCR in the urine through day (D) +100 to analyze the relationship between BK viruria and HC, serum creatinine (Cr), and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years (range, 20 to 73), received T cell-depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BK viruria ≥ 10(7) copies/mL. By D +100, 53 (54%) patients had BK viruria. BKV load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7 of 10 with BK viruria. In competing risk analyses, BK viruria ≥ 10(7) copies/mL, older age, cytomegalovirus reactivation, and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3, and 6 months after HSCT were similar between patients with and without BK viruria. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

MR Imaging Evaluation of Intracerebral Hemorrhages and T2 Hyperintense White Matter Lesions Appearing after Radiation Therapy in Adult Patients with Primary Brain Tumors.

PubMed

Yoo, Dong Hyun; Song, Sang Woo; Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Park, Chul-Kee; Kim, Il Han; Choi, Seung Hong

2015-01-01

The purpose of our study was to determine the frequency and severity of intracerebral hemorrhages and T2 hyperintense white matter lesions (WMLs) following radiation therapy for brain tumors in adult patients. Of 648 adult brain tumor patients who received radiation therapy at our institute, magnetic resonance (MR) image data consisting of a gradient echo (GRE) and FLAIR T2-weighted image were available three and five years after radiation therapy in 81 patients. Intracerebral hemorrhage was defined as a hypointense dot lesion appearing on GRE images after radiation therapy. The number and size of the lesions were evaluated. The T2 hyperintense WMLs observed on the FLAIR sequences were graded according to the extent of the lesion. Intracerebral hemorrhage was detected in 21 (25.9%) and 35 (43.2) patients in the three- and five-year follow-up images, respectively. The number of intracerebral hemorrhages per patient tended to increase as the follow-up period increased, whereas the size of the intracerebral hemorrhages exhibited little variation over the course of follow-up. T2 hyperintense WMLs were observed in 27 (33.3%) and 32 (39.5) patients in the three and five year follow-up images, respectively. The age at the time of radiation therapy was significantly higher (p < 0.001) in the patients with T2 hyperintense WMLs than in those without lesions. Intracerebral hemorrhages are not uncommon in adult brain tumor patients undergoing radiation therapy. The incidence and number of intracerebral hemorrhages increased over the course of follow-up. T2 hyperintense WMLs were observed in more than one-third of the study population.

Do Anesthetic Techniques Influence the Threshold for Glomerular Capillary Hemorrhage Induced in Rats by Contrast-Enhanced Diagnostic Ultrasound?

PubMed

Miller, Douglas L; Lu, Xiaofang; Fabiilli, Mario; Dou, Chunyan

2016-02-01

Glomerular capillary hemorrhage can be induced by ultrasonic cavitation during contrast-enhanced diagnostic ultrasound (US) exposure, an important nonthermal US bioeffect. Recent studies of pulmonary US exposure have shown that thresholds for another nonthermal bioeffect of US, pulmonary capillary hemorrhage, is strongly influenced by whether xylazine is included in the specific anesthetic technique. The objective of this study was to determine the influence of xylazine on contrast-enhanced diagnostic US-induced glomerular capillary hemorrhage. In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for induction of glomerular capillary hemorrhage in rats by 1.6-MHz intermittent diagnostic US with a microsphere contrast agent (similar to Definity; Lantheus Medical Imaging, Inc, North Billerica, MA). Glomerular capillary hemorrhage was measured as a percentage of glomeruli with hemorrhage found in histologic sections for groups of rats scanned at different peak rarefactional pressure amplitudes. There was a significant difference between the magnitude of the glomerular capillary hemorrhage between the anesthetics at 2.3 MPa, with 45.6% hemorrhage for ketamine only, increasing to 63.2% hemorrhage for ketamine plus xylazine (P < .001). However, the thresholds for the two anesthetic methods were virtually identical at 1.0 MPa, based on linear regression of the exposure response data. Thresholds for contrast-enhanced diagnostic US-induced injury of the microvasculature appear to be minimally affected by anesthetic methods. © 2016 by the American Institute of Ultrasound in Medicine.

Ursolic Acid Inhibits Superoxide Production in Activated Neutrophils and Attenuates Trauma-Hemorrhage Shock-Induced Organ Injury in Rats

PubMed Central

Hwang, Tsong-Long; Shen, Hsin-I; Liu, Fu-Chao; Tsai, Hsin-I; Wu, Yang-Chang; Chang, Fang-Rong; Yu, Huang-Ping

2014-01-01

Neutrophil activation is associated with the development of organ injury after trauma–hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma–hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma–hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma–hemorrhagic shock-induced organ injury in rats. PMID:25360589

Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Philippe, Michael; Ranchon, Florence; Gilis, Lila; Schwiertz, Vérane; Vantard, Nicolas; Ader, Florence; Labussiere-Wallet, Hélène; Thomas, Xavier; Nicolini, Franck-Emmanuel; Wattel, Eric; Ducastelle-Leprêtre, Sophie; Barraco, Fiorenza; Lebras, Laure; Salles, Gilles; Michallet, Mauricette; Rioufol, Catherine

2016-04-01

After allogeneic hematopoietic stem cell transplantation (HSCT), BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication. Although supportive measures have been the standard of care for many years, several studies suggested the efficacy of cidofovir. The aim of this study was to assess the safety profile and efficacy of cidofovir. A retrospective study was conducted on all patients treated with cidofovir in our HSCT unit between March 2011 and May 2013. Data for efficacy (partial [PR] or complete response [CR]), prescription (dose, frequency, number of doses, and administration route), and toxicity were collected from published reports and medical files. Renal toxicity was evaluated using creatinine clearance calculated with the Cockcroft and Gault formula. A parallel literature search using PubMed (last search, May 2015) was performed. From March 2011 to June 2013, 27 of 181 patients undergoing allogeneic HSCT in our department received cidofovir for BKV-HC: 24 (88.9%) intravenously, 1 intravesically, and 2 via both routes. Mean dose was 5 mg/kg per administration, for a median of 4 injections (range, 1 to 11), from twice a week to once every 2 weeks. CR was achieved in 22 patients (81.5%), PR in 2, and no response in 2 patients. Eight patients presented renal failure (29.6%): 6 moderate (creatinine clearance < 60 mL/min) and 2 severe (creatinine clearance < 30 mLmin). Mean decrease in creatinine clearance after cidofovir was 27% (35 mL/min; range, 2 to 159). In 3 cases renal insufficiency and hematologic toxicity led to discontinuation of treatment or switch to intravesical instillation. For 3 patients cidofovir dose was reduced because of nephrotoxicity. Thirteen studies have reported on the use of cidofovir for BKV-HC (204 patients) since 2005. Intravenous cidofovir was used for 91.3% of patients, with doses ranging from .5 to 5 mg/kg. The main toxicity reported was renal failure (9% to 50% in 9 studies). Between 60% and 100% of CRs

[Antibacterial therapy for acute cystitis in the age of growing pathogen resistance].

PubMed

Siniakova, L A

2014-01-01

Acute cystitis refers to uncomplicated lower urinary tract infections, with the recurrence rates after the first cystitis episode being 50%. The basic treatment for the above diseases is antibacterial therapy, whose efficiency depends entirely on the right choice of a drug during initial empiric therapy. The paper gives the European Association of Urology guidelines and Russian guidelines, which are based on the results of both international (ARESC) and Russian (DARMIS) studies of urinary tract infection pathogens and their susceptibility to antibacterial drugs. Phosphomycin trometamol and furasidine potassium are the drugs of choice to treat acute cystitis in Russia now.

Melatonin mitigate cerebral vasospasm after experimental subarachnoid hemorrhage: a study of synchrotron radiation angiography

NASA Astrophysics Data System (ADS)

Cai, J.; He, C.; Chen, L.; Han, T.; Huang, S.; Huang, Y.; Bai, Y.; Bao, Y.; Zhang, H.; Ling, F.

2013-06-01

Cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) is a devastating and unsolved clinical issue. In this study, the rat models, which had been induced SAH by prechiasmatic cistern injection, were treated with melatonin. Synchrotron radiation angiography (SRA) was employed to detect and evaluate CV of animal models. Neurological scoring and histological examinations were used to assess the neurological deficits and CV as well. Using SRA techniques and histological analyses, the anterior cerebral artery diameters of SAH rats with melatonin administration were larger than those without melatonin treatment (p < 0.05). The neurological deficits of SAH rats treated with melatonin were less than those without melatonin treatment (p < 0.05). We concluded that SRA was a precise and in vivo tool to observe and evaluate CV of SAH rats; intraperitoneally administration of melatonin could mitigate CV after experimental SAH.

Case-control study of medical comorbidities in women with interstitial cystitis.

PubMed

Clemens, J Quentin; Meenan, Richard T; O'Keeffe Rosetti, Maureen C; Kimes, Teresa A; Calhoun, Elizabeth A

2008-06-01

We used physician assigned diagnoses in an electronic medical record to assess comorbidities associated with interstitial cystitis. A computer search of the administrative database at Kaiser Permanente Northwest, Portland, Oregon was performed for May 1, 1998 to April 30, 2003. All women with a medical record diagnosis of interstitial cystitis (ICD-9 code 595.1) were identified. These cases were then matched with 3 controls each based on age and duration in the health plan. The medical diagnoses (using ICD-9 codes restricted to 3 digits) assigned to these 2 groups were compared using the OR. A total of 239 cases and 717 matched controls were analyzed. There were 23 diagnoses that were significantly more common in cases than in controls (p < or = 0.005). Seven of these 23 diagnoses were other urological or gynecological codes used to describe pelvic symptoms. Additional specific conditions associated with interstitial cystitis were gastritis (OR 12.2), child abuse (OR 9.3), fibromyalgia (OR 3.0), anxiety disorder (OR 2.8), headache (OR 2.5), esophageal reflux (OR 2.2), unspecified back disorder (OR 2.2) and depression (OR 2.0). A diagnosis of interstitial cystitis was associated with multiple other unexplained physical symptoms and certain psychiatric conditions. Studies to explore the possible biological explanations for these associations are needed. Interstitial cystitis was also associated with a history of child abuse, although 96% of patients with IC did not have this diagnosis.

Hypoxia induces hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.

PubMed

Xiao, Zhengzheng; Liu, Qin; Zhao, Boxi; Wu, Jun; Lei, Ting

2011-12-01

The hypoxia inducible factor 1 α (HIF-1α) activity has been associated with various hemorrhagic events. The biological role of HIF-1α in the hemorrhagic transformation of pituitary adenomas remains unknown. We hypothesized that fast growing tumor cells tend to predispose themselves to sublethal hypoxia and activate the HIF-1α signaling pathway, leading to hemorrhagic transformation in pituitary adenomas. Here, we used apoplectic and non-apoplectic pituitary adenomas to determine the involvement of HIF-1α signaling in intratumoral hemorrhage. We employed HIF-1α overexpression/knockdown strategies to examine the association between HIF-1α signaling and hemorrhagic presentation in vitro and in vivo. In support of our hypothesis, compared with non-hemorrhagic pituitary adenomas, higher cellular proliferation was observed in hemorrhagic ones and it correlated with increased HIF-1α signaling. HIF-1α overexpression activated its downstream genes, vascular endothelial growth factor and the proapoptotic BNIP3, in MMQ pituitary adenoma cells and this up-regulation was attenuated by HIF-1 siRNA. In vivo studies using MMQ cell xenografts in nude mice showed that HIF-1α overexpression significantly promoted hemorrhagic transformation. Our study indicates that tumor hypoxia, following rapid tumor growth, may promote hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.

Eosinophilic cystitis with recurrent urinary retention: case report.

PubMed

Park, Hongzoo

2017-01-01

Eosinophilic cystitis is a rare inflammatory disease of the bladder whose origin, pathogenesis, and treatment are unknown. Frequency, dysuria, and hematuria are frequent symptoms. Here, we report a rare occurrence of recurrent urinary retention and repetitive catheterization. A 67-year-old male presented with acute urinary retention and intermittent gross hematuria of 2 weeks duration. Urethral catheterization followed by a trial without catheter, was successful. Complete blood count showed presence of eosinophils (eosinophilia) and computed tomography of kidneys, ureter and bladder with contrast showed thickened bladder wall and small prostate. Cystoscopy revealed an erythematous lesion over the anterior wall. The rest of the mucosa was normal. Transurethral biopsies of the lesion were performed and histologic examination showed features of eosinophilic cystitis. Despite multiple medication regimens containing corticosteroids and antihistamines, he presented with recurrent urinary retention, approximately once every month. After 6 months, he was started on bethanechol, which led to no catheterization for up to 2 years. To the best of our knowledge, this is the first report on the successful use of bethanechol as a treatment for eosinophilic cystitis with recurrent urinary retention.

Cystoscopic diagnosis of polypoid cystitis in two pet rabbits.

PubMed

Di Girolamo, Nicola; Bongiovanni, Laura; Ferro, Silvia; Melidone, Raffaele; Nicoletti, Annalisa; Duca, Valeria Del; Donnelly, Thomas M; Selleri, Paolo

2017-07-01

CASE DESCRIPTION AS-year-old male Dwarf rabbit and 4-year-old female Mini-Rex rabbit were evaluated because of anorexia and urine scalding of the perineum. CLINICAL FINDINGS Abdominal radiography revealed a diffuse increase in the opacity of the urinary bladder attributable to urinary sludge. In 1 rabbit, abdominal ultrasonography revealed several mass-like lesions protruding from the mucosal surface into the lumen of the urinary bladder. Rabbits were anesthetized, and cystoscopy was performed with a rigid 2.7-mm, 30° endoscope. Histologic analysis of tissue samples obtained through the cystoscope operating channel revealed findings consistent with polypoid cystitis. TREATMENT AND OUTCOME To remove the urinary sludge from each rabbit, the urinary bladder was filled with sterile saline (0.9% NaCl) solution and emptied with a gentle massage several times until the ejected fluid was transparent. Rabbits were treated with NSAIDs, antimicrobials (chosen following microbial culture of urine and antimicrobial susceptibility testing), bathing of the perineum, and a low-calcium diet. The male rabbit died of unrelated causes 18 months later; postmortem examination findings confirmed the polypoid cystitis. The female rabbit remained disease free through to last follow-up (12 months after initial evaluation). CLINICAL RELEVANCE This was the first report of polypoid cystitis in pet rabbits. Although ultrasonographic findings supported this diagnosis, a definitive diagnosis was achieved through cystoscopy and lesion biopsy. Treatments administered were intended to reduce the potential sources of irritation. Research is needed to investigate the effectiveness of the applied interventions and the association between excessive urinary calcium excretion and polyploid cystitis in rabbits.

Pressure threshold for shock wave induced renal hemorrhage.

PubMed

Mayer, R; Schenk, E; Child, S; Norton, S; Cox, C; Hartman, C; Cox, C; Carstensen, E

1990-12-01

Studies were performed with an interest in determining a pressure threshold for extracorporeal shock wave induced renal damage. Histological evidence of intraparenchymal hemorrhage was used as an indicator of tissue trauma. Depilated C3H mice were anesthetized and placed on a special frame to enhance visualization and treatment of the kidneys in situ. A Wolf electrohydraulic generator and 9 French probe designed for endoscopic use were utilized to expose the kidneys to 10 double spherically divergent shock waves. Measurements of the shock waves revealed two positive pressure peaks of similar magnitude for each spark discharge. The kidneys were exposed to different peak pressures by choice of distance from the spark source and were removed immediately after treatment for histologic processing. A dose response was noted with severe corticomedullary damage apparent following 15 to 20 MPa shocks. Hemorrhage was more apparent in the medulla where evidence of damage could be seen following pressures as low as three to five MPa. When a latex membrane was interposed to prevent possible collapse of the initial bubble from the spark source against the skin surface, histological evaluation revealed substantial reduction of severe tissue damage associated with the highest pressures tested, 20 MPa. However, the threshold level for evidence of hemorrhage remained about three to five MPa. Hydrophonic measurements indicated that the membrane allowed transmission of the acoustic shock waves and suggested that collapse of the bubble generated by electrohydraulic probes may have local effects due to a cavitation-like mechanism.

Blocking mammalian target of rapamycin alleviates bladder hyperactivity and pain in rats with cystitis.

PubMed

Liang, Simin; Li, Jie; Gou, Xin; Chen, Daihui

2016-01-01

Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity. The expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E-binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated bladder hyperactivity and pain. In addition, blocking PI3K signal pathway attenuated activities of mTOR, which was accompanied with decreasing bladder hyperactivity and pain. Inhibition of either mTOR or PI3K blunted the enhanced spinal substance P and calcitonin gene-related peptide in cyclophosphamide rats. The data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis. © The Author(s) 2016.

Drug-induced iatrogenic intraparenchymal hemorrhage.

PubMed

Lapsiwala, Samir; Moftakhar, Roham; Badie, Behnam

2002-07-01

Intracerebral hemorrhage is bleeding into the brain parenchyma with possible extension into the ventricles and subarachnoid space. Each year, approximately 37,000 to 52,400 people suffer from intraparenchymal hemorrhage (IPH) in the United States. This rate is expected to rise dramatically in the next few decades as a result of the increasing age of the population and a change in racial demographics. IPH accounts for 8% to 13% of all stroke cases and is associated with the highest mortality rate.

Protective effects of batimastat against hemorrhagic injuries in delayed jellyfish envenomation syndrome models.

PubMed

Wang, Beilei; Liu, Dan; Liu, Guoyan; Zhang, Xin; Wang, Qianqian; Zheng, Jiemin; Zhou, Yonghong; He, Qian; Zhang, Liming

2015-12-15

Previously, we established delayed jellyfish envenomation syndrome (DJES) models and proposed that the hemorrhagic toxins in jellyfish tentacle extracts (TE) play a significant role in the liver and kidney injuries of the experimental model. Further, we also demonstrated that metalloproteinases are the central toxic components of the jellyfish Cyanea capillata (C. capillata), which may be responsible for the hemorrhagic effects. Thus, metalloproteinase inhibitors appear to be a promising therapeutic alternative for the treatment of hemorrhagic injuries in DJES. In this study, we examined the metalloproteinase activity of TE from the jellyfish C. capillata using zymography analyses. Our results confirmed that TE possessed a metalloproteinase activity, which was also sensitive to heat. Then, we tested the effect of metalloproteinase inhibitor batimastat (BB-94) on TE-induced hemorrhagic injuries in DJES models. Firstly, using SR-based X-ray microangiography, we found that BB-94 significantly improved TE-induced hepatic and renal microvasculature alterations in DJES mouse model. Secondly, under synchrotron radiation micro-computed tomography (SR-μCT), we also confirmed that BB-94 reduced TE-induced hepatic and renal microvasculature changes in DJES rat model. In addition, being consistent with the imaging results, histopathological and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL)-like staining observations also clearly corroborated this hypothesis, as BB-94 was highly effective in neutralizing TE-induced extensive hemorrhage and necrosis in DJES rat model. Although it may require further clinical studies in the near future, the current study opens up the possibilities for the use of the metalloproteinase inhibitor, BB-94, in the treatment of multiple organ hemorrhagic injuries in DJES. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc

The NACHT, LRR and PYD Domains-Containing Protein 3 (NLRP3) Inflammasome Mediates Inflammation and Voiding Dysfunction in a Lipopolysaccharide-Induced Rat Model of Cystitis

PubMed Central

Hughes, Francis M; Kennis, James G; Youssef, Melissa N; Lowe, Danielle W; Shaner, Brooke E; Purves, J Todd

2016-01-01

Objective NOD-like receptors (NLRs) sense sterile and non-sterile signals and form inflammasomes which trigger an inflammatory response through the activation of caspase-1 and release of IL-1β. Recently we have shown the presence of several NLRs in the bladder urothelia and demonstrated the importance of NLRP3 in bladder outlet obstruction and cyclophosphamide-induced cystitis, both models of sterile inflammation. In this study we explore a role for NLRP3 in mediating the response to LPS, a key antigen of uropathogenic bacteria. Method In order to bypass the protective glycosaminoglycan layer lining the urothelium, LPS was directly injected into the bladder wall of Sprague-Dawley rats. Glyburide (a NLRP3 inhibitor) or vehicle was administered orally prior to and after injection. Rats were analyzed 24 h later. Inflammasome activity (caspase-1 activity, IL-1β release) and inflammation (Evan’s Blue extravasation, bladder weight) were assessed, as was physiological bladder function (urodynamics). Results Injection of LPS stimulated inflammasome activation (caspase-1 activity) and the release of IL-1β into the urine which was prevented by glyburide. Likewise, LPS increased inflammation, (bladder weight and the extravasation of Evan’s blue dye), and this was reversed by glyburide. Functionally, animals injected with saline alone demonstrated decreased voiding volume as measured by urodynamics. In the presence of LPS, additional urinary dysfunction was evident with decreased voiding pressures and threshold pressures. The decrease in voiding pressure was blocked by glyburide but the decrease in threshold pressure was not, suggesting that LPS has significant effects mediated by inflammasome-dependent and -independent mechanisms. Conclusion Overall, the results demonstrate the potential importance of inflammasomes in bacterial cystitis as well as the ability of the bladder wall injection technique to isolate the in vivo effects of specific inflammasome ligands to the

Current role of transcatheter arterial embolization for bladder and prostate hemorrhage.

PubMed

Loffroy, R; Pottecher, P; Cherblanc, V; Favelier, S; Estivalet, L; Koutlidis, N; Moulin, M; Cercueil, J P; Cormier, L; Krausé, D

2014-11-01

Intractable hematuria from the bladder or the prostate can be life-threatening and its management remains a difficult clinical problem. Severe bleeding can arise as a result of radiation cystitis, bladder carcinoma, cyclophosphamide-induced cystitis, severe infection, transurethral resection of the prostate and prostate cancer. When irrigation of the bladder through a three-way catheter and fulguration of the bleeding lesions fail to stop the hematuria, a life-threatening situation can develop, when blood transfusion fails to keep pace with the rate of blood loss. Patients with massive uncontrollable hematuria are often elderly and unfit for cystectomy as a treatment. Many urologists have had to manage this difficult problem, and several different treatments have been attempted and described, with varying degrees of success. Transcatheter arterial embolization of the vesical or prostatic arteries is occasionally indicated in these patients when all other measures have failed. There is limited published experience with this procedure, but success in 90% of patients is reported when the vesical or prostatic arteries can be identified. The aim of this review is to describe the current place of transcatheter arterial embolization in the management of severe bladder or prostate bleeding after failed conservative therapy, and to review its efficacy and morbidity. Copyright © 2014 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Radiation-induced ocular injury in the dog: a histological study.

PubMed

Ching, S V; Gillette, S M; Powers, B E; Roberts, S M; Gillette, E L; Withrow, S J

1990-08-01

Radiation-induced ocular injury secondary to treatment of nasal cancer occurs in humans and animals. Dogs with nasal carcinomas were randomized to receive 36 to 67.5 Gy in fractionated doses given in 4 weeks using a 6 MV linear accelerator. Ophthalmic examinations were performed according to a predetermined protocol and eyes were removed for histologic examination when dogs were euthanatized. The eye in the radiation field exhibited greater injury than the contralateral eye with nasal areas of the globe having more severe lesions than temporal areas. Lesions occurred in all dogs and at all doses. At 1 month or less postirradiation treatment, all dogs had blepharitis, keratoconjunctivitis and corneal epithelial atrophy. Surface lesions persisted in all eyes, becoming less severe and more chronic with time. At 3-6 months postirradiation treatment, degenerative angiopathy of retinal vessels appeared with multifocal retinal hemorrhage and mild diffuse retinal degeneration which affected outer layers first and progressed inwardly with time. At 6 months postirradiation treatment, there were cataracts, fibrosis of retinal vessel walls with loss of vascular smooth muscle, retinal hemorrhage, and mild to moderate retinal degeneration. At 1 year postirradiation treatment, retinal vessels remained sclerotic, retinal hemorrhage was less frequent, and there was moderate retinal degeneration with swelling and loss of ganglion cells. By 2 years or more postirradiation treatment, optic nerve axonal degeneration secondary to retinal changes had appeared. Tapetal and choroidal atrophy were inconsistently seen. Thus, ocular lesions at the doses received developed along a relatively predictable time course and recovery was not seen. Structures of the canine eye appear sufficiently sensitive that even relatively low total doses given in small doses per fraction cause significant long-term injury.

Voided Midstream Urine Culture and Acute Cystitis in Premenopausal Women

PubMed Central

Hooton, Thomas M; Roberts, Pacita L.; Cox, Marsha E.; Stapleton, Ann E.

2014-01-01

BACKGROUND The cause of acute uncomplicated cystitis is determined on the basis of cultures of voided midstream urine, but few data guide the interpretation of such results, especially when gram-positive bacteria grow. METHODS Women from 18 to 49 years of age with symptoms of cystitis provided specimens of midstream urine, after which we collected urine by means of a urethral catheter for culture (catheter urine). We compared microbial species and colony counts in the paired specimens. The primary outcome was a comparison of positive predictive values and negative predictive values of organisms grown in midstream urine, with the presence or absence of the organism in catheter urine used as the reference. RESULTS The analysis of 236 episodes of cystitis in 226 women yielded 202 paired specimens of midstream urine and catheter urine that could be evaluated. Cultures were positive for uropathogens in 142 catheter specimens (70%), 4 of which had more than one uropathogen, and in 157 midstream specimens (78%). The presence of Escherichia coli in midstream urine was highly predictive of bladder bacteriuria even at very low counts, with a positive predictive value of 102 colony-forming units (CFU) per milliliter of 93% (Spearman’s r = 0.944). In contrast, in midstream urine, enterococci (in 10% of cultures) and group B streptococci (in 12% of cultures) were not predictive of bladder bacteriuria at any colony count (Spearman’s r = 0.322 for enterococci and 0.272 for group B streptococci). Among 41 episodes in which enterococcus, group B streptococci, or both were found in midstream urine, E. coli grew from catheter urine cultures in 61%. CONCLUSIONS Cultures of voided midstream urine in healthy premenopausal women with acute uncomplicated cystitis accurately showed evidence of bladder E. coli but not of enterococci or group B streptococci, which are often isolated with E. coli but appear to rarely cause cystitis by themselves. (Funded by the National Institute of

[Application of Monural to treat pregnant women with asymptomatic bacteriuria and acute cystitis].

PubMed

Michova, M; Ivanov, St; Batashki, I

2009-01-01

Asymptomatic bacteriuria (AB) and cystitis affect 4-9% of pregnancies and are associated with pyelonephritis and preterm labor. Screening for AB and adequate antimicrobal therapy prevent most of these serious complications. Twenty- nine pregnant patients, suffering from AB and 9 cases with cystitis were treated with single dose Monura (Fosfomycin trometamol) in a prospective study.

Microbubbles induce renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats.

PubMed

Wible, James H; Galen, Karen P; Wojdyla, Jolette K; Hughes, Michael S; Klibanov, Alexander L; Brandenburger, Gary H

2002-01-01

The generation of ultrasound (US) bioeffects using a clinical imaging system is controversial. We tested the hypothesis that the presence of microbubbles in the US field of a medical imager induces biologic effects. Both kidneys of anesthetized rats were insonified for 5 min using a medical imaging system after the administration of microbubbles. One kidney was insonified using a continuous mode (30 Hz) and the opposite kidney was insonified using an intermittent (1 Hz) technique. The microbubbles were exposed to three different transducer frequencies and four transducer output powers. After insonification, the animals were euthanized, the kidneys were removed and their gross appearance scored under "blinded" conditions using a defined scale. After the administration of microbubbles, US imaging of the kidney caused hemorrhage in the renal tissue. The severity and area of hemorrhage increased with an increase in the transducer power and a decrease in the transducer frequency. Intermittent insonification in the presence of microbubbles produced a greater degree of renal hemorrhage than continuous imaging techniques.

Interstrain Differences in CO2-Induced Pulmonary Hemorrhage in Mice.

PubMed

Fisher, Suhrim; Burgess, Winona L; Hines, Kenneth D; Mason, Gary L; Owiny, James R

2016-11-01

Carbon dioxide is the most commonly used gas for euthanasia of rodents. The current AVMA Guidelines recommend slowly filling the container with CO2 (SF) and now indicate that the practice of placing conscious animals in containers prefilled with CO2 (PF) is unacceptable. An investigator noted pulmonary hemorrhage (PH) in BALB/c mice euthanized by SF that was not observed after PF. Here we evaluated whether the air-displacement rate (SF compared with PF) influenced the development of PH or nasal hemorrhage (NH) in 2 commonly used mouse strains. In addition, we investigated the prevalence of PH and NH in mice euthanized by isoflurane overdose (IO). Male and female (age groups, 6 wk and 6 mo) BALB/c and C57BL/6 mice were euthanized by SF or PF. In addition, 6-mo-old BALB/c male mice were euthanized by IO. Lung, nasal turbinates, brain, and reproductive organs were collected for gross and histologic evaluation and scored for degree of hemorrhage (score, 0 to 3). Severity of hemorrhage did not differ according to mouse age or sex. PH in BALB/c mice was more severe after SF than PF, and SF and PF induced more severe PH in BALB/c than in C57BL/6 mice. PH in 6-mo-old male BALB/c mice was more severe after SF than IO. Neither SF, PF, nor IO influenced the prevalence of NH in any group. This study demonstrates that the method of euthanasia may need to be altered depending on the mouse strain used.

A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration

PubMed Central

Winter, Benjamin J.; O'Connell, Helen E.; Bowden, Scott; Carey, Marcus; Eisen, Damon P.

2015-01-01

Objectives To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. Subjects and Methods A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Results Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4). Conclusion The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation. PMID:26325074

Intravesical application of rebamipide promotes urothelial healing in a rat cystitis model.

PubMed

Funahashi, Yasuhito; Yoshida, Masaki; Yamamoto, Tokunori; Majima, Tsuyoshi; Takai, Shun; Gotoh, Momokazu

2014-12-01

Rebamipide is used as a topical therapeutic agent for various organs. We examined the healing effects of intravesical rebamipide on damaged urothelium in a rat model of chemically induced cystitis. Hydrochloride was injected in the bladder of female Sprague Dawley® rats to induce cystitis. On days 1 and 4 rebamipide (1 or 10 mM) or vehicle was administered in the bladder and maintained for 1 hour. Histopathology, urothelial permeability, cystometrogram and nociceptive behaviors were evaluated on day 7. Also, tissue rebamipide concentrations after the 1-hour bladder instillation were quantified using high performance liquid chromatography. Intravesically administered rebamipide permeated the bladder, particularly in hydrochloride treated rats, and the pharmacologically effective tissue dose remained for greater than 6 hours. Bladder histological evaluation revealed polymorphological inflammatory cell infiltration and decreased positive staining for uroplakin 3A in hydrochloride treated rats. Scanning electron microscopy showed damaged tight junctions in the hydrochloride group. Evans blue absorption in the bladder wall was increased in hydrochloride treated rats. These findings, which were associated with urothelial injury and increased permeability, were dependently suppressed by the rebamipide treatment dose. Cystometrogram demonstrated that the intercontraction interval was shorter in hydrochloride treated rats but prolonged by rebamipide. The increased nociceptive behaviors observed after intravesical resiniferatoxin administration were also suppressed by rebamipide. Intravesical rebamipide accelerated the repair of damaged urothelium, protected urothelial barrier function and suppressed bladder overactivity and nociception. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Insights into the Mechanisms Involved in Strong Hemorrhage and Dermonecrosis Induced by Atroxlysin-Ia, a PI-Class Snake Venom Metalloproteinase.

PubMed

Freitas-de-Sousa, Luciana Aparecida; Colombini, Mônica; Lopes-Ferreira, Mônica; Serrano, Solange M T; Moura-da-Silva, Ana Maria

2017-08-02

Hemorrhage is the most prominent effect of snake venom metalloproteinases (SVMPs) in human envenomation. The capillary injury is a multifactorial effect caused by hydrolysis of the components of the basement membrane (BM). The PI and PIII classes of SVMPs are abundant in viperid venoms and hydrolyze BM components. However, hemorrhage is associated mostly with PIII-class SVMPs that contain non-catalytic domains responsible for the binding of SVMPs to BM proteins, facilitating enzyme accumulation in the tissue and enhancing its catalytic efficiency. Here we report on Atroxlysin-Ia, a PI-class SVMP that induces hemorrhagic lesions in levels comparable to those induced by Batroxrhagin (PIII-class), and a unique SVMP effect characterized by the rapid onset of dermonecrotic lesions. Atroxlysin-Ia was purified from B. atrox venom, and sequence analyses indicated that it is devoid of non-catalytic domains and unable to bind to BM proteins as collagen IV and laminin in vitro or in vivo. The presence of Atroxlysin-Ia was diffuse in mice skin, and localized mainly in the epidermis with no co-localization with BM components. Nevertheless, the skin lesions induced by Atroxlysin-Ia were comparable to those induced by Batroxrhagin, with induction of leukocyte infiltrates and hemorrhagic areas soon after toxin injection. Detachment of the epidermis was more intense in skin injected with Atroxlysin-Ia. Comparing the catalytic activity of both toxins, Batroxrhagin was more active in the hydrolysis of a peptide substrate while Atroxlysin-Ia hydrolyzed more efficiently fibrin, laminin, collagen IV and nidogen. Thus, the results suggest that Atroxlysin-Ia bypasses the binding step to BM proteins, essential for hemorrhagic lesions induced by PII- and P-III class SVMPs, causing a significantly fast onset of hemorrhage and dermonecrosis, due to its higher proteolytic capacity on BM components.

Insights into the Mechanisms Involved in Strong Hemorrhage and Dermonecrosis Induced by Atroxlysin-Ia, a PI-Class Snake Venom Metalloproteinase

PubMed Central

Lopes-Ferreira, Mônica; Serrano, Solange M. T.

2017-01-01

Hemorrhage is the most prominent effect of snake venom metalloproteinases (SVMPs) in human envenomation. The capillary injury is a multifactorial effect caused by hydrolysis of the components of the basement membrane (BM). The PI and PIII classes of SVMPs are abundant in viperid venoms and hydrolyze BM components. However, hemorrhage is associated mostly with PIII-class SVMPs that contain non-catalytic domains responsible for the binding of SVMPs to BM proteins, facilitating enzyme accumulation in the tissue and enhancing its catalytic efficiency. Here we report on Atroxlysin-Ia, a PI-class SVMP that induces hemorrhagic lesions in levels comparable to those induced by Batroxrhagin (PIII-class), and a unique SVMP effect characterized by the rapid onset of dermonecrotic lesions. Atroxlysin-Ia was purified from B. atrox venom, and sequence analyses indicated that it is devoid of non-catalytic domains and unable to bind to BM proteins as collagen IV and laminin in vitro or in vivo. The presence of Atroxlysin-Ia was diffuse in mice skin, and localized mainly in the epidermis with no co-localization with BM components. Nevertheless, the skin lesions induced by Atroxlysin-Ia were comparable to those induced by Batroxrhagin, with induction of leukocyte infiltrates and hemorrhagic areas soon after toxin injection. Detachment of the epidermis was more intense in skin injected with Atroxlysin-Ia. Comparing the catalytic activity of both toxins, Batroxrhagin was more active in the hydrolysis of a peptide substrate while Atroxlysin-Ia hydrolyzed more efficiently fibrin, laminin, collagen IV and nidogen. Thus, the results suggest that Atroxlysin-Ia bypasses the binding step to BM proteins, essential for hemorrhagic lesions induced by PII- and P-III class SVMPs, causing a significantly fast onset of hemorrhage and dermonecrosis, due to its higher proteolytic capacity on BM components. PMID:28767072

Combined effects of radiation and trauma

NASA Astrophysics Data System (ADS)

Messerschmidt, Otfried

Injuries, caused by both whole-body irradiation and wounds or burns, have been relatively little studied. Possibly because many investigators think that these injuries are just modified radiation-induced diseases for which the same treatment principles are valid. Other authors had the impression that, for instance, the radiation burn trauma is a new kind of disease which differs significantly from either radiation syndrome alone or from burn disease. There are many experimental data on animals which suggest that the pathology of combined injuries differs significantly from that of radiation-induced disease or of thermal or mechanical traumas. Wounds or burns which, in general, do not cause septicaemia could become entrance ports for bacteria when animals are exposed to whole-body irradiation. Thrombocytopenia is the reason for hemorrhages in wounds. The susceptibility to shock is increased considerably in combined injuries and the formation of callus in the bone fractures is significantly delayed. The healing of wounds and burns in the initial phase of the radiation syndrome does not always differ from healing in the non-irradiated organism. However, a few days or weeks later very serious wound infections and hemorrhages can occur. The additional injuries almost always worsen the development and prognosis of radiation-induced disease. The recommended treatment for combined injuries will differ in many respects from the treatment of wounds and burns or the radiation syndrome.

Zinc deficiency promotes cystitis-related bladder pain by enhancing function and expression of Cav3.2 in mice.

PubMed

Ozaki, Tomoka; Matsuoka, Junki; Tsubota, Maho; Tomita, Shiori; Sekiguchi, Fumiko; Minami, Takeshi; Kawabata, Atsufumi

2018-01-15

Ca v 3.2 T-type Ca 2+ channel activity is suppressed by zinc that binds to the extracellular histidine-191 of Ca v 3.2, and enhanced by H 2 S that interacts with zinc. Ca v 3.2 in nociceptors is upregulated in an activity-dependent manner. The enhanced Ca v 3.2 activity by H 2 S formed by the upregulated cystathionine-γ-lyase (CSE) is involved in the cyclophosphamide (CPA)-induced cystitis-related bladder pain in mice. We thus asked if zinc deficiency affects the cystitis-related bladder pain in mice by altering Ca v 3.2 function and/or expression. Dietary zinc deficiency for 2 weeks greatly decreased zinc concentrations in the plasma but not bladder tissue, and enhanced the bladder pain/referred hyperalgesia (BP/RH) following CPA at 200mg/kg, a subeffective dose, but not 400mg/kg, a maximal dose, an effect abolished by pharmacological blockade or gene silencing of Ca v 3.2. Acute zinc deficiency caused by systemic N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylendiamine (TPEN), a zinc chelator, mimicked the dietary zinc deficiency-induced Ca v 3.2-dependent promotion of BP/RH following CPA at 200mg/kg. CPA at 400mg/kg alone or TPEN plus CPA at 200mg/kg caused Ca v 3.2 overexpression accompanied by upregulation of Egr-1 and USP5, known to promote transcriptional expression and reduce proteasomal degradation of Ca v 3.2, respectively, in the dorsal root ganglia (DRG). The CSE inhibitor, β-cyano-l-alanine, prevented the BP/RH and upregulation of Ca v 3.2, Egr-1 and USP5 in DRG following TPEN plus CPA at 200mg/kg. Together, zinc deficiency promotes bladder pain accompanying CPA-induced cystitis by enhancing function and expression of Ca v 3.2 in nociceptors, suggesting a novel therapeutic avenue for treatment of bladder pain, such as zinc supplementation. Copyright © 2017 Elsevier B.V. All rights reserved.

BK virus (BKV) quantification in urine samples of bone marrow transplanted patients is helpful for diagnosis of hemorrhagic cystitis, although wide individual variations exist.

PubMed

Priftakis, Peter; Bogdanovic, Gordana; Kokhaei, Parviz; Mellstedt, Håkan; Dalianis, Tina

2003-01-01

Hemorrhagic cystitis (HC) in allogeneic bone marrow transplanted (BMT) patients is associated with BK virus (BKV) reactivation manifested as BK viruria. However, since 77-90% of all adult BMT patients excrete BKV, viral reactivation alone cannot be responsible for HC. Recently, a significant overrepresentation of C-->G mutations in the Sp1 binding site in the non-coding control region (NCCR) of BKV was shown to be present in HC patients and absent in non-HC patients. We aimed to investigate if this mutation resulted in excessive BKV excretion in HC patients. A Real-Time PCR was developed and used to quantify BKV in urine samples from 21 patients with HC, with and without the mutations, as well as from patients without HC. Quantification of BKV was successful in 18 of 21 urine patients (six with and six without C-->G mutations) and six patients without HC. A mean of 3.0 x 10(6) BKV copies/microl was detected in urine samples of HC patients with C-->G mutations, compared to a mean of 1.5 x 10(6) BKV copies/microl in HC patients without C-->G mutations and a mean of 1.0 x 10(6) BKV copies/microl in patients without HC. The obtained differences were however not statistically significant, due to one individual non-HC patient with an extremely high BKV copy number. Nevertheless, while 50% of the samples in the HC groups expressed 1 x 10(6) copies/microl or more, only one of the samples in the non-HC group contained a virus quantity higher than 5 x 10(5) copies. Although we could not confirm that the C-->G mutations in the Sp1 site of BKV were responsible for an increased viral load in patients with HC, our data suggest that levels of BKV above 10(4) copies/microl may indicate a risk for HC.

Recurrent uncomplicated cystitis in women: allowing patients to self-initiate antibiotic therapy.

PubMed

2014-02-01

Acute uncomplicated cystitis is a lower urinary tract infection occurring in the absence of anatomic or functional abnormalities of the urinary tract or any other complicating factors.The organism responsible is often an enterobacterium, especially Escherichia coli. What is the role of antibiotic therapy for non-pregnant women with recurrent acute uncomplicated cystitis? We reviewed the available evidence using the standard Prescrire methodology. A single oral dose of fosfomycin trometamol is the antibiotic of choice for treating an episode of acute uncomplicated cystitis. Alternative antibiotics are certain fluoroquinolones or co-trimoxazole (a fixed-dose combination of sulfamethoxazole and trimethoprim). For recurrent acute uncomplicated cystitis, cranberry juice has modest efficacy in reducing the frequency of episodes. A number of non-drug measures are typically proposed, although their effects are unproven: drinking sufficient fluids and urinating regularly; urinating after sexual intercourse; and avoiding spermicides. The strategy that results in the lowest antibiotic exposure is a short course of antibiotics for each episode of urinary tract infection, initiated as soon as clinical symptoms appear. Long-term antibiotic therapy is sometimes offered. According to one systematic review, women taking long-term prophylactic antibiotic therapy had about 6 times fewer clinical recurrences than with placebo. According to one randomised trial, 3 g of fosfomycin trometamol taken as a single dose every ten days reduced the frequency of recurrence, resulting in 0.14 episodes of infection per year on average versus about 3 episodes with placebo (p < 0.001). The amount of antibiotic used when fosfomycin trometamol is taken every 10 days for 6 months is equivalent to treatment of 18 acute episodes of cystitis. When cystitis appears to be associated with sexual intercourse, two small randomised trials suggest that routine postcoital antibiotic treatment is more effective

Xanthogranulomatous cystitis: a challenging imitator of bladder cancer.

PubMed

Ekici, Sinan; Dogan Ekici, Isin; Ruacan, Sevket; Midi, Ahmet

2010-06-29

Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature.

Xanthogranulomatous Cystitis: A Challenging Imitator of Bladder Cancer

PubMed Central

Ekici, Sinan; Dogan Ekici, Isin; Ruacan, Sevket; Midi, Ahmet

2010-01-01

Xanthogranulomatous cystitis is a rare, benign, chronic inflammatory disease of the bladder, mimicking malignancy with unknown etiology. Herein, we report a 57-year-old man who presented with pollakiuria, nocturia, dysuria, left flank pain, and a palpable mass on the right lower abdomen. Computerized tomography demonstrated an obstructing 10-mm stone in the lower third of the left ureter and a 6-cm solid mass on the right at the anterolateral wall of the bladder. The mass presented local perivesical invasion at the anterolateral side. Cystouretroscopy revealed a mass protruding into the bladder cavity with edematous smooth surface. Frozen section analysis of the partial cystectomy specimen could not rule out malignancy. Therefore, radical cystoprostatectomy and ureterolithotomy were performed. Histologically, fibrosis, numerous plasma cells, eosinophils, and, immunohistochemically, CD68-positive epithelioid and foamy macrophages were detected. Localized prostatic adenocarcinoma was also found. The present case of xanthogranulomatous cystitis is the 23rd to be reported in the world literature. PMID:20602075

Polyomavirus BK infection in blood and marrow transplant recipients

PubMed Central

Dropulic, LK; Jones, RJ

2011-01-01

The association of BK virus infection with hemorrhagic cystitis in blood and marrow transplant (BMT) recipients was first demonstrated two decades ago. During this time, therapeutic interventions focused on supportive measures such as hyperhydration, continuous bladder irrigation and topical administration of agents that alter the mucosal surface of the bladder wall. In recent years, PCR amplification of viral DNA in the urine and plasma has solidified the association of BK virus infection with hemorrhagic cystitis, demonstrating that higher urine and plasma viral loads occur in the setting of disease. The evaluation of virus-specific therapy has lagged behind assessment of the viral load and theories of pathogenesis. Extrapolating from successes in the treatment of BK virus nephropathy in the renal transplant population, cidofovir and leflunomide are identified as potential effective agents for the treatment of BK virus-associated hemorrhagic cystitis. The fluoroquinolone antibiotics may prove to be effective as prophylactic agents. Given the manifestation of BK virus infection in organs outside of the urinary tract in an increasing immunocompromised patient population and the availability of potential antiviral agents, therapeutic trials need to progress beyond the small case series in order to improve the morbidity and mortality caused by BK virus-associated hemorrhagic cystitis in the BMT population. PMID:17952131

Acquired Flucytosine Resistance during Combination Therapy with Caspofungin and Flucytosine for Candida glabrata Cystitis

PubMed Central

El Sissy, Carine; Bachelier-Bassi, Sophie; Scemla, Anne; Quesne, Gilles; Sitterlé, Emilie; Legendre, Christophe; Lortholary, Olivier; Bougnoux, Marie-Elisabeth

2015-01-01

Treatment of Candida glabrata cystitis remains a therapeutic challenge, and an antifungal combination using flucytosine is one option. We describe two patients with refractory C. glabrata cystitis who failed flucytosine combined with caspofungin with early-acquired high-level resistance to flucytosine due to nonsense mutations in the FUR1 gene. Rapidly acquired flucytosine resistance with microbiological failure should discourage combination of caspofungin and flucytosine during urinary candidiasis. PMID:26525799

Role of the Human Polyomavirus, BKV, in Prostate Cancer

DTIC Science & Technology

2005-08-01

reactivated upon immunosuppression of the host and is The BKV genome is divided into regulatory, early, associated with hemorrhagic cystitis and polyomavirus...in the BKV life cycle is replication of its urinary tract, which can lead to hemorrhagic cystitis and DNA. To assess this step, we isolated low...AD Award Number: DAMD17-01-1-0076 TITLE: Role of the Human Polyomavirus, BKV , in Prostate Cancer PRINCIPAL INVESTIGATOR: Michael Imperiale, Ph.D

Recombinant Factor XIII Mitigates Hemorrhagic Shock-Induced Organ Dysfunction

PubMed Central

Zaets, Sergey B.; Xu, Da-Zhong; Lu, Qi; Feketova, Eleonora; Berezina, Tamara L.; Malinina, Inga V.; Deitch, Edwin A.; Olsen, Eva H.

