Effect of two different extracts of red maca in male rats with testosterone-induced prostatic hyperplasia.

PubMed

Gonzales, Gustavo F; Vasquez, Vanessa; Rodriguez, Daniella; Maldonado, Carmen; Mormontoy, Juliet; Portella, Jimmy; Pajuelo, Monica; Villegas, León; Gasco, Manuel

2007-03-01

To determine the effect of two different extracts of red maca in male rats. Prostatic hyperplasia was induced in male rats with testosterone enanthate (TE). The study comprised six groups: one control group (group 1), one group treated with TE (group 2), two groups treated with TE and aqueous extract of red maca (groups 3 and 4), one group treated with hydroalcoholic extract of red maca (group 5) and one group treated with finasteride (0.1 mg, group 6). Differences in the aqueous extract dependent on the length of time of boiling, whether for 2 or 3 hours, for groups 3 and 4 was assessed. Extracts of red maca contained 0.1 mg of benzylglucosinolate. Thereafter, a dose-response effect of different doses of benzylglucosinolates (0.02-0.08 mg) in red maca extracts was assessed. Prostate weight was similar in rats treated with freeze-dried aqueous extract of red maca prepared after 2 and 3 hours of boiling. Freeze-dried aqueous extract of red maca, hydroalcoholic extract of red maca and finasteride reduced prostate weight in rats with prostatic hyperplasia. No difference was observed between the data obtained from aqueous extract or hydroalcoholic extract of red maca. A dose dependent reduction of prostate weight was observed with the increase of the dose of benzylglucosinolates in red maca extracts. The present study showed that hydroalcoholic or aqueous extract of red maca containing 0.1 mg of benzylglucosinolate can reduce prostate size in male rats in which prostatic hyperplasia had been induced by TE.

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

PubMed

Simão, Vinícius Augusto; Berloffa Belardin, Larissa; Araújo Leite, Gabriel Adan; de Almeida Chuffa, Luiz Gustavo; Camargo, Isabel Cristina Cherici

2015-10-01

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg body weight, or received mineral oil (control group) for 15 days, subcutaneously. All animals were divided into three groups according to the treatment periods: (i) ND treatment for 15 days; (ii) ND treatment followed by a 30-day recovery; and (iii) ND treatment followed by a 60-day recovery. Estrous cycle was monitored daily, and at the end of each period, the animals were euthanized for histopathological analysis. During ND treatment and after 30-day recovery, all animals exhibited persistent diestrus. After a 60-day recovery, persistent diestrus was only maintained in the group that had received the highest dose. Ovarian weight was decreased significantly after the 30-day recovery, regardless of ND doses, compared with the control group. There was a reduction (P < 0.05) in the number of corpora lutea and antral and growing follicles, in contrast to an increase (P < 0.05) in atretic follicles in a dose- and time-dependent manner. Remarkable histopathological changes occurred in the ovaries of all ND-treated groups. In conclusion, the different doses of ND caused changes in the estrous cycle and ovarian tissue of rats, and recovery periods (30 and 60 days) were insufficient to completely restore the damage in the animals treated with the highest dose. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina.

PubMed

Sacristán, J A; Gómez, J C; Montejo, A L; Vieta, E; Gregor, K J

2000-05-01

The objectives of this study were to determine the doses of olanzapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical practice in outpatients with schizophrenia and the rates of occurrence of extrapyramidal symptoms (EPS) and other adverse events, clinical response, and use of concomitant medications. The present study involved a subset of patients from a 6-month, open-label, prospective observational study. Data were collected by 293 psychiatrists at mental health centers and other outpatient treatment facilities in Spain. Medications and doses used, occurrence of EPS and other adverse events, and scores on the Clinical Global Impression (CGI) of Severity Scale and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of > or = 2 points on the CGI, with a final CGI score < or = 4. A total of 2657 patients were included in the analysis. The initial and overall mean daily doses for the 3 groups were as follows: OLZ, 12.2 and 13.0 mg, respectively; RIS, 5.2 and 5.4 mg; and HAL, 13.9 and 13.6 mg. Initial and overall median daily doses were the same in each group: OLZ, 10 mg; RIS, 6 mg; and HAL, 10 mg. A significantly lower proportion of OLZ-treated patients (36.9%) experienced EPS compared with RIS-treated (49.6%) and HAL-treated (76.0%) patients (P < or = 0.001). A significantly lower proportion of patients in the OLZ group (47.8%) experienced adverse events compared with patients in the RIS (57.2%) and HAL (79.8%) groups (P < or = 0.001). A significantly greater proportion of OLZ-treated patients (37.3%) were responders compared with RIS-treated patients (31.5%) (P < 0.05). In all 3 groups, patients who had an initial CGI score > or = 5 received significantly higher overall mean daily doses than did patients with an initial CGI score < 5 (P < 0.001). A significantly lower proportion of OLZ-treated patients (10.2%) were receiving concomitant anticholinergic medication at the end of the study (month 6) compared with RIS-treated (19.9%) and HAL-treated (44.0%) patients (P < 0.001). The mean daily doses recorded in this analysis based on data from a naturalistic setting are consistent with recommendations based on clinical trials. Compared with both RIS- and HAL-treated patients, OLZ-treated patients were less likely to experience EPS or other adverse events, and less likely to use concomitant anticholinergic medications. OLZ-treated patients were also more likely to respond to treatment than were RIS-treated patients.

An evaluation of aversive memory and hippocampal oxidative status in streptozotocin-induced diabetic rats treated with resveratrol.

PubMed

Bagatini, Pamela Brambilla; Xavier, Léder Leal; Bertoldi, Karine; Moysés, Felipe; Lovatel, Gisele; Neves, Laura Tartari; Barbosa, Sílvia; Saur, Lisiani; de Senna, Priscylla Nunes; Souto, André Arigony; Siqueira, Ionara Rodrigues; Achaval, Matilde

2017-01-01

The present study evaluated the effects of streptozotocin (STZ)-induced diabetes on aversive memory, free radical content and enzymatic antioxidant activity in the hippocampus of adult Wistar rats submitted to oral treatment with resveratrol. Animals were divided into eight groups: non-diabetic rats treated with saline (ND SAL), non-diabetic rats treated with resveratrol at a dose 5mg/kg (ND RSV 5), non-diabetic rats treated with resveratrol at a dose 10mg/kg (ND RSV 10), non-diabetic rats treated with resveratrol at a dose 20mg/kg (ND RSV 20), diabetic rats treated with saline (D SAL), diabetic rats treated with resveratrol at a dose 5mg/kg (D RSV 5), diabetic rats treated with resveratrol at a dose 10mg/kg (D RSV 10) and diabetic rats treated with resveratrol at a dose 20mg/kg (D RSV 20). The animals received oral gavage for 35days. The contextual fear conditioning task was performed to evaluate aversive-based learning and memory. The oxidative status was evaluated in the hippocampus, by measuring the free radical content - using a 2',7'-dichlorofluorescein diacetate probe - and enzymatic antioxidant activities, such as superoxide dismutase and glutathione peroxidase. Our main behavioral results demonstrated that rats from the D RSV 10 and D RSV 20 groups showed an increase in freezing behavior when compared, respectively, to the ND RSV 10 (p<0.01) and ND RSV 20 (p<0.05). Oxidative stress parameters remained unchanged in the hippocampus of all the experimental groups. In contrast to previous experimental findings, our study was unable to detect either cognitive impairments or oxidative stress in the hippocampus of the diabetic rats. We suggest additional long-term investigations be conducted into the temporal pattern of STZ-induced diabetic disruption in memory and hippocampal oxidative status, as well as the effects of resveratrol on these parameters, in a time and dose-dependent manner. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Light, electron microscopic and immunohistochemical study of the effect of low-dose aspirin during the proestrus phase on rat endometrium in the preimplantation period.

PubMed

Ateş, Utku; Baka, Meral; Turgut, Mehmet; Uyanikgil, Yiğit; Ulker, Sibel; Yilmaz, Ozlem; Tavmergen, Erol; Yurtseven, Mine

2007-04-01

To evaluate structural alterations in rat endometrium at preimplantation following treatment with aspirin beginning from proestrus by light microscopy, electron microscopy and immunohistochemical techniques. Twenty rats were divided into control (n = 10) and experimental (n = 10) groups. Experimental rats were treated with low-dose aspirin daily (2 mg/kg/day) during estrus, beginning from the proestrus phase, mated at end of cycle and treated with aspirin. Untreated pregnant rats were the control group. Rats in both groups were sacrificed at the 84th pregnancy hour; the uterus was rapidly removed and dissected free of surrounding adipose tissue. Uteri specimens from nonpregnant rats were transferred into fixative solution and processed for light, electron microscopic and immunohistochemical study. Light and electron microscopy of endometrium from control rats conformed to mid-diestrus phase; endometrial histology of the aspirin-treated group conformed to late diestrus phase. The endometrial layer was significantly thicker in the aspirin-treated group compared to the untreated control group (p <0.001). No significant difference was found in vessel number between groups. Staining with alphaV integrin was more dense in the aspirin-treated group. Based on histologic findings, we suggest low-dose aspirin has positive effects on preparing endometrium before implantation.

Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated with mycophenolate mofetil combined with low cyclosporine and steroid doses.

PubMed

Moreso, F; Serón, D; Morales, J M; Cruzado, J M; Gil-Vernet, S; Pérez, J L; Fulladosa, X; Andrés, A; Grinyó, J M

1998-06-01

Mycophenolate mofetil (MMF) combined with conventional cyclosporine and steroids doses efficiently prevents acute rejection in kidney transplants. However, this regimen has been associated with an increased incidence of cytomegalovirus (CMV) disease and leukopenia, specially in patients receiving MMF at 3 g/d, suggesting that the combination of two powerful immunosuppressants carries the risk of overimmunosuppression. For this reason, we treated a group of patients with MMF 3 g/d combined with low cyclosporine and steroids doses. Eighty-two kidney transplants performed at two centers and enrolled in the European Mycophenolate Mofetil Cooperative Study were randomized to receive: A) placebo (n = 27); B) MMF 2 g/d (n = 27); and C) MMF 3 g/d (n = 28). In this double blind study all patients received cyclosporine and steroids at conventional doses. Fifteen kidney transplants enrolled in an MMF open pharmacokinetic study were treated with MMF 3 g/day combined with low cyclosporine and steroid doses (group D). Efficacy was evaluated as the incidence of biopsy proven acute rejection, and safety focused on CMV disease and leukopenia. Patients receiving MMF showed a low incidence of biopsy proven rejection (B) 18.5%; C) 10.7%; and D) 13.3%). Patients of group C had a high incidence of CMV disease (35.7%) when compared with the other groups (lower than 8%). Incidence of leukopenia was higher in patients treated with MMF (B) 25.9%; C) 39.3%; and D) 40%) than in placebo treated patients (7.4%). Patients in group (C) displayed leukopenia mainly in the context of CMV disease, while patients of group (D) had leukopenia not related to CMV infection. All patients of group (D) who presented leukopenia recovered after MMF reduction dose, while in group (C) there were 5 out of 28 patients who required MMF withdrawal. We propose that a reasonable approach to take advantage of a powerful non-nephrotoxic immunosuppressant such as MMF, could be the administration of this drug at 3 g/d from the time of transplantation combined with low CsA and steroid doses.

Lipid metabolism abnormalities in alcohol-treated rabbits: a morphometric and haematologic study comparing high and low alcohol doses.

PubMed

Ikemura, Satoshi; Yamamoto, Takuaki; Motomura, Goro; Iwasaki, Kenyu; Yamaguchi, Ryosuke; Zhao, Garida; Iwamoto, Yukihide

2011-08-01

The pathogenesis of alcohol-induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol-treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low-dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high-dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low-dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Trivillin, Verónica A; Schwint, Amanda E

2012-01-01

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th- hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th- animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th- BPA-BNCT): 84 ± 3% compared to 67 ± 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 ± 5% in Group III (Th+ BO) and 18 ± 5% in Group IV (Th- BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 ± 7% in Group V (Th+ hdBO) and 47 ± 10% in Group VI (Th- hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3-4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beam-only Group IV (Th- BO) reached Grade 2 mucositis. High-dose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th- hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.

Interferon-gamma and interlukin-4 patterns in BALB/c mice suffering from cutaneous leishmaniasis treated with cantharidin.

PubMed

Maroufi, Yahya; Ghaffarifar, Fatemeh; Dalimi, Abdolhosein; Sharifi, Zohreh

2014-06-01

Cutaneous leishmaniasis is a health problem in the world. Lesions should be treated on cosmetically or functionally important sites, such as the face and hands. Cantharidin is a terpenoid compound produced naturally by beetles of Meloidae and Oedemeridae families. The current study aimed to investigate the effect of cantharidin on Cutaneous Leishmaniasis (CL) lesions and IFN-γ and IL-4 patterns in infected BALB/c mice. INFECTED BALB/C MICE WERE DIVIDED INTO FIVE GROUPS AS: untreated (control group), eucerin-treated and 0.05%, 0.1% and 0.5% cantharidin-treated. Lesions diameter was measured by Vernier caliper every three days for four weeks. Cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA) using U-CyTech kit. The results indicated that treatment with cantharidin exacerbates lesions compared with the controls, except for 0.05% cantharidin dose that restrained lesion growth significantly. Interferon gamma level in cantharidin-treated groups was significantly less than that of the control group. But interlukin-4 level was similar among the groups. The current study results indicated that high doses of cantharidin exacerbates leishmaniasis lesion, but low dose of cantharidin inhibits lesion growth.

Interferon-Gamma and Interlukin-4 Patterns in BALB/c Mice Suffering From Cutaneous Leishmaniasis Treated With Cantharidin

PubMed Central

Maroufi, Yahya; Ghaffarifar, Fatemeh; Dalimi, Abdolhosein; Sharifi, Zohreh

2014-01-01

Background: Cutaneous leishmaniasis is a health problem in the world. Lesions should be treated on cosmetically or functionally important sites, such as the face and hands. Cantharidin is a terpenoid compound produced naturally by beetles of Meloidae and Oedemeridae families. Objectives: The current study aimed to investigate the effect of cantharidin on Cutaneous Leishmaniasis (CL) lesions and IFN-γ and IL-4 patterns in infected BALB/c mice. Materials and Methods: Infected BALB/c mice were divided into five groups as: untreated (control group), eucerin-treated and 0.05%, 0.1% and 0.5% cantharidin-treated. Lesions diameter was measured by Vernier caliper every three days for four weeks. Cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA) using U-CyTech kit. Results: The results indicated that treatment with cantharidin exacerbates lesions compared with the controls, except for 0.05% cantharidin dose that restrained lesion growth significantly. Interferon gamma level in cantharidin-treated groups was significantly less than that of the control group. But interlukin-4 level was similar among the groups. Conclusions: The current study results indicated that high doses of cantharidin exacerbates leishmaniasis lesion, but low dose of cantharidin inhibits lesion growth. PMID:25371808

Differences in Clinical Results After LINAC-Based Single-Dose Radiosurgery Versus Fractionated Stereotactic Radiotherapy for Patients With Vestibular Schwannomas

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

Combs, Stephanie E., E-mail: Stephanie.Combs@med.uni-heidelberg.d; Welzel, Thomas; Schulz-Ertner, Daniela

2010-01-15

Purpose: To evaluate the outcomes of patients with vestibular schwannoma (VS) treated with fractionated stereotactic radiotherapy (FSRT) vs. those treated with stereotactic radiosurgery (SRS). Methods and Materials: This study is based on an analysis of 200 patients with 202 VSs treated with FSRT (n = 172) or SRS (n = 30). Patients with tumor progression and/or progression of clinical symptoms were selected for treatment. In 165 out of 202 VSs (82%), RT was performed as the primary treatment for VS, and for 37 VSs (18%), RT was conducted for tumor progression after neurosurgical intervention. For patients receiving FSRT, a medianmore » total dose of 57.6 Gy was prescribed, with a median fractionation of 5 x 1.8 Gy per week. For patients who underwent SRS, a median single dose of 13 Gy was prescribed to the 80% isodose. Results: FSRT and SRS were well tolerated. Median follow-up time was 75 months. Local control was not statistically different for both groups. The probability of maintaining the pretreatment hearing level after SRS with doses of <=13 Gy was comparable to that of FSRT. The radiation dose for the SRS group (<=13 Gy vs. >13 Gy) significantly influenced hearing preservation rates (p = 0.03). In the group of patients treated with SRS doses of <=13 Gy, cranial nerve toxicity was comparable to that of the FSRT group. Conclusions: FSRT and SRS are both safe and effective alternatives for the treatment of VS. Local control rates are comparable in both groups. SRS with doses of <=13 Gy is a safe alternative to FSRT. While FSRT can be applied safely for the treatment of VSs of all sizes, SRS should be reserved for smaller lesions.« less

Anti-fatigue activities of polysaccharides extracted from Hericium erinaceus.

PubMed

Liu, Jianqing; DU, Congxin; Wang, Yifei; Yu, Zhihua

2015-02-01

Hericium erinaceus (HEP) is a notable medicinal fungus grown in China and other oriental countries. Polysaccharides from HEP have recently attracted considerable attention due to their numerous physiological activities. The objective of this study was to evaluate the anti-fatigue activity of HEP in a mouse model. After one week of acclimation, mice were randomly divided into four groups: a control group, a low-dose HEP-treated group, a moderate-dose HEP-treated group, and a high-dose HEP-treated group. The treated groups received HEP (50, 100 and 200 mg/kg, ig), while the control group received saline solution. Following treatment for 28 days, the mice performed a forced swimming test until they were exhausted, then the exhaustive swimming time was recorded along with certain biochemical parameters related to fatigue, including blood lactic acid (BLA), serum urea nitrogen (SUN), tissue glycogen, superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). These results suggested that HEP has significant anti-fatigue activity by decreasing BLA, SUN and MDA content, as well as increasing tissue glycogen content and antioxidant enzyme activity. Based on these results, this study provided theoretical support for the application of HEP in the field of sports nutrition.

Anti-fatigue activities of polysaccharides extracted from Hericium erinaceus

PubMed Central

LIU, JIANQING; DU, CONGXIN; WANG, YIFEI; YU, ZHIHUA

2015-01-01

Hericium erinaceus (HEP) is a notable medicinal fungus grown in China and other oriental countries. Polysaccharides from HEP have recently attracted considerable attention due to their numerous physiological activities. The objective of this study was to evaluate the anti-fatigue activity of HEP in a mouse model. After one week of acclimation, mice were randomly divided into four groups: a control group, a low-dose HEP-treated group, a moderate-dose HEP-treated group, and a high-dose HEP-treated group. The treated groups received HEP (50, 100 and 200 mg/kg, ig), while the control group received saline solution. Following treatment for 28 days, the mice performed a forced swimming test until they were exhausted, then the exhaustive swimming time was recorded along with certain biochemical parameters related to fatigue, including blood lactic acid (BLA), serum urea nitrogen (SUN), tissue glycogen, superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). These results suggested that HEP has significant anti-fatigue activity by decreasing BLA, SUN and MDA content, as well as increasing tissue glycogen content and antioxidant enzyme activity. Based on these results, this study provided theoretical support for the application of HEP in the field of sports nutrition. PMID:25574220

Defining the "Hostile Pelvis" for Intensity Modulated Radiation Therapy: The Impact of Anatomic Variations in Pelvic Dimensions on Dose Delivered to Target Volumes and Organs at Risk in Patients With High-Risk Prostate Cancer Treated With Whole Pelvic Radiation Therapy.

PubMed

Yirmibeşoğlu Erkal, Eda; Karabey, Sinan; Karabey, Ayşegül; Hayran, Mutlu; Erkal, Haldun Şükrü

2015-07-15

The aim of this study was to evaluate the impact of variations in pelvic dimensions on the dose delivered to the target volumes and the organs at risk (OARs) in patients with high-risk prostate cancer (PCa) to be treated with whole pelvic radiation therapy (WPRT) in an attempt to define the hostile pelvis in terms of intensity modulated radiation therapy (IMRT). In 45 men with high-risk PCa to be treated with WPRT, the target volumes and the OARs were delineated, the dose constraints for the OARs were defined, and treatment plans were generated according to the Radiation Therapy Oncology Group 0924 protocol. Six dimensions to reflect the depth, width, and height of the bony pelvis were measured, and 2 indexes were calculated from the planning computed tomographic scans. The minimum dose (Dmin), maximum dose (Dmax), and mean dose (Dmean) for the target volumes and OARs and the partial volumes of each of these structures receiving a specified dose (VD) were calculated from the dose-volume histograms (DVHs). The data from the DVHs were correlated with the pelvic dimensions and indexes. According to an overall hostility score (OHS) calculation, 25 patients were grouped as having a hospitable pelvis and 20 as having a hostile pelvis. Regarding the OHS grouping, the DVHs for the bladder, bowel bag, left femoral head, and right femoral head differed in favor of the hospitable pelvis group, and the DVHs for the rectum differed for a range of lower doses in favor of the hospitable pelvis group. Pelvimetry might be used as a guide to define the challenging anatomy or the hostile pelvis in terms of treatment planning for IMRT in patients with high-risk PCa to be treated with WPRT. Copyright © 2015 Elsevier Inc. All rights reserved.

Five-year prospective patient evaluation of bladder and bowel symptoms after dose-escalated radiotherapy for prostate cancer with the BeamCath (registered) technique

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

Fransson, Per; Bergstroem, Per; Loefroth, Per-Olov

2006-10-01

Purpose: Late side effects were prospectively evaluated up to 5 years after dose-escalated external beam radiotherapy (EBRT) and were compared with a previously treated series with conventional conformal technique. Methods and Materials: Bladder and bowel symptoms were prospectively evaluated with the Prostate Cancer Symptom Scale (PCSS) questionnaire up to 5 years posttreatment. In all, 257 patients completed the questionnaire 5 years posttreatment. A total of 168 patients were treated with the conformal technique at doses <71 Gy, and 195 were treated with the dose-escalated stereotactic BeamCath (registered) technique comprising three dose levels: 74 Gy (n = 68), 76 Gy (nmore » = 74), and 78 Gy (n = 53). Results: For all dose groups analyzed together, 5 years after treatment, urinary starting problems decreased and urinary incontinence increased in comparison to baseline values. No increase in other bladder symptoms or frequency was detected. When comparing dose groups after 5 years, both the 74-Gy and 78-Gy groups reported increased urinary starting problems compared with patients given the conventional dose (<71 Gy). No increased incontinence was seen in the 76-Gy or the 78-Gy groups. Bowel symptoms were slightly increased during the follow-up period in comparison to baseline. Dose escalation with stereotactic EBRT (74-78 Gy) did not increase gastrointestinal late side effects after 5 years in comparison to doses <71 Gy. Conclusion: Dose-escalated EBRT with the BeamCath (registered) technique with doses up to 78 Gy is tolerable, and the toxicity profile is similar to that observed with conventional doses <71 Gy.« less

A randomized controlled trial of conventional fraction and late course accelerated hyperfraction three-dimensional conformal radiotherapy for esophageal cancer.

PubMed

Wang, Jian-Hua; Lu, Xu-Jing; Zhou, Jian; Wang, Feng

2012-01-01

We compared the curative and side-effects in esophageal carcinoma treated by conventional fraction (CF) and late course accelerated hyperfraction (LCAF) three-dimensional conformal radiotherapy. Ninety-eight patients were randomly assigned to two different radiotherapy model groups. Fifty patients were treated using CF three-dimensional conformal radiotherapy at a total dose of 60-68 Gy; 2 Gy/F; 5 fractions/week (median 64 Gy), 48 patients were treated with LCAF (First CF-treated at the dose 40 Gy. Later, LCAF-treated 1.5 Gy/F; 2 fractions/day; 21-27 Gy; a total dose of 61-67 Gy; median 64 Gy). The data showed that the 1-, 2- and 3-year-survival rates in LCAF group were 79.2, 56.3, and 43.8%, compared to 74, 54, and 36% in CF group (P = 0.476). The 1-, 2- and 3-year-local control rates in LCAF group were 81.3, 62.5, and 50%, compared to 78, 58, and 42% in CF group (P = 0.454). In CF group, the incidence of radiation-induced esophagitis was lower than that in LCAF group (72 vs. 93.8%; P = 0.008) and there was no significant difference between rates of radiation-induced pneumonitis in CF and LCAF groups (10 vs. 6.25%; P = 0.498). It was concluded that the 1-, 2- and 3-year-local control and survival rates of esophageal carcinoma patients treated with LCAF were slightly better than CF radiotherapy; however, the radiation side-effects in LCAF group were greater than those in CF group.

[Influence of shenxu gutong capsule on femoral inorganic elements content and ash weight in rats].

PubMed

Chen, X; Wei, J; Chen, Y

1998-02-01

To explore the mechanism of Shenxu Gutong Capsule (SXGTC) in treating postmenopausal osteoporosis. Using ovariectomized rats as the model of postmenopausal osteoporosis, the effect of SXGTC on inorganic element content of femur and femoral ash weight of the model rats were surveyed. Animals were divided into model group, SXGTC high dose group, SXGTC low dose group, positive control group (treated with Gushukang) and normal control group. The medication began at one week after operation and lasting for 120 days. The contents of inorganic elements, including Ca, P, Mg, Zn, Cu and Mn in the three medicated groups were higher than those of the model group (P < 0.01). The effect of SXGTC was dose dependent. The difference between the SXGTC groups and the positive control group was insignificant. The femoral ash weight of the SXGTC high dose group and the positive control group was significantly higher than that of the model group (P < 0.01). SXGTC could antagonize the rat's bony change caused by ovariectomy to increase the inorganic contents in bone, which may, in grneral, lead to a bone-strengthening effect.

The beneficial effects of l-cysteine on brain antioxidants of rats affected by sodium valproate.

PubMed

Hamza, R Z; El-Shenawy, N S

2017-11-01

Oxidative stress caused by sodium valproate (SV) is known to play a key role in the pathogenesis of brain tissue. The present study was designed to evaluate the protective effect of l-cysteine (LC) on the antioxidants of brain tissue of rats. The animals were divided into six groups: control group 1 was treated with saline as vehicle, groups 2 and 3 were treated with low and high doses of SV (100 and 500 mg/kg, respectively), group 4 was treated with LC (100 mg/kg), and groups 5 and 6 were treated with low-dose SV + LC and high-dose SV + LC, respectively. All the groups were treated orally by gastric tube for 30 successive days. Some antioxidant parameters were determined. Brain tissue (cerebral cortex) of SV-treated animals showed an increase in lipid peroxidation (LPO) and reduction in activity of enzymatic antioxidant and total antioxidant levels. Histopathological examination of cerebral cortex of SV rats showed astrocytic swelling, inflammation, and necrosis. After 4 weeks of the combination treatment of SV and LC daily, results showed significant improvement in the activity of cathepsin marker enzymes and restored the structure of the brain. LC was able to ameliorate oxidative stress deficits observed in SV rats. LC decreased LPO level and was also able to restore the activity of antioxidant enzymes as well as structural deficits observed in the brain of SV animals. The protective effect of LC in SV-treated rats is mediated through attenuation of oxidative stress, suggesting a therapeutic role for LC in individuals treated with SV.

Retrospective analysis of factors that affect the success of single-dose methotrexate treatment in ectopic pregnancy

PubMed Central

Var, Altan; Özyurt, Ramazan; Şık, Bulat Aytek; Kumbasar, Serkan; Sever, Erman; Deveci, Mustafa; Çöt, Özgür; Salman, Süleyman; Güzel, Yılmaz

2015-01-01

Objective: Detection of factors that affect the success of single-dose methotrexate treatment in ectopic pregnancy. Materials and Methods: We investigated 99 patients who had been treated with single-dose methotrexate for ectopic pregnancy in our clinic between January 2009 and June 2014. Demographic, clinical, and laboratory results of possible factors that affect treatment success were retrospectively analyzed. Successfully and unsuccessfully treated patients were compared based on their pre-treatment results. Results: The success rate of single-dose methotrexate treatment was found to be 70.7%. No significant difference was found between succesfully and unsuccessfully treated patients before treatment in terms of factors such as gestational weeks, mass size, presence of yolk sac, and presence of free fluid (p=0.224, p=0.201, p=0.200, p=0.200). Serum β-hCG values in patients whose treatment was unsuccessful was found to be higher compared with the successfully treated group (mean β-hCG value of unsuccessful group: 4412±3501 mIU/mL; mean β-hCG value of successful group: 1079±942 mIU/mL; p<0.001). Conclusion: Single-dose methotrexate treatment is an effective and reliable method in the treatment of ectopic pregnancy. Elevation of serum β-hCG value stands as the main prognostic factor that affects the success of single-dose methotrexate treatment. PMID:28913072

Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

PubMed Central

Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim

2014-01-01

Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

Effect of the aqueous extract of Foeniculum vulgare (fennel) on the kidney in experimental PCOS female rats.

PubMed

Sadrefozalayi, Somayyeh; Farokhi, Farah

2014-03-01

Foeniculum vulgare seed (F. vulgare) is an herbal plant which is used with phytoestrogene compounds for polycystic ovary syndrome (PCOS) treatment. In this research, renoprotective effect of the aqueous extract of Foeniculum vulgare (AEF) in experimental PCOS female rats is studied. Forty female rats were randomly divided into five groups. The first group served as control, was injected with an equivalent volume (0.2 ml) of normal saline, and received normal diet. Animals in the second group were non poly cystic ovary syndrome (PCOS) rats which were treated with intragastric administration of aqueous extract of F. vulgare (150 mg/kg b.w.). In the third group, the rats were treated with intraperitoneal injection of estradiolvalerate (EV) (4 mg in 0.2 ml of sesame oil). The fourth groups were treated with EV and AEF (150mg/kg bw) with the same route. The fifth groups were treated with EV and AEF (100mg/kg bw). After 4 weeks of study, all of the rats were sacrificed, their kidneys tissues were processed for light microscopy, and some biochemical parameters of serum were measured. The mean values of blood urea nitrogen in PCOS rats treated with low dose of AEF and EV and non-treated, was significantly (p<0.05) increased compared with non-PCOS and PCOS rats treated with high dose of AEF. Moreover, histopathological changes of kidney samples were comparable in PCOS rats with respect to treated groups with AEF. Aqueous extract of fennel seed showed the beneficial effect (especially at dose of 150 mg/kg b.w.) on renal function in PCOS rats.

Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

PubMed

Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

2018-05-01

We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

The Impact of Low-Dose Disease-modifying Anti-rheumatics Drugs (DMARDs) on Bone Mineral Density of Premenopausal Women in Early Rheumatoid Arthritis.

PubMed

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan; Boshnjaku, Shkumbin

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarthritis and multisystemic involvement. The aim of this study was to assess the impact of low dose of methotrexate on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). This paper follows a retrospective study, which involves 60 female patients with early onset RA diagnosed according to the American Rheumatism Association Criteria (ACR/EULAR 2010). The patients were divided into two groups group I was composed of thirty patients treated with dose of 7.5 mg/weekly methotrexate (MTX), while group II included thirty patients treated with dose of 2 g/daily sulfasalazine (SSZ). The Disease Activity was measured by a combination of Erythrocyte Sedimentation Rate (ESR) and Disease Activity Score (DAS-28). Bone mineral density of the lumbar spine (L2-4), and femoral neck, was measured by dual energy X-ray absorptiometry (DEXA) (Stratos 800). Laboratory findings included: In this study, we found no negative effect on BMD in RA patients treated with low dose MTX in comparison to patients treated with SSZ. There was not observed significant difference in BMD of the lumbar spine, femur neck or trochanter, of MTX and SSZ patients in the pretreatment phase, nor after 12 months of treatment. No significant change in the biochemical parameters of the both groups. Based on the results of our study, low dose of methotrexate has no negative effect on BMD in premenopausal RA patients. We believe that these results might provide new insights and that further longitudinal studies with larger groups of premenopausal RA patients are required.

The Impact of Low-Dose Disease-modifying Anti-rheumatics Drugs (DMARDs) on Bone Mineral Density of Premenopausal Women in Early Rheumatoid Arthritis

PubMed Central

Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan; Boshnjaku, Shkumbin

2016-01-01

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarthritis and multisystemic involvement. Objective: The aim of this study was to assess the impact of low dose of methotrexate on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). Materials and methods: This paper follows a retrospective study, which involves 60 female patients with early onset RA diagnosed according to the American Rheumatism Association Criteria (ACR/EULAR 2010). The patients were divided into two groups group I was composed of thirty patients treated with dose of 7.5 mg/weekly methotrexate (MTX), while group II included thirty patients treated with dose of 2 g/daily sulfasalazine (SSZ). The Disease Activity was measured by a combination of Erythrocyte Sedimentation Rate (ESR) and Disease Activity Score (DAS-28). Bone mineral density of the lumbar spine (L2–4), and femoral neck, was measured by dual energy X-ray absorptiometry (DEXA) (Stratos 800). Laboratory findings included: In this study, we found no negative effect on BMD in RA patients treated with low dose MTX in comparison to patients treated with SSZ. There was not observed significant difference in BMD of the lumbar spine, femur neck or trochanter, of MTX and SSZ patients in the pretreatment phase, nor after 12 months of treatment. No significant change in the biochemical parameters of the both groups. Conclusion: Based on the results of our study, low dose of methotrexate has no negative effect on BMD in premenopausal RA patients. We believe that these results might provide new insights and that further longitudinal studies with larger groups of premenopausal RA patients are required. PMID:27147781

Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway.

PubMed

Wei, Liang; Zhang, Yanfei; Yang, Cheng; Wang, Qi; Zhuang, Zhongwei; Sun, Zhiyang

2014-02-01

Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg) ebselen-treated group. The TBI model was created according using a modified weight-drop model. Neurological severity score (NSS), brain water content and histopathological deficits were assessed as parameters of injury severity. Expression of nitric oxide (NO), inducible NO synthase (iNOS) mRNA, Toll-like receptor (TLR) and phosphorylated (p-) p38 mitogen-activated protein kinase (MAPK) were examined by chemical colorimetry, quantitative polymerase chain reaction and western blotting 24 h after intragastric ebselen administration. Rats in the TBI model group exhibited markedly more severe neurological injury (higher NSS, more brain water content and more histopathological deficits) than those in the sham-operated group. Ebselen treatment significantly ameliorated the neurological injury of TBI rats in a dose-dependent manner. Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI. © 2013 Wiley Publishing Asia Pty Ltd.

[Antiurolithic Activity of the Ethanolic Extract of Ayacuchano Propolis in Rats].

PubMed

López-Cabanillas, Rita; Huayanay-Conde, Ronal; Gonzales, Cinthya; Maguiña, Mahli; Granados, Italo; Ccasani, Mila; Laguna, Astrid; León, Ernesto; Romero-Caballero, Nuria; Chacón, Jessenia

2017-01-01

To determine the antiurolytic activity of the ethanolic extract of Ayacuchan propolis in a preventive model of urolithiasis in rats. A total of 45 male Sprague-Dawley albino rats were studied. The antiurolithic effect was analyzed in five groups of six animals each: blank, control (treated with 1 mL of 5% ethylene glycol and 1 mL of 5% ammonium chloride), and three experimental groups (treated with the ethanol extract of propolis at a daily dose of 250, 350, and 500 mg/kg, respectively). The drugs were administered by orogastric cannulation for 16 days. The diuretic effect was evaluated in 15 rats distributed in five groups: blank, control (treated with furosemide at 20 mg/kg), and three experimental groups (treated with the ethanol extract of propolis at daily doses of 250, 350, and 500 mg/kg, respectively). Urinary pH, urinary density, and sedimentation of calcium oxalate were measured. The presence of kidney stones was evaluated by examination of hematoxylin-eosin-stained histopathological sections under polarized light. The ethanolic extract of Ayacuchan propolis caused significant changes in the levels of uric acid, serum lactate dehydrogenase, pH, and urinary density in the three dose groups. The results of histological analysis indicated a lower presence of calcium oxalate crystals in kidney tubular cells in the group treated with 250 mg/kg. The diuretic effect in the group treated with 250 mg/kg was higher than that in the control group. The ethanolic extract of Ayacuchan propolis demonstrated antiurolytic activity in a preventive rat model of urolithiasis.

Radiation field size and dose determine oncologic outcome in esophageal cancer.

PubMed

Gemici, Cengiz; Yaprak, Gokhan; Batirel, Hasan Fevzi; Ilhan, Mahmut; Mayadagli, Alpaslan

2016-10-13

Locoregional recurrence is a major problem in esophageal cancer patients treated with definitive concomitant chemoradiotherapy. Approximately half of the patients fail locoregionally. We analyzed the impact of enlarged radiation field size and higher radiation dose incorporated to chemoradiotherapy on oncologic outcome. Seventy-four consecutive patients with histologically proven nonmetastatic squamous or adenocarcinoma of the esophagus were included in this retrospective analysis. All patients were locally advanced cT3-T4 and/or cN0-1. Treatment consisted of either definitive concomitant chemoradiotherapy (Def-CRT) (n = 49, 66 %) or preoperative concomitant chemoradiotherapy (Pre-CRT) followed by surgical resection (n = 25, 34 %). Patients were treated with longer radiation fields. Clinical target volume (CTV) was obtained by giving 8-10 cm margins to the craniocaudal borders of gross tumor volume (GTV) instead of 4-5 cm globally accepted margins, and some patients in Def-CRT group received radiation doses higher than 50 Gy. Isolated locoregional recurrences were observed in 9 out of 49 patients (18 %) in the Def-CRT group and in 1 out of 25 patients (3.8 %) in the Pre-CRT group (p = 0.15). The 5-year survival rate was 59 % in the Def-CRT group and 50 % in the Pre-CRT group (p = 0.72). Radiation dose was important in the Def-CRT group. Patients treated with >50 Gy (11 out of 49 patients) had better survival with respect to patients treated with 50 Gy (38 out of 49 patients). Five-year survivals were 91 and 50 %, respectively (p = 0.013). Radiation treatment planning by enlarged radiation fields in esophageal cancer decreases locoregional recurrences considerably with respect to the results reported in the literature by standard radiation fields (18 vs >50 %). Radiation dose is as important as radiation field size; patients in the Def-CRT group treated with ≥50 Gy had better survival in comparison to patients treated with 50 Gy.

Impact of sleeve gastrectomy on gastroesophageal reflux disease in a morbidly obese population undergoing bariatric surgery.

PubMed

Hendricks, LéShon; Alvarenga, Emanuela; Dhanabalsamy, Nisha; Lo Menzo, Emanuele; Szomstein, Samuel; Rosenthal, Raul

2016-01-01

Laparoscopic sleeve gastrectomy (LSG) has established popularity as a weight loss procedure based on its success. However, LSG's effect on gastroesophageal reflux disease (GERD) is unknown. To analyze the incidence of GERD after LSG and to compare the results in patients with preexisting and de novo GERD. Tertiary Medical center. The authors performed a retrospective review of primary LSG from 2005 to 2013 and compared patients with pre-existing and de novo GERD who underwent LSG. A total of 919 patients underwent LSG. GERD was present in 38 (4%) of the LSG cohort. We identified 2 groups: Group A consisted of 25 (3%) patients with de novo GERD, and Group B consisted of 13 (1%) patients with pre-existing GERD. Diagnosis of GERD in both groups was determined by symptoms and history of proton pump inhibitor (PPI) treatment, upper gastrointestinal endoscopy, esophagogastroduodenoscopy, and pH manometry. In Group A, 1 (4%) patient was managed with over-the-counter drugs, 17 (68%) patients were treated with low-dose PPI, 6 (24%) patients were treated with high-dose PPI, and 1 (4%) patient was lost to follow-up. Group B consisted of 9 (69%) patients treated with low-dose PPI and 4 (31%) patients treated with high-dose PPI. Medical treatment failed in 4 patients (10.5%) who subsequently required conversion to laparoscopic Roux-en-Y gastric bypass (LRYGB). In Group A, 1 patient (4%) required LRYGB, and in Group B, 3 patients (23%) required LRYGB. The outcome of conversion for Group A was incomplete resolution of symptoms in the 1 patient, whereas in Group B, all 3 patients (100%) had complete resolution of GERD symptoms after LRYGB. In this study, 3% of patients developed de novo GERD, but most responded to either low- or high-dose PPI, with 4% requiring conversion to LRYGB. Copyright © 2016 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Efficacy evaluation of Bauhinia variegata L. stem bark powder as adjunct therapy in chronic Staphylococcus aureus mastitis in goat

PubMed Central

Dash, Jeevan Ranjan; Sar, Tapas Kumar; Samanta, Indranil; Pal, Subodh; Khan, Madhuchhanda; Patra, Nimai Charan; Sarkar, Uttam; Maji, Asit Kumar; Mandal, Tapan Kumar

2014-01-01

Objective: The objective was to study the effect of Bauhinia variegata L. stem bark powder as adjunct therapy in chronic Staphylococcus aureus mastitis in goat. Materials and Methods: Mastitis was induced by intracisternal inoculation of coagulase positive S. aureus (J638) at the concentration of 2000 colony forming units. Group I animals were treated with repeated dose of ceftriaxone at 20 mg/kg intravenously, and Group II animals were treated with once daily oral administration of B. variegata L. stem bark powder at 6 g/kg for 7 days followed by maintenance dose at 3 g/kg for next 7 days along with repeated dose of the antibiotic at 20 mg/kg intravenously at 4 days interval. Results: No significant improvement in the clinical condition of the udder was noticed in the group treated with repeated dose of ceftriaxone alone. However, in the group treated with B. variegata L. stem bark powder along with repeated dose of ceftriaxone, no S. aureus colony was seen at 96 h and onwards in milk samples with a marked decrease in somatic cell count and milk alkaline phosphatase activity and increased lactoperoxidase activity. Further, plasma and milk concentration of ceftriaxone/ceftizoxime was increased, which indicated antibacterial, bioenhancing and antiinflammatory properties of the bark powder. The Group II animals also exhibited marked reduction in polymorphonuclear cells and fibrous tissue indicating antifibrotic property of B. variegata L. Conclusion: B. variegata L. stem bark powder can be considered as an effective adjunct therapy to intravenous ceftriaxone in S. aureus chronic mastitis in goat. PMID:25298668

Inhibitive effect on apoptosis in splenic lymphocytes of mice pretreated with lingzhi (Ganoderma lucidum) spores.

PubMed

Wang, Quanxi; Huang, Yifan; Wu, Baocheng; Mei, Jingliang; Zhang, Honglei; Qi, Baomin

2014-04-01

To investigate how the pretreatment of mice with Ganoderma spores affected the apoptosis of their splenic lymphocytes induced by dexamethasone after 19 days treatment. Sixty Kunming mice were randomly divided into six groups: blank control groupdrenched with normal saline; a drug control group drenched with 150 mg/mL Ganoderma spores; a model group treated with saline; a low dose group with 50 mg/mL Ganoderma spores; a moderate dose group with 100 mg/mL Ganoderma spores; and a high dose group with 150 mg/mL Ganoderma spores. The effect of Ganoderma spores on apoptosis in spleen lymphocytes was analyzed. All groups were treated for 19 days. On day 20, the model group and the 3 treatment groups were intraperitoneally injected dexamethasone to induce apoptosis. Splenic index and apoptosis indes were employed to measure cell apoptosis. The results showed that Ganoderma spores reduced the splenic index to different degrees in each group and the best effect was seen in the high dose group (P < 0.05).Terminal dexynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine 5'-Triphosphate nick end labeling staining revealed that the apoptotic index in all groups administered Ganoderma spores differed significantly from the model group, and a dose-response was observed. Flow cytometric analysis indicated that spleen lymphocyte apoptosis in the model group was extensive. Each dose of Ganoderma spores inhibited dexamethasone-induced apoptosis in spleen lymphocytes, and a dose-response was observed as well. The highest dose of Ganoderma spores decreased Malondialdehyde content in serum induced by dexamethasone (P < 0.05). The findings imply that the pretreatment of the mice with Ganoderma spores could reduce the apoptosis rate induced by dexamethasone in their splenic lymphocytes.

Chronic treatment of haloperidol induces pathological changes in striatal neurons of guinea pigs: a light and electron microscopical study.

PubMed

Altunkaynak, B Zuhal; Ozbek, Elvan; Unal, Bunyami; Aydin, Nazan; Aydin, M Dumlu; Vuraler, Ozgen

2012-10-01

In the present work, we investigated whether there would be any change in histological structure of striatal neurons after haloperidol applications at different doses. Adult male guinea pigs were treated once-daily with saline (group 4, control) or haloperidol during 6 weeks, and the dose was 1, 2, or 3 mg/kg (groups 1, 2, and 3, respectively). After treatment, all animals were anesthetized and striata were dissected and examined. When striata were evaluated histologically, dark neurons and some degenerating striatal neurons had distinctive morphological changes consistent with cell death, including reduced neuronal size with nuclear and cytoplasmic shrinkage. Also, in sections of striata in groups 1 and 2, but not in group 3, more glial cells were observed than in those of the control group. In all treated groups, fibrous content of intersititium was paralelly increased by increasing dose. Ultrastructural investigation of striatal neurons in haloperidol-treated rats showed notched nuclei and many lysosomes. Moreover, degeneration of myelin, scarce microglial macrophages, expansion of nuclear intermembranous space, degenerated mitochondria, and vacuoles were found. Also, cytoplasmic swelling, lysosomes, and apoptotic bodies were present. These results suggest that haloperidol treatment may lead to damage in neurons via the necrotic process in both low- and high-dose applications.

Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study.

PubMed

Jensterle, Mojca; Goricar, Katja; Janez, Andrej

2016-04-01

Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Higher doses are more effective than lower doses, although higher doses are also more poorly tolerated. Metformin may enhance the weight-lowering potential of LIRA via the stimulatory modulation of incretin in addition to its direct beneficial effects in PCOS. The aim of the present study was to evaluate whether metformin as an adjunct to low-dose LIRA affects body weight with increased efficacy compared with low-dose LIRA alone in obese patients with PCOS. In a 12-week study, 44 obese women with PCOS were randomly offered either combined treatment (COMBO) with 1,000 mg metformin twice a day and 1.2 mg LIRA once a day, or treatment with 1.2 mg LIRA alone. The primary outcome of treatment was an alteration in the levels of obesity. A total of 43 patients [aged 30.3±4.4 years; body mass index (BMI) 37.2±4.5 kg/m 2 ; mean ± standard deviation] completed the study. The subjects treated with COMBO lost on average 6.2±2.4 kg compared with a 3.8±3.5 kg weight loss in the patients treated with LIRA alone (P=0.024). The BMI decreased by 2.2±0.8 kg/m 2 in patients treated with COMBO and by 1.4±1.2 kg/m 2 in patients treated with LIRA alone (P=0.024). A clinically significant ≥5% weight reduction was achieved in 59.1% of patients treated with COMBO and 42.9% of patients treated with LIRA alone. Reductions in glucose levels following oral glucose tolerance testing, as well as in androstenedione levels in the COMBO group were significantly greater compared with those in the LIRA group. The side effects were mild and transient in the two treatment groups. A combination of metformin and low-dose LIRA was more effective than low-dose LIRA alone in reducing body weight in obese patients with PCOS.

High-dose versus standard-dose radiotherapy with concurrent chemotherapy in stages II-III esophageal cancer.

PubMed

Suh, Yang-Gun; Lee, Ik Jae; Koom, Wong Sub; Cha, Jihye; Lee, Jong Young; Kim, Soo Kon; Lee, Chang Geol

2014-06-01

In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of aspirin and enoxaparin in a rat model of liver fibrosis.

PubMed

Li, Chen-Jie; Yang, Zhi-Hui; Shi, Xiao-Liu; Liu, De-Liang

2017-09-21

To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis. METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group (n = 5) and model group (n = 40). Thioacetamide (TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously (n = 9), TAA + low-dose aspirin (n = 9), TAA + high-dose aspirin (n = 9) or TAA + enoxaparin (n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed. Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer) and 4T1 (Breast cancer) cell lines.

PubMed

Shahbazfar, Amir Ali; Zare, Payman; Ranjbaran, Mehrdad; Tayefi-Nasrabadi, Hossein; Fakhri, Omid; Farshi, Yashar; Shadi, Sahar; Khoshkerdar, Afsaneh

2014-01-01

Anticancer properties of artemisinin and its derivatives have been shown in many experiments. Addition of butyric acid, miconazole, and iron to this traditional drug has been done in order to enhance its anticancer potency. Cell lines 5637 and 4T1, were cultivated and classified into 13 groups of three each. Different doses of artemisinin with constant doses of iron, miconazole and butyric acid, were added to the cultures. At the end of exposure pathological and enzymatic studies were performed. In four groups treated with different doses of artemisinin and iron, dose-dependent changes were observed. These changes included apoptosis and necrosis with dominance of apoptosis. The supernatant lactate dehydrogenase (LDH) level was increased in a dose-dependent manner, but there was no significant increase in the cell fraction of malonyldialdehyde (MDA) or LDH. In four other groups, which received miconazole, butyric acid and iron in addition to different doses of artemisinin, necrosis was more prominent than apoptosis, and the MDA level did not show any significant change, but LDH was increased. The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis. A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution.

Comparative proteomic analysis of fluoride treated rat bone provides new insights into the molecular mechanisms of fluoride toxicity.

PubMed

Wei, Yan; Zeng, Beibei; Zhang, Hua; Chen, Cheng; Wu, Yanli; Wang, Nanlan; Wu, Yanqiu; Zhao, Danqing; Zhao, Yuxi; Iqbal, Javed; Shen, Liming

2018-07-01

Long-term excessive intake of fluoride (F) could lead to chronic fluorosis. To explore the underlying molecular mechanisms, present study is designed to elucidate the effect of fluoride on proteome expression of bone in sodium fluoride (NaF)-treated SD rats. Hematoxylin and eosin (H&E) staining was used to determine the severity of osteofluorosis, and bone samples were submitted for iTRAQ analysis. The results showed that the cortical thickness and trabecular area of femur bone in medium- and high-dose groups were higher than in control group. Contrary to this, trabecular area was reduced in the low-dose group, indicating that the bone mass was increased in medium- and high-dose groups, and decreased in the low-dose group. Thirteen (13), 35, and 34 differentially expressed proteins were identified in low-, medium-, and high-dose group, respectively. The medium- and high-dose groups shared a more similar protein expression pattern. These proteins were mainly associated with collagen metabolism, proteoglycans (PGs), matrix metalloproteinases (MMPs), etc. The results suggested that the effect of NaF on SD rats is in a dose-dependent manner. Some key proteins found here may be involved in affecting the bone tissues and bone marrow or muscle, and account for the complex pathology and clinical symptoms of fluorosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Relationship between dose of antithyroid drugs and adverse events in pediatric patients with Graves’ disease

PubMed Central

Yasuda, Kie; Miyoshi, Yoko; Tachibana, Makiko; Namba, Noriyuki; Miki, Kazunori; Nakata, Yukiko; Takano, Toru; Ozono, Keiichi

2017-01-01

Abstract. Graves’ disease (GD) accounts for a large proportion of pediatric hyperthyroidism, and the first-line treatment is antithyroid drug (ATD) therapy. Methimazole (MMI) is effective in most patients but is associated with significant adverse events (AEs). We reviewed the medical records of GD patients (n = 56) with onset age of <15 yr and investigated the relationship between MMI dose and AEs. The study population comprised 11 male and 45 female patients and the median age at diagnosis was 11 yr. All patients were initially treated with ATDs. Among the 52 patients initially treated with MMI, 20 received a low dose, and 32 received a high dose of MMI (< 0.7 vs ≥ 0.7 mg/kg/day, respectively). AEs occurred in 20% of the patients in the low-dose MMI group, and in 50% patients in the high-dose MMI group (p = 0.031). A greater variety of AEs was observed in the high-dose group. Neutropenia and rash were observed in both groups. With treatment transition to low-dose MMI according to the Japanese Society for Pediatric Endocrinology guidelines, we expect a decrease in the incidence of AEs in future. However, we should be careful as neutropenia and rash can occur independently of the MMI dose. PMID:28203042

Relationship between dose of antithyroid drugs and adverse events in pediatric patients with Graves' disease.

PubMed

Yasuda, Kie; Miyoshi, Yoko; Tachibana, Makiko; Namba, Noriyuki; Miki, Kazunori; Nakata, Yukiko; Takano, Toru; Ozono, Keiichi

2017-01-01

Graves' disease (GD) accounts for a large proportion of pediatric hyperthyroidism, and the first-line treatment is antithyroid drug (ATD) therapy. Methimazole (MMI) is effective in most patients but is associated with significant adverse events (AEs). We reviewed the medical records of GD patients (n = 56) with onset age of <15 yr and investigated the relationship between MMI dose and AEs. The study population comprised 11 male and 45 female patients and the median age at diagnosis was 11 yr. All patients were initially treated with ATDs. Among the 52 patients initially treated with MMI, 20 received a low dose, and 32 received a high dose of MMI (< 0.7 vs ≥ 0.7 mg/kg/day, respectively). AEs occurred in 20% of the patients in the low-dose MMI group, and in 50% patients in the high-dose MMI group (p = 0.031). A greater variety of AEs was observed in the high-dose group. Neutropenia and rash were observed in both groups. With treatment transition to low-dose MMI according to the Japanese Society for Pediatric Endocrinology guidelines, we expect a decrease in the incidence of AEs in future. However, we should be careful as neutropenia and rash can occur independently of the MMI dose.

Neuroprotective effects of fermented soybean products (Cheonggukjang) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on trimethyltin-induced cognitive defects mice.

PubMed

Go, Jun; Kim, Ji Eun; Kwak, Moon Hwa; Koh, Eun Kyoung; Song, Sung Hwa; Sung, Ji Eun; Kim, Dong Sup; Hong, Jin Tae; Hwang, Dae Youn

2016-07-01

This study aimed to investigate the beneficial effects of Cheonggukjang (CGK) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on neurotoxic damages. The specific aspects of brain functions were measured in Institute for Cancer Research (ICR) mice that had been pretreated for 4 weeks with three difference doses of CGK before trimethyltin (TMT) treatment. The short- and long-term memory loss induced by TMT treatment was significantly improved in the CGK-pretreated group in a dose-dependent manner. The number of dead cells in the granule cell layer of the dentate gyrus was decreased in the TMT/CGK-cotreated group relative to the TMT/vehicle-treated group, whereas significant suppression of acetylcholinesterase (AChE) activity was observed in the same group. Additionally, a dose-dependent increase in nerve growth factor (NGF) concentration, activation of the NGF receptor signaling pathway including the TrkA high affinity receptor and p75(NTR) low affinity receptor, and decline in Bax/Bcl-2 level was measured in all TMT/CGK-treated groups, although a decrease in the active form of caspase-3 was observed in the TMT/H-CGK-treated group. Furthermore, superoxide dismutase (SOD) activity was enhanced in the TMT/CGK-treated group, whereas the level of malondialdehyde (MDA), a marker of lipid peroxidation, was 43-58% lower in the TMT/CGK-treated group than the TMT/vehicle-treated group. These results demonstrate that CGK fermented by mixed culture of B. subtilis and L. sakei could exert a wide range of beneficial activities for neurodegenerative diseases, including Alzheimer, Parkinson, and Huntington disease.

Defining the “Hostile Pelvis” for Intensity Modulated Radiation Therapy: The Impact of Anatomic Variations in Pelvic Dimensions on Dose Delivered to Target Volumes and Organs at Risk in Patients With High-Risk Prostate Cancer Treated With Whole Pelvic Radiation Therapy

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

Yirmibeşoğlu Erkal, Eda, E-mail: eyirmibesoglu@yahoo.com; Karabey, Sinan; Karabey, Ayşegül

2015-07-15

Purpose: The aim of this study was to evaluate the impact of variations in pelvic dimensions on the dose delivered to the target volumes and the organs at risk (OARs) in patients with high-risk prostate cancer (PCa) to be treated with whole pelvic radiation therapy (WPRT) in an attempt to define the hostile pelvis in terms of intensity modulated radiation therapy (IMRT). Methods and Materials: In 45 men with high-risk PCa to be treated with WPRT, the target volumes and the OARs were delineated, the dose constraints for the OARs were defined, and treatment plans were generated according to themore » Radiation Therapy Oncology Group 0924 protocol. Six dimensions to reflect the depth, width, and height of the bony pelvis were measured, and 2 indexes were calculated from the planning computed tomographic scans. The minimum dose (D{sub min}), maximum dose (D{sub max}), and mean dose (D{sub mean}) for the target volumes and OARs and the partial volumes of each of these structures receiving a specified dose (V{sub D}) were calculated from the dose-volume histograms (DVHs). The data from the DVHs were correlated with the pelvic dimensions and indexes. Results: According to an overall hostility score (OHS) calculation, 25 patients were grouped as having a hospitable pelvis and 20 as having a hostile pelvis. Regarding the OHS grouping, the DVHs for the bladder, bowel bag, left femoral head, and right femoral head differed in favor of the hospitable pelvis group, and the DVHs for the rectum differed for a range of lower doses in favor of the hospitable pelvis group. Conclusions: Pelvimetry might be used as a guide to define the challenging anatomy or the hostile pelvis in terms of treatment planning for IMRT in patients with high-risk PCa to be treated with WPRT.« less

[The effect of edaravone on MAPKs signal pathway associated with Abeta(25-35) treatment in PC12 cells].

PubMed

Zhang, Gui-lian; Guo, Ying-ying; Zhang, Lei; Li, Ting-ting; Du, Yun; Yao, Li; Zhang, Wang-gang; Wu, Hai-qin; Ma, Zhu-lin

2015-03-01

To explore whether edaravone protects cells damage via mitogen-activated protein kinases (MAPKs) signal pathway, and which procedure of p38 be affected so as to add theories for AD pathogenesis and treatments. According to different drugs treated, PC12 cells in vitro were divided into four groups. Negative control group: cells were treated with media alone. AD model group: cells were treated with 30 pmol/L Abeta(25-35). Inhibitor control group: cells were treated with 10 micromol/L SB203580 Cp38 mitogen-activated protein kinase (p38) inhibitor], 10 micromol/L SP600125 [c-Jun NH2 terminal kinase (JNK) inhibitor], or 10 micromol/L PD98059 extracelular signal regulated kinase (ERK) inhibitor]. Low-dose, middle-dose and high-dose edaravone group: cells plated for 24 hours treated with 30 micromol/L Abeta(25-35) and co-treated with 20, 40, 80 micromol/L edaravone 3 hours, respectively. The morphology of the treated cells were observed, the p-p38, p-JNK and p-ERK proteins in each group were tested by the Western blot. The p38 mRNA were tested in each group above (only add SB203580 10 micromol/L in third group) by the real time PCR. (1) The p-p38 protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-p38 protein in the inhibitor group and edaravone groups was decreased significantly (P<0.05) when compared with that in model control group. The p-p38 proteins were significantly increased in the three edaravone groups compared with that in inhibiter control group (P<0.05). The p-p38 protein in middle-dose edaravone group was decreased compared with that in low-dose edaravone group (P<0.05). There was no relationship in dose-dependent manner about edaravone. Compared with three edaravone groups, the p-p38 protein was lower than it in high-dose edaravone & inhibiter group (P<0.05). (2) The p-JNK protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-JNK protein in the inhibitor group was decreased compared with that in model control group (P<0.05). (3) No significantly difference of p-ERK protein concentration was observed in other groups when compared with that in negative control group (P>0.05 each). (4) Compared with negative control group, the p38 mRNA in model control group was significantly increased, and it was significantly decreased in inhibitor control group (P<0.05 each). In 40 micromol/L and 80 micromol/L edaravone groups, the p38 mRNA was significantly decreased compared with that in model control group, and it still was decreased compared with that in inhibitor control group (P<0.05). The p38 mRNA in 40 micromol/L edaravone group was the lowest among three edaravone groups, and it was obviously different from that in 20 micromol/L and 80 micromol/L edaravone groups (P<0.05). Abeta(25-35) could increase the p-p38 and p-JNK protein expression in cultured PC12 cells, but there was no obviously expression of p-ERK protein. These indicated that Abeta(25-35) might activate MAPKs signal pathway, especially p38 and JNK, and lead to PC12 cell damage. Edaravone could decrease p38 mRNA induced-Abeta(25-35), which indicated edaravone could protect PC12 cell damage via blocking p38 signal pathway in mRNA stage and protein stage simultaneously. Hence, it is promising that edaravone would be a new medicine for AD.

The Effects of Aloe Vera on TNF-a Levels, the Percentage of Nk Cells and Th 17 Cells in Rat That Received Izoniazid and Rifampycin.

PubMed

Mawarti, Herin; Rajin, Mukhamad; Asumta, Zulfikar

2017-10-01

The present study was undertaken to investigate the hepatoprotective effect of Aloe vera against side effect of antituberculosis drug. Twenty-five rats will be divided into five groups, namely the control group (without any treatment), the group of rats treated with anti-tuberculosis drugs, and a group of rats were treated antituberculosis drugs and got Aloe vera extract at a dose of 40; 80; and 120 mg/kg body weight. Antituberculosis drugs are isoniazid and rifampicin a dose of 50 mg/kg body weight. Antituberculosis treated group showed significantly increase levels of TNF-a, the percentage of NK cells and the number of Th17 cells compared with the control group ( p < 0.05). All doses of Aloe vera reduce levels of TNF-a compared with the antituberculosis group ( p < 0.05), although it has not yet reached levels comparable to the control group ( p > 0.05). Aloe vera at first and the third dose lower the number of NK cells compared to the antituberculosis group, although it has not yet reached a significant difference ( p > 0.05). The first dose of Aloe vera was significantly decreased the percentage of Th17 cells compared to the antituberculosis drug group ( p < 0.05), although it has not yet reached levels comparable to the control group ( p > 0.05). It was concluded that administration of Aloe vera can suppress the production of TNF-a and the percentage of Th17 cells as a result of antituberculosis drug administration. Thus, Aloe vera can be a useful alternative to natural materials in the successful treatment of tuberculosis through the inhibition of side effect.

[Research on the expression of Survivin and PTEN in laryngeal squamous cell carcinoma transplanted on the back sides of nude mice treated by gold throat tablets].

PubMed

Guo, Qiangzhong; Li, Yunying

2012-12-01

To explore the positive expressing rates of oncogene Survivin and tumor-suppressor gene PTEN in transplanted laryngo-carcinoma of nude mice treated by Gold Throat Tablets (GTT) which can improve circulation and remove haemostasis in TCM theory. The 32 nude mice seeded with cultured laryngeal carcinoma cells subcutaneously at the back were randomly divided into high, middle, low (according to 6 : 3: 1 proportion of GTT dosing given by intragastric administration) dose groups and blank control groups. The changes on weight and size of tumors originated from these cells were observed for 28 days, and the density of tumors and expression of Survivin and PTEN were examined with tumor sections by immunohistochemical assay after separating tumors from back of nude mice. The weight and size of subcutaneous laryngo-carcinoma on backs of high dose group nude mice were both the smallest among all the experimental groups with the average density of tumors as 1.202 g/cm3. The positive expressing rates of Survivin and PTEN both revealed the following tendency that high dose group < middle dose group < low dose group < blank control group. Six times of regular doses of GTT can prevent overgrowth of laryngo-carcinoma transplanted on nude mice and decrease the excessive expression of oncogene Survivin in the tumor. PTEN, expressing lower than Survivin in all groups, shows a subordinative relationship with it, maybe due to a competition mechanism.

Streptozotocin Aggravated Osteopathology and Insulin Induced Osteogenesis Through Co-treatment with Fluoride.

PubMed

Yang, Chen; Zhang, Mengmeng; Li, Yagang; Wang, Yan; Mao, Weixian; Gao, Yuan; Xu, Hui

2015-12-01

The role of insulin in the mechanism underlying the excessive fluoride that causes skeletal lesion was studied. The in vitro bone marrow stem cells (BMSC) collected from Kunming mice were exposed to varying concentrations of fluoride with or without insulin. The cell viability and early differentiation of BMSC co-treated with fluoride and insulin were measured by using cell counting kit-8 and Gomori modified calcium-cobalt method, respectively. We further investigated the in vivo effects of varying dose of fluoride on rats co-treated with streptozotocin (STZ). Wistar rats were divided into six groups which included normal control, 10 mg fluoride/kg day group, 20 mg fluoride/kg day group, STZ control, STZ+10 mg fluoride/kg day group, and STZ+20 mg fluoride/kg day group. The rats were administered with sodium fluoride (NaF) by gavage with water at doses 10 and 20 mg fluoride/kg day for 2 months. In a period of one month, half of rats in every group were treated with streptozotocin (STZ) once through intraperitoneal injection at 52 mg/kg body weight. The serum glucose, HbA1c, and insulin were determined. Bone mineral content and insulin release were assessed. The results showed insulin combined with fluoride stimulated BMSC cell viability in vitro. The bone mineral content reduced in rats treated with higher dose of fluoride and decreased immensely in rat co-treated with fluoride and STZ. Similarly, a combination treatment of a high dose of fluoride and STZ decreased insulin sensitivity and activity. To sum up, these data indicated fluoride influenced insulin release, activity, and sensitivity. Furthermore, the insulin state in vivo interfered in the osteogenesis in turn and implied there was a close relation between insulin and bone pathogenesis in the mechanism of fluoride toxicity.

Prolactin is a peripheral marker of manganese neurotoxicity

PubMed Central

Marreilha dos Santos, AP; Lopes Santos, M; BatorÉu, Maria C; Aschner, M

2011-01-01

Excessive exposure to Mn induces neurotoxicity, referred to as manganism. Exposure assessment relies on Mn blood and urine analyses, both of which show poor correlation to exposure. Accordingly, there is a critical need for better surrogate biomarkers of Mn exposure. The aim of this study was to examine the relationship between Mn exposure and early indicators of neurotoxicity, with particular emphasis on peripheral biomarkers. Male Wistar rats (180–200 g) were injected intraperitoneally with 4 or 8 doses of Mn (10 mg/kg). Mn exposure was evaluated by analysis of Mn levels in brain and blood along with biochemical end-points (see below). Results Brain Mn levels were significantly increased both after 4 and 8 doses of Mn compared with controls (p<0.001). Blood levels failed to reflect a dose-dependent increase in brain Mn, with only the 8-dose treated group showing significant differences (p<0.001). Brain glutathione (GSH) levels were significantly decreased in the 8-dose-treated animals (p<0.001). A significant and dose-dependent increase in prolactin levels was found for both treated groups (p<0.001) compared to controls. In addition, a decrease in motor activity was observed in the 8-dose-treated group compared to controls. Conclusions 1) The present study demonstrates that peripheral blood level is a poor indicator of Mn brain accumulation and exposure; 2) Mn reduces GSH brain levels, likely reflecting oxidative stress; 3) Mn increases blood prolactin levels, indicating changes in the integrity of the dopaminergic system. Taken together these results suggest that peripheral prolactin levels may serve as reliable predictive biomarkers of Mn neurotoxicity. PMID:21262206

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin.

PubMed

Vogelbaum, Michael A; Angelov, Lilyana; Lee, Shih-Yuan; Li, Liang; Barnett, Gene H; Suh, John H

2006-06-01

The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3-83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134-0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78-92%) in tumors treated with 24 Gy, compared with 49% (CI 30-68%) in tumors treated with 18 Gy and 45% (CI 23-67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.

Proof of Principle of Ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy

PubMed Central

Lawrence, Jessica A.; Forrest, Lisa J.; Turek, Michelle M.; Miller, Paul E.; Mackie, T. Rockwell; Jaradat, Hazim A.; Vail, David M.; Dubielzig, Richard R.; Chappell, Richard; Mehta, Minesh P.

2010-01-01

Intensity modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared to a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT treated and 2D treated dogs was 420 days and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared to historical controls treated with 2D-RT. PMID:20973393

Histopathological and biochemical assessment of d-limonene-induced liver injury in rats.

PubMed

Ramos, Carlos Alberto F; Sá, Rita de Cássia da S; Alves, Mateus F; Benedito, Rubens B; de Sousa, Damião P; Diniz, Margareth de Fátima F M; Araújo, Maria Salete T; de Almeida, Reinaldo N

2015-01-01

The aim of the present work was to develop a biochemical, histologic and immunohistochemical study about the potential hepatotoxic effect of d-limonene - a component of volatile oils extracted from citrus plants. Blood alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) from d-limonene-treated animals were determined and compared to morphologic hepatic lesions in order to investigate the possible physiopathologic mechanisms involved in the liver toxicity, in experimental animals treated with d-limonene. Wistar rats were randomly divided into seven groups: two control groups (untreated or receiving only vehicle, tween-80); one positive control (vehicle); two experimental groups treated with d-limonene at doses of 25 mg/kg/day and 75 mg/kg/day for 45 days, and two other groups treated with the same doses for 30 days and kept under observation during 30 more days. Biochemical data showed significant reduction in ALT levels in the animals treated with 75 mg/kg of d-limonene. Histological analysis revealed some hepatocyte morphological lesions, including hydropic degeneration, microvesicular steatosis and necrosis, Kupffer cell hyperplasia and incipient fibrosis. By immunohistochemistry, influx of T (CD3+) and cytotoxic (CD8+) lymphocytes was observed in the rats treated with d-limonene at both dose levels. In conclusion, it is possible that d-limonene has been directly responsible for hepatic parenchymal and matrix damage following subchronic treatment with d-limonene.

Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial.

PubMed

Ishibashi, Keiichiro; Ishida, Hideyuki; Kuwabara, Kouki; Ohsawa, Tomonori; Okada, Norimichi; Yokoyama, Masaru; Kumamoto, Kensuke

2014-04-01

To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of flomoxef after the surgery. All the patients had received preoperative oral antibiotic prophylaxis (kanamycin and erythromycin) after mechanical cleansing within 24 h prior to surgery, and had received intravenous flomoxef during surgery. A total of 279 patients (including 139 patients in group 1 and 140 in group 2) were enrolled in the study. The incidence of SSIs was 13.7% in group 1 and 13.6% in group 2 (difference [95% confidence interval]: -0.2% [-0.9 to 0.7%]). The incidence of SSIs was not significantly different in patients undergoing elective rectal surgery who were treated using a single dose of postoperative antibiotics compared to those treated using multiple-dose antibiotics when preoperative mechanical and chemical bowel preparations were employed.

Impact of the Amount of Liquid Intake on the Dose Rate of Patients Treated with Radioiodine.

PubMed

Haghighatafshar, Mahdi; Banani, Aida; Zeinali-Rafsanjani, Banafsheh; Etemadi, Zahra; Ghaedian, Tahereh

2018-01-01

Despite therapeutic effects of radioiodine in patients with differentiated thyroid cancer, there are some disadvantages due to harmful radiation to other tissues. According to the current guidelines, patients are recommended to drink lots of water and frequent voiding to reduce the amount of 131 I in the body. This study was designed to assess the impact of the amount of liquid intake on reduction of the measured dose rate of radioiodine-treated patients. A total of 42 patients with differentiated thyroid cancer without metastasis who had undergone total thyroidectomy and had been treated with radioiodine were selected. The patients were divided into two groups according to the amount of their fluid intake which was measured during the first 48 h after 131 I administration. In all patients, the dose rate was measured immediately and 48 h after iodine administration. Each group included 21 patients. Dose rate ratio (the ratio of the second dose rate to the first dose rate) and dose rate difference ratio (the ratio of the difference between the two measured dose rates to the first dose rate) were calculated for each patient. Despite the significant difference in the amount of the liquid drunk, no statistically significant difference was seen between the different groups in parameters of dose-rate ratio and dose-rate difference ratio. Higher fluid intake (>60 ml/h in our study) alone would not effectively reduce the patient's radiation dose rate at least not more than a well-hydrated state. It seems that other interfering factors in the thyroidectomized patients may also have some impacts on this physiologic process.

Effect of parsley (Petroselinum crispum, Apiaceae) juice against cadmium neurotoxicity in albino mice (Mus musculus).

PubMed

Maodaa, Saleh N; Allam, Ahmed A; Ajarem, Jamaan; Abdel-Maksoud, Mostafa A; Al-Basher, Gadah I; Wang, Zun Yao

2016-02-04

Parsley was employed as an experimental probe to prevent the behavioral, biochemical and morphological changes in the brain tissue of the albino mice following chronic cadmium (Cd) administration. Non-anesthetized adult male mice were given parsley juice (Petroselinum crispum, Apiaceae) daily by gastric intubation at doses of 10 and 20 g/kg/day. The animals were divided into six groups: Group A, mice were exposed to saline; Groups B and C, were given low and high doses of parsley juice, respectively; Group D, mice were exposed to Cd; Groups E and F, were exposed to Cd and concomitantly given low and high doses of parsley, respectively. Cd intoxication can cause behavioral abnormalities, biochemical and histopathological disturbances in treated mice. Parsley juice has significantly improved the Cd-associated behavioral changes, reduced the elevation of lipid peroxidation and normalized the Cd effect on reduced glutathione and peroxidase activities in the brain of treated mice. Histological data have supported these foundations whereas Cd treatment has induced neuronal degeneration, chromatolysis and pyknosis in the cerebrum, cerebellum and medulla oblongata. The low dose (5 g/kg/day) of parsley exhibited beneficial effects in reducing the deleterious changes associated with Cd treatment on the behavior, neurotransmitters level, oxidative stress and brain neurons of the Cd-treated mice.

Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases

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

Kim, Yeon-Joo; Cho, Kwan Ho, E-mail: kwancho@ncc.re.kr; Kim, Joo-Young

2011-10-01

Purpose: To evaluate the efficacy of stereotactic radiotherapy in patients with brain metastases by comparing two different treatment regimens, single-dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Between November 2003 and December 2008, 98 patients with brain metastases were included. Fifty-eight patients were treated with SRS, and forty were treated with FSRT. Fractionated stereotactic radiotherapy was used for large lesions or lesions located near critical structures. The median doses were 20 Gy for the SRS group and 36 Gy in 6 fractions for the FSRT group. Results: With a median follow-up period of 7 months, the medianmore » survival was 7 months for all patients, with a median of 6 months for the SRS group and 8 months for the FSRT group (p = 0.89). Local progression-free survival (LPFS) rates at 6 months and 1 year were 81% and 71%, respectively, for the SRS group and 97% and 69%, respectively, for the FSRT group (p = 0.31). Despite the fact that FSRT was used for large lesions and lesions in adverse locations, LPFS was not inferior to SRS. Toxicity was more frequently observed in the SRS group than in the FSRT group (17% vs. 5%, p = 0.05). Conclusions: Because patients treated with FSRT exhibited similar survival times and LPFS rates with a lower risk of toxicity in comparison to those treated with SRS, despite the fact that FSRT was used for large lesions and lesions in adverse locations, we find that FSRT can particularly be beneficial for patients with large lesions or lesions located near critical structures. Further investigation is warranted to determine the optimal dose/fractionation.« less

Protective effects of vitamin E against myocardial ischemia/reperfusion injury in rats.

PubMed

Saleh, Nermine K; Saleh, Hanan A

2010-02-01

To clarify the cardioprotective effects of a short course of vitamin E treatment (vit E) as compared with a nitric oxide donor, nitroglycerin (GTN) against ischemia-reperfusion induced heart injury in rats. This randomized control study was conducted in the Physiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt from 1st June to 31 August 2009. This work was undertaken on 28 female Wistar rats weighing 150- 200 gm. Rats were allocated into 4 groups; control group (non-treated), GTN-treated group (rats received GTN intraperitoneally 25 minutes before sacrifice, in a dose of 120 ug/kg body weight), vit E-treated group (rat received vit E by oral tubal feeding 16-20 hours before sacrifice, in a dose of 250 mg/rat), and vit E and GTN-treated group (rats received vit E and GTN as in both GTN-treated group and vit E -treated group). After sacrifice, the hearts were excised and perfused in a Langendorff preparation and subjected to 30 minutes global ischemia and reperfused for 30 minutes. Following reperfusion, heart tissues were used for assessment of malondialdehyde (MDA) and nicotinamide adenine dinucleotide (NAD)+, and for histological examination. Vitamin E treatment resulted in an enhanced post-ischemic recovery of systolic function in vit E-treated groups (vit E-treated group, and vit E and GTN-treated group) compared to the control group. Post-ischemic recovery of coronary flow was enhanced in the vit E-treated group compared to the GTN-treated group. Post ischemic tissue degeneration indicators: MDA, and NAD+ indicated a cardioprotective effect of vit E. Histological study revealed marked improvement of myocytes and mitochondrial structure in the vit E-treated group as compared with the control group. Preconditioning with vit E treatment afforded substantial recovery of post-ischemic contractile, and vascular functions compared to GTN treatment, the mechanism might involve less opening of mitochondrial permeability transition during postischemic reperfusion.

[Treatment of acute full-thickness chondral defects with high molecular weight hyaluronic acid; an experimental model].

PubMed

Figueroa, D; Espinosa, M; Calvo, R; Scheu, M; Valderrama, J J; Gallegos, M; Conget, P

2014-01-01

To evaluate the effect of 2 different protocols of intra-articular hyaluronic acid (HA, hylan G-F20) to articular cartilage regeneration in acute full-thickness chondral defects. Full-thickness chondral defects of 3 x 6 mm were performed into the lateral femoral condyles of New Zealand rabbits, treated with a single or three doses of HA. The animals were sacrified at 12 weeks and the regenerated tissue was evaluated by direct observation and histology with the ICRS scale. Macroscopically, in both groups treated with HA the defects were filled with irregular tissue with areas similar to hyaline cartilage and others in which depressed areas with exposed subchondral bone were observed. Histological analysis showed in both groups treated with HA a hyaline-like cartilage compared to control group. However, the score of the International Cartilage Repair Society (ICRS) scale did not show differences between the groups treated with HA. The use of single dose or 3 doses of AH in acute chondral lesions has a limited and similar benefit in articular cartilage regeneration. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats.

PubMed

Vranic, Aleksandra; Simovic, Stefan; Ristic, Petar; Nikolic, Tamara; Stojic, Isidora; Srejovic, Ivan; Zivkovic, Vladimir; Jakovljevic, Vladimir; Djuric, Dusan

2017-11-01

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

Efficacy of albendazole against nematode parasites isolated from a goat farm in Ethiopia: relationship between dose and efficacy in goats.

PubMed

Eguale, Tadesse; Chaka, Hassen; Gizaw, Daniel

2009-10-01

A suspected case of albendazole resistance in a goat farm of Hawassa University was examined using faecal egg count reduction test (FECRT), controlled anthelmintic efficacy test and egg hatch assay (EHA) to verify the development of resistance and/or the need for higher doses of the drug in goats than in sheep. The experiment was conducted in 12 sheep (2 groups: treatment versus control) and 24 goats (4 groups: 3 treatments versus control, n = 6; per group) following artificial infection with infective larvae of Haemonchus contortus and Oesophagostomum columbianum. The first group of sheep and goats were treated orally with albendazole at the dose rate of 3.8 mg/kg body weight (i.e. manufacturer's recommended dose for sheep) while the second group of sheep and the fourth group of goats were left untreated. The second and the third group of goats were treated with albendazole at 5.7 and 7.6 mg/kg respectively. The FECRT showed an efficacy of albendazole in goats to be 65.5, 81.4 and 84.1% at the dose rate of 3.8, 5.7 and 7.6 mg/kg body weight respectively while in sheep it was 62% at the dose rate of 3.8 mg/kg. Increasing the dose to 1.5 the sheep recommended dose induced minor improvement of efficacy in goats; however the efficacy was almost the same at 1.5 and twice the dose recommended for sheep. Worm counts at day 15 post-treatment revealed that H. contortus has developed resistance to albendazole. EHA results also supported these findings. On the other hand, O. columbianum was 100% susceptible at all dose levels tested.

[Clinical trial on treatment of Parkinson's disease of Gan-Shen yin deficiency type by recipe for nourishing Gan-Shen].

PubMed

Zhao, Hong; Li, Wen-Wei; Gao, Jun-Peng

2007-09-01

To observe the curative effect of the recipe for nourishing Gan-Shen on Parkinson's disease (PD) of Gan-Shen yin deficiency type. One hundred and twenty-one PD patients were ran-domly assigned by blocking design to the control group and the treated group in the ratio of 1:1. All were treated according to the international medication guiding principle for PD treatment, but the treated group was ad-ministered with the recipe for nourishing Gan-Shen additionally. The treatment course lasted for 12 consecutive months, and the end point was the end of the 12th month. The unified Parkinson's disease rating scale (UP-DRS) score, TCM primary and secondary symptom scores were evaluated before treatment, every 3 months of treatment and at the end point. The average daily levodopa dose and the Hoehn & Yahr grading were assessed before treatment and at the end point. After treatment, UPDRS score in both groups showed an ascending trend at a slower rate in the treated groups than in the control group. At the 9th and 12th month of medication, a significant difference was found in UPDRS score between the two groups (P < 0.05), and the TCM symptom score was obviously lower in the treated group than in the control group (P < 0.05). At the end point of the trial, the average daily levodopa dose used was lower in the treated group than in the control group (P < 0.05) and there was no significant difference in the Hoehn & Yahr score between the two groups (P > 0.05). The recipe for norishing Gan-Shen can slow the ascending trend of UPDRS score in the PD patients, improve the symptoms of Gan-Shen yin deficiency, and decrease the daily levodopa dose used, showing a curative effect on PD of Gan-Shen yin deficiency type.

Analysis of buprenorphine/naloxone dosing impact on treatment duration, resource use and costs in the treatment of opioid-dependent adults: a retrospective study of US public and private health care claims.

PubMed

Khemiri, Amine; Kharitonova, Elizaveta; Zah, Vladimir; Ruby, Jane; Toumi, Mondher

2014-09-01

The buprenorphine/naloxone combination is used to treat the chronic relapsing disorder of opioid dependence. Adequate dosing levels are important to control cravings, prevent withdrawal syndrome, and maintain patients in treatment. The objective of this study was to estimate the impact of dosing on treatment persistence, resource utilization, and total direct health care costs. A retrospective cohort analysis was performed using administrative claims extracted from the MarketScan and Clinformatics databases from January 2007 to June and November 2012. Patients initiating treatment with buprenorphine/naloxone were classified into 2 groups based on the prescribed average dose over the entire treatment period and matched by multiple criteria. The threshold for differentiating the dosing groups was set at 15 and 15.7 mg/day for publicly and privately insured patients, respectively. Resource utilization and related costs were calculated over the 12-month period after the treatment initiation. Patient characteristics at baseline were considerably different between the privately and publicly insured patients. Publicly insured patients were slightly younger (33.1 vs 34.3 years old for privately insured) and had a higher prevalence of mental disorders (70.9% vs 64.9%). In both groups, patients treated with higher doses (> 15 mg and > 15.7 mg per day for publicly and privately insured patients, respectively) had lower risk of discontinuation (public: 11% lower; private: 9% lower) and lower probability of a psychiatric hospitalization than patients treated with lower doses (public: 17% lower; private: 41% lower). Total costs were comparable between the 2 groups (public: $14 600; private: $21 000) despite the expected higher cost of pharmacy in the higher-dose group. Treatment with higher doses of buprenorphine/naloxone was associated with a longer time to treatment discontinuation, less resource use, and lower total medical costs despite higher pharmacy acquisition cost.

Industrial hemp decreases intestinal motility stronger than indian hemp in mice.

PubMed

Sabo, A; Horvat, O; Stilinovic, N; Berenji, J; Vukmirovic, S

2013-02-01

Indian hemp has shown beneficial effects in various gastrointestinal conditions but it is not widely accepted due to high content of tetrahydrocannabinol resulting in unwanted psychotropic effects. Since industrial hemp rich in cannabidiol lacks psychotropic effects the aim of research was to study the effects of industrial hemp on intestinal motility. Animals were randomly divided in six groups (each group consisting of 6 animals): Control group, Cind group - receiving indian hemp infuse for 20 days, Cids group-receiving industrial hemp infuse for 20 days, M group - treated with single dose of morphine (5 mg/kg i.m.) Cind+M group - treated with indian hemp infuse and single dose of morphine (5 mg/kg i.m.), Cids+M - treated with industrial hemp infuse and single dose of morphine (5 mg/kg i.m.). On the 20th day of the study animals were administered charcoal meal, and were sacrificed 35 minutes after administration. Intestinal motility was estimated according to distance between carbo medicinalis and cecum in centimeters. Decrease of intestinal motility in animals treated with indian hemp infuse was not significant compared to controls and it was smaller compared to animals treated with morphine (Indian hemp =15.43±10.5 cm, morphine = 20.14±5.87 cm). Strongest decrease of intestinal motility was recorded in animals treated with industrial hemp infuse, and it was significant compared to controls and morphine (industrial hemp = 26.5±9.90 cm, morphine = 20.14±5.87 cm; p < 0.005). Although not completely without psychotropic activity cannabidiol could be a potential replacement for tetrahydrocannabinol. Since industrial hemp infuse rich in cannabidiol reduces intestinal motility in healthy mice cannabidiol should be further evaluated for the treatment of intestinal hypermotility.

Protective capabilities of silymarin and inulin nanoparticles against hepatic oxidative stress, genotoxicity and cytotoxicity of Deoxynivalenol in rats.

PubMed

Abdel-Wahhab, Mosaad A; El-Nekeety, Aziza A; Salman, Asmaa S; Abdel-Aziem, Sekena H; Mehaya, Fathy M; Hassan, Nabila S

2018-02-01

Deoxynivalenol (DON) is a Fusarium mycotoxin that frequently contaminates cereal and cereal-based food and induces liver injury. This study evaluated the protective role of silymarin nanoparticles (SILNPs) and inulin nanoparticles (INNPs) against DON-induced liver injury in rats. Eleven groups of rats were treated orally for 3 weeks as follows: the control group, DON-treated group (5 mg/kg b.w.); INNPs-treated groups at low (LD) or high (HD) dose (100 or 200 mg/kg b.w.); SILPNs-treated group (50 mg/kg b.w.); SILNPs plus INNPs(LD) or INNPs(HD)-treated groups; INNPs(LD) or INNPs(HD) plus DON-treated groups and DON plus SILNPs and INNPs(LD) or INNPs(HD)-treated groups. Blood and tissue samples were collected for different analyses. The results revealed that the practical sizes were 200 and 98 nm for SILNPs and INNPs respectively. DON increased liver enzymes activity, lipid profile, serum cytokines, number and percentage of chromosomal aberration, DNA fragmentation and comet score. It disturbed the oxidative stress markers, down regulated gene expression and induced histological changes in the liver tissue. Treatment with DON and SILNPs and/or INNPs at the two tested doses improved all the tested parameters and SILNPs plus INNPs(HD) normalized most of these parameters in DON-treated animals. SILNPs and INNPs could be promising candidates as hepatoprotective against DON or other hepatotoxins. Copyright © 2017 Elsevier Ltd. All rights reserved.

Traditional Chinese medicine versus western medicine as used in China in the management of rheumatoid arthritis: a randomized, single-blind, 24-week study.

PubMed

He, Yi-Ting; Ou, Ai-Hua; Yang, Xiao-Bo; Chen, Wei; Fu, Li-Yuan; Lu, Ai-Ping; Yan, Xiao-Ping; Feng, Xing-Hua; Su, Li; Song, Yue-Jin; Zeng, Sheng-Ping; Liu, Wei; Qian, Xian; Zhu, Wan-Hua; Lao, Ying-Rong; Xu, Wei-Hua; Wen, Ze-Huai; He, Xiao-Hong; Wang, Bao-Juan; Chen, Geng-Xin; Xue, Su-Qin

2014-12-01

This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.

Evaluation of Medicated Gel as a Supplement to Providing Acetaminophen in the Drinking Water of C57BL/6 Mice after Surgery

PubMed Central

Christy, Amanda C; Byrnes, Kimberly R; Settle, Timothy L

2014-01-01

After surgery, rodents frequently receive acetaminophen-treated drinking water for pain relief, but the effectiveness of this practice is often questioned. Gel products are now available to facilitate the delivery of oral medication to rodents after surgery. We sought to compare consumption of flavored medicated gel and medicated water after surgery and to determine whether providing supplemental acetaminophen in gel form ensures the ingestion of a therapeutic dose of an analgesic after surgery. Male C57BL/6 mice were allocated into 3 groups after surgery: those that received acetaminophen-treated water and untreated gel (MW group); those that received medicated gel and untreated water (MG group); and those that received acetaminophen in both forms (MWG group). Total water and gel consumption were monitored daily from the day before surgery until 2 d thereafter. Mice in the MG group consumed significantly less gel than water, and consequently, the total acetaminophen dose per mouse in the MG group (49 mg/kg) was significantly less than that of the MWG group (347 mg/kg). Although the dose consumed by mice in the MW group (158 mg/kg) approached the targeted acetaminophen dose of 200 mg/kg, only mice in the MWG group actually achieved the desired dose. The results of this study indicate that flavored acetaminophen-containing gel can be used in combination with medicated water to ensure that rodents ingest the targeted dose of medication. PMID:24602545

Antitrypanosomal Activity of Fexinidazole Metabolites, Potential New Drug Candidates for Chagas Disease

PubMed Central

Nascimento, Alvaro F. S.; Mazzeti, Ana Lia; Marques, Luiz F.; Gonçalves, Karolina R.; Mota, Ludmilla W. R.; Diniz, Lívia de F.; Caldas, Ivo S.; Talvani, André; Shackleford, David M.; Koltun, Maria; Saunders, Jessica; White, Karen L.; Scandale, Ivan; Charman, Susan A.; Chatelain, Eric

2014-01-01

This study was designed to verify the in vivo efficacy of sulfoxide and sulfone fexinidazole metabolites following oral administration in a murine model of Chagas disease. Female Swiss mice infected with the Y strain of Trypanosoma cruzi were treated orally once per day with each metabolite at doses of 10 to 100 mg/kg of body weight for a period of 20 days. Parasitemia was monitored throughout, and cures were detected by parasitological and PCR assays. The results were compared with those achieved with benznidazole treatment at the same doses. Fexinidazole metabolites were effective in reducing the numbers of circulating parasites and protecting mice against death, compared with untreated mice, but without providing cures at daily doses of 10 and 25 mg/kg. Both metabolites were effective in curing mice at 50 mg/kg/day (30% to 40%) and 100 mg/kg/day (100%). In the benznidazole-treated group, parasitological cure was detected only in animals treated with the higher dose of 100 mg/kg/day (80%). Single-dose pharmacokinetic parameters for each metabolite were obtained from a parallel group of uninfected mice and were used to estimate the profiles following repeated doses. Pharmacokinetic data suggested that biological efficacy most likely resides with the sulfone metabolite (or subsequent reactive metabolites formed following reduction of the nitro group) following administration of either the sulfoxide or the sulfone and that prolonged plasma exposure over the 24-h dosing window is required to achieve high cure rates. Fexinidazole metabolites were effective in treating T. cruzi in a mouse model of acute infection, with cure rates superior to those achieved with either fexinidazole itself or benznidazole. PMID:24841257

Anti-Fatigue Effect of Green Tea Polyphenols (-)-Epigallocatechin-3-Gallate (EGCG).

PubMed

Teng, Yu-Song; Wu, Di

2017-01-01

(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant of the green tea polyphenols that exhibit a variety of bioactivities. The objective of this study was to evaluate the anti-fatigue effect of EGCG by forced swimming exercise. The mice were divided into one control group and three EGCG-treated groups. The control group was administered with distilled water and EGCG-treated groups were administered with different dose of EGCG (50, 100, and 200 mg/kg) by oral gavage for 28 days. On the last day of experiment, the forced swimming exercise was performed and corresponding biochemical parameters were measured. The data showed that EGCG prolonged exhaustive swimming time, decreasing the levels of blood lactic acid, serum urea nitrogen, serum creatine kinase and malondialdehyde, which were accompanied by corresponding increase in liver and muscle glycogen contents, and superoxide dismutase, catalase, and glutathione peroxidase activities. This study indicated that EGCG had an anti-fatigue effect. EGCG significantly prolonged exhaustive swimming time and decreased the levels of BLA, SUN, SCK and MDA, which were accompanied by corresponding increases in liver and muscle glycogen contents, and SOD, CAT, and GPx activities.EGCG can be used to design nutraceutical supplements aimed to facilitate recovery from fatigue and attenuate exhaustive exercise-induced oxidative damage. Abbreviations used: EGCG: (-)-Epigallocatechin-3-gallate, ROS: reactive oxygen species, BLA: blood lactic acid, SUN: serum urea nitrogen, SOD: superoxide dismutase, GPx: glutathione peroxidase, CAT: catalase, SCK: serum creatine kinase, MDA: malondialdehyde, C: control, LET: Low-dose EGCG-treated, MET: Middle-dose EGCG-treated, HET: High-dose EGCG-treated, GTE: green tea extract.

Antihyperlipidemic effects of Citrus sinensis, Citrus paradisi, and their combinations

PubMed Central

Mallick, Neelam; Khan, Rafeeq Alam

2016-01-01

Objective: Hyperlipidemia, extensively contributes in the progression of coronary heart diseases and atherosclerosis, but may be managed through alterations in the nutritional pattern. Several studies show that diet rich in polyphenols and antioxidants have antiatherogenic effects. Citrus sinensis and Citrus paradisi are widely known for health benefits and have found to produce antioxidant, anti-inflammatory, and hypolipidemic effects, hence current research was planned to determine the hypolipidemic effects of C. sinensis and C. paradisi in rats receiving diet rich in cholesterol. Materials and Methods: All rats were divided into 11 groups each comprising 10 animals: Normal control group and hyperlipidemic control. C. sinensis treated three groups, C. paradisi treated three groups, C. sinensis and C. paradisi combination treated two groups, and group treated atorvastatin. All rats in the respective groups were treated orally with sterile water, juices, and standard drug for 8 weeks and lipid profile was estimated at the end of dosing. Results: Cholesterol, triglycerides (TGs), and low-density lipoprotein (LDL) were decreased at all the three doses of C. sinensis and C. paradisi but rise in high-density lipoprotein (HDL) was only significant at 8 ml/kg, and 0.3 ml/kg, respectively. Animals received the combination doses of C. sinensis and C. paradisi also showed a highly significant fall in cholesterol, LDL, and TGs, however HDL level was significantly elevated by SPJ-2 combination. Conclusion: Results suggest that C. sinensis and C. paradisi possess antihyperlipidemic activity due to phytochemicals and other essential nutrients, hence may serve as cardioprotective by preventing thrombosis. PMID:27134462

Developmental-stage-dependent radiosensitivity of neural cells in the ventricular zone of telencephalon in mouse and rat fetuses

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

Hoshino, K.; Kameyama, Y.

1988-03-01

Pregnant ICR mice were treated with single whole-body X-radiation at a dose of 0.24 Gy on day 10, 13, or 15 of gestation. Fetuses were obtained from mothers during 1 and 24 hours after irradiation. Pyknotic cells in the ventricular zone of telencephalon were counted in serial histological sections. Incidence of pyknotic cells peaked during 6 and 9 hours after irradiation in each gestation day group. Then, dose-response curves were obtained 6 hours after 0-0.48 Gy of irradiation. All three dose-response curves showed clear linearity in the dose range lower than 0.24 Gy. Ratios of radiosensitivity estimated from the slopesmore » of dose-response curves in day 10, 13, and 15 groups were 1, 1.4, and 0.4, respectively. These demonstrated that ventricular cells in the day 13 fetal telencephalon were the most radiosensitive among the three different age groups. In order to confirm the presence of the highly radiosensitive stage common to mammalian cerebral cortical histogenesis, pregnant F344 rats were treated with single whole-body gamma-irradiation at a dose of 0.48 Gy on day 13, 14, 15, 17, or 19 of gestation. The incidence of pyknotic cells in the ventricular zone of telencephalon was examined microscopically during 1 and 24 hours after irradiation. The peak incidence was shown 6 hours after irradiation in all the treated groups, and the highest peak incidence was shown in day-15-treated group. The developmental stage of telencephalon of day 15 rat fetuses was comparable to that of day 13 mouse fetuses. Thus, the highest radiosensitivity in terms of acute cell death was shown in the same developmental stage of brain development, i.e., the beginning phase of cerebral cortical histogenesis, in both mice and rats.« less

Post-training scopolamine treatment induced maladaptive behavior in open field habituation task in rats.

PubMed

Popović, Natalija; Caballero-Bleda, María; Popović, Miroljub

2014-01-01

The effects of scopolamine on memory consolidation are controversial and depend on several factors (i.e. site of administration, time of administration and testing, dose, cognitive task, experimental protocol, specie, strain, etc.). Generally, the range dose of systemic administered scopolamine, used in memory consolidation studies, has varied from 0.05 to 50 mg/kg. However, according to the literature, the most frequently used doses of scopolamine efficient on memory consolidation, are 1 and 30 mg/kg, low and high doses, respectively. In open field habituation studies only lower doses of scopolamine were used to test memory consolidation. Therefore, in the present study we compared the effects of low (1 mg/kg) and high (30 mg/kg) scopolamine dose, on the open field habituation task, in male Wistar rats. Scopolamine was administered immediately after the acquisition task and animals were retested 48 h later on. On the retested day, the ambulation and rearing in the open field decreased in the same manner in all tested groups. In saline- and 1 mg/kg scopolamine-treated animals, the time spent in grooming significantly decreased in the habituation task, while the same parameter significantly increased in animals treated with 30 mg/kg of scopolamine. The defecation rate significantly decreased (control group), maintained (1 mg/kg of scopolamine treated animals) or significantly increased (30 mg/kg of scopolamine treated group) on retention test. In conclusion, the present data suggest that post-training scopolamine administration does not affect locomotion neither exploration in the habituation to a novel environment, but increases defecation and grooming, two behaviours associated with fearful and stressful situations.

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.

PubMed

Yuan, Hong; Zhang, Lei; Frank, Jonathan E; Inscoe, Christina R; Burk, Laurel M; Hadsell, Mike; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

2015-09-01

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

PubMed

Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

1992-02-01

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (3)--One- and three-month repeated oral dose toxicity studies in rats].

PubMed

Kato, I; Sato, K; Ueno, M; Inoue, S; Harihara, A; Moriyama, T; Nishimura, K; Yabuuchi, K; Hirata, M; Muraoka, Y; Kitamura, T; Furukawa, H

2001-05-01

One- or three-month repeated oral dose toxicity studies of Cefmatilen hydrochloride hydrate (S-1090) in rats were conducted. Doses were set at 80, 200, 500 and 1250 mg potency/kg/day in the one-month toxicity study, and 100, 300 and 1000 mg potency/kg/day in the three-month toxicity study. Body weights increased favorably and no deaths occurred in all treated groups of both studies. The changes observed in both studies were soft feces, abdominal distention, increased food and water consumption, decreases of urine volume and pH, and a decrease of blood neutrophils in almost all treated groups, reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) in groups dosed at 300 mg potency/kg or more, and a lower mature granulocyte ratio in the bone marrow in groups dosed at 1000 mg potency/kg or more. In necropsy, cecal enlargement with a large amount of muddy content was observed in all treated groups of both studies. In the three-month toxicity study, elevated drug-metabolizing enzyme activities were noted in the liver of the males in the 1000 mg potency/kg group. These changes were slight except for the cecal enlargement and the rats recovered well with drug withdrawal. Since no toxicologically significant changes were noted in either study, the NOAEL of S-1090 was estimated to be 1250 mg potency/kg/day in the one-month toxicity study and 1000 mg potency/kg/day in the three-month toxicity study.

Dosimetric and delivery efficiency investigation for treating hepatic lesions with a MLC-equipped robotic radiosurgery-radiotherapy combined system.

PubMed

Jin, Lihui; Price, Robert A; Wang, Lu; Meyer, Joshua; Fan, James Jiajin; Ma, Chang Ming Charlie

2016-02-01

The CyberKnife M6 (CK-M6) Series introduced a multileaf collimator (MLC) for extending its capability from stereotactic radiosurgery/stereotactic radiotherapy (SBRT) to conventionally fractionated radiotherapy. This work is to investigate the dosimetric quality of plans that are generated using MLC-shaped beams on the CK-M6, as well as their delivery time, via comparisons with the intensity modulated radiotherapy plans that were clinically used on a Varian Linac for treating hepatic lesions. Nine patient cases were selected and divided into three groups with three patients in each group: (1) the group-one patients were treated conventionally (25 fractions); (2) the group-two patients were treated with SBRT-like hypofractionation (5 fractions); and (3) the group-three patients were treated similar to group-one patients, but with two planning target volumes (PTVs) and two different prescription dose levels correspondingly. The clinically used plans were generated on the eclipse treatment planning system (TPS) and delivered on a Varian Linac (E-V plans). The multiplan (MP) TPS was used to replan these clinical cases with the MLC as the beam device for the CK-M6 (C-M plans). After plans were normalized to the same PTV dose coverage, comparisons between the C-M and E-V plans were performed based on D(99%) (percentage of prescription dose received by 99% of the PTV), D(0.1cm(3)) (the percentage of prescription dose to 0.1 cm(3) of the PTV), and doses received by critical structures. Then, the delivery times for the C-M plans will be obtained, which are the MP TPS generated estimations assuming having an imaging interval of 60 s. The difference in D(99%) between C-M and E-V plans is +0.6% on average (+ or - indicating a higher or lower dose from C-M plans than from E-V plans) with a range from -4.1% to +3.8%, and the difference in D(0.1cm(3)) was -1.0% on average with a range from -5.1% to +2.9%. The PTV conformity index (CI) for the C-M plans ranges from 1.07 to 1.29 with a mean of 1.19, slightly inferior to the E-V plans, in which the CI ranges from 1.00 to 1.15 with a mean of 1.07. Accounting for all nine patients in three groups, 45% of the critical structures received a lower mean dose for the C-M plans as compared with the E-V plans, and similarly, 48% received a lower maximum dose. Furthermore, the average difference of the mean critical structure dose between the C-M and E-V plans over all critical structures for all patients showed only +2.10% relative to the prescription dose and the similar comparison finds the average difference of the maximum critical structure dose of only +1.24%. The estimated delivery times for the C-M plans on the CK-M6 range from 18 to 24 minutes while they are from 7 to 13.7 min for the E-V plans on the Varian Linac. For treating hepatic lesions, for the C-M plans that are comparable to E-V plans in quality, the times needed to deliver these C-M plans on the CK-M6 are longer than the delivery time for the E-V plans on the Varian Linac, but may be clinically acceptable.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

PubMed Central

Sandrini, G; Cerbo, R; Del Bene, E; Ferrari, A; Genco, S; Grazioli, I; Martelletti, P; Nappi, G; Pinessi, L; Sarchielli, P; Tamburro, P; Uslenghi, C; Zanchin, G

2007-01-01

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57–1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82–1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf. PMID:17627707

Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease.

PubMed

Nunes, Marielza Andrade; Viel, Tania Araujo; Buck, Hudson Sousa

2013-01-01

A lower incidence of dementia in bipolar patients treated with lithium has been described. This metal inhibits the phosphorylation of glycogen-synthase-kinase 3-α and β, which are related to amyloid precursor protein processing and tau hyperphosphorylation in pathological conditions, respectively. Following the same rationale, a group just found that lithium has disease-modifying properties in amnestic mild cognitive impairment with potential clinical implications for the prevention of Alzheimer's Disease (AD) when a dose ranging from 150 to 600 mg is used. As lithium is highly toxic in regular doses, our group evaluated the effect of a microdose of 300 μg, administered once daily on AD patients for 15 months. In the evaluation phase, the treated group showed no decreased performance in the mini-mental state examination test, in opposition to the lower scores observed for the control group during the treatment, with significant differences starting three months after the beginning of the treatment, and increasing progressively. This data suggests the efficacy of a microdose lithium treatment in preventing cognitive loss, reinforcing its therapeutic potential to treat AD using very low doses.

Clinical efficacy of Spasmofen® suppository in the emergency treatment of renal colic: a randomized, double-blind, double-dummy comparative trial.

PubMed

Yakoot, Mostafa; Salem, Amel; Yousef, Sameh; Helmy, Sherine

2014-01-01

Renal colic is typically characterized by the sudden onset of severe pain radiating from the flank to the groin and its acute management in emergency departments essentially aims at rapid pain relief. Spasmofen(®) is a brand of Amriya Pharmaceutical Industries in the form of rectal suppositories containing ketoprofen 100 mg and hyoscine butylbromide 10 mg. This combination is intended for the rapid relief of severe colicky pain in the renal system, hepatobiliary system, or gastrointestinal tract. This trial aims to compare a single-dose of Spasmofen rectal suppository to a single intravenous (IV) ketorolac tromethamine 30 mg/2 mL dose in patients with acute renal colic. A total of 80 eligible consecutive patients presenting to the emergency departments of two medical centers with acute renal colic were included in the study. Eligible patients who signed the informed consent were randomly assigned into two treatment groups: an experimental group (Spasmofen group) who received one Spasmofen rectal suppository plus an IV injection of 2 mL of normal saline solution; and a control group (ketorolac group) who received one ketorolac 30 mg/2 mL ampoule IV plus one placebo suppository. Treatment success, defined as a change in the verbal rating score from severe or moderate pain to none or mild at 60 minutes after the dose, was compared between groups using the chi-square/Fisher's exact test. Percentage reductions in visual pain analog scale (VPAS) scores at 15 and 60 minutes after the dose were compared between groups using the Z-test for proportions. Successful treatment at 60 minutes occurred in 35 of 40 (87.5%) of Spasmofen-treated patients and in 33 of 40 (82.5%) of ketorolac-treated patients. The difference was not statistically significant by Fisher's exact test (P=0.755). The mean percentage reduction of VPAS after 15 minutes was 61.82% in the Spasmofen-treated group and 64.76% in the ketorolac-treated group. The difference was also not statistically significant by the Z-test for proportions (P=0.795). Sixty minutes after being treated, Spasmofen was associated with a statistically significant greater reduction in VPAS (mean% reduction =92.36%) than ketorolac (75.06%; P=0.0466). Single-dose Spasmofen rectal suppository might be a safe and effective first-aid treatment for the emergency department relief of acute renal colic.

Radiation dose rates of differentiated thyroid cancer patients after 131I therapy.

PubMed

Jin, Pingyan; Feng, Huijuan; Ouyang, Wei; Wu, Juqing; Chen, Pan; Wang, Jing; Sun, Yungang; Xian, Jialang; Huang, Liuhua

2018-05-01

Postoperative 131 I treatment for differentiated thyroid cancer (DTC) can create a radiation hazard for nearby persons. The present prospective study aimed to investigate radiation dose rates in 131 I-treated DTC patients to provide references for radiation protection. A total of 141 131 I-treated DTC patients were enrolled, and grouped into a singular treatment (ST) group and a repeated treatment (RT) group. The radiation dose rate of 131 I-treated patients was measured. The rate of achieving discharge compliance and restricted contact time were analyzed based on Chinese regulations. Multivariate logistic regression analysis was used to analyze the independent factors associated with the clearance of radioiodine. The rate of achieving discharge compliance ( 131 I retention < 400 MBq) was 79.8 and 93.7% at day 2 (D2) for the ST and RT groups, respectively, and reached 100% at D7 and D4, respectively. The restricted contact time with 131 I-treated patients at 0.5 m for medical staff, caregivers, family members, and the general public ranged from 4 to 7 days. Multivariate logistic regression analysis showed that the 24-h iodine uptake rate was the only significant factor associated with radioiodine clearance. For the radiation safety of 131 I-treated DTC patients, the present results can provide radiometric data for radiation protection.

Saw palmetto extract enhances erectile responses by inhibition of phosphodiesterase 5 activity and increase in inducible nitric oxide synthase messenger ribonucleic acid expression in rat and rabbit corpus cavernosum.

PubMed

Yang, Surong; Chen, Changrui; Li, Yiying; Ren, Zhenghua; Zhang, Yungang; Wu, Gantong; Wang, Hao; Hu, Zhenzhen; Yao, Minghui

2013-06-01

To evaluate whether saw palmetto extract (SPE) relaxes corpus cavernosum and explore the underlying mechanisms. Forty Sprague-Dawley rats and 30 New Zealand rabbits were randomly allocated into 3 SPE-treated groups (low-, middle-, and high-dose) and 1 saline-treated control group. SPE was administered intragastrically for 7 consecutive days. Another 23 rats treated with sildenafil were used to appraise the erectile response to electrical stimulation of nerves in the corpus cavernosum. The erectile functions of rats and rabbits were evaluated 24 hours after the last SPE administration or 15 minutes after intragastric sildenafil. Outcome measures included corpus cavernosum electrical activity recording, phosphodiesterase 5 (PDE5) activity detected by the colorimetric quantitative method, and messenger ribonucleic acid (mRNA) expression level for PDE5 and inducible nitric oxide synthase (iNOS) determined using real-time polymerase chain reaction. In the SPE-treated animals, the relaxant response to electrical stimulation of nerves in the corpus cavernosum, reflected by the amplitude of the electrical activity within the cavernosum, was significantly and dose-dependently augmented. Similar effects were observed in the sildenafil-treated rats. PDE5 activity in rat and rabbit corpus cavernosum tissues was significantly and dose-dependently inhibited in SPE-treated animals, whereas the iNOS mRNA level increased compared with the saline group. PDE5 mRNA, however, was only significantly enhanced in the rats treated with the middle dose of SPE. The results suggest that SPE may have potential application value for the prevention or treatment of erectile dysfunction through an increase in iNOS mRNA expression and inhibition of PDE5 activity in corpus cavernosum smooth muscles. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of vitamin E and selenium separately and in combination on biochemical, immunological and histological changes induced by sodium azide in male mice.

PubMed

El-Shenawy, Nahla S; AL-Harbi, Mohammad S; Hamza, Reham Z

2015-01-01

Sodium azide (SA) is used as an active ingredient to control a broad spectrum of soil borne pathogens including insects, weeds, nematodes, fungi, and bacteria. The purpose of this study was to evaluate the ameliorator property of vitamin E (Vit E) or/and selenium (Se) against SA-induced injury in male mice at the biochemical, immunological and histological levels. The mice were divided into nine groups (10/group). The first three groups were served as control, Vit E and Se while, the second three groups were treated with three different doses of SA. The last three groups were treated with high dose of SA with Vit E or Se or Vit E and Se and all animals were treated for a period of 30 days. Exposure to SA at the three doses to mice led to an alternation of liver and kidney functions, decrease the testosterone concentration, decreased IgG and IgM levels as well as the increasing the TNF-α. The effects of SA on the biochemical parameters of mice were dose-dependent. Administration of Se or/and Vit E to SA-treated mice attenuates the toxicity of this compound, objectified by biochemical and histological improvement of liver, kidney and testis. But, the alleviation is more pronounced with the both antioxidants. Thus, the synergistic effect of Se and Vit E is most powerful in reducing the toxicity induced by SA and improving the humoral immune response of mice. Copyright © 2014 Elsevier GmbH. All rights reserved.

Modulating Effects of Spirulina platensis against Tilmicosin-Induced Cardiotoxicity in Mice.

PubMed

Ibrahim, Abdelaziz E; Abdel-Daim, Mohamed Mohamed

2015-01-01

Tilmicosin (TIL) is a long-acting macrolide antibiotic used to treat cattle for pathogens that cause bovine respiratory disease. However, overdoses of this medication have been reported to induce cardiac damage. Our experimental objective was to evaluate the protective effects of Spirulina platensis (SP) administration against TIL-induced cardiotoxicity in mice. Our experimental in vivo animal study used 40 male albino mice that were divided into five groups of eight mice per group. The first group served as a control group and was injected with saline. The second group received SP at dose of 1000 mg/kg body weight for five days. The third group received a single dose of TIL (75 mg/kg, subcutaneously). Groups 4 and 5 were given SP at doses of 500 and 1000 mg/kg body weight for five consecutive days just before administration of TIL at the same dose and regimen used for group 3. TIL treated animals showed a significant increase in serum cardiac injury biomarkers as well as cardiac lipid peroxidation, however they had evidence of an inhibition in antioxidant biomarkers. SP normalized elevated serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB. Furthermore, SP reduced TIL-induced lipid peroxidation and oxidative stress in a dose-dependent manner. Administration of SP minimized the toxic effects of TIL by its free radicalscavenging and potent antioxidant activity.

Modulating Effects of Spirulina platensis against Tilmicosin-Induced Cardiotoxicity in Mice

PubMed Central

Ibrahim, Abdelaziz E.; Abdel-Daim, Mohamed Mohamed

2015-01-01

Objective Tilmicosin (TIL) is a long-acting macrolide antibiotic used to treat cattle for pathogens that cause bovine respiratory disease. However, overdoses of this medication have been reported to induce cardiac damage. Our experimental objective was to evaluate the protective effects of Spirulina platensis (SP) administration against TIL-induced cardiotoxicity in mice. Materials and Methods Our experimental in vivo animal study used 40 male albino mice that were divided into five groups of eight mice per group. The first group served as a control group and was injected with saline. The second group received SP at dose of 1000 mg/kg body weight for five days. The third group received a single dose of TIL (75 mg/kg, subcutaneously). Groups 4 and 5 were given SP at doses of 500 and 1000 mg/kg body weight for five consecutive days just before administration of TIL at the same dose and regimen used for group 3. Results TIL treated animals showed a significant increase in serum cardiac injury biomarkers as well as cardiac lipid peroxidation, however they had evidence of an inhibition in antioxidant biomarkers. SP normalized elevated serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB. Furthermore, SP reduced TIL-induced lipid peroxidation and oxidative stress in a dose-dependent manner. Conclusion Administration of SP minimized the toxic effects of TIL by its free radicalscavenging and potent antioxidant activity. PMID:25870843

Quercetin dose affects the fate of hepatic ischemia and reperfusion injury in rats: An experimental research.

PubMed

Uylaş, Mustafa Ufuk; Şahin, Adnan; Şahintürk, Varol; Alataş, İbrahim Özkan

2018-05-01

Quercetin found in fruits and vegetables has an antioxidative effect. We aimed to investigate the protective effects of quercetin according to different doses on hepatic and ischemia-reperfusion (I/R) injury. Fifty mature male Sprague-Dawley rats were randomly divided into five groups (n = 10 for each). All the animal groups underwent laparotomy. Group 1 rats served as a sham-operated group. Groups 2-5 underwent 1 h hepatic ischemia and were followed by 2 h reperfusion. Group 3-5 animals received an additional intraperitoneal dose of 25, 50 or 100 mg/kg quercetin respectively before I/R operation. Blood samples were collected for determining serum aspartate transaminase (AST), alanine transaminase (ALT) and malondialdehyde (MDA) levels. Also, liver tissue samples were taken for measuring of liver MDA concentration and for histopathology assessment. The highest levels of biochemical parameters were observed in group 2. In quercetin-treated groups, serum AST, ALT, MDA levels, and tissue MDA concentration were decreased as inversely with increasing quercetin dose. Microscopic evaluation revealed that most conspicuous histological improvement was observed in 50 mg/kg quercetin co-treated rats. 25 and 100 mg/kg quercetin co-treatment could not protect completely against hepatic I/R injury. Quercetin can be effective in preventing of hepatic I/R injury when the correct dose was used. Copyright © 2018. Published by Elsevier Ltd.

[Comparation study of incidental irradiation dose to the internal mammary chain during postmastectomy radiotherapy for patients treated with different irradiation techniques].

PubMed

Wang, W; Meng, Y T; Song, Y F; Sun, T; Xu, M; Shao, Q; Zhang, Y J; Li, J B

2018-05-23

Objective: To evaluated the unplanned coverage dose to the internal mammary chain (IMC) in patient treated with postmastectomy radiotherapy (PMRT). Methods: One hundred and thirty eight patients with breast cancer receiving radiotherapy (RT) in our hospital were retrospectively analyzed. Patients were divided into three groups: three-dimensional conformal radiotherapy (3D-CRT) group, forward intensity-modulated radiotherapy (F-IMRT) group and inverse IMRT (I-IMRT) group. The IMC were contoured according to Radiation Therapy Oncology Group (RTOG) consensus, and were not include into the planning target volume (PTV). The incidental irradiation dose to IMC among the three groups and the first three intercostal spaces IMC (ICS-IMC 1-3) were all compared, and explored the relationship between the mean doses (Dmean) of IMC and the OARs (ipsilateral lung and heart). Results: The dose delivered to IMC showed no difference in CRT, F-IMRT and I-IMRT(33.80 Gy, 29.65 Gy and 32.95 Gy). And 10.42%, 2.04%, and 9.76% patients achieved ≥45 Gy when treated with CRT, F-IMRT and I-IMRT. For the IMC dose in the first three intercostal spaces (ICS1-3), there was no difference to the three treatment plannings. The Dmean, V(20), V(30), V(40) and V(50) of the ICS-IMC2 and ICS-IMC3 were all obviously superior than ICS-IMC1 for all these three plannings. Moderate positive correlation was founded between Dmean for IMC and Dmean for heart for left breast cancer patients underwent CRT ( r =0.338, P =0.01). Whereas for F-IMRT and I-IMRT groups, positive correlation were founded between Dmean for IMC and Dmean and V(20) for ipsilateral lung for all patients (F-IMRT: r =0.366, P =0.010; r =0.318, P =0.026; I-IMRT: r =0.427, P =0.005; r =0.411, P =0.008). Conclusions: In 3D-CRT, F-IMRT and I-IMRT planning methods, partial patients get IMC irradiated doses that could achieve therapeutic doses. Compared with 3D-CRT, F-IMRT and I-IMRT further reduced the dose of irradiated organs. However, there is no difference in the dose coverage of IMC for the three planned approaches when the IMC made an unplanned target.

Doxycycline Stabilizes Vulnerable Plaque via Inhibiting Matrix Metalloproteinases and Attenuating Inflammation in Rabbits

PubMed Central

Dong, Mei; Zhong, Lin; Chen, Wen Qiang; Ji, Xiao Ping; Zhang, Mei; Zhao, Yu Xia; Li, Li; Yao, Gui Hua; Zhang, Peng Fei; Zhang, Cheng; Zhang, Lei; Zhang, Yun

2012-01-01

Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, P<0.05). There was no significant difference between doxycycline-treated group and simvastatin-treated group in any serological, ultrasonographic, pathologic, immunohistochemical and mRNA expression measurement except for the serum lipid levels that were higher with doxycycline than with simvastatin treatment. In conclusion, doxycycline at a common antimicrobial dose stabilizes atherosclerotic lesions via inhibiting matrix metalloproteinases and attenuating inflammation in a rabbit model of vulnerable plaque. These effects were similar to a large dose of simvastatin and independent of serum lipid levels. PMID:22737253

Atorvastatin repurposing for the treatment of cryptosporidiosis in experimentally immunosuppressed mice.

PubMed

Madbouly Taha, Noha; Salah A Yousof, Hebat-Allah; El-Sayed, Shaimaa H; Younis, Azza Ibrahim; Ismail Negm, Mohamed Sherif

2017-10-01

The present study was conducted on 200 male mice for the detection of the effect of Atorvastatin on Cryptosporidium spp. infection versus the commercially used drug Nitazoxanide in experimentally immunosuppressed mice. Atorvastatin was used alone at low dose (20 mg/kg), high dose (40 mg/kg), and combined with Nitazoxanide (1000 mg/kg) with either the low dose or high dose for five consecutive days. Parasitological assessment of the drug effect was done using Modified Z-N staining of stool samples collected from mice. Results revealed a reduction of the number of oocysts shed with percentage of reduction on the 21st day post infection by 53.7%, 67.2%, 70.1% &77.5%, respectively, compared to the infected untreated group. The Nitazoxanide treated group showed 52.7% reduction. In addition, examination of small and large intestinal contents after mice scarification revealed reduced numbers of oocysts by 56.2%-58.8%, 65.1%-65.3%, 70.6%-73.9% and 77.8%-79.9%, respectively, compared to 51.2%-54.1% in Nitazoxanide treated group. The histopathological examination of sections from duodenum, jejunum, ileum, colon, stomach and lungs also revealed a significant improvement of the histopathological changes in Atorvastatin treated groups and more remarkable improvement in the groups treated with combined drugs as compared to infected untreated group. Accordingly, the combination of Atorvastatin and Nitazoxanide showed a synergistic effect through reduction of the number of oocysts shed and improvement of the histopathological changes induced by Cryptosporidium spp. infection in the small intestine, colon, stomach and lungs of infected immunosuppressed mice in comparison to that induced by either Nitazoxanide or Atorvastatin alone. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative effects of Bisphenol S and Bisphenol A on the development of female reproductive system in rats; a neonatal exposure study.

PubMed

Ahsan, Nida; Ullah, Hizb; Ullah, Waheed; Jahan, Sarwat

2018-04-01

Bisphenol A (BPA) has been well documented for its endocrine disrupting potential however, very little is known about endocrine disrupting abilities of bisphenol S (BPS). The present study aimed to compare the endocrine disrupting potentials of BPS with BPA, using female rats as an experimental animal model. On postnatal day 1 (PND 1) female pups born were randomly assigned to seven different treatments. Control group received subcutaneous injection of castor oil (50 μL) from PND 1 to PND 10. Three groups of female pups were injected subcutaneously with different concentrations (0.5, 5 and 50 mg/kg in 50 μL castor oil) of BPS, while remaining three groups were treated with 0.5, 5 and 50 mg/kg BPA. Highest doses treatments of both compounds resulted in delayed puberty onset and altered estrous cyclicity. Final body weight was significantly high in the highest dose treated groups of both BPS and BPA. Gonadosomatic index, absolute and relative weight of uteri was significantly reduced in BPS (5 and 50 mg/kg) and BPA (5 and 50 mg/kg) treated groups than control. Plasma concentrations of testosterone and estradiol were significantly increased, while plasma progesterone, Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) concentrations were significantly reduced in highest doses treated groups. Dose dependent increase in the number of cystic follicles in the ovaries was evident along with an increase in the number of atratic follicles. The results suggest that neonatal exposure to higher concentrations of BPS can lead to BPA like structural and endocrine alterations in female rats. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effects of prednisolone and serum malondialdehyde levels in puppies with experimentally induced meconium aspiration syndrome.

PubMed

Kirimi, E; Tuncer, O; Kösem, M; Ceylan, E; Tas, A; Tasal, I; Balahoroğlu, R; Caksen, H

2003-01-01

The aim of this study was to investigate the effect of different doses of prednisolone in puppies experimentally induced with meconium aspiration syndrome (MAS). Meconium was collected from human babies in the first day of life and was released into the trachea of 11 newborn puppies to induce MAS. Puppies were treated with 2 mg/kg prednisolone (standard dose), 30 mg/kg prednisolone (megadose) or 0.9% saline, all administered intravenously. The study ended 20 h after meconium aspiration and the lungs were then scored for histopathology. Animals not treated with prednisolone deteriorated after 8 h while respiration rate, oxygenation, pH and partial pressure of carbon dioxide values were better in the prednisolone-treated groups. Histopathology scores were better in the treatment groups compared with the control group, with megadose giving the best result. At the end of the study, serum malondialdehyde levels were significantly higher in the megadose prednisolone group compared with the other two groups. In conclusion, we determined that prednisolone reduced physiological and histological changes in puppies with MAS and that a 30 mg/kg dose was more effective than 2 mg/kg.

Biological equivalence between LDR and PDR in cervical cancer: multifactor analysis using the linear-quadratic model.

PubMed

Couto, José Guilherme; Bravo, Isabel; Pirraco, Rui

2011-09-01

The purpose of this work was the biological comparison between Low Dose Rate (LDR) and Pulsed Dose Rate (PDR) in cervical cancer regarding the discontinuation of the afterloading system used for the LDR treatments at our Institution since December 2009. In the first phase we studied the influence of the pulse dose and the pulse time in the biological equivalence between LDR and PDR treatments using the Linear Quadratic Model (LQM). In the second phase, the equivalent dose in 2 Gy/fraction (EQD(2)) for the tumor, rectum and bladder in treatments performed with both techniques was evaluated and statistically compared. All evaluated patients had stage IIB cervical cancer and were treated with External Beam Radiotherapy (EBRT) plus two Brachytherapy (BT) applications. Data were collected from 48 patients (26 patients treated with LDR and 22 patients with PDR). In the analyses of the influence of PDR parameters in the biological equivalence between LDR and PDR treatments (Phase 1), it was calculated that if the pulse dose in PDR was kept equal to the LDR dose rate, a small the-rapeutic loss was expected. If the pulse dose was decreased, the therapeutic window became larger, but a correction in the prescribed dose was necessary. In PDR schemes with 1 hour interval between pulses, the pulse time did not influence significantly the equivalent dose. In the comparison between the groups treated with LDR and PDR (Phase 2) we concluded that they were not equivalent, because in the PDR group the total EQD(2) for the tumor, rectum and bladder was smaller than in the LDR group; the LQM estimated that a correction in the prescribed dose of 6% to 10% was ne-cessary to avoid therapeutic loss. A correction in the prescribed dose was necessary; this correction should be achieved by calculating the PDR dose equivalent to the desired LDR total dose.

Biological equivalence between LDR and PDR in cervical cancer: multifactor analysis using the linear-quadratic model

PubMed Central

Bravo, Isabel; Pirraco, Rui

2011-01-01

Purpose The purpose of this work was the biological comparison between Low Dose Rate (LDR) and Pulsed Dose Rate (PDR) in cervical cancer regarding the discontinuation of the afterloading system used for the LDR treatments at our Institution since December 2009. Material and methods In the first phase we studied the influence of the pulse dose and the pulse time in the biological equivalence between LDR and PDR treatments using the Linear Quadratic Model (LQM). In the second phase, the equivalent dose in 2 Gy/fraction (EQD2) for the tumor, rectum and bladder in treatments performed with both techniques was evaluated and statistically compared. All evaluated patients had stage IIB cervical cancer and were treated with External Beam Radiotherapy (EBRT) plus two Brachytherapy (BT) applications. Data were collected from 48 patients (26 patients treated with LDR and 22 patients with PDR). Results In the analyses of the influence of PDR parameters in the biological equivalence between LDR and PDR treatments (Phase 1), it was calculated that if the pulse dose in PDR was kept equal to the LDR dose rate, a small the-rapeutic loss was expected. If the pulse dose was decreased, the therapeutic window became larger, but a correction in the prescribed dose was necessary. In PDR schemes with 1 hour interval between pulses, the pulse time did not influence significantly the equivalent dose. In the comparison between the groups treated with LDR and PDR (Phase 2) we concluded that they were not equivalent, because in the PDR group the total EQD2 for the tumor, rectum and bladder was smaller than in the LDR group; the LQM estimated that a correction in the prescribed dose of 6% to 10% was ne-cessary to avoid therapeutic loss. Conclusions A correction in the prescribed dose was necessary; this correction should be achieved by calculating the PDR dose equivalent to the desired LDR total dose. PMID:23346123

Hepatitis B virus-related mortality in rheumatoid arthritis patients undergoing long-term low-dose glucocorticoid treatment: A population-based study.

PubMed

Yang, Sheng-Shun; Hung, Chin-Tun; Li, Shu-Fen; Lee, Horng-Mo; Chung, Yueh-Chin; Chen, Hsin-Hua; Chang, Shu-Chuan

2017-09-04

Glucocorticoids (GC) are commonly used in rheumatoid arthritis (RA) patients which bears a risk of hepatitis B virus (HBV) reactivation. The purpose of this study was to investigate the risk of HBV-related mortality under long-term low-dose GCs in Taiwanese RA patients. We retrospectively analyzed 45,423 RA patients using National Health Insurance Research Database from January 1999 to December 2011. Of them, 2204 patients had the diagnosis of HBV and were classified into four groups according to GCs regimens. Outcome comparison by Cox model analysis for liver-related mortality was performed. In this cohort, 90.5% were older than 40. One hundred and five patients had been treated with short-term large-dose GCs (Group A); 862 patients received GCs ≥20 mg/day for ≥3 days or a variable dose but did not meet Group C criteria (Group B); 689 patients were continuously treated with low-dose (<20 mg/day) GCs for ≥3 months for at least one session (Group C); and 548 patients had never been exposed to GCs (Group D). Two hundred and sixty-one patients had been exposed to antiviral agents, which was significantly higher in Group C. Fifty-eight patients (2.63%) died of acute hepatic failure, while no statistically significant difference between each groups (p = 0.074). Groups C and D comparison by two-sample test showed that long-term low-dose GC treatment was not associated with liver-related death after adjusting for malignancy. Long-term low-dose GC treatment was not associated with liver-related mortality in RA with concomitant HBV patients probably due to commonly applied antiviral therapy by rheumatologists. Copyright © 2017. Published by Elsevier B.V.

Effect of Variable Doses of Zinc Oxide Nanoparticles on Male Albino Mice Behavior.

PubMed

Zahra, Javeria; Iqbal, Shahid; Zahra, Kiran; Javed, Zulha; Shad, Muhammad Aslam; Akbar, Atif; Ashiq, Muhammad Naeem; Iqbal, Furhan

2017-02-01

Zinc oxide nanoparticles (ZnO NPs) have diverse utility these days ranging from being part of nanosensors to be ingredient of cosmetics. Present study was designed to report the effect of variable doses of ZnO NPs on selected aspects of male albino mice behavior. Nano particles were synthesized by sol-gel auto-combustion method (Data not shown here). 10 week old male albino mice were divided into four experimental groups; group A, B and C were orally supplemented with 50 (low dose), 300 (medium dose) and 600 mg/ml solvent/kg body weight (high dose) of ZnO NPs for 4 days. Group D (control) orally received 0.2 M sodium phosphate buffer (solvent for ZnO NPs) for the same duration. A series of neurological tests (Rota rod, open field, novel object and light-dark box test) were conducted in all groups and performance was compared between ZnO NPs treated and control group. Muscular functioning during rota rod test was significantly improved in all ZnO NPs treated mice as compared to control group. While no significant differences in open field, novel object and light-dark box test performance were observed when data from studied parameters of specific ZnO NPs treatment were compared with the control group indicating that applied doses of ZnO NPs did not affect the exploratory, anxiolytic behavior and object recognition capability of adult male albino mice.

Effects of long-term corticosterone implants on growth and immune function in juvenile alligators, Alligator mississippiensis.

PubMed

Morici, L A; Elsey, R M; Lance, V A

1997-10-01

Sixty juvenile alligators were implanted subcutaneously with slow release pellets of corticosterone or placebo. Alligators were divided into five different groups such that each group received a different dose. A blood sample was taken prior to and 4 days after the implants were in place to measure hormone levels. Additional blood samples were collected at 1 month and 3 months. At 4 days corticosterone levels ranged from 3,400 ng/ml in the group treated with the high dose to 40 ng/ml in the group implanted with the low dose. The extremely high dose caused 40% mortality within 4 weeks. It was evident that the pellets did not release the hormone for the expected 90 days. Circulating levels of corticosterone were back to baseline levels by 3 months. Hormone levels achieved at 4 days were a reliable predictor of subsequent growth. Rate of growth was negatively correlated with plasma corticosterone at 4 days (r2 = 0.711) and at 1 month (r2 = 0.544) posttreatment. Differential white blood cell counts performed after 1 month of treatment showed a clear effect of the implant. Alligators treated with corticosterone had decreased percentages of lymphocytes, eosinophils, and basophils and had a higher heterophil/lymphocyte (H/L) ratio than the placebo group. Furthermore, histological examination of the spleen revealed a significant depletion of lymphoid cells in alligators treated with the highest dose of hormone. The results from this study demonstrate that exogenous corticosterone can mimic the effects of prolonged stress in juvenile alligators.

Anti-Fatigue Effect of Green Tea Polyphenols (-)-Epigallocatechin-3-Gallate (EGCG)

PubMed Central

Teng, Yu-song; Wu, Di

2017-01-01

Background: (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant of the green tea polyphenols that exhibit a variety of bioactivities. The objective of this study was to evaluate the anti-fatigue effect of EGCG by forced swimming exercise. Materials and Methods: The mice were divided into one control group and three EGCG-treated groups. The control group was administered with distilled water and EGCG-treated groups were administered with different dose of EGCG (50, 100, and 200 mg/kg) by oral gavage for 28 days. On the last day of experiment, the forced swimming exercise was performed and corresponding biochemical parameters were measured. Results: The data showed that EGCG prolonged exhaustive swimming time, decreasing the levels of blood lactic acid, serum urea nitrogen, serum creatine kinase and malondialdehyde, which were accompanied by corresponding increase in liver and muscle glycogen contents, and superoxide dismutase, catalase, and glutathione peroxidase activities. Conclusions: This study indicated that EGCG had an anti-fatigue effect. SUMMARY EGCG significantly prolonged exhaustive swimming time and decreased the levels of BLA, SUN, SCK and MDA, which were accompanied by corresponding increases in liver and muscle glycogen contents, and SOD, CAT, and GPx activities.EGCG can be used to design nutraceutical supplements aimed to facilitate recovery from fatigue and attenuate exhaustive exercise-induced oxidative damage. Abbreviations used: EGCG: (-)-Epigallocatechin-3-gallate, ROS: reactive oxygen species, BLA: blood lactic acid, SUN: serum urea nitrogen, SOD: superoxide dismutase, GPx: glutathione peroxidase, CAT: catalase, SCK: serum creatine kinase, MDA: malondialdehyde, C: control, LET: Low-dose EGCG-treated, MET: Middle-dose EGCG-treated, HET: High-dose EGCG-treated, GTE: green tea extract. PMID:28539729

[UV-induced DNA damage and protective effects of antioxidants on DNA damage in human lens epithelial cells studied with comet assay].

PubMed

Wu, Zhi-hong; Wang, Mian-rong; Yan, Qi-chang; Pu, Wei; Zhang, Jin-song

2006-11-01

To investigate the mechanism of UV-induced DNA damage and repair and the protective effects of antioxidants on DNA damage in human lens epithelial cells. Human lens epithelial cells were irradiated at UV-doses 0.0 (control group), 2.5, 5.0, 7.5, 10.0 mJ/cm(2) (treated group 1 - 4). The amounts of DNA single strand breaks (SSB) were measured with the alkaline comet assay (CA). The spontaneous repair of DNA SSB after exposure to UV at 10.0 mJ/cm(2) was also determined in human lens epithelial cells. Human lens epithelial cells were treated with different concentration of VitaminC (VitC), taurine, superoxide dismutase (SOD) and epigallocatechin gallate (EGCG) before and after ultraviolet radiation, the effects of antioxidants on DNA damage was examined with alkaline comet assay. The amount of DNA SSB in control group and treated groups 1 - 4 showed increased tendency, was dose-dependent to the dose of UV irradiation, the differences of DNA SSB in 5 group were significantly (P < 0.01). UV-induced DNA SSB at 10.0 mJ/cm(2) in human lens epithelial cells, the half repair time was 60 minutes. Human lens epithelial cells were treated with different concentrations of taurine, SOD and EGCG before ultraviolet radiation. The differences of DNA damage in control and various antioxidant treated groups was statistically significant (F = 6.591, 13.542, 4.626 in cells treated with taurine, SOD and EGCG, respectively, P < 0.01), the difference of VitC effect on DNA in control and treated group were not significantly (F = 1.451, P > 0.05). Human lens epithelial cells were treated with different concentration of VitC, taurine, SOD and EGCG after ultraviolet radiation. The differences of DNA damage between the control and treated group were statistically significant (F = 6.571, 4.810, 6.824, 9.182 in cells treated with VitC, taurine, SOD and EGCG, respectively, P < 0.01). The differences of protective effects on DNA damage in these four different kinds of antioxidants added before UV irradiation were statistically significant (P < 0.01). The differences of protective effects on DNA damage in these four different kinds of antioxidant added after UV irradiation were not significantly (P > 0.05). UV irradiation has a dose-dependent effect on the DNA SSB of lens epithelial cells. Exogenesis VitC, taurine, SOD, EGCG possess protective effective to UV-induced DNA damage. SOD is one of the most powerful antioxidants if added before the UV irradiation and followed by EGCG, taurine and VitC orderly. Four kinds of antioxidants show no apparently differences added after UV-irradiation. SOD and EGCG both are powerful antioxidants.

Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat.

PubMed

Pic-Taylor, Aline; da Motta, Luciana Gueiros; de Morais, Juliana Alves; Junior, Willian Melo; Santos, Alana de Fátima Andrade; Campos, Leandro Ambrósio; Mortari, Marcia Renata; von Zuben, Marcus Vinicius; Caldas, Eloisa Dutra

2015-09-01

Ayahuasca, a psychoactive beverage used by indigenous and religious groups, is generally prepared by the coction of Psychotria viridis and Banisteriopsis caapi plants containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids, respectively. To investigate the acute toxicity of ayahuasca, the infusion was administered by gavage to female Wistar rats at doses of 30X and 50X the dose taken during a religious ritual, and the animals observed for 14 days. Behavioural functions were investigated one hour after dosing at 15X and 30X using the open field, elevated plus maze, and forced swimming tests. Neuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areas of rats treated with a 30X ayahuasca dose. The actual lethal oral dose in female Wistar rats could not be determined in this study, but was shown to be higher than the 50X (which corresponds to 15.1mg/kg bw DMT). The ayahuasca and fluoxetine treated groups showed a significant decrease in locomotion in the open field and elevated plus-maze tests compared to controls. In the forced swimming test, ayahuasca treated animals swam more than controls, a behaviour that was not significant in the fluoxetine group. Treated animals showed higher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent damage was detected. These results suggest that ayahuasca has antidepressant properties in Wistar female at high doses, an effect that should be further investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

Ketamine rapidly relieves acute suicidal ideation in cancer patients: a randomized controlled clinical trial.

PubMed

Fan, Wei; Yang, HaiKou; Sun, Yong; Zhang, Jun; Li, Guangming; Zheng, Ying; Liu, Yi

2017-01-10

This study was designed to examine the rapid antidepressant effects of single dose ketamine on suicidal ideation and overall depression level in patients with newly-diagnosed cancer. Forty-two patients were enrolled into the controlled trial and randomized into two groups: ketamine group and midazolam group. Patients from the two groups received a sub-anesthetic dose of racemic ketamine hydrochloride or midazolam. Suicidal ideation score, measured with the Beck Scale and suicidal part of the Montgomery-Asberg Depression Rating Scale, significantly decreased on day 1 and day 3 in ketamine-treated patients when compared to those treated with midazolam. Consistently, overall depression levels measured using the Montgomery-Asberg Depression Rating Scale indicated a significant relief of overall depression on day 1 in ketamine-treated patients. Collectively, this study provides novel information about the rapid antidepressant effect of ketamine on acute depression and suicidal ideation in newly-diagnosed cancer patients.

Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs

PubMed Central

Græsbøll, Kaare; Damborg, Peter; Mellerup, Anders; Herrero-Fresno, Ana; Larsen, Inge; Holm, Anders; Nielsen, Jens Peter; Christiansen, Lasse Engbo; Angen, Øystein; Ahmed, Shahana

2017-01-01

ABSTRACT This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for Lawsonia intracellularis-induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg). All groups were treated once a day for 5 days. In all groups, treatment caused a rise in the numbers and proportions of tetracycline-resistant coliform bacteria right after treatment, followed by a significant drop by the time that the pigs left the nursery unit. The counts and proportions of tetracycline-resistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated with tiamulin did not show significant changes in the numbers or proportions of tetracycline-resistant coliforms. Selection for tetracycline-resistant coliforms was significantly correlated to selection for ampicillin- and sulfonamide-resistant strains but not to selection for cefotaxime-resistant strains. In conclusion, the difference in the dose of oxytetracycline and the way in which the drug was applied did not cause significantly different levels of selection of tetracycline-resistant coliform bacteria under the conditions tested. IMPORTANCE Antimicrobial resistance is a global threat to human health. Treatment of livestock with antimicrobials has a direct impact on this problem, and there is a need to improve the ways that we use antimicrobials in livestock production. We hypothesized that antibiotic resistance development following treatment of diarrhea in nursery pigs could be reduced either by lowering the dose of oxytetracycline or by replacing the commonly used practice of flock treatment with individual or small-group treatments, since this would reduce the number of pigs treated. However, the study showed no significant difference between treatment groups with respect to the number or proportion of tetracycline-resistant coliforms selected. The most important conclusion is that under practical field conditions, there will be no added value, in terms of lowering resistance development, by exchanging flock treatment for individual or small-group treatment of nursery pigs. The reason for the lack of an effect of single-animal treatment is probably that such animals share the environment with treated animals and take up resistant bacteria from the environment. PMID:28389548

Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs.

PubMed

Græsbøll, Kaare; Damborg, Peter; Mellerup, Anders; Herrero-Fresno, Ana; Larsen, Inge; Holm, Anders; Nielsen, Jens Peter; Christiansen, Lasse Engbo; Angen, Øystein; Ahmed, Shahana; Folkesson, Anders; Olsen, John Elmerdahl

2017-06-15

This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for Lawsonia intracellularis -induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg). All groups were treated once a day for 5 days. In all groups, treatment caused a rise in the numbers and proportions of tetracycline-resistant coliform bacteria right after treatment, followed by a significant drop by the time that the pigs left the nursery unit. The counts and proportions of tetracycline-resistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated with tiamulin did not show significant changes in the numbers or proportions of tetracycline-resistant coliforms. Selection for tetracycline-resistant coliforms was significantly correlated to selection for ampicillin- and sulfonamide-resistant strains but not to selection for cefotaxime-resistant strains. In conclusion, the difference in the dose of oxytetracycline and the way in which the drug was applied did not cause significantly different levels of selection of tetracycline-resistant coliform bacteria under the conditions tested. IMPORTANCE Antimicrobial resistance is a global threat to human health. Treatment of livestock with antimicrobials has a direct impact on this problem, and there is a need to improve the ways that we use antimicrobials in livestock production. We hypothesized that antibiotic resistance development following treatment of diarrhea in nursery pigs could be reduced either by lowering the dose of oxytetracycline or by replacing the commonly used practice of flock treatment with individual or small-group treatments, since this would reduce the number of pigs treated. However, the study showed no significant difference between treatment groups with respect to the number or proportion of tetracycline-resistant coliforms selected. The most important conclusion is that under practical field conditions, there will be no added value, in terms of lowering resistance development, by exchanging flock treatment for individual or small-group treatment of nursery pigs. The reason for the lack of an effect of single-animal treatment is probably that such animals share the environment with treated animals and take up resistant bacteria from the environment. Copyright © 2017 American Society for Microbiology.

[Morphologic studies of the protective role of catechin on kanamycin otoneurotoxicity in SD rats].

PubMed

Liu, Guo-hui; Xie, Ding-hua; Wu, Wei-jing

2002-12-28

To determine the protection of catechin on aminoglycoside antibiotics otoneurotoxicity in SD rats, and observe the morphologic changes of cochlear efferent nerve terminals and outer hair cells after the injection of kanamycin and the feeding of catechin by the stomach tube. Thirty-eight SD rats were randomly assigned into three experimental groups (KM-treated, catechin-treated, KM and catechin in combination) and one control group. The KM-treated group was given kanamycin in a dose of 500 mg.(kg.d)-1 for 14 days. The catechin-treated group was given catechin once by the stomach tube in a dose of 400 mg.(kg.d)-1. Two kinds of medicine were simultaneously given in the KM+ catechin group. Transmission electron microscopy was utilized to observe the subcellular structure of efferent nerve fibers and outer hair cells. The densities of efferent nerve fibers and terminals were examined and the numbers of efferent nerve fibers and terminals were numerated by the surface preparation using modified histochemical staining for acetylcholinesterase (AchE). The damage in the group protected by catechin was relieved compared with the unprotected group. No damage was found in the catechin-treated alone group and controls. The densities and numbers of efferent nerve fibers and terminals were obviously fewer in the unprotected group than in the protected group and controls(P < 0.05). There was no significant difference in the numbers of efferent nerve fibers and terminals of the group protected by catechin compared with the controls and the catechin-treated group (P > 0.05). Catechin significantly protects MOC efferent nerves in kanamycin otoneurotoxicity.

[Neuroprotective effect of naloxone in brain damage caused by repeated febrile seizure].

PubMed

Shan, Ying; Qin, Jiong; Chang, Xing-zhi; Yang, Zhi-xian

2004-04-01

The brain damage caused by repeated febrile seizure (FS) during developing age is harmful to the intellectual development of children. So how to decrease the related damage is a very important issue. The main purpose of the present study was to find out whether the non-specific opiate antagonist naloxone at low dose has the neuroprotective effect on seizure-induced brain damage. Warm water induced rat FS model was developed in this study. Forty-seven rats were randomly divided into two groups: normal control group (n = 10) and hyperthermic seizure groups (n = 37). The latter was further divided into FS control group (n = 13) and naloxone-treated group (n = 24). The dose of naloxone is different in two naloxone-treated groups (12/each group), in one group the dose was 1 mg/kg, in the other one 2 mg/kg. Seven febrile seizures were induced in each rat of hyperthermic seizure groups with the interval of 2 days. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of the other groups were injected with 0.9% sodium chloride. Latency, duration and grade of FS in different groups were observed and compared. HE-staining and the electron microscopy (EM) were used to detect the morphologic and ultrastructural changes of hippocampal neurons. In naloxone-treated group, the rats' FS duration and FS grade (5.02 +/- 0.63, 2.63 +/- 0.72) were significantly lower (t = 5.508, P < 0.01; t = 8.439, P < 0.01) than those in FS control group (7.70 +/- 2.25 min, 4.52 +/- 0.49), although no significant gap was observed on FS latency between them. In FS control group, HE-staining pattern of hippocampal CA(1) and CA(2) showed lots of disordered neurons with confused polarity and vacuoles formed. Nuclei were with various size, some rounded and some oblong. While in naloxone-treated groups, the arrangement of neurons was regular, only a small quantity of neurons had changed polarity and vacuoles formed. Most nuclei were oblong and in the same size. In hippocampal CA(1) region and dentate gyrus of rats from FS control group, EM showed that the most mitochondrion volumes obviously increased with vacuoles formed, the matrix condensed, the ridge obscured or disappeared, apoptosis body emerged. Minor to moderate dilation of rough endoplasmic reticulum and Golgi's complex was also observed. However, in naloxone-treated groups, the number of neurons with swollen mitochondrion and endoplasmic reticulum was much fewer than that in FS control group. No apoptosis body was observed. The comparison between them showed much lighter brain damage in naloxone-treated groups than in FS control group. Although low-dose naloxone could not totally stop the occurrence of febrile seizure, it could lighten the brain damage resulted from repeated FS to some extent.

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

PubMed

Levitchi, Mihai; Charra-Brunaud, Claire; Quetin, Philippe; Haie-Meder, Christine; Kerr, Christine; Castelain, Bernard; Delannes, Martine; Thomas, Laurence; Desandes, Emmanuel; Peiffert, Didier

2012-06-01

To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(β)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(β)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effect of aqueous fruit extract of Xylopia aethiopica on intestinal fluid and glucose transfer in rats.

PubMed

Okwari, O O; Nneli, R O; Osim, E E

2010-11-28

Intestinal fluid and glucose absorption was studied in jejunal and ileal segments in Xylopia aethiopica fed rats using inverted sac technique. Thirty male Wistar rats were assigned into three groups of 10 rats each; control, 100mg/kg and 200mg/kg Xylopia aethiopica treated groups. The control group received normal rat chow and water while the low dose and high dose groups received oral administration of Xylopia aethiopica extract at doses of 100mg/kg and 200mg/kg body weight respectively in addition to daily rat chow and water intake for 28 days. The results showed significant reduction and increase in fluid transfer in the jejunum and ileum respectively compared with control. 100mg/kg increased gut fluid uptake in the ileum while 200mg/kg treatment reduced uptake in jejunum compared with control. Both doses had significantly increased jejunal and ileal glucose transfer. Gut glucose uptake was increased in jejunum and ileum of Xylopia aethiopica treated groups. Both doses increased the crypt depth but significantly decreased the villus height in the ileum. In conclusion, increased ileal gut fluid uptake may be beneficial in diarrheal state while an enhanced glucose uptake implies that glucose substrate may be made available to cells for synthesize of ATP for cellular activities.

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract.

PubMed

Bousquet, J; Hejjaoui, A; Skassa-Brociek, W; Guérin, B; Maasch, H J; Dhivert, H; Michel, F B

1987-10-01

Forty-five grass pollen-allergic patients were randomly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis. Eleven patients were treated with placebo (group 1), 19 patients (group 2) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure, and 15 other patients were treated with a standardized orchard grass-pollen extract (group 3). Because of a different immunotherapy schedule, only patients placed in groups 1 and 2 received the extracts in a double-blind fashion. Rush immunotherapy was performed in 3 to 6 days, and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season. During the season, a coseasonal treatment was administered. Systemic reactions occurred during the rush protocol in 36.8% of patients treated with allergoid and 20% of patients who received the standardized extract. Only patients treated with allergoid had systemic reactions during maintenance dose. The reactions observed with the standardized extract were more severe. Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units. Symptoms and medication scores during the peak of the season were analyzed. Patients treated with the standardized allergen had a significant reduction of the number of days of symptoms during the month of June (9.5 +/- 6.7 days; p less than 0.005) and of medication scores (1.3 +/- 1.4; p less than 0.01) compared to patients receiving placebo (19.4 +/- 8.1 days; medication score, 2.8 +/- 2.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats.

PubMed

Wood, Robert C; Wyatt, Jarrett E; Bullins, Kenny W; Hanley, Angela V; Hanley, Gregory A; Denham, James W; Panus, Peter C; Harirforoosh, Sam

2013-11-15

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is primarily limited by renal and gastrointestinal adverse effects. Rebamipide suppresses gastric mucosal injury when administered with NSAIDs. This study aimed to determine rebamipide's influence upon renal effects following concomitant use with celecoxib or diclofenac. On day 0, rats were randomly divided into 6 groups (n≥6). On days 1 and 2, three groups received placebo and three groups were administered rebamipide (30 mg/kg) twice daily. On day 3, the rats treated with placebo received another dose of placebo and ten minutes later a single dose of celecoxib (40 mg/kg), diclofenac (10mg/kg), or placebo, respectively. The rats treated with rebamipide received one more dose of rebamipide and ten minutes later one single dose of celecoxib, diclofenac, or placebo, respectively. Urine and blood samples were collected on days 0, 2, and 3. Sodium and potassium excretion rates decreased significantly in the rats treated with celecoxib, diclofenac, rebamipide plus celecoxib, or rebamipide plus diclofenac on day 3. Blood urea nitrogen (BUN) levels significantly increased in placebo plus diclofenac and rebamipide plus diclofenac groups on day 3. Comparing the two groups, the levels of BUN was significantly higher in the rebamipide plus diclofenac group compared to that of placebo plus diclofenac group. Concomitant administration of rebamipide with either NSAID caused a rise in concentrations of urinary kidney injury molecule-1. Histopathological evaluations revealed an intensified NSAID-induced tubular necrosis by rebamipide. Based upon the results obtained, concomitant administration of rebamipide with NSAIDs enhances the effect of NSAIDs on tubular injury. © 2013 Elsevier B.V. All rights reserved.

Cytogenetic effects of sildenafil citrate (Viagra) on SWR/J mouse bone marrow cells.

PubMed

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy

2010-10-01

The present study was conducted to investigate the cytogenetic effects of sildenafil citrate in SWR/J mouse bone marrow cells. Thirty-six males and 36 females were used and divided into four groups. Each group contained 18 animals (9 males and 9 females), weighing 30-35 g. These animals were orally administered with a single dose of 13, 26 or 40 mg/kg sildenafil citrate solution. A control group received normal saline in an identical condition. The animals were sacrificed at 12, 24 or 48 h, after the treatment. Chromosome aberrations were investigated in 50 metaphases per animal. No significant differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between treated male and female mice at any doses or at any time intervals used, therefore, data from the two sexes were pooled when analyzed statistically. No significant (p < 0.05) differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between sildenafil citrate-treated groups and the control group at any doses or at any time intervals used. However, the percentages of centromeric adhesions increased significantly (p < 0.01) in treated groups as compared with the control group at all doses and at all time intervals used. In conclusion, the results of the present study suggest that sildenafil citrate does not have cytogenetic effects on mouse bone marrow cells, but the centromeric adhesions induced by this drug need further studies to confirm them and to investigate the possible mechanism(s) responsible for such effect.

Use of nandrolone decanoate as an adjuvant for erythropoietin dose reduction in treating anemia in patients on hemodialysis.

PubMed

Sheashaa, Hussein; Abdel-Razek, Waleed; El-Husseini, Amr; Selim, Amal; Hassan, Nabil; Abbas, Tarek; El-Askalani, Hassan; Sobh, Mohamed

2005-01-01

Use of androgen as an adjuvant therapy to treat anemia in patients on hemodialysis is debated. Our target is to assess the safety and the efficacy of nandrolone decanoate (ND) as an effective adjunctive therapy to treat such anemia. This study included 32 anemic adult hemodialysis patients who had adequate iron stores. They were randomized into two equal groups: the first group received subcutaneously a low dose of erythropoietin (EPO) 1,000 U three times weekly combined with ND, 50 mg intramuscularly twice weekly, and the second group received only the same low dose of EPO for the 6-month study period. All patients were subjected to a serial follow-up of hemoglobin (Hb), hematocrit % (Hct%), iron store indices, serum insulin-like growth factor-1 (IGF-1) concentration and liver function tests. A significant rise of both Hb and Hct in both groups was found at the end of the study (p < 0.001). Although the rise of both Hb and Hct was higher in the androgen group, it was not rated as being statistically significant. Both groups showed a significant rise of serum IGF-1 concentration at the end of the study in comparison to its initial value. Moreover, the androgen group attained a more statistically significant rise of IGF-1 serum concentration. Four female patients discontinued ND because of related adverse effects, principally distressing hirsutism and hepatic dysfunction. Addition of ND to a low-dose EPO regimen does not offer a significant benefit. Androgen-related side effects limit its use in female patients.

Assessment of copper nanoparticles (Cu-NPs) and copper (II) oxide (CuO) induced hemato- and hepatotoxicity in Cyprinus carpio

NASA Astrophysics Data System (ADS)

Noureen, Aasma; Jabeen, Farhat; Tabish, Tanveer A.; Yaqub, Sajid; Ali, Muhammad; Shakoor Chaudhry, Abdul

2018-04-01

Recently, Cu-based nanoparticles have drawn considerable attention for their various fascinating roles in multiple biological systems. It is recognized that their frequent use can create compatibility challenges for the recipient systems. Nevertheless, it is unclear how various biological interactions affect the compatibility of Cu oxide II (CuO) and Cu oxide nanoparticles (Cu-NPs) for different organisms. Consequently, it has been difficult to perform structured risk assessments for their use in biological systems. Therefore, this study compared the effects of different doses of waterborne Cu-NPs and CuO on the blood and liver of selected groups of Cyprinus (C) carpio. These fish while housed in suitable water tanks were exposed to one of the following treatments for 14 d: control (no added Cu) or 0.5 or 1 or 1.5 mg Cu as Cu-NPs or CuO l-1 of water. We found significant changes in all assessed blood parameters of fish in response to increasing doses from 0 to 1.5 mg of Cu-NPs or CuO. Similarly, increased levels of lipid peroxide and reduced glutathione (GSH) were also observed in the livers of C. carpio in Cu-NPs or CuO treated groups. Enhanced levels of lipid peroxidation and GSH were also recorded in the Cu-NP treated groups compared with the CuO treated groups in a dose dependent manner. The lowest catalase activity was observed in the liver of C. carpio treated with the higer dose of Cu-NPs. Cu-NP or CuO exposure induced significant histological alterations in the liver of C. carpio including focal necrosis, cloudy swelling of hepatocytes, degenerative hepatocytes, vacuolization, pyknotic nuclei, damaged central vein, nuclear hypertrophy, dilated sinusoid, vacuolated degeneration, congestion, and complete degeneration in a dose dependent manner. Substantial alterations in blood and liver specimens were observed in the Cu-NP treated fish when compared with the CuO treated fish. It appeared that the Cu-NPs were more toxic than the CuO as shown by the hemato- and hepatotoxicity in C. carpio of this study.

Initial Dosing and Taper Complexity of Methadone and Morphine for Treatment of Neonatal Abstinence Syndrome

PubMed Central

Ibach, Bethany W.; Johnson, Peter N.; Ernst, Kimberly D.; Harrison, Donald; Miller, Jamie L.

2016-01-01

Background: Methadone and morphine are commonly used to treat neonatal abstinence syndrome (NAS). Limited data exist to describe the most appropriate initial doses and taper regimens of these agents. Objectives: Describe the median initial dose and frequency of methadone and morphine for NAS. Compare dose adjustments, time to symptom relief, and taper complexity between groups. Methods: Retrospective study of neonates receiving enteral methadone or morphine for NAS over a 4-year period. Data collection included medication regimen, abstinence scores based on the Modified Finnegan Neonatal Abstinence Scoring Tool, and adverse events. Planned home taper complexity was assessed using the Medication Taper Complexity Score–Revised (MTCS-R). The primary outcome was initial opioid dose. Secondary outcomes included number of dose adjustments, time to symptom relief, and MTCS-R score. Results: Fifty neonates were initially treated for NAS with methadone (n = 36) or morphine (n = 14). The median initial dose was 0.09 mg/kg (range = 0.03-0.2) for methadone and 0.04 mg/kg (range = 0.03-0.4) for morphine. The most common initial dosing interval was q8h for methadone versus q3h for morphine. Number of dose adjustments and time to symptom relief were similar between groups. Median MTCS-R scores were similar between groups. There was no difference in adverse events between groups. Limitations included small sample size, preference toward methadone use, and variability of initial opioid dosing and titration. Conclusions: There was significant variability in initial doses of both agents. Neonates receiving methadone required less frequent dosing than morphine, which may result in easier administration and may allow for safer outpatient administration.

Metabolite Profiling Reveals the Effect of Dietary Rubus coreanus Vinegar on Ovariectomy-Induced Osteoporosis in a Rat Model.

PubMed

Lee, Mee Youn; Kim, Hyang Yeon; Singh, Digar; Yeo, Soo Hwan; Baek, Seong Yeol; Park, Yoo Kyoung; Lee, Choong Hwan

2016-01-26

The study was aimed at exploring the curative effects of Rubus coreanus (RC) vinegar against postmenopausal osteoporosis by using ovariectomized rats as a model. The investigations were performed in five groups: sham, ovariectomized (OVX) rats without treatment, low-dose RC vinegar (LRV)-treated OVX rats, high-dose RC vinegar (HRV)-treated OVX rats and alendronate (ALEN)-treated OVX rats. The efficacy of RC vinegar was evaluated using physical, biochemical, histological and metabolomic parameters. Compared to the OVX rats, the LRV and HRV groups showed positive effects on the aforementioned parameters, indicating estrogen regulation. Plasma metabolome analysis of the groups using gas chromatography-time of flight mass spectrometry (GC-TOF-MS) and ultra-performance liquid chromatography quadrupole-TOF-MS (UPLC-Q-TOF-MS) with multivariate analysis revealed 19 and 16 metabolites, respectively. Notably, the levels of butyric acid, phenylalanine, glucose, tryptophan and some lysophosphatidylcholines were marginally increased in RC vinegar-treated groups compared to OVX. However, the pattern of metabolite levels in RC vinegar-treated groups was found similar to ALEN, but differed significantly from that in sham group. The results highlight the prophylactic and curative potential of dietary vinegar against postmenopausal osteoporosis. RC vinegar could be an effective natural alternative for the prevention of postmenopausal osteoporosis.

Effect of phosphate supplementation on oxygen delivery at high altitude

NASA Astrophysics Data System (ADS)

Jain, S. C.; Singh, M. V.; Rawal, S. B.; Sharma, V. M.; Divekar, H. M.; Tyagi, A. K.; Panwar, M. R.; Swamy, Y. V.

1987-09-01

In the present communication, effect of low doses of phosphate supplementation on short-term high altitude adaptation has been examined. Studies were carried out in 36 healthy, male, sea-level residents divided in a double blind fashion into drug and placebo treated groups. 3.2 mmol of phosphate were given orally to each subject of the drug treated group once a day for 4 days on arrival at an altitude of 3,500 m. Sequential studies were done in the subjects in both groups on the 3rd, 7th, 14th and 21st day of their altitude stay. Haemoglobin, haematocrit, erythrocyte and reticulocyte counts increased to the similar extent in both groups. Blood pH, pO2 and adenosine tri-phosphate (ATP) did not differ between the two groups. On 3rd day of the altitude stay, inorganic phosphate and 2,3-diphosphoglycerate (2,3 DPG) levels in the drug treated group increased significantly as compared to the placebo group. No significant difference in inorganic phosphate and 2,3 DPG was observed later on in the two groups. Psychological and clinical tests also indicated that the drug treated subjects felt better as compared to the placebo treated subjects. The present study suggests that low doses of phosphate increases circulating 2,3-DPG concentration which in turn brings about beneficial effect towards short term high altitude adaptation.

Low or High Fractionation Dose {beta}-Radiotherapy for Pterygium? A Randomized Clinical Trial

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

Viani, Gustavo Arruda, E-mail: gusviani@gmail.com; De Fendi, Ligia Issa; Fonseca, Ellen Carrara

2012-02-01

Purpose: Postoperative adjuvant treatment using {beta}-radiotherapy (RT) is a proven technique for reducing the recurrence of pterygium. A randomized trial was conducted to determine whether a low fractionation dose of 2 Gy within 10 fractions would provide local control similar to that after a high fractionation dose of 5 Gy within 7 fractions for surgically resected pterygium. Methods: A randomized trial was conducted in 200 patients (216 pterygia) between February 2006 and July 2007. Only patients with fresh pterygium resected using a bare sclera method and given RT within 3 days were included. Postoperative RT was delivered using a strontium-90more » eye applicator. The pterygia were randomly treated using either 5 Gy within 7 fractions (Group 1) or 2 Gy within 10 fractions (Group 2). The local control rate was calculated from the date of surgery. Results: Of the 216 pterygia included, 112 were allocated to Group 1 and 104 to Group 2. The 3-year local control rate for Groups 1 and 2 was 93.8% and 92.3%, respectively (p = .616). A statistically significant difference for cosmetic effect (p = .034), photophobia (p = .02), irritation (p = .001), and scleromalacia (p = .017) was noted in favor of Group 2. Conclusions: No better local control rate for postoperative pterygium was obtained using high-dose fractionation vs. low-dose fractionation. However, a low-dose fractionation schedule produced better cosmetic effects and resulted in fewer symptoms than high-dose fractionation. Moreover, pterygia can be safely treated in terms of local recurrence using RT schedules with a biologic effective dose of 24-52.5 Gy{sub 10.}.« less

Is digitalis compound-induced cardiotoxicity, mediated through guinea-pig cardiomyocytes apoptosis?

PubMed

Ramirez-Ortega, Margarita; Zarco, Gabriela; Maldonado, Vilma; Carrillo, Jose F; Ramos, Pilar; Ceballos, Guillermo; Melendez-Zajgla, Jorge; Garcia, Noemí; Zazueta, Cecilia; Chanona, Jose; Suarez, Jorge; Pastelin, Gustavo

2007-07-02

Our aim in performing this study was to analyze in vivo the cell death mechanism induced by toxic doses of digitalis compounds on guinea-pig cardiomyocytes. We analyzed three study groups of five male guinea pigs each. Guinea pigs were intoxicated under anesthesia with ouabain or digoxin (at a 50-60% lethal dose); the control group did not receive digitalis. A 5-hours period elapsed before guinea pig hearts were extracted to obtain left ventricle tissue. We carried out isolation of mitochondria and cytosol, cytochrome c and caspase-3 and -9 determination, and electrophoretic analysis of nuclear DNA. TdT-mediated DUTP-X nick end labeling (TUNEL) reaction was performed in histologic preparations to identify in situ apoptotic cell death. Ultrastructural analysis was performed by electron microscopy. Electrophoretic analysis of DNA showed degradation into fragments of 200-400 base pairs in digitalis-treated groups. TUNEL reaction demonstrated the following: in the control group, <10 positive nuclei per field; in the digoxin-treated group, 2-14 positive nuclei per field, while in the ouabain-treated group counts ranged from 9-30 positive nuclei per field. Extracts from ouabain-treated hearts had an elevation of cytochrome c in cytosol and a corresponding decrease in mitochondria; this release of cytochrome c provoked activation of caspase-9 and -3. Electron microscopy revealed presence of autophagic vesicles in cytoplasm of treated hearts. Toxic dosages of digitalis at 50-60% of the lethal dose are capable of inducing cytochrome c release from mitochondria, processing of procaspase-9 and -3, and DNA fragmentation; these observations are mainly indicative of apoptosis, although a mixed mechanism of cell death cannot be ruled out.

Polysaccharides from Cordyceps sinensis mycelium ameliorate exhaustive swimming exercise-induced oxidative stress.

PubMed

Yan, Feng; Wang, Beibei; Zhang, Yan

2014-02-01

Cordyceps sinensis (Berk.) Sacc. (Clavicipitaceae) is a famous medicinal fungus (mushroom) in Chinese herbal medicine. Polysaccharides from Cordyceps sinensis (CSP) have been identified as active ingredients responsible for its biological activities. Although many pharmacological actions of CSP have received a great deal of attention, research in this area continues. The current study was designed to investigate the effects of CSP on exhaustive exercise-induced oxidative stress. The mice were divided into four groups: control (C), low-dose CSP treated (LC), intermediate-dose CSP treated (IC) and high-dose CSP treated (HC). The treated groups received CSP (100, 200 and 400 mg/kg, ig), while the control group received drinking water for 28 days, followed by being forced to undergo exhaustive swimming exercise, and some biochemical parameters including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured using detection kits according to the manufacturers' instructions. Compared with the C group, exhaustive swimming time was significantly prolonged in the LC, IC and HC groups (p < 0.05); SOD activities in serum, liver and muscle were significantly higher in the IC and HC groups (p < 0.05); GPx activities in serum, liver and muscle were significantly higher in the LC, IC and HC groups (p < 0.05); CAT activities in serum, liver and muscle were significantly higher in the HC groups (p < 0.05); MDA and 8-OHdG levels in serum, liver and muscle were significantly lower in the LC, IC and HC groups (p < 0.05). The results obtained herein indicate that CSP could ameliorate exhaustive exercise-induced oxidative stress.

Dose-dependent effects and reversibility of the injuries caused by nandrolone decanoate in uterine tissue and fertility of rats.

