Mitochondrial and redox dysfunction in post-menopause as risk factor of neurodegenerative disease: a pilot study testing the role of a validated Japanese functional food.

During the menopause women may experience increased oxidative stress and decreased antioxidant capacity and, together with the decline of neurosteroids, this represents a risk factor for Alzheimer's disease. The aim of the present study was to test a functional food (FPP-ORI, Osato Research Institute, Gifu, Japan) on redox and mitochondrial efficiency in post-menopausal women. The study population consisting of 69 untreated post-menopausal women were given supplements as follows: Group A was given a multivitamin (MV) 1c 2 times a day, and group B was given FPP 4.5 g 2 times a day. Group C consisted of 23 fertile premenopausal women as the control group. The tests carried out on entry, and at 3 and 6 months were erythrocyte redox parameters, plasma oxidated proteins, brain-derived neurotrophic factor (BDNF) and peripheral blood mononuclear cell (PBMC) mitochondria cytochrome c oxidase Vmax activity. Menopausal women showed an increased malondialdehyde (MDA) (p<0.05 vs control) which was normalized by both treatments (p<0.05), but MV failed to do so in the BMI ≥26 subgroup (p<0.05). All other redox enzymes and BDNF were significantly lower in menopausal women and they responded only to FPP (p<0.05). Carbonyl protein level was higher in "BMI ≥ 26" subgroup (p<0.05) and reduced only by FPP (p<0.05). The PBMC cyclooxygenase to citrate synthase activity was reduced (<40%) in the menopausal group (p<0.01) and only FPP caused a significant restoration (p<0.05). Although preliminary, these data confirm the redox and mitochondrial dysfunction occurring in post-menopause and responsive to FPP but very poorly to high dosage antioxidants. This may lead to potential preventive opportunities in menopause-associated neurodegenerative disease.

Ultrasound assisted formation of essential oil nanoemulsions: Emerging alternative for Culex pipiens pipiens Say (Diptera: Culicidae) and Plodia interpunctella Hübner (Lepidoptera: Pyralidae) management.

Over the last years, nanotechnology has contributed to the development of new botanical insecticides formulations based on essential oils (EO), which are safe for the human health and the environment. Nanoemulsions (NEs) can enhance the bioactivity of the EO to prevent the premature volatility and degradation of the active ingredients. In our work, geranium EO (Geranium maculatum L.) was used to develop micro and nanoemulsions adding Tween 80 as surfactant. For NEs formulation, ultrasound was applied and the physicochemical and ultrasound parameters were optimized: oil: surfactant ratio = 1:2, ultrasound power = 65 W, sonication time = 2 min, cycles = 30 on/20 off and ultrasonic probe distance = 3.7 cm. The NEs obtained had 13.58 nm and polydisperse index (PDI) values of 0.069. They were stored at 25 °C and were stable for 60 days. The present study also demonstrated the potential of NEs to enhance the toxicity of geranium EO against larvae of Culex pipiens pipiens (EO LC50 = 80.97 ppm, NEs LC50 = 48.27 ppm) and Plodia interpunctella (EO + ß-cypermethrin LD50 = 0.16 µg larvae-1, NEs + ß-cypermethrin LD50 = 0.07 µg larvae-1). Overall, our findings pointed out that NEs can increase twofold the insecticidal efficacy of EO, and thus, they can be considered further for the development of botanical insecticides.

Iron supplementation in young iron-deficient females causes gastrointestinal redox imbalance: protective effect of a fermented nutraceutical.