2012-01-01

Background Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Since FXIII has also been shown to modulate inflammation, endothelial permeability, as well as diminish multiple organ dysfunction (MOD) after gut ischemia-reperfusion injury, we hypothesized that FXIII would reduce MOD caused by trauma-hemorrhagic shock (THS). Materials and methods Rats were subjected to a 90 min THS or trauma sham shock (TSS) and treated with either recombinant human FXIII A2 subunit (rFXIII) or placebo immediately after resuscitation with shed blood or at the end of the TSS period. Lung permeability, lung and gut myeloperoxidase (MPO) activity, gut histology, neutrophil respiratory burst, microvascular blood flow in the liver and muscles, and cytokine levels were measured 3 h after the THS or TSS. FXIII levels were measured before THS or TSS and after the 3-h post-shock period. Results THS-induced lung permeability as well as lung and gut MPO activity was significantly lower in rFXIII-treated than in placebo-treated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and less ileal mucosal injury. rFXIII-treated rats also had a higher liver microvascular blood flow compared with the placebo group. Cytokine response was more favorable in rFXIII-treated animals. Trauma-hemorrhagic shock did not cause a drop in FXIII activity during the study period. Conclusions Administration of rFXIII diminishes THS-induced MOD in rats, presumably by preservation of the gut barrier function, limitation of polymorphonuclear leukocyte (PMN) activation, and modulation of the cytokine response. PMID:21276979

[A case of eosinophilic cystitis mimicking an invasive bladder cancer].

PubMed

Okazaki, Satoshi; Hori, Jun-Ichi; Kita, Masafumi; Yamaguchi, Satoshi; Kawakami, Norihiro; Kakizaki, Hidehiro

2014-12-01

A 60-year-old woman was referred to our hospital because of gross hematuria, right lumbar pain and lower abdominal pain. Computed tomography (CT) scan revealed hydronephrosis of the right kidney, irregular bladder wall thickening at the right lateral and posterior portion and external iliac lymph node swelling of the right side. Laboratory data revealed disseminated intravascular coagulation syndrome (DIC) and eosinophilia. Because she developed a high fever that was caused by acute obstructive pyelonephritis of the right kidney, percutaneous nephrostomy was placed and the therapy for DIC was initiated. Pathological examination of transurethral resection of bladder tumor performed twice showed no malignancy but inflammatory infiltration of many eosinocytes, leading to the diagnosis of eosinophilic cystitis (EC). We considered the possibility of allergic reaction to the drugs she was taking as the etiology of EC and discontinued all drugs. Although eosinophilia was resolved afterward, she then developed brain infarction, followed by cerebral hemorrhage. She was transferred to a rehabilitation hospital for long-term care. CT scan that was performed 4 months after the initial presentation showed the resolution of hydronephrosis of the right kidney and external iliac lymph node swelling and the improvement of bladder wall thickness. Hydronephrosis of the right kidney has not recurred after removing the nephrostomy catheter. EC is a rare condition that could mimic an invasive bladder cancer. EC should be considered if bladder tumor is associated with eosinophilia. Therapeutic consideration for thromboembolic events should be made in patients with EC.

Acquired Flucytosine Resistance during Combination Therapy with Caspofungin and Flucytosine for Candida glabrata Cystitis.

PubMed

Charlier, Caroline; El Sissy, Carine; Bachelier-Bassi, Sophie; Scemla, Anne; Quesne, Gilles; Sitterlé, Emilie; Legendre, Christophe; Lortholary, Olivier; Bougnoux, Marie-Elisabeth

2016-01-01

Treatment of Candida glabrata cystitis remains a therapeutic challenge, and an antifungal combination using flucytosine is one option. We describe two patients with refractory C. glabrata cystitis who failed flucytosine combined with caspofungin with early-acquired high-level resistance to flucytosine due to nonsense mutations in the FUR1 gene. Rapidly acquired flucytosine resistance with microbiological failure should discourage combination of caspofungin and flucytosine during urinary candidiasis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis.

PubMed

Towner, Rheal A; Wisniewski, Amy B; Wu, Dee H; Van Gordon, Samuel B; Smith, Nataliya; North, Justin C; McElhaney, Rayburt; Aston, Christopher E; Shobeiri, S Abbas; Kropp, Bradley P; Greenwood-Van Meerveld, Beverley; Hurst, Robert E

2016-03-01

Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement

Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway.

PubMed

Duan, Zhen-Zhen; Zhou, Xiao-Ling; Li, Yi-Hang; Zhang, Feng; Li, Feng-Ying; Su-Hua, Qi

2015-01-01

It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.

Effects of Saw Palmetto Extract on Urodynamic Parameters, Bladder Muscarinic and Purinergic Receptors and Urinary Cytokines in Rats with Cyclophosphamide-Induced Cystitis.

PubMed

Nasrin, Sweety; Masuda, Eiji; Kugaya, Haruna; Osano, Ayaka; Ito, Yoshihiko; Yamada, Shizuo

2014-01-01

To clarify the effect of saw palmetto extract (SPE), a phytotherapeutic agent, on urodynamic parameters, bladder muscarinic and purinergic receptors, and urinary cytokines in rats with cystitis induced by cyclophosphamide (CYP). Saw palmetto extract (60 mg/kg per day) was administered orally twice a day for 7 days to rats. The urodynamic parameters in CYP (150 mg/kg i.p.)-treated rats were monitored by a cystometric method under anesthesia. The muscarinic and purinergic receptors in the bladder and submaxillary gland were measured by radioreceptor assays using [N-methyl-(3) H] scopolamine chloride([(3) H]NMS) and αβ-methylene-ATP [2,8-(3) H] tetrasodium salt ([(3) H]αβ-MeATP), respectively. Urinary cytokines (interleukin-1β [IL-1β], IL-6 and L-17) were measured with enzyme linked immunosorbent assay kits. Micturition interval and micturition volume were significantly decreased and the frequency of micturition and basal pressure were significantly increased in the CYP-treated rats compared with sham-operated rats. Orally administered SPE significantly increased the micturition interval and micturition volume and decreased the frequency of micturition and basal pressure. The maximal number of sites (Bmax ) for the specific binding of [(3) H]NMS and [(3) H]αβ-MeATP was significantly decreased in the bladder. The decrease in receptors was attenuated by repeated treatment with SPE. An elevation in urinary cytokine (IL-1β and IL-17) levels were seen, and this increase was effectively suppressed by SPE treatment. Saw palmetto extract attenuates the alteration of urodynamic parameters, pharmacologically relevant receptors, and urinary cytokines in CYP-treated rats. Therefore, SPE may be a potential therapeutic agent for improving the clinical symptoms of cystitis. © 2013 Wiley Publishing Asia Pty Ltd.

A case of pulmonary hemorrhage due to drug-induced pneumonitis secondary to ticagrelor therapy.

PubMed

Whitmore, Timothy J; O'Shea, John P; Starac, Diana; Edwards, Mark G; Waterer, Grant W

2014-03-01

We report a case of significant pulmonary hemorrhage developing shortly after commencing ticagrelor and aspirin therapy and requiring coronary artery bypass grafting to safely cease the antiplatelet therapy. Lung biopsy findings were consistent with drug-induced lung injury. Clinicians should be aware of this significant adverse event with this drug class.

Intravesical application of rebamipide suppresses bladder inflammation in a rat cystitis model.

PubMed

Funahashi, Yasuhito; Yoshida, Masaki; Yamamoto, Tokunori; Majima, Tsuyoshi; Takai, Shun; Gotoh, Momokazu

2014-04-01

We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model. Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters. Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1β, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide. Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Selective Insulin-like Growth Factor Resistance Associated with Heart Hemorrhages and Poor Prognosis in a Novel Preclinical Model of the Hematopoietic Acute Radiation Syndrome.

PubMed

Kenchegowda, Doreswamy; Legesse, Betre; Hritzo, Bernadette; Olsen, Cara; Aghdam, Saeed; Kaur, Amandeep; Culp, William; Derrien-Colemyn, Alexandrine; Severson, Grant; Moroni, Maria

2018-05-29

Although bone marrow aplasia has been considered for the past decades as the major contributor of radiation-induced blood disorders, cytopenias alone are insufficient to explain differences in the prevalence of bleeding. In this study, the minipig was used as a novel preclinical model of hematopoietic acute radiation syndrome to assess if factors other than platelet counts correlated with bleeding and survival. We sought to determine whether radiation affected the insulin-like growth factor-1 (IGF-1) pathway, a growth hormone with cardiovascular and radioprotective features. Gottingen and Sinclair minipigs were exposed to ionizing radiation at hematopoietic doses. The smaller Gottingen minipig strain was more sensitive to radiation; differences in IGF-1 levels were minimal, suggesting that increased sensitivity could depend on weak response to the hormone. Radiation caused IGF-1 selective resistance by inhibiting the anti-inflammatory anti-oxidative stress IRS/PI3K/Akt but not the pro-inflammatory MAPK kinase pathway, shifting IGF-1 signaling towards a pro-oxidant, pro-inflammatory environment. Selective IGF-1 resistance associated with hemorrhages in the heart, poor prognosis, increase in C-reactive protein and NADPH oxidase 2, uncoupling of endothelial nitric oxide synthase, inhibition of nitric oxide (NO) synthesis and imbalance between the vasodilator NO and the vasoconstrictor endothelin-1 molecules. Selective IGF-1 resistance is a novel mechanism of radiation injury, associated with a vicious cycle amplifying reactive oxygen species-induced damage, inflammation and endothelial dysfunction. In the presence of thrombocytopenia, selective inhibition of IGF-1 cardioprotective function may contribute to the development of hemostatic disorders. This finding may be particularly relevant for individuals with low IGF-1 activity, such as the elderly or those with cardiometabolic dysfunctions.

Spontaneous heparin-induced thrombocytopenia presenting as bilateral adrenal hemorrhages and pulmonary embolism after total knee arthroplasty.

PubMed

Elshoury, Amro; Khedr, Maha; Abousayed, Mostafa M; Mehdi, Syed

2015-09-01

Heparin-induced thrombocytopenia syndrome is an acquired potentially life-threatening prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 bound to heparin or heparin-like molecules. It typically occurs after exposure to unfractionated heparin, to a lesser extent after exposure to low-molecular-weight heparins, and rarely after exposure to fondaparinux. Herein, we report the case of a 48-year-old woman who developed severe thrombocytopenia, bilateral pulmonary embolism, and bilateral adrenal hemorrhages after total knee arthroplasty without evidence of heparin exposure. Antibodies to the heparin-platelet factor 4 complex and serotonin-release assay were positive. Spontaneous heparin-induced thrombocytopenia syndrome should be considered in patients with unexplained thrombocytopenia after knee replacement surgery even without heparin exposure, and a high index of suspicion for adrenal hemorrhage is needed in patients with fever, abdominal pain, and shock.

Embolization of Rectal Arteries: An Alternative Treatment for Hemorrhagic Shock Induced by Traumatic Intrarectal Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pichon, Nicolas, E-mail: nicolas.pichon@unilim.fr, E-mail: nicolas.pichon@chu-limoges.fr; Francois, Bruno; Pichon-Lefievre, Florence

2005-05-15

Rectal injuries caused by foreign bodies or iatrogenic insertions may lead to severe complications whose therapeutic management remains controversial. At times, both the rapid identification and treatment of subsequent active rectal bleeding may be challenging, especially when endoscopy fails to locate and control the arterial hemorrhage. We present the first two successful cases of middle rectal artery embolization in patients presenting with sustained bleeding and hemorrhagic shock.

Radiation-induced genomic instability

NASA Technical Reports Server (NTRS)

Kronenberg, A.

1994-01-01

Quantitative assessment of the heritable somatic effects of ionizing radiation exposures has relied upon the assumption that radiation-induced lesions were 'fixed' in the DNA prior to the first postirradiation mitosis. Lesion conversion was thought to occur during the initial round of DNA replication or as a consequence of error-prone enzymatic processing of lesions. The standard experimental protocols for the assessment of a variety of radiation-induced endpoints (cell death, specific locus mutations, neoplastic transformation and chromosome aberrations) evaluate these various endpoints at a single snapshot in time. In contrast with the aforementioned approaches, some studies have specifically assessed radiation effects as a function of time following exposure. Evidence has accumulated in support of the hypothesis that radiation exposure induces a persistent destabilization of the genome. This instability has been observed as a delayed expression of lethal mutations, as an enhanced rate of accumulation of non-lethal heritable alterations, and as a progressive intraclonal chromosomal heterogeneity. The genetic controls and biochemical mechanisms underlying radiation-induced genomic instability have not yet been delineated. The aim is to integrate the accumulated evidence that suggests that radiation exposure has a persistent effect on the stability of the mammalian genome.

Interstitial cystitis intravesical therapy

PubMed Central

2017-01-01

Interstitial cystitis (IC) is a progressive bladder disorder that presents with symptoms of bladder urgency, frequency and pain. The aetiology of the disease remains uncertain, but it is postulated that there is an initial infective insult which damages the glycosaminoglycan (GAG) layer of the bladder urothelium. This defect allows an influx of ions, particularly potassium, which initiates an inflammatory reaction in the bladder wall, which incites the symptoms described above. Treatment initially involves behavioural and oral medication, with second line being intravesical instillation therapy. Treatment strategies focus on restoring lower urinary tract epithelial function, inhibiting neural activation, controlling allergies and relieving symptoms. In this review, current intravesical therapy will be discussed, as well as what lies on the horizon for intravesical therapy in IC. PMID:28791236

Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

PubMed

Malik, Shabana T; Birch, Brian R; Voegeli, David; Fader, Mandy; Foria, Vipul; Cooper, Alan J; Walls, Andrew F; Lwaleed, Bashir A

2018-05-15

To identify the presence and geographical distribution of mast cell (MC) subtypes: MC T (tryptase positive-chymase negative) and MC TC (tryptase positive-chymase positive) in bladder tissue. Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MC T and MC TC ) and anti-MC chymase (for MC TC ). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MC TC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MC TC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cofilin Knockdown Attenuates Hemorrhagic Brain Injury-induced Oxidative Stress and Microglial Activation in Mice.

PubMed

Alhadidi, Qasim; Nash, Kevin M; Alaqel, Saleh; Sayeed, Muhammad Shahdaat Bin; Shah, Zahoor A

2018-05-08

Intracerebral hemorrhage (ICH) resulting from the rupture of the blood vessels in the brain is associated with significantly higher mortality and morbidity. Clinical studies focused on alleviating the primary injury, hematoma formation and expansion, were largely ineffective, suggesting that secondary injury-induced inflammation and the formation of reactive species also contribute to the overall injury process. In this study, we explored the effects of cofilin knockdown in a mouse model of ICH. Animals given stereotaxic injections of cofilin siRNA, 72-h prior to induction of ICH by collagenase injection within the area of siRNA administration showed significantly decreased cofilin expression levels and lower hemorrhage volume and edema, and the animals performed significantly better in neurobehavioral tasks i.e., rotarod, grip strength and neurologic deficit scores. Cofilin siRNA knocked-down mice had reduced ICH-induced DNA fragmentation, blood-brain barrier disruption and microglial activation, with a concomitant increase in astrocyte activation. Increased expression of pro-survival proteins and decreased markers of oxidative stress were also observed in cofilin siRNA-treated mice possibly due to the reduced levels of cofilin. Our results suggest that cofilin plays a major role in ICH-induced secondary injury, and could become a potential therapeutic target. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Efficacy of N-acetylcysteine, D-mannose and Morinda citrifolia to Treat Recurrent Cystitis in Breast Cancer Survivals

PubMed Central

MARCHIORI, DEBORA; PAOLO ZANELLO, PIER

2017-01-01

Background/Aim: Breast cancer survivors in adjuvant therapy, frequently experience the estrogen deficiency with genitourinary symptoms mostly represented by recurrent bacterial cystitis. The objective of the present study was to evaluate the effectiveness of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract (NDM), when associated to antibiotic therapy, in reducing the persistence of recurrent cystitis in this risk population. Patients and Methods: Sixty breast cancer survived women with recurrent cystitis were retrospectively examined. Group 1, comprised of 40 patients treated with antibiotic therapy associated with NDM lasting for six months, Group 2 comprised of 20 patients treated with antibiotics alone. Results: The use of NDM in combination with antibiotic therapy showed a significant reduction in positive urine cultures, compared to antibiotics alone. Subjects of Group 1 rather than those of Group 2, showed improvement in symptoms score of urgency, frequency, urge incontinence, recurrent cystitis, bladder and urethral pain. Conclusion: In breast cancer survived women affected by genitourinary discomfort, the combination of NDM and antibiotic therapy showed a greater efficacy in reducing urinary tract infections and urinary discomfort with respect to antibiotic use only. PMID:28882961

Efficacy of N-acetylcysteine, D-mannose and Morinda citrifolia to Treat Recurrent Cystitis in Breast Cancer Survivals.

PubMed

Marchiori, Debora; Zanello, Pier Paolo

2017-01-01

Breast cancer survivors in adjuvant therapy, frequently experience the estrogen deficiency with genitourinary symptoms mostly represented by recurrent bacterial cystitis. The objective of the present study was to evaluate the effectiveness of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract (NDM), when associated to antibiotic therapy, in reducing the persistence of recurrent cystitis in this risk population. Sixty breast cancer survived women with recurrent cystitis were retrospectively examined. Group 1, comprised of 40 patients treated with antibiotic therapy associated with NDM lasting for six months, Group 2 comprised of 20 patients treated with antibiotics alone. The use of NDM in combination with antibiotic therapy showed a significant reduction in positive urine cultures, compared to antibiotics alone. Subjects of Group 1 rather than those of Group 2, showed improvement in symptoms score of urgency, frequency, urge incontinence, recurrent cystitis, bladder and urethral pain. In breast cancer survived women affected by genitourinary discomfort, the combination of NDM and antibiotic therapy showed a greater efficacy in reducing urinary tract infections and urinary discomfort with respect to antibiotic use only. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Comparison of Bladder Directed and Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain Syndrome

DTIC Science & Technology

2017-09-01

PROJECT NUMBER Kenneth M. Peters 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...AWARD NUMBER: W81XWH-16-1-0307 TITLE: Comparison of Bladder-Directed and Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain...Pelvic Floor Therapy in Women With Interstitial Cystitis/Bladder Pain Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

Selective embolization of the internal iliac arteries for the treatment of intractable hemorrhage in children with malignancies.

PubMed

Bae, Sul Hee; Han, Dong Kyun; Baek, Hee Jo; Park, Sun Ju; Chang, Nam Kyu; Kook, Hoon; Hwang, Tai Ju

2011-04-01

Acute internal hemorrhage is an occasionally life-threatening complication in pediatric cancer patients. Many therapeutic approaches have been used to control bleeding with various degrees of success. In this study, we evaluated the efficacy of selective internal iliac artery embolization for controlling acute intractable bleeding in children with malignancies. We retrospectively evaluated the cases of 6 children with various malignancies (acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, T-cell prolymphocytic leukemia, Langerhans cell histiocytosis, and rhabdomyosarcoma), who had undergone selective arterial embolization (SAE) of the internal iliac artery at the Chonnam National University Hwasun Hospital between January 2004 and December 2009. SAE was performed by an interventional radiologist using Gelfoam® and/or Tornado® coils. The patients were 5 boys and 1 girl with median age of 6.9 years (range, 0.7-14.8 years) at the time of SAE. SAE was performed once in 4 patients and twice in 2, and the procedure was unilateral in 2 and bilateral in 4. The causes of hemorrhage were as follows: hemorrhagic cystitis (HC) in 3 patients, procedure-related internal iliac artery injuries in 2 patients, and tumor rupture in 1 patient. Initial attempt at conservative management was unsuccessful. Of the 6 patients, 5 (83.3%) showed improvement after SAE without complications. SAE may be a safe and effective procedure for controlling acute intractable hemorrhage in pediatric malignancy patients. This procedure may obviate the need for surgery, which carries an attendant risk of morbidity and mortality in cancer patients with critical conditions.

A Prospective Multi-center Trial of Escherichia coli Extract for the Prophylactic Treatment of Patients with Chronically Recurrent Cystitis

PubMed Central

Kim, Kun Suk; Kim, Ji-Yoon; Jeong, In Gab; Paick, Jae-Seung; Son, Hwancheol; Lim, Dae Jung; Shim, Hong Bang; Park, Won Hee; Jung, Hee Chang

2010-01-01

We have assessed the efficacy and safety of Escherichia coli extract (ECE; Uro-Vaxom®) which contains active immunostimulating fractions, in the prophylactic treatment of chronically recurrent cystitis. Forty-two patients with more than 2 episodes of cystitis in the proceeding 6 months were treated for 3 months with one capsule daily of ECE and observed for a further 6 months. The primary efficacy criterion was the number of episodes of recurrent cystitis during the 6 months after treatment compared to those during the 6 months before treatment. At the end of the 9-month trial, 34 patients (all women) were eligible for statistical analysis. Their mean age was 56.4 yr (range, 34-75 yr), and they had experienced recurrent urinary tract infections for 7.2±5.2 yr. The number of recurrences was significantly lower during the 6-month follow-up period than during the 6 months preceding the trial (0.35 vs. 4.26, P<0.001). During the follow-up, 28 (82.4%) patients had no recurrences and 4 (11.8%) had 1 each. In patients who relapsed, ECE alleviated cystitis symptoms, including painful voiding, frequency and urgency. There were no serious adverse events related to the study drug. Our study demonstrates the efficacy and safety of ECE in the prophylactic treatment of chronically recurrent cystitis. PMID:20191044

Crosstalk between the angiotensin and endothelin system in the cerebrovasculature after experimental induced subarachnoid hemorrhage.

PubMed

Wanderer, Stefan; Mrosek, Jan; Vatter, Hartmut; Seifert, Volker; Konczalla, Juergen

2018-04-01

Under physiologic conditions, losartan showed a dose-dependent antagonistic effect to the endothelin-1 (ET-1)-mediated vasoconstriction. This reduced vasoconstriction was abolished after preincubation with an endothelin B 1 receptor (ET(B 1 )-receptor) antagonist. Also, an increased ET(B 1 )-receptor-dependent relaxation to sarafotoxin S6c (S6c; an ET(B 1 )-receptor agonist) was detected by preincubation with losartan. Investigations after experimental induced subarachnoid hemorrhage (SAH) are still missing. Therefore, we analyzed losartan in a further pathological setup. Cerebral vasospasm was induced by a modified double hemorrhage model. Rats were sacrificed on day 3 and isometric force of basilar artery ring segments was measured. Parallel to physiological conditions, after SAH, the ET-1-induced vasoconstriction was decreased by preincubation with losartan. This reduced contraction has been abolished after preincubation with BQ-788, an ET(B 1 )-receptor antagonist. In precontracted vessels, ET-1 induced a higher vasorelaxation under losartan and the endothelin A receptor (ET(A)-receptor) antagonist BQ-123. After SAH, losartan caused a modulatory effect on the ET(B 1 )-receptor-dependent vasorelaxation. It further induced an upregulation of the NO pathway. Under losartan, the formerly known loss of the ET(B 1 )-receptor vasomotor function was abolished and a significantly increased relaxation, accompanied with an enhanced sensitivity of the ET(B 1 )-receptor, has been detected. Also, the dose-dependent antagonistic effect to the ET-1-induced contraction can be effected by angiotensin II type 1 receptor (AT 1 -receptor) antagonism due to losartan directly via the ET(B 1 )-receptor.

Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats.

PubMed

Yang, Long; Dong, Xiujuan

2017-06-01

We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12h and 24h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role. Copyright © 2017 Elsevier B.V. All rights reserved.

Fluorescein angiography of the bladder: technique and relevance to bladder cancer and interstitial cystitis patients.

PubMed

Zimmern, P E; Laub, D; Leach, G E

1995-07-01

Fluorescein angiography has been used in the study of bleeding vessels, neovascularity, tumors and ischemic tissues in a variety of disorders. This pilot study was designed to evaluate the feasibility, safety and relevance of this interesting technology for the evaluation of bladder wall vessels in patients with interstitial cystitis and bladder cancer. Five patients with National Institutes of Health defined interstitial cystitis symptoms and 10 with bladder cancer were studied during cytoscopy while they were under general anesthesia. A yellow-green barrier filter (520 nm.) was placed over the cystoscope eyepiece and a blue exciter filter (465 nm.) was attached to the light source. Patients received a 5 ml. bolus of 10% fluorescein intravenously. After hydrodistension, glomerulations in interstitial cystitis patients were more prominent with fluorescein angiography and occurred in the venule phase. Areas of papillary transitional cell tumor and carcinoma in situ developed a brilliant yellow-green fluorescence. Adjacent normal urothelium was nonfluorescent and provided a contrasting dark background facilitating the detection of all lesions. No allergic reaction or other adverse effect related to the fluorescein injection was observed. These unique observations in a limited number of patients suggest that fluorescein angiography of the bladder is a safe and simple procedure. This preliminary report underscores the relevance of fluorescein angiography in the detection of bladder tumor and offers a new approach to the evaluation of bladder wall vessels in interstitial cystitis patients.

Hemorrhagic

MedlinePlus

... Hemorrhagic diseases are caused by bleeding, or they result in bleeding (hemorrhaging). Related topics include: Primary thrombocythemia (hemorrhagic thrombocythemia) Stroke Yellow fever Bleeding disorders Ebola fever Dengue hemorrhagic ...

Antibiotic-resistant Escherichia coli in women with acute cystitis in Canada

PubMed Central

McIsaac, Warren J; Moineddin, Rahim; Meaney, Christopher; Mazzulli, Tony

2013-01-01

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) has been a traditional first-line antibiotic treatment for acute cystitis; however, guidelines do not recommend TMP-SMX in regions where Escherichia coli resistance exceeds 20%. While resistance is increasing, there are no recent Canadian estimates from a primary care setting to guide prescribing decisions. METHODS: A total of 330 family physicians assessed 752 women with suspected acute cystitis between 2009 and 2011. Physicians documented clinical features and collected urine for cultures for 430 (57.2%) women. The proportion of resistant isolates of E coli and exact binomial 95% CIs were estimated nationally, and compared regionally and demographically. These estimates were compared with those from a 2002 national study. RESULTS: The proportion of TMP-SMX-resistant E coli was 16.0% nationally (95% CI 11.3% to 21.8%). This was not statistically higher than 2002 (10.9% [P=0.14]). TMP-SMX resistance was increased in women ≤50 years of age (21.4%) compared with older women (10.7% [P=0.037]). In women with no antibiotic exposure in the previous three months, TMP-SMX-resistant E coli remained more prevalent in younger women (21.8%) compared with older women (4.4% [P=0.003]). The proportion of ciprofloxacin-resistant E coli was 5.5% nationally (95% CI 2.7% to 9.9%), and was increased compared with 2002 (1.1% [P=0.036]). Ciprofloxacin resistance was highest in British Columbia (17.7%) compared with other regions (2.7% [P=0.003]), and was increased compared with 2002 levels in this province (0.0% [P=0.025]). Nitrofurantoin-resistant E coli levels were low (0.5% [95% CI 0.01% to 2.7%). DISCUSSION: The proportion of TMP-SMX-resistant E coli causing acute cystitis in women in Canada remains below 20% nationally, but may exceed this level in premenopausal women. Ciprofloxacin resistance has increased, notably in British Columbia. Nitrofurantoin resistance levels are low across the country. These observations indicate that

Voiding diary might serve as a useful tool to understand differences between bladder pain syndrome/interstitial cystitis and overactive bladder.

PubMed

Kim, Sung Han; Oh, Shin Ah; Oh, Seung-June

2014-02-01

To identify the voiding characteristics of bladder pain syndrome/interstitial cystitis and overactive bladder. Between September 2005 and June 2010, 3-day voiding diaries of 49 consecutive bladder pain syndrome/interstitial cystitis patients and 301 overactive bladder patients were prospectively collected at an outpatient clinic and retrospectively analyzed. The characteristics of the two groups were not significantly different. However, all voiding variables including volume and frequency were significantly different except for the total voided volume: patients with bladder pain syndrome/interstitial cystitis showed significantly higher voiding frequencies, smaller maximal and mean voided volume, and more constant and narrower ranges of voided volume compared with overactive bladder patients (P < 0.005). Furthermore, mean intervals between voiding in bladder pain syndrome/interstitial cystitis were shorter and more consistent during the day and night (P < 0.001), although mean night-time variances were greater than daytime variances. Logistic regression analysis showed that total night-time frequency, maximal night-time voided volume and mean variance of daytime voiding intervals most significantly differentiated the two groups. Some voiding characteristics of bladder pain syndrome/interstitial cystitis and overactive bladder patients differ significantly according to 3-day voiding diary records. These findings provide additional information regarding the differences between these two diseases in the outpatient clinical setting. © 2013 The Japanese Urological Association.

Regional cerebral (18)FDG uptake during subarachnoid hemorrhage induced vasospasm.

PubMed

Novak, Laszlo; Emri, Miklos; Molnar, Peter; Balkay, Laszlo; Szabo, Sandor; Rozsa, Laszlo; Lengyel, Zsolt; Tron, Lajos

2006-12-01

The aim was to elucidate whether aneurysmal subarachnoid hemorrhage (SAH)-induced vasospasm induces changes of regional glucose uptake in surgically treated, asymptomatic cases. (18)FDG uptake (standardized uptake value, SUV) was analysed with PET in eight surgically treated aneurismal patients with a mean middle cerebral artery flow velocity >120 cm/seconds measured with transcranial Doppler ultrasound. Data were compared with a healthy control group using Statistical Parametric Mapping (SPM99b). Six of the eight patients had no focal neurological signs. The inhomogeneous bilateral increase in SUV (p<0.0001) was asymmetrical, with an almost 70% larger volume on the operated side. Reduced glucose uptake was found in the frontal and temporobasal regions of the two patients with neurological deficits (p<0.0001); the affected volume was 40% larger on the operated side. SAH-induced vasospasm results in widespread increase of glucose uptake-probably reflecting increased glycolysis. This was earlier than neurological focal signs appear. Decreased glucose uptake can be detected in severe cases of vasospasm reflected by neurological deficit. Although the changes are more prominent where surgery had taken place our results suggest that not only the surgery, but also subarachnoid blood might have resulted in our findings.

Exercise-induced pulmonary hemorrhage in barrel racing horses in the Pacific Northwest region of the United States

USDA-ARS?s Scientific Manuscript database

Background: Exercise-induced pulmonary hemorrhage (EIPH) refers to bleeding from the lungs in association with strenuous exercise. It has been documented in race horses but little information exists on EIPH in barrel racing horses. Hypothesis/Objectives: Our goals were to evaluate the presence of EI...

Radiation-induced genomic instability: radiation quality and dose response

NASA Technical Reports Server (NTRS)

Smith, Leslie E.; Nagar, Shruti; Kim, Grace J.; Morgan, William F.

2003-01-01

Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.

Cloaca prolapse and cystitis in green iguana (Iguana iguana) caused by a novel Cryptosporidium species.

PubMed

Kik, Marja J L; van Asten, Alphons J A M; Lenstra, Johannes A; Kirpensteijn, Jolle

2011-01-10

Cryptosporidium infection was associated with colitis and cystitis in 2 green iguanas (Iguana iguana). The disease was characterized by a chronic clinical course of cloacal prolapses and cystitis. Histological examination of the gut and urinary bladder showed numerous Cryptosporidium developmental stages on the surface of the epithelium with mixed inflammatory response in the lamina propria. Cryptosporidium oocysts were visualised in a cytological preparation of the faeces. Based on the small subunit ribosomal RNA gene the cryptosporidia were characterized as belonging to the intestinal cryptosporidial lineage, but not to Cryptosporidium saurophilum or Cryptosporidium serpentis species. Copyright © 2010 Elsevier B.V. All rights reserved.

The Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial

ClinicalTrials.gov

2018-04-24

Cerebral Hemorrhage; Stroke; Hypertension; Diabetes; Anticoagulant-induced Bleeding; Cerebral Vascular Disorder; Brain Disorder; Hemorrhage; Intracranial Hemorrhages; Cardiovascular Diseases; Central Nervous System Diseases

Cerebrovascular Acute Radiation Syndrome : Radiation Neurotoxins, Mechanisms of Toxicity, Neuroimmune Interactions.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Introduction: Cerebrovascular Acute Radiation Syndrome (CvARS) is an extremely severe in-jury of Central Nervous System (CNS) and Peripheral Nervous System (PNS). CvARS can be induced by the high doses of neutron, heavy ions, or gamma radiation. The Syndrome clinical picture depends on a type, timing, and the doses of radiation. Four grades of the CvARS were defined: mild, moderate, severe, and extremely severe. Also, four stages of CvARS were developed: prodromal, latent, manifest, outcome -death. Duration of stages depends on the types, doses, and time of radiation. The CvARS clinical symptoms are: respiratory distress, hypotension, cerebral edema, severe disorder of cerebral blood microcirculation, and acute motor weakness. The radiation toxins, Cerebro-Vascular Radiation Neurotoxins (SvARSn), determine development of the acute radiation syndrome. Mechanism of action of the toxins: Though pathogenesis of radiation injury of CNS remains unknown, our concept describes the Cv ARS as a result of Neurotoxicity and Excitotoxicity, cell death through apoptotic necrosis. Neurotoxicity occurs after the high doses radiation exposure, formation of radiation neuro-toxins, possible bioradicals, or group of specific enzymes. Intracerebral hemorrhage can be a consequence of the damage of endothelial cells caused by radiation and the radiation tox-ins. Disruption of blood-brain barrier (BBB)and blood-cerebrospinal fluid barrier (BCFB)is possibly the most significant effect of microcirculation disorder and metabolic insufficiency. NMDA-receptors excitotoxic injury mediated by cerebral ischemia and cerebral hypoxia. Dam-age of the pyramidal cells in layers 3 and 5 and Purkinje cell layer the cerebral cortex , damage of pyramidal cells in the hippocampus occur as a result of cerebral ischemia and intracerebral bleeding. Methods: Radiation Toxins of CV ARS are defined as glycoproteins with the molec-ular weight of RT toxins ranges from 200-250 kDa and with high enzymatic activity

Ultrasound bladder wall thickness measurement in diagnosis of recurrent urinary tract infections and cystitis cystica in prepubertal girls.

PubMed

Milošević, Danko; Trkulja, Vladimir; Turudić, Daniel; Batinić, Danica; Spajić, Borislav; Tešović, Goran

2013-12-01

To evaluate urinary bladder wall thickness (BWT) assessed by ultrasound as a diagnostic tool for cystitis cystica. This was a 9-year prospective study comprising 120 prepubertal girls. Sixty subjects of whom half underwent cystoscopy represented cases while the other 60 (those with a single urinary tract infection and healthy subjects) represented controls. Based on receiver operating characteristics (ROC) analysis, BWT discriminated very well between cases and controls with area under the ROC curve close to 1.0. At the optimum cut-off defined at 3.9 mm, negative predictive value (NPV) was 100% leaving no probability of cystic cystitis with BWT <3.9 mm. Positive predictive value (PPV) was also very high (95.2%), indicating only around 4.82% probability of no cystic cystitis in patients with BWT values ≥3.9 mm. BWT could also distinguish between healthy subjects and those with a cured single urinary tract infection, although discriminatory properties were moderate (area under ROC 86.7%, PPV 78.8%, NPV 85.2%). Ultrasound mucosal bladder wall measurement is a non-invasive, simple and quite reliable method in diagnosis of cystitis cystica in prepubertal girls with recurrent urinary tract infections. Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Stereotactic Administration of Edaravone Ameliorates Collagenase-Induced Intracerebral Hemorrhage in Rat.

PubMed

Zhang, Yan; Yang, Yang; Zhang, Guang-Zhu; Gao, Mou; Ge, Guang-Zhi; Wang, Qin-Qin; Ji, Xin-Chao; Sun, Yi-Lin; Zhang, Hong-Tian; Xu, Ru-Xiang

2016-10-01

Edaravone is widely used for treating ischemic stroke, but it is not still confirmed in intracerebral hemorrhage (ICH) as an ideal medication targeting the brain parenchyma. We aimed to investigate the neuroprotective effects of stereotactic administration of edaravone (SI) into the brain parenchyma. Intracerebral hemorrhage rat models were established by infusion of collagenase into the caudate nucleus. Neural functional recovery was assessed using modified neurological severity scores (mNSS). A comparative study of therapeutic effects between SI and intraperitoneal injection of edaravone (IP) involved in cerebral edema, blood-brain barrier (BBB) permeability, hematoma absorption, inflammatory response and neuronal apoptosis. Compared with IP, the mNSS was significantly (P < 0.05) improved by SI; cerebral edema and BBB permeability were dramatically ameliorated (P < 0.05); IL-4 and IL-10 levels increased, but IL-1β and TNF-α levels significantly decreased; neuron apoptosis decreased markedly (P < 0.05); and caspase-3 and Bax expression significantly dropped, but Bcl-2 increased in SI group (P < 0.05). SI markedly improved neurological deficits in ICH rat models via antiinflammatory and antiapoptosis mechanisms and promoted M2-type microglia differentiation. SI was effective in rats with collagenase-induced ICH. © 2016 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Consequences of interstitial cystitis/bladder pain symptoms on women's work participation and income: results from a national household sample.

PubMed

Beckett, Megan K; Elliott, Marc N; Clemens, J Quentin; Ewing, Brett; Berry, Sandra H

2014-01-01

We describe differences in work participation and income by bladder symptom impact and comorbidities among women with interstitial cystitis/bladder pain syndrome. Cross-sectional data from 2,767 respondents younger than 65 years identified with interstitial cystitis/bladder pain syndrome symptoms were analyzed. The data were taken from the RAND Interstitial Cystitis Epidemiology (RICE) survey, and included retrospective self-reports of interstitial cystitis/bladder pain syndrome impact, severity, years since onset, related comorbidities (depressive symptomatology, number of conditions), work participation and income, and personal characteristics. Multiple regressions predicted 5 current work outcomes of works now, kept from working by pain, missed work days, days worked when bothered by symptoms and real income change since symptom onset. Controlling for work status at symptom onset and personal characteristics, greater bladder symptom impact predicted a greater likelihood of not now working, kept more days from working by pain, missed more work days and working more days with symptoms. More depressive symptomatology and greater number of comorbidities predicted reduced work participation. Women experienced no growth in real income since symptom onset. Measures of symptom severity were not associated with any of the economic outcomes. Greater interstitial cystitis/bladder pain syndrome symptom impact, depressive symptomatology and count of comorbidities (but not symptom severity) were each associated with less work participation and leveling of women's long-term earnings. Management of bladder symptom impact on nonwork related activities and depressive symptomatology may improve women's work outcomes. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Radiation-induced leukemia: lessons from history.

PubMed

Finch, Stuart C

2007-03-01

Beginning in 1895, with the discovery of x-rays, alpha and beta radiation, uranium, radium, thorium, and polonium, the fascinating story of the beginning of knowledge concerning the existence of ionizing radiation unfolds. This brief history of radiation and leukemia is divided into two main parts: the first 50 years, which deals with the confusion regarding radiation effects and the failure to clearly recognize that exposure to ionizing radiation may induce leukemia. The second part focuses on the last 60 years, when the radiation induction of leukemia was accepted and some progress achieved in understanding the clinical and pathophysiological characteristics of radiation-induced leukemia. Particular attention in this is paid to the effects of radiation on the survivors of Hiroshima and Nagasaki. The discussion in this section also covers some concepts of radiation-induced cell damage and ruminations on unanswered questions.

An Unusual Consolidation: Lobar Pulmonary Hemorrhage Due to Antithrombotic Therapy.

PubMed

D'Amore, Katrina; Traficante, David; McGovern, Terrance; Propersi, Marco; Barnes, Stacey

2017-11-01

Alveolar hemorrhage is a rare yet devastating clinical entity if not identified and treated aggressively. Exceedingly rare are the cases of anticoagulant-induced alveolar hemorrhage with very few cases described in the current literature. The nonspecific presentation of an alveolar hemorrhage makes its diagnosis and appropriate treatment difficult in the emergency department. We report a case of a patient on warfarin for atrial fibrillation who was initially misdiagnosed as having community-acquired pneumonia, but subsequently was identified to have a fatal alveolar hemorrhage.

A Sphingosine-1 Phosphate agonist (FTY720) limits trauma/hemorrhagic shock induced multiple organ dysfunction syndrome

PubMed Central

Bonitz, Joyce A.; Son, Julie Y.; Chandler, Benjamin; Tomaio, Jacquelyn N.; Qin, Yong; Prescott, Lauriston M.; Feketeova, Eleonora; Deitch, Edwin A.

2014-01-01

BACKGROUND Trauma/hemorrhagic shock is one of the major consequences of battlefield injury as well as civilian trauma. FTY720 (sphingosine-1 phosphate agonist) has the capability to decrease the activity of the innate and adaptive immune systems and, at the same time, maintain endothelial cell barrier function and vascular homeostasis during stress. For this reason, we hypothesize that FTY720, as part of resuscitation therapy, would limit T/HS induced multiple organ dysfunction syndrome (MODS) in a rodent trauma-hemorrhagic shock (T/HS) model. METHODS Rats subjected to trauma/sham-shock (T/SS) or T/HS (30 mm Hg × 90 min), were administered FTY720 (1 mg/kg) post-T/HS during volume resuscitation. Lung injury (permeability to Evans Blue dye), PMN priming (respiratory burst activity), and RBC rigidity were measured. In addition, lymph duct cannulated rats were used to quantify the effect of FTY720 on gut injury (permeability and morphology) and the biologic activity of T/HS vs. T/SS lymph on PMN-RB and RBC deformability. RESULTS T/HS-induced increased lung permeability, PMN priming and RBC rigidity were all abrogated by FTY720. The systemic protective effect of FTY720 was only partially at the gut level, since FTY720 did not prevent T/HS-induced gut injury (morphology or permeability,) however, it did abrogate T/HS lymph-induced increased respiratory burst and RBC rigidity. CONCLUSION FTY720 limited T/HS-induced MODS (lung injury, red cell injury, and neutrophil priming) as well as T/HS lymph bioactivity, although it did not limit gut injury. PMID:25004059

Effects of intravesical dexpanthenol use on lipid peroxidation and bladder histology in a chemical cystitis animal model.

PubMed

Bayrak, Omer; Seckiner, Ilker; Solakhan, Mehmet; Karakok, Metin; Erturhan, Sakip M; Yagci, Faruk

2012-05-01

To demonstrate the effects of intravesical dexpanthenol use on bladder histology and lipid peroxidation in a chemical cystitis animal model. Thirty-five New Zealand rabbits were divided into 3 groups. Cystitis was conducted with transurethral intravesical hydrochloric acid instillation on the subjects in groups I and II. Then, Group I subjects were transurethrally administered intravesical dexpanthenol therapy twice a week, Group II subjects were given only intravesical isotonic NaCl instillation, and Group III subjects were administered intravesical isotonic NaCl instillation without conducting chemical cystitis to create the same stress. Treatment schemes of all groups were arranged in the same manner. After 6-week therapy, the rabbits were sacrificed and histopathologic investigations were carried out to demonstrate changes in the urinary bladder. Serum and tissue malondialdehyde (MDA) values were examined to investigate the effect of dexpanthenol on lipid peroxidation. We observed that the basal membrane and mucosal integrity were maintained, inflammatory cells were suppressed, and MDA levels decreased in group I, which received dexpanthenol therapy. However, it was also observed that mucosal integrity was spoiled, numerous inflammatory cells were accumulated, and MDA levels were significantly increased in group II, which was administered isotonic NaCl. In light of our findings, intravesical dexpanthenol therapy could be a new therapeutic approach in the treatment of interstitial cystitis because of its low cost and acceptable side effects. Copyright © 2012 Elsevier Inc. All rights reserved.

