Randomized controlled trial on Dryland And Thermal Aquatic standardized exercise protocol for chronic venous disease (DATA study).

OBJECTIVE: The present investigation aims to compare the effect of a standardized exercise protocol in thermal aquatic immersion vs dryland (DL) on patients with chronic venous disease (CVD). METHODS: Thirty-four patients with CVD (C3,Ep,As,Pr) were included in the study and randomly assigned to perform a standardized exercise protocol in a DL environment (DL group) or in a thermal water (TW group) from a natural hot spring at 33°C with a high mineral content. Leg volumetry, ankle range of motion (ROM), ultrasound-detected subcutaneous tissue and great saphenous vein (GSV) diameter were assessed. Quality of life was measured by VVSymQ and CIVIQ-20. RESULTS: After five TW sessions the average volume decrease was -432.4 ± 122.4 mL (P < .0001) in the right leg and -358.8 ± 109.3 mL (P < .0001) in the left. No significant volume change was reported at the end of the five sessions in DL. In TW, the subcutaneous tissue thickness significantly decreased (all assessment points P < .0001 right and P < .0001 left). In contrast, no significant changes were found in the DL group. The TW group showed a significant great saphenous vein caliber reduction, both in the right and left legs (6.2 ± 5.9%, P < .002; 6.1 ± 2.2%, P < .0001), whereas in the DL group no significant differences were found. After five sessions, ankle ROM significantly increased in both groups, both in dorsiflexion and in plantarflexion (right leg: TWdorsiflexionP < .0001, TWplantarflexionP < .0001; DLdorsiflexionP < .003, DLplantarflexionP < .007) (left leg: TWdorsiflexionP < .0001, TWplantarflexionP < .0001; DLdorsiflexionP < .006, DLplantarflexionP < .001). Only the TW group showed a linear correlation between volume and ankle ROM variation (right leg: R2 = 0.80, R2 = 0.75, P < .0001; left leg: R2 = 0.82, R2 = 0.81, P < .0001). The VVSymQ and CIVQ20 scores significantly improved in TW (P < .0001 and P < .0001, respectively), whereas DL showed a significant improvement only in CIVQ20 score (P < .02). CONCLUSIONS: Thermal aquatic immersion enhances the clinical benefits of a standardized exercise protocol for patients with CVD. Compared with the data available in the literature on non-TW, the present investigation shows a potential role of higher density types of water in lower limb volume control. Intense and rigorous data collection is needed to move from empirical evidence to evidence-based science in TW, a potentially very useful treatment modality for CVD.

Calcium micro-depositions in jugular truncular venous malformations revealed by Synchrotron-based XRF imaging.

It has been recently demonstrated that the internal jugular vein may exhibit abnormalities classified as truncular venous malformations (TVMs). The investigation of possible morphological and biochemical anomalies at jugular tissue level could help to better understand the link between brain venous drainage and neurodegenerative disorders, recently found associated with jugular TVMs. To this end we performed sequential X-ray Fluorescence (XRF) analyses on jugular tissue samples from two TVM patients and two control subjects, using complementary energies at three different synchrotrons. This investigation, coupled with conventional histological analyses, revealed anomalous micro-formations in the pathological tissues and allowed the determination of their elemental composition. Rapid XRF analyses on large tissue areas at 12.74 keV showed an increased Ca presence in the pathological samples, mainly localized in tunica adventitia microvessels. Investigations at lower energy demonstrated that the high Ca level corresponded to micro-calcifications, also containing P and Mg. We suggest that advanced synchrotron XRF micro-spectroscopy is an important analytical tool in revealing biochemical changes, which cannot be accessed by conventional investigations. Further research on a larger number of samples is needed to understand the pathogenic significance of Ca micro-depositions detected on the intramural vessels of vein walls affected by TVMs.

Inhibitory effect of natural anti-inflammatory compounds on cytokines released by chronic venous disease patient-derived endothelial cells.

Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n = 31) in CVD patients' plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF- α2, G-CSF, MIP-1ß, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that αLipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets.

Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options.

Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer's disease, Parkinson's disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario.