A Proposal for Clinical Biomarkers in Multiple Chemical Sensitivity.

Multiple chemical sensitivity (MCS) is increasingly widespread disease, characterized by non-specific and recurring symptoms from various organs associated with exposure to common chemicals, even if inhaled at low concentrations, usually harmless for normal people. MCS is not yet well recognized from common point of view and for this reason affected patients risk marginalization and their symptoms are often trivialized. It is actually a devastating chronic disease that affects not only the patients in the daily routine but partly conditions their survival. Despite more than 50 years of research, the action mechanisms of MCS is still undefined. In this study we examine the theories about the etiopathogenesis of multiple chemical sensitivity that include genetic susceptibility factors, immunological factors, neurological factors and psychiatric factors. Since no specific diagnostic markers are currently available for the MCS, the diagnosis can only be supposed on the basis symptomatic criteria and patient's medical history. However new biochemical markers and diagnostic imaging techniques have emerged, useful to postulate at least the clinical-diagnostic hypothesis of MCS and in this paper we discuss a list of biomarkers studied for the diagnosis of MCS, based on the available scientific literature. At last but not least, we propose four-levels MCS tests that could help the clinician in the diagnosis of the pathology both through the use of quantifiable serological parameters, both through diagnostic tools, genetic testing and through clinical observation of symptoms.

Comparative analysis of volatile metabolites, quality and sensory attributes of Actinidia chinensis fruit.

Volatile organic compounds, quality and sensory parameters of four yellow- ('Dorì', 'G3', 'Jintao' and 'Soreli') and two green-fleshed ('Hayward' and 'Summer') kiwifruit cultivars were assessed. Statistical analysis was performed on volatiles, quality and sensory data for the identification of biomarkers of different kiwifruit cultivars. Principal component analysis showed that for all six samples a very good discrimination based on the cultivar was achieved. In particular, 2-pentylfuran can be used to distinguish between the green- and yellow-fleshed kiwifruit cultivars, while seven volatiles, can be identified as biomarkers of 'Dorì'. These findings are in agreement with the sensory analysis, which revealed that 'Dorì', the richest cultivar in esters, showed very high values of both ripe fruit smell and sweet sensory traits. Altogether, these results could offer recommendations for future breeding efforts for the production of kiwifruit cultivars with improved nutritional and aroma quality.

A therapeutic effect of cbd-enriched ointment in inflammatory skin diseases and cutaneous scars.

OBJECTIVE: To investigate the therapeutic effect of CBD-ointment administered on severe skin chronic diseases and/or on their outcome scars. METHODS: A spontaneous, anecdotal, retrospective study of 20 patients with two most frequent skin disorders: psoriasis (n: 5 patients), atopic dermatitis (n: 5) and resulting outcome scars (n: 10). The subjects were instructed to administer topical CBD-enriched ointment to lesioned skin areas twice daily for three months treatment. RESULTS: Based on skin evaluations (hydration, TEWL, elasticity), clinical questionnaires (SCORAD, ADI, PASI), and supported by photographic data and investigators' clinical assessment, the results showed that topical treatment with CBD-enriched ointment significantly improved the skin parameters, the symptoms and also the PASI index score. No irritant or allergic reactions were documented during the period treatment. CONCLUSIONS: The topical administration of CBD ointment, without any THC, is a safe and effective non-invasive alternative for improve the quality of life in patients with some skin disorders, especially on inflammatory background.

Review of the molecular mechanisms in wound healing: new therapeutic targets?

The restoration of the skin barrier in acute and chronic wounds is controlled by several molecular mechanisms that synergistically regulate cell kinetics, enzymatic functions, and neurovascular activation. These pathways include genetic and epigenetic activation, which modulate physiological wound healing. Our review describes the genetic background of skin repair, namely transcription-independent diffusible damage signals, individual variability, epigenetic mechanism, controlled qualitative traits, post-translational mechanisms, antioxidants, nutrients, DNA modifications, bacteria activation, mitochondrial activity, and oxidative stress. The DNA background modulating skin restoration could be used to plan new diagnostics and therapeutics.

