Preventive and healing effect of high dosing grape seed flour on CKD patients of various stages and aetiologies.

INTRODUCTION: Chronic kidney disease (CKD) is a worldwide public health concern characterised by a progressive alteration of renal function, and obesity, diabetes and hypertension are major risk factors. Oxidative stress is commonly observed in CKD patients resulting from an imbalance between overproduction of reactive oxygen species (ROS) and impairment of defense mechanisms. Therefore, strategies that alleviate oxidative stress may have major clinical implications towards improving vascular health and reducing the burden of CKD. Also, CKD worsens the quality of life of patients, therefore it is fundamental to implement new therapeutic strategies aimed at slowing down its progression. MATERIALS AND METHODS: This interventional study is a randomised placebo-controlled clinical trial consisting at the daily oral supplementation with high dosing grape seed flour (GSF ≈ 1 g/kg) for experimental (n = 30) or starch for placebo (n = 10) to patients suffering from CKD of various stages and aetiologies. Blood and urine samples were collected at baseline and after a six-month-long supplementation period to follow up the disease evolution through the determination of renal function biomarkers, as well as antioxidant, anti-inflammatory and blood parameters. RESULTS: Supplementation with high dosing GSF was safe and well tolerated during the entire period of investigation. GSF clearly improved the main renal function biomarkers as GFR, proteinuria, blood pressure, oxidative stress and inflammation as well as the overall patient welfare as indicated by several blood parameters. CONCLUSION: Most importantly high dosing GSF specifically halted and even reversed the progression of diabetic nephropathy a major cause of CKD and end stage renal disease.

How effective is wastewater treatment? A case study under the light of taxonomic and feeding features of meiobenthic nematodes.

A microcosm bioassay was designed to assess the efficacy of wastewater treatment methods used in sewage plants. The taxonomic and feeding characteristics of a meiobenthic nematode assemblage from Ghar El Melh lagoon (Tunisia) were used to achieve this goal. Nematode assemblages were exposed for 30 days to untreated wastewater (UW) obtained from the sewage treatment plant of Sidi Ahmed (Tunisia) and three mixtures with treated wastewater (TW33 = 33%, TW66 = 66%, and TW100 = 100%). Concerning the nematode abundance, the exposure to either treated wastewater (TW33-100) or untreated wastewater (UW) had no significant effect. In contrast, Shannon-Wiener index and Pielou's Evenness were clearly reduced by contamination with both types of wastewater, with a more pronounced negative impact prior to treatment in the sewage plant. The multivariate analyzes revealed a change in the taxonomic composition of the nematofauna in response to the contamination by untreated or treated wastewater. The relative abundances of species in wastewater replicates compared to controls reflected this taxonomic restructuring. Finally, Ascolaimus elongatus, Terschellingia communis, and Kraspedonema octogoniata were less represented in all experimentally treated units and could be considered as 'sensitive taxa to wastewater'. While, Paracomesoma dubium, appears to be a 'tolerant and/or opportunistic' species, showing increased relative abundances under all wastewater treatments.

Grape Seed Flour Extends Longevity by Improving Multi-Organ Dysfunction and Age-Associated Oxidative Stress and Inflammation in Healthy Rat.

According to the free-radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout life span leads to impairment of the main biological macromolecules as DNA, lipids, and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains a high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anticarcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective. The present study aimed at testing the ability of high dosing GSF (4 g/kg bw) used as a nutritional supplement to slow down aging and prolong life span of Wistar rats when administered from early life (1-month-old animals) till their natural death. Data clearly show that high-dose GSF extends organism longevity and health span by improving multi-organ damages, systemic fueling metabolism declines, and alleviated oxidative stress and inflammation in aging rats. Our data support the extending longevity effect of grape polyphenols especially when used as high dosing nutritional supplement or as natural medicine whose appropriate galenic form as solid lipid nanoformulation is currently under investigation.

Change of the litter fall, decomposition, and nutrient release in cork oak forest after anthropogenic disturbances in North West of Tunisia.

In Mediterranean forests, anthropogenic disturbances received little interest in regards to their shrub layer induced enlargement. We studied in the cork oak forest of Beni Métir and in undisturbed and disturbed sites, the relative contribution of the tree (LT, DLT) and shrub (LS, DLS) layers to litter fall, litter decomposition, and nutrients dynamic. Our results showed that disturbance significantly (p < 0.001) reduced (-43%) total litter fall in DS in comparison with S (583 g m-2 year-1); the increased (+ 54%) shrub layer contribution to site litter fall did not counterbalance the decreased input by the tree layer. Leaf litter decomposition was negatively affected (p < 0.001) by disturbance, the remaining mass value being after 2 years, approximately 14 and 33%, respectively, for S and DS. This resulted into a gain of above ground soil organic matter 1.3 higher in DS than it was in S whereas the shrub layer contribution to litter fall increased by 50%. The prevailing driver of decomposition was very probably not related to litter quality but rather site-dependent. Indeed, layers of the same site shared the same remaining mass in spite of significant differences (p < 0.05) in initial content of minerals (N, Ca, and Mn) implicated in biological decomposition. In the disturbed site, the nutrient input by the shrub layer increased by more than double, but its low nutrient quality drastically impaired litter decomposition and mineral return at the site level. In conclusion, this study highlighted the importance of shrub layer which must be taken into account when considering any disturbance assessment and management of Mediterranean forests.

Outcomes of Halo Immobilization for Cervical Spine Fractures.

STUDY DESIGN: Retrospective. OBJECTIVES: To evaluate complications and outcomes of halo immobilization in patients with cervical spine fractures treated at a level I trauma center. METHODS: A retrospective evaluation of patients treated at a single institution with halo immobilization from August 2000 to February 2016 was performed. Demographic information, mechanism of injury, level and type of spine fracture, length of halo immobilization, complications associated with halo immobilization, and length of patient follow-up were collected. RESULTS: A total of 189 patients treated with halos were identified. Of the 189 patients, 121 (64%) received halos for the management of cervical spine fractures and were included in the study. A total of 49.6% were males and 50.4% were females. The average age was 50.8 years (range 1-89 years). Overall, 10.7% sustained C1 fractures, 71.1% C2 fractures, and 18.2% subaxial spine (C3-C7) fractures. In all, 47.1% of the upper cervical fractures were either odontoid or hangman-type fractures. A total of 25.1% of patients had multiple cervical fractures. At latest follow-up, 81% had healed fractures with good alignment, minimal pain, and return to normal activities. There was an 8.3% mortality rate. The mortality group had an average age of 64.7 years (range 19-84 years). A total of 10.7% of patients failed halo immobilization and 46.3% of patients had complications such as pin site infections (5.8%), loose pins (1.7%), neck pain (20.7%), decreased range of motion (14%), thoracic skin ulcers (2.4%), and dysphagia (1.7%). CONCLUSIONS: The use of halo immobilization for cervical spine fractures resulted in clinical success in 81% of patients. Complication rates in geriatric patients were lower than previously reported in the literature.

Safety evaluation, anti-oxidative and anti-inflammatory effects of subchronically dietary supplemented high dosing grape seed powder (GSP) to healthy rat.

Grape seed powder (GSP) contains high amount of bioactive polyphenols usually used as nutritional supplement or food preservatives due to their antioxidant and scavenging properties. The purpose of the present work was to evaluate the safety of increasing dosage GSP (w/w) of 0.5%, 5%, 10% and 20% corresponding to 0.4, 4, 8 and 16 g/kg bw respectively, when administered sub-chronically to Wistar rats in a 2 month-repeated dosing oral toxicity trial. Overally GSP had no effect on food intake, decreased body weight gain without affecting brain, liver, heart or kidney relative weight. GSP did not alter haematology except an increase in platelets, slightly decreased plasma transaminases, creatinine, urea and xanthine oxidase activity, without affecting uricemia, glycemia, triglyceridemia and cholesterolemia. GSP did not affect intracellular mediators as calcium, free iron or H2O2, but exerted real anti-oxidative properties in the four selected organs as assessed by lower lipoperoxidation and carbonylation, higher non protein thiols and antioxidant enzyme activities as CAT, GPx and SOD. Besides GSP exerted anti-inflammatory properties as supported by lower plasma IL17 A and CRP and higher IL10 and adiponectin. Histopathologically GSP provoked the dilation of heart and kidney arterioles and increased the size of the hippocampal dentate gyrus reflecting higher neurogenesis as assessed by Ki-67 labeling. Under the experimental conditions of the current study, GSP appeared as highly safe even when administered at very high dosage and could find potential applications in a variety of biotic or abiotic stresses-induced multi-organ dysfunction.

