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1.
Cell ; 180(5): 862-877.e22, 2020 03 05.
Article in English | MEDLINE | ID: mdl-32142679

ABSTRACT

Using untargeted metabolomics (n = 1,162 subjects), the plasma metabolite (m/z = 265.1188) phenylacetylglutamine (PAGln) was discovered and then shown in an independent cohort (n = 4,000 subjects) to be associated with cardiovascular disease (CVD) and incident major adverse cardiovascular events (myocardial infarction, stroke, or death). A gut microbiota-derived metabolite, PAGln, was shown to enhance platelet activation-related phenotypes and thrombosis potential in whole blood, isolated platelets, and animal models of arterial injury. Functional and genetic engineering studies with human commensals, coupled with microbial colonization of germ-free mice, showed the microbial porA gene facilitates dietary phenylalanine conversion into phenylacetic acid, with subsequent host generation of PAGln and phenylacetylglycine (PAGly) fostering platelet responsiveness and thrombosis potential. Both gain- and loss-of-function studies employing genetic and pharmacological tools reveal PAGln mediates cellular events through G-protein coupled receptors, including α2A, α2B, and ß2-adrenergic receptors. PAGln thus represents a new CVD-promoting gut microbiota-dependent metabolite that signals via adrenergic receptors.


Subject(s)
Cardiovascular Diseases/blood , Gastrointestinal Microbiome/genetics , Glutamine/analogs & derivatives , Thrombosis/metabolism , Animals , Arteries/injuries , Arteries/metabolism , Arteries/microbiology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Blood Platelets/metabolism , Blood Platelets/microbiology , Cardiovascular Diseases/genetics , Cardiovascular Diseases/microbiology , Cardiovascular Diseases/pathology , Death, Sudden, Cardiac/pathology , Glutamine/blood , Glutamine/genetics , Humans , Male , Metabolome/genetics , Metabolomics/methods , Mice , Myocardial Infarction/blood , Myocardial Infarction/microbiology , Platelet Activation/genetics , Receptors, Adrenergic, alpha/blood , Receptors, Adrenergic, alpha/genetics , Receptors, Adrenergic, beta/blood , Receptors, Adrenergic, beta/genetics , Risk Factors , Stroke/blood , Stroke/microbiology , Stroke/pathology , Thrombosis/genetics , Thrombosis/microbiology , Thrombosis/pathology
2.
J Cardiovasc Pharmacol ; 78(Suppl 6): S40-S52, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34840258

ABSTRACT

ABSTRACT: Human obesity is associated with insulin resistance and often results in a number of metabolic abnormalities and cardiovascular complications. Over the past decades, substantial advances in the understanding of the cellular and molecular pathophysiological pathways underlying the obesity-related vascular dysfunction have facilitated better identification of several players participating in this abnormality. However, the complex interplay between the disparate mechanisms involved has not yet been fully elucidated. Moreover, in medical practice, the clinical syndromes stemming from obesity-related vascular dysfunction still carry a substantial burden of morbidity and mortality; thus, early identification and personalized clinical management seem of the essence. Here, we will initially describe the alterations of intravascular homeostatic mechanisms occurring in arteries of obese patients. Then, we will briefly enumerate those recognized causative factors of obesity-related vasodilator dysfunction, such as vascular insulin resistance, lipotoxicity, visceral adipose tissue expansion, and perivascular adipose tissue abnormalities; next, we will discuss in greater detail some emerging pathophysiological mechanisms, including skeletal muscle inflammation, signals from gut microbiome, and the role of extracellular vesicles and microRNAs. Finally, it will touch on some gaps in knowledge, as well as some current acquisitions for specific treatment regimens, such as glucagon-like peptide-1 enhancers and sodium-glucose transporter2 inhibitors, that could arrest or slow the progression of this abnormality full of unwanted consequences.


Subject(s)
Arteries/physiopathology , Cardiovascular Diseases/physiopathology , Obesity/physiopathology , Vasodilation , Arteries/metabolism , Arteries/microbiology , Bacteria/metabolism , Cardiovascular Diseases/genetics , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/microbiology , Dysbiosis , Gastrointestinal Microbiome , Host-Pathogen Interactions , Humans , Inflammation Mediators/metabolism , Insulin Resistance , Lipid Metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Obesity/genetics , Obesity/metabolism , Obesity/microbiology , Risk Factors , Signal Transduction
3.
Am J Physiol Heart Circ Physiol ; 317(5): H923-H938, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31469291

ABSTRACT

Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The largest and most complex of these communities is located in the gastrointestinal system and, with its associated genome, is known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension, and heart failure. Although there have been advances in the characterization and analysis of the gut microbiota and associated bacterial metabolites, the exact mechanisms through which they exert their action are not well understood. This review will focus on the role of the gut microbiome and associated functional components in the development and progression of atherosclerosis. Potential treatments to alter the gut microbiome to prevent or treat atherosclerosis and CVD are also discussed.


