scholarly journals Evidence of Less Severe Aortic Valve Destruction after Treatment of Experimental Staphylococcal Endocarditis with Vancomycin and Dexamethasone

2001 ◽  
Vol 45 (12) ◽  
pp. 3531-3537 ◽  
Author(s):  
Peter Siaperas ◽  
Angelos Pefanis ◽  
Dimitrios Iliopoulos ◽  
Ioannis Katsarolis ◽  
Aspassia Kyroudi-Voulgari ◽  
...  

ABSTRACT The beneficial effects of therapy combining an antibiotic and dexamethasone have been reported in human studies on meningitis and in experimental studies on septic arthritis, nephritis, and endophthalmitis. Since most patients with staphylococcal endocarditis need a combination of medical and surgical treatment, the purpose of this study was to determine whether the addition of dexamethasone to vancomycin has any beneficial effect regarding the degree of valve tissue damage or the course of experimental aortic valve endocarditis caused by a methicillin-resistant strain of Staphylococcus aureus. Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group and to groups receiving dexamethasone (0.5 mg/kg of body weight, intravenously [i.v.], twice a day [b.i.d]), vancomycin (30 mg/kg, i.v., b.i.d), or dexamethasone plus vancomycin, for a total of 10 doses (two doses per day for 5 days). The severity of valve tissue damage was significantly less in groups receiving vancomycin plus dexamethasone compared with that of the group receiving vancomycin alone (P < 0.001). The severity of tissue damage was inversely correlated with the mean polymorphonuclear leukocyte number in valve tissue. No statistically significant differences were observed between the vancomycin-treated group and the vancomycin-plus-dexamethasone-treated group in survival, blood culture sterilization rate, or reduction of the microbial burden (in CFU per gram) in valvular tissue. In conclusion, treatment with a combination of vancomycin and dexamethasone for 5 days reduces the severity of valve tissue damage in experimental staphylococcal aortic valve endocarditis. These findings could have significant implications in the treatment of staphylococcal endocarditis and deserve further confirmation in clinical trials.

2007 ◽  
Vol 51 (8) ◽  
pp. 2848-2854 ◽  
Author(s):  
Ioannis Skiadas ◽  
Angelos Pefanis ◽  
Apostolos Papalois ◽  
Aspasia Kyroudi ◽  
Helen Triantafyllidi ◽  
...  

ABSTRACT Although the beneficial effects of dexamethasone have frequently been investigated in various serious-infection settings, insufficient data on valve histology and cardiac function for infective endocarditis are available. The efficacy of moxifloxacin for the treatment of experimental aortic valve endocarditis due to methicillin-susceptible Staphylococcus aureus and the long-term effects of dexamethasone were evaluated in the current study. Sixty-eight rabbits were randomly assigned to four groups: A, B, C, and D. Group A consisted of 18 animals and functioned as a control group. Groups B and C consisted of 11 and 23 subjects, respectively, which received moxifloxacin for 5 days in a human-like pharmacokinetic simulation. Group D consisted of 16 animals that were administered moxifloxacin plus dexamethasone (0.25 mg/kg of body weight twice a day intravenously). The group B animals were sacrificed a day after the completion of treatment, and group C and D animals were sacrificed after 12 days in order to monitor any possible relapse and allow microbiological, histopathological, and echocardiographic evaluation of the long-term effects of glucocorticoids. No differences in survival, sterilization rates, or inflammatory infiltration and calcification of valve tissue were observed among the treated groups. However, the degrees of valve damage and collagenization were significantly worse, the fibroblast content was higher, and fractional shortening of the left ventricle fluctuated significantly in group C compared to group D (all groups, P < 0.05). We concluded that dexamethasone treatment for experimental S. aureus endocarditis attenuates valve destruction and preserves overall cardiac function without impeding the efficacy of moxifloxacin.


