Molecular basis of cholesterol efflux via ABCG subfamily transporters.

The ABCG1 homodimer (G1) and ABCG5-ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter G family, are required for maintenance of cellular cholesterol levels. G5G8 mediates secretion of neutral sterols into bile and the gut lumen, whereas G1 transports cholesterol from macrophages to high-density lipoproteins (HDLs). The mechanisms used by G5G8 and G1 to recognize and export sterols remain unclear. Here, we report cryoelectron microscopy (cryo-EM) structures of human G5G8 in sterol-bound and human G1 in cholesterol- and ATP-bound states. Both transporters have a sterol-binding site that is accessible from the cytosolic leaflet. A second site is present midway through the transmembrane domains of G5G8. The Walker A motif of G8 adopts a unique conformation that accounts for the marked asymmetry in ATPase activities between the two nucleotide-binding sites of G5G8. These structures, along with functional validation studies, provide a mechanistic framework for understanding cholesterol efflux via ABC transporters.

Presence of the toxigenic fungi Aspergillus spp. and Fusarium spp. in Musca domestica L. (Diptera: Muscidae) collected from dairy farms.

The objective of the study was to identify the presence of toxigenic fungi Aspergillus spp. and Fusarium spp. in domestic flies collected from dairy farms. We selected 10 dairy farms distributed in the central valley of the state of Aguascalientes, México. The flies were trapped using entomological traps with an olfactory attractant in 7 sites of the farm (silo-cutting surface, feed store, milking parlor, 3 feeders, and the rearing room). The fungi were cultivated in Sabouraud agar through direct sowing by serial dilutions to obtain the isolates, and a taxonomical identification was carried out under the microscope. The aflatoxins and zearalenone production capacity of the pure isolates were quantified using the ELISA test. The flies were present in all of the capture sites (45.3 flies, 567 mg, trap per day). We obtained 50 isolates of Aspergillus spp. genus, 12 of which produced aflatoxins (327 ± 143 µg/kg), whereas from 56 of the Fusarium spp. isolates, 10 produced large quantities of zearalenone (3,132 ± 665 µg/kg). These results suggest that the presence of domestic flies on dairy farms can constitute a source of dissemination for toxigenic fungi that can eventually contaminate grains and forage that are part of the daily cattle diet.

Determination of the discriminant doses to identify resistance to fipronil, flumethrin and coumaphos, in Rhipicephalus sanguineus s.l. (Acari: Ixodidae) from Mexico.

Rhipicephalus sanguineus s.l. is an intra- and peridomiciliary tick of medical and veterinary importance, whose control is carried out through the application of various ixodicides, to which it can develop resistance. The objective of this work was to determine the discriminant doses (d.d.) to identify resistance against three ixodicides - fipronil, flumethrin and coumaphos - in R. sanguineus s.l. larvae originating from Mexico. Engorged ticks were collected from naturally infested dogs residing in rural communities in five Mexican states; the dogs had no history of recent treatment with ixodicides. All ticks were identified as R. sanguineus s.l. They were incubated for 25 days and their progeny was used in the larval package test (LPT) to be exposed to d.d. as determined in Rhipicephalus microplus, and those that were susceptible were analyzed using the LPT with six concentrations, for fipronil from 0.1 to 0.003125%, for flumethrin from 0.02 to 0.000625% and for coumaphos from 0.4 to 0.0125%. Mortality was analyzed with Probit methodology, to calculate the 50 and 99% lethal concentrations (LC50 and LC99). The d.d. was determined as a consensus value by multiplying the LC99 value × 2. Nine double susceptible samples (fipronil + flumethrin) and one triple susceptible sample (fipronil + flumethrin + coumaphos) were found; the d.d. determined were fipronil 0.05%, flumethrin 0.01% and coumaphos 0.43%. These doses can be used to rapidly and inexpensively identify resistant populations in samples collected in the field.

Implication of miR-155-5p and miR-143-3p in the Vascular Insulin Resistance and Instability of Human and Experimental Atherosclerotic Plaque.