The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer.

PubMed

Son, Yeonghoon; Lee, Hae June; Rho, Jin Kyung; Chung, Soo Young; Lee, Chang Geun; Yang, Kwangmo; Kim, Sung Ho; Lee, Minyoung; Shin, In Sik; Kim, Joong Sun

2015-07-05

Silibinin has been known for its role in anti-cancer and radio-protective effect. Radiation therapy for treating lung cancer might lead to late-phase pulmonary inflammation and fibrosis. Thus, this study aimed to investigate the effects of silibinin in radiation-induced lung injury with a mouse model. In this study, we examined the ability of silibinin to mitigate lung injury in, and improve survival of, C57BL/6 mice given 13 Gy thoracic irradiation and silibinin treatments orally at 100 mg/kg/day for seven days after irradiation. In addition, Lewis lung cancer (LLC) cells were injected intravenously in C57BL/6 mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with lung radiation therapy at 13 Gy and with silibinin at a dose of 100 mg/day for seven days after irradiation. Silibinin was shown to increase mouse survival, to ameliorate radiation-induced hemorrhage, inflammation and fibrosis in lung tissue, to reduce the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and to reduce inflammatory cell infiltration in the respiratory tract. In LLC tumor injected mice, lung tissue from mice treated with both radiation and silibinin showed no differences compared to lung tissue from mice treated with radiation alone. Silibinin treatment mitigated the radiation-induced lung injury possibly by reducing inflammation and fibrosis, which might be related with the improved survival rate. Silibinin might be a useful agent for lung cancer patients as a non-toxic complementary approach to alleviate the side effects by thorax irradiation.

Emphysematous cystitis occurred in the case treated with steroid for autoimmune hepatitis.

PubMed

Yoshino, Tateki; Ohara, Shinya; Moriyama, Hiroyuki

2013-01-01

Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients, which was characterized by air within the bladder wall and lumen. A 83-year-old woman was introduced to our department with fever elevation and abnormal findings of computed tomography (CT). She took orally prednisolone for autoimmune hepatitis. Pelvic CT revealed diffuse air throughout the bladder wall. Urinalysis showed combined hematuria and pyuria. Escherichia coli was detected in blood culture. Abnormal findings of complete blood count and laboratory examination included an elevated WBC count (12,200/μL), C-reactive protein (11.7 mg/dL), and creatinine (1.07 mg/dL). Cystoscopy confirmed diffuse submucosal emphysema throughout. On the basis of diagnosis with emphysematous cystitis, she was treated with antibiotics based on the results of blood culture and indwelling Foley catheter. After treatment, the improvement of inflammatory findings and submucosal emphysema on cystoscopy and CT were achieved.

Emphysematous Cystitis Occurred in the Case Treated with Steroid for Autoimmune Hepatitis

PubMed Central

Yoshino, Tateki; Ohara, Shinya; Moriyama, Hiroyuki

2013-01-01

Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients, which was characterized by air within the bladder wall and lumen. A 83-year-old woman was introduced to our department with fever elevation and abnormal findings of computed tomography (CT). She took orally prednisolone for autoimmune hepatitis. Pelvic CT revealed diffuse air throughout the bladder wall. Urinalysis showed combined hematuria and pyuria. Escherichia coli was detected in blood culture. Abnormal findings of complete blood count and laboratory examination included an elevated WBC count (12,200/μL), C-reactive protein (11.7 mg/dL), and creatinine (1.07 mg/dL). Cystoscopy confirmed diffuse submucosal emphysema throughout. On the basis of diagnosis with emphysematous cystitis, she was treated with antibiotics based on the results of blood culture and indwelling Foley catheter. After treatment, the improvement of inflammatory findings and submucosal emphysema on cystoscopy and CT were achieved. PMID:23936723

Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials.

PubMed

Falagas, Matthew E; Vouloumanou, Evridiki K; Togias, Antonios G; Karadima, Maria; Kapaskelis, Anastasios M; Rafailidis, Petros I; Athanasiou, Stavros

2010-09-01

Cystitis is a common infection. The alarmingly high resistance rates exhibited by contemporary uropathogens necessitate the re-evaluation of old antibiotics. To evaluate the effectiveness and safety of fosfomycin compared with other antibiotics for the treatment of patients with cystitis. We performed a meta-analysis of randomized controlled trials (RCTs), generated from searches performed in PubMed, Scopus and Cochrane CENTRAL, which involved patients with cystitis treated with fosfomycin versus other antibiotics. Twenty-seven trials (eight double-blind) were included. Sixteen of these 27 trials involved exclusively non-pregnant female patients, 3 involved adult mixed populations of older age, 5 involved pregnant patients and 3 involved paediatric patients. Regarding clinical success, no difference was found in the comprehensive analysis regarding all comparators combined [10 RCTs, 1657 patients, risk ratio (RR) = 1.00, 95% confidence interval (CI) = 0.98-1.03] in trials involving non-pregnant females and in trials involving mixed populations. Insufficient relevant data were provided from trials involving paediatric and pregnant patients. No difference between fosfomycin and comparators was also found in all comparisons regarding the remaining effectiveness outcomes (namely microbiological success/relapse/re-infection). Fosfomycin had a comparable safety profile with the evaluated comparators in non-pregnant women, mixed and paediatric populations, whereas it was associated with significantly fewer adverse events in pregnant women (4 RCTs, 507 patients, RR = 0.35, 95% CI = 0.12-0.97). In the era of high drug resistance rates, reported even among community-acquired uropathogens, fosfomycin may provide a valuable alternative option for the treatment of cystitis in non-pregnant and pregnant women and in elderly and paediatric patients.

A pilot study using synthetic feline facial pheromone for the management of feline idiopathic cystitis.

PubMed

Gunn-Moore, D A; Cameron, M E

2004-06-01

Synthetic feline facial pheromone (FFP) (Feliway; Ceva Animal Health) was assessed for the management of cats with recurrent feline idiopathic cystitis (FIC). Nine of 12 cats completed the randomised, double-blinded, placebo-controlled, crossover pilot study. They had their environment treated daily with either FFP or placebo for 2 months, after which time the treatment groups were reversed. Owners used visual analogue scales to define the severity of their cat's clinical signs and behavioural changes. Five (56%) of the owners stated that their cat's overall health was better when they were using FFP. Four (44%) of the owners noticed no difference between when using the FFP and when using the placebo. While there were no statistical differences between the two treatment groups there was a trend for the cats exposed to FFP to show fewer days with clinical signs of cystitis (FFP total, mean per cat+/-standard deviation, 30, 4.3+/-6.7; placebo 69, 9.9+/-19.1), a lower overall clinical score (1667, 238+/-476; 2009, 287+/-425), a reduced number of episodes of cystitis (9, 1.3+/-2.0; 10, 1.4+/-2.1) and reduced negative behavioural traits (e.g., less aggression and fear) (-128, -18.3+/-65.8; -73, -10.4+/-35.1).

Radiation-induced instability and its relation to radiation carcinogenesis

NASA Technical Reports Server (NTRS)

Ullrich, R. L.; Ponnaiya, B.

1998-01-01

PURPOSE: A model that identifies radiation-induced genetic instability as the earliest cellular event in the multi-step sequence leading to radiation-induced cancer was previously proposed. In this paper ongoing experiments are discussed which are designed to test this model and its predictions in mouse mammary epithelial cells. RESULTS: Several lines of evidence are presented that appear to support this model: first, the development of delayed mutations in p53 following irradiation in altered growth variants; secondly, the high frequencies for the induction of both instability and transformation following irradiation in mammary epithelial cells; and finally, the demonstration that susceptibility to the induction of cytogenetic instability is a heritable trait that correlates with susceptibility to transformation and radiation-induced mammary cancer. Mice resistant to transformation and mammary cancer development are also resistant to the development of instability after irradiation. In contrast, mice sensitive to transformation and cancer are also sensitive to the development of cytogenetic instability. CONCLUSIONS: Data from this laboratory and from the studies cited above suggest a specific, and perhaps unique, role for radiation-induced instability as a critical early event associated with initiation of the carcinogenic process.

Gastroesphageal Variceal Hemorrhage Induced by Metastatic Liver Tumor of Lung Cancer

PubMed Central

Honda, Takayuki; Kobayashi, Hiroaki; Saiki, Masafumi; Sogami, Yusuke; Miyashita, Yoshihiro; Inase, Naohiko

2012-01-01

Gastroesophageal variceal hemorrhage is a lethal complication of portal hypertension. Liver cirrhosis is often the principal cause of the portal hypertensive state. Malignant tumors coexist with portal hypertension in some cases. Non-small-cell lung cancer (NSCLC) is likely to become metastatic. Liver is a frequent site of cancer metastasis, but diffuse hepatic sinusoidal metastasis is uncommon as a metastatic form of NSCLC. This report describes a patient with gastroesophageal variceal hemorrhage owing to a metastatic liver tumor of NSCLC. The patient, a male smoker with stage IV NSCLC, was free of any hepatitis viral infection and had no alcohol addiction. Liver dysfunction and liver disease had never been pointed out in his medical history. His tumor harbored an L858R epidermal growth factor receptor mutation. Gefitinib was initiated but had to be ceased because of interstitial lung disease. Sequential steroid therapy was effective and bevacizumab-containing chemotherapy was commenced. Both chemotherapy regimens produced favorable effects against the metastatic liver tumor, eliciting atrophic change regardless of the chemotherapy-free interval. One day the patient was admitted to our hospital because of black stool and hypotension. Upper gastrointestinal endoscopy revealed a beaded appearance of the gastroesophageal varix with bloody gastric contents. The portal hypertension might have been caused by changes in portal vein hemodynamics induced by the conformational changes underlying the favorable response of the liver tumor to molecular targeted chemotherapy and notable regression. PMID:23275780

[Hemorrhagic and edema-forming activity and histologic changes in the mouse footpad induced by venoms from Argentinian Bothrops and Crotalus genuses].

PubMed

Acosta de Pérez, O C; Koscinczuk, P; Teibler, P; Sánchez Negrette, M; Ruiz, R; Maruñak, S; Bogarín, G

1998-08-01

Hemorrhagic, oedema-forming activities and histopathological alterations in the mouse footpad induced by Bothrops and Crotalus snake venoms from Argentina. Hemorrhagic and oedema-forming activities of various Bothrops and Crotalus snake venoms from Argentina were studied, together with histological alterations in the mouse footpad. The highest oedema-forming activity was found in the venom of B. jararaca, followed by B. jararacussu, B. neuwiedii diporus, B. alternatus, and Crotalus durissus terrificus. Regarding hemorrhage, the highest activity was found in the venom of B. neuwiedii diporus, followed by B. jararacussu, B. alternatus, and B. jararaca. No hemorrhage was observed after injection of Crotalus durissus terrificus venom, in agreement with histological observations of injected footpads. Histological analysis revealed a conspicuous inflammatory reaction in the injected footpad, characterized by oedema and an inflammatory infiltrate rich in polymorphonuclear leucocytes. Necrotic blood vessels and dilated lymphatic vessels were observed after injection of B. jararaca and B. jararacussu venoms, and myonecrosis was evident in tissue of mice injected with B. alternatus and B. neuwiedii diporus.

Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

PubMed

Lorimore, S A; Wright, E G

2003-01-01

To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

Increased Expression of Interleukin-6 Family Members and Receptors in Urinary Bladder with Cyclophosphamide-Induced Bladder Inflammation in Female Rats

PubMed Central

Girard, Beatrice M.; Cheppudira, Bopaiah P.; Malley, Susan E.; Schutz, Kristin C.; May, Victor; Vizzard, Margaret A.

2011-01-01

Recent studies suggest that janus-activated kinases–signal transducer and activator of transcription signaling pathways contribute to increased voiding frequency and referred pain of cyclophosphamide (CYP)-induced cystitis in rats. Potential upstream chemical mediator(s) that may be activated by CYP-induced cystitis to stimulate JAK/STAT signaling are not known in detail. In these studies, members of the interleukin (IL)-6 family of cytokines including, leukemia inhibitory factor (LIF), IL-6, and ciliary neurotrophic factor (CNTF) and associated receptors, IL-6 receptor (R) α, LIFR, and gp130 were examined in the urinary bladder in control and CYP-treated rats. Cytokine and receptor transcript and protein expression and distribution were determined in urinary bladder after CYP-induced cystitis using quantitative, real-time polymerase chain reaction (Q-PCR), western blotting, and immunohistochemistry. Acute (4 h; 150 mg/kg; i.p.), intermediate (48 h; 150 mg/kg; i.p.), or chronic (75 mg/kg; i.p., once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Q-PCR analyses revealed significant (p ≤ 0.01) CYP duration- and tissue- (e.g., urothelium, detrusor) dependent increases in LIF, IL-6, IL-6Rα, LIFR, and gp130 mRNA expression. Western blotting demonstrated significant (p ≤ 0.01) increases in IL-6, LIF, and gp130 protein expression in whole urinary bladder with CYP treatment. CYP-induced cystitis significantly (p ≤ 0.01) increased LIF-immunoreactivity (IR) in urothelium, detrusor, and suburothelial plexus whereas increased gp130-IR was only observed in urothelium and detrusor. These studies suggest that IL-6 and LIF may be potential upstream chemical mediators that activate JAK/STAT signaling in urinary bladder pathways. PMID:21373362

Assessing urgency in interstitial cystitis/painful bladder syndrome.

PubMed

Diggs, Christina; Meyer, Walter A; Langenberg, Patricia; Greenberg, Patty; Horne, Linda; Warren, John W

2007-02-01

Interstitial cystitis/painful bladder syndrome (IC/PBS) at present is a symptom-based diagnosis. The Interstitial Cystitis Symptom Index (ICSI), also known as the O'Leary-Sant Symptom Index, is a widely used scale that assesses the four cardinal symptoms of IC/PBS (ie, bladder pain, urgency, frequency, and nocturia), by asking how often each is experienced. In an ongoing case-control study of recent-onset IC/PBS, we compared the ICSI with a series of questions that addressed the severity of these symptoms. Recruiting nationally, we enrolled women with IC/PBS symptoms of 12 months' duration or less. We assessed the severity of pain, frequency, and urgency using Likert and categorical scales, and how often these symptoms were experienced using the ICSI. We compared these scales by frequency distributions and interscale correlations. In 138 women with recent-onset IC/PBS, the scores for frequency were correlated and, for pain, appeared to be complementary. However, for urgency, the ICSI question of "the strong need to urinate with little or no warning" consistently yielded lower scores than the severity question of "the compelling urge to urinate that is difficult to postpone." Some patients denied urgency to the ICSI question yet reported intense urgency to the severity question. Compared with the severity question, the ICSI underestimated the prevalence and degree of urgency. This observation is consistent with the views of others that sudden urgency does not define the sensation experienced by many patients with IC/PBS. Clarifying this symptom description may assist in developing a usable case definition for IC/PBS.

LeuX tRNA-dependent and -independent mechanisms of Escherichia coli pathogenesis in acute cystitis

PubMed Central

Hannan, Thomas J.; Mysorekar, Indira U.; Chen, Swaine L.; Walker, Jennifer N.; Jones, Jennifer M.; Pinkner, Jerome S.; Hultgren, Scott J.; Seed, Patrick C.

2013-01-01

Summary Uropathogenic Escherichia coli (UPEC) contain multiple horizontally acquired pathogenicity-associated islands (PAI) implicated in the pathogenesis of urinary tract infection. In a murine model of cystitis, type 1 pili-mediated bladder epithelial invasion and intracellular proliferation are key events associated with UPEC virulence. In this study, we examined the mechanisms by which a conserved PAI contributes to UPEC pathogenesis in acute cystitis. In the human UPEC strain UTI89, spontaneous excision of PAI IIUTI89 disrupts the adjacent leuX tRNA locus. Loss of wild-type leuX-encoded tRNA5Leu significantly delayed, but did not eliminate, FimB recombinase-mediated phase variation of type 1 pili. FimX, an additional FimB-like, leuX-independent recombinase, was also found to mediate type 1 pili phase variation. However, whereas FimX activity is relatively slow in vitro, it is rapid in vivo as a non-piliated strain lacking the other fim recombinases rapidly expressed type 1 pili upon experimental infection. Finally, we found that disruption of leuX, but not loss of PAI IIUTI89 genes, reduced bladder epithelial invasion and intracellular proliferation, independent of type 1 piliation. These findings indicate that the predominant mechanism for preservation of PAI IIUTI89 during the establishment of acute cystitis is maintenance of wild-type leuX, and not PAI IIUTI89 gene content. PMID:18036139

Hydroperoxide in internal jugular venous blood reflects occurrence of subarachnoid hemorrhage-induced delayed cerebral vasospasm.

PubMed

Uekusa, Hiroyuki; Miyazaki, Chikao; Kondo, Kosuke; Harada, Naoyuki; Nomoto, Jun; Sugo, Nobuo; Nemoto, Masaaki

2014-10-01

To investigate the association between subarachnoid hemorrhage-induced delayed cerebral vasospasm (DCVS) and oxidative stress, an oxidation product, hydroperoxide, was measured in 3 specimens: peripheral arterial blood, cerebrospinal fluid (CSF), and internal jugular venous blood (IJVB). Hydroperoxide was measured using the diacron reactive oxygen metabolites (d-ROMs) test. The hydroperoxide levels were evaluated based on the rate of change in the d-ROMs test value on day 6 relative with that on day 3 (d-ROMs change rate). The subjects were 20 patients. The d-ROMs change rate in IJVB was significantly higher in patients with DCVS on day 6 than in those without it (P < .01). When the patients were classified into the following 3 groups: Group A (no DCVS occurred throughout the clinical course); Group B (DCVS occurred, but no cerebral infarction [CI] was induced); and Group C (DCVS occurred and caused CI), the d-ROMs change rate in IJVB was the highest in Group C, followed by Group B then A (P < .01). The d-ROMs change rates in peripheral arterial blood and CSF were not related to the development of DCVS. It was concluded that the more severe DCVS occurs and is more likely to progress to CI as the IJVB hydroperoxide level rises early after the development of subarachnoid hemorrhage. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Epidemiology of radiation-induced cancer.

PubMed Central

Radford, E P

1983-01-01

The epidemiology of radiation-induced cancer is important for theoretical and practical insights that these studies give to human cancer in general and because we have more evidence from radiation-exposed populations than for any other environmental carcinogen. On theoretical and experimental grounds, the linear no-threshold dose-response relationship is a reasonable basis for extrapolating effects to low doses. Leukemia is frequently the earliest observed radiogenic cancer but is now considered to be of minor importance, because the radiation effect dies out after 25 or 30 years, whereas solid tumors induced by radiation develop later and the increased cancer risk evidently persists for the remaining lifetime. Current estimates of the risk of particular cancers from radiation exposure cannot be fully evaluated until the population under study have been followed at least 40 or 50 years after exposure. Recent evidence indicates that for lung cancer induction, combination of cigarette smoking and radiation exposure leads to risks that are not multiplicative but rather nearly additive. PMID:6653538

18F-positron-emitting/fluorescent labeled erythrocytes allow imaging of internal hemorrhage in a murine intracranial hemorrhage model

PubMed Central

Wang, Ye; An, Fei-Fei; Chan, Mark; Friedman, Beth; Rodriguez, Erik A; Tsien, Roger Y; Aras, Omer

2017-01-01

An agent for visualizing cells by positron emission tomography is described and used to label red blood cells. The labeled red blood cells are injected systemically so that intracranial hemorrhage can be visualized by positron emission tomography (PET). Red blood cells are labeled with 0.3 µg of a positron-emitting, fluorescent multimodal imaging probe, and used to non-invasively image cryolesion induced intracranial hemorrhage in a murine model (BALB/c, 2.36 × 108 cells, 100 µCi, <4 mm hemorrhage). Intracranial hemorrhage is confirmed by histology, fluorescence, bright-field, and PET ex vivo imaging. The low required activity, minimal mass, and high resolution of this technique make this strategy an attractive alternative for imaging intracranial hemorrhage. PET is one solution to a spectrum of issues that complicate single photon emission computed tomography (SPECT). For this reason, this application serves as a PET alternative to [99mTc]-agents, and SPECT technology that is used in 2 million annual medical procedures. PET contrast is also superior to gadolinium and iodide contrast angiography for its lack of clinical contraindications. PMID:28054494

Intravesical Glycosaminoglycan Replacement with Chondroitin Sulphate (Gepan(®) instill) in Patients with Chronic Radiotherapy- or Chemotherapy-Associated Cystitis.

PubMed

Schwalenberg, Thilo; Berger, Frank Peter; Horn, Lars Christian; Thi, Phuc Ho; Stolzenburg, Jens-Uwe; Neuhaus, Jochen

2015-08-01

Intravesical instillation of glycosaminoglycans is a promising option for the treatment of chronic cystitis, as it supports the regeneration of the damaged urothelial layer. We investigated the efficacy of short-term intravesical chondroitin sulphate treatment (six courses of instillation) in patients with chronic radiotherapy- or chemotherapy-associated cystitis. This prospective, observational study included patients with chronic radiotherapy- or chemotherapy-associated cystitis, who received six once-weekly intravesical instillations of 0.2% chondroitin sulphate 40 mL. Every week, patients recorded their symptoms and their benefits and tolerance of treatment, using a self-completed questionnaire. The study included 16 patients (mean age 68.5 years; 50% male). During the study, a reduction in all evaluated parameters was observed. After one dose of chondroitin sulphate, symptom improvement was observed in 38% of patients, and after the second dose, an additional 31% of patients showed improvement. At week 6, 80% of patients had either improved or were symptom free, and significant improvements in urinary urgency (p = 0.0082), pollakisuria (p = 0.0022), urge frequency (p = 0.0033) and lower abdominal pain (p = 0.0449) were observed. Haematuria, present in 9 of the 16 patients at baseline, was completely resolved in all cases after 6 weeks. The majority of patients (93%) evaluated the tolerance of chondroitin sulphate as 'good' or 'very good'. No treatment-related adverse events were reported. Intravesical administration of chondroitin sulphate was effective for the treatment of radiotherapy- or chemotherapy-associated cystitis. Even short-term treatment appears to be effective in reducing symptoms and improving the quality of life of patients.

Radiation-induced cardiovascular effects

NASA Astrophysics Data System (ADS)

Tapio, Soile

Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in the radiation-response of the endothelium and myocardium, respectively. We have recently started co-operation with GSI in Darmstadt to study the effect of heavy ions on the endothelium. Our research will facilitate the identification of biomarkers associated with adverse cardiac effects of ionising radiation and may lead to the development of countermeasures against radiation-induced cardiac damage.

Review article: BK virus in systemic lupus erythematosus.

PubMed

Gupta, Nirupama; Lawrence, Robert M; Nguyen, Cuong; Modica, Renee F

2015-08-21

BK virus (BKV) is a human polyomavirus with a seroprevalence of 60-80 % in the general population. In renal transplant patients, it is known to cause renal failure, ureteric stenosis and hemorrhagic cystitis. In bone marrow transplant patients, it is evident that BKV can also cause hemorrhagic cystitis along with BK virus nephropathy (BKVN) in the native kidneys, with subsequent renal failure. However, little is known about BVKN in non-transplanted immune-compromised patients, such as systemic lupus erythematosus (SLE) who may have underlying nephritis and have a compromised immune system due to therapy and/or systemic illness. Thus, this article will focus on the clinical aspects of BKV and its association in patients with SLE.

Complications of bladder distension during retrograde urethrography.

PubMed

Barsanti, J A; Crowell, W; Losonsky, J; Talkington, F D

1981-05-01

A severe, ulcerative cystitis that resulted in macroscopic hematuria occurred in 8 of 20 healthy dogs undergoing a series of diagnostic tests. Four of the remaining 12 dogs had mild bladder lesions consisting of submucosal edema and hemorrhage. Nine of the 20 dogs developed urinary tract infection after the procedures. These complications seemed associated with the radiographic technique of retrograde urethrography performed when the urinary bladder was distended. To test this hypothesis, retrograde urethrography was performed on 5 additional dogs. With the bladder undistended, no complications occurred. However, distention of these same dogs' bladders for 1 minute or less with sterile lactated Ringer's solution administered through a Foley catheter in the penile urethra resulted in a macroscopic hematuria in all 5 dogs which persisted for 24 hours. A microscopic hematuria continued for 5 days. One dog developed a bacterial urinary tract infection. A severe fibrinopurulent cystitis was present at necropsy of 2 dogs 2 days after distention. The morphologic changes in the bladder gradually diminished over 7 days, but mild submucosal edema and hemorrhage were still present when 2 dogs were necropsied, 7 days after distention. These studies indicated that retrograde urethrography in dogs may be complicated by hemorrhagic cystitis and urinary tract infection if performed with urinary bladder distention.

Posterior thalamic hemorrhage induces "pusher syndrome".

PubMed

Karnath, Hans-Otto; Johannsen, Leif; Broetz, Doris; Küker, Wilhelm

2005-03-22

Recent findings argue for a pathway in humans for sensing the orientation of gravity and controlling upright body posture, separate from the one for orientation perception of the visual world. Stroke patients with contraversive pushing were shown to experience their body as oriented upright when actually tilted about 20 degrees to the ipsilesional side, in spite of normal visual-vestibular functioning. A recent study suggested the involvement of posterolateral thalamus typically associated with the disorder. To evaluate the relationship between pushing behavior and thalamic function. Over a 3-year period the authors prospectively investigated 40 patients with left- or right-sided thalamic strokes. Twenty-eight percent showed contraversive pushing. The authors found a strong relationship between etiology, vascular territory, lesion size, and neurologic disorders associated with contraversive pushing. Pusher patients had larger lesions that typically were caused by hemorrhage (vs infarcts) located in the posterior thalamus (vs anterior thalamic lesions in those patients without pushing behavior). A paresis of the contralesional extremities was more frequent and more severe in pusher patients. Further, these patients showed more additional spatial neglect with right thalamic lesions, while they tended to be more aphasic with left thalamic lesions. Posterior thalamus seems to be fundamentally involved in our control of upright body posture. Higher pressure, swelling, and other secondary pathologic processes associated with posterior thalamic hemorrhage (vs thalamic infarction) may provoke contraversive pushing in combination with additional neurologic symptoms.

Bladder pain in an LL-37 interstitial cystitis and painful bladder syndrome model.

PubMed

Jia, Wanjian; Schults, Austin J; Jensen, Mark Martin; Ye, Xiangyang; Alt, Jeremiah A; Prestwich, Glenn D; Oottamasathien, Siam

2017-01-01

Our goal was to evaluate the pain response in an LL-37 induced murine model for interstitial cystitis/painful bladder syndrome (IC/PBS). In particular, we sought to characterize the dose dependence, time-course, and relationship of LL-37 induced bladder inflammation and pain. The IC/PBS model was induced in C57Bl/6 mice by instilling 50 μL of LL-37, an immunomodulatory human cathelicidin (anti-microbial peptide), in the bladder for 1 hr. Pain responses were measured using von Frey filaments (0.04 gm to 4.0 gm) before and after LL-37 instillation. Inflammation was evaluated using tissue myeloperoxidase (MPO) assay, gross inspection, and microscopic histologic examination. The dose response experiment demonstrated a graded pain response, with higher concentrations of LL-37 challenge yielding higher pain responses across all stimuli tested. Statistical significance was seen when comparing 1.0 gm von Frey filament results at 320 μM (68 ± 8% response) vs. 0 μM (38 ± 6% response). Interestingly, pain responses did not attenuate across time but increased significantly after 5 (p=0.0012) and 7 days (p=0.0096). Comparison with MPO data suggested that pain responses could be independent of inflammation. We demonstrated within our LL-37 induced IC/PBS model pain occurs in a dose-dependent fashion, pain responses persist beyond the initial point of insult, and our dose response and time course experiments demonstrated that pain was independent of inflammation.

Mechanisms of Vascular Damage by Hemorrhagic Snake Venom Metalloproteinases: Tissue Distribution and In Situ Hydrolysis

PubMed Central

Baldo, Cristiani; Jamora, Colin; Yamanouye, Norma; Zorn, Telma M.; Moura-da-Silva, Ana M.

2010-01-01

Background Envenoming by viper snakes constitutes an important public health problem in Brazil and other developing countries. Local hemorrhage is an important symptom of these accidents and is correlated with the action of snake venom metalloproteinases (SVMPs). The degradation of vascular basement membrane has been proposed as a key event for the capillary vessel disruption. However, SVMPs that present similar catalytic activity towards extracellular matrix proteins differ in their hemorrhagic activity, suggesting that other mechanisms might be contributing to the accumulation of SVMPs at the snakebite area allowing capillary disruption. Methodology/Principal Findings In this work, we compared the tissue distribution and degradation of extracellular matrix proteins induced by jararhagin (highly hemorrhagic SVMP) and BnP1 (weakly hemorrhagic SVMP) using the mouse skin as experimental model. Jararhagin induced strong hemorrhage accompanied by hydrolysis of collagen fibers in the hypodermis and a marked degradation of type IV collagen at the vascular basement membrane. In contrast, BnP1 induced only a mild hemorrhage and did not disrupt collagen fibers or type IV collagen. Injection of Alexa488-labeled jararhagin revealed fluorescent staining around capillary vessels and co-localization with basement membrane type IV collagen. The same distribution pattern was detected with jararhagin-C (disintegrin-like/cysteine-rich domains of jararhagin). In opposition, BnP1 did not accumulate in the tissues. Conclusions/Significance These results show a particular tissue distribution of hemorrhagic toxins accumulating at the basement membrane. This probably occurs through binding to collagens, which are drastically hydrolyzed at the sites of hemorrhagic lesions. Toxin accumulation near blood vessels explains enhanced catalysis of basement membrane components, resulting in the strong hemorrhagic activity of SVMPs. This is a novel mechanism that underlies the difference between

Characterization of subclinical bacteriuria, bacterial cystitis, and pyelonephritis in dogs with chronic kidney disease.

PubMed

Foster, Jonathan D; Krishnan, Harathi; Cole, Stephen

2018-05-15

OBJECTIVE To determine the prevalence of bacteriuria (ie, a positive microbial culture result for ≥ 1 urine sample) in dogs with chronic kidney disease (CKD) and characterize findings of subclinical bacteriuria (SBU), bacterial cystitis, or pyelonephritis in these patients. DESIGN Retrospective, observational study. ANIMALS 182 dogs. PROCEDURES Medical records from January 2010 through July 2015 were reviewed to identify dogs with CKD that underwent urinalysis and urine microbial culture. Signalment, clinicopathologic data, stage of CKD according to previously published guidelines, results of urinalysis and urine culture, and abdominal ultrasonographic findings were recorded. Dogs with positive urine culture results were categorized as having SBU, bacterial cystitis, or pyelonephritis on the basis of these data. Prevalence of bacteriuria was calculated. Associations between CKD stage, presence of bacteriuria, and diagnosis category were analyzed statistically. RESULTS 33 of 182 (18.1%) dogs (40/235 [17.0%] urine samples) had positive culture results. All dogs received antimicrobials on the basis of culture and susceptibility test findings. Most positive culture results (18/40 [45%] samples) were found for dogs with SBU, followed by dogs with pyelonephritis (16/40 [40%]) and cystitis (6/40 [15%]). Escherichia coli was the most frequently observed isolate (29/40 [73%] cultures from 25/33 dogs). The CKD stage was not associated with presence of bacteriuria or diagnosis category. CONCLUSIONS AND CLINICAL RELEVANCE The prevalence of positive urine culture results in dogs with CKD was lower than that reported for dogs with some systemic diseases that may predispose to infection. Prospective research is needed to assess the clinical importance of SBU in dogs with CKD.

IL-33 mast cell axis is central in LL-37 induced bladder inflammation and pain in a murine interstitial cystitis model.

PubMed

Martin Jensen, M; Jia, Wanjian; Schults, Austin J; Ye, Xiangyang; Prestwich, Glenn D; Oottamasathien, Siam

2018-05-18

Interstitial cystitis (IC), also known as painful bladder syndrome (PBS), is a debilitating chronic condition that afflicts over 3 million women above the age of 18 in the U.S., and most patients fail to respond to current treatment options. Mast cells have previously been implicated as both a diagnostic and prognostic marker in IC/PBS. Patients with IC/PBS have been shown to have elevated levels of IL-33, a cytokine released in response to tissue insult, in their urine. We hypothesize that mast cell-mediated inflammation induced from IL-33 may play an important role in initiating pain and inflammation in IC/PBS. A human cathelicidin, LL-37, which is found at elevated levels in IC/PBS patients, was used to induce an IC/PBS-like state of inflammation and bladder pain in mast cell deficient C-kit (-/-) and wild type C57Bl/6 (WT) mice. Inflammation was quantified using myeloperoxidase (MPO) expression in bladder tissues measured via ELISA. Response rate to suprapubic stimulation from von Frey filaments was used to assess the relative pain and discomfort. Both types of mice increased IL-33 expression in response to LL-37 exposure. However, mast cell deficient mice demonstrated significantly lower levels of inflammation (p < 0.001) and reduced pain response (p < 0.001) compared to WT mice. These findings implicate an IL-33-mast cell dependent axis with a potential etiology of pain and inflammation in IC/PBS. Future therapeutics aimed at targeting the IL-33 - mast cell axis could potentially serve as useful targets for treating IC/PBS. Copyright © 2018. Published by Elsevier Ltd.

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

PubMed Central

Xu, Dun-quan; Gao, Cao; Niu, Wen; Li, Yan; Wang, Yan-xia; Gao, Chang-jun; Ding, Qian; Yao, Li-nong; Chai, Wei; Li, Zhi-chao

2013-01-01

Aim: To investigate the protective effects of hydrogen sulfide (H2S) against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. Methods: Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35–40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NaHS (28 μmol/kg, ip) was injected before the resuscitation. Results: Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-α, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H2O2 and ·OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin 1 expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NaHS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. Conclusion: NaHS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway. PMID:24122010

Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis.

PubMed

Gugliotta, Giorgio; Calagna, Gloria; Adile, Giorgio; Polito, Salvatore; Saitta, Salvatore; Speciale, Patrizia; Palomba, Stefano; Perino, Antonino; Granese, Roberta; Adile, Biagio

2015-10-01

Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. This was a retrospective review of two different cohorts of women affected by recurrent bacterial cystitis. Cases (experimental group) were women who received intravesical instillations of a sterile solution of high concentration of HA + CS in 50 mL water with calcium chloride every week during the 1(st) month and then once monthly for 4 months. The control group included women who received traditional therapy for recurrent cystitis based on daily antibiotic prophylaxis using sulfamethoxazole 200 mg plus trimethoprim 40 mg for 6 weeks. Ninety-eight and 76 patients were treated with experimental and control treatments, respectively. At 12 months after treatment, 69 and 109 UTIs were detected in the experimental and control groups, respectively. The proportion of patients free from UTIs was significantly higher in the experimental than in the control group (36.7% vs. 21.0%; p = 0.03). Experimental treatment was well tolerated and none of the patients stopped it. The intravesical instillation of HA + CS is more effective than long-term antibiotic prophylaxis for preventing recurrent bacterial cystitis. Copyright © 2015. Published by Elsevier B.V.

[Treatment of interstitial cystitis by intravesical instillation of hyaluronic acid: A prospective study on 31 patients].

PubMed

Van Agt, S; Gobet, F; Sibert, L; Leroi, A-M; Grise, P

2011-03-01

We evaluate the efficacy of hyaluronate acid instillation for treatment of interstitial cystitis (IC). From March 2008 to May 2009, a prospective study included 31 patients. We used the new definition of IC established by the ICS in 2002. Patients have a urinalysis, a cystoscopy, a hydrodistension test and bladder biopsies. The urodynamic evaluation was not systematic. Patients received weekly six instillations of 40mg (50ml) intravesical hyaluronate acid. We evaluated the efficacy and safety of treatment with two specific questionnaires of interstitial cystitis filled before and after 6 weeks of treatment: the O'Leary-Sant and Pelvic pain and Urgency/Frequency (PUF). Four groups were defined: good response, partial response, poor response and no response. They were composed by 14 patients (45%), two (7%), seven (22%) and eight patients (26%). We obtained 52% positive response (good response and partial response) after 6 weeks of treatment. Patients with cystoscopy and histology abnormal had a response rate of 60%. No serious side effects were observed. Hyaluronate acid has a place in the treatment of interstitial cystitis with an efficiency comparable to other treatments and good tolerance. The response rate to treatment can be improved by better selection of patients, particularly those having a cystoscopy and histology abnormal. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Pharmacologic Suppression of Inflammation by a Diphenyldifluoroketone, EF24, in a Rat Model of Fixed-Volume Hemorrhage Improves Survival

PubMed Central

Yadav, Vivek R.; Sahoo, Kaustuv; Roberts, Pamela R.

2013-01-01

An exaggerated release of proinflammatory cytokines and accompanying inflammation contributes to the development of multiple organ failure after hemorrhagic shock. Here, we tested the nuclear factor (NF) κ-light-chain-enhancer of activated B cell (NF-κB)–mediated transcriptional control of inflammatory pathways as a target in the management of hemorrhage-induced inflammation. We performed a study in a rat model of fixed-volume hemorrhage to investigate the anti-inflammatory effects of the diphenyldifluoroketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one], an NF-κB inhibitor, in lung tissue. EF24 treatment (0.4 mg/kg) significantly prevented the upregulation of inflammatory biomarkers in rats subjected to 50% hemorrhage and preserved the pulmonary histology in hemorrhaged rats. The lung tissue from treated rats showed marked suppression of the hemorrhage-mediated induction of Toll-like receptor 4, phospho-p65 NF-κB, inducible nitric-oxide synthase, heme oxygenase–1, and cyclooxygenase-2 (COX-2). The hemorrhage-induced COX-2 activity was also significantly inhibited by the EF24 treatment. At the same time, EF24 induced nuclear factor (erythroid-derived 2)-like 2–mediated protective mechanisms against oxidative stress. EF24 also reduced hemorrhage-induced lung myeloperoxidase activity. The plasma levels of proinflammatory tumor necrosis factor-α, interleukin (IL)-6, IL-1α, and IL-1β were lower in EF24-treated rats than in untreated rats. Moreover, there was a significant reduction in the pulmonary expression of high-mobility group B1 protein. These biochemical effects were accompanied by a significant improvement in the survival of rats administered with EF24 as compared with the rats receiving vehicle control (P < 0.05). Overall, the results suggest that EF24 attenuates hemorrhage-induced inflammation and could serve as a salutary anti-inflammatory agent in resuscitation strategies. PMID:23995597

Radiation-induced vaginal stenosis: current perspectives

PubMed Central

Morris, Lucinda; Do, Viet; Chard, Jennifer; Brand, Alison H

2017-01-01

Treatment of gynecological cancer commonly involves pelvic radiation therapy (RT) and/or brachytherapy. A commonly observed side effect of such treatment is radiation-induced vaginal stenosis (VS). This review analyzed the incidence, pathogenesis, clinical manifestation(s) and assessment and grading of radiation-induced VS. In addition, risk factors, prevention and treatment options and follow-up schedules are also discussed. The limited available literature on many of these aspects suggests that additional studies are required to more precisely determine the best management strategy of this prevalent group after RT. PMID:28496367

Role of neurotensin in radiation-induced hypothermia in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kandasamy, S.B.; Hunt, W.A.; Harris, A.H.

1991-05-01

The role of neurotensin in radiation-induced hypothermia was examined. Intracerebroventricular (ICV) administration of neurotensin produced dose-dependent hypothermia. Histamine appears to mediate neurotensin-induced hypothermia because the mast cell stabilizer disodium cromoglycate and antihistamines blocked the hypothermic effects of neurotensin. An ICV pretreatment with neurotensin antibody attenuated neurotensin-induced hypothermia, but did not attenuate radiation-induced hypothermia, suggesting that radiation-induced hypothermia was not mediated by neurotensin.

A novel intracerebral hemorrhage-induced rat model of neurogenic voiding dysfunction: Analysis of lower urinary tract function

PubMed Central

CHO, YOUNG-SAM; KO, IL-GYU; KIM, CHANG-JU; KIM, KHAE-HAWN

2015-01-01

Neurogenic lower urinary tract dysfunction (NLUTD) is a major problem in patients with various neurological disorders, and may result in debilitating symptoms and serious complications, including chronic renal failure and recurrent urinary tract infections. Clinically, stroke is associated with voiding dysfunction. However, lower urinary tract function evaluation in an intracerebral hemorrhage (ICH) model has not, to the best of our knowledge, been reported. Therefore, in the present study, lower urinary tract function in ICH-induced rats was investigated and the results were compared with those obtained in normal rats. The effects of ICH on peripheral bladder function and central micturition centers [medial preoptic area, ventrolateral gray, pontaine micturition center and spinal cord (lumbar 4 (L4)-L5)] were also examined. Adult female Sprague-Dawley rats were divided into two groups: Control ICH-induced. Induction of ICH in the hippocampal CA1 region was performed using a stereotaxic frame and type IV collagenase. The effects of ICH on the central micturition centers were investigated by simultaneously determining the extent of neuronal activation (c-Fos) and nerve growth factor (NGF) expression, and assessing voiding function (urodynamically using cystometry). The results revealed that induction of ICH significantly enhanced bladder contraction pressure and time, while simultaneously reducing voiding pressure and time. Furthermore, the c-Fos and NGF expression levels in the neuronal voiding centers were significantly increased in the rats with induced ICH as compared with the control rats. Therefore, this ICH-induced NLUTD rat model may be a more appropriate method to analyze NLUTD in stroke patients than a cerebral infarction model, as the former more accurately reflects the nature of the hemorrhage in the two types of stroke. PMID:25954993

Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

PubMed

Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

1996-08-01

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

Androstenediol inhibits the trauma-hemorrhage-induced increase in caspase-3 by downregulating the inducible nitric oxide synthase pathway.

PubMed

Kiang, Juliann G; Peckham, Russell M; Duke, Leah E; Shimizu, Tomoharu; Chaudry, Irshad H; Tsokos, George C

2007-03-01

Soft tissue trauma and hemorrhage (T-H) diminishes various aspects of liver function, while it increases hepatic nitrate/nitrite, inducible nitric oxide synthase (iNOS), and endothelin-1 levels. Treatment with androstenediol (AED) inhibits the T-H-induced alterations of the above parameters. We sought to identify the molecular events underlying the beneficial effect of AED. Exposure of rats to T-H significantly increased the caspase-3 activity and protein, whereas treatment with AED significantly limited these increases. AED treatment also suppressed the T-H-induced increase in iNOS by effectively altering the levels of key transcription factors involved in the regulation of iNOS expression. Immunoprecipitation and immunoblotting analyses indicate that T-H increased apoptosome formation, and AED treatment significantly decreased it. Modulating the iNOS protein by transfecting cells with iNOS gene or small interfering RNA further confirmed the correlation between iNOS and caspase-3. Our data indicate that AED limits caspase-3 expression by suppressing the expression of transcription factors involved in the production of iNOS, resulting in decreased apoptosome. AED can potentially be a useful adjuvant for limiting liver apoptosis following T-H shock.

Radiation-induced genomic instability and its implications for radiation carcinogenesis

NASA Technical Reports Server (NTRS)

Huang, Lei; Snyder, Andrew R.; Morgan, William F.

2003-01-01

Radiation-induced genomic instability is characterized by an increased rate of genetic alterations including cytogenetic rearrangements, mutations, gene amplifications, transformation and cell death in the progeny of irradiated cells multiple generations after the initial insult. Chromosomal rearrangements are the best-characterized end point of radiation-induced genomic instability, and many of the rearrangements described are similar to those found in human cancers. Chromosome breakage syndromes are defined by chromosome instability, and individuals with these diseases are cancer prone. Consequently, chromosomal instability as a phenotype may underlie some fraction of those changes leading to cancer. Here we attempt to relate current knowledge regarding radiation-induced chromosome instability with the emerging molecular information on the chromosome breakage syndromes. The goal is to understand how genetic and epigenetic factors might influence the onset of chromosome instability and the role of chromosomal instability in carcinogenesis.

Dimethyl Sulfoxide Attenuates Acute Lung Injury Induced by Hemorrhagic Shock/Resuscitation in Rats.

