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.

Current trends in etiology, prognosis and therapeutic aspects of Parkinson's disease: a review.

Parkinson's disease (PD) is a movement disorder, mainly affecting population consisting of the aged. PD occurs chiefly due to progressive loss of dopaminergic neurons in nigrostriatal pathway. Largely, PD patients suffer from non-motor symptoms, such as depression, anxiety, fatigue, and sleep disorders, that needs further investigation and addressing during PD research. Depression in PD is a predominant and complex symptom, and its pathology exists extrinsic to the nigrostriatal system. This disease can  ultimately be managed by a combination of regular physiotherapy and proper medication. Taking together the present scenario of PD, including the nature of disease, characteristics, treatment, diagnosis of the patients with PD, these outcomes were reviewed to be explored along with many speech-based solutions to PD in this study. This neurodegenerative disorder needs advancement in  research and development which  can help patients with PD to lead a normal life.

Gut microbiota in health and disease: an overview focused on metabolic inflammation.

In concern to the continuously rising global prevalence of obesity, diabetes and associated diseases, novel preventive and therapeutic approaches are urgently required. However, to explore and develop such innovative strategies, a meticulous comprehension of the biological basis of these diseases is extremely important. Past decade has witnessed an enormous amount of research investigation and advancement in the field of obesity, diabetes and metabolic syndrome, with the gut microbiota receiving a special focus in the triangle of nutrition, health and diseases. In particular, the role of gut microbiota in health and diseases has been one of the most vigorous and intriguing field of recent research; however, much still remains to be elucidated about its precise role in host metabolism and immune functions and its implication in the onset, progression as well as in the amelioration of metabolic ailments. Recent investigations have suggested a significant contribution of the gut microbiota in the regulation and impairment of energy homeostasis, thereby causing metabolic disorders, such as metabolic endotoxemia, insulin resistance and type 2 diabetes. Numerous inflammatory biomarkers have been found to be associated with obesity, diabetes and risk of other associated adverse outcomes, thereby suggesting that a persistent low-grade inflammatory response is a potential risk factor. In this milieu, this review intends to discuss potential evidences supporting the disturbance of the gut microbiota balance and the intestinal barrier permeability as a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.

The gut microbiota and its correlations with the central nervous system disorders.

A mutual impact of gastrointestinal tract (GIT) and central nervous system (CNS) functions has been recognized since the mid-twentieth century. It is accepted that the so-called gut-brain axis provides a two-way homeostatic communication, through immunological, hormonal and neuronal signals. A dysfunction of this axis has been associated with the pathogenesis of some diseases both within and outside the GIT, that have shown an increase in incidence over the last decades. Studies comparing germ-free animals and animals exposed to pathogenic bacterial infections, probiotics or antibiotics suggest the participation of the microbiota in this communication and a role in host defense, regulation of immunity and autoimmune disease appearance. The GIT could represent a vulnerable area through which pathogens influence all aspects of physiology and even induce CNS neuro-inflammation. All those concepts may suggest the modulation of the gut microbiota as an achievable strategy for innovative therapies in complex disorders. Moving from this background, the present review discusses the relationship between intestinal microbiota and CNS and the effects in health and disease. We particularly look at how the commensal gut microbiota influences systemic immune response in some neurological disorders, highlighting its impact on pain and cognition in multiple sclerosis, Guillain-Barrè Syndrome, neurodevelopmental and behavioral disorders and Alzheimer's disease. In this review we discuss recent studies showing that the potential microbiota-gut-brain dialogue is implicated in neurodegenerative diseases. Gaining a better understanding of the relationship between microbiota and CNS could provide an insight on the pathogenesis and therapeutic strategies of these disorders.

Irritable bowel syndrome: new findings in pathophysiological and therapeutic field.

Irritable bowel syndrome (IBS) is a high prevalence disease, whose symptoms are reported by a large number of young adults with significant effects on quality of life and social costs. Traditionally, IBS has been treated with dietary and lifestyle modification, fiber supplementation, psychological and pharmacological therapy. Since its complex and multifactorial etiopathogenesis is only partially known, therapeutic choices may be difficult and not always effective. New research efforts focused on the role of relationship between central nervous system and gut disorders (brain-gut axis), altered composition of gut microbiota (e.g. an eight times increased risk for IBS after Salmonella infection), immune activation with an increased number of T lymphocytes and mast cells associated with mucosa as well as an increased level of pro-inflammatory cytokines (IL-10 and IL-12, suggesting Th1 polarization), visceral hypersensitivity causing perception of pain even for minimal abdominal distension. Based on these findings, new possibilities of treatment are emerging with encouraging outcomes. Attention is directed to drugs that showed good tolerability profile and poor systemic absorption, which may make them suitable for repeated or long term treatments, as frequently required in patients with IBS. They have been successfully used drugs such as tachykinin receptors antagonists, tryptophan hydroxylase inhibitors, bile acid sequestrants, µ agonist and δ antagonist opioid receptors. Recent studies are discussed in this review, focusing both on new therapeutic approaches and innovative adaptation of previously available treatments.