(1) Background: Cardiovascular diseases (CVDs) are the main cause of death in developed countries, being atherosclerosis, a recurring process underlying their apparition. MicroRNAs (miRNAs) modulate the expression of their targets and have emerged as key players in CVDs; (2) Methods: 18 miRNAs were selected (Pubmed and GEO database) for their possible role in promoting atherosclerosis and were analysed by RT-qPCR in the aorta from apolipoprotein E-deficient (ApoE-/-) mice. Afterwards, the altered miRNAs in the aorta from 18 weeks-ApoE-/- mice were studied in human aortic and carotid samples; (3) Results: miR-155-5p was overexpressed and miR-143-3p was downregulated in mouse and human atherosclerotic lesions. In addition, a significant decrease in protein kinase B (AKT), target of miR-155-5p, and an increase in insulin-like growth factor type II receptor (IGF-IIR), target of miR-143-3p, were noted in aortic roots from ApoE-/- mice and in carotid plaques from patients with advanced carotid atherosclerosis (ACA). Finally, the overexpression of miR-155-5p reduced AKT levels and its phosphorylation in vascular smooth muscle cells, while miR-143-3p overexpression decreased IGF-IIR reducing apoptosis in vascular cells; (4) Conclusions: Our results suggest that miR-155-5p and miR-143-3p may be implicated in insulin resistance and plaque instability by the modulation of their targets AKT and IGF-IIR, contributing to the progression of atherosclerosis.

Seroepidemiology of Toxoplasma gondii infection and parasite DNA in free-range chickens in Aguascalientes, Mexico.

The objectives of the study were to estimate the prevalence of anti-Toxoplasma gondii antibodies in free-range chickens in Aguascalientes, Mexico, its association with certain risk factors, and the frequency of parasite DNA in the heart. Eighty-one small rural family farms were included, and blood and heart samples were taken from 150 clinically healthy, adult, free-range chickens. Serum samples were processed by indirect immunofluorescence antibody test considering a dilution of 1:16 as a positive reaction, while the DNA detection was done by PCR. The correlation between the presence of antibodies and the potential risk factors was estimated with logistic regression. The overall seroprevalence in the examined populations was 67%, with a range from 33% to 100% among municipalities, and 78% of the farms having at least one seropositive bird. The PCR test identified the presence of parasite DNA for one case only. Among the variables, the presence of cats and the presence of other animal species on the farm were the ones that had the highest values, while the presence of feral cats and the presence of noxious fauna were also identified as potential risk factors. The results indicate high soil contamination by T. gondii oocysts, which implies the active role of cats living on the farms.

Epidemiology of Neospora caninum infection in free-range chickens (Gallus gallus domesticus) in north central Mexico.

The objective of the present study was to investigate the epidemiology of natural infection by N. caninum in free-range chickens from Aguascalientes, Mexico, through identifying the presence of antibodies, its association with certain risk factors, and estimate the frequency of parasite DNA detection in the brain. The study included 150 clinically healthy chickens from 81 small family farms distributed throughout the state, from which blood and brain samples were taken. Serum samples were processed by indirect immunofluorescence considering a dilution of 1:50 as a positive reaction, while the DNA detection was done by PCR; the association between the presence of antibodies and the potential risk factors was estimated through logistic regression. The general anti-N. caninum presence of antibodies in the studied population was 46% (69/150, CI 95% 38-54), with titers of 1:50 in 38, 1:100 in 24, and 1:200 in 7, finding positive cases in 49% of the farms and in 91% of the municipalities that integrate the state. The presence of antibodies found in the municipalities was estimated in a range of 20 to 75%. The frequency of DNA detection was 6% (9/150, CI 95% 2-11). The grain supplementation was identified as the unique risk factor for infection (OR = 2.82; 95% CI, 1.18-6.73, p < 0.019).

Prevalence and risk factors of Neospora caninum infection in ovine flocks of central-western Mexico.

This study, carried out in 13 sheep flocks of central-western Mexico, aimed to identify the prevalence of anti-N. caninum antibodies, to develop a risk analysis of the infection and to estimate the prevalence of parasite DNA in blood. A total of 368 serum and blood samples were subjected to ELISA and PCR tests, respectively, and the association between the prevalence of antibodies and some management factors was estimated. The overall prevalence of anti-N. caninum antibodies was 13.5% [50/368; 95% confidence interval (CI) 10-17], ranging from 2.7 to 90% per flock, and 92% of the farms had seropositive animals. In ewes the prevalence was 14% (48/348, 95% CI 10-17) and in rams 10% (2/20; 95% CI 1- 33). The mean prevalence of Neospora DNA in blood was 27% (99/368, 95% CI 22-31), implying a range between 16 and 82%. In rams, the prevalence was 5% (1/20 95% CI 2-26), while in ewes it was 28% (98/348, 95% CI 23-33). The agreement between the tests was k = 0.19. The presence of other domestic animal species in the farms [odds ratio (OR) 4.4] and the consumption of placental debris, fetuses and stillborn lambs by dogs living in the farms (OR 5.8) were demonstrated to be risk factors.