PubMed

Belardin, Larissa Berloffa; Simão, Vinícius Augusto; Leite, Gabriel Adan Araújo; Chuffa, Luiz Gustavo de Almeida; Camargo, Isabel Cristina Cherici

2014-04-01

This study is the first to investigate the effects of different doses of nandrolone decanoate (ND) upon uterine tissue and fertility, and if the reproductive alterations can be restored after cessation of the treatment. Wistar female rats were treated with ND at doses of 1.87, 3.75, 7.5, and 15 mg/kg body weight, diluted in vehicle (n = 30/group), or received only mineral oil (control group, n = 45). The animals were divided into three periods of study: ND-treated receiving a daily subcutaneous injection for 15 consecutive days (1), and treatment with ND followed by 30-day recovery (2), and 60-day recovery (3). At the end of each period, five females per group were induced to death to histopathological analysis and the others were allowed to fertility evaluation (at 19th gestational day). Animals that received ND followed by 30-day recovery exhibited persistent diestrous and marked suppression of reproductive capacity. Conversely, after 60-day recovery, only lowest doses females (1.87 and 3.75 mg/kg) exhibited restoration of normal estrous cyclicity. Uterine weights were increased after ND treatment similarly to that of the controls after 60-day recovery. The ND-treated groups showed histopathological changes in the endometrium, myometrium, and perimetrium, and an increase in the thickness of both muscular and serous layers. Notably, the recovery of uterine tissue after ND treatment was dose- and period-dependent. We reported that administration of ND promoted damage in uterine tissue and fertility of rats, and the recovery periods were insufficient to restore all of the side effects caused by ND under a dose-dependent response. © 2014 Wiley Periodicals, Inc.

Phase II trial of irinotecan plus cisplatin in patients with recurrent or metastatic squamous carcinoma of the head and neck.

PubMed

Gilbert, Jill; Cmelak, Anthony; Shyr, Yu; Netterville, James; Burkey, Brian B; Sinard, Robert J; Yarbrough, Wendall G; Chung, Christine H; Aulino, Joseph M; Murphy, Barbara A

2008-07-01

Patients with recurrent or metastatic HNC have a poor response and survival with currently available chemotherapy agents. Thus, new agents are needed. The authors report the results of a phase II trial of irinotecan and cisplatin in patients with metastatic or recurrent HNC. Patients were treated with irinotecan 65 mg/m2 IV over 90 minutes and cisplatin 30 mg/m2 were administered intravenously weekly for four weeks, followed by a two week rest. However, after 17 patients were treated with weekly irinotecan at a dose of 65 mg/m2, toxicity analysis demonstrated the poor tolerance of that dose in this patient population. Thus, the protocol was amended, and irinotecan was dose reduced to a starting dose of 50 mg/m2. Twenty-three additional patients were treated with this dose. Forty patients were enrolled on study between February 2002 and April 2006, 17 patients at the first dose level and 23 patients at the amended dose level. Overall, 12 of 17 patients (71%) treated with irinotecan 65 mg/m2 experienced clinically significant grade 3 or 4 toxicity. Twelve patients required dose reductions. Toxicity was reduced but 17% of patients still experienced grade 3 or 4 toxicity on the lower irinotecan dose. The response rate was 35% for patients treated at irinotecan 65 mg/m2 and 22% for patients treated at 50 mg/m2. No complete responses were noted. The combination of irinotecan and cisplatin is efficacious in a poor prognosis group of patients but toxicity is substantial. (Copyright) 2008 American Cancer Society.

The expression of Msi-1 and its significance in small intestinal mucosa severely damaged by high-dose 5-FU.

PubMed

Yuqi, Luo; Chengtang, Wu; Ying, Wen; Shangtong, Lei; Kangxiong, Liao

2008-09-01

The purpose was to investigate the expression of musashi-1 (msi-1) and its significances in small intestinal mucosa that was severely damaged by high-dose 5-FU. A total of 40 adult C57BL/6J mice were divided into two groups: the control group (n = 8, group A) and experimental group (n = 32). The mice in the control group were treated with PBS by intraperitoneal injection, and the other mice were treated with high-dose 5-FU (150 mg/kg body weight for 5 consecutive days) by intraperitoneal injection. At the 1st (group B), 3rd (group C) and 5th (group D) day after treatment with high-dose 5-FU, the dying mice were killed, HE staining and immunohistochemical techniques were used to detect the expression of the putative marker of intestinal epithelial stem cells, msi-1, in samples of the middle intestine from these mice, and the percentage of the msi-1-positive cells from the intestinal mucosal cells of the mice in group B was detected by FACS. After treatment with high-dose 5-FU, the intestinal mucosa suffered severe damage: the villi and crypts disappeared, the number of msi-1-positive cells increased greatly, the intestinal epithelial cells could be divided into two fractions by FACS, and the percentage of msi-1-positive cells was up to 67.75% in the fraction in which the value of FSC was higher. After treatment with high-dose 5-FU, the percentage of intestinal stem cells had increased significantly, which was useful for the further isolation and enrichment of intestinal epithelial stem cells.

Whole body protection against lethal ionizing radiation in mice by REC-2001: a semi-purified fraction of Podophyllum hexandrum.

PubMed

Lata, M; Prasad, J; Singh, S; Kumar, R; Singh, L; Chaudhary, P; Arora, R; Chawla, R; Tyagi, S; Soni, N L; Sagar, R K; Devi, M; Sharma, R K; Puri, S C; Tripathi, R P

2009-01-01

The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.

[Skin sensitization of 3, 4-bis (4'-aminofurazano-3') furoxan in mice evaluated by BrdU-ELISA local lymph node assay].

PubMed

Wang, H; Gao, J H; Liu, Z Y; Yue, H; Gao, Y C; Xue, Z; Zhang, Z Z; Zhou, Y S

2016-08-20

Objective: To investigate skin sensitization of 3, 4-bis (4'-aminofurazano-3') furoxan (DATF) in mice using 5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay (BrdU-ELISA) . Methods: A total of 30 specific pathogen-free BALB/C mice were randomly divided into high-, medium-, and low-dose DATF groups, positive control group, and solvent control group, with six mice in each group. The mice in the high-, medium-, and low-dose DATF groups were treated with 50%, 25%, and 10% (0.5, 0.25, and 0.10 g/ml) DATF solution, those in the positive control group were treated with 1% 2, 4-dinitrochlorobenzol (DNCB) , and those in the solvent control group were treated with acetone/olive oil (4∶1) . After treatment, retroauricular lymph nodes were collected and cell suspension was prepared. ELISA was used to measure the level of cell proliferation after the addition of 5-bromo-2'-deoxyuridine (BrdU) , and the BrdU labeling index (LI) and test substance concentration at a stimulation index (SI) of 1.6 (EC 1.6 ) were calculated. Results: There were no significant differences in auricular thickness between groups ( P >0.05) , and DAFT did not have skin irritation. Compared with the solvent control group, the high-dose DATF group and the positive control group showed significant increases in the weight of lymph nodes ( P <0.05) . Compared with the solvent control group, all the other groups showed significant increases in BrdU LI ( P <0.01) . The low-, medium-, and high-dose DATF groups had SIs of 6.1, 8.8, and 12.1, respectively, and the EC 1.6 of DATF was 2.2%, which suggested that DATF had strong sensitization. Conclusion: DATF has strong skin sensitization in mice, with reference to the guideline of Organization for Economic Co-operation and Development Item No. 442B (OECD TG 442B) .

High-versus low-dose erythropoietin in extremely low birth weight infants. The European Multicenter rhEPO Study Group.

PubMed

Maier, R F; Obladen, M; Kattner, E; Natzschka, J; Messer, J; Regazzoni, B M; Speer, C P; Fellman, V; Grauel, E L; Groneck, P; Wagner, M; Moriette, G; Salle, B L; Verellen, G; Scigalla, P

1998-05-01

To investigate whether a weekly 1500 IU/kg dose of recombinant human erythropoietin (rhEPO) is more effective than a dose of 750 IU/kg/week in preventing anemia and reducing the transfusion need in infants with birth weights less than 1000 gm. In a randomized, double-blind, multicenter trial, 184 infants with birth weights between 500 and 999 gm were treated with either rhEPO 750 (low-dose group) or 1500 IU/kg/week (high-dose group) from day 3 of life until 37 weeks' corrected age. Thirty-two percent of the infants in each group did not receive any transfusion during the treatment period. The total volume of erythrocytes received was similar in each group. The success rate, defined as no transfusion needed and hematocrit value 0.30 L/L or greater, was 27.6% in the low-dose and 29.5% in the high-dose group (p = 0.96). Doubling the rhEPO dose of 750 IU/kg/week is not indicated in infants with birth weights less than 1000 gm.

Clinical trial: oral colon-release parnaparin sodium tablets (CB-01-05 MMX) for active left-sided ulcerative colitis.

PubMed

Celasco, G; Papa, A; Jones, R; Moro, L; Bozzella, R; Surace, M M; Naccari, G C; Gasbarrini, G

2010-02-01

The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX) has been proposed as a novel approach for the treatment of ulcerative colitis (UC). To assess the efficacy and the tolerability of 8 weeks' oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates. This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS). A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005). CB-01-05 MMX was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates.

Breast neoplasms in women treated with x-rays for acute postpartum mastitis

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

Shore, R.E.; Hempelmann, L.H.; Kowaluk, E.

1977-09-01

Breast cancer has been studied by mail survey up to 34 years in 571 of 606 women treated with x-rays for acute postpartum mastitis. The incidence of neoplasms was compared with that of three nonirradiated control groups--nonirradiated sisters of the treated women, women with acute postpartum mastitis not treated with X-rays, and their nonirradiated sisters. For the irradiated group, with a mean dose of 247 rads to both breasts, the overall relative risk of breast cancer was 2.2 for years 10 to 34 post irradiation and 3.6 for 20 to 34. The dose response for malignant and benign breast neoplasmsmore » was compatible with a linear fit. For comparable total doses, fractionation of exposure did not reduce carcinogenic action. Women over age 30 years at radiation treatment had as great an excess risk of breast cancer as did younger women. The overall excess risk of developing breast cancer was about 8 to 10 cases per million women per rad per year, an increase of about 0.5% per rad.« less

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

Castle, Katherine O., E-mail: kocastle@mdanderson.org; Hoffman, Karen E.; Levy, Lawrence B.

Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis basedmore » on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF.« less

What is the optimal radiation dose for non-operable esophageal cancer? Dissecting the evidence in a meta-analysis.

PubMed

Chen, Yong; Zhu, Hui-Ping; Wang, Tao; Sun, Chang-Jiang; Ge, Xiao-Lin; Min, Ling-Feng; Zhang, Xian-Wen; Jia, Qing-Qing; Yu, Jie; Yang, Jian-Qi; Allgayer, Heike; Abba, Mohammed L; Zhang, Xi-Zhi; Sun, Xin-Chen

2017-10-24

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose-response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

Immunization against strontium-90 induction of bone tumors with inactivated FBJ virus and irradiated syngeneic strontium-90-induced tumor cells

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

Reif, A.E.; Triest, W.E.

1981-01-01

Three hundred six C57BL/6J female mice were subdivided into a control group left untreated and an experimental group treated intraperitoneally with 1.0 ..mu..Ci strontium-90/g of body weight at an age of 66 days. Treatments for the groups were as follows: none, 6 injections of formalin-inactivated FBJ viral preparation, 6 injections of active FBJ viral preparation, and 2 injections of 10,000 rad irradiated transplantable osteosarcoma previously induced in C57BL/6J mice by strontium-90. In addition to the above groups, two other groups were treated with respectively 0.032 and 0.10 ..mu..Ci strontium-90/g body weight in order to obtain information on the dose-response relationshipmore » between the injection of strontium-90 and the yield of bone tumors. In the groups not treated with strontium-90, only 1 bone tumor developed; this occurred in the group injected with FBJ virus. The incidence of bone tumors in the groups treated with 1.0 ..mu..Ci strontium-90 was significantly lower (18.5% or 18.2%) in the two groups that had received injections of inactivated FBJ virus or irradiated isogenic osteosarcoma when compared to the group left uninjected, which developed 43.5% tumors. In contrast, the strontium-90-treated group that also received injections of active FBJ virus developed 63.0% tumors. Only a single bone tumor developed in the groups treated solely with intermediate doses of strontium-90. The results indicate that immunization with inactivated FBJ virus or with irradiated syngeneic strontium-90-induced tumor cells can significantly decrease the development of strontium-90-induced tumors.« less

Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

PubMed

Ma, Ning; Xu, Ziqi; Mo, Dapeng; Gao, Feng; Gao, Kun; Sun, Xuan; Xu, Xiaotong; Liu, Lian; Song, Ligang; Wang, Tiejun; Zhao, Xingquan; Wang, Yilong; Wang, Yongjun; Miao, Zhongrong

2014-01-01

To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5%) with acute thrombosis, 5 patients (1.8%) with subacute thrombosis, 17 patients (6.2%) with stroke, and 2 death (0.7%) in low-dose aspirin group, compared with no patient (0%) with acute thrombosis, 2 patient (2.1%) with subacute thrombosis, 6 patients (6.2%) with stroke, and 2 death (2.1%) in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

The Role of Chlorogenic Acid Supplementation in Anemia and Mineral Disturbances Induced by 4-Tert-Octylphenol Toxicity.

PubMed

Koriem, Khaled M M; Arbid, Mahmoud S S; Gomaa, Nawal E

2018-01-02

4-tert-octylphenol (OP) is an endocrine-disrupting chemical that causes harmful effects to human health. Chlorogenic acid is the major dietary polyphenol present in various foods and beverages. The aim of the present study was to evaluate the protective role of chlorogenic acid in anemia and mineral disturbance occurring in OP toxicity in rats. Thirty-two male albino rats were divided into four equal groups (8 rats/group) as follows. The first (control) group was treated daily with an oral dose of 1 ml saline for two weeks. The second group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for two weeks. The third and fourth groups received daily intraperitoneal (ip) injections with 100 mg OP/kg body weight for two weeks; the fourth group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for three weeks starting one week before OP injections. The results revealed that OP induced significant decreases in hemoglobin, hematocrit, red blood cells, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, white blood cells, lymphocyte and neutrophil percent, transferrin receptor, serum calcium, phosphorous, sodium, potassium, chloride, glutathione-S-transferase, glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase. Moreover, significant increases in serum hepcidin, ferritin, transferrin, erythropoietin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, selenium, zinc, manganese, copper, iron, malondialdehyde, and protein carbonyl levels were found in OP groups. OP exposure also induced cell apoptosis. Chlorogenic acid pretreatment in OP-treated groups restored all the mentioned parameters to approach the normal values. In conclusion, chlorogenic acid protects from anemia and mineral disturbances in 4-tert-octylphenol toxicity by ameliorating oxidative stress and apoptosis.

Effect of Calendula officinalis Flower Extract on Acute Phase Proteins, Antioxidant Defense Mechanism and Granuloma Formation During Thermal Burns

PubMed Central

Chandran, Preethi K.; Kuttan, Ramadasan

2008-01-01

Effect of Calendula officinalis flower extract was investigated against experimentally induced thermal burns in rats. Burn injury was made on the shaven back of the rats under anesthesia and the animals were treated orally with different doses of the flower extract (20 mg, 100 mg and 200 mg/kg body weight). The animals treated with the extract showed significant improvement in healing when compared with the control untreated animals. The indicators of the wound healing such as collagen-hydroxyproline and hexosamine contents were significantly increased in the treated group indicating accelerated wound healing in the treated animals. The acute phase proteins—haptoglobin and orosomucoid which were increased due to burn injury were found to be decreased significantly in 200 mg/kg body weight extract treated animals. The antioxidant defense mechanism, which was decreased in the liver during burn injury, was found to be enhanced in treated animals. The lipid peroxidation was significantly lowered in the treated group when compared to control animals. Tissue damage marker enzymes- alkaline phosphatase, alanine and aspartate transaminases were significantly lowered in the treated groups in a dose dependant manner. The histopathological analyses of skin tissue also give the evidence of the increased healing potential of the extract after burn injury. PMID:18818737

The efficacy and safety of clotrimazole vaginal tablet vs. oral fluconazole in treating severe vulvovaginal candidiasis.

PubMed

Zhou, Xiaofang; Li, Ting; Fan, Shangrong; Zhu, Yuxia; Liu, Xiaoping; Guo, Xuedong; Liang, Yiheng

2016-07-01

To compare the efficacy and safety of two doses of clotrimazole vaginal tablet 500 mg with two doses of oral fluconazole 150 mg in treating severe vulvovaginal candidiasis (SVVC), 240 consecutive patients with SVVC were studied at the Department of Obstetrics and Gynaecology of Peking University Shenzhen Hospital between June 2014, and September 2015. Patients were randomly assigned in a 1 : 1 ratio to receive treatment with either two doses of clotrimazole vaginal tablet or two doses of oral fluconazole. The clinical cure rates in the clotrimazole group and the fluconazole group at days 7-14 follow-up were 88.7% (102/115) and 89.1% (98/110) respectively; the clinical cure rates at days 30-35 in the two groups were 71.9% (82/114) and 78.0% (85/109) respectively. The mycological cure rates at days 7-14 follow-up in the two groups were 78.3% (90/115) and 73.6% (81/110) respectively. The mycological cure rates of the patients at days 30-35 in the two groups were 54.4% (62/114) and 56.0% (61/109) respectively (P > 0.05). The adverse events of clotrimazole were mainly local. This study demonstrated that two doses of clotrimazole vaginal tablet 500 mg were as effective as two doses of oral fluconazole 150 mg in the treatment of patients with SVVC and could be an appropriate treatment for this disorder. © 2016 The Authors Mycoses Published by Blackwell Verlag GmbH.

The efficacy of low dose azathioprine/6-mercaptopurine in patients with inflammatory bowel disease.

PubMed

Kim, Dong Uk; Kim, Young-Ho; Kim, Beom Jin; Chang, Dong Kyung; Son, Hee Jung; Rhee, Poong-Lyul; Kim, Jae J; Rhee, Jong Chul

2009-01-01

Azathioprine (AZA) and 6-mercaptopurine (6-MP) have been widely used in patients with ulcerative colitis (UC) and Crohn's disease (CD). However, some patients cannot tolerate standard doses (2-2.5 mg/kg for AZA or 1-1.5 mg/kg for 6-MP) due to side effects such as leukopenialneutropenia. The aim of this study was to evaluate the efficacy of low dose AZA/6-MP compared to the standard dose. From 1995 to 2005, 122 patients with UC or CD treated with AZA/6-MP at Samsung Medical Center in Korea were enrolled. We divided these patients into 2 groups (standard dose group versus low dose group) according to the maintenance dose. Among the 122 patients, 17 received the standard dose and 105 received a low dose. The mean maintenance doses were 2.25 mg/kg for the standard dose group and 1.35mg/kg for the low dose group. The clinical outcomes of remission induction, maintenance of remission and relapse rate showed no significant difference in comparisons between these two groups. Low dose AZA/6-MP was as effective as the standard dose for remission induction and maintenance of remission in patients with UC and CD. For patients that develop leukopenia/neutropenia during dose escalation, maintenance therapy with low dose AZA/6-MP should be considered.

Efficacy Study of Novel Diamidine Compounds in a Trypanosoma evansi Goat Model

PubMed Central

Gillingwater, Kirsten; Gutierrez, Carlos; Bridges, Arlene; Wu, Huali; Deborggraeve, Stijn; Ali Ekangu, Rosine; Kumar, Arvind; Ismail, Mohamed; Boykin, David; Brun, Reto

2011-01-01

Three diamidines (DB 75, DB 867 and DB 1192) were selected and their ability to cure T. evansi experimentally infected goats was investigated. A toxicity assessment and pharmacokinetic analysis of these compounds were additionally carried out. Goats demonstrated no signs of acute toxicity, when treated with four doses of 1 mg/kg/day (total dose 4 mg/kg). Complete curative efficacy of experimentally infected goats was seen in the positive control group treated with diminazene at 5 mg/kg and in the DB 75 and DB 867 groups treated at 2.5 mg/kg. Drug treatment was administered once every second day for a total of seven days. Complete cure was also seen in the group of goats treated with DB 75 at 1.25 mg/kg. DB 1192 was incapable of curing goats at either four-times 2.5 mg/kg or 1.25 mg/kg. Pharmacokinetic analysis clearly demonstrated that the treatment failures of DB 1192 were due to sub-therapeutic compound levels in goat plasma, whilst compound levels for DB 75 and DB 867 remained well within the therapeutic window. In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection. PMID:21698106

Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model.

PubMed

Gillingwater, Kirsten; Gutierrez, Carlos; Bridges, Arlene; Wu, Huali; Deborggraeve, Stijn; Ekangu, Rosine Ali; Kumar, Arvind; Ismail, Mohamed; Boykin, David; Brun, Reto

2011-01-01

Three diamidines (DB 75, DB 867 and DB 1192) were selected and their ability to cure T. evansi experimentally infected goats was investigated. A toxicity assessment and pharmacokinetic analysis of these compounds were additionally carried out. Goats demonstrated no signs of acute toxicity, when treated with four doses of 1 mg/kg/day (total dose 4 mg/kg). Complete curative efficacy of experimentally infected goats was seen in the positive control group treated with diminazene at 5 mg/kg and in the DB 75 and DB 867 groups treated at 2.5 mg/kg. Drug treatment was administered once every second day for a total of seven days. Complete cure was also seen in the group of goats treated with DB 75 at 1.25 mg/kg. DB 1192 was incapable of curing goats at either four-times 2.5 mg/kg or 1.25 mg/kg. Pharmacokinetic analysis clearly demonstrated that the treatment failures of DB 1192 were due to sub-therapeutic compound levels in goat plasma, whilst compound levels for DB 75 and DB 867 remained well within the therapeutic window. In conclusion, two diamidine compounds (DB 75 and DB 867) presented comparable efficacy at lower doses than the standard drug diminazene and could be considered as potential clinical candidates against T. evansi infection.

Association of Thiazolidinedione with a Lower Risk of Parkinson's Disease in a Population with Newly-Diagnosed Diabetes Mellitus.

PubMed

Lin, Hsiu-Li; Lin, Hsiu-Chen; Tseng, Yuan-Fu; Chao, Jane Chen-Jui; Hsu, Chien-Yeh

2018-06-11

We investigated the association of thiazolidinedione and its dose effect with the risk of Parkinson's disease (PD) in patients with diabetes mellitus (DM). This study enrolled 38,521 patients with newly-diagnosed DM between 2001 and 2013 and compared them to matched subjects without DM. The hazard ratios (HRs) for PD were compared between the thiazolidinedione-treated and non-thiazolidinedione-treated groups of the study cohort, and between subgroups who received different cumulative dosages of thiazolidinedione. We observed 544 (1.4%) patients with PD during the follow up of median duration of 6.2 years in patients with newly-diagnosed DM who had a higher risk for PD than patients without DM (HR = 1.150). In the study cohort, the risk of PD was significantly lower in the thiazolidinedione-treated group (HR = 0.399) compared to the non-thiazolidinedione-treated group. Thiazolidinedione reduced the risk of PD in a dose-dependent manner, with HRs ranging from 0.613 to 0.081 with defined daily doses of 0-90 to > 720, respectively. Thiazolidinedione use was associated with a significantly reduced risk of PD in patients with newly-diagnosed DM. Further studies to elucidate the common mechanism of PD and DM may provide novel therapies for these two diseases.

Effect of DETOX as an adjuvant for melanoma vaccine.

PubMed

Schultz, N; Oratz, R; Chen, D; Zeleniuch-Jacquotte, A; Abeles, G; Bystryn, J C

1995-04-01

The identification of effective adjuvants is critical for tumor vaccine development. Towards this end, we examined whether the immunogenicity of a melanoma vaccine could be potentiated by DETOX, an adjuvant consisting of monophosphoryl lipid A (MPL) and purified mycobacterial cell-wall skeleton (CWS). Nineteen patients with resected stage III melanoma were immunized with a polyvalent melanoma antigen vaccine (40 micrograms) admixed with DETOX, q3 wks x 4. Seven patients received vaccine + low-dose DETOX (10 micrograms MPL + 100 micrograms CWS) and 12 received vaccine + high-dose DETOX (20 micrograms MPL + 200 micrograms CWS). A non-randomized control group of 35 patients was treated similarly with 40 micrograms vaccine + alum. One week after the fourth vaccine immunization, melanoma antibodies were increased over baseline in 7/7 (100%) patients treated with vaccine + low-dose DETOX, 8/12 (67%) patients treated with vaccine + high-dose DETOX, and in 4/19 (21%) of vaccine + alum patients. For the entire DETOX group, the antibody response rate was 15/19 (79%) compared 4/19 (21%) in the alum group (p < 0.001). In contrast, a strong delayed-type hypersensitivity (DTH) response (> or = 15 mm increase in DTH response over baseline) was induced in 50% of the entire DETOX group versus in 47% of the alum group. Median disease-free (DF) survival for the entire DETOX group was 17.8 months compared with 32.1 months in the alum group (p < 0.05). In conclusion, DETOX markedly potentiated antibody but had little effect on DTH responses to melanoma vaccine immunization. It did not appear to improve disease-free survival in comparison to alum in this non-randomized study.

Cytogenetic effects of sildenafil citrate (Viagra) on SWR/J mouse bone marrow cells

PubMed Central

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy

2010-01-01

The present study was conducted to investigate the cytogenetic effects of sildenafil citrate in SWR/J mouse bone marrow cells. Thirty-six males and 36 females were used and divided into four groups. Each group contained 18 animals (9 males and 9 females), weighing 30–35 g. These animals were orally administered with a single dose of 13, 26 or 40 mg/kg sildenafil citrate solution. A control group received normal saline in an identical condition. The animals were sacrificed at 12, 24 or 48 h, after the treatment. Chromosome aberrations were investigated in 50 metaphases per animal. No significant differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between treated male and female mice at any doses or at any time intervals used, therefore, data from the two sexes were pooled when analyzed statistically. No significant (p < 0.05) differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between sildenafil citrate-treated groups and the control group at any doses or at any time intervals used. However, the percentages of centromeric adhesions increased significantly (p < 0.01) in treated groups as compared with the control group at all doses and at all time intervals used. In conclusion, the results of the present study suggest that sildenafil citrate does not have cytogenetic effects on mouse bone marrow cells, but the centromeric adhesions induced by this drug need further studies to confirm them and to investigate the possible mechanism(s) responsible for such effect. PMID:23961094

Dosimetric and delivery efficiency investigation for treating hepatic lesions with a MLC-equipped robotic radiosurgery–radiotherapy combined system

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

Jin, Lihui, E-mail: lihui.jin@fccc.edu; Price, Robert A.; Wang, Lu

Purpose: The CyberKnife M6 (CK-M6) Series introduced a multileaf collimator (MLC) for extending its capability from stereotactic radiosurgery/stereotactic radiotherapy (SBRT) to conventionally fractionated radiotherapy. This work is to investigate the dosimetric quality of plans that are generated using MLC-shaped beams on the CK-M6, as well as their delivery time, via comparisons with the intensity modulated radiotherapy plans that were clinically used on a Varian Linac for treating hepatic lesions. Methods: Nine patient cases were selected and divided into three groups with three patients in each group: (1) the group-one patients were treated conventionally (25 fractions); (2) the group-two patients weremore » treated with SBRT-like hypofractionation (5 fractions); and (3) the group-three patients were treated similar to group-one patients, but with two planning target volumes (PTVs) and two different prescription dose levels correspondingly. The clinically used plans were generated on the ECLIPSE treatment planning system (TPS) and delivered on a Varian Linac (E-V plans). The multiplan (MP) TPS was used to replan these clinical cases with the MLC as the beam device for the CK-M6 (C-M plans). After plans were normalized to the same PTV dose coverage, comparisons between the C-M and E-V plans were performed based on D{sub 99%} (percentage of prescription dose received by 99% of the PTV), D{sub 0.1cm{sup 3}} (the percentage of prescription dose to 0.1 cm{sup 3} of the PTV), and doses received by critical structures. Then, the delivery times for the C-M plans will be obtained, which are the MP TPS generated estimations assuming having an imaging interval of 60 s. Results: The difference in D{sub 99%} between C-M and E-V plans is +0.6% on average (+ or − indicating a higher or lower dose from C-M plans than from E-V plans) with a range from −4.1% to +3.8%, and the difference in D{sub 0.1cm{sup 3}} was −1.0% on average with a range from −5.1% to +2.9%. The PTV conformity index (CI) for the C-M plans ranges from 1.07 to 1.29 with a mean of 1.19, slightly inferior to the E-V plans, in which the CI ranges from 1.00 to 1.15 with a mean of 1.07. Accounting for all nine patients in three groups, 45% of the critical structures received a lower mean dose for the C-M plans as compared with the E-V plans, and similarly, 48% received a lower maximum dose. Furthermore, the average difference of the mean critical structure dose between the C-M and E-V plans over all critical structures for all patients showed only +2.10% relative to the prescription dose and the similar comparison finds the average difference of the maximum critical structure dose of only +1.24%. The estimated delivery times for the C-M plans on the CK-M6 range from 18 to 24 minutes while they are from 7 to 13.7 min for the E-V plans on the Varian Linac. Conclusions: For treating hepatic lesions, for the C-M plans that are comparable to E-V plans in quality, the times needed to deliver these C-M plans on the CK-M6 are longer than the delivery time for the E-V plans on the Varian Linac, but may be clinically acceptable.« less

Vitamin E reduces hepatic fibrosis in mice with Schistosoma japonicum infection.

PubMed

Wang, Xuefeng; Zhang, Rongbo; Du, Jiuwei; Hu, Youying; Xu, Lifa; Lu, Jun; Ye, Song

2012-02-01

To investigate whether vitamin E protects against hepatic fibrosis in mice with Schistosoma japonicum infection, 24 pathogen-free Kunming mice were selected and randomly divided into four groups: control (uninfected, untreated), model (infected, untreated), low-dose intervention (infected, vitamin E-treated, 30 mg/g bodyweight/day) and high-dose intervention (infected, vitamin E-treated, 60 mg/g bodyweight/day). Mice were infected with Schistosoma japonicum by inoculating abdominal skin with snail hosts. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were detected in hepatic tissue by colorimetry. The expression levels of laminin (LN), hyaluronic acid (HA), procollagen type Ⅲ (PC-III) and type Ⅳ collagen (IV-C) were detected in the serum by radioimmunoassay. Finally, areas and numbers of granulomas were assessed through histopathology 42 days following treatment. The results revealed that mean areas of granulomas were smaller in the low- and high-dose intervention groups compared to those in the model group. Furthermore, the higher dose of vitamin E resulted in smaller granulomas than the low dose. The levels of LN, HA, PC-III and IV-C in the serum were lower following vitamin E treatment than in the model group. By contrast, activity of SOD, GPx and CAT in hepatic tissue was higher following vitamin E treatment compared to the model group. The activity of MDA was lower in hepatic tissue following vitamin E treatment compared to the model group, but was higher compared to controls. In general, the higher dose of vitamin E affected measurements to a greater extent than the lower dose. In conclusion, vitamin E treatment may reduce the growth of granulomas, slowing the process of hepatic fibrosis, and this effect may be the result of the altered activity of the oxidation-reduction enzyme system.

Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

PubMed

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered.

Can we avoid dose escalation for intermediate-risk prostate cancer in the setting of short-course neoadjuvant androgen deprivation?

PubMed Central

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Background Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74 Gy in this setting. We aimed to determine whether DE-EBRT >74 Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74 Gy to 76 Gy and then to 78 Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70 months. For the 74 Gy, 76 Gy, and 78 Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion There was no benefit for DE-EBRT >74 Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. PMID:27073327

Sub-Chronic Safety Evaluation of Ayurvedic Immunostimulant Formulation ‘Immuforte’ in Rats in Reverse Pharmacology

PubMed Central

Dhumal, Rohit; Patil, Prakash; Selkar, Nilakash; Chawda, Mukesh; Vahlia, Mahesh; Vanage, Geeta

2013-01-01

Objective: The present study was undertaken to determine target organ safety of “Immuforte” to establish relationship between dose or exposure and response and also to identify potential parameters for monitoring adverse effects of “Immuforte” in clinical studies, if any. Materials and Methods: A total of 40 males and 40 females were randomly assigned to the four groups, namely group I (vehicle control; gum acacia), group II (120 mg/kg BW of Immuforte in gum acacia), group III (360 mg/kg BW of Immuforte in gum acacia), and group IV (600 mg/kg BW of Immuforte in gum acacia) consisting of 10 males and 10 females in each group. Additionally, a recovery group (600 mg/kg BW of Immuforte in gum acacia) containing 5 males and 5 females was included. Results: The results showed significant decrease in percent lymphocyte count of high and mid dose groups as compared to control group. The percent neutrophil counts in all the three treated groups of male and female rats were found to be significantly higher than that of control group (P < 0.05). In females MCV values in low dose and mid dose were significantly higher as compared to control (P < 0.05). The males from low dose group showed significant decrease in total serum protein, globulin, electrolytes, direct bilirubin, creatinine levels, whereas in mid dose group along with albumin, globulin. A significant decrease in AST and cholesterol was observed. In females, significant decrease was observed in total protein and globulin of low dose and mid dose of Immuforte-treated rats (P < 0.05). Though few hematological and biochemical parameters were different from control group, no does related response was observed and further, all these values were comparable with historical control data of the colony. Terminal body weight, organ weight, gross, and histopathology did not reveal any toxicity-related any adverse effects. Heavy metal analysis of the blood samples collected from terminally sacrificed animals did not show presence of heavy metals viz. lead (Pb), mercury (Hg), cadmium (Cd), and arsenic (As). Conclusion: The results of the present study demonstrated that Immuforte does not cause any observable toxicity at doses used in the study when administered for the period of 90 days and is safe for the human use and thus, Immuforte could be used safely for therapeutic use in humans. PMID:23833443

An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat.

PubMed

Mitchell, J M; Mengs, U; McPherson, S; Zijlstra, J; Dettmar, P; Gregson, R; Tigner, J C

2006-01-01

Senna (Tinnevelly senna fruits), a known laxative derived from plants, was administered by gavage to Sprague-Dawley (Crl:CD (SD) BR) rats once daily at dose levels of 0, 25, 100 and 300 mg/kg/day for up to 104 consecutive weeks. Based upon clinical signs related to the laxation effect of senna, the highest dose (300 mg/kg/day) was considered to be a maximum tolerated dose. Sixty animals per sex were assigned to the control and dose groups. Assessments included clinical chemistry, hematology, full histology (control and high-dose groups; in addition, low and mid dose: intestinal tract, adrenals, liver, kidneys, brain and gross lesions) and toxicokinetics. The primary treatment-related clinical observation was mucoid feces seen at 300 mg/kg/day. When compared to controls, animals administered 300 mg/kg/day had slightly reduced body weights, increased water consumption and notable changes in electrolytes in serum (increases in potassium and chloride) and urine (decreases in sodium, potassium and chloride). The changes in electrolytes are most likely physiologic adaptations to the laxative effect of senna. At necropsy, dark discoloration of the kidneys was observed in animals in all treated groups. Histological changes were seen in the kidneys of animals from all treated groups and included slight to moderate tubular basophilia and tubular pigment deposits. In addition, for all treated groups, minimal to slight hyperplasia was evident in the colon and cecum. These histological changes, together with the changes seen in the evaluation of clinical chemistry and urine parameters, have been shown to be reversible in a previous 13-week rat study of senna. No treatment-related neoplastic changes were observed in any of the examined organs. Based upon these data, it is concluded that senna is not carcinogenic even after daily administration for 2 years at dosages of up to 300 mg/kg/day in Sprague-Dawley rats.

Low dose isotretinoin combined with tretinoin is effective to correct abnormalities of acne.

PubMed

Plewig, Gerd; Dressel, Heidrun; Pfleger, Maike; Michelsen, Silke; Kligman, Albert M

2004-01-01

Isotretinoin is well known in the therapy of acne papulopustulosa and acne conglobata. No study has investigated the pathophysiological changes of the skin of acne patients, especially when low dose oral isotretinoin is given in combination with topical tretinoin. 28 patients were treated for 6 months with oral isotretinoin. In the acne conglobata group (A-C) patients were treated with 10 mg (Group A) or 20 mg isotretinoin (Groups B, C) in combination with topical 0.05% tretinoin cream. Group C was treated the first 2 weeks with 0.05% betamethasone valerate cream instead of tretinoin cream. In the acne papulopustulosa group, the patients received 0.5 mg isotretinoin/kg bodyweight and 0.05% tretinoin cream, either alone (Group E), or with oral methylprednisolone during induction (Group D). Acne conglobata--A reduction of inflammatory lesion by 87-94% and of non-inflammatory lesions by 81-88% was achieved (Groups A-C). A reduction of sebaceous gland size by 35-58%, sebum production by 90-95%, follicular keratinization by 55-70% and Propionibacteria by 33-73% was seen (Groups B and C better than Group A). In Group A the amount of lipids was only reduced by 6%, in Group B by 35% and in Group C by 40%. Acne papulopustulosa--Sebum excretion rate and follicular keratinization were reduced in Group D by 89% and 50% respectively, with isotretinoin alone by 94% and 53%. The amount of lipids was reduced in Group D by 40% and in Group E by 21%. Because of the efficacy and cost-benefit relationship of isotretinoin in the treatment of acne compared to other therapeutic approaches, further use low dose isotretinoin in the described settings seems to justified.

[Effects of control-releasing arsenic trioxide-eluting stent on intimal smooth muscle cells and type III collagen in canine coronary artery post-stent model].

PubMed

Zhao, Jun-Li; Sun, Bao-Gui; Wen, Qin-Zhu

2010-06-01

To study the safety and efficacy of control-releasing arsenic trioxide (As2O3)-eluting stent on intimal smooth muscle cells (SMC) and type III collagen (CIII) in canine coronary artery post-stent model. Twenty-four experimental canines were equally divided into 4 groups, the three tested groups were deployed by stents with different dosage of As2O3 (1.6 microg/mm2, 2.4 microg/mm2 and 3.2 microg/mm2 in low, median and high dose groups, respectively) and coated with polybutyl methacrylate/nano silica and poly-lactide-coglycolide in mild oversizing (stent/vessel ratio of 1.3:1) in left anterior descending (LAD) or circumflex coronary arteries (LCX), while the control group only by simple coated stent without As2O3. The effect was assessed 4 weeks after stent implantation in terms of vascular histomorphology, and changes of SMC and C III expressions were detected using immunohistochemical analysis. Subintimal hemorrhage, medial/adventitial necrosis, thrombosis and inflammatory cell infiltration were not found and integral endothelium could be seen under screening electron microscopy in all groups. Positive expression of SMC and CIII in the tested groups, especial in the high dose As2O3 group, was more weaker than that in control group. Histo-morphological analysis showed that the neo-genetic intimal area and vascular stenosis were lower, but the mean luminal diameter was larger in the three tested groups than that in the control group (P < 0.01). Comparisons of various indices between tested groups treated by different doses of As2O3 showed that the difference between high/median dose vs. low dose was significant (P < 0.01), but that between high dose vs. median dose was insignificant (P > 0.05). Control-releasing As2O3-eluting stent shows a reliable and safe effect in preventing and treating post-stent restenosis by its dose-dependent inhibition on expressions of SMC and CIII to suppress the neo-genesis of intimal hyperplasia.

The mechanism underlying dibutyl phthalate induced shortened anogenital distance and hypospadias in rats.

PubMed

Li, Ning; Chen, Xuyong; Zhou, Xuefeng; Zhang, Wen; Yuan, Jiyan; Feng, Jiexiong

2015-12-01

The purpose of this study was to investigate the mechanism of dibutyl phthalate (DBP) induced hypospadias and shortened anogenital distance (AGD). AGD, hypospadias, and cryptorchidism incidence was observed in male offspring of DBP treated pregnant Wistar rats. Testicular development and testosterone levels of normal and DBP-treated rat embryos were compared. Male offspring of 300mg and 900mg DBP-treated pregnant Wistar rats exhibited shortened average AGD compared with the control group. A 22.7% hypospadias incidence was observed in the 300mg group, but no offspring with cryptorchidism were identified. In the 900mg group, hypospadias and cryptorchidism incidence reached 43.5% and 17.4%, respectively. Between E15.5 and E17.5, the 300mg group exhibited delayed testicular development and testosterone secretion. However, testicular development and testosterone secretion subsequently recovered. The 300mg treated and control groups had similar measures after E19.5. Contrastingly, testicular development and testosterone secretion were significantly diminished throughout development in the 900mg group. Exogenous testosterone partially counteracted DBP-induced changes in the reproductive organs of male offspring of DBP-treated rats. High-dose DBP exposure may induce testicular dysgenesis in rat embryos. Additionally, low-dose DBP may delay testicular development and testosterone secretion during urethral development. This disruption may result in hypospadias. Copyright © 2015 Elsevier Inc. All rights reserved.

Cortisol receptor blockade and seawater adaptation in the euryhaline teleost Fundulus heteroclitus

USGS Publications Warehouse

Marshall, W.S.; Cozzi, R.R.F.; Pelis, Ryan M.; McCormick, S.D.

2005-01-01

To examine the role of cortisol in seawater osmoregulation in a euryhaline teleost, adult killifish were acclimated to brackish water (10???) and RU486 or vehicle was administered orally in peanut oil daily for five days at low (40 mg.kg-1) or high dose (200 mg.kg-1). Fish were transferred to 1.5 x seawater (45???) or to brackish water (control) and sampled at 24 h and 48 h after transfer, when Cl- secretion is upregulated. At 24 h, opercular membrane Cl- secretion rate, as Isc, was increased only in the high dose RU486 group. Stimulation of membranes by 3-isobutyl-1-methylxanthine and cAMP increased Isc in vehicle treated controls but those from RU486-treated animals were unchanged and membranes from brackish water animals showed a decrease in Isc. At 48 h, Isc increased and transepithelial resistance decreased in vehicle and RU486 groups, compared to brackish water controls. Plasma cortisol increased in all groups transferred to high salinity, compared to brackish water controls. RU486 treated animals had higher cortisol levels compared to vehicle controls. Vehicle treated controls had lower cortisol levels than untreated or RU486 treated animals, higher stimulation of Isc, and lower hematocrit at 24 h, beneficial effects attributed to increased caloric intake from the peanut oil vehicle. Chloride cell density was significantly increased in the high dose RU486 group at 48 hours, yet Isc was unchanged, suggesting a decrease in Cl- secretion per cell. Thus cortisol enhances NaCl secretion capacity in chloride cells, likely via glucocorticoid type receptors. ?? 2005 Wiley-Liss, Inc.

[Effect of red maca (Lepidium meyenii) on INF-γ levels in ovariectomized rats].

PubMed

Leiva-Revilla, Johanna; Guerra-Castañon, Félix; Olcese-Mori, Paola; Lozada, Iván; Rubio, Julio; Gonzales, Carla; Gonzales, Gustavo F

2014-01-01

Compare the effect of different doses of red maca on gamma interferon (IFN-γ) levels in ovariectomized rats (OVX). Adult female rats were randomly divided into the following six groups: Group 1: pseudo-ovariectomized rats (PO); Group 2: OVX rats; Group 3: OVX rats treated with 4 ug/kg estradiol; and Group 4, 5 and 6: OVX rats treated with red maca extracts with 2.15, 4.3 and 8.6 mg polyphenols/body weight kilogram, respectively. OVX rats showed low levels of IFN-γ compared to PO rats. Estradiol and red maca reversed the effect of ovariectomy on the IFN-γ levels. A positive dose-response effect of red maca on IFN-γ levels was shown (r = 0.57, p <0.05). Red maca administration increases levels of IFN-γ in ovariectomized rats.

Alterations in kidney enzyme pattern in acute hypervitaminosis A.

PubMed

Alarcón, O M; Reinosa Fuller, J; García de Méndez, G; Agudelo, R; Carnevalí de Tatá, E; Silva, T

1998-06-01

The relation of excessive doses of vitamin A with various kidney pathologies is well known however, information concerning the relation of kidney enzyme activity with acute hypervitaminosis A is rather scarce. In this study we describe the kidney enzymatic alterations observed in rats that received daily intramuscular injections of 10,000, 30,000, 50,000 and 100,000 IU of vitamin A palmitate (VA) during seven days (TREATED GROUPS). A comparison is made with the enzyme activity in healthy rats pair-fed and treated with sodium palmitate by intramuscular injection (CONTROL GROUP). The treated rats showed a proportional increase (p < 0.05) in activity of acid maltase, transminases or aminotransferases (GOT and GPT), alkaline phosphatase (ALP) and acid protease with all doses of VA administered. Amylase, lipase and arginase tend to decrease (p < 0.05) in activity only with doses of 50,000 and 100,000 I.U. of VA. Several factors are responsible for these findings, such as kidney necrosis due to release of lysosomal acid hydrolases produced by hypervitaminosis A.

Low-intensity laser therapy to treat dentin hypersensitivity: comparative clinical study using different light doses

NASA Astrophysics Data System (ADS)

Lizarelli, Rosane F. Z.; Mazzetto, Marcello O.; Bagnato, Vanderlei S.

2001-04-01

Dentin hypersensitivity is the most common patient's complain related to pain. In fact, this is a challenge to treat specially if conventional techniques are used. The possibility to treat pain through a low intensity laser gives us an opportunity to solve this important clinical problem without promote a discomfort to patient. The main point here is not if this kind of treatment is anti- inflammatory to pulp and/or biostimulatory to production of irregular secondary dentin. The most important point here is to understand how much energy is necessary to reach conditions where to tooth become insensible to external stimulus. Our double-blinded study compared a group without laser (Placebo) with five other groups where different doses at 660 nm low intensity laser were employed. The final conclusion is that for 660 nm laser therapy, the doses from 0.13 to 2.0 J/cm2 were more efficiency than the others. The follow up care in this study was of 45 days.

Dipyrone in association with atropine inhibits the effect on gastric emptying induced by hypoglycemia in rats

PubMed Central

Collares, E.F.; Vinagre, A.M.; Collares-Buzato, C.B.

2017-01-01

Atropine (AT) and dipyrone (Dp) induce a delay of gastric emptying (GE) of liquids in rats by inhibiting muscarinic receptors and activating β2-adrenergic receptors, respectively. The objective of the present study was to determine the effects of pretreatment with AT and Dp, given alone or in combination, on the effect of hypoglycemia in the liquid GE in rats. Male Wistar adult rats (280-310 g) were pretreated intravenously with AT, Dp, AT plus Dp or their vehicle and then treated 30 min later with iv insulin or its vehicle (n=8-10 animals/group). Thirty min after treatment, GE was evaluated by determining, in awake rats, the percent gastric retention (%GR) of a saline meal labeled with phenol red administered by gavage. The results indicated that insulin induced hypoglycemia in a dose-dependent manner resulting in a significant reduction in %GR of liquid only at the highest dose tested (1 U/kg). Pretreatment with AT significantly increased %GR in the rats treated with 1 U/kg insulin. Surprisingly, after pretreatment with AT, the group treated with the lowest dose of insulin (0.25 U/kg) displayed significantly lower %GR compared to its control (vehicle-treated group), which was not seen in the non-pretreated animals. Pretreatment with Dp alone at the dose of 40 mg/kg induced an increase in %GR in both vehicle and 0.25 U/kg-treated rats. A higher dose of Dp alone (80 mg/kg) significantly reduced the effect of a marked hypoglycemia induced by 1 U/kg of insulin on GE while in combination with AT the effect was completely abolished. The results with AT suggest that moderate hypoglycemia may render the inhibitory mechanisms of GE ineffective while Dp alone and in combination with AT significantly overcame the effect of hypoglycemia on GE. PMID:28876363

Phytochemical analysis and a study on the antiestrogenic antifertility effect of leaves of Piper betel in female albino rat

PubMed Central

Biswal, Sasmita

2014-01-01

Objective: To study the effect of graded doses of the aqueous and methanolic extract of the leaves of Piper betel (PB) Linn (PBL) on the estrous cycle of female albino rats. Materials and Methods: Both the extracts were tested for their effect on the estrous cycle at three dose levels of 500, 1000 and 1500 mg/kg/day and the vaginal smears were examined daily microscopically for the different phases of the estrous cycle for a period of 30 days. Result: The estrous cycle was irregular and prolonged in the treated groups indicating anestrus condition, which would result in infertility. Both types of the extract showed a significant decrease in the duration of proestrus and estrus with a prolonged diestrus at 1000 mg/kg/day and 1500 mg/kg/day doses as compared with control. However, no change was seen in the metestrus phase. The rats treated with PB showed a significant (P < 0.05), dose-dependent decrease in the estrus phase, in comparison to the control group, the effect was more with the methanolic extract. Large, cornified cells appeared after proestrus phase with decreased number of cornified cells. There was a significant reduction in the number of the estrous cycle, in the PBL treated group. Anestrus phase appeared in all the rats treated with the aqueous and methanolic PB extract, which was not observed in the control group. However, the aqueous extract at a dose of 500 mg/kg/day had no effect either on the estrous cycle or on its different phases. The observed effect of PB leaves could be due to the flavonoids and saponin contents, which also contributes to its antiestrogenic mechanism of action. Conclusion: Both the aqueous and methanolic extract of PBL possesses antifertility effect in female albino rats. PMID:25737606

Study of pentoxifylline effects on motility and viability of spermatozoa from infertile asthenozoospermic males

PubMed Central

Ghasemzadeh, Aliye; Karkon-Shayan, Farid; Yousefzadeh, Solmaz; Naghavi-Behzad, Mohammad; Hamdi, Kobra

2016-01-01

Background: The quality of semen is one of the major parameters in male infertility. Pentoxifylline, a methylxanthine derivative, is an agent primarily used in the treatment of intermittent claudication and other vascular disorders. Studies have shown that pentoxifylline enhances the quality and quantity of sperms. In this study, we have investigated the in vitro effects of pentoxifylline on viability and motility of spermatozoa in samples of infertile oligoasthenozoospermic males. Materials and Methods: In this observer-blinded clinical trial, semen samples of 25 infertile oligoasthenozoospermic males were collected in Alzahra Educational Medical Center of Tabriz University of Medical Sciences from August 2010 to August 2012. After the isolation of spermatozoa by the swim-up method, they were randomized into four groups in ISM1 environment: The controls treated normally: Group 1 treated by pentoxifylline at a dose of 50 μg/ml, Group 2 treated by pentoxifylline at a dose of 100 μg/ml, and Group 3 treated by pentoxifylline at a dose of 200 μg/ml. Sperm viability and motility were compared among the groups on 45 min, 24 h, 36 h, and 48 h intervals. Results: Mean percentages of live sperms were 98.40%, 51.40%, 20.60%, and 6.00% in control group and 98.40%, 69.20%, 38.60%, and 14.60% in Group 3 on the mentioned intervals, respectively. This mean percentage decrease of live sperms was significantly lower in Group 3 comparing with that of other groups (P = 0.01). Mean percentages of motile sperms were 54%, 8.40%, 2.80%, and 0% in control group; and 54%, 16%, 4.80%, and 1.40% in Group 3 on the mentioned intervals, respectively. There was not a significant difference between the four groups in this regard (P = 0.19). Conclusion: Pentoxifylline can enhance the viability of sperm of infertile oligoasthenozoospermic males with no significant effect on its motility. PMID:27942099

Study of pentoxifylline effects on motility and viability of spermatozoa from infertile asthenozoospermic males.

PubMed

Ghasemzadeh, Aliye; Karkon-Shayan, Farid; Yousefzadeh, Solmaz; Naghavi-Behzad, Mohammad; Hamdi, Kobra

2016-01-01

The quality of semen is one of the major parameters in male infertility. Pentoxifylline, a methylxanthine derivative, is an agent primarily used in the treatment of intermittent claudication and other vascular disorders. Studies have shown that pentoxifylline enhances the quality and quantity of sperms. In this study, we have investigated the in vitro effects of pentoxifylline on viability and motility of spermatozoa in samples of infertile oligoasthenozoospermic males. In this observer-blinded clinical trial, semen samples of 25 infertile oligoasthenozoospermic males were collected in Alzahra Educational Medical Center of Tabriz University of Medical Sciences from August 2010 to August 2012. After the isolation of spermatozoa by the swim-up method, they were randomized into four groups in ISM1 environment: The controls treated normally: Group 1 treated by pentoxifylline at a dose of 50 μg/ml, Group 2 treated by pentoxifylline at a dose of 100 μg/ml, and Group 3 treated by pentoxifylline at a dose of 200 μg/ml. Sperm viability and motility were compared among the groups on 45 min, 24 h, 36 h, and 48 h intervals. Mean percentages of live sperms were 98.40%, 51.40%, 20.60%, and 6.00% in control group and 98.40%, 69.20%, 38.60%, and 14.60% in Group 3 on the mentioned intervals, respectively. This mean percentage decrease of live sperms was significantly lower in Group 3 comparing with that of other groups ( P = 0.01). Mean percentages of motile sperms were 54%, 8.40%, 2.80%, and 0% in control group; and 54%, 16%, 4.80%, and 1.40% in Group 3 on the mentioned intervals, respectively. There was not a significant difference between the four groups in this regard ( P = 0.19). Pentoxifylline can enhance the viability of sperm of infertile oligoasthenozoospermic males with no significant effect on its motility.

Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental Escherichia coli infections in poultry.

PubMed

Kromann, Sofie; Kudirkiene, Egle; Li, Lili; Thoefner, Ida; Daldorph, Elisabeth; Christensen, Jens Peter; Meng, Hecheng; Olsen, Rikke Heidemann

2017-01-01

There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity in vitro, including increasing the susceptibility of Escherichia coli to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E. coli strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant E. coli infections exacerbate the pathological outcome of infection in chickens.

Treatment with high-dose antidepressants severely exacerbates the pathological outcome of experimental Escherichia coli infections in poultry

PubMed Central

Kromann, Sofie; Kudirkiene, Egle; Li, Lili; Thoefner, Ida; Daldorph, Elisabeth; Christensen, Jens Peter; Meng, Hecheng

2017-01-01

There is an urgent need for novel antibiotics as the current antibiotics are losing their value due to increased resistance among clinically important bacteria. Sertraline, an on-marked anti-depressive drug, has been shown to modify bacterial activity in vitro, including increasing the susceptibility of Escherichia coli to antibiotics. The aim of the present study was to investigate if the antimicrobial activity of sertraline could be documented under clinical settings, hereunder if sertraline could potentiate the effect of tetracycline in treatment of an experimentally induced ascending infection in poultry. A total of 40 chickens were divided in four groups of 10 chickens each. All chickens were challenged with 4x103 colony forming units (CFU) of a tetracycline resistant E. coli strain using a surgical infection model, and subsequently treated with either high-dose sertraline, tetracycline, a combination hereof or received no treatment. Seven days post challenge all birds were submitted to necropsy and scored pathologically for lesions. The average lesion scores were significantly higher (P<0.05) in the groups that were treated with high-dose sertraline or high-dose sertraline combined with tetracycline. In conclusion high-dose treatments (four times the maximum therapeutic dose for treating human depression) with sertraline as an adjuvant for treatment of antibiotic resistant E. coli infections exacerbate the pathological outcome of infection in chickens. PMID:29020098

Evaluation of Sub-acute Oral Toxicity of Lithium Carbonate Microemulsion (Nano Size) on Liver and Kidney of Mice

PubMed Central

Kalantari, Heibatullah; Salimi, Anayatollah; Rezaie, Anahita; Jazayeri Shushtari, Fereshteh; Goudarzi, Mehdi

2015-01-01

Background: The development of drug delivery systems has improved the therapeutic and toxic properties of existing drugs in therapy. Microemulsion systems are novel vehicles for drug delivery, which have been developed in recent years. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating into a wide range of drug molecules. Although these systems improved solubility and bioavailability of drugs, they may have potential toxic effects on the body organs. Objectives: The purpose of this study was to examine a possible hepatotoxic and nephrotoxic effect of lithium carbonate microemulsion (LCME) in a mice model. Materials and Methods: Eighty male Swiss albino mice were randomly allocated to eight experimental groups, as follows: Group 1, as negative control group were treated orally with normal saline (0.9% NaCl); Group 2, received microemulsion base without drug as control group; Groups 3 to 5, received lithium carbonate (LC) solution in doses of 50, 100, and 200 mg/kg, respectively; Groups 6 to 8, received LCME orally in doses of 50, 100, and 200 mg/kg, respectively. All drugs were administered orally for ten consecutive days. Serum glutamate pyruvate aminotransferase (SGPT), serum glutamate oxaloacetate aminotransferase (SGOT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and plasma creatinine (Cr), as markers of liver and kidney toxicity in treated mice, were measured. Furthermore, the changes of tissue were assessed by histopathologic examination. Results: The findings showed that serum activity of ALP, SGOT, and SGPT and the levels of BUN and Cr in microemulsion base group was greater than normal saline group. However, this difference was not significant. Administration of LC and LCME in all doses resulted in a significant increase in the levels of BUN and serum activity of SGOT and SGPT in comparison to normal saline group (P < 0.05). Histopathological changes were observed in mice treated with LC or LCME. Conclusions: This study showed that subacute oral administration of different doses of LCME with severe toxicity in comparison to the same dose of LC. PMID:25866723

EFFECT OF THE INCORPORATION OF 5-BROMODESOXYURIDINE ON MITOSIS AND THE SENSITIVITY TO X RAYS (in French)

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

Gontcharoff, M.; Rao, B.

1963-12-16

The effect of 5-bromodesoxyuridine (Budr) on cellular division and on sensitivity to x radiation was studied on fertilized eggs of the roundworm Strongylocentrus pur puratus. Four groups of samples were studied: a control group not treated with Budr and unexposed to x radiation; a group not treated with Budr but exposed to x radiation; a group treated with Budr but not exposed to x radiation; and a group treated with Budr and exposed to x radiation. The results are shown graphically. When the nontreated eggs are irradiated, the delay in cellular division is 55 min; the delay is 63 minmore » for treated samples irradiated with the same dose. The significance of these results is discussed. (J.S.R.)« less

188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas

PubMed Central

Allard, Emilie; Hindré, François; Passirani, Catherine; Lemaire, Laurent; Lepareur, Nicolas; Noiret, Nicolas; Menei, Philippe; Benoit, Jean-Pierre

2008-01-01

Purpose Lipid nanocapsules (LNC) entrapping lipophilic complexes of 188Re (188Re(S3CPh)2(S2CPh) [188Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intracerebral administration of 188Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model. Methods Female Fischer rats with 9L glioma were treated with a single injection of 188Re-SSS LNC by CED 6 days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8, and 3 Gy in comparison with blank LNC, perrhenate solution (4Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring 188Re elimination in faeces and urine over 72h after the CED injection. The therapeutic effect of 188Re-SSS LNC was assessed based on animal survival. Results CED of 188Re perrhenate solution resulted in rapid drug clearance with a brain T1/2 of 7h. In contrast, when administered in LNC, 188Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72h. Rat median survival was significantly improved for the group treated with 8Gy 188Re-SSS LNC compared to the control group and blank-LNC treated animals. The increase in the median survival time (ISTmedian) was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8Gy proved to be a very effective dose, between toxic (10–12Gy) and ineffective (3–4Gy) doses. Conclusions These findings show that CED of Rhenium-188-loaded lipid nanocapsules is a safe and potent antitumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of Rhenium-188 internal radiotherapy for the treatment of brain malignancy. PMID:18465130

Cognitive performance of juvenile monkeys after chronic fluoxetine treatment.

PubMed

Golub, Mari S; Hackett, Edward P; Hogrefe, Casey E; Leranth, Csaba; Elsworth, John D; Roth, Robert H

2017-08-01

Potential long term effects on brain development are a concern when drugs are used to treat depression and anxiety in childhood. In this study, male juvenile rhesus monkeys (three-four years of age) were dosed with fluoxetine or vehicle (N=16/group) for two years. Histomorphometric examination of cortical dendritic spines conducted after euthanasia at one year postdosing (N=8/group) suggested a trend toward greater dendritic spine synapse density in prefrontal cortex of the fluoxetine-treated monkeys. During dosing, subjects were trained for automated cognitive testing, and evaluated with a test of sustained attention. After dosing was discontinued, sustained attention, recognition memory and cognitive flexibility were evaluated. Sustained attention was affected by fluoxetine, both during and after dosing, as indexed by omission errors. Response accuracy was not affected by fluoxetine in post-dosing recognition memory and cognitive flexibility tests, but formerly fluoxetine-treated monkeys compared to vehicle controls had more missed trial initiations and choices during testing. Drug treatment also interacted with genetic and environmental variables: MAOA genotype (high- and low transcription rate polymorphisms) and testing location (upper or lower tier of cages). Altered development of top-down cortical regulation of effortful attention may be relevant to this pattern of cognitive test performance after juvenile fluoxetine treatment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

TIME COURSE AND DOSE RESPONSE ASSESSMENT OF CHOLINESTERASE (CHE) INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL, METHOMYL, METHIOCARB, OXAMYL, OR PROPOXUR.

EPA Science Inventory

To compare the toxicity of 5 N-methyl carbamates, the time course and dose response profiles for ChE inhibition were established for each. For the time course comparison, adult male Long Evans rats (n=5 dose group) were dosed orally with either carbaryl (CB; 30 mg/kg in corn oi...

Novel Pharmacological Approaches for Treatment of Neurotoxicity Induced by Chronic Exposure to Depleted Uranium

DTIC Science & Technology

2010-09-01

control group and low (300 mg load) and high dose (600 mg load) DU exposure conditions, but utilized a vehicle and three drug-treated groups ( memantine ...applied long after exposure was initiated. The minipumps were filled with drug solutions of 30 mg/ml memantine (3.6 mg/kg/day dose) and/or 10 mg/ml...riluzole (1.2 mg/kg/day dose). Besides its potential usefulness as an uncompetitive NMDA receptor antagonist, memantine also has been reported to have

Long-term results of a pilot study of low dose cranial-spinal irradiation for cerebellar medulloblastoma

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

Brand, W.N.; Schneider, P.A.; Tokars, R.P.

1987-11-01

Between May 1974 and March 1983, 44 children with histologically verified cerebellar medulloblastoma were seen for post-operative cranial-spinal irradiation following attempted total tumor removal. Six patients were excluded from review because they received all or part of their treatment at another institution (3 patients) or did not complete the planned course of irradiation (3 patients). All of the 38 remaining patients were treated by a previously described technique on a 4 MeV Linear Accelerator with 55 Gy delivered to the primary tumor site. Prior to December 1978, 19 consecutive children (Group A) had spinal prophylactic doses of 30-40 Gy andmore » brain prophylactic doses of 40-50 Gy. After the date, 25 Gy was given to the cranial-spinal axis of 19 consecutive children (Group B). This lower dose was arbitrarily selected with the hope of reducing morbidity in treated survivors and achieving the same tumor control. Risk factors that define good and poor prognosis were evaluated for each group, and there were no differences noted. Myelography and CSF cytology were not routinely performed. Follow-up for the 38 patients ranges from 20 months to 124 months. For the low risk patients, survival (12/15 or 80%) was independent of cranial-spinal radiation dose (Group A 6/8, Group B 6/7). For the high risk patients survival was poor (9/23 or 39%), not dependent on cranial-spinal radiation dose (Group A 5/11, Group B 4/12), and associated with failure at the primary site (10/14), often with CSF seeding (8/10). The other 4 failures include 2 who had moved outside the United States (details of failure are unknown), 1 with supratentorial, CSF seeding and distant metastases, and 1 with distant metastasis only.« less

Phase I Trial Using Patupilone (Epothilone B) and Concurrent Radiotherapy for Central Nervous System Malignancies

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

Fogh, Shannon; Machtay, Mitchell; Werner-Wasik, Maria

Purpose: Based on preclinical data indicating the radiosensitizing potential of epothilone B, the present study was designed to evaluate the toxicity and response rate of patupilone, an epothilone B, with concurrent radiotherapy (RT) for the treatment of central nervous system malignancies. Methods and Materials: The present Phase I study evaluated the toxicities associated with patupilone combined with RT to establish the maximal tolerated dose. Eligible patients had recurrent gliomas (n = 10) primary (n = 5) or metastatic (n = 17) brain tumors. Dose escalation occurred if no dose-limiting toxicities, defined as any Grade 4-5 toxicity or Grade 3 toxicitymore » requiring hospitalization, occurred during treatment. Results: Of 14 patients, 5 were treated with weekly patupilone at 1.5 mg/m{sup 2}, 4 at 2.0 mg/m{sup 2}, 4 at 2.5 mg/m{sup 2}, and 1 at 4 mg/m{sup 2}. Of 18 patients, 7 were treated in the 6-mg/m{sup 2} group, 6 in the 8-mg/m{sup 2} group, and 5 in the 10-mg/m{sup 2} group. Primary central nervous system malignancies received RT to a median dose of 60 Gy. Central nervous system metastases received whole brain RT to a median dose of 37.4 Gy, and patients with recurrent gliomas underwent stereotactic RT to a median dose of 37.5 Gy. One dose-limiting toxicity (pneumonia) was observed in group receiving 8-mg/m{sup 2} every 3 weeks. At the subsequent dose level (10 mg/m{sup 2}), two Grade 4 dose-limiting toxicities occurred (renal failure and pulmonary hemorrhage); thus, 8 mg/m{sup 2} every 3 weeks was the maximal tolerated dose and the recommended Phase II dose. Conclusion: Combined with a variety of radiation doses and fractionation schedules, concurrent patupilone was well tolerated and safe, with a maximal tolerated dose of 8 mg/m{sup 2} every 3 weeks.« less

Liver and kidney toxicity induced by Afzal smokeless tobacco product in Oman.

PubMed

Al-Mukhaini, Nawal; Ba-Omar, Taher; Eltayeb, Elsadig; Al-Shihi, Aisha; Al-Riyami, Nafila; Al-Belushi, Jamila; Al-Adawi, Kawthar

2017-04-01

Afzal, the common smokeless tobacco product (STP) in Oman, is believed to contain toxins that may impair the function of some organs such as liver and kidney. An aqueous extract from Afzal was added to drinking water to be administrated orally to Wistar albino rats (n=72) young and adult from both genders weighing between 60-80g and 150-240g respectively for 8 weeks. Animals were divided into three groups: control (distilled water instead of Afzal extract), low-dose (3mgnicotine/kgbodyweight/day) and high-dose (6mgnicotine/kgbodyweight/day). The animals were euthanized and their blood, liver and kidney were collected for biochemical and histopathological investigations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed for the liver function, while blood urea nitrogen (BUN) and creatinine (CRT) were assayed for the kidney function. The results showed a significant increase in the ALT, AST, BUN and CRT levels (P<0.05) in both Afzal-treated groups (low and high doses) compared with the control. Histopathological findings revealed the initial but seem to be serious degenerative alterations of periportal fibrosis in liver and edematous and calcified changes in renal glomerulus among Afzal-treated groups. Additionally, the weight gain of the Afzal-treated groups was lower than the control group. Our findings show that the exposure of Wistar rats to the Afzal extract has the potentials of causing decreased weight gain and dose-dependent functional and structural damage to the biochemical and histological profiles of liver and kidney as well as serious biochemical effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial.

PubMed

Solish, Nowell; Rivers, Jason K; Humphrey, Shannon; Muhn, Channy; Somogyi, Chris; Lei, Xiaofang; Bhogal, Meetu; Caulkins, Carrie

2016-03-01

Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates.

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Bacillus anthracis Infection in BALB/c Mice and Cynomolgus Macaques.

PubMed

Grossman, Trudy H; Anderson, Michael S; Drabek, Lindsay; Gooldy, Melanie; Heine, Henry S; Henning, Lisa N; Lin, Winston; Newman, Joseph V; Nevarez, Rene; Siefkas-Patterson, Kaylyn; Radcliff, Anne K; Sutcliffe, Joyce A

2017-10-01

The fluorocycline TP-271 was evaluated in mouse and nonhuman primate (NHP) models of inhalational anthrax. BALB/c mice were exposed by nose-only aerosol to Bacillus anthracis Ames spores at a level of 18 to 88 lethal doses sufficient to kill 50% of exposed individuals (LD 50 ). When 21 days of once-daily dosing was initiated at 24 h postchallenge (the postexposure prophylaxis [PEP] study), the rates of survival for the groups treated with TP-271 at 3, 6, 12, and 18 mg/kg of body weight were 90%, 95%, 95%, and 84%, respectively. When 21 days of dosing was initiated at 48 h postchallenge (the treatment [Tx] study), the rates of survival for the groups treated with TP-271 at 6, 12, and 18 mg/kg TP-271 were 100%, 91%, and 81%, respectively. No deaths of TP-271-treated mice occurred during the 39-day posttreatment observation period. In the NHP model, cynomolgus macaques received an average dose of 197 LD 50 of B. anthracis Ames spore equivalents using a head-only inhalation exposure chamber, and once-daily treatment of 1 mg/kg TP-271 lasting for 14 or 21 days was initiated within 3 h of detection of protective antigen (PA) in the blood. No (0/8) animals in the vehicle control-treated group survived, whereas all 8 infected macaques treated for 21 days and 4 of 6 macaques in the 14-day treatment group survived to the end of the study (56 days postchallenge). All survivors developed toxin-neutralizing and anti-PA IgG antibodies, indicating an immunologic response. On the basis of the results obtained with the mouse and NHP models, TP-271 shows promise as a countermeasure for the treatment of inhalational anthrax. Copyright © 2017 American Society for Microbiology.

The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Bacillus anthracis Infection in BALB/c Mice and Cynomolgus Macaques

PubMed Central

Anderson, Michael S.; Drabek, Lindsay; Gooldy, Melanie; Heine, Henry S.; Henning, Lisa N.; Lin, Winston; Newman, Joseph V.; Nevarez, Rene; Siefkas-Patterson, Kaylyn; Radcliff, Anne K.; Sutcliffe, Joyce A.

2017-01-01

ABSTRACT The fluorocycline TP-271 was evaluated in mouse and nonhuman primate (NHP) models of inhalational anthrax. BALB/c mice were exposed by nose-only aerosol to Bacillus anthracis Ames spores at a level of 18 to 88 lethal doses sufficient to kill 50% of exposed individuals (LD50). When 21 days of once-daily dosing was initiated at 24 h postchallenge (the postexposure prophylaxis [PEP] study), the rates of survival for the groups treated with TP-271 at 3, 6, 12, and 18 mg/kg of body weight were 90%, 95%, 95%, and 84%, respectively. When 21 days of dosing was initiated at 48 h postchallenge (the treatment [Tx] study), the rates of survival for the groups treated with TP-271 at 6, 12, and 18 mg/kg TP-271 were 100%, 91%, and 81%, respectively. No deaths of TP-271-treated mice occurred during the 39-day posttreatment observation period. In the NHP model, cynomolgus macaques received an average dose of 197 LD50 of B. anthracis Ames spore equivalents using a head-only inhalation exposure chamber, and once-daily treatment of 1 mg/kg TP-271 lasting for 14 or 21 days was initiated within 3 h of detection of protective antigen (PA) in the blood. No (0/8) animals in the vehicle control-treated group survived, whereas all 8 infected macaques treated for 21 days and 4 of 6 macaques in the 14-day treatment group survived to the end of the study (56 days postchallenge). All survivors developed toxin-neutralizing and anti-PA IgG antibodies, indicating an immunologic response. On the basis of the results obtained with the mouse and NHP models, TP-271 shows promise as a countermeasure for the treatment of inhalational anthrax. PMID:28784679

Lung dose and the potential risk of death in postoperative radiation therapy for non-small cell lung cancer: A study using the method of stratified grouping.

PubMed

Heo, Jaesung; Noh, O Kyu; Kim, Hwan-Ik; Chun, Mison; Cho, Oyeon; Park, Rae Woong; Yoon, Dukyong; Oh, Young-Taek

2018-04-19

Postoperative radiation therapy may have a detrimental effect on survival in patients with non-small cell lung cancer. We investigated the association of the lung radiation dose with the risk of death in patients treated with postoperative radiation therapy. We analyzed 178 patients with non-small cell lung cancer who received postoperative radiation therapy. The mean lung dose was calculated from dose-volume data, and we categorized patients into the high and low lung dose groups using 2 different methods; (1) simple grouping using the median lung dose of all patients, and (2) stratified grouping using the median lung dose of each subgroup sharing the same confounders. We compared clinical variables, and survival between the high and low lung dose groups. In the simple grouping, there were no significant differences in survivals between the high and low lung dose groups. After stratification, the overall survival of low lung dose group was significantly longer than that of high lung dose group (5-year survival, 60.1% vs. 35.3%, p = 0.039). On multivariable analyses, the lung dose remained a significant prognostic factor for overall survival (hazard ratio, HR = 2.08, p = 0.019). The lung dose was associated with the risk of death in patients with non-small cell lung cancer having the same confounders. Further studies evaluating the risk of death according to the lung dose will be helpful to administer more precise and individualized postoperative radiation therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevention of posttraumatic hypoxaemia in isolated lower limb long bone fractures with a minimal prophylactic dose of corticosteroids.

PubMed

Babalis, George A; Yiannakopoulos, Christos K; Karliaftis, Konstantinos; Antonogiannakis, Emmanuel

2004-03-01

The efficacy of a minimum dose of methylprednisolone for the prevention of posttraumatic hypoxaemia and fat embolism syndrome (FES) was prospectively studied in 87 patients with isolated, closed or grade I open, femoral and tibial fractures. On admission, the patients were randomly allocated either to a control group given placebo (40 patients) or to a methylprednisolone-treated group (47 patients). A total dose of 6 mg/kg BW methylprednisolone (SoluMedrol, Upjohn) was administered intravenously, divided in six equal doses at 8 h intervals. Six patients (12.8%) in the control group and one patient (2.5%) in the trial group developed FES (P = 0.079) but the difference is not statistically significant. Twenty-four hours after admission, the steroid-treated patients displayed statistically significant higher p(O2) values compared to the control group (P = 0.035) and this difference persisted on the second and the third post-admission day as well (P = 0.008). No corticosteroid-related side-effects were noticed in any of the patients during hospitalisation. Our results support the prophylactic administration of methylprednisolone in small dosage to prevent posttraumatic hypoxaemia and probably FES in patients with isolated lower limb long bone fractures, especially when early fracture stabilisation is not possible.

Cognitive Behavior Therapy as Augmentation for Sertraline in Treating Patients with Persistent Postural-Perceptual Dizziness.

PubMed

Yu, Yi-Chuan; Xue, Hui; Zhang, Ying-Xin; Zhou, Jiying

2018-01-01

Persistent postural-perceptual dizziness (PPPD) is a common vestibular disorder. This study was conducted to assess whether the addition of cognitive behavior therapy (CBT) could significantly improve the efficacy and acceptability of sertraline in treating PPPD. PPPD patients were recruited and randomly assigned to control and experiment groups. Patients in both groups received sertraline 50-200 mg/day, and only patients in the experiment group received CBT (twice a week, one hour per time). The treatment was continued for eight weeks. At baseline, week 2, week 4, and week 8, the 25-item Dizziness Handicap Inventory (DHI), Hamilton Anxiety Rating Scale (HARS), and Hamilton Depression Rating Scale (HDRS) were used to assess the self-perceived handicapping effects caused by PPPD, anxiety, and depressive symptoms, respectively. The dose of sertraline used and the adverse events in both groups were recorded and analyzed. In total, 91 PPPD patients were randomly assigned to the control group ( n = 45) and experiment group ( n = 46). After eight weeks of treatment, the average DHI scores, HDRS scores, and HARS scores were significantly decreased in both groups. But compared to the control group, the experiment group had significantly lower average DHI score, HDRS score, and HARS score at weeks 4 and 8. Moreover, the dose of sertraline used in the experiment group was significantly lower than that in the control group, and adverse events occurred more frequently in the control group than in the experiment group (48.9% versus 26.1%, p = 0.025). These results demonstrated that the addition of CBT could significantly improve the efficacy and acceptability of sertraline in treating PPPD and reduce the dose of sertraline used.

Aripiprazole and Risperidone for Treatment of Methamphetamine-Associated Psychosis in Chinese Patients.

PubMed

Wang, Gang; Zhang, Yao; Zhang, Sheng; Chen, Huijing; Xu, Zaifeng; Schottenfeld, Richard S; Hao, Wei; Chawarski, Marek Cezary

2016-03-01

We evaluated tolerability and efficacy of aripiprazole and risperidone for treatment of methamphetamine (METH) associated psychotic symptoms in China. Patients with acute METH-associated psychotic symptoms (N=42) and with Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 were randomized to aripiprazole (initial dose 5-10mg per day followed by flexible doses 5-15 mg per day) or risperidone (initial dose 2-4 mg per day followed by flexible doses 4-6 mg per day) from day 3 to 25 of inpatient hospital stay. Outcome measures included PANSS and Clinical Global Impressions-Severity of Illness scale (CGI-S), METH craving Visual Analogue Scale (VAS), Simpson Angus Scale (SAS), Barnes Assessments Akathasia Rating Scale (BARS), and self-reported adverse effects evaluated during treatment. Retention was evaluated using Kaplan-Meier survival analysis and the MIXED models procedure was used to compare the groups on measures of psychotic and extra-pyramidal symptoms. Patients in both aripiprazole and risperidone groups showed statistically significant reductions in psychotic symptomatology from baseline during treatment (p<0.001) with no statistically significant differences between the treatment groups (p=0.73 and p=0.15, respectively). Risperidone-treated patients reported significantly greater METH craving reductions (p<0.001). Overall, 71% of patients completed the entire study, but the aripiprazole group had a significantly lower retention than the risperidone group (p=0.007), primarily due to medication related adverse effects. Aripiprazole-treated patients also had significantly more akathisia (p=0.03) and agitation (p=0.02) than risperidone-treated patients. Patients in both groups who tolerated their medications and completed the entire study achieved comparable reductions of psychotic symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

In vitro and in vivo anthelmintic activity of crude extracts of Coriandrum sativum against Haemonchus contortus.

PubMed

Eguale, T; Tilahun, G; Debella, A; Feleke, A; Makonnen, E

2007-04-04

In vitro anthelmintic activities of crude aqueous and hydro-alcoholic extracts of the seeds of Coriandrum sativum (Apiaceae) were investigated on the egg and adult nematode parasite Haemonchus contortus. The aqueous extract of Coriandrum sativum was also investigated for in vivo anthelmintic activity in sheep infected with Haemonchus contortus. Both extract types of Coriandrum sativum inhibited hatching of eggs completely at a concentration less than 0.5 mg/ml. ED(50) of aqueous extract of Coriandrum sativum was 0.12 mg/ml while that of hydro-alcoholic extract was 0.18 mg/ml. There was no statistically significant difference between aqueous and hydro-alcoholic extracts (p>0.05). The hydro-alcoholic extract showed better in vitro activity against adult parasites than the aqueous one. For the in vivo study, 24 sheep artificially infected with Haemonchus contortus were randomly divided into four groups of six animals each. The first two groups were treated with crude aqueous extract of Coriandrum sativum at 0.45 and 0.9 g/kg dose levels, the third group with albendazole at 3.8 mg/kg and the last group was left untreated. Efficacy was tested by faecal egg count reduction (FECR) and total worm count reduction (TWCR). On day 2 post treatment, significant FECR was detected in groups treated with higher dose of Coriandrum sativum (p<0.05) and albendazole (p<0.001). On days 7 and 14 post treatment, significant FECR was not detected for both doses of Coriandrum sativum (p>0.05). Significant (p<0.05) TWCR was detected only for higher dose of Coriandrum sativum compared to the untreated group. Reduction in male worms was higher than female worms. Treatment with both doses of Coriandrum sativum did not help the animals improve or maintain their PCV while those treated with albendazole showed significant increase in PCV (p<0.05).

Effect of Laser Therapy on Chronic Osteoarthritis of the Knee in Older Subjects

PubMed Central

Youssef, Enas Fawzey; Muaidi, Qassim Ibrahim; Shanb, Alsayed Abdelhameed

2016-01-01

Introduction: Osteoarthritis (OA) is a common degenerative joint disease particularly in older subjects. It is usually associated with pain, restricted range of motion, muscle weakness, difficulties in daily living activities and impaired quality of life. To determine the effects of adding two different intensities of low-level laser therapy (LLLT) to exercise training program on pain severity, joint stiffness, physical function, isometric muscle strength, range of motion of the knee, and quality of life in older subjects with knee OA. Methods: Patients were randomly assigned into three groups. They received 16 sessions, 2 sessions/week for 8 weeks. Group-I: 18 patients were treated with a laser dose of 6 J/cm2 with a total dose of 48 J. Group-II: 18 patients were treated with a laser dose of 3 J/cm2 with a total dose of 27 J. Group-III: 15 patients were treated with laser without emission as a placebo. All patients received same exercise training program including stretching and strengthening exercises. Patients were evaluated before and after intervention by visual analogue scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index for quality of life, handheld dynamometer and universal goniometer. Results: T test revealed that there was a significant reduction in VAS and pain intensity, an increase in isometric muscle strength and range of motion of the knee as well as increase in physical functional ability in three treatment groups. Also analysis of variance (ANOVA) proved significant differences among them and the post hoc tests (LSD) test showed the best improvements for patients of the first group. Conclusion: It can be concluded that addition of LLLT to exercise training program is more effective than exercise training alone in the treatment of older patients with chronic knee OA and the rate of improvement may be dose dependent, as with 6 J/cm2 or 3 J/cm2. PMID:27330707

[Emodin alleviates pulmonary fibrosis through inactivation of TGF-β1/ADAMTS-1 signaling pathway in rats].

PubMed

Liu, Lijing; Qian, Hong; Xiao, Hua; He, Jianbin; Xie, Maofeng; Wang, Zaiyan; Long, Xingyun

2016-10-01

Objective To explore the role of transforming growth factor-β1 (TGF-β1)/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) signaling pathway in emodin's anti-pulmonary fibrosis. Methods Sixty SD rats were randomly divided into 6 groups: normal control group, sham-operated group, model group, low-dose emodin intervention group (20 mg/kg), high-dose emodin intervention group (80 mg/kg) and prednisone group (5 mg/kg). Each group included 10 animals. Rats in the latter 4 groups were intratracheally injected with bleomycin A5 to induce pulmonary fibrosis, whereas bleomycin A5 was replaced by normal saline in sham-operated group. From the second day, rats in the low- and high-dose emodin intervention groups were intragastrically treated with 2 mL of 20 and 80 mg/kg emodin, respectively. Rats in the prednisone group were intragastrically administrated with 2 mL of 5 mg/kg prednisone acetate. However, rats in the normal control and sham-operated and model groups were treated with 2 mL of normal saline. All rats were sacrificed on day 28 after modeling. Subsequently, blood and pulmonary tissue specimen were taken. The pathological changes of pulmonary tissues were observed using routine HE and Masson staining. The expressions of TGF-β1, ADAMTS-1, collagen type 1 (Col1) and Col3 in pulmonary tissues were measured by quantitative real-time PCR and Western blotting. Serum levels of procollagen type 1 carboxy terminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) were detected by ELISA. Results Compare with the model group, the alveolitis and pulmonary fibrosis extent in each drug-treated group were significantly alleviated. In comparison with normal control group or sham-operated group, the mRNA and protein levels of TGF-β1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP increased, but the mRNA and protein levels of ADAMTS-1 decreased in model group. After treatment with low- and high-dose emodin or prednisone, the mRNA and protein levels of TGF-β1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP were significantly downregulated, while the mRNA and protein levels of ADAMTS-1 in pulmonary tissues were significantly upregulated as compared with the model group. Moreover, In comparison with the low-dose emodin intervention group, the above indicators were significantly improved in the high-dose emodin intervention or prednisone group. However, the above indicators were not significantly different between the high-dose emodin intervention group and the prednisone group. Conclusion Increased degradation of Col1 and Col3 in pulmonary tissues due to the inactivation of TGF-β1/ADAMTS-1 signaling pathway may be a significant mechanism by which emodin protects rats against pulmonary fibrosis.