Dogs'olfactory diagnostics applied on human species: state of the art and clinical perspectives.

Dogs'smell ability is about 10000-100000 more developed than humans' one. Dogs smell is usually exploited in forensic medicine, to find missing people and specific substances showing peculiar sensorial features. In clinic, there is the possibility to take advantage of dogs smell, which are conveniently trained, for the screening of cancers and other diseases. The common feature is the presence of molecules in organic samples that may be considered as biomarkers of a specific pathology. In cancer, scientific evidences exist about screening of melanoma, lung, breast, rectum, ovarian, prostate and bladder cancer. Instead, other pathologies manifest the presence of organic volatile compounds in biologic materials, such as spit, faeces and urine that may be studied by dogs smell in order to identify the presence of a specific disease. This review shows the state of the art of actual dogs' olfactory ability based on scientific principles and the advantages and the disadvantages of this method. The authors also reveal some potential pathologies joined by the presence of organic volatile compounds, which may be investigated by dogs smell.

Cross-linked hyaluronic acid in pressure ulcer prevention.

OBJECTIVE: Long-term bedridden patients are at high risk of acquring pressure ulcers (PUs). In this group of patients, prevention is necessary to cut the health costs, improve quality of life and reduce the mortality. Here, we evaluated the effectiveness of a cross-linked hyaluronic acid (HA) as plastic bulking-agent filling and remodelling the deep dermis and subcutaneous space of the skin areas exposed to the risk of necrosis. Our work hypothesis has been to inflate a sub-dermal elastic cushion, filled with a natural ECM component, with the aim to induce a stronger tissue background resistant to the ulcerative process. METHOD: All the patients had an increased risk of PUs, at the sacral, ileum or heel skin. Patients were being nursed accordingly to the standard orthopaedic ward management with a pressure relieveing air mattress. The standard protocol consisted in body mobilisation every 3 hours, 24 hours a day and accurate cleaning of the skin with liquid soap and water without any towel friction and without adding any cream or lotion for the skin protection. Our filling protocol enclosed: accurate disinfection of the skin to be injected with povidone-iodine solution, followed by a local anaesthesia with 28G 13 mm needle, injecting 1.5 ml of 1% xylocaine. Then slow, deep, subcutaneous injection of cross-linked HA was performed with a 18G long needle, in order to deliver a homogeneous, soft gel layer underneath and around the whitish erythematous skin edges at risk of ulceration. Patients' tolerability of the compound and adverse events were also recorded. RESULTS: There were 15 patients (78-94 years old) who participated in the study. All tolerated the procedure very well and no serious side effects were declared. No skin pressure ulceration was detected in the four weeks follow-up Conclusion: We have demonstrated the safety and tolerability of a cross-linked HA subdermal injection in PUs prevention. The compound stratifies in a soft, elastic, interstitial bulk into the deep dermis, thus reducing the exogenous pressure stress: thus, the induction of a thick hydrophilic substrate supports adequate mesenchymal and blood cells traffic to immediately restore any early or impending damage to the skin. DECLARATION OF INTEREST: The authors certify that there is no conflict of interest with any financial organisation regarding the material discussed in the manuscript.

[Web Babel Syndrome and false expectations during own multimedia oncological search]. / La sindrome di Babele del Web: fonte di false aspettative durante la ricerca della terapia oncologica multimediale personalizzata.