Subject(s)
Arteries/microbiology , Atherosclerosis/microbiology , Bacteria/metabolism , Gastrointestinal Microbiome , Intestines/microbiology , Animals , Anti-Bacterial Agents/therapeutic use , Arteries/metabolism , Arteries/pathology , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/therapy , Diet, Healthy , Dietary Supplements , Dysbiosis , Fecal Microbiota Transplantation , Host-Pathogen Interactions , Humans , Plaque, Atherosclerotic , Signal Transduction
4.
Eur J Vasc Endovasc Surg ; 58(2): 258-281, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31178356

ABSTRACT

OBJECTIVE: Aortic graft infection (AGI) is a disastrous complication with an incidence of 0.2-6% in operated patients. With little or no high quality evidence, the best treatment option remains unclear. Therefore, the literature on the management of open abdominal AGI was systematically reviewed to determine optimal treatment. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review and meta-analysis was conducted for AGI. MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched. Methodological quality was assessed using the Methodological Index for Non-randomised Studies (MINORS) score. Primary outcomes were 30 day mortality and one year survival. Secondary outcomes were survival, infection recurrence, limb salvage, and graft patency. RESULTS: Of 1574 studies identified, 32 papers were included in the study. The overall quality of the studies was moderate, with an average MINORS score of 11.9. Pooled overall 30 day mortality and one year survival were 13.5% (95% CI 10.5-16.4) and 73.6% (95% CI 68.8-78.4), respectively. The lowest 30 day mortality and highest one year survival were found for in situ repair compared with extra-anatomic repair and for prosthetic grafts compared with venous grafts or arterial allografts. The infection recurrence rate was highest for prosthetic grafts. CONCLUSIONS: There is a lack of well designed, qualitative comparative studies making conclusive recommendations impossible. The current best available data suggests that partial graft removal should be avoided and the lowest 30 day mortality and best one year survival are achieved with in situ repair using prosthetic grafts. Initiatives such as the MAGIC database to collaboratively collect prospective data are an important step forward in obtaining more solid answers on this topic.


Subject(s)
Aorta, Abdominal/surgery , Arteries/transplantation , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis/adverse effects , Prosthesis-Related Infections/surgery , Veins/transplantation , Adult , Aged , Aged, 80 and over , Aorta, Abdominal/physiopathology , Arteries/microbiology , Blood Vessel Prosthesis Implantation/mortality , Female , Humans , Limb Salvage , Male , Middle Aged , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/mortality , Recurrence , Reoperation , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Vascular Patency , Veins/microbiology
5.
Eur J Vasc Endovasc Surg ; 58(6): 912-919, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31631006

ABSTRACT

OBJECTIVE: This study introduces a novel technique for supra-inguinal arterial reconstructions with cryopreserved femoral vein and caval allografts with a low re-infection rate and an acceptable graft re-intervention rate on early mid term analysis. METHODS: Patients treated from February 2012 to March 2018 with cryopreserved venous allograft reconstructions owing to infection in the supra-inguinal area were reviewed retrospectively. The primary end points were re-infection and the treatment related mortality rate. Secondary end points were 30 and 90 day and overall mortality and graft re-intervention rate. RESULTS: Of the 23 patients treated with cryopreserved venous allografts for infection in aorto-iliac area, 21 (91%) patients underwent reconstruction with cryopreserved femoral veins and two (9%) with vena cava. Indications for treatment were aortic graft infections (n = 12 [52%]), mycotic aneurysms (n = 5 [22%]), femorofemoral prosthetic infections (n = 3 [13%]), anastomotic pseudo-aneurysms (n = 2 [9%]), and aortic thrombosis with intestinal spillage (n = 1 [4%]). In hospital and 90 day mortality were 9% (n = 2); overall treatment related mortality during the median follow up of 15 months was 13% (n = 3). During the follow up, two allografts were re-operated on owing to anastomotic dilatation and one because of re-infection, resulting in a re-intervention rate of 13% (n = 3). None of the grafts was lost and there were no amputations. At the end of follow up 17 patients (74%) were alive. Kaplan-Meier estimation for survival was 76% (95% confidence interval [CI] 57%-95%) at one year and 70% (95% CI 49%-91%) at two years. CONCLUSION: Cryopreserved venous allografts appear to be an infection resistant and reasonably safe reconstruction material in the aorto-iliac axis based upon the early mid term analysis from a single centre experience. Further research is needed to compare their performance with other biological reconstruction material.