The aim of this study was to assess whether the concomitant supplementation of certified fermented papaya preparation (FPP, ORI, Gifu, Japan) together with iron supplementation could beneficially affect lipid peroxidation either systemically and at a intraluminal gut level in women with low iron stores. Treatment compliance and iron absorption was assessed as well. Fifty-two non-pregnant, fertile, non-smokers, healthy women with iron deficiency were recruited. The women were given iron supplements (100 mg Fe/d as ferrous sulfate) to be taken daily for 12 weeks (group A). Group B patients were also supplemented with 6g/day of a FPP. A detailed life style questionnaire was administered to all subjects. Iron, ferritin, transferrin receptors (Tf R) and malondialdehyde (MDA) in plasma were measured. The RBCs lysate was used for the estimation of superoxide dismutase (SOD) and glutathione peroxidase (GPx). The total and free iron concentration as well as analysis of oxidative stress in the feces was measured. FPP-supplemented subjects showed a significantly lower degree of gastrointestinal discomfort (p less than 0.05) and abolished the iron supplementation-induced increase of MDA (p less than 0.001) and the depletion of SOD and GPx (p less than 0.01). Moreover, the nutraceutical co-administration brought about a significant reduction of gut oxidative damage and lower fecal content of either total and free iron (p less than 0.05 vs group A). Overall, group B showed a better TfR/ferritin ratio response (p less than 0.05 vs group A). While iron supplementation maintains its clinical relevance considering the prevalence of iron deficiency among females, a careful clinical evaluation and a protective nutraceutical co-administration, as our data suggest with FPP, should be considered.

Beneficial effect of a sturgeon-based bioactive compound on gene expression of tumor necrosis factor-alpha, matrix metalloproteinases and type-10 collagen in human chondrocytes.

In the present study, we examined the effect of a marine bioactive compound containing high-purity caviar-derived DNA, collagen elastin and protein extracts from sturgeon (LD-1227, Caviarlieri, Laboratoires Dom, Switzerland) on IL-1beta-induced activation and production of TNFalpha and MMP-13 in human osteo-arthritis (OA) chondrocytes and intracellular signaling factors. Human chondrocytes were derived from OA cartilage and stimulated with IL-1beta. Gene expression of TNFalpha, MMP-13, MMP-1 and Col10A1 was measured by quantitative RT-PCR. TNFalpha protein in culture medium was determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the MMP-13 production in the culture medium and the activation of NF-kB. DNA binding activity of NF-kB p65 was determined using a highly sensitive and specific ELISA. MMP-13 activity in the culture medium was assayed by gelatine zymography. LD-1227 significantly decreased IL-1beta-stimulated gene expression and production of TNFalpha, MMP-1, MMP-13 and Col10A1 in human chondrocytes. The inhibitory effect of LD-1227 on the IL-1beta-induced expression of these genes was mediated at least in part via suppression of NF-kB p65. These data show that LD-1227 can inhibit IL-1beta-induced proliferation and inflammatory reactions via inhibited activation of the transcription factor NF-kB pathway in human chondrocytes derived from OA patients. These novel pharmacological actions of LD-1227 on IL-1beta-stimulated human OA chondrocytes provide suggestions that this marine biology compound may inhibit cartilage degradation by suppressing IL-1beta-mediated activation and the catabolic response in human chondrocytes.

Effective properties of a sturgeon-based bioactive compound on stress-induced hippocampal degeneration and on in vitro neurogenesis.

The aim of this study is to test the activity of a marine bioactive compound containing high-purity caviar-derived DNA, collagen elastin and protein extracts from sturgeon (LD-1227, Caviarlieri, Laboratoires Dom, Switzerland) to exert neuroprotective properties in an experimental setting while also being potential triggers of neurogenesis in a separate in vitro study. Supplementation with high-DHA mixture of LD-1227 was applied for 30 days to stress model rats. Both supplementations significantly mitigated the histological brain damage when analyzing hippocampal subregions and corticosterone level. However, LD-1227 was most significantly efficient in preventing SOD, Catalase and ascorbic acid decrease in brain tissue. Both supplementations stimulated neurogenesis in vitro and neuron markers in particular but og olygodendrocyte markers and glia increased only in LD-1227-enriched medium. Taken together, these data suggest that LD-1227 is able to significantly protect the brain structure redox system to higher degree than DHA. Moreover, from in vitro study it appears that marine bioactive compound, through it wide array of small unsaturated fatty acids, phospholipids and neurotransmitter precursors, is likely to influence neuronal and glial lineage to act differently from a DHA-rich mixture.

Is there a potential application of a fermented nutraceutical in acute respiratory illnesses? An in-vivo placebo-controlled, cross-over clinical study in different age groups of healthy subjects.