Attenuation of early atherosclerotic lesions by immunotolerance with ß2 glycoprotein I and the immunomodulatory effectors interleukin 2 and 10 in a murine model.

OBJECTIVE: This study assessed the effect of cellular and humoral autoimmune response inhibition after immunization with ß2-glycoprotein I (ß2-GPI) and the effect of immunomodulation with interleukin (IL)-2 and IL-10 in the development of early atherosclerotic vascular lesion in a murine model. Atherosclerosis is increasingly considered a chronic inflammatory disease with pathogenic autoimmune processes. Regulatory T cells, and their cytokines, have been implicated in the inhibition of the development of atherosclerotic lesions and involved in the immunologic tolerance induction. METHODS: Eight-week-old male C57BL6 LDL-receptor deficient (LDLR(-/-)) mice were fed a cholesterol-rich (2.8%), high-saturated-fat (82%) diet for a week and divided in five groups. The groups received the following intravenous immunizations: group I (control group): one dose of 5 µg ß2-GPI; group II: 5 µg ß2-GPI I and 1 µg IL-2; group III: 5 µg ß2-GPI and 0.75 µg of IL-10; and group IV: 5 µg ß2-GPI, 1 µg IL-2, and 0.75 µg IL-10. The aortas of the mice were assessed 8 weeks after inoculation to determine the aortic lesion size and composition in all groups. RESULTS: ß2-GPI immunization attenuated the early atherosclerotic lesions development compared with the control group (P = .001). Macroscopic and histologic aortic atherosclerotic lesions were significantly decreased in the IL-2 and IL-10-treated groups in ß2-GPI-tolerant mice compared with the ß2-GPI-tolerant group without cytokine injection (P = .001). The association of both cytokines did not provoke a major inhibition in the atherosclerosis development when compared with groups injected with the two cytokines separately. CONCLUSIONS: The immunotolerance induction against ß2-GPI attenuates the development of atherosclerosis lesions in an animal model, enhanced by downregulation of the cellular and humoral autoimmune response provoked by IL-2 and IL-10.

Biochemical parameters in the blood of Holstein calves given immunoglobulin Y-supplemented colostrums.

BACKGROUND: In any calf rearing system it is desirable to obtain healthy animals, and reduce morbidity, mortality, and economic losses. Bovine syndesmochorial placentation prevents the direct transfer of bovine immunoglobulins to the fetus, and calves are born hypogammaglobulinemic. These calves therefore require colostrum immediately after birth. Colostrum is rich in immunoglobulins (Ig) and its consumption results in the transfer of passive immunity to calves. The Ig absorption occurs within the first 12 h after birth. Immunoglobulin Y (IgY), derived from chicken egg yolk, has been used in the prevention and control of diseases affecting calves because it is very similar in structure and function to immunoglobulin G (IgG). In the current study, we sought to establish whether administration routes of colostrum supplemented with avian IgY affected passive immunity in calves. RESULTS: No significant differences were observed with respect to route of administration for colostrum. However, we did observe some differences in certain interactions between the various treatments. Calves fed colostrum containing egg yolk had higher levels of TP, ALB, and IgG, along with increased GGT activity. CONCLUSIONS: Our results suggest that supplementing colostrum with egg yolk has a beneficial effect when given to calves, regardless of administration route.

Safety and efficacy outcomes of infrapopliteal endovascular procedures performed in patients with critical limb ischemia according to the Society for Vascular Surgery objective performance goals.

