Distinct effects of surgical denervation on hepatic perfusion, bowel ischemia, and oxidative stress in brain dead and living donor porcine models.

The liver function and perfusion following brain death is mainly influenced by the sympathetic nerves and hormones. We examined the specific influence of surgical liver denervation on systemic and hepatic perfusion parameters, bowel ischemia and oxidative stress in hemodynamically stable BD and control (living donor [LD]) pigs. Brain death was induced in 8 pigs via saline infusion into the balloon of an epidural Tieman-catheter (1 mL/15 minutes) and compared to the control group (n = 6) over 4 hours. At 2 hours postoperatively, complete liver denervation was initiated. We analyzed systemic cardiocirculatory parameters (mean arterial pressure, aortic flow, bowel ischemia (endotoxin, and endotoxin-neutralizing capacity) and oxidative stress (total glutathione in erythrocytes [tGSH(E)]) and compared them to local/hepatic perfusion parameters (hepatic artery and portal venous flow, liver blood flow index, and microperfusion), local bowel ischemia (intramucosal pH [pHi] of stomach [pHi(S)]/colon[pHi(C)]), and liver oxidative stress (glutathione [rGSH(L), GSSG(L)]). Following brain death, the parameters including mean arterial pressure, aortic flow, pHi, endotoxin, and tGSH(E) showed no significant changes at 2 hours. Portal venous flow and microperfusion were decreased significantly and hepatic arterial buffer response was ineffective. Hepatic oxidative stress was increased in BD animals (decrease rGSH(L), increase GSSG(L)). Surgical denervation/manipulation increased portal venous flow significantly, hepatic arterial buffer response became effective, and stomach pHi decreased (BD and LD groups). Hepatic oxidative stress was reduced in the BD group (increase rGSH(L)/GSSG(L); P < 0.001) while it was increased in the LD group (decrease rGSH(L)/GSSG(L); P < 0.001). In conclusion, denervation reduces hepatic oxidative stress in BD only in contrast to the LD. The reciprocal effect of denervation depends on the state of neural activation and postulates a potential benefit of surgical denervation before organ harvesting in brain death.     

A one-year survey on the use of a powder from Rosa canina lito in acute exacerbations of chronic pain

This pilot surveillance included 152 patients with acute exacerbations of chronic pain, 124 (Back group) with non-specific low back pain (NSLBP), 20 with NSLBP overridden by osteoarthritic pain (Knee-Hip group), and eight with specific LBP (included in the safety analysis). Patients were recommended the rose hip and seed powder Litozin at a dose providing up to 3 mg of galactolipid/day for up to 54 weeks. Clinical symptoms and well-being were assessed every 6 weeks. The patients also kept a diary of their pain and the requirement for rescue medication. Data were analysed by intention to treat with last observation carried forward. Only 77 patients completed the year of surveillance. Multivariate analysis suggested an appreciable overall improvement during the surveillance, irrespective of group, and this was reflected for most of the individual measures in repeated measures ANOVA. The degree and time-course of improvement echoed that seen in similar surveillances of patients receiving an aqueous extract of Harpagophytum. Multiple regression analyses indicated that percentage changes from baseline tended to be greater in patients with greater degrees of pain and disability, but were otherwise largely unrelated to the patients' characteristics. There were no serious adverse events. The rose hip and seed powder, Litozin, seems to deserve further, more definitive studies as a possible option in long-term management of NSLBP with or without osteoarthritic pain.     

A systematic review on the Rosa canina effect and efficacy profiles

Rose hip, rose hip and seed and rose hip seed, all were negatively monographed by the German Commission E due to insufficient evidence of effects and effectiveness. Therefore a comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of Rosa canina L. to reevaluate its usefulness in traditional medicine. For various preparations of rose hip and rose hip and seed, antioxidative and antiinflammatory effects have been demonstrated. Lipophilic constituents are involved in those mechanisms of action. The proprietary rose hip and seed powder Litozin has been employed successfully in a number of exploratory studies in patients suffering from osteoarthritis, rheumatoid arthritis and low back pain. However, the sizes of the clinical effects for the different indications need to be determined to assure clinical significance. There is also a rationale behind the use of Litozin as part of a hypocaloric diet based on the rose hip probiotic, stool regulating and smooth muscle-relaxing actions, as well as the rose hip seed lipid-lowering, antiobese and antiulcerogenic effects. Further research is needed to clarify the importance of the reported promising experimental effects in clinical use and to characterize the optimum rose hip seed oil preparation for topical use in the treatment of skin diseases.     

Transcatheter arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma

BACKGROUND/AIMS: Substantial differences about the efficacy of transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma are reported in literature. This probably depends on the fact that in each single study, different patient selection criteria, type of epidemiological approach, end points adopted and kind of technical approach were used. This study aims to evaluate the efficacy of segmental transcatheter arterial chemoembolization in amelioring patient survival and to determine which patients might really benefit from this treatment. METHODOLOGY: To achieve our goals 193 consecutive patients (110 treated and 83 untreated) were studied. They were selected in the same period of time and matched as far as their demographic and clinical characteristics. RESULTS: Our results demonstrate that both in treated and control patients, Child class, alpha-fetoprotein and tumor diameter significantly influenced survival, resulting important prognostic factors. Transcatheter arterial chemoembolization significantly ameliorated survival in treated patients compared to controls (p < 0.0001). CONCLUSIONS: Transcatheter arterial chemoembolization significantly ameliorates survival in patients with hepatocellular carcinoma. However, the presence of large tumors producing high alpha-fetoprotein levels in patients with advanced Child class should discourage treatment.     