The role of oxidants in viral diseases is fairly complex because it includes metabolic regulation both of host metabolism and viral replication. However, a role for reactive oxygen species (ROS) and reactive nitrogen species (RNS) as mediators of virus-induced lung damage is supported by studies and antioxidants can thus be expected to act at many different levels. The aim of the present pilot study was to test an antioxidant nutraceutical approach on some relevant immunological parameters known to be affected in common seasonal respiratory tract infection. The study population consisted of 90 sedentary healthy patients, previously selected as being GSTM1-positive, divided into three groups: A) 20-40 years; B) 41-65 years; B) over 65 years. Each patients was administered a life style and dietary questionnaire. Subjects were supplemented for 6 weeks with either 9g/day (4.5g twice a day sublingually) of a fermented papaya preparation (Osato Research Institute, Gifu, Japan) or placebo. After a further month period of wash out, subjects were treated again in a crossover manner. Parameters checked were as follows: routine blood tests with WBC formula, saliva flow rate and secretary IgA and lysozyme production and redox gene expression of Phase II enzyme and SOD from upper airways cells (from nasal lavage). Salivary secretion rate showed an age-related decline and was significantly increased by FPP supplementation only in the youngest age-group (p less than 0.05). Subjects treated with FPP showed a significantly higher lever of IgA and lisozyme production., irrespective of age group while their baseline production was significantly lower in the oldest age-group as compared to the youngest one (C vs A, p less than 0.05). FPP treatment brought about a significant upregulation of all phase II enzyme and SOD gene expression tested in nasal lavage cells. In conclusion, FPP supplementation during 1 month resulted in higher salivary IgA and increase in phase II and SOD enzyme expression, i.e the most important antioxidant in the respiratory tract. The biological significance of these effects i.e., whether it will help reducing the whole respiratory oxidative stress in the human airway and, hopefully, the incidence and/or severity of URTI remains to be demonstrated in longer clinical trials.

Effect of a fermented nutraceutical on thioredoxin level and TNF-alpha signalling in cirrhotic patients.

The aim of this study is to gain further insights into the possible nutraceutical effect on redox balance via thioredoxin (Trx) modulation and on the intrinsic susceptibility of monocytes to generate an inflammatory response. The study group consisted of thirty-two patients with compensated Child A-C, HCV-related cirrhosis. The patients were supplemented for 6 months with 6g/day of a certified fermented papaya preparation (FPP). Fifteen unsupplemented, age/gender-matched healthy subjects served as controls. The patients filled in a detailed diet-life style questionnaire, and blood samples were collected to test routine biochemistry, Trx, redox status (GSH, GSSG, GSH/GSSG ratio, 4-HNE and alpha-tocopherol). Moreover, isolated monocytes were tested for ex-vivo LPS-stimulated TNF-alpha production and TNF-alpha mRNA. As compared to control, patients with liver cirrhosis showed a significantly higher serum level of Trx. A significant correlation occurred with GSH/GSSG ratio in Child B and C patients. FPP supplementation brought about a significant reduction of Trx with levels comparable to the ones of healthy controls. Ten patients Child C (31.2 percent) showed borderline low levels of alpha-tocopherol while all cirrhotic patients, as a whole, showed a significantly abnormal redox balance. Supplementation with FPP did not modify alpha-tocopherol depletion but significantly improved redox balance parameters. Patients with liver cirrhosis showed a significantly upregulated TNF-alpha production in a time-dependent manner and this effect was more pronounced in more advanced stages of the disease and showed a significant correlation with alpha-tocopherol level. Supplementation with FPP significantly, although partially, downregulated TNF-alpha production from monocytes. Taken altogether, it would appear that the typical oxidative-inflammatory biochemical milieu of these patients is mirrored by a significant TNF-alpha upregulation at a monocyte level while a targeted nutraceutical might be a potentially amenable intervention to be part of validated scheduled treatments.

Inhibition of human breast cancer cell growth and enzymatic activity by a fermented nutraceutical: an in vitro and in vivo study .

