Dual effect of Lutzomyia longipalpis saliva on Leishmania braziliensis infection is mediated by distinct saliva-induced cellular recruitment into BALB/c mice ear

Abstract Background Leishmania parasites are transmitted to their vertebrate hosts by infected Phlebotomine sand flies during the blood meal of the flies. Sand fly saliva is known to enhance Leishmania spp. infection, while pre-exposure to saliva protects mice against parasitic infections. In this study, we investigated the initial inflammatory leucocyte composition induced by one or three inocula of salivary gland extract (SGE) from Lutzomyia longipalpis in the presence or absence of Leishmania braziliensis. Results We demonstrated that inoculating SGE once (SGE-1X) or three times (SGE-3X), which represented a co-inoculation or a pre-exposure to saliva, respectively, resulted in different cellular infiltrate profiles. Whereas SGE-1X led to the recruitment of all leucocytes subtypes including CD4+ T cells, CD4+CD25+ T cells, dendritic cells, macrophages and neutrophils, the immune cell profile in the SGE-3X group differed dramatically, as CD4+ T cells, CD4+CD25+ T cells, dendritic cells, macrophages and neutrophils were decreased and CD8+ T cells were increased. The SGE-1X group did not show differences in the ear lesion size; however, the SGE-1X group harbored a higher number of parasites. On the other hand, the SGE-3X group demonstrated a protective effect against parasitic disease, as the parasite burden was lower even in the earlier stages of the infection, a period in which the SGE-1X group presented with larger and more severe lesions. These effects were also reflected in the cytokine profiles of both groups. Whereas the SGE-1X group presented with a substantial increase in IL-10 production, the SGE-3X group showed an increase in IFN-γ production in the draining lymph nodes. Analysis of the inflammatory cell populations present within the ear lesions, the SGE-1X group showed an increase in CD4+FOXP3+ cells, whereas the CD4+FOXP3+ population was reduced in the SGE-3X group. Moreover, CD4+ T cells and CD8+ T cells producing IFN-γ were highly detected in the ears of the SGE-3X mice prior to infection. In addition, upon treatment of SGE-3X mice with anti-IFN-γ monoclonal antibody, we observed a decrease in the protective effect of SGE-3X against L. braziliensis infection. Conclusions These results indicate that different inocula of Lutzomyia longipalpis salivary gland extract can markedly modify the cellular immune response, which is reflected in the pattern of susceptibility or resistance to Leishmania braziliensis infection.

Effect of thermal treatment on the chemical characteristics of wood from Eucalyptus grandis W. Hill ex Maiden under different atmospheric conditions

Thermal treatment (thermal rectification) is a process in which technological properties of wood are modified using thermal energy, the result of which is often value-added wood. Thermally treated wood takes on similar color shades to tropical woods and offers considerable resistance to destructive microorganisms and climate action, in addition to having high dimensional stability and low hygroscopicity. Wood samples of Eucalyptus grandis were subjected to various thermal treatments, as performed in presence (140ºC; 160ºC; 180ºC) or in absence of oxygen (160ºC; 180ºC; 200ºC) inside a thermal treatment chamber, and then studied as to their chemical characteristics. Increasing the maximum treatment temperatures led to a reduction in the holocellulose content of samples as a result of the degradation and volatilization of hemicelluloses, also leading to an increase in the relative lignin content. Except for glucose, all monosaccharide levels were found to decrease in samples after the thermal treatment at a maximum temperature of 200ºC. The thermal treatment above 160ºC led to increased levels of total extractives in the wood samples, probably ascribed to the emergence of low molecular weight substances as a result of thermal degradation. Overall, it was not possible to clearly determine the effect of presence or absence of oxygen in the air during thermal treatment on the chemical characteristics of the relevant wood samples.

Influence of treatment with and without extractions on the growth pattern of dolichofacial patients

OBJECTIVE: The objective of this retrospective study was to compare, by means of lateral cephalograms, the facial growth pattern changes due to the treatment with and without extractions of four first premolars in dolichofacial individuals. METHODS: Groups 1 and 2 were constituted of 23 dolichofacial patients each, with Class II malocclusion, division 1 and initial age average of 12.36 and 12.29 years, respectively. Patients from Group 1 were treated without extractions and Group 2 was treated with extraction of the four first premolars, given that both used occipital headgear. Groups were compatibilized according to age, treatment period, gender and malocclusion severity. The t test was applied for intergroups comparison. RESULTS: Most variables (SN.PP, SN.Ocl and FMA) did not present statistically significant difference between groups. CONCLUSION: Although the treatment with extractions tend to reduce the mandibular plane angle (SN.GoGn) and the facial axis (NS.Gn), the analyzed treatment protocols did not affect in a clinically relevant way the facial growth pattern.

