Athanasios Katsargyris

Current clinical status on the preventive effects of cranberry consumption against urinary tract infections.

Urinary tract infections (UTIs) represent a common and quite costly medical problem, primarily affecting the female population which may be due to a shorter urethra. The bacterium Escherichia coli are mainly responsible for most uncomplicated UTIs. Cranberry antibacterial effects have widely been studied in vitro, and laboratory and clinical studies have also been performed to elucidate the mechanisms of cranberry actions and the clinical benefits of cranberry consumption against UTIs. The present review aimed to summarize the proposed mechanisms of cranberry actions against UTIs and the clinical trials that evaluated the efficacy of supplementing cranberry products in different subpopulations. Taking into consideration the existing data, cranberry consumption may prevent bacterial adherence to uroepithelial cells which reduces the development of UTI. Cranberry consumption could also decreasing UTI related symptoms by suppressing inflammatory cascades as an immunologic response to bacteria invasion. The existing clinical trials suggest that the beneficial effects of cranberry against UTIs seem to be prophylactic by preventing the development of infections; however, they exert low effectiveness in populations at increased risk for contracting UTIs. Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized cranberry products are strongly justified in order to determine the efficiency of cranberry on the prevention of UTIs in susceptible populations.

Toll like receptors in liver ischemia reperfusion injury: A novel target for therapeutic modulation?

Background: There is increasing evidence that Toll-like receptors (TLRs) sense host tissue damage by engaging with endogenous ligands. TLRs are considered to be involved in many primarily non-immune-related diseases. Hepatic ischemia reperfusion injury (IRI) represents one of these disorders. Objective: To present the latest findings supporting the involvement of TLRs in liver IRI and to explore their role as potential targets for therapeutic intervention. Methods: A review of the literature summarizing the latest advances in TLR signaling, the role of TLRs in each hepatic cell population and the involvement of TLRs in the pathophysiology of hepatic IRI. The potential role of TLR-targeting treatment strategies in liver IRI is discussed. Conclusions: Recent experimental evidence suggests that TLR activation on Kupffer cells provides the triggering signal for pro-inflammatory responses that lead to liver IRI. Modulating TLR signaling could have a beneficial effect in patients with liver IRI.

Toll-like receptor modulation: a novel therapeutic strategy in cardiovascular disease?

Background: Toll-like receptors (TLRs) have been recently recognised as primary receptors in the innate immune system. Apart from initiating a prompt immune response against invading pathogens, TLRs are also considered to be an important link between innate immunity, inflammation and a variety of clinical disorders, including cardiovascular diseases. TLR signalling manipulation with novel drugs could offer important opportunities for cardiovascular disease modification. Objective: To present the latest knowledge supporting the involvement of TLRs in the pathogenesis and progress of cardiovascular diseases and explore the role of TLRs as potential targets for therapeutic intervention in cardiovascular territory. Methods: A review of the literature documenting implication of TLR signalling in cardiovascular disorders. Current progress in TLR-targeting drug development and the potential role of such a treatment strategy in cardiovascular disorders are discussed. Conclusions: A growing body of evidence supports a role for TLRs in cardiovascular disease initiation and progression. Altering TLR signalling with novel drugs could be a beneficial therapeutic strategy for patients with cardiovascular disorders.

Enhanced TLR4 endothelial cell immunohistochemical expression in symptomatic carotid atherosclerotic plaques

Background and Purpose: Toll-like receptor-4 (TLR4) has been linked to the pathogenesis of atherosclerosis. Carotid atheroma endothelial cells (ECs) express TLR4, nevertheless correlations with cerebrovascular symptomatology, epidemiological and clinical variables remain unresolved. Methods: Carotid atherosclerotic plaques were obtained by standard carotid endarterectomy from 157 patients with carotid artery disease (84 asymptomatic – Group A, 73 symptomatic – Group B). TLR4 expression was detected by immunohistochemistry and TLR4 positivity, overexpression and intensity of immunostaining in ECs were correlated with cerebrovascular symptomatology, epidemiological and clinical variables. Results: A significant association was found between TLR4 positivity in ECs and the occurrence of any cerebrovascular event (overall response (OR): 2.85, 95% CI 1.33 – 6.11, p = 0.009). TLR4 overexpression and staining intensity in ECs were both significantly enhanced in symptomatic patients (p < 0.0001 and p = 0.003, respectively). These associations were stronger for the occurrence of a major cerebrovascular accident (CVA) compared with a transient ischemic attack (TIA) or amaurosis fugax. TLR4 expression in ECs was less prominent in statin users (OR: 0.25, 95%CI 0.1 – 0.58, p = 0.001], while it was enhanced in restenotic plaques compared with primary atherosclerotic lesions (p = 0.012). Conclusions: TLR4 expression in ECs of carotid atheroma was enhanced in symptomatic patients with most commonly ‘unstable’ – ‘more prone to rupture’ carotid plaques.