Nowadays Internet has become the new gold standard, for most of web users, when performing a screening on medical updates and/or cares. Although provided with some scientific background most of websites, blogs and videos (which as main source have Youtube) lack some institution that can garantee their contents and quality; thus one generates ambiguities among users giving light to a particular pathology called "Web Babel Syndrome"

A combined enrichment/polymerase chain reaction based method for the routine screening of Streptococcus agalactiae in pregnant women

Group B Streptococcus (GBS) is the most common cause of life-threatening infection in neonates. Guidelines from CDC recommend universal screening of pregnant women for rectovaginal GBS colonization. The objective of this study was to compare the performance of a combined enrichment/PCR based method targeting the atr gene in relation to culture using enrichment with selective broth medium (standard method) to identify the presence of GBS in pregnant women. Rectovaginal GBS samples from women at ¡Ý36 weeks of pregnancy were obtained with a swab and analyzed by the two methods. A total of 89 samples were evaluated. The prevalence of positive results for GBS detection was considerable higher when assessed by the combined enrichment/PCR method than with the standard method (35.9% versus 22.5%, respectively). The results demonstrated that the use of selective enrichment broth followed by PCR targeting the atr gene is a highly sensitive, specific and accurate test for GBS screening in pregnant women, allowing the detection of the bacteria even in lightly colonized patients. This PCR methodology may provide a useful diagnostic tool for GBS detection and contributes for a more accurate and effective intrapartum antibiotic and lower newborn mortality and morbidity.

A combined enrichment/polymerase chain reaction based method for the routine screening of Streptococcus agalactiae in pregnant women.

Group B Streptococcus (GBS) is the most common cause of life-threatening infection in neonates. Guidelines from CDC recommend universal screening of pregnant women for rectovaginal GBS colonization. The objective of this study was to compare the performance of a combined enrichment/PCR based method targeting the atr gene in relation to culture using enrichment with selective broth medium (standard method) to identify the presence of GBS in pregnant women. Rectovaginal GBS samples from women at ≥36 weeks of pregnancy were obtained with a swab and analyzed by the two methods. A total of 89 samples were evaluated. The prevalence of positive results for GBS detection was considerable higher when assessed by the combined enrichment/PCR method than with the standard method (35.9% versus 22.5%, respectively). The results demonstrated that the use of selective enrichment broth followed by PCR targeting the atr gene is a highly sensitive, specific and accurate test for GBS screening in pregnant women, allowing the detection of the bacteria even in lightly colonized patients. This PCR methodology may provide a useful diagnostic tool for GBS detection and contributes for a more accurate and effective intrapartum antibiotic and lower newborn mortality and morbidity.

Clinical and ultrasonographic correlation between scapular dyskinesia and subacromial space measurement among junior elite tennis players.

OBJECTIVES: In this study, the hypothesis that tennis players with scapular dyskinesia present a smaller subacromial space than non-athletes was investigated. Additionally, the correlation between the size of the subacromial space and abnormalities in scapular movement during arm abduction was studied. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 53 elite tennis players and 20 control participants were enrolled in the study. Participation was restricted to elite-level, junior tennis players who had no current shoulder pain or history of shoulder injuries. INTERVENTION: Each individual was examined for scapular dyskinesia by a single physician and by ultrasound, with the results analysed in a blind fashion by a single radiologist. RESULTS: 43.4% of the tennis players and 20% of control participants presented with scapular dyskinesia. Of the 106 shoulders evaluated, 39.6% of tennis players and 10% of control participants presented with scapular dyskinesia in the clinical examination (p = 0.005). Ultrasonographic measurements demonstrated that tennis players presented statistically smaller subacromial spaces compared with control participants (p<0.001). A decrease in the subacromial space was observed in tennis players when the shoulder was raised from 0 degrees to 60 degrees of abduction; however, dyskinesia-afflicted athletes demonstrated a significantly greater decrease following this movement (19.3 vs 13.8 mm, p = 0.002). CONCLUSIONS: The results of this study demonstrated that tennis players with scapular dyskinesia present a smaller subacromial space than control participants. Furthermore, when the shoulder was analysed dynamically, moving from neutral abduction to 60 degrees of elevation, the tennis players with scapular dyskinesia presented a greater reduction in the subacromial space compared with unaffected athletes.

Sacral stress fracture: an unusual cause of low back pain in an amateur tennis player.

