scholarly journals Candidalysin impedes the development of embryonic zebrafish (Danio rerio)

Author(s):  
Jing Shen ◽  
JingCong Tan ◽  
Haochun Shi ◽  
Jie Zhou ◽  
Yanbin Zhao ◽  
...  

Abstract Candidalysin is a cytolytic peptide secreted by Candida albicans, an opportunistic human fungal pathogen that was widely spread in clinic and in the environment. However, its impacts on the development of aquatic organisms remain limited. Herein, we explored the developmental effects of candidalysin on embryonic zebrafish at concentrations from 0.008 to 160 mg/L. In acute exposure, decreased survival rate with EC50 at 49.5 mg/L were observed. Meanwhile, in high-dose exposure groups (5-160 mg/L), an increased swimming frequency were observed at candidalysin concentrations of 10 mg/L and above. In chronic exposure, decreased spontaneous contraction, hatching rate and heart rate were identified in low-dose exposure groups (0.008-5 mg/L). Especially for the heart rate, significant changes were observed at candidalysin concentrations as low as 0.008 mg/L (environmentally relevant). The present study first time pointed out the developmental toxicities of candidalysin on fish that was rarely investigated, and thus contributed to its environmental risk assessment.

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Naomi Even-Zohar ◽  
Yael Sofer ◽  
Iris Yaish ◽  
Merav Serebro ◽  
Karen Tordjman ◽  
...  

Abstract Introduction : Transgender women with intact gonads receive lifelong hormonal treatment in order to suppress physiologic androgen production. Cyproterone acetate (CA) is the most comon antiandrogenic drug prescribed for this indication in Europe, with a dose range between 25-100 mg/day. Aim: To assess the effectiveness and safety of low dose (<20 mg/day), compared with high dose (>50 mg/day) CA treatment. Methods: Historical cohort study of transgender women treated in our department between January 2000 and October 2018. Results: There were 42 transgender women in the low dose group (LDG) and 32 in the high dose group (HDG). Age (27.9 ± 1.6 vs.28.9 ± 1.7 years) and follow up time (16.2 ± 2.2 vs. 20.1 ± 2.1 months) were similar in the LDG and HDG, respectively. At the last available visit, testosterone levels were effectively and similarly suppressed in both treatment groups (0.6 ± 0.1 vs 0.8 ± 0.3 nmol/l; p=0.37, for LDG and HDG respectively). Prolactin (659 ± 64 vs 486 ± 42 mIU/ml, p=0.02), LDL cholesterol (96.1 ± 5 vs 78.5 ± 4 mg/dl, p= 0.02) and triglycerides (93.3 ± 9 vs 69 ± 5 mg/dl; p=0.02) were higher in the HDG compared with LDG respectively. Side effects were common in the HDG (four cases of increased liver enzymes, one case of pulmonary embolism and one case of sudden death). Conclusion: We show for the first time that anti-androgenic treatment of transgender women with low dose CA is as effective as high dose treatment, but safer. We suggest incorporation of this observation in future guidelines.


2019 ◽  
Vol 22 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Pablo Nejamkin ◽  
Verónica Cavilla ◽  
María Clausse ◽  
Florencia Landivar ◽  
Augusto M Lorenzutti ◽  
...  

Objectives The aim of this study was to describe the sedative and some physiological effects of tiletamine–zolazepam following buccal administration (BA) in cats. Methods Seven healthy spayed European shorthair cats (three males, four females) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine–zolazepam by BA: the low-dose (LD) group consisted of 5 mg/kg of each drug, and the high-dose (HD) group consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO2) were recorded at predefined intervals for the next 2 h. Results All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD groups, respectively ( P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for the HD than for the LD group. No values for hemoglobin saturation <95% were observed. Conclusions and relevance BA of tiletamine–zolazepam at the doses studied here is a simple and effective method for chemical restraint in cats, where the LD group had a lower impact on SAP and RR than the HD group.


2020 ◽  
Vol 75 (Supplement_1) ◽  
pp. i88-i99
Author(s):  
D Torumkuney ◽  
A Tunger ◽  
B Sancak ◽  
A Bıçakçıgil ◽  
B Altun ◽  
...  

