Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study

It is estimated that one-third of the world’s population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcome via dietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with curly endive without biofortification (Intervention Study on Iodine Biofortification Vegetables (Nutri-I-Food – Full-Text View - ClinicalTrials.gov). The effects on whole-body homeostasis and specifically on I, glucose, lipid, and hepatic, iron metabolism was investigated. Blood samples were obtained at baseline and after 12 days of supplementation with curly endive and compared with controls. Hematochemical and urinary parameters were analyzed at baseline and after 12 days. The results showed that short-term I curly endive intervention did not affect the whole body homeostasis in healthy people and revealed an increase in I concentration in urine samples and an increase in vitamin D, calcium, and potassium concentration in blood samples only in the biofortified cohort respect to controls. This study suggests that short-term consumption of I curly endive crops is safe and could positively impact body health

Inflammatory mediators as biomarkers in brain disorders.

Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules involved in this process could be a strategy for finding new biomarkers. The ideal inflammatory biomarker needs to be easily measurable, must be reproducible, not subject to wide variation in the population, and unaffected by external factors. Our review summarizes the most important inflammation biomarkers currently available, whose specificity could be utilized for identifying and monitoring distinctive phases of different neurodegenerative diseases

Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect

Clinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes aggregation of Aβ. In the experimental conditions utilized the drug causes oxidative stress, mitochondrial damage, decrease of Hexokinase-II levels and cytochrome C release, all of which lead to cell death. Several changes in oxidative stress-related genes following metformin treatment were detected by PCR arrays specific for the oxidative stress pathway. These effects of metformin were found to be antagonized by the addition of insulin, which reduced Aβ levels, oxidative stress, mitochondrial dysfunction and cell death. Similarly, antioxidant molecules, such as ferulic acid and curcumin, are able to revert metformin's effect. Comparable results were obtained using peripheral blood mononuclear cells. Finally, the involvement of NF-κB transcription factor in regulating APP and Pres 1 expression was investigated. Upon metformin treatment, NF-κB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription. The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression

Microclimatic Alteration after Logging Affects the Growth of the Endangered Lichen Lobaria pulmonaria

Microclimatic conditions are important in determining lichen distribution at small scale, and may determine whether the species persist when the surrounding environmental conditions have drastically changed. This is the case with forest management, since a sudden variation of microclimatic conditions (increase of solar radiation, temperature, wind and a reduction of humidity) may occur after logging. In this study, the combined effect of forest logging and microclimatic conditions on the growth probabilities and growth rates of the model species Lobaria pulmonaria was assessed in mixed oak stands. To this purpose, 800 fragments of L. pulmonaria (<1 cm) were transplanted in logged and unlogged stands for two years. Young and adult fragments were positioned on Turkey oak boles according to distance from the ground (100 and 50 cm) and aspect (north and south). The results, evaluated by generalized linear mixed models on a yearly basis, highlighted differences in growth—particularly on isolated trees in the logged stand. South-exposed samples in the logged stand showed a low probability of growth, while samples transplanted north in the unlogged stand showed higher growth probabilities. However, the highest annual growth coefficients corresponded to south-exposed samples 50 cm from the ground in the unlogged stand. In general, higher growth rates were observed in young thallus fragments when compared with adult ones. Beyond confirming the importance of microclimate for lichen ecology, these results could be implemented in conservation actions to preserve L. pulmonaria populations in logged forests

Outcome following a short period of adalimumab dose escalation as rescue therapy in psoriatic patients

Background: Advances in biologic treatments have led to a new therapeutic frontier for moderate-to-severe psoriasis. Nevertheless, the efficacy of anti-TNFα decreases with time, requiring adjustments to maintain valuable Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) responses. Objectives: To evaluate the efficacy and safety of adalimumab dose escalation (40 mg, subcutaneous, once a week for 24 weeks) in psoriatic adult patients with secondary loss of response (PASI ≥50 to ≤75 or PASI≥75 and DLQI ≥5). Materials and Methods: A multicentre, observational study involving different Italian third-level referral centres for psoriasis enrolled a total of 64 adult patients with moderate-to-severe psoriasis who were treated with adalimumab and experienced a secondary loss of response. Primary end-points were PASI&lt; 75 or PASI ≥50 to ≤ 75 with DLQI ≤ 5, and the secondary end-point was the ability to maintain a therapeutic response, resuming adalimumab every other week. Results: At Week 16 and Week 24, 29/64 (45.3%) and 35/64 (54.6%) responded based on PASI, and mean DLQI was 4.9 and 4.09, respectively. At Week 36 and Week 48, 45.3% and 28.1% patients achieved the second end-point, respectively. No adverse events were recorded except for one patient with recurrent tonsillitis. Conclusion: Adalimumab escalation could be considered in cases with loss of response before switching to alternative biologic therapy