Stress fractures are common in athletes, and their incidence in sport is estimated at 2-4%. A case is reported of a stress fracture of the sacrum in an amateur tennis player. The patient was treated with rest and physiotherapy, focusing on stretching programmes and analgesic treatments, followed by an educational programme of tennis training and muscle strengthening. This appears to be the first report of this pathology in a tennis player.

Human autoantibodies to diacyl-phosphatidylethanolamine recognize a specific set of discrete cytoplasmic domains.

The aim of this study was to characterize a novel human autoantibody-autoantigen system represented as cytoplasmic discrete speckles (CDS) in indirect immunofluorescence (IIF). A distinct CDS IIF pattern represented by 3-20 discrete speckles dispersed throughout the cytoplasm was identified among other cytoplasmic speckled IIF patterns. The cytoplasmic domains labelled by human anti-CDS-1 antibodies did not co-localize with endosome/lysosome markers EEA1 and LAMP-2, but showed partial co-localization with glycine-tryptophan bodies (GWB). CDS-1 sera did not react with several cellular extracts in immunoblotting and did not immunoprecipitate recombinant GW182 or EEA1 proteins. The typical CDS-1 IIF labelling pattern was abolished after delipidation of HEp-2 cells. Moreover, CDS-1 sera reacted strongly with a lipid component co-migrating with phosphatidylethanolamine (PE) in high performance thin-layer chromatography (HPTLC)-immunostaining of HEp-2 cell total lipid extracts. The CDS-1 major molecular targets were established by electrospray ionization-mass spectrometry (ESI-MS), HPTLC-immunostaining and chemiluminescent enzyme-linked immunosorbent assay as diacyl-PE species, containing preferentially a cis-C18 : 1 fatty acid chain at C-2 of the glycerol moiety, namely 1,2-cis-C18 : 1-PE and 1-C16 : 0-2-cis-C18 : 1-PE. The clinical association of CDS-1 sera included a variety of systemic and organ-specific autoimmune diseases but they were also observed in patients with no evidence of autoimmune disease.

Shoulder strength profile in elite junior tennis players: horizontal adduction and abduction isokinetic evaluation.

OBJECTIVE: To establish normative data for muscle performance during isokinetic horizontal abduction and adduction of the shoulder in elite junior tennis players. METHODS: Thirty six tennis players were evaluated (23 male, 13 female; mean age 14 years (range 12-18)). An isokinetic dynamometer was used to test the shoulder horizontal abductors and adductors at 60 and 180 degrees/s. Absolute and relative peak torque (PT and PT/BW), total work (TW), endurance ratio (ER), and the ratio of the peak torque between horizontal abductors and adductors (HAB/HAD ratio) were recorded. Data were compared for the dominant and non-dominant shoulders, horizontal abductor and adductor muscles, and between players grouped according to age. RESULTS: The dominant shoulder was significantly (p<0.05) stronger than the non-dominant shoulder in all variables except ER and HAB/HAD ratio. The abductors were significantly (p<0.05) weaker than the adductors in all subjects. The type of backhand (one handed or two handed) did not influence the strength of the shoulder horizontal abductors on the dominant side. The number of years of tennis practice had an effect on muscle strength as evaluated by absolute data (PT and TW) but not relative measurements (PT/BW and TW/BW). CONCLUSION: The findings confirm that horizontal abduction and adduction are stronger in the dominant shoulder of junior tennis players. The clinical relevance of these findings is not established, and more studies are needed to compare tennis players with athletes from other sports and non-athletes.

Effects of alpha-interferon on insulin-like growth factor-I, insulin-like growth factor-II and insulin-like growth factor binding protein-3 secretion by a human lung cancer cell line in vitro.