BACKGROUND: Objective performance goals (OPGs) are a set of standardized end points generated from well documented historical controls against which new therapeutic procedures may be compared in single-arm studies. Recently, the Society for Vascular Surgery suggested a set of OPGs designed from vein bypass controls that could be used to evaluate the safety and efficacy of endovascular devices applied to critical limb ischemia through a noninferiority analysis. Our aim is to analyze the results of infrapopliteal endovascular procedures performed in patients with critical limb ischemia according to these OPG end points. METHODS: This is a retrospective study of 121 infrapopliteal endovascular procedures. The tibial intervention was combined with a femoropopliteal angioplasty in 70 procedures. Major adverse cardiovascular events (MACEs), major adverse limb events (MALEs), and major amputations at 30 days were recorded as safety outcomes. Freedom from any MALE or perioperative death (Freedom from MALE + POD) and amputation-free survival were calculated as primary efficacy end points at both 12 months and at 8 years. The 95% confidence intervals (CIs) of all the end points were calculated to perform a noninferiority comparison using OPGs as the reference. RESULTS: The incidence of MACEs, MALEs, and amputation at 30 days were 5% (95% CI: 2-10% [OPG-MACE <10%]), 2.5% (95% CI: 0.5-7% [OPG-MALE <9%]), and 1.7% (95% CI: 0.2-6% [OPG-major amputation <4%]), respectively. We recorded a freedom from MALE + POD of 76% (95% CI: 67-83% [OPG-MALE + POD >67%]) and an amputation-free survival of 78% (95% CI: 69-85% [OPG-amputation-free survival >68%]) at 12 months. Freedom from MALE + POD and amputation-free survival at 8 years decreased to 60% (95% CI: 49-69%) and to 26% (95% CI: 11-44%), respectively. CONCLUSIONS: Infrapopliteal endovascular procedures performed in everyday vascular surgery practice could meet the main OPG end points proposed for catheter-based treatment of critical limb ischemia.

Epidemiology of Neospora caninum and Toxoplasma gondii infection in venison from Aguascalientes, Mexico.

The objective of the study was to estimate the seroprevalence of Neospora caninum and Toxoplasma gondii in venison from Aguascalientes, Mexico, their possible association with some risk factors, and to identify the presence of parasite DNA in blood and tissues. For this study, 5 farms and four species of venison were included, where 43 blood serum samples were obtained and in 37 of these animals a peripheral blood sample was also obtained; from hunted deer, 6 liver and 2 heart samples were obtained. The samples were analyzed by ELISA and PCR tests, respectively. The association between the serological status and the possible risk factors was estimated. The overall seroprevalence in N. caninum was 47% (20/43; CI 95% 31-62), with positive animals in all farms in a range of 18 to 100%, while for T. gondii it was 49% (21/43; CI 95% 33-64), with positive animals in 80% of farms in a range of 18 to 100%. The prevalence of N. caninum DNA detection in blood was 59% (22/37; CI 95% 42-74), with positive animals in all farms, in a range of 45 to 100%, while in T. gondii it was 76% (28/37; CI 95% 58-87), with positive animals in all farms, in a range of 56 to 100%. Age (> 4 years) was identified as associated with seroprevalence in N. caninum (OR 5.2) and in T. gondii (OR 12.7). DNA from both parasites was detected in the liver and heart samples. The results shown that venison populations included in the study are living in an environment highly contaminated with oocysts excreted by the definitive host.

Inflammatory burden predicts long-term outcomes in endovascular therapy in peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is a systemic inflammatory disorder that affects the entire vascular system. Endovascular therapy (EVT) is the first surgical treatment choice in a large number of patients who suffer from this disease. However, late clinical failure after primarily successful interventions, with the need of a new reintervention, is the major drawback of this technique. The aim of this study is to determine the possible association between serum high sensitivity C-reactive protein (hsCRP) and fibrinogen levels both preintervention and during follow-up, and the outcomes of EVT and their association with the incidence of cardiovascular events or death in these patients. METHODS: This is a prospective cohort study in patients diagnosed with PAD in the iliac, femoral, popliteal, or distal sectors, within Rutherford category 3-5 who underwent EVT de novo. We determined levels of hsCRP and fibrinogen before surgery and during the follow-up period (at 1, 3, 6, and 12 months). We analyzed the possible association among inflammatory markers levels before EVT, during 1 year of follow-up and its variation during that year, and the incidence of reintervention, reintervention-free survival, and the occurrence of cardiovascular events or death. RESULTS: Over the course of 1 year, 246 patients underwent a revascularizing treatment of the lower limbs; 64 patients qualified for inclusion in this study. In these 64 patients, a significant increase between basal hsCRP and fibrinogen levels and the incidence of reintervention (P=0.002 and 0.013, respectively) and death (P=0.001 and 0.013, respectively) during follow-up was found. A significant increase between higher hsCRP basal levels and the incidence of cardiovascular events during the follow-up period was also noted (P=0.004). Levels of basal hsCRP were related to reintervention-free survival after EVT (P=0.04). On the basis of the rate of hsCRP variation and its association with reintervention-free survival, we observed a progressive reduction of the levels of hsCRP until 12 months after the primary procedure. CONCLUSIONS: Basal levels of inflammatory markers and their variation during follow-up allowed us to identify a subgroup of patients with PAD that will require a greater number of (and earlier) reinterventions after EVT and who will have higher rates of cardiovascular morbidity and mortality.

EPIDEMIOLOGY OF TOXOPLASMA GONDII AND NEOSPORA CANINUM INFECTION IN GOATS FROM AGUASCALIENTES, MEXICO.

The objective of this study was to describe the epidemiology of Toxoplasma gondii and Neospora caninum infection by estimating seroprevalence and its association with certain risk factors in goats from Aguascalientes, Mexico. A total of 150 blood samples was taken from 10 farms and serum samples were subjected to enzyme-linked immunosorbent assay indirect test to detect T. gondii and N. caninum antibodies; the association between seroprevalence and some potential risk factors was estimated through logistic regression analysis. The general seroprevalence for T. gondii was 12.6%, observed in the farms in a range of 6.6 to 60%, finding seropositive animals in 80% of them; for N. caninum the seroprevalence was 3.3% and in farms a range of 6.6 to 13.3% was identified and 30% of them had at least 1 seropositive animal. The coinfection was 0.66%. The risk analysis for T. gondii identified a history of abortions (odds ratio 9.25) as a factor associated with seroprevalence; for N. caninum, no risk factor was identified.

Role of miR-15a-5p and miR-199a-3p in the inflammatory pathway regulated by NF-κB in experimental and human atherosclerosis.

BACKGROUND: Cardiovascular diseases (CVDs) prevalence has significantly increased in the last decade and atherosclerosis development is the main trigger. MicroRNAs (miRNAs) are non-coding RNAs that negatively regulate gene expression of their target and their levels are frequently altered in CVDs. METHODS: By RT-qPCR, we analysed miR-9-5p, miR-15a-5p, miR-16-5p and miR-199a-3p levels in aorta from apolipoprotein knockout (ApoE-/- ) mice, an experimental model of hyperlipidemia-induced atherosclerosis, and in human aortic and carotid atherosclerotic samples. By in silico studies, Western blot analysis and immunofluorescence studies, we detected the targets of the altered miRNAs. RESULTS: Our results show that miR-15a-5p and miR-199a-3p are significantly decreased in carotid and aortic samples from patients and mice with atherosclerosis. In addition, we found an increased expression in targets of both miRNAs that participate in the inflammatory pathway of nuclear factor kappa B (NF-κB), such as IKKα, IKKß and p65. In human vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs), the overexpression of miR-15a-5p or miR-199a-3p decreased IKKα, IKKß and p65 protein levels as well as NF-κB activation. On the other hand, miR-15a-5p and miR-199a-3p overexpression reduced ox-LDL uptake and the inflammation regulated by NF-κB in VSMCs. Moreover, although miR-15a-5p and miR-199a-3p were significantly increased in exosomes from patients with advanced carotid atherosclerosis, only in the ROC analyses for miR-15a-5p, the area under the curve was 0.8951 with a p value of .0028. CONCLUSIONS: Our results suggest that the decrease of miR-199a-3p and miR-15a-5p in vascular samples from human and experimental atherosclerosis could be involved in the NF-κB activation pathway, as well as in ox-LDL uptake by VSMCs, contributing to inflammation and progression atherosclerosis. Finally, miR-15a-5p could be used as a novel diagnostic biomarker for advanced atherosclerosis.

Determination of a Discriminant Dose to Identify Resistance to Amitraz in Rhipicephalus sanguineus s.l. (Acari: Ixodidae) from Mexico.

