Cholesterol photosensitized oxidation in food and biological systems

Lipid oxidation is one of the main chemical degradations occurring in biological systems and leads to the formation of compounds that are related to aging and various chronic and degenerative diseases. The extent of oxidation will depend on the presence of antioxidants/pro-oxidants, the unsaturation degree of fatty acids, and environmental conditions. Lipid oxidation can also affect other molecules that have double bonds in their chemical structures, such as cholesterol. Cholesterol oxidation products (COPs) have been studied in depth, because of their negative and controversial biological effects. The formation of COPs can be particularly favored in the presence of light and photosensitizers, since they generate excited singlet oxygen that rapidly reacts with the double bond by a non radical mechanism and without any induction period. The present review intends to provide an overall and critical picture of cholesterol photosensitized oxidation in food and biological systems, and its possible impact on human health and well-being.     

Barcoding Eophila crodabepis sp. nov. (Annelida,Oligochaeta, Lumbricidae), a Large Stripy Earthworm from Alpine Foothills of Northeastern Italy Similar to Eophila tellinii (Rosa, 1888)

A new Italian earthworm morphologically close to the similarly large and anecic Eophila tellinii (Rosa, 1888) is described. Distribution of Eophila crodabepis sp. nov. extends over 750 km² from East to West on the Asiago Plateau and Vittorio Veneto Hills, from North to South on mounts Belluno Prealps (Praderadego and Cesen), Asiago, Grappa and onto the Montello foothills. This range abuts that of Eophila tellinii in northern Friuli Venezia Giulia region. Known localities of both E. tellinii and E.crodabepis sp. nov. are mapped. mtDNA barcoding definitively separates the new western species from classical Eophila tellinii (Rosa, 1888).     

Conformation-sensitive antibodies against alzheimer amyloid-beta by immunization with a thioredoxin-constrained B-cell epitope peptide

Immunotherapy against the amyloid-beta (Abeta) peptide is a valuable potential treatment for Alzheimer disease (AD). An ideal antigen should be soluble and nontoxic, avoid the C-terminally located T-cell epitope of Abeta, and yet be capable of eliciting antibodies that recognize Abeta fibrils and neurotoxic Abeta oligomers but not the physiological monomeric species of Abeta. We have described here the construction and immunological characterization of a recombinant antigen with these features obtained by tandem multimerization of the immunodominant B-cell epitope peptide Abeta1-15 (Abeta15) within the active site loop of bacterial thioredoxin (Trx). Chimeric Trx(Abeta15)n polypeptides bearing one, four, or eight copies of Abeta15 were constructed and injected into mice in combination with alum, an adjuvant approved for human use. All three polypeptides were found to be immunogenic, yet eliciting antibodies with distinct recognition specificities. The anti-Trx(Abeta15)4 antibody, in particular, recognized Abeta42 fibrils and oligomers but not monomers and exhibited the same kind of conformational selectivity against transthyretin, an amyloidogenic protein unrelated in sequence to Abeta. We have also demonstrated that anti-Trx(Abeta15)4, which binds to human AD plaques, markedly reduces Abeta pathology in transgenic AD mice. The data indicate that a conformational epitope shared by oligomers and fibrils can be mimicked by a thioredoxin-constrained Abeta fragment repeat and identify Trx(Abeta15)4 as a promising new tool for AD immunotherapy.     

Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation

The t(4;8)(p16;p23) translocation, in either the balanced form or the unbalanced form, has been reported several times. Taking into consideration the fact that this translocation may be undetected in routine cytogenetics, we find that it may be the most frequent translocation after t(11q;22q), which is the most common reciprocal translocation in humans. Case subjects with der(4) have the Wolf-Hirschhorn syndrome, whereas case subjects with der(8) show a milder spectrum of dysmorphic features. Two pairs of the many olfactory receptor (OR)-gene clusters are located close to each other, on both 4p16 and 8p23. Previously, we demonstrated that an inversion polymorphism of the OR region at 8p23 plays a crucial role in the generation of chromosomal imbalances through unusual meiotic exchanges. These findings prompted us to investigate whether OR-related inversion polymorphisms at 4p16 and 8p23 might also be involved in the origin of the t(4;8)(p16;p23) translocation. In seven case subjects (five of whom both represented de novo cases and were of maternal origin), including individuals with unbalanced and balanced translocations, we demonstrated that the breakpoints fell within the 4p and 8p OR-gene clusters. FISH experiments with appropriate bacterial-artificial-chromosome probes detected heterozygous submicroscopic inversions of both 4p and 8p regions in all the five mothers of the de novo case subjects. Heterozygous inversions on 4p16 and 8p23 were detected in 12.5% and 26% of control subjects, respectively, whereas 2.5% of them were scored as doubly heterozygous. These novel data emphasize the importance of segmental duplications and large-scale genomic polymorphisms in the evolution and pathology of the human genome.     

Preventive study in subjects at risk of fatal familial insomnia: Innovative approach to rare diseases

The text describes a preventive clinical trial with drug treatment in a very rare neurodegenerative disease (Fatal familial Insomnia, FFI) designed with the help of individuals at genetic risk of developing the disease, asymptomatic carriers, who have agreed to be exposed over a 10-year period to doxycycline, an antibiotic with anti-prion activity. At least 10 carriers of the FFI mutation over 42 y old will be treated with doxycycline (100 mg/die) and the incidence of the disease will be compared to that of an historical dataset. For ethical reasons a randomized, double-blind, placebo-controlled trial was not feasible, however the study design and the statistical analysis ensure the scientific value of the results. This approach might represent an important breakthrough in terms of potential therapy and knowledge of rare diseases that could give some hopes to these neglected patients.     