Abstract Objectives To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015–17 from Turkey. Methods MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results A total of 179 S. pneumoniae and 239 H. influenzae isolates were collected. Few (27.9%) pneumococci were penicillin susceptible by CLSI oral or EUCAST low-dose breakpoints, but by EUCAST high-dose or CLSI IV breakpoints 84.4% were susceptible. The most active antibiotics (excluding penicillin IV) by CLSI breakpoints were fluoroquinolones (98.9% of isolates susceptible), ceftriaxone (83.2%), amoxicillin (78.8%) and amoxicillin/clavulanic acid (78.8%). Pneumococcal susceptibility to amoxicillin and amoxicillin/clavulanic acid was lower using EUCAST low-dose breakpoints (49.7%), although susceptibility increased when using EUCAST high-dose (57.0%–58.1%) and PK/PD (78.8%–87.7%) breakpoints. Twenty-three H. influenzae isolates were β-lactamase positive, with 11 characterized as β-lactamase negative and ampicillin resistant following EUCAST criteria and 5 by CLSI criteria. Generally antibiotic susceptibility was high using CLSI breakpoints: ≥92.9% for all antibiotics except ampicillin (87% by CLSI and EUCAST breakpoints) and trimethoprim/sulfamethoxazole (67.4% and 72% by CLSI and EUCAST breakpoints, respectively). Susceptibility using EUCAST breakpoints (where these are published) was similar, except for cefuroxime (oral) with 3.8% of isolates susceptible. PK/PD breakpoints indicated low susceptibility to macrolides (5.9%–10%) and cefaclor (13%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Conclusions Antibiotic susceptibility of S. pneumoniae was generally low, which is in keeping with evidence of inappropriate and high antibiotic use in Turkey. H. influenzae susceptibility was high. These data are important for empirical therapy of CA-RTIs.


Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 645 ◽  
Author(s):  
Helena Tiekou Lorinczova ◽  
Owen Fitzsimons ◽  
Leah Mursaleen ◽  
Derek Renshaw ◽  
Gulshanara Begum ◽  
...  

Brain-derived neurotrophic factor (BDNF) is key for the maintenance of normal neuronal function and energy homeostasis and has been suggested to improve cognitive function, including learning and memory. Iron and the antioxidant curcumin have been shown to influence BDNF homeostasis. This 6-week, double blind, randomized, placebo-controlled study examined the effects of oral iron supplementation at low (18 mg) and high (65 mg) ferrous (FS) iron dosages, compared to a combination of these iron doses with a bioavailable formulated form of curcumin (HydroCurcTM; 500 mg) on BDNF levels in a healthy adult cohort of 155 male (26.42 years ± 0.55) and female (25.82 years ± 0.54) participants. Participants were randomly allocated to five different treatment groups: both iron and curcumin placebo (FS0+Plac), low dose iron and curcumin placebo (FS18+Plac), low dose iron and curcumin (FS18+Curc), high dose iron and curcumin placebo (FS65+Plac) and high dose iron and curcumin (FS65+Curc). Results showed a significant increase in BDNF over time (26%) in the FS18+Curc group (p = 0.024), and at end-point between FS18+Curc and FS18+Plac groups (35%, p = 0.042), demonstrating for the first time that the combination with curcumin, rather than iron supplementation alone, results in increased serum BDNF. The addition of curcumin to iron supplementation may therefore provide a novel approach to further enhance the benefits associated with increased BDNF levels.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
S Simovic ◽  
J Jeremic ◽  
G Davidovic ◽  
I Srejovic ◽  
V Zivkovic ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Verapamil, a calcium channel blocker, is used for treatment of hypertension, paroxysmal supraventricular tachycardia  and angina pectoris. It primarily blocks L-type calcium channels preventing excessive influx of calcium into cardiomyocytes, leading to negative inotropic effect, and smooth muscle cells resulting in reduced relaxation of vasculature. With calcium antagonism it also causes negative chronotropic effect. However, there is no data on it’s dose-dependent effects on cardiac dynamic parameters and heart rate on isolated rat heart with hypertension. Purpose To investigate chronic, dose-dependent effects of Verapamil on cardiodynamic parameters in isolated rat heart with hypertension. Methods The present 4-week study was carried out on 24 spontaneously hypertensive Wistar Kyoto male rats  (6 weeks old): Control (n = 6), rats treated with 0.5 mg/kg/day of Verapamil (n = 6), rats treated with 5 mg/kg/day of Verapamil (n = 6) and rats treated with 50 mg/kg/day of Verapamil (n = 6). Isolated rat hearts were perfused on Langendorff perfusion apparatus. Results Chronic, low-dose Verapamil treatment significantly depressed function of all cardiodynamic parameters of the hypertensive heart when compared to the rats treated with higher doses of Verapamil (p &lt; 0.001), except on the coronary flow and heart rate when compared to the Control (p= 0.137; p = 1.000, respectively). There was no significant differences between Verapamil in middle dose (5 mg/kg/day) and the Control group in inotropic (p = 0.415) and lusitropic (p = 1.000) effects, while it significantly lowered values of coronary flow (p = 0.002). It achieved significantly lower inotropic, lusitropic and chronotropic effects (p &lt; 0.001) than high Verapamil dose and significantly better inotropic (p = 0.017), lusitropic (p &lt; 0.001), but not chronotropic effects than low-dose Verapamil treatment (p = 0.179). High-dose, chronic treatment with Verapamil significantly intensified function of  the isolated rat heart with hypertension when compared to Control and lower doses of Verapamil (p &lt; 0.001), without significant effects on coronary flow (p = 0.363). Conclusions Chronic treatment with Verapamil in high dose achieved better inotropic, chronotropic and lusitropic effects than treatment in low and middle doses of Verapamil, without significant effects on coronary flow. There is dose-depended effect of chronic Verapamil treatment on cardiac function of isolated rat heart with hypertension.