Supplementation of grape seed and skin extract to orlistat therapy prevents high-fat diet-induced murine spleen lipotoxicity.

Spleen is the largest lymphoid organ and obesity is related to an elevated risk of immunity dysfunction. The mechanism whereby fat adversely affects the spleen is poorly understood. This study was designed to assess the effectiveness of grape seed and skin extract (GSSE) and orlistat (Xenical, Xe) on high-fat diet (HFD)-induced spleen lipotoxicity. Obese rats were treated either with GSSE (4 g/kg body weight) or Xe (2 mg/kg body weight) or GSSE+Xe and monitored for weight loss for 3 months. Animals were then sacrificed and their spleen used for the evaluation of lipotoxicity-induced oxidative stress and inflammation as well as the putative protection afforded by GSSE and Xe treatment. HFD induced body weight gain and glycogen accumulation into the spleen; ectopic deposition of cholesterol and triglycerides and an oxidative stress characterized by increased lipoperoxidation and carbonylation; inhibition of antioxidant enzyme activities, such as catalase, glutathione peroxidase, and superoxide dismutase; depletion of zinc and copper; and a concomitant increase in calcium. HFD also increased plasma pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17A, tumour necrosis factor alpha, and C-reactive protein, and decreased plasma IL-10 and adiponectin. Importantly, GSSE counteracted all the deleterious effects of HFD on spleen (i.e., lipotoxicity, oxidative stress, and inflammation) and the best protection was obtained when combining Xe+GSSE. Combining GSSE with Xe prevented against fat-induced spleen lipotoxicity, oxidative stress, and inflammation; this combination may be beneficial in other diseases related to the spleen.

Grape seed and skin extract as an adjunct to xenical therapy reduces obesity, brain lipotoxicity and oxidative stress in high fat diet fed rats.

BACKGROUND: Obesity is a public health problem and a major risk factor for metabolic syndrome. This study was designed to assess the effectiveness of grape seed and skin extract (GSSE) and Xenical (Xe) on high fat diet (HFD)-induced obesity and brain lipotoxicity. METHOD: Rats were rendered obese and then treated either with vehicle (control) or GSSE (4g/kg bw) or Xe (1, 2, 4 or 8mg/kg bw) or (GSSE+Xe) and monitored for weight loss during 3 months. Animals were then sacrificed and their brain utilised for the evaluation of lipotoxicity-induced oxidative stress as well as the putative protection offered by GSSE and Xe treatment. RESULTS: As expected HFD-induced body and adipose tissue weight gain, dyslipidemia, accumulation of lipid into the brain, a drop in adiponectin, increased oxidative stress and disruption of Mn, Ca2+ and of related enzyme activities as glutamine synthetase and calpain. Xe alone exerted anti-obesity effect during the first 2 months and became inefficient thereafter. GSSE per se exhibited potent anti-obesity effect whereas the combination (GSSE+Xe), by acting in concert, was the most efficient against obesity and brain lipotoxicity. GSSE acted partially through its anti-oxidative properties, whereas Xe did not. CONCLUSION: Combining GSSE with Xe improved outcomes in body weight and fat reduction as well as in brain lipotoxicity.

Dietary supplementation of grape seed and skin flour mitigates brain oxidative damage induced by a high-fat diet in rat: Gender dependency.

It is unknown whether gender has an impact on brain injury in obesity, and, if so, whether treatment with grape seed and skin flour could exert a protective effect. Both male and female rats were fed a standard diet (SD) or a high fat diet (HFD) during eight weeks and treated with high dosage grape seed and skin flour (GSSF). Fat-induced oxidative stress was evaluated into the brain with a special emphasis on transition metals determination. HFD induced male-cholesterol overload (+78.12%) and an oxidative stress status characterized by increased lipoperoxidation (+68.97%), carbonylation (+40.28%), decreased antioxidant enzyme activities as glutathione peroxidase (-61.07%) and manganese-superoxide dismutase (-35.47%) but not catalase. Additionally HFD depleted the brain from manganese (-71.31%) and dropped glutamine synthetase activity (-36.16%), without affecting copper nor iron nor their associated enzymes. HFD also altered intracellular mediators as superoxide anion (+36.12%), calcium (+44.41%) and also calpain (+76.54%) a calcium dependent protease. Importantly all these alterations were detected exclusively in male brain and were efficiently corrected upon GSSF treatment. In conclusion, GSSF has the potential to alleviate the deleterious lipotoxic effect of HFD treatment that occurred in male brain and perhaps in post-menauposal female brain.