Safety and Pharmacokinetics of Multiple 750-Milligram Doses of Intravenous Levofloxacin in Healthy Volunteers

PubMed Central

Chow, Andrew T.; Fowler, Cynthia; Williams, R. Rex; Morgan, Nancy; Kaminski, Susan; Natarajan, Jaya

2001-01-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation. PMID:11408234

Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers.

PubMed

Chow, A T; Fowler, C; Williams, R R; Morgan, N; Kaminski, S; Natarajan, J

2001-07-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

PubMed

Fortin, Israël; Fortin, Bernard; Lambert, Louise; Clavel, Sébastien; Alizadeh, Moein; Filion, Edith J; Soulières, Denis; Bélair, Manon; Guertin, Louis; Nguyen-Tan, Phuc Felix

2014-09-01

In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria. Copyright © 2013 Wiley Periodicals, Inc.

Clinical outcomes of radiotherapy for esophageal cancer between 2004 and 2008: the second survey of the Japanese Radiation Oncology Study Group (JROSG).

PubMed

Nishimura, Yasumasa; Jingu, Keiichi; Itasaka, Satoshi; Negoro, Yoshiharu; Murakami, Yuji; Karasawa, Katsuyuki; Kawaguchi, Gen; Isohashi, Fumiaki; Kobayashi, Masao; Itoh, Yoshiyuki; Ariga, Takuro

2016-02-01

This second questionnaire-based survey was performed to determine the clinical results of definitive esophageal cancer treatment with radiotherapy (RT) or chemoradiotherapy (CRT) between 2004 and 2008. Clinical results of definitive RT for patients were collected from major Japanese institutions. Patients were classified into three groups: (A) stage I, (B) resectable stages II-III, (C) unresectable stages III-IVA. For group A, all patients treated with RT alone or CRT were included. For groups B and C, only those treated with CRT were included. In total, 990 patients (group A 259, group B 333, group C 398 patients) were included from 11 institutions. In group A, 199 patients (78 %) were treated with CRT, and 60 patients (23 %) received RT alone. In groups B and C, 420 patients (57 %) were treated with full-dose cisplatin/5-FU, and 181 patients (25 %) with low-dose protracted-infusion cisplatin/5-FU. The median and range of the 5-year overall survival rate were 73 % (40-94 %) for group A, 40 % (0-57 %) for group B, and 18 % (6-26 %) for group C, respectively. The 5-year overall survival rates were consistently good for five high-volume centers where more than 20 patients/year with esophageal cancer were treated definitively as compared with the remaining six medium-volume centers (5-15 patients/year). The median and range of the incidence of grade ≥3 late toxicities were 10 % and 6-22 %, respectively. A wide disparity in 5-year overall survival rates among the institutions was still apparent in the second survey for groups A and B.

Effects of postnatal administration of diethylstilbestrol on puberty and thyroid function in male rats.

PubMed

Shin, Jae-Ho; Kim, Tae Sung; Kang, Il Hyun; Kang, Tae Seok; Moon, Hyun Ju; Han, Soon-Young

2009-10-01

To examine the effects of diethylstilbestrol (DES) on male pubertal development and thyroid function, juvenile male Sprague-Dawley rats were given DES daily by oral intubation at doses of 10, 20 and 40 microg/kg/day from postnatal day 33 for 20 days. Prepuce separation was significantly delayed at the dose of 20 microg/kg/day and above in the DES-treated rats. DES treatment induced a significant reduction in the weights of testes, epididymides, the ventral prostate, seminal vesicles plus coagulating glands and fluid, levator ani bulbocavernosus muscles, Cowper's glands and the glans penis. The weights of the liver and adrenals increased in the DES-treated animals. DES caused a dose-dependent reduction in germ cells; in particular the spermatids were mainly affected. The serum levels of testosterone and luteinizing hormone were significantly reduced in the DES-treated groups, but that of estradiol decreased. No differences were observed in the serum thyroxine levels of the control and DES-treated groups. In microscopic observation of the DES-treated animals, degeneration of germ cells and tubular atrophy in the testis were noted, but there were no microscopic changes in the thyroid. These results indicate that DES affected the pubertal development of juvenile male rats and that its mode of action may be related to alterations in hormone levels.

Monosodium glutamate induced testicular toxicity and the possible ameliorative role of vitamin E or selenium in male rats.

PubMed

Hamza, Reham Z; Al-Harbi, Mohammad S

2014-01-01

Monosodium glutamate (MSG) has been recognized as flavor enhancer that adversely affects male reproductive systems. The present study was carried out to evaluate the potential protective role of vitamin E (vit E) or selenium against MSG induced oxidative stress and histopathological changes in testis tissues of rats. Mature male Wistar rats weighing 150-200 g BW were allocated to evenly twelve groups each group of ten animals, the first group was maintained as control group, the 2nd, 3rd and 4th groups were administered MSG in three different dose levels (low, medium and high) (6, 17.5 and 60 mg/kg BW), the 5th and 6th groups were given vit E in two doses (low and high) (150 and 200 mg/kg), the 7th and 8th groups were administered selenium in two doses (low and high) (0.25 and 1 mg/kg) daily via gavage for a period of 30 days. Meanwhile the 9th and 10th groups were given combinations of MSG (high dose) and vit E while, the 11th and 12th groups were given MSG (high dose) plus selenium in two recommended doses for each one. Monosodium glutamate caused an elevation in lipid peroxidation level parallel with significant decline in SOD, CAT as well as GPx activities in testis tissues. Administration of vit E or selenium to MSG-treated groups declined lipid peroxidation, increased SOD, CAT, GPx activities. Selenium or vit E significantly reduced MSG induced histopathological changes by the entire restoration of the histological structures and the testicular antioxidant status to great extent in treated rats. In conclusion, supplementation of selenium or vit E could ameliorate the MSG induced testicular toxicity to great extent and reduce the oxidative stress on testis tissues.

Crataegus monogyna fruit aqueous extract as a protective agent against doxorubicin-induced reproductive toxicity in male rats

PubMed Central

Shalizar Jalali, Ali; Hasanzadeh, Shapour

2013-01-01

Objective: Doxorubicin (DOX) is a broad spectrum chemotherapeutic agent used in the treatment of several malignancies. The use of DOX in clinical chemotherapy has been restricted due to its diverse toxicities, including reproductive toxicity. Crataegus monogyna (C. monogyna) is one of the oldest medicinal plants that have been shown to be cytoprotective because of scavenging free radicals. The present study was undertaken to determine whether C. monogyna fruits aqueous extract could serve as a protective agent against reproductive toxicity during DOX treatment in a rat model through antioxidant-mediated mechanisms. Materials and Methods: Male Wistar rats were allocated to four groups. Two groups of rats were treated with DOX at a dose of 4 mg/kg intraperitoneally on days 1, 7, 14, 21, and 28 (accumulated dose of 20 mg/kg). One of the groups received C. monogyna fruits aqueous extract at a dose of 20 mg/kg per day orally for 28 days along with DOX. A vehicle-treated control group and a C. monogyna control group were also included. Results: The DOX-treated group showed significant decreases in the body and organ weights and spermatogenic activities as well as many histological alterations. DOX treatment also caused a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. Moreover, significant decrease in serum levels of testosterone and increased serum concentrations of FSH, LH, LDH, CPK, and SGOT were observed in DOX-treated rats. Notably, Crataegus co-administration caused a partial recovery in above-mentioned parameters. Conclusion: These findings indicated that doxorubicin can adversely damage the testicular tissue, while Crataegus co-administration could effectively prevent these adverse effects by effective inhibiting oxidative processes and restoration of antioxidant defense system. PMID:25050270

Efficiency analysis of using tailored individual doses of radioiodine and fine tuning using a low-dose antithyroid drug in the treatment of Graves' disease.

PubMed

Liu, Chang-Jiang; Dong, Yan-Yu; Wang, Yi-Wei; Wang, Kai-Hua; Zeng, Qun-Yan

2011-03-01

To evaluate the effect of using tailored individual doses of radioiodine (¹³¹I) and fine tuning using low-dose antithyroid drug (ATD) in the treatment of Graves' disease, and an attempt to establish a therapeutic strategy that can keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine was calculated using the calculated dose formula, and low-dose ATD was used as a way of fine tuning during follow-up. The intended dose of radioiodine was modified according to the patient's age at radioiodine therapy, thyroid size, and duration of hyperthyroidism before radioiodine therapy in the study group; it was set as 2.96 MBq/g of thyroid in the control group. Twenty patients with Graves' disease were nonrandomly assigned to the control group and 98 patients with Graves' disease to the study group. The outcomes, which included euthyroidism, hypothyroidism, and persistent hyperthyroidism, were determined according to the patients' states at the end of follow-up. In the study group, 74 patients (75.5%) achieved the euthyroid state, six patients (6.1%) became hypothyroid, and 18 patients (18.4%) remained hyperthyroid. The rate of euthyroidism was statistically different between the study group and the control group (75.5 vs. 50%, P=0.03). Of 98 patients with Graves' disease in the study group, 19 patients were additionally treated with ATD during follow-up, and 12 patients achieved euthyroidism. In different age groups or duration of hyperthyroidism groups, the rate of euthyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). Similarly, in different age groups or duration of hyperthyroidism groups, the incidence of hypothyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). However, binary logistic regression analysis showed that thyroid size was associated with overtreatment and undertreatment in our study. Individual doses of radioiodine, adjusted according to the patient's age, thyroid size, and duration of hyperthyroidism, combined with low-dose ATD for some patients, 1 month or more after radioiodine therapy, was an effective method for treating Graves' disease. Our data showed that using tailored individual doses of radioiodine and fine tuning using low-dose ATD may well be a way to keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine should be decreased a little for small goiter and increased a little for large goiter on the basis of our treatment protocol in future study.

[Evaluation of immunotoxicity tests using cyclosporin A-treated rats: the International Collaborative Immunotoxicity Study II (cyclosporin A)].

PubMed

Ochiai, T; Naito, K; Murakami, O; Ohno, K; Sekita, K; Furuya, T; Kurokawa, Y; Matsumoto, K; Saito, Y; Hachisuka, A

1993-01-01

Immunotoxicological effects of cyclosporin A (CsA) were studied by enhanced histopathological and functional tests in rats. Male F344 rats were orally administered with CsA in doses of 0, 2.5, 10, and 40 mg/kg/day for 28 successive days. Hematological examination revealed that the CsA treatment brought about a marked dose-dependent decrease in the number of WBCs, which was attributed to a decrease in the number of lymphocytes. In the femoral bone marrow, a significant reduction in the number of nucleated cells was observed, which was attributed to a decrease in the number of lymphocytes and erythroblasts. Histopathologically, diminution of thymic medullas, appearance of tangible body macrophages in thymic cortices, and calcification and basophilic changes in kidneys were observed in the middle and high dose groups. Immunohistological examination with anti-rat T lymphocyte antibody showed a decrease in the number of T cells at the periarterial lymphatic sheaths in the spleens. As for the functional tests, CsA treatment remarkably reduced the PFC number even in the low dose group. The Con A response of spleen cells was decreased in the middle and high dose groups. The STM response was reduced only in the high dose group. The NK activity was little affected. Thus, in the CsA-treated F344 rats, the enhanced histopathological and some functional tests which were proposed by ICICIS, were found to be useful to detect damages to the immune system.

Comparative study of LDR (Manchester system) and HDR image-guided conformal brachytherapy of cervical cancer: patterns of failure, late complications, and survival.

PubMed

Narayan, Kailash; van Dyk, Sylvia; Bernshaw, David; Rajasooriyar, Chrishanthi; Kondalsamy-Chennakesavan, Srinivas

2009-08-01

To compare patterns of failure, late toxicities, and survival in locally advanced cervical cancer patients treated by either low-dose-rate (LDR) or conformal high-dose-rate (HDRc) brachytherapy as a part of curative radiotherapy. A retrospective comparative study of 217 advanced cervix cancer patients was conducted; 90 of these patients received LDR and 127 received HDRc brachytherapy. All patients were staged using International Federation of Gynecology and Obstetrics (FIGO) rules, had pretreatment magnetic resonance imaging (MRI), and were treated with concurrent cisplatin chemoradiotherapy. Both groups matched for FIGO stage, MRI tumor volume, and uterine invasion status. Local and pelvic failures were similar 12-13% and 14% both in both groups. Abdominal and systemic failures in LDR group were 21% and 24%, whereas corresponding failures in HDRc group were 20% and 24%. Sixty-eight percent (87/127) of patients treated by HDRc remained asymptomatic, whereas 42% (38/90) of patients were asymptomatic from the bowel and bladder symptoms after treatment with LDR. The 5-year OS rate was 60% (SE = 4%). The 5-year failure-free survival rate was 55% (SE = 3%). There was no significant difference between the groups. Image-guided HDRc planning led to a large decrease in late radiation effects in patients treated by HDRc. Patterns of failure and survival were similar in patients treated either by LDR or HDRc.

Frequency of Acute Kidney Injury Caused by Tazobactam/Piperacillin in Patients with Pneumonia and Chronic Kidney Disease: A Retrospective Observational Study.

PubMed

Morimoto, Takeyori; Nagashima, Hiroki; Morimoto, Yasuko; Tokuyama, Shogo

2017-01-01

 Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function. We studied a cohort of 57 patients with impaired renal function hospitalized with pneumonia and treated with TAZ/PIPC between January 2015 and November 2016. Patients were classified into four groups according to TAZ/PIPC dose: 2.25 g three times daily (Group A); 2.25 g four times daily (B); 4.5 g twice daily (C) and 4.5 g three times daily (D). We examined the frequency of acute kidney injury (AKI) and treatment effectiveness. In Groups A, B, C and D, AKI occurred in 5.6%, 0.0%, 25.0% and 38.5% of patient. In groups C and D, hydration and dose reduction were required to address early signs of impending AKI. Our findings suggest that the higher TAZ/PIPC dose of 4.5 g was responsible for the decline in renal function, even if the dose frequency was reduced.

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

PubMed Central

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

PubMed

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered.

Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats

PubMed Central

Omidi, Arash; Riahinia, Narges; Montazer Torbati, Mohammad Bagher; Behdani, Mohammad-Ali

2014-01-01

Objectives: Acetaminophen (APAP) toxicity is known to be common and potentially fatal. This study aims to investigate the protective effects of hydroalcoholic extract, remaining from Crocus sativus petals (CSP) against APAP-induced hepatotoxicity by measuring the blood parameters and studying the histopathology of liver in male rats. Materials and Methods: Wister rats (24) were randomly assigned into four groups including: I) healthy, receiving normal saline; II) Intoxicated, receiving only APAP (600 mg/kg); III) pre-treated with low dose of CSP (10 mg /kg) and receiving APAP (600 mg/kg); IV) pre-treated with high dose of CSP (20 mg/kg) and receiving APAP (600 mg/kg). Results: The APAP treatment resulted in higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin, along with lower total protein and albumin concentration than the control group. The administration of CSP with a dose of 20 mg/kg was found to result in lower levels of AST, ALT and bilirubin, with a significant higher concentration of total protein and albumin. The histopathological results regarding liver pathology, revealed sever conditions including cell swelling, severe inflammation and necrosis in APAP-exposed rats, which was quiet contrasting compared to the control group. The pre-treated rats with low doses of ‍CSP showed hydropic degeneration with mild necrosis in centrilobular areas of the liver, while the same subjects with high doses of ‍CSP appeared to have only mild hepatocyte degeneration. Conclusions: Doses of 20 mg/kg of CSP ameliorates APAP–induced acute liver injury in rats. It was concluded that the antioxidant property of CSP resulted in reducing the oxidative stress complications of toxic levels of APAP in intoxicated rats. PMID:25386395

Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity.

PubMed

Yasasvini, S; Anusa, R S; VedhaHari, B N; Prabhu, P C; RamyaDevi, D

2017-03-01

A prolonged release drug delivery system was developed by loading Simvastatin-chitosan microparticles into poly vinyl alcohol (PVA) hydrogels for enhanced wound healing efficiency. The microparticles prepared by ionic gelation method with varying composition of chitosan and surfactants (Tween 80/Pluronic F-127) were optimized for entrapment efficiency, morphology and drug-polymer interactions. Microparticles prepared with 0.3% between 80 and 0.5:5 chitosan: drug ratio showed maximum entrapment efficiency of 82% with spherical morphology and mild interaction between drug and chitosan. 5% PVA solutions loaded with pure drug and drug loaded microparticles at three different doses (2.5mg, 5mg and 10mg equivalent of drug) were chemically cross linked using gluteraldehyde and HCl. The formulated hydrogels were optimized for swelling, in vitro release behavior and in vivo wound healing effect. Hydrogels containing 2.5mg equivalent dose of Simvastatin microparticles exhibited maximum cumulative percentage drug release of 92% (n=3) at the end of 7days. The in vitro drug release data was supported by the higher swelling index of the low dose hydrogels. The in vivo wound healing study was performed using Wistar rats (n=30, 5 groups with 6 animals in each group) for the formulated hydrogels (at 3 doses) and compared with the untreated animals and the positive control group treated with conventional topical Simvastatin ointment (1%). The wound healing effect was comparable to the in vitro results, wherein the animals treated with low dose hydrogels (replaced every 7days) exhibited considerable reduction in the wound area compared to medium and high dose hydrogels. Statistically significant difference (P<0.05) was observed in the wound area of the animals treated with low dose hydrogels compared to 1% ointment and untreated animals, as estimated by two-way ANOVA. The histopathology images of the different groups of animals also displayed the comparative changes in the wound healing process. Hence, the incorporation of Simvastatin-chitosan microparticles in PVA hydrogels has demonstrated significant wound healing efficiency at optimum dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Embryotoxicity of orally administered chromium in mice: exposure during the period of organogenesis.

PubMed

Junaid, M; Murthy, R C; Saxena, D K

1996-03-01

Administration of chromium (VI)(250, 500 and 750 ppm as potassium dichromate) via drinking water during organogenesis (days 6-14 of gestation) in mice revealed embryo- and fetotoxic effects. Reduced fetal weight, retarded fetal development, number of fetuses (live and dead) per mother and high incidences of dead fetuses and resorptions in treated mothers in the highest dosed group were evident. No significant gross structural abnormalities were observed in any of the fetuses of chromium (VI)-treated mothers. Significant incidences of reduced ossification were found in the highest dosed group. Chromium levels were increased in a dose-dependent manner in maternal blood, placenta and fetuses. The present study suggests a risk to the developing embryo if the mother is exposed to a sufficiently high concentration of chromium (VI) through drinking water during the period of organogenesis.

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

PubMed Central

Yan, Bing Chun; Yoo, Ki-Yeon; Park, Joon Ha; Lee, Choong Hyun; Choi, Jung Hoon

2011-01-01

Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 mg/kg EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice. PMID:22025974

Fructo-oligosaccharide improved brain β-amyloid, β-secretase, cognitive function, and plasma antioxidant levels in D-galactose-treated Balb/cJ mice.

PubMed

Yen, Chi-Hua; Wang, Cheng-Hsin; Wu, Wen-Tzu; Chen, Hsiao-Ling

2017-05-01

Long-term d-galactose injection induces accelerated aging in experimental rodent models. The aim of this study was to determine the effects of dietary fructo-oligosaccharide (FO) on the brain β-amyloid (Aβ), amyloid-associated enzymes, cognitive function, and plasma antioxidant levels in d-galactose-treated Balb/c mice. The subcutaneous (s.c.) injection and the dietary treatment were conducted simultaneously for 49 days. Mice (12 weeks of age) were divided into five groups (n = 14/group): control (s.c. saline, control diet) serving as a young control, DG (s.c. 1.2 g d-galactose/kg body weight, control diet), DG + LFO (2.5% w/w FO, low-dose FO diet), DG + HFO (5% w/w FO, high-dose FO diet), and DG + E (α-tocopherol 0.2% w/w, vitamin E diet) as an antioxidant reference group. Another group of older mice (64 weeks of age) without any injection served as a natural aging (NA) group. The DG and NA groups had greater Aβ levels in the cortex, hippocampus, and the whole brain. High-dose FO, similar to α-tocopherol, attenuated the d-galactose-induced Aβ density in the cortex and hippocampus. In addition, FO attenuated the d-galactose-induced protein expression of Aβ and beta-site amyloid precursor cleaving enzyme of the whole brain in a dose-response manner. Either dose of FO supplementation, similar to α-tocopherol, attenuated the d-galactose-induced cognitive dysfunction. In addition, FO improved the plasma ascorbic acid level in a dose-response manner. Dietary FO (2.5-5% w/w diet) could attenuate the development of Alzheimer's disease, which was likely to be associated with its systematic antioxidant effects.

Acceleration of skin wound healing by low-dose indirect ionizing radiation in male rats.

PubMed

Jabbari, Nasrollah; Farjah, Gholam Hossein; Ghadimi, Behnam; Zanjani, Hajar; Heshmatian, Behnam

2017-08-01

A recent hypothesis has revealed that low-dose irradiation (LDI) with ionizing radiation might have a promoting effect on fracture healing. The aim of this study was to investigate the influence of direct (electron beam) and indirect (gamma-ray) low-dose ionizing irradiations on the wound healing process in male rats. In 72 male rats, a full-thickness wound was incised. The animals were randomly assigned to three groups, each with 24 rats. The first two groups were named IG-I and IG-II and respectively exposed to electron and gamma-radiations (75 cGy) immediately after the surgical procedure. The third group was considered as the control (CG) and remained untreated. Skin biopsies from the subgroups were collected on days 3, 7, 15, and 21 after the operation and evaluated using histological and biomechanical methods. Data were analyzed by one-way ANOVA, followed by Tukey's post hoc test using SPSS 20 software. Histological studies of tissues showed that the mean number of fibroblasts, macrophages, blood vessel sections, and neutrophils on the third and seventh days after the surgery in the gamma-treated group was higher than that in both other groups. In contrast, on day 21, the mean number of mentioned cells in the gamma-treated group was lower than in the other two groups. In addition, the mean maximum stress value was significantly greater in the gamma-treated group. Results of this study showed that gamma-ray irradiation is effective in the acceleration of wound healing. Copyright © 2017. Published by Elsevier Taiwan.

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

40 CFR 798.3260 - Chronic toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... dose groups and in the controls should be low to permit a meaningful evaluation of the results. For non... meaningful and valid statistical evaluation of chronic effects. (2) Control groups. (i) A concurrent control group is suggested. This group should be an untreated or sham treated control group or, if a vehicle is...

Antigenotoxic and anticytotoxic effect of camel milk in mice treated with cisplatin

PubMed Central

Salwa, M. Quita; Lina, A.F. Kurdi

2010-01-01

Camel milk (CM) has good nutritive value, in addition to its antigenotoxic and anticytotoxic effects. Therefore the aim of this investigation was to evaluate the capacity of CM to inhibit the micronucleated polychromatic erythrocytes (MnPCEs) in the bone marrow and improve the mitotic activity produced by cisplatin. Cisplatin is one of the most widely used antineoplastic drugs in the treatment of cancer. The 70 adult male Swiss albino mice were divided into seven groups:Gr. I: treated with distilled water and considered as a control group.Gr. II: treated with camel milk (33 ml/kg, b.w).Gr. III: treated previously with cisplatin (0.5 mg/kg, b.w).Gr. IV: treated with camel milk and followed after 2 h. with cisplatin (33 ml/kg → 0.5 mg/kg, b.w).Gr. V: treated with camel milk and cisplatin at the same time (33 ml/kg + 0.5 mg/kg, b.w).Gr. VI: treated with an acute single dose of cisplatin (2.5 mg/kg, b.w).Gr. VII: treated with camel milk prior and followed with an acute single dose of cisplatin (33 ml/kg → 2.5 mg /kg, b.w). The animals were sacrificed 24 h after cisplatin injection. The pretreatment with CM dose caused a significant decrease (P < 0.001) in the frequency of MnPCEs and increase (P < 0.001) in the mitotic index (MI) induced by cisplatin when compared with the groups treated with cisplatin alone. The possible explanation for the antigenotoxic and anticytotoxic effects observed in the pretreatment with CM is ascribed to its contents. In conclusion, from the findings we suggest that this milk has some antioxidant effect, and the antigenotoxic mechanism of this milk needs to be explored further before their use during cisplatin chemotherapy. PMID:23961073

Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ)-Induced Diabetic Rats

PubMed Central

Liu, Jing; Zhou, Feng; Li, Guang-Yong; Wang, Lin; Li, Hui-Xi; Bai, Guang-Yi; Guan, Rui-Li; Xu, Yong-De; Gao, Ze-Zhu; Tian, Wen-Jie; Xin, Zhong-Cheng

2013-01-01

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment. PMID:23698784

Evaluation of the effect of different doses of low energy shock wave therapy on the erectile function of streptozotocin (STZ)-induced diabetic rats.

PubMed

Liu, Jing; Zhou, Feng; Li, Guang-Yong; Wang, Lin; Li, Hui-Xi; Bai, Guang-Yi; Guan, Rui-Li; Xu, Yong-De; Gao, Ze-Zhu; Tian, Wen-Jie; Xin, Zhong-Cheng

2013-05-21

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment.

Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

PubMed

Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

2016-10-01

Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation

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

Speiser, B.L.; Spratling, L.

The purpose of the study was to describe a new clinical entity observed in follow-up bronchoscopies in patients who were treated with high dose rate and medium dose rate remote afterloading brachytherapy of the tracheobronchial tree. Patients were treated by protocol with medium dose rate, 47 patients receiving 1000 cGy at a 5 mm depth times three fractions, high dose rate 144 patients receiving 1000 cGy at a 10 mm depth for three fractions and high dose rate 151 patients receiving cGy at a 10 mm depth for three fractions followed by bronchoscopy. Incidence of this entity was 9% formore » the first group, 12% for the second, and 13% for the third group. Reactions were grade 1 consisting of mild inflammatory response with a partial whitish circumferential membrane in an asymptomatic patient; grade 2, thicker complete white circumferential membrane with cough and/or obstructive problems requiring intervention; grade 3, severe inflammatory response with marked membranous exudate and mild fibrotic reaction; and grade 4 a predominant fibrotic reaction with progressive stenosis. Variables associated with a slightly increased incidence of radiation bronchitis and stenosis included: large cell carcinoma histology, curative intent, prior laser photoresection, and/or concurrent external radiation. Survival was the strongest predictor of the reaction. Radiation bronchitis and stenosis is a new clinical entity that must be identified in bronchial brachytherapy patients and treated appropriately. 23 refs., 3 figs., 7 tabs.« less

Comparison of space flight and heavy ion radiation induced genomic/epigenomic mutations in rice (Oryza sativa)

NASA Astrophysics Data System (ADS)

Shi, Jinming; Lu, Weihong; Sun, Yeqing

2014-04-01

Rice seeds, after space flight and low dose heavy ion radiation treatment were cultured on ground. Leaves of the mature plants were obtained for examination of genomic/epigenomic mutations by using amplified fragment length polymorphism (AFLP) and methylation sensitive amplification polymorphism (MSAP) method, respectively. The mutation sites were identified by fragment recovery and sequencing. The heritability of the mutations was detected in the next generation. Results showed that both space flight and low dose heavy ion radiation can induce significant alterations on rice genome and epigenome (P < 0.05). For both genetic and epigenetic assays, while there was no significant difference in mutation rates and their ability to be inherited to the next generation, the site of mutations differed between the space flight and radiation treated groups. More than 50% of the mutation sites were shared by two radiation treated groups, radiated with different LET value and dose, while only about 20% of the mutation sites were shared by space flight group and radiation treated group. Moreover, in space flight group, we found that DNA methylation changes were more prone to occur on CNG sequence than CG sequence. Sequencing results proved that both space flight and heavy ion radiation induced mutations were widely spread on rice genome including coding region and repeated region. Our study described and compared the characters of space flight and low dose heavy ion radiation induced genomic/epigenomic mutations. Our data revealed the mechanisms of application of space environment for mutagenesis and crop breeding. Furthermore, this work implicated that the nature of mutations induced under space flight conditions may involve factors beyond ion radiation.

Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group.

PubMed Central

Riviere, A.

1994-01-01

The efficacy and safety of three different doses of granisetron (2 micrograms kg-1, group A; 10 micrograms kg-1, group B; 40 micrograms kg-1, group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin. PMID:8180032

Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields.

PubMed

Tanabe, Satoshi; Myojin, Miyako; Shimizu, Shinichi; Fujino, Masaharu; Takahashi, Hiroaki; Shirato, Hiroki; Ito, Yoichi M; Ishikawa, Masayori; Hosokawa, Masao

2013-11-01

We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0-1 RP (RPG≤1) group and the Grade 2-5 RP (RPG≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Of these 86 patients, 10 (12%) developed RPG≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RPG≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV. The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.

Frequency of booster injections of allergoids.

PubMed

Norman, P S; Creticos, P S; Marsh, D G

1990-01-01

In 1982, 43 ragweed-sensitive patients receiving maintenance injections of full doses of ragweed allergoid were selected for a study of the immunologic and clinical efficacy of booster injections only four times a year. These patients had participated for 2 to 7 years as part of a trial of mixes of up to four allergoids to common pollens in the mid-Atlantic area tailored to each patient's skin test sensitivity. They were divided into a group (21 patients) to receive injections every 3 months and a group (22 patients) to receive injections about every 6 weeks (eight injections per year). Patients were rerandomized after 1 year so that half of each original group switched to the alternate treatment, and this program was continued until after the ragweed season of 1985. Thirty-four patients were still under study the last year. Doses, per injection, were 100 allergoid units (1 allergoid unit equals 100 PNU) of each allergen in the mixture. Symptom scores during the 8 weeks of each of the four ragweed seasons were not significantly higher in the 3-month treated group. IgG antibody levels to Amb a I (antigen E) were followed until early 1984 and were not significantly different in the two groups, even though the 6-week treated patients received a two times higher cumulative dose per year. Rates of local and systemic reactions (percent of injections eliciting reactions) were not different in the groups, which means that the 3-month treated group had about half as many reactions by virtue of taking half as many injections.(ABSTRACT TRUNCATED AT 250 WORDS)

[Dose-effect relationship of orally administered Pyritinol in the chronic organic brain syndrome (author's transl)].

PubMed

Glatzel, J

1978-08-04

161 patients with the chronic organic brain syndrome (average age 64 years) were treated with various oral doses of Pyritinol for various periods of time. Statistical analysis of the data by means of "Konfigurationsfrequenzanalyse" showed that the success rate of treatment increases significantly with increasing dose and duration of the treatment. This means that the recommended daily dose should be exceeded if - for example at the start of treatment and in severe cases or in hospitalized patients - there is no immediate clear improvement in the condition. From the point of view of method this study shows that a retrospective analysis of a group of patients treated in a clinic can also provide interesting results and appropriately supplement controlled studies.

Trigeminal Neuralgia Treated With Stereotactic Radiosurgery: The Effect of Dose Escalation on Pain Control and Treatment Outcomes

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

Kotecha, Rupesh; Kotecha, Ritesh; Modugula, Sujith

Purpose: To analyze the effect of dose escalation on treatment outcome in patients undergoing stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). Methods and Materials: A retrospective review was performed of 870 patients who underwent SRS for a diagnosis of TN from 2 institutions. Patients were typically treated using a single 4-mm isocenter placed at the trigeminal nerve dorsal root entry zone. Patients were divided into groups based on treatment doses: ≤82 Gy (352 patients), 83 to 86 Gy (85 patients), and ≥90 Gy (433 patients). Pain response was classified using a categorical scoring system, with fair or poor pain control representing treatment failure.more » Treatment-related facial numbness was classified using the Barrow Neurological Institute scale. Log-rank tests were performed to test differences in time to pain failure or development of facial numbness for patients treated with different doses. Results: Median age at first pain onset was 63 years, median age at time of SRS was 71 years, and median follow-up was 36.5 months from the time of SRS. A majority of patients (827, 95%) were clinically diagnosed with typical TN. The 4-year rate of excellent to good pain relief was 87% (95% confidence interval 84%-90%). The 4-year rate of pain response was 79%, 82%, and 92% in patients treated to ≤82 Gy, 83 to 86 Gy, and ≥90 Gy, respectively. Patients treated to doses ≤82 Gy had an increased risk of pain failure after SRS, compared with patients treated to ≥90 Gy (hazard ratio 2.0, P=.0007). Rates of treatment-related facial numbness were similar among patients treated to doses ≥83 Gy. Nine patients (1%) were diagnosed with anesthesia dolorosa. Conclusions: Dose escalation for TN to doses >82 Gy is associated with an improvement in response to treatment and duration of pain relief. Patients treated at these doses, however, should be counseled about the increased risk of treatment-related facial numbness.« less

MANAGEMENT OF DIABETES MELLITUS (PRAMEHA) WITH INULA RACEMOSA AND CINNAMOMUM TAMALA

PubMed Central

Singh, T. N.; Upadhyay, B. N.; Tewari, C. M.; Tripathi, S. N.

1985-01-01

35 patients of Maturity onset diabetes mellitus having the complaints of polyurea polydypsia and polyphagia etc. have been selected. For the diagnosis of diabetes mellitus the fasting and 1st hour and 2nd hour post parandial blood sugar were estimated. Patients were classified into two groups. 20 patients were treated with powder of C. Tamal leaves in the dose of 2 TSF T. D. S. and 15 patients were treated with Inula racemosa in the dose of 1 TSF T. D. S. for the period of three months. The response was estimated on the parameter of Joslin's Clinica in C. Tamal group 50% cases were in good control. 33.33% were in fair control and 16.67% cases were in poor control. Inula racemosa treated group 100% cases were in good control. Thus it can be inferred that both of the drugs are useful in the treatment of Diabetes mellitus of Maturity onset. However, the response of Inula racemosa is better as compared to C. Tamala. PMID:22557492

Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study.

PubMed

DeVincenzo, John P; McClure, Matthew W; Symons, Julian A; Fathi, Hosnieh; Westland, Christopher; Chanda, Sushmita; Lambkin-Williams, Rob; Smith, Patrick; Zhang, Qingling; Beigelman, Leo; Blatt, Lawrence M; Fry, John

2015-11-19

BACKGROUND Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality. There is no known effective therapy. METHODS We conducted a randomized, double-blind, clinical trial in healthy adults inoculated with RSV. Participants received the oral nucleoside analogue ALS-008176 or placebo 12 hours after confirmation of RSV infection or 6 days after inoculation. Treatment was administered every 12 hours for 5 days. Viral load, disease severity, resistance, and safety were measured throughout the 28-day study period, with measurement beginning before inoculation. The primary end point was the area under the curve (AUC) for viral load, which was assessed immediately before administration of the first dose through the 12th day after inoculation in participants infected with RSV. RESULTS A total of 62 participants received placebo or one of three ALS-008176 dosing regimens: 1 loading dose of 750 mg followed by 9 maintenance doses of 500 mg (group 1), 1 loading dose of 750 mg followed by 9 maintenance doses of 150 mg (group 2), or 10 doses of 375 mg (group 3). In the 35 infected participants (23 of whom were treated with ALS-008176), the AUCs for viral load for groups 1, 2, and 3 and the placebo group were 59.9, 73.7, 133.4, and 500.9 log10 plaque-forming-unit equivalents × hours per milliliter, respectively (P≤0.001). The time to nondetectability on polymerase-chain-reaction assay (P<0.001), the peak viral load (P≤0.001), the AUC for symptom score (P<0.05), and the AUC for mucus weight were lower in all groups receiving ALS-008176 than in the placebo group. Antiviral activity was greatest in the two groups that received a loading dose--viral clearance was accelerated (P≤0.05), and the AUC for viral load decreased by 85 to 88% as compared with the placebo group. Within this small trial, no viral rebound or resistance was identified. There were no serious adverse events, and there was no need for premature discontinuation of the study drug. CONCLUSIONS In this RSV challenge study, more rapid RSV clearance and a greater reduction of viral load, with accompanying improvements in the severity of clinical disease, were observed in the groups treated with ALS-008176 than in the placebo group. (Funded by Alios BioPharma; ClinicalTrials.gov number, NCT02094365.).

Conditioned pharmacotherapeutic effects: a preliminary study.

PubMed

Ader, Robert; Mercurio, Mary Gail; Walton, James; James, Deborra; Davis, Michael; Ojha, Valerie; Kimball, Alexa Boer; Fiorentino, David

2010-02-01

To test the hypothesize that psoriasis patients treated under a partial schedule of pharmacologic (corticosteroid) reinforcement would show less severe symptoms and relapse than those given the same amount of drug under standard conditions. Behavioral conditioning as an inherent component of many pharmacotherapeutic protocols has never been examined. A double-blind, simple randomization intervention was conducted with 46 patients from California and New York. Initially, lesions were treated with 0.1% acetonide triamcinolone under standard treatment conditions. Thereafter, a Standard Therapy group continued on continuous reinforcement (active drug every treatment) with 100% of the initial dose; Partial Reinforcement patients received a full dose 25% to 50% of the time and placebo medication other times; Dose Control patients received continuous reinforcement with 25% to 50% of the initial dose. Severity of disease scores in California neither supported nor refuted the hypothesis. In New York, where there was no difference between Partial Reinforcement and Dose Control groups at baseline, partial reinforcement effected a greater reduction in lesion severity than Dose Control conditions and did not differ from Standard Therapy patients receiving two to four times more drug. For the entire population, the frequency of relapse under partial reinforcement (26.7%) was lower than in Dose Control patients (61.5%) and did not differ from full-dose treatment (22.2%). A partial schedule of pharmacotherapeutic reinforcement could maintain psoriasis patients with a cumulative amount of corticosteroid that was relatively ineffective when administered under standard treatment conditions. Conceivably, corticosteroid administration only one quarter or half as frequently as currently prescribed is sufficient to treat psoriasis. We posit, however, that these preliminary observations implicate conditioning processes in-and for the design of-regimens of pharmacotherapy.

Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients

PubMed Central

Peng, Xiang; Zhi, Min; Wei, Ming; Li, Ting-Ting; Zhang, Min; Zhang, Yuan-Qi; He, Huan; Su, Mingli; Wang, Wei; Chen, Jun-rong; Tang, Jian; Gao, Xiang; Hu, Pin-Jin; Liang, Xiao-Yan

2017-01-01

Abstract The effectiveness of thalidomide in treating inflammatory bowel disease (IBD) has been widely recognized. Meanwhile, many serious adverse drug reactions have been observed, but no know reports on ovarian reserve function. Female patients, ranging in age between 18 and 40, were referred to our institution to undergo sex hormone detection and ultrasonic scanning for ovarian function assessment, between February 1, 2016 and September 31, 2016. Thirty-three patients treated with thalidomide (group A), 73 patients without thalidomide (group B), and 78 healthy women as control were studied. Menstrual disorder was higher in group A than group B (78.8% vs 57.2%, P < 0.05), and both groups were higher than control group 33.3%, P < 0.05. Anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) in group A were lower than group B, P < 0.05, while estradiol (E2) and follicle-stimulating hormone (FSH) levels were no different between 2 groups. Crohn Disease Endoscopic Index of Severity (CDEIS) and thalidomide were the independent risk factors in diminished ovarian reserve (DOR), and when dose reached 75 mg/day, 5 g total, or when treatment time reached 10 months respectively. These influence may increasing (P < 0.05), but they may recover after stopping (P < 0.05). Thalidomide was an independent risk factor leading to DOR in female IBD patients, the influence may increasing when daily dose and accumulated dose reached 75 mg/day and 5 g total dose, but may be reversed by stopping. PMID:28538364

Attenuation of hepatotoxicity and oxidative stress in diabetes STZ-induced type 1 by biotin in Swiss albino mice

PubMed Central

Aldahmash, Badr Abdullah; El-Nagar, Doaa Mohamed; Ibrahim, Khalid Elfakki

2015-01-01

Diabetes mellitus is one of the major health problems. This study was designed to investigate the effect of biotin to regulate blood glucose level, reduced toxicity and oxidative stress in liver of diabetic mice STZ-induced type 1. Male mice were divided into three groups, the first one served as the control group, the second and the third groups received single ip dose of 150 mg/kg of STZ, the second group served as the untreated diabetic group, the third group received daily oral dose of 15 mg/kg of biotin, livers and liver index showed insignificant difference among groups. Blood glucose level showed a significant decrease in treated diabetic mice compared to untreated diabetic mice. Biochemical analysis showed a significant decrease in liver enzymes AST and ALT compared to the control group. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and moderate to severe histopathological score, whereas, treated diabetic mice with biotin showed reduction in hepatotoxicity represented by appearance of relative healthy hepatocytes and normal histopathological score. Immunohistochemistry of acrolein showed intense immunoreactions in liver section of untreated diabetic mice and faint immunoreactions in treated diabetic mice with biotin as evidence to oxidative stress reduction. PMID:26981014

Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration.

PubMed

Tamrazi, Benita; Nguyen, Binh; Liu, Chia-Shang J; Azen, Colleen G; Nelson, Mary B; Dhall, Girish; Nelson, Marvin D

2018-05-01

Purpose To determine whether whole-brain irradiation, chemotherapy, and primary brain pathologic conditions affect magnetic resonance (MR) imaging signal changes in pediatric patients independent of the administration of gadolinium-based contrast agents (GBCAs). Materials and Methods This institutional review board-approved, HIPAA-compliant study included 144 pediatric patients who underwent intravenous GBCA-enhanced MR imaging examinations (55 patients with primary brain tumors and whole-brain irradiation, 19 with primary brain tumors and chemotherapy only, 52 with primary brain tumors without any treatment, and 18 with neuroblastoma without brain metastatic disease). The signal intensities (SIs) in the globus pallidus (GP), thalamus (T), dentate nucleus (DN), and pons (P) were measured on unenhanced T1-weighted images. GP:T and DN:P SI ratios were compared between groups by using the analysis of variance and were analyzed relative to group, total cumulative number of doses of GBCA, age, and sex by using multivariable linear models. Results DN:P ratio for the radiation therapy group was greater than that for the other groups except for the group of brain tumors treated with chemotherapy (P < .05). The number of GBCA doses was correlated with the DN:P ratio for the nontreated brain tumor group (P < .0001). The radiation therapy-treated brain tumor group demonstrated higher DN:P ratios than the nontreated brain tumor group for number of doses less than or equal to 10 (P < .0001), whereas ratios in the nontreated brain tumor group were higher than those in the radiation therapy-treated brain tumor group for doses greater than 20 (P = .05). The GP:T ratios for the brain tumor groups were greater than that for the neuroblastoma group (P = .01). Conclusion Changes in SI of the DN and GP that are independent of the administration of GBCA occur in patients with brain tumors undergoing brain irradiation, as well as in patients with untreated primary brain tumors. © RSNA, 2017.

Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

PubMed

Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

1999-03-17

Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

Brief Report: The Euro-Lupus Low-Dose Intravenous Cyclophosphamide Regimen Does Not Impact the Ovarian Reserve, as Measured by Serum Levels of Anti-Müllerian Hormone.

PubMed

Tamirou, Farah; Husson, Séverine Nieuwland; Gruson, Damien; Debiève, Frédéric; Lauwerys, Bernard R; Houssiau, Frédéric A

2017-06-01

The Euro-Lupus regimen of low-dose intravenous cyclophosphamide (IV CYC) (cumulative dose of 3 gm) was developed to reduce gonadal toxicity. To address the possibility of a marginal effect on the ovarian reserve, we measured serum titers of anti-Müllerian hormone (AMH) in patients with systemic lupus erythematosus (SLE) treated with the Euro-Lupus regimen and compared them with those measured in patients who were treated with higher doses of IV CYC or were never treated with IV CYC. Serum AMH levels were measured by enzyme-linked immunosorbent assay in a cohort of 155 premenopausal SLE patients; 30 of these patients had been treated with the Euro-Lupus regimen, and 24 had received higher doses of IV CYC. None had received oral CYC. AMH levels were age-adjusted using a slope computed from levels measured across the group of SLE patients who had not been treated with IV CYC. Demographic and clinical data were collected. Serum titers of AMH measured in SLE patients treated with the Euro-Lupus IV CYC regimen (median dose 1.46 ng/ml) did not differ from those measured in patients never treated with the cytotoxic drug (median 1.85 ng/ml). As expected, patients given >6 gm of IV CYC had significantly lower serum titers of AMH (median 0.83 ng/ml) compared with those never treated with IV CYC (P = 0.047). Median serum AMH titers did not change before (1.24 ng/ml) and after (2.50 ng/ml) treatment with the Euro-Lupus IV CYC regimen in the subset of patients for whom paired samples could be tested (P = 0.43). The Euro-Lupus regimen of low-dose IV CYC does not impact the ovarian reserve of SLE patients and can therefore be proposed as treatment in patients seeking to become pregnant. © 2017, American College of Rheumatology.

Quantifying the impact of immediate reconstruction in postmastectomy radiation: a large, dose-volume histogram-based analysis.

PubMed

Ohri, Nisha; Cordeiro, Peter G; Keam, Jennifer; Ballangrud, Ase; Shi, Weiji; Zhang, Zhigang; Nerbun, Claire T; Woch, Katherine M; Stein, Nicholas F; Zhou, Ying; McCormick, Beryl; Powell, Simon N; Ho, Alice Y

2012-10-01

To assess the impact of immediate breast reconstruction on postmastectomy radiation (PMRT) using dose-volume histogram (DVH) data. Two hundred forty-seven women underwent PMRT at our center, 196 with implant reconstruction and 51 without reconstruction. Patients with reconstruction were treated with tangential photons, and patients without reconstruction were treated with en-face electron fields and customized bolus. Twenty percent of patients received internal mammary node (IMN) treatment. The DVH data were compared between groups. Ipsilateral lung parameters included V20 (% volume receiving 20 Gy), V40 (% volume receiving 40 Gy), mean dose, and maximum dose. Heart parameters included V25 (% volume receiving 25 Gy), mean dose, and maximum dose. IMN coverage was assessed when applicable. Chest wall coverage was assessed in patients with reconstruction. Propensity-matched analysis adjusted for potential confounders of laterality and IMN treatment. Reconstruction was associated with lower lung V20, mean dose, and maximum dose compared with no reconstruction (all P<.0001). These associations persisted on propensity-matched analysis (all P<.0001). Heart doses were similar between groups (P=NS). Ninety percent of patients with reconstruction had excellent chest wall coverage (D95 >98%). IMN coverage was superior in patients with reconstruction (D95 >92.0 vs 75.7%, P<.001). IMN treatment significantly increased lung and heart parameters in patients with reconstruction (all P<.05) but minimally affected those without reconstruction (all P>.05). Among IMN-treated patients, only lower lung V20 in those without reconstruction persisted (P=.022), and mean and maximum heart doses were higher than in patients without reconstruction (P=.006, P=.015, respectively). Implant reconstruction does not compromise the technical quality of PMRT when the IMNs are untreated. Treatment technique, not reconstruction, is the primary determinant of target coverage and normal tissue doses. Published by Elsevier Inc.

Effects of pyrophosphate delivery in a peritoneal dialysis solution on bone tissue of apolipoprotein-E knockout mice with chronic kidney disease.

PubMed

Barreto, Fellype C; de Oliveira, Rodrigo B; Benchitrit, Joyce; Louvet, Loïc; Rezg, Raja; Poirot, Sabrina; Jorgetti, Vanda; Drüeke, Tilman B; Riser, Bruce L; Massy, Ziad A

2014-11-01

Vascular calcification (VC) is a risk factor for cardiovascular mortality in the setting of chronic kidney disease (CKD). Pyrophosphate (PPi), an endogenous molecule that inhibits hydroxyapatite crystal formation, has been shown to prevent the development of VC in animal models of CKD. However, the possibility of harmful effects of exogenous administration of PPi on bone requires further investigation. To this end, we examined by histomorphometry the bone of CKD mice after intraperitoneal PPi administration. After CKD creation or sham surgery, 10-week-old female apolipoprotein-E knockout (apoE(-/-)) mice were randomized to one non-CKD group or 4 CKD groups (n = 10-35/group) treated with placebo or three distinct doses of PPi, and fed with standard diet. Eight weeks later, the animals were killed. Serum and femurs were sampled. Femurs were processed for bone histomorphometry. Placebo-treated CKD mice had significantly higher values of osteoid volume, osteoid surface and bone formation rate than sham-placebo mice with normal renal function. Slightly higher osteoid values were observed in CKD mice in response to very low PPi dose (OV/BV, O.Th and ObS/BS) and, for one parameter measured, to high PPi dose (O.Th), compared to placebo-treated CKD mice. Treatment with PPi did not modify any other structural parameters. Mineral apposition rates, and other parameters of bone formation and resorption were not significantly different among the treated animal groups or control CKD placebo group. In conclusion, PPi does not appear to be deleterious to bone tissue in apoE(-/-) mice with CKD, although a possible stimulatory PPi effect on osteoid formation may be worth further investigation.

Excess aldosterone-induced changes in insulin signaling molecules and glucose oxidation in gastrocnemius muscle of adult male rat.

PubMed

Selvaraj, Jayaraman; Sathish, Sampath; Mayilvanan, Chinnaiyan; Balasubramanian, Karundevi

2013-01-01

Emerging evidences demonstrate that excess aldosterone and insulin interact at target tissues. It has been shown that increased levels of aldosterone contribute to the development of insulin resistance and thus act as a risk factor for the development of type-2 diabetes mellitus. However, the molecular mechanisms involved in this scenario are yet to be identified. This study was designed to assess the dose-dependent effects of aldosterone on insulin signal transduction and glucose oxidation in the skeletal muscle (gastrocnemius) of adult male rat. Healthy adult male albino rats of Wistar strain (Rattus norvegicus) weighing 180-200 g were used in this study. Rats were divided into four groups. Group I: control (treated with 1 % ethanol only), group II: aldosterone treated (10 μg /kg body weight, twice daily for 15 days), group III: aldosterone treated (20 μg /kg body weight, twice daily for 15 days), and group IV: aldosterone treated (40 μg/kg body weight, twice daily for 15 days). Excess aldosterone caused glucose intolerance in a dose-dependent manner. Serum insulin and aldosterone were significantly increased, whereas serum testosterone was decreased. Aldosterone treatment impaired the rate of glucose uptake, oxidation, and insulin signal transduction in the gastrocnemius muscle through defective expression of IR, IRS-1, Akt, AS160, and GLUT4 genes. Phosphorylation of IRS-1, β-arrestin-2, and Akt was also reduced in a dose-dependent manner. Excess aldosterone results in glucose intolerance as a result of impaired insulin signal transduction leading to decreased glucose uptake and oxidation in skeletal muscle. In addition to this, it is inferred that excess aldosterone may act as one of the causative factors for the onset of insulin resistance and thus increased incidence of type-2 diabetes.

[Nephro-protective effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats].

PubMed

Kuang, Qiao-Ting; Zhao, Jing-Jing; Ye, Chun-Ling; Wang, Jing-Ru; Ye, Kai-He; Zhang, Xiao-Qi; Wang, Ying; Ye, Wen-Cai

2012-01-01

To investigate the nephro-protective effects of total triterpenoids from Psidium guajava leaves (TTPGL) on type 2 diabetic rats. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) and a high-fat diet. Diabetic rats were divided into five groups: diabetic model control, low-dose TTPGL-treated (60 mg/kg, L-TTPGL), medium-dose TTPGL-treated (120 mg/kg, M-TTPGL), high-dose TTPGL-treated (240 mg/kg, H-TTPGL) and rosiglitazone-treated (3 mg/kg, RSG). The rats received daily treatment for six weeks. At the end of the period,the levels of fasting blood glucose (FPG), fasting insulin (FINS), creatinine (Cr) and blood urea nitrogen (BUN) in serum were measured. Kidneys for histopathological evaluation were stained with Hematoxylin and Eosin (HE). Compared with normal control group, the level of FPG was increased, the insulin and insulin sensitivity index were decreased in the model group; The levels of BUN and Cr were increased with histopathological changes related to diabetic nephropathy in the kidney, which were the glomerular endothelium and mesangial cell proliferation, capillary narrowed, the base-membrane incrassation, glomerular swelling, cysts narrowed and tubules edema. Compared with the model group, the levels of FPG were decreased, serum insulin and insulin sensitivity index were increased significantly in M-TTPGL and H-TTPGL groups (P<0.01 or P<0.05); The levels of BUN and Cr were decreased significantly (P<0.01 or P<0.05) and the renal structural damages were improved significantly. TTPGL could decrease the level of blood glucose of diabetic rat effectively, increase the insulin sensitivity index and protect renal lesions in diabetic rats.

Half dose sugammadex combined with neostigmine is non-inferior to full dose sugammadex for reversal of rocuronium-induced deep neuromuscular blockade: a cost-saving strategy.

PubMed

Aouad, Marie T; Alfahel, Waseem S; Kaddoum, Roland N; Siddik-Sayyid, Sahar M

2017-04-11

Sugammadex reverses the effect of rocuronium more rapidly and effectively than neostigmine, at all levels of neuromuscular blockade (NMB). However, its cost is prohibitive. The combination of half dose sugammadex with neostigmine would be non-inferior to full dose sugammadex for the reversal of deep NMB. This approach would reduce the cost of sugammadex while preserving its efficacy. Patients were randomly allocated to receive sugammadex 4 mg/kg (Group S) or sugammadex 2 mg/kg with neostigmine 50 μg/kg and glycopyrrolate 10 μg/kg (Group NS) for reversal of rocuronium deep NMB. The primary outcome was the percentage of patients who recovered to 90% Train of Four (TOF) ratio within 5 min. The non-inferiority margin was set at 10%. Twenty eight patients were enrolled in each group. The number of patients who reached 90% TOF ratio within 5 min was 27 out of 28 (96%) in group S versus 25 out of 28 (89%) in group NS by intention-to-treat (difference: 7%, 95% CI of the difference: -9% to 24%). The number of patients who reached 90% TOF ratio within 5 min was 26 out of 26 (100%) in group S versus 23 out of 25 (92%) in group NS by per-protocol (difference: 8%, 95% CI of the difference: -6% to 25%). Sugammadex 2 mg/kg with neostigmine 50 μg/kg was at worst 9% and 6% less effective than sugammadex 4 mg/kg by intention-to-treat and by per-protocol analysis respectively. Hence, the combination is non-inferior to the recommended dose of sugammadex. Clinicaltrials.gov NCT 02375217 , registered on February 11, 2015.

Effect of lipoprotein-associated phospholipase A2 inhibitor on insulin resistance in streptozotocin-induced diabetic pregnant rats.

PubMed

Wang, Guo-Hua; Jin, Jun; Sun, Li-Zhou

2018-06-21

This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.

Tapering dose of inhaled budesonide in subjects with mild-to-moderate persistent asthma treated with montelukast: a 16-week single-blind randomized study.

PubMed

Riccioni, Graziano; Vecchia, Rosanna Della; Castronuovo, Marco; Di Ilio, Carmine; D'Orazio, Nicolantonio

2005-01-01

Pharmacological therapy with inhaled steroids (IS) is currently considered the gold-standard of treatment for mild-persistent asthma. Leukotriene receptor antagonist drugs (LTRAs) play an important role associated with IS, allowing dose tapering and maintaining control of asthma symptoms. The aim of this study was to determine the effectiveness of montelukast (MON) to allow tapering of the inhaled dose of budesonide (BUD) in patients with mild-moderate persistent asthma. This 16-wk single-blind randomized study included 40 asthmatic patients divided in 2 treatment groups. After a run-in period (4 wk), in which all patients inhaled 400 microg of BUD twice daily (bid), group A (20 patients) received MON (oral, 10 mg/day) combined with inhaled BUD (400 microg/bid), while group B (20 patients) was treated with BUD for the whole period of the study. In both groups, at every 4 wk the dose of BUD was halved. After 12 wk of treatment the mean value of forced expiratory volume during the first sec (FEV1, as % of predicted value) was significantly greater in group A compared with group B (94 +/- 7.5 vs 83.1 +/- 6.9; p<0.005). The mean values of peak expiratory flow (PEF), the percentages of asthmatic exacerbations, and the use of beta2-short-acting agonist (SABA) were similar in the 2 groups at 4, 8, and 12 wk. In conclusion, in patients with mild-moderate persistent asthma, MON therapy is useful in tapering the dose of IS in order to reduce its side effects and to maintain the clinical stability of the disease.

[Antiurolithiasic effect of a plant mixture of Herniaria glabra, Agropyron repens, Equisetum arvense and Sambucus nigra (Herbensurina®) in the prevention of experimentally induced nephrolithiasis in rats].

PubMed

Crescenti, Anna; Puiggròs, Francesc; Colomé, Arnau; Poch, Josep Antón; Caimari, Antoni; Bas, Josep Maria; Boqué, Noemí; Arola, Lluís

2015-12-01

To determine the effect of a botanical formulation of Herniaria glabra, Agropyron repens, Equisetum arvense, and Sambucus nigra as a preventive agent in an experimentally induced nefrolithiasis model in rats. Six groups of six Wistar male rats each were induced for nefrolithiasis by treatment with 0.75% ethylene glycol (EG) and 1% ammonium chloride for three days and then EG only for 15 days. One group was treated with placebo (control group) and the other groups (treated groups) were treated with 30 mg/Kg, 60 mg/Kg, 125 mg/Kg, 250 mg/Kg and 500 mg/Kg of the plant extract formulation (PEF). 24-h urine and water samples were collected one day before EG administration and at 7, 13 and 18 days to determine diuresis, crystalluria and urine biochemistry. The kidneys were removed for histological analysis. The phytochemical characterization of PEF and each of its component plant extracts was performed using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Animals treated with 125 mg/Kg of the PEF had statistically significantly lower calcium oxalate crystals deposits content compared to the control group. All PEF doses statistically significantly decreased the number of microcalcifications compared to the control group. Furthermore, the number of kidneys affected by subcapsular fibrosis was statistically significantly higher in control group than in treated groups with the PEF. The diuresis of the 125 mg/Kg and 500 mg/Kg PEF-treated groups was statistically significantly higher than that of the control group. A phytochemical analysis demonstrated the presence of flavonoids, dicarboxylic acids and saponins. Treatment with PEF prevents deposits of calcium oxalate crystals formation and of microcalcifications in the kidney, and reduces the risk of fibrosis subcapsular. 125 mg/Kg of PEF is the dose that has a greater effect on the studied parameters.

Effects of D-004, a lipid extract of the fruit of the Cuban royal palm (Roystonea regia) or the lipidosterolic extract of saw palmetto (Serenoa repens) on the sexual activity in male rats: A controlled, experimental study.

PubMed

Fernández, Lilia C; Mas, Rosa; Fernández, Julio; Mendoza, Sarahí; Gámez, Rafael; Pardo, Balia

2008-02-01

The etiology of benign prostatic hyperplasia (BPH) is not completely understood, but hormonal changes in aging men seem to be pivotal. Dihydrotestosterone, a potent, active metabolite of testosterone, is formed by the enzymatic action of prostate 5α-reductase and causes cell growth and hyperplasia. Consistent with this action, male sexual dysfunction has been clinically documented to be among the drug-related adverse events associated with 5α-reductase inhibitors. The lipidosterolic extract of saw palmetto (LESP) fruit (Serenoa repens) has been used to treat BPH. D-004, a lipid extract of Roystonea regia Royal palm fruit, has been found to prevent prostatic hyperplasia induced by testoste-rone in rodents and to competitively inhibit prostate 5α-reductase activity in vitro. The purpose of this study was to assess the effects of D-004 and LESP, administered as single or repeated doses, on the sexual activity in male rats. This controlled, experimental study was conducted at the Pharmacology Department, Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba. Adult male Wistar rats weighing 250 to 300 g were randomized into 5 groups: 2 groups treated orally with D-004 (400 and 800 mg/kg); 2 groups treated orally with LESP (400 and 800 mg/kg); and 1 control group orally administered a water vehicle. Sexual activity behavior (the number of mounts and intromissions, mount latency, and intromission latency) was assessed during 2 observation periods: 90 minutes after the initial dose and at the end of the 30-day treatment. Latency was defined as time elapsed between the first mount and intromission. A total of 50 rats (mean [SD] age, 10 [3] weeks; mean [SD] weight, 295 [10] g) were included in the experiment. There were no significant difterences in the mean number of mounts, intromissions, mount latency, or intromission latency in the groups treated with single or repeated doses of D-004 or LESP (400 and 800 mg/kg) compared with the controls. There was also no between-group difterence in mating behavior among the active treatment groups. All rats survived up to study completion, with normal behavior (weight gain, food intake, daily observations, without any sign of toxicity). There were no observable adverse events during the study. D-004 and LESP administered as a single dose or repeated doses for 30 days did not significantly affect male rat sexual activity behavior compared with a vehicle control group.

Intravaginal high-dose-rate brachytherapy for stage I endometrial cancer: A randomized study of two dose-per-fraction levels

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

Sorbe, Bengt; Straumits, Andris; Karlsson, Leif

2005-08-01

Purpose To compare two different fractionation schedules for postoperative vaginal high-dose-rate (HDR) irradiation in endometrial carcinomas. Methods and Materials In a complete geographic series of 290 low-risk endometrial carcinomas, the efficacy and side effects of two different fractionation schedules for postoperative vaginal irradiation were evaluated. The patients were treated during the years 1989-2003. The tumors were in International Federation of Gynecology and Obstetrics Stages IA-IB and Grades 1-2. The HDR MicroSelectron afterloading equipment (iridium-192) was used. Perspex vaginal applicators with diameters of 20-30 mm were used, and the dose was specified at 5 mm from the surface of the applicator.more » Six fractions were given, and the overall treatment time was 8 days. The size of the dose per fraction was randomly set to 2.5 Gy (total dose of 15.0 Gy) or 5.0 Gy (total dose of 30.0 Gy). One hundred forty-four patients were treated with the 2.5-Gy fraction and 146 patients with the 5.0-Gy fraction. Results The overall locoregional recurrence rate of the complete series was 1.4% and the rate of vaginal recurrences 0.7%. There was no difference between the two randomized groups. The vaginal shortening measured by colpometry was not significant (p = 0.159) in the 2.5-Gy group (mean, 0.3 cm) but was highly significant (p < 0.000001) in the 5.0-Gy group (mean 2.1 cm) after 5 years. Mucosal atrophy and bleedings were significantly more frequent in the 5.0-Gy group. Symptoms noted in the 2.5-Gy group were not different from what could be expected in a normal group of postmenopausal women. Conclusion The fractionation schedule recommended for postoperative vaginal irradiation in low-risk endometrial carcinoma is six fractions of 2.5 Gy when the HDR technique is used.« less

40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... employed. (2) Number of animals. Ten hens should be used for each treatment and control group. (3) Control group—(i) General. A concurrent control group should be used. This group should be treated in a manner... control group(s). The highest dose level should result in toxic effects, preferably delayed neurotoxicity...

40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... employed. (2) Number of animals. Ten hens should be used for each treatment and control group. (3) Control group—(i) General. A concurrent control group should be used. This group should be treated in a manner... control group(s). The highest dose level should result in toxic effects, preferably delayed neurotoxicity...

40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... employed. (2) Number of animals. Ten hens should be used for each treatment and control group. (3) Control group—(i) General. A concurrent control group should be used. This group should be treated in a manner... control group(s). The highest dose level should result in toxic effects, preferably delayed neurotoxicity...

40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... employed. (2) Number of animals. Ten hens should be used for each treatment and control group. (3) Control group—(i) General. A concurrent control group should be used. This group should be treated in a manner... control group(s). The highest dose level should result in toxic effects, preferably delayed neurotoxicity...

40 CFR 798.6560 - Subchronic delayed neuro-toxicity of organophosphorus substances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... employed. (2) Number of animals. Ten hens should be used for each treatment and control group. (3) Control group—(i) General. A concurrent control group should be used. This group should be treated in a manner... control group(s). The highest dose level should result in toxic effects, preferably delayed neurotoxicity...

Randomized dose-ranging study of the safety and efficacy of WR 238605 (Tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand.

PubMed

Walsh, D S; Looareesuwan, S; Wilairatana, P; Heppner, D G; Tang, D B; Brewer, T G; Chokejindachai, W; Viriyavejakul, P; Kyle, D E; Milhous, W K; Schuster, B G; Horton, J; Braitman, D J; Brueckner, R P

1999-10-01

WR 238605 is an 8-aminoquinoline developed for the radical cure of Plasmodium vivax. Forty-four P. vivax-infected patients were randomly assigned to 1 of 4 treatment regimens: 3 groups received a blood schizonticidal dose of chloroquine followed by WR 238605: group A (n=15) received 300 mg daily for 7 days; group B (n=11), 500 mg daily for 3 days, repeated 1 week after the initial dose; group C (n=9), 1 dose of 500 mg. A fourth group (D; n=9) received chloroquine only. Among patients who completed 2-6 months of follow-up (n=23), there was 1 relapse in group B (day 120) and 1 in group C (day 112). Among patients treated with chloroquine only, there were 4 relapses (days 40, 43, 49, and 84). WR 238605 was safe, well tolerated, and effective in preventing P. vivax relapse.

Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice.

PubMed

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu

2015-01-01

The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory. Mice were divided randomly into seven groups. Intra-peritoneal treatment of normal saline (10 ml/kg), caffeine (10 mg/kg), duloxetine (10 mg/kg), bupropion alone (10 mg/kg), caffeine + duloxetine (5 mg/kg, each), caffeine + bupropion (5 mg/kg, each), and bupropion + duloxetine (5 mg/kg, each) were given to groups I-VII, respectively. Elevated plus maze was used to evaluate transfer latency (TL) and Morris water maze was used to estimate the time spent in target quadrant. Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded. Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies.

The evaluation of different treatment protocols for trauma-induced lung injury in rats

PubMed Central

Güzel, Aygül; Katı, Celal; Duran, Latif; Alaçam, Hasan; Gacar, Ayhan; Güvenç, Tolga; Murat, Naci; Şişman, Bülent

2014-01-01

Background Lung contusion is an important factor that affects mortality and morbidity of lung injury after blunt chest trauma (BCT). The present study aims to evaluate the effectiveness of different treatment regimens on BCT-induced lung injury. Methods A total of 35 Sprague Dawley rats were divided into five experimental groups (n=7): sham, control; BCT; BCT + MP, BCT group treated with methylprednisolone (MP; 30 mg/kg on first day and 3 mg/kg/d on the following days); BCT + Q, BCT group treated with quercetin (Q; 50 mg/kg/d for seven days); and BCT + MP + Q, BCT group treated with the same doses of MP and Q. Serum Clara Cell Protein-16 (CC-16), thiobarbituric acid reactive substances (TBARS), and superoxide dismutase (SOD) levels were analyzed to determine histopathological changes in the lung tissues. Results Elevated serum CC-16 and TBARS levels and reduced serum SOD levels were found in the BCT group compared to the Sham group. There was a significant change in the serum CC-16 levels in the BCT + MP group compared to the Sham group. Serum TBARS levels were significantly lower in the BCT + MP and BCT + Q group compared to the BCT group. The combined therapy regimen yielded significantly decreased CC-16 levels and increased serum SOD levels compared to the individual treatment groups. Serum TBARS levels did not significantly differ between the BCT + MP + Q group and the other treatment groups. Compared to the BCT + MP + Q group, the BCT + MP group showed significantly lower alveolar edema (AED) and alveolar exudate (AEX) scores, while the BCT + Q group showed significantly lower peribronchial inflammatory cell infiltration (PICI) and AED scores. Conclusions The combined usage of quercetin and low dose MP treatment after initial high dose MP at the early stage of lung injury after BCT is more effective. PMID:24605218

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats

PubMed Central

Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

2018-01-01

Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke. PMID:29399121

Protective effects of beef decoction rich in carnosine on cerebral ischemia injury by permanent middle cerebral artery occlusion in rats.

PubMed

Wang, Ai-Hong; Ma, Qian; Wang, Xin; Xu, Gui-Hua

2018-02-01

Inflammation has a role in the cerebral injury induced by ischemia and the present study aimed to determine the mechanism of the protective effect of beef decoction (BD) with carnosine against it. A rat model of permanent middle cerebral artery occlusion was established using a suture method in the vehicle and each of the BD groups. In experiment 1, 72 Sprague Dawley (SD) rats were randomly divided into three groups: Sham, vehicle and BD-treated group. Rats in the BD group were given 600 mg/kg BD by oral gavage for 1, 3 and 7 days. The sham and vehicle group rats received an equivalent amount of normal saline. In experiment 2, 60 SD rats were randomly divided into six groups: Sham-operated I, sham-operated II, vehicle, low-dose BD, medium-dose BD and high-dose BD group. Rats in the low-, medium- and high-dose BD groups were given BD at the dose of 200, 400 and 600 mg/kg, respectively, by oral gavage for 7 days. Rats in the sham-operated II group were given 600 mg/kg BD. Rats in the sham-operated I group and vehicle group were given the same volume of normal saline by oral gavage. The body weight, neurological deficits and infarct volume were recorded at 1, 3 and 7 days after the operation. Furthermore, the effect of different doses of BD on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in peripheral blood was measured at 7 days. BD-treated rats showed less neurological deficits and a smaller infarct volume at 7 days. BD at 400 and 600 mg/kg significantly decreased the infarct volume in rats. At 600 mg/kg BD, a decline in IL-6, TNF-α, IFN-γ and an increase in IL-4 expression was observed in the BD groups, while no difference in body weight and neurological dysfunction was detected. In conclusion, BD is a neuroprotective agent that may be used as a supplement treatment of ischemic stroke.

Incidence of hypothyroidism following small doses of /sup 131/I in the treatment of Graves' disease

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

McCullagh, F.P.; Jelden, G.L.; Rodriguez-Antunez, A.

1976-09-01

In a group of 147 patients treated with /sup 131/I in doses of 3.0 millicuries or less for Graves' disease, the incidence of hypothyroidism was calculated 10 to 17 years after treatment. This paper emphasizes the frequency of hypothyroidism after treatment with /sup 131/I in small doses, if sufficient time lapse is considered.

Vitamin K3 increased BMD at 1 and 2 months post-surgery and the maximum stress of the middle femur in the rat.

PubMed

Hong, You-jia; Liu, Sheng; Jiang, Ning-yi; Jiang, Sen; Liang, Jiu-gen

2015-02-01

The therapeutic effects of vitamin K3 (VK3) on osteoporosis are still unknown. In this study, we hypothesized that VK3 possesses therapeutic effects on osteoporosis; to verify this hypothesis, the ovariectomized rat was used as an osteoporosis model. Fifty-six Sprague-Dawley female rats aged 8 to 9 months were randomly assigned to 4 groups: sham surgery, ovariectomy with saline, ovariectomy with low-dose VK3, and ovariectomy with high-dose VK3. Intramuscular injection of VK3 was performed every other day beginning 1 month postoperatively. The therapeutic effects of VK3 on osteoporosis were evaluated by measurement of bone mineral density (BMD), bone biochemical markers, biomechanical properties, and bone morphometric parameters. The overall average BMD in VK3-treated groups increased to a level between those of the ovariectomy group and the sham surgery group. The procollagen I N-terminal peptide level peaked at 2 months after surgery in all groups except in the group that had undergone ovariectomy with low-dose VK3. The tartrate-resistant acid phosphatase 5b level increased more slowly at 4 months after surgery than at 2 months after surgery in the VK3-treated groups. The ovariectomy with high-dose VK3 group had the highest maximum stress of the middle femur of all groups. With VK3 treatment, the trabecular bone area percentage increased. All morphometric indicators for the middle tibia in the VK3-treated groups reached the levels found in the sham surgery group. In summary, VK3 therapy increased BMD at 1 and 2 months postsurgery and the maximum stress of the middle femur. In addition, VK3 therapy slowed the increase in bone turnover in ovariectomized rats. Furthermore, VK3 can improve morphometric indicators for the middle tibia. Our preliminary study indicates that VK3 has a potential therapeutic effect on osteoporosis and is worthy of further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

2,3-Butanedione monoxime facilitates successful resuscitation in a dose-dependent fashion in a pig model of cardiac arrest.

PubMed

Lee, Byung Kook; Kim, Mu Jin; Jeung, Kyung Woon; Choi, Sung Soo; Park, Sang Wook; Yun, Seong Woo; Lee, Sung Min; Lee, Dong Hun; Min, Yong Il

2016-06-01

Ischemic contracture compromises the hemodynamic effectiveness of cardiopulmonary resuscitation (CPR) and resuscitability from cardiac arrest. In a pig model of cardiac arrest, 2,3-butanedione monoxime (BDM) attenuated ischemic contracture. We investigated the effects of different doses of BDM to determine whether increasing the dose of BDM could improve the hemodynamic effectiveness of CPR further, thus ultimately improving resuscitability. After 16minutes of untreated ventricular fibrillation and 8minutes of basic life support, 36 pigs were divided randomly into 3 groups that received 50mg/kg (low-dose group) of BDM, 100mg/kg (high-dose group) of BDM, or an equivalent volume of saline (control group) during advanced cardiovascular life support. During advanced cardiovascular life support, the control group showed an increase in left ventricular (LV) wall thickness and a decrease in LV chamber area. In contrast, the BDM-treated groups showed a decrease in the LV wall thickness and an increase in the LV chamber area in a dose-dependent fashion. Mixed-model analyses of the LV wall thickness and LV chamber area revealed significant group effects and group-time interactions. Central venous oxygen saturation at 3minutes after the drug administration was 21.6% (18.4-31.9), 39.2% (28.8-53.7), and 54.0% (47.5-69.4) in the control, low-dose, and high-dose groups, respectively (P<.001). Sustained restoration of spontaneous circulation was attained in 7 (58.3%), 10 (83.3%), and 12 animals (100%) in the control, low-dose, and high-dose groups, respectively (P=.046). 2,3-Butanedione monoxime administered during CPR attenuated ischemic contracture and improved the resuscitability in a dose-dependent fashion. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic lead poisoning in horses

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

Dollahite, J.W.; Younger, R.L.; Crookshank, H.R.

1978-06-01

Lead Acetate was fed to 4 groups of 2 horses each to study chronic lead intoxication. A 5th group of 3 horses was maintained as controls. The lead was fed in capsules, with the minimum dosage of 6.25 mg/kg/day of lead as lead acetate (group I). The dose was increased from group I through group IV in an approximate geometric series, with each group being given about 125% of the dose given the previous group. These doses were given for 105 days, a period designated as phase 1. Since clinical signs were not observed after 105 days, the doses weremore » increased and fed for an additional 190 days (days 106 to 295). This period was designated phase 2. The smallest daily dose in phase 2 was set at about 125% of the largest daily dose in phase 1. The doses in each group was increased by about 125% of that of the previous group, as was done in phase 1. Seven horses died or were euthanatized after 18 to 190 days of phase 2 (123 to 295 days after the 1st dose). One horse in group I did not develop any clinical signs of intoxication. Dose-related responses were unnoticed with doses larger than 15.3 mg/kg/day. All horses given lead had increased blood lead and serum iron concentrations. During phase 2, the hematocrit and hemoglobin contents were depressed. The lead concentration in kidney, liver, spleen, pancreas, brain, bone, and heart was increased in the treated horses. The dose level required to produce lead intoxication was greater than that reported for cattle and that estimated in epizootiologic studies of horses.« less

Comparative evaluation of hepatoprotective activity of carotenoids of microalgae.

PubMed

Murthy, K N Chidambara; Rajesha, J; Swamy, M Mahadeva; Ravishankar, G A

2005-01-01

The present study deals with evaluation of the hepatotoprotective activity of carotenoids from two well-known microalgae, Spirulina platensis and Dunaliella salina. Carotenoids were extracted in hexane:isopropyl alcohol (1:1 vol/vol) and fed orally in olive oil to Wistar albino rats at a dose of 100 microg/kg of body weight/day (in terms of carotenoids). The degree of hepatoprotection was measured by estimation of biochemical parameters like serum transaminases [serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT)], serum alkaline phosphatase, total albumin, and total protein. The results were compared with those for a control group, a CCl4-induced hepatic damage group, and a group treated with synthetic beta-carotene (all-trans) at the same dose. The protein content of the CCl4-treated group, which received normal diet and a dose of toxin, showed a significant decrease, i.e., 3.92 mg/mL, whereas the protein levels were higher, i.e., 6.96 and 6.32 mg/mL, in the case of the Dunaliella and Spirulina, respectively, carotenoid-treated groups. The CCl4-treated group shown higher activity of transaminases (128.68 units/mL SGPT and 171.52 units/mL SGOT). However, the activity of SGPT was 62.83 units/mL for Dunaliella and 76.83 units/mL for Spirulina, i.e., carotenoids of Dunaliella showed a higher degree of protection. For serum alkaline phosphatase, the standard beta-carotene value was 81.52 units/mL, compared with 84.46 units/mL for the CCl4-treated group; however, natural algal carotenoids yielded 38.45 units/mL (D. salina) and 44.73 units/mL (Spirulina). The total albumin value diminished with CCl4 treatment (2.46 mg/mL); the effect was highest for Dunaliella, followed by the Spirulina carotenoid-treated group. The results clearly indicate that carotenoids from Dunaliella possess better hepatoprotection compared with those from Spirulina. High-performance liquid chromatography of the carotenoids indicated that Spirulina contains only beta-carotene and Dunaliella contains other carotenoids and xanthophyll. The increase in protection with Dunaliella indicates that mixed carotenoids exhibit better biological activity than beta-carotene alone. The results of this study indicate that carotenoids obtained from an algal source have a higher antihepatotoxic effect, compared with synthetic beta-carotene and with beta-carotene alone from a natural source.

Repeated-Doses Toxicity Study of the Essential Oil of Hyptis martiusii Benth. (Lamiaceae) in Swiss Mice

PubMed Central

Freire Rocha Caldas, Germana; Araújo, Alice Valença; Albuquerque, Giwellington Silva; Silva-Neto, Jacinto da Costa; Costa-Silva, João Henrique; de Menezes, Irwin Rose Alencar; Leite, Ana Cristina Lima; da Costa, José Galberto Martins; Wanderley, Almir Gonçalves

2013-01-01

Hyptis martiusii Benth. (Lamiaceae) is found in abundance in Northeastern Brazil where it is used in traditional medicine to treat gastric disorders. Since there are no studies reporting the toxicity and safety profile of this species, we investigated repeated-doses toxicity of the essential oil of Hyptis martiusii (EOHM). Swiss mice of both sexes were orally treated with EOHM (100 and 500 mg/kg) for 30 days, and biochemical, hematological, and morphological parameters were determined. No toxicity signs or deaths were recorded during the treatment with EOHM. The body weight gain was not affected, but there was an occasional variation in water and food consumption among mice of both sexes treated with both doses. The hematological and biochemical profiles did not show significant differences except for a decrease in the MCV and an increase in albumin, but these variations are within the limits described for the species. The microscopic analysis showed changes in liver, kidneys, lungs, and spleen; however, these changes do not have clinical relevance since they varied among the groups, including the control group. The results indicate that the treatment of repeated-doses with the essential oil of Hyptis martiusii showed low toxicity in mice. PMID:24151521

Does measuring BHR add to guideline derived clinical measures in determining treatment for patients with persistent asthma?

PubMed

Koenig, Steven M; Murray, John J; Wolfe, James; Andersen, Leslie; Yancey, Steve; Prillaman, Barbara; Stauffer, John; Dorinsky, Paul

2008-05-01

Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management. The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR. After a 2-week run-in period, subjects (> or = 12 years) were randomized to one of three treatment groups. Two groups followed a BHR treatment strategy (based on clinical parameters [lung function, asthma symptoms, and bronchodilator use] and BHR) and were treated with either fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate (FP(BHR) group) (n=156 each). The third group followed a clinical treatment algorithm (based on clinical parameters alone) and were treated with fluticasone propionate (FP(REF) group; n=154). All treatments were administered via Diskus. Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject's derived severity class, which was based on clinical measures of asthma control with or without BHR. The mean total daily inhaled corticosteroids (ICS) dose during the double-blind treatment period was lower, although not statistically significant, in the FSC(BHR) group compared with the FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF) group, the mean total daily ICS dose was higher in the FSC(BHR) group (a difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a difference of 131.2 mcg, p=0.037). This study demonstrated that for most subjects, control of BHR was maintained when treatment was directed toward control of clinical parameters. In addition, there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol.

Does propolis have any effect on non-alcoholic fatty liver disease?

PubMed

Kismet, Kemal; Ozcan, Cigdem; Kuru, Serdar; Gencay Celemli, Omur; Celepli, Pinar; Senes, Mehmet; Guclu, Tuncay; Sorkun, Kadriye; Hucumenoglu, Sema; Besler, Tanju

2017-06-01

The aim of this study was to evaluate the therapeutic effect of propolis on non-alcoholic fatty liver disease (NAFLD) in rats. The rats were randomly divided into 3 groups of 10 as the NAFLD, NAFLD+100 and NAFLD+200 groups. The rats were fed with a fatty diet (25g/kg/day) to provoke NAFLD. Then after the formation of fatty liver, a standard diet (SD) (25g/kg/day) was given to the NAFLD group and the other two groups were fed with SD and 100mg/kg (NAFLD+100 Group) or 200mg/kg propolis (NAFLD+200 Group) for two weeks. At the end of two weeks the animals were sacrificed. Blood and tissue samples were taken for biochemical and histopathological evaluations. The propolis-treated groups had better results in serum lipids (total cholesterol, non-HDL cholesterol, triglyceride), ALT, and ALP values. When compared with the NAFLD group, IL-6 and TNF-α values decreased in the NAFLD+100 and NAFLD+200 groups. The administration of propolis to the rats significantly reduced serum and tissue MDA and GPX values and increased SH in serum when compared with the NAFLD group. No difference was determined between the groups treated with two different doses of propolis in respect of biochemical values. When the mean histological scores of the groups were compared, statistically significant differences were found between the NAFLD group and the propolis-treated groups. No difference was determined between the groups treated with the two different doses of propolis in respect of histopathological results. Propolis had positive effects on histopathological and biochemical parameters of NAFLD and these effects were related to the anti-oxidant and anti-inflammatory effects of propolis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

High dose chemoradiation for unresectable hilar cholangiocarcinomas using intensity modulated external beam radiotherapy: a single tertiary care centre experience

PubMed Central

Mehta, Shaesta; Kalyani, Nikhil; Chaudhari, Suresh; Dharia, Tejas; Shetty, Nitin; Chopra, Supriya; Goel, Mahesh; Kulkarni, Suyash; Shrivastava, Shyam Kishore

2017-01-01

Background We present results of patients diagnosed with unresectable hilar cholangiocarcinomas treated with high dose radiotherapy and concurrent chemotherapy. Methods From Aug 2005 to Dec 2012, 68 consecutive patients were treated. Fifty patients (group 1) presenting to us with obstructive jaundice were planned for endobiliary brachytherapy (EBBT 14 Gy) followed external beam radiotherapy (EBRT 45 Gy). Twenty-two patients (group 2) who had previously undergone biliary drainage underwent EBRT (57 Gy). All patients received injection Gemcitabine 300 mg/m2/weekly along with EBRT. Results Twenty-nine patients in group 1 and 22 patients in group 2 completed the treatment. Twenty-six (55%) patients achieved complete radiological response, 16 (64%) belonging to group 1 and 8 (44%) of group 2 (P=0.05). The median overall survival (MOS) was 17.5 and 16 months for group 1 and 2 respectively (P=0.07). The 1- and 2-year survival was 63%, and 18% for group I and 61% and 22% for group II respectively. The MOS was 5 months and 1 year survival was 14% for patients receiving EBBT only. MOS was significantly better after complete response (P=0.001). Conclusions Intensity modulated radiotherapy (IMRT) modulated high dose radiotherapy used either alone or with brachytherapy demonstrates potential to prolonged overall survival in unresectable hilar cholangiocarcinomas. PMID:28280622

Measurement of radiation exposure in relatives of thyroid cancer patients treated with (131)I.