PubMed

Tsung, Yu-Chi; Chung, Chih-Yang; Wan, Hung-Chieh; Chang, Ya-Ying; Shih, Ping-Cheng; Hsu, Han-Shui; Kao, Ming-Chang; Huang, Chun-Jen

2017-04-01

Inflammation following hemorrhagic shock/resuscitation (HS/RES) induces acute lung injury (ALI). Dimethyl sulfoxide (DMSO) possesses anti-inflammatory and antioxidative capacities. We sought to clarify whether DMSO could attenuate ALI induced by HS/RES. Male Sprague-Dawley rats were allocated to receive either a sham operation, sham plus DMSO, HS/RES, or HS/RES plus DMSO, and these were denoted as the Sham, Sham + DMSO, HS/RES, or HS/RES + DMSO group, respectively (n = 12 in each group). HS/RES was achieved by drawing blood to lower mean arterial pressure (40-45 mmHg for 60 min) followed by reinfusion with shed blood/saline mixtures. All rats received an intravenous injection of normal saline or DMSO immediately before resuscitation or at matching points relative to the sham groups. Arterial blood gas and histological assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced ALI. Significant increases in pulmonary expression of tumor necrosis factor-α (TNF-α), malondialdehyde, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) confirmed that HS/RES induced pulmonary inflammation and oxidative stress. DMSO significantly attenuated the pulmonary inflammation and ALI induced by HS/RES. The mechanisms for this may involve reducing inflammation and oxidative stress through inhibition of pulmonary NF-κB, TNF-α, iNOS, and COX-2 expression.

Fisetin Protects against Intracerebral Hemorrhage-Induced Neuroinflammation in Aged Mice.

PubMed

Chen, Cheng; Yao, Li; Cui, Jing; Liu, Bao

2018-01-01

Fisetin is commonly used as an anti-inflammatory and neuroprotective drug. In this study, we aimed to investigate the efficacy of fisetin in alleviating intracerebral hemorrhage (ICH)-induced brain injury. Mouse ICH models were constructed using the collagenase-induction method. ICH mice received fisetin treatment at the dose of 10-90 mg/kg, followed by the evaluation of neurological deficit through neurologic severity scores (mNSS), brain water content and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis of cell apoptosis. Cytokine levels were also assessed with enzyme-linked immunosorbent assay. The activation of astrocytes and microglia was evaluated through S100 staining and Western blot analysis of ionized calcium-binding adaptor molecule 1 respectively. Nuclear factor kappa-B (NF-κB) signaling was also evaluated by Western blot. ICH mice demonstrated dramatic increase in mNSS, brain edema and cell apoptosis, indicating severe brain deficit. Fisetin treatment lowered these parameters, suggesting the alleviation of brain injury. Levels of proinflammatory cytokines were reduced, accompanied by a prominent decrease in activated astrocytes and microglia. NF-κB signaling was also attenuated by fisetin treatment. Fisetin effectively alleviates ICH by downregulating proinflammatory cytokines and attenuating NF-κB signaling. These data suggest fisetin as a valuable natural flavonol for clinical management of ICH-induced brain injury. © 2018 S. Karger AG, Basel.

Radar detection of radiation-induced ionization in air

DOEpatents

Gopalsami, Nachappa; Heifetz, Alexander; Chien, Hual-Te; Liao, Shaolin; Koehl, Eugene R.; Raptis, Apostolos C.

2015-07-21

A millimeter wave measurement system has been developed for remote detection of airborne nuclear radiation, based on electromagnetic scattering from radiation-induced ionization in air. Specifically, methods of monitoring radiation-induced ionization of air have been investigated, and the ionized air has been identified as a source of millimeter wave radar reflection, which can be utilized to determine the size and strength of a radiation source.

[German validation of the Acute Cystitis Symptom Score].

PubMed

Alidjanov, J F; Pilatz, A; Abdufattaev, U A; Wiltink, J; Weidner, W; Naber, K G; Wagenlehner, F

2015-09-01

The Uzbek version of the Acute Cystitis Symptom Score (ACSS) was developed as a simple self-reporting questionnaire to improve diagnosis and therapy of women with acute cystitis (AC). The purpose of this work was to validate the ACSS in the German language. The ACSS consists of 18 questions in four subscales: (1) typical symptoms, (2) differential diagnosis, (3) quality of life, and (4) additional circumstances. Translation of the ACSS into German was performed according to international guidelines. For the validation process 36 German-speaking women (age: 18-90 years), with and without symptoms of AC, were included in the study. Classification of participants into two groups (patients or controls) was based on the presence or absence of typical symptoms and significant bacteriuria (≥ 10(3) CFU/ml). Statistical evaluations of reliability, validity, and predictive ability were performed. ROC curve analysis was performed to assess sensitivity and specificity of ACSS and its subscales. The Mann-Whitney's U test and t-test were used to compare the scores of the groups. Of the 36 German-speaking women (age: 40 ± 19 years), 19 were diagnosed with AC (patient group), while 17 women served as controls. Cronbach's α for the German ACSS total scale was 0.87. A threshold score of ≥ 6 points in category 1 (typical symptoms) significantly predicted AC (sensitivity 94.7%, specificity 82.4%). There were no significant differences in ACSS scores in patients and controls compared to the original Uzbek version of the ACSS. The German version of the ACSS showed a high reliability and validity. Therefore, the German version of the ACSS can be reliably used in clinical practice and research for diagnosis and therapeutic monitoring of patients suffering from AC.

Development and Resuscitation of a Sedated, Mature Male Miniature Swine Severe Hemorrhage Model

DTIC Science & Technology

2011-07-01

control. Results: Hemorrhage resulted in a characteristic hypotension and metabolic acidosis . Survival time for the control swine was 64 minutes...domestic swine4 and was characteristic of a hemorrhage- induced metabolic acidosis , with a decrease in blood HCO3, and BE and an increase in blood...Hammett M, Asher L, et al. Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock. 2005;24:145–152

Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoo, Hyun; Kang, Jeong Wook; Lee, Dong Won

Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a highmore » cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. - Highlights: • The effects of radiation on skin thickness in mice. • Next generation sequencing revealed that radiation inhibited pyruvate dehydrogenase kinase 2 expression. • PDK2 inhibited irradiation-induced cytokine gene expression. • Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness.« less

Mechanisms of Hydrocephalus after Neonatal and Adult Intraventricular Hemorrhage

PubMed Central

Strahle, Jennifer; Garton, Hugh J.L.; Maher, Cormac O.; Muraszko, Karin M.; Keep, Richard F.; Xi, Guohua

2013-01-01

Intraventricular hemorrhage (IVH) is a cause of significant morbidity and mortality and is an independent predictor of a worse outcome in intracerebral hemorrhage (ICH) and germinal matrix hemorrhage (GMH). IVH may result in both injuries to the brain as well as hydrocephalus. This paper reviews evidence on the mechanisms and potential treatments for IVH-induced hydrocephalus. One frequently cited theory to explain hydrocephalus after IVH involves obliteration of the arachnoid villi by microthrombi with subsequent inflammation and fibrosis causing CSF outflow obstruction. Although there is some evidence to support this theory, there may be other mechanisms involved, which contribute to the development of hydrocephalus. It is also unclear whether the causes of acute and chronic hydrocephalus after hemorrhage occur via different mechanisms; mechanical obstruction by blood in the former, and inflammation and fibrosis in the latter. Management of IVH and strategies for prevention of brain injury and hydrocephalus are areas requiring further study. A better understanding of the pathogenesis of hydrocephalus after IVH, may lead to improved strategies to prevent and treat post-hemorrhagic hydrocephalus. PMID:23976902

Diffuse gastrointestinal bleeding and BK polyomavirus replication in a pediatric allogeneic haematopoietic stem cell transplant patient.

PubMed

Koskenvuo, M; Lautenschlager, I; Kardas, P; Auvinen, E; Mannonen, L; Huttunen, P; Taskinen, M; Vettenranta, K; Hirsch, H H

2015-01-01

Patients undergoing haematopoietic stem cell transplantation (HSCT) are at high risk of severe gastrointestinal bleeding caused by infections, graft versus host disease, and disturbances in haemostasis. BK polyomavirus (BKPyV) is known to cause hemorrhagic cystitis, but there is also evidence of BKV shedding in stool and its association with gastrointestinal disease. We report putative association of BKPyV replication with high plasma viral loads in a pediatric HSCT patient developing hemorrhagic cystitis and severe gastrointestinal bleeding necessitating intensive care. The observation was based on chart review and analysis of BKPyV DNA loads in plasma and urine as well as retrospective BKPyV-specific IgM and IgG measurements in weekly samples until three months post-transplant. The gastrointestinal bleeding was observed after a >100-fold increase in the plasma BKPyV loads and the start of hemorrhagic cystitis. The BKPyV-specific antibody response indicated past infection prior to transplantation, but increasing IgG titers were seen following BKPyV replication. The gastrointestinal biopsies were taken at a late stage of the episode and were no longer informative of BK polyomavirus involvement. In conclusion, gastrointestinal complications with bleeding are a significant problem after allogeneic HSCT to which viral infections including BKPyV may contribute. Copyright © 2014 Elsevier B.V. All rights reserved.

The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages

PubMed Central

Semyachkina-Glushkovskaya, Oxana; Borisova, Ekaterina; Abakumov, Maxim; Gorin, Dmitry; Avramov, Latchezar; Fedosov, Ivan; Namykin, Anton; Abdurashitov, Arkady; Serov, Alexander; Pavlov, Alexey; Zinchenko, Ekaterina; Lychagov, Vlad; Navolokin, Nikita; Shirokov, Alexander; Maslyakova, Galina; Zhu, Dan; Luo, Qingming; Chekhonin, Vladimir; Tuchin, Valery; Kurths, Jürgen

2016-01-01

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health. PMID:27378933

Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

PubMed Central

Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

1996-01-01

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges. PMID:8764013

Modulation of Radiation-Induced Apoptosis by Thiolamines

NASA Technical Reports Server (NTRS)

Warters, R. L.; Roberts, J. C.; Wilmore, B. H.; Kelley, L. L.

1997-01-01

Exposure to the thiolamine radioprotector N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) induced apoptosis in the mouse TB8-3 hybridoma after 60-minute (LD(sub50) = 4.5mM) or during a 20-hour (LD(sub50) = 0.15 mM) exposure. In contrast, a 20-hour exposure to 17 mM L-cysteine or 10 mM cysteamine was required to induce 50 percent apoptosis within 20 hours. Apoptosis was not induced by either a 60-minute or 20-hour exposure to 10 mM of the thiazolidime prodrugs ribose-cysteine (RibCys) or ribose-cysteamine (RibCyst). Thiolamine-induced apoptosis appeared to be a p53-independent process since it was induced by WR-1065 exposure in human HL60 cells. Exposure to WR-1065 (4mM for 15 minutes) or cysteine (10mM for 60 minutes) before and during irradiation protected cells against the induction of both DNA double-strand breaks and apoptosis, while exposure to RibCys (10 mM for 3 hours) did not. Treatment with either WR-1065, cysteine, RibCys or RibCyst for 60 minutes beginning 60 minutes after irradiation did not affect the level of radiation-induced apoptosis. In contrast, treatment with either cysteine, cysteamine or RibCys for 20 hours beginning 60 minutes after irradiation enhanced radiation-induced apoptosis. Similar experiments could not be conducted with WR-1065 because of its extreme toxicity. Our results indicate that thiolamine enhancement of radiation-induced apoptosis is not involved in their previously reported capacity to reduce radiation-induced mutations.

Alterations of Mg2+ After Hemorrhagic Shock.

PubMed

Lee, Mun-Young; Yang, Dong Kwon; Kim, Shang-Jin

2017-11-01

Hemorrhagic shock is generally characterized by hemodynamic instability with cellular hypoxia and diminishing cellular function, resulting from an imbalance between systemic oxygen delivery and consumption and redistribution of fluid and electrolytes. Magnesium (Mg) is the fourth most abundant cation overall and second most abundant intracellular cation in the body and an essential cofactor for the energy production and cellular metabolism. Data for blood total Mg (tMg; free-ionized, protein-bound, and anion-bound forms) and free Mg 2+ levels after a traumatic injury are inconsistent and only limited information is available on hemorrhagic effects on free Mg 2+ as the physiologically active form. The aim of this study was to determine changes in blood Mg 2+ and tMg after hemorrhage in rats identifying mechanism and origin of the changes in blood Mg 2+ . Hemorrhagic shock produced significant increases in blood Mg 2+ , plasma tMg, Na + , K + , Cl - , anion gap, partial pressures of oxygen, glucose, and blood urea nitrogen but significant decreases in RBC tMg, blood Ca 2+ , HCO 3 - , pH, partial pressures of carbon dioxide, hematocrit, hemoglobin, total cholesterol, and plasma/RBC ATP. During hemorrhagic shock, K + , anion gap, and BUN showed significant positive correlations with changes in blood Mg 2+ level, while Ca 2+ , pH, and T-CHO correlated to Mg 2+ in a negative manner. In conclusion, hemorrhagic shock induced an increase in both blood-free Mg 2+ and tMg, resulted from Mg 2+ efflux from metabolic damaged cell with acidosis and ATP depletion.

The management of acute uncomplicated cystitis in adult women by family physicians in Canada

PubMed Central

McIsaac, Warren J; Prakash, Preeti; Ross, Susan

2008-01-01

INTRODUCTION There are few Canadian studies that have assessed prescribing patterns and antibiotic preferences of physicians for acute uncomplicated cystitis. A cross-Canada study of adult women with symptoms of acute cystitis seen by primary care physicians was conducted to determine current management practices and first-line antibiotic choices. METHODS A random sample of 2000 members of The College of Family Physicians of Canada were contacted in April 2002, and were asked to assess two women presenting with new urinary tract symptoms. Physicians completed a standardized checklist of symptoms and signs, indicated their diagnosis and antibiotics prescribed. A urine sample for culture was obtained. RESULTS Of the 418 responding physicians, 246 (58.6%) completed the study and assessed 446 women between April 2002 and March 2003. Most women (412 of 420, for whom clinical information about antibiotic prescriptions was available) reported either frequency, urgency or painful urination. Physicians would have usually ordered a urine culture for 77.0% of the women (95% CI 72.7 to 80.8) and prescribed an antibiotic for 86.9% of the women (95% CI 83.3 to 90.0). The urine culture was negative for 32.8% of these prescriptions. The most commonly prescribed antibiotic was trimethoprim/sulfamethoxazole (40.8%; 95% CI 35.7 to 46.1), followed by fluoroquinolones (27.4%; 95% CI 22.9 to 32.3) and nitrofurantoin (26.6%; 95% CI 22.1 to 31.4). CONCLUSION Empirical antibiotic prescribing is standard practice in the community, but is associated with high levels of unnecessary antibiotic use. While trimethoprim/sulfamethoxazole is the first-line empirical antibiotic choice, fluoroquinolone antibiotics have become the second most commonly prescribed empirical antibiotic for acute cystitis. The effect of current prescribing patterns on community levels of quinolone-resistant Escherichia coli may need to be monitored. PMID:19436509

COSTS OF INTERSTITAL CYSTITIS IN A MANAGED CARE POPULATION

PubMed Central

Clemens, J. Quentin; Meenan, Richard T.; O’Keeffe Rosetti, Maureen C.; Kimes, Terry; Calhoun, Elizabeth A.

2008-01-01

Objective This study assessed the direct medical costs, medication and procedure use associated with interstitial cystitis (IC) in women in the Kaiser Permanente Northwest (KPNW) managed care population. Methods The KPNW electronic medical record was utilized to identify women diagnosed with interstitial cystitis (n=239). Each of these cases was matched with three controls based on age and duration in the health plan. Health plan cost accounting data were used to determine inpatient, outpatient, and pharmacy costs for 1998-2003. An analysis of prescription medication use, cystoscopic and urodynamic procedures commonly associated with IC was also performed. To evaluate for comorbidities, an automated risk-adjustment model (RxRisk) linked to 28 chronic medical conditions was applied to the administrative datasets from both groups. Results The mean duration from the date of IC diagnosis to the end of the study period was 36.6 months (range 1.4-60). Mean yearly costs were 2.4-fold greater in cases than controls ($7100 vs. $2994), and median yearly costs were 3.8-fold greater ($5000 vs. $1304). These cost differences were predominantly due to outpatient and pharmacy expenses. Medication and procedure use were significantly greater in cases than controls. These findings were consistent across RxRisk categories, which suggest that the observed cost differences are IC-specific. Conclusions The direct per-person costs of IC are high, with average yearly costs approximately $4000 greater than age-matched controls. This cost differential is an underestimate, as costs preceding the diagnosis, use of alternative therapies, indirect costs and costs of those with IC that is not diagnosed are not included. PMID:18329077

Apatinib in refractory radiation-induced brain edema

PubMed Central

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-01-01

Abstract Rationale: Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Patient concerns: Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Diagnoses: Two patients were both diagnosed as refractory radiation-induced brain edema. Interventions: Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Outcomes: Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Lessons: Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study. PMID:29145238

Innovative Approach for Interstitial Cystitis: Vaginal Pessaries Loaded Diazepam—A Preliminary Study

PubMed Central

Capra, P.; Perugini, P.; Bleve, M.; Pavanetto, P.; Musitelli, G.; Rovereto, B.; Porru, D.

2013-01-01

Bladder pain is a characteristic disorder of interstitial cystitis. Diazepam is well known for its antispasmodic activity in the treatment of muscular hypertonus. The aim of this work was to develop and characterize vaginal pessaries as an intravaginal delivery system of diazepam for the treatment of interstitial cystitis. In particular, the performance of two types of formulations, with and without beta-glucan, was compared. In particular, the preparation of pessaries, according to the modified Pharmacopeia protocol, the setup of the analytical method to determine diazepam, pH evaluation, dissolution profile, and photostability assay were reported. Results showed that the modified protocol permitted obtaining optimal vaginal pessaries, without air bubbles, with good consistency and handling and with good pH profiles. In order to determine the diazepam amount, calibration curves with good correlation coefficients were obtained, by the spectrophotometric method, using placebo pessaries as matrix with the addition of diazepam standard solution. This method was demonstrated sensible and accurate to determine the amount of drug in batches. Dissolution profiles showed a complete diazepam release just after 15 minutes, even if beta-glucan pessaries released drug more gradually. Finally, a possible drug photodegradation after exacerbated UV-visible exposition was evaluated. PMID:26555976

[Intravesical electrostimulation and magnetotherapy in chronic pyelonephritis and cystitis in children with urodynamic disorders].

PubMed

Sharkov, S M; Iatsik, S P; Bolotova, N V; Raĭgorodskiĭ, Iu M; Konova, O M; Tkacheva, E N

2011-01-01

The results of the treatment of 38 children (6 boys and 32 girls, age 6-14 years) with chronic pyelonephritis and/or cystitis complicated with neurogenic dysfunction of the urinary bladder (NDUB) and/or vesicoureteral reflux (VUR) of the first-third degree demonstrate efficacy of intravesical electrostimulation (IVES) and adrenal magnetotherapy. IVES was conducted with high-frequency current impulses (2.2 kHz) by means of INTRASTIM attachment to the device AMUS-01-INTRAMAG in the region of the urethrovesical anastomosis via solution of the drugs for instillation. As the result of exposure to both physical factors in the presence of standard medication, NDUB symptoms alleviated (by E.L. Vishnevsky's criteria) by 59.5% against 38.1% in the control group. Dopplerographic examination of renal vessels stated a 24.3% increase in blood flow in the major renal artery in the study group against 10.5% in the control. The proposed complex pharmacological plus physiotherapeutic treatment of chronic pyelonephritis and cystitis in abnormal urodynamics resulted in a 2.2-fold decrease in the number of recurrences compared to the standard treatment.

Gastrointestinal Impedance Spectroscopy to Detect Hypoperfusion During Hemorrhage.

PubMed

Bloch, Andreas; Kohler, Andreas; Posthaus, Horst; Berger, David; Santos, Laura; Jakob, Stephan; Takala, Jukka; Haenggi, Matthias

2017-08-01

Changes in tissue impedance (Ω) have been proposed as early signs of impaired tissue perfusion. We hypothesized that hemorrhage may induce early changes in alimentary tract tissue impedance and that these can be detected by impedance spectroscopy. We evaluated impedance spectroscopy in an acute hemorrhage model in pigs. Twenty anesthetized pigs were randomized to stepwise hemorrhage to mean arterial blood pressure (MAP) targets of 60 mm Hg, 50 mm Hg, 45 mm Hg, and 40 mm Hg, followed by retransfusion in two steps, or control (n = 10 each). In the end, 500 mL of enteral nutrition was administered in both groups. Ω in four sites (sublingually, esophagus, stomach, proximal jejunum) and cardiac output (Qtot thermodilution), superior mesenteric artery blood flow (QSMA; Doppler ultrasound), and jejunal mucosal blood flow (LDF; laser Doppler) were measured. The bleeding (total volume 838 ± 185 mL; mean ± SD) resulted in progressive hypotension (actual MAP 65 ± 3 mm Hg, 59 ± 4 mm Hg, 55 ± 5 mm Hg, and 46 ± 6 mm Hg) and decrease in Qtot, QSMA, and mucosal LDF. Bleeding did not change Ω in any of the monitoring sites. Retransfusion restored the blood flows to at least baseline levels, again without change in Ω. Enteral nutrition did not alter Ω or any of the blood flows.Five animals (three in the hemorrhage group, two in the control group) had histologically proven acute gastric focal necrosis at the site of It transducer. Gastrointestinal impedance spectroscopy does not detect early changes in tissue perfusion during progressive hemorrhage or retransfusion. Ω spectroscopy is unlikely to provide any additional information of hypovolemia-induced early changes in gastrointestinal perfusion.

Radiation-induced sarcoma of the thyroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griem, K.L.; Robb, P.K.; Caldarelli, D.D.

1989-08-01

A 23-year-old white man presented with a thyroid mass 12 years after receiving high-dose radiotherapy for a T2 and N1 lymphoepithelioma of the nasopharynx. Following subtotal thyroidectomy, a histopathologic examination revealed liposarcoma of the thyroid gland. The relationship between sarcomas and irradiation is described and Cahan and colleagues' criteria for radiation-induced sarcomas are reviewed. To our knowledge, we are presenting the first such case of a radiation-induced sarcoma of the thyroid gland.

Ciprofloxacin and furagin in acute cystitis: comparison of early immune and microbiological results.

PubMed

Dybowski, Bartosz; Jabłońska, Olga; Radziszewski, Piotr; Gromadzka-Ostrowska, Joanna; Borkowski, Andrzej

2008-02-01

Furagin (a nitrofurantoin analogue) has the same efficacy in treating acute cystitis as ciprofloxacin, however the duration of therapy is longer. We established a hypothesis that therapy with ciprofloxacin results in faster resolution of mucosal inflammation in comparison with furagin. Rates of urinary secretion of immunoglobulins class A, M and G and interleukin-8 (IL-8) were evaluated before and after initiation of therapy in adult women presenting with acute cystitis confirmed by urine culture. Women were randomised into two groups receiving either ciprofloxacin 250mg twice a day for 3 days (n=13) or furagin 100mg three times a day for 7 days (n=14). Median lengths of follow-up were 4 days and 5 days in the ciprofloxacin and furagin groups, respectively. Treatment with ciprofloxacin resulted in faster eradication of pathogens. No bacteria or nitrates were detected in the ciprofloxacin group, whilst leukocyte esterase was positive in only one case. In the furagin group there were four positive cultures, seven cases with positive nitrates and five cases with positive esterase. Secretion rates of all four substances dropped significantly, but the changes over time were similar in both groups.

Extracorporeal shock wave therapy ameliorates cyclophosphamide-induced rat acute interstitial cystitis though inhibiting inflammation and oxidative stress-in vitro and in vivo experiment studies

PubMed Central

Chen, Yen-Ta; Yang, Chih-Chao; Sun, Cheuk-Kwan; Chiang, Hsin-Ju; Chen, Yi-Ling; Sung, Pei-Hsun; Zhen, Yen-Yi; Huang, Tein-Hung; Chang, Chia-Lo; Chen, Hong-Hwa; Chang, Hsueh-Wen; Yip, Hon-Kan

2014-01-01

Background: We investigated whether extracorporeal shock wave (ECSW) therapy can attenuate cyclophosphamide (CYP)-induced acute interstitial cystitis (AIC) in rats. Methods and Results: Eighteen male-adult Sprague-Dawley rats were equally divided into group 1 (sham control), group 2 (AIC induced by 150 mg/kg CYP by intra-peritoneal injection) and group 3 (AIC + ECSW 200 impulses at 0.11 mJ/mm2 to the urinary bladder at 3 and 24 h after CYP treatment). Smooth-muscle cells co-culture with menadione (25 µM) with and without ECSW treatment was performed. Western-blot results demonstrated that ECSW significant attenuated oxidative stress and inflammatory reactions in this in-vitro studies (all p < 0.001). 24-hour urine amount and microscopic findings of red-blood-cell count (i.e., hematuria) were higher in group 2 than in groups 1 and 3, and significantly higher in group 3 than in group 1 (all p < 0.001). The urine levels of albumin and interleukin-6 showed an identical pattern of hematuria among all three groups (all p < 0.001). The cellular and mRNA expressions of macrophage migration inhibitory factor (MIF)+, CD74+, CD68+, substance p+, and Cox-2+ cells in the bladder tissue exhibited an identical pattern of hematuria among all groups (all p < 0.0001). The integrity of epithelial layer and collagen-deposition area as stained by Sirius red displayed an opposite pattern of hematuria among the three groups (p < 0.0001). The protein expression of IL-12, iNOS, TNF-α, NF-κB, MMP-9, NOX-1, NOX-2, RANTES, and Oxyblot displayed an identical pattern of hematuria among all groups (all p < 0.01). Conclusion: ECSW therapy markedly attenuated CYP-induced AIC through inhibitions of the inflammation and oxidative stress. PMID:25628776

Bladder pain syndrome/interstitial cystitis: a sense of urgency.

PubMed

Hanno, Philip M; Chapple, Chris R; Cardozo, Linda D

2009-12-01

A classic triad of symptoms (bladder pain, urinary frequency, and urgency) has served to define bladder pain syndrome/painful bladder syndrome/interstitial cystitis (BPS/PBS/IC) syndrome. BPS/PBS/IC is a distinct condition and it is likely that the urgency experienced by these patients differs from that experienced by those with overactive bladder syndrome. It is unclear how best to define urgency in the BPS/PBS/IC setting. Differences in the other primary symptoms associated with these conditions probably influence how urgency is perceived. Advances in research into the pathophysiology of urgency and underlying disease processes will help to optimize both the diagnosis and treatment of BPS/PBS/IC.

Unusual presentations of BK virus infections in pediatric renal transplant recipients.

PubMed

Drake, Keri A; Najera, Lydia; Reed, Robyn C; Verghese, Priya S

2013-02-01

BKV has emerged as a significant pathogen in the field of transplantation, predominantly causing BKV nephropathy in renal transplant recipients and hemorrhagic cystitis in HSCT recipients. However, case reports describe more diverse complications, and we too present three unusual cases of BKV infections in pediatric renal transplant recipients. First, we describe a case of biopsy-proven renal damage secondary to BKV prior to the onset of viremia, demonstrating that BKV nephropathy can occur without preceding viremia. We also present two renal transplant recipients with persistent BK viruria, one with BKV-associated hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we conclude that BKV manifestations may be more diverse than previously thought and suggest clinical utility in urine BKV qPCR testing in specific transplant recipients. © 2012 John Wiley & Sons A/S.

Hepatoprotective Effects of Corilagin Following Hemorrhagic Shock are Through Akt-Dependent Pathway

PubMed Central

Liu, Fu-Chao; Chaudry, Irshad H.; Yu, Huang-Ping

2017-01-01

ABSTRACT Corilagin, a component of Phyllanthus urinaria extract, possesses antioxidant, thrombolytic, antiatherogenic, and hepatoprotective properties, but the mechanism underlying these effects remains unclear. Previous studies showed that the Akt (protein kinase B) signaling pathway exerts anti-inflammatory and organ protective effects. The aim of this study was to investigate the mechanism of action of corilagin and determine whether these effects are mediated through the Akt-dependent pathway in a trauma-hemorrhagic shock-induced liver injury rodent model. Hemorrhagic shock was induced in male Sprague–Dawley rats; mean blood pressure was maintained at 35 mm Hg to 40 mm Hg for 90 min, followed by fluid resuscitation. During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered. Furthermore, a single dose of corilagin (5 mg/kg) with and without Wortmannin (1 mg/kg, PI3K inhibitor), Wortmannin alone, or vehicle was administered. Twenty-four hours after resuscitation, plasma alanine aminotransferase and aspartate aminotransferase concentration and hepatic parameters were measured. One-way ANOVA was used for statistical analysis. Hepatic myeloperoxidase activity and the concentrations of plasma alanine aminotransferase and aspartate aminotransferase, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) and CINC-3 increased following hemorrhagic shock. These parameters were significantly attenuated in corilagin-treated rats following hemorrhagic shock. Hepatic phospho-Akt expression was also higher in corilagin-treated rats than in vehicle-treated rats. The elevation of phospho-Akt was abolished by combined treatment with Wortmannin and corilagin. Our results suggest that corilagin exerts its protective effects on hemorrhagic shock-induced liver injury, at least, via the Akt-dependent pathway. PMID:27559697

Radiation-Induced Second Cancer Risk Estimates From Radionuclide Therapy

NASA Astrophysics Data System (ADS)

Bednarz, Bryan; Besemer, Abigail

2017-09-01

The use of radionuclide therapy in the clinical setting is expected to increase significantly over the next decade. There is an important need to understand the radiation-induced second cancer risk associated with these procedures. In this study the radiation-induced cancer risk in five radionuclide therapy patients was investigated. These patients underwent serial SPECT imaging scans following injection as part of a clinical trial testing the efficacy of a 131Iodine-labeled radiopharmaceutical. Using these datasets the committed absorbed doses to multiple sensitive structures were calculated using RAPID, which is a novel Monte Carlo-based 3D dosimetry platform developed for personalized dosimetry. The excess relative risk (ERR) for radiation-induced cancer in these structures was then derived from these dose estimates following the recommendations set forth in the BEIR VII report. The radiation-induced leukemia ERR was highest among all sites considered reaching a maximum value of approximately 4.5. The radiation-induced cancer risk in the kidneys, liver and spleen ranged between 0.3 and 1.3. The lifetime attributable risks (LARs) were also calculated, which ranged from 30 to 1700 cancers per 100,000 persons and were highest for leukemia and the liver for both males and females followed by radiation-induced spleen and kidney cancer. The risks associated with radionuclide therapy are similar to the risk associated with external beam radiation therapy.

Crimean-Congo Hemorrhagic Fever Virus Subunit Vaccines Induce High Levels of Neutralizing Antibodies But No Protection in STAT1 Knockout Mice.

PubMed

Kortekaas, Jeroen; Vloet, Rianka P M; McAuley, Alexander J; Shen, Xiaoli; Bosch, Berend Jan; de Vries, Laura; Moormann, Rob J M; Bente, Dennis A

2015-12-01

Crimean-Congo hemorrhagic fever virus is a tick-borne bunyavirus of the Nairovirus genus that causes hemorrhagic fever in humans with high case fatality. Here, we report the development of subunit vaccines and their efficacy in signal transducer and activator of transcription 1 (STAT1) knockout mice. Ectodomains of the structural glycoproteins Gn and Gc were produced using a Drosophila insect cell-based expression system. A single vaccination of STAT129 mice with adjuvanted Gn or Gc ectodomains induced neutralizing antibody responses, which were boosted by a second vaccination. Despite these antibody responses, mice were not protected from a CCHFV challenge infection. These results suggest that neutralizing antibodies against CCHFV do not correlate with protection of STAT1 knockout mice.

Grey Turner's and Cullen's signs induced by spontaneous hemorrhage of the abdominal wall after coughing.

PubMed

Fan, Zhe; Zhang, Yingyi

2017-08-01

Grey Turner's and Cullen's signs are rare clinical signs, which most appear in patients with severe acute pancreatitis. The present patient complained of abdominal pain after coughing. However, contrast-enhanced CT revealed a hemorrhage of the abdominal wall. Therefore, spontaneous hemorrhage of the abdominal wall was diagnosed. The patient recovered through immobilization and hemostasis therapy. This case report and literature review aims to remind clinicians of manifestations and treatment of spontaneous hemorrhage.

Protection from radiation-induced pneumonitis using cerium oxide nanoparticles.

PubMed

Colon, Jimmie; Herrera, Luis; Smith, Joshua; Patil, Swanand; Komanski, Chris; Kupelian, Patrick; Seal, Sudipta; Jenkins, D Wayne; Baker, Cheryl H

2009-06-01

In an effort to combat the harmful effects of radiation exposure, we propose that rare-earth cerium oxide (CeO(2)) nanoparticles (free-radical scavengers) protect normal tissue from radiation-induced damage. Preliminary studies suggest that these nanoparticles may be a therapeutic regenerative nanomedicine that will scavenge reactive oxygen species, which are responsible for radiation-induced cell damage. The effectiveness of CeO(2) nanoparticles in radiation protection in murine models during high-dose radiation exposure is investigated, with the ultimate goal of offering a new approach to radiation protection, using nanotechnology. We show that CeO(2) nanoparticles are well tolerated by live animals, and they prevent the onset of radiation-induced pneumonitis when delivered to live animals exposed to high doses of radiation. In the end, these studies provide a tremendous potential for radioprotection and can lead to significant benefits for the preservation of human health and the quality of life for humans receiving radiation therapy.

Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice.

PubMed

Maa, J; Grady, E F; Yoshimi, S K; Drasin, T E; Kim, E H; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-08-01

The neuropeptide substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin 1-receptor (NK1-R). SP-induced neurogenic inflammation is terminated by the cell surface enzyme neutral endopeptidase (NEP), which degrades SP. We determined whether genetic deletion of the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP increases mortality in a lethal model of hemorrhagic pancreatitis. Necrotizing pancreatitis was induced by feeding mice a diet deficient in choline and supplemented with ethionine. We determined the length of survival, the severity of pancreatitis (by measuring the neutrophil enzyme myeloperoxidase [MPO] and by histologic evaluation), and the severity of pancreatitis-associated lung injury (lung MPO and histology) in NK1-R (+/+)/(-/-) and NEP (+/+)/(-/-) mice. Genetic deletion of the NK1-R significantly improved survival (100% vs 8% at 120 hours, P <.001) and reduced pancreatic MPO and acinar cell necrosis. Conversely, genetic deletion of NEP significantly worsened survival (0% vs 90% at 120 hours, P <.001) and exacerbated pancreatic MPO and pancreatitis-associated lung injury. Substance P is an important determinant of lethality in this model of necrotizing pancreatitis. Defects in NEP expression could lead to uncontrolled inflammation.

Chromosome aberrations induced by high-LET radiations

NASA Technical Reports Server (NTRS)

Kawata, Tetsuya; Ito, Hisao; George, Kerry; Wu, Honglu; Cucinotta, Francis A.

2004-01-01

Measurements of chromosome aberrations in peripheral blood lymphocytes are currently the most sensitive and reliable indicator of radiation exposure that can be used for biological dosimetry. This technique has been implemented recently to study radiation exposures incurred by astronauts during space flight, where a significant proportion of the dose is delivered by high-LET particle exposure. Traditional methods for the assessing of cytogenetic damage in mitotic cells collected at one time point after exposure may not be suitable for measuring high-LET radiation effects due to the drastic cell cycle perturbations and interphase cell death induced by this type of exposure. In this manuscript we review the recent advances in methodology used to study high-LET induced cytogenetic effects and evaluate the use of chemically-induced Premature Chromosome Condensation (PCC) as an alternative to metaphase analysis. Published data on the cytogenetic effects of in vitro exposures of high-LET radiation is reviewed, along with biodosimetry results from astronauts after short or long space missions.

Gemcitabine-induced rectus abdominus radiation recall.

PubMed

Fakih, Marwan G

2006-05-09

Radiation recall has been described in the context of gemcitabine chemotherapy. However, this phenomenon has been largely limited to skin. We hereby report a case of radiation recall dermatitis and myositis occurring on gemcitabine monotherapy, five months after completing chemoradiation for locally advanced pancreatic cancer. Radiation recall resolved spontaneously with withdrawal of gemcitabine. This is the second case report that describes gemcitabine-induced radiation recall in rectus abdominus muscles after gemcitabine-based radiation therapy. Given the wide use of gemcitabine following chemoradiation for pancreatic cancer, providers should be aware of this potential complication.

Involvement of connexin 43 phosphorylation and gap junctional communication between smooth muscle cells in vasopressin-induced ROCK-dependent vasoconstriction after hemorrhagic shock.

PubMed

Yang, Guangming; Peng, Xiaoyong; Wu, Yue; Li, Tao; Liu, Liangming

2017-10-01

We examined the roles played by gap junctions (GJs) and the GJ channel protein connexin 43 (Cx43) in arginine vasopressin (AVP)-induced vasoconstriction after hemorrhagic shock and their relationship to Rho kinase (ROCK) and protein kinase C (PKC). The results showed that AVP induced an endothelium-independent contraction in rat superior mesenteric arteries (SMAs). Blocking the GJs significantly decreased the contractile response of SMAs and vascular smooth muscle cells (VSMCs) to AVP after shock and hypoxia. The selective Cx43-mimetic peptide inhibited the vascular contractile effect of AVP after shock and hypoxia. AVP restored hypoxia-induced decrease of Cx43 phosphorylation at Ser 262 and gap junctional communication in VSMCs. Activation of RhoA with U-46619 increased the contractile effect of AVP. This effect was antagonized by the ROCK inhibitor Y27632 and the Cx43-mimetic peptide. In contrast, neither an agonist nor an inhibitor of PKC had significant effects on AVP-induced contraction after hemorrhagic shock. In addition, silencing of Cx43 with siRNA blocked the AVP-induced increase of ROCK activity in hypoxic VSMCs. In conclusion, AVP-mediated vascular contractile effects are endothelium and myoendothelial gap junction independent. Gap junctions between VSMCs, gap junctional communication, and Cx43 phosphorylation at Ser 262 play important roles in the vascular effects of AVP. RhoA/ROCK, but not PKC, is involved in this process. Copyright © 2017 the American Physiological Society.

Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine

DTIC Science & Technology

2011-07-01

Decay-Accelerating Factor Mitigates Controlled Hemorrhage- Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine Jurandir J. Dalle...DAF treatment improved hemorrhage- induced hyperkalemia . The protective effects of DAF appear to be related to its ability to reduce tissue complement...Decay-accelerating factor mitigates controlled hemorrhage-instigated intestinal and lung tissue damage and hyperkalemia in swine 5a. CONTRACT NUMBER

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

PubMed Central

2014-01-01

This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood–brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer’s disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH-induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke. PMID:25120903

Inhibition of BTK protects lungs from trauma-hemorrhagic shock-induced injury in rats.

PubMed

Liu, Xinwei; Zhang, Jingdong; Han, Wenfeng; Wang, Yu; Liu, Yunen; Zhang, Yubiao; Zhou, Dapeng; Xiang, Liangbi

2017-07-01

The present study aimed to investigate the role of Bruton's tyrosine kinase (BTK) in the pathogenesis of lung injury induced by trauma‑hemorrhagic shock (THS), and to examine the pulmonary protective effects of BTK inhibition. Male Sprague‑Dawley rats were divided into four groups (n=12/group): i) A Sham group, which received surgery without induced trauma; ii) a THS‑induced injury group; iii) a THS‑induced injury group that also received treatment with the BTK inhibitor LFM‑A13 prior to trauma induction; and iv) a Sham group that was pretreated with LFM‑A13 prior to surgery but did not receive induced trauma. The expression of phosphorylated‑BTK protein in the lungs was measured by immunohistochemistry and western blot analysis. The bronchoalveolar lavage fluid (BALF) protein concentration, total leukocyte and eosinophil numbers, and the expression levels of peripheral blood proinflammatory factors were measured. Morphological alterations in the lungs were detected by hematoxylin and eosin staining. Pulmonary nitric oxide (NO) concentration and inducible NO synthase (iNOS) expression were also assessed. Activities of the nuclear factor (NF)‑κB and mitogen‑activated protein kinase (MAPK) signaling pathways were determined by western blotting or electrophoretic mobility shift assay. BTK was notably activated in lungs of THS rats. BALF protein concentration, total leukocytes and eosinophils, peripheral blood expression levels of tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and monocyte chemotactic protein 1 were significantly upregulated after THS induction, and each exhibited decreased expression upon LFM‑A13 treatment. THS‑induced interstitial hyperplasia, edema and neutrophilic infiltration in lungs were improved by the inhibition of BTK. In addition, THS‑induced NO release, iNOS overexpression, and NF‑κB and MAPK signaling were suppressed by BTK inhibition. Results from the present study demonstrate that BTK may serve

Postconditioning with sevoflurane ameliorates spatial learning and memory deficit via attenuating endoplasmic reticulum stress induced neuron apoptosis in a rat model of hemorrhage shock and resuscitation.

PubMed

Hu, Xianwen; Wang, Jingxian; Zhang, Li; Zhang, Qiquan; Duan, Xiaowen; Zhang, Ye

2018-06-02

Hemorrhage shock could initiate endoplasmic reticulum stress (ERS) and then induce neuronal apoptosis. The aim of this study was to investigate whether sevoflurane postconditioning could attenuate brain injury via suppressing apoptosis induced by ERS. Seventy male rats were randomized into five groups: sham, shock, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%) and high concentration (sevo3, 3.6%) of sevoflurane postconditioning. Hemorrhage shock was induced by removing 40% of the total blood volume during an interval of 30 min. 1h after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The spatial learning and memory ability of rats were measured by Morris water maze (MWM) test three days after the operation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region were assessed after the MWM test. The expression of C/EBP-homologousprotein (CHOP) and glucose-regulated protein 78 (GRP78) in the hippocampus were measured at 24h after reperfusion. We found that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability, decreased the TUNEL-positive cells, and reduced the GRP78 and CHOP expression compared with the shock group. These results suggested that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% could ameliorate spatial learning and memory deficit after hemorrhage shock and resuscitation injury via suppressing apoptosis induced by ERS. Copyright © 2018. Published by Elsevier B.V.

Radiation-Induced Immune Modulation in Prostate Cancer

DTIC Science & Technology

2008-01-01

cancers. 15. SUBJECT TERMS Radiation, Dendritic Cells , Cytokines, PSA 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...radiation is more than a cytotoxic agent. Our recent study has shown that radiation modulates the immune system by affecting dendritic cell (DC...translate radiation-induced tumor cell death into generation of tumor immunity in the hope of optimizing therapy for localized and disseminated prostate

Mechanism of salutary effects of melatonin-mediated liver protection after trauma-hemorrhage: p38 MAPK-dependent iNOS/HIF-1α pathway.

PubMed

Hsu, Jun-Te; Le, Puo-Hsien; Lin, Chun-Jung; Chen, Tsung-Hsing; Kuo, Chia-Jung; Chiang, Kun-Chun; Yeh, Ta-Sen

2017-05-01

Although melatonin attenuates the increases in inflammatory mediators and reduces organ injury during trauma-hemorrhage, the mechanisms remain unclear. This study explored whether melatonin prevents liver injury after trauma-hemorrhage through the p38 mitogen-activated protein kinase (MAPK)-dependent, inducible nitrite oxide (iNOS)/hypoxia-inducible factor (HIF)-1α pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ~40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), melatonin plus p38 MAPK inhibitor SB203580 (2 mg/kg), or melatonin plus the melatonin receptor antagonist luzindole (2.5 mg/kg). At 2 h after trauma-hemorrhage, histopathology score of liver injury, liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and asparate aminotransferase levels were significantly increased compared with sham-operated control. Trauma-hemorrhage resulted in a significant decrease in the p38 MAPK activation compared with that in the sham-treated animals. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression and attenuated cleaved caspase 3 and receptor interacting protein kinase-1 levels. Coadministration of SB203580 or luzindole abolished the melatonin-mediated attenuation of the trauma-hemorrhage-induced increase of iNOS/HIF-1α protein expression and liver injury markers. Taken together, our results suggest that melatonin prevents trauma-hemorrhage-induced liver injury in rats, at least in part, through melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway. NEW & NOTEWORTHY Trauma-hemorrhage resulted in a significant decrease in liver p38 MAPK activation and increase in nitrite oxide synthase (iNOS) and hypoxia-inducible factor (HIF)-1α expression. Administration of melatonin after trauma-hemorrhage

Vesical Artery Embolization in Haemorrhagic Cystitis in Children

DOE Office of Scientific and Technical Information (OSTI.GOV)

García-Gámez, Andrés, E-mail: agargamez@gmail.com; Bermúdez Bencerrey, Patricia, E-mail: PBERMUDE@clinic.ub.es; Brio-Sanagustin, Sonia, E-mail: sbrio@santpau.cat

Haemorrhagic cystitis is an uncommon and, in its severe form, potentially life-threatening complication of haematopoietic stem cell transplantation or cancer therapy in children. The severe form involves macroscopic haematuria with blood clots, urinary obstruction and/or renal impairment. There are many therapeutic options to treat acute haemorrhage, but only recombinant factor VII has a high level of clinical evidence in children. Supraselective vesical artery embolization (SVAE) is an increasingly used therapeutic procedure for controlling haemorrhage in adults, but is less commonly used in children. This might be due to several factors, such as the invasive nature of the procedure, lack ofmore » appropriate medical experience and possible long-term side effects. We present three cases of children successfully treated by means of effective SVAE.« less

AICAR Administration Attenuates Hemorrhagic Hyperglycemia and Lowers Oxygen Debt in Anesthetized Male Rabbits.