Author(s):  
Huihui Chen ◽  
Huiting Yang ◽  
Yanyan Zhao ◽  
Xiaohong Gu ◽  
Christopher J. Martyniuk

Concerns regarding environmental exposures and the impacts of pharmaceuticals on non-target aquatic organisms continue to increase. The antiepileptic drug carbamazepine (CBZ) is often detected as an aquatic contaminant and can disrupt various behaviors of fishes. However, there are few reports which investigate the mechanism of CBZ action in fish. The aim of the current study was to evaluate the effects of CBZ on embryonic development (i.e., hatching rate, heart rate, and body length) and early spontaneous movement. Moreover, we sought to investigate potential mechanisms by focusing on the gamma-aminobutyric acid (GABA) neurotransmitter system in zebrafish 6 days after of exposure. The results show that CBZ exposure did not cause significant effects on embryo development (hatching rate, heart rate, nor body length) at the test concentrations. However, the early spontaneous movement of embryos was inhibited following 10 μg/L CBZ exposure at 28–29 h post-fertilization (hpf). In addition, acetylcholinesterase (AChE) activity and GABA concentrations were increased with exposure, whereas glutamate (Glu) concentrations were decreased in larval zebrafish. Gene expression analysis revealed that GABA and glutamate metabolic pathways in zebrafish larvae were altered following exposure to CBZ. GABA transaminase (abat) and glutamic acid decarboxylase (gad1b) decreased to 100 µg/L, and glutamate receptor, ionotropic, N-methyl D-aspartate 1b (grin1b) as well as the glutamate receptor, ionotropic, α-amino-3hydroxy-5methylisoxazole-4propionic 2b (gria2b) were down-regulated with exposure to 1 µg/L CBZ. Our study suggests that CBZ, which can act as an agonist of the GABAA receptor in humans, can also induce alterations in the GABAergic system in fish. Overall, this study improves understanding of the neurotoxicity and behavioral toxicity of zebrafish exposed to CBZ and generates data to be used to understand mechanisms of action that may underlie antiepileptic drug exposures.