Author(s):  
Ashraf Albrakati

Tramadol, a broadly in recent years, is an effective analgesic agent for the treatment of moderate to acute pain. Its metabolites are excreted by the kidney which may cause nephrotoxicity. Moringa oleifera leaves are commonly used to provide herbal and plant-derived medicinal products especially in developing nations. The present study was carried out to determine the biochemical and histopathological changes in the kidney of tramadol-treated albino mice and to evaluate the possible protective role of Moringa oleifera leaves against tramadol-induced nephrotoxicity. Twenty adult albino mice were divided into four groups. Control group (group i) received daily intraperitoneal injection of normal saline only, group ii received oral dose of Moringa oleifera leaves extract (20 mg/kg/bw) for three weeks, group iii received daily intraperitoneal dose of tramadol (0.3 mg/kg/bw) for the same period, group iv, received daily oral dose of Moringa oleifera leaves extract, (20 mg/kg/bw) three hours before injecting intraperitoneal dose of tramadol (0.3 mg/kg/bw), for the same period. Blood samples were withdrawn at the end of the experiment for kidney function tests and specimens from the kidney were processed for histological study. No significant differences in the mean values of the kidney function tests were noticed between Moringa oleifera group and control group. However, there was highly significant increase in the mean values of serum, urea and creatinine in tramadol-treated group as compared to the control group. Although tramadol + Moringa oleifera group revealed significant difference in the mean values of urea and creatinine when compared with tramadol-treated group. So, Moringa oleifera leaves extract have been shown to attenuate the renal dysfunction, improve the renal architecture, with nearly normalization of serum urea and creatinine levels which indicate improvement of renal function. In conclusion, in the light of biochemical results and histological findings, co-administration of Moringa oleifera leaves lessened the negative effects of tramadol-induced nephrotoxicity; possibly by its antioxidant action. Further investigation of these promising protective effects of Moringa oleifera leaves against tramadol-induced renal injury may have considerable impact on developing an adjunct therapy aiming to improve the therapeutic index of some nephrotoxic drugs.


2020 ◽  
Vol 8 (1) ◽  
pp. 209-228
Author(s):  
Layla Parast ◽  
Priscillia Hunt ◽  
Beth Ann Griffin ◽  
David Powell

AbstractIn some applications, researchers using the synthetic control method (SCM) to evaluate the effect of a policy may struggle to determine whether they have identified a “good match” between the control group and treated group. In this paper, we demonstrate the utility of the mean and maximum Absolute Standardized Mean Difference (ASMD) as a test of balance between a synthetic control unit and treated unit, and provide guidance on what constitutes a poor fit when using a synthetic control. We explore and compare other potential metrics using a simulation study. We provide an application of our proposed balance metric to the 2013 Los Angeles (LA) Firearm Study [9]. Using Uniform Crime Report data, we apply the SCM to obtain a counterfactual for the LA firearm-related crime rate based on a weighted combination of control units in a donor pool of cities. We use this counterfactual to estimate the effect of the LA Firearm Study intervention and explore the impact of changing the donor pool and pre-intervention duration period on resulting matches and estimated effects. We demonstrate how decision-making about the quality of a synthetic control can be improved by using ASMD. The mean and max ASMD clearly differentiate between poor matches and good matches. Researchers need better guidance on what is a meaningful imbalance between synthetic control and treated groups. In addition to the use of gap plots, the proposed balance metric can provide an objective way of determining fit.


2012 ◽  
Vol 109 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Jeong Sook Noh ◽  
Yung Hyun Choi ◽  
Yeong Ok Song

The present study investigated the effects of 3′-(4′-hydroxyl-3′,5′-dimethoxyphenyl)propionic acid (HDMPPA), the active principle compound of kimchi, on vascular damage in the experimental atherosclerotic animal. HDMPPA was administrated by an intraperitoneal injection of 10 mg/kg per d for 8 weeks to apoE knockout (KO) mice with an atherogenic diet containing 1 % cholesterol, and its effects were compared with vehicle-treated control mice. HDMPPA increased NO content in the aorta, accompanied by a decrease in reactive oxygen species (ROS) concentration. Furthermore, in the HDMPPA-treated group, aortic endothelial NO synthase (eNOS) expression was up-regulated compared with the control group. These results suggested that HDMPPA could maintain NO bioavailability through an increasing eNOS expression and preventing NO degradation by ROS. Furthermore, HDMPPA treatment in apoE KO mice inhibited eNOS uncoupling through an increase in vascular tetrahydrobiopterin content and a decrease in serum asymmetric dimethylarginine levels. Moreover, HDMPPA ameliorates inflammatory-related protein expression in the aorta of apoE KO mice. Therefore, the present study suggests that HDMPPA, the active compound of kimchi, a Korean functional food, may exert its vascular protective effect through the preservation of NO bioavailability and suppression of the inflammatory response.


2018 ◽  
Vol 3 (2) ◽  
pp. 1-11 ◽  
Author(s):  
Ana Paula Resende ◽  
Serge G. Rosolen ◽  
Telmo Nunes ◽  
Berta São Braz ◽  
Esmeralda Delgado

Purpose: The present study aimed to assess functional and structural benefits of erythropoietin (EPO) when administered subconjunctivally in the retina of glaucomatous rats using electroretinography (ERG) and retinal thickness (RT) measurements. Methods: Glaucoma was experimentally induced in 26 Wistar Hannover albino rats. Animals were divided into 2 groups of 13 animals each: a treated group receiving a unique subconjunctival injection of 1,000 IU of EPO and a control group receiving a saline solution. In each group, 7 animals were used for retinal function evaluation (ERG) and 6 animals were used for retinal structural evaluation (histology). RT was measured, dorsally and ventrally, at 500 μm (RT1) and at 1,500 μm (RT2) from the optic nerve. Results: Retinal function evaluation: for both scotopic and photopic conditions, ERG wave amplitudes increased in the treated group. This increase was statistically significant (p < 0.05) in photopic conditions. Structural evaluation: for both locations RT1 and RT2, the retinas were significantly (p < 0.05) thicker in the treated group. Conclusion: Subconjunctival EPO administration showed beneficial effects both on retinal structure and on retinal function in induced glaucoma in albino rats. This neuroprotective effect should be applied in other animal species.


2019 ◽  
Vol 7 (2) ◽  
pp. 66
Author(s):  
Richard Fritzgerald ◽  
Cecilia Lunardhi ◽  
Ruslan Effendy ◽  
Tamara Yuanita

Background. Root canal treatment is a main role in decreasing infection from root canal and pulp. The main cause of periapical damage mostly are bacteries. E.faecalis is a bactery that is found as an etiology of endodontic treatment failure. Cell wall of this bacteria is containing Lipoteichoic acid (LTA). LTA can penetrate into the periradicular tissue, act as endotoxin in host and cause periradicular inflammation then lead to bone destruction. LTA stimulates immunology reaction that produce Tumor Necrosis Factor alpha (TNF-α) and Transforming growth factors beta (TGF-ß). TNF-α is a main mediator and also have an important role in inflamation response otherwise TGF-ß is working as a multifunction  regulator of cell growth and differentiation during reforming and remodelling.  Purpose. The aim of this study is to know about the expression of TNF-α and TGF-ß during the periapical tissue damage due to induction of E.faecalis. Method. This study used laboratory experimental with the post test only control group design. A total of 30 male rats were randomly divided into 3 main groups, Group A (control negative) : normal tooth. Group B (control positive) : every tooth was induced only by sterile BHI-b. Group C (treated group) : every tooth  was induced by 10 μl BHI-b E.faecalis ATCC212(106 CFU). The animals were sacrificed 21 days later and prepared for histological examination of tissue damage, then we did the immunohistochemistry  followed by calculation on the light microscope. Result. The analysis revealed that the expression of TNF-α at treated group are higher than negative control and positive control but the expression of  TGF-ß at treated group are higher than the negative control group but lower than positive control. Conclusion. From this study we know that the expression of TNF-α and TGF-ß are changing during the periapical tissue damage that induced by E.faecalis.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
David Busseuil ◽  
Yanfen Shi ◽  
Mélanie Mecteau ◽  
Geneviéve Brand ◽  
Teodora Avram ◽  
...  

Purpose : Aortic valve stenosis is the most common valvular heart disease, and standard curative therapy remains open-heart surgical valve replacement. The aim of our experimental study was to determine if ApoA-I mimetic peptide infusions could induce regression of aortic valve stenosis. Methods : Twenty-seven New-Zealand White male rabbits received a cholesterol-enriched diet and vitamin D 2 until significant aortic valve stenosis was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were randomized to receive saline (control group, n =14) or an ApoA-I mimetic peptide (treated group, n =13), 3 times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed. Results : Aortic valve area improved significantly in the treated group compared to controls after 7 days (20.9±0.9 mm 2 vs. 18.2±0.6 mm 2 , P <0.0001) (corresponding to increases of 15.9% and 1.9%), 10 days (21.5±1.0 mm 2 vs. 19.5±0.6 mm 2 , P =0.0032) (increases of 19.2% vs. 9.1%), and 14 days of treatment (22.4±0.9 mm 2 vs. 20.4±0.6 mm 2 , P =0.0028) (increases of 24.4% vs. 14.2%). Likewise, aortic valve thickness decreased by 19% after 14 days of treatment in the treated group (0.951±0.070 mm at baseline vs. 0.768±0.074 mm at follow-up) whereas it was unchanged in controls ( P <0.0001). Histological analysis revealed that lesion extent at the base of valve leaflets and sinuses of Valsalva was smaller in the treated compared to control group (52.8±12.5% vs. 66.7±9.9%, P =0.032). The ApoA-I mimetic peptide treatment also leads to a reduction in aortic valve calcifications as revealed by the loss of the positive relationship observed in the control group ( r =0.87, P =0.004) between calcifications area and aortic valve thickness. Conclusions : Infusions of an ApoA-I mimetic peptide lead to regression of experimental aortic valve stenosis. These positive results justify the further testing of HDL-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform our clinical approach of this disease.


2001 ◽  
Vol 95 (2) ◽  
pp. 179-189 ◽  
Author(s):  
Hans-Peter Richter ◽  
Erich Kast ◽  
Rainer Tomczak ◽  
Werner Besenfelder ◽  
Wilhelm Gaus

Object. Failed-back syndrome is still an unsolved problem. Use of ADCON-L gel, already commercially available, has been proven to reduce postoperative scarring in animal experiments. The authors of two controlled clinical studies have also shown positive results when applying the gel. They did not, however, establish patient-oriented endpoints. The authors report a study of ADCON-L in which they focus on patient-oriented endpoints. Methods. Patients with lumbar disc herniation were randomized to an ADCON-L—treated or control group. Therapeutic success was evaluated using the validated Hannover Questionnaire on Activities of Daily Living (FFbH) 6 months after surgery. The study took place between November 14, 1996, and April 20, 1998, in eight neurosurgical centers in Germany. A total of 398 patients was recruited; 41 patients dropped out during follow up. The mean functional FFbH score (100 points = all activities are possible without problem; 0 points = no activity is possible) was 78.5 points in the ADCON-L—treated group compared with 80 points in the control group. Furthermore, in terms of secondary outcome variables, the ADCON-L group did not have an advantage over the control group. Only the mean magnetic resonance imaging score showed a slight advantage of ADCON-L over the control group. Conclusions. The authors found no positive effect of treatment with ADCON-L gel in patients in whom one-level lumbar microdiscectomy was performed. Because of its rather large sample size and its homogeneity, the study had sufficient power to detect even small differences between the two groups.


1987 ◽  
Vol 32 (6) ◽  
pp. 171-172 ◽  
Author(s):  
G.R. Nimmo ◽  
M.J. Ryan ◽  
N. Chalmers ◽  
A.W. Patrick

A neurological history was obtained and examination performed on 62 outpatient epileptics on anticonvulsant therapy. Blood counts, folate and B12 assays were performed on all patients and on a control group of 59 adult non-epileptic neurological outpatients. None of the anticonvulsant treated group had clinical peripheral neuropathy; there was one patient with microcytic anaemia and one with normochromic, normocytic anaemia. In 5 of this group the mean corpuscular volume (MCV) was slightly raised but there was no significant overall difference from the control group. In 17 patients serum folate was subnormal and in 7 the red cell folate was subnormal and this was significantly different to the control group (P <0.001). Vitamin B12 levels were normal in all subjects. It is concluded that despite subnormal measured folate levels, there is no increased incidence of clinical peripheral neuropathy or of significant macrocytosis. In view of this, we recommend that folate replacement should not be given to non anaemic asymptomatic patients, with subnormal folate levels, on anticonvulsant therapy.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Anousakis-Vlachochristou ◽  
K Toutouzas ◽  
M Kyriakidou ◽  
E Varela ◽  
A Kapelouzou ◽  
...  

Abstract Background Advanced glycation end products (AGPs) promote human aortic smooth muscle cell calcification in vitro. Moreover, reduction of AGPs levels and inhibition of RAGE signaling decrease vascular calcification in vivo in animal studies. The role of AGPs in aortic valve calcification has not been investigated. Purpose We sought to investigate the role of AGPs in aortic valve calcification, in the absence of diabetes mellitus (DM). Methods We used human and animal cohorts. Firstly, we obtained aortic valves from patients without DM that underwent aortic valve replacement due to aortic valve stenosis. We studied the valves with Fourier-Transformed Infrared spectroscopy (FT-IR, Nicolet 6700 spectrometer, with Attenuated Total Reflection-ATR accessory, each spectrum consisted of 120 co-added spectra) in order to evaluate chemical changes. In the animal cohort, New Zealand male rabbits where randomized in calcification diet (normal chow+cholesterol 0,5%+3500 IU ergocalciferol/kg daily) and control group and sacrificed at 2, 4, 6, 8 10 and 12 weeks. The valves were longitudinally assessed with FT-IR. Results A total of 200 human aortic valves were studied (age 64–78). All patients demonstrated characteristic vibrations at the area about 1165 cm-1, where the C-O-C bonds absorb, attributed to AGPs. Thirty six rabbit valves were used, 3 per group. Glucose levels were within normal range and did not differ between groups. The FT-IR spectra of the rabbit aortic valves showed increasing intensity of the C-O-C band at 1165 cm-1 in experimental group in comparison to control group. The band at 1744 cm-1 is attributed to aldehyde formation due to oxidative stress and inflammation. Shifts and shape changes were detected at the bands of amide I and II at 1650 cm-1 and 1550 cm-1, respectively, concerning protein misfolding, fiber formation and sclerosis. The bands in the region 1299–900 cm-1 correspond to phosphate groups of phospholipidsand the formed calcium phosphate salts and non-biological hydroxyapatite Ca3(PO4)2 formation. All vibrations increased significantly longitudinally during experimental diet period. Representative FT-IR spectra of valves Conclusions Advanced glycation end products are detected in human calcified aortic valves irrespectively of DM. Moreover, AGPs correlate with presence and gradual development of aortic valve calcification in experimental rabbit model, along with acidosis, oxidation and protein secondary misfolding. Accumulation of AGPs in valve tissue is implicated in mechanisms of disease development.


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