PubMed

Huang, Yi; Ratz, Paul H; Miner, Amy S; Locke, Victoria A; Chen, Grace; Chen, Yang; Barbee, Robert W

2017-01-01

Background: Many strategies have been utilized to treat traumatic shock via improved oxygen delivery (DO 2 ), while fewer have been used to in an attempt to reduce oxygen demand (VO 2 ). The cellular energy sensor 5' adenosine monophosphate-activated protein kinase (AMPK) has the potential to modulate both whole-body DO 2 and VO 2 . Therefore, we determined the effect of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside) given acutely or chronically on key metabolites, hemodynamics, and oxygen consumption/delivery before and during hemorrhage in anesthetized male rabbits. Methods: Chronically treated animals received AICAR (40 mg/kg/day, IV) for 10 days prior to hemorrhage, while rabbits in the acute study were infused with AICAR (7.5 mg/kg bolus, 2 mg/kg/min infusion) or vehicle (0.3 ml/kg saline bolus, 0.03 ml/kg/min infusion) IV for 2 h prior to severe hemorrhage. Both acutely and chronically treated animals were sedated (ketamine/xylazine cocktail) the morning of the terminal experiment and surgically prepared for hemorrhage, including the implantation of arterial and venous catheters (for blood removal/sampling and drug/vehicle administration) and thoracotomy for implantation of transit-time flow transducers (for cardiac output determination). Results: AICAR given acutely lowered arterial blood glucose and increased blood lactate levels before hemorrhage, and abolished the well-documented hemorrhage-induced hyperglycemia seen in vehicle treated animals. Animals given AICAR chronically had blunted hemorrhage-induced hyperglycemia without prior baseline changes. Chronically treated AICAR animals showed significantly lower lactate levels during hemorrhage. Rabbits receiving AICAR both acutely and chronically experienced similar falls in mean arterial pressure, cardiac output and hence DO 2 to their vehicle counterparts throughout the hemorrhage period. However, rabbits treated either acutely or chronically with AICAR accumulated lower

Radiation-Induced Oral Mucositis

PubMed Central

Maria, Osama Muhammad; Eliopoulos, Nicoletta; Muanza, Thierry

2017-01-01

Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients. It is a normal tissue injury caused by radiation/radiotherapy (RT), which has marked adverse effects on patient quality of life and cancer therapy continuity. It is a challenge for radiation oncologists since it leads to cancer therapy interruption, poor local tumor control, and changes in dose fractionation. RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients. In the United Sates, its economic cost was estimated to reach 17,000.00 USD per patient with head and neck cancers. This review will discuss RIOM definition, epidemiology, impact and side effects, pathogenesis, scoring scales, diagnosis, differential diagnosis, prevention, and treatment. PMID:28589080

Intrauterine Growth Restriction Is a Direct Consequence of Localized Maternal Uropathogenic Escherichia coli Cystitis

PubMed Central

Bolton, Michael; Horvath, Dennis J.; Li, Birong; Cortado, Hanna; Newsom, David; White, Peter; Partida-Sanchez, Santiago; Justice, Sheryl S.

2012-01-01

Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20–80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organs PMID:22470490

Macular hemorrhages associated with neonatal polycythemia and thrombocytopenia: A case report.

PubMed

Cui, Z; Zhang, Y; Liang, L; Li, Z; Hao, Q

2017-02-01

Thrombocytopenia occurs in 51% of neonates with polycythemia and is independently associated with growth restriction. Increased hematocrit is associated with decreased platelet count. The possibility of a hemorrhage should be noted. A Chinese male newborn presented with elevated hemoglobin and hematocrit levels. The platelet count decreased to 10×10 9 /L during the 1st week after birth and remained abnormal at day 12. Vitreous turbidity of the right eye was detected 2 days later and was suspected of stemming from endophthalmitis or ocular inflammation. Two weeks later, vitreous turbidity decreased and a macular hemorrhage became visible. Optical coherence tomography confirmed the diagnosis of a retinal hemorrhage. Thrombocytopenia associated with polycythemia can induce a vitreous hemorrhage, which may be confused with ocular infection or inflammation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mechanisms for Induction of Pulmonary Capillary Hemorrhage by Diagnostic Ultrasound: Review and Consideration of Acoustical Radiation Surface Pressure

PubMed Central

Miller, Douglas L.

2016-01-01

Diagnostic ultrasound can induce pulmonary capillary hemorrhage (PCH) in rats and other mammals. This phenomenon represents the only clearly demonstrated biological effect of (non-contrast enhanced) diagnostic ultrasound and thus presents a uniquely important safety issue. However, the physical mechanism responsible for PCH remains uncertain more than 25 y after its discovery. Experimental research has indicated that neither heating nor acoustic cavitation, the predominant mechanisms for bioeffects of ultrasound, is responsible for PCH. Furthermore, proposed theoretical mechanisms based on gas body activation, on alveolar resonance and on impulsive generation of liquid droplets all appear unlikely to be responsible for PCH, owing to unrealistic model assumptions. Here, a simple model based on the acoustic radiation surface pressure (ARSP) at a tissue-air interface is hypothesized as the mechanism for PCH. The ARSP model seems to explain some features of PCH, including the approximate frequency independence of PCH thresholds, and the dependence of thresholds on biological factors. However, ARSP evaluated for experimental threshold conditions appear to be too weak to fully account for stress failure of pulmonary capillaries, gauging by known stresses for injurious physiological conditions. Furthermore, consideration of bulk properties of lung tissue suggests substantial transmission of ultrasound through the pleura, with reduced ARSP and potential involvement of additional mechanisms within the pulmonary interior. Although these recent findings advance our knowledge, only a full understanding of PCH mechanisms will allow development of science-based safety assurance for pulmonary ultrasound. PMID:27649878

Dengue viral protease interaction with NF-κB inhibitor α/β results in endothelial cell apoptosis and hemorrhage development.

PubMed

Lin, Jung-Chen; Lin, Shih-Ching; Chen, Wen-Yu; Yen, Yu-Ting; Lai, Chin-Wen; Tao, Mi-Hua; Lin, Yi-Ling; Miaw, Shi-Chuen; Wu-Hsieh, Betty A

2014-08-01

Hemorrhagic manifestations occur frequently accompanying a wide range of dengue disease syndromes. Much work has focused on the contribution of immune factors to the pathogenesis of hemorrhage, but how dengue virus (DENV) participates in the pathogenic process has never been explored. Although there is no consensus that apoptosis is the basis of vascular permeability in human dengue infections, we showed in dengue hemorrhage mouse model that endothelial cell apoptosis is important to hemorrhage development in mice. To explore the molecular basis of the contribution of DENV to endothelial cell death, we show in this study that DENV protease interacts with cellular IκBα and IκBβ and cleaves them. By inducing IκBα and IκBβ cleavage and IκB kinase activation, DENV protease activates NF-κB, which results in endothelial cell death. Intradermal inoculation of DENV protease packaged in adenovirus-associated virus-9 induces endothelial cell death and dermal hemorrhage in mice. Although the H51 activity site is not involved in the interaction between DENV protease and IκB-α/β, the enzymatic activity is critical to the ability of DENV protease to induce IκBα and IκBβ cleavage and trigger hemorrhage development. Moreover, overexpression of IκBα or IκBβ protects endothelial cells from DENV-induced apoptosis. In this study, we show that DENV protease participates in the pathogenesis of dengue hemorrhage and discover IκBα and IκBβ to be the new cellular targets that are cleaved by DENV protease. Copyright © 2014 by The American Association of Immunologists, Inc.

Radiation-induced valvular heart disease.

PubMed

Gujral, Dorothy M; Lloyd, Guy; Bhattacharyya, Sanjeev

2016-02-15

Radiation to the mediastinum is a key component of treatment with curative intent for a range of cancers including Hodgkin's lymphoma and breast cancer. Exposure to radiation is associated with a risk of radiation-induced heart valve damage characterised by valve fibrosis and calcification. There is a latent interval of 10-20 years between radiation exposure and development of clinically significant heart valve disease. Risk is related to radiation dose received, interval from exposure and use of concomitant chemotherapy. Long-term outlook and the risk of valve surgery are related to the effects of radiation on mediastinal structures including pulmonary fibrosis and pericardial constriction. Dose prediction models to predict the risk of heart valve disease in the future and newer radiation techniques to reduce the radiation dose to the heart are being developed. Surveillance strategies for this cohort of cancer survivors at risk of developing significant heart valve complications are required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Hemorrhagic Stroke

MedlinePlus

A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Hemorrhagic stroke is the less common type. It happens when ... an artery wall that breaks open. Symptoms of stroke are Sudden numbness or weakness of the face, ...

Effectiveness of the herbal medicine daikenchuto for radiation-induced enteritis.

PubMed

Takeda, Takashi; Kamiura, Shouji; Kimura, Tadashi

2008-07-01

Radiation-induced enteritis is a serious clinical problem for which there is currently no recommended standard management. Daikenchuto (DKT) is a Japanese herbal medicine that has been used to treat adhesive bowel obstruction in Japan. This report describes a patient with radiation-induced enteritis whose clinical symptoms were much improved by treatment with DKT. The patient was administered DKT, a traditional Japanese herbal formula, orally (2.5 g 3 times daily). Abdominal distention was evaluated objectively with computed tomography. Gastrointestinal symptoms associated with radiation-induced enteritis were controlled successfully with DKT treatment. DKT treatment may be useful for the management of radiation-induced enteritis.

Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis

PubMed Central

Shim, Grace; Ricoul, Michelle; Hempel, William M.; Azzam, Edouard I.; Sabatier, Laure

2014-01-01

It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked to telomeric proteins and telomere maintenance. Long-term propagation of this radiation-induced chromosomal damage during cell proliferation results in chromosomal instability. Many studies have shown the link between radiation exposure and radiation-induced changes in oxidative stress and DNA damage repair in both targeted and non-targeted cells. However, the effect of these factors on telomeres, long established as guardians of the genome, still remains to be clarified. In this review, we will focus on what is known about how telomeres are affected by exposure to low- and high-LET ionizing radiation and during proliferation, and will discuss how telomeres may be a key player in the process of radiation-induced carcinogenesis. PMID:24486376

Radiation induced detwinning in nanotwinned Cu

DOE PAGES

Chen, Youxing; Wang, Haiyan; Kirk, Mark A.; ...

2016-11-15

Superior radiation tolerance has been experimentally examined in nanotwinned metals. The stability of nanotwinned structure under radiation is the key factor for advancing the application of nanotwinned metals for nuclear reactors. We thus performed in situ radiation tests for nanotwinned Cu with various twin thicknesses inside a transmission electron microscope. We found that there is a critical twin thickness (10 nm), below which, radiation induced detwinning is primarily accomplished through migration of incoherent twin boundaries. Lastly, detwinning is faster for thinner twins in this range, while thicker twins are more stable.

Protection from radiation-induced apoptosis by the radioprotector amifostine (WR-2721) is radiation dose dependent.

PubMed

Ormsby, Rebecca J; Lawrence, Mark D; Blyth, Benjamin J; Bexis, Katrina; Bezak, Eva; Murley, Jeffrey S; Grdina, David J; Sykes, Pamela J

2014-02-01

The radioprotective agent amifostine is a free radical scavenger that can protect cells from the damaging effects of ionising radiation when administered prior to radiation exposure. However, amifostine has also been shown to protect cells from chromosomal mutations when administered after radiation exposure. As apoptosis is a common mechanism by which cells with mutations are removed from the cell population, we investigated whether amifostine stimulates apoptosis when administered after radiation exposure. We chose to study a relatively low dose which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400 mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or 6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow. We observed a significant increase in radiation-induced apoptosis in the spleen of mice when amifostine was administered before or after 0.25 Gy X-rays. In contrast, when a high dose of radiation was used (6 Gy), amifostine caused a reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone marrow similar to previously published studies. This is the first study to investigate the effect of amifostine on radiation-induced apoptosis at a relatively low radiation dose and the first to demonstrate that while amifostine can reduce apoptosis from high doses of radiation, it does not mediate the same effect in response to low-dose exposures. These results suggest that there may be a dose threshold at which amifostine protects from radiation-induced apoptosis and highlight the importance of examining a range of radiation doses and timepoints.

Obesity-induced hepatic hypoperfusion primes for hepatic dysfunction after resuscitated hemorrhagic shock.

PubMed

Matheson, Paul J; Hurt, Ryan T; Franklin, Glen A; McClain, Craig J; Garrison, R Neal

2009-10-01

Obese patients (BMI>35) after blunt trauma are at increased risk compared to non-obese for organ dysfunction, prolonged hospital stay, infection, prolonged mechanical ventilation, and mortality. Obesity and non-alcoholic fatty liver disease (NAFLD) produce a low grade systemic inflammatory response syndrome (SIRS) with compromised hepatic blood flow, which increases with body mass index. We hypothesized that obesity further aggravates liver dysfunction by reduced hepatic perfusion following resuscitated hemorrhagic shock (HEM). Age-matched Zucker rats (Obese, 314-519 g & Lean, 211-280 g) were randomly assigned to 4 groups (n = 10-12/group): (1) Lean-Sham; (2) Lean, HEM, and resuscitation (HEM/RES); (3) Obese-Sham; and (4) Obese-HEM/RES. HEM was 40% of mean arterial pressure (MAP) for 60 min; RES was return of shed blood/5 min and 2 volumes of saline/25 min. Hepatic blood flow (HBF) using galactose clearance, liver enzymes and complete metabolic panel were measured over 4 h after completion of RES. Obese rats had increased MAP, heart rate, and fasting blood glucose and BUN concentrations compared to lean controls, required less blood withdrawal (mL/g) to maintain 40% MAP, and RES did not restore BL MAP. Obese rats had decreased HBF at BL and during HEM/RES, which persisted 4 h post RES. ALT and BUN were increased compared to Lean-HEM/RES at 4 h post-RES. These data suggest that obesity significantly contributes to trauma outcomes through compromised vascular control or through fat-induced sinusoidal compression to impair hepatic blood flow after HEM/RES resulting in a greater hepatic injury. The pro-inflammatory state of NAFLD seen in obesity appears to prime the liver for hepatic ischemia after resuscitated hemorrhagic shock, perhaps intensified by insidious and ongoing hepatic hypoperfusion established prior to the traumatic injury or shock.

Radiation-induced alternative transcripts as detected in total and polysome-bound mRNA.

PubMed

Wahba, Amy; Ryan, Michael C; Shankavaram, Uma T; Camphausen, Kevin; Tofilon, Philip J

2018-01-02

Alternative splicing is a critical event in the posttranscriptional regulation of gene expression. To investigate whether this process influences radiation-induced gene expression we defined the effects of ionizing radiation on the generation of alternative transcripts in total cellular mRNA (the transcriptome) and polysome-bound mRNA (the translatome) of the human glioblastoma stem-like cell line NSC11. For these studies, RNA-Seq profiles from control and irradiated cells were compared using the program SpliceSeq to identify transcripts and splice variations induced by radiation. As compared to the transcriptome (total RNA) of untreated cells, the radiation-induced transcriptome contained 92 splice events suggesting that radiation induced alternative splicing. As compared to the translatome (polysome-bound RNA) of untreated cells, the radiation-induced translatome contained 280 splice events of which only 24 were overlapping with the radiation-induced transcriptome. These results suggest that radiation not only modifies alternative splicing of precursor mRNA, but also results in the selective association of existing mRNA isoforms with polysomes. Comparison of radiation-induced alternative transcripts to radiation-induced gene expression in total RNA revealed little overlap (about 3%). In contrast, in the radiation-induced translatome, about 38% of the induced alternative transcripts corresponded to genes whose expression level was affected in the translatome. This study suggests that whereas radiation induces alternate splicing, the alternative transcripts present at the time of irradiation may play a role in the radiation-induced translational control of gene expression and thus cellular radioresponse.

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques

PubMed Central

Vatter, Heather A.; Donaldson, Eric F.; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F.; Lewis, Anne D.; Colgin, Lois M.A.; Axthelm, Michael K.; Pecotte, Jerilyn K.; Baric, Ralph S.; Wong, Scott W.; Brinton, Margo A.

2014-01-01

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages showed a very high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100 PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. PMID:25463617

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques.

PubMed

Vatter, Heather A; Donaldson, Eric F; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F; Lewis, Anne D; Colgin, Lois M A; Axthelm, Michael K; Pecotte, Jerilyn K; Baric, Ralph S; Wong, Scott W; Brinton, Margo A

2015-01-01

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100-1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages had a high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. Copyright © 2014 Elsevier Inc. All rights reserved.

RADIATION INDUCED AGING IN MICE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Curtis, H.J.; Gebhard, K.L.

1958-10-31

. Experiments were undertaken in an effort to determine the degree of similarity between natural and radiation induced aging, and to determine the causes for the latter. Several severe non-specific stresses were applied to mice either as single massive doses or as smaller doses administered over a large fraction of the life span of the animals. Stresses used included typhoid vaccine, tetanus toxin and tetanus toxoid and turpentine. None of these produced any premature aging comparable to that produced by radiation. The somatic mutation theory of aging and expecially radiationinduced aging has been tested by applying the chemical mutatgen, nitrogenmore » mustard, either as a massive single dose or as smaller single doses repeated over long periods of time. No shortening of the life span has been observed and it is concluded that the somatic mutation theory is untenable. Experiments designed to determine the organ system responsible for radiation induced aging have demonstrated that the hematopoietic system is not primarily involved in this phenomenon. (auth)« less

T Cells Prevent Hemorrhagic Transformation in Ischemic Stroke by P-Selectin Binding.

PubMed

Salas-Perdomo, Angélica; Miró-Mur, Francesc; Urra, Xabier; Justicia, Carles; Gallizioli, Mattia; Zhao, Yashu; Brait, Vanessa H; Laredo, Carlos; Tudela, Raúl; Hidalgo, Andrés; Chamorro, Ángel; Planas, Anna M

2018-06-14

Hemorrhagic transformation is a serious complication of ischemic stroke after recanalization therapies. This study aims to identify mechanisms underlying hemorrhagic transformation after cerebral ischemia/reperfusion. We used wild-type mice and Selplg -/- and Fut7 -/- mice defective in P-selectin binding and lymphopenic Rag2 -/- mice. We induced 30-minute or 45-minute ischemia by intraluminal occlusion of the middle cerebral artery and assessed hemorrhagic transformation at 48 hours with a hemorrhage grading score, histological means, brain hemoglobin content, or magnetic resonance imaging. We depleted platelets and adoptively transferred T cells of the different genotypes to lymphopenic mice. Interactions of T cells with platelets in blood were studied by flow cytometry and image stream technology. We show that platelet depletion increased the bleeding risk only after large infarcts. Lymphopenia predisposed to hemorrhagic transformation after severe stroke, and adoptive transfer of T cells prevented hemorrhagic transformation in lymphopenic mice. CD4 + memory T cells were the subset of T cells binding P-selectin and platelets through functional P-selectin glycoprotein ligand-1. Mice defective in P-selectin binding had a higher hemorrhagic score than wild-type mice. Adoptive transfer of T cells defective in P-selectin binding into lymphopenic mice did not prevent hemorrhagic transformation. The study identifies lymphopenia as a previously unrecognized risk factor for secondary hemorrhagic transformation in mice after severe ischemic stroke. T cells prevent hemorrhagic transformation by their capacity to bind platelets through P-selectin. The results highlight the role of T cells in bridging immunity and hemostasis in ischemic stroke. © 2018 American Heart Association, Inc.

Uncontrolled Hemorrhage Differs From Volume- or Pressure-Matched Controlled Hemorrhage in Swine

DTIC Science & Technology

2007-10-01

differences between these models, we evaluated the relationship between blood volume loss and blood pressure in controlled versus uncontrolled hemorrhage...aortotomy; (2) group P, controlled hemorrhage matched to the blood pressure profile of group U; or (3) group V, controlled hemorrhage matched to the...hemorrhage and received no fluid resuscitation. Group U resulted in a blood loss of 17.6 T 0.7 mL kgj1 and a reduction in blood pressure to 28 T 3 mmHg at

Radiation-induced schwannomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinstein, A.B.; Reichenthal, E.; Borohov, H.

1989-06-01

The histopathology and clinical course of three patients with schwannomas of the brain and high cervical cord after therapeutic irradiation for intracranial malignancy and for ringworm of the scalp are described. Earlier reports in the literature indicated that radiation of the scalp may induce tumors in the head and neck. It is therefore suggested that therapeutic irradiation in these instances was a causative factor in the genesis of these tumors.

Simulating Space Radiation-Induced Breast Tumor Incidence Using Automata.

PubMed

Heuskin, A C; Osseiran, A I; Tang, J; Costes, S V

2016-07-01

Estimating cancer risk from space radiation has been an ongoing challenge for decades primarily because most of the reported epidemiological data on radiation-induced risks are derived from studies of atomic bomb survivors who were exposed to an acute dose of gamma rays instead of chronic high-LET cosmic radiation. In this study, we introduce a formalism using cellular automata to model the long-term effects of ionizing radiation in human breast for different radiation qualities. We first validated and tuned parameters for an automata-based two-stage clonal expansion model simulating the age dependence of spontaneous breast cancer incidence in an unexposed U.S. We then tested the impact of radiation perturbation in the model by modifying parameters to reflect both targeted and nontargeted radiation effects. Targeted effects (TE) reflect the immediate impact of radiation on a cell's DNA with classic end points being gene mutations and cell death. They are well known and are directly derived from experimental data. In contrast, nontargeted effects (NTE) are persistent and affect both damaged and undamaged cells, are nonlinear with dose and are not well characterized in the literature. In this study, we introduced TE in our model and compared predictions against epidemiologic data of the atomic bomb survivor cohort. TE alone are not sufficient for inducing enough cancer. NTE independent of dose and lasting ∼100 days postirradiation need to be added to accurately predict dose dependence of breast cancer induced by gamma rays. Finally, by integrating experimental relative biological effectiveness (RBE) for TE and keeping NTE (i.e., radiation-induced genomic instability) constant with dose and LET, the model predicts that RBE for breast cancer induced by cosmic radiation would be maximum at 220 keV/μm. This approach lays the groundwork for further investigation into the impact of chronic low-dose exposure, inter-individual variation and more complex space radiation

Intravesical treatments of bladder pain syndrome/interstitial cystitis.

PubMed

Neuhaus, Jochen; Schwalenberg, Thilo

2012-12-01

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a disabling chronic condition that affects up to 7% of women in the USA. In men, BPS/IC seems to be less common, but might be underestimated because it can be confused with chronic prostatitis. The aetiology and pathophysiology of BPS/IC are not well understood. Consequently, diagnosis and treatment is challenging and most therapies used to date are off-label. These therapies include bladder instillation with dimethyl sulfoxide (DMSO) and BCG, as well as hyperbaric oxygen therapy. Overall, botulinum neurotoxin A injection, intravesical sodium hyaluronate instillation and DMSO instillation seem to be the best-performing treatments, with response rates of 79%, 76% and 75%, respectively, and can be used effectively as second-line or third-line therapies for BPS/IC. However, additional high-quality randomized controlled trials are necessary to improve the available data.

Activation of the Notch-1 signaling pathway may be involved in intracerebral hemorrhage-induced reactive astrogliosis in rats.

PubMed

Zhong, Jian-Hua; Zhou, Hua-Jun; Tang, Tao; Cui, Han-Jin; Yang, A-Li; Zhang, Qi-Mei; Zhou, Jing-Hua; Zhang, Qiang; Gong, Xun; Zhang, Zhao-Hui; Mei, Zhi-Gang

2017-10-27

OBJECTIVE Reactive astrogliosis, a key feature that is characterized by glial proliferation, has been observed in rat brains after intracerebral hemorrhage (ICH). However, the mechanisms that control reactive astrogliosis formation remain unknown. Notch-1 signaling plays a critical role in modulating reactive astrogliosis. The purpose of this paper was to establish whether Notch-1 signaling is involved in reactive astrogliosis after ICH. METHODS ICH was induced in adult male Sprague-Dawley rats via stereotactic injection of autologous blood into the right globus pallidus. N-[ N-(3,5-difluorophenacetyl)-l-alanyl]- S-phenylglycine t-butyl ester (DAPT) was injected into the lateral ventricle to block Notch-1 signaling. The rats' brains were perfused to identify proliferating cell nuclear antigen (PCNA)-positive/GFAP-positive nuclei. The expression of GFAP, Notch-1, and the activated form of Notch-1 (Notch intracellular domain [NICD]) and its ligand Jagged-1 was assessed using immunohistochemical and Western blot analyses, respectively. RESULTS Notch-1 signaling was upregulated and activated after ICH as confirmed by an increase in the expression of Notch-1 and NICD and its ligand Jagged-1. Remarkably, blockade of Notch-1 signaling with the specific inhibitor DAPT suppressed astrocytic proliferation and GFAP levels caused by ICH. In addition, DAPT improved neurological outcome after ICH. CONCLUSIONS Notch-1 signaling is a critical regulator of ICH-induced reactive astrogliosis, and its blockage may be a potential therapeutic strategy for hemorrhagic injury.

17-DMAG Diminishes Hemorrhage-Induced Small Intestine Injury by Elevating Bcl-2 Protein and Inhibiting iNOS Pathway, TNF-alpha Increase, and Caspase-3 Activation

DTIC Science & Technology

2011-06-03

reduces hemorrhage-induced injuries. In our laboratory we have shown that geldanamycin, a natural product from the bacterium Streptomyces ...product produced by Streptomyces hygroscopicus that binds with high affinity to the ATP binding pocket of HSP-90 [9, 10]. 17-DMAG is water soluble, less

Differences in Neuropeptide Y Secretion Between Intracerebral Hemorrhage and Aneurysmal Subarachnoid Hemorrhage.

PubMed

Schebesch, Karl-M; Bründl, Elisabeth; Schödel, Petra; Hochreiter, Andreas; Scheitzach, Judith; Bele, Sylvia; Brawanski, Alexander; Störr, Eva-M; Lohmeier, Anette; Proescholdt, Martin

2017-07-01

Neuropeptide Y (NPY) is one of the most potent endogenous vasoconstrictors, and its contribution to the multifactorial cascade of cerebral vasospasm due to nontraumatic subarachnoid hemorrhage (SAH) is not yet fully understood. This experimental study compared the hemorrhage-specific course of NPY secretion into cerebrospinal fluid (CSF) and into plasma between 2 groups: patients with SAH and patients with basal ganglia hemorrhage (BGH) or cerebellar hemorrhage (CH) over the first 10 days after hemorrhage. Seventy-nine patients were prospectively included: SAH patients (n=66) (historic population) and intracerebral hemorrhage patients (n=13). All patients received an external ventricular drain within 24 hours of the onset of bleeding. CSF and plasma were drawn daily from day 1 to day 10. The levels of NPY were determined by means of competitive enzyme immunoassay. The CSF samples of 29 patients (historic population) who had undergone spinal anesthesia due to orthopedic surgery served as the control group. NPY levels in CSF were significantly higher in the 2 hemorrhage groups than in the control group. However, the 2 hemorrhage groups showed significant differences in NPY levels in CSF (SAH mean, 0.842 ng/mL vs. BGH/CH mean, 0.250 ng/mL; P<0.001) as well as in the course of NPY secretion into CSF over the 10-day period. NPY levels in plasma did not differ significantly among SAH, BGH/CH, and controls. Our findings support the hypothesis that excessive release of NPY into CSF but not into plasma is specific to aneurysmal SAH in the acute period of 10 days after hemorrhage. In BGH/CH, CSF levels of NPY were also increased, but the range was much lower.

Mechanisms of Radiation-Induced Conditioned Taste Aversion Learning

DTIC Science & Technology

1986-01-01

to Walter A. Hunt. 86 4 21 144 . J Jr -.W U *’ = 7 . 7 .: M: W. ,WLW;i , .-, -’ .’P. %k T .- - ’ .: ’W ; .a --,.-" -. t .:-. , 56 RABIN AND HUNT can...8217. 7m. U RADIATION-INDUCED TASTE AVERSIONS 57 induced CTA 11021. Alternatively, when the antihistamine is [ 21 . A radiation-induced CTA can be...in rats. Pharmmad psychioactive drugs. J (omp Phvsiod Pvchld .;’: 21 -26. 1972. Biochem Behav 17: 305-311. 1982. 4. Berger. B. D.. C. D. Wise and L

A report on radiation-induced gliomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salvati, M.; Artico, M.; Caruso, R.

1991-01-15

Radiation-induced gliomas are uncommon, with only 73 cases on record to date. The disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia (ALL). Three more cases are added here, two after irradiation for ALL and one after irradiation for tinea capitis. In a review of the relevant literature, the authors stress the possibility that the ALL-glioma and the retinoblastoma-glioma links point to syndromes in their own right that may occur without radiation therapy.56 references.

Epigenetic Analysis of Heavy-ion Radiation Induced Bystander Effects in Mice

NASA Astrophysics Data System (ADS)

Zhang, Meng; Sun, Yeqing; Cui, Changna; Xue, Bei

Abstract: Radiation-induced bystander effect was defined as the induction of damage in neighboring non-hit cells by signals released from directly-irradiated cells. Recently, low dose of high LET radiation induced bystander effects in vivo have been reported more and more. It has been indicated that radiation induced bystander effect was localized not only in bystander tissues but also in distant organs. Genomic, epigenetic and proteomics plays significant roles in regulating heavy-ion radiation stress responses in mice. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were exposed head-only to 40, 200, 2000mGy dose of (12) C heavy-ion radiation, while the rest of the animal body was shielded. Directly radiation organ ear and the distant organ liver were detected on 1h, 6h, 12h and 24h after radiation, respectively. Methylation-sensitive amplification polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that heavy-ion irradiated mouse head could induce genomic DNA methylation changes significantly in both the directly radiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate was highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation. The global DNA methylation changes tended to occur in the CG sites. The results illustrated that genomic methylation changes of heavy ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of

Contribution of placenta accreta to the incidence of postpartum hemorrhage and severe postpartum hemorrhage.

PubMed

Mehrabadi, Azar; Hutcheon, Jennifer A; Liu, Shiliang; Bartholomew, Sharon; Kramer, Michael S; Liston, Robert M; Joseph, K S

2015-04-01

To quantify the contribution of placenta accreta to the rate of postpartum hemorrhage and severe postpartum hemorrhage. All hospital deliveries in Canada (excluding Quebec) for the years 2009 and 2010 (N=570,637) were included in a retrospective cohort study using data from the Canadian Institute for Health Information. Placenta accreta included placental adhesion to the uterine wall, musculature, and surrounding organs (accreta, increta, or percreta). Severe postpartum hemorrhage included postpartum hemorrhage with blood transfusion, hysterectomy, or other procedures to control bleeding (including uterine suturing and ligation or embolization of pelvic arteries). Rates, rate ratios, population-attributable fractions (ie, incidence of postpartum hemorrhage attributable to placenta accreta), and 95% confidence intervals (CIs) were estimated. Logistic regression was used to quantify associations between placenta accreta and risk factors. The incidence of placenta accreta was 14.4 (95% CI 13.4-15.4) per 10,000 deliveries (819 cases among 570,637 deliveries), whereas the incidence of placenta accreta with postpartum hemorrhage was 7.2 (95% CI 6.5-8.0) per 10,000 deliveries. Postpartum hemorrhage among women with placenta accreta was predominantly third-stage hemorrhage (41% of all cases). Although placenta accreta was strongly associated with postpartum hemorrhage (rate ratio 8.3, 95% CI 7.7-8.9), its low frequency resulted in a small population-attributable fraction (1.0%, 95% CI 0.93-1.16). However, the strong association between placenta accreta and postpartum hemorrhage with hysterectomy (rate ratio 286, 95% CI 226-361) resulted in a population-attributable fraction of 29.0% (95% CI 24.3-34.3). Placenta accreta is too infrequent to account for the recent temporal increase in postpartum hemorrhage but contributes substantially to the proportion of postpartum hemorrhage with hysterectomy.

[Psychosocial aspects of interstitial cystitis. Do biographical factors have a relevant impact on the disease course?].

PubMed

Oemler, M; Grabhorn, R; Vahlensieck, W; Jonas, D; Bickeböller, R

2006-06-01

The present study explores the influence of psychosocial adversities on the etiology and progress of interstitial cystitis (IC). A systematic survey of the childhood risk factors was carried out using a specially developed, structured interview for pain patients (MSBA-Mainzer Strukturierte Biographische Anamnese) and additionally the Brief Symptom Inventory (BSI). Essentially a descriptive evaluation was performed. Thirty IC patients who fulfilled the current diagnostic criteria participated in the study. The investigation showed higher values for relevant childhood adversities in IC patients. A poor emotional relationship with both parents, chronic diseases of the parents, and physical maltreatment were frequently reported. In the cumulative adverse childhood experience score IC patients showed higher levels than published data of healthy control groups. The contemporary social history did not show relevant psychosocial adversities. The quality of life is extremely reduced because of IC symptoms. The BSI showed high levels especially in the dimensions somatization, anxiety, and phobic anxiety. The results of this study argue for a participatory role of psychosomatic factors in the assumed multifactorial etiology of interstitial cystitis.

[A case of hemorrhagic cholecystitis associated with Churg-Strauss syndrome].

PubMed

Koizumi, Satomi; Kamisawa, Terumi; Kuruma, Sawako; Chiba, Kazuro; Tabata, Taku; Koizumi, Koichi; Kurata, Masanao; Horiguchi, Shinichiro; Hishima, Tsunekazu

2016-01-01

A woman in her 70s with Churg-Strauss syndrome presented with epigastric pain. She was being treated with steroids at the time of admission. Computed tomography showed swelling of the gallbladder, and percutaneous transhepatic cholangiography revealed bloody secretion. On duodenoscopy, bleeding was observed from the orifice of the major duodenal papilla. Emergency cholecystectomy was performed under a diagnosis of hemorrhagic cholecystitis;intraoperatively, extensive hematoma was detected in the thickened wall of the gallbladder. Subsequent histopathological examination revealed mucosal ulceration with infiltration of inflammatory cells, torn small vessels, and extensive transmural bleeding and abscess formation in the thickened wall of the gallbladder. We considered that the hemorrhagic cholecystitis was induced by either vasculitis or corticosteroid therapy. To the best of our knowledge, this is the first report of hemorrhagic cholecystitis associated with Churg-Strauss syndrome.

Antioxidant Supplementation: A Linchpin in Radiation-Induced Enteritis

PubMed Central

Anwar, Mumtaz; Ahmad, Shabeer; Akhtar, Reyhan; Mahmood, Akhtar

2017-01-01

Radiation enteritis is one of the most feared complications of abdominal and pelvic regions. Thus, radiation to abdominal or pelvic malignancies unavoidably injures the intestine. Because of rapid cell turnover, the intestine is highly sensitive to radiation injury, which is the limiting factor in the permissible dosage of irradiation. Bowel injuries such as fistulas, strictures, and chronic malabsorption are potentially life-threatening complications and have an impact on patient quality of life. The incidence of radiation enteritis is increasing because of the current trend of combined chemotherapy and radiation. The consequences of radiation damage to the intestine may result in considerable morbidity and even mortality. The observed effects of ionizing radiation are mediated mainly by oxygen-free radicals that are generated by its action on water and are involved in several steps of signal transduction cascade, leading to apoptosis. The oxyradicals also induce DNA strand breaks and protein oxidation. An important line of defense against free radical damage is the presence of antioxidants. Therefore, administration of antioxidants may ameliorate the radiation-induced damage to the intestine. PMID:28532242

Clinical Characteristic Picture and Impact of Symptoms on Quality of Life of Interstitial Cystitis Patients in Taiwan.

PubMed

Lee, Ming-Huei; Lin, Alex Tong-Long; Kuo, Hann-Chorng; Chen, Yung-Fu

2014-01-01

No clinical characteristic picture and impact of symptoms on quality of life (QOL) of interstitial cystitis (IC) patients in Taiwan had been reported. This paper is intended to provide preliminary descriptive results of IC research in Taiwan. A total of 319 patients, based on National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK) criteria, were enrolled in the study from February 2004 through March 2006. Evaluation data included baseline demographic information, patient and family medical history, dietary effects, pregnancy data, sexual relationships with symptoms, and impact of symptoms on quality of life. The main responsibility of the hospitals discussed was patient care and data collection. Taichung Hospital presents the results. The Interstitial Cystitis Database (ICDB) patients were predominantly female, that is, 86% of the total, with an average enrollment age of 46. The analysis of various symptoms indicates the following distribution: (i) 94% frequency; (ii) 80% pain; (iii) 53% nocturia; (iv) 43% urgency; and (v) 10% associated incontinence. Approximately 83% reported pain over the bladder while in full stage, and 74% reported pain relief after voiding. The predominant characteristic of pain was full sensation (54%) with the predominant position on low abdominal area (52%). Moreover, 80% reported sleeping disturbance due to disease, and 66% reported difficulty in performing daily work. Interstitial cystitis patients in Taiwan have lower economic status but lower impact on QOL than Western patients. However, the sexual-related pain and sleeping disorder were higher than previously thought and deserve our attention. Accordingly, this research provides a foundation for further investigations of baseline associations and longitudinal trends. © 2013 Wiley Publishing Asia Pty Ltd.

Therapeutic efficacy of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome.

PubMed

Kajiwara, Mitsuru; Inoue, Shougo; Kobayashi, Kanao; Ohara, Shinya; Teishima, Jun; Matsubara, Akio

2014-04-01

Narrow band imaging cystoscopy can increase the visualization and detection of Hunner's lesions. A single-center, prospective clinical trial was carried out aiming to show the effectiveness of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome. A total of 23 patients (19 women and 4 men) diagnosed as having ulcer-type interstitial cystitis/painful bladder syndrome were included. All typical Hunner's lesions and suspected areas identified by narrow band imaging were electrocoagulated endoscopically after the biopsy of those lesions. Therapeutic efficacy was assessed prospectively by using visual analog scale score of pain, O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score. The mean follow-up period was 22 months. All patients (100%) experienced a substantial improvement in pain. The average visual analog scale pain scores significantly decreased from 7.3 preoperatively to 1.2 1 month postoperatively. A total of 21 patients (91.3%) who reported improvement had at least a 50% reduction in bladder pain, and five reported complete resolution. Daytime frequency was significantly decreased postoperatively. O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score were significantly decreased postoperatively. However, during the follow-up period, a total of six patients had recurrence, and repeat narrow band imaging-assisted transurethral electrocoagulation of the recurrent lesions was carried out for five of the six patients, with good response in relieving bladder pain. Our results showed that narrow band imaging-assisted transurethral electrocoagulation could be a valuable therapeutic alternative in patients with ulcer-type interstitial cystitis/painful bladder syndrome, with good efficacy and reduction of recurrence rate. © 2014 The Japanese Urological Association.

Novel Radiomitigator for Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

2016-01-01

Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

[Marburg and Ebola hemorrhagic fevers--pathogens, epidemiology and therapy].

PubMed

Stock, Ingo

2014-09-01

Marburg and Ebola hemorrhagic fevers are severe, systemic viral diseases affecting humans and non-human primates. They are characterized by multiple symptoms such as hemorrhages, fever, headache, muscle and abdominal pain, chills, sore throat, nausea, vomiting and diarrhea. Elevated liver-associated enzyme levels and coagulopathy are also associated with these diseases. Marburg and Ebola hemorrhagic fevers are caused by (Lake victoria) Marburg virus and different species of Ebola viruses, respectively. They are enveloped, single-stranded RNA viruses and belong to the family of filoviridae. Case fatality rates of filovirus disease outbreaks are among the highest reported for any human pathogen, ranging from 25 to 90% or more. Outbreaks of Marburg and Ebola hemorrhagic fever occur in certain regions of equatorial Africa at irregular intervals. Since 2000, the number of outbreaks has increased. In 2014, the biggest outbreak of a filovirus-induced hemorrhagic fever that has been documented so far occurred from March to July 2014 in Guinea, Sierra Leone, Liberia and Nigeria. The outbreak was caused by a new variant of Zaire Ebola-Virus, affected more than 2600 people (stated 20 August) and was associated with case-fatality rates of up to 67% (Guinea). Treatment of Marburg and Ebola hemorrhagic fevers is symptomatic and supportive, licensed antiviral agents are currently not available. Recently, BCX4430, a promising synthetic adenosine analogue with high in vitro and in vivo activity against filoviruses and other RNA viruses, has been described. BCX4430 inhibits viral RNA polymerase activity and protects cynomolgus macaques from Marburg virus infection when administered as late as 48 hours after infection. Nucleic acid-based products, recombinant vaccines and antibodies appear to be less suitable for the treatment of Marburg and Ebola hemorrhagic fevers.

Intracerebral hemorrhage (image)

MedlinePlus

Intracerebral hemorrhage may be caused by trauma (brain injury) or abnormalities of the blood vessels (aneurysm or angioma), but it is most commonly associated with high blood pressure (hypertensive intracerebral hemorrhage).

Acute radiation impacts contractility of guinea-pig bladder strips affecting mucosal-detrusor interactions.

PubMed

McDonnell, Bronagh M; Buchanan, Paul J; Prise, Kevin M; McCloskey, Karen D

2018-01-01

Radiation-induced bladder toxicity is associated with radiation therapy for pelvic malignancies, arising from unavoidable irradiation of neighbouring normal bladder tissue. This study aimed to investigate the acute impact of ionizing radiation on the contractility of bladder strips and identify the radiation-sensitivity of the mucosa vs the detrusor. Guinea-pig bladder strips (intact or mucosa-free) received ex vivo sham or 20Gy irradiation and were studied with in vitro myography, electrical field stimulation and Ca2+-fluorescence imaging. Frequency-dependent, neurogenic contractions in intact strips were reduced by irradiation across the force-frequency graph. The radiation-difference persisted in atropine (1μM); subsequent addition of PPADs (100μM) blocked the radiation effect at higher stimulation frequencies and decreased the force-frequency plot. Conversely, neurogenic contractions in mucosa-free strips were radiation-insensitive. Radiation did not affect agonist-evoked contractions (1μM carbachol, 5mM ATP) in intact or mucosa-free strips. Interestingly, agonist-evoked contractions were larger in irradiated mucosa-free strips vs irradiated intact strips suggesting that radiation may have unmasked an inhibitory mucosal element. Spontaneous activity was larger in control intact vs mucosa-free preparations; this difference was absent in irradiated strips. Spontaneous Ca2+-transients in smooth muscle cells within tissue preparations were reduced by radiation. Radiation affected neurogenic and agonist-evoked bladder contractions and also reduced Ca2+-signalling events in smooth muscle cells when the mucosal layer was present. Radiation eliminated a positive modulatory effect on spontaneous activity by the mucosa layer. Overall, the findings suggest that radiation impairs contractility via mucosal regulatory mechanisms independent of the development of radiation cystitis.

N-acetylcysteine reduces the renal oxidative stress and apoptosis induced by hemorrhagic shock.

PubMed

Moreira, Miriam Aparecida; Irigoyen, Maria Claudia; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Koike, Marcia Kiyomi; Montero, Edna Frasson de Souza; Martins, José Luiz

2016-06-01

Renal ischemia/reperfusion injury induced by hemorrhagic shock (HS) and subsequent fluid resuscitation is a common cause of acute renal failure. The objective of this study was to evaluate the effect of combining N-acetylcysteine (NAC) with fluid resuscitation on renal injury in rats that underwent HS. Two groups of male Wistar rats were induced to controlled HS at 35 mm Hg mean arterial pressure for 60 min. After this period, the HS and fluid resuscitation (HS/R) group was resuscitated with lactate containing 50% of the blood that was withdrawn. The HS/R + NAC group was resuscitated with Ringer's lactate combined with 150 mg/kg of NAC and blood. The sham group animals were catheterized but were not subjected to shock. All animals were kept under anesthesia and euthanized after 120 min of fluid resuscitation or observation. Animals treated with NAC presented attenuation of histologic lesions, reduced oxidative stress, and apoptosis markers when compared with animals from the HS/R group. The serum creatinine was similar in all the groups. NAC is a promising drug for combining with fluid resuscitation to attenuate the kidney injury associated with HS. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural Injuries Induced by Hydrostatic Pressure Associated With Mass Effect after Intracerebral Hemorrhage.

PubMed

Guo, Tingwang; Ren, Peng; Li, Xiaofei; Luo, Tiantian; Gong, Yuhua; Hao, Shilei; Wang, Bochu

2018-06-15

Mass effect induced by growing hematoma is one of the mechanisms by which intracerebral hemorrhage (ICH) may result in brain injuries. Our goal was to investigate the damage mechanism of hydrostatic pressure associated with mass effect and the cooperative effect of hydrostatic pressure plus hemoglobin on neural injuries. Loading hydrostatic pressure on neurons and injecting agarose gel in the right striatum of rats was performed to establish the in vitro and vivo ICH models, respectively. The elevated hydrostatic pressure associated with ICH suppressed neurons and neural tissues viability, and disturbed the axons and dendrites in vitro and vivo. Moreover, hydrostatic pressure could upregulate the expression of cleaved-caspase-3 and BAX, and downregulate Bcl-2 and Bcl-xL. Meanwhile, the toxicity of hemoglobin would be enhanced when conducted with hydrostatic pressure together. Furthermore, the exclusive hydrostatic pressure could upregulate the Piezo-2 expression, which reached a plateau at 8 h after ICH. And hemoglobin increased Piezo-2 expression significantly in vivo, and that was also promoted significantly by the elevated volume of Gel in the cooperative groups. Results indicated that hydrostatic pressure induced by mass effect not only gave rise to brain injuries directly, but also increased the toxicity of hemoglobin in the progress of secondary brain injury after ICH.