PubMed

Ramírez-Garzón, Y T; Ávila, O; Medina, L A; Gamboa-deBuen, I; Rodríguez-Laguna, A; Buenfil, A E; Ruíz-Trejo, C; Estrada, E; Brandan, M E

2014-11-01

This work evaluates the radiological risk that patients treated with I for differentiated thyroid cancer could present to relatives and occupationally exposed workers. Recently, the International Atomic Energy Agency issued document K9010241, which recommends that patient discharge from the hospital must be based on the particular status of each patient. This work measures effective dose received by caregivers of patients treated with I at the Instituto Nacional de Cancerología, Mexico City. Thermoluminescent dosimeters were carried during a 15-d period by 40 family caregivers after patient release from hospital. Relatives were classified into two groups, ambulatory and hospitalized, according to the release mode of the patient, and three categories according to the individual patient home and transport facilities. Categories A, B, and C were defined going from most to least adequate concerning public exposure risk. Measurements were performed for 20 family caregivers in each group. The effective dose received by all caregivers participating in this study was found to be less than 5 mSv, the recommended limit per event for caregivers suggested by ICRP 103. In addition, 70 and 90% of ambulatory and hospitalized groups, respectively, received doses lower than 1 mSv. Caregivers belonging to category C, with home situations that are not appropriate for immediate release, received the highest average doses; i.e., 2.2 ± 1.3 and 3.1 ± 1.0 mSv for hospitalized and ambulatory patients, respectively. Results of this work have shown that the proper implementation of radiation protection instructions for relatives and patients can reduce significantly the risk that differentiated thyroid cancer patients treated with I can represent for surrounding individuals. The results also stress the relevance of the patient's particular lifestyle and transport conditions as the prevailing factors related to the dose received by the caregiver. Therefore, the patient's status should be the criterion used to decide his/her release modality. This work provides support to recommend the implementation of the "patient specific release criteria" in accordance with ICRP 94, IAEA Safety Report No. 63, and IAE document K9010241 A for patients treated with radiopharmaceuticals.

Memory-enhancing effect of aspirin is mediated through opioid system modulation in an AlCl3-induced neurotoxicity mouse model

PubMed Central

RIZWAN, SAIMA; IDREES, AYESHA; ASHRAF, MUHAMMAD; AHMED, TOUQEER

2016-01-01

Neurodegenerative disorders such as Alzheimers disease (AD) are multifaceted and there are currently a limited number of therapeutic strategies available to treat them. Aspirin is known to act on multiple therapeutic targets and is a successful anti-inflammatory agent in various tissues. The present study aimed to ascertain the performance of aspirin when employed as a therapeutic agent to treat neurodegeneration on novel targets, including opioid system genes, in an AlCl3-induced neurotoxicity mouse model. The effects of two doses of aspirin (5 and 20 mg/kg aspirin for 12 days) were investigated in an AlCl3-induced neurotoxicity mouse model (150 mg/kg AlCl3 for 12 days). Neurological improvements were assessed through different behavioral tests and the effects of aspirin on opioid system gene expression levels were assessed by reverse transcription-polymerase chain reaction. Both doses resulted in improvements in cognitive behavior. A 5 mg/kg dose of aspirin was revealed to be effective for spatial memory improvement (7.14±0.84 sec), whilst a 20 mg/kg dose was superior for improving extinction learning (7.63±4.04%). Aspirin (5 mg/kg) also significantly improved contextual memory (48.05±10.6%) when compared with the AlCl3-treated group (1.49±0.62%; P<0.001). Aspirin was also observed to significantly decrease δ-opioid receptor expression in the cortex (1.09±0.08 and 1.27±0.08, respectively) at both doses (5 and 20 mg/kg) when compared with the AlCl3-treated group (3.69±1.43; P<0.05). Furthermore, aspirin at 5 mg/kg significantly reduced expression of prodynorphin in the cortex (0.57±0.20) when compared with the AlCl3-treated group (1.95±0.84; P<0.05). Notably, the effect of aspirin was significant in the cortex but not in the hippocampus. In summary, aspirin was effective in ameliorating the AD-like symptoms via the modulation of opioid systems. However, additional studies are required to determine the long term effects of aspirin on such conditions. PMID:27168835

Efficacy of nitazoxanide to treat natural Giardia infections in dogs.

PubMed

Moron-Soto, Mario; Gutierrez, Lilia; Sumano, Héctor; Tapia, Graciela; Alcala-Canto, Yazmin

2017-01-31

Giardia parasites cause gastrointestinal disease in humans, dogs, and many other animals worldwide. The treatment of dogs for giardiasis requires further investigation to ascertain levels of drug efficacy and the possibility of adverse side effects. Nitazoxanide (NTZ) has shown good clinical anti-Giardia activity in humans, yet it has not been evaluated for the treatment of giardiasis in dogs. Thirty-five dogs, naturally infected with Giardia were divided into five groups (n = 7): dogs in group NTZ1, NTZ2, and NTZ3 were treated with a single oral dose of 37.5 mg/kg, 75 mg/kg, and 150 mg/kg, respectively, of NTZ on days 0 and 14. The fourth group was treated with a commercially available regimen that includes a combination of pyrantel, praziquantel, and febantel (FEB) administered orally for three consecutive days. Additionally, an untreated control group was established. Giardia cysts from the stool of each dog were quantified on days -3, 0, 5, 7, 9, 11, 14, 18, 25, and 28. Biochemical parameters were evaluated in all dogs, before the first treatment and after concluding the experiment. Shedding of Giardia cysts was reduced in all treated groups when compared to untreated controls (P < 0.01). However, NTZ2, NTZ3, and FEB had a lower risk during the study. Furthermore, NTZ was also effective against another protozoan, Cryptosporidium spp. at doses of 75 mg/kg and 150 mg/kg, in contrast to the combination of febantel + pyrantel + praziquantel. Biochemical parameters of treated animals, namely, aspartate transaminase and alanine transaminase enzymes, remained within physiological ranges. Based on these results, the implementation of NTZ as a treatment for giardiasis in dogs is proposed. The administration of a single dose is an important advantage of NTZ because it reduces workload, particularly in animals placed in shelters and kennels, where handling of large numbers of animals is required, and personnel is frequently scarce.

Evaluation of the Effectiveness of Sugammadex for Digoxin Intoxication: An Experimental Study.

PubMed

Ozbilgin, Sule; Yurtlu, Derya Aslan; Küçükoztaş, Beyza; Kamacı, Gonca; Korkut, Sezen; Yurtlu, Bülent Serhan; Ensari Güneli, M; Hancı, Volkan; Günerli, Ali

2018-03-16

Previous studies have shown that cyclodextrin group medicines bind to various drugs. The hypothesis of our study is to determine whether sugammadex could bind to digoxin and delay the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with digoxin at 3 mg/h (0.25 mg/ml). Five minutes after the start of infusion, animals were treated with a bolus of either 16 mg/kg (Sgdx16), 100 mg/kg (Sgdx100), or 1000 mg/kg (Sgdx1000) sugammadex. The control group infusion did not contain sugammadex. Heart rate, electrocardiography, and respiratory rate were monitored. The primary endpoint was time to asystole. Digoxin infusion continued until the animals arrested. The time to asystole for the Sgdx1000 group was significantly longer compared to that for the control group (p < 0.05). The mean lethal dose of digoxin was 5.35 ± 2.06 mg/kg in the saline-treated rats. On the other hand, the mean lethal dose of digoxin was 8.54 ± 1.51 mg/kg in the sugammadex 1000 group (p < 0.05). The mean lethal dose of digoxin was significantly higher than control group (p < 0.05). We found that the 1000 mg/kg dose of sugammadex delayed digoxin cardiotoxicity in a rat model of digoxin toxicity. We conclude that further research must be conducted on the interaction between digoxin and sugammadex.

Dosimetric and toxicity comparison between prone and supine position IMRT for endometrial cancer

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

Beriwal, Sushil; Jain, Sheena K.; Heron, Dwight E.

2007-02-01

Purpose: To determine the dosimetric and toxicity differences between prone and supine position intensity-modulate radiotherapy in endometrial cancer patients treated with adjuvant radiotherapy. Methods: Forty-seven consecutive endometrial cancer patients treated with adjuvant RT were analyzed. Of these, 21 were treated in prone position and 26 in the supine position. Dose-volume histograms for normal tissue structures and targets were compared between the two groups. Acute and chronic toxicity were also compared between the cohorts. Results: The percentage of volume receiving 10, 20, 30, 40, 45, and 50 Gy for small bowel was 89.5%, 69%, 33%, 12.2%, 5%, and 0% in themore » prone group and 87.5%, 62.7%, 26.4%, 8%, 4.3%, and 0% in the supine group, respectively. The difference was not statistically significant. The dose-volume histograms for bladder and rectum were also comparable, except for a slightly greater percentage of volume receiving 10 Gy (1.5%) and 20 Gy (5%) for the rectum in the prone group. Acute small bowel toxicities were Grade 1 in 7 patients and Grade 2 in 14 patients in the prone group vs. Grade 1 in 6 patients and Grade 2 in 19 patients in the supine group. Chronic toxicity was Grade 1 in 7 patients and Grade 3 in 1 patient in the prone group and Grade 1 in 5 patients in the supine group. Conclusion: These preliminary results suggest that no difference exists in the dose to the normal tissue and toxicity between prone and supine intensity-modulated radiotherapy for endometrial cancer. Longer follow-up and more outcome studies are needed to determine whether any differences exist between the two approaches.« less

Influence of radiotherapy treatment concept on the outcome of patients with localized ependymomas.

PubMed

Combs, Stephanie E; Kelter, Verena; Welzel, Thomas; Behnisch, Wolfgang; Kulozik, Andreas E; Bischof, Marc; Hof, Holger; Debus, Jürgen; Schulz-Ertner, Daniela

2008-07-15

To assess the outcome of 57 patients with localized ependymomas treated with radiotherapy (RT). Fifty-seven patients with localized ependymomas were treated with RT. Histology was myxopapillary ependymoma (n = 4), ependymoma (n = 23), and anaplastic ependymoma (n = 30). In 16 patients, irradiation of the craniospinal axis (CSI) was performed with a median dose of 20 Gy. Forty-one patients were treated with local RT, with a local dose of 45 Gy to the posterior fossa, including a boost to the tumor bed of 9 Gy. In 19 patients, the tumor bed was irradiated with a median dose of 54 Gy. Overall survival after primary diagnosis was 83% and 71% at 3 and 5 years. Five-year overall survival was 80% in low-grade and 79% in high-grade tumors. Survival from RT was 79% at 3 and 64% at 5 years. We could not show a significant difference in overall survival between CSI and local RT only. Freedom of local failure was 67% at 5 years in patients treated with CSI and 60% at 5 years after local RT. A rate of 83% for distant failure-free survival could be observed in the CSI group as opposed to 93% in the group receiving local RT only. Local RT in patients with localized tumors is equieffective to CSI. The radiation oncologist must keep in mind that patients with localized ependymomas benefit from local doses > or =45 Gy.

SU-E-T-545: A MLC-Equipped Robotic Radiosurgery-Radiotherapy Combined System in Treating Hepatic Lesions: Delivery Efficiency as Compared to a Standard Linac for Treating Hepatic Lesions

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

Jin, L; Price, R; Wang, L

Purpose: The CyberKnife (CK) M6 Series introduced a mulitleaf collimator (MLC) beam for extending its capability to the conventional radiotherapy. This work is to investigate delivery efficiency of this system as compared to a standard Varian linac when treating hepatic lesions. Methods: Nine previously treated patients were divided into three groups with three patients in each. Group one: fractionated radiotherapy; Group two: SBRT-like treatments and Group three: fractionated radiotherapy targeting two PTVs. The clinically used plans were generated with the Eclipse treatment planning system (TPS). We re-planned these cases using a Mulitplan (MP) TPS for the CK M6 and normalizedmore » to the same PTV dose coverage. CK factors (CF) (defined as modulation scaling factor in this work), number of nodes (NN), number of MLC segments (NS) and beam delivery time (BT) with an estimated image interval of 60 seconds, were used for evaluation of delivery efficiency. Results: Generated plans from the MP and Eclipse TPS demonstrated the similar quality in terms of PTV confomality index, minimum and maximum PTV doses, and doses received by critical structures. Group one: CF ranged from 8.1 to 8.7, NN from 30 to 40, NS from 120 to 155 and BT from 20 to 23 minutes; group two: CF from 4.7 to 8.5, NN from 15 to 19, NS from 82 to 141 and BT from 18 to 24 minutes; and group three: CF from 7.9 to 10, NN from 47 to 49, NS from 110 to 113 and BT from 20 to 22 minutes. Conclusions: Delivery time is longer for the CK M6 than for the Varian linac (7.8 to 13.7 minutes). Further investigation will be necessary to determine if a PTV reduction from the tracking feature will shorten the delivery time without decreasing plan quality.« less

Comparative effects of vildagliptin and sitagliptin determined by continuous glucose monitoring in patients with type 2 diabetes mellitus.

PubMed

Koyanagawa, Naohide; Miyoshi, Hideaki; Ono, Kota; Nakamura, Akinobu; Cho, Kyu Yong; Yamamoto, Kohei; Takano, Yoshinari; Dan-Noura, Midori; Atsumi, Tatsuya

2016-08-31

The dipeptidyl peptidase-4 inhibitors vildagliptin and sitagliptin are effective in treating patients with type 2 diabetes mellitus. Patients receiving standard doses of sitagliptin plus insulin may require increased doses of sitagliptin or switching to vildagliptin to improve blood glucose control. This study compared the effects of increasing sitagliptin and switching to vildagliptin in type 2 diabetes patients receiving standard doses of sitagliptin plus insulin. This prospective, randomized, parallel-group comparison trial enrolled 33 type 2 diabetes patients receiving 50 mg sitagliptin once daily plus insulin. Seventeen patients were randomized to 50 mg vildagliptin twice daily, and 16 to 100 mg sitagliptin once daily, and evaluated by continuous glucose monitoring at baseline and after 8 weeks. The primary end-point was the change in mean amplitude of glycemic excursions (MAGE). MAGE decreased from baseline in both the vildagliptin (-13.4 ± 35.7 mg/dL) and sitagliptin (-8.4 ± 24.3 mg/dL) groups, but neither within- nor between-group changes were statistically significant. Similarly, the areas under the curve for blood glucose levels ≥180 mg/dL and <70 mg/dL tended to improve in both groups, but these differences were not statistically significant. In contrast, HbA1c was significantly reduced only in the vildagliptin group, from 7.1 ± 0.6% at baseline to 6.8 ± 0.6% at 8 weeks (p=0.006). Increasing sitagliptin dose and switching to vildagliptin had limited effects in improving MAGE in type 2 diabetic patients treated with standard doses of sitagliptin.

Small Versus Large-Sized Drug-Eluting Beads (DEBIRI) for the Treatment of Hepatic Colorectal Metastases: A Propensity Score Matching Analysis

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

Akinwande, Olaguoke K., E-mail: gokeakin@gmail.com; Philips, Prejesh, E-mail: prejesh.philips@louisville.edu; Duras, Petr, E-mail: durasp@seznam.cz

2015-04-15

PurposeTo compare the feasibility, safety, and efficacy with small and large irinotecan drug-eluting beads (DEBIRI) for treating hepatic colorectal metastases.MethodsUsing our prospectively maintained, multi-center, intra-arterial therapy registry, we identified 196 patients treated with a combination of large beads (100–300 to 500–700 μm) and patients treated with a combination of small beads (70–150 to 100–300 μm). To minimize selection bias, a propensity score analysis was performed to compare both groups.ResultsUnadjusted analysis consisted of 196 and 30 patients treated with large and small beads, respectively. The adjusted analysis consisted of 19 patients each. Unadjusted analysis showed decreased all-grade (p = <0.001) and high-grade adverse effects (p = 0.02)more » in the small bead group, with a persisting trend toward decreased overall side effects in the adjusted analysis favoring small beads (p = 0.09) The adjusted analysis showed the percentage dose delivered (delivered dose/intended dose) was significantly greater in the small bead group compared to the large bead group (96 vs 79 %; p = 0.005). There were also a lower percentage of treatments terminating in complete stasis in the adjusted analysis (0.0035). Adjusted analysis also showed increased objective response rate (ORR) at 12 months (p = 0.04), with a corresponding trend also seen in the unadjusted analysis (0.09).ConclusionSmaller beads result in increased dose delivery probably due to less propensity to reach complete stasis. It may also lead to more durable long-term efficacy. Smaller beads also demonstrate similarly low toxicity compared to large-sized beads with a trend toward less toxicity.« less

Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin.

PubMed

Yokoyama, Shota; Tsuji, Hideyuki; Hiraoka, Sachiko; Nishihara, Masayuki

2016-01-01

Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.

Bifidobacterium lactis B94 plus inulin for Treatment of Helicobacter pylori infection in children: does it increase eradication rate and patient compliance?

PubMed

Islek, A; Sayar, E; Yilmaz, A; Artan, R

2015-01-01

The aim of this study is to investigate the effects of Bifidobacterium lactis B94 and inulin (synbiotic) treatment on eradication rate and patient compliance in subjects treated for symptomatic H. pylori infection. Patients with symptomatic H. pylori infection were divided into two groups. One group was treated with standard triple therapy (lansoprazole, amoxicillin, and clarithromycin) and B. lactis B94 (5 × 109 CFU/dose) plus inulin (900 mg) twice daily for seven days. The control group was treated with standard triple therapy and placebo. The side effects and eradication rates were evaluated at the end of the study. Ninety-three patients with H. pylori infection were treated with either synbiotic plus triple therapy (n = 47) or placebo plus triple therapy (n = 46). The infection eradication rates were not significantly different between the synbiotic and placebo groups [intent-to-treat (ITT), 80.8% and 67.3%, p = 0.13, respectively; per-protocol (PP), 86.3% and 81.5%, p = 0.55, respectively]. The drug side effects were significantly higher in the placebo group than in the synbiotic group (63% and 17%, respectively, p < 0.01). Although no intolerable adverse side effects were observed in the synbiotic group, intolerable adverse side effects were observed in 13% of the placebo group (p = 0.01). Our results suggest that twice daily 5 × 109 CFU/dose B. lactis B94 plus 900 mg inulin treatment did not have a direct positive effect on the H. pylori eradication rate. However, this treatment had significantly reduced side effects and indirectly increased eradication rates by increasing patient compliance. © Acta Gastro-Enterologica Belgica.

Potential antimalarial activity of Methyl Jasmonate and its effect on lipid profiles in Plasmodium Berghei infected mice.

PubMed

Oyinloye, Oladapo E; Kosoko, Ayokulehin M; Emikpe, Benjamin; Falade, Catherine O; Ademowo, Olusegun G

2015-09-01

The antimalarial activity and lipid profiles of Methyl Jasmonate (MJ) were investigated against established malaria infection in vivo using BALB/c mice. Arteether (AE) and chloroquine (CQ) were used as reference drugs while ethanol was used as the vehicle for drug delivery for MJ. Mice treated with 10 and 25 mg/kg MJ showed a remarkable reduction in percentage parasitemia by 68.3% and 78.2% on day 10(post treatment) respectively while 45.4% and 87.2% reduction in percentage parasitemia were observed in the group treated with 50 mg/kg on day 3 and 10 (post treatment) respectively. The highest mean survival time was observed in CQ followed by AE and MJ in dose-dependent manner. A progressive decrease in packed cell volume (PCV) was observed in infected untreated mice which led to the death of all the mice by day 9 (post treatment). Infected mice treated with MJ showed reduced level of HDL and LDL compared with infected untreated group. As the dose of MJ increased in infected mice cholesterol levels increased while there was reduction in triglyceride. Overall there was marked decrease in parasitemia in Plasmodium berghei infected mice treated with graded doses of MJ but appears to have reduced antimalarial activity compared with CQ and AE.

[Therapy of arrhythmia induced by myocardial ischemia. Association of L-carnitine, propafenone and mexiletine].

PubMed

Mondillo, S; Faglia, S; D'Aprile, N; Mangiacotti, L; Campolo, M A; Agricola, E; Palazzuoli, V

1995-12-01

To assess the anti-arrythmic effect of L-carnitina, propafenone and mexiletine, we tested the drugs in 50 patients with effort angina and ventricular ectopic beats (VEB). The patients were randomized in 5 groups: Group A: was treated with oral L-carnitine at the dose of 2 g x 3 for two weeks. Group B: oral propafenone at the dose of 300 mg x 3 for two weeks. Group C: as group B+L-carnitine+g x 3 at the second weeks. Group D: oral mexiletine at the dose of 200 mg x 3 for two weeks. Group E: as group D+L-carnitine 2 gr x 3 at the second week. After 7 and 14 days of treatment, in all patients an Holter examination was performed. Our results show that L-carnitine exerts a significant reduction of the VEB and its administration potentiates the anti-arrythmic effect of propafenone and mexiletine.

Anti-Gastric Ulcer Effect of Betulinic Acid in Male Albino Rats.

PubMed

Onwuchekwa, C; Oluwole, F S

2015-12-20

Betulinic acid (BA) is a lupane-type triterpene that has been identified and isolated from various plant species used in ethnomedicine in various cultures across the world. This study was undertaken to elucidate the mechanisms underlying the anti-ulcer effect of Betulinic acid. The effect of BA on indomethacin-induced ulcer, gastric mucus secretion, gastric mucus cells count, basal and histamine-induced gastric acid secretion and levels of malondialdehyde formation were studied using dose of 0.5, 1.5, and 3.0 mg/kg. The results showed that BA reduced indomethacin-induced ulceration significantly and significantly increased  gastric mucus secretion in the 1.5 mg/kg and 3.0 mg/kg BA treated rats compared to the control rats. There was a significant increase  in the mucus cells count in all the treated groups which is in a dose- dependent manner compared to the control group. There was significant decrease  in gastric acid secretion in each of the BA treated groups compared to the control. Malondialdehyde concentration significantly decrease in all the treated groups compared to the control. The anti-gastric ulcer effect of BA may be mediated via decreasing gastric acid secretion, increasing gastric mucus secretions, increasing the number of gastric mucus cells and also by reducing the level of MDA concentration.

In HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization : A retrospective cohort study.

PubMed

De Vecchis, R; Ariano, C; Di Biase, G; Noutsias, M

2018-03-08

In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan. Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00). During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.

Influence of the estrus cycle on the evaluation of a vaginal irritation study in intact and ovariectomized rats

PubMed Central

Ishii, Aiko; Ogawa, Bunichiro; Koyama, Tomoko; Nakanishi, Yutaka; Sasaki, Minoru

2017-01-01

When conducting vaginal irritation studies, ovariectomized rats or rabbits are typically used according to practical reports. In the present study, we evaluated the influence of the estrus cycle in a vaginal irritation study using intact rats and ovariectomized rats, which exhibit a late diestrus-like condition, to determine whether intact rats can be useful for evaluating vaginal irritancy. Rats were divided into 4 groups: proestrus, estrus, and metestrus or diestrus in intact rats and ovariectomized rats. All the rats in each group were treated with a vehicle or sodium dodecyl sulfate, as the irritant, in single-dose and 4-day repeat-dose vaginal irritation studies. Each rat’s vagina was examined histopathologically, and the irritation score was calculated using a semiquantitative scoring system. In the single-dose study, the irritation scores for the proestrus or ovariectomized groups treated with sodium dodecyl sulfate were higher than those of the estrus group or metestrus or diestrus group. In the 4-day repeat-dose study, a significant histopathological difference was not found among the intact rats (proestrus, estrus, and metestrus or diestrus groups), and the irritation score range of the intact rats was similar to that of the ovariectomized rats, though the mean score of the intact rats was slightly lower than that of the ovariectomized rats. These results suggest that intact rats might be well suited for 4-day vaginal irritation studies and useful for evaluating vaginal irritancy using not only the mean score, but also individual irritation score ranges, whereas the estrus cycle would need to be identified in single-dose vaginal irritation studies. PMID:28458454

Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites

PubMed Central

Liu, Da-Quan; Gao, Qiao-Ying; Liu, Hong-Bin; Li, Dong-Hua; Wu, Shang-Wei

2013-01-01

AIM: To investigate the benefits of probiotics treatment in septic rats. METHODS: The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus. We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined. RESULTS: Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly compared with septic model group (80% and 55% vs 30%, P < 0.05). The total viable counts of bacteria in ascites decreased significantly in probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P < 0.05). The total positive rate of hemoculture decreased significantly in probiotics treated group compared with septic model group (33.3% vs 100.0%, P < 0.05). The population of Escherichia coli and Staphylococcus aureus in ascites of probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P < 0.05; 2.80 ± 1.04 vs 5.39 ± 1.21, P < 0.05). With probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25 vs 2.88 ± 0.14, P < 0.01). CONCLUSION: Escherichia coli and Staphylococcus aureus may be primary pathogens in septic rats. Probiotics improve survival of septic rats by suppressing these conditioned pathogens. PMID:23840152

Free fatty acid suppositories are as effective as docusate sodium and sorbitol enemas in treating constipation in children.

PubMed

Ormarsson, Orri Thor; Asgrimsdottir, Gudrun Marta; Loftsson, Thorsteinn; Stefansson, Einar; Lund, Sigrun Helga; Bjornsson, Einar Stefan

2016-06-01

A well-documented, clinically proven per rectum treatment for childhood constipation is needed. This phase two clinical trial evaluated the efficacy of suppositories containing free fatty acids (FFA) compared with Klyx docusate sodium and sorbitol enemas. A randomised, controlled, single-blind study was undertaken on 77 children aged between one and 17 who presented to an emergency department in Iceland and were diagnosed with constipation. In stage one, 23 patients were randomised to receive lower dose FFA suppositories or Klyx (n = 33). In stage two, 21 different patients were randomised to receive higher dose suppositories and compared with the same Klyx control subjects. The suppositories were effective at bowel emptying in 39% of the group who received the lower FFA doses and 81% of the group receiving higher doses, compared with 88% in the Klyx control group. Symptom relief was obtained in 30% of the group receiving the lower doses and 71% of the group receiving the higher doses, compared with 73% in the control group. The higher dose FFA suppositories were as effective as the Klyx enemas with regard to bowel emptying and symptom relief and might provide an important and less invasive alternative for childhood constipation. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Immunocontraception for Managing Feral Cattle in Hong Kong

PubMed Central

Massei, Giovanna; Koon, Ka-Kei; Benton, Steven; Brown, Richard; Gomm, Matt; Orahood, Darcy S.; Pietravalle, Stéphane; Eckery, Douglas C.

2015-01-01

Conflicts between human interests and feral cattle in Hong Kong derive from growing numbers of free-roaming cattle. Public antipathy towards lethal population control led the local authorities to consider fertility control to reduce cattle numbers. This study assessed the potential side effects of the immunocontraceptive GonaCon on individual female cattle and established the effectiveness of GonaCon to induce infertility. We evaluated GonaCon in 34 captive cattle assigned to four groups: Control administered a sham solution; Webbed (surgically sterilized through removal of the oviducts), administered one dose of GonaCon; Webbed, administered one dose of GonaCon and a booster dose three months later, and Treated, administered one dose of GonaCon. The side effects of GonaCon were assessed by monitoring injection site, body weight, body condition, size of lymph nodes, body temperature, and feeding behaviour 1 week and 1, 3, 6, 9 and 12 months after vaccination and by haematological and biochemical variables at vaccination and three months post-vaccination. The effectiveness of GonaCon to cause infertility was monitored by quantifying anti-GnRH antibody titres and by using kits to detect cycling and pregnancy. GonaCon-treated cattle showed no injection site reaction, limping, or abnormal behaviour. No differences were observed in all physiological and welfare indicators between control and vaccinated cattle. All control cattle and 4 of the 12 cattle in the Treated group became pregnant. Cattle administered a booster dose had higher anti-GnRH antibody titres than cattle that received one dose. We concluded that GonaCon does not compromise the animals’ welfare and is effective in reducing fertility in cattle. A booster dose is likely to increase the duration of infertility. Further studies are required to assess the feasibility and costs of immunocontraception for controlling free-roaming cattle populations. PMID:25856283

Immunocontraception for managing feral cattle in Hong Kong.

PubMed

Massei, Giovanna; Koon, Ka-Kei; Benton, Steven; Brown, Richard; Gomm, Matt; Orahood, Darcy S; Pietravalle, Stéphane; Eckery, Douglas C

2015-01-01

Conflicts between human interests and feral cattle in Hong Kong derive from growing numbers of free-roaming cattle. Public antipathy towards lethal population control led the local authorities to consider fertility control to reduce cattle numbers. This study assessed the potential side effects of the immunocontraceptive GonaCon on individual female cattle and established the effectiveness of GonaCon to induce infertility. We evaluated GonaCon in 34 captive cattle assigned to four groups: Control administered a sham solution; Webbed (surgically sterilized through removal of the oviducts), administered one dose of GonaCon; Webbed, administered one dose of GonaCon and a booster dose three months later, and Treated, administered one dose of GonaCon. The side effects of GonaCon were assessed by monitoring injection site, body weight, body condition, size of lymph nodes, body temperature, and feeding behaviour 1 week and 1, 3, 6, 9 and 12 months after vaccination and by haematological and biochemical variables at vaccination and three months post-vaccination. The effectiveness of GonaCon to cause infertility was monitored by quantifying anti-GnRH antibody titres and by using kits to detect cycling and pregnancy. GonaCon-treated cattle showed no injection site reaction, limping, or abnormal behaviour. No differences were observed in all physiological and welfare indicators between control and vaccinated cattle. All control cattle and 4 of the 12 cattle in the Treated group became pregnant. Cattle administered a booster dose had higher anti-GnRH antibody titres than cattle that received one dose. We concluded that GonaCon does not compromise the animals' welfare and is effective in reducing fertility in cattle. A booster dose is likely to increase the duration of infertility. Further studies are required to assess the feasibility and costs of immunocontraception for controlling free-roaming cattle populations.

High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study.

PubMed

Villafane, G; Thiriez, C; Audureau, E; Straczek, C; Kerschen, P; Cormier-Dequaire, F; Van Der Gucht, A; Gurruchaga, J-M; Quéré-Carne, M; Evangelista, E; Paul, M; Defer, G; Damier, P; Remy, P; Itti, E; Fénelon, G

2018-01-01

Studies of the effects of nicotine on motor symptoms in Parkinson's disease (PD) brought out discordant results. The aim of the present study was to evaluate the efficacy and safety of high doses of transdermal nicotine on motor symptoms in PD. Forty PD patients were randomly assigned to a treated and untreated arm in an open-label study. Treated patients received increasing doses of nicotine to reach 90 mg/day by 11 weeks. This dosage was maintained for 28 weeks (W39) and then reduced over 6 weeks. Final evaluation was performed 6 weeks after washout. The main outcome measure was the OFF-DOPA Unified Parkinson's Disease Rating Scale (UPDRS) motor score measured on video recordings by raters blinded to the medication status of the patients. There was no significant difference in OFF-DOPA UPDRS motor scores between the nicotine-treated and non-treated groups, neither at W39 (19.4 ± 9.3 vs. 21.5 ± 14.2) nor considering W39 differences from baseline (-1.5 ± 12.1 vs. +0.9 ± 12.1). The 39-item Parkinson's disease questionnaire scores decreased in nicotine-treated patients and increased in non-treated patients, but the difference was not significant. Overall tolerability was acceptable, and 12/20 treated patients reached the maximal dosage. High doses of transdermal nicotine were tolerated, but our study failed to demonstrate significant improvement in UPDRS motor scores. Improvement in unblinded secondary outcomes (UPDRS-II, UPDRS-IV, doses of l-DOPA equivalents) suggest a possible benefit for patients treated with nicotine, which should be confirmed in larger double blind, placebo-controlled studies. © 2017 EAN.

Evaluation of the mutagenic and cytotoxic effects of mercurous chloride by the micronuclei technique in golden Syrian hamsters.

PubMed

Cortés-Gutiérrez, Elva I; Cerda-Flores, Ricardo M; González-Ramírez, Diego; Zúñiga-Charles, Miguel A; Lazcano-Martínez, Sigifredo; Sampayo-Reyes, Adriana; Leal-Garza, Carlos H

2004-05-01

The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h).

General 4-week toxicity study with EMS in the rat.

PubMed

Pfister, Thomas; Eichinger-Chapelon, Anne

2009-11-12

In this subacute toxicity study, ethyl methanesulfonate (EMS) was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 20, 60 and 180/120 mg/kg body weight (bw)/day for a period of 28 days (for 19 days in the high-dose group). A control group was treated similarly with the vehicle, bidistilled water, only. The groups comprised 10 animals per sex, which were sacrificed after 28 days, respectively 19 days in the high-dose group, of treatment. Additional five rats per sex and group were treated accordingly and then allowed a 14 days treatment-free recovery period. Additional six rats per sex and group (three rats per sex in the control group) were treated accordingly and used for hemoglobin adduct analysis after EMS exposure. All animals survived until their scheduled necropsy. Treatment with EMS had a direct dose-dependent effect on food consumption and consequently on body weight at doses > or =20mg/kgbw/day in male rats and at > or =60 mg/kgbw/day in females rats. Hence, treatment with the high dose of 180 mg/kgbw/day had to be interrupted for 9 days after which, the animals were re-dosed at 120 mg/kgbw/day. This dose was also poorly tolerated over the remaining two treatment weeks causing again a marked reduction in food consumption and body weight. A dose of 60 mg/kgbw/day was moderately tolerated over 4 weeks treatment with mean daily food consumption and body weight distinctly lower than in controls. Primary targets of systemic toxicity were the hematopoietic system, thymolymphatic system and sexual organs. Characteristic changes in hematology parameters were decreased red blood cell counts, hematocrit, and hemoglobin concentration. White blood cell counts were also decreased due to reduced lymphocyte and granulocyte populations of each fraction. The corresponding histopathology findings were fatty atrophy of bone marrow and minimal hypocellularity of the white pulp of the spleen. Similarly, treatment with EMS caused an involution of the thymolymphatic system characterized by decreased organ weight of thymus, lymph nodes, and spleen microscopically associated with atrophy of the thymus and hypocellularity of Peyer's patches, lymph nodes and the white pulp of the spleen. The effects on sexual organs included lower organ weight/reduced size for testes, epididymides, seminal vesicles, prostate, and uterus. Tubular atrophy, single cell necrosis of the germ cells and in epididymides reduced spermatozoa were recorded microscopically. The described findings occurred at doses of 60 and 180/120 mg/kgbw/day and were dose-dependent with regard to incidence and severity. Other target organs were the pancreas (acinar cell vacuolation), thyroid gland (follicular cell hypertrophy), and salivary gland (secretory depletion of convoluted ducts). The systemic exposure to EMS was monitored by hemoglobin ethylvaline adduct measurement. The concentration of hemoglobin ethylvaline adducts was linear with the dose and accumulated 11-26-fold over the treatment period. In summary, decreases in food consumption and body weight were the dose-limiting effects of treatment with EMS. Organ toxicity was characterized by depression of cell proliferation (hematopoiesis and spermatogenesis) and changes suggestive of reduced metabolism and/or physiological imbalances (e.g. thymolymphatic system and thyroid gland) without signs of inflammatory or necrotic lesions. For some findings, especially the effects on the thymolymphatic system and sexual organs, it cannot be excluded that starvation-like condition contributed to the occurrence of such changes. The low dose of 20 mg/kgbw/day was basically free of adverse effects despite of a clear evidence for hemoglobin adducts.

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

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

Hong, Linda X.; Garg, Madhur; Lasala, Patrick

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters {<=}20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55{+-}0.79 with HI 1.23{+-}0.06; the average R{sub 50}-R{sub 100} was 0.41{+-}0.08, 0.55{+-}0.10, and 0.65{+-}0.09 cm, respectively, for tumors {<=}20 mm, between 20 and 30 mm, and >30 mm. Conclusions: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system.« less

Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus.

PubMed

Davis, Angela M; Mao, Jiude; Naz, Bushra; Kohl, Jessica A; Rosenfeld, Cheryl S

2008-10-01

Selective estrogen receptor modulators (SERMs) are potentially useful in treating various endometrial disorders, including endometrial cancer, as they block some of the detrimental effects of estrogen. It remains unclear whether each SERM regulates a unique subset of genes and, if so, whether the combination of a SERM and 17beta-estradiol has an additive or synergistic effect on gene expression. We performed microarray analysis with Affymetrix Mouse Genome 430 2.0 short oligomer arrays to determine gene expression changes in uteri of ovariectomized mice treated with estradiol (low and high dose), methyl-piperidino-pyrazole (MPP), ICI 182 780, raloxifene, and combinations of high dose of estradiol with one of the SERM and dimethyl sulfoxide (DMSO) vehicle control. The nine treatments clustered into two groups, with MPP, raloxifene, and high dose of estradiol in one, and low dose of estradiol, ICI + estradiol, ICI, MPP + estradiol, and raloxifene + estradiol in the second group. Surprisingly, combining a high dose of estradiol with a SERM markedly increased (P<0.02) the number of regulated genes compared with each individual treatment. Analysis of expression for selected genes in uteri of estradiol and SERM-treated mice by quantitative (Q)RT-PCR generally supported the microarray results. For some cancer-associated genes, including Klk1, Ihh, Cdc45l, and Cdca8, administration of MPP or raloxifene with estradiol resulted in greater expression than estradiol alone (P<0.05). By contrast, ICI 182 780 suppressed more genes governing DNA replication compared with MPP and raloxifene treatments. Therefore, ICI 182 780 might be superior to MPP and raloxifene to treat estrogen-induced endometrial cancer in women.

Topical Application of Aloe vera Accelerated Wound Healing, Modeling, and Remodeling: An Experimental Study.

PubMed

Oryan, Ahmad; Mohammadalipour, Adel; Moshiri, Ali; Tabandeh, Mohammad Reza

2016-01-01

Treatment of large wounds is technically demanding and several attempts have been taken to improve wound healing. Aloe vera has been shown to have some beneficial roles on wound healing but its mechanism on various stages of the healing process is not clear. This study was designed to investigate the effect of topical application of A. vera on cutaneous wound healing in rats. A rectangular 2 × 2-cm cutaneous wound was created in the dorsum back of rats. The animals were randomly divided into 3 groups of control (n = 20), low-dose (n = 20), and high-dose (n = 20) A. vera. The control and treated animals were treated daily with topical application of saline, low-dose (25 mg/mL), and high-dose (50 mg/mL) A. vera gel, up to 10 days, respectively. The wound surface, wound contraction, and epithelialization were monitored. In each group, the animals were euthanized at 10 (n = 5), 20 (n = 5), and 30 (n = 10) days post injury (DPI). At 10, 20, and 30 DPI, the skin samples were used for histopathological and biochemical investigations; and at 30 DPI, the skin samples were also subjected for biomechanical studies. Aloe vera modulated the inflammation, increased wound contraction and epithelialization, decreased scar tissue size, and increased alignment and organization of the regenerated scar tissue. A dose-dependent increase in the tissue level of dry matter, collagen, and glycosaminoglycans' content was seen in the treated lesions, compared to the controls. The treated lesions also demonstrated greater maximum load, ultimate strength, and modulus of elasticity compared to the control ones (P < 0.05). Topical application of A. vera improved the biochemical, morphological, and biomechanical characteristics of the healing cutaneous wounds in rats. This treatment option may be valuable in clinical practice.

2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in yellow perch (Perca flavescens)

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

Spitsbergen, J.M.; Kleeman, J.M.; Peterson, R.E.

1988-01-01

Growth, mortality and morphologic lesions in juvenile, hatchery-reared yellow perch, Perca flavescens, were studied after treatment with graded single doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1-125 ..mu..g/kg, intraperitoneally). TCDD doses of 25 and 125 ..mu..g/kg caused 95% mortality by 28 d after treatment, without decreasing body weight. A TCDD dose of 5 ..mu..g/kg resulted in progressive loss of body weight with cumulative mortality of 80% by 80 d posttreatment. Periodic handling stress did not affect the time course of mortality or cumulative percent lethality in TCDD-treated perch. Fin necrosis, petechial cutaneous hemorrhage, and ascites occurred in perch treated with 5 ..mu..g/kg ormore » more of TCDD. Thymic atrophy, decreased hematopoiesis in the head kidney, fibrinous pericarditis, focal myocardial necrosis, submucosal gastric edema, and hyperplasia of the epithelium of gill filaments and lamellae occurred in perch dosed with 25 or 125 ..mu..g/kg. Dose-related splenic lymphoid depletion occurred in perch receiving 5 ..mu..g/kg or more TCDD, and hepatocycte lipidosis occurred in groups treated with doses of 1 ..mu..g/kg or more TCDD. Thus yellow perch are as responsive to the acute toxic effects of TCDD as some of the more sensitive mammalian species, and neither loss of body weight nor histologic lesions in TCDD-treated perch are sufficient to explain mortality.« less

Radiochemotherapy in Patients With Primary Glioblastoma Comparing Two Temozolomide Dose Regimens

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

Combs, Stephanie E.; Wagner, Johanna; Bischof, Marc

2008-07-15

Purpose: To evaluate toxicity and outcomes in patients with primary glioblastoma (GB) treated with postoperative radiochemotherapy (RCHT) with temozolomide (TMZ) comparing two dose regimens. Methods and Materials: A total of 160 patients with histologically confirmed GB were treated with postoperative RCHT with TMZ. Of the patients, 66 were female and 94 were male, with a median age of 60 years. After the primary diagnosis, a biopsy had been performed in 42 patients; a subtotal and total resection was conducted in 66 and 52 patients. Postoperative radiotherapy was applied with a median dose of 60 Gy with a median fractionation ofmore » 5 x 2Gy/week. Concomitant TMZ was prescribed at 50 mg/m{sup 2} in 123 patients (Group A) and at 75 mg/m{sup 2} in 37 patients (Group B). Patients were followed in 3-months intervals, with a median follow-up of 13 months. Results: Overall survival (OS) rates in Group A vs. Group B were 67% and 79% at 1 year and 43% vs. 49% at 2 years, respectively (p = 0.69). Progression-free survival was 49% vs. 54% at 1 year and 22% vs. 29% at 2 years (p = 0.31). Hematologic toxicity was not statistically significant over the 6-week RCHT period except for a significant decrease in platelets during Week 6 (p = 0.01) in Group B. Conclusions: Overall survival seems to be comparable in both groups, although longer follow-up and a larger group of patients are needed to corroborate these results. Lower dosing of TMZ also is associated with a more beneficial toxicity profile.« less

Efficacy and safety of Lian-Ju-Gan-Mao capsules for treating the common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

PubMed

Wang, Shengjun; Jiang, Hongli; Yu, Qin; She, Bin; Mao, Bing

2017-01-05

The common cold is a common and frequent respiratory disease mainly caused by viral infection of the upper respiratory tract. Chinese herbal medicine has been increasingly prescribed to treat the common cold; however, there is a lack of evidence to support the wide utility of this regimen. This protocol describes an ongoing phase II randomized controlled clinical trial, based on the theory of traditional Chinese medicine (TCM), with the objective of evaluating the efficacy and safety of Lian-Ju-Gan-Mao capsules (LJGMC), a Chinese patent medicine, compared with placebo in patients suffering from the common cold with wind-heat syndrome (CCWHS). This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. A total of 240 patients will be recruited and randomly assigned to a high-dose group, medium-dose group, low-dose group, and placebo-matched group in a 1:1:1:1 ratio. The treatment course is 3 consecutive days, with a 5-day follow-up. The primary outcome is time to all symptoms' clearance. Secondary outcomes include time to the disappearance of primary symptoms and each secondary symptom, time to fever relief, time to fever clearance, and change in TCM symptom and sign scores. This trial is a well-designed study according to principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide high-quality evidence on the efficacy and safety of LJGMC in treating CCWHS and help to optimize the dose for the next phase III clinical trial. Moreover, the protocol presents a detailed and practical methodology for future clinical trials of drugs developed based on TCM. Chinese Clinical Trial Registry, ChiCTR-IPR-15006504 . Registered on 4 June 2015.

Triptolide: a potential male contraceptive.

PubMed

Lue, Y; Sinha Hikim, A P; Wang, C; Leung, A; Baravarian, S; Reutrakul, V; Sangsawan, R; Chaichana, S; Swerdloff, R S

1998-01-01

The antifertility effect of triptolide and other related compounds, isolated from Tripterygium wilfordii, has been demonstrated in male rats. The exact sites and mechanism of action of triptolide remain unknown. Our objectives were to determine whether triptolide at selected dose levels that induce infertility has any detrimental effects on the testes and to determine the sites and the possible mechanisms of its action. Groups of six adult male Sprague-Dawley rats were given oral administration of either vehicle (control group) or triptolide (50 or 100 microg/kg body weight) daily for 35 or 70 days. Body weight gain was normal in all treated groups. All six rats treated with a high dosage of triptolide were infertile during the second (63-70 days) mating trial. A lower dose (50 microg) of triptolide gave intermediate fertility values. Plasma levels of luteinizing hormone, follicle-stimulating hormone, testosterone, and intratesticular testosterone were not significantly different between control and triptolide-treated groups. Cauda epididymal sperm content was decreased by 68% and the motility, which averaged 58.2% in the control rat, was reduced to almost zero. No effects of triptolide were observed on testis and accessory organs weight, volumes of tubular lumen and the total Leydig cells, tubule diameter, and the number of Sertoli cells, spermatogonia, preleptotene (PL), and pachytene (P) spermatocytes. There were, however, modest but significant decreases in tubule volume and the number of round spermatids at stages VII-VIII. No changes in the germ cell apoptotic index measured at stages VII-VIII and XIV-I were noted between controls and rats rendered infertile with a high dose of triptolide. Thus, triptolide, at a dose level that induces complete infertility in the adult rats, has minimal adverse effects on the testes and acts primarily on the epididymal sperm making triptolide an attractive lead as a post-testicular male contraceptive.

Dose-volume analysis for respiratory toxicity in intrathoracic esophageal cancer patients treated with definitive chemoradiotherapy using extended fields

PubMed Central

Tanabe, Satoshi; Myojin, Miyako; Shimizu, Shinichi; Fujino, Masaharu; Takahashi, Hiroaki; Shirato, Hiroki; Ito, Yoichi M.; Ishikawa, Masayori; Hosokawa, Masao

2013-01-01

Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0–1 RP (RPG≤1) group and the Grade 2–5 RP (RPG≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RPG≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RPG≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP. PMID:23660276

Fasciolicidal efficacy of Albizia anthelmintica and Balanites aegyptiaca compared with albendazole.

PubMed

Koko, W S; Galal, M; Khalid, H S

2000-07-01

An attempt was made to evaluate the oral doses of 9 g/kg-body weight of Albizzia anthelmintica Brong. Mimoaseae stem bark water extract and 9 g/kg body weight of B. aegyptiaca (L) Del. (Balanitaceae) fruit mesocarp water extract (traditionally used as an anthelmintic in the Sudan) compared with 20 mg/kg body weight (recommended dose) of albendazole against Fasciola gigantica adult worm (12 weeks old) in five groups each of three goats (6 month old). Group (I) uninfected control, group (II) infected untreated control, group (III, IV and V) infected and treated as mentioned above respectively. Based on the percentage reduction in fluke counts from the liver post mortum 2 weeks after treatment, the efficacy of the mentioned therapeutics was 95.5, 93.2 and 97.7%, respectively. The characteristic lesions of liver fasciolosis, egg/gm of faeces (EPG), packed cell volume (PCV), haemoglobin concentration, total red blood cells count (RBC), total white blood cells count (WBC) and oesinophil% were significantly different from control and treated groups (P<0.05).

The Analgesic Effects of Different Extracts of Aerial Parts of Coriandrum Sativum in Mice

PubMed Central

Fatemeh Kazempor, Seyedeh; Vafadar langehbiz, Shabnam; Hosseini, Mahmoud; Naser Shafei, Mohammad; Ghorbani, Ahmad; Pourganji, Masoomeh

2015-01-01

Regarding the effects of Coriandrum sativum (C. sativum) on central nervous system, in the present study analgesic properties of different extracts of C. sativum aerial partswere investigated. The mice were treated by saline, morphine, three doses (20, 100 and 500 mg/kg) of aqueous, ethanolic, choloroformic extracts of C. sativum and one dose (100 mg/kg) of aqueous, two doses of ethanolic (100 and 500 mg/kg) and one dose of choloroformic (20 mg/kg) extracts of C. sativum pretreated by naloxone. Recording of the hot plate test was performed 10 min before injection of the drugs as a base and it was consequently repeated every 10 minutes after the extracts injection. The maximal percent effect (MPE) in the groups treated by three doses of aqueous, ethanolic and chloroformic extracts were significantly higher than saline group which were comparable to the effect of morphine. The effects of most effective doses of extracts were reversed by naloxone. The results of present study showed analgesic effect of aqueous, ethanolic and chloroformic extracts of C. sativum extract. These effects of the extracts may be mediated by opioid system. However, more investigations are needed to elucidate the exact responsible mechanism(s) and the effective compound(s).

Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice.

PubMed

Cavuşoğlu, Kültiğin; Yapar, Kürşad; Oruç, Ertan; Yalçın, Emine

2011-10-01

The aim of the present study was to investigate the protective role of Ginkgo biloba L. leaf extract against the active agent of Roundup® herbicide (Monsanto, Creve Coeur, MO, USA). The Swiss Albino mice were randomly divided into six groups, with each group consisting of six animals: Group I (control) received an intraperitoneal injection of dimethyl sulfoxide (0.2 mL, once only), Group II received glyphosate at a dose of 50 mg/kg of body weight, Group III received G. biloba at a dose of 50 mg/kg of body weight, Group IV received G. biloba at a dose of 150 mg/kg of body weight, Group V received G. biloba (50 mg/kg of body weight) and glyphosate (50 mg/kg of body weight), and Group VI received G. biloba (150 mg/kg of body weight) and glyphosate (50 mg/kg of body weight). The single dose of glyphosate was given intraperitoneally. Animals from all the groups were sacrificed at the end of 72 hours, and their blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and glutathione (GSH) levels and the presence of micronucleus (MN), chromosomal aberrations (CAs), and pathological damages. The results indicated that serum AST, ALT, BUN, and creatinine levels significantly increased in mice treated with glyphosate alone compared with the other groups (P<.05). Besides, glyphosate-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels of the liver and kidney tissues. Moreover, glyphosate alone-treated mice presented higher frequencies of CAs, MNs, and abnormal metaphases compared with the controls (P<.05). These mice also displayed a lower mean mitotic index than the controls (P<.05). Treatment with G. biloba produced amelioration in indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity relative to Group II. Each dose of G. biloba provided significant protection against glyphosate-induced toxicity, and the strongest effect was observed at a dose of 150 mg/kg of body weight. Thus, in vivo results showed that G. biloba extract is a potent protector against glyphosate-induced toxicity, and its protective role is dose-dependent.

Evaluation of Ratnaprash for its effect on strength, stamina and fatigue using swim endurance test and biochemical estimation in swiss albino mice

PubMed Central

Gupta, Arun; Kumar, Satyendra; Rajput, Rashmi; Srivastava, Ruchi; Rai, Rajiv K.; Sastry, J. L. N.

2015-01-01

Context: Traditional medicines have been considered as important resources for postponing fatigue, accelerating elimination of fatigue related metabolites and improving physical ability. Rasāyanās or rejuvenative therapies are mentioned as one of the eight clinical specialties in Ayurveda for attaining longevity, healthy life and regulation of bodily balance. Eventhough more detailed studies are needed to confirm the claims of benefits in the light of evidence based research, Ratnaprash, a herbo-mineral rasāyana formulation, is proposed here to be an antifatigue supplement that is good in promoting strength and stamina. Materials and Methods: In the present study, anti fatigue, strength and stamina enhancing properties of Ratnaprash were examined based on swim endurance capacity and the change in biochemical parameters in Swiss Albino mice. Treatment groups were orally administered Ratnaprash at various test doses (500, 1000, 2000 mg/Kg per day), while the control group received distilled water at similar dose volumes. Effect of therapy was evaluated after 28 days of treatment. Results: At the end of study period, the swimming times to exhaustion were longer in the treated groups than in the control group. Plasma lactate levels of treated groups were lower than those of the control group (P < 0.05) while tissue ATP levels were higher. These effects were dose dependent and the strongest effect was seen in groups treated at 1000 mg/Kg. Conclusion: Ratnaprash enhanced the forced swimming capacity of mice and exhibited elevated anti-fatigue activity, reduced blood lactate levels and increased tissue ATP levels in preclinical models in comparison to vehicle control, exhibiting possible role in increasing strength and stamina and contributing anti-fatigue activity. PMID:26600664

Evaluation of Ratnaprash for its effect on strength, stamina and fatigue using swim endurance test and biochemical estimation in swiss albino mice.

PubMed

Gupta, Arun; Kumar, Satyendra; Rajput, Rashmi; Srivastava, Ruchi; Rai, Rajiv K; Sastry, J L N

2015-01-01

Traditional medicines have been considered as important resources for postponing fatigue, accelerating elimination of fatigue related metabolites and improving physical ability. Rasāyanās or rejuvenative therapies are mentioned as one of the eight clinical specialties in Ayurveda for attaining longevity, healthy life and regulation of bodily balance. Eventhough more detailed studies are needed to confirm the claims of benefits in the light of evidence based research, Ratnaprash, a herbo-mineral rasāyana formulation, is proposed here to be an antifatigue supplement that is good in promoting strength and stamina. In the present study, anti fatigue, strength and stamina enhancing properties of Ratnaprash were examined based on swim endurance capacity and the change in biochemical parameters in Swiss Albino mice. Treatment groups were orally administered Ratnaprash at various test doses (500, 1000, 2000 mg/Kg per day), while the control group received distilled water at similar dose volumes. Effect of therapy was evaluated after 28 days of treatment. At the end of study period, the swimming times to exhaustion were longer in the treated groups than in the control group. Plasma lactate levels of treated groups were lower than those of the control group (P < 0.05) while tissue ATP levels were higher. These effects were dose dependent and the strongest effect was seen in groups treated at 1000 mg/Kg. Ratnaprash enhanced the forced swimming capacity of mice and exhibited elevated anti-fatigue activity, reduced blood lactate levels and increased tissue ATP levels in preclinical models in comparison to vehicle control, exhibiting possible role in increasing strength and stamina and contributing anti-fatigue activity.

Vitis vinifera Extract Ameliorate Hepatic and Renal Dysfunction Induced by Dexamethasone in Albino Rats

PubMed Central

Hasona, Nabil A.; Alrashidi, Ahmed A.; Aldugieman, Thamer Z.; Alshdokhi, Ali M.; Ahmed, Mohammed Q.

2017-01-01

This study was conducted to evaluate the biochemical effects of grape seed extract against dexamethasone-induced hepatic and renal dysfunction in a female albino rat. Twenty-eight adult female rats were divided randomly into four equal groups: Group 1: animals were injected subcutaneously with saline and consider as normal control one. Group 2: animals were injected subcutaneously with dexamethasone in a dose of 0.1 mg/kg body weight. Group 3: animals were injected subcutaneously with 0.1 mg/kg body weight of dexamethasone, and then treated with a grape seed extract in a dose of 200 mg/kg body weight by oral gavage. Group 4: animals were injected subcutaneously with 0.1 mg/kg body weight of dexamethasone, and then treated with a grape seed extract in a dose of 400 mg/kg body weight by oral gavage. After 4 weeks, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, albumin, uric acid, creatinine, and glucose levels were assayed. Hepatic reduced glutathione (GSH), total protein content, and catalase and glucose-6-phosphate dehydrogenase activities were also assayed. Dexamethasone administration caused elevation of serum levels of glucose, uric acid, creatinine, ALT, AST activities, and a decrease in other parameters such as hepatic glutathione, total protein levels, and catalase enzyme activity. Treatment with Vitis vinifera L. seed extract showed a significant increase in the body weight of rats in the group treated with Vitis vinifera L. seed extract orally compared with the dexamethasone control group. An increase in GSH and catalase activity in response to oral treatment with Vitis vinifera L. seed extract was observed after treatment. Grape seed extract positively affects glucocorticoid-induced hepatic and renal alteration in albino rats. PMID:29051443

Therapeutic potency of bee pollen against biochemical autistic features induced through acute and sub-acute neurotoxicity of orally administered propionic acid.

PubMed

Al-Salem, Huda S; Bhat, Ramesa Shafi; Al-Ayadhi, Laila; El-Ansary, Afaf

2016-04-23

It is now well documented that postnatal exposure to certain chemicals has been reported to increase the risk of autism spectrum disorder. Propionic acid (PA), as a metabolic product of gut microbiotaandas a commonly used food additive, has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental neurotoxic agents and drugs that can ameliorate neurotoxicity and may thereby aid in the treatment of autism. The present study investigated the ameliorative effects of natural bee pollen against acute and sub-acute brain intoxication induced by (PA) in rats. Twenty-four young male Western Albino ratswere enrolled in the present study. They were classified into four equal groups, eachwith6 rats. The control group received only phosphate buffered saline; the oral buffered PA-treated groups (II and III) received a neurotoxic dose of 750 mg/kg body weight divided in 3 dose of 250 mg/kg body weight/day serving asthe acute group and 750 mg/kg body weight divided in 10 equal dose of 75 mg/kg body weight/day as the sub-acute group. The fourth group received 50 mg bee pollen for 30 days after PA-acute intoxication. The obtained data showed that the PA-treated groups demonstrated multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), dopamine and nor-adrenaline, together withan increase in IFN-γ and caspase 3. Bee pollen was effective in ameliorating the neurotoxic effect of PA. All measured parameters demonstrated minimal alteration in comparison with thecontrol animal than did those of acute and sub-acute PA-treated animals. In conclusion, bee pollen demonstrates anti-inflammatory and anti-apoptotic effects while ameliorating the impaired neurochemistry of PA-intoxicated rats.

Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis.

PubMed

Koie, Takuya; Mitsuzuka, Koji; Yoneyama, Takahiro; Narita, Shintaro; Kawamura, Sadafumi; Kaiho, Yasuhiro; Tsuchiya, Norihiko; Tochigi, Tatsuo; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara; Yoneyama, Tohru; Tobisawa, Yuki

2015-10-01

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca. The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS. The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110). Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.

Concomitant Anticonvulsants With Bitemporal Electroconvulsive Therapy: A Randomized Controlled Trial With Clinical and Neurobiological Application.

PubMed

Rakesh, Gopalkumar; Thirthalli, Jagadisha; Kumar, Channaveerachari Naveen; Muralidharan, Kesavan; Phutane, Vivek H; Gangadhar, Bangalore N

2017-03-01

Electroconvulsive therapy (ECT) is an effective treatment for major affective disorders. The combined use of ECT and anticonvulsant mood stabilizers is a common clinical scenario. There is dearth of systematic studies on the use of this combination with regard to clinical or cognitive outcomes. We aimed to compare clinical improvement and cognitive adverse effects between patients who received only ECT versus those who received ECT and anticonvulsants. We hypothesized that improvement would be fastest in patients who received only ECT. We conducted a randomized controlled trial in which patients prescribed ECT while being treated with anticonvulsants were randomized into 3 groups: full-dose (FD), half-dose (HD), and stop anticonvulsant. A blind rater assessed clinical improvement in patients using rating scales [Young's Mania Rating Scale (YMRS) and Clinical Global Impression] for clinical improvement and cognitive adverse effects (Postgraduate Institute memory scale). Analysis was done using mixed-effects modeling to delineate differences in clinical and cognitive outcomes across the 3 arms of the study over the course of ECT. Of the 54 patients recruited, 36 patients went into treatment allocation arms per the initial randomization plan. The main anticonvulsants prescribed were sodium valproate and carbamazepine. Patients in the 3 groups were comparable on clinical features. The most common diagnosis was bipolar affective disorder-with current episode of mania. Overall, there was no difference across the 3 groups in final clinical outcome scores (YMRS and Clinical Global Impression) when analyzed as intention to treat (ITT) or "as treated." In both analyses, group × time interaction was significant when comparing trend of YMRS scores between the FD anticonvulsant group and the HD group from baseline to last ECT (P = 0.0435 in ITT and P = 0.0055 in as treated). Patients in the FD group improved faster than those in the HD group. There were no differences across the 3 groups with regard to their cognitive adverse effects in the ITT analysis; "as-treated analysis" showed the HD patients to have performed poorly on some domains. Seizure parameters showed no significant difference across the 3 groups. This is a preliminary prospective study examining whether coprescription of anticonvulsants with ECT affected clinical or cognitive outcomes. The most important takeaway point from this study is the significant reduction in YMRS scores when ECT was given with FD anticonvulsant compared with halving the dose (HD) of anticonvulsant. This difference was shown in both ITT and as-treated analysis. There is a need for more prospective studies to examine this clinical question.

After low and high dose-rate interstitial brachytherapy followed by IMRT radiotherapy for intermediate and high risk prostate cancer.

PubMed

Nakamura, Satoshi; Murakami, Naoya; Inaba, Koji; Wakita, Akihisa; Kobayashi, Kazuma; Takahashi, Kana; Okamoto, Hiroyuki; Umezawa, Rei; Morota, Madoka; Sumi, Minako; Igaki, Hiroshi; Ito, Yoshinori; Itami, Jun

2016-05-03

The study aimed to compare urinary symptoms in patients with clinically localized prostate cancer after a combination of either low-dose-rate or high-dose-rate interstitial brachytherapy along with intensity-modulated radiation therapy (LDR-ISBT + IMRT or HDR-ISBT + IMRT). From June 2009 to April 2014, 16 and 22 patients were treated with LDR-ISBT + IMRT and HDR-ISBT + IMRT, respectively. No patient from these groups was excluded from this study. The prescribed dose of LDR-ISBT, HDR-ISBT, and IMRT was 115 Gy, 20 Gy in 2 fractions, and 46 Gy in 23 fractions, respectively. Obstructive and irritative urinary symptoms were assessed by the International Prostate Symptom Score (IPSS) examined before and after treatments. After ISBT, IPSS was evaluated in the 1st and 4th weeks, then every 2-3 months for the 1st year, and every 6 months thereafter. The median follow-up of the patients treated with LDR-ISBT + IMRT and HDR-ISBT + IMRT was 1070.5 days and 1048.5 days, respectively (p = 0.321). The IPSS-increment in the LDR-ISBT + IMRT group was greater than that in the HDR-ISBT + IMRT between 91 and 180 days after ISBT (p = 0.015). In the LDR-ISBT + IMRT group, the IPSS took longer time to return to the initial level than in the HDR-ISBT + IMRT group (in LDR-ISBT + IMRT group, the recovery time was 90 days later). The dose to urethra showed a statistically significant association with the IPSS-increment in the irritative urinary symptoms (p = 0.011). Clinical outcomes were comparable between both the groups. Both therapeutic modalities are safe and well suited for patients with clinically localized prostate cancer; however, it took patients longer to recover from LDR-ISBT + IMRT than from HDR-ISBT + IMRT. It is possible that fast dose delivery induced early symptoms and early recovery, while gradual dose delivery induced late symptoms and late recovery. Urethral dose reductions were associated with small increments in IPSS.

Study on the protection of CDP-choline against nicotine intoxication.

PubMed

Grau, T; Romero, A; Sacristán, A; Ortiz, J A

1983-01-01

Cytidine diphosphate choline (CDP-choline, citicoline, Somazina) was orally administered to a group of mice at a dose of 1 g/kg for 4 days. Simultaneously, another group of mice were treated under similar conditions with 0.25% agar suspension. Then, animals were distributed into subgroups of 10 mice each and intravenous increasing doses of nicotine bitartrate were administered. By comparing the toxicity induced by nicotine in the animals receiving CDP-choline with that in animals receiving agar solution, a remarkable difference of the LD50 was observed between both groups.

Controlling Mitochondrial Dynamics to Mitigate Noise-Induced Hearing Loss

DTIC Science & Technology

2017-10-01

protection against outer hair cell loss at the high frequency responsive region of the organ of Corti was observed. Importantly, these findings demonstrated...a high dose would be detrimental to hearing sensitivity or to outer hair cell viability. The 25 and 100 µM doses were similar to the 50 µM dose in...Completion of outer hair cell counts on the 200 µM study group revealed that this higher dose did not reduce OHC survival in the treated ear

Characteristics and Treatment of Breakthrought Pain (BTcP) in Palliative Care

PubMed Central

Husic, Samir; Imamovic, Semir; Matic, Srecko; Sukalo, Aziz

2017-01-01

Introduction: This research was to follow characteristics of breakthrough pain caused by cancer (BTcP) and other most common sympthoms (ESAS) at patients in advanced stage of cancer disease in palliative care. Patients and methods: Prospective study included 433 patients which were treated in Palliative Care Centre in UKC Tuzla, Bosnia and Herzegovina. Group 1 was consisted of 353 patients whose basal cancer pain of intensity 4-7 NRS was treated weak opiates (basal analgetic- fixed combination of tramadol/paracetamol (37.5 mg/325 mg) in initial dose 3x1tbl for pain intensity 4, to 4x2tbl (for pain intensity 7). In Group 2 (80 patients) basal pain of intensity 8-10 was treated strong opiates as basal analgetic (oral morphine and transdermal fentanil). If the previous day were 2 or more breakthrough pain that required ‘’rescue dose’’ of analgetics (tramadol 50-100 mg orally in group 1 ie. Oral morphine 8-12 mg in the group 2), the dose of basal analgetic was increased. Results: The total number of reported breakthrough pain in all 433 patients for 10 days of treatment was 3 369 (0.78 BTcP /per patient/day), where at Group 1 patients showed significantly lower BTcP (0.56 BTcP/patient/day). The average intensity of BTcP was 5.91 where in the Group1 was 4.51 while in the Group 2 8.04. 582 (17.28%) was rated grade 7, of which 539 were successfully coupled by strong and 43 (7.39%) successfully coupled by weak opiates. From 556 BTcP who were rated with 8, 540 of them were coupled strong and only 16 successfully coupled by weak opiates. 1967 (58.39 %) of breakthrough pain has occured in the evening hours (18-06 h), while 1402 (41.62%) BTCP occured during day hours (06-18h). Most (1290 or 38.29%) of breakthrough pain lasted less than 10 minutes, 882 (26.18%) between 16 and 20 minutes, 752 (22.32%) between 11 and 15 minutes, 407 (12.8%) between 21 and 30 minutes and 38 (1.13%) lasted longer than 20 minutes. Conclusion: Duriong our study, we noted a relatively large number of breakthrough pain with lower intensity (3-6) in patients treated with weak opiates, which are also adversely affected patients satisfaction with pain treatment and required additional doses of analgetics. In the small percentage is possible the breakthrough pain of stronger intensity (7-8) treat by maximum doses of weak opiates. PMID:28974843

Random Forest Segregation of Drug Responses May Define Regions of Biological Significance.

PubMed

Bukhari, Qasim; Borsook, David; Rudin, Markus; Becerra, Lino

2016-01-01

The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF) method to detect differences in the pharmacological MRI (phMRI) response in rats to treatment with an analgesic drug (buprenorphine) as compared to control (saline). Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD), and high dose (HD), and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus, and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow a supervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies.

Mal-Development of the Penis and Loss of Fertility in Male Rats Treated Neonatally with Female Contraceptive 17α-Ethinyl Estradiol: A Dose-Response Study and a Comparative Study with a Known Estrogenic Teratogen Diethylstilbestrol

PubMed Central

Mathews, Ensa; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Bolden-Tiller, Olga; Goyal, Hari O.

2009-01-01

The objectives of this study were to find a minimal dose of 17α-ethinyl estradiol (EE) that is detrimental to the developing penis and fertility and to compare estrogenic effects between EE and diethylstilbestrol (DES). Neonatal rats received EE at 10 ng (1 μg/kg), 100 ng, 1 μg, or 10 μg per pup on alternate days from postnatal days 1 to 11 (dose-response study) or received EE or DES at 100 ng per pup daily from postnatal days 1 to 6 (comparative study). Effects of EE were dose dependent, with ≥ 100-ng dose inducing significant (p < 0.05) reductions in penile length, weight, and diameter. Additionally, the penis was malformed, characterized by underdeveloped os penis and accumulation of fat cells. Fertility was 0% in the ≥ 1-μg groups, in contrast to 60% in the 100-ng group and 100% in the 10-ng and control groups. Animals treated with ≥ 10 ng had significant reductions in the weight of bulbospongious muscle, testis, seminal vesicle, epididymal fat pad, and in epididymal sperm numbers. A comparison of EE and DES effects showed similar reductions in penile weight and length and the weight of bulbospongiosus muscle, testis, seminal vesicle, epididymis, and epididymal fat pad in both adolescent and adult rats. While 5/6 control males sired, only 1/6 in the EE group and 0/6 in the DES group sired. Hence, neonatal exposure to EE at 10 ng (environmentally relevant dose) adversely affects male reproductive organs. A dose ten times higher than this leads to permanently mal-developed penis and infertility. Furthermore, EE and DES exposures show similar level of toxicity to male reproductive organs. PMID:19729556

The anti-hyperuricemic effect of epigallocatechin-3-gallate (EGCG) on hyperuricemic mice.

PubMed

Zhu, Chuang; Xu, Yan; Liu, Zeng-Hui; Wan, Xiao-Chun; Li, Da-Xiang; Tai, Ling-Ling

2018-01-01

Epigallocatechin-3-gallate (EGCG), a major constituent of green tea catechin, has been used for antioxidant. This study aimed to evaluate the antihyperuricemic activity of EGCG on hyperuricemic mice. We demonstrated that serum uric acid (UA) level was decreased significantly with dose-dependence by EGCG treated with 10, 20, and 50mg/kg. Compared with the model, data on blood urea nitrogen (BUN) supported that there was significance with high dose of EGCG (50mg/kg). Levels of serum creatinine (Cr) in each EGCG-treated group were decreased but not significant; the activities of hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) in high dose groups' EGCG were notably lower than those of model group. EGCG could downregulate the renal mRNA expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) on hyperuricemic mice. These results presented that EGCG had obvious hypouricemic and renal protective effects on hyperuricemic mice. Our data may have a potential value in clinical practice in the treatment of hyperuricemia. Copyright © 2017. Published by Elsevier Masson SAS.

Maternal and developmental toxicity of ayahuasca in Wistar rats.

PubMed

Oliveira, Carolina Dizioli Rodrigues; Moreira, Camila Queiroz; de Sá, Lilian Rose Marques; Spinosa, Helenice de Souza; Yonamine, Mauricio

2010-06-01

Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five-fold TD and 10-fold TD] during the gestational period (6-20 days). Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate- and high-dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose-dependent.

Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine--results from phase 1 of the REALIZE Study.

PubMed

Gawel, Marek; Aschoff, Jürgen; May, Arne; Charlesworth, Bruce R

2005-01-01

The objective of phase 1 (reported here) of this two-phase study was to assess the efficacy of zolmitriptan 5 mg nasal spray, in terms of ability to provide relief from all migraine symptoms, in a controlled setting, designed to replicate clinical practice. Zolmitriptan nasal spray has been shown to be fast acting and highly effective in the treatment of migraine, as assessed using standard endpoints, such as headache response and pain-free rates. In the double-blind first phase of the study, patients with migraine were randomized to receive zolmitriptan 5 mg nasal spray or placebo to treat a single migraine attack. Attacks were treated according to patients' normal patterns of use, in order to closely reflect clinical practice; that is, no specific regimen was dictated in terms of time to treatment or at what level of pain intensity the headache should be treated. Patients could take a second dose of study medication or an agreed escape medication if adequate pain relief had not been achieved 2 hours after the first dose. The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the first dose. Secondary efficacy endpoints included headache response, pain-free status and sustained pain-free status, and ability to perform normal activities. The intention-to-treat population comprised 461 zolmitriptan nasal spray recipients and 451 placebo recipients. The total symptom relief rate 1 hour post-dose was significantly higher in the zolmitriptan 5 mg nasal spray group than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the groups was significant from 30 minutes post-dose. Treatment with zolmitriptan nasal spray, compared with placebo, also produced a higher headache response rate from 10 minutes post-dose (15.1% vs. 9.1%; P = .0079) and a higher pain-free rate from 30 minutes post-dose (7.7% vs. 3.2%; P = .0039). Zolmitriptan nasal spray was also significantly superior to placebo in terms of sustained pain-free status and patients' ability to perform normal activities. Zolmitriptan nasal spray was well tolerated. These findings confirm the efficacy demonstrated by zolmitriptan nasal spray in previous clinical trials.

Reduction of radiation dose during facet joint injection using the new image guidance system SabreSource™: a prospective study in 60 patients

PubMed Central

Proschek, Dirk; Kafchitsas, K.; Rauschmann, M. A.; Kurth, A. A.; Vogl, T. J.

2008-01-01

Interventional procedures are associated with high radiation doses for both patients and surgeons. To reduce the risk from ionizing radiation, it is essential to minimize radiation dose. This prospective study was performed to evaluate the effectiveness in reducing radiation dose during facet joint injection in the lumbar spine and to evaluate the feasibility and possibilities of the new real time image guidance system SabreSource™. A total of 60 patients, treated with a standardized injection therapy of the facet joints L4–L5 or L5–S1, were included in this study. A total of 30 patients were treated by fluoroscopy guidance alone, the following 30 patients were treated using the new SabreSource™ system. Thus a total of 120 injections to the facet joints were performed. Pain, according to the visual analogue scale (VAS), was documented before and 6 h after the intervention. Radiation dose, time of radiation and the number of exposures needed to place the needle were recorded. No significant differences concerning age (mean age 60.5 years, range 51–69), body mass index (mean BMI 26.2, range 22.2–29.9) and preoperative pain (VAS 7.9, range 6–10) were found between the two groups. There was no difference in pain reduction between the two groups (60 vs. 61.5%; P = 0.001) but the radiation dose was significantly smaller with the new SabreSource™ system (reduction of radiation dose 32.7%, P = 0.01; reduction of mean entrance surface dose 32.3%, P = 0.01). The SabreSource™ System significantly reduced the radiation dose received during the injection therapy of the lumbar facet joints. With minimal effort for the setup at the beginning of a session, the system is easy to handle and can be helpful for other injection therapies (e.g. nerve root block therapies). PMID:19082641

Acute Effects of Ecstasy on Memory Are more Extensive than Chronic Effects.

PubMed

Shariati, Mohamad Bakhtiar Hesam; Sohrabi, Maryam; Shahidi, Siamak; Nikkhah, Ali; Mirzaei, Fatemeh; Medizadeh, Mehdi; Asl, Sara Soleimani

2014-01-01

Exposure to 3, 4- methylenedioxymethamphetamine (MDMA) could lead to serotonergic system toxicity in the brain. This system is responsible for learning and memory functions. Studies show that MDMA causes memory impairment dose-dependently and acutely. The present study was designed to evaluate the chronic and acute effects of MDMD on spatial memory and acquisition of passive avoidance. Adult male Wistar rats (200-250 g) were given single or multiple injections of MDMA (10 mg/kg, IP). Using passive avoidance and Morris Water Maze (MWM) tasks, learning and spatial memory functions were assessed. The data were analyzed by SPSS 16 software and one- way analysis of variance (ANOVA) test. Our results showed that there were significant differences in latency to enter the dark compartment (STL) between sham and MDMA- treated groups. Acute group significantly showed more STL in comparison with chronic group. Furthermore, MDMA groups spent more time in dark compartment (TDS) than the sham group. Administration of single dose of MDMA significantly caused an increase in TDS compared with the chronic group. In the MWM, MDMA treatment significantly increased the traveled distance and escaped latency compared to the sham group. Like to passive avoidance task, percentage of time spent in the target quadrant in MDMA- treated animals impaired in MWM compared with sham group. These data suggest that MDMA treatment impairs learning and memory functions that are more extensive in acute- treated rats.

A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes.

PubMed

Goldberg, R B; Einhorn, D; Lucas, C P; Rendell, M S; Damsbo, P; Huang, W C; Strange, P; Brodows, R G

1998-11-01

The objective of the study was to assess the efficacy and safety of repaglinide compared with placebo in the treatment of patients with type 2 diabetes. This was a phase II multicenter, double-blind, placebo-controlled, randomized, dose-adjustment and maintenance trial. After screening and a 2-week washout period, 99 patients were randomized to receive either repaglinide (n = 66) or placebo (n = 33). Patients underwent 6 weeks of dose adjustment followed by 12 weeks of dose maintenance. Fasting and stimulated glycosylated hemoglobin (HbA1c), plasma glucose, insulin, and C-peptide were measured at predetermined intervals. Adverse events and hypoglycemic episodes were recorded. From baseline to last visit, mean HbA1c decreased from 8.5 to 7.8% in patients treated with repaglinide and increased from 8.1 to 9.3% in patients receiving placebo, with a statistically significant difference of - 1.7% (P < 0.0001) between treatment groups at the last visit. Mean fasting plasma glucose and postprandial glucose increased in patients receiving placebo and decreased in patients treated with repaglinide, with statistically significant (P < 0.01) differences between groups at the last visit. Concentrations of fasting and postprandial insulin and C-peptide were lower at the last visit compared with baseline for patients treated with placebo and higher for patients treated with repaglinide, and the differences between groups were statistically significant (P < 0.05). Overall, repaglinide was well tolerated. This study demonstrated that repaglinide was safe and efficacious in lowering blood glucose concentrations. In addition to overall improvement in glycemic control noted with repaglinide in both sulfonylurea-treated patients and oral hypoglycemic agent-naive patients, repaglinide had a potent glucose-lowering effect in the postprandial period.

The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

PubMed

Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

2015-02-01

Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.

A Comparison Study of Quetiapine and Risperidone's Effectiveness and Safety on Treating Alcohol-induced Mental Disorder.

PubMed

Lv, Bei; Duan, Haishui

2016-08-25

Compared with Risperidone, Quetiapine's effectiveness and safety on treating alcohol-induced mental disorder is still unclear. To investigate the clinical effectiveness and safety of Quetiapine on treating alcohol-induced mental disorder. One hundred and forty-eight patients with alcohol-induced mental disorder were divided into the experimental group (75 patients) and the control group (73 patients) by the treatments they received. The patients in the experimental group were treated with Quetiapine by taking it three times per day orally. The mean (sd) maintenance dose was 151.2(27.3) mg/d, and the treatment cycle was 6 weeks. Patients in the control group received Risperidone once per day orally with a mean (sd) maintenance dose being 2.3(0.9) mg/d, and the treatment cycle was 6 weeks as well. The PANSS scale was used to assess patients' before and after treatment. The researchers also observed any adverse reactions in both treatment strategies and evaluated the effectiveness and safety of both treatment strategies. The mean (sd) PANSS scale score of the experimental group after two weeks of treatment was 71.9 (10.2), which was clearly better than the mean (sd) score before treatment (82.6 [11.4]), and was significantly better than the control group's mean (sd) score after two weeks (76.5[12.8]). Also, the experimental group's scores after 4 weeks of treatment and 6 weeks of treatment were significantly better than the control group. The experimental group's efficacy rate (94.7%) was higher than the control group's (90.4%); the cure rate of the experimental group (33.3%) was higher than that of the control group (24.7%), and the difference was statistically significant. The rates of adverse reactions in the experimental and control groups were 13.3% and 19.2% respectively, and they were significantly different from each other. Treating alcohol-induced mental disorder with Quetiapine is more effective than treating it with Risperidone. Quetiapine can improve patients' symptoms quickly, and lower the chance of adverse reactions. It is effective and safe.

High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery.

PubMed

Johnson, Daniel J; Johnson, Christine C; Goobie, Susan M; Nami, Nina; Wetzler, Joshua A; Sponseller, Paul D; Frank, Steven M

2017-12-01

Our objective was to quantify blood loss and transfusion requirements for high-dose and low-dose tranexamic acid (TXA) dosing regimens in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis. Previous investigators have established the efficacy of TXA in pediatric scoliosis surgery; however, the dosing regimens vary widely and the optimal dose has not been established. We retrospectively analyzed electronic medical records for 116 patients who underwent spinal fusion surgery for idiopathic scoliosis by a single surgeon and were treated with TXA. In total, 72 patients received a 10 mg/kg loading dose with a 1 mg/kg/h maintenance dose (low-dose) and 44 patients received 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose (high-dose). Estimated blood loss and transfusion requirements were compared between dosing groups. Patient characteristics were nearly identical between the 2 groups. Compared with the low-dose TXA group, the high-dose TXA group had decreased estimated blood loss (695 vs. 968 mL, P=0.01), and a decrease in both intraoperative (0.3 vs. 0.9 units, P=0.01) and whole hospitalization (0.4 vs. 1.0 units, P=0.04) red blood cell transfusion requirements. The higher-dose TXA was associated with decreased intraoperative (P=0.01), and whole hospital transfusion (P=0.01) requirements, even after risk-adjustment for potential confounding variables. High-dose TXA is more effective than low-dose TXA in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. Level-III, retrospective cohort study.

Comparative effects of cholesteryl ester transfer protein inhibition, statin or ezetimibe on lipid factors: The ACCENTUATE trial.