Human breast cancer cell lines MCF-7 (ER-positive) and Hs578T (ER-negative) were cultured and one lot incubated for 48 h with 5-50 mug/ml of a fermented phytocompound (MK: Manda-Koso, Innoshima, Japan). In vitro, it appeared a dose-dependent decrease of cell viability (5-57%) in MK group in both cell lines (P < 0.001, plateau: 30 microg/ml), decreased beta-galactosidase activity, enhanced apoptosis, and inversely increased Bax/Bcl2 ratio (P < 0.01) with an upregulation of p53 (P < 0.05). In the in vivo model, Balb-c mice were inoculated with tumor cells and the treatment group was fed with 20 mg of MK. Tumor weight in MK-fed group was time-course reduced by 22% to 51% at 2 and 4 weeks, respectively (P < 0.05) with increased survival (P < 0.05). Tumour tissue of MK-fed mice showed a downregulated Bcl-2 with increased Bax/Bcl-2 ratio, reduced PCNA, and activated caspase 3. Although more studies are ongoing to foster the clinical applicability of MK integrated within a rational chemopreventive and therapeutic strategy, a p53-mediated mechanism is likely to play a relevant role, besides its reported antioxidant capacity, NK cell activity enhancement, cancer-cytostatic activity properties.

Effect of modified alkaline supplementation on bone metabolic turnover in rats.

This study aims to determine the effects of a high protein diet and alkaline supplementation on bone metabolic turnover in rats. Eight-week-old male Sprague-Dawley rats were investigated by bone status, including bone mineral density (BMD) and biomechanical markers from blood and urine. Thirty rats were randomly divided into three groups and treated for 8 weeks as follows: baseline control group (n. 10, C), high-protein supplemented diet group (n. 10, chronic acidosis, CA group) and supplemented chronic acidosis (n.10, SCA). Diet-treated rats were fed an acidic high-protein diet and the supplementation consisted in a modified alkaline formula (Basenpulver, NaMed, Italy). At the end of the experimental period, the rats were sacrificed, blood samples were drawn and femur and tibia were removed for analysis of bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA). In the CA group, 24-hour urinary calcium (Ca) and phosphorus (P) excretion were increased 2.1-fold (p<0.05 vs normal diet controls) as well as kidney weight. However, serum Ca and P concentration, as well as urinary Dpd excretion were not significantly changed. Femural and tibial BMD was significantly decreased in the CA group (p<0.05), but alkaline supplementation prevented such phenomenon (p<0.05 vs CA). These results suggest that blood Ca and P concentrations in chronic acidosis condition during the 12-week supplementation might be maintained by hypercalciuria and hyperphosphaturia at the expenses of bone structure. However, modified alkaline supplementation is able to prevent such derangements.

Nutraceutical strategy in aging: targeting heat shock protein and inflammatory profile through understanding interleukin-6 polymorphism.

The aging process is paralleled by two- to fourfold increases in plasma/serum levels of inflammatory mediators, such as cytokines and acute-phase proteins. In this study we assessed the inflammatory profile and polymorphism of healthy elderly subjects and the influence of a nutraceutical supplement. Forty elderly, generally healthy subjects were recruited, divided into two matched groups, and given either a fermented papaya preparation 9 g/day by mouth or the same amount of placebo. Treatments were carried out in a cross-over manner with a 3-month supplementation period followed by a 6-week washout period between treatments. Ten healthy young subjects served as controls. Interleukin-6 (IL-6) promoter -174 G/C polymorphism genotype was determined together with blood levels for redox status, proinflammatory cytokines, high sensitivity C-reactive protein, and serum 70 kDa heat shock protein (Hsp70) concentrations. Tumor necrosis factor-alpha and IL-6 were higher in elderly subjects (P < 0.05 versus young controls). The concentration of Hsp70 inversely correlated with markers of inflammation in -174 G/C-negative subjects (r = 0.62, P < 0.05). Nutraceutical intervention normalized the inflammatory parameters (P < 0.05) with a rise of Hsp70 (P < 0.05). This suggests that healthy elderly individuals may have a proinflammatory profile playing as a downregulating factor for inducible Hsp70, particularly if -174 G/C-negative. A nutraceutical intervention seems able to beneficially modulate such a phenomenon.