2020 ◽  
Vol 75 (Supplement_1) ◽  
pp. i76-i87
Author(s):  
D Torumkuney ◽  
S Anwar ◽  
S Nizamuddin ◽  
N Malik ◽  
I Morrissey

Abstract Objectives To determine antibiotic susceptibility of community-acquired respiratory tract infection (CA-RTI) isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2015–17 from Pakistan. Methods MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results A total of 94 S. pneumoniae and 122 H. influenzae isolates were collected. Susceptibility to penicillin was noted in 23.4% of the S. pneumoniae isolates by CLSI oral/EUCAST low-dose IV breakpoints, although by CLSI IV and EUCAST high-dose breakpoints all isolates were characterized as susceptible. Susceptibility to trimethoprim/sulfamethoxazole (10.6%), macrolides (33%) and cefaclor (28.7%) was low but higher susceptibility was observed to ceftriaxone (100%), amoxicillin and amoxicillin/clavulanic acid (98.9%), cefuroxime (oral, 97.9%), cefpodoxime (96.8%), fluoroquinolones (93.6%–96.8%) and cefdinir (76.6%) by CLSI breakpoints. However, using EUCAST breakpoints, susceptibility to cefpodoxime (70.2%) and cefuroxime (oral, 61.7%) was reduced. H. influenzae isolates were almost all β-lactamase negative (96.7%). Using CLSI breakpoints, ≥93.4% of isolates were susceptible to all antibiotics tested except fluoroquinolones (75.4%–77.1%) and trimethoprim/sulfamethoxazole (41%). The proportion of isolates susceptible using EUCAST breakpoints was similar or identical for penicillins, trimethoprim/sulfamethoxazole and the cephalosporins that have EUCAST breakpoints; the proportion of isolates susceptible using EUCAST breakpoints was similar or identical to that using CSLI breakpoints except for cefuroxime (oral), where only 1.6% of isolates were considered susceptible. Susceptibility of H. influenzae to fluoroquinolones was also lower by EUCAST breakpoints (33.6%–34.4%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Conclusions Antibiotic susceptibility in these important respiratory tract pathogens varied in Pakistan based on different breakpoints. These data are important for empirical therapy choices in the treatment of CA-RTIs.


1995 ◽  
Vol 82 (3) ◽  
pp. 620-633 ◽  
Author(s):  
P. Talke ◽  
J. Li ◽  
U. Jain ◽  
J. Leung ◽  
K. Drasner ◽  
...  

Background Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease. Methods Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively. Results Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results. Conclusions Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate.


1997 ◽  
Vol 16 (6) ◽  
pp. 327-333 ◽  
Author(s):  
Mohamed Alaa A Omran ◽  
Ismail M Abdel-Nabi

1 The effect of Egyptian cobra (Naja haje) venom on the normal electrical activity of the cardiac muscles (ECG) and arterial blood pressure of envenomated rats were investigated in this study. 2 Rats were divided into three groups. The first group was injected im with saline and considered as control group. Rats of the second and third groups were injected IM with 0.02 μg and 0.04 μg cobra venom/ gim b.wt, respectively. 3 Mean blood pressure (MBP), heart rate (HR) and four different ECG parameters (PR and QT intervals, R and T wave amplitudes) were measured over 1 h following envenomation. 4 The low dose (0.02 μg/g) of N. haje venom caused hypotension accompanied by an increase in the HR, whereas hypertension and bradycardia developed after injection of the high dose (0.04 μg/g) of venom. 5 There was a decrease in the P-R interval after administration of the low dose and prolongation of it after the high dose. The Q-T interval and R-wave amplitude were significantly increased after injection of both doses. T-wave amplitude was significantly elevated only after injection of the high dose. 6 The present results indicate that the Egyptian cobra (N. haje) venom significantly alters the arterial blood pressure and ECG parameters of envenomated rats. This suggests that impairment of the electrical activity of cardiac muscle may be one of the reasons why victims of cobra bite die.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Cristina Campos ◽  
Karina Rabello Casali ◽  
Dhãniel Baraldi ◽  
Adriana Conzatti ◽  
Alex Sander da Rosa Araújo ◽  
...  

This study tested whether a low dose (40% less than the pharmacological dose of 17-βestradiol) would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n=9/group) were divided in three groups: (1) ovariectomized (Ovx), (2) ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg), and (3) high dose (HE; 0.5 mg) 17-βestradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD) and catalase (CAT) activities, redox ratio (GSH/GSSG), total radical-trapping antioxidant potential (TRAP), hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy.


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