Subject(s)
Allografts/transplantation , Aneurysm, Infected/surgery , Cryopreservation , Plastic Surgery Procedures/methods , Prosthesis-Related Infections/surgery , Vascular Grafting/methods , Adult , Aged , Aged, 80 and over , Aneurysm, Infected/microbiology , Aneurysm, Infected/mortality , Arteries/microbiology , Arteries/surgery , Blood Vessel Prosthesis/adverse effects , Female , Femoral Vein/transplantation , Follow-Up Studies , Groin/blood supply , Hospital Mortality , Humans , Male , Middle Aged , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/mortality , Plastic Surgery Procedures/adverse effects , Reoperation/statistics & numerical data , Retrospective Studies , Secondary Prevention/methods , Treatment Outcome , Vascular Grafting/adverse effects , Venae Cavae/transplantation , Young Adult
6.
J Vasc Surg ; 67(6): 1902-1907, 2018 06.
Article in English | MEDLINE | ID: mdl-28847664

ABSTRACT

OBJECTIVE: Increasing data supports the role of bacterial inflammation in adverse events of cardiovascular and cerebrovascular diseases. In our previous research, DNA of bacterial species found in coronary artery thrombus aspirates and ruptured cerebral aneurysms were mostly of endodontic and periodontal origin, where Streptococcus mitis group DNA was the most common. We hypothesized that the genomes of S mitis group could be identified in thrombus aspirates of patients with lower limb arterial and deep venous thrombosis. METHODS: Thrombus aspirates and control blood samples taken from 42 patients with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb) owing to arterial or graft thrombosis (n = 31) or lower limb deep venous thrombosis (n = 11) were examined using a quantitative real-time polymerase chain reaction to detect all possible bacterial DNA and DNA of S mitis group in particular. The samples were considered positive, if the amount of bacterial DNA in the thrombus aspirates was 2-fold or greater in comparison with control blood samples. RESULTS: In the positive samples the mean difference for the total bacterial DNA was 12.1-fold (median, 7.1), whereas the differences for S mitis group DNA were a mean of 29.1 and a median of 5.2-fold. Of the arterial thrombus aspirates, 57.9% were positive for bacterial DNA, whereas bacterial genomes were found in 75% of bypass graft thrombosis with 77.8% of the prosthetic grafts being positive. Of the deep vein thrombus aspirates, 45.5% contained bacterial genomes. Most (80%) of bacterial DNA-positive cases contained DNA from the S mitis group. Previous arterial interventions were significantly associated with the occurrence of S mitis group DNA (P = .049, Fisher's exact test). CONCLUSIONS: This is the first study to report the presence of bacterial DNA, predominantly of S mitis group origin, in the thrombus aspirates of surgical patients with lower limb arterial and deep venous thrombosis, suggesting their possible role in the pathogenesis of thrombotic events. Additional studies will, however, be needed to reach a final conclusion.


Subject(s)
Arteries/pathology , DNA, Bacterial/genetics , Lower Extremity/blood supply , Streptococcal Infections/microbiology , Streptococcus mitis/genetics , Thrombosis/microbiology , Veins/pathology , Adult , Aged , Aged, 80 and over , Arteries/microbiology , Female , Humans , Male , Middle Aged , Prospective Studies , Real-Time Polymerase Chain Reaction , Streptococcal Infections/pathology , Streptococcus mitis/isolation & purification , Thrombosis/pathology , Veins/microbiology
7.
Ann Vasc Surg ; 52: 201-206, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29678647

ABSTRACT

BACKGROUND: Cryopreserved arterial allografts are vascular substitutes used for arterial reconstructions in a septic field. Their use remains however limited by the shortage of donors. One of the possibilities to address this lack of grafts is to multiply the sources of retrieval. The objective of this preliminary study was the evaluation of the early clinical results and the microbiological safety of arterial grafts retrieved after death. METHODS: In addition to the standard conditions of arterial sampling, the criteria of inclusion for postmortem retrieval comprised the refrigeration of the body of the donor within 4 hr following the death, a 24-hr time limit from the death, and the availability of an adapted place for retrieval (surgical unit or death chamber respecting the required aseptic conditions). We only retrieved the femoral axes (FAs) and the aortoiliac bifurcation. The conditions of retrieval, transportation, preparation, and conservation were identical to those of cryopreserved arterial allografts harvested during standard multiple organs retrieval. We evaluated the bacteriological risk of contamination and the patency of the grafts in the short and medium term. RESULTS: In 2015 and 2016, 6 donors were included. Eleven FAs and 2 aortic bifurcations were harvested. The bacteriological samples done on arrival in bank and after thawing were negative in the 6 donors, but one of the 6 donors presented a bacterial contamination of other removed tissues, and the arterial grafts obtained from this donor were destroyed as a precaution (3 grafts). The quality of the grafts evaluated by the surgeon during harvesting was good in all the cases. The indications of allografts were arterial reconstruction in a septic field (n = 8) and aorto-hepatic bypass during hepatic transplantation (n = 1). One graft was unhopefully thawed without being used. At the end of the follow-up, 8 out of 9 grafts were patent. Two ruptures occurred in a context of locally persistent sepsis (crural abscess due to Salmonella typhi and persistent groin wound disunion with a polymicrobial flora). One allograft thrombosis was observed (aorto-hepatic bypass for transplantation). These complications were unrelated to the mode of graft harvesting. No aneurysmal evolution was observed. CONCLUSIONS: The preliminary results of this protocol are encouraging because the immediate quality of the grafts was good with a risk of microbiological contamination identical with that of the usual harvesting mode. This mode of harvesting looks promising to reduce the shortage in arterial allografts and could be extended to harvest thoracic aortic allografts. However, results at a larger scale are necessary to confirm these data.