Experimental radiotherapy-induced enteritis: a probiotic interventional study.

OBJECTIVE: Acute radiation of the small intestine causes an immediate and potentially reversible effect on the sensitive regenerative epithelium of the intestinal mucosa while markedly altering the overall intestinal ecosystem. The aim of the present study was test a novel probiotic mixture formulation (Microflorana-F) in an experimental model of acute radiation enteritis with particular interest in endotoxinemia and bacterial translocation. MATERIALS AND METHODS: Male Wistar rats allocated to three groups were fed for 7 days with: (A) a standard balanced diet; (B) a standard diet with the addition of 1 mL t.i.d. of Microflorana-F and (C) the same probiotic but after heat inactivation. Under ketamine anesthesia, abdominal irradiation was performed at a single dose rate of 20 Gy. Sham-radiated healthy rats served as a control (D). Standard food and active/inactive probiotic supplementation schedule was maintained throughout the study period. When they were killed 14 days later a midline laparotomy and a medium sternotomy was carried out. The mesenteric lymph nodes, whole spleen and liver samples as well as blood, the portal vein and bile samples were cultured. Endotoxinemia was also measured. RESULTS: Early deaths (1 week) occurred mostly in rats fed standard food or inactivated probiotic. The endotoxin level significantly increased in irradiated rats fed standard food and inactivated probiotic while supplementation with the active form of the probiotic mixture significantly improved such parameters (P < 0.05). After radiation injury, mesenteric lymph nodes and portal blood were the samples most frequently yielding bacterial growth. Treatment with only the active form of probiotic significantly reduced the incidence of bacterial contamination in all samples. CONCLUSIONS: These data suggest that the manipulation of gut ecosystem by biologically effective probiotic preparations might be a worthwhile therapeutic and preventive tool in radiation-induced enteritis.

Phytotherapeutic compound YHK exerts an inhibitory effect on early stage of experimentally-induced neoplastic liver lesions.

The aim of this study was to investigate the effects of the herbal compound YHK on hepatocarcinogenesis induced by diethylntrosamine (DEN) in Sprague Dawley rats. Rats were randomly divided into 3 groups and followed up for 15 weeks. Groups 1 was given standard food and represented the healthy control. Liver preneoplastic foci were induced using the DEN method in groups 2 and 3 (20 rats each). However, group 3 was concomitantly given 50mg/kg/day of YHK. For quantitative assessment of liver preneoplastic foci, the placental form of glutathione-S-transferase (GST-P) positive foci were measured using immunohistochemical staining and image analysis. Treatment using DEN caused a significant decrease in body weight and increase in liver weight compared to the control group while concomitant supplementation with YHK prevented body weight loss and liver weight increase. As compared to DENonly treated rats, the group given YHK showed a significant decrease in the number, size and volume of GSTP- positive foci. Moreover, co-administration of YHK significantly reduced the incidence, number, size and volume of hepatocellular carcinoma. Anti-inflammatory, anti-fibrotic as well as antioxidative properties of this compound are mechanisms which are likely to be advocated for to explain its protective effect. It is concluded that herbal compound YHK by preventing hepatocarcinogenesis in DEN-induced liver preneoplastic lesions in rats has the potential to a large clinical application as a functional food.

Liver exposure to xenobiotics: the aging factor and potentials for functional foods.

Hepatocytes isolated from 20- and 4-month Wistar rats and cultured with or without alpha-linolenic acid (LNA) were then added with nutraceutical YHK or sylibin before the test with iron or copper. Overall, YHK proved to be more effective than sylibin in Fe/Cu-induced peroxidative damage on normal and LNA-loaded hepatocytes (p < 0.05). YHK exerted a significant protection against DPPH radical-scavenging activity in the "old" group (p versus sylibin) and against lipophilic generators in both age groups (p < 0.05 versus sylibin). Both compounds were ineffective on age-related increase of surface-charge density. These preliminary data suggest that age per se enhances the vulnerability of hepatocytes to xenobiotics, whereas some safe nutraceuticals seem to exert significant protective effects.