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.

A double-blind, rct testing beneficial modulation of BDNF in middle-aged, life style-stressed subjects: a clue to brain protection?

INTRODUCTION: The aim of this prospective study was to see whether LD-1227, a quality-controlled marine nutraceuticals shown to protect experimental stress-induced hyppocampal degeneration, could beneficially modulate BDNF, as measured in the serum, in otherwise healthy but work-stressed individuals. MATERIALS AND METHODS: Forty-eight men and women between the ages of 38 and 62 reporting high-demanding work activity but with an overall positive attitude towards their personal life were recruited. Subjects were divided in two group (24 patients each) and blindly supplemented for 2 month with: a) LD-1227 400mg or b) placebo. A third group of healthy non-stressed subjects was used as well. Blood samples were taken before and after the supplementation period. Unstimulated saliva was collected and tested for amylase while serum levels were used to measure BDNF. State Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI) and psychological well-being assessment (PSWB) were measured too. Patients with Val66Met functional polymorphism of BDNF excluded those given their reported association with an impaired release of BDNF. RESULTS: RESULTS showed that, as compared to healthy, non-stressed individuals, stressed ones has a trend decrease of BDNF and this was significantly increased by LD 12-1227 supplementation and the same inverse phenomenon occurred to salivary amylase (p<0.05). No change was noted in the PSQI score but, either STAI or PSWB tests scored better in LD-1227 supplemented subjects. CONCLUSION: The present data suggest that LD-1227 is beneficially affecting neuromodulation and related symptoms during common stressful life conditions and may have the potential as tools in a neuroprotective clinical strategy.

Effect of Celergen, a marine derivative, on in vitro hepatocarcinogenesis.

The aim of this study was to test for a potential anticarcinogenic effect of Celergen, a marine derivative devoid of traceable amounts of inorganic arsenic, on cell proliferation, cell cycle progression and apoptosis in the HepG2 human liver cancer cell line. Celergen significantly inhibited the proliferation of cancer cells in a dose-dependent manner while limiting the cell cycle progression at the G1 phase and significantly inducing apoptosis. Further examination showed that Celergen enhanced expression of the p21(CIPl1WAF1), GADD153 genes and downregulated the c-myc gene. These results suggest that Celergen exerts promising chemopreventive properties to be further investigated.

Prophylactic strategies in recurrent vulvovaginal candidiasis: a 2-year study testing a phytonutrient vs itraconazole.

The aim of the present study was to assess the clinical efficacy of a one week/month treatment with a phytocompound with antimycotic properties (K-712, with following 100 mg composition: 10 mg of oleoresin from Pseudowintera colorata at 30 percent concentration in Polygodial together with trace amounts of Olea europea) in recurrent vulvo-vaginal candidiasis (RVVC), as compared to once a week treatment with an azole drug for 24 months follow up. This prospective randomized study involving 122 women (19 to 63 years old) with a history of proven episodes of RVVC in the prior 12 months. Patients were allocated in two treatment groups of 61 patients each and given A) Itraconazole 200 mg orally once a week or B) 1 tab twice a day of K-712 for one week/month. Each treatment schedule was well tolerated with 19 patients in the azole group complaining of transient mild symptoms (nausea, abdominal discomfort, unpleasant taste), while only 3 patients on K-712 reported slight dyspepsia. The number of relapses was significantly lower in the K-712-treated group as compared to the itraconazole-group (22 vs 39, p less than 0.05). Moreover, the former group showed a significantly decreased number of cases resistant or dose-dependent susceptible as compared to group A (p less than 0.05 vs itraconazole) and the same occurred for the occurrence of non-albicans species (group A 64.1 percent vs group B 31.8 percent, p less than 0.05). The overall mycological cure at the end of the 2-year study showed a comparable benefit between the two groups. From these data it appears that the present antifungal phytonutrient is equally effective as itraconazole in the overall treatment of RVVC over a 2-year follow-up, but yielding a significantly better prophylactic effect and also maintenance benefit with lower relapse rate, antifungal susceptibility and growth of azole-resistant species.

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.