BK Virus and Its Role in Hematopoietic Stem Cell Transplantation: Evolution of a Pathogen.

PubMed

delaCruz, Jennifer; Pursell, Kenneth

2014-08-01

We reviewed the literature regarding disease induced by BK virus (BKV) in the hematopoietic stem cell transplant (HSCT) population, particularly hemorrhagic cystitis (HC) and nephritis. The association between BKV and HC has been reported over the past four decades. BKV has been clinically implicated and widely accepted as an etiologic agent of HC and nephritis in HSCT and nephropathy in renal transplant patients. We discuss the potential benefit of early initiation of therapy in patients who fail supportive care alone as well as the different treatment strategies for HC induced by BKV. Treatments that have been used such as cidofovir and leflunomide are accompanied by risks, and the benefits are not as concrete as with other viral illness in the HSCT population.

Methylglyoxal-bis(guanylhydrazone), a polyamine analogue, sensitized γ-radiation-induced cell death in HL-60 leukemia cells Sensitizing effect of MGBG on γ-radiation-induced cell death.

PubMed

Kim, Jin Sik; Lee, Jin; Chung, Hai Won; Choi, Han; Paik, Sang Gi; Kim, In Gyu

2006-09-01

Methylglyoxal-bis(guanylhydrazone) (MGBG), a polyamine analogue, has been known to inhibit the biosynthesis of polyamines, which are important in cell proliferation. We showed that MGBG treatment significantly affected γ-radiation-induced cell cycle transition (G(1)/G(0)→S→G(2)/M) and thus γ-radiation-induced cell death. As determined by micronuclei and comet assay, we showed that it sensitized the cytotoxic effect induced by γ-radiation. One of the reasons is that polyamine depletion by MGBG treatment did not effectively protect against the chemical (OH) or physical damage to DNA caused by γ-radiation. Through in vitro experiment, we confirmed that DNA strand breaks induced by γ-radiation was prevented more effectively in the presence of polyamines (spermine and spermidine) than in the absence of polyamines. MGBG also blocks the cell cycle transition caused by γ-radiation (G(2) arrest), which helps protect cells by allowing time for DNA repair before entry into mitosis or apoptosis, via the down regulation of cyclin D1, which mediates the transition from G(1) to S phase of cell cycle, and ataxia telangiectasia mutated, which is involved in the DNA sensing, repair and cell cycle check point. Therefore, the abrogation of G(2) arrest sensitizes cells to the effect of γ-radiation. As a result, γ-radiation-induced cell death increased by about 2.5-3.0-fold in cells treated with MGBG. However, exogenous spermidine supplement partially relieved this γ-radiation-induced cytotoxicity and cell death. These findings suggest a potentially therapeutic strategy for increasing the cytotoxic efficacy of γ-radiation.

Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.

Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100%more » mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.« less

Evidence for radiation-induced disseminated intravascular coagulation as a major cause of radiation-induced death in ferrets.

PubMed

Krigsfeld, Gabriel S; Savage, Alexandria R; Billings, Paul C; Lin, Liyong; Kennedy, Ann R

2014-03-15

The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. The lethal dose of radiation to 50% of the population (LD50) of the ferrets was established at ∼ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

[The occupational radiation-induced cataract in five industrial radiographers].

PubMed

Benzarti Mezni, A; Loukil, I; Hriz, N; Kallel, K; Mlaiki, N; Ben Jemaâ, A

2012-04-01

The industrial uses of ionizing radiation in Tunisia are expanding, especially in industry and most particularly in the nondestructive testing of welds. Thus workers operating in the non-destructive testing of welds may develop a radiation-induced cataract varying in time to onset depending on the dose. To describe the characteristics of the radiation-induced cataract in patients exposed to ionizing radiation, determine the risk factors of radiation-induced cataracts. This was an anamnestic, clinical, and environmental study of five cases of radiation-induced cataract in workers employed in non-destructive testing of welds. This series of five cases had a mean age of 30.2 years and 5.53 years of work experience, ranging from 14 months to 15 years. All the patients were male and industrial radiographers specialized in nondestructive testing of welds. The average duration of exposure to ionizing radiation was 5.53 years. None of the patients had worn protective gear such as eye goggles. The ophthalmic check-up for the five special industrial radiographers showed punctuate opacities in three cases, punctiform opacities in one eye in one case, and phacosclerosis with bilateral lens multiple crystalline stromal opacities in a case of micro-lens opacities in both eyes with opalescence of both eyes in one case. These cataracts had been declared as occupational diseases. The value of a specialized ophthalmologic surveillance among these workers and the early diagnosis of lens opacities must be emphasized. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Mechanisms for Induction of Pulmonary Capillary Hemorrhage by Diagnostic Ultrasound: Review and Consideration of Acoustical Radiation Surface Pressure.

PubMed

Miller, Douglas L

2016-12-01

Diagnostic ultrasound can induce pulmonary capillary hemorrhage (PCH) in rats and other mammals. This phenomenon represents the only clearly demonstrated biological effect of (non-contrast enhanced) diagnostic ultrasound and thus presents a uniquely important safety issue. However, the physical mechanism responsible for PCH remains uncertain more than 25 y after its discovery. Experimental research has indicated that neither heating nor acoustic cavitation, the predominant mechanisms for bioeffects of ultrasound, is responsible for PCH. Furthermore, proposed theoretical mechanisms based on gas-body activation, on alveolar resonance and on impulsive generation of liquid droplets all appear unlikely to be responsible for PCH, owing to unrealistic model assumptions. Here, a simple model based on the acoustical radiation surface pressure (ARSP) at a tissue-air interface is hypothesized as the mechanism for PCH. The ARSP model seems to explain some features of PCH, including the approximate frequency independence of PCH thresholds and the dependence of thresholds on biological factors. However, ARSP evaluated for experimental threshold conditions appear to be too weak to fully account for stress failure of pulmonary capillaries, gauging by known stresses for injurious physiologic conditions. Furthermore, consideration of bulk properties of lung tissue suggests substantial transmission of ultrasound through the pleura, with reduced ARSP and potential involvement of additional mechanisms within the pulmonary interior. Although these recent findings advance our knowledge, only a full understanding of PCH mechanisms will allow development of science-based safety assurance for pulmonary ultrasound. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Nrf2 activator ameliorates hemorrhagic transformation in focal cerebral ischemia under warfarin anticoagulation.

PubMed

Imai, Takahiko; Takagi, Toshinori; Kitashoji, Akira; Yamauchi, Keita; Shimazawa, Masamitsu; Hara, Hideaki

2016-05-01

Oxidative stress has been reported to be a main cause of neuronal cell death in ischemia reperfusion injury (IRI). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important factor involved in anti-oxidative responses. We previously reported that bardoxolone methyl (BARD), an Nrf2 activator, prevented damage induced by IRI. In this study, we investigated the effect of BARD on hemorrhagic transformation in the context of blood brain barrier (BBB) protection. Mice received pre-treatment with warfarin (4.0 mg/kg, p.o.). IRI was subsequently induced 18 h after the warfarin administration by transient middle cerebral artery occlusion (MCAO) for 6 h. BARD (0.06, 0.2, 0.6 or 2.0 mg/kg) or saline was injected intravenously immediately after reperfusion. The infarct volume, neurological score, intracranial hemorrhage volume, and BBB permeability were evaluated 24 h after MCAO. The survival rate and behavioral functional recovery were evaluated for 7 days following IRI. Furthermore, the effects of BARD on BBB components were investigated by western blotting and immunostaining analysis. BARD suppressed warfarin-mediated increases in the intracranial hemorrhage volume without affecting the infarct volume. BBB permeability was also suppressed by administration of BARD. Western blotting showed that BARD increased expression of BBB components such as endothelial cells, pericytes, and tight junction proteins. Furthermore, immunostaining showed that BARD induced localization of Nrf2 to endothelial cells and pericytes. BARD suppressed the exacerbation hemorrhage caused by warfarin pretreatment and ameliorated BBB disruption by protecting endothelial cells, pericytes, and tight junction protein expressions. These results indicate that Nrf2 activators may be an effective therapy against hemorrhagic transformation caused by anticoagulant drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Viral Hemorrhagic Fevers

MedlinePlus

... Controls Cancel Submit Search the CDC Viral Hemorrhagic Fevers (VHFs) Note: Javascript is disabled or is not ... visit this page: About CDC.gov . Viral Hemorrhagic Fevers (VHFs) Virus Families Arenaviruses Old World/New World ...

Alexithymia and anesthetic bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Chiu, Chui-De; Lee, Ming-Huei; Chen, Wei-Chih; Ho, Hoi Lam; Wu, Huei-Ching

2017-09-01

In contrast to the inconsistent results of organic causes, it has been found that psychological risk factors are reliably related to functional somatic syndromes (FSSs), including interstitial cystitis/bladder pain syndrome (IC/BPS). Compared to patients with acute cystitis, a subgroup of IC/BPS patients with a history of childhood relational trauma reported intensified unregulated affective states (i.e., anxiety and depression) and trauma-related psychopathology (i.e., dissociation). Nevertheless, it remains unknown whether psychosocial risk factors can be separated from bladder-centric factors. This study aimed to verify whether psychosocial factors such as alexithymia, which is a key psychological factor of FSSs, are less likely to be linked to a low bladder capacity in patients with IC/BPS. Ninety-four female IC/BPS patients were recruited from the outpatient departments of urology, obstetrics, and gynecology. Anxiety, depression, dissociation, childhood relational trauma, and alexithymia were assessed using standardized scales, and anesthetic bladder capacity was examined by cystoscopic hydrodistention. Positive correlations were found between anesthetic bladder capacity and the psychosocial variables, including alexithymia. An increased bladder capacity was associated with anxiety, dissociation, and childhood relational trauma, and a combination of high cognitive and low affective alexithymia mediated the correlations between bladder capacity and the psychosocial variables. Psychosocial variables that are associated with an aversive childhood relational environment and affect dysregulation may constitute a pathogenic trajectory that differs from bladder-centric defects such as a lower bladder capacity. The findings of this study support the notion that IC/BPS in some patients may be due to an FSS. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiation-induced lichen sclerosus of the vulva : First report in the medical literature.

PubMed

Edwards, Lisa R; Privette, Emily D; Patterson, James W; Tchernev, Georgi; Chokoeva, Anastasiya Atanasova; Wollina, Uwe; Lotti, Torello; Wilson, Barbara B

2017-03-01

A 67-year-old woman presented with a firm plaque in the perineal region, 16 months after diagnosis of a high-grade basaloid squamous cell carcinoma of the vagina and treatment by external beam radiation therapy and vaginal cuff brachytherapy. The differential diagnosis included radiation-induced morphea, radiation dermatitis, or, possibly, radiation-induced lichen sclerosus. Biopsy findings, including special staining, confirmed the diagnosis of radiation-induced lichen sclerosus. To our knowledge, this is the first report of radiation-induced lichen sclerosus of the vulvar region.

Real-space analysis of radiation-induced specific changes with independent component analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borek, Dominika; Bromberg, Raquel; Hattne, Johan

A method of analysis is presented that allows for the separation of specific radiation-induced changes into distinct components in real space. The method relies on independent component analysis (ICA) and can be effectively applied to electron density maps and other types of maps, provided that they can be represented as sets of numbers on a grid. Here, for glucose isomerase crystals, ICA was used in a proof-of-concept analysis to separate temperature-dependent and temperature-independent components of specific radiation-induced changes for data sets acquired from multiple crystals across multiple temperatures. ICA identified two components, with the temperature-independent component being responsible for themore » majority of specific radiation-induced changes at temperatures below 130 K. The patterns of specific temperature-independent radiation-induced changes suggest a contribution from the tunnelling of electron holes as a possible explanation. In the second case, where a group of 22 data sets was collected on a single thaumatin crystal, ICA was used in another type of analysis to separate specific radiation-induced effects happening on different exposure-level scales. Here, ICA identified two components of specific radiation-induced changes that likely result from radiation-induced chemical reactions progressing with different rates at different locations in the structure. In addition, ICA unexpectedly identified the radiation-damage state corresponding to reduced disulfide bridges rather than the zero-dose extrapolated state as the highest contrast structure. The application of ICA to the analysis of specific radiation-induced changes in real space and the data pre-processing for ICA that relies on singular value decomposition, which was used previously in data space to validate a two-component physical model of X-ray radiation-induced changes, are discussed in detail. This work lays a foundation for a better understanding of protein-specific radiation

Radiation enteritis and radiation scoliosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shah, M.; Eng, K.; Engler, G.L.

1980-09-01

Any patient with radiation scoliosis should be suspected of having a visceral lesion as well. Chronic radiation enteritis may be manifested by intestinal obstruction, fistulas, perforation, and hemorrhage. Intestinal obstruction is the most common complication, and must be differentiated from postoperative cast or from spinal-traction syndrome. Obstruction that does not respond promptly to conservative measures must be treated surgically. Irradiated bowel is ischemic, and necrosis with spontaneous perforation can only be avoided with early diagnosis and surgical intervention.

Modeling radiation induced segregation in Iron-Chromium alloys

DOE PAGES

Senninger, Oriane; Soisson, Frederic; Martinez Saez, Enrique; ...

2015-10-16

Radiation induced segregation in ferritic Fe-Cr alloys is studied by Atomistic Kinetic Monte Carlo simulations that include di usion of chemical species by vacancy and interstitial migration, recombination, and elimination at sinks. The parameters of the di usion model are tted to DFT calculations. Transport coe cients that control the coupling between di usion of defects and chemical species are measured in dilute and concentrated alloys. Radiation induced segregation near grain boundaries is directly simulated with this model. We nd that the di usion of vacancies toward sinks leads to a Cr depletion. Meanwhile, the di usion of self-interstitials causesmore » an enrichment of Cr in the vicinity of sinks. For concentrations lower than 15%Cr, we predict that sinks will be enriched with Cr for temperatures lower than a threshold. When the temperature is above this threshold value, the sinks will be depleted in Cr. These results are compared to previous experimental studies and models. Cases of radiation induced precipitation and radiation accelerated precipitation are considered.« less

Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage.

PubMed

Martin, Nicole M; Abu Dayyeh, Barham K; Chung, Raymond T

2008-07-28

Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re-growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.

Oxygen therapy reduces secondary hemorrhage after thrombolysis in thromboembolic cerebral ischemia.

PubMed

Sun, Li; Zhou, Wei; Mueller, Christian; Sommer, Clemens; Heiland, Sabine; Bauer, Alexander T; Marti, Hugo H; Veltkamp, Roland

2010-09-01

Hyperbaric oxygen (HBO) and normobaric hyperoxia (NBO) protect the brain parenchyma and the cerebral microcirculation against ischemia. We studied their effect on secondary hemorrhage after thrombolysis in two thromboembolic middle cerebral artery occlusion (MCAO) (tMCAO) models. Beginning 60 minutes after tMCAO with either thrombin-induced thromboemboli (TT) or calcium-induced thromboemboli (CT), spontaneously hypertensive rats (n=96) breathed either air, 100% O(2) (NBO), or 100% O(2) at 3 bar (HBO) for 1 hour. Immediately thereafter, recombinant tissue plasminogen activator (rt-PA, 9 mg/kg) was injected. Although significant reperfusion was observed after thrombolysis in TT-tMCAO, vascular occlusion persisted in CT-tMCAO. In TT-tMCAO, NBO and HBO significantly reduced diffusion-weighted imaging-magnetic resonance imaging (MRI) lesion volume and postischemic blood-brain barrier (BBB) permeability on postcontrast T1-weighted images. NBO and, significantly more potently, HBO reduced macroscopic hemorrhage on T2* MRI and on corresponding postmortem cryosections. Oxygen therapy lowered hemoglobin content and attenuated activation of matrix metalloproteinases in the ischemic hemisphere. In contrast, NBO and HBO failed to reduce infarct size in CT but both decreased BBB damage and microscopic hemorrhagic transformation. Only HBO reduced hemoglobin extravasation in the ischemic hemisphere. In conclusion, NBO and HBO decrease infarct size after thromboembolic ischemia only if recanalization is successful. As NBO and HBO also reduce postthrombolytic intracerebral hemorrhage, combining the two with thrombolysis seems promising.

Blood autotransfusion outcomes compared with Ringer lactate infusion in dogs with hemorrhagic shock induced by controlled bleeding.

PubMed

Safaei, Mansour; Takami, Hassan Mousavi

2011-10-01

The most common cause of shock in the surgical or trauma patient is hemorrhage. Crystalloid solutions and blood transfusion are the mainstays of treatment of hemorrhagic shock. Considering the disadvantages of allogeneic blood transfusion, such as risk of transmission of infectious diseases, and access and maintenance limitations, treatment of shock with autologous blood seems to be a decent solution. Autologous blood accumulated in body cavities in traumatic bleeding (such hemothorax), and bloodshed in operation field during open heart or vascular surgeries, and similar situations, can be utilized again. In this study, autotransfusion effects compared with crystalloid fluid in the treatment of hemorrhagic shock was investigated. After induction of hemorrhagic shock in dogs by Wiggers type controlled bleeding, treating them in a group with autologous blood and another group with Ringer lactate were performed, and the results of treatment were studied. There was no mortality in both treatment approaches. Immediately after treatment, crystalloid positive effects such as renormalized vital signs and appropriate consciousness were more noticeable than autotransfusion, while twenty-four hours after, the desired effects of autologous blood were more pronounced like decreased metabolic acidosis and improvement of diuresis. Crystalloid during the first hours after treatment of hemorrhagic shock may be better than autologous blood as preferred treatment, while autotransfusion showed its benefits some hours after. This finding can be used to develop better strategies for treatment of hemorrhagic shock.

Moyamoya disease associated with asymptomatic mosaic Turner syndrome: a rare cause of hemorrhagic stroke.

PubMed

Manjila, Sunil; Miller, Benjamin R; Rao-Frisch, Anitha; Otvos, Balint; Mitchell, Anna; Bambakidis, Nicholas C; De Georgia, Michael A

2014-01-01

Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial carotid arteries that can present clinically with either ischemic or hemorrhagic disease. Moyamoya syndrome, indistinguishable from moyamoya disease at presentation, is associated with multiple clinical conditions including neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down syndrome, and Turner syndrome. We present the first reported case of an adult patient with previously unrecognized mosaic Turner syndrome with acute subarachnoid and intracerebral hemorrhage as the initial manifestation of moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid hemorrhage with associated flame-shaped intracerebral hemorrhage in the left frontal lobe. Physical examination revealed short stature, pectus excavatum, small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography showed features consistent with bilateral moyamoya disease, aberrant intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our case report is the first documented presentation of adult moyamoya syndrome with subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic Turner syndrome. It illustrates the utility of genetic evaluation in patients with cerebrovascular disease and dysmorphism. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction

PubMed Central

Rajandram, Retnagowri; Ong, Teng Aik; Razack, Azad H. A.; MacIver, Bryce; Zeidel, Mark

2016-01-01

Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg−1·day−1 ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis. PMID:26911853

Countermeasures for space radiation induced adverse biologic effects

NASA Astrophysics Data System (ADS)

Kennedy, A. R.; Wan, X. S.

2011-11-01

Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction

PubMed Central

Acharya, Munjal M.; Baulch, Janet E.; Lusardi, Theresa A.; Allen, Barrett. D.; Chmielewski, Nicole N.; Baddour, Al Anoud D.; Limoli, Charles L.; Boison, Detlev

2016-01-01

Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal-dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered

Radiation-induced cerebrovascular disease in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, T.L.; Bresnan, M.J.

1976-06-01

Radiation-induced internal carotid artery occlusion has not been well recognized previously as a cause of childhood cerebrovascular disease. A child who had received radiation as a neonate for a hemangioma involving the left orbit at the age of 6 years experienced a recurrent right-sided paresis, vascular headaches, and speech difficulties. Angiography showed a hypoplastic left carotid artery with occlusion of both the anterior and middle cerebral arteries. Collateral vessels bypassed the occluded-stenotic segments. Review of the literature showed two additional cases of large vessel occlusion in childhood associated with anastomatic telangiectatic vessel development following early radiation therapy of facial hemangioma.

[Treatment of radiation-induced iliofemoral arterial complications with groin radionecrosis].

PubMed

Fichelle, J-M

2017-12-01

Long-term iliofemoral complications induced by radiation include vascular (arterial and venous) lesions, nervous lesions and soft tissue loss that can be cutaneous and subcutaneous and potentially lead to radionecrosis with vessel exposure. We present five cases of groin radionecrosis. There were three men and two women (age 30-73 years). Radiotherapy had been delivered 15 years earlier in three cases, and 2 years earlier in two cases. Symptoms were intermittent claudication (n=1), critical ischemia (n=1), and septic hemorrhage (n=1). Two patients had no vascular symptoms. Four patients underwent scheduled surgery after complete cardiac and cardiovascular evaluation with duplex-Doppler, CT scan and/or intra-arterial angiography. One woman underwent emergency surgery after septic hemorrhage of a previous in situ femoral revascularization fashioned 2 months earlier. Revascularization was achieved with trans-iliac (n=3), trans-muscular (n=1, and in situ (n=1) iliofemoral bypass. A retroperitoneal approach with section of large muscles was used. In three cases, a trans-iliac route was used by perforating the iliac wing with a 8-mm PTFE graft. Proximal anastomosis was done on the abdominal aorta (n=1) and the homolateral common iliac artery (n=2). Distal anastomosis was done on the distal profunda artery and popliteal artery (n=1) and on the distal femoral superficial artery (n=2). In two cases, an iliofemoral bypass was done with a 7-mm PTFE vascular graft. The proximal anastomosis was done on the proximal external iliac artery and the distal anastomosis on the proximal superficial femoral artery. A plastic procedure was performed in four cases. Three patients had a homolateral (n=1) or controlateral (n=2) rectus abdominis flap. In one case, plastic coverage was done with an antebrachial flap (Chinese flap), which has been released at 6 weeks. One patient had post-radiotherapy iliofemoral vascular disease, but there was no vascular exposure, and no plastic

Encapsulated Bifidobacteria reduced bacterial translocation in rats following hemorrhagic shock and resuscitation.

PubMed

Ruan, Xiangcai; Shi, Hanping; Xia, Gengfeng; Xiao, Ying; Dong, Jiaxi; Ming, Feiping; Wang, Shenming

2007-10-01

The aim of the present study was to determine the effects of peroral encapsulated Bifidobacteria on intestinal microflora, bacterial translocation (BT), plasma endotoxin, and ileal villi injury in a rat model of hemorrhagic shock. Sprague-Dawley rats were fed daily with three different diet supplements: phosphate buffered saline, Bifidobacteria (10(9) colon-forming units/day), or microencapsulated Bifidobacteria (10(9) colony-forming units/day). After 7 d of treatment, rats were anesthetized for hemorrhagic or sham shock. Then a laparotomy was performed to determine microbiological analysis of cecal content, BT to mesenteric lymph nodes, plasma endotoxin, and terminal ileal villous damage. In the hemorrhagic-shock model, rats pretreated with Bifidobacteria showed decreases in total aerobes in cecum, magnitude of total aerobes to BT, levels of plasma endotoxin, and percentage of ileal villous damage when compared with rats treated with phosphate buffered saline. Encapsulated Bifidobacteria induced greater decreases than intact Bifidobacteria in this model, except for no difference in percentage of ileal villous damage between the two groups. In addition, the incidence of BT was decreased in hemorrhagic rats pretreated with Bifidobacteria compared with control. However, the magnitude of total anaerobes and Bifidobacteria BT were similar among hemorrhagic-shocked rats receiving three different supplements. Bifidobacteria can be useful in preventing BT in hemorrhagic-shocked rats, and encapsulated Bifidobacteria can augment this effect further. Peroral administration of Bifidobacteria may be a favorable strategy to prevent sepsis and multiple organ dysfunction syndrome in hemorrhagic shock.

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer

PubMed Central

King, Suzanne N.; Dunlap, Neal E.; Tennant, Paul A.; Pitts, Teresa

2017-01-01

Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia is comprised of a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration. PMID:27098922

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

PubMed

King, Suzanne N; Dunlap, Neal E; Tennant, Paul A; Pitts, Teresa

2016-06-01

Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration.

[Effects of granulocyte-macrophage colony stimulating factor on nuclear factor-KappaB activation in multiple organs of hemorrhage-induced acute lung injury in mice].

PubMed

Wang, Qian; Song, Yong; Shi, Yi

2007-05-01

To investigate the effects of nuclear factor-KappaB (NF-KappaB) activation in multiple organs of hemorrhage-induced acute lung injury (ALI) by the specific granulocyte-macrophage colony stimulating factor (GM-CSF)-neutralizing antibody (22E9) and dexamethasone (DEX) in mice. Twenty male C57BL/6 mice were used to reproduce a model of hemorrhagic shock by cardiac puncture. Before cardiac puncture, mice in different groups were transnasally administered with phosphate buffered solution (PBS, PCG group), PBS plus 1 microg 22E9 (HS1 group), PBS plus 10 microg 22E9 (HS10 group) and PBS plus 20 microg DEX (DEX group), respectively. In negative control group (NCG group) received cardiac puncture without shock followed by transnasal administration with PBS without shock. Lungs, hearts, livers and kidneys tissues of mice were harvested at 4 hours after hemorrhagic shock. The activities of NF-KappaB in different organs was determined by electrophoretic mobility shift assay (EMSA). The tumor necrosis factor-alpha (TNF-alpha) in lung and heart were determined by enzyme-linked immunosorbent assay (ELISA). 22E9 in both low or high doses could significantly inhibit NF-KappaB activities in lung, heart and liver, and elevated NF-KappaB activity in kidney compared with those of PCG group (all P<0.05). The effect of 22E9 was much better in HS1 group than in HS10 group (all P<0.05). DEX significantly strengthened NF-KappaB activity in kidney (P<0.05) and didn't significantly inhibit NF-KappaB activities in heart and liver compared with those of PCG group. 22E9 significantly inhibited TNF-alpha in lung and heart, while DEX significantly inhibited TNF-alpha in heart (all P<0.05). 22E9 can inhibit the NF-KappaB activation and inflammatory reaction in multiple organs after hemorrhage-induced ALI and reduce injury in multiple organs, while DEX has no significant effect.

IL-6-Mediated Activation of Stat3α Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

PubMed Central

Moran, Ana; Thacker, Stephen A.; Arikan, Ayse Akcan; Mastrangelo, Mary-Ann A.; Wu, Yong; Yu, Bi; Tweardy, David J.

2011-01-01

Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3β, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome. PMID:21738667

Blood autotransfusion outcomes compared with Ringer lactate infusion in dogs with hemorrhagic shock induced by controlled bleeding*

PubMed Central

Safaei, Mansour; Takami, Hassan Mousavi

2011-01-01

BACKGROUND: The most common cause of shock in the surgical or trauma patient is hemorrhage. Crystalloid solutions and blood transfusion are the mainstays of treatment of hemorrhagic shock. Considering the disadvantages of allogeneic blood transfusion, such as risk of transmission of infectious diseases, and access and maintenance limitations, treatment of shock with autologous blood seems to be a decent solution. Autologous blood accumulated in body cavities in traumatic bleeding (such hemothorax), and bloodshed in operation field during open heart or vascular surgeries, and similar situations, can be utilized again. In this study, autotransfusion effects compared with crystalloid fluid in the treatment of hemorrhagic shock was investigated. METHODS: After induction of hemorrhagic shock in dogs by Wiggers type controlled bleeding, treating them in a group with autologous blood and another group with Ringer lactate were performed, and the results of treatment were studied. RESULTS: There was no mortality in both treatment approaches. Immediately after treatment, crystalloid positive effects such as renormalized vital signs and appropriate consciousness were more noticeable than autotransfusion, while twenty-four hours after, the desired effects of autologous blood were more pronounced like decreased metabolic acidosis and improvement of diuresis. CONCLUSIONS: Crystalloid during the first hours after treatment of hemorrhagic shock may be better than autologous blood as preferred treatment, while autotransfusion showed its benefits some hours after. This finding can be used to develop better strategies for treatment of hemorrhagic shock. PMID:22973328

Effectiveness of an association of a cranberry dry extract, D-mannose, and the two microorganisms Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09 in women affected by cystitis: a pilot study.

PubMed

Vicariotto, Franco

2014-01-01

Urinary tract infections (UTIs) are the most common bacterial infection in women. Most UTIs are acute uncomplicated cystitis caused by Escherichia coli (86%). This study was undertaken to assess the effectiveness of an association of a cranberry dry extract, D-mannose, a gelling complex composed of the exopolysaccharides produced by Streptococcus thermophilus ST10 (DSM 25246) and tara gum, as well as the 2 microorganisms Lactobacillus plantarum LP01 (LMG P-21021) and Lactobacillus paracasei LPC09 (DSM 24243) in women affected by acute uncomplicated cystitis. Thirty-three premenopausal, nonpregnant women diagnosed with acute uncomplicated cystitis were enrolled in a pilot prospective study and completed the treatment protocol. Subjects were instructed to take 2 doses per day during the first month, and then to continue with 1 sachet per day until the sixtieth day. Nitrites and leukocyte esterase on urine dipstick testing were used as indicators of cystitis, with analysis performed at enrollment, after 30 and 60 days, and after 1 month of follow-up. Typical UTI symptoms, namely dysuria, frequent voiding of small volumes, urinary urgency, suprapubic pain, and gross hematuria were scored 0 to 3 and evaluated at each visit. Positive results for the presence of nitrites and leukocyte esterase were found in 14 and 20 subjects after 30 days and in 9 and 14 women after 60 days, respectively (P<0.001). At the end of the follow-up period, positive results for nitrites and leukocyte esterase were recorded in only 4 and 3 of 24 and 19 subjects (16.7%, P=0.103; 15.8%, P=0.325, respectively), with negative results after 60 days. Typical symptoms of cystitis, specifically dysuria, frequent voiding, urgency, and suprapubic pain were significantly improved as well. No significant differences were recorded in the incidence and severity of hematuria at any visit. The long-term ability of an association of cranberry, D-mannose, an innovative gelling complex, and the 2 microorganisms

Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice.

PubMed

Manaenko, Anatol; Lekic, Tim; Ma, Qingyi; Zhang, John H; Tang, Jiping

2013-05-01

Hydrogen inhalation was neuroprotective in several brain injury models. Its mechanisms are believed to be related to antioxidative stress. We investigated the potential neurovascular protective effect of hydrogen inhalation especially effect on mast cell activation in a mouse model of intracerebral hemorrhage. Controlled in vivo laboratory study. Animal research laboratory. One hundred seventy-one 8-week-old male CD-1 mice were used. Collagenase-induced intracerebral hemorrhage model in 8-week-old male CD-1 mice was used. Hydrogen was administrated via spontaneous inhalation. The blood-brain barrier permeability and neurologic deficits were investigated at 24 and 72 hours after intracerebral hemorrhage. Mast cell activation was evaluated by Western blot and immuno-staining. The effects of hydrogen inhalation on mast cell activation were confirmed in an autologous blood injection model intracerebral hemorrhage. At 24 and 72 hours post intracerebral hemorrhage, animals showed blood-brain barrier disruption, brain edema, and neurologic deficits, accompanied with phosphorylation of Lyn kinase and release of tryptase, indicating mast cell activation. Hydrogen treatment diminished phosphorylation of Lyn kinase and release of tryptase, decreased accumulation and degranulation of mast cells, attenuated blood-brain barrier disruption, and improved neurobehavioral function. Activation of mast cells following intracerebral hemorrhage contributed to increase of blood-brain barrier permeability and brain edema. Hydrogen inhalation preserved blood-brain barrier disruption by prevention of mast cell activation after intracerebral hemorrhage.

Radiation-induced chondrosarcoma of the maxilla 7-year after combined chemoradiation for tonsillar lymphoma.

PubMed

Mohammadianpanah, M; Gramizadeh, B; Omidvari, Sh; Mosalaei, A

2004-01-01

Radiation-induced sarcoma is a rare complication of radiation therapy. We report a case of radiation-induced chondrosarcoma of the maxilla. An 80-year-old Persian woman developed radiation-induced chondrosarcoma of the left maxilla 7 years after combined chemotherapy and external beam radiation therapy for the Ann Arbor stage IE malignant lymphoma of the right tonsil. She underwent suboptimal tumour resection and died due to extensive locoregional disease 8 months later. An English language literature search of Medline using the terms chondrosarcoma, radiation-induced sarcoma and maxilla revealed only one earlier reported case. We describe the clinical and pathological features of this case and review the literature on radiation-induced sarcomas.

Perioperative spontaneous bilateral suprachoroidal hemorrhage

PubMed Central

Haridas, Anjana; Litwin, Andre S.; Coker, Timothy

2011-01-01

Summary Suprachoroidal hemorrhage is a rare condition, occurring most commonly in the perioperative period, although cases of unilateral spontaneous hemorrhages have been reported. We report a case of bilateral spontaneous suprachoroidal hemorrhage and discuss the potential causative factors. PMID:23362387

Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever.

PubMed

Bowick, Gavin C; Airo, Adriana M; Bente, Dennis A

2012-06-19

Crimean Congo hemorrhagic fever (CCHF) is a tick-borne hemorrhagic zoonosis associated with high mortality. Pathogenesis studies and the development of vaccines and antivirals against CCHF have been severely hampered by the lack of suitable animal model. We recently developed and characterized a mature mouse model for CCHF using mice carrying STAT1 knockout (KO). Given the importance of interferons in controlling viral infections, we investigated the expression of interferon pathway-associated genes in KO and wild-type (WT) mice challenged with CCHF virus. We expected that the absence of the STAT1 protein would result in minimal expression of IFN-related genes. Surprisingly, the KO mice showed high levels of IFN-stimulated gene expression, beginning on day 2 post-infection, while in WT mice challenged with virus the same genes were expressed at similar levels on day 1. We conclude that CCHF virus induces similar type I IFN responses in STAT1 KO and WT mice, but the delayed response in the KO mice permits rapid viral dissemination and fatal illness.

Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

PubMed

Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

2017-03-01

The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

PubMed

Okamura, Koichi; Tsubokawa, Tamiji; Johshita, Hiroo; Miyazaki, Hiroshi; Shiokawa, Yoshiaki

2014-01-01

Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion. In this study, we investigated the effects of edaravone on hemorrhagic infarction in a rat model of hemorrhagic transformation. We used a previously established hemorrhagic transformation model of rats with hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of glucose to all rats (n  =  20). The rats with hyperglycemia showed a high incidence of hemorrhagic infarction. Middle cerebral artery occlusion (MCAO) for 1.5 hours followed by reperfusion for 24 hours was performed in edaravone-treated rats (n  =  10) and control rats (n  =  10). Upon completion of reperfusion, both groups were evaluated for infarct size and hemorrhage volume and the results obtained were compared. Edaravone significantly decreased infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm(3)) being significantly lower than that in the control rats (264.0 mm(3)). Edaravone treatment also decreased the postischemic hemorrhage volumes (53.4 mm(3) in edaravone-treated rats vs 176.4 mm(3) in controls). In addition, the ratio of hemorrhage volume to infarct volume was lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%). Edaravone attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

Ionizing radiation-induced mutagenesis: radiation studies in Neurospora predictive for results in mammalian cells

NASA Technical Reports Server (NTRS)

Evans, H. H.; DeMarini, D. M.

1999-01-01

Ionizing radiation was the first mutagen discovered and was used to develop the first mutagenicity assay. In the ensuing 70+ years, ionizing radiation became a fundamental tool in understanding mutagenesis and is still a subject of intensive research. Frederick de Serres et al. developed and used the Neurospora crassa ad-3 system initially to explore the mutagenic effects of ionizing radiation. Using this system, de Serres et al. demonstrated the dependence of the frequency and spectra of mutations induced by ionizing radiation on the dose, dose rate, radiation quality, repair capabilities of the cells, and the target gene employed. This work in Neurospora predicted the subsequent observations of the mutagenic effects of ionizing radiation in mammalian cells. Modeled originally on the mouse specific-locus system developed by William L. Russell, the N. crassa ad-3 system developed by de Serres has itself served as a model for interpreting the results in subsequent systems in mammalian cells. This review describes the primary findings on the nature of ionizing radiation-induced mutagenesis in the N. crassa ad-3 system and the parallel observations made years later in mammalian cells.

IRREVERSIBLE HEMORRHAGIC SHOCK IN GERMFREE RATS

PubMed Central

Zweifach, B. W.; Gordon, H. A.; Wagner, M.; Reyniers, J. A.

1958-01-01

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock. PMID:13513911

Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation

PubMed Central

Ye, Tianyu; Liu, Han-Chun; Wang, Zhuo; Wegscheider, W.; Mani, Ramesh G.

2015-01-01

A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. For circularly polarized radiation, the oscillatory magnetoresistive response is hardly sensitive to θ. PMID:26450679

Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation.

PubMed

Ye, Tianyu; Liu, Han-Chun; Wang, Zhuo; Wegscheider, W; Mani, Ramesh G

2015-10-09

A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. For circularly polarized radiation, the oscillatory magnetoresistive response is hardly sensitive to θ.

Childhood bladder and bowel dysfunction predicts irritable bowel syndrome phenotype in adult interstitial cystitis/bladder pain syndrome patients.

PubMed

Doiron, R Christopher; Kogan, Barry A; Tolls, Victoria; Irvine-Bird, Karen; Nickel, J Curtis

2017-08-01

Many clinicians have suggested that a history of bladder and bowel dysfunction (BBD) in childhood predisposes to the development of interstitial cystitis/bladder pain syndrome (IC/BPS) or irritable bowel syndrome (IBS) in adulthood. We hypothesized that BBD symptoms in childhood would predict the IBS-associated phenotype in adult IC/BPS patients. Consecutive female patients (n=190) with a diagnosis of IC/BPS were administered a modified form of a clinical BBD questionnaire (BBDQ) to capture childhood BBD-like symptoms, as well as Interstitial Cystitis Symptoms Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency (PUF) questionnaires and UPOINT categorization. Patients were stratified to IBS-positive or IBS-negative according to clinical assessment of IBS-like symptoms. The 127 patients (67%) identified with IBS-like symptoms recalled significantly higher BBDQ scores than the 63 patients (33%) who were IBS-negative (2.8 vs. 2.3; p=0.05). The IBS-positive patients also reported a higher number of UPOINT domains than their non-IBS counterparts (3.8 vs. 2.9; p=0.0001), while their PUF total scores were significantly higher (13.6 vs. 12.3; p=0.04). IBS-positive patients more often recalled that in childhood they did not have a daily bowel movement (BM) (p=0.04) and had "to push for a BM" (p=0.009). In childhood, they "urinated only once or twice per day" (p=0.03) and recalled "painful urination" more than those without IBS (p=0.03). There were no significant differences between the groups in answers to the other five questions of the BBDQ. Our symptom recollection survey was able to predict the IBS phenotype of IC/BPS based on a childhood BBDQ. Further prospective studies are needed to further evaluate these novel findings.

Updates in diagnosis and management of Ebola hemorrhagic fever

PubMed Central

El Sayed, Salah Mohamed; Abdelrahman, Ali A.; Ozbak, Hani Adnan; Hemeg, Hassan Abdullah; Kheyami, Ali Mohammed; Rezk, Nasser; El-Ghoul, Mohamed Baioumy; Nabo, Manal Mohamed Helmy; Fathy, Yasser Mohamed

2016-01-01

Ebola hemorrhagic fever is a lethal viral disease transmitted by contact with infected people and animals. Ebola infection represents a worldwide health threat causing enormous mortality rates and fatal epidemics. Major concern is pilgrimage seasons with possible transmission to Middle East populations. In this review, we aim to shed light on Ebola hemorrhagic fever as regard: virology, transmission, biology, pathogenesis, clinical picture, and complications to get the best results for prevention and management. We also aim to guide future research to new therapeutic perspectives to precise targets. Our methodology was to review the literature extensively to make an overall view of the biology of Ebola virus infection, its serious health effects and possible therapeutic benefits using currently available remedies and future perspectives. Key findings in Ebola patients are fever, hepatic impairment, hepatocellular necrosis, lymphopenia (for T-lymphocyte and natural killer cells) with lymphocyte apoptosis, hemorrhagic manifestations, and complications. Pathogenesis in Ebola infection includes oxidative stress, immune suppression of both cell-mediated and humoral immunities, hepatic and adrenal impairment and failure, hemorrhagic fever, activation of deleterious inflammatory pathways, for example, tumor necrosis factor-related apoptosis-inducing ligand, and factor of apoptotic signal death receptor pathways causing lymphocyte depletion. Several inflammatory mediators and cytokines are involved in pathogenesis, for example, interleukin-2, 6, 8, and 10 and others. In conclusion, Ebola hemorrhagic fever is a serious fatal viral infection that can be prevented using strict health measures and can be treated to some extent using some currently available remedies. Newer treatment lines, for example, prophetic medicine remedies as nigella sativa may be promising. PMID:28163730

Updates in diagnosis and management of Ebola hemorrhagic fever.

PubMed

El Sayed, Salah Mohamed; Abdelrahman, Ali A; Ozbak, Hani Adnan; Hemeg, Hassan Abdullah; Kheyami, Ali Mohammed; Rezk, Nasser; El-Ghoul, Mohamed Baioumy; Nabo, Manal Mohamed Helmy; Fathy, Yasser Mohamed

2016-01-01

Ebola hemorrhagic fever is a lethal viral disease transmitted by contact with infected people and animals. Ebola infection represents a worldwide health threat causing enormous mortality rates and fatal epidemics. Major concern is pilgrimage seasons with possible transmission to Middle East populations. In this review, we aim to shed light on Ebola hemorrhagic fever as regard: virology, transmission, biology, pathogenesis, clinical picture, and complications to get the best results for prevention and management. We also aim to guide future research to new therapeutic perspectives to precise targets. Our methodology was to review the literature extensively to make an overall view of the biology of Ebola virus infection, its serious health effects and possible therapeutic benefits using currently available remedies and future perspectives. Key findings in Ebola patients are fever, hepatic impairment, hepatocellular necrosis, lymphopenia (for T-lymphocyte and natural killer cells) with lymphocyte apoptosis, hemorrhagic manifestations, and complications. Pathogenesis in Ebola infection includes oxidative stress, immune suppression of both cell-mediated and humoral immunities, hepatic and adrenal impairment and failure, hemorrhagic fever, activation of deleterious inflammatory pathways, for example, tumor necrosis factor-related apoptosis-inducing ligand, and factor of apoptotic signal death receptor pathways causing lymphocyte depletion. Several inflammatory mediators and cytokines are involved in pathogenesis, for example, interleukin-2, 6, 8, and 10 and others. In conclusion, Ebola hemorrhagic fever is a serious fatal viral infection that can be prevented using strict health measures and can be treated to some extent using some currently available remedies. Newer treatment lines, for example, prophetic medicine remedies as nigella sativa may be promising.

Lack of photoprotection against UVB-induced erythema by immediate pigmentation induced by 382 nm radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Black, G.; Matzinger, E.; Gange, R.W.

Immediate pigment darkening (IPD) was induced on the backs of 11 human volunteers of skin types III and IV by exposing the skin to UVA radiation (382 nm). The minimum erythema dose (MED) of UVB radiation was also determined by exposing sites to graduated doses of 304 nm radiation. The order of exposure of distinct anatomic areas was as follow: UVB followed by IPD induction; IPD induction followed by UVB; IPD induction followed 3 h later by UVB; and UVB only. Erythema responses induced by UVB were graded by inspection 24 h later and the MEDs in the 4 areasmore » were compared. The induction of IPD before UVB exposure caused no significant change in the MED compared to sites receiving UVB only, or receiving UVA radiation after UVB, confirming that the IPD reaction does not protect against UVB-induced erythema. There was also no evidence of photorecovery, i.e., an increase in the MED of UVB resulting from exposure to longer wavelength, UV or visible radiation following UVB exposure.« less

Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications.

PubMed

Iqbal, Sana; Hayman, Erik G; Hong, Caron; Stokum, Jesse A; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

2016-01-01

Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH.

A randomized controlled trial of a diagnostic algorithm for symptoms of uncomplicated cystitis at an out-of-hours service.