Subject(s)
Arteries/transplantation , Bioprosthesis , Blood Vessel Prosthesis Implantation/methods , Blood Vessel Prosthesis , Tissue Donors/supply & distribution , Tissue and Organ Harvesting/methods , Adult , Allografts , Arteries/microbiology , Arteries/physiopathology , Autopsy , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Cryopreservation , Female , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Humans , Male , Preliminary Data , Prosthesis-Related Infections/microbiology , Risk Assessment , Risk Factors , Time Factors , Tissue and Organ Harvesting/adverse effects , Treatment Outcome , Vascular Patency
8.
J Vasc Surg ; 65(6): 1824-1829, 2017 06.
Article in English | MEDLINE | ID: mdl-28359717

ABSTRACT

OBJECTIVE: Endografts (eg, aortic aneurysm device or covered stent) are increasingly being used to temporize or treat arterial and graft infections in inaccessible areas, in patients with compromised anatomy, or in the presence of active bleeding or rupture. This summary examines the evidence for "in situ" endografting in the treatment these conditions. METHODS: A two-level search strategy of the literature (MEDLINE, PubMed, Google Scholar, and The Cochrane Library) was performed for relevant articles listed between January 2000 and December 2015. The review was confined to patients with primary and secondary bacterial or viral arterial infections, with or without fistulization and infection of bypass grafts and arteriovenous accesses. For the purposes of this summary, endografts can be considered to be an aortic aneurysm device or a covered stent. RESULTS: There are no societal guidelines. Endografts have been successfully applied to mycotic arterial aneurysms, aortoenteric, aortobronchial, and arterioureteric fistulae, and to anastomotic bleeds secondary to infection. Multiple reports indicate success at the control of hemorrhage in all locations. Short-term outcomes are good, but fatal infection-related complications, especially if antibiotic therapy is halted, are well reported and necessitate a more definitive plan for the long term. CONCLUSIONS: Stent grafts remain an important and viable option for the treatment of mycotic aneurysms, aortoesophageal and aortobronchial fistulae, and infected pseudoaneurysms in anatomically or technically inaccessible locations. In patients with a short life span (<6 months), no further intervention is generally required. In patients with a predicted life span >6 months, careful consideration should be given to a more definitive procedure. Life-long appropriate antibiotic therapy is strongly recommended for any patient receiving an endograft in an infected field.


Subject(s)
Aneurysm, False/surgery , Aneurysm, Infected/surgery , Arteries/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis/adverse effects , Prosthesis-Related Infections/surgery , Stents , Aneurysm, False/diagnostic imaging , Aneurysm, False/microbiology , Aneurysm, Infected/diagnostic imaging , Aneurysm, Infected/microbiology , Anti-Bacterial Agents/administration & dosage , Arteries/diagnostic imaging , Arteries/microbiology , Computed Tomography Angiography , Humans , Prosthesis Design , Prosthesis-Related Infections/diagnostic imaging , Prosthesis-Related Infections/microbiology , Reoperation , Risk Factors , Treatment Outcome
10.
Cell Tissue Bank ; 13(2): 297-304, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21512894

ABSTRACT

To evaluate the efficiency of decontamination practice in European Homograft Bank (EHB), the data of the cardiovascular tissues received during recent 2 years were retrospectively analysed in this study. After initial assessment, the tissues were incubated in a 3-antibiotics' cocktail at 4°C for 20-48 h. The states of contamination were evaluated before and after incubation with the focus on the differences in donor type, tissue type, germ type and incubation time. Amongst 1,055 eligible tissues, 77.2% were hearts and 22.8% were arteries. 82.2% of the tissues were retrieved from the multi-organ donors (MOD), 15.4% from the recipients of heart transplantation (RHT) and 2.4% from the non-heart beating donors (NHBD). The initial contamination rate was 27.4% with a significantly higher incidence in arteries. The RHT tissues had the lowest contamination rate comparing to that of MOD and NHBD. Staphylococcus species was the major source of contamination. After antibiotic incubation, 76.8% of the contaminated tissues were disinfected, which was significantly higher for the hearts than the arteries. The RHT tissues had the highest decontamination rate than that of MOD and NHBD tissues. Propionibacterium acnes was detected in 48.1% of the remaining contaminated cases. The average incubation time of the Propionibacterium-positive tissues was significantly shorter than that of decontaminated tissues. In conclusion, the current decontamination protocol of EHB is sufficient for most of the initially contaminated bacteria, whereas it is inadequate for Propionibacterium acnes. This may be related to the slow-growing nature of this bacterium and thereby the relative shorter antibiotic incubation time.