PubMed

Nicholls, Stephen J; Ray, Kausik K; Ballantyne, Christie M; Beacham, Lauren A; Miller, Debra L; Ruotolo, Giacomo; Nissen, Steven E; Riesmeyer, Jeffrey S

2017-06-01

The optimal approaches to management of patients treated with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study aimed to compare the effects of adding the cholesteryl ester transfer protein inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin-treated high-vascular risk patients on lipid parameters. 366 patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40 mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the United States. Lipid parameters, safety and tolerability were measured. Addition of evacetrapib significantly reduced LDL-C (-33%) compared with ezetimibe (-27%, p=0.045), increasing statin dose (-6%) and statin alone (0%, p<0.001). Evacetrapib also decreased apoB by 23% compared to 19% with ezetimibe (p=0.06) and 7% with increased statin dose (p<0.001), and reduced Lp(a) by 29% (p<0.001 vs. other groups). Evacetrapib increased HDL-C (+125%), apoA-I (+46%), apoC-III (+50%) and apoE (+28%) (p<0.001 vs. other groups). Non-ABCA1-mediated efflux increased by 53% (p<0.001 vs. other groups) with evacetrapib. ABCA1-mediated efflux also increased by 13% with evacetrapib (p<0.001 vs. ezetimibe, p=0.002 vs. increasing statin dose, and p=0.004 vs. statin alone). Addition of evacetrapib to atorvastatin produced an increase in hsCRP compared with ezetimibe (p=0.02). While evacetrapib improved traditional atherogenic and putative protective lipid measures compared with ezetimibe and increasing statin dose in patients with ASCVD and/or diabetes, it also adversely affected novel atherogenic risk factors. These findings may contribute to the lack of clinical benefit observed in the ACCELERATE trial. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term consumption of aspartame and brain antioxidant defense status.

PubMed

Abhilash, M; Sauganth Paul, M V; Varghese, Mathews V; Nair, R Harikumaran

2013-04-01

The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later?

PubMed

Cabanillas, Fernando

2010-09-01

In 1976 an article co-authored by Linus Pauling described that 100 terminal cancer patients treated with intravenous vitamin C, followed by oral maintenance, lived four times longer than a control group of 1,000 patients who did not receive vitamin C. The study was strongly criticized because the control group was very different from the group treated with vitamin C. The latter were declared terminally ill much sooner than the control group thus resulting in an artificially longer survival for the vitamin C group. Three double blind placebo controlled randomized trials performed at Mayo Clinic using oral vitamin C for cancer patients were negative. In a phase I-II trial performed by Riordan et al, none of 24 cancer patients treated with i.v. vitamin C responded. At this point we don't have information as to which is the actual plasma level of vitamin C that can produce tumor shrinkage. We don't have consistent information either regarding what is the clinical dose necessary to yield therapeutic plasma levels. In view of this lack of data after trials which have included at least 1,591 patients over 33 years, we have to conclude that we still do not know whether Vitamin C has any clinically significant antitumor activity. Nor do we know which histological types of cancers, if any, are susceptible to this agent. Finally, we don't know what the recommended dose of Vitamin C is, if there is indeed such a dose, that can produce an anti-tumor response.

Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

PubMed

Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-02-01

Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

Evaluating the effectiveness of a Mexican strain of Duddingtonia flagrans as a biological control agent against gastrointestinal nematodes in goat faeces.

PubMed

Ojeda-Robertos, N F; Mendoza-de Gives, P; Torres-Acosta, J F J; Rodríguez-Vivas, R I; Aguilar-Caballero, A J

2005-06-01

The use of Duddingtonia flagrans in the control of goat nematodes was investigated. Initially, the time of passage of chlamydospores through the digestive tract of goats was evaluated. Two groups of seven parasite-free kids were formed. Group A received a single dose of 3.5x10(6) D. flagrans chlamydospores (FTHO-8 strain) per kg of live weight. Group B did not receive any chlamydospores. Faeces were obtained from each kid daily from day 4 prior to inoculation until day 5 post-inoculation (PI) and were placed in Petri dishes containing water agar. Gastrointestinal nematode infective larvae were added to each Petri dish and incubated at 25 degrees C for 7 days. Petri dishes were examined to detect the fungus and trapped nematodes. A second trial evaluated the effect of D. flagrans on the number of gastrointestinal nematode larvae harvested from goat faecal cultures in naturally infected goats. Two groups of seven goats were formed. The treated group received a single dose of 3.5x10(6) D. flagrans chlamydospores per kg of liveweight. The control group did not receive any chlamydospores. Faeces were obtained twice daily from each kid. Two faecal cultures were made for each kid. One was incubated for 7 days and the other for 14 days. Gastrointestinal nematode larvae were recovered from each culture and counted. Percentage of larval development reduction was determined using a ratio of larvae/eggs deposited in the control and treated groups. Duddingtonia flagrans survived the digestive process of goats, and maintained its predatory activity, being observed from 21 to 81 h PI (3 to 4 days). A reduction in the infective larvae population in the treated group compared to the non-treated group was observed in both incubation periods (7 days: 5.3-36.0%; 14 days: 0-52.8%, P>0.05). Although a single inoculation of D. flagrans can induce a reduction of infective larvae collected from faeces, a different scheme of dosing may be needed to enhance the efficacy of D. flagrans in goats.

Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats

PubMed Central

Soffritti, Morando; Belpoggi, Fiorella; Tibaldi, Eva; Esposti, Davide Degli; Lauriola, Michelina

2007-01-01

Background In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the life span. Objective The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life. Methods We studied groups of 70–95 male and female Sprague-Dawley rats administered APM (2,000, 400, or 0 ppm) with feed from the 12th day of fetal life until natural death. Results Our results show a) a significant dose-related increase of malignant tumor–bearing animals in males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05). Conclusions The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of APM’s multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its carcinogenic effects are increased. PMID:17805418

COCAINE AND PAVLOVIAN FEAR CONDITIONING: DOSE-EFFECT ANALYSIS

PubMed Central

Wood, Suzanne C.; Fay, Jonathon; Sage, Jennifer R.; Anagnostaras, Stephan G.

2007-01-01

Emerging evidence suggests that cocaine and other drugs of abuse can interfere with many aspects of cognitive functioning. The authors examined the effects of 0.1 – 15 mg/kg of cocaine on Pavlovian contextual and cued fear conditioning in mice. As expected, pre-training cocaine dose-dependently produced hyperactivity and disrupted freezing. Surprisingly, when the mice were tested off-drug later, the group pre-treated with a moderate dose of cocaine (15 mg/kg) displayed significantly less contextual and cued memory, compared to saline control animals. Conversely, mice pre-treated with a very low dose of cocaine (0.1 mg/kg) showed significantly enhanced fear memory for both context and tone, compared to controls. These results were not due to cocaine’s anesthetic effects, as shock reactivity was unaffected by cocaine. The data suggest that despite cocaine’s reputation as a performance-enhancing and anxiogenic drug, this effect is seen only at very low doses, whereas a moderate dose disrupts hippocampus and amygdala-dependent fear conditioning. PMID:17098299

Evaluation of methyl methanesulfonate, 2,6-diaminotoluene and 5-fluorouracil: Part of the Japanese center for the validation of alternative methods (JaCVAM) international validation study of the in vivo rat alkaline comet assay.

PubMed

Plappert-Helbig, Ulla; Junker-Walker, Ursula; Martus, Hans-Joerg

2015-07-01

As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay (comet assay), we examined methyl methanesulfonate, 2,6-diaminotoluene, and 5-fluorouracil under coded test conditions. Rats were treated orally with the maximum tolerated dose (MTD) and two additional descending doses of the respective compounds. In the MMS treated groups liver and stomach showed significantly elevated DNA damage at each dose level and a significant dose-response relationship. 2,6-diaminotoluene induced significantly elevated DNA damage in the liver at each dose and a statistically significant dose-response relationship whereas no DNA damage was obtained in the stomach. 5-fluorouracil did not induce DNA damage in either liver or stomach. Copyright © 2015 Elsevier B.V. All rights reserved.

Cocaine and Pavlovian fear conditioning: dose-effect analysis.

PubMed

Wood, Suzanne C; Fay, Jonathan; Sage, Jennifer R; Anagnostaras, Stephan G

2007-01-25

Emerging evidence suggests that cocaine and other drugs of abuse can interfere with many aspects of cognitive functioning. The authors examined the effects of 0.1-15mg/kg of cocaine on Pavlovian contextual and cued fear conditioning in mice. As expected, pre-training cocaine dose-dependently produced hyperactivity and disrupted freezing. Surprisingly, when the mice were tested off-drug later, the group pre-treated with a moderate dose of cocaine (15mg/kg) displayed significantly less contextual and cued memory, compared to saline control animals. Conversely, mice pre-treated with a very low dose of cocaine (0.1mg/kg) showed significantly enhanced fear memory for both context and tone, compared to controls. These results were not due to cocaine's anesthetic effects, as shock reactivity was unaffected by cocaine. The data suggest that despite cocaine's reputation as a performance-enhancing and anxiogenic drug, this effect is seen only at very low doses, whereas a moderate dose disrupts hippocampus and amygdala-dependent fear conditioning.

Analysis of grayanatoxin in Rhododendron honey and effect on antioxidant parameters in rats.

PubMed

Sibel, Silici; Enis, Yonar M; Hüseyin, Sahin; Timucin, Atayoğlu A; Duran, Ozkok

2014-10-28

Rhododendron honey, locally known as "mad honey", contains gryanotoksin (GTX) and thus induces toxic effects when consumed in large amounts. But, it is still popularly used for treating medical conditions such as high blood pressure or gastro-intestinal disorders. The aim of this study was to evaluate the effect of GTX on antioxidant parameters measured from rats fed with Rhododendron honey. A total of sixty Sprague-Dawley female rats were divided into five groups of 12 rats each, one being the control group (Group 1) and the others being the experimental groups (Groups 2 to 5). Group 2 was treated with 0.015 mg/kg/bw of Grayanotoxin-III (GTX-III) standard preparation via intraperitoneal injection. Groups 3, 4 and 5 were respectively given Rhododendron honey (RH) at doses of 0.1, 0.5, and 2.5 g/kg/bw via oral gavage. After one hour, blood samples were collected from the rats. Glutathione peroxidase (GSh-Px), superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) contents were examined in blood, heart, lungs, liver, kidney, testicles, epididiymis, spleen and brain specimens. The data from the rats in Groups 2 (GTX) and 5 (RH at 2.5 g/kg/bw) showed negative effect on the antioxidants parameters in blood and all tissue samples examined at the specified doses and time period. Administration of GTX to rats at dose of 0.015 mg/kg/bw resulted in lipid peroxidation. (This part needs to be enhanced more). It has been observed that both Grayanotoxin and high dose Rhododendron honey treatments showed oxidant effect on blood plasma and organ tissues investigated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Piper sarmentosum is comparable to glycyrrhizic acid in reducing visceral fat deposition in adrenalectomised rats given dexamethasone.

PubMed

Fairus, A; Ima Nirwana, S; Elvy Suhana, M R; Tan, M H; Santhana, R; Farihah, H S

2013-01-01

Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.

Efficacy of oxfendazole and fenbendazole against tortoise (Testudo hermanni) oxyurids.

PubMed

Giannetto, S; Brianti, E; Poglayen, G; Sorgi, C; Capelli, G; Pennisi, M G; Coci, G

2007-04-01

Thirty-six tortoises (Testudo hermanni) with naturally acquired oxyurids infections were used to assess the anthelmintic efficacy of oxfendazole (Dolthene; Merial) and fenbendazole (Panacur; Hoechst Roussel Vet). Animals were randomly assigned to three groups (A, B, and C) based on sex and weight. Animals in group A (seven males and six females) were orally treated with oxfendazole at dose rate of 66 mg/kg, group B animals (nine males and eight females) were orally treated with fenbendazole at dose rate of 100 mg/kg, and group C animals (three males and three females) were not treated and served as controls. All animals were individually stabled in plexiglas boxes under controlled conditions of temperature, humidity, and light beginning 7 days pretreatment and continuing for the duration of the trial. Individual tortoises feces were examined daily by the McMaster technique and drugs efficacy was assessed by the fecal eggs count reduction (FECR) test. Both drugs showed 100% of FECR. However, oxfendazole reached this level 12 days after treatment, whereas 31 days after treatment were necessary to obtain the same stable result with fenbendazole. The two drugs were well tolerated by all the animals and no adverse reactions were observed after treatment.

[Effects of low doses of desmopressin (DDAPV) on gonadal and adrenal development, and on the testicular function and sperm motility].

PubMed

García-Pascual, I J; Sánchez-Yagüe, J; Rodríguez Hernández, M C; Paniagua Gómez-Alvárez, R

1994-04-01

The present study proved that desmopressin (DDAVP) (1 microgram DDAVP/12 h/5 días) does not affect ovary, testis and adrenal development in immature Wistar rats (17 days old), because the DDAVP does not modify the weight of the aforementioned organs as compared with the control group. Nevertheless, the male adults Wistar rats (80 days old) showed lower serum testosterone concentrations than the control group, after injection of 4 micrograms/day (2 micrograms/12 h) or 8 micrograms/day (4 micrograms/12 h) of DDAVP during a 5 days period time. Moreover, paradoxical significant lower concentrations of serum testosterone were found in 4 micrograms DDAVP/day-treated rats than in 8 micrograms DDAVP/day-treated ones. The former also showed a decreased number of spermatozoa as compared with the latter and with the control group. The percentage of mobile spermatozoa was lower in rats treated with both concentrations of DDAVP as compared with the control group. Therefore, desmopressin does not delay gonadal and adrenal growth in immature rats, but, at low doses, it affects the testicular function and the mobility of the spermatozoa in male adult rats.

Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia.

PubMed

Pierce, Dwayne A; Russell, Greg; Pirkle, James L

2015-12-01

Hyperkalemia is a potentially life-threatening condition that is common in kidney disease patients. Insulin is used to treat hyperkalemia, but may cause hypoglycemia, especially in kidney disease when insulin may be metabolized more slowly. We compared the rates of hypoglycemia in patients with low estimated glomerular filtration rate (eGFR) using high versus low doses of insulin for hyperkalemia to determine if lower doses of insulin would decrease the incidence of hypoglycemia. This was a retrospective study of hospitalized patients receiving intravenous insulin for hyperkalemia during a 6-month period. Patients with low eGFR were analyzed based on how much insulin they received: high dose (10 units, n = 78) versus low dose (5 units, n = 71). Postdose nadir blood glucose values were examined for up to 8 hours after the dose. The percentage of hypoglycemia (blood glucose ≤70 mg/dl) and a subset of severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose group. A total of 149 doses were identified in patients with low eGFR. The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic episodes with high doses occurred after 4 hours (median = 2.5 hours) compared with 14.3% with low doses (median = 2.38 hours). There was no difference in the rate of hypoglycemia or severe hypoglycemia between high or low doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours after insulin use in hyperkalemia. © The Author(s) 2015.

Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

PubMed

Rathi, N K; Tanner, A R; Dinh, A; Dong, W; Feng, L; Ensor, J; Wallace, S K; Haque, S A; Rondon, G; Price, K J; Popat, U; Nates, J L

2015-03-01

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.

Pregabalin attenuates excitotoxicity in diabetes.

PubMed

Huang, Chin-Wei; Lai, Ming-Chi; Cheng, Juei-Tang; Tsai, Jing-Jane; Huang, Chao-Ching; Wu, Sheng-Nan

2013-01-01

Diabetes can exacerbate seizures and worsen seizure-related brain damage. In the present study, we aimed to determine whether the standard antiepileptic drug pregabalin (PGB) protects against pilocarpine-induced seizures and excitotoxicity in diabetes. Adult male Sprague-Dawley rats were divided into either a streptozotocin (STZ)-induced diabetes group or a normal saline (NS) group. Both groups were further divided into subgroups that were treated intravenously with either PGB (15 mg/kg) or a vehicle; all groups were treated with subcutaneous pilocarpine (60 mg/kg) to induce seizures. To evaluate spontaneous recurrent seizures (SRS), PGB-pretreated rats were fed rat chow containing oral PGB (450 mg) for 28 consecutive days; vehicle-pretreated rats were fed regular chow. SRS frequency was monitored for 2 weeks from post-status epilepticus day 15. We evaluated both acute neuronal loss and chronic mossy fiber sprouting in the CA3 area. In addition, we performed patch clamp recordings to study evoked excitatory postsynaptic currents (eEPSCs) in hippocampal CA1 neurons for both vehicle-treated rats with SRS. Finally, we used an RNA interference knockdown method for Kir6.2 in a hippocampal cell line to evaluate PGB's effects in the presence of high-dose ATP. We found that compared to vehicle-treated rats, PGB-treated rats showed less severe acute seizure activity, reduced acute neuronal loss, and chronic mossy fiber sprouting. In the vehicle-treated STZ rats, eEPSC amplitude was significantly lower after PGB administration, but glibenclamide reversed this effect. The RNA interference study confirmed that PGB could counteract the ATP-sensitive potassium channel (KATP)-closing effect of high-dose ATP. By opening KATP, PGB protects against neuronal excitotoxicity, and is therefore a potential antiepileptogenic in diabetes. These findings might help develop a clinical algorithm for treating patients with epilepsy and comorbid metabolic disorders.

Vitamin D(3) is more potent than vitamin D(2) in humans.

PubMed

Heaney, Robert P; Recker, Robert R; Grote, James; Horst, Ronald L; Armas, Laura A G

2011-03-01

Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2) (D2) and D(3) (D3) are biologically equivalent. Published studies yield mixed results. The aim of the study was to compare the potencies of D2 and D3. The trial used a single-blind, randomized design in 33 healthy adults. Calciferols were dosed at 50,000 IU/wk for 12 wk. Principal outcome variables were area under the curve for incremental total 25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat. Incremental mean (sd) 25(OH)D area under the curve at 12 wk was 1366 ng · d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P < 0.001). Mean (sd) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2 (10.3) and 45 ng/ml (16.2) for D3 (P <0.001). Subcutaneous fat content of D2 rose by 50 μg/kg in the D2-treated group, and D3 content rose by 104 μg/kg in the D3-treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated, whereas it rose by 104 μg/kg in the D3-treated group. Extrapolating to total body fat D3, storage amounted to just 17% of the administered dose. D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.

Retrospective Analysis of Local Control and Cosmetic Outcome of 147 Periorificial Carcinomas of the Face Treated With Low-Dose Rate Interstitial Brachytherapy

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

Ducassou, Anne, E-mail: anned40@hotmail.com; David, Isabelle; Filleron, Thomas

2011-11-01

Purpose: Skin cancer is the most common malignancy in white populations. We evaluated the local cure rate and cosmetic outcome of patients with basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the face treated with low-dose rate brachytherapy. Methods and Materials: Between February 1990 and May 2000, 147 facial carcinomas in 132 patients were treated by {sup 192}Ir wire implantation. Side effects of brachytherapy were noted. Follow-up was 2 years or more. Locoregional recurrence-free survival (LRFS) and overall survival were recorded. Group A included patients treated by primary brachytherapy, and Group B included those treated after recurrence. Results:more » A total of 121 carcinomas were BCCs (82.3%) and 26 were SCCs (17.7%); the median tumor size was 10 mm. Of the tumors, 86 (58.5%) were in men and 61 (41.5%) were in women; the median age was 71 years. Group A comprised 116 lesions (78.9%), and Group B, 31 (21.1%). There were 17 relapses (11.6%) after a median follow-up of 72 months: 12 local, 4 nodal, and 1 local and nodal. Locoregional-free survival was 96.6% at 2 years and 87.3% at 5 years. Five-year LRFS was 82.6% in men and 93.3% in women (p = 0.027). After adjustment for gender, LRFS was better after primary treatment than after recurrence (hasard ratio HR, 2.91; 95% confidence interval, 1.06-8.03; p = 0.039). Five-year LRFS was 90.4% for BCC and 70.8% for SCC (p = 0.03). There were no Grade 3 complications. Conclusions: Low-dose rate brachytherapy offers good local control and cosmetic outcome in patients with periorificial skin carcinomas, with no Grade 3 complications. Brchytherapy is more efficient when used as primary treatment.« less

Comparison of Antivenom Dosing Strategies for Rattlesnake Envenomation.

PubMed

Spyres, Meghan B; Skolnik, Aaron B; Moore, Elizabeth C; Gerkin, Richard D; Padilla-Jones, Angela; Ruha, Anne-Michelle

2018-06-01

This study compares maintenance with clinical- and laboratory-triggered (as-needed [PRN]) antivenom dosing strategies with regard to patient-centered outcomes after rattlesnake envenomation. This is a retrospective cohort study of adult rattlesnake envenomations treated at a regional toxicology center. Data on demographics, envenomation details, antivenom administration, length of stay, and laboratory and clinical outcomes were compared between the PRN and maintenance groups. Primary outcomes were hospital length of stay and total antivenom used, with a hypothesis of no difference between the two dosing strategies. A single regional toxicology center PATIENTS:: Three-hundred ten adult patients envenomated by rattlesnakes between 2007 and 2014 were included. Patients were excluded if no antivenom was administered or for receiving an antivenom other than Crofab (BTG International, West Conshohocken, PA). This is a retrospective study of rattlesnake envenomations treated with and without maintenance antivenom dosing. One-hundred forty-eight in the maintenance group and 162 in the PRN group were included. There was no difference in demographics or baseline envenomation severity or hemotoxicity (32.7% vs 40.5%; respectively; p = 0.158) between the two groups. Comparing the PRN with the maintenance group, less antivenom was used (8 [interquartile range, 6-12] vs 16 [interquartile range, 12-18] vials, respectively; p < 0.001), and hospital length of stay was shorter (27 hr [interquartile range, 20-44 hr] vs 34 hr [interquartile range, 24-43 hr], respectively; p = 0.014). There were no differences in follow-up outcomes of readmission, retreatment, or bleeding and surgical complications. Hospital length of stay was shorter, and less antivenom was used in patients receiving a PRN antivenom dosing strategy after rattlesnake envenomation.

IN VIVO EFFECT OF RUTA CHALEPENSIS EXTRACT ON HEPATIC CYTOCHROME 3A1 IN RATS

PubMed Central

Martínez-Pérez, Edith Fabiola; Hernández-Terán, Fernando; Serrano-Gallardo, Luis Benjamín

2017-01-01

Background: Since the time when drugs began to be used, it became evident that they could produce a therapeutic effect, but also a clinical condition of toxicity or no effect at all on humans, despite using the same doses in different patients. Such untoward effects were termed “drug idiosyncrasy” and also “idiosyncratic drug effects”, but the factors producing such diverse responses were never taken into account. Materials and Methods: Ruta chalepensis L. (fringed rue) is an herbaceous plant of the Rutaceae family used in traditional medicine due to its properties, such as its analgesic and antipyretic effects. This study used 25 male rats divided into five groups. Plant extract was administered to Groups 1 and 2 at doses of 100 and 30 mg/kg/day, respectively, for three days; Group 3 was administered 100 mg/kg/day of dexamethasone (DEX), as well as 100 mg/kg/day of Ruta chalepensis extract; Group 4 was administered 100 mg/kg/day of DEX and treated as positive control; Group 5 was treated as negative control and was administered a physiological solution. Twenty-four hours after the the last dose, the animals were sacrificed and their livers were extracted. Results: The aqueous extract of Ruta chalepensis, intraperitoneally administered, was able to induce cytochrome 3A1 in doses of 30 mg/kg/day, and a greater inducing effect occurs when the plant is co-administered in doses of 100 mg/kg/day with dexamethasone. Conclusion: This study suggests that aqueous extract of Ruta chalepensis can induce cytochrome 3a1. This study helps provide a better understanding of CYP3a regulation. Future in vitro work is needed to determine the compounds that produce the cytochrome modulation. PMID:28638868

Effect of palm oil (Elaeis guineensis) tocotrienols on mesenteric adipose tissue deposition and the expression of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1) in adrenalectomized rats treated with dexamethasone.

PubMed

Azwan, K; Farihah, H S; Fairus, A; Elvy, M R

2015-01-01

A study was done to investigate the effect of palm oil (Elaeis guineensis) tocotrienols on (1) rats mesenteric adipose tissue deposition (2) and 11β-HSD1 enzyme expression in mesenteric adipocyte. There is a necessity to find an inhibitor for the 11β-HSD1 enzyme which enhances the proliferation of mesenteric adipocyte tissue therefore curbing the onset of metabolic syndrome. A total of 35 male Spraque Dawley rats were divided into 5 different groups, i.e., a baseline control group (n=7), a sham operated group (n=7) and three experimental adrenalectomised groups (ADR) (n=21). Each of the experimental ADR group was given intramuscular dexamethasone (Dexa) with a dose of 120 μg/kg after 2 weeks post adrenalectomy and were divided into adrenalectomised control (n=7), Glycyrrhizic acid (GCA) treated (dose=120 mg/kg/day; n=7) and Palm Tocotrienol treated (dose=60 mg/kg/day; n=7) groups. These various treatments were given 6 days a week for 8 weeks via gastric gavage (following 2 weeks of adrenalectomy). Data is expressed as mean ± standard error mean (SEM), compared to each other using one-way analysis-of-variance (ANOVA) followed by Tukey's post hoc test and then a t-test. The results show that palm tocotrienol tend to slightly increase mesenteric adipose tissue deposition in rats. However, palm tocotrienol was also found to have potential in inhibiting the expression of 11β-HSD1 enzyme in mesenteric adipocytes. This study suggests palm tocotrienol inhibits 11β-HSD1 enzyme expression and activity.

Effects of nicotine on sperm characteristics and fertility profile in adult male rats: a possible role of cessation.

PubMed

Oyeyipo, Ibukun Peter; Raji, Yinusa; Emikpe, Benjamin Obukowho; Bolarinwa, Adeyombo Folashade

2011-07-01

Infertility is common among couples of child-bearing age and approximately half of known causes of primary infertility are attributable to male factor. It is still unclear whether the injurious effects of cigarette smoking on sperm characteristics and infertility are due to nicotine. Therefore, the present study investtigated the effects of orally administered of nicotine on sperm characteristics and libido in adult male albino rats. The study also sought nicotine effects on fertility rate, litter size and weight in female animals cohabited with nicotine treated male rats. Forty male and twenty-five female rats were used for the study. The male rats were divided into five groups and were treated for a period of 30 days with nicotine 0.5 mg/kg (low dose) and 1.0 mg/kg (high dose) per body weight while the control rats received 0.2 ml/kg normal saline. The fourth and fifth groups were gavaged with 0.5 mg/kg and 1.0 mg/kg body weight of nicotine but were left untreated for another 30 days. These groups served as the recovery groups. At the end of each experimental period, sperm analysis, fertility study, litter weight and size were determined. Sperm motility and count significantly decreased (P < 0.05) while the percentage of abnormality significantly increased (P < 0.05) in both treatment groups. However, there was an insignificant decrease (P > 0.05) in the viability and semen volume of the treated groups. Fertility studies revealed that nicotine reduced libido in male rats, litter weight and number delivered by the untreated female during the experiments. The present study showed that nicotine has a dose-dependent deleterious effect on the sperm characteristics and that fertility is ameliorated by nicotine cessation in male rats.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction Versus Treatment Switch

PubMed Central

Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; González, Hans Guerrero; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-01-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3–0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m2 (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0–606) mg/g to 216 (0–2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate. PMID:24556354

Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch.

PubMed

Weidemann, Frank; Krämer, Johannes; Duning, Thomas; Lenders, Malte; Canaan-Kühl, Sima; Krebs, Alice; Guerrero González, Hans; Sommer, Claudia; Üçeyler, Nurcan; Niemann, Markus; Störk, Stefan; Schelleckes, Michael; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Wanner, Christoph; Brand, Eva

2014-04-01

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3-0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m(2) (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0-606) mg/g to 216 (0-2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.

Effects of D-004, a lipid extract of the fruit of the Cuban royal palm (Roystonea regia) or the lipidosterolic extract of saw palmetto (Serenoa repens) on the sexual activity in male rats: A controlled, experimental study

PubMed Central

Fernández, Lilia C.; Mas, Rosa; Fernández, Julio; Mendoza, Sarahí; Gámez, Rafael; Pardo, Balia

2008-01-01

Background: The etiology of benign prostatic hyperplasia (BPH) is not completely understood, but hormonal changes in aging men seem to be pivotal. Dihydrotestosterone, a potent, active metabolite of testosterone, is formed by the enzymatic action of prostate 5α-reductase and causes cell growth and hyperplasia. Consistent with this action, male sexual dysfunction has been clinically documented to be among the drug-related adverse events associated with 5α-reductase inhibitors. The lipidosterolic extract of saw palmetto (LESP) fruit (Serenoa repens) has been used to treat BPH. D-004, a lipid extract of Roystonea regia Royal palm fruit, has been found to prevent prostatic hyperplasia induced by testoste-rone in rodents and to competitively inhibit prostate 5α-reductase activity in vitro. Objective: The purpose of this study was to assess the effects of D-004 and LESP, administered as single or repeated doses, on the sexual activity in male rats. Methods: This controlled, experimental study was conducted at the Pharmacology Department, Centre of Natural Products, National Centre for Scientific Research, Havana City, Cuba. Adult male Wistar rats weighing 250 to 300 g were randomized into 5 groups: 2 groups treated orally with D-004 (400 and 800 mg/kg); 2 groups treated orally with LESP (400 and 800 mg/kg); and 1 control group orally administered a water vehicle. Sexual activity behavior (the number of mounts and intromissions, mount latency, and intromission latency) was assessed during 2 observation periods: 90 minutes after the initial dose and at the end of the 30-day treatment. Latency was defined as time elapsed between the first mount and intromission. Results: A total of 50 rats (mean [SD] age, 10 [3] weeks; mean [SD] weight, 295 [10] g) were included in the experiment. There were no significant difterences in the mean number of mounts, intromissions, mount latency, or intromission latency in the groups treated with single or repeated doses of D-004 or LESP (400 and 800 mg/kg) compared with the controls. There was also no between-group difterence in mating behavior among the active treatment groups. All rats survived up to study completion, with normal behavior (weight gain, food intake, daily observations, without any sign of toxicity). There were no observable adverse events during the study. Conclusions: D-004 and LESP administered as a single dose or repeated doses for 30 days did not significantly affect male rat sexual activity behavior compared with a vehicle control group. PMID:24692784

Effect of chronic administration of sildenafil citrate (Viagra) on the histology of the retina and optic nerve of adult male rat.

PubMed

Eltony, Sohair A; Abdelhameed, Sally Y

2017-04-01

Abnormal vision has been reported by 3% of patients treated with sildenafil citrate (Viagra). Although many men use Viagra for an extended period for treatment of erectile dysfunction, the implications of the long term-daily use of it on the retina and optic nerve are unclear. To investigate the effect of chronic daily use of sildenafil citrate in a dose equivalent to men preferred therapeutic dose on the histology of the retina and optic nerve of adult male rat. Eighteen adult male Wistar rats were equally divided into three groups. Group I: control. Group II: treated with sildenafil citrate orally (10mg/kg/day) for 8 weeks. Group III (withdrawal): treated as group II and then left for 4 weeks without treatment. Specimens from the retina and optic nerve were processed for light and electron microscopy. In sildenafil citrate treated group, the retina and optic nerve revealed vacuolations and congested blood capillaries with apoptotic endothelial and pericytic cells, and thickened basal lamina. Caspase-3 (apoptotic marker) and CD31 (endothelial marker) expression increased. Glial cells revealed morphological changes: Müller cells lost their processes, activated microglia, astrocytic clasmatodendrosis, degenerated oligodendrocytes surrounded by disintegrated myelin sheathes of the optic nerve fibers. The retina and optic nerve of the withdrawal group revealed less vacuolations and congestion, and partial recovery of the glial cells. Chronic treatment with sildenafil citrate (Viagra) caused toxic effect on the structure of the retina and optic nerve of the rat. Partial recovery was observed after drug withdrawal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ameliorative effect of hydro-methanolic extract from roots of Rauwolfia serpentina on some biochemical parameters of type 1 diabetic mice.

PubMed

Azmi, Muhammad Bilal; Qureshi, Shamim A; Ahmed, Syed Danish Haseen; Mudassir, Hina Akram; Imtiaz, Fauzia; Rais, Sumera; Khan, Auwais Ahmed; Ahsan, Muhammad

2018-03-01

Present work seeks to investigate the biochemical parameters in terms of hypoglycemic and hypolipidemic effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 (alloxan induced) diabetic mice. Animals were divided into seven groups, four control groups, and three were test groups (HyMREt at 50, 100, & 150mg/kg). Each treatment was repeated for 14 days regularly in all seven respective groups and afterwards the body weights, fasting blood glucose (FBG), insulin, and serum lipid levels were determined. Total body weights of diabetic mice treated with HyMREt extract were dose dependently (p<0.05) improved. FBG of test groups were significantly (p<0.0001) reduced in comparison with diabetic controls which displayed elevated fasting blood glucose level. The insulin levels of HyMREt treated groups were significantly (p<0.0001) higher than those of diabetic controls. Lower triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and very low density lipoprotein cholesterol (VLDL-c) whereas elevated level of high density lipoprotein cholesterol (HDL-c) were observed in test dose treated groups. In comparison with diabetic controls, the converse levels of serum lipid were observed. Significant improvement in cardio-protective indices and coronary risk index was also observed. Findings of present study support the hypoglycemic and hypolipidemic potential of HyMREt of R. serpentina.

Effects of molybdenum and cadmium on the oxidative damage and kidney apoptosis in Duck.

PubMed

Shi, Lele; Cao, Huabin; Luo, Junrong; Liu, Ping; Wang, Tiancheng; Hu, Guoliang; Zhang, Caiying

2017-11-01

Molybdenum (Mo) is an essential element for human beings and animals; however, high dietary intake of Mo can lead to adverse reactions. Cadmium (Cd) is one of the major transitional metals which has toxic effects in animals. To investigate the co-induced toxic effects of Mo and Cd on oxidative damage and kidney apoptosis in duck, 120 ducks were randomly divided into control group and 5 treatment groups which were treated with a commercial diet containing different dosages of Mo and Cd. Kidney samples were collected on the 60th and 120th days to determine the mRNA expression levels of ceruloplasmin (CP), metallothionein (MT), Bak-1, and Caspase-3 by quantitative RT-PCR. Additionally, we also determined the antioxidant activity indexes and contents of Mo, Cd, copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) in serum. Meanwhile, ultrastructural changes of the kidney were observed. The results showed that glutathione reductase (GR) activity and CP level in serum were decreased in combination groups. In addition, the antioxidant indexes were decreased in co-treated groups compared with single treated groups. The mRNA expression levels of Bak-1 and Caspase-3 increased in co-treated groups. The mRNA expression level of CP in high-dose combination group was downregulated, while the mRNA expression of MT was upregulated except for low-dose Mo group. Additionally, in the later period the content of Cu in serum decreased in joint groups while the contents of Mo and Cd increased. In addition, ultrastructural changes showed mitochondrial crest fracture, swelling, deformed nuclei, and karyopyknosis in co-treated groups. Taken together, it was suggested that dietary Mo and Cd might lead to oxidative stress, kidney apoptosis and disturb homeostasis of trace elements in duck, and it showed a possible synergistic relationship between the two elements. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of levetiracetam on penicillin induced epileptic activity in rats.

PubMed

Arık, Aliye Erguvan; Bağırıcı, Faruk; Sefil, Fatih; Marangoz, Cafer

2014-01-01

The aim of this study was to investigate the effects of levetiracetam (LEV) on penicillin-induced epileptiform activity in rats. Penicillin was applied intracerebroventricularly (icv) at a dose of 500 IU to induce epileptiform activity. LEV was given intraperitoneally (ip) at doses of 20, 40, 80 mg/kg before penicillin injection. This agent reduced epileptiform activity by decreasing spike frequencies. The mean spike frequencies decreased significantly in all the LEV treated groups. There was no significant change in the spike amplitudes of the LEV groups compared with the control group. 40 mg/kg of LEV was determined as the most effective dose on reducing epileptiform activity. The results of this study suggest that LEV is an effective antiepileptic agent in penicillin-induced epilepsy.

Efficacy of Continuous Dosing of Tadalafil Once Daily vs Tadalafil On Demand in Clinical Subgroups of Men With Erectile Dysfunction: A Descriptive Comparison Using the Integrated Tadalafil Databases.

PubMed

Brock, Gerald; Ni, Xiao; Oelke, Matthias; Mulhall, John; Rosenberg, Matt; Seftel, Allen; D'Souza, Deborah; Barry, Jane

2016-05-01

Various factors play a role in the development of erectile dysfunction (ED). To provide a descriptive comparison of erectile function response for tadalafil on-demand (PRN) and once-daily (OAD) dosing regimens in patients with common comorbid conditions, treatments, or risk factors that can be considered when treating ED. In total, 17 PRN and 4 OAD placebo-controlled studies were included in the integrated database in these pooled analyses. Data were analyzed from patients treated with placebo, tadalafil 10 mg (low dose), and 20 mg (high dose) for the PRN studies and placebo, tadalafil 2.5 mg (low dose), and 5 mg (high dose) for the OAD studies. The effects of tadalafil were measured using the International Index of Erectile Function administered from baseline to week 12. A descriptive comparison of the efficacy of tadalafil PRN vs OAD was examined in the clinical populations. Baseline characteristics of 4,354 men were comparable between the PRN and OAD groups, with differences seen only in the variables of race, body mass index (BMI) of at least 30 kg/m(2), and alcohol use. Tadalafil was efficacious at improving erectile function for all clinical populations, except for the low-dose OAD group, which demonstrated a weaker effect vs placebo than the high-dose OAD group, and the low- and high-dose PRN groups vs placebo for patients with BMI of at least 30 kg/m(2) for patients without a cardiovascular disorder, smokers, patients with ED duration shorter than 1 year, and patients without previous phosphodiesterase type 5 inhibitor use. Tadalafil was efficacious for patients with or without diabetes mellitus, arterial hypertension, hyperlipidemia, and alcohol use at baseline. Tadalafil OAD and PRN regimens showed efficacy in patients with ED. No clinical populations of patients with ED seemed to benefit overwhelmingly from one dose regimen over the other. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of the therapeutic dose of warfarin in HIV-infected and HIV-uninfected patients: a study of clinical practice.

PubMed

Jackson, B S; Mokoena, T

2017-02-08

People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients. A prospective and retrospective descriptive study of induction time to therapeutic warfarin dose, as well as of ambulant therapeutic warfarin dose, was performed. HIV-infected and HIV-uninfected patients being treated after deep venous thrombosis with or without pulmonary embolism were compared. Sex and use of antiretroviral drugs (ARVs) were also compared in the groups. 234 patients were entered into the study. Induction time to therapeutic warfarin dose did not differ between the 2 groups. The mean therapeutic dose of warfarin was higher in the HIV-infected than the HIV-uninfected group: 6.06 vs 5.72 mg/day, but this was not statistically significant (p=0.29). There was no difference in therapeutic warfarin dose between ARV-naïve groups-HIV-uninfected and HIV-infected patients not on ARVs. There appears to be little effect of HIV infection on warfarin dosing. Warfarin therapy should be administered conventionally in HIV-infected patients. 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/.

Long-term outcome in patients with germ cell tumours treated with POMB/ACE chemotherapy: comparison of commonly used classification systems of good and poor prognosis.

PubMed Central

Hitchins, R. N.; Newlands, E. S.; Smith, D. B.; Begent, R. H.; Rustin, G. J.; Bagshawe, K. D.

1989-01-01

We analysed outcome in 206 consecutive male patients treated for metastatic non-seminomatous germ cell tumour (NSGCT) of testicular or extragonadal origin treated with the POMB/ACE (cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, etoposide) regimen after division into prognostic groups by commonly used clinical classification systems and definitions of adverse prognosis. The adverse prognostic groups of all classification systems and definitions examined showed similar, but only moderate, sensitivity (71-81%) and specificity (52-56%) in predicting death. A simple definition of poor prognosis based on raised initial levels of serum tumour markers alpha fetoprotein (aFP) and human chorionic gonadotrophin (hCG) proved at least as useful (sensitivity 80%, specificity 55%) as other more complicated systems in predicting failure to achieve long-term survival. Comparison of survival between ultra-high dose cisplatin-based combination chemotherapy and patients treated with POMB/ACE shows no advantage from this more toxic approach. This suggests that good results in adverse prognosis patients can be achieved using conventional dose regimens administered intensively. PMID:2467682

Effect of enrofloxacin on Haemophilus parasuis infection, disease and immune response.

PubMed

Macedo, Nubia; Cheeran, Maxim C J; Rovira, Albert; Holtcamp, Andrew; Torremorell, Montserrat

2017-02-01

Haemophilus parasuis, the causative agent of Glasser's disease, is a pathogen that colonizes the upper respiratory tract (URT) of pigs, invades the bloodstream and causes polyserositis. Because antimicrobials are highly effective against H. parasuis, we hypothesized that they could have a detrimental effect on the establishment of an immune response if given at the time of URT colonization. In this study, we characterized clinical outcomes and antibody and IFN-γ responses to H. parasuis in pigs treated with enrofloxacin before or after low dose inoculation with a pathogenic H. parasuis strain. Pigs that were only inoculated with the agent (EXP group) and pigs that were treated with enrofloxacin and then inoculated (ABT/EXP group) developed signs of disease starting at 4days post inoculation (DPI), presented a significant increase in serum IgG and were protected against a subsequent homologous challenge. In contrast, pigs treated with antibiotic after inoculation (EXP/ABT group) neither showed signs of disease nor seroconverted (IgG) after low dose inoculation. EXP/ABT pigs as well as naïve control pigs [enrofloxacin only (ABT) and challenge only (CHA)] were susceptible to challenge. Variable levels of antibodies in bronchioalveolar fluid and IFN-γ in peripheral blood mononuclear cells were observed after H. parasuis inoculation, but were not associated with protection. In summary, only pigs treated before low dose H. parasuis inoculation seroconverted and were protected against subsequent challenge. Results from this study can help determine timing of antimicrobial use and contribute to our current understanding of judicious antibiotic use. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals.

PubMed

Khakzad, Mohammad Reza; Mirsadraee, Majid; Mohammadpour, Amirhooshang; Ghafarzadegan, Kamram; Hadi, Raziye; Saghari, Mahdiye; Meshkat, Mojtaba

2012-04-01

Goblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice. Male BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale. Inflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57±1.30% for low dose; 1.50±0.93% for high dose versus 12.93±7.55%, P<0.05, respectively). Mucus production of goblet cells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45±0.30 for low dose; 0.81±1.00 for high dose versus 2.85±0.86 in the sensitized control group, P<0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized mice (15.1±0.43 versus 4.7±0.96, P<0.05 and 91.8±47.7 versus 14.8±4.6, P<0.01, respectively). Verapamil is a useful drug with therapeutic targeting on GCH and a potential way to limit mucous production and improve bronchial inflammation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Houttuynia cordata Thunb extract induces cytotoxicity in human nasopharyngeal carcinoma cells: Raman spectroscopic studies

NASA Astrophysics Data System (ADS)

Chen, Weiwei; Li, Zuanfang; Yu, Yun; Lin, Duo; Huang, Hao; Shi, Hong

2016-01-01

The molecular mechanisms of cytotoxicity induced by Houttuynia cordata Thunb (HCT) in nasopharyngeal carcinoma (NPC) cells was investigated by Raman spectroscopy (RS). The average Raman spectra of cell groups treated with HCT (0, 62.5, 125, 250, and 500 μg ml-1) for 24 h were measured separately. Compared to the control group, the intensities of the selected bands (1002, 1338, and 1448 cm-1) related to protein, DNA, and lipid in the treatment groups decreased obviously as the concentration of HCT increased. Both cell groups treated with 250 and 500 μg ml-1 of HCT could be differentiated from the control group by principal component analysis (PCA) combined with linear discriminate analysis (LDA) with a diagnostic accuracy of 100%, suggesting that cytotoxicity occurred and that 250 μg ml-1 was the proper dose for treatment. Simultaneously, the Raman spectra of cells treated with different treatment times with 250 μg ml-1 of HCT were obtained. We can get that treatment with HCT decreased cell viability in a dose and time-dependent fashion. The results indicated that the RS combined with PCA-LDA can be used for pharmacokinetics studies of HCT in NPC cells, which could also provide useful data for clinical dosage optimization for HCT.

Cisplatin encapsulated nanoparticle as a therapeutic agent for anticancer treatment

NASA Astrophysics Data System (ADS)

Eka Putra, Gusti Ngurah Putu; Huang, Leaf; Hsu, Yih-Chih

2016-03-01

The knowledge of manipulating size of biomaterials encapsulated drug into nano-scale particles has been researched and developed in treating cancer. Cancer is the second worldwide cause of death, therefore it is critical to treat cancers challenging with therapeutic modality of various mechanisms. Our preliminary investigation has studied cisplatin encapsulated into lipid-based nanoparticle and examined the therapeutic effect on xenografted animal model. We used mice with tumor volume ranging from 195 to 214 mm3 and then few mice were grouped into three groups including: control (PBS), lipid platinum chloride (LPC) nanoparticles and CDDP (cis-diamminedichloroplatinum(II) at dose of 3mg cisplatin /kg body weight. The effect of the treatment was observed for 12 days post-injection. It showed that LPC NPs demonstrated a better therapeutic effect compared to CDDP at same 3mg cisplatin/kg drug dose of tumor size reduction, 96.6% and 11.1% respectively. In addition, mouse body weight loss of LPC, CDDP and PBS treated group are 12.1%, 24.3% and 1.4%. It means that by compared to CDDP group, LPC group demonstrated less side effect as not much reduction of body weight have found. Our findings have shown to be a potential modality to further investigate as a feasible cancer therapy modality.

Effect of Methanolic Leaf Extract of Ocimum basilicum L. on Benzene-Induced Hematotoxicity in Mice

PubMed Central

Saha, S.; Mukhopadhyay, M. K.; Ghosh, P. D.; Nath, D.

2012-01-01

The aim of the present study was to investigate the protective role of methanolic leaf extract of Ocimum basilicum L. against benzene-induced hematotoxicity in Swiss albino mice. GC analysis and subacute toxicity level of the extract were tested. Mice were randomly divided into three groups among which II and III were exposed to benzene vapour at a dose 300 ppm × 6 hr/day × 5 days/week for 2 weeks and group I was control. Group III of this experiment was treated with the leaf methanolic extract at a dose of 100 mg/kg body weight, a dose in nontoxic range. Hematological parameters (Hb%, RBC and WBC counts), cell cycle regulatory proteins expression and DNA fragmentation analysis of bone marrow cells was performed. There was an upregulation of p53 and p21 and downregulation of levels of CDK2, CDK4, CDK6, and cyclins D1 and E in leaf extract-treated group. DNA was less fragmented in group III compared to group II (P < 0.05). The present study indicates that the secondary metabolites of O. basilicum L. methanolic leaf extract, comprising essential oil monoterpene geraniol and its oxidized form citral as major constituents, have modulatory effect in cell cycle deregulation and hematological abnormalities induced by benzene in mice. PMID:22988471

Immediate and residual effects of low-dose nandrolone decanoate and treadmill training on adipose and reproductive tissues of male Wistar rats.

PubMed

Rodrigues, Josilene M; Oliveira, Vinicius P P; P Furlan, Julia; Munhoz, Ana Claudia; S Rempel, Marcelo R; Brito, Marcia N; Brito, Nilton A; Pedrosa, Maria M D; M Costa, Cecília E

2017-05-01

Residual effects after nandrolone decanoate (ND) treatment are not reported. Immediate and residual effects of low-dose ND and treadmill training were investigated. Male rats were trained and/or ND-treated for four weeks and the assessments were made after this period or four weeks later. The groups did not differ in final plasma glucose or AUC of the ivGTT, but hyperinsulinemia was noticed in some trained/treated groups. Training with ND increased muscle mass and ND decreased the reproductive structures. Decreased fat with training was reversed by detraining. The anabolic action of ND on skeletal muscle was enhanced by training. Fat and lipid changes were more linked to training/detraining, but the effects of ND on the reproductive structures persisted after treatment. The effects of training on fat and muscle were not maintained after detraining, but low-dose ND had persistent effects on the reproductive structures.

Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice

PubMed Central

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu

2015-01-01

Objective: The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory. Materials and Methods: Mice were divided randomly into seven groups. Intra-peritoneal treatment of normal saline (10 ml/kg), caffeine (10 mg/kg), duloxetine (10 mg/kg), bupropion alone (10 mg/kg), caffeine + duloxetine (5 mg/kg, each), caffeine + bupropion (5 mg/kg, each), and bupropion + duloxetine (5 mg/kg, each) were given to groups I-VII, respectively. Elevated plus maze was used to evaluate transfer latency (TL) and Morris water maze was used to estimate the time spent in target quadrant. Results: Caffeine with duloxetine treated group was better than other combination treated groups in terms of a significant decrease in TL and increase in the time spent in target quadrant recorded. Conclusion: Combining lower dose of caffeine with duloxetine may enhance cognitive benefits than respective monotherapies. PMID:25878382

A study of the time of hospital discharge of differentiated thyroid cancer patients after receiving iodine-131 for thyroid remnant ablation treatment.

PubMed

Azizmohammadi, Zahra; Tabei, Faraj; Shafiei, Babak; Babaei, Ali Akbar; Jukandan, Seyed Mohsen Qutbi; Naghshine, Reza; Javadi, Hamid; Nabipour, Iraj; Assadi, Majid; Asli, Isa Neshandar

2013-01-01

The aim of this study was to measure the radiation exposure rate from differentiated thyroid carcinoma (DTC) patients who had received iodine-131 ((131)I) treatment, and to evaluate hospital discharge planning in relation to three different sets of regulations. We studied 100 patients, 78 females and 22 males, aged 13 to 79 years (mean 44.40±15.83 years) with DTC, in three Groups who were treated with 3.7, 5.5 or 7.4GBq of (131)I, respectively. The external whole-body dose rates following oral administration of (131)I were measured after each one of the first three hospitalization days. A multivariant linear analysis was performed, considering exposure rates as dependent variables to the administered dose for treatment, age, gender, regional and/or distant metastases, thyroglobulin (Tg), antibodies to Tg and thyroid remnant in the three dose groups. We found that the exposure rates after each of the three first days of hospitalization were 30, 50 and 70μSvh-1 at 1m. All our DTC patients had an acceptable dose rate on days 2 and 3 that allowed their hospital discharge. After only 1 day of hospitalization, just 3/11 cases showed not permissible exposure rates above 70μSvh-1. In conclusion, it is the opinion of the authors that after measuring the exposure rates, most treated, DTC patients could be discharged after only one day of hospitalization, even some of those treated with high doses of (131)I (7.4GBq). Patients, who received the higher doses of (131)I, should not be released before their individual exposure rate is measured.

Success rates of single-dose methotrexate and additional dose requirements among women with first and previous ectopic pregnancies.

PubMed

Cirik, Derya Akdag; Kinay, Tugba; Keskin, Ugur; Ozden, Eda; Altay, Metin; Gelisen, Orhan

2016-04-01

To compare the success of the single-dose methotrexate regimen and the requirement for a second or third dose of methotrexate between women with their first ectopic pregnancy (EP) and those with previous EP. In a retrospective cohort study, data were analyzed from women treated for EP by single-dose methotrexate at a Turkish tertiary referral center between January 2010 and December 2013. Data were compared between women with at least one previous EP and those with their first EP. The success rate of the protocol in the first and previous EP groups was similar: 93.0% (320/344) and 87.3% (48/55), respectively. History of previous EP was not a predictor of treatment failure. However, the requirement for additional methotrexate doses was significantly higher in the previous EP group (16/48 [33.4%]) than in the first EP group (55/320 [17.2%]; P=0.03). Multivariate analysis showed that history of tubal surgery (P=0.006) and initial levels of the β-subunit of human chorionic gonadotropin (P=0.001) were significant predictors of treatment failure. Although the single-dose regimen had similar success rates in the previous EP and first EP groups, additional doses of methotrexate were more frequently required in the previous EP group. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Endovascular aortic sealing with Nellix reduces intraoperative radiation dose when compared to endovascular aortic repair.

PubMed

Ockert, Stefan; Heinrich, Mirjam; Kaufmann, Thomas; Syburra, Thomas; Lopez, Ruben; Seelos, Robert

2018-04-01

To analyze radiation exposure during endovascular aortic sealing (EVAS) in comparison with standard endovascular aortic repair (EVAR) in clinical practice. From December 2013 to October 2016 (35 months), 60 patients were analyzed for intraoperative radiation exposure during EVAR: 30 consecutive patients (mean age, 73.10 years; 28 male) received EVAS (Nellix Endologix); within the same time frame, 30 patients were treated with standard EVAR (mean age, 71.87 years; 30 male). An indirect dose analysis was performed for both groups of patients, including effective dose and cumulative air kerma. Furthermore, fluoroscopy time (FT), dose area product, and time of procedure were included in the study. The effective dose was significantly reduced in the EVAS group (3.72 mSv) compared with the group treated with standard EVAR (6.8 mSv; P ≤ .001). The cumulative air kerma was also lowered in EVAS (67.65 mGy vs 139 mGy in EVAR; P ≤ .001). FT for the entire group was 13 minutes and was shorter (P < .001) for EVAS (9 minutes) in comparison with EVAR (19 minutes). The dose area product for the entire cohort was 16.95 Gy.cm 2 and was lower during EVAS (12.4 Gy.cm 2 ) than during EVAR (22.6 Gy.cm 2 ; P < .001). The median operating time for the entire group was 123.5 minutes and was significantly shorter (P < .01) for EVAS (119 minutes vs EVAR at 132 minutes). The FT shows a significant correlation with the patient's weight (P = .022), body mass index (P = .004), and time of procedure (P = .005). EVAS is associated with a relevant decrease in indirect measured radiation dose and time of procedure compared with standard EVAR. A relevant reduction in dose during EVAS is highly likely to result in lower exposure to radiation for physicians and staff. Such a result would be highly advantageous and calls for further analysis. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

[Study on protective effect of Tianji soft capsule on blood lipids, internal antioxidant system and vascular endothelial system in hyperlipidemia rats].

PubMed

Ma, Hai-ying; Chen, Jin-yao; Zhang, Li-shi

2011-11-01

To study the protective effects of Tianji soft capsule (TJSC) on blood lipids, internal antioxidant system and vascular endothelial system in hyperlipidemia rats. Seventy two healthy male rats were divided into six groups. The rats in control group were administered with ordinary diet. The rats in model group were fed with high cholesterol/lipid diet to induce hyperlipidemia. The rats in TJSC and CoQ10 groups were fed with high cholesterol/lipid diet, and treated with TJSC at different doses of 83 (low-dose group, L), 250 (middle-dose group, M), 750 (high-dose group, H) mg/kg, and CoQ10 at the dose of 83 mg/kg, respectively. All animals were put to death after four weeks, effects on lipid level; antioxidant system and endothelial system were evaluated through detection of total cholesterol (TC), triglyceride (TG), very low density lipoprotein (VLDL), atherogenic index (AI), malondidehyde (MDA) and plasma endothelin (ET), HDL/TC ratio, activities of superoxide dismutase (SOD) and nitric oxide (NO). Compared with model group, serum TC, TG, VLDL, AI, MDA and ET reduced and the HDL/TC ratio increased, meanwhile activities of SOD and NO were enhanced. TJSC can regulate the lipid metabolism, enhance antioxidant system and protect the vascular endothelia system in hyperlipiemic rats.

Acute toxic effects of single dose dacarbazine: hematological and histological changes in an animal model.

PubMed

Milijašević, B; Stefanović, D; Lalić-Popović, M; Tomić, Z; Kolarović, J; Lalošević, D; Mikov, M

2014-11-01

Treatment of advanced soft tissue sarcoma usually includes dacarbazine (DTIC), an alkylating agent that methylates DNA and is active during all phases of the cell cycle. Common side effects of DTIC include nausea, vomiting, impaired liver and kidney function, myelosuppression, and pneumonia. There are no accounts, however, of histological and hematological changes caused by DTIC. We investigated acute hematological and morphological changes in different organs and in tumors that were caused by a single dose of DTIC. Adult Syrian golden hamsters were inoculated with a suspension of tumorigenic baby hamster kidney (BHK) cells by subcutaneous injection. On day 14 after inoculation, doses of 1.4, 1.6, 1.8 or 2.0 g/m(2) DTIC were injected intraperitoneally into the hamsters. Hamsters in the control group were injected with physiological saline in the same way. Seven days after drug or saline injection the animals were sacrificed and samples of blood, heart, kidney, liver, lungs, spleen, small intestine and tumor were excised, processed and analyzed. Mitoses were counted using an ocular extension with engraved frame. Anemia, thrombocytopenia and leukocytosis were found in the control group of hamsters with fibrosarcoma, whereas animals with fibrosarcoma treated with DTIC developed anemia, thrombocytopenia and leukopenia. Severe pneumonia and moderate hepatitis were detected in all DTIC treated groups. Effects of DTIC on tumor cells included rounding and enlargement of nuclei and rarefaction of chromatin. The number of mitoses was reduced with increasing doses of DTIC. Hepatitis, myelosuppression, pneumonia, and dose-related inhibition of tumor cell proliferation were observed after a single dose of DTIC.

Exercise and supraphysiological dose of nandrolone decanoate increase apoptosis in spermatogenic cells.

PubMed

Shokri, Saeed; Aitken, Robert John; Abdolvahhabi, Mirabbas; Abolhasani, Farid; Ghasemi, Fahimeh Mohammad; Kashani, Iraj; Ejtemaeimehr, Shahram; Ahmadian, Shahin; Minaei, Bagher; Naraghi, Mohammad Ali; Barbarestani, Mohammad

2010-04-01

Anabolic-androgenic steroids are used at high doses by athletes for improving athletic ability, physical appearance and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of anabolic-androgenic steroids may influence the hypothalamic-pituitary-gonadal axis, which can in turn affect testicular apoptosis. However, the effect of the combination of exercise and high dose of anabolic-androgenic steroids on testicular apoptosis is not known. We investigated the combined effects of exercise and high doses of nandrolone decanoate on apoptosis in the spermatogenic cell lineage. Five groups of male Wistar strain albino rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (Sham); nandrolone decanoate (10 mg/kg/weekly) (nandrolone decanoate); exercise (1 hr/day, 5 days a week) (exercise); nandrolone decanoate (10 mg/kg/weekly) and exercise (1 hr/day, 5 days a week) (nandrolone decanoate exercise); and sedentary control without any injection or exercise (Control). Apoptosis in the male germ line was characterized by TUNEL, caspase-3 assay and transmission electron microscopy. The weights of the testis and accessory sex organs, as well as sperm parameters significantly decreased in the experimental groups relative to the sham and control groups (p < or = 0.05). Germ cell apoptosis and a significant decrease in the number of germ cell layers in nandrolone decanoate exercise-treated testes were observed (p < or = 0.05). Exercise training seems to increase the extent of apoptotic changes caused by supraphysiological dose of nandrolone decanoate in rats, which in turn affects fertility.

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

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

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

[The role of CYP2E1 in the protection of garlic oil's from n-hexane-induced neurotoxicity].

PubMed

Bi, Ye; Chen, Jing-jing; Li, Yang; Fu, Qiang-qiang; Zeng, Tao; Xie, Ke-qin

2011-11-01

To study the role of CYP2E1 in the protective effects and mechanism of garlic oil (GO) on the peripheral nerve injuries induced by n-hexane. Fifty male Wistar rats were randomly divided into five groups (n = 10): the control, the GO (80 mg/kg) control, the n-hexane (2000 mg/kg) model, the low dose GO (40 mg/kg) plus n-hexane, and the high dose GO (80 mg/kg) plus n-hexane groups. All rats were treated by intragastric administration 6 times a week for 10 weeks. The gait scores were determined every two weeks for monitoring the peripheral neurotrosis. All rats were sacrificed in 10 weeks, the activities and expression levels of hepatic CYP2E1 and 2, 5-HD in serum were examined. As compared with control group, the content and activity of hepatic CYP2E1 in GO control group reduced by 83.1% and 48.3% respectively (P < 0.01), the content and activity of hepatic CYP2E1 in model group increased by 112.5% and 72.2% respectively (P < 0.01). As compared with model group, the contents of hepatic CYP2E1 in low dose and high dose GO groups reduced by 32.9% and 39.1% respectively, the activities of hepatic CYP2E1 in low dose and high dose GO groups reduced by 27.4% and 44.5% respectively (P < 0.01); the contents of serum 2,5-HD in low dose and high dose GO groups reduced by 47.7% and 78.7% respectively (P < 0.01). The gait scores in model, low dose and high dose GO groups were significantly lower than that in control group, but the gait scores in low dose and high dose GO groups were significantly lower than that in model group (P < 0.05). Garlic oil can effectively reduce the peripheral neurotrosis induced by n-hexane due to the decreased content and activity of hepatic CYP2E1, resulting in the reduced formation of 2, 5-HD from n-hexane.

Field Evaluation of the Prophylactic Effect of an Isometamidium Sustained-Release Device against Trypanosomiasis in Cattle

PubMed Central

Diarra, B.; Diall, O.; Geerts, S.; Kageruka, P.; Lemmouchi, Y.; Schacht, E.; Eisler, M. C.; Holmes, P.

1998-01-01

In order to compare the prophylactic effect provided by a poly(d,l-lactide) sustained-release device (SRD) containing isometamidium (ISMM) with that provided by the classical intramuscular injection of the drug, a field trial was carried out at the Madina Diassa Ranch in Mali. One- to 3-year-old N’Dama cattle were randomly divided into three groups. The first group (n = 42) was treated with ISMM at a dose of 1 mg/kg of body weight, the second group (n = 44) received the same dose of the drug via an SRD, which was subcutaneously implanted in the shoulder region, and the third group (n = 36) was kept as an untreated control group. All animals were treated with diminazene aceturate (7 mg/kg of body weight) 2 weeks before the start of the experiment and were tested monthly by the buffy coat technique for a period of 8 months. Glossina morsitans submorsitans was the most important tsetse species, with apparent densities (number of catches/trap/day) varying between 11.9 and 38.7 over the experimental period. Eight months after treatment the cumulative infection rates were 27.7, 58.5, and 77.4% in the group with the SRD implant, the group receiving the intramuscular injection, and the control group, respectively. Statistical analysis showed that the incidence of trypanosomiasis was significantly lower (P = 0.006) in the group which received ISMM via the SRD than in the one which was treated with ISMM intramuscularly. PMID:9593118

The effect of Stevia rebaudiana on serum omentin and visfatin level in STZ-induced diabetic rats.

PubMed

Akbarzadeh, Samad; Eskandari, Fatemeh; Tangestani, Hadis; Bagherinejad, Somaieh Tangerami; Bargahi, Afshar; Bazzi, Parviz; Daneshi, Adel; Sahrapoor, Azam; O'Connor, William J; Rahbar, Ali Reza

2015-03-01

Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of β-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats.

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Bowers, Karen J; McAllister, Kelly B; Ray, Meredith; Heitz, Corey

2017-06-01

This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids; 2) to measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids; 3) to compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids; 4) to monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids; and 5) to identify effect variation between different subgroups of patients, with the purpose of focusing future research. We hypothesized that low-dose ketamine, compared to placebo, as an adjunctive treatment to opioids would result in better pain control over 2 hours and greater patient satisfaction with pain control; further, this protocol will result in a lower opioid dosage over 2 hours. This was a randomized, double-blinded, placebo-controlled trial at a single academic emergency department evaluating the use of ketamine versus placebo in conjunction with opioids for moderate to severe pain. Subjects with a continued high level of pain after an initial dose of opioid analgesia were randomized to receive either 0.1 mg/kg ketamine or placebo prior to protocol-based dosing of additional opioid analgesia, if required. Over 120 minutes, subjects were assessed for pain level (0-10), satisfaction with pain control (0-4), side effects, sedation level, and need for additional pain medication. Total opioid dose, including the initial dose, was compared between groups. Sixty-three subjects were randomized to the placebo group and 53 to the ketamine group. No significant differences were found in demographics between the groups. Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo (p = 0.015). Total opioid dose was lower in the ketamine group (mean ± SD = 9.95 ± 4.83 mg) compared to placebo (mean ± SD = 12.81 ± 6.81 mg; p = 0.02). Satisfaction did not differ between groups. Fewer patients in the ketamine group required additional opioid doses. More patients reported light-headedness and dizziness in the ketamine group. Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia. More side effects were reported in the ketamine group (51% vs. 19%), but the side effect profile appears tolerable. © 2017 by the Society for Academic Emergency Medicine.

Protective effect of heat-treated cucumber (Cucumis sativus L.) juice on alcohol detoxification in experimental rats.

PubMed

Bajpai, Vivek K; Kim, Na-Hyung; Kim, Ji-Eun; Kim, Kangmin; Kang, Sun Chul

2016-05-01

In this study, heat-treated cucumber juice was assessed for its protective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats. Initially, during detoxification of alcohol, all groups were orally dosed to 22% alcohol (6ml/kg body weight) along with different concentrations of heat-treated cucumber juice (10, 100 and 500mg/kg) and commercial goods for hangover-removal on sale (2ml/kg). Cucumber juice was dosed before 30 min, and simultaneously after 30min of alcohol administration, and its hepatoprotective effect on blood alcohol levels and hepatic alcohol metabolic enzyme system in experimental rats was evaluated. As a result, after 7h, remarkable reduction was found in the blood alcohol levels for all concentrations of cucumber juice treatment. Treatment with cucumber juice resulted in increasing dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) enzymatic activities in rat liver at 9h after alcohol administration thereby stimulated blood alcohol metabolism as compared with control group. The effect of heat-treated cucumber juice on alcohol detoxification was observed only in the rats treated before 30min from alcohol administration. These findings indicate that heat-treated cucumber juice has significant protective effect on alcohol detoxification in experimental rats, suggesting its usefulness in the treatment of liver injury caused by alcohol consumption.

Skin dose for head and neck cancer patients treated with intensity-modulated radiation therapy(IMRT)

NASA Astrophysics Data System (ADS)

Fu, Hsiao-Ju; Li, Chi-Wei; Tsai, Wei-Ta; Chang, Chih-Chia; Tsang, Yuk-Wah

2017-11-01

The reliability of thermoluminescent dosimeters (ultrathin TLD) and ISP Gafchromic EBT2 film to measure the surface dose in phantom and the skin dose in head-and-neck patients treated with intensity-modulated radiation therapy technique(IMRT) is the research focus. Seven-field treatment plans with prescribed dose of 180 cGy were performed on Eclipse treatment planning system which utilized pencil beam calculation algorithm(PBC). In calibration tests, the variance coefficient of the ultrathin TLDs were within 3%. The points on the calibration curve of the Gafchromic film was within 1% variation. Five measurements were taken on phantom using ultrathin TLD and EBT2 film respectively. The measured mean surface doses between ultrathin TLD or EBT2 film were within 5% deviation. Skin doses of 6 patients were measured for initial 5 fractions and the mean dose per-fraction was calculated. If the extrapolated doses for 30 fractions were below 4000 cGy, the skin reaction grading observed according to Radiation Therapy Oncology Group (RTOG) was either grade 1 or grade 2. If surface dose exceeded 5000 cGy in 32 fractions, then grade 3 skin reactions were observed.

Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules

PubMed Central

Sutiman, Natalia; Zhang, Zhenxian; Tan, Eng Huat; Ang, Mei Kim; Tan, Shao-Weng Daniel; Toh, Chee Keong; Ng, Quan Sing; Chowbay, Balram; Lim, Wan-Teck

2016-01-01

Purpose This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV) and metronomic (MSV) dosing schedules in patients with advanced non-small cell lung cancer (NSCLC). Methods This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m2 on day 1 and 8 in the CSV group (N = 16) and at 100 mg/week in the MSV group (N = 14). Erlotinib was administered orally daily. Results The maximum tolerated dose was vinorelbine 80 mg/m2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13%) and hyponatremia (N = 1; 6%) in the CSV group, and neutropenia (N = 5; 36%) in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher Cmax, higher Cmin and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state Cmin, Cavg and AUCss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group. Conclusions Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups. Trial Registration ClinicalTrials.gov NCT00702182 PMID:27135612

Comparison of different dosing strategies of intratracheally instilled budesonide on meconium injured piglet lungs.

PubMed

Lin, Chih-Hsueh; Jeng, Mei-Jy; Yang, Yi-Chiang; Hsiao, Yu-Hsuan; Kou, Yu Ru

2017-07-01

Severe inflammation plays a vital role in the pathogenesis of meconium aspiration syndrome (MAS). Intratracheal (IT) instillation of corticosteroids may be beneficial for MAS in optimizing local effect and reducing systemic adverse effects, but the optimum dosing course remains open to question. Thirty meconium-injured newborn piglets were enrolled into six study groups. The first four groups consisted of the IT instillation of 0.25/0.5 mg/kg using either one (IT-B251/IT-B501) or two (IT-B252/IT-B502) doses of budesonide, while the other two groups were the intravenous (IV) dexamethasone (0.5 mg/kg) (IV-Dex) group and the control group (Ctrl). Vital signs and cardiopulmonary functions were monitored throughout the experiments. Pulmonary histology was examined after completing the experiments. Both the IV-Dex and IT-B501 groups got significant improvement in oxygenation (P < 0.05). Lung compliance became worse after one dose of 0.25 mg/kg of IT budesonide. Pulmonary histology revealed that there were significantly lower lung injury scores for all treatment groups compared to control group, especially at the non-dependent sites of both the IT-B501 and IT-B502 groups. There was no significant difference between double- and single-dose groups, no matter whether 0.25 or 0.5 mg/kg of budesonide was used. IT instillation of one dose of 0.5 mg/kg budesonide is beneficial in treating meconium-injured piglet lungs during the first 8 h of injury, but a second dose at an interval of 4 h does not have a superior beneficial effect compared to one dose. © 2017 Wiley Periodicals, Inc.

Histological Evaluation of Retina after Photo Disruption for Vitreous Humor by Q-Switched Neodymium-Doped Yttrium Aluminium Garnet (Nd:YAG) Laser

PubMed Central

Kameel Ghaly, Sally; Foad Ghoneim, Dina; Abdelkawi Ahmed, Salwa; Medhat Abdel-Salam, Ahmed

2013-01-01

Introduction: Rabbits’ eyes were exposed to vitreous humor liquefaction with Q - switched (sometimes called “ giant pulses”) Neodymium-Doped Yttrium Aluminium Garnet (Nd:YAG) laser using two different energy protocols (5 mJ X 100 pulse and 10 mJ X 50 pulse)with and without vitamin C administration. The histological changes in the retina were investigated to evaluate the protective role of vitamin C. Methods: The rabbits were divided into four main groups (n= 12 each). The first group was divided into three subgroups (n=4) and then treated with 5 mJ X 100 pulse (X means times) delivered to the anterior, middle and posterior vitreous humor respectively. The second group received a daily dose of 25 mg/Kg vitamin C for two weeks then was divided into three subgroups and treated with laser in the same manner as the first group.The third group was divided into three subgroups (n=4) and then treated with 10 mJ X 50 pulse delivered to the anterior, middle and posterior vitreous respectively. The fourth group received a daily dose of 25 mg/Kg vitamin C for two weeks then was divided into three subgroups and treated with laser in the same manner as the third group. After two weeks, rabbits were decapitated and histological examination for the retina was performed. Results: The results showed that, the anterior vitreous group exposed to 5mJX100 pulse and supplemented with vitamin C, showed no obvious change. Furthermore, all other treated groups showed alteration in retina’s tissues histology after laser. Conclusion: Application of Q-switched Nd: YAG laser in vitreous humor liquefaction induces changes in retina’s layers. Although there were some sorts of improvements in retinas supplemented with vitamin C, it cannot protect them against laser oxidative damage. PMID:25606329

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase II trial.

PubMed

Jeong, Jae Yoon; Sohn, Joo Hyun; Baek, Yang Hyun; Cho, Yong Kyun; Kim, Yongsoo; Kim, Hyeonjin

2017-08-28

To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease (NAFLD). Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose (400 mg) HL tablet, low dose (133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content (HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase (ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index (BMI). The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment (high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were -1.7% ± 3.1% in the high dose group ( P = 0.018), -1.21% ± 4.97% in the low dose group ( P = 0.254) and 0.61% ± 3.87% in the placebo group (relative changes compared to baseline, high dose were: -12.1% ± 23.5%, low dose: -3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study. HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects.

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase II trial

PubMed Central

Jeong, Jae Yoon; Sohn, Joo Hyun; Baek, Yang Hyun; Cho, Yong Kyun; Kim, Yongsoo; Kim, Hyeonjin

2017-01-01

AIM To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease (NAFLD). METHODS Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose (400 mg) HL tablet, low dose (133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content (HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase (ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index (BMI). RESULTS The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment (high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were -1.7% ± 3.1% in the high dose group (P = 0.018), -1.21% ± 4.97% in the low dose group (P = 0.254) and 0.61% ± 3.87% in the placebo group (relative changes compared to baseline, high dose were: -12.1% ± 23.5%, low dose: -3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study. CONCLUSION HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects. PMID:28932090

Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.

PubMed

Singh, Anurag K; Lockett, Mary Ann; Bradley, Jeffrey D

2003-02-01

To evaluate the incidence and clinical/dosimetric predictors of acute and late Radiation Therapy Oncology Group Grade 3-5 esophageal toxicity in patients with non-small-cell lung cancer (NSCLC) treated with definitive three-dimensional conformal radiotherapy (3D-CRT). We retrospectively reviewed the charts of 207 consecutive patients with NSCLC who were treated with high-dose, definitive 3D-CRT between March 1991 and December 1998. This population consisted of 107 men and 100 women. The median age was 67 years (range 31-90). The following patient and treatment parameters were studied: age, gender, race, performance status, sequential chemotherapy, concurrent chemotherapy, presence of subcarinal 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. All doses are reported without heterogeneity corrections. The median prescription dose to the isocenter in this population was 70 Gy (range 60-74) delivered in 2-Gy daily fractions. All patients were treated once daily. Acute and late esophageal toxicities were graded by Radiation Therapy Oncology Group criteria. Patient and clinical/dosimetric factors were coded and correlated with acute and late Grade 3-5 esophageal toxicity using univariate and multivariate regression analyses. Of 207 patients, 16 (8%) developed acute (10 patients) or late (13 patients) Grade 3-5 esophageal toxicity. Seven patients had both acute and late Grade 3-5 esophageal toxicity. One patient died (Grade 5 esophageal toxicity) of late esophageal perforation. Concurrent chemotherapy, maximal point dose to the esophagus >58 Gy, and a mean dose to the entire esophagus >34 Gy were significantly associated with a risk of Grade 3-5 esophageal toxicity on univariate analysis. Concurrent chemotherapy and maximal point dose to the esophagus >58 Gy retained significance on multivariate analysis. Of 207 patients, 53 (26%) received concurrent chemotherapy. Fourteen (88%) of the 16 patients who developed Grade 3-5 esophageal toxicity had received concurrent chemotherapy (p = 0.0001, Pearson's chi-square test). No case of Grade 3-5 esophageal toxicity occurred in patients who received a maximal point dose to the esophagus of <58 Gy (p = 0.0001, Fisher's exact test, two-tail). Only 2 patients developed Grade 3-5 esophageal toxicity in the absence of concurrent chemotherapy; both received a maximal esophageal point dose >69 Gy. All assessable patients who developed Grade 3-5 esophageal toxicity had a mean dose to the entire esophagus >34 Gy (p = 0.0351, Pearson's chi-square test). However, the mean dose was not predictive on multivariate analysis. Concurrent chemotherapy and the maximal esophageal point dose were significantly associated with a risk of Grade 3-5 esophageal toxicity in patients with NSCLC treated with high-dose 3D-CRT. In patients who received concurrent chemotherapy, the threshold maximal esophageal point dose for Grade 3-5 esophageal toxicity was 58 Gy. An insufficient number of patients developed Grade 3-5 esophageal toxicity in the absence of chemotherapy to allow a valid statistical analysis of the relationship between the maximal esophageal point dose and esophagitis.

Dopamine treatment does not need speed recovery of newborns from transient tachypnea.

PubMed

Guzoglu, Nilufer; Uras, Nurdan; Aksoy, Hatice T; Eras, Zeynep; Oguz, Serife S; Dilmen, Ugur

2016-05-01

Transient tachypnea of the newborn (TTN) results from inadequate neonatal lung fluid clearance. Low-dose dopamine induces natriuresis in the kidneys and it has been assumed that, at this low dosage, dopamine increases renal perfusion in critically ill patients. Medium doses have positive inotropic and chronotropic effects via increased β-receptor activation. Recent studies have demonstrated that dopamine stimulates the clearance of pulmonary edema. Furthermore, β-adrenergic agonists regulate Na+ channels and Na-K-ATPase activity in the pulmonary epithelium. This study investigated the effect of dopamine at different dosages on TTN treatment. A prospective controlled study examined 60 infants with TTN older than 34 weeks of gestation who required at least 24 h of O2 and nasal continuous positive airway pressure (nCPAP) treatment. The infants were randomized into three groups of 20: controls, infants treated with low-dose dopamine (3 μg/kg/min), and infants treated with a medium dose (5 μg/kg/min). The control and study groups were compared in terms of the requirement for mechanical ventilation, and the durations of nCPAP, oxygen requirement, and hospitalization. The requirement for mechanical ventilation, and durations of nCPAP, oxygen requirement, and hospitalization did not differ significantly among the three groups (P=0.54, 0.16 and 0.11, respectively). Dopamine treatment in low-moderate doses does not improve the outcome in TTN. Thus, further studies in this area are needed.

Effect of Carthamus tinctorius (Safflower) on fasting blood glucose and insulin levels in alloxan induced diabetic rabbits.

PubMed

Qazi, Nasreen; Khan, Rafeeq Alam; Rizwani, Ghazala H; Feroz, Zeeshan

2014-03-01

Diabetes mellitus is a major threat to present and future generations. The role of herbal medication has emerged as a safe alternative to currently available medication due to its decreased potential to produce side effects, hence effect of Carthamus tinctorius was observed on fasting blood glucose and insulin levels in alloxan induced diabetic rabbits. Thirty five healthy male rabbits were divided into 5 groups with 7 rabbits in each (Normal control, diabetic control, diabetic treated with glibenclamide, diabetic treated with Carthamus tinctorius extract at doses of 200 and 300mg/kg of body weight). Drug and extract were given orally for 30 days and the values for blood glucose levels were observed after 15(th) and 30(th) day of treatment by using standard reagent kits provided by Human Germany. While insulin levels were checked at the end of the study by using Architect i1000 by Abbott Diagnostics USA. Animals were also observed for any gross toxicity during the study. Results revealed that Carthamus tinctorius has significant hypoglycemic effect at 200mg/kg and 300mg/kg doses as compared to diabetic control group. Insulin levels were significantly increased in Glibenclamide treated as well as Carthamus tinctorius treated groups as compared to diabetic control.

Analysis of dose-volume parameters predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-conformal radiation therapy or IMRT.

PubMed

Kumar, Gaurav; Rawat, Sheh; Puri, Abhishek; Sharma, Manoj Kumar; Chadha, Pranav; Babu, Anand Giri; Yadav, Girigesh

2012-01-01

Multimodality therapy for esophageal cancer can cause various kinds of treatment-related sequelae, especially pulmonary toxicities. This prospective study aims to investigate the clinical and dosimetric parameters predicting lung injury in patients undergoing radiation therapy for esophageal cancer. Forty-five esophageal cancer patients were prospectively analyzed. The pulmonary toxicities (or sequelae) were evaluated by comparing chest X-ray films, pulmonary function tests and symptoms caused by pulmonary damage before and after treatment. All patients were treated with either three-dimensional radiotherapy (3DCRT) or with intensity-modulated radiotherapy (IMRT). The planning dose volume histogram was used to compute the lung volumes receiving more than 5, 10, 20 and 30 Gy (V5, V10, V20, V30) and mean lung dose. V20 was larger in the IMRT group than in the 3DCRT group (p = 0.002). V20 (>15%) and V30 (>20%) resulted in a statistically significant increase in the occurrence of chronic pneumonitis (p = 0.03) and acute pneumonitis (p = 0.007), respectively. The study signifies that a larger volume of lung receives lower doses because of multiple beam arrangement and a smaller volume of lung receives higher doses because of better dose conformity in IMRT plans. Acute pneumonitis correlates more with V30 values, whereas chronic pneumonitis was predominantly seen in patients with higher V20 values.

Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults.

PubMed

Setyawan, Juliana; Hodgkins, Paul; Guérin, Annie; Gauthier, Geneviève; Cloutier, Martin; Wu, Eric; Erder, M Haim

2013-10-01

To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically significant when compared to OROS MPH and MPH LA patients. This study did not control for ADHD severity. Overall, compared to LDX-treated patients, patients initiated on other ADHD medications were equally or more likely to have a therapy augmentation and more likely to deviate from the recommended once-daily dosing regimen.

Study of 201 non-small cell lung cancer patients given stereotactic ablative radiation therapy shows local control dependence on dose calculation algorithm.

PubMed

Latifi, Kujtim; Oliver, Jasmine; Baker, Ryan; Dilling, Thomas J; Stevens, Craig W; Kim, Jongphil; Yue, Binglin; Demarco, Marylou; Zhang, Geoffrey G; Moros, Eduardo G; Feygelman, Vladimir

2014-04-01

Pencil beam (PB) and collapsed cone convolution (CCC) dose calculation algorithms differ significantly when used in the thorax. However, such differences have seldom been previously directly correlated with outcomes of lung stereotactic ablative body radiation (SABR). Data for 201 non-small cell lung cancer patients treated with SABR were analyzed retrospectively. All patients were treated with 50 Gy in 5 fractions of 10 Gy each. The radiation prescription mandated that 95% of the planning target volume (PTV) receive the prescribed dose. One hundred sixteen patients were planned with BrainLab treatment planning software (TPS) with the PB algorithm and treated on a Novalis unit. The other 85 were planned on the Pinnacle TPS with the CCC algorithm and treated on a Varian linac. Treatment planning objectives were numerically identical for both groups. The median follow-up times were 24 and 17 months for the PB and CCC groups, respectively. The primary endpoint was local/marginal control of the irradiated lesion. Gray's competing risk method was used to determine the statistical differences in local/marginal control rates between the PB and CCC groups. Twenty-five patients planned with PB and 4 patients planned with the CCC algorithms to the same nominal doses experienced local recurrence. There was a statistically significant difference in recurrence rates between the PB and CCC groups (hazard ratio 3.4 [95% confidence interval: 1.18-9.83], Gray's test P=.019). The differences (Δ) between the 2 algorithms for target coverage were as follows: ΔD99GITV = 7.4 Gy, ΔD99PTV = 10.4 Gy, ΔV90GITV = 13.7%, ΔV90PTV = 37.6%, ΔD95PTV = 9.8 Gy, and ΔDISO = 3.4 Gy. GITV = gross internal tumor volume. Local control in patients receiving who were planned to the same nominal dose with PB and CCC algorithms were statistically significantly different. Possible alternative explanations are described in the report, although they are not thought likely to explain the difference. We conclude that the difference is due to relative dosimetric underdosing of tumors with the PB algorithm. Copyright © 2014 Elsevier Inc. All rights reserved.

Rosa damascena Mill. Essential Oil Has Protective Effect Against Testicular Damage in Diabetic Rats.