The brown dog tick, Rhipicephalus sanguineus s.l., is considered the most widely distributed three-host tick in the world and has medical and veterinary importance; the control of infestation is carried out with acaricides, towards which it can develop resistance. This study aimed to determine the discriminant dose (d.d) of amitraz to identify resistance in R. sanguineus s.l. larvae natives from Mexico and to evaluate its application in field-collected ticks. Engorged ticks were collected from naturally infested dogs residing in rural communities and were incubated for 25 days, and their progeny was used in a larval immersion test (LIT) to be exposed to the d.d. determined in Rhipicephalus microplus, and those that were susceptible were analyzed using the LIT in six concentrations. Mortality was analyzed through probit methodology to calculate the lethal concentration (LC) 50 and 99. The d.d. was determined as a consensus value by multiplying the LC99 × 2, and then, we proceeded to evaluate it in in-field samples by using the LIT technique. The d.d. calculated was 4 ppm. The in-field evaluation found 64% of the resistant samples to amitraz with mortality percentages between 98.3% and 0.35%. This dose can be used to rapidly and inexpensively identify resistant populations in samples collected in the field.

Seroprevalence of Toxoplasma gondii Infection and Associated Risk Factors in Different Populations of Dogs from Aguascalientes, Mexico.

CONTEXT AND PURPOSE: This work aimed to study the seroprevalence of natural infection by T. gondii in different population segments of dogs from Aguascalientes, Mexico as well as its possible association with some risk factors. METHODS: The study included 210 clinically healthy dogs from three population segments: rural, stray and pet. A blood serum sample was collected on a single occasion and processed by indirect immunofluorescence considering a dilution of 1:16 as a positive reaction; the association between the presence of antibodies and the potential risk factors was estimated with logistic regression. RESULTS: The overall prevalence of anti-T. gondii antibodies in the studied population was 59% (123/210; CI 95% 51-65) being different between population segments, in rural dogs 74% (59/80; CI 95% 62-82), in stray dogs 60% (48/80; CI 95% 48-70) and in pet dogs 32% (16/50; CI 95% 19-46), the titers of the positive sera were in a range of 1:16-1:128. In rural dogs the seroprevalence according to the municipality was in a range of 55% to 100% finding positive dogs in all the studied municipalities. The zootechnical function of guarding the property in rural dogs was identified as a risk factor (OR 2.4), while in pet dogs it was living with cats (OR 7) as well as sharing the drinking water container (OR 4); in stray dogs it was not possible to identify any risk factor. CONCLUSIONS: This study documents the wide presence of anti-T. gondii antibodies in the population groups examined, this being more important in rural dogs.

Impact of VEGF polymorphisms on the severity of peripheral artery disease in diabetic patients.

OBJECTIVE: To determine the potential genotype vascular endothelial growth factor (VEGF) gene differences in diabetic patients with peripheral arterial disease (PAD), which might be associated with different stages of the vascular disease. METHODS: A study was conducted with type 2 diabetic patients with PAD [n = 70; 32 intermittent claudication and 38 critical limb ischaemia (CLI)]. Genotyping of the VEGF gene insertion/deletion - 2549, - 2578 C/A and +405 G/C polymorphisms was done in both groups and correlated them with the severity of PAD. We compared serum VEGF levels in both groups. RESULTS: There was a higher frequency of +405 CC and - 2578 CC genotypes in claudication group [(31.3% vs. 5.4%, p = 0.01) and (37.5% vs. 15.8%, p = 0.05), respectively]. The presence of +405 GG and - 2578 AA genotypes was more common among CLI patients [(57.8% vs. 37.5%, p = 0.01) and (42.1% vs. 18.8%, p = 0.05), respectively]. There were higher serum VEGF levels in patients with CLI (p = 0.029). CONCLUSIONS: We found preliminary evidence regarding the association between VEGF polymorphisms and different stages of PAD in diabetic patients.

Prediction of asymptomatic abdominal aortic aneurysm expansion by means of rate of variation of C-reactive protein plasma levels.

OBJECTIVE: C-reactive protein (CRP) is an independent risk factor for arteriosclerosis, but its role in abdominal aortic aneurysm (AAA) expansion remains not completely verified. There are no data about the prognostic significance of rates of variation of the CRP levels in asymptomatic AAAs. This study investigated the association between plasma CRP levels and AAA diameter and assessed the relationship between the gradient of CRP levels and rates of expansion in asymptomatic AAAs. METHODS: Plasma levels of high-sensitive CRP (hs-CRP) were measured using a high-sensitivity technique and AAA size was determined by computed tomography in 435 patients with asymptomatic AAAs followed up in our outpatient department. RESULTS: The median hs-CRP level was 4.23 mg/L. The aorta diameter increased in the four groups of patients determined according to hs-CRP quartiles (35 ± 2, 40 ± 3, 49 ± 4, and 58 ± 5 mm; P = .01). The median rate of CRP level variation per year was 1.4 mg/L. Patients with an elevation >1.4 mg/L had an expansion rate of 4.8 mm vs 3.9 mm in those <1.4 mg/L (P < .01). The multivariate age-adjusted logistic model confirmed initial diameter and variation of CRP level were the only factors associated with expansion, with odds ratios (95% confidence intervals) of 6.3 (3.1-7.5) and 3.4 (2.1-5.6). CONCLUSIONS: These results confirm a statistical association between AAA diameter and hs-CRP plasma levels. This cohort study corroborates this potential causal association and contributes information about the value of the hs-CRP plasma level gradient as a marker of disease progression and rate of expansion.