PubMed

Bollestad, Marianne; Grude, Nils; Lindbaek, Morten

2015-06-01

To compare the clinical outcome of patients presenting with symptoms of uncomplicated cystitis who were seen by a doctor, with patients who were given treatment following a diagnostic algorithm. Randomized controlled trial. Out-of-hours service, Oslo, Norway. Women with typical symptoms of uncomplicated cystitis were included in the trial in the time period September 2010-November 2011. They were randomized into two groups. One group received standard treatment according to the diagnostic algorithm, the other group received treatment after a regular consultation by a doctor. Women (n = 441) aged 16-55 years. Mean age in both groups 27 years. Number of days until symptomatic resolution. No significant differences were found between the groups in the basic patient demographics, severity of symptoms, or percentage of urine samples with single culture growth. A median of three days until symptomatic resolution was found in both groups. By day four 79% in the algorithm group and 72% in the regular consultation group were free of symptoms (p = 0.09). The number of patients who contacted a doctor again in the follow-up period and received alternative antibiotic treatment was insignificantly higher (p = 0.08) after regular consultation than after treatment according to the diagnostic algorithm. There were no cases of severe pyelonephritis or hospital admissions during the follow-up period. Using a diagnostic algorithm is a safe and efficient method for treating women with symptoms of uncomplicated cystitis at an out-of-hours service. This simplification of treatment strategy can lead to a more rational use of consultation time and a stricter adherence to National Antibiotic Guidelines for a common disorder.

Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage.

PubMed

Li, Jianru; Chen, Jingsen; Mo, Hangbo; Chen, Jingyin; Qian, Cong; Yan, Feng; Gu, Chi; Hu, Qiang; Wang, Lin; Chen, Gao

2016-05-01

Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH.

Characterization of radiation-induced emesis in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.L.

1988-06-01

Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral /sup 60/Co gamma radiation at 100 cGy min-1 at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED50 was calculated at 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenously ormore » subcutaneously with 30 to 300 micrograms/kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n = 4) or 401 (n = 4) cGy radiation and their emetic responses were compared with NaCl-injected-irradiated controls (n = 8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species.« less

Characterization of radiation-induced emesis in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.L.

1988-01-01

Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral cobalt 60 gamma radiation at 100 cGy min at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED 50 was calculated as 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenouslymore » or subcutaneously with 30 to 300 micrograms /kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n=4) or 401 (n=4) cGy radiation and their emetic responses were compared with NaCi-injected-irradiated controls (n=8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species.« less

Frequency and determinants for hemorrhagic transformation of posterior cerebral stroke : Posterior ischemic stroke and hemorrhagic transformation.

PubMed

Valentino, Francesca; Gentile, Luana; Terruso, Valeria; Mastrilli, Sergio; Aridon, Paolo; Ragonese, Paolo; Sarno, Caterina; Savettieri, Giovanni; D'Amelio, Marco

2017-11-13

hemorrhagic transformation is a threatening ischemic stroke complication. Frequency of hemorrhagic transformation differs greatly among studies, and its risk factors have been usually studied in patients with anterior ischemic stroke who received thrombolytic therapy. We evaluated, in a hospital-based series of patients with posterior ischemic stroke not treated with thrombolysis, frequency and risk factors of hemorrhagic transformation. Patients with posterior circulation stroke were seen in our Department during the period January 2004 to December 2009. Demographic and clinical information were collected. We estimated risk for spontaneous hemorrhagic transformation by means of uni- and multivariate logistic regression analyses. 119 consecutive patients were included (73 males, 61.3%). Hemorrhagic transformation was observed in 7 patients (5.9%). Only clinical worsening was significantly associated with hemorrhagic transformation (OR 6.8, 95% CI 1.3-34.5). Our findings indicate that patients with posterior have a low risk of spontaneous hemorrhagic transformation, suggesting that these patients might have greater advantage from intravenous thrombolysis.

Imaging of Hemorrhagic Stroke.

PubMed

Hakimi, Ryan; Garg, Ankur

2016-10-01

Hemorrhagic stroke comprises approximately 15% to 20% of all strokes. This article provides readers with an understanding of the indications and significance of various neuroimaging techniques available for patients presenting with hemorrhagic strokes of distinct causes. The most common initial neuroimaging study is a noncontrast head CT, which allows for the identification of hemorrhage. Once an intracranial hemorrhage has been identified, the pattern of blood and the patient's medical history, neurologic examination, and laboratory studies lead the practitioner to pursue further neuroimaging studies to guide the medical, surgical, and interventional management. Given that hemorrhagic stroke constitutes a heterogeneous collection of diagnoses, the subsequent neuroimaging pathway necessary to better evaluate and care for these patients is variable based on the etiology.With an increasing incidence and prevalence of atrial fibrillation associated with the aging population and the introduction of three new direct factor Xa inhibitors and one direct thrombin inhibitor to complement vitamin K antagonists, oral anticoagulant use continues to increase. Patients on oral anticoagulants have a sevenfold to tenfold increased risk for intracerebral hemorrhage (ICH). Furthermore, patients who have an ICH associated with oral anticoagulant use have a higher mortality rate than those with primary ICH. Despite the reduced incidence of hypertension-related ICH over the past decade, it is expected that the incidence of ICH will continue to increase. Neuroimaging studies are integral to the identification of hemorrhagic stroke, determination of the underlying etiology, prevention of hematoma expansion, treatment of acute complications, and treatment of the underlying etiology, if indicated. Neuroimaging is essential for prognostication and thus directly impacts patient care.

[Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

PubMed

Sevost'ianova, N N; Trofimov, A V; Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

2010-01-01

The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats.

PubMed

Wang, Jun; Wu, Yajing; Yuan, Fang; Liu, Yixian; Wang, Xuefeng; Cao, Feng; Zhang, Yi; Wang, Sheng

2016-09-01

Radiation-induced heart damage (RIHD) is becoming an increasing concern for patients and clinicians due to the use of radiotherapy for thoracic tumor. Chronic intermittent hypobaric hypoxia (CIHH) preconditioning has been documented to exert a cardioprotective effect. Here we hypothesized that CIHH was capable of attenuating functional and structural damage in a rat model of RIHD. Male adult Sprague-Dawley rats were randomly divided into 4 groups: control, radiation, CIHH and CIHH plus radiation. Cardiac function was measured using Langendorff perfusion in in vitro rat hearts. Cardiac fibrosis, oxidative stress and endoplasmic reticulum stress (ERS) was assessed by quantitative analysis of protein expression. No significant difference between any two groups was observed in baseline cardiac function as assessed by left ventricular end diastolic pressure (LVEDP), left ventricular developing pressure (LVDP) and the derivative of left ventricular pressure (±LVdp/dt). When challenged by ischemia/reperfusion, LVEDP was increased but LVDP and ±LVdp/dt was decreased significantly in radiation group compared with controls, accompanied by an enlarged infarct size and decreased coronary flow. Importantly, CIHH dramatically improved radiation-induced damage of cardiac function and blunted radiation-induced cardiac fibrosis in the perivascular and interstitial area. Furthermore, CIHH abrogated radiation-induced increase in malondialdehyde and enhanced total superoxide dismutase activity, as well as downregulated expression levels of ERS markers like GRP78 and CHOP. CIHH pretreatment alleviated radiation-induced damage of cardiac function and fibrosis. Such a protective effect was closely associated with suppression of oxidative stress and ERS responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Hemorrhage Near Fetal Rat Bone: Preliminary Results

NASA Astrophysics Data System (ADS)

Bigelow, Timothy A.; Miller, Rita J.; Blue, James P.; O'Brien, William D.

2006-05-01

High-intensity ultrasound has shown potential in treating many ailments requiring noninvasive tissue necrosis. However, little work has been done on using ultrasound to ablate pathologies on or near the developing fetus. For example, Congenital Cystic Adenomatoid Malformation (cyst on lungs), Sacrococcygeal Teratoma (benign tumor on tail bone), and Twin-Twin Transfusion Syndrome (one twin pumps blood to other twin) are selected problems that will potentially benefit from noninvasive ultrasound treatments. Before these applications can be explored, potential ultrasound-induced bioeffects should be understood. Specifically, ultrasound-induced hemorrhage near the fetal rat skull was investigated. An f/1 spherically focused transducer (5.1-cm focal length) was used to expose the skull of 18- to 19-day-gestation exteriorized rat fetuses. The ultrasound pulse had a center frequency of 0.92 MHz and pulse duration of 9.6 μs. The fetuses were exposed to 1 of 4 exposure conditions (denoted A, B, C, and D) in addition to a sham exposure. Three of the exposures consisted of a peak compressional pressure of 10 MPa, a peak rarefactional pressure of 6.7 MPa, and pulse repetition frequencies of 100 Hz (A), 250 Hz (B), and 500 Hz (C), corresponding to time-average intensities of 1.9 W/cm2, 4.7 W/cm2, and 9.4 W/cm2, respectively. Exposure D consisted of a peak compressional pressure of 6.7 MPa, a peak rarefactional pressure of 5.0 MPa, and a PRF of 500 Hz corresponding to a time-average intensity of 4.6 W/cm2. Hemorrhage occurrence increased slightly with increasing time-average intensity (i.e., 11% for A, 28% for B, 31% for C, and 19% for D with a 9% occurrence when the fetuses were not exposed). The low overall occurrence of hemorrhaging may be attributed to fetal motion (observed in over half of the fetuses from the backscattered echo during the exposure). The mean hemorrhage sizes were 3.1 mm2 for A, 2.5 mm2 for B, 2.7 mm2 for C, and 5.1 mm2 for D. The larger lesions at D may

Rebamipide ameliorates radiation-induced intestinal injury in a mouse model.

PubMed

Shim, Sehwan; Jang, Hyo-Sun; Myung, Hyun-Wook; Myung, Jae Kyung; Kang, Jin-Kyu; Kim, Min-Jung; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Jin, Young-Woo; Lee, Seung-Sook; Park, Sunhoo

2017-08-15

Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased. The intestinal damage reached a maximum level on day 6 post-IR and intestinal regeneration occurred thereafter. We found that rebamipide significantly ameliorated radiation-induced intestinal injury. In mice treated with rebamipide after IR, intestinal barrier function recovered and expression of the tight junction components of the intestinal barrier were upregulated. Rebamipide administration reduced radiation-induced intestinal mucosal injury. The levels of proinflammatory cytokines and matrix metallopeptidase 9 (MMP9) were significantly reduced upon rebamipide administration. Intestinal cell proliferation and β-catenin expression also increased upon rebamipide administration. These data demonstrate that rebamipide reverses impairment of the intestinal barrier by increasing intestinal cell proliferation and attenuating the inflammatory response by inhibiting MMP9 and proinflammatory cytokine expression in a murine model of radiation-induced enteritis. Copyright © 2017 Elsevier Inc. All rights reserved.

Antimicrobial Resistance of Urinary Tract Isolates in Acute Uncomplicated Cystitis among College-Aged Women: Choosing a First-Line Therapy

ERIC Educational Resources Information Center

Hames, Leesa; Rice, Craig E.

2007-01-01

Objective and Participants: The authors of this retrospective case study focused on antimicrobial susceptibility of urinary tract isolates in cases of acute uncomplicated cystitis in college-aged women, aged 18 to 24 years, diagnosed at a major south-central university student health center. Methods: The authors obtained pertinent data from…

Angiotensin (1-7) contributes to nitric oxide tonic inhibition of vasopressin release during hemorrhagic shock in acute ethanol intoxicated rodents

PubMed Central

Whitaker, Annie M.; Molina, Patricia E.

2013-01-01

Aims Acute ethanol intoxication (AEI) attenuates the arginine vasopressin (AVP) response to hemorrhage leading to impaired hemodynamic counter-regulation and accentuated hemodynamic stability. Previously we identified that the ethanol-induced impairment of circulating AVP concentrations in response to hemorrhage was the result of augmented central nitric oxide (NO) inhibition. The aim of the current study was to examine the mechanisms underlying ethanol-induced up-regulation of paraventricular nucleus (PVN) NO concentration. Angiotensin (ANG) (1-7) is an important mediator of NO production through activation of the Mas receptor. We hypothesized that Mas receptor inhibition would decrease central NO concentration and thus restore the rise in circulating AVP levels during hemorrhagic shock in AEI rats. Main Methods Conscious male Sprague Dawley rats (300-325 g) received a 15h intra-gastric infusion of ethanol (2.5g/kg + 300mg/kg/h) or dextrose prior to a fixed-pressure (~40mmHg) 60 minute hemorrhage. The Mas receptor antagonist A-779 was injected through an intracerebroventricular (ICV) cannula 15 min prior to hemorrhage. Key Findings PVN NOS activity and NO were significantly higher in AEI compared to DEX-treated controls at the completion of hemorrhage. ICV A-779 administration decreased NOS activity and NO concentration, partially restoring the rise in circulating AVP levels completion of hemorrhage in AEI rats. Significance These results suggest that Mas receptor activation contributes to the NO-mediated inhibitory tone of AVP release in the ethanol-intoxicated hemorrhaged host. PMID:24002017

Influence of Scan Duration on Pulmonary Capillary Hemorrhage Induced by Diagnostic Ultrasound.

PubMed

Miller, Douglas L; Dong, Zhihong; Dou, Chunyan; Raghavendran, Krishnan

2016-08-01

Diagnostic ultrasound can induce pulmonary capillary hemorrhage (PCH) in rats and display this as "comet tail" artifacts (CTAs) after a time delay. To test the hypothesis that no PCH occurs for brief scans, anesthetized rats were scanned using a 6-MHz linear array for different durations. PCH was characterized by ultrasound CTAs, micro-computed tomography (μCT), and measurements of fixed lung tissue. The μCT images revealed regions of PCH, sometimes penetrating the entire depth of a lobe, which were reflected in the fixed tissue measurements. At -3 dB of power, PCH was substantial for 300-s scans, but not significant for 25-s scans. At 0 dB, PCH was not strongly dependent on scan durations of 300 to 10 s. Contrary to the hypothesis, CTAs were not evident during most 10-s scans (p > 0.05), but PCH was significant (p = 0.02), indicating that PCH could occur without evidence of the injury in the images. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

NASA Technical Reports Server (NTRS)

Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

2006-01-01

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low

Apatinib in refractory radiation-induced brain edema: A case report.

PubMed

Hu, Wei Guo; Weng, Yi Ming; Dong, Yi; Li, Xiang Pan; Song, Qi-Bin

2017-11-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has observed to be effective and safe in refractory radiation-induced brain edema, like Avastin did. Till now, there is no case report after apatinib came in the market. Two patients who received brain radiotherapy developed clinical manifestations of brain edema, including dizziness, headache, limb activity disorder, and so on. Two patients were both diagnosed as refractory radiation-induced brain edema. Two patients received apatinib (500 mg/day) for 2 and 4 weeks. Two patients got symptomatic improvements from apatinib in different degrees. Magnetic resonance imaging after apatinib treatments showed that compared with pre-treatment imaging, the perilesional edema reduced dramatically. However, the toxicity of apatinib was controllable and tolerable. Apatinib can obviously relieve the symptoms of refractory radiation-induced brain edema and improve the quality of life, which offers a new method for refractory radiation-induced brain edema in clinical practices. But that still warrants further investigation in the prospective study.

Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Tianyu; Liu, Han -Chun; Wang, Zhuo

A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. As a result, for circularly polarized radiation, the oscillatory magnetoresistive response ismore » hardly sensitive to θ.« less

Comparative study of microwave radiation-induced magnetoresistive oscillations induced by circularly- and linearly- polarized photo-excitation

DOE PAGES

Ye, Tianyu; Liu, Han -Chun; Wang, Zhuo; ...

2015-10-09

A comparative study of the radiation-induced magnetoresistance oscillations in the high mobility GaAs/AlGaAs heterostructure two dimensional electron system (2DES) under linearly- and circularly- polarized microwave excitation indicates a profound difference in the response observed upon rotating the microwave launcher for the two cases, although circularly polarized microwave radiation induced magnetoresistance oscillations observed at low magnetic fields are similar to the oscillations observed with linearly polarized radiation. For the linearly polarized radiation, the magnetoresistive response is a strong sinusoidal function of the launcher rotation (or linear polarization) angle, θ. As a result, for circularly polarized radiation, the oscillatory magnetoresistive response ismore » hardly sensitive to θ.« less

Anosmia after perimesencephalic nonaneurysmal hemorrhage.

PubMed

Greebe, Paut; Rinkel, Gabriël J E; Algra, Ale

2009-08-01

Anosmia frequently occurs after aneurysmal subarachnoid hemorrhage not only after clipping, but also after endovascular coiling. Thus, at least in part, anosmia is caused by the hemorrhage itself and not only by surgical treatment. However, it is unknown whether anosmia is related to rupture of the aneurysm with sudden increase in intracranial pressure or to the presence of blood in the basal cisterns. Therefore, we studied the prevalence of anosmia in patients with nonaneurysmal perimesencephalic hemorrhage. We included all patients admitted to our hospital with perimesencephalic hemorrhage between 1983 and 2005. Patients were interviewed with a structured questionnaire. We calculated the proportion of patients with anosmia with corresponding 95% CIs. Nine of 148 patients (6.1%; 95% CI, 2.8% to 11%) had noticed anosmia shortly after the perimesencephalic hemorrhage. In 2, the anosmia had disappeared after 8 to12 weeks; in the other 7, it still persisted after a mean period of follow-up of 9 years. Anosmia occurs in one of every 16 patients with perimesencephalic hemorrhage, which is lower than previously reported rates after coiling in patients with subarachnoid hemorrhage but higher than rates after coiling for unruptured aneurysms. These data suggest that blood in the vicinity of the olfactory nerves plays a role in the development of anosmia.

Osthole attenuates hepatic injury in a rodent model of trauma-hemorrhage.

PubMed

Yu, Huang-Ping; Liu, Fu-Chao; Tsai, Yung-Fong; Hwang, Tsong-Long

2013-01-01

Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway.

Osthole Attenuates Hepatic Injury in a Rodent Model of Trauma-Hemorrhage

PubMed Central

Yu, Huang-Ping; Liu, Fu-Chao; Tsai, Yung-Fong; Hwang, Tsong-Long

2013-01-01

Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway. PMID:23755293

Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acute radiation syndrome

PubMed Central

Kindekov, Ivan; Mileva, Milka; Krastev, Dimo; Vassilieva, Vladimira; Raynova, Yuliana; Doumanova, Lyuba; Aljakov, Mitko; Idakieva, Krassimira

2014-01-01

The radioprotective effect of Rapana thomasiana hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 – dose that kills 100% of the mice at 30 days) from 137Cs with a dose of 2.05 Gy/min. Radiation injuries were manifested by inducing а hematopoietic form of acute radiation syndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2) ulceration in the stomach mucosa and (3) decrease formation of spleen colonies as a marker of endogenous haemopoiesis. Administration of RtH at a dose of 200 mg/kg provided better protection against radiation-induced stomach ulceration, mitigated the lethal effects of radiation exposure and recovered endogenous haemopoiesis versus irradiated but not supplemented mice. It could be expected that RtH will find a use in mitigating radiation induced injury and enhanced radiorecovery. PMID:26019540

Radioprotective effect of Rapana thomasiana hemocyanin in gamma induced acute radiation syndrome.

PubMed

Kindekov, Ivan; Mileva, Milka; Krastev, Dimo; Vassilieva, Vladimira; Raynova, Yuliana; Doumanova, Lyuba; Aljakov, Mitko; Idakieva, Krassimira

2014-05-04

The radioprotective effect of Rapana thomasiana hemocyanin (RtH) against radiation-induced injuries (stomach ulcers, survival time and endogenous haemopoiesis) and post-radiation recovery was investigated in male albino mice (C3H strain). Radiation course was in a dose of 7.5 Gy (LD 100/30 - dose that kills 100% of the mice at 30 days) from 137 Cs with a dose of 2.05 Gy/min. Radiation injuries were manifested by inducing а hematopoietic form of acute radiation syndrome. RtH was administered intraperitoneally in a single dose of 50, 100, 150 and 200 mg/kg body weight (b. w.) once a day for five consecutive days before irradiation. The results obtained showed that radiation exposure led to (1) 100% mortality rate, (2) ulceration in the stomach mucosa and (3) decrease formation of spleen colonies as a marker of endogenous haemopoiesis. Administration of RtH at a dose of 200 mg/kg provided better protection against radiation-induced stomach ulceration, mitigated the lethal effects of radiation exposure and recovered endogenous haemopoiesis versus irradiated but not supplemented mice. It could be expected that RtH will find a use in mitigating radiation induced injury and enhanced radiorecovery.

Paradoxical undressing associated with subarachnoid hemorrhage in a non-hypothermia case?

PubMed

Descloux, Emilienne; Ducrot, Kewin; Scarpelli, Maria Pia; Lobrinus, Alexander; Palmiere, Cristian

2017-09-01

Paradoxical undressing is a phenomenon characterizing some fatal hypothermia cases. The victims, despite low environmental temperatures, paradoxically remove their clothes due to a sudden feeling of warmth. In this report, we describe a case of suspected paradoxical undressing in a non-hypothermia case. The victim, a 51-year-old Caucasian man, was found dead wearing only sneakers and socks. All other clothing was found in his car. Postmortem investigations allowed the hypothesis of hypothermia to be ruled out and revealed the presence of a ruptured cerebral aneurysm that caused a subarachnoid hemorrhage, the latter responsible for the death. The absence of any elements suggesting a voluntary undressing or any third party's DNA profile or involvement along with the possibility that the subarachnoid hemorrhage might have determined a hypothalamic injury, somehow rendered conceivable the hypothesis of an inappropriate feeling of warmth due to hemorrhage-induced dysregulation of the hypothalamic temperature-regulating centers.

Immune Thrombocytopenic Purpura Presenting as Unprovoked Gingival Hemorrhage: a Case Report

PubMed Central

Bal, Mehmet V; Koyuncuoglu, Cenker Z; Saygun, Işıl

2014-01-01

Immune thrombocytopenic purpura is an autoimmune disease characterized by auto-antibody induced platelet destruction and reduced platelet production, leading to low blood platelet count. In this case report, the clinical diagnose of a patient with immune thrombocytopenic purpura and spontaneous gingival hemorrhage by a dentist is presented. The patient did not have any systemic disease that would cause any spontaneous hemorrhage. The patient was referred to a hematologist urgently and her thrombocyte number was found to be 2000/μL. Other test results were in normal range and immune thrombocytopenic purpura diagnose was verified. Then hematological treatment was performed and patient’s health improved without further problems. Hematologic diseases like immune thrombocytopenic purpura, in some cases may appear firstly in the oral cavity and dentists must be conscious of unexplained gingival hemorrhage. In addition, the dental treatment of immune thrombocytopenic purpura patients must be planned with a hematologist. PMID:25317211

The potential influence of radiation-induced microenvironments in neoplastic progression

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1998-01-01

Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

Mechanism of Salutary Effects of Astringinin on Rodent Hepatic Injury following Trauma-Hemorrhage: Akt-Dependent Hemeoxygenase-1 Signaling Pathways

PubMed Central

Liu, Fu-Chao; Hwang, Tsong-Long; Lau, Ying-Tung; Yu, Huang-Ping

2011-01-01

Astringinin can attenuate organ injury following trauma-hemorrhage, the mechanism remains unknown. Protein kinase B/hemeoxygenase-1 (Akt/HO-1) pathway exerts potent anti-inflammatory effects in various tissues. The aim of this study is to elucidate whether Akt/HO-1 plays any role in astringinin-mediated attenuation of hepatic injury following trauma-hemorrhage. For study this, male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 35–40 mmHg for 90 min) followed by fluid resuscitation. A single dose of astringinin (0.3 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or a HO antagonist (chromium-mesoporphyrin) was administered during resuscitation. Various parameters were measured at 24 h post-resuscitation. Results showed that trauma-hemorrhage increased plasma aspartate and alanine aminotransferases (AST and ALT) concentrations and hepatic myeloperoxidase activity, cytokine induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels. These parameters were significantly improved in the astringinin-treated rats subjected to trauma-hemorrhage. Astringinin treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of wortmannin or chromium-mesoporphyrin abolished the astringinin-induced beneficial effects on post-resuscitation pro-inflammatory responses and hepatic injury. These findings collectively suggest that the salutary effects of astringinin administration on attenuation of hepatic injury after trauma-hemorrhage are likely mediated via Akt dependent HO-1 up-regulation. PMID:22022464

Mechanism of salutary effects of astringinin on rodent hepatic injury following trauma-hemorrhage: Akt-dependent hemeoxygenase-1 signaling pathways.

PubMed

Liu, Fu-Chao; Hwang, Tsong-Long; Lau, Ying-Tung; Yu, Huang-Ping

2011-01-01

Astringinin can attenuate organ injury following trauma-hemorrhage, the mechanism remains unknown. Protein kinase B/hemeoxygenase-1 (Akt/HO-1) pathway exerts potent anti-inflammatory effects in various tissues. The aim of this study is to elucidate whether Akt/HO-1 plays any role in astringinin-mediated attenuation of hepatic injury following trauma-hemorrhage. For study this, male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 35-40 mmHg for 90 min) followed by fluid resuscitation. A single dose of astringinin (0.3 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or a HO antagonist (chromium-mesoporphyrin) was administered during resuscitation. Various parameters were measured at 24 h post-resuscitation. Results showed that trauma-hemorrhage increased plasma aspartate and alanine aminotransferases (AST and ALT) concentrations and hepatic myeloperoxidase activity, cytokine induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels. These parameters were significantly improved in the astringinin-treated rats subjected to trauma-hemorrhage. Astringinin treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of wortmannin or chromium-mesoporphyrin abolished the astringinin-induced beneficial effects on post-resuscitation pro-inflammatory responses and hepatic injury. These findings collectively suggest that the salutary effects of astringinin administration on attenuation of hepatic injury after trauma-hemorrhage are likely mediated via Akt dependent HO-1 up-regulation.

Neuroprotective effects of Quercetin on radiation-induced brain injury in rats.

PubMed

Kale, Aydemir; Piskin, Özcan; Bas, Yilmaz; Aydin, Bengü Gülhan; Can, Murat; Elmas, Özlem; Büyükuysal, Çagatay

2018-04-24

Extensive research has been focused on radiation-induced brain injury. Animal and human studies have shown that flavonoids have remarkable toxicological profiles. This study aims to investigate the neuroprotective effects of quercetin in an experimental radiation-induced brain injury. A total of 32 adult male Wistar-Albino rats were randomly divided into four groups (control, quercetin, radiation, and radiation+quercetin groups, with eight rats in each group). Doses (50 mg/kg) of quercetin were administered to the animals in the quercetin and radiation+quercetin groups; radiation and radiation+quercetin groups were exposed to a dose of 20 Gy to the cranium region. Tissue samples, and biochemical levels of tissue injury markers in the four groups were compared. In all measured parameters of oxidative stress, administration of quercetin significantly demonstrated favorable effects. Both plasma and tissue levels of malondialdehyde and total antioxidant status significantly changed in favor of antioxidant activity. Histopathological evaluation of the tissues also demonstrated a significant decrease in cellular degeneration and infiltration parameters after quercetin administration. Quercetin demonstrated significant neuroprotection after radiation-induced brain injury. Further studies of neurological outcomes under different experimental settings are required in order to achieve conclusive results.

Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion.

PubMed

Hughes, Adrienne; Brown, Alisha; Valento, Matthew

2016-09-01

Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.

Modulating factors in the expression of radiation-induced oncogenic transformation.

PubMed Central

Hall, E J; Hei, T K

1990-01-01

Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitative are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing alpha-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene. Images FIGURE 4. PMID:2272310

Dietary eicosapentaenoic acid prevents systemic immunosuppression in mice induced by UVB radiation.

PubMed

Moison, R M; Beijersbergen Van Henegouwen, G M

2001-07-01

Moison, R. M. W. and Beijersbergen van Henegouwen, G. M. J. Dietary Eicosapentaenoic Acid Prevents Systemic Immunosuppression in Mice Induced by UVB Radiation. Radiat. Res. 156, 36-44 (2001). Reactive oxygen species (ROS) contribute to the immunosuppression induced by UVB radiation. Omega-3 fatty acids in fish oil, e.g. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can modulate immunoresponsiveness, but because of their susceptibility to ROS-induced damage, they can also challenge the epidermal antioxidant defense system. The influence of dietary supplementation with different omega-3 fatty acids on systemic immunosuppression induced in mice by UVB radiation was studied using the contact hypersensitivity response to trinitrochlorobenzene. In an attempt to study the mechanisms involved, UVB-radiation-induced changes in epidermal antioxidant status were also studied. Mice received high-fat (25% w/w) diets enriched with either oleic acid (control diet), EPA, DHA, or EPA + DHA (MaxEPA). Immunosuppression induced by UVB radiation was 53% in mice fed the oleic acid diet and 69% in mice fed the DHA diet. In contrast, immunosuppression was only 4% and 24% in mice fed the EPA and MaxEPA diets, respectively. Increased lipid peroxidation and decreased vitamin E levels (P < 0.05) were found in unirradiated mice fed the MaxEPA and DHA diets. For all diets, exposure to UVB radiation increased lipid peroxidation (P < 0.05), but levels of glutathione (P < 0.05) and vitamin C (P > 0.05) decreased only in the mice given fish oil. UVB irradiation did not influence vitamin E levels. In conclusion, dietary EPA, but not DHA, protects against UVB-radiation-induced immunosuppression in mice. The degree of protection appears to be related to the amount of EPA incorporated and the ability of the epidermis to maintain an adequate antioxidant level after irradiation.

Entanglement-induced quantum radiation

NASA Astrophysics Data System (ADS)

Iso, Satoshi; Tatsukawa, Rumi; Ueda, Kazushige; Yamamoto, Kazuhiro

2017-08-01

Quantum entanglement of the Minkowski vacuum state between left and right Rindler wedges generates thermal behavior in the right Rindler wedge, which is known as the Unruh effect. In this paper, we show that there is another consequence of this entanglement, namely entanglement-induced quantum radiation emanating from a uniformly accelerated object. We clarify why it is in agreement with our intuition that incoming and outgoing energy fluxes should cancel each other out in a thermalized state.

Distinctions in manifestation of the hemorrhagic syndrome related to chronic, long-term and acute irradiation. [Rats;. gamma. rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arlashchenko, N.I.; Gorlov, V.G.; Maksimova, E.N.

Two phenomena, decrease in strength of the vascular wall and decreased amount of thrombocytes in blood, must coincide for manifestation of the hemorrhagic syndrome. Either almost simultaneous injury to the vascular wall and thrombocyte function (with acute irradiation) or dissociation of these two processes (with long-term irradiation) may be observed, depending on the radiation dose. Chronic exposure at low (subliminal) dose rates does not elicit hemorrhagic manifestations or death of rats due to pathological bleeding.

Intraretinal hemorrhages in cystoid macular edema.

PubMed

Bovino, J A; Kelly, T J; Marcus, D F

1984-08-01

Retinal hemorrhages can be associated with typical cystoid macular edema. We examined the fundus photographs and fluorescein angiograms of 313 eyes of 264 patients with documented cystoid macular edema to establish the incidence and characteristics of associated intraretinal hemorrhages. As we wanted to study only those hemorrhages unique to cystoid macular edema, we excluded 86 eyes because the patients had diseases known to be associated with retinal hemorrhages. These diseases included diabetes mellitus, branch retinal vein occlusion, hypertensive retinopathy, venous stasis retinopathy, and perifoveal telangiectasia. Of the remaining 227 eyes with cystoid macular edema, 56 (24.7%) were identified with retinal hemorrhages not associated with systemic disease. The hemorrhages were characteristically oval, round, or linear and frequently filled or partially filled the intraretinal cystoid space. In many patients, a blood-fluid level was observed.

RIP1 and RIP3 complex regulates radiation-induced programmed necrosis in glioblastoma.

PubMed

Das, Arabinda; McDonald, Daniel G; Dixon-Mah, Yaenette N; Jacqmin, Dustin J; Samant, Vikram N; Vandergrift, William A; Lindhorst, Scott M; Cachia, David; Varma, Abhay K; Vanek, Kenneth N; Banik, Naren L; Jenrette, Joseph M; Raizer, Jeffery J; Giglio, Pierre; Patel, Sunil J

2016-06-01

Radiation-induced necrosis (RN) is a relatively common side effect of radiation therapy for glioblastoma. However, the molecular mechanisms involved and the ways RN mechanisms differ from regulated cell death (apoptosis) are not well understood. Here, we compare the molecular mechanism of cell death (apoptosis or necrosis) of C6 glioma cells in both in vitro and in vivo (C6 othotopically allograft) models in response to low and high doses of X-ray radiation. Lower radiation doses were used to induce apoptosis, while high-dose levels were chosen to induce radiation necrosis. Our results demonstrate that active caspase-8 in this complex I induces apoptosis in response to low-dose radiation and inhibits necrosis by cleaving RIP1 and RI. When activation of caspase-8 was reduced at high doses of X-ray radiation, the RIP1/RIP3 necrosome complex II is formed. These complexes induce necrosis through the caspase-3-independent pathway mediated by calpain, cathepsin B/D, and apoptosis-inducing factor (AIF). AIF has a dual role in apoptosis and necrosis. At high doses, AIF promotes chromatinolysis and necrosis by interacting with histone H2AX. In addition, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. Analysis of inflammatory markers in matched plasma and cerebrospinal fluid (CSF) isolated from in vivo specimens demonstrated the upregulation of chemokines and cytokines during the necrosis phase. Using RIP1/RIP3 kinase specific inhibitors (Nec-1, GSK'872), we also establish that the RIP1-RIP3 complex regulates programmed necrosis after either high-dose radiation or TNF-α-induced necrosis requires RIP1 and RIP3 kinases. Overall, our data shed new light on the relationship between RIP1/RIP3-mediated programmed necrosis and AIF-mediated caspase-independent programmed necrosis in glioblastoma.

A randomized controlled trial of a diagnostic algorithm for symptoms of uncomplicated cystitis at an out-of-hours service

PubMed Central

Grude, Nils; Lindbaek, Morten

2015-01-01

Objective. To compare the clinical outcome of patients presenting with symptoms of uncomplicated cystitis who were seen by a doctor, with patients who were given treatment following a diagnostic algorithm. Design. Randomized controlled trial. Setting. Out-of-hours service, Oslo, Norway. Intervention. Women with typical symptoms of uncomplicated cystitis were included in the trial in the time period September 2010–November 2011. They were randomized into two groups. One group received standard treatment according to the diagnostic algorithm, the other group received treatment after a regular consultation by a doctor. Subjects. Women (n = 441) aged 16–55 years. Mean age in both groups 27 years. Main outcome measures. Number of days until symptomatic resolution. Results. No significant differences were found between the groups in the basic patient demographics, severity of symptoms, or percentage of urine samples with single culture growth. A median of three days until symptomatic resolution was found in both groups. By day four 79% in the algorithm group and 72% in the regular consultation group were free of symptoms (p = 0.09). The number of patients who contacted a doctor again in the follow-up period and received alternative antibiotic treatment was insignificantly higher (p = 0.08) after regular consultation than after treatment according to the diagnostic algorithm. There were no cases of severe pyelonephritis or hospital admissions during the follow-up period. Conclusion. Using a diagnostic algorithm is a safe and efficient method for treating women with symptoms of uncomplicated cystitis at an out-of-hours service. This simplification of treatment strategy can lead to a more rational use of consultation time and a stricter adherence to National Antibiotic Guidelines for a common disorder. PMID:25961367

Augmented catecholamine uptake by the heart during hemorrhage in the conscious dog

NASA Technical Reports Server (NTRS)

Woodman, O. L.; Amano, J.; Hintze, T. H.; Vatner, S. F.

1986-01-01

Changes in arterial and coronary sinus concentrations of norepinephrine (NE) and epinephrine (E) in response to hemorrhage were examined in conscious dogs. Hemorrhage (45 +/- 3.2 ml/kg) decreased mean arterial pressure by 47 +/- 6%, left ventricular (LV) dP/dt by 38 +/- 6%, and mean left circumflex coronary blood flow by 47 +/- 6%, while heart rate increased by 44 +/- 13%. Increases in concentrations of arterial NE (5,050 +/- 1,080 from 190 +/- 20 pg/ml) and E (12,700 +/- 3,280 from 110 +/- 20 pg/ml) were far greater than increases in coronary sinus NE (1,700 +/- 780 from 270 +/- 50 pg/ml) and E (4,300 +/- 2,590 from 90 +/- 10 pg/ml). Net release of NE from the heart at rest was converted to a fractional extraction of 66 +/- 9% after hemorrhage. Fractional extraction of E increased from 16 +/- 6% at rest to 73 +/- 8% after hemorrhage. In cardiac-denervated dogs, hemorrhage (46 +/- 2.8 ml/kg) decreased mean arterial pressure by 39 +/- 15%, LV dP/dt by 36 +/- 10%, and mean left circumflex coronary blood flow by 36 +/- 13%, while heart rate increased by 24 +/- 10%. Hemorrhage increased arterial NE (1,740 +/- 150 from 210 +/- 30 pg/ml) and E (3,050 +/- 880 from 140 +/- 20 pg/ml) more than it increased coronary sinus NE (460 +/- 50 from 150 +/- 30 pg/ml) and E (660 +/- 160 from 90 +/- 20 pg/ml) but significantly less (P less than 0.05) than observed in intact dogs. These experiments indicate that hemorrhage, unlike exercise and sympathetic nerve stimulation, does not induce net overflow of NE from the heart.(ABSTRACT TRUNCATED AT 250 WORDS).

Single Phase Dual-energy CT Angiography: One-stop-shop Tool for Evaluating Aneurysmal Subarachnoid Hemorrhage.

PubMed

Ni, Qian Qian; Tang, Chun Xiang; Zhao, Yan E; Zhou, Chang Sheng; Chen, Guo Zhong; Lu, Guang Ming; Zhang, Long Jiang

2016-05-25

Aneurysmal subarachnoid hemorrhages have extremely high case fatality in clinic. Early and rapid identifications of ruptured intracranial aneurysms seem to be especially important. Here we evaluate clinical value of single phase contrast-enhanced dual-energy CT angiograph (DE-CTA) as a one-stop-shop tool in detecting aneurysmal subarachnoid hemorrhage. One hundred and five patients who underwent true non-enhanced CT (TNCT), contrast-enhanced DE-CTA and digital subtraction angiography (DSA) were included. Image quality and detectability of intracranial hemorrhage were evaluated and compared between virtual non-enhanced CT (VNCT) images reconstructed from DE-CTA and TNCT. There was no statistical difference in image quality (P > 0.05) between VNCT and TNCT. The agreement of VNCT and TNCT in detecting intracranial hemorrhage reached 98.1% on a per-patient basis. With DSA as reference standard, sensitivity and specificity on a per-patient were 98.3% and 97.9% for DE-CTA in intracranial aneurysm detection. Effective dose of DE-CTA was reduced by 75.0% compared to conventional digital subtraction CTA. Thus, single phase contrast-enhanced DE-CTA is optimal reliable one-stop-shop tool for detecting intracranial hemorrhage with VNCT and intracranial aneurysms with DE-CTA with substantial radiation dose reduction compared with conventional digital subtraction CTA.

Single Phase Dual-energy CT Angiography: One-stop-shop Tool for Evaluating Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Ni, Qian Qian; Tang, Chun Xiang; Zhao, Yan E; Zhou, Chang Sheng; Chen, Guo Zhong; Lu, Guang Ming; Zhang, Long Jiang

2016-01-01

Aneurysmal subarachnoid hemorrhages have extremely high case fatality in clinic. Early and rapid identifications of ruptured intracranial aneurysms seem to be especially important. Here we evaluate clinical value of single phase contrast-enhanced dual-energy CT angiograph (DE-CTA) as a one-stop-shop tool in detecting aneurysmal subarachnoid hemorrhage. One hundred and five patients who underwent true non-enhanced CT (TNCT), contrast-enhanced DE-CTA and digital subtraction angiography (DSA) were included. Image quality and detectability of intracranial hemorrhage were evaluated and compared between virtual non-enhanced CT (VNCT) images reconstructed from DE-CTA and TNCT. There was no statistical difference in image quality (P > 0.05) between VNCT and TNCT. The agreement of VNCT and TNCT in detecting intracranial hemorrhage reached 98.1% on a per-patient basis. With DSA as reference standard, sensitivity and specificity on a per-patient were 98.3% and 97.9% for DE-CTA in intracranial aneurysm detection. Effective dose of DE-CTA was reduced by 75.0% compared to conventional digital subtraction CTA. Thus, single phase contrast-enhanced DE-CTA is optimal reliable one-stop-shop tool for detecting intracranial hemorrhage with VNCT and intracranial aneurysms with DE-CTA with substantial radiation dose reduction compared with conventional digital subtraction CTA. PMID:27222163

Placenta previa and maternal hemorrhagic morbidity.

PubMed

Gibbins, Karen J; Einerson, Brett D; Varner, Michael W; Silver, Robert M

2018-02-01

Placenta previa is associated with maternal hemorrhage, but most literature focuses on morbidity in the setting of placenta accreta. We aim to characterize maternal morbidity associated with previa and to define risk factors for hemorrhage. This is a secondary cohort analysis of the NICHD Maternal-Fetal Medicine Units Network Cesarean Section Registry. This analysis included all women undergoing primary Cesarean delivery without placenta accreta. About 496 women with previa were compared with 24,201 women without previa. Primary outcome was composite maternal hemorrhagic morbidity. Non-hemorrhagic morbidities and risk factors for hemorrhage were also evaluated. Maternal hemorrhagic morbidity was more common in women with previa (19 versus 7%, aRR 2.6, 95% CI 1.9-3.5). Atony requiring uterotonics (aRR 3.1, 95% CI 2.0-4.9), red blood cell transfusion (aRR 3.8, 95% CI 2.5-5.7), and hysterectomy (aRR 5.1, 95% CI 1.5-17.3) were also more common with previa. For women with previa, factors associated with maternal hemorrhage were pre-delivery anemia, thrombocytopenia, diabetes, magnesium use, and general anesthesia. Placenta previa is an independent risk factor for maternal hemorrhagic morbidity. Some risk factors are modifiable, but many are intrinsic to the clinical scenario.

Effects of C1 Inhibitor on Tissue Damage in a Porcine Model of Controlled Hemorrhage

DTIC Science & Technology

2012-07-01

and cytokine release and improves metabolic acidosis in a porcine model of hemorrhagic shock. Male Yorkshire swine were assigned to experimental groups...damage in a dose-dependent man- ner (100 and 250 IU/kg). In addition, rhC1-INH (250 IU/kg) markedly improved hemorrhage-induced metabolic acidosis ... acidosis , reduced circulating tumor necrosis factor !, and attenuated tissue damage in this model. The observed beneficial effects of rhC1-INH treatment on

Complementary and Alternative Therapies as Treatment Approaches for Interstitial Cystitis

PubMed Central

Whitmore, Kristene E

2002-01-01

The management of interstitial cystitis (IC) is predominantly the reduction of the symptoms of frequency, urgency, and pain. Multimodal treatment approaches for IC are helpful in customizing therapy for individual patients. Complementary and alternative therapies are a quintessential addition to the therapeutic armamentarium and frequently include dietary modification, nutraceuticals, bladder training, neuromodulation, stress reduction, and sex therapy. Dietary modification involves elimination of bladder irritants, fluid regulation, and a bowel regimen. Nutraceuticals studied for the treatment of IC include calcium glycerophosphate, L-arginine, mucopolysaccharides, bioflavinoids, and Chinese herbs. Bladder training is effective after pain reduction. The neuromodulation of high-tone pelvic-floor muscle dysfunction is achieved with physical therapy and acupuncture. Stress reduction and sex therapy are best administered by a qualified stress manager and sex therapist. Multimodal, nonconventional management may add efficacy to the treatment of IC. PMID:16986031

Interstitial cystitis patients' use and rating of complementary and alternative medicine therapies.

PubMed

O'Hare, Peter Gregory; Hoffmann, Amy Rejba; Allen, Penny; Gordon, Barbara; Salin, Linda; Whitmore, Kristene

2013-06-01

The purpose of this study was to describe the use of complementary and alternative medicine (CAM) therapies among interstitial cystitis (IC) patients, patients' perception of CAM therapies' effectiveness, and the association of time since diagnosis with perceived effectiveness of these therapies. In April 2009, the Interstitial Cystitis Association (ICA) initiated an Internet-based survey on CAM. Respondents indicated whether they received an IC diagnosis and how long ago, whether they tried CAM, and who recommended it. On a 5-point scale, respondents rated 49 therapies. For respondents confirming a diagnosis, we used a chi-square goodness-of-fit test to assess which therapies were rated positively or negatively by a majority of patients who tried them. Using separate one-way analyses of variance, we assessed differences in mean perceived effectiveness among groups based on time since diagnosis and conducted post hoc tests, if necessary. Using chi-square tests, we explored the association of time since diagnosis with the use of CAM and the number of therapies tried. A total of 2,101 subjects responded to the survey; 1,982 confirmed an IC diagnosis. Most (84.2 %) had tried CAM, and 55 % said physicians had recommended CAM. Of those trying CAM, 82.8 % had tried diet or physical therapy and 69.2 % other therapies. Of the therapies, 22 were rated positively and 20 negatively; 7 were inconclusive. Therapies patients perceived to be helpful included dietary management and pain management adjuncts such as physical therapy, heat and cold, meditation and relaxation, acupuncture, stress reduction, exercise, and sleep hygiene. Many therapies worked better for those diagnosed recently than for those diagnosed long before. Randomized, placebo-controlled studies are needed to demonstrate which therapies may indeed control IC symptoms and help send research in new and productive directions.