The aging gut motility decay: may symbiotics be acting as "implantable" biologic pace-makers?

Motility recording of small and large intestine was performed in old Wistar rats divided into three groups: (a) standard diet, (b) standard diet plus a symbiotic preparation, and (c) standard diet plus a heat-inactivated symbiotic preparation. SCM-III. significantly increased the myoelectric activity of small intestine and colon (p < 0.01 versus [a] and [c]) paralleling "young" values of 4-month-old rats and increased the spike burst frequency in the proximal-distal colon (p < 0.05). SCM-III significantly increased the frequency and duration of spike bursts in the jejunum, transverse-distal colon, and defecation frequency, while decreasing the intervals of migrating motor complex in the colon (p < 0.01) to "young" values with an increased mRNA expression of VIP (p < 0.05). Gut flora manipulation aimed to modulate myoelectric activity can tentatively help reversing age-related motility decay.

Preventive strategy for Candida gut translocation during ischemia-reperfusion injury supervening on protein-calorie malnutrition.

OBJECTIVE: The aim of the present study was to test the hypothesis that protein-calorie malnutrition aggravates the gut translocation of Candida albicans triggered by mesenteric ischemia-reperfusion (IR) injury in an experimental model while testing a natural product containing the antifungal anethole/polygodial mixture (Kolorex). METHODS: MFI strain white mice (n = 90) were randomly allocated to a 4-week dietary regimen: (1) standard pellet diet containing 25% casein; (2) low-protein (2.5%) casein diet; (3) as group 2 plus oral supplementation with 20 microL of a 5% solution of Kolorex during the last 4 days. Twenty rats from each of these groups (termed 1a, 2a and 3a) were orally inoculated with Candida suspension 6 h prior to mesenteric IR injury. Animals of each group but without Candida inoculation (termed 1b, 2b and 3b) served as control. A colon permeability study was carried out as well. Rats were killed prior to the IR injury and 3 h afterwards. Control rats were killed at the same time. RESULTS: Over 60% of the mesenteric lymph nodes and 30% of kidney samples were positive for C. albicans in the low-protein-fed rats after IR injury. Kolorex significantly decreased that rate of positivity and also significantly reduced the concentration of C. albicans per gram of each positive tissue sample examined. Protein-calorie malnourished animals showed a statistically significant increase in colon permeability and this phenomenon further increased after IR injury. The groups of rats treated with Kolorex compound showed a partial, although significant, improvement of this parameter. CONCLUSIONS: These results suggest that Kolorex might exert a competitive effect against with C. albicans colonization. The present study represents the first experimental in vivo investigation of the anethole/polygodial-containing compound under the specific conditions of calorie-protein malnutrition and the results have potential clinical interest.

Anti-inflammatory and neuroprotective effect of a phytoestrogen compound on rat microglia.

Ovariectomized Wistar rats received orally 15 mg/kg of a phytoestrogen compound (genistein, daidzein, glycitein, black cohosh, angelica sin., licorice, vitex agnus) for 2 weeks to test its ability to modulate inflammatory microglia response. Microglial proliferation was tested by trypan blue and by absorbance. Serial supernatant sampling was performed for 24 h to check TNF-alpha, IL-beta, IL-6, and TGF-beta. LPS caused a time course increase of all cytokines, with IL-beta and TNF-alpha peaking at the 12th hour, whereas IL-6 and TGF-beta peaked at the 24 h observation. Rats fed with the phytoestrogen displayed a significantly lower level of proinflammatory cytokines and a higher level of TGF-beta, as shown also by Western blot analysis. This finding may offer promise in the field of nutraceutical intervention.

Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect.

OBJECTIVE: The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. METHODS: Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. RESULTS: Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. CONCLUSIONS: Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.

Reinforcing effect of organo-modified layered silicates in high-density polyethylene.