Subject(s)
Arteries/microbiology , Decontamination/methods , Heart Valves/microbiology , Tissue Banks , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/isolation & purification , Europe , Heart Transplantation , Humans , Microbial Sensitivity Tests , Retrospective Studies , Time Factors , Tissue Donors , Transplantation, Homologous
11.
Ann Vasc Surg ; 25(7): 982.e11-4, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21680145

ABSTRACT

A 69-year-old man was referred to our facility owing to the sudden onset of a compression-like pain in the right leg, without limb-threatening acute ischemia. The duplex scan examination, followed by a selective leg angiography, showed the presence of a peroneal artery aneurysm. A diagnosis of mycotic aneurysm was made on the basis of the patient's clinical condition, positive blood cultures, and the unusual location of the lesion. Endovascular repair was performed by using a coil embolization and covered stent release. The patient was discharged in good general condition with complete pain relief. In previously published data, only four cases of peroneal artery aneurysm with a mycotic etiology have been reported. In this case, the endovascular treatment was safe and resolutive.


Subject(s)
Aneurysm, Infected/therapy , Embolization, Therapeutic , Endocarditis, Bacterial/microbiology , Endovascular Procedures , Lower Extremity/blood supply , Streptococcus mitis/isolation & purification , Aged , Aneurysm, Infected/diagnosis , Aneurysm, Infected/microbiology , Anti-Bacterial Agents/therapeutic use , Arteries/microbiology , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/surgery , Endovascular Procedures/instrumentation , Humans , Male , Stents , Ultrasonography, Doppler, Duplex
12.
Sci Rep ; 10(1): 14606, 2020 09 03.
Article in English | MEDLINE | ID: mdl-32884071

ABSTRACT

Porphyromonas gingivalis is a periodontal pathogen implicated in a range of pregnancy disorders that involve impaired spiral artery remodeling (ISAR) with or without fetal growth restriction (FGR). Using a rodent periodontitis model, we assessed the ability of P. gingivalis to produce ISAR and FGR in Sprague Dawley (SD) and Wistar (WIS) rats. Both infected SD and WIS rats developed ISAR, but only WIS rats developed FGR despite both rat strains having equivalent microbial loads within the placenta. Neither maternal systemic inflammation nor placental (fetal) inflammation was a feature of FGR in WIS rats. Unique to infected WIS rats, was loss of trophoblast cell density within the junctional zone of the placenta that was not present in SD tissues. In addition, infected WIS rats had a higher proportion of junctional zone trophoblast cells positive for cytoplasmic high temperature requirement A1 (Htra1), a marker of cellular oxidative stress. Our results show a novel phenomenon present in P. gingivalis-induced FGR, with relevance to human disease since dysregulation of placental Htra1 and placental oxidative stress are features of preeclamptic placentas and preeclampsia with FGR.


Subject(s)
Arteries/pathology , Bacteroidaceae Infections/complications , Fetal Growth Retardation/etiology , Porphyromonas gingivalis/pathogenicity , Trophoblasts/pathology , Vascular Remodeling , Animals , Arteries/microbiology , Bacteroidaceae Infections/microbiology , Female , Fetal Growth Retardation/pathology , Male , Pregnancy , Rats , Rats, Sprague-Dawley , Rats, Wistar , Trophoblasts/microbiology
13.
Vasa ; 38(4): 365-73, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19998257

ABSTRACT

BACKGROUND: To evaluate homograft implantation for the urgent treatment of vascular infections on the basis of the course of infection using microbiological findings in perioperatively obtained specimens and during homograft processing. PATIENTS AND METHODS: 85 patients were treated with cryopreserved homografts from 2004-2007. The microbiological findings of the decontamination process of homografts in the tissue bank were evaluated. The perioperative infection profile (microorganisms, CRP, leukocytes, body temperature) of the patients was analysed. RESULTS: Complete microbiological and clinical follow-up for the postoperative course was available for 35 patients, who were treated with homografts from the same tissue bank and finally included into this study. 55 cryopreserved homografts were implanted. 35/55 (64%) homografts were positive for microorganisms before decontamination. 3/35 (9%) homografts remained positive after the decontamination. 33 patients were operated for prosthetic graft infection and 2 for an infiltration of a large vessel from neighbouring malignant disease. The most common infection agent was Staphylococcus aureus. Thirty-day mortality was 20% (7/35). Only in 4/35 (11%) patients were the microorganisms of the intraoperative swabs also detected during the postoperative course. The microorganisms were ORSA, Enterococcus faecium, Enterobacter aerogenes and Burkholderia cepacia. The patient with ORSA infection died on POD 11 from multiple organ failure and all other patients recovered. None of the postoperative swabs showed the homograft predecontamination microorganisms. Interestingly, a significant association (P = 0.003) between C-reactive protein increase two weeks after surgery and donor-recipient ABO mismatch was found. CONCLUSIONS: The implantation of homografts following the established decontamination is an alternative urgent therapeutic option in vascular infections with encouraging outcomes. The absence of the predecontamination focus in the postoperative specimens of patients, suggests that the postoperative course and outcomes show no strong relation to potential homograft contamination prior to the decontamination process.