First outbreak of food poisoning caused by Salmonella enterica subspecies enterica serovar Berta in Italy.

AIMS: To provide an epidemiologic interpretation of a suspected outbreak of food poisoning caused by Salmonella enterica subspecies enterica serovar Berta strains isolated from humans and from the leftovers of the implicated foods (cream, dairy-based desserts and eggs). METHODS AND RESULTS: We have correlated the similarity between the strains through genotyping with Pulsed Field Gel Electrophoresis (PFGE), studying antimicrobial sensitivity patterns and epidemiological investigation. The clonal origin of the outbreak was confirmed by all laboratory tests. PFGE analysis of the restriction profiles obtained with XbaI and SpeI revealed a certainly correlation from the strains isolated from the various sources, while the antimicrobial sensitivity pattern was the same in all cases, with all strains sensitive to all antibiotics tested. CONCLUSIONS: Poor hygiene conditions in the facility concerned, lack of hygiene in food handling, high summer temperatures and positive cultures from asymptomatic staff could all be implicated in the infection, with food being the means through which it spread. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes the first outbreak of food poisoning caused by Salmonella enterica subspecies enterica serovar Berta (Salmonella Berta) reported in Italy. It confirms the importance of correlating epidemiological investigations with genotyping and phenotyping to understand the dynamics of infection.

Milk, milk products, and disease free health: an updated overview.

The cow and its milk have been held sacred in the world since the dawn of human civilization. Indian ancient Vedic texts describe the virtues of milk and dairy products, as is authenticated by modern scientific principles and proofs. Therefore, milk has been considered as one of the most natural and highly nutritive part of a daily balanced diet. Currently, the integration of advanced scientific knowledge with traditional information is gaining incredible momentum toward developing the concept of potential therapeutic foods. Furthermore, new advances toward understanding the therapeutic roles of milk and milk products have also given a new impetus for unraveling the age old secrets of milk. At present, the best-known examples of therapeutic foods are fermented milk products containing health promoting probiotic bacteria. In the present article, we have tried to review the various aspects of the therapeutic nature of milk and fermented dairy products in a highly up-dated manner, and offer an in-depth insight into the development of targeted therapeutic future foods as per the requirements of consumers.

Effects of chronic slow release-lanreotide treatment on insulin-like growth factor system and metabolic parameters in acromegalic patients.

Insulin and IGF binding protein (IGFBP)-1 are linked by negative association. Somatostatin (SS) reduces insulin secretion by acting on pancreatic ß-cell and also by decreasing GH secretion. SS analogues in acromegaly reduce total IGF-I levels inhibiting GH hypersecretion, but they also reduce free IGF-I bioactivity increasing IGFBP-1 levels by inducing insulin decrease. In 13 acromegalic patients we studied GH, IGF system, insulin, and glucagon levels at baseline and at 7 days, 1 and 6 months under treatment with slow release (SR)-lanreotide (LAN) (60 mg im monthly). The hormonal and metabolic response to arginine (ARG) (0.5 g/kg iv in 30 min) was also studied at each time point. LAN decreased GH, total IGF-I, and IGFBP-3 levels at each time point. Insulin and glucagon levels were reduced, while IGFBP-1 and free IGF-I levels were increased by LAN at day 7 and after 1 month only. LAN did not modify the GH, insulin, glucagon, glucose, and IGFBP-1 responses to ARG. At each time point ARG-induced insulin increase was coupled to increase in glucagon and IGFBP-1 levels. This study shows that acromegalic patients under chronic treatment with LAN display: a) inhibition of GH and total IGF-I levels, not coupled to persistent decrease in free IGF-I levels; b) persistent decrease in IGFBP- 3 but transient decrease and increase in insulin and IGFBP- 1, respectively; c) unchanged hormonal and metabolic response to ARG. Our findings also show that ARG stimulates IGFBP-1 despite marked increase in insulin secretion; this escape from the negative relationship linking insulin and IGFBP- 1 would likely reflect the ARG-induced glucagon increase.

Advantage of carbonate-versus citrate-based alkalinization on bone metabolism in moderately exercising aged male rats fed an acidogenic diet.