Hypertension of neurogenic origin: effect of microvascular decompression of the CN IX-X root entry/exit zone and ventrolateral medulla on blood pressure in a prospective series of 48 patients with hemifacial spasm associated with essential hypertension.

OBJECT: In spite of solid anatomical and physiological arguments and the promising results of Jannetta in the 1970s, treating essential hypertension by microvascular decompression (MVD) of the brainstem has not gained acceptance as a mainstream technique. The main reason has been a lack of established selection criteria. Because of this, the authors' attempts have been limited to patients referred for MVD for hemifacial spasm (HFS) who also had hypertension likely to be related to neurovascular compression (NVC). METHODS: Of 201 patients referred for HFS, 48 (23.8%) had associated hypertension. All had high-resolution MR images that demonstrated NVC. All underwent MVD of the root exit/entry zone (REZ) of the ninth and tenth cranial nerves (CN IX-X) and adjacent ventrolateral medulla in addition to the CN VII REZ. Effects on hypertension, graded using the WHO classification, were studied up to the latest follow-up, which was 2-16 years from the time of surgery, 7 years on average. Also, effects of MVD on blood pressure (BP) according to the side of vascular compression were evaluated. RESULTS: Preoperatively, hypertension was severe in all but 1 of the patients; in spite of medical treatment, 47 patients still had WHO Grade 1 or 2 hypertension, and 18 still had unstable BP. After MVD, at latest follow-up, BP had returned to normal (i.e., systolic pressure < 140 mm Hg) in 28 patients; 14 of these patients (29.10% of the whole series) were able to maintain normal BP without any antihypertensive treatment; the other 14 still required some medication to maintain their BP below 140 mm Hg (p < 0.0001). Also, at latest follow-up, BP remained unstable in only 8 of the 18 patients with instability prior to MVD (p < 0.02). Analysis according to side of compression showed that of the 30 patients with left-sided compression, 17 had their BP normalized (without medication in 11 cases), and of the 18 patients with right-sided compression, 11 had their BP normalized (without medication in 3 cases). The difference between sides was not significant. CONCLUSIONS: These results argue for considering MVD for the treatment of hypertension likely to be due to NVC at the CN IX-X REZ and adjacent ventrolateral medulla. Criteria for selecting patients with hypertension alone still need to be established and could include the following indications: apparently essential hypertension, likely to be neurogenic, in patients in whom high-resolution MRI shows clear-cut images of NVC at the CN IX-X REZ and adjacent ventrolateral medulla and in whom BP cannot be controlled by medical treatment.

Grape seed and skin extract mitigates heart and liver oxidative damage induced by a high-fat diet in the rat: gender dependency.

Obesity is a public health problem contributing to morbidity and mortality from metabolic syndrome. It has long been recognized that there is a gender dependency in several obesity-related health risks. Using a high fat diet (HFD) to induce obesity in Wistar rats, we studied the gender dependency of fat-induced oxidative stress in the heart and liver, with a special emphasis on the distribution of transition metals, as well as the protective effects of grape seed and skin extract (GSSE). HFD induced obesity in both male and female rats, characterized by increased body weight as well as relative liver mass in both genders, and increased relative heart mass in the males only. HFD also provoked the accumulation of triglycerides and total cholesterol into the male hearts, and into the livers of both genders. HFD induced oxidative stress in the male hearts and also in the livers of both genders. Furthermore, HFD affected cardiac levels of copper in the males, and hepatic levels of copper and zinc in both genders, whereas HFD affected free iron in the male hearts and female livers, specifically. In conclusion, HFD treatment altered transition metal homeostasis more drastically in the male heart than in the female liver, and GSSE efficiently protected these organs against fat-induced disturbances, regardless of gender.