Statin treatment is associated with reduced toll-like receptor 4 immunohistochemical expression on carotid atherosclerotic plaques: a novel effect of statins

Toll-like receptor 4 (TLR4) has been recently implicated in inflammatory pathways involved in carotid plaque destabilization. Given that statins have plaque stabilization and inflammation reduction effects, we investigated whether TLR4 expression on carotid atherosclerotic plaques correlates with statin intake. Carotid atherosclerotic plaques were obtained on 140 patients (preoperative statin intake, n = 70). TLR4 immunohistochemical expression was investigated in endothelial cells (ECs), macrophages (MACs) and smooth muscle cells (SMCs) of carotid atheroma. TLR4 positivity, over-expression and intensity of immunostaining were compared in statin versus no-statin users. The results of this study showed that statin users had a significantly lower expression of TLR4 in ECs (P = 0.02, 0.001, 0.006 for TLR4 positivity, increased intensity and over-expression, respectively). Similarly, TLR4 positivity was less pronounced in carotid plaque MACs of statin users (P = 0.03). No carotid specimen with increased EC TLR4 intensity or over-expression was observed among statin users. The prevalence of any cerebrovascular accident was 61.4% in the ‘no statin’ versus 18.6% in the ‘statin’ group (odds ratio for statin use: 0.14, 95% CI: 0.07–0.31, P < 0.001). In conclusion, statin treatment is associated with attenuated TLR4 expression on human carotid atherosclerotic plaques and a reduced risk of carotid-related cerebrovascular events. TLR4 may potentially mediate statins plaque stabilization effects. Further investigation is necessary.

Correlation of plasma osteoprotegerin (OPG) and receptor activator of the nuclear factor κB ligand (RANKL) levels with clinical risk factors in patients with advanced carotid atherosclerosis

Summary Background Osteoprotegerin (OPG) is considered to be a crucial regulatory mediator of bone metabolism by acting as a decoy receptor of the receptor activator of nuclear factor κB ligand (RANKL). OPG and RANKL have further become the subject of intense interest for their potential role in cardiovascular disease. The present study aimed to assess the clinical implication of plasma OPG and RANKL levels in patients with advanced carotid atherosclerosis Material/Methods Plasma OPG and RANKL concentrations measured by solid-phase enzyme-linked immunosorbent assay (ELISA) were correlated with medical history, risk factors and medication intake in 131 patients who underwent carotid endarterectomy for vascular repair. Results Plasma OPG concentrations were associated with patients’ age (p=0.0258), homocysteine levels (p<0.00001), eGFR (p=0.0254), history of diabetes (p=0.0324), statins therapy (p=0.0044), hyperlipidemia (p=0.0407), smoking (p=0.0226) and CAD (p=0.0377). Plasma RANKL concentrations were associated with patients’ age (p=0.0191), homocysteine levels (p<0.00001), history of smoking (p=0.0185) and statins therapy (p=0.0004). Diabetes, CAD, smoking status, statins therapy and homocysteine were identified as independent predictors of OPG concentrations (p=0.0157, p=0.0030, p=0.0249, p=0.0047 and p=0.0072, respectively), whereas smoking showed an independent effect for RANKL (p=0.0010). Conclusions The present data reinforce the clinical utility of OPG in carotid atherosclerosis, whereas the clinical implication of RANKL seems uncertain.

The role of carotid plaque echogenicity in baroreflex sensitivity.

OBJECTIVEnThe baroreflex sensitivity is impaired in patients with carotid atherosclerosis. The purpose of our study was to assess the impact of carotid plaque echogenicity on the baroreflex function in patients with significant carotid atherosclerosis, who have not undergone carotid surgery.nnnMETHODnSpontaneous baroreflex sensitivity (sBRS) was estimated in 45 patients with at least a severe carotid stenosis (70%-99%). sBRS calculation was performed noninvasively, with the spontaneous sequence method, based on indirectly estimated central blood pressures from radial recordings. This method failed in three patients due to poor-quality recordings, and eventually 42 patients were evaluated. After carotid duplex examination, carotid plaque echogenicity was graded from 1 to 4 according to Gray-Weale classification and the patients were divided into two groups: the echolucent group (grades 1 and 2) and the echogenic group (grades 3 and 4).nnnRESULTSnSixteen patients (38%) and 26 patients (62%) were included in the echolucent and echogenic group, respectively. Diabetes mellitus was observed more frequently among echolucent plaques (χ(2) = 8.0; P < .004), while those plaques were also more commonly symptomatic compared with echogenic atheromas (χ(2) = 8.5; P < .003). Systolic arterial pressure, diastolic arterial pressure, and heart rate were similar in the two groups. Nevertheless, the mean value of baroreflex sensitivity was found to be significantly lower in the echogenic group (2.96 ms/mm Hg) compared with the echolucent one (5.0 ms/mm Hg), (F [1, 42] = 10.1; P < .003).nnnCONCLUSIONSnThese findings suggest that echogenic plaques are associated with reduced baroreflex function compared with echolucent ones. Further investigation is warranted to define whether such an sBRS impairment could be responsible for cardiovascular morbidity associated with echogenic plaques.

Endovascular Repair of Two Tandem Profunda Femoris Artery Aneurysms

Editor: Isolated aneurysms of the profunda femoris artery (PFA) are rare and account for only 0.5% of all peripheral aneurysms and 1%–2.6% of all femoral aneurysms. However, PFA aneuryms have a higher rate of rupture than other peripheral aneurysms and are associated with significant morbidity (1). PFA aneurysms have an asymptomatic course and are not easily detected unless they are complicated with rupture or critical limb ischemia; indeed, approximately 58% of patients present with a complicated PFA aneurysm (2). In general, repair is indicated when their diameter exceeds 2 cm, even if they are asymptomatic (3). Surgical arterial reconstruction with aneurysmectomy and femoral interposition graft are currently the standard treatment. Endovascular therapy of PFA aneurysms has been scarcely reported to date basically due to the rarity of such cases. Herein, we report a case of two tandem PFA aneurysms that were treated endovascularly with percutaneous stent-graft deployment. Our institution does not require approval for retrospective reporting of cases such as the present report. A 75–year-old man with a history of aortoiliac occlusive disease who underwent aortobifemoral bypass grafting 8 years ago visited our department for his regular follow-up. His medical history was notable for hypertension, smoking, chronic obstructive pulmonary disease, and coronary artery disease for which he had undergone coronary artery bypass grafting 6 years before current admission. Physical examination revealed a pulsatile mass within the anterior-medial aspect of his left thigh. Ultrasonography of the groins suggested a left femoral artery aneurysm. Subsequent digital subtraction angiography demonstrated two tandem aneurysms of the left PFA in the middle and distal portions of the PFA, with maximum transverse diameters of 44 and 24 mm, respectively (Figure, a). Diffuse stenotic lesions in the left superficial femoral artery (SFA) as well as occlusion of the right SFA were also revealed. No other peripheral arterial aneurysms were identified, and the previously conducted aortobifemoral bypass graft was patent. Due to the patient’s severe comorbidities and previous surgery in the left groin area, an endovascular approach was chosen for PFA aneurysm treatment. Informed consent was obtained. A percutaneous ipsilateral antegrade approach was used. The left graft limb of the previously conducted aortobifemoral bypass was

Stent-Graft Repair of Isolated Iliac Aneurysms with Wide or Ectatic Necks with Use of Inverted Zenith Device Legs

Although there is considerable experience in the management of iliac artery aneurysms (IAAs) accompanying abdominal aortic aneurysms, less is known about endovascular management of isolated IAAs. The distal landing zone can be secured if necessary by extending the graft to the external iliac artery, but the proximal landing zone remains a challenging issue, on which technical success is dependent. The present report describes a novel technique for endovascular management of isolated IAAs with wide proximal necks for which no commercially available grafts with fitting sizes exist: inversion of the iliac leg of a Zenith device.

Toll-like receptors: a novel target for therapeutic intervention in intestinal and hepatic ischemia–reperfusion injury?

Importance of the field: Toll-like receptors (TLRs) are transmembrane proteins that act mainly as sensors of microbes, orchestrating an organisms defense against infections, while they sense also host tissue injury by recognizing products of dying cells. Ischemia–reperfusion injury (IRI) represents one of these tissue damage states in which TLR-mediated mechanisms might be implicated. Areas covered in this review: The most recent data on TLR signaling and the latest knowledge regarding the involvement of TLRs in the pathogenesis and progression of intestinal and hepatic IRI are presented. The potential effectiveness of TLR-modulating therapy in intestinal and liver IRI is also analyzed. What the reader will gain: A comprehensive summary of the data suggesting TLR involvement in intestinal and hepatic IRI. Knowledge required for developing TLR modulation strategies against intestinal and hepatic IRI. Take home message: TLRs play a significant role in both intestinal and hepatic IRI pathophysiology. Better understanding of TLR involvement in such processes may enable the invention of novel TLR-based therapies for IRI in the intestine and liver.