Characteristics of endocrine disorders in the early stages of the development of chronic experimental pancreatitis

The experiments on normal mongrel dogs and those with chronic experimental pancreatitis were performed to reveal the early changes of the endocrine pancreas function. The concentration of immunoreactive insulin and glucagon were studied in afferent vessels of the organ after intraarterial glucose-loading during pancreatic perfusion in situ. The data obtained have shown that in chronic pancreatitis the maximum secretion of insulin is decreased and delayed, as compared to normal animals. At the same time insulin-glucagon secretion ratio remains unchanged. That was indicative of the normal alpha-cell function at the early stages of the disease.     

An in vitro evaluation of the effects of a Yucca schidigera extract and chestnut tannins on composition and metabolic profiles of canine and feline faecal microbiota

The in vitro effect of a Yucca schidigera extract (YSE) and tannins from chestnut wood on composition and metabolic activity of canine and feline faecal microbiota was evaluated. Four treatments were carried out: control diet, chestnut tannins (CT), YSE and CT + YSE. The YSE was added to canine and feline faecal cultures at 0.1 g/l, while CT were added at 0.3 g/l for a 24-h incubation. A total of 130 volatile compounds were detected by means of headspace-solid phase microextraction gas-chromatography/mass spectrometry analyses. Several changes in the metabolite profiles of fermentation fluids were found, including a decrease of alcohols (?19%) and esters (?42%) in feline and canine inoculum, respectively, which was due to the antibacterial properties of tannins. In canine inoculum, after 6 h, YSE + CT caused lower cadaverine concentrations (?37%), while ammonia (?4%) and quinolone (?27%) were reduced by addition of CT. After 24 h, the presence of CT resulted in a decrease of sulphur compounds, such as dimethyl sulphide (?69%) and dimethyl disulphide (?20%). In feline faecal cultures, after 6 h, CT lowered the amount of indole (?48%), whereas YSE tended to decrease trimethylamine levels (?16%). Both in canine and feline inoculum, addition of CT and, to a minor extent, YSE affected volatile fatty acids patterns. In canine faecal cultures, CT exerted a marginal inhibitory effect on Escherichia coli population (?0.45 log 10 numbers of DNA copies/ml), while enterococci were increased (+2.06 log 10 numbers of DNA copies/ml) by YSE. The results from the present study show that YSE and tannins from chestnut wood exert different effects on the composition and metabolism of canine and feline faecal microbiota. In particular, the supplementation of YSE and tannins to diets for dogs and cats may be beneficial due to the reduction of the presence of some potentially toxic volatile metabolites in the animals’ intestine.     

Le allergopatie respiratorie in abitanti nell'isola di Capri: Correlazione con i fattori meteorologici

Riassunto Sia le piante spontanee, in particolare la Parietaria e le Graminacee, sia le piante coltivate, i cui pollini hanno in vario grado importanza allergologica, sono abbondantemente rappresentate e diffuse sull'isola di Capri. Gli estratti di acari Dermatophagoides, però, risultano di gran lunga gli allergeni più frequenti nel determinismo delle allergie respiratorie. Gli AA. hanno studiato la composizione bioatmosferica che gravita sul piccolo territorio caprese al fine di stabilire eventuale relazione tra fattori meteoclimatici e positività diagnostica allergica. I fattori meteorologici presi in esame sono stati i seguenti: precipitazioni piovose, umidità relativa, temperatura dell'aria, velocità e direzione dei venti. L'elevata umidità relativa (valori fino a 76% UR), le precipitazioni (valori fino a 108 mm), la velocità del vento (4–7 m/sec), ostacolano l'immissione e la dispersione aerea del polline delle piante anemofile diffuse sull'isola. L'elevata umidità relativa con le variazioni della temperatura (valori fino a 28,5°C) determinano, invece, il microclima caldo-umido delle abitazioni capresi, habitat ideale per lo sviluppo e la crescita degli acari Dermatophagoides. Gli AA. concludono sottolineando l'importanza di tali condizioni meteoclimatiche nel determinismo delle allergopatie respiratorie da allergeni inalanti e, particolarmente, il prevalere delle sensibilizzazioni da acari Dermatophagoides. Evidenziano inoltre come la profilassi ambientale possa rappresentare un momento fondamentale nella prevenzione dalla sensibilizzazione da acari Dermatophagoides per gli abitanti in Capri.

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Summary Spontaneous plants, particularly Parietaria and Grasses, and coltived plants, are aboundantly diffused on the Isle of Capri. Dermatophagoides mites are however the most frequent allergens that cause respiratory allergy. The AA. studied the bioatmospheric composition of the little Isle of Capri to find the possible connexion among meteoclimatic factors and allergy. The meteorological factors precipitations, relative humidity, temperature of air, speed and direction of winds, were studied. The high relative humidity (≥76%), the precipitations (≥108 mm), the speed of wind (4–7 m/sec), obstruct the dispersion of pollens of anemophilous plants. The high relative humidity and the variations of temperature (≥25°C), cause in the houses on Capri, a hot microclimate, an ideal habitat for the growth of Dermatophagoides. The AA. conclude emphasizing the importance of meteoclimatic conditions to determine the respiratory allergy caused by inhalant allergens and, particularly, the prevalence of Dermatophagoides sensitization. The AA. emphasize, moreover, that ambiental prophilaxis essential to prevent Dermatophagoides sensitization in Capri.