PubMed

Hamedi, Somayeh; Shomali, Tahoora; Haghighat, Aliakbar

2018-05-04

This study investigates the protective effect of Rosa damascena essential oil on diabetes-induced testicular damage in rats. Thirty-six male Wistar rats were randomly divided into 6 equal groups: Group I: negative control (no treatment); Group II: positive control (diabetic by alloxan injection); Groups III-VI that rendered diabetic and received, respectively, 50, 100, 200, and 400 µg/kg/day rose oil, orally for 28 days. Rose oil did not significantly change body weight and blood glucose level as compared to positive control. Serum testosterone level of rose oil-treated rats remained statistically the same with both negative and positive control groups (Groups I and II). Rats treated with rose oil especially at 2 higher dosages (Groups V and VI) had higher sperm count and increased diameters of seminiferous tubules as compared to Group II. Rose oil even at the lowest dosage significantly increased cell count of spermatogonia, primary spermatocytes, Sertoli cells, and Leydig cells, with better outcomes for higher dosages. It appears that short-term repeated dose administration of rose oil can dose-dependently improve structural deteriorations of testes and epididymal sperm count in diabetic rats.

Ovarian and endocrine responses in tropical sheep treated with reduced doses of cloprostenol.

PubMed

Contreras-Solis, Ignacio; Vasquez, B; Diaz, T; Letelier, C; Lopez-Sebastian, A; Gonzalez-Bulnes, A

2009-09-01

The present study aimed to assess the efficacy of reduced doses of cloprostenol for synchronizing estrus and ovulation in hair sheep. With the aim to evaluate the luteolytic activity of reduced cloprostenol doses, a first experiment was performed using a relatively large (group H: 126 microg; n=8), medium (group M: 68.25 microg; n=6) and small (group L: 38.5 microg; n=6) cloprostenol dose. Luteolysis was assessed at Days 3 and 6 after injection (Day 0) by progesterone concentrations (P(4)) and transrectal ultrasonography (US). In Experiment 2, sheep were randomly assigned to the same three doses to evaluate a protocol for estrous synchronization using two injections administered 9 days apart. A third trial was performed with ewes treated (9 days apart) with the large dose (H=126 microg; n=12) and with a small dose adjusted for facilitating volume management (LA=43.75 microg; n=12). Presence of estrous cycling was determined in all the ewes by US and P(4) assay, at Days -9, -6, -2, 0 (Day of second cloprostenol injection), 8 and 11. Bleeding and US were done every 4h from 16 h of the beginning of the estrus during the third trial to assess the preovulatory LH surge and timing of ovulation. Additionally, blood samples were drawn at Days 0, 1, 2 and 3 to assess estradiol (Experiments 2 and 3) and P(4) (Experiment 2) concentrations during the ovarian follicular phase. In all experiments, percentage of animals showing luteolysis, preovulatory follicular dynamics and function and percentage of ewes showing behavioral estrus in response to treatment was similar among groups. Timing of estrus for group H was earlier than group L (28.6+/-1.8h compared with 37.1+/-2.4h; P<0.05). In the third trial, the preovulatory LH peak was higher in the LA group than group H, in terms of maximum mean concentration during the surge (27.7+/-1.8 ng/mL compared with 21.3+/-2.2 ng/mL; P<0.05) and area under the curve (AUC; 183.4+/-12.7 ng/mL compared with 127.7+/-10.9 ng/mL; P<0.01). However, timing of ovulation was similar for H and LA groups. Thereafter, ovulation rate and luteal function at Day 11 were similar. Current results demonstrate that reduced doses of cloprostenol may be applied in a practical manner for reproductive management of sheep, with the additional advantage of reducing treatment costs.

[Protective effect of pretreatment of Salvia miltiorrhiza Bunge. f. alba plasma against oxygen-glucose deprivation-induced injury of cultured rat hippocampal neurons by inhibiting apoptosis].

PubMed

Li, Mei-Yi; Zhang, Yan-Bo; Zuo, Huan; Liu, Li-Li; Niu, Jing-Zhong

2012-02-25

The present study was to investigate the effect of Salvia miltiorrhiza Bunge. f. alba (SMA) pharmacological pretreatment on apoptosis of cultured hippocampal neurons from neonate rats under oxygen-glucose deprivation (OGD). Cultured hippocampal neurons were randomly divided into five groups (n = 6): normal plasma group, low dose SMA plasma (2.5%) group, middle dose SMA plasma (5%) group, high dose SMA plasma (10%) group and control group. The hippocampal neurons were cultured and treated with plasma from adult Wistar rats intragastrically administered with saline or aqueous extract of SMA. The apoptosis of neurons was induced by glucose-free Earle's solution containing 1 mmol/L Na2S2O4 and labeled by MTT and Annexin V/PI double staining. Moreover, protein expressions of Bcl-2 and Bax were detected by immunofluorescence. The results showed that few apoptotic cells were observed in control group, whereas the number of apoptotic cells was greatly increased in normal plasma group and low dose SMA plasma group. Both middle and high dose SMA plasma could protect cultured hippocampal neurons from apoptosis induced by OGD (P < 0.05). The protective effect of high dose SMA plasma was stronger than that of middle one (P < 0.05). Compared to control, normal plasma and low dose SMA plasma groups, middle and high dose SMA plasma groups both showed significantly higher levels of Bcl-2 (P < 0.05 or 0.01), whereas expressions of Bax was opposite. There were no significant differences of Bcl-2 and Bax expressions between middle and high dose SMA plasma groups. Number of Bcl-2- and Bax-positive cells had similar tendency. Bcl-2/Bax (number of positive cells) ratio was higher in high dose SMA plasma group than those of all the other groups (P < 0.05 or 0.01). These results suggest that pharmacological pretreatment of blood plasma containing middle and high dose SMA could raise viability and inhibit apoptosis of OGD-injured hippocampal neurons by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax.

[Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats].

PubMed

Lei, Yang; Zhou, Ai-Min; Guo, Tao; Tan, Ye; Tao, Yan-Yan; Liu, Cheng-Hai

2013-04-01

To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats. Rats were randomly divided into the normal group and the model group, and injected subcutaneously with 100% CCl4 5 mL x kg(-1) to establish the single CCl4 infection model, in order to observe the changes in rat liver injury after 3 h and 6 h. Subsequently, the multiple CCl4 infection liver injury model was reproduced by subcutaneously injecting 100% CCl4 (5 mL x kg(-1)), 50% CCl4 olive oil solution (2 mL x kg(-1)) and then 20% CCl4 olive oil solution (2 mL x kg(-1)). At 6 h after the first CCl4 injection, the rats were divided into six groups: the model group, the control group, the diammonium glycyrrhizinate-treated group, and TRQ high, middle and low dose groups. They were injected through caudal veins, while a normal control group was set up. Their weight and liver-body ratio were observed. Hepatic inflammation was observed with HE staining. Assay kits were adopted to detect ALT, AST, T. Bil, D. Bil, CHE, TBA, gamma-GT and Alb. According to the single injection model, serum AST and T. Bil of model rats were obviously increased at 6 h after single subcutaneous injection of CCl4, with disordered lobular structure in liver tissues, notable swollen liver cells and remarkable liver injury. According to the results of the multiple injection pharmacological experiment, compared with the normal group, the model group had higher serum ALT, AST, and gamma-GT activities (P < 0. 05), TBA and T. Bil contents (P < 0.05) and lower CHE activity (P < 0.05). HE staining showed disorganized lobular structure in liver tissues and notable ballooning degeneration in liver cells. Compared with the model group, TRQ high and middle dose groups and the diammonium glycyrrhizinate-treated group showed significant charges in serum liver function and inflammation in liver cells. Specifically, TRQ high and middle dose groups were superior to the diammonium glycyrrhizinate-treated group. Tanreqing injection has significant protective effect on CCl4-induced acute hepatic injury in rats.

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

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

Kountouri, Melpomeni; Zilli, Thomas; Rouzaud, Michel

2016-02-01

Purpose: This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. Methods and Materials: 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities weremore » scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. Results: There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). Conclusions: A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.« less

Does low-dose rifaximin ameliorate endotoxemia in patients with liver cirrhosis: a prospective study.

PubMed

Zeng, Xin; Tang, Xia Jiao; Sheng, Xia; Ni, Wu; Xin, Hai Guang; Chen, Wei Zhong; Jiang, Cai Feng; Lin, Yong; Shi, Jian; Shi, Bin; Chen, Yue Xiang; Yuan, Zong Li; Xie, Wei Fen

2015-11-01

To evaluate the efficacy, safety and tolerability of different doses of rifaximin in Chinese patients with liver cirrhosis. This random prospective study included a screening visit, a 2-week treatment period and a subsequent 4-week observation phase. Patients with liver cirrhosis were randomly assigned to a low-dose rifaximin group, a high-dose rifaximin group and the control group in a ratio of 1:1:1. The low-dose and high-dose groups received 400 mg or 600 mg rifaximin per 12 h for 2 weeks, respectively. All other therapeutic strategies remained unchanged in the three groups as long as possible. In total, 60 patients with liver cirrhosis were screened and 43 of them met the eligibility criteria. After 2-week treatment serum endotoxin levels in the low-dose (1.1 ± 0.8 EU/mL) and high-dose rifaximin groups (1.0 ± 0.8 EU/mL) were significantly lower than that in the control group (2.5 ± 1.8 EU/mL), while no significant difference was found between the two rifaximin-treated groups. The effect of high-dose rifaximin on endotoxemia lasted for at least 4 weeks after drug withdrawal. A significant reduction in the abundance of the Veillonellaceae taxa and an increase in the abundance of Bacteroidaceae were shown after 2 weeks of rifaximin therapy. The incidence of adverse events and severe adverse events was similar among the three groups. Low-dose (800 mg/day) rifaximin could be analogous to high-dose (1200 mg/day) rifaximin to reduce the serum endotoxin level after 2 weeks of treatment. © 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Benefits of High-dose Steroid + Hespander + Mannitol Administration in the Treatment of Bell's Palsy.

PubMed

Furukawa, Takatoshi; Abe, Yasuhiro; Ito, Tsukasa; Kubota, Toshinori; Kakehata, Seiji

2017-02-01

Large-scale investigations have not been recently conducted on the efficacy of high-dose steroid administration of prednisolone (PSL) for Bell's palsy. We compared treatment results between normal-dose steroid (PSL 60 mg/d) and high-dose steroid (PSL 200 mg/d) + Hespander + Mannitol administration. We also investigated the recovery rate for antiviral agents. Retrospective case review. Tertiary referral center. A total of 675 patients with Bell's palsy who had grade V and grade VI on the House-Brackmann (HB) scale were treated in our department between 1995 and 2014. These patients could be divided into a normal-dose group and high-dose group. We separately assessed treatment outcomes for HB grade V patients and HB grade VI patients. Logistic regression analysis was also performed to investigate factors that can impact treatment outcomes, i.e., sex, age, days to start of treatment, PSL dosage, and antiviral drug administration. Recovery rates were significantly better in the high-dose steroid + Hespander + Mannitol group in comparison with the normal-dose steroid group for HB grade V (100% versus 77.7%) and HB grade VI (92.5% versus 68.2%). Additional effects of antiviral agents were only shown in the normal-dose group. Significant factors for treatment outcomes were PSL 200 mg/d administration and early initiation of treatment. Insignificant factors were sex, age, and the antiviral agent. We showed the high-dose steroid + Hespander + Mannitol administration produced significantly better outcomes than normal-dose steroid administration in the treatment of patients with Bell's palsy.

Efficacy and Safety of a Single-Pill Fixed-Dose Combination of Azilsartan and Amlodipine.

PubMed

Motozato, Kota; Miura, Shin-Ichiro; Shiga, Yuhei; Kusumoto, Takaaki; Saku, Keijiro

2016-12-01

Guidelines for the management of hypertension recommend the use of drugs with different mechanisms of action in antihypertensive regimens that include single-pill fixed-dose combinations of medications. There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). Forty hypertensive patients who were receiving a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day were enrolled. They were randomly divided into two treatment groups, a group that changed to a single-pill fixed-dose combination of azilsartan 20 mg/day and amlodipine 5 mg/day (changeover group) and a group that continued to receive valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day (control group), and treated for 16 weeks. There were no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP) or pulse rate (PR) at 16 weeks between the control and changeover groups. In addition, there were no significant changes in biochemical parameters throughout the study period in both groups. The ability of a single-pill fixed-dose combination of azilsartan and amlodipine to reduce BP may be comparable to that of a combination of valsartan and amlodipine or irbesartan and amlodipine.

Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients.

PubMed

Lin, Zhixiong; Wang, Xiaoyan; Xie, Wenjia; Yang, Zhining; Che, Kaijun; Wu, Vincent W C

2013-12-01

Radiation-induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC. Sixty-five NPC patients treated with radiotherapy were recruited. Baseline thyroid hormone levels comprising free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated radiotherapy plan was generated for each patient. Thyroid and pituitary gland dose volume histograms were generated, dividing the patients into four groups: high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low pituitary doses (HTLP group); low thyroid and high pituitary doses; and low thyroid and pituitary doses. Incidence of hypothyroidism was analysed. Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary doses, respectively. At 18 months, 23.1% of patients manifested various types of hypothyroidism. The HTHP group showed the highest incidence (83.3%) of hypothyroidism, followed by the HTLP group (50%). NPC patients with high thyroid and pituitary gland doses carried the highest risk of abnormal thyroid physiology. The dose to the thyroid was more influential than the pituitary dose at 18 months after radiotherapy, and therefore more attention should be given to the thyroid gland in radiotherapy planning. © 2013 The Royal Australian and New Zealand College of Radiologists.

The effects of Sutaehwan-Gami on menopausal symptoms induced by ovariectomy in rats.

PubMed

Kim, Dong-Il; Choi, Min Sun; Pak, Sok Cheon; Lee, Seung-Bok; Jeon, Songhee

2012-11-23

This study was undertaken to evaluate the beneficial effects of a modified prescription of Sutaehwan named Sutaehwan-Gami (SG), created by adding Rhizoma dioscoreae and Carthami semen to Sutaehwan, on menopausal symptoms. To evaluate the estrogenic effect of SG, we first examined estrogen receptor (ER) activation by SG treatment in breast adenocarcinoma cells and confirmed the estrogenic effect of SG in vivo ovariectomized rats. The animals were randomized into four groups: Sham operated group (Sham), saline treated ovariectomized group (OVX), SG treated group (SG) and raloxifene treated group (RLX). Animals were provided with SG at a dose of 500 mg/kg bw/day and RLX at a dose of 5.4 mg/kg bw/day with standard rat pellets for 3 months. SG significantly increased ERα phosphorylation, and its downstream effectors, extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) phosphorylation in breast adenocarcinoma cells. Treatment with SG reversed ovariectomy-induced uterine weight reduction and weight gain. Decreases in the levels of GOT and GPT were observed in the SG group. The significantly reduced E2β level in OVX rats was raised by treatment with SG. Moreover, SG significantly increased the phosphorylation levels of ERK and Akt in the uterus. Taken together, these data indicate that SG has phytoestrogen-like properties through ERK and Akt activation, implying that it could be protective and beneficial for the management of menopausal symptoms.

Ameliorative effects of rutin against metabolic, biochemical and hormonal disturbances in polycystic ovary syndrome in rats.

PubMed

Jahan, Sarwat; Munir, Faryal; Razak, Suhail; Mehboob, Anam; Ain, Qurat Ul; Ullah, Hizb; Afsar, Tayyaba; Shaheen, Ghazala; Almajwal, Ali

2016-12-07

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. The study was commenced to assess the favorable effects of Rutin against metabolic, biochemical, histological, and androgenic aspects of polycystic ovary syndrome in rats. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) per orally (p.o) for a period of 21 days for the induction of PCOS, followed by dose of rutin (100 mg/kg and 150 mg/kg, p.o) for 15 days using 0.5% w/v CMC as vehicle. Metformin was also given as a standard control to one of the rat groups. Serum estradiol, progesterone, testosterone, serum lipid parameters, CRP and glucose levels were evaluated. Furthermore, antioxidant activity was tested using superoxide dismutase, catalase, glutathione per-oxidase and reactive-oxygen species level. Rutin flavonoid had a dose-dependent effect on androgenic levels depicting more recovery in the rutin-I treated group, while rutin-II treated groups showed better antioxidant and lipid profiles as compared with PCOS groups. A decrease in the value of C reactive protein (CRP) and a restoration in the proportion of estrous phase smears were observed in the rutin treated groups. Histopathological examination of ovary revealed a significant decrease in the number of cystic follicles in post treated groups. The effects observed with rutin were moderately similar to that with standard metformin, a widely used treatment drug for PCOS. The study provides evidence for the potential ameliorative effects of rutin against clinical and biochemical features of PCOS.

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study.

PubMed

Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M; Kirk, Jeremy; Donaldson, Malcolm; Ivarsson, Sten-A; Söder, Olle; Roche, Edna; Hoey, Hilary; Dunger, David B; Juul, Anders

2014-10-01

Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups. IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children. © 2014 European Society of Endocrinology.

Random Forest Segregation of Drug Responses May Define Regions of Biological Significance

PubMed Central

Bukhari, Qasim; Borsook, David; Rudin, Markus; Becerra, Lino

2016-01-01

The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF) method to detect differences in the pharmacological MRI (phMRI) response in rats to treatment with an analgesic drug (buprenorphine) as compared to control (saline). Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD), and high dose (HD), and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus, and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow a supervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies. PMID:27014046

A Randomized Cross‐over Study of High‐dose Metoclopramide plus Dexamethasone versus Granisetron plus Dexamethasone in Patients Receiving Chemotherapy with High‐dose Cisplatin

PubMed Central

Eguchi, Kenji; Shinkai, Tetsu; Tamura, Tomohide; Ohe, Yuichiro; Nisio, Masato; Kunikane, Hiroshi; Arioka, Hitoshi; Karato, Atsuya; Nakashima, Hajime; Sasaki, Yasutsuna; Tajima, Kinuko; Tada, Noriko; Saijo, Nagahiro

1994-01-01

We carried out a randomized, single‐blind, cross‐over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high‐dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty‐four patients with primary or metastatic lung cancer, given single‐dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively (P=0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P= 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty‐four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed. PMID:7829401

Low-dose intravenous ketamine for postcardiac surgery pain: Effect on opioid consumption and the incidence of chronic pain.

PubMed

Cogan, Jennifer; Lalumière, Geneviève; Vargas-Schaffer, Grisell; Deschamps, Alain; Yegin, Zeynep

2017-01-01

Recent meta-analyses have concluded that low-dose intravenous ketamine infusions (LDKIs) during the postoperative period may help to decrease acute and chronic postoperative pain after major surgery. This study aims to evaluate the level of pain at least 3 months after surgery for patients treated with a postoperative LDKI versus patients who were not treated with a postoperative LDKI. Administrative and Ethics Board approval were obtained for this study. We performed a retrospective chart review for all patients receiving LDKI, and equal number of age-, sex-, and surgery-matched patients who did not receive LDKI. Low-dose ketamine was prepared using 100 mg of ketamine in 100 ml of normal saline and run between 50 and 200 mcg/kg/h. We reviewed 115 patients with LDKI and 115 without LDKI. The average age was 63.1 years, 73% of the patients were men and sex was evenly distributed between LDKI and non-LDKI. The average duration of the ketamine infusions was 26.8 h with the average dose being 169.9 mg. At an average of 9 months after surgery, 42% of the ketamine group and 38% of the nonketamine group stated that they had had pain on discharge. Of these patients, 30% of the ketamine group and 26% of the nonketamine group still had pain at the time of the phone call. Women in both groups had more acute and chronic pain than men. These results show that LDKI does not promote a decrease in long-term postoperative pain.

Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy

PubMed Central

Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

2018-01-01

AIM: This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). METHODS: In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen’s method. RESULTS: Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic progression comparing to the group of patients with monotherapy. CONCLUSIONS: Based on our results achieved during 2 years we can conclude that ETN in combination with MTX reduced disease activity, slowed radiographic progression and improved clinical manifestations more effectively than MTX alone. No serious adverse events were noticed in the group with combination treatment. PMID:29875847

Evaluation of the Efficacy of Combined Therapy of Methotrexate and Etanercept versus Methotrexate as a Mono-Therapy.

PubMed

Rexhepi, Sylejman; Rexhepi, Mjellma; Rexhepi, Blerta; Sahatçiu-Meka, Vjollca; Mahmutaj, Vigan

2018-05-20

This study aims to evaluate the efficacy of Methotrexate (MTX) alone and combined therapy with Etanercept (ETN) and Methotrexate in patients with active rheumatoid arthritis (RA). In the randomised control study, conducted in the period from March 2014 until March 2016, we evaluated the efficacy of the treatment of patients with RA with MTX as monotherapy and combination treatment with MTX and ETN. In the Clinic of Rheumatology in Prishtina, 90 adult patients with RA were treated in combination with ETN (doses of 50 mg subcutaneously/weekly), with oral MTX (doses up to 20 mg weekly), and MTX alone (doses up to 20 mg weekly) during this period of two years. Clinical response was assessed using European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria and the Disease Activity Score (DAS28). Radiographic changes were measured in the beginning and at the end of the study using Larsen's method. Of the cohort groups of 90 patients, mean age of 55.63, 15 patients, (16.6 %) were treated with combined therapy (ETN plus MTX) and 75 patients (83.3%) with monotherapy (MTX). After two years of treatment the group with combined therapy resulted with improvement of acute phase reactants as erythrocyte sedimentation rate (ESR) for the first hour (41.1 vs. 10.3 mm/hour) and C - reactive protein (CRP) (40.8 vs. 6 mg/liter), and compared to the group treated with monotherapy, there were no significant changes (ESR: 45.7 vs 34.3 mm/hour; CRP: 48 vs 24 mg/liter). Before the treatment, the severity of the disease was high, wherein the group with combined therapy DAS28 was 5.32, compared to the monotherapy group whom DAS28 was 5.90. After 2 years of treatment, we had significant changes in the results of DAS28, wherein the group treated with ETN plus MTX DAS28 was 2.12 ± 0.15, while in the group of patients treated with MTX DAS28 were 3.75 ± 0.39 (t = 13.03; df = 58; p < 0.0001). The group with combined therapy showed no evidence of radiographic progression comparing to the group of patients with monotherapy. Based on our results achieved during 2 years we can conclude that ETN in combination with MTX reduced disease activity, slowed radiographic progression and improved clinical manifestations more effectively than MTX alone. No serious adverse events were noticed in the group with combination treatment.

Anti cancerous efficacy of Ayurvedic milk extract of Semecarpus anacardium nuts on hepatocellular carcinoma in Wistar rats.

PubMed

Joseph, Joice P; Raval, Sunant K; Sadariya, Kamlesh A; Jhala, Mayur; Kumar, Pranay

2013-01-01

The objective of the study was to determine the anticancerous efficacy of Ayurvedic preparation made of Semecarpus anacardium (SA) nuts. Five groups of rats were used for the study. Group I served as water control. Hepatocellular carcinoma (HCC) was induced in groups II, III and IV animals using N-nitrosodiethylamine as inducing agent followed by phenobarbitone as promoter for 13 weeks. Group-II animals were kept untreated as hepatocellular carcinoma control. Group-III animals were treated with Ayurvedic milk extract of Semecarpus anacardium nuts at dose mentioned in Ashtangahridaya, an authentic book of Ayurveda for 49 days and group-IV animals were treated with doxorubicin as reference drug at dose of 1mg/kg twice a week for 7 weeks. Group V animals were kept as drug (SA nut milk extract) control for studying the effect of nut milk extract on normal rats. After 154 days of experiment, all animals were subjected to screening for HCC by estimation of liver enzymes, HCC marker (alpha-2 macroglobulin) and histopathology. Both liver enzymes and HCC marker were increased in hepatocellular carcinoma control along with neoplastic changes in liver and were decreased in Semecarpus anacardium nut milk extract treated group. The Ayurvedic drug showed positive correlation with the action of doxorubicin. This study demonstrated the efficacy of Semecarpus anacardium nut milk extract for the treatment of hepatocellular carcinoma either alone or along with chemotherapy.

Acute Effects of Ecstasy on Memory Are more Extensive than Chronic Effects

PubMed Central

Shariati, Mohamad Bakhtiar Hesam; Sohrabi, Maryam; Shahidi, Siamak; Nikkhah, Ali; Mirzaei, Fatemeh; Medizadeh, Mehdi; Asl, Sara Soleimani

2014-01-01

Introduction Exposure to 3, 4- methylenedioxymethamphetamine (MDMA) could lead to serotonergic system toxicity in the brain. This system is responsible for learning and memory functions. Studies show that MDMA causes memory impairment dose-dependently and acutely. The present study was designed to evaluate the chronic and acute effects of MDMD on spatial memory and acquisition of passive avoidance. Methods Adult male Wistar rats (200-250 g) were given single or multiple injections of MDMA (10 mg/kg, IP). Using passive avoidance and Morris Water Maze (MWM) tasks, learning and spatial memory functions were assessed. The data were analyzed by SPSS 16 software and one- way analysis of variance (ANOVA) test. Results Our results showed that there were significant differences in latency to enter the dark compartment (STL) between sham and MDMA- treated groups. Acute group significantly showed more STL in comparison with chronic group. Furthermore, MDMA groups spent more time in dark compartment (TDS) than the sham group. Administration of single dose of MDMA significantly caused an increase in TDS compared with the chronic group. In the MWM, MDMA treatment significantly increased the traveled distance and escaped latency compared to the sham group. Like to passive avoidance task, percentage of time spent in the target quadrant in MDMA- treated animals impaired in MWM compared with sham group. Discussion These data suggest that MDMA treatment impairs learning and memory functions that are more extensive in acute- treated rats. PMID:25337384

Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity.

PubMed

Mancebo, A; Casacó, A; González, B; Ledón, N; Sorlozabal, J; León, A; Gómez, D; González, Y; Bada, A M; González, C; Arteaga, M E; Ramírez, H; Fuentes, D

2012-05-09

CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly mediated by the oil-based adjuvant Montanide ISA 51, probably enhanced by the immunological properties of the antigen. This study showed evidences that intramuscular administration during 26 weeks of CIMAvax-EGF at doses up to 15× human total dose is well tolerated in rats and it has a clinical importance since this long lasting study in relevant species allows to treat cancer patients with tumors during long periods with relative weight safety margin. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pharmacist intervention in primary care to improve outcomes in patients with left ventricular systolic dysfunction.

PubMed

Lowrie, Richard; Mair, Frances S; Greenlaw, Nicola; Forsyth, Paul; Jhund, Pardeep S; McConnachie, Alex; Rae, Brian; McMurray, John J V

2012-02-01

Meta-analysis of small trials suggests that pharmacist-led collaborative review and revision of medical treatment may improve outcomes in heart failure. We studied patients with left ventricular systolic dysfunction in a cluster-randomized controlled, event driven, trial in primary care. We allocated 87 practices (1090 patients) to pharmacist intervention and 87 practices (1074 patients) to usual care. The intervention was delivered by non-specialist pharmacists working with family doctors to optimize medical treatment. The primary outcome was a composite of death or hospital admission for worsening heart failure. This trial is registered, number ISRCTN70118765. The median follow-up was 4.7 years. At baseline, 86% of patients in both groups were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. In patients not receiving one or other of these medications, or receiving less than the recommended dose, treatment was started, or the dose increased, in 33.1% of patients in the intervention group and in 18.5% of the usual care group [odds ratio (OR) 2.26, 95% CI 1.64-3.10; P< 0.001]. At baseline, 62% of each group were treated with a β-blocker and the proportions starting or having an increase in the dose were 17.9% in the intervention group and 11.1% in the usual care group (OR 1.76, 95% CI 1.31-2.35; P< 0.001). The primary outcome occurred in 35.8% of patients in the intervention group and 35.4% in the usual care group (hazard ratio 0.97, 95% CI 0.83-1.14; P = 0.72). There was no difference in any secondary outcome. A low-intensity, pharmacist-led collaborative intervention in primary care resulted in modest improvements in prescribing of disease-modifying medications but did not improve clinical outcomes in a population that was relatively well treated at baseline.

Pulmonary toxicity of simulated lunar and Martian dusts in mice: II. Biomarkers of acute responses after intratracheal instillation

NASA Technical Reports Server (NTRS)

Lam, Chiu-Wing; James, John T.; Latch, Judith N.; Hamilton, Raymond F Jr; Holian, Andrij

2002-01-01

Volcanic ashes from Arizona and Hawaii, with chemical and mineral properties similar to those of lunar and Martian soils, respectively, are used by the National Aeronautics and Space Administration (NASA) to simulate lunar and Martian environments for instrument tests. NASA needs toxicity data on these volcanic soils to assess health risks from potential exposures of workers in facilities where these soil simulants are used. In this study we investigated the acute effects of lunar soil simulant (LSS) and Martian soil simulant (MSS), as a complement to a histopathological study assessing their subchronic effects (Lam et al., 2002). Fine dust of LSS, MSS, TiO(2), or quartz suspended in saline was intratracheally instilled into C57Bl/6J mice (4/group) in single doses of 0.1 mg/mouse or 1 mg/mouse. The mice were euthanized 4 or 24 h after the dust treatment, and bronchoalveolar lavage fluid (BALF) was obtained. Statistically significant lower cell viability and higher total protein concentration in the BALF were seen only in mice treated with the high dose of quartz for 4 h and with the high dose of MSS or quartz for 24 h, compared to mice treated only with saline. A significant increase in the percentage of neutrophils was not observed with any dust-treated group at 4 h after the instillation, but was observed after 24 h in all the dust-treated groups. This observation indicates that these dusts were not acutely toxic and the effects were gradual; it took some time for neutrophils to be recruited into and accumulate significantly in the lung. A statistically significant increase in apoptosis of lavaged macrophages from mice 4 h after treatment was found only in the high-dose silica group. The overall results of this study on the acute effects of these dusts in the lung indicate that LSS is slightly more toxic than TiO(2), and that MSS is comparable to quartz. These results were consistent with the subchronic histopathological findings in that the order of severity of lung toxicity was TiO(2) < LSS < MSS < quartz.

Long-term Survival and Toxicity in Patients Treated With High-Dose Intensity Modulated Radiation Therapy for Localized Prostate Cancer

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

Spratt, Daniel E.; Pei, Xin; Yamada, Josh

2013-03-01

Purpose: To report long-term survival and toxicity outcomes with the use of high-dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Methods and Materials: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified by prognostic risk group based on National Comprehensive Cancer Network risk classification criteria. A total of 587 patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range, 1-14 years). Results: For low-, intermediate-,more » and high-risk groups, 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9%, respectively (P<.001), and distant metastasis-free survival rates were 99.4%, 94.1%, and 82.0% (P<.001), respectively. On multivariate analysis, T stage (P<.001), Gleason score (P<.001), and >50% of initial biopsy positive core (P=.001) were predictive for distant mestastases. No prostate cancer-related deaths were observed in the low-risk group. The 7-year prostate cancer-specific mortality (PCSM) rates, using competing risk analysis for intermediate- and high-risk groups, were 3.3% and 8.1%, respectively (P=.008). On multivariate analysis, Gleason score (P=.004), percentage of biopsy core positivity (P=.003), and T-stage (P=.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This study represents the largest cohort of patients treated with high-dose radiation to 86.4 Gy, using IMRT for localized prostate cancer, with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes with acceptable toxicity.« less

Side Effects of Standard Adjuvant and Neoadjuvant Chemotherapy Regimens According to Age Groups in Primary Breast Cancer

PubMed Central

Reinisch, Mattea; von Minckwitz, Gunter; Harbeck, Nadia; Janni, Wolfgang; Kümmel, Sherko; Kaufmann, Manfred; Elling, Dirk; Nekljudova, Valentina; Loibl, Sibylle

2013-01-01

Summary Background Elderly breast cancer patients are underrepresented in clinical trials and this leads to a lack of knowledge regarding the tolerance and side effects of modern chemotherapy regimens, especially in dose-dense (dd) or dose-intensified combination. Patients and Methods In this analysis, data from 4 German, randomized (neo-)adjuvant trials, including anthracycline-based chemotherapy, were evaluated for toxicity, compliance and feasibility. Patients were grouped according to age. Results Of the 4,775 patients, 73.6% were < 60 years, 15.8% were 60–64 years and 10.6% were > 64 years. The patients’ compliance decreased with increasing age, the rate of therapy discontinuations was 10.3%; 16.0% were > 64 years old (p < 0.001). The rate of dose reductions also increased with increasing age in the docetaxel/doxorubicin/cyclophosphamide (TAC) (p overall = 0.02) and 5-fluorouracil/epirubicin-cyclophosphamide (FE120C) (p overall < 0.001) treatment groups. Neutropenia grade 3 + 4 in patients of > 64 years was 77% in FE120C- compared to 55% in TAC-treated patients (with primary granulocyte colony-stimulating factors (G-CSFs)). The incidence of febrile neutropenia (FN) was lowest in the regimens without additional taxanes. FN in patients aged > 64 years was lower in the FE120C- than in TAC-and dd-doxorubicin/docetaxel-treated groups. Conclusion The range and intensity of toxicity increased with age. Neutropenia did not increase significantly in the dd groups; the highest rate was seen in FE120C-treated patients. FE120C without G-CSFs is not an option in patients older than 64 years. PMID:24715845

Possible therapeutic uses of Salvia triloba and Piper nigrum in Alzheimer's disease-induced rats.

PubMed

Ahmed, Hanaa H; Salem, Ahmed M; Sabry, Gilane M; Husein, Ahmed A; Kotob, Soheir E

2013-05-01

This study aimed to investigate the role of Salvia triloba L. and Piper nigrum extracts in ameliorating neuroinflammatory insults characteristic of Alzheimer's disease (AD) in an experimentally induced rat model. Adult male Sprague-Dawley rats were classified into Group 1 (n=10): normal healthy animals serving as the negative control group; Group 2 (n=60): the AD-induced group. After AD induction, animals in the AD-induced group were divided randomly and equally into 6 subgroups. The first subgroup served as AD control; the second one, which served as positive control, was treated orally with the conventional therapy for AD (rivastigmine) at a dose of 0.3 mg/kg body weight (b.w.) daily for 3 months. The third and fourth subgroups were, respectively, treated orally with the S. triloba extract at a dose of 750 and 375 mg/kg b.w. daily for 3 months. The fifth and sixth subgroups were, respectively, treated orally with the P. nigrum extract at a dose of 187.5 and 93.75 mg/kg b.w. daily for 3 months. Levels of brain acetylcholine (Ach), serum and brain acetylcholinesterase (AchE) activity, C-reactive protein (CRP), total nuclear factor kappa-B (NF-κB), and monocyte chemoattractant protein-1 (MCP-1) were estimated. The results showed that administration of AlCl3 resulted in a significant elevation in the levels of AchE activity, CRP, NF-κB, and MCP-1 accompanied with a significant depletion in the Ach level. Treatment of AD rats with each of the selected medicinal plant extracts caused marked improvement in the measured biochemical parameters. In conclusion, S. triloba and P. nigrum methanolic extracts have potent anti-inflammatory effects against neuroinflammation characterizing AD.

TIME COURSE OF CHOLINESTERASE INHIBITION IN ADULT RATS TREATED ACUTELY WITH CARBARYL CARBOFURAN, FORMETANATE, METHOMYL, METHIOCARB, OXAMYL ON PROPOXUR.

EPA Science Inventory

To compare the toxicity of seven N-methyl carbamates, time course profiles for brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with either carbaryl (30 mg/kg in corn oil); ...

The Johns Hopkins RTR Consortium: A Collaborative Approach to Advance Translational Science and Standardize Clinical Monitoring of Restorative Transplantation

DTIC Science & Technology

2016-10-01

received non-myeloablative conditioning with 50cGy total body and 350cGy thymic irradiation for induction. Aim1: Group I was treated with high-dose...regimen of non-myeloablative irradiation and peritransplant tacrolimus. The long-term graft survival off of immunosuppression for animals treated

Preliminary toxicity study of dichloromethane extract of Kielmeyera coriacea stems in mice and rats.

PubMed

Obici, Simoni; Otobone, Fernanda Jacques; da Silva Sela, Vânia Ramos; Ishida, Kelly; da Silva, José Carlos; Nakamura, Celso Vataru; Garcia Cortez, Diógenes Aparício; Audi, Elisabeth Aparecida

2008-01-04

Kielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo" or "Saco de Boi" in the central Brazilian plateau region, is used to treat several tropical diseases. The present study evaluated the toxic effects of dichloromethane (DcM) extract of Kielmeyera coriacea stems, administered to rodents. In the acute toxicity tests, mice receiving doses of this extract by the oral and intraperitoneal routes, showed reversible effects, with LD50 values of 1503.0 and 538.8 mg/kg, respectively. In the repeated-dose oral (90 days) toxicity tests, male and female Wistar rats were treated by gavage with different doses of DcM extract (5, 25 or 125 mg/kg). In biochemical and haematological evaluations, the results varied widely in respect to dose and sex, with no linear profile, and did not show clinical correlations. In the histopathological examinations, the groups exhibited some changes, but there were no significant differences between the groups compared to the controls. In conclusion, these investigations appeared to indicate the safety of acute and repeated oral administration of the DcM extract of Kielmeyera coriacea stems, which can therefore be continuously used with safety.

Assessment of the anti-protozoal activity of crude Carica papaya seed extract against Trypanosoma cruzi.

PubMed

Jiménez-Coello, Matilde; Guzman-Marín, Eugenia; Ortega-Pacheco, Antonio; Perez-Gutiérrez, Salud; Acosta-Viana, Karla Y

2013-10-11

In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of the three main compounds (oleic, palmitic and stearic acids in a proportion of 45.9% of oleic acid, 24.1% of palmitic and 8.52% of stearic acid previously identified in the crude extract of C. papaya was evaluated at doses of 100, 200 and 300 mg/kg. Both doses of the extracts were orally administered for 28 days. A significant reduction (p < 0.05) in the number of blood trypomastigotes was observed in animals treated with the evaluated doses of the C. papaya extract in comparison with the positive control group (allopurinol 8.5 mg/kg). Parasitemia in animals treated with the fatty acids mixture was also significantly reduced (p < 0.05), compared to negative control animals. These results demonstrate that the fatty acids identified in the seed extracts of C. papaya (from ripe fruit) are able to reduce the number of parasites from both parasite stages, blood trypomastigote and amastigote (intracellular stage).

Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model.

PubMed

Pezeshki, Zahra; Nematbakhsh, Mehdi; Nasri, Hamid; Talebi, Ardeshir; Pilehvarian, Ali-Asghar; Safari, Tahereh; Eshraghi-Jazi, Fatemeh; Haghighi, Maryam; Ashrafi, Farzaneh

2013-01-01

Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood. Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r (2) = 0.63, P < 0.01). Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.

Endotoxin-induced intravascular coagulation in rabbits: effect of tissue plasminogen activator vs urokinase of PAI generation, fibrin deposits and mortality.

PubMed

Paloma, M J; Páramo, J A; Rocha, E

1995-12-01

We have evaluated the effect of plasminogen activators (t-PA and urokinase) on an experimental model of disseminated intravascular coagulation (DIC) in rabbits by injection of 20 micrograms/kg/h of E. coli lipopolysaccharide during 6 h t-PA (0.2 mg/kg and 0.7 mg/kg), urokinase (3000 U/kg/h) and saline (control) were given simultaneously with endotoxin. Results indicated that urokinase and low dose of t-PA significantly reduced the increase of plasminogen activator inhibitor (PAI) activity observed 2 h after endotoxin (p < 0.001). High t-PA dose also diminished the PAI levels at 6 h (p < 0.001). A significant reduction of fibrin deposits in kidneys was observed din both t-PA treated groups as compared with findings in the group of rabbits infused with saline solution (p < 0.005), whereas urokinase had no significant effect on the extent of fibrin deposition. Finally, the mortality rate in the control group (70%) was reduced to 50% in rabbits receiving high doses of t-PA. In conclusion, treatment with t-PA resulted in reduced PAI generation, fibrin deposits and mortality in endotoxin-treated rabbits.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (7)--Three-month repeated oral dose toxicity study in juvenile dogs].

PubMed

Sawada, T; Karaki, K; Hayashi, T; Yoneyama, S; Mizushima, Y; Moriyama, T; Nishimura, K; Kimura, Y; Nakano, M; Kato, I

2001-05-01

To evaluate the repeated oral dose toxicity of Cefmatilen hydrochloride hydrate (S-1090) in juvenile dogs, S-1090 was administered to juvenile beagle dogs at dose levels of 50, 100, 200 and 400 mg potency/kg/day for 3 months. No deaths occurred. Urinalysis in the 400 mg potency/kg group revealed positive reactions of occult blood and protein, and erythrocytes in sediments. Cystitis was observed in the 200 and 400 mg potency/kg groups. In the thyroids, an increased weight in some animals in the groups dosed at 100 mg potency/kg or more and an increased follicular colloid in the 400 mg potency/kg group were observed. However, no related changes were noted in other examination items. Red to dark-red feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet) were observed in all treated groups. Plasma S-1090 concentrations increased in a manner less than dose-proportional. The lesions of urinary bladder were judged as S-1090-induced toxic changes and the NOAEL of S-1090 in this study was assessed to be 100 mg potency/kg/day.

Comparison of Re-irradiation Outcomes for Charged Particle Radiotherapy and Robotic Stereotactic Radiotherapy Using CyberKnife for Recurrent Head and Neck Cancers: A Multi-institutional Matched-cohort Analysis.

PubMed

Yamazaki, Hideya; Demizu, Yusuke; Okimoto, Tomoaki; Ogita, Mikio; Himei, Kengo; Nakamura, Satoaki; Suzuki, Gen; Yoshida, Ken; Kotsuma, Tadayuki; Yoshioka, Yasuo

2016-10-01

To compare survival outcomes for charged particle radiotherapy (CP) and stereotactic body radiotherapy using CyberKnife (CK) in patients who had undergone re-irradiation for head and neck cancers. We conducted a retrospective multi-institutional matched-cohort analysis on 25 patients treated with CP and 25 matched patients treated with CK according to three prognostic factors (nasopharyngeal cancer or not, interval between initial radiotherapy and re-irradiation, and planning target volume). CP was used more often to treat non-squamous cell cancer ((non-SCC): 52% vs. 0%) with a higher prescribed dose (median=57.6 Gy(RBE)/16 fractions) than CK (32 Gy/5 fractions). The local control rate (LC) for patients treated with CP was 71.2% at 1 year and that for patients treated with CK was 63.8% (p=0.24). The 1-year overall survival (OS) rates were 67.1% for CP and 36.3% for CK (p=0.0002), respectively. Non-SCC patients showed better OS rates at 1 year than SCC patients. In the SCC sub-group analysis, the 1-year LC, OS rates were 65%, 58.3% in the CP group and 64%, 36.3% in the CK group (p=0.81, p=0.02), respectively. A total of 16 patients (32%) experienced grade 3 or worse toxicities (24% in CK and 40% in CP, p=0.36), including six grade 5 toxicities. CP produced higher survival rates than CK, treated more non-SCC patients and used a higher prescribed dose. On the other hand, severe toxicities occurred in both groups, which, however, require further investigation. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea

PubMed Central

2013-01-01

Background Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma aldosterone levels to its anti-hypertensive effect. Methods In the acute experiments, methanol leaf extracts (MLE) of T. violacea (30–120 mg/kg), muscarine (0.16 -10 μg/kg), and atropine (0.02 - 20.48 mg/kg), and/or the vehicle (dimethylsulfoxide (DMSO) and normal saline (NS)) were respectively and randomly administered intravenously in a group of spontaneously hypertensive (SHR) weighing 300 to 350 g and aged less than 5 months. Subsequently, T. violacea (60 mg/kg) or muscarine (2.5 μg/kg) was infused into eight SHRs, 20 min after atropine (5.12 mg/kg) pre-treatment. In the chronic (21 days) experiments, the SHRs were randomly divided into three groups, and given the vehicle (0.2 ml/day of DMSO and NS), T. violacea (60 mg/kg/day) and captopril (10 mg/kg/day) respectively into the peritoneum, to investigate their effects on blood pressure (BP), heart rate (HR), and plasma aldosterone levels. Systolic BP and HR were measured using tail-cuff plethysmography during the intervention. BP and HR were measured via a pressure transducer connecting the femoral artery and the Powerlab at the end of each intervention in the acute experiment; and on day 22 in the chronic experiment. Results In the acute experiments, T. violacea, muscarine, and atropine significantly (p < 0.05) reduced BP dose-dependently. T. violacea and muscarine produced dose-dependent decreases in HR, while the effect of atropine on HR varied. After atropine pre-treatment, dose-dependent increases in BP and HR were observed with T. violacea; while the BP and HR effects of muscarine were nullified. In the chronic experiments, the T. violacea-treated and captropril-treated groups had signicantly lower levels of aldosterone in plasma when compared to vehicle-treated group. Compared to the vehicle-treated group, significant reduction in BP was only seen in the captopril-treated group; while no difference in HR was observed among the groups. Conclusion The results obtained in this study suggest that stimulation of the muscarinic receptors and a reduction in plasma aldosterone levels contribute to the anti-hypertesive effect of T. violacea. PMID:23311308

Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output and vascular resistance in acute heart failure in the anaesthetized rat

PubMed Central

Nekooeian, Ali A; Tabrizchi, Reza

1998-01-01

The effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output, blood pressure, mean circulatory filling pressure (Pmcf), arterial and venous resistances, heart rate and left ventricular end-diastolic pressure were assessed in rats with acute heart failure by means of coronary artery occlusion.Animals (n=6 in each group) were divided into five groups: group I, sham-operated vehicle-treated (0.9% saline; 0.018 mL min−1); groups II-V, subject to coronary artery occlusion and treated with vehicle (0.9% saline; 0.018 ml min−1) and CGS 21680 (0.1, 0.3 and 1.0 μg kg−1 min−1), respectively. Haemodynamic measurements were taken one hour after completion of surgery, ninety minutes after coronary artery occlusion (except in group I), and fifteen minutes after infusion of saline or CGS 21680.Baseline haemodynamic measurements before occlusion were found not to differ significantly between the different groups of animals. However, after occlusion, cardiac output, rate of rise in left ventricular pressure (+dP/dt) and blood pressure were significantly reduced when compared to corresponding values in sham-operated animals. In addition, occlusion of the coronary artery resulted in a significant elevation in venous resistance, Pmcf and left ventricular end-diastolic pressure as compared to corresponding values in sham-operated animals.Infusion with CGS 21680 at the highest dose significantly reduced blood pressure, arterial resistance and left ventricular end-diastolic pressure when compared to occluded vehicle-treated animals (group II). Administration of CGS 21680 at the highest dose also significantly increased cardiac output (28%) and heart rate (10%) in comparison to occluded vehicle-treated animals. In addition, the highest dose of CGS 21680 significantly reduced Pmcf (9%) and venous resistance (62%) in comparison to occluded vehicle-treated animals. Administration of CGS 21680 did not significantly affect +dP/dt when compared to occluded vehicle-treated animals.The results from the present investigation indicate that occlusion of the coronary artery in rats results in a state of heart failure characterized by reduced arterial pressure and cardiac output, and increased venous resistance, Pmcf and left ventricular end-diastolic pressure. Administration of CGS 21680 to animals with acute heart failure resulted in increased cardiac output which was due to reduced venous resistance, as well as increased heart rate. PMID:9605574

Effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output and vascular resistance in acute heart failure in the anaesthetized rat.

PubMed

Nekooeian, A A; Tabrizchi, R

1998-04-01

1. The effects of CGS 21680, a selective A2A adenosine receptor agonist, on cardiac output, blood pressure, mean circulatory filling pressure (Pmcf), arterial and venous resistances, heart rate and left ventricular end-diastolic pressure were assessed in rats with acute heart failure by means of coronary artery occlusion. 2. Animals (n=6 in each group) were divided into five groups: group I, sham-operated vehicle-treated (0.9% saline; 0.018 mL min(-1)); groups II-V, subject to coronary artery occlusion and treated with vehicle (0.9% saline; 0.018 ml min(-1)) and CGS 21680 (0.1, 0.3 and 1.0 microg kg(-1) min(-1)), respectively. Haemodynamic measurements were taken one hour after completion of surgery, ninety minutes after coronary artery occlusion (except in group I), and fifteen minutes after infusion of saline or CGS 21680. 3. Baseline haemodynamic measurements before occlusion were found not to differ significantly between the different groups of animals. However, after occlusion, cardiac output, rate of rise in left ventricular pressure (+ dP/dt) and blood pressure were significantly reduced when compared to corresponding values in sham-operated animals. In addition, occlusion of the coronary artery resulted in a significant elevation in venous resistance, Pmcf and left ventricular end-diastolic pressure as compared to corresponding values in sham-operated animals. 4. Infusion with CGS 21680 at the highest dose significantly reduced blood pressure, arterial resistance and left ventricular end-diastolic pressure when compared to occluded vehicle-treated animals (group II). Administration of CGS 21680 at the highest dose also significantly increased cardiac output (28%) and heart rate (10%) in comparison to occluded vehicle-treated animals. In addition, the highest dose of CGS 21680 significantly reduced Pmcf (9%) and venous resistance (62%) in comparison to occluded vehicle-treated animals. Administration of CGS 21680 did not significantly affect +dP/dt when compared to occluded vehicle-treated animals. 5. The results from the present investigation indicate that occlusion of the coronary artery in rats results in a state of heart failure characterized by reduced arterial pressure and cardiac output, and increased venous resistance, Pmcf and left ventricular end-diastolic pressure. Administration of CGS 21680 to animals with acute heart failure resulted in increased cardiac output which was due to reduced venous resistance, as well as increased heart rate.

Alteration in apoptotic rate of testicular cells and sperms following administration of Bisphenol A (BPA) in Wistar albino rats.

PubMed

Srivastava, Seema; Gupta, Priya

2018-05-21

The aim of the study was to evaluate the effect of Bisphenol A [BPA] widely used as a plasticizer in the formation of polycarbonate plastics and epoxy resins, exposure causing alteration in apoptosis rate, and protective effect of Vitamin E when supplemented with BPA orally. Adult male Wistar albino rats aged 3 months were randomly divided into seven groups: control (olive oil treated) BPA-treated (dose 5, 50,100 μg/100gmBW) and Vitamin E intervention group (dose 5, 50, 100 μg/100gmBW BPA+ Vitamin E dose 4 mg/100gmBW). Animals were sacrificed 3 months later, and blood and tissue samples were collected. Apoptotic changes were analyzed in epididymal spermatozoa and testis tissue by binding of annexin V apoptotic biomarker. A significant decline in the weight of testis, testosterone level, and sperm count was observed. Histopathological and apoptotic changes were observed in testis tissue. In epididymal sperms, the early apoptotic cells were observed by staining of annexin V-conjugated FITC and PI green fluorescence in spermatozoa head which indicated the damage of membrane and late apoptotic cells. These changes reduced significantly in Vitamin E-treated groups though were not found to be comparable to control animals. All these changes were attributed to disrupted spermatogenesis that would interfere with sperm formation. Thus, the study infers that BPA affects the apoptosis process in the testis and epididymal sperm that would interfere with its function and contribute to infertility, whereas Vitamin E-supplemented dose has a protective effect towards these changes, indicating its role in improving male fertility.

DNA damage, p53, Ki-67 and COX-2 expression in rat tongue cells exposed to nandrolone decanoate.

PubMed

Pozzi, Renan; Fernandes, Kelly Rosseti; Foot Gomes de Moura, Carolina; Ferrari, Raquel Agnelli Mesquita; Fernandes, Kristianne Porta Santos; Chaves, Marcelo Donizeti; Renno, Ana Claudia Muniz; Ribeiro, Daniel Araki

2013-05-01

The objective of this article was to evaluate the impact potential of nandrolone decanoate on DNA damage, cellular regulatory proteins and cyclooxygenase (COX)-2 in oral mucosa cells of Wistar rats. A total of 40 rats were distributed into four groups. Two experimental groups were treated with nandrolone decanoate, at 5 mg/kg doses, subcutaneously, three times a week in two periods: 15 and 30 days. The remaining groups received only 0.9% saline subcutaneously, three times a week. To evaluate genetic damage, nandrolone decanoate at 15 mg/kg dose was exposed to 24 h. In the histopathological analysis, no remarkable morphological changes were observed in tongue tissue in all groups. Significant increase in immunoexpression of Ki-67, p53, COX-2 proteins was detected in the groups treated with nandrolone decanoate during 15 and 30 days, when compared to their respective controls. A positive correlation between immunoexpression of p53 and COX-2 protein was detected following nandrolone decanoate exposure. DNA damage was induced by nandrolone decanoate in oral mucosa cells at 15 mg/kg dose. Our results suggest that nandrolone decanoate was able to alter the expression of cell cycle-related proteins, as well as to induce genetic damage and COX-2 immunoexpression in tongue cells of Wistar rats.

Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1,2-dimethylhydrazine in rats.

PubMed

Anisimov, Vladimir N; Khavinson, Vladimir Kh; Popovich, I G; Zabezhinski, Mark A

2002-09-08

The effect of synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on colon carcinogenesis was firstly studied in rats. Eighty 2-month-old outbred male LIO rats were subdivided into four groups and were weekly exposed to five subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg body weight. Additionally, 5 days a week, some of the rats were given subcutaneous injections of saline at a dose of 0.1 ml during the whole experiment (group 1, control) or Epitalon at a single dose of 1 microg during the whole experiment (group 2), Epitalon after termination of carcinogen injections (group 3) or during the period of DMH exposure (group 4). Colon carcinomas developed in 90-100% of DMH-treated rats. The number of total colon tumors per rat was 4.1; 2.7; 3.7; 2.9 in groups 1, 2, 3, 4, respectively (the difference in groups 2 and 4 compared with group 1 is significant). In rats from group 2, colon tumors were smaller than in control animals. In group 2, the incidence, as well the multiplicity of tumors in ascending and descending colon, were significantly decreased in comparison with group 1. In group 4, the mean number of tumors per rat was significantly decreased, too. A trend to decrease the number of tumors in the rectum in rats from groups 2, 3 and 4, treated with Epitalon was found. Epitalon inhibited also the development of tumors in jejunum and ileum. Thus, our results demonstrated an inhibitory effect of Epitalon on chemically induced bowel carcinogenesis in rats.

Randomized trial of betahistine mesilate tablets as augmentation for oxcarbazepine and carbamazepine in treating vestibular paroxysmia.

PubMed

Xue, Hui; Xiang, Wenping; Yu, Yichuan; Liu, Guorong; Chong, Yi; Zhou, Jiying

2018-01-01

Vestibular paroxysmia (VP) is a rare episodic peripheral vestibular disorder. This study was conducted to compare the efficacy and acceptability of carbamazepine (CBZ) plus betahistine mesilate tablets (BMT) (CBZ+BMT) and oxcarbazepine (OXC) plus BMT (OXC+BMT) in treating VP, and investigated whether the synergistic effect could be increased along with the increased dose of BMT. VP patients were recruited and randomly assigned to receive CBZ+BMT or OXC+BMT. The doses of CBZ and OXC were set to 200 and 300 mg/time, twice daily, respectively. The doses of BMT were set to 12 and 18 mg/time, twice daily. Half of the patients in each group received BMT 12 mg/time and the other half received BMT 18 mg/time. The treatment was continued for 12 weeks. The vertigo frequency, vertigo score, vertigo duration, response rate, and drug-related side effects were analyzed. In total, 92 patients in the CBZ+BMT group and 93 patients in the OXC+BMT group completed this trial. After 12 weeks of treatment, the two groups had similar average vertigo frequency, average vertigo score, average vertigo duration, and response rate. But the incidence of side effects was significantly higher in the CBZ+BMT group than in the OXC+BMT group ( p =0.04). Subgroup analysis found that patients receiving BMT (18 mg) had greater reductions in average vertigo frequency, average vertigo duration, and average vertigo score, and higher response rates than patients receiving BMT (12 mg). These results demonstrated that OXC+BMT may be suitable as an alternative method in VP patients with CBZ hypersensitivity, and the synergistic effect could be increased along with the increased dose of BMT.

Hepatoprotective activity of the neem-based constituent azadirachtin-A in carbon tetrachloride intoxicated Wistar rats.

PubMed

Baligar, N S; Aladakatti, R H; Ahmed, Mukhtar; Hiremath, M B

2014-04-01

The aim of this study was to investigate the hepatoprotective role of azadirachtin-A in carbon tetrachloride (CCl4) induced hepatotoxicity in rats. The group allotment for the animals used in the hepatoprotective study included a vehicle treatment group, CCl4 (1 mL · (kg body mass)(-1)) treatment group, silymarin (100 μg · (kg body mass)(-1) · day(-1)) + CCl4 treatment group, and groups treated with different doses of azadirachtin-A (100 or 200 μg · (kg body mass)(-1) · day(-1)) + CCl4. On the 9th day, blood was obtained for measuring the biochemical parameters, and liver tissue was obtained for pathological examination. The acute toxicity test with azadirachtin-A (500, 1000, or 2000 μg · (kg body mass)(-1)) indicated no mortality after 14 days of treatment; further, there was no change in behavior, food consumption, or organ mass. However with the higher dose, some hematological parameters showed changes. Hepatoprotective studies revealed that the CCl4 treatment group exhibited a decrease in total protein and albumin levels, whereas a significant increase in BUN, AST, ALT, and ALP levels were noticed compared with the vehicle-treated control, indicating that there was liver damage caused by CCl4. Histology and ultrastructure study confirmed that pretreatment with azadirachtin-A dose-dependently reduced hepatocellular necrosis and, therefore, protected the liver against toxicity caused by CCl4. The results from this study indicate that pretreatment with azadirachtin-A at the higher dose levels, moderately restores the rat liver to normal. This study confirms that azadirachtin-A possesses greater hepatoprotective action; however, the effective concentration needs to be determined.

The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid.

PubMed

Hassanin, Kamel M A; Abd El-Kawi, Samraa H; Hashem, Khalid S

2013-01-01

Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets. The objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity. Twenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 μg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3-20 nm) 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration. Blood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4]) and oxidative and antioxidant parameters (malondialdehyde [MDA], reduced glutathione [GSH], catalase, and superoxide dismutase [SOD]). Upon dissection, thyroid glands were taken for histopathological examination by using paraffin preparations stained with hematoxylin and eosin (H&E) and Masson's trichrome. Immunohistochemical staining was performed for detecting cellular proliferation using Ki67 antibodies. The present study shows that K2Cr2O7 has a toxic effect on the thyroid gland as a result of inducing a marked oxidative damage and release of reactive oxygen species. This was shown by the significant decrease in free T3 and T4 and GSH levels, which was accompanied by significant increases in catalase, SOD, and MDA in the chromium-treated group compared to the control group. Se nanoparticles have a protective effect on K2Cr2O7-induced thyroid damage, as a result of correcting the free T3 and T4 levels and GSH, catalase, SOD, and MDA compared to the K2Cr2O7-treated group. Administration of nano-selenium alone in the nano-selenium-treated group had no toxic effect on rats' thyroid compared to the control group. The biochemical results were confirmed by histopathological, immunohistochemical and pathomorphological studies.

Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials.

PubMed

Stoffel, Nicole U; Cercamondi, Colin I; Brittenham, Gary; Zeder, Christophe; Geurts-Moespot, Anneke J; Swinkels, Dorine W; Moretti, Diego; Zimmermann, Michael B

2017-11-01

Current guidelines to treat iron deficiency recommend daily provision of ferrous iron divided through the day to increase absorption. However, daily dosing and split dosing might increase serum hepcidin and decrease iron absorption from subsequent doses. Our study aim was to compare iron absorption from oral iron supplements given on consecutive versus alternate days and given as single morning doses versus twice-daily split dosing. We did two prospective, open-label, randomised controlled trials assessing iron absorption using ( 54 Fe)-labelled, ( 57 Fe)-labelled, or ( 58 Fe)-labelled ferrous sulfate in iron-depleted (serum ferritin ≤25 μg/L) women aged 18-40 years recruited from ETH Zurich and the University of Zurich, Switzerland. In study 1, women were randomly assigned (1:1) to two groups. One group was given 60 mg iron at 0800 h (±1 h) on consecutive days for 14 days, and the other group was given the same doses on alternate days for 28 days. In study 2, women were assigned to two groups, stratified by serum ferritin so that two groups with similar iron statuses could be formed. One group was given 120 mg iron at 0800 h (±1 h) and the other was given the dose split into two divided doses of 60 mg at 0800 h (±1 h) and 1700 h (±1 h) for three consecutive days. 14 days after the final dose, the groups were each crossed over to the other regimen. Within-individual comparisons were done. The co-primary outcomes in both studies were iron bioavailability (total and fractional iron absorption), assessed by measuring the isotopic label abundance in erythrocytes 14 days after administration, and serum hepcidin. Group allocations in both studies were not masked and primary and safety analyses were done on an intention-to-treat basis. The studies were registered at ClinicalTrials.gov, numbers NCT02175888 (study 1) and NCT02177851 (study 2) and are complete. For study 1, 40 women were enrolled on Oct 15-29, 2015. 21 women were assigned to the consecutive-day group and 19 to the alternate-day group. At the end of treatment (14 days for the consecutive-day group and 28 days for the alternate-day group), geometric mean (-SD, +SD) cumulative fractional iron absorptions were 16·3% (9·3, 28·8) in the consecutive-day group versus 21·8% (13·7, 34·6) in the alternate-day group (p=0·0013), and cumulative total iron absorption was 131·0 mg (71·4, 240·5) versus 175·3 mg (110·3, 278·5; p=0·0010). During the first 14 days of supplementation in both groups, serum hepcidin was higher in the consecutive-day group than the alternate-day group (p=0·0031). In study 2, 20 women were enrolled between Aug 13 and 18, 2015. Ten women were assigned to receive once-daily dosing and ten were assigned to receive twice-daily divided dosing. No significant differences were seen in fractional (day 1-3 geometric mean: 11·8% [7·1, 19·4] once daily vs 13·1% [8·2, 20·7] twice daily; p=0·33) or total iron absorption (day 1-3: 44·3 mg [29·4, 66·7] once daily vs 49·4 [35·2, 69·4] twice daily; p=0·33) between the two dosing regimens. Twice-daily divided doses resulted in a higher serum hepcidin concentration than once-daily dosing (p=0·013). No grade 3 or 4 adverse events were reported in either study. In iron-depleted women, providing iron supplements daily as divided doses increases serum hepcidin and reduces iron absorption. Providing iron supplements on alternate days and in single doses optimises iron absorption and might be a preferable dosing regimen. These findings should be confirmed in iron-deficient anaemic patients. Swiss National Science Foundation, Bern, Switzerland. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Anethum graveolens L. (dill) on Oocyte and Fertility of Adult Female Rats

PubMed Central

Monsefi, Malihezaman; Ghasemi, Aazam; Alaee, Sanaz; Aliabadi, Elham

2015-01-01

Background Our previous studies revealed Anethum graveolens L. caused some changes in female reproductive system that induced infertility. Therefore, in this study, oocyte changes as one of probable reasons of infertility were investigated. Methods In this study, 59 adult female rats were divided into 3 groups of control, low dose (0.5 g/kg) and high dose (5 g/kg) of dill seed aqueous extract (LDE and HDE) treated groups that were gavaged with 1 ml of each dose for 10 days (2 estrous cycles). Vaginal smears were prepared daily. Oocytes of superovulated animals were extracted and their morphometrical changes were measured (n = 5). Oocyte cell membrane glycoconjugates were stained with UEA, PNA, and DBA-FITC lectins (n = 5). Ultrastructural studies of oocytes were performed using TEM (n = 5). The number, weight, and crown-rump length of newborns were examined in three groups after mating with untreated males (n = 5). Data were analyzed using SPSS software. Results Results demonstrated that the duration of the estrous cycle, the diestrus phase and progesterone concentration in the experimental groups increased significantly compared to the control group (p < 0.05). Granulosa cells of corpus luteum in HDE-treated group were larger and clearer. The intensity reactions of galactose/Nacetylgalactoseamine terminal sugar of oocyte decreased insignificantly in experimental groups compared to the control group p > 0.05. Duration of mating to pregnancy increased and the weight and crown-rump length of newborns decreased in experimental groups significantly (p < 0.05). Conclusion Dill seed aqueous extract can induce infertility without any effect on oocyte structure. PMID:25717430

The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker.

PubMed

Metoki, Hirohito; Ohkubo, Takayoshi; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Obara, Taku; Hirose, Takuo; Sato, Michihiro; Hashimoto, Takanao; Imai, Yutaka

2012-07-01

The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements. Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111). The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6  mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model. Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

Cytogenetic toxicity of vincristine.

PubMed

Choudhury, R C; Das, B; Misra, S; Jagdale, M B

2000-01-01

The anticancer drugs vincristine sulphate (VCR) and cyclophosphamide (CTX) were tested for their cytogenetic effects in the bone marrow cells of Swiss mice. The end points investigated were chromosomal aberrations and mitotic index at 24 hours posttreatment and micronuclei (MN) at 30 hours posttreatment in bone marrow cells of male and female mice after a single intraperitoneal exposure. The doses tested were VCR 0.25, 0.5, and 1.0 mg/kg and CTX 40 mg/kg b.w. of mice. Significant percentages of chromosomal aberrations and significant numbers of micronuclei per thousand polychromatic erythrocytes (PCEs) that were induced were recorded from bone marrow of each of the VCR-treated groups of mice. There were no significant differences between the percentages of dividing cells in the VCR-treated group and the vehicle control groups of mice. Peculiarly, in the chromosomal aberration study, the male mice were found to be more responsive to VCR than the females, and the aberrations per hundred metaphases were found to be decreased when the dose of VCR was increased. The percentage of dividing cells was also higher with the lowest dose of VCR tested. However, there was a dose-dependent, but nonlinear, increase in MN per thousand PCEs. The results were compared with the already available fragmentary and self-contradictory data on the genotoxicity of VCR in mice and in other mammalian test systems.

Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim-sulfamethoxazole: lessons from an observational cohort study.

PubMed

Creemers-Schild, Dina; Kroon, Frank P; Kuijper, Ed J; de Boer, Mark G J

2016-06-01

The recommended treatment of Pneumocystis jirovecii pneumonia (PCP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) in an equivalent of TMP 15-20 mg/kg/day and SMX 75-100 mg/kg/day for 2 or 3 weeks. High rates of adverse events are reported with this dose, which raises the question if lower doses are possible. All adult patients diagnosed with PCP in various immune dysfunctions and treated with TMP-SMX between January 1, 2003 and July 1, 2013 in a tertiary university hospital were included. Per institutional protocol, patients initiated treatment on intermediate-dose TMP-SMX (TMP 10-15 mg/kg/day) and could be stepped down to low-dose TMP-SMX (TMP 4-6 mg/kg/day) during treatment. Clinical variables at presentation, relapse rate and mortality rates were compared between intermediate- and step-down treatment groups by uni- and multivariate analyses. A total of 104 patients were included. Twenty-four patients (23 %) were switched to low-dose TMP-SMX after a median of 4.5 days (IQR 2.8-7.0 days). One relapse (4 %) occurred in the step-down group versus none in the intermediate-dose group. The overall 30-day mortality was 13 %. There was 1 death in the step-down group (4 %) compared to 13 deaths (16 %) in the intermediate-dose group. We observed high cure rates of PCP by treatment with intermediate-dose TMP-SMX. In addition, a step-down strategy to low-dose TMP-SMX during treatment in selected patients appears to be safe and does not compromise the outcome of treatment.

Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction.

PubMed

Guo, Yiru; Wysoczynski, Marcin; Nong, Yibing; Tomlin, Alex; Zhu, Xiaoping; Gumpert, Anna M; Nasr, Marjan; Muthusamy, Senthikumar; Li, Hong; Book, Michael; Khan, Abdur; Hong, Kyung U; Li, Qianhong; Bolli, Roberto

2017-03-01

We have recently demonstrated that repeated administrations of c-kit POS cardiac progenitor cells (CPCs) have cumulative beneficial effects in rats with old myocardial infarction (MI), resulting in markedly greater improvement in left ventricular (LV) function compared with a single administration. To determine whether this paradigm applies to other species and cell types, mice with a 3-week-old MI received one or three doses of cardiac mesenchymal cells (CMCs), a novel cell type that we have recently described. CMCs or vehicle were infused percutaneously into the LV cavity, 14 days apart. Compared with vehicle-treated mice, the single-dose group exhibited improved LV ejection fraction (EF) after the 1st infusion (consisting of CMCs) but not after the 2nd and 3rd (vehicle). In contrast, in the multiple-dose group, LV EF improved after each CMC infusion, so that at the end of the study, LV EF averaged 35.5 ± 0.7% vs. 32.7 ± 0.6% in the single-dose group (P < 0.05). The multiple-dose group also exhibited less collagen in the non-infarcted region vs. the single-dose group. Engraftment and differentiation of CMCs were negligible in both groups, indicating paracrine effects. These results demonstrate that, in mice with ischemic cardiomyopathy, the beneficial effects of three doses of CMCs are significantly greater than those of one dose, supporting the concept that multiple treatments are necessary to properly evaluate the full therapeutic potential of cell therapy. Thus, the repeated-treatment paradigm is not limited to c-kit POS CPCs or to rats, but applies to other cell types and species. The generalizability of this concept dramatically augments its significance.

Multicenter, dose-ranging study of efegatran sulfate versus heparin with thrombolysis for acute myocardial infarction: The Promotion of Reperfusion in Myocardial Infarction Evolution (PRIME) trial.

PubMed

2002-01-01

Adjunctive therapies that increase the incidence of normal reperfusion after thrombolysis for acute myocardial infarction (MI) could enhance clinical outcomes. Direct thrombin inhibitors may offer an advantage over standard adjunctive therapies. We randomized 336 patients with acute MI at 33 sites to receive 1 of 5 doses of efegatran sulfate, a direct thrombin inhibitor, or heparin for 72 to 96 hours, both with accelerated alteplase and aspirin. The primary end point was the incidence of thrombolytic failure (death, reinfarction, or TIMI grade 0-2 flow in the infarct artery from 90 minutes to discharge or 30 days, whichever occurred earlier). Significantly more patients randomized to efegatran had evidence of heart failure at admission. The lowest-dose efegatran arm was terminated at 15 patients because of unacceptably increased thrombolytic failure. The primary end point occurred in 53.0% of patients treated with heparin, in 53.8% of patients treated with efegatran overall (P =.90), and in 55.4% of patients given intermediate-dose efegatran (P =.74). These findings were unaffected after adjustment was done for baseline differences. Most bleeding was minor; major bleeding and the use of blood transfusions did not differ significantly by treatment. Three patients in the high-dose efegatran group had intracranial hemorrhage, as did 1 patient in the heparin group. Continuous ST monitoring showed a shorter time to recovery for the efegatran group (median 107 minutes) compared with the heparin group (154 minutes; P =.025). Efegatran sulfate appeared to offer no clear advantage over heparin as an adjunct to thrombolysis for acute myocardial infarction, although there may be a modest improvement in time to reperfusion.

I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life

PubMed Central

Lorenzo-Zúñiga, Vicente; Llop, Elba; Suárez, Cristina; Álvarez, Beatriz; Abreu, Luis; Espadaler, Jordi; Serra, Jordi

2014-01-01

AIM: To determine the dose-related effects of a novel probiotic combination, I.31, on irritable bowel syndrome (IBS)-related quality of life (IBS-QoL). METHODS: A multicenter, randomized, double-blind, placebo-controlled intervention clinical trial with three parallel arms was designed. A total of 84 patients (53 female, 31 male; age range 20-70 years) with IBS and diarrhea according to Rome-III criteria were randomly allocated to receive one capsule a day for 6 wk containing: (1) I.31 high dose (n = 28); (2) I.31 low dose (n = 27); and (3) placebo (n = 29). At baseline, and 3 and 6 wk of treatment, patients filled the IBSQoL, Visceral Sensitivity Index (VSI), and global symptom relief questionnaires. RESULTS: During treatment, IBS-QoL increased in all groups, but this increment was significantly larger in patients treated with I.31 than in those receiving placebo (P = 0.008). After 6 wk of treatment, IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups, respectively (P = 0.041 and P = 0.023 vs placebo), but only 9 ± 3 in the placebo group. Gut-specific anxiety, as measured with VSI, also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics (by 10 ± 2 and 14 ± 2 points, high and low dose respectively, P < 0.05 for both vs 7 ± 1 score increment in placebo). Symptom relief showed no significant changes between groups. No adverse drug reactions were reported following the consumption of probiotic or placebo capsules. CONCLUSION: A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea. PMID:25024629

I.31, a new combination of probiotics, improves irritable bowel syndrome-related quality of life.

PubMed

Lorenzo-Zúñiga, Vicente; Llop, Elba; Suárez, Cristina; Alvarez, Beatriz; Abreu, Luis; Espadaler, Jordi; Serra, Jordi

2014-07-14

To determine the dose-related effects of a novel probiotic combination, I.31, on irritable bowel syndrome (IBS)-related quality of life (IBS-QoL). A multicenter, randomized, double-blind, placebo-controlled intervention clinical trial with three parallel arms was designed. A total of 84 patients (53 female, 31 male; age range 20-70 years) with IBS and diarrhea according to Rome-III criteria were randomly allocated to receive one capsule a day for 6 wk containing: (1) I.31 high dose (n = 28); (2) I.31 low dose (n = 27); and (3) placebo (n = 29). At baseline, and 3 and 6 wk of treatment, patients filled the IBSQoL, Visceral Sensitivity Index (VSI), and global symptom relief questionnaires. During treatment, IBS-QoL increased in all groups, but this increment was significantly larger in patients treated with I.31 than in those receiving placebo (P = 0.008). After 6 wk of treatment, IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups, respectively (P = 0.041 and P = 0.023 vs placebo), but only 9 ± 3 in the placebo group. Gut-specific anxiety, as measured with VSI, also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics (by 10 ± 2 and 14 ± 2 points, high and low dose respectively, P < 0.05 for both vs 7 ± 1 score increment in placebo). Symptom relief showed no significant changes between groups. No adverse drug reactions were reported following the consumption of probiotic or placebo capsules. A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea.

Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study.

PubMed

Hotta, N; Toyota, T; Matsuoka, K; Shigeta, Y; Kikkawa, R; Kaneko, T; Takahashi, A; Sugimura, K; Koike, Y; Ishii, J; Sakamoto, N

2001-10-01

The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy. A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms. Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group. The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.

Low-dose memantine-induced working memory improvement in the allothetic place avoidance alternation task (APAAT) in young adult male rats

PubMed Central

Wesierska, Malgorzata J.; Duda, Weronika; Dockery, Colleen A.

2013-01-01

N-methyl-D-aspartate receptors (NMDAR) are involved in neuronal plasticity. To assess their role simultaneously in spatial working memory and non-cognitive learning, we used NMDAR antagonists and the Allothetic Place Avoidance Alternation Task (APAAT). In this test rats should avoid entering a place where shocks were presented on a rotating arena which requires cognitive coordination for the segregation of stimuli. The experiment took place 30 min after intraperitoneal injection of memantine (5, 10, 20 mg/kg b.w.: MemL, MemM, MemH, respectively) and (+)MK-801 (0.1, 0.2, 0.3 mg/kg b.w.: MK-801L, MK-801M, MK-801H, respectively). Rats from the control group were intact or injected with saline (0.2 ml/kg). Over three consecutive days the rats underwent habituation, two avoidance training intervals with shocks, and a retrieval test. The shock sector was alternated daily. The after-effects of the agents were tested on Day 21. Rats treated with low dose memantine presented a longer maximum time avoided and fewer entrances than the MemH, MK-801M, MK-801H and Control rats. The shocks per entrances ratio, used as an index of cognitive skill learning, showed skill improvement after D1, except for rats treated by high doses of the agents. The activity levels, indicated by the distance walked, were higher for the groups treated with high doses of the agents. On D21 the MK801H rats performed the memory task better than the MemH rats, whereas the rats' activity depended on condition, not on the group factor. These results suggest that in naïve rats mild NMDAR blockade by low-dose memantine improves working memory related to a highly challenging task. PMID:24385956

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2015-07-01

High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

Patterns of Radiotherapy Practice for Pancreatic Cancer in Japan: Results of the Japanese Radiation Oncology Study Group (JROSG) Survey

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

Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.j; Ito, Yoshinori; Karasawa, Katsuyuki

2010-07-01

Purpose: To determine the patterns of radiotherapy practice for pancreatic cancer in Japan. Methods and Materials: A questionnaire-based national survey of radiotherapy for pancreatic cancer treated between 2000 and 2006 was conducted by the Japanese Radiation Oncology Study Group (JROSG). Detailed information on 870 patients from 34 radiation oncology institutions was accumulated. Results: The median age of all patients was 64 years (range, 36-88), and 80.2% of the patients had good performance status. More than 85% of patients had clinical Stage T3-T4 disease, and 68.9% of patients had unresectable disease at diagnosis. Concerning radiotherapy (RT), 49.8% of patients were treatedmore » with radical external beam RT (EBRT) (median dose, 50.4 Gy), 44.4% of patients were treated with intraoperative RT (median dose, 25 Gy) with or without EBRT (median dose, 45 Gy), and 5.9% of patients were treated with postoperative radiotherapy (median dose, 50 Gy). The treatment field consisted of the primary tumor (bed) only in 55.6% of the patients. Computed tomography-based treatment planning and conformal RT was used in 93.1% and 83.1% of the patients treated with EBRT, respectively. Chemotherapy was used for 691 patients (79.4%; before RT for 66 patients; during RT for 531; and after RT for 364). Gemcitabine was the most frequently used drug, followed by 5-fluorouracil. Conclusion: This study describes the general patterns of RT practice for pancreatic cancer in Japan. Most patients had advanced unresectable disease, and radical EBRT, as well as intraoperative RT with or without EBRT, was frequently used. Chemotherapy with gemcitabine was commonly used in conjunction with RT during the survey period.« less

High-dose versus weekly cisplatin definitive chemoradiotherapy for HPV-related oropharyngeal squamous cell carcinoma of the head and neck.

PubMed

Perez, Cesar Augusto; Wu, Xiaoyong; Amsbaugh, Mark J; Gosain, Rahul; Claudino, Wederson M; Yusuf, Mehran; Roberts, Teresa; Jain, Dharamvir; Jenson, Alfred; Khanal, Sujita; Silverman, Craig I; Tennant, Paul; Bumpous, Jeffrey M; Dunlap, Neal E; Rai, Shesh N; Redman, Rebecca A

2017-04-01

To compare the outcomes and toxicity of high-dose cisplatin (HDC) versus weekly cisplatin (WC) definitive chemoradiotherapy (CRT) for patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (SCCOPx). All patients with p16 positive SCCOPx treated with definitive CRT with cisplatin between 2010 and 2014 at a single institution were retrospectively reviewed. CTCAE v 4.03 toxicity criteria were used. The Kaplan-Meier method was used to estimate event-free survival (EFS) and the overall survival (OS). Of the 55 patients included, 22 were patients treated with HDC at dose of 100mg/m 2 on days 1 and 22; and the remaining 33 patients were treated with WC at 40mg/m 2 . Both cohorts received a median total dose of cisplatin of 200mg/m 2 . At median follow-up of 31months, there was one local failure and no distant failures in the HDC cohort. In the WC group, there were 6 total failures (2 local, 4 distant). Estimated 2-year EFS was better in HDC cohort as compared to WC (96% vs. 75%; p=0.04). There was no significant difference in 2-year OS (95% vs. 94%; p=0.40). Weight loss, gastric tube dependence at six months, acute renal injury and grade 3 or 4 hematological toxicity were all similar between both groups. HPV-related SCCOPx treated with definitive CRT with either HDC or WC had similar toxicity profile. HDC had better EFS when compared with WC and this seems to be driven by increased distant failure rates, although the OS was similar. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dose-Effect Relationships for Adverse Events After Cranial Radiation Therapy in Long-term Childhood Cancer Survivors

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

Dijk, Irma W.E.M. van, E-mail: i.w.vandijk@amc.uva.nl; Cardous-Ubbink, Mathilde C.; Pal, Helena J.H. van der

Purpose: To evaluate the prevalence and severity of clinical adverse events (AEs) and treatment-related risk factors in childhood cancer survivors treated with cranial radiation therapy (CRT), with the aim of assessing dose-effect relationships. Methods and Materials: The retrospective study cohort consisted of 1362 Dutch childhood cancer survivors, of whom 285 were treated with CRT delivered as brain irradiation (BI), as part of craniospinal irradiation (CSI), and as total body irradiation (TBI). Individual CRT doses were converted into the equivalent dose in 2-Gy fractions (EQD{sub 2}). Survivors had received their diagnoses between 1966 and 1996 and survived at least 5 yearsmore » after diagnosis. A complete inventory of Common Terminology Criteria for Adverse Events grade 3.0 AEs was available from our hospital-based late-effect follow-up program. We used multivariable logistic and Cox regression analyses to examine the EQD{sub 2} in relation to the prevalence and severity of AEs, correcting for sex, age at diagnosis, follow-up time, and the treatment-related risk factors surgery and chemotherapy. Results: There was a high prevalence of AEs in the CRT group; over 80% of survivors had more than 1 AE, and almost half had at least 5 AEs, both representing significant increases in number of AEs compared with survivors not treated with CRT. Additionally, the proportion of severe, life-threatening, or disabling AEs was significantly higher in the CRT group. The most frequent AEs were alopecia and cognitive, endocrine, metabolic, and neurologic events. Using the EQD{sub 2}, we found significant dose-effect relationships for these and other AEs. Conclusion: Our results confirm that CRT increases the prevalence and severity of AEs in childhood cancer survivors. Furthermore, analyzing dose-effect relationships with the cumulative EQD{sub 2} instead of total physical dose connects the knowledge from radiation therapy and radiobiology with the clinical experience.« less

Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4-methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi-organ carcinogenesis model.

PubMed

Hirose, M; Takesada, Y; Tanaka, H; Tamano, S; Kato, T; Shirai, T

1998-01-01

The carcinogenicity of low dietary levels of the antioxidants butylated hydroxyanisole (BHA), caffeic acid, sesamol, 4-methoxyphenol (4-MP) and catechol, known to target the forestomach or glandular stomach, were examined alone or in combination in a 2-year long-term experiment and their modifying effects assessed in a medium-term multiorgan model. In the carcinogenicity study, groups of 30-31 male F344 rats were treated with 0.4% BHA, 0.4% caffeic acid, 0.4% sesamol, 0.4% 4-MP and 0.16% catechol either alone or in combination for up to 104 weeks and then killed. In the medium-term multi-organ model, groups of 10 to 15 male F344 rats were given diethylnitrosamine (DEN), N-methylnitrosourea (MNU), 1,2-dimethylhydrazine (DMH), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) for a total multiple initiation period of 4 weeks (DMBDD treatment). BHA, caffeic acid, sesamol and 4-MP, each at doses of 0.4% or 0.08%, and catechol at doses of 0.16% or 0.032% were administered in the diet either alone or in combination after completion of the initiation regimen. All surviving animals were killed at the end of week 28, and major organs were examined histopathologically. In the carcinogenicity study, slightly increased incidences of forestomach papillomas were found in the sesamol- (15.8%), caffeic acid- (14.8%), catechol- (3%) and 4-MP- (11.5%) treated groups as compared with basal diet (0%), and a significant increase was observed with the five antioxidants in combination (42.9%, P < 0.001). In a medium-term multiorgan carcinogenesis model, incidences of forestomach papillomas and/or carcinomas were increased in each high dose group, but additive or synergistic effects were not found in the combination group. In the low dose case, the incidence of forestomach papillomas was significantly increased only in the combination group. With regard to other organs, the incidence of colon tumors was significantly decreased only in the high dose combination group. The results indicate that even at low dose levels phenolic compounds can exert additive/synergistic effect on carcinogenesis.