Subject(s)
Aneurysm, Infected/surgery , Aneurysm, Ruptured/surgery , Arteries/transplantation , Blood Vessel Prosthesis/adverse effects , Cryopreservation , Decontamination , Heart Valve Prosthesis/adverse effects , Prosthesis-Related Infections/surgery , Tissue and Organ Harvesting , Aged , Aneurysm, Infected/microbiology , Aneurysm, Infected/mortality , Aneurysm, Ruptured/microbiology , Aneurysm, Ruptured/mortality , Arteries/microbiology , Blood Grouping and Crossmatching , Female , Graft Survival , Hospital Mortality , Humans , Iliac Artery/microbiology , Iliac Artery/pathology , Iliac Artery/surgery , Male , Middle Aged , Neoplasm Invasiveness , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/mortality , Pulmonary Artery/microbiology , Pulmonary Artery/pathology , Pulmonary Artery/surgery , Reoperation , Time Factors , Transplantation, Homologous , Treatment Outcome
14.
Clin Exp Dent Res ; 5(5): 497-504, 2019 10.
Article in English | MEDLINE | ID: mdl-31687183

ABSTRACT

Objectives: Our study investigated the pathological outcome of experimental thrombi that incorporate oral bacteria. Material and methods: A small artery and vein in the rats' groins were injected with a solution containing periodontal bacteria Porphyromonas gingivalis and followed up for 28 days. In all, 18 limbs of nine male rats (500-650 g) were used for the arterial study, and eight limbs of four rats were used for the veins. Two densities of the bacterial solution and two arterial thicknesses sizes were used in the arterial study. Both proximal and distal arteries and veins were ligated loosely using a monofilament nylon suture before bacterial suspensions or control solutions were injected into the ligated vessels. Results: After 7, 14-18, and 28 days, the rats were sacrificed. Pathology and immunohistochemistry were performed. All specimens exhibited thrombus formation and an acute inflammation reaction with granulocytes at 7 days and then settled down to chronic fibrous change with plasma cells or macrophages at 28 days in the arterial thrombus. CD3 (Pan T-cells), CD79a (Pan B cells in the rats), and IgG were observed in the process of the healing of the arterial thrombus. Venous changes showed relatively clear recanalization that appeared at 7 days, which is slightly different from the artery. Granulocytes were present from 7 to 28 days. Conclusions: Periodontal bacteria act as an inflammatory core in the vessels, but not as an infectious agent, in our experiments, because of their low ability to invade tissues.


Subject(s)
Arteries/immunology , Arteries/pathology , Bacteroidaceae Infections/complications , Thrombosis/immunology , Thrombosis/pathology , Veins/immunology , Veins/pathology , Animals , Arteries/microbiology , Bacteroidaceae Infections/microbiology , Male , Porphyromonas gingivalis/isolation & purification , Rats , Thrombosis/microbiology , Veins/microbiology
15.
Ann Vasc Surg ; 22(3): 412-6, 2008.
Article in English | MEDLINE | ID: mdl-18411025

ABSTRACT

Oral bacteria have been detected at atherosclerotic plaque, aneurysms, and thrombosed arteries in Buerger disease. We explored a possible relationship between the oral bacterium Porphyromonas gingivalis and arterial thrombosis at proximal and distal sites in rats. Eighteen rats underwent subcutaneous placement of an infusion pump connected to the jugular vein. The Pg infusion group received a continuous infusion of P. gingivalis for 2 weeks, and the controls received normal saline. At 2 and 4 weeks, specimens were obtained from the iliac, superficial, and below-knee arteries, which were studied pathologically and by polymerase chain reaction (PCR) analysis to detect P. gingivalis-specific DNA. The Pg infusion group had thrombosis in 33.3% at 2 weeks and in 55.6% at 4 weeks, but normal arterial wall structure was preserved without any features of infection. Positive PCR findings were recognized in 73.3% and 22.2% at 2 and 4 weeks, respectively. At 4 weeks, thrombosis was observed in a higher proportion, with the below-knee specimens having an especially high thrombus rate (83.3%). No control specimen had thrombosis or positive PCR results. Bacteremia due to the oral pathogen P. gingivalis may lead to thrombus formation in the peripheral arteries, especially in small-sized arteries.