This study focuses on the understanding of the reinforcing effect given by organo-modified layered silicates to a high-density polyethylene and the influence on the crystallization properties of this polymer. The addition of organo-modified clay to high-density polyethylene resulted in an evident increase in the tensile and flexural Young's modulus of the material with respect to unfilled polymer. The morphology, crystallinity, and thermo-oxidative stability of such nanocomposites were investigated using X-ray diffraction, transmission electron microscopy, differential scanning calorimetry, and oxidation induction time test. The materials obtained show tactoid as well as intercalated and exfoliated structures with different dominant states depending on the loading level and process conditions. It was observed that organic ions not only change mixing behavior but also influence material properties, including the degree of crystallinity and the stability to the thermo-oxidative phenomena.

CBF changes during headache-free periods and spontaneous/induced attacks in migraine with and without aura: a TCD and SPECT comparison study.

BACKGROUND: The aim of the present study was to compare cranial arteries blood flow velocity as measured by means of transcranial Doppler sonography (TCD) with mean regional cerebral blood flow (rCBF) as measured by means of single photon emission computed tomography (SPECT) in migraine with and without aura during headache-free periods and spontaneous and/or induced attacks. METHODS: Regional cerebral blood flow (rCBF) and systematic ultrasonic Doppler flow were studied by Technetium-99m hexamethylpropilaminoxime (99mTc-HM-PAO) single photon emission computed tomography (SPECT) and transcranial Doppler sonography (TCD) respectively in controls (n=14) and in migraine with (n=13) and without aura (n=35) during headache free-intervals and spontaneous/histamine-induced attacks. RESULTS: In the migraine without aura group, Doppler flow examinations of the common carotid artery, external and internal carotid artery, ophthalmic artery and middle cerebral artery bilaterally did not reveal significant changes as compared with controls. During attacks, TCD examinations showed a moderate, although not statistically significant, reduction of blood flow velocity in the middle cerebral artery and in the internal carotid artery bilaterally as related to the interictal phase, concomitant with an increase of the flow velocity in the ophthalmic and external carotid artery. SPECT of these patients did not show, on the average, rCBF asymmetries during pain-free periods, although positive findings (i.e., focal hypoperfusion) were found in approximately half of the cases. During attacks, 74% of patients displayed a unilateral hypoperfusion, mainly in the occipital region. Low-flow areas were generally but not always consistent with the site of pain. In the migraine with aura group, significant reduction of blood flow velocity in middle cerebral artery was recorded by TCD on the affected side during attacks, as compared with the pain-free side. Hypoperfusion was registered between attacks by SPECT in approximately 2/3 of the patients. During attacks, a marked reduction of rCBF occurred in most patients (85%), mainly in the parieto-occipital region. The posterior rCBF asymmetries revealed at the SPECT and consistent with the general reduction of blood flow velocity documented by TCD may be related to cerebrovascular tone instability. CONCLUSIONS: Our findings do not support the paradigm that migraine with and without aura are two different entities.

Postoperative pain in neurosurgery: a pilot study in brain surgery.

The incidence, magnitude, and duration of acute pain experienced by neurosurgical patients after various brain operations are not precisely known, because of a lack of well-designed clinical and epidemiological studies. We assessed these important pain variables in 37 consecutive patients who underwent various brain neurosurgical procedures. Postoperative pain was more common than generally assumed (60%). In two-thirds of the patients with postoperative pain, the intensity was moderate to severe. Pain most frequently occurred within the first 48 hours after surgery, but a significant number of patients endured pain for longer periods. Pain was predominantly superficial (86%), suggesting somatic rather than visceral origin and possibly involving pericranial muscles and soft tissues. Subtemporal and suboccipital surgical routes yielded the highest incidence of postoperative pain. Age and sex were significantly associated with the onset of pain, with female and younger patients reporting higher percentages of postoperative pain. Psychological Minnesota Multiphasic Personality Inventory profiles of patients with and without pain significantly differed on the Hypochondriasis scale, with patients without pain scoring unexpectedly higher than patients with pain. It is possible that hypochondriasis serves as a defense mechanism against pain, at least in some patients. Results of this pilot study indicate that postoperative pain after brain surgery is an important, although neglected, clinical problem, that deserves greater attention by surgical teams, to provide better and more appropriate treatment.