The aim of our study was to evaluate the effect of alpha-interferon (alpha-IFN) on cell growth and on the different IGF system components in a human non-small cell lung cancer line (Calu-6) in vitro. Our results confirm the release of IGF-I and IGF-II by these cells. The amount of IGF-II in conditioned media (10.25 +/- 3.95 nM/10(6) cells, mean +/- SE) was more than 10-fold higher than that of IGF-I. alpha-IFN treatment reduced IGF-II levels in the media, with a maximal effect between 1 and 10 U/ml (delta% of control: -31 and -55%, respectively, p < 0.05). IGF-I was significantly reduced at 0.5 U/ml (p < 0.01). No difference, however, was observed in IGF mRNA expression between untreated and alpha-IFN treated cells. An increase in IGF-I and IGF-II intracellular levels in alpha-IFN treated cultures was observed, suggesting that alpha-IFN can regulate the transfer of these peptides into the cells. Furthermore, IGF type-I and particularly type-lI receptor expression was increased after alpha-IFN treatment. IGFBP-3 was detected only in trace amounts in the conditioned media; however, it showed an increase after alpha-IFN treatment (+110% at 1 U/ml). IGFBP-3 mRNA expression showed a slight increase after treatment with 1 and 10 U/ml. alpha-IFN (1-10 U/ml) reduced the stimulatory effect of IGF-I on cell replication (p < 0.01), inhibited (p < 0.01) cell replication in untreated and in fetal calf serum (FCS)-stimulated cells, and increased apoptosis in Calu-6 cells. Our data suggest that alpha-IFN may exert its effects at the cellular level in part through modification of the local IGF system.

Reduction of adiposity with prolonged growth hormone treatment in old obese rats: effects on glucose handling and early insulin signaling.

OBJECTIVES: Growth Hormone (GH) promotes loss of body fat and causes insulin resistance. It is debated whether reduction of body fat mass during long term growth hormone (GH) administration improves carbohydrate metabolism. To answer this question we assessed carbohydrate handling and tissue specific function of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) during prolonged GH treatment of obese rats. METHODS: Body fat % estimated by DEXA scanning, plasma IGF-I, glucose and insulin were studied in 17 months old dietary induced obese rats treated for 4, 21 or 41 days (GH: 4 mg/kg/d or saline total n=90). Adipose tissue, muscle and liver samples were obtained after 21 days and expression and tyrosine phosphorylation of IR and IRS-1 proteins and the degree of IRS-1-Janus Kinase-2 (JAK2) interaction were analyzed by immunoprecipitation and immunoblotting. RESULTS: Forty-one days GH treatment caused the body fat to decline significantly to 20+/-3% (Mean+/-SEM), whereas it remained steady on 51+/-4% in the pair fed group. Insulin levels in response to OGTT were significantly elevated throughout the experiment. IR amount was elevated in adipose tissue but decreased in liver after GH treatment while IR phosphorylation was increased in muscle only. IRS-1 amount was elevated in adipose tissue and muscle while IRS-1 phosphorylation was increased only in liver. The association of IRS-1 with JAK-2 was increased in liver and muscle. CONCLUSIONS: An extensive reduction of fat mass did not improved signs of insulin resistance in GH treated old obese rats. The molecular events associated with GH treatment included tissue specific changes in the function of IR and IRS-1 suggesting the liver to be the primary site of insulin resistance. Furthermore, the association of IRS-1with JAK-2 in the course of GH signaling could present a mechanism for GH to directly induce insulin resistance.

Role of IRS-1 and SHC activation in 3T3-L1 fibroblasts differentiation.

The early steps of 3T3-L1 fibroblasts differentiation to adipocytes are characterized by a proliferation phase, termed clonal expansion, that ends after the first 48 h of exposure of confluent cells to high doses of insulin, dexamethasone, 3-methyl-isobutylxanthine and FCS (differentiation mix). Since insulin is a key hormone for adipocyte conversion, and IRS-1 (insulin receptor substrate -1) and Shc (Src homology collagen)-proximal intracellular substrates of the insulin receptor-control cell proliferation, the aim of this study was to investigate the role of IRS-1 and Shc in the early steps of differentiation. At the end of clonal expansion