Subject(s)
Arterial Occlusive Diseases/microbiology , Arteries/microbiology , Bacteroidaceae Infections/complications , Mouth/microbiology , Porphyromonas gingivalis/pathogenicity , Thrombosis/microbiology , Animals , Arterial Occlusive Diseases/pathology , Arteries/pathology , Bacteroidaceae Infections/microbiology , Bacteroidaceae Infections/pathology , DNA, Viral/metabolism , Disease Models, Animal , Iliac Artery/microbiology , Infusion Pumps, Implantable , Infusions, Intravenous , Male , Polymerase Chain Reaction , Porphyromonas gingivalis/genetics , Rats , Rats, Wistar , Thrombosis/pathology , Time Factors
16.
J Infect Dev Ctries ; 12(12): 1088-1095, 2018 12 31.
Article in English | MEDLINE | ID: mdl-32027610

ABSTRACT

INTRODUCTION: There is a known connection between periodontitis and atherosclerosis and the presence of periopathogens in blood vessels. However, changes of the oral microflora related to the aging process and its possible effects on atherosclerosis, have yet to be analyzed. The aim of this study was to assess temporal changes in the frequency of periodontal bacteria in the subgingival plaque and in atherosclerotic blood vessels of patients with atherosclerosis. METHODOLOGY: The study included 100 patients with atherosclerosis and periodontitis, divided into two groups, below and over 60 years of age. Clinical examinations were performedand subgingival plaque specimens were collected as well as biopsy specimens from the following arteries: coronary (34), carotid (29), abdominal (10), femoral (10), mammary (13) and iliac (4). Subgingival and artery specimens were subjected to PCR detection of 5 major periodontal pathogens: Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Aggregatibacter actinomycetemcomitans (Aa), Tannerella forsythensis (Tf) and Treponema denticola (Td). RESULTS: Tf was the most and Td the least frequent bacteria in both age groups and in both types of samples. The frequencies of bacteria in subgingival versus atherosclerotic samples were: Tf (76%:53%), Pi (71%:31%), Pg (60%:38%), Aa (39%:14%) and Td (21%:6%). Only Aa and Pi showed a significant difference of prevalence between younger and older patients. The most colonized artery was a. coronaria, followed by a. carotis, a. abdominalis, a. mammaria, and a. femoralis. CONCLUSIONS: Patient's age and the distance of a given blood vessel from the oral cavity influenced microbiological findings in the atherotic plaque.


Subject(s)
Arteries/microbiology , Dental Plaque/microbiology , Periodontitis/microbiology , Plaque, Atherosclerotic/microbiology , Adult , Age Factors , Aged , Aged, 80 and over , Aggregatibacter actinomycetemcomitans/genetics , Aggregatibacter actinomycetemcomitans/isolation & purification , Biofilms , Female , Humans , Male , Middle Aged , Porphyromonas gingivalis/genetics , Porphyromonas gingivalis/isolation & purification , Prevotella intermedia/genetics , Prevotella intermedia/isolation & purification , Tannerella forsythia/genetics , Tannerella forsythia/isolation & purification , Treponema denticola/genetics , Treponema denticola/isolation & purification
17.
Clin Rheumatol ; 36(1): 205-208, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27604701

ABSTRACT

The objective of this study was to demonstrate the presence of mycobacterial nucleic acid sequences in peripheral blood and arteries from patients with Takayasu arteritis (TA). Polymerase chain reaction was performed to detect mycobacterial DNA from three different nucleic acid sequences including the insertion sequence (IS) 6110, the 65-kDa heat shock protein gene (HSP65), and the 16S ribosomal RNA (rRNA) gene in peripheral blood from 32 TA patients and in arterial specimens from 10 TA patients. Twenty-eight HIV-negative patients with pulmonary tuberculosis prior to therapy were tested for IS6110 in peripheral blood as positive controls, and 24 blood donors were evaluated as healthy controls (HC). All TA patients were negative for the insertion sequence IS6110 and for HSP65 and 16S rRNA genes in blood samples and in arterial specimens. IS6110 sequence was found in peripheral blood from 22 (78.5 %) patients with pulmonary tuberculosis but not in HC. In conclusion, the strategy of mycobacterial-specific nucleic acid amplification in the peripheral blood and arterial specimens of TA patients was unable to lend support to the association between TA and tuberculosis long suggested in the literature.


Subject(s)
Arteries/microbiology , DNA, Bacterial/blood , Takayasu Arteritis/microbiology , Adolescent , Adult , Bacterial Proteins/genetics , Case-Control Studies , Chaperonin 60/genetics , Female , Humans , Male , Middle Aged , Mycobacterium tuberculosis , Polymerase Chain Reaction , RNA, Ribosomal, 16S/genetics , Takayasu Arteritis/blood , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/epidemiology
18.
Atherosclerosis ; 187(1): 50-6, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16202418

ABSTRACT

The role of the obligate intracellular pathogen Chlamydia pneumoniae in the development of atherosclerosis could not be completely clarified. Reasons are the highly discrepant results obtained in the hitherto existing studies and the lack of an experimental system allowing the direct examination of chlamydial effects in the human vasculature. We established a human ex vivo organ culture model for the characterization of vascular chlamydial infection. Ninety sections of renal arteries, obtained from nephrectomies, were inoculated with Chlamydia pneumoniae. Using a monoclonal FITC-conjugated antibody, chlamydial LPS was broadly detected in inoculated arteries during the entire observation period of 35 days. However, recultivation of viable organisms from the artery vessel wall was impossible, indicating that productive infection in human arteries did not occur even under optimized conditions. This was substantiated by low recovery rates of Chlamydia pneumoniae, low amounts of detectable chlamydial 16S rRNA and ultramorphological presence of polymorph multilamellar bodies in experimentally infected smooth muscle cells originating from aortas, coronary and renal arteries. We could demonstrate that the complex environment of a human artery did not support the growth of Chlamydia pneumoniae although the presence of chlamydial LPS in the artery vessel wall following experimental infection was a common event. The presence of chlamydial LPS in the absence of viable organisms within the artery vessel wall may explain the failure of antibiotic treatment strategies for atherosclerosis.


Subject(s)
Arteries/microbiology , Arteries/pathology , Atherosclerosis/diagnosis , Atherosclerosis/pathology , Chlamydophila Infections/pathology , Chlamydophila pneumoniae/metabolism , Organ Culture Techniques/methods , Aged , Cells, Cultured , Female , Humans , In Situ Hybridization, Fluorescence , Lipopolysaccharides/metabolism , Male , Microscopy, Electron, Transmission , Middle Aged , Monocytes/metabolism , Myocytes, Smooth Muscle/metabolism
19.
Crit Care ; 10(3): R83, 2006.
Article in English | MEDLINE | ID: mdl-16723035

ABSTRACT

INTRODUCTION: Which particular arterial catheter site is associated with a higher risk of infection remains controversial. The Centers for Disease Control and Prevention guidelines of 1996 and the latest guidelines of 2002 make no recommendation about which site or sites minimize the risk of catheter-related infection. The objective of the present study was to analyze the incidence of catheter-related local infection (CRLI) and catheter-related bloodstream infection (CRBSI) of arterial catheters according to different access sites. METHODS: We performed a prospective observational study of all consecutive patients admitted to the 24 bed medical and surgical intensive care unit of a 650 bed university hospital during three years (1 May 2000 to 30 April 2003). RESULTS: A total of 2,018 patients was admitted to the intensive care unit during the study period. The number of arterial catheters, the number of days of arterial catheterization, the number of CRLIs and the number of CRBSIs were as follows: total, 2,949, 17,057, 20 and 10; radial, 2,088, 12,007, 9 and 3; brachial, 112, 649, 0 and 0; dorsalis pedis, 131, 754, 0 and 0; and femoral, 618, 3,647, 11 and 7. The CRLI incidence was significantly higher for femoral access (3.02/1,000 catheter-days) than for radial access (0.75/1,000 catheter-days) (odds ratio, 1.5; 95% confidence interval, 1.10-2.13; P = 0.01). The CRBSI incidence was significantly higher for femoral access (1.92/1,000 catheter-days) than for radial access (0.25/1,000 catheter-days) (odds ratio, 1.9; 95% confidence interval, 1.15-3.41; P = 0.009). CONCLUSION: Our results suggest that a femoral site increases the risk of arterial catheter-related infection.


Subject(s)
Catheterization, Peripheral , Cross Infection/microbiology , Equipment Contamination , Femoral Artery/microbiology , Adult , Aged , Arteries/microbiology , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/methods , Cross Infection/etiology , Cross Infection/prevention & control , Equipment Contamination/prevention & control , Female , Femoral Artery/pathology , Humans , Intensive Care Units , Male , Middle Aged , Prospective Studies
20.
Ann Transplant ; 11(4): 30-7, 2006.
Article in English | MEDLINE | ID: mdl-17715575

ABSTRACT

The mammal organisms carry on their surfaces and in their tissues cohorts of microorganisms of various nature. There is a balance of interests and profits between the host and microbial inhabitants. The bacteria and fungi behave like comensals, colonizers, dormants, however, under certain, mostly unknown, conditions may evoke reaction of the host. This process is damaging both for the host and microbes. Large surgical trauma and allograft itself, as well as, immunosuppression create favorable conditions for imbalance between inhabiting microorganism and the recipient. The host flora and that transplanted with the organ graft become activated. Active combating of the proliferating bacteria with antibiotics becomes necessary. Our knowledge of the bacterial flora of the so called "sterile" tissues remains rudimentary. There is still a great deal of prejudice on the sterility of deep tissues e.g. muscles, fat tissue, etc. This review cumulates pertinent literature data on the microorganisms-host interactions. Our own findings on colonization of arteries and adjacent tissues are discussed in the context of atherosclerosis and grafting.


Subject(s)
Bacterial Infections/etiology , Mycoses/etiology , Organ Transplantation/adverse effects , Arteries/microbiology , Atherosclerosis/microbiology , Bacteria/isolation & purification , Bacterial Physiological Phenomena , Bone and Bones/microbiology , Femoral Artery/microbiology , Fungi/physiology , Gastrointestinal Tract/microbiology , Humans , Immunosuppressive Agents/adverse effects , Joints/microbiology , Mouth/microbiology
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