Preventive Impact of Long-Term Ingestion of Chestnut Honey on Glucose Disorders and Neurodegeneration in Obese Mice

The purpose of the present study was to evaluate the impact of long-term honey ingestion on metabolic disorders and neurodegeneration in mice fed a high-fat diet (HFD). Three groups of mice were fed with a standard diet (STD), HFD or HFD supplemented with honey (HFD-H) for 16 weeks. Biochemical, histological, Western blotting, RT-PCR and Profiler PCR array were performed to assess metabolic parameters, peripheral and central insulin resistance and neurodegeneration. Daily honey intake prevented the HFD-induced glucose dysmetabolism. In fact, it reduced plasma fasting glucose, insulin and leptin concentrations and increased adiponectin levels. It improved glucose tolerance, insulin sensitivity and HOMA index without affecting plasma lipid concentration. HFD mice showed a significantly higher number of apoptotic nuclei in the superficial and deep cerebral cortex, upregulation of Fas-L, Bim and P27 (neuronal pro-apoptotic markers) and downregulation of Bcl-2 and BDNF (anti-apoptotic factors) in comparison with STD- and HFD-H mice, providing evidence for honey neuroprotective effects. PCR-array analysis showed that long-term honey intake increased the expression of genes involved in insulin sensitivity and decreased genes involved in neuroinflammation or lipogenesis, suggesting improvement of central insulin resistance. The expressions of p-AKT and p-GSK3 in HFD-H mice, which were decreased and increased, respectively, in HFD mouse brain, index of central insulin resistance, were similar to STD animals supporting the ability of regular honey intake to protect brain neurons from insulin resistance. In conclusion, the present results provide evidence for the beneficial preventative impact of regular honey ingestion on neuronal damage caused by HFD

Paralytic ileus, a new rare toxicity of capecitabine: Two case reports

Paralytic ileus (or adynamic ileus) refers to a lack of passage of intestinal contents due to disturbances of normal intestinal motility, in absense of mechanical obstruction. The most common causes are intra-abdominal surgery, severe metabolic problems, drugs. We present two clinical cases related to patients with breast cancer and admitted with paralytic ileus following treatment with capacitabine in local Lanciano Hospital. Naranjo, Jones algoritms suggest a direct causal relationship. Our two cases, to our knowledge, represent the first published report of this particular intestinal toxicity of capecitabine. Pathophisiological explanation is difficult because no data are known about fluoropyrimidines effects on enteric motor functions (motor system, neural influences, hormonal factors): Tegafur (UFT) also, another oral fluoropyrimidine, induces paralytic ileus. We hypothesize that some 5-flourouracil metabolites (5-fluorocitrate; fluoro-beta-alanine), seldom responsible for central and peripherical neurotoxicity from fluoropyrimidines, can sometimes cause a neuropathy, and so a paralytic ileus. Paralytic ileus is probably a rare complication of capecitabine, but the oncologist should take it into careful consideration, because of his possible seriousness and because a suitable management of early signs of abdominal distension (with nasogastric suction and/or rectal tube, i.v. infusion of fluids and electrolytes, etc.) can avoid a unnecessary operative treatment

Metabolic abnormalities associated with initiation of systemic treatment for psoriasis: evidence from the Italian Psocare Registry.

Objective To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees.Design Prospective cohort study.Setting Italian public referral centres for psoriasis treatment.Patients First-time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks.Main outcome measure Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinicallymeaningful increase in serum levels (week 16) of total and low-density lipoprotein cholesterol, triglycerides, aspartateamino transferase, alanine amino transferase and creatinine, as well as week-16 cumulative incidences of newdiagnoses of diabetes mellitus and arterial hypertension.Results Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin orcyclosporine. Mean triglyceride levels also increased in efalizumab- and etanercept-treated patients. Meantransaminase values increased in methotrexate-treated patients, and mean aspartate amino transferase levelsincreased in infliximab-treated patients. The average serum creatinine value increased in cyclosporine-treatedpatients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34)and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated withrisk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanineamino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension anddiabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88).Conclusion Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed.Received: 1 September 2011; Accepted: 12 January 201