Studies on a suitable antibiotic therapy for treating swine brucellosis.

PubMed

Dieste-Pérez, L; Fraile, L; de Miguel, M J; Barberán, M; Blasco, J M; Muñoz, P M

2015-08-01

The aim of this work was developing effective treatments against Brucella suis biovar 2, responsible for swine brucellosis in Europe. MICs for antibiotics used classically in brucellosis and two new macrolides (tulathromycin and tildipirosin) were determined for 33 B. suis biovar 2 field and B. suis reference strains. MIC90 values ranged from 0.01 to 0.25 μg/mL. The best candidates, given alone or combined, were then evaluated in mice. Ten groups (n = 7) of BALB/c mice were inoculated (1 × 10(5) CFU/mouse) with a virulent B. suis biovar 2 field strain. All groups, excepting untreated control, were treated for 14 days with, respectively, doxycycline, dihydrostreptomycin, tulathromycin (one or two doses), or tildipirosin (one or two doses) given alone, and doxycycline combined with dihydrostreptomycin, tulathromycin, or tildipirosin. Combined tildipirosin treatment was the most effective, then selected for pig studies. Sixteen B. suis biovar 2 naturally infected sows were treated with oxytetracycline (20 mg/kg BW/daily) for 21 days. The half of these received also tildipirosin (4 mg/kg BW) in two doses with a 10-day interval. An extensive bacteriological study conducted ten days after ceasing treatments proved the efficacy of this combined oxytetracycline/tildipirosin treatment. © 2014 John Wiley & Sons Ltd.

Low dose radiation prevents doxorubicin-induced cardiotoxicity.

PubMed

Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

2018-01-02

This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study

PubMed Central

Okada, Sadanori; Morimoto, Takeshi; Ogawa, Hisao; Sakuma, Mio; Soejima, Hirofumi; Nakayama, Masafumi; Jinnouchi, Hideaki; Waki, Masako; Akai, Yasuhiro; Ishii, Hitoshi; Saito, Yoshihiko

2016-01-01

Background Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes. Methods We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR). Results Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995–1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92–1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, −0.8 ± 2.9; no aspirin, −0.9 ± 2.5 ml/min/1.73m2/year). Conclusion Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes. PMID:26808136

Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study.

PubMed

Okada, Sadanori; Morimoto, Takeshi; Ogawa, Hisao; Sakuma, Mio; Soejima, Hirofumi; Nakayama, Masafumi; Jinnouchi, Hideaki; Waki, Masako; Akai, Yasuhiro; Ishii, Hitoshi; Saito, Yoshihiko

2016-01-01

Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes. We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR). Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995-1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92-1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, -0.8 ± 2.9; no aspirin, -0.9 ± 2.5 ml/min/1.73 m(2)/year). Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes.

Whole-brain Irradiation Field Design: A Comparison of Parotid Dose.

PubMed

Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish; Saraf, Anurag; Tai, Cheng-Hung; Lapa, Matthew E; Andrew, Jacquelyn I S; Tiwari, Akhil; Saadatmand, Heva J; Isaacson, Steven R; Cheng, Simon K; Wang, Tony J C

2017-01-01

Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: mean <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED 3 , the parotid doses were lower than BED 3 constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED 3 conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose constraint with BED 3 should be less than 32.83 Gy. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Whole-brain Irradiation Field Design: A Comparison of Parotid Dose

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

Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish

Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: meanmore » <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED{sub 3}, the parotid doses were lower than BED{sub 3} constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED{sub 3} conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose constraint with BED{sub 3} should be less than 32.83 Gy.« less

Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity.

PubMed

Sakakura, Kenichi; Roth, Austin; Ladich, Elena; Shen, Kai; Coleman, Leslie; Joner, Michael; Virmani, Renu

2015-02-01

The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall. Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment. In the gel model, the peak temperature was highest in the low power-long duration (LP-LD) dose, followed by the mid-low power-mid duration (MLP-MD) dose and the mid-high power-short duration (MHP-SD) dose, and lowest in the mid power-short duration (MP-SD) dose and the high power-ultra short duration (HP-USD) dose. In the animal study, total ablation area was significantly greater in the LP-LD group, followed by the MLP-MD group, and it was least in the HP-USD, MP-SD and MHP-SD groups (p=0.02). Maximum distance was significantly greater in the LP-LD group, followed by the MLP-MD group, the MHP-SD group, and the HP-USD group, and shortest in the MP-SD group (p=0.007). The short spare distance was not different among the five groups (p=0.38). Renal artery damage was minimal, while preserving significant nerve damage in all groups. The Paradise Ultrasound Renal Denervation System is a controllable system where total ablation area and depth of ablation can be optimised by changing ultrasound power and duration while sparing renal arterial tissue damage but allowing sufficient peri-arterial nerve damage.

[Effect of Acaí (Euterpe oleracea) on biological expression characteristics of deficiency-heat and deficiency-cold rats].

PubMed

Wang, Lin-Yuan; Zhang, Jian-Jun; Wang, Chun; Zhu, Ying-Li; Wang, Zi-Chen; He, Cheng; Qu, Yan; Wang, Sha

2016-10-01

To study the effects of Acaí on biological expression characteristics in rats with deficiency-heat and deficiency-cold syndromes, SD rats were divided into blank group, deficiency-heat model group, deficiency-heat+Phellodendri Chinensis Cortex group, deficiency-heat+Acaí high dose and low dose groups, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Acaí high dose and low dose groups. The rats were treated with intramuscular injection of hydrocortisone (20 mg•kg⁻¹) or dexamethasone sodium phosphate (0.35 mg•kg⁻¹) for 21 days to set up deficiency-heat model and deficiency-cold models. The levels of cAMP, cGMP, T3, T4 and rT3 were detected by radioimmunoassay. The levels of TP, UA, TC, TG and ALB were detected by colorimetry. The level of cAMP, cAMP/cGMP in serum were reduced in Acaí high dose group (P<0.05, P<0.001). The levels of T3, T4 and rT3 were significantly reduced in the Acaí high dose group (P<0.01, P<0.001, P<0.05). The levels of TP, UA, TC, TG and ALB were significantly reduced in the Acaí high dose group (P<0.001, P<0.05, P<0.05, P<0.05, P<0.01). However, Acaí had no obvious effects on deficiency-cold models. Acaí showed the same effect with Phellodendri Chinensis Cortex in adjusting the levels of deficiency-heat rats; but unlike Cinnamomi Cortex, Acaí showed no obvious effects in adjusting the levels of deficiency-cold rats. Copyright© by the Chinese Pharmaceutical Association.

Effect of atomoxetine on hyperactivity in an animal model of attention-deficit/hyperactivity disorder (ADHD).

PubMed

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.

Effect of Atomoxetine on Hyperactivity in an Animal Model of Attention-Deficit/Hyperactivity Disorder (ADHD)

PubMed Central

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Background Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). Purpose To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Methods Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. Results The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Conclusion Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway. PMID:25271814

Dose assessment of 2% chlorhexidine acetate for canine superficial pyoderma.

PubMed

Murayama, Nobuo; Terada, Yuri; Okuaki, Mio; Nagata, Masahiko

2011-10-01

The dose of 2% chlorhexidine acetate (2CA; Nolvasan(®) Surgical Scrub; Fort Dodge Animal Health, Fort Dodge, IA, USA) for canine superficial pyoderma was evaluated. The first trial compared three doses (group 1, 57 mL/m(2) body surface area; group 2, 29 mL/m(2) body surface area; and group 3, 19 mL/m(2) body surface area) in a randomized, double-blind, controlled fashion. Twenty-seven dogs with superficial pyoderma were treated with 2CA at the allocated doses every 2 days for 1 week. The owners and investigators subjectively evaluated the dogs, and investigators scored skin lesions, including erythema, papules/pustules, alopecia and scales, on a 0-4 scale. There were no significant differences in response between the treatment groups. The second trial established a practical dose-measuring method for 2CA. Sixty-eight owners were asked to apply 2CA on their palm in an amount corresponding to a Japanese ¥500 coin, 26.5 mm in diameter. This yielded an average dose of 0.90±0.40 mL. Mathematically, the doses used in groups 1, 2 and 3 can be represented as one coin per approximately one-, two- and three-hand-sized lesions, respectively. The results therefore suggest that owners instructed to apply one coin of the product per two-hand-sized areas of superficial pyoderma would use the range of doses evaluated in this trial. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

Prolonged exposure to a low-dose of bisphenol A increases spontaneous motor activity in adult male rats.

PubMed

Nojima, Kazuo; Takata, Tomoyo; Masuno, Hiroshi

2013-07-01

We investigated the effects of bisphenol A (BPA), an environmental endocrine-disrupting chemical, on spontaneous motor activity in adult male rats. The rats were implanted intraperitoneally with mini-osmotic pumps containing either BPA (50 μg/kg body weight per day) in sesame oil (BPA-treated group) or sesame oil only (vehicle-treated group). Spontaneous motor activity during a 24-h period was measured over 5 days from day 9 to day 13 after implantation using an animal movement analysis system. Spontaneous motor activity during the last 2 h of the dark phase and during the first 1-h of the light phase was increased in the BPA-treated group. Total spontaneous motor activity during the 12-h light phase, but not the 12-h dark phase, was higher in the BPA-treated group than in the vehicle-treated group. These findings suggest that BPA may induce hyperactivity in adult male rats during the 12-h light phase, especially during the 2 h immediately preceding sleep-onset and 1 h immediately following sleep-onset.

Effect of apitherapy in piglets with preweaning diarrhea.

PubMed

Choi, Seok Hwa; Cho, Seong Koo; Kang, Seong Soo; Bae, Chun Sik; Bai, Young Hoon; Lee, Seung Hoo; Pak, Sok Cheon

2003-01-01

This study was designed to examine the therapeutic effect of honeybee (Apis mellifera L.) venom in piglets with bacterial diarrhea Comparison between bee venom- and drug-treated groups was our main concern in the present study. Preweaning piglets were assigned to treated and non-treated control groups. In the treated group, 47 piglets were acupunctured with the worker honeybee once a day for three consecutive days. Two acupoints, GV-1 (Jiao-chao) and ST-25 (Hai-men), were selected for apitherapy. In the control group, 44 piglets were intramuscularly injected with a standard dose of a known antibacterial drug, colistin sulfate (300,000 IU/kg of body weight), and an antidiarrheal drug (berberine, 2 ml/kg) once a day for three consecutive days. At post-treatment, 90.9% of the control piglets and 93.6% of piglets in the treated group recovered from bacterial diarrhea. Bee acupuncture therapy did not show any side effects such as allergy, intoxication, hemorrhage or infection. It is concluded that bee venom therapy was effective in controlling bacterial diarrhea in preweaning piglets.

Comparative assessment of onion and garlic extracts on endogenous hepatic and renal antioxidant status in rat.

PubMed

Suru, Stephen M; Ugwu, Chidiebere E

2015-07-01

Despite growing claims of functional health benefits in folkloric medicine, the safety of chronic/elevated intakes of onion and garlic cannot be assumed. Therefore, this study assesses oral administration of varied doses of onion and garlic on some biomarkers of hepatic and renal functions in rats. Animals were divided into five groups: control group received vehicle and extract-treated groups received varied doses of onion or garlic extract (0.5 mL and 1.0 mL/100 g bwt/day) for 6 weeks. Both doses of onion caused marked (p<0.05) increase in hepatic and renal levels of glutathione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and marked (p<0.05) decrease in malondialdehyde (MDA). Treatment with low dose of garlic elicited similar trend except in hepatic CAT, renal SOD and GST levels. A high dose of garlic only caused marked (p<0.05) increase in hepatic GST, renal GST, and SOD. Both doses of onion and low dose of garlic significantly (p<0.05) enhanced renal Na+/K+-ATPase activity. Only a high dose of onion caused significant (p<0.05) increase in hepatic aspartate transaminase (AST), alkaline phosphatase (ALP), and decrease in plasma AST activities. These findings suggest antioxidant enhancing capability for both doses of onion and low dose of garlic, while high dose of garlic elicited pro-oxidant conditions.

Pre-harvest UV-C irradiation triggers VOCs accumulation with alteration of antioxidant enzymes and phytohormones in strawberry leaves.

PubMed

Xu, Yanqun; Luo, Zisheng; Charles, Marie Thérèse; Rolland, Daniel; Roussel, Dominique

2017-11-01

Recent studies have highlighted the biological and physiological effects of pre-harvest ultraviolet (UV)-C treatment on growing plants. However, little is known about the involvement of volatile organic compounds (VOCs) and their response to this treatment. In this study, strawberry plants were exposed to three different doses of UV-C radiation for seven weeks (a low dose: 9.6kJm -2 ; a medium dose: 15kJm -2 ; and a high-dose: 29.4kJm -2 ). Changes in VOC profiles were investigated and an attempt was made to identify factors that may be involved in the regulation of these alterations. Principle compounds analysis revealed that VOC profiles of UV-C treated samples were significantly altered with 26 VOCs being the major contributors to segregation. Among them, 18 fatty acid-derived VOCs accumulated in plants that received high and medium dose of UV-C treatments with higher lipoxygenase and alcohol dehydrogenase activities. In treated samples, the activity of the antioxidant enzymes catalase and peroxidase was inhibited, resulting in a reduced antioxidant capacity and higher lipid peroxidation. Simultaneously, jasmonic acid level was 74% higher in the high-dose group while abscisic acid content was more than 12% lower in both the medium and high-dose UV-C treated samples. These results indicated that pre-harvest UV-C treatment stimulated the biosynthesis of fatty acid-derived VOCs in strawberry leaf tissue by upregulating the activity of enzymes of the LOX biosynthetic pathway and downregulating antioxidant enzyme activities. It is further suggested that the mechanisms underlying fatty acid-derived VOCs biosynthesis in UV-C treated strawberry leaves are associated with UV-C-induced changes in phytohormone profiles. Crown Copyright © 2017. Published by Elsevier GmbH. All rights reserved.

A retrospective Aliskiren and Losartan study in non-diabetic chronic kidney disease.

PubMed

Woo, Keng-Thye; Choong, Hui-Lin; Wong, Kok-Seng; Tan, Han-Kim; Foo, Marjorie; Stephanie, Fook-Chong; Lee, Evan Jc; Anantharaman, Vathsala; Lee, Grace Sl; Chan, Choong-Meng

2013-11-06

To assess the efficacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease (CKD). This is a retrospective study of 143 patients with non-diabetic CKD comparing combined Aliskiren (150 mg/d) with Losartan (100 mg/d) therapy vs High dose Angiotensin receptor blockers (ARB) (Losartan 200 mg/d) and the third group Aliskiren (150 mg/d) alone. This study involved only patient medical records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate (eGFR) < 15 mL/min or end stage renal failure. Patients treated with high dose ARB compared to the other two treatment groups had significantly less proteinuria at the end of 36 mo (P < 0.007). All 3 groups had significant reduction of proteinuria (P < 0.043, P < 0.001). Total urinary protein was significantly different between the 3 groups over the 3-year study period (P = 0.008), but not eGFR. The changes in eGFR from baseline to each year were not significantly different between the 3 therapeutic groups (P < 0.119). There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia (> 5.5 mmol/L) was 14.2% (7/49) in the Combined Aliskiren and ARB group, 8.7% (4/46) in the Aliskiren alone group and 6.3% (3/48) in the High dose ARB group (P < 0.001). This study in non-diabetic CKD patients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was associated with a high prevalence of hyperkalaemia.

Patients' perspectives on management and barriers of regular antiepileptic drug intake.

PubMed

May, Theodor W; Berkenfeld, Ralf; Dennig, Dieter; Scheid, Brigitte; Hausfeld, Heiko; Walther, Sonja; Specht, Ulrich

2018-02-01

The aim of our study was to assess the management of drug intake and potential barriers to adherence reported by two different patient groups. The study was performed in cooperation with the Regional Chamber of Pharmacists of Rhineland-Palatinate and three neurologists in private practice specialized in epileptology. In total, 108 patients surveyed in 43 pharmacies (Group P) and 118 patients treated by the specialized neurologists (Group N) completed anonymously a questionnaire on intake of antiepileptic drugs (AEDs). The statistical evaluation was performed using nonparametric tests and logistic regression analyses. Group N more often used adherence aids, compared with Group P (68.6% vs. 46.3%, p<0.01), and the number of doses per day was significantly lower in Group N (Mann-Whitney test, p=0.046), but the percentage of patients who reported problems with the regular intake of their medication did not differ significantly between groups (Group N vs. P: 47.0% vs. 40.0%). If patients noticed that they missed a dose, 45.3% completely skipped the missed dose (Group N vs. P: 43.0% vs. 48.1%, n.s.). In a multivariate analysis, significant risk factors of problems with regular drug intake were age<25yrs. (p<0.01) and patient-reported adverse effect of AED (p<0.01), followed by the number of AED doses per day (p<0.05), while gender, intake habits, usage of adherence aids, and patient-rated efficacy of AEDs were not significant. Patients treated by neurologists specialized in epileptology did not report less problems with adherence than patients surveyed in pharmacies. Since barriers for a regular intake are diverse, the use of a short questionnaire on management of drug intake may lead to an individually tailored counseling of patients to improve adherence. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Musa sapientum Stem Extract on Animal Models of Depression

PubMed Central

Reddy, Aditya J.; Handu, Shailendra S.; Dubey, Ashok Kumar; Mediratta, Pramod Kumari; Shukla, Rimi; Ahmed, Qazi Mushtaq

2016-01-01

Background: Musa sapientum, the banana plant, has shown to possess antioxidant activity in previous studies. Oxidative stress has been linked to the pathogenesis of major depressive disorder (MDD) with evidence of increased serum levels of oxidative stress biomarkers in MDD patients. Objective: The present study aimed to evaluate the antidepressant activity of M. sapientum stem extract (MSSE) in experimental models in mice. Materials and Methods: Forced swim test (FST) and tail suspension test (TST) were carried out in five different groups (n = 6/group) of mice. The vehicle, standard drug, and the three test groups were orally administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and incremental doses of 25, 50, and 100 mg of MSSE, respectively, 45 min prior to the experiment. Results: On FST, the duration of immobility in control group, which was 161.5 ± 6.78 (in seconds, mean ± standard error of mean [SEM]), decreased to 149.33 ± 2.70 (25 mg/kg MSSE), 120.17 ± 8.35 (50 mg/kg MSSE), and 45.17 ± 4.11 (100 mg/kg MSSE) in the treated groups. On TST, the duration of immobility in control group, which was 173.83 ± 12.65 (mean ± SEM), decreased to 163.17 ± 6.91 (25 mg/kg MSSE), 139.0 ± 5.9 (50 mg/kg MSSE), and 124.0 ± 4.42 (100 mg/kg MSSE) in the treated groups. The difference in the duration of immobility was statistically significant at middle and higher doses, i.e. 50 and 100 mg/kg MSSE (P < 0.05) respectively, when compared with the control group in both the tests. Conclusion: A significant antidepressant-like activity was found in MSSE, which could be a potential natural compound for use in depression. SUMMARY The five groups – vehicle, standard drug, and the three test groups were administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and incremental doses of 25, 50, and 100 mg of Musa sapientum stem extract (MSSE), respectivelyThe duration of immobility decreased in the treated groups as compared to the control group on both, forced swim and tail suspension, testsThe difference in the duration of immobility was statistically significant at middle and higher doses, i.e., 50 and 100 mg/kg MSSE (P < 0.05), when compared with the control group in both the tests. Abbreviations Used: MDD: Major depressive disorder; MSSE: Musa sapientum stem extract; FST: Forced swim test; TST: Tail suspension test; GSH: Glutathione, MDA: Malondialdehyde; SOD: Superoxide dismutase PMID:27695263

A study comparing the safety and efficacy of febuxostat, allopurinol, and benzbromarone in Chinese gout patients: a retrospective cohort study
.

PubMed

Zhou, Qiao; Su, Jiang; Zhou, Ting; Tian, Juan; Chen, Xixi; Zhu, Jing

2017-02-01

To evaluate and compare the safety and efficacy of three urate lowering agents: febuxostat, allopurinol, and benzbromarone, when used to treat Chinese gout patients. A total of 120 patients treated in our department from November 2011 to December 2014 were randomly selected and divided into four groups: febuxostat (40 mg per day), febuxostat (80 mg per day), allopurinol (100 mg, 3 × per day) or benzbromarone (50 mg per day), (n = 30 patients/group). The serum uric acid (UA) concentrations of the patients in each group were recorded and compared from week 2 through week 24 after the treatments, and all adverse events were evaluated to determine the safety of the various treatment regimens. Treatment with febuxostat (40 mg) significantly reduced serum UA levels to those achieved with allopurinol or benzbromarone treatment. The treatment with febuxostat (80 mg) produced the best therapeutic effect and achieved the targeted UA level as early as week 2. However, the total number of patients experiencing adverse events was significantly higher in the febuxostat 80-mg group. The incidences of abnormal liver function, hyperlipidemia, and gout flare were higher in both febuxostat treatment groups. The allopurinol group had a higher incidence of hypersensitivity, and the benzbromarone group had a higher incidence of renal dysfunction. Chinese patients treated with the 40-mg dose of febuxostat experienced a treatment effect and total rate of adverse events similar to those produced by allopurinol or benzbromarone. To achieve a better therapeutic effect, the dose of febuxostat can be elevated to 80 mg per day; however, patients receiving the higher dose must be closely monitored for signs of liver dysfunction. Febuxostat is an alternative treatment for Chinese gout patients who are at a much higher risk for severe cutaneous adverse reactions as well as for patients with a history of kidney stones.
.

Immune response in pigs treated with therapeutic doses of enrofloxacin at the time of vaccination against Aujeszky's disease.

PubMed

Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Rachubik, Jarosław; Lipowski, Andrzej; Pejsak, Zygmunt

2015-06-01

The effect of treatment with enrofloxacin was studied on the postvaccinal immune response in pigs. Forty pigs were used (control not vaccinated (C), control vaccinated (CV), vaccinated, received enrofloxacin (ENRO)). From day -1 to day 3 pigs from ENRO group received enrofloxacin at the recommended dose. Pigs from ENRO and CV groups were vaccinated twice against Aujeszky's disease virus (ADV). There was a significant delay in the production of humoral response of enrofloxacin dosed pigs when compared with CV group. Moreover, in ENRO group the significant decrease in IFN-γ production and significantly lower values of stimulation index after ADV restimulation was noted, as compared with CV group. The secretion of IL-6, IL-10 and TNF-α by PBMC after recall stimulation was also affected in ENRO group. The results indicate that enrofloxacin, in addition to its antimicrobial properties, possess significant immunomodulatory effects and may alter the immune response to vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Time and dose-response effects of honokiol on UVB-induced skin cancer development.

PubMed

Guillermo, Ruth F; Chilampalli, Chandeshwari; Zhang, Xiaoying; Zeman, David; Fahmy, Hesham; Dwivedi, Chandradhar

2012-06-01

Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 μg), and then the effects of different honokiol doses (30, 45, and 60 μg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 μg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 μg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 μg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 μg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 μg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 μg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.

Enhanced UV-B radiation during pupal stage reduce body mass and fat content, while increasing deformities, mortality and cell death in female adults of solitary bee Osmia bicornis.

PubMed

Wasielewski, Oskar; Wojciechowicz, Tatiana; Giejdasz, Karol; Krishnan, Natraj

2015-08-01

The effects of enhanced UV-B radiation on the oogenesis and morpho-anatomical characteristics of the European solitary red mason bee Osmia bicornis L. (Hymenoptera: Megachilidae) were tested under laboratory conditions. Cocooned females in the pupal stage were exposed directly to different doses (0, 9.24, 12.32, and 24.64 kJ/m(2) /d) of artificial UV-B. Our experiments revealed that enhanced UV-B radiation can reduce body mass and fat body content, cause deformities and increase mortality. Following UV exposure at all 3 different doses, the body mass of bees was all significantly reduced compared to the control, with the highest UV dose causing the largest reduction. Similarly, following UV-B radiation, in treated groups the fat body index decreased and the fat body index was the lowest in the group receiving the highest dose of UV radiation. Mortality and morphological deformities, between untreated and exposed females varied considerably and increased with the dose of UV-B radiation. Morphological deformities were mainly manifested in the wings and mouthparts, and occurred more frequently with an increased dose of UV. Cell death was quantified by the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (DNA fragmentation) during early stages of oogenesis of O. bicornis females. The bees, after UV-B exposure exhibited more germarium cells with fragmented DNA. The TUNEL test indicated that in germarium, low doses of UV-B poorly induced the cell death during early development. However, exposure to moderate UV-B dose increased programmed cell death. In females treated with the highest dose of UV-B the vast majority of germarium cells were TUNEL-positive. © 2014 Institute of Zoology, Chinese Academy of Sciences.

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

PubMed

Narula, Neeraj; Cooray, Mohan; Anglin, Rebecca; Muqtadir, Zack; Narula, Alisha; Marshall, John K

2017-02-01

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. NCT02615288.

The regeneration of thermal wound on mice skin (Mus Musculus) after Q-Switch Nd: YAG laser irradiation for cancer therapy candidate

NASA Astrophysics Data System (ADS)

Apsari, R.; Nahdliyatun, E.; Winarni, D.

2017-09-01

The aims of this study are to investigate the regeneration of mice skin tissue (Mus Musculus) irradiated by Q-Switch Nd: YAG laser and morphological change due to Q-Switch Nd: YAG laser irradiation compared to conventional heating (hairdryer). The 2-3 month of twenty-seven mice were used for experimental animals. Mice were incised in the dorsum by the damage effect of laser energy dose (therapeutic dose) of 29.5 J/cm2 with 10 seconds of exposure time, 10 Hz of repetition rate, and 100 pulses of the given single pulse energy. The mice skin tissue was injuried by hairdryer to get burned effect. Mice were divided into three groups, Group I (control) were not treated by anything, Group II were treated by Q-Switch Nd: YAG laser irradiation and sacrificed on (0, 1, 3, 5) days, and Group III were treated by hairdryer then sacrificed on (0, 1, 3, 5) days. Pathology examination showed that the energy of 29,5 J/cm2 dose produced the hole effect (ablation) through the hypodermic layer caused by optical breakdown and collagen coagulation. Thus, the 60 °C temperature of burn showed coagulation necrosis because piknosis discovered in the injured area. The regeneration process showed that the mice skin tissue's ability to regenerate was irradiated by fast laser because of the focus of Q-Switch Nd: YAG laser. It was showed by the scab releases on third day and completely reepithelialization formation on the fifth day. The collagen fibers distribution was same as normal skin tissue on day 5 and so did angiogenesis. Therefore, Q-Switch Nd: YAG laser can be applied for problems of dermatology medical therapies, especially melasma, nevus of ota and tatto therapy. For skin cancer therapy application, energy dose of unregenerated skin tissue is chosen because the death expected effect is permanent.

The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

PubMed Central

Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Al-Henhena, Nawal; Kunasegaran, Thubasni; Hasanpourghadi, Mohadeseh; Looi, Chung Yeng; Abd Malek, Sri Nurestri; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

2015-01-01

Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation in AOM-treated rats and may offer protection against colon cancer development. PMID:26251570

Teriparatide versus low-dose bisphosphonates before and after surgery for adult spinal deformity in female Japanese patients with osteoporosis.

PubMed

Seki, Shoji; Hirano, Norikazu; Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Suzuki, Kayo; Watanabe, Kenta; Makino, Hiroto; Kanamori, Masahiko; Kimura, Tomoatsu

2017-08-01

Complications of adult spinal deformity surgery are problematic in osteoporotic individuals. We compared outcomes between Japanese patients treated perioperatively with teriparatide vs. low-dose bisphosphonates. Fifty-eight osteoporotic adult Japanese female patients were enrolled and assigned to perioperative teriparatide (33 patients) and bisphosphonate (25 patients) groups in non-blinded fashion. Pre- and post-operative X-ray and computed tomography imaging were used to assess outcome, and rates were compared between the groups and according to age. Pain scores and Oswestry Disability Indices (ODI) were calculated before and 2 years after surgery. Adjacent vertebral fractures and implant failure, fusion failure, and poor pain and ODI outcomes were significantly more common in the bisphosphonates group than the teriparatide group. Perioperative administration of teriparatide is more effective than that of low-dose bisphosphonates in preventing complications and maintaining fusion rates in osteoporotic Japanese females with spinal deformities undergoing surgery.

Induction dosing of peginterferon alfa-2a (40 KD) and/or high-dose ribavirin in genotype 1 CHC patients with difficult-to-treat characteristics: pharmacokinetic and viral kinetic (PK/VK) assessment from PROGRESS.

PubMed

Morcos, Peter N; Leong, Ruby; Thommes, James A; DePamphilis, Jean; Grippo, Joseph F; Brennan, Barbara J

2015-01-01

PROGRESS randomized chronic hepatitis C genotype 1 patients with a baseline viral load ≥400,000 IU/mL weighing ≥85 kg to regimens of 180 μg/week for 48 weeks or 360 μg/week for 12 weeks followed by 180 μg/week for 36 weeks peginterferon alfa-2a plus ribavirin. This analysis explored pharmacokinetics and early viral kinetics (VK) and evaluates differences between groups. Blood samples for pharmacokinetic and VK analyses were collected from 51 patients enrolled in the PROGRESS study. Mean peginterferon alfa-2a trough concentration at week 12 was 11.7±4.3 ng/mL for 180 μg and 23.4±11.3 ng/mL for 360 μg. Early VK profiles suggested a trend towards an enhanced viral decline in the 360 μg groups with a mean decrease in HCV RNA at 48 hours post first dose of 1.04 log10 (IU/mL) compared with 0.76 log10 (IU/mL) in the 180 μg groups. Mean beta slope increased with dose, ranging from 0.38±0.26 log10 IU/week at 180 μg to 0.52±0.32 log10 IU/week at 360 μg. Early viral de clines may be enhanced with the 360 μg dose. These data may suggest the utility of high-dose peginterfer on alfa-2a plus direct-acting antivirals (DAA) in select difficult-to-treat populations.

Incidental irradiation of mediastinal and hilar lymph node stations during 3D-conformal radiotherapy for non-small cell lung cancer.

PubMed

Kepka, Lucyna; Bujko, Krzysztof; Zolciak-Siwinska, Agnieszka; Garmol, Dariusz

2008-01-01

To estimate the doses of incidental irradiation in particular lymph node stations (LNS) in different extents of elective nodal irradiation (ENI) in 3D-conformal radiotherapy (3D-CRT) for non-small cell lung cancer (NSCLC). METHODS; Doses of radiotherapy were estimated for particular LNS delineated according to the recommendations of the University of Michigan in 220 patients treated using 3D-CRT with different (extended, limited and omitted) extents of ENI. Minimum doses and volumes of LNS receiving 40 Gy or more (V40) were compared for omitted vs. limited+ extended ENI and limited vs. extended ENI. For omission of the ENI the minimum doses and V40 for particular LNS were significantly lower than for patients treated with ENI. For the limited ENI group, the minimum doses for LNS 5, 6 lower parts of 3A and 3P (not included in the elective area) did not differ significantly from doses given to respective LNS for extended ENI group. When the V40 values for extended and limited ENI were compared, no significant differences were seen for any LNS, except for group 1/2R, 1/2L. Incidental irradiation of untreated LNS seems play a part in case of limited ENI, but not in cases without ENI. For subclinical disease the delineation of uninvolved LNS 5, 6, and lower parts of 3A, 3P may be not necessary, because these stations receive the substantial part of irradiation incidentally, if LNS 4R, 4L, 7, and ipsilateral hilum are included in the elective area while this is not case for stations 1 and 2.

Icariin Improves Cognitive Impairment after Traumatic Brain Injury by Enhancing Hippocampal Acetylation.

PubMed

Zhang, Zi-Gang; Wang, Xin; Zai, Jin-Hai; Sun, Cai-Hua; Yan, Bing-Chun

2018-05-01

To examine the effect of icariin (ICA) on the cognitive impairment induced by traumatic brain injury (TBI) in mice and the underlying mechanisms related to changes in hippocampal acetylation level. The modifified free-fall method was used to establish the TBI mouse model. Mice with post-TBI cognitive impairment were randomly divided into 3 groups using the randomised block method (n=7): TBI (vehicle-treated), low-dose (75 mg/kg) and high-dose (150 mg/kg) of ICA groups. An additional sham-operated group (vehicle-treated) was employed. The vehicle or ICA was administrated by gavage for 28 consecutive days. The Morris water maze (MWM) test was conducted. Acetylcholine (ACh) content, mRNA and protein levels of choline acetyltransferase (ChAT), and protein levels of acetylated H3 (Ac-H3) and Ac-H4 were detected in the hippocampus. Compared with the sham-operated group, the MWM performance, hippocampal ACh content, mRNA and protein levels of ChAT, and protein levels of Ac-H3 and Ac-H4 were signifificantly decreased in the TBI group (P<0.05). High-dose of ICA signifificantly ameliorated the TBI-induced weak MWM performance, increased hippocampal ACh content, and mRNA and protein levels of ChAT, as well as Ac-H3 protein level compared with the TBI group (P<0.05). ICA improved post-TBI cognitive impairment in mice by enhancing hippocampal acetylation, which improved hippocampal cholinergic function and ultimately improved cognition.

Proton-pump inhibitors for prevention of upper gastrointestinal bleeding in patients undergoing dialysis.

PubMed

Song, Young Rim; Kim, Hyung Jik; Kim, Jwa-Kyung; Kim, Sung Gyun; Kim, Sung Eun

2015-04-28

To investigate the preventive effects of low-dose proton-pump inhibitors (PPIs) for upper gastrointestinal bleeding (UGIB) in end-stage renal disease. This was a retrospective cohort study that reviewed 544 patients with end-stage renal disease who started dialysis at our center between 2005 and 2013. We examined the incidence of UGIB in 175 patients treated with low-dose PPIs and 369 patients not treated with PPIs (control group). During the study period, 41 patients developed UGIB, a rate of 14.4/1000 person-years. The mean time between the start of dialysis and UGIB events was 26.3 ± 29.6 mo. Bleeding occurred in only two patients in the PPI group (2.5/1000 person-years) and in 39 patients in the control group (19.2/1000 person-years). Kaplan-Meier analysis of cumulative non-bleeding survival showed that the probability of UGIB was significantly lower in the PPI group than in the control group (log-rank test, P < 0.001). Univariate analysis showed that coronary artery disease, PPI use, anti-coagulation, and anti-platelet therapy were associated with UGIB. After adjustments for the potential factors influencing risk of UGIB, PPI use was shown to be significantly beneficial in reducing UGIB compared to the control group (HR = 13.7, 95%CI: 1.8-101.6; P = 0.011). The use of low-dose PPIs in patients with end-stage renal disease is associated with a low frequency of UGIB.

Effects of exogenous human leptin on heat shock protein 70 expression in MCF-7 breast cancer cells and breast carcinoma of nude mice xenograft model.

PubMed

Xue, Rong-quan; Gu, Jun-chao; Yu, Wei; Wang, Yu; Zhang, Zhong-tao; Ma, Xue-mei

2012-02-01

It is important to identify the multiple sites of leptin activity in obese women with breast cancer. In this study, we examined the effect of exogenous human leptin on heat shock protein 70 (HSP70) expression in MCF-7 human breast cancer cells and in a breast carcinoma xenograft model of nude mice. We cultured MCF-7 human breast cancer cells and established nude mice bearing xenografts of these cells, and randomly divided them into experimental and control groups. The experimental group was treated with human leptin, while the control group was treated with the same volume of normal saline. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed to quantify the mRNA expression of HSP70 in the MCF-7 human breast cancer cells and in tumor tissues. Western blotting analysis was applied to quantify the protein expression of HSP70 in the MCF-7 cells. Immunohistochemical staining was done to assess the positive rate of HSP70 expression in the tumor tissues. Leptin activated HSP70 in a dose-dependent manner in vitro: leptin upregulated significantly the expression of HSP70 at mRNA and protein levels in MCF-7 human breast cancer cells (P < 0.001). There was no significant difference in expression of HSP70 mRNA in the implanted tumors between the leptin-treated group and the control group (P > 0.05). Immunohistochemical staining revealed no significant difference in tumor HSP70 expression between the leptin-treated group and the control group (P > 0.05). A nude mouse xenograft model can be safely and efficiently treated with human leptin by subcutaneous injections around the tumor. HSP70 may be target of leptin in breast cancer. Leptin can significantly upregulate the expression of HSP70 in a dose-dependent manner in vitro.

Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy.

PubMed

Corletto, Anna; Fröhlich, Hanna; Täger, Tobias; Hochadel, Matthias; Zahn, Ralf; Kilkowski, Caroline; Winkler, Ralph; Senges, Jochen; Katus, Hugo A; Frankenstein, Lutz

2018-05-17

Beta blockers improve survival in patients with chronic systolic heart failure (CHF). Whether physicians should aim for target dose, target heart rate (HR), or both is still under debate. We identified 1,669 patients with systolic CHF due to ischemic heart disease or idiopathic dilated cardiomyopathy from the University Hospital Heidelberg and the Clinic of Ludwigshafen, Germany. All patients were treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker and had a history of CHF known for at least 6 months. Target dose was defined as treatment with ≥ 95% of the respective published guideline-recommended dose. Target HR was defined as 51-69 bpm. All-cause mortality during the median follow-up of 42.8 months was analysed with respect to beta blocker dosing and resting HR. 201 (12%) patients met the dose target (group A), 285 (17.1%) met the HR target (group B), 627 (37.6%) met no target (group C), and 556 (33.3%) did not receive beta blockers (Group D). 5-year mortality was 23.7, 22.7, 37.6, and 55.6% for group A, B, C, and D, respectively (p <  0.001). Survival for group A patients with a HR ≥ 70 bpm was 28.8% but 14.8% if HR was 50-70 bpm (p = 0.054). Achieving guidelines recommended beta blocker dose or to HR control has a similar positive impact on survival. When on target dose, supplemental HR control additionally improves survival.

A 13-week repeated-dose oral toxicity and bioaccumulation of aluminum oxide nanoparticles in mice.

PubMed

Park, Eun-Jung; Sim, Jaehoon; Kim, Younghun; Han, Beom Seok; Yoon, Cheolho; Lee, Somin; Cho, Myung-Haing; Lee, Byoung-Seok; Kim, Jae-Ho

2015-03-01

Because of an increase in the commercial applications of manufactured nanoparticles, the issue of potential adverse health effects of nanoparticles following intended or unintended exposure is rapidly gaining attention. In this study, we evaluated the toxicity of aluminum oxide nanoparticles (AlNPs, rod-type, 1.5, 3, and 6 mg/kg) after oral administration to mice for 13 weeks. Compared with the control group, the consumption of diet and drinking water and body weight gain decreased in the group treated with AlNPs. The group treated with 6 mg/kg AlNPs also showed a marked elevation in the count of white blood cells that associated with a significant decrease and increase to the proportion of eosinophils and lymphocytes, respectively. In addition, the secretion of IL-6 and monocyte chemotactic protein-1 increased in a dose-dependent manner in the treated groups. Furthermore, AlNPs showed the highest accumulation in the liver and kidneys compared with the control group, increased the lactate dehydrogenase level in the blood, and induced the development of a pathological lesion in the liver and kidneys. Taken together, we suggest that the target organs of rod-type AlNPs may be the liver, kidneys and the immune system, and the not-observed adverse effect level may be lower than 6 mg/kg.

Expression of β-nerve growth factor and homeobox A10 in experimental cryptorchidism treated with exogenous nerve growth factor.

PubMed

Xian, Hua; Xian, Yun; Liu, Lili; Wang, Yongjun; He, Jianghong; Huang, Jianfei

2015-04-01

With the exception of standard inguinal orchidopexy, treatment of cryptorchidism with human chorionic gonadotropin has been performed for several years; however, its side effects have limited its application. The β‑nerve growth factor (NGF) and homeobox A10 (HoxA10) genes are closely associated with the development of the testes. To the best of our knowledge, whether exogenous NGF alters the endogenous levels of NGF and HoxA10 in cryptorchidism in rats remains to be elucidated. The aim of the present study was to evaluate the gene and protein expression of NGF and HoxA10 in experimental cryptorchidism following treatment with exogenous NGF. A unilateral mechanical cryptorchidism model in Sprague-Dawley rats was established and different concentrations of exogenous NGF were administered to observe the effects of NGF on cryptorchidism. Changes in the gene and protein expression levels of NGF and HoxA10 in the cryptorchid tissues of each group were identified using one step reverse transcription-quantitative polymerase chain reaction, in situ hybridization with digoxigenin‑labeled‑β‑NGF RNA probes, immunofluorescence and immunohistochemistry, respectively. The expression levels of NGF and HoxA10 were markedly higher in the group treated with a high dose of exogenous NGF compared with the group treated with a low dose of exogenous NGF and the group treated with human chorionic gonadotropin. These results confirmed the potential therapeutic effect of exogenous NGF in human cryptorchidism.

Effect of Shenkang granules on the progression of chronic renal failure in 5/6 nephrectomized rats

PubMed Central

ZHANG, YU; ZHOU, NAN; WANG, HONGYING; WANG, SICEN; HE, JIANYU

2015-01-01

Shenkang granules (SKGs) are a Chinese herbal medicinal formula, consisting of rhubarb (Rheum palmatum L.), Salvia miltiorrhiza, milkvetch root [Astragalus membranaceus (Fisch.) Bunge] and safflower (Carthamus tinctorius L.). The aim of the present study was to investigate the effect of SKG on chronic renal failure (CRF) in 5/6 nephrectomized (5/6 Nx) rats. The rats were randomly divided into seven groups (n=10 per group) as follows: (i) 5/6 Nx (model group; 2.25 ml/kg/day normal saline); (ii) SKGL (low dose; 5/6 Nx treated with 2 g crude drug/kg/day SKG); (iii) SKGM (moderate dose; 5/6 Nx treated with 4 g crude drug/kg/day SKG); (iv) SKGH (high dose; 5/6 Nx treated with 8 g crude drug/kg/day SKG); (v) benazepril treatment group (5/6 Nx treated with 5 mg/kg/day benazepril); (vi) Shenkang injection (SKI) group (5/6 Nx with 13.3 ml/kg/day SKI); and (vii) sham-operated group (2.25 ml/kg/day normal saline). After 30 days, the levels of microalbumin, total protein, serum creatinine, blood urea nitrogen and serum lipid were found to be significantly decreased in the SKGL and SKGM rats, showing histological improvement compared with the untreated 5/6 Nx rats, as determined by hematoxylin and eosin, and Masson's trichrome staining. In addition, SKG was found to significantly improve the levels of glutathione peroxidase and reduce the damage caused by free radicals to the kidney tissues. Furthermore, SKG prevented the accumulation of extracellular matrix by decreasing the expression of collagen I and III and inhibiting the expression of matrix metalloproteinases-2 and −9 in the renal tissue, as determined by western blot analysis. SKG was also shown to decrease the concentrations of serum transforming growth factor-β1, as determined by ELISA, and kidney angiotensin II, as determined using a radioimmunoassay kit. In conclusion, SKG was demonstrated to ameliorate renal injury in a 5/6 Nx rat model of CRF. Thus, SKG may exert a good therapeutic effect on CRF. PMID:26136932

Intervention effects of QRZSLXF, a Chinese medicinal herb recipe, on the DOR-β-arrestin1-Bcl2 signal transduction pathway in a rat model of ulcerative colitis.

PubMed

Fan, Heng; Liu, Xing-xing; Zhang, Li-juan; Hu, Hui; Tang, Qing; Duan, Xue-yun; Zhong, Min; Shou, Zhe-xing

2014-05-28

Qingre Zaoshi Liangxue Fang (QRZSLXF) is a Chinese medicinal herb recipe that is commonly prescribed for the treatment of ulcerative colitis. It includes 5 quality assured herbs: Sophora flavescens Aiton., Baphicacanthus cusia (Nees) Bremek., Bletilla striata Rchb.f., Glycyrrhiza uralensis Fisch. and Coptis chinensis Franch. The main phytochemical ingredient of QRZSLXF includes ammothamnine, sophocarpidine, liquiritin, berberine and indirubin. QRZSLXF has been clinically proven for use in the treatment of ulcerative colitis for over twenty years. In the past ten years, research has confirmed the therapeutic effect of QRZSLXF in ulcerative colitis and partially revealed its mechanism of action. Here, we further reveal the therapeutic mechanism of QRZSLXF in ulcerative colitis. To investigate the role of the DOR-β-arrestin1-Bcl-2 signal transduction pathway in ulcerative colitis and to determine the effects of QRZSLXF on this signal transduction pathway. Eighty-four Sprague-Dawley rats were randomly divided into six groups: normal control group, model group, mesalazine group, and QRZSLXF high-dose, medium-dose group and low-dose groups (n=14). Experimental colitis was induced by trinitrobenzenesulfonic acid (TNBS) in each group, except the normal control group. After modeling, bloody stool, mental state and diarrhea were observed and recorded. Two rats were randomly selected from the model groups adfnd sacrificed on day 3 to observe pathological changes in the colon tissue by microscopy. The rats in the QRZSLXF-treated groups received intramuscular injections of different concentrations of QRZSLXF for 15 days. The rats in the mesalazine group were treated with mesalazine solution (0.5 g/kg/day) by gastric lavage for 15 days. The rats in the normal control group and the model group were treated with 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the remaining rats were sacrificed and their colon tissues were used to detect the mRNA and protein expressions of DOR, β-arrestin1 and Bcl-2 by Real-time PCR and immunohistochemistry, respectively. Histological changes in the colon tissues were also examined. The expressions of DOR, β-arrestin1 and Bcl-2 were significantly different among the four groups. The expressions of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group compared with the other groups (P<0.05). In contrast to the model group, the expressions of DOR, β-arrestin1 and Bcl-2 were significantly decreased in the mesalazine group and the groups that received different doses of QRZSLXF (P<0.05), and there were no statistically significant differences among the mesalazine and QRZSLXF-treated groups (P>0.05). This study indicates that the DOR-beta-arrestin1-Bcl-2 signal transduction pathway may participate in the pathologic course of ulcerative colitis. Moreover, QRZSLXF could attenuate ulcerative colitis by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pseudoephedrine induces sperm abnormalities, lower sperm counts and increased apoptosis in rat testis.

PubMed

Nudmamud-Thanoi, Sutisa; Thanoi, Samur

2012-08-01

Pseudoephedrine, an over-the-counter drug, is commonly used for the treatments of asthma, nasal congestion, and obesity. Furthermore, it can be used as a psychostimulant drug if taken in large doses; however, there have been no reports on its effects on reproduction. The aim of this study was therefore to investigate the effects of pseudoephedrine administration on sperm morphology, sperm concentration and apoptotic activity in the rat testis. Rats were administered intraperitoneally (IP) with pseudoephedrine at 120 mg/kg for the acute group and 80 mg/kg, IP, once daily for 15 days for the chronic group, while a control group was treated with vehicle. The percentages of normal sperm morphology were significantly decreased in both acute and chronic groups when compared with controls while the total sperm count was significantly decreased in the acute group. Apoptotic activities were increased significantly in both pseudoephedrine-treated groups. The results indicate that pseudoephedrine can induce sperm abnormalities, decrease sperm numbers and increase apoptotic activity in the testis of rats if taken at high doses. The results of this study suggest that the users of pseudoephedrine in medical treatments need to be aware of its potential toxicity involving spermatogenesis.

[Combined therapy for children and adolescents with Ewing tumors (a 25-year experience)].

PubMed

Yukhta, T V; Punanov, Yu A; Kazantsev, I V; Malinin, A P; Safonova, S A; Gafton, G I; Gevorgyan, A G; Morozova, E V; Zubarovskaya, L S; Fanasiev, B V A

2015-01-01

A total of 115 children (median age 10.5 years, range 2-17) with Ewing sarcoma family tumors (ESFT) received therapy in N.N. Petrov Institute of Oncology pediatric department from April 1985 till August 2013. These patients were divided into two groups depending on treatment tactics used: patients treated according to modified T9 protocol (n = 64) and patients treated according to EICESS-92 or Euro-Ewing 99 regimens (n = 51). Twenty four patients from the second group with adverse prognostic factors received high-dose chemotherapy with autologous stem cell transplantation. All patients received surgical treatment and/or irradiation for primary tumor local control. Five-year overall and disease-free survival was 39% and 37,9% in the first group. In the second group these values were significantly higher; 55% and 39.5%, accordingly (p = 0.03 and 0.25). All patients from the first group with primary metastatic ESFT died of disease progression, while in the second group OS and DFS reached 45.8% and 28.9%, accordingly. There was a statistically significant correlation between local relapse rate and irradiation dose biological equivalent (in TDF units). The local relapse cumulative rate was minimal (12,6%) in patients receiving 80 TDF.

Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study

PubMed Central

2011-01-01

Introduction We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis. Methods In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to - or had contraindications for - non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version). Results At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab 150 mg group approached those for the US general population by seven days post-dose and reached norm values by eight weeks post-dose. Conclusions Canakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvements in HRQoL were seen in both treatment groups with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg. Trial registration clinicaltrials.gov: NCT00798369. PMID:21439048

Developmental and genetic toxicity of stannous chloride in mouse dams and fetuses.

PubMed

El-Makawy, Aida I; Girgis, Shenouda M; Khalil, Wagdy K B

2008-12-08

Humans are exposed to stannous chloride (SnCl2) present in packaged food, soft drinks, biocides, dentifrices, etc. Health effects in children exposed to tin and tin compounds have not been investigated yet. Therefore, we evaluated the possible teratogenic and genotoxic effects of SnCl2 in pregnant female mice and their fetuses. Teratogenic effects including morphological malformation of the fetus and its skeleton were observed. Exposures to environmental stressors including toxic chemicals that have the potential of modulating the immune system can often be linked to ecologically relevant endpoints, such as reduced resistance to disease. Therefore, the semi-quantitative reverse-transcription PCR (RT-PCR) assay was used to evaluate the expression of immune-response genes in the liver of SnCl2-treated dams and their fetuses. Bone-marrow cells of dams and fetuses were investigated for the presence of aberrant chromosomes. Three oral doses of SnCl2 (2, 10 and 20 mg/kg bw) were tested. The results of the teratological study show that SnCl2 induced a significant decrease in the number of living fetuses and a significant increase in the number of post-implantation losses. The high dose of SnCl2 induced complete post-implantation loss. Furthermore, SnCl2 caused reduction in the ossification of the fetal skeleton. The RT-PCR assay showed that the immune-response genes GARP and SIMP were not expressed in the liver of dams and fetuses in the controls or in the group treated with SnCl2 at 2 mg/kg bw. However, the expression of these genes was up-regulated in the groups treated with the other doses of SnCl2. Regarding the chromosome analysis, SnCl2 induced a dose-dependent increase in the frequency of individual and total chromosomal aberrations (P

Subantibiotic dose of azithromycin attenuates alveolar bone destruction and improves trabecular microarchitectures in a rat model of experimental periodontitis: A study using micro-computed tomography.

PubMed

Park, Hye-Shin; Lee, Yong Sun; Choi, Eun-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2017-06-01

Azithromycin, a macrolide antibiotic, has anti-inflammatory and immunomodulatory activities apart from its antibacterial properties. In this study, we examined the efficacy of subantibiotic dose of azithromycin on ligature-induced periodontitis in rats using micro-computed tomography (micro-CT) imaging and bone parameter analysis. Male Sprague-Dawley rats were allocated to the following four groups: non-ligation (NL) group; ligation-only (L) group; ligation-plus-subantibiotic dose azithromycin (SA) group; and 4) ligation-plus-antibiotic dose azithromycin (AA) group. The rats from Groups L, SA and AA were subjected to periodontitis by placing a ligature around lower right first molar. Immediately after ligation, the rats in SA and AA groups received daily intraperitoneal injections of azithromycin at a dosage of 3.5 or 10mg/kg body weight, respectively. The ligatures were maintained for 2weeks at which time the rats had their mandibles hemisected for micro-CT analysis. Subantibiotic dose of azithromycin strongly suppressed reductions in alveolar bone height and bone volume fraction caused by experimental periodontitis. When subantibiotic dosage of azithromycin was administered to rats, ligature-induced alterations in microarchitectural parameters of trabecular bone were significantly reversed. Rats treated with subantibiotic dose of azithromycin presented no significant difference compared to rats with antibiotic dosage in all parameters. While further studies are necessary, subantibiotic dose of azithromycin could be utilized as a host modulator for the treatment of periodontitis. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy and Safety of a Single-Pill Fixed-Dose Combination of Azilsartan and Amlodipine

PubMed Central

Motozato, Kota; Miura, Shin-ichiro; Shiga, Yuhei; Kusumoto, Takaaki; Saku, Keijiro

2016-01-01

Background Guidelines for the management of hypertension recommend the use of drugs with different mechanisms of action in antihypertensive regimens that include single-pill fixed-dose combinations of medications. There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). Methods Forty hypertensive patients who were receiving a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day were enrolled. They were randomly divided into two treatment groups, a group that changed to a single-pill fixed-dose combination of azilsartan 20 mg/day and amlodipine 5 mg/day (changeover group) and a group that continued to receive valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day (control group), and treated for 16 weeks. Results There were no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP) or pulse rate (PR) at 16 weeks between the control and changeover groups. In addition, there were no significant changes in biochemical parameters throughout the study period in both groups. Conclusion The ability of a single-pill fixed-dose combination of azilsartan and amlodipine to reduce BP may be comparable to that of a combination of valsartan and amlodipine or irbesartan and amlodipine. PMID:27829955

WE-AB-207B-09: Margin Reduction for Planning Target Volume (PTV) in Patients with Localized Prostate Cancer: Impact On Delivered Dose and Quality of Life

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

Kumarasiri, A; Liu, C; Brown, S

Purpose: To estimate the delivered (cumulative) dose to targets and organs at risk for localized prostate cancer patients treated with reduced PTV margins and to evaluate preliminary patient reported quality-of-life (QOL). Methods: Under an IRB-approved protocol, 20 prostate cancer patients (including 11 control patients) were treated with reduced planning margins (5 mm uniform with 4 mm at prostate/rectum interface). Control patients had standard margin (10/6 mm)-based treatments. A parameter-optimized Elastix algorithm along with energy-mass mapping was used to deform and resample dose of the day onto the planning CT for each fraction to estimate the delivered dose over all fractions.more » QOL data were collected via Expanded Prostate cancer Index Composite (EPIC-26) questionnaires at time points pre-treatment, post-treatment, and at 2, 6, 12, 18 month follow-ups. Standardized QOL scores [range: 0–100] were determined and baseline-corrected by subtracting pre-treatment QOL data. Mean QOL differences between the margin reduced group and control group (QOLmr-QOLcontrol) were calculated for first 18 months. Results: The difference between the cumulative mean dose (Dmean) and the planned mean dose (±SD) for PTV, prostate, bladder, and rectum were −2.2±1.0, 0.3±0.5, −0.7±2.6, and −2.1±1.3 Gy respectively for the margin-reduced group, and −0.8±2.0, 0.9±1.4, - 0.7±3.1 and −1.0±2.4 Gy for the control group. Difference between the two groups was statistically insignificant (p=0.1). Standardized and baseline corrected QOLmr-QOLcontrol for EPIC domains categorized as “Urinary Incontinence”, “Urinary Irritative/Obstructive”, “Bowel”, “Sexual”, and “Hormonal” were 0.6, 12.1, 9.1, 13.3, and −0.9 for the 18 months following radiation therapy (higher values better). Delivered dose to rectum showed a weak correlation to “Bowel” domain (Pearson’s coefficient −0.24, p<0.001), while bladder dose did not correlate to Urinary Incontinence/Irritative/Obstructive QOL domains. Conclusion: The margin-reduced group exhibited clinically meaningful improvement of QOL without compromising the PTV dose. A larger number of patients and greater follow-up is needed to draw unequivocal conclusions. This work was supported in part by a research grant from Varian Medical Systems, Palo Alto, CA.« less

Phytochemical investigation and nephroprotective potential of Sida cordata in rat.

PubMed

Shah, Naseer Ali; Khan, Muhammad Rashid; Nigussie, Dereje

2017-08-04

Plants are an efficient source of natural antioxidant against free radicals causing kidney damages. Sida cordata ethyl acetate fraction has been reported for strong in vitro antioxidant potency, previously. In the present study, our objective was to evaluate its in vivo antioxidant potency against CCl 4 induced nephrotoxicity and investigates the bioactive phytochemicals by HPLC-DAD analysis. Phytochemical analysis was performed by HPLC-DAD methodology. For in vivo study, 42 male Sprague-Dawley rats were treated with alternatively managed doses for 60 days. Group I animals were remained untreated. Group II animals were treated with vehicle (1 mL of olive oil) by intragastric route on alternate days. Group III was treated with 30% CCl 4 (1 mL/kg b.w.) i.p. Group IV was treated with 30% CCl 4 (1 mL/kg b.w.) i.p and silymarin intragastric. Group V and VI rats were treated with 30% CCl 4 and SCEE (150 and 300 mg/kg b.w., respectively) intragastric. Group VII animals were treated with SCEE (300 mg/kg b.w.) intragastrically. Blood parameters, Serum proteins and urine profile were investigated. Activities of tissue enzyme i.e. catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione reductase, GSH and γ-GT were evaluated. Histopathological observations, total protein contents, lipid peroxidation, DNA damage and relative weight were also analyzed. Gallic acid, catechin and caffeic acid were identified in SCEE fraction by HPLC-DAD. Decrease in the count of red blood cells, neutrophils, eosinophils and concentration of hemoglobin whereas increase in lymphocyte count and estimation of sedimentation rate (ESR) with 1 mL CCl 4 (30% in Olive oil) administration (30 doses in 60 days) was restored dose dependently with co-treatment of SCEE (150 and 300 mg/kg b.w.). Treatment of rats with CCl 4 markedly (P < 0.01) increased the count of urinary red blood cells and leucocytes, concentration of urea, creatinine and urobilinogen and specific gravity whereas creatinine clearance was reduced. Serum level of total protein, albumin, globulin, nitrite, creatinine and blood urea nitrogen (BUN) was significantly increased (P < 0.01) by CCl 4 treatment. The activity of antioxidant enzymes; catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase and content of reduced glutathione was decreased (P < 0.01) significantly. However, increased concentration (P < 0.01) of thiobarbituric acid reactive substances and histopathological injuries were noticed in the renal tissues of rats after the treatment with CCl 4 . Co-administration of SCEE, dose dependently, protected the alterations in the studied parameters of rats at 150 and 300 mg/kg b.w. The present study revealed that SCEE could be used as a possible remedy for renal toxicity abnormalities. These results are an evidence of the renal protective role of S.cordat ethyl acetate fraction against CCl 4 induced nephrotoxicity in rats which may be due to its antioxidant compounds.

Antimicrobial prophylaxis for major head and neck surgery in cancer patients: sulbactam-ampicillin versus clindamycin-amikacin.

PubMed

Phan, M; Van der Auwera, P; Andry, G; Aoun, M; Chantrain, G; Deraemaecker, R; Dor, P; Daneau, D; Ewalenko, P; Meunier, F

1992-09-01

A total of 99 patients with head and neck cancer who were to undergo surgery were randomized in a prospective comparative study of sulbactam-ampicillin (1:2 ratio; four doses of 3 g of ampicillin and 1.5 g of sulbactam intravenously [i.v.] every 6 h) versus clindamycin (four doses of 600 mg i.v. every 6 h)-amikacin (two doses of 500 mg i.v. every 12 h) as prophylaxis starting at the induction of anesthesia. The two groups of evaluable patients (43 in the clindamycin-amikacin treatment group and 42 in the sulbactam-ampicillin treatment group) were comparable as far as age (mean, 57 years; range, 21 to 84 years), sex ratio (71 males, 28 females), weight (mean, 66 kg; range, 40 to 69 kg), indication for surgery (first surgery, 48 patients; recurrence, 37 patients), previous anticancer treatment (surgery, radiation therapy, chemotherapy), type of surgery, and stage of cancer. The overall infection rate (wound, bacteremia, and bronchopneumonia) within 20 days after surgery was 20 patients in each group. Wound infections occurred in 14 (33%) sulbactam-ampicillin-treated patients and 9 (21%) clindamycin-amikacin-treated patients (P = 0.19; not significant). The rates of bacteremia were 2 and 4%, respectively. The rates of bronchopneumonia were 14.3 and 23.2%, respectively (P was not significant). Most infections were polymicrobial, but strict anaerobes were recovered only from patients who received sulbactam-ampicillin. Antimicrobial treatment was required within 20 days after surgery for 42% of the sulbactam-ampicillin-treated patients and 44% of the clindamycin-amikacin-treated patients. By comparison with previous studies, we observed a decreased efficacy of antimicrobial prophylaxis in patients with head and neck cancer undergoing surgery because of the increased proportion of patients who were at very high risk for infection (extensive excision and plastic reconstruction in patients with recurrent stage III and IV cancers) and because of the longer duration of surgery.

Antimicrobial prophylaxis for major head and neck surgery in cancer patients: sulbactam-ampicillin versus clindamycin-amikacin.

PubMed Central

Phan, M; Van der Auwera, P; Andry, G; Aoun, M; Chantrain, G; Deraemaecker, R; Dor, P; Daneau, D; Ewalenko, P; Meunier, F

1992-01-01

A total of 99 patients with head and neck cancer who were to undergo surgery were randomized in a prospective comparative study of sulbactam-ampicillin (1:2 ratio; four doses of 3 g of ampicillin and 1.5 g of sulbactam intravenously [i.v.] every 6 h) versus clindamycin (four doses of 600 mg i.v. every 6 h)-amikacin (two doses of 500 mg i.v. every 12 h) as prophylaxis starting at the induction of anesthesia. The two groups of evaluable patients (43 in the clindamycin-amikacin treatment group and 42 in the sulbactam-ampicillin treatment group) were comparable as far as age (mean, 57 years; range, 21 to 84 years), sex ratio (71 males, 28 females), weight (mean, 66 kg; range, 40 to 69 kg), indication for surgery (first surgery, 48 patients; recurrence, 37 patients), previous anticancer treatment (surgery, radiation therapy, chemotherapy), type of surgery, and stage of cancer. The overall infection rate (wound, bacteremia, and bronchopneumonia) within 20 days after surgery was 20 patients in each group. Wound infections occurred in 14 (33%) sulbactam-ampicillin-treated patients and 9 (21%) clindamycin-amikacin-treated patients (P = 0.19; not significant). The rates of bacteremia were 2 and 4%, respectively. The rates of bronchopneumonia were 14.3 and 23.2%, respectively (P was not significant). Most infections were polymicrobial, but strict anaerobes were recovered only from patients who received sulbactam-ampicillin. Antimicrobial treatment was required within 20 days after surgery for 42% of the sulbactam-ampicillin-treated patients and 44% of the clindamycin-amikacin-treated patients. By comparison with previous studies, we observed a decreased efficacy of antimicrobial prophylaxis in patients with head and neck cancer undergoing surgery because of the increased proportion of patients who were at very high risk for infection (extensive excision and plastic reconstruction in patients with recurrent stage III and IV cancers) and because of the longer duration of surgery. PMID:1416895

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

PubMed

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank; Brand, Eva

2016-03-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. Copyright © 2016 by the American Society of Nephrology.

Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-Up

PubMed Central

Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank

2016-01-01

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3–0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C–based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used. PMID:26185201

Investigation of the effect of traditional Chinese medicine on pain and inflammation in chronic nonbacterial prostatitis in rats.

PubMed

Liu, Y-J; Song, G-H; Liu, G T

2016-08-01

According to traditional Chinese medicine, the symptoms of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CNP/CPPS) may be treated using a cocktail of herbs that stimulate blood circulation ('activating blood circulation formula'). We investigated the effect of three doses of this formula on a rat model of CNP/CPPS. Male Wistar rats were injected with a saline extract of male sex accessory glands on days 0 and 30 to induce prostatitis and then treated daily by gavage between days 32 and 60. Treatment with low, medium and high doses of activating blood circulation formula resulted in an almost total rescue of paw withdrawal threshold at day 60, and treatment with the highest dose also significantly decreased prostate inflammation (assessed histopathologically). We further observed elevated serum prostaglandin E2 levels in the CNP/CPPS model which decreased upon high-dose treatment, and increased Cox-2 expression in the prostate and spinal cord dorsal horn which was rescued in both tissues in the high-dose group and in the prostate in the medium-dose group. These results shed light on a possible mechanism by which activating blood circulation therapy may alleviate pain in a rat model of CNP/CPPS by downregulating Cox-2 expression in the spinal cord, thereby raising the pain threshold. Further research will be needed to fully characterise the mechanism by which activating blood circulation therapy produces this therapeutic effect. © 2016 Blackwell Verlag GmbH.

Bolus dose response characteristics of single chain urokinase plasminogen activator and tissue plasminogen activator in a dog model of arterial thrombosis.

PubMed

Badylak, S F; Voytik, S; Klabunde, R E; Henkin, J; Leski, M

1988-11-15

Tissue plasminogen activator (t-PA) and single chain urokinase-plasminogen activator (scu-PA) are relatively "fibrin-specific" thrombolytic drugs with short plasma half lives of 6-8 minutes. Most treatment regimens with these agents utilize a bolus injection followed by continuous drug infusion, usually combined with anticoagulant therapy. The purpose of this study was to establish the dose-response characteristics for scu-PA and t-PA, when given as a single intravenous bolus injection, in a dog model of arterial thrombosis. Eight groups of 6 dogs each were given one of the following doses of scu-PA (mg/kg): 0.20, 0.50, 1.00, 2.00; or t-PA: 0.05, 0.10, 0.20; or an equivalent amount of saline (control group). All doses were given as a single bolus injection 60 minutes after formation of a totally occlusive femoral artery thrombus. Thrombolysis was measured by monitoring the continuous decrement of 125I activity from a radiolabelled thrombus. Ninety minutes after drug injection, all scu-PA treated dogs showed greater thrombolysis (30%, 45%, 56%, and 67%, respectively) than the control group (15%, p less than 0.01). The 0.10 and 0.20 mg/kg t-PA treated dogs showed greater thrombolysis (35% and 49%, respectively) than the control group (15%, p less than 0.01). Both scu-PA and t-PA caused a partial and dose-dependent decrease in alpha 2-antiplasmin activity but scu-PA caused a greater depletion (72% vs. 18%, respectively, p less than 0.05) at 60 minutes after the highest dose of drug administration. Both drugs showed a longer than expected thrombolytic effect based upon the known half lives. Neither drug caused significant changes in the prothrombin time, activated partial thromboplastin time, thrombin time, hematocrit, platelet count, or fibrin degradation product concentration. Single bolus injections of scu-PA and t-PA produce safe and effective thrombolysis in this dog model of arterial thrombosis.

Effects of acute chlorpyrifos exposure on in vivo acetylcholine accumulation in rat striatum

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

Karanth, Subramanya; Liu, Jing; Mirajkar, Nikita

2006-10-01

This study examined the acute effects of chlorpyrifos (CPF) on cholinesterase inhibition and acetylcholine levels in the striatum of freely moving rats using in vivo microdialysis. Adult, male Sprague-Dawley rats were treated with vehicle (peanut oil, 2 ml/kg) or CPF (84, 156 or 279 mg/kg, sc) and functional signs of toxicity, body weight and motor activity recorded. Microdialysis was conducted at 1, 4 and 7 days after CPF exposure for measurement of acetylcholine levels in striatum. Rats were then sacrificed and the contralateral striatum and diaphragm were collected for biochemical measurements. Few overt signs of cholinergic toxicity were noted inmore » any rats. Body weight gain was significantly affected in the high-dose (279 mg/kg) group only, while motor activity (nocturnal rearing) was significantly reduced in all CPF-treated groups at one day (84 mg/kg) or from 1-4 days (156 and 279 mg/kg) after dosing. Cholinesterase activities in both diaphragm and striatum were markedly inhibited (50-92%) in a time-dependent manner, but there were relatively minimal dose-related changes. In contrast, time- and dose-dependent changes in striatal acetylcholine levels were noted, with significantly higher levels noted in the high-dose group compared to other groups. Maximal increases in striatal acetylcholine levels were observed at 4-7 days after dosing (84 mg/kg, 7-9-fold; 156 mg/kg, 10-13-fold; 279 mg/kg, 35-57-fold). Substantially higher acetylcholine levels were noted when an exogenous cholinesterase inhibitor was included in the perfusion buffer, but CPF treatment-related differences were substantially lower in magnitude under those conditions. The results suggest that marked differences in acetylcholine accumulation can occur with dosages of CPF eliciting relatively similar degrees of cholinesterase inhibition. Furthermore, the minimal expression of classic signs of cholinergic toxicity in the presence of extensive brain acetylcholine accumulation suggests that some compensatory process(es) downstream from synaptic neurotransmitter accumulation limits the expression of toxicity following acute CPF exposure.« less

The Effect of Taraxacum officinale Hydroalcoholic Extract on Blood Cells in Mice

PubMed Central

Modaresi, Mehrdad; Resalatpour, Narges

2012-01-01

Objectives. Dandelion (Taraxacum officinale) is a herbaceous perennial plant of the family Asteraceae and has medicinal and culinary uses. Dandelion has been used as a remedy for anemia, purifing the blood, and providing immune modulation. Therefore, the aim of this study was to investigate the effect of hydro alcoholic extract on blood cells in mice. Methods. Five groups each including ten adult female (Balb/C) mice weighing 30 ± 5 g were chosen. Normal saline was administered as placebo for group, and dandelion hydro alcoholic extract in doses of 50,100, and 200 mg/kg was injected intraperitoneally for 20 days to test groups and the last group was control group.WBC, RBC, HB, HCT, platelet, and other cells were measured with automated cell counter. Main Results. The number of RBC and the rate of HB in three doses of 100 and 200 mg/kg significantly increased (P < 0.05). As compared with control group, the number of WBC in three doses of 50, 100, and 200 mg/kg increased, but it was significantly in 200 mg/kg dandelion treated group as compared with control group(P < 0.05). The rate of platelet in three doses of 50, 100 and 200 mg/kg significantly decreased as compared with control group (P < 0.01). 3 doses of dandelion increased lymphocyte numbers significantly compared with controls. Conclusion. The study indicates efficacy of dandelion extract on RBC and HB in doses of 50, 100, and 200 mg/kg and in 200 mg/kg on WBC to achieve normal body balance. PMID:22844289

Dietary supplementation with low-dose omega-3 fatty acids reduces salivary tumor necrosis factor-α levels in patients with chronic periodontitis: a randomized controlled clinical study.

PubMed

Keskiner, I; Saygun, I; Bal, V; Serdar, M; Kantarci, A

2017-08-01

Recent studies have demonstrated the beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) on physiological processes and on a variety of chronic inflammatory diseases, including periodontal diseases. In this study, we evaluated the impact of omega-3 PUFAs in conjunction with scaling and root planing (SRP) on salivary markers in patients with chronic periodontitis. Thirty systemically healthy subjects with chronic periodontitis were enrolled and randomly allocated into two groups. The control group (n = 15) was treated with SRP + placebo whereas the test group was treated with SRP and dietary supplementation of low-dose omega-3 PUFAs (6.25 mg eicosapentaenoic acid and 19.19 mg docosahexaenoic acid). Clinical parameters were taken at baseline, 1, 3 and 6 mo following therapy. Saliva samples were obtained at the same time intervals and analyzed for tumor necrosis factor-α (TNF-α) and superoxide dismutase (SOD). Both groups showed significant changes in clinical parameters in response to treatment compared to baseline with no significant difference between groups. Salivary TNF-α levels showed a statistically significant decrease in the test group at 6 mo compared to the control group. Salivary SOD levels increased significantly at 3 and 6 mo in the test group and at 6 mo in placebo groups compared to baseline with no statistically significant differences between the groups. The results demonstrated that dietary supplementation with low-dose omega-3 PUFAs improves salivary TNF-α without any significant impact on clinical parameters in patients with chronic periodontitis, suggesting that the systemic benefits of dietary omega-3 PUFAs may not be translated to periodontal health. (ClinicalTrials.gov ID NCT02719587). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pharmacological Effect of Berberine Chloride in Propyl Thiouracil Induced Thyroidal Dysfunction - A Time Bound Study in Female Rats.

PubMed

Maurya, Harikesh; Dhiman, Sheena; Dua, Kamal; Gupta, Gaurav

2016-01-01

The present study is aimed at bringing out the information on the effect of berberine chloride in hyper and hypo thyroidal model with two dose levels. The research article also reviewed details of various existing patents associated with comprehensive compilation regarding the therapeutic application of berberine and related forms. Sixty female wistar rats weighing between 150-250 gm were divided in to 10 groups. The animals were grouped in to solvent control; hypothyroid; hyperthyroid; prophylactic with two different doses of berberine chloride (50 and 100 mg/kg); treatment groups similar to that of the prophylactic and therapeutic group. To substantiate the dose dependent effect of berberine chloride in 6-n-propyL-2-thiouracil (PTU) induced hypothyroidism, lipid profile, thyroid profile, enzymes profiles and blood profiles, in addition to histopathological studies were also carried out. There was no any significant difference in the lipid profile among solvent control, treatment and prophylactic groups. However, there was a significant difference (***p<0.001) in serum triglycerides, LDL and VLDL of hypothyroid group when compound to that of the rest. As far as thyroid profile is concerned, T3 level of berberine chloride (50 mg/kg) treated groups (prophylactic+ treatment) showed a significant rise compared to hypothyroid group. TSH level in prophylactic groups was far higher than the rest of the groups (3.002±0.0192, 1.051±0.0008 against the solvent control, 0.308±0.008). SGOT, SGPT levels were significantly higher with the therapeutic group than that of the normal and hypo-thyroidal group. Blood profile of berberine chloride (100 mg/kg) treated therapeutic group was comparable to that of the solvent control than all other groups. The probable mechanism underlying may be that inactivation of type I 5.-iodothyronine deiodinase (5.DI) enzyme by NF-kB pathway. From the findings of the current study it can be concluded that berberine chloride possesses both thyroid stimulating and suppressing activities depending on its dose, especially berberine chloride 50 mg/kg supports thyroid stimulating property.

Enzyme-potentiated desensitization in children with asthma and mite allergy: a double-blind study.

PubMed

Cantani, A; Ragno, V; Monteleone, M A; Lucenti, P; Businco, L

1996-01-01

The aim of this study was to evaluate the efficacy and safety of enzyme-potentiated desensitization (EPD) in children with asthma. Twenty asthmatic children (14 males and 6 females; median age: 8.5 years) were included in the study. They had positive skin tests to Dermatophagoides pteronyssinus (Dpt), no history of other allergy and had suffered from asthma for at least two years. The children were examined before starting the trial, at the first EPD dose, after 8 weeks, at the second EPD dose and 3 months after the second EPD dose. Blood samples for PRIST and RAST were drawn before the first and at the second EPD dose, and at the last follow-up. Conjunctival provocation tests (CPT) and skin test endpoint determinations were performed with dilutions of a freeze-dried Dpt extract (10-100,000 SQ-U/ml) at the start of the trial and at the last follow-up. Parents kept a diary record of the days with asthma and daily drug usage. The children were randomized to receive either two intradermal placebo injections or the active material with an 8-week interval (November 1991 and January 1992). Ten children received EPD and 10 children placebo. The intradermal injection of EPD (0.05 ml) contained 0.01 ml of beta-glucuronidase (40 Fishman units) and 0.04 ml of a mixture of inhalant allergens (1 Noon unit). The placebo injection consisted of buffer solution only. The EPD-treated children had significantly fewer days with asthma (p = 0.00000). In addition, the EPD-treated children used significantly less medication for the management of asthma attacks (p = 0.00000). At the start of the trial, three out of 10 children in the EPD group and two out of 10 in the placebo group reacted only to the highest dose of allergen used in the CPT (100,000 SQ/ml) (NS). At the last follow-up, the threshold dose in the CPT was 100,000 SQ/ml or more in nine out of 10 children in the EPD group and in four out of 10 children of the placebo group (p = 0.0349). At the last follow-up, one child in the EPD group had a negative CPT with all doses tested. Global clinical evaluation by the investigators showed that eight out of 10 EPD-treated children improved, in comparison with three out of 10 children in the placebo group (p = 0.0349). Assessment by the parents was six out of 10 and four out of 10 improved, respectively (NS). Specific IgE to Dpt, total IgE and skin prick test endpoints before and after EPD showed no significant changes. One child in the placebo group experienced mild urticaria several hours following the second injection. No other local or systemic side effects were reported. The results of the present study provide further data on the effectiveness and safety of EPD in patients with asthma.

Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5'-pyrophosphate) in Sprague-Dawley rats.

PubMed

Schauss, A G; Somfai-Relle, S; Financsek, I; Glavits, R; Parent, S C; Endres, J R; Varga, T; Szücs, Z; Clewell, A

2009-01-01

The dietary supplement Citicoline free-base (choline cytidine 5'-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.

A study on toxicity of gasoline and GM-10 on liver of mice and it's amelioration by black tea extract.

PubMed

Verma, Ramtej Jayram; Dave, Manjeet; Mathuria, Neeta

2008-01-01

The aim of present study is to investigate the ameliorative effect of black tea extract on gasoline and GM-10 induced toxicity in liver of mice. Eighty healthy male mice weighing 38-40 g approximately were divided into eight groups which included untreated control and various treated groups. Mice were treated with Gasoline 462 mg/kg/day and GM-10 low dose (206 mg/kg/day) and high dose (412 mg/kg/day) subcutaneously for 30 days. Black tea extract was given as 2 g/100 mL drinking water (2% w/v) instead of pure drinking water. All the animals were sacrificed on 31st day by cervical dislocation and livers were isolated and weighed. Parameters such as lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase, glutathione and total ascorbic acid were studied. The results revealed dose-dependent toxicity of gasoline and GM-10 on liver. Administration of black tea extract ameliorates this toxicity of gasoline and GM-10 in liver of mice. This proves the effective ameliorative effect of black tea extract.

Implications of low-power He-Ne laser and monochromatic red light biostimulation in the metabolism of proteins and glucosides

NASA Astrophysics Data System (ADS)

Onac, I.; Pop, L.; Ungur, Rodica; Giurgiu, Ioana

2001-06-01

We checked the changes occurring in the metabolism of proteins (seric cholinesterase, total proteins) and in the metabolism of glycosides (seric glucose) in Cavia cobaia. A simple blind study was carried out and the results were checked on the first, tenth and twentieth days of treatment. The data thus obtained were graphically represented and statistically processed according to the Duncan test. The technique and treatment doses were similar and they were compared with the data obtained from controls and environment controls. In the groups biostimulated with He-Ne laser, seric cholinesterase levels increased proportionally with the dose reaching a peak on day 10, which was not the case with the controls. Monochromatic red light caused a similar but quantitatively lower effect. The same results were obtained in the case of seric proteins as well, however, the effect did not depend on the dose and it was less significant statistically than in the case of seric cholinesterase both in laser treated and in monochromatic red light treated groups.

Green Tea Increases the Concentration of Total Mercury in the Blood of Rats following an Oral Fish Tissue Bolus

PubMed Central

Freiser, Helene; Manganais, Christopher; Santerre, Charles R.

2015-01-01

Fish has many health benefits but is also the most common source of methylmercury. The bioavailability of methylmercury in fish may be affected by other meal components. In this study, the effect of green tea on the bioavailability of methylmercury from an oral bolus of fish muscle tissue was studied in rats and compared to a water treated control group and a group treated with meso-2,3-dimercaptosuccinic acid (DMSA), a compound used medically to chelate mercury. Rats were given a single oral dose of fish tissue via gavage and one of the treatments. Rats were given access to food for 3 h at 12 h intervals. They were dosed with each of the treatments with each meal. Blood samples were collected for 95 hours. Green tea significantly increased the concentration of total mercury in blood relative to the control, whereas DMSA significantly decreased it. In addition, feeding caused a slight increase in blood mercury for several meals following the initial dose. PMID:26301246

Comparison of the therapeutic dose of warfarin in HIV-infected and HIV-uninfected patients: a study of clinical practice

PubMed Central

Jackson, B S; Mokoena, T

2017-01-01

Background People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients. Methods A prospective and retrospective descriptive study of induction time to therapeutic warfarin dose, as well as of ambulant therapeutic warfarin dose, was performed. HIV-infected and HIV-uninfected patients being treated after deep venous thrombosis with or without pulmonary embolism were compared. Sex and use of antiretroviral drugs (ARVs) were also compared in the groups. Results 234 patients were entered into the study. Induction time to therapeutic warfarin dose did not differ between the 2 groups. The mean therapeutic dose of warfarin was higher in the HIV-infected than the HIV-uninfected group: 6.06 vs 5.72 mg/day, but this was not statistically significant (p=0.29). There was no difference in therapeutic warfarin dose between ARV-naïve groups—HIV-uninfected and HIV-infected patients not on ARVs. Conclusions There appears to be little effect of HIV infection on warfarin dosing. Warfarin therapy should be administered conventionally in HIV-infected patients. PMID:28179414

The role of fluoride and chlorhexidine in preserving hardness and mineralization of enamel and cementum after gamma irradiation.

PubMed

Abdalla, Rowida; Niazy, Maha A; Jamil, Wael E; Hazzaa, Hala A; Elbatouti, Amal A

2017-05-01

The purpose of this study was to evaluate the effect of 0.05% sodium fluoride and 0.12% chlorhexidine mouthwashes on the micro-hardness of tooth enamel and cementum that was exposed to therapeutic doses of gamma radiation. Sixty extracted human teeth were divided into two groups, one was irradiated, the other was not irradiated. The two groups were further subdivided into three subgroups, which were each treated either with 0.05% sodium fluoride or with 0.12% chlorhexidine; the third subgroup served as a control. After demineralization-remineralization cycling, teeth from the irradiated groups showed a significantly lower micro-hardness when compared to those from the non-irradiated groups. Both in the irradiated and non-irradiated groups, teeth from the control subgroups showed a significantly lower micro-hardness, as compared to teeth treated with sodium fluoride and chlorhexidine. For non-irradiated enamel samples, those treated with chlorhexidine showed a significantly less micro-hardness compared to those treated with sodium fluoride. In contrast, irradiated enamel showed no significant difference in micro-hardness, whatever treatment (chlorhexidine or sodium fluoride) was applied. For cementum, treatment with chlorhexidine resulted in a significantly lower micro-hardness compared to sodium fluoride, both for the irradiated and non-irradiated groups. It is concluded that gamma irradiation with therapeutic doses typically used for head and neck carcinoma treatment has a direct effect in reducing micro-hardness of tooth enamel and cementum. Mouthwash protocols including, for example, application of 0.05% sodium fluoride or 0.12% chlorhexidine three times per day for 6 weeks, can protect enamel and cementum against the reduction in hardness and demineralization caused by gamma irradiation. Sodium fluoride offers more protection compared to chlorhexidine.