3D ultrasound Nakagami imaging for radiation-induced vaginal fibrosis

NASA Astrophysics Data System (ADS)

Yang, Xiaofeng; Rossi, Peter; Shelton, Joseph; Bruner, Debrorah; Tridandapani, Srini; Liu, Tian

2014-03-01

Radiation-induced vaginal fibrosis is a debilitating side-effect affecting up to 80% of women receiving radiotherapy for their gynecological (GYN) malignancies. Despite the significant incidence and severity, little research has been conducted to identify the pathophysiologic changes of vaginal toxicity. In a previous study, we have demonstrated that ultrasound Nakagami shape and PDF parameters can be used to quantify radiation-induced vaginal toxicity. These Nakagami parameters are derived from the statistics of ultrasound backscattered signals to capture the physical properties (e.g., arrangement and distribution) of the biological tissues. In this paper, we propose to expand this Nakagami imaging concept from 2D to 3D to fully characterize radiation-induced changes to the vaginal wall within the radiation treatment field. A pilot study with 5 post-radiotherapy GYN patients was conducted using a clinical ultrasound scanner (6 MHz) with a mechanical stepper. A serial of 2D ultrasound images, with radio-frequency (RF) signals, were acquired at 1 mm step size. The 2D Nakagami shape and PDF parameters were calculated from the RF signal envelope with a sliding window, and then 3D Nakagami parameter images were generated from the parallel 2D images. This imaging method may be useful as we try to monitor radiation-induced vaginal injury, and address vaginal toxicities and sexual dysfunction in women after radiotherapy for GYN malignancies.

The influence of oxazaphosphorines alkylating agents on autonomic nervous system activity in rat experimental cystitis model.

PubMed

Dobrek, Łukasz; Baranowska, Agnieszka; Thor, Piotr J

2013-01-01

The oxazaphosphorines alkylating agents (cyclophosphamide; CP and ifosfamide; IF) are often used in common clinical practice. However, treatment with CP/IF is burdened with the risk of many adverse drug reactions, especially including hemorrhagic cystitis (HC) that is associated with bladder overactivity symptoms (OAB). The HC pathophysiology is still not fully displayed; it seems that autonomic nervous system (ANS) functional abnormalities play important role in this disturbance. The aim of our study was to reveal the potential ANS differences in rat experimental HC model, evoked by CP and IF by an indirect ANS assessment--heart rate variability (HRV) study. We carried out our experimental research in three essential groups: control group (group 1), cyclophosphamide-induced HC (CP-HC; group 2) one and ifosfamide-induced HC (IF-HC; group 3) one. CP was i.p. administrated four times in dose of 75 mg/kg body weight while IF-treated rats received i.p. five drug doses; 50 mg/kg body weight. Control rats were administrated i.p. vehicle in appropriate volumes as CP/IF treated animals. HRV studies were performed the next day after the last oxazaphosphorines dose. Standard time- and spectral (frequency) domain parameters were estimated. We confirmed the HC development after both CP/IF in macroscopic assessment and bladder wet weight measurement; however, it was more aggravated in CP-HC group. Moreover, we demonstrated HRV disturbances, suggesting ANS impairment after both studied oxazaphosphorines, however, consistent with the findings mentioned above, the autonomic dysfunction was more emphasized after CP. CP treatment was also associated with changes of non-normalized HRV spectral components percentage distribution--a marked very low frequency--VLF [%] increase together with low frequency--LF [%] and high frequency--HF [%] decrease were observed. Taking into consideration the next findings, demonstrating the lack of both normalized power spectral components (nLF and n

Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study.

PubMed

Miglioretti, Diana L; Lange, Jane; van den Broek, Jeroen J; Lee, Christoph I; van Ravesteyn, Nicolien T; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J; Melnikow, Joy; de Koning, Harry J; Hubbard, Rebecca A

2016-02-16

Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. 2 simulation-modeling approaches. U.S. population. Women aged 40 to 74 years. Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened. Annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100,000 women) than other women (113 cancer cases and 15 deaths per 100,000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold. Life-years lost from radiation-induced breast cancer could not be estimated. Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer. Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

Clinical and dosimetric factors of radiation-induced esophageal injury: radiation-induced esophageal toxicity.

PubMed

Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

2005-05-07

To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus > or =60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). Concurrent chemotherapy and the maximal esophageal point dose > or =60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT.

Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

PubMed

Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

2013-05-01

Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. Copyright © 2013 Elsevier B.V. All rights reserved.

Purinergic signaling triggers endfoot high-amplitude Ca2+ signals and causes inversion of neurovascular coupling after subarachnoid hemorrhage

PubMed Central

Pappas, Anthony C; Koide, Masayo

2016-01-01

Neurovascular coupling supports brain metabolism by matching focal increases in neuronal activity with local arteriolar dilation. Previously, we demonstrated that an emergence of spontaneous endfoot high-amplitude Ca2+ signals (eHACSs) caused a pathologic shift in neurovascular coupling from vasodilation to vasoconstriction in brain slices obtained from subarachnoid hemorrhage model animals. Extracellular purine nucleotides (e.g., ATP) can trigger astrocyte Ca2+ oscillations and may be elevated following subarachnoid hemorrhage. Here, the role of purinergic signaling in subarachnoid hemorrhage-induced eHACSs and inversion of neurovascular coupling was examined by imaging parenchymal arteriolar diameter and astrocyte Ca2+ signals in rat brain slices using two-photon fluorescent and infrared-differential interference contrast microscopy. We report that broad-spectrum inhibition of purinergic (P2) receptors using suramin blocked eHACSs and restored vasodilatory neurovascular coupling after subarachnoid hemorrhage. Importantly, eHACSs were also abolished using a cocktail of inhibitors targeting Gq-coupled P2Y receptors. Further, activation of P2Y receptors in brain slices from un-operated animals triggered high-amplitude Ca2+ events resembling eHACSs and disrupted neurovascular coupling. Neither tetrodotoxin nor bafilomycin A1 affected eHACSs suggesting that purine nucleotides are not released by ongoing neurotransmission and/or vesicular release after subarachnoid hemorrhage. These results indicate that purinergic signaling via P2Y receptors contributes to subarachnoid hemorrhage-induced eHACSs and inversion of neurovascular coupling. PMID:27207166

Purinergic signaling triggers endfoot high-amplitude Ca2+ signals and causes inversion of neurovascular coupling after subarachnoid hemorrhage.

PubMed

Pappas, Anthony C; Koide, Masayo; Wellman, George C

2016-11-01

Neurovascular coupling supports brain metabolism by matching focal increases in neuronal activity with local arteriolar dilation. Previously, we demonstrated that an emergence of spontaneous endfoot high-amplitude Ca 2+ signals (eHACSs) caused a pathologic shift in neurovascular coupling from vasodilation to vasoconstriction in brain slices obtained from subarachnoid hemorrhage model animals. Extracellular purine nucleotides (e.g., ATP) can trigger astrocyte Ca 2+ oscillations and may be elevated following subarachnoid hemorrhage. Here, the role of purinergic signaling in subarachnoid hemorrhage-induced eHACSs and inversion of neurovascular coupling was examined by imaging parenchymal arteriolar diameter and astrocyte Ca 2+ signals in rat brain slices using two-photon fluorescent and infrared-differential interference contrast microscopy. We report that broad-spectrum inhibition of purinergic (P2) receptors using suramin blocked eHACSs and restored vasodilatory neurovascular coupling after subarachnoid hemorrhage. Importantly, eHACSs were also abolished using a cocktail of inhibitors targeting G q -coupled P2Y receptors. Further, activation of P2Y receptors in brain slices from un-operated animals triggered high-amplitude Ca 2+ events resembling eHACSs and disrupted neurovascular coupling. Neither tetrodotoxin nor bafilomycin A1 affected eHACSs suggesting that purine nucleotides are not released by ongoing neurotransmission and/or vesicular release after subarachnoid hemorrhage. These results indicate that purinergic signaling via P2Y receptors contributes to subarachnoid hemorrhage-induced eHACSs and inversion of neurovascular coupling. © The Author(s) 2016.

The Effects of the Contact Activation System on Hemorrhage

PubMed Central

Simão, Fabrício; Feener, Edward P.

2017-01-01

The contact activation system (CAS) exerts effects on coagulation via multiple mechanisms, which modulate both the intrinsic and extrinsic coagulation cascades as well as fibrinolysis and platelet activation. While the effects of the CAS on blood coagulation measured as activated partial thromboplastin time shortening are well documented, genetic mutations that result in deficiencies in the expression of either plasma prekallikrein (PPK) or factor XII (FXII) are not associated with spontaneous bleeding or increased bleeding risk during surgery. Deficiencies in these proteins are often undiagnosed for decades and detected later in life during routine coagulation assays without an apparent clinical phenotype. Increased interest in the CAS as a potentially safe target for antithrombotic therapies has emerged, in large part, from studies on animal models with provoked thrombosis, which have shown that deficiencies in PPK or FXII can reduce thrombus formation without increasing bleeding. Gene targeting and pharmacological studies in healthy animals have confirmed that PPK and FXII blockade does not cause coagulopathies. These findings support the conclusion that CAS is not required for hemostasis. However, while deficiencies in FXII and PPK do not significantly affect bleeding associated with peripheral wounds, recent reports have demonstrated that these proteins can promote hemorrhage in the retina and brain. Intravitreal injection of plasma kallikrein (PKal) induces retinal hemorrhage and intracerebral injection of PKal increases intracranial bleeding. PPK deficiency and PKal inhibition ameliorates hematoma formation following cerebrovascular injury in diabetic animals. Moreover, both PPK and FXII deficiency are protective against intracerebral hemorrhage caused by tissue plasminogen activator-mediated thrombolytic therapy in mice with thrombotic middle cerebral artery occlusion. Thus, while the CAS is not required for hemostasis, its inhibition may provide an

An experimental study of the neurophysical mechanisms of photophobia induced by subarachnoid hemorrhage.

PubMed

Aydin, Nazan; Kotan, Dilcan; Keles, Sadullah; Ondas, Osman; Aydin, Mehmet Dumlu; Baykal, Orhan; Gundogdu, Betul

2016-09-06

Photophobia is defined as a painful psychosomatic discomfort triggered by intense light flow through the pupils to the brain, but the exact mechanism through which photophobia is induced by subarachnoid hemorrhage (SAH) is not well understood. In this study, we aimed to investigate whether there was any relationship between the mydriasis induced by the degeneration of the ciliary ganglion (CG) and photophobia in instances of SAH. Five of a total of 25 rabbits were used as the intact control group; five were used in the sham-operated control group; and the remaining 15 were used as the SAH group, which was created by injecting autologous blood into their cisterna magna. All animals were examined daily for 20days to evaluate their level of photophobia, after which their brains, CGs and superior cervical ganglia (SCGs) were extracted bilaterally. The densities of normal and degenerated neurons in these ganglia were examined by stereological methods. In SAH animals with a high photophobia score, the mean pupil diameter and density of degenerated neurons density in the CG were greater than in cases with a low photophobia score (p<0.05). Further analysis revealed that the increase in the density of degenerated neurons in the CG following SAH resulted in the paralysis of the parasympathetic pathway of the pupillary muscles and mydriasis, which facilitates the excessive transfer of light to the brain and photophobia. Our findings indicate that SAH results in a high density of degenerated neurons in the CG, which induces mydriasis and is an important factor in the onset of photophobia. This phenomenon is likely due to more light energy being transferred through mydriatic pupils to the brain, resulting in vasospasm of the supplying arteries. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

PubMed Central

Hughes, Adrienne; Brown, Alisha; Valento, Matthew

2016-01-01

Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects. PMID:27625729

Radiation-Induced Breast Cancer Incidence and Mortality from Digital Mammography Screening: A Modeling Study

PubMed Central

Miglioretti, Diana L.; Lange, Jane; van den Broek, Jeroen J.; Lee, Christoph I.; van Ravesteyn, Nicolien T.; Ritley, Dominique; Kerlikowske, Karla; Fenton, Joshua J.; Melnikow, Joy; de Koning, Harry J.; Hubbard, Rebecca A.

2016-01-01

Background Estimates of radiation-induced breast cancer risk from mammography screening have not previously considered dose exposure variation or diagnostic work-up after abnormal screening. Objective To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening, considering exposure from screening and diagnostic mammography and dose variation across women. Design Two simulation-modeling approaches using common data on screening mammography from the Breast Cancer Surveillance Consortium and radiation dose from mammography from the Digital Mammographic Imaging Screening Trial. Setting U.S. population. Patients Women aged 40–74 years. Interventions Annual or biennial digital mammography screening from age 40, 45, or 50 until 74. Measurements Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality per 100,000 women screened (harms). Results On average, annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancers (95% confidence interval [CI]=88–178) leading to 16 deaths (95% CI=11–23) relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 radiation-induced breast cancers leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete breast examination (8% of population) were projected to have higher radiation-induced breast cancer incidence and mortality (266 cancers, 35 deaths per 100,000 women), compared to women with small or average breasts (113 cancers, 15 deaths per 100,000 women). Biennial screening starting at age 50 reduced risk of radiation-induced cancers 5-fold. Limitations We were unable to estimate years of life lost from radiation-induced breast cancer. Conclusions Radiation-induced breast cancer incidence and mortality from digital mammography screening are impacted by dose

Novel Potential Interacting Partners of Fibronectin in Spontaneous Animal Model of Interstitial Cystitis

PubMed Central

Treutlein, Gudrun; Dorsch, Roswitha; Euler, Kerstin N.; Hauck, Stefanie M.; Amann, Barbara; Hartmann, Katrin; Deeg, Cornelia A.

2012-01-01

Feline idiopathic cystitis (FIC) is the only spontaneous animal model for human interstitial cystitis (IC), as both possess a distinctive chronical and relapsing character. Underlying pathomechanisms of both diseases are not clearly established yet. We recently detected increased urine fibronectin levels in FIC cases. The purpose of this study was to gain further insight into the pathogenesis by assessing interacting partners of fibronectin in urine of FIC affected cats. Several candidate proteins were identified via immunoprecipitation and mass spectrometry. Considerable changes in FIC conditions compared to physiological expression of co-purified proteins were detected by Western blot and immunohistochemistry. Compared to controls, complement C4a and thioredoxin were present in higher levels in urine of FIC patients whereas loss of signal intensity was detected in FIC affected tissue. Galectin-7 was exclusively detected in urine of FIC cats, pointing to an important role of this molecule in FIC pathogenesis. Moderate physiological signal intensity of galectin-7 in transitional epithelium shifted to distinct expression in transitional epithelium under pathophysiological conditions. I-FABP expression was reduced in urine and urinary bladder tissue of FIC cats. Additionally, transduction molecules of thioredoxin, NF-κB p65 and p38 MAPK, were examined. In FIC affected tissue, colocalization of thioredoxin and NF-κB p65 could be demonstrated compared to absent coexpression of thioredoxin and p38 MAPK. These considerable changes in expression level and pattern point to an important role for co-purified proteins of fibronectin and thioredoxin-regulated signal transduction pathways in FIC pathogenesis. These results could provide a promising starting point for novel therapeutic approaches in the future. PMID:23236492

Low dose or low dose rate ionizing radiation-induced health effect in the human.

PubMed

Tang, Feng Ru; Loganovsky, Konstantin

2018-06-05

The extensive literature review on human epidemiological studies suggests that low dose ionizing radiation (LDIR) (≤100 mSv) or low dose rate ionizing radiation (LDRIR) (<6mSv/H) exposure could induce either negative or positive health effects. These changes may depend on genetic background, age (prenatal day for embryo), sex, nature of radiation exposure, i.e., acute or chronic irradiation, radiation sources (such as atomic bomb attack, fallout from nuclear weapon test, nuclear power plant accidents, 60 Co-contaminated building, space radiation, high background radiation, medical examinations or procedures) and radionuclide components and human epidemiological experimental designs. Epidemiological and clinical studies show that LDIR or LDRIR exposure may induce cancer, congenital abnormalities, cardiovascular and cerebrovascular diseases, cognitive and other neuropsychiatric disorders, cataracts and other eye and somatic pathology (endocrine, bronchopulmonary, digestive, etc). LDIR or LDRIR exposure may also reduce mutation and cancer mortality rates. So far, the mechanisms of LDIR- or LDRIR -induced health effect are poorly understood. Further extensive studies are still needed to clarify under what circumstances, LDIR or LDRIR exposure may induce positive or negative effects, which may facilitate development of new therapeutic approaches to prevent or treat the radiation-induced human diseases or enhance radiation-induced positive health effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Non-radiation induced signals in TL dosimetry.

PubMed

German, U; Weinstein, M

2002-01-01

One source of background signals, which are non-radiation related, is the reader system and it includes dark current, external contaminants and electronic spikes. These factors can induce signals equivalent to several hundredths of mSv. Mostly, the effects are minimised by proper design of the TLD reader, but some effects are dependent on proper operation of the system. The other main group of background signals originates in the TL crystal and is due to tribothermoluminescence, dirt, chemical reactions and stimulation by visible or UV light. These factors can have a significant contribution, equivalent to over several mSv, depending on whether the crystal is bare or protected by PTFE. Working in clean environments, monitoring continuously the glow curves and performing glow curve deconvolution are suggested to minimise non-radiation induced spurious signals.

Trichostatin A inhibits radiation-induced epithelial-to-mesenchymal transition in the alveolar epithelial cells

PubMed Central

Nagarajan, Devipriya; Wang, Lei; Zhao, Weiling; Han, Xiaochen

2017-01-01

Radiation-induced pneumonitis and fibrosis are major complications following thoracic radiotherapy. Epithelial-to-mesenchymal transition (EMT) plays an important role in tissue injury leading to organ fibrosis, including lung. Our previous studies have reported that radiation can induce EMT in the type II alveolar epithelial cells in both in vitro and in vivo. HDAC inhibitors are a new family of anti-cancer agents currently being used in several clinical trials. In addition to their intrinsic anti-tumor properties, HDAC inhibition is also important in other human diseases, including fibrosis and radiation-induced damage. In this study, we evaluated the effect of Trichostatin A (TSA), a HDAC inhibitor, on radiation-induced EMT in type II alveolar epithelial cells (RLE-6TN). Pre-treatment of RLE-6TN cells with TSA inhibited radiation-induced EMT-like morphological alterations including elevated protein level of α-SMA and Snail, reduction of E-cadherin expression, enhanced phosphorylation of GSK3β and ERK1/2, increased generation of ROS. Radiation enhanced the protein level of TGF-β1, which was blocked by N-acetylcysteine, an antioxidant. Treating cells with SB-431542, TGF-β1 type I receptor inhibitor, diminished radiation-induced alterations in the protein levels of p-GSK-3β, Snail-1 and α-SMA, suggesting a regulatory role of TGF-β1 in EMT. Pre-incubation of cells with TSA showed significant decrease in the level of TGF-β1 compared to radiation control. Collectively, these results demonstrate that i] radiation-induced EMT in RLE-6TN cells is mediated by ROS/MEK/ERK and ROS/TGF-β1 signaling pathways and ii] the inhibitory role of TSA in radiation-induced EMT appears to be due, at least in part, to its action of blocking ROS and TGF-β1 signaling. PMID:29254201

Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.

PubMed

Ou, Sai-Hong Ignatius; Weitz, Michael; Jalas, John R; Kelly, Daniel F; Wong, Vanessa; Azada, Michele C; Quines, Oliver; Klempner, Samuel J

2016-06-01

Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Progranulin Reduced Neuronal Cell Death by Activation of Sortilin 1 Signaling Pathways After Subarachnoid Hemorrhage in Rats.

PubMed

Li, Bo; He, Yue; Xu, Liang; Hu, Qin; Tang, Junjia; Chen, Yujie; Tang, Jiping; Feng, Hua; Zhang, John H

2015-08-01

Progranulin has been reported to have neuroprotective actions in cultured neurons. This study investigated the effect of recombinant rat progranulin on early brain injury after subarachnoid hemorrhage. Controlled in vivo laboratory study. Animal research laboratory. Two hundred thirty adult male Sprague-Dawley rats weighing 280-320 g. Subarachnoid hemorrhage was induced in rats by endovascular perforation. Rat recombinant progranulin (1 and 3 ng) was administrated intracerebroventricularly at 1.5 hours after subarachnoid hemorrhage. Progranulin small interfering RNA was administrated by intracerebroventricularly at 1 day before subarachnoid hemorrhage induction. Subarachnoid hemorrhage grade, neurologic score, and brain water content were measured at 24 and 72 hours after subarachnoid hemorrhage. Neural apoptosis was evaluated by double immunofluorescence staining using terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick-end labeling and neuronal nuclei. For mechanistic study, the expression of progranulin, phosphorylated Akt, Akt, p-Erk, Erk, Bcl-2, and cleaved caspase-3 were analyzed by Western blot at 24 hours after subarachnoid hemorrhage. siRNA for sortilin 1 (a progranulin receptor) was used to intervene the downstream pathway. The expression of progranulin decreased and reached the lowest point at 24 hours after subarachnoid hemorrhage. Administration of rat recombinant progranulin decreased brain water content and improved neurologic functions at both 24 and 72 hours after subarachnoid hemorrhage, while knockdown of endogenous progranulin aggravated neurologic deficits after subarachnoid hemorrhage. Rat recombinant progranulin treatment reduced neuronal apoptosis, while progranulin deficiency promoted neuronal apoptosis at 24 hours after subarachnoid hemorrhage. Rat recombinant progranulin promoted Akt activation, increased Bcl-2 level, but reduced caspase-3 level. Knockdown of progranulin binding factor sortilin 1

Dengue and Dengue Hemorrhagic Fever

PubMed Central

Gubler, Duane J.

1998-01-01

Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in the waning years of the 20th century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. A major challenge for public health officials in all tropical areas of the world is to devleop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever. PMID:9665979

NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages

PubMed Central

Liu, Yan-gang; Chen, Ji-kuai; Zhang, Zi-teng; Ma, Xiu-juan; Chen, Yong-chun; Du, Xiu-ming; Liu, Hong; Zong, Ying; Lu, Guo-cai

2017-01-01

A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death. We observed an increasing proportion of pyroptosis and elevating Caspase-1 activation in 10 and 20 Gy radiation groups. Nlrp3 knock out significantly diminished the quantity of cleaved-Caspase-1 (p10) and IL-1β as well as the proportion of pyroptosis. Additionally, in vivo research shows that 9.5 Gy of radiation promotes Caspase-1 activation in marginal zone cells and induces death in mice, both of which can be significantly inhibited by knocking out Nlrp3. Thus, based on these findings, we conclude that the NLRP3 inflammasome activation mediates radiation-induced pyroptosis in BMDMs. Targeting NLRP3 inflammasome and pyroptosis may serve as effective strategies to diminish injury caused by radiation. PMID:28151471

Multifocal lymphangioendotheliomatosis with devastating intracranial hemorrhage.

PubMed

Huang, Christina; Rizk, Elias; Iantosca, Mark; Zaenglein, Andrea L; Helm, Klaus F; Choudhary, Arabinda K; Dias, Mark S

2013-11-01

An in utero female was found to have a small hemorrhage at the foramen of Monro, hydrocephalus, and what was originally interpreted as a Dandy-Walker variant. At birth she had macrocephaly and numerous cutaneous, multifocal, red-pink blanchable macules. Postnatal MRI demonstrated a hemorrhagic soft-tissue mass involving the upper brainstem, thalamus, and basal ganglia most consistent with in utero complex multifocal intracranial hemorrhage. The skin lesions were thought to be consistent with multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT). The size and location of the hemorrhage precluded operative intervention, although the hydrocephalus was treated with a ventricular shunt. The child continues to have severe developmental delays. Multifocal lymphangioendotheliomatosis with thrombocytopenia is a multifocal vascular disorder most commonly involving the skin and gastrointestinal tract. Intracranial hemorrhages are rare in this context. This case is the third reported instance of MLT with associated intracranial hemorrhage and the only case described in the neurosurgical literature. The authors review the presenting features and pathophysiology of this condition.

Behavioral and Psychosocial Risk Factors Associated with First and Recurrent Cystitis in Indian Women: A Case-control Study

PubMed Central

Mishra, Bharti; Srivastava, Richa; Agarwal, Jyotsna; Srivastava, Sugandha; Pandey, Amita

2016-01-01

Background: The risk factors for urinary tract infections (UTIs) from developed countries are not applicable to women from developing world. Objective: To analyze the behavioral practices and psychosocial aspects pertinent to women in our region and assess their association with acute first time or recurrent UTI. Materials and Methods: Sexually active premenopausal women with their first (145) and recurrent (77) cystitis with Escherichia coli as cases and women with no prior history of UTI as healthy controls (257) were enrolled at a tertiary care hospital in India, between June 2011 and February 2013. Questionnaire-based data was collected from each participant through a structured face-to-face interview. Results: Using univariate and multivariate regression models, independent risk factors for the first episode of cystitis when compared with healthy controls were (presented in odds ratios [ORs] with its 95% confidence interval [CI]): Anal sex (OR = 3.68, 95% CI = 1.59-8.52), time interval between last sexual intercourse and current episode of UTI was <5 days (OR = 2.27, 95% CI = 1.22-4.23), use of cloth during menstrual cycle (OR = 2.36, 95% CI = 1.31-4.26), >250 ml of tea consumption per day (OR = 4.73, 95% CI = 2.67-8.38), presence of vaginal infection (OR = 3.23, 95% CI = 1.85-5.62) and wiping back to front (OR = 2.52, 95% CI = 1.45-4.38). Along with the latter three, history of UTI in a first-degree female relative (OR = 10.88, 95% CI = 2.41-49.07), constipation (OR = 4.85, 95% CI = 1.97-11.92) and stress incontinence (OR = 2.45, 95% CI = 1.18-5.06) were additional independent risk factors for recurrent cystitis in comparison to healthy controls. Conclusion: Most of the risk factors for initial infection are potentially modifiable but sufficient to also pose risk for recurrence. Many of the findings reflect the cultural and ethnic practices in our country. PMID:26917870

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock.

PubMed

Braga, D; Barcella, M; D'Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, M H; DeLano, F A; Baselli, G; Schmid-Schönbein, G W; Kistler, E B; Aletti, F; Barlassina, C

2017-08-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger's shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients.

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock

PubMed Central

Braga, D; Barcella, M; D’Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, MH; DeLano, FA; Baselli, G; Schmid-Schönbein, GW; Kistler, EB; Aletti, F

2017-01-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger’s shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients. PMID:28661205

Management of obstetric hemorrhage.

PubMed

Shevell, Tracy; Malone, Fergal D

2003-02-01

A reluctance to proceed with hysterectomy for obstetric hemorrhage may be a more likely cause of preventable death in obstetrics than a lack of surgical or medical skills. Every obstetric unit should have protocols available to deal with hemorrhage and, in addition, have specific guidelines for patients who object to blood transfusions for various reasons. Risk factors for hemorrhage should be identified antenatally, using all possible imaging modalities available, and utilizing multidisciplinary resources whenever possible. Novel strategies for prenatal diagnosis of abnormal placentation include advanced sonography and magnetic resonance imaging. Placement and utilization of arterial catheters for uterine artery embolization is becoming more widespread and new surgical technology such as the argon beam coagulator seems promising. When intra or postpartum hemorrhage is encountered, a familiar protocol for dealing with blood loss should be triggered. Timely hysterectomy should be performed for signs of refractory bleeding. Application of medical and surgical principles combined with recent technologic advances will help the obstetrician avoid disastrous outcomes for both mother and fetus.

Microwave hemorrhagic stroke detector

DOEpatents

Haddad, Waleed S.; Trebes, James E.

2002-01-01

The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stroke in human or animal patients as well as for the detection of hemorrhage within a patient's body.

Microwave hemorrhagic stroke detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haddad, Waleed S; Trebes, James E

The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device ismore » based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stoke in human or animal patients as well as for the detection of hemorrhage within a patient's body.« less

Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

PubMed

Langgartner, Dominik; Wachter, Ulrich; Hartmann, Clair; Gröger, Michael; Vogt, Josef; Merz, Tamara; McCook, Oscar; Fink, Marina; Kress, Sandra; Georgieff, Michael; Kunze, Julia F; Radermacher, Peter L; Reber, Stefan O; Wepler, Martin

2018-06-08

Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multiple-organ-failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

“Post partum hemorrhage: causes and management”

PubMed Central

2013-01-01

Background Post partum hemorrhage is defined as blood loss of 500 ml or above. It is the most common cause of pre-mature mortality of women world wide. Our objective was to evaluate the most common etiology and method of management of Post partum Hemorrhage in a tertiary care hospital of Karachi. Findings It was a cross sectional study conducted at Liaquat National Hospital Karachi, during the period of July 2011 to May 2012. Review include mode of delivery, possible cause of postpartum hemorrhage, supportive, medical and surgical interventions. All the women admitted with post partum hemorrhage or develop PPH in hospital after delivery were included in our study. Bleeding disorder and use of anticoagulants were set as exclusion criteria. Diagnosis was made on the basis of blood loss assessment which was made via subjective and objective evaluation. During the targeted months, out of total 1493 deliveries (26/1493 = 1.741%) 26 cases of post partum hemorrhage were reported with a mean age of 26.153 ± 7.37. No deaths were reported and all cases were referred and unbooked cases. All Patients were conscious, tachycardiac and hypotensive. Most of the women were suffering from hemorrhage during or after the birth of their 1st child. Primary post partum hemorrhage emerge as the most common type of post partum hemorrhage and uterine atony was detected as the most common cause of primary post partum hemorrhage. Retained products of conception was the most common cause of secondary post partum hemorrhage and hysterectomy was found to be the most frequent method of management of post partum hemorrhage. Conclusion This study highlights the existing variable practices for the management of postpartum hemorrhage. Hemorrhage associated morbidity and mortality can be prevented by critical judgment, early referral and resuscitation by attendants. Introduction of an evidence-based management model can potentially reduce the practice variability and improve the quality of

Results of endovesical hyaluronic acid/chondroitin sulfate in the treatment of Interstitial Cystitis/Painful Bladder Syndrome.

PubMed

Porru, D; Cervigni, M; Nasta, L; Natale, F; Lo Voi, R; Tinelli, C; Gardella, B; Anghileri, A; Spinillo, A; Rovereto, B

2008-05-01

The aim of our study was to test the effect of a more viscous compound than existent hyaluronic acid formulation in helping to restore a defective glycosaminoglycan layer, and therefore in improving Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) symptoms when administered intravesically in IC/PBS patients. A total of 23 female patients completed the study. Patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline, 40 ml, weekly for 12 weeks and then bi-weekly for 6 months, if there was initial response. After 12 weeks treatment both Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), pelvic pain and Urgency/Frequency Symptom Scale (PUF) showed a mean significant improvement, which was maintained thereafter. The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks' treatment period, with a significant reduction and increase, respectively. Mean voiding volume increased from 143 ml to 191, which apparently was not reflected in a corresponding reduction of number of daily voids (from 15,5 to 14). VAS values decreased from 5,4 to 3,6 (pain) and from 6,0 to 3,5 (urgency) after the treatment cycle, showing a significant improvement. In our preliminary experience, the administration of intravesical hyaluronic acid plus chondroitine sulphate appears to be a safe and efficacious method of treatment in IC/PBS.

Ionizing radiation-induced acoustics for radiotherapy and diagnostic radiology applications.

PubMed

Hickling, Susannah; Xiang, Liangzhong; Jones, Kevin C; Parodi, Katia; Assmann, Walter; Avery, Stephen; Hobson, Maritza; El Naqa, Issam

2018-04-21

Acoustic waves are induced via the thermoacoustic effect in objects exposed to a pulsed beam of ionizing radiation. This phenomenon has interesting potential applications in both radiotherapy dosimetry and treatment guidance as well as low dose radiological imaging. After initial work in the field in the 1980s and early 1990s, little research was done until 2013 when interest was rejuvenated, spurred on by technological advances in ultrasound transducers and the increasing complexity of radiotherapy delivery systems. Since then, many studies have been conducted and published applying ionizing radiation-induced acoustic principles into three primary research areas: Linear accelerator photon beam dosimetry, proton therapy range verification, and radiological imaging. This review article introduces the theoretical background behind ionizing radiation-induced acoustic waves, summarizes recent advances in the field, and provides an outlook on how the detection of ionizing radiation-induced acoustic waves can be used for relative and in vivo dosimetry in photon therapy, localization of the Bragg peak in proton therapy, and as a low-dose medical imaging modality. Future prospects and challenges for clinical implementation of these techniques are discussed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pathological examination of cerebral amyloid angiopathy in patients who underwent removal of lobar hemorrhages.

PubMed

Lin, Chien-Min; Arishima, Hidetaka; Kikuta, Ken-Ichiro; Naiki, Hironobu; Kitai, Ryuhei; Kodera, Toshiaki; Matsuda, Ken; Hashimoto, Norichika; Isozaki, Makoto; Tsunetoshi, Kenzo; Neishi, Hiroyuki; Higashino, Yoshifumi; Akazawa, Ayumi; Arai, Hiroshi; Yamada, Shinsuke

2018-03-01

Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-β (Aβ) deposition in the brain microvessels. CAA is also known to contribute not only to cortical microbleeds but also lobar hemorrhages. This retrospective study examined CAA pathologically in patients who underwent direct surgeries for lobar hemorrhage. Thirty-three patients with lobar hemorrhage underwent open surgery with biopsy from 2007 to 2016 in our hospital. Cortical tissues over hematomas obtained surgically were pathologically examined using hematoxylin, eosin stain, and anti-Aβ antibody to diagnose CAA. We also investigated the advanced degree of CAA and clinical features of each patient with lobar hemorrhage. In the 33 patients, 4 yielded specimens that were insufficient to evaluate CAA pathologically. Twenty-four of the remaining 29 patients (82.8%) were pathologically diagnosed with CAA. The majority of CAA-positive patients had moderate or severe CAA based on a grading scale to estimate the advanced degree of CAA. About half of the CAA-positive patients had hypertension, and four took anticoagulant or antiplatelet agents. In five patients who were not pathologically diagnosed with CAA, one had severe liver function disorder, three had uncontrollable hypertension, and one had no obvious risk factor. Our pathological findings suggest that severe CAA with vasculopathic change markedly contributes to lobar hemorrhage. The coexistence of severe CAA and risk factors such as hypertension, anticoagulants or antiplatelets may readily induce lobar hemorrhage.

Diffuse optical monitoring of peripheral tissues during uncontrolled internal hemorrhage in a porcine model

PubMed Central

Vishwanath, Karthik; Gurjar, Rajan; Wolf, David; Riccardi, Suzannah; Duggan, Michael; King, David

2018-01-01

Reliable, continuous and noninvasive blood flow and hemoglobin monitoring in trauma patients remains a critical, but generally unachieved goal. Two optical sensing methods - diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) – are used to monitor and detect internal hemorrhage. Specifically, we investigate if cutaneous perfusion measurements acquired using DCS and DRS in peripheral (thighs and ear-lobe) tissues could detect severe hemorrhagic shock in a porcine model. Four animals underwent high-grade hepato-portal injury in a closed abdomen, to induce uncontrolled hemorrhage and were subsequently allowed to bleed for 10 minutes before fluid resuscitation. DRS and DCS measurements of cutaneous blood flow were acquired using fiber optical probes placed on the thigh and earlobe of the animals and were obtained repeatedly starting from 1 to 5 minutes pre-injury, up to several minutes post shock. Clear changes were observed in measured optical spectra across all animals at both sites. DCS-derived cutaneous blood flow decreased sharply during hemorrhage, while DRS-derived vascular saturation and hemoglobin paralleled cardiac output. All derived optical parameters had the steepest changes during the rapid initial hemorrhage unambiguously. This suggests that a combined DCS and DRS based device might provide an easy-to-use, non-invasive, internal-hemorrhage detection system that can be used across a wide array of clinical settings. PMID:29552394

Superstition and post-tonsillectomy hemorrhage.

PubMed

Kumar, Veena V; Kumar, Naveen V; Isaacson, Glenn

2004-11-01

The objective was to determine whether post-tonsillectomy hemorrhages occur more frequently in redheaded children, in patterns of threes, on Friday-the-13th days, or with the full moon. Case-control analysis. The authors performed multiple statistical analyses of all children undergoing tonsillectomy at Temple University Children's Medical Center (Philadelphia, PA) during a 29-month period. Children readmitted to the hospital with or without surgical control of bleeding were compared with children who did not bleed. Relation of post-tonsillectomy hemorrhages to the phase of the moon was evaluated using a standard normal deviate. The frequency of surgery performed on Friday-the-13th days was compared with a differently dated Friday chosen at random. Clusters of three hemorrhages in a 7-day period were recorded. Families of children were contacted and asked whether their child had red hair. A chi analysis compared redheaded and non-redheaded tonsillectomy patients. Twenty-eight of 589 tonsillectomy cases performed required readmission for bleeding events. Twenty tonsillectomies occurred on a full-moon day, resulting in one bleeding event. One cluster of three post-tonsillectomy hemorrhages occurred in a 7-day period. Four of the children who bled had red hair. Two tonsillectomies occurred on Friday the 13th, with no associated hemorrhage. Statistical analysis revealed a random pattern to post-tonsillectomy hemorrhage. Post-tonsillectomy hemorrhages do not occur in clusters of three and are not more frequent with the full moon or on Friday the 13th. The bleeding rate among children with red hair is similar to that of non-redheaded children.

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

PubMed Central

Balentova, Sona; Adamkov, Marian

2015-01-01

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

The effect of radiation dose on the onset and progression of radiation-induced brain necrosis in the rat model.

PubMed

Hartl, Brad A; Ma, Htet S W; Hansen, Katherine S; Perks, Julian; Kent, Michael S; Fragoso, Ruben C; Marcu, Laura

2017-07-01

To provide a comprehensive understanding of how the selection of radiation dose affects the temporal and spatial progression of radiation-induced necrosis in the rat model. Necrosis was induced with a single fraction of radiation exposure, at doses ranging between 20 and 60 Gy, to the right hemisphere of 8-week-old Fischer rats from a linear accelerator. The development and progression of necrosis in the rats was monitored and quantified every other week with T1- and T2-weighted gadolinium contrast-enhanced MRI studies. The time to onset of necrosis was found to be dose-dependent, but after the initial onset, the necrosis progression rate and total volume generated was constant across different doses ranging between 30 and 60 Gy. Radiation doses less than 30 Gy did not develop necrosis within 33 weeks after treatment, indicating a dose threshold existing between 20 and 30 Gy. The highest dose used in this study led to the shortest time to onset of radiation-induced necrosis, while producing comparable disease progression dynamics after the onset. Therefore, for the radiation-induced necrosis rat model using a linear accelerator, the most optimum results were generated from a dose of 60 Gy.

Challenges in Clinical Management of Radiation-Induced Illnesses in Exploration Spaceflight

NASA Technical Reports Server (NTRS)

Blue, Rebecca; Chancellor, Jeffery; Suresh, Rahul; Carnell, Lisa; Reyes, David; Nowadly, Craig; Antonsen, Erik

2018-01-01

Historical solar particle events (SPEs) provide context for some understanding of acute radiation exposure risk to astronauts traveling outside of low Earth orbit. Modeling of potential doses delivered to exploration crewmembers anticipates limited radiation-induced health impacts, including prodromal symptoms of nausea, emesis, and fatigue, but suggests that more severe clinical manifestations are unlikely. Recent large animal-model research in space-analogs closely mimicking SPEs has identified coagulopathic events independent of the hematopoietic sequelae of higher radiation doses, similar in manifestation to disseminated intravascular coagulation (DIC). We explored the challenges of clinical management of radiation-related clinical manifestations, using currently accepted modeling techniques and anticipated physiological sequelae, to identify medical capabilities needed to successfully manage SPE-induced radiation illnesses during exploration spaceflight.

[Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications].

PubMed

Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna

2009-08-18

It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a

Heparin use in a rat hemorrhagic shock model induces biologic activity in mesenteric lymph separate from shock

PubMed Central

Qin, Yong; Prescott, Lauriston M.; Deitch, Edwin A.; Kaiser, Vicki L.

2011-01-01

Experimental data has shown that mesenteric lymph from rats subjected to trauma-hemorrhagic shock (THS) but not trauma-sham shock (TSS) induces neutrophil activation, cytotoxicity, decreased red blood cell deformability and bone marrow colony growth suppression. These data have lead to the hypothesis that gut factors produced from THS enter the systemic circulation via the mesenteric lymphatics and contribute to the progression of Multiple Organ Failure (MOF) following THS. Ongoing studies designed to identify bioactive lymph agents implicated factors associated with the heparin use in the THS procedure. We investigated if heparin itself was responsible for reported toxicity to human umbilical vein endothelial cells (HUVECs). HUVEC toxicity was not induced by lymph when alternate anti-coagulants (citrate and EDTA) were used in THS. HUVEC toxicity was induced by lymph after heparin but not saline or citrate injection into TSS and naïve animals and was dose dependent. Activities of both heparin-releasable lipases (lipoprotein (LPL) and hepatic (HL)) were detected in the plasma and lymph from THS and naïve animals receiving heparin but not citrate or saline. Lymph-induced HUVEC toxicity correlated with lymph lipase activities. Finally, incubation of HUVECs with purified LPL added to naïve lymph induced toxicity in vitro. These data show that heparin, not THS, is responsible for the reported lymph-mediated HUVEC toxicity through its release of lipases into the lymph. These findings can provide alternative explanations for several of the THS effects reported in the literature using heparin models thus necessitating a review of previous work in this field. PMID:21063238

Heparin use in a rat hemorrhagic shock model induces biologic activity in mesenteric lymph separate from shock.

PubMed

Qin, Yong; Prescott, Lauriston M; Deitch, Edwin A; Kaiser, Vicki L

2011-04-01

Experimental data have shown that mesenteric lymph from rats subjected to trauma-hemorrhagic shock (THS) but not trauma-sham shock induces neutrophil activation, cytotoxicity, decreased red blood cell (RBC) deformability, and bone marrow colony growth suppression. These data have led to the hypothesis that gut factors produced from THS enter the systemic circulation via the mesenteric lymphatics and contribute to the progression of multiple organ failure after THS. Ongoing studies designed to identify bioactive lymph agents implicated factors associated with the heparin use in the THS procedure. We investigated if heparin itself was responsible for reported toxicity to human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cell toxicity was not induced by lymph when alternate anticoagulants (citrate and EDTA) were used in THS. Human umbilical vein endothelial cell toxicity was induced by lymph after heparin but not saline or citrate injection into trauma-sham shock and naive animals and was dose dependent. Activities of both heparin-releasable lipases (lipoprotein and hepatic) were detected in the plasma and lymph from THS and naive animals receiving heparin but not citrate or saline. Lymph-induced HUVEC toxicity correlated with lymph lipase activities. Finally, incubation of HUVECs with purified lipoprotein lipase added to naive lymph-induced toxicity in vitro. These data show that heparin, not THS, is responsible for the reported lymph-mediated HUVEC toxicity through its release of lipases into the lymph. These findings can provide alternative explanations for several of the THS effects reported in the literature using heparin models, thus necessitating a review of previous work in this field.

THE 5-LIPOXYGENASE PATHWAY IS REQUIRED FOR ACUTE LUNG INJURY FOLLOWING HEMORRHAGIC SHOCK

PubMed Central

Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijón, Miguel A.; Murphy, Robert C.

2012-01-01

The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury. PMID:22392149

Rebamipide alleviates radiation-induced colitis through improvement of goblet cell differentiation in mice.

PubMed

Jang, Hyosun; Park, Sunhoo; Lee, Janet; Myung, Jae Kyung; Jang, Won-Suk; Lee, Sun-Joo; Myung, Hyunwook; Lee, Changsun; Kim, Hyewon; Lee, Seung-Sook; Jin, Young-Woo; Shim, Sehwan

2018-04-01

Radiation-induced colitis is a common clinical problem associated with radiotherapy and accidental exposure to ionizing radiation. Goblet cells play a pivotal role in the intestinal barrier against pathogenic bacteria. Rebamipide, an anti-gastric ulcer drug, has the effects to promote goblet cell proliferation. The aim of this study was to investigate whether radiation-induced colonic injury could be alleviated by rebamipide. This study orally administered rebamipide for 6 days to mice, which were subjected to 13 Gy abdominal irradiation, to evaluate the therapeutic effects of rebamipide against radiation-induced colitis. To confirm the effects of rebamipide on irradiated colonic epithelial cells, this study used the HT29 cell line. Rebamipide clearly alleviated the acute radiation-induced colitis, as reflected by the histopathological data, and significantly increased the number of goblet cells. The drug also inhibited intestinal inflammation and protected from bacterial translocation during acute radiation-induced colitis. Furthermore, rebamipide significantly increased mucin 2 expression in both the irradiated mouse colon and human colonic epithelial cells. Additionally, rebamipide accelerated not only the recovery of defective tight junctions but also the differentiation of impaired goblet cells in an irradiated colonic epithelium, which indicates that rebamipide has beneficial effects on the colon. Rebamipide is a therapeutic candidate for radiation-induced colitis, owing to its ability to inhibit inflammation and protect the colonic epithelial barrier. © 2017 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Viral hemorrhagic septicemia

USGS Publications Warehouse

Batts, William N.; Winton, James R.

2012-01-01

Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae

Acral Hemorrhagic Darier Disease.