Chlamydophila pneumoniae phospholipase D (CpPLD) drives Th17 inflammation in human atherosclerosis

Phospholipases are produced from bacterial pathogens causing very different diseases. One of the most intriguing aspects of phospholipases is their potential to interfere with cellular signaling cascades and to modulate the host-immune response. Here, we investigated the role of the innate and acquired immune responses elicited by Chlamydophila pneumoniae phospholipase D (CpPLD) in the pathogenesis of atherosclerosis. We evaluated the cytokine and chemokine production induced by CpPLD in healthy donors' monocytes and in vivo activated T cells specific for CpPLD that infiltrate atherosclerotic lesions of patients with C. pneumoniae antibodies. We also examined the helper function of CpPLD-specific T cells for monocyte matrix metalloproteinase (MMP)-9 and tissue factor (TF) production as well as the CpPLD-induced chemokine expression by human venular endothelial cells (HUVECs). We report here that CpPLD is a TLR4 agonist able to induce the expression of IL-23, IL-6, IL-1β, TGF-β, and CCL-20 in monocytes, as well as CXCL-9, CCL-20, CCL-4, CCL-2, ICAM-1, and VCAM-1 in HUVECs. Plaque-derived T cells produce IL-17 in response to CpPLD. Moreover, CpPLD-specific CD4(+) T lymphocytes display helper function for monocyte MMP-9 and TF production. CpPLD promotes Th17 cell migration through the induction of chemokine secretion and adhesion molecule expression on endothelial cells. These findings indicate that CpPLD is able to drive the expression of IL-23, IL-6, IL-1β, TGF-β, and CCL-20 by monocytes and to elicit a Th17 immune response that plays a key role in the genesis of atherosclerosis.     

Typical and severe tumor necrosis factor receptor–associated periodic syndrome in the absence of mutations in the TNFRSF1A gene: a case series

Tumor necrosis factor receptor-1?Cassociated periodic syndrome (TRAPS) is the most common autosomal dominant autoinflammatory disorder and is caused by mutations in the TNFRSF1A gene encoding the 55-kDa receptor for tumor necrosis factor (TNF)-??. TRAPS is characterized by recurrent attacks of fever, typically lasting from 1 to 3?weeks. In addition to fever, common clinical features include periorbital edema, a migratory erythematous plaque simulating erysipela with underlying myalgia, and arthralgia or arthritis. Serosal membrane inflammation is also a common feature, usually in the form of polyserositis. To date, at least 40 different TNFRSF1A mutations have been identified, but few patients with symptoms highly suggestive of TRAPS with no mutations in the TNFRSF1A gene have recently been described, thus suggesting that not all mutations are yet known or that alternative mechanisms might be involved in the pathogenesis of the disease. We report on three such patients here.     

Systemic-onset juvenile idiopathic arthritis complicated by early onset amyloidosis in a patient carrying a mutation in the <Emphasis Type="Italic">MEFV</Emphasis> gene

Systemic juvenile idiopathic arthritis (SJIA) is a disorder characterized by arthritis in children starting before 16 years of age associated with daily high fever, persisting for more than 2 weeks, and at least one of the following clinical features: evanescent cutaneous rash, lymphadenopathy, serositis or hepatosplenomegaly. SJIA patients carry a significantly higher frequency of MEFV mutations, the gene responsible for familial Mediterranean fever, and may be characterized by a more aggressive disease. In this line, we describe a 9-year-old girl affected with SJIA who carried a heterozygous G196W mutation in MEFV. Our patient was characterized by an aggressive disease course, resistance to conventional immunosuppressive agents and developed renal amyloidosis just 2 years after the disease onset.     

Hyaluronic acid in ankle osteoarthritis: why evidence of efficacy is still lacking?

Intra-articular injections of hyaluronic acid (HA) are useful in the treatment of osteoarthritis (OA), as shown by studies on knee, hip, and trapezio-metacarpal joints. The positive results can be explained by several factors: the restoration of elastic and viscous properties of intra-articular fluid, the anti-inflammatory and the anti-nociceptive activity, and the normalisation of hyaluronan synthesis and inhibition of hyaluronic acid degradation. However, evidence of efficacy of hyaluronic acid in ankle osteoarthritis is still lacking: several studies have been performed without a control group, or have shown similar results to those obtained with different therapeutic procedures. The aim of this paper is to analyse the reasons which can explain the discrepancy between the sound biological background and the inconclusive clinical results. First, it must be considered that the ankle joint, from a biomechanical point of view, is more complex than other joints, and that greater stress is sustained by the articular surfaces. Second, the limited benefit can be related to the use of hyaluronic acid mostly in cases of post-traumatic osteoarthritis, where the treatment must be addressed to solve the biomechanical problems, and then to restore the rheological properties of the ankle joint. A third important explanation of the failure may be the improper technique of administration, that has been performed in all studies, but one, without imaging guidance. Indeed, it is well known that hyaluronic acid, if not delivered directly into the intra-articular space, is unlikely to be effective.