Primary nitinol stenting in femoropopliteal occlusive disease: a meta-analysis of randomized controlled trials.

PURPOSE: To determine the efficacy and safety of balloon angioplasty (BA) with optional stenting vs. routine stenting with current open cell nitinol stents for femoropopliteal occlusive disease by analyzing the overall results from all available randomized controlled trials. METHODS: A bibliographic search of electronic medical databases (MEDLINE, Embase, ISI Web of Knowledge, and the Cochrane Central Register of Controlled Trials) was conducted to identify relevant articles from 1960 to July 2011. Of the 701 published articles retrieved, 17 clinical trials randomized patients with symptomatic femoropopliteal occlusive disease to either primary BA or primary stenting. Of these, 4 RCTs involved the use of currently employed high flexibility nitinol stents. Thirteen other trials that employed obsolete, steel, or coated stents were excluded. The technical success rate, the target lesion revascularization (TLR) rate, and the binary restenosis rate at 12 months were primary efficacy endpoints; mortality was the primary safety endpoint. The results are reported as the odds ratio (OR) with 2-tailed 95% confidence intervals (95% CI). RESULTS: The study population was made up of 627 patients (416 men; mean age 67±10 years) and 665 lesions (361 assigned to the primary stenting and 304 to BA). The mean length of the treated lesion was similar in both groups (74.6±45.7 mm in the stenting group vs. 66.7±41.3 mm in the BA group). Technical success was significantly higher in the stenting group compared to BA (95.8% vs. 64.2%; OR 0.31, 95% CI 0.09 to 0.92, p<0.001). Follow-up ranged from 12 to 24 months. Based on 3 studies, the TLR at 12 months favored the stent group (OR 2.47, 95% CI 0.72 to 8.49, p=0.065), but the difference did not reach statistical significance. However, the 12-month binary restenosis rate was significantly lower in the primary stenting group (OR 3.02, 95% CI 1.3 to 6.71, p<0.001). With respect to the safety endpoint, mortality was similar in both groups (OR 0.83, 95% CI 0.39 to 1.77, p<0.001). CONCLUSION: This meta-analysis supports the use of the primary stenting, mainly for long lesions, as a first-line endovascular treatment for symptomatic disease in the femoropopliteal segment, contrary to indications for use in current clinical guidelines.

Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan.

BACKGROUND: This study assessed the effectiveness and safety of bosentan when administered to thromboangiitis obliterans (Buerger's disease) patients. METHODS: A clinical pilot study was designed in which patients with ulcer and/or pain at rest were treated with bosentan p.o. at a dose of 62.5 mg twice daily during the first month, which was thereafter up-titrated to 125 mg twice daily. The study endpoints were clinical improvement rate, major or minor amputation rate, haemodynamic changes, changes in endothelial function and angiographic changes. RESULTS: Seven out of 12 patients were male (58%). Median age was 39 years (range 29-49). The median follow-up was 20 months (range 11-40). All patients were smokers. With bosentan treatment, new ischaemic lesions were observed in only one patient. Overall, clinical improvement was observed in 12 of the 13 extremities (92%). Only two out of 13 extremities underwent amputation (one major and one minor) after bosentan treatment. After being assessed by digital arteriography with subtraction or angio-magnetic resonance imaging, an increase of distal flow was observed in 10 out of the 12 patients. All patients experienced a statistically significant improvement in their BAFMD values (mean: 1.8 at baseline; 6.6 at the end of the treatment; 12.7 three months after the end of the treatment; p < 0.01). CONCLUSION: Bosentan treatment may result in an improvement of clinical, angiographic and endothelial function outcomes. Bosentan should be investigated further in the management of TAO patients. Larger studies are required to confirm these results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01447550.