This study aims to determine the effects of different alkaline supplementations on high protein diet-induced abnormalities affecting bone metabolism in rats which were also undergoing physical exercise of moderate intensity. Sixty elderly Sprague-Dawley rats were randomly divided into four groups of 10 rats each and treated for 16 weeks as follows: baseline control group fed normal food (C); acidic high-protein diet supplemented group (chronic acidosis, CA group), bicarbonate-based alkaline formula (Basenpulver, Named, Italy) supplemented chronic acidosis (BB-CA) and citrate-based alkaline supplement (CB-CA). Throughout the supplementation period, rats were put on a treadmill training mimicking a moderate level of exercise. In the CA group, 24-hour urinary calcium (Ca) and phosphorus (P) excretion were increased over 30 percent (p<0.05 vs normal diet controls). However serum Ca was not significantly changed. Femural and tibial BMD and BMC was significantly decreased in the CA group (p<0.05) but both alkaline supplementations prevented such phenomenon (p<0.05 vs CA), without significant difference between the two formulations although the BB-CA group showed significantly more preserved trabecular bone volume (p<0.05 vs CB-CA group). An increased level of over 50 percent of urinary Dpd observed in the CA group (p<0.001) was reverted to normal by both supplementations (p<0.001 vs CA group). The same applied to urinary net acid excretion (p<001) with BB-supplementation performing better than CB-supplementation (p<0.05). Moreover, while the latter did not modify Nterminal telopeptide value, BB-supplementation significantly normalized this parameter (p<0.05 vs CA group) which exercise and acidic protein diet had modified (p<0.01 vs control diet). Overall, the present study shows that a bicarbonate-based alkaline formula, when administered to a dose amenable to clinical use, may significantly protect bone structure in exercising aged animals to a greater extent than a quali/quantitavely similar citrate-based formula.

Beneficial nutraceutical modulation of cerebral erythropoietin expression and oxidative stress: an experimental study.

The main object of this study is to examine the effect of Klamin®, a nutraceutical containing phenylethylamine, phycocyanins, mycosporine-like aminoacids and aphanizomenon flos aquae-phytochrome on the learning and memory ability, the oxidative status and cerebral erythropoietin and its receptor EPO/EPOR system in prematurely senescent (PS) mice. A total of 28 PS mice, selected according to a prior T-maze test, and 26 non-prematurely senescent mice (NPS) mice were chosen. PS animals were divided into 3 groups and followed for 4 weeks: A) normal chow diet; B) added with Klamin® at 20 mg/kg/day (low dose); C) added with Klamin® at 100mg/kg/day (high dose). A further group of NPS mice given either normal food (group D) or high dose Klamin® (group E) was also considered. The behavioral procedures of spatial learning ability (Morris test) showed that PS mice had significantly longer learning time as compared to their NPS counterpart (p<0.01), but this effect was prevented especially in mice supplemented with high-dose Klamin® (p<0.05) which improved performances in NPS mice (p<0.05). High-dose Klamin® supplementation restored the depleted total thiol concentration in the brain observed in PS mice while normalizing their increased malonildialdehyde level (p<0.05). Moreover, the high-dosage only caused a significant upregulation of EPO/EPOR system both in PS and in NPS animals (p<0.05). Taken together, these data suggest that this specific alga Klamath extract has considerable antioxidant and adaptogenic properties, also through a stimulatory effect of cerebral EPO/EPO system.

Redox balance signalling in occupational stress: modification by nutraceutical intervention.

There is increasing evidence that psychosocial stress can be viewed as a system-wide derangement of cellular homeostasis, with heightened oxidative stress and triggered proinflammatory mechanisms. The aim of this study is twofold: a) to replicate findings that psychological stress increases oxidative damage and b) to determine whether a fermented papaya preparation known to exert significant protective antioxidant properties could buffer such increases in nuclear DNA damage while also inducing epigenetic protective mechanisms. Twenty-eight sedentary men and women (age range: 28-52), who reported living a stressful lifestyle but with an overall positive attitude, were recruited for this study. Chronic diseases as well as severe burnout and use of drugs for anxiety constituted exclusion criteria. Subjects were supplemented for 1 month with 9 g/day (4.5 g twice a day) of a certified fermented papaya preparation. All subjects were given a stress and sleep quality questionnaire together with a diet and life style assessment. Blood was collected at 2 and 4 week, erythrocyte and leukocyte were separated to assess redox balance and heme oxygenase-1 (HO-1) gene expression while bilirubin oxidized metabolites (BOMs) were tested in the urine. Stressed individuals showed a significant abnormality of redox status with increased MDA of erythrocyte and increased level of 8-0HdG in leukocyte and BOMs excretion (p<0.05). Nutraceutical supplementation brought about a normalization of such values already at the 2 week observation (p<0.05) together with a significant upregulation of HO-1 (p<0.01). Taken together, the results of this study confirm that stressful occupational life per se, without any overt psychiatric illness, may be associated to increased oxidative stress. Supplementation with functional food affecting redox regulation may be part of the therapeutic armamentarium to be considered in this clinical setting.

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.