Insulin-like growth factor-I treatment in primary growth hormone insensitivity: effect of recombinant human IGF-I (rhIGF-I) and rhIGF-I/rhIGF-binding protein-3 complex

Growth hormone insensitivity syndrome (GHIS) is a rare cause of growth retardation characterized by high serum GH levels, and low serum insulin-like growth factor I (IGF-I) levels associated with a genetic defect of the GH receptor (GHR) as well post-GHR signaling pathway. Based on clinical, as well as biochemical characteristics, GHIS can be genetically classified as classical/Laron's syndrome and nonclassical/atypical GHIS. Recombinant human IGF-I (rhIGF-I) treatment is effective in promoting growth in subjects who have GHIS. Further, pharmacological studies of a IGF-I compound containing a 1:1 molar complex of rhIGF-I and rhIGF-binding protein-3 (BP-3) demonstrated that the complex was effective in increasing levels of circulating total and free IGF-I and that the administration in patients with GHIS should be safe, well-tolerated and more effective than rhIGF-I on its own.

A randomised determination of the effect of fluvastatin and atorvastatin on top of dual antiplatelet treatment on platelet aggregation after implantation of coronary drug-eluting stents. The EFA-Trial

Drug-drug interaction between statins metabolised by cytochrome P450 3A4 and clopidogrel have been claimed to attenuate the inhibitory effect of clopidogrel. However, published data regarding this drug-drug interaction are controversial. We aimed to determine the effect of fluvastatin and atorvastatin on the inhibitory effect of dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel. One hundred one patients with symptomatic stable coronary artery disease undergoing percutaneous coronary intervention and drug-eluting stent implantation were enrolled in this prospective randomised study. After an interval of two weeks under dual antiplatelet therapy with ASA and clopidogrel, without any lipid-lowering drug, 87 patients were randomised to receive a treatment with either fluvastatin 80 mg daily or atorvastatin 40 mg daily in addition to the dual antiplatelet therapy for one month. Platelet aggregation was assessed using light transmission aggregometry and whole blood impedance platelet aggregometry prior to randomisation and after one month of receiving assigned statin and dual antiplatelet treatment. Platelet function assessment after one month of statin and dual antiplatelet therapy did not show a significant change in platelet aggregation from 1st to 2nd assessment for either statin group. There was also no difference between atorvastatin and fluvastatin treatment arms. In conclusion, neither atorvastatin 40 mg daily nor fluvastatin 80 mg daily administered in combination with standard dual antiplatelet therapy following coronary drug-eluting stent implantation significantly interfere with the antiaggregatory effect of ASA and clopidogrel.

A sequential Cox approach for estimating the causal effect of treatment in the presence of time-dependent confounding applied to data from the Swiss HIV Cohort Study

When estimating the effect of treatment on HIV using data from observational studies, standard methods may produce biased estimates due to the presence of time-dependent confounders. Such confounding can be present when a covariate, affected by past exposure, is both a predictor of the future exposure and the outcome. One example is the CD4 cell count, being a marker for disease progression for HIV patients, but also a marker for treatment initiation and influenced by treatment. Fitting a marginal structural model (MSM) using inverse probability weights is one way to give appropriate adjustment for this type of confounding. In this paper we study a simple and intuitive approach to estimate similar treatment effects, using observational data to mimic several randomized controlled trials. Each 'trial' is constructed based on individuals starting treatment in a certain time interval. An overall effect estimate for all such trials is found using composite likelihood inference. The method offers an alternative to the use of inverse probability of treatment weights, which is unstable in certain situations. The estimated parameter is not identical to the one of an MSM, it is conditioned on covariate values at the start of each mimicked trial. This allows the study of questions that are not that easily addressed fitting an MSM. The analysis can be performed as a stratified weighted Cox analysis on the joint data set of all the constructed trials, where each trial is one stratum. The model is applied to data from the Swiss HIV cohort study.

Effect of smoking on the results of a chlorhexidine digluconate treatment extended up to 3 months after scaling and root planing-a pilot study

The aim of the study was to evaluate the impact of smoking on a prolongated chlorhexidine digluconate regimen after scaling and root planing. Forty-two smokers (test group) and 85 nonsmoking patients (control group) with generalized chronic periodontitis were examined for clinical attachment level (CAL), probing depth (PD), bleeding on probing (BoP), and Plaque Index (Pl) at baseline and after 1 and 3 months. During scaling and root planing, a 0.2% chlorhexidine digluconate solution and a 1% chlorhexidine digluconate gel were used. The subjects used a 0.2% chlorhexidine digluconate solution twice daily for 3 months. The Mann-Whitney U and Wilcoxon tests were used for statistical analysis. There were significant improvements of all studied variables after 1 and 3 months in both groups. After 3 months, the mean improvement in the test group was 1.62 mm for CAL, 2.85 mm for PD, and 48% for BoP; in the control group, the values were 2.18 mm for CAL, 2.81 mm for PD, and 47% for BoP. Only the maximum changes of CAL between 1 and 3 months (test group, 0.32 mm vs 0.69 mm in the control group) and PD (test group, 0.47 mm vs 0.76 mm in the control group) were significantly different between the groups (P < .05 and P = .05, respectively). The present data appear to suggest that the use of chlorhexidine digluconate twice daily during a period of 3 months following nonsurgical periodontal therapy may result in significant clinical improvements in smokers and nonsmokers.

Effect on false-lumen status of a combined vascular and endovascular approach for the treatment of acute type A aortic dissection

The aim of the study is to evaluate midterm results with regard to false-lumen status of a combined vascular and endovascular approach for the treatment of acute type A aortic dissection.

The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment.

Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis.

Early treatment in sepsis may improve outcome. The aim of this study was to evaluate how the delay in starting resuscitation influences the severity of sepsis and the treatment needed to achieve hemodynamic stability.

Experimental Evaluation of Immediate Recanalization Effect and Recanalization Efficacy of a New Thrombus Retriever for Acute Stroke Treatment In Vivo

BACKGROUND AND PURPOSE: Currently, several new stent retriever devices for acute stroke treatment are under development and early clinical evaluation. Preclinical testing under standardized conditions is an important first step to evaluate the technical performance and potential of these devices. The aim of this study was to evaluate the immediate recanalization effect, recanalization efficacy, thrombus-device interaction, and safety of a new stent retriever intended for thrombectomy in patients with acute stroke. MATERIAL AND METHODS: The pREset thrombectomy device (4 × 20 mm) was evaluated in 16 vessel occlusions in an established swine model. Radiopaque thrombi (10-mm length) were used for visualization of thrombus-device interaction during application and retrieval. Flow-restoration effect immediately after deployment and after 5-minute embedding time before retrieval, recanalization rate after retrieval, thromboembolic events, and complications were assessed. High-resolution FPCT was performed to illustrate thrombus-device interaction during the embedding time. RESULTS: Immediate flow restoration was achieved in 75% of occlusions. An increase or stable percentage of recanalizations during embedding time before retrieval was seen in 56.3%; a decrease, in 12.5%; reocclusion of a previously recanalized vessel, in 18.8%; and no recanalization effect at all, in 12.5%. Complete recanalization (TICI 3) after retrieval was achieved in 93.8%; partial recanalization (TICI 2b), in 6.2%. No distal thromboembolic events were observed. High-resolution FPCT illustrated entrapment of the thrombus between the stent struts and compression against the contralateral vessel wall, leading to partial flow restoration. During retrieval, the thrombus was retained in a straight position within the stent struts. CONCLUSIONS: In this experimental study, the pREset thrombus retriever showed a high recanalization rate in vivo. High-resolution FPCT allows detailed illustration of the thrombus-device interaction during embedding time and is advocated as an add-on tool to the animal model used in this study.

Effect of eprinomectin treatment on milk yield and quality in dairy cows in South Tyrol, Italy

The effect of treatment with eprinomectin on milk yield, milk composition and somatic cell counts (SCCs) was studied in 105 dairy cows located on seven farms in South Tyrol, Italy. On each farm, half of the animals were treated with eprinomectin and the other half were used as an untreated control group. Three test day records per animal were obtained before treatment (days -117, -75 and -33) and another three test day records were obtained after treatment (days 22, 62 and 131). Test day records comprised milk yield, milk composition, SCC and days in milk. On the day of treatment, blood samples and faecal samples were taken for parasitological analysis. Cows with positive faecal egg counts yielded less milk. A significant effect of eprinomectin on milk yield was observed after treatment and was most pronounced on the second and the third test days after treatment (+1.90 kg [P=0.002] and +2.63 kg [P<0.001], respectively). Furthermore, a significant decrease in SCC was observed on the second test day after treatment.

Peri-interventional antibiotic prophylaxis only vs continuous low-dose antibiotic treatment in patients with JJ stents: a prospective randomised trial analysing the effect on urinary tract infections and stent-related symptoms

To evaluate the antibiotic treatment regime in patients with indwelling JJ stents, the benefits and disadvantages of a peri-interventional antibiotic prophylaxis were compared with those of a continuous low-dose antibiotic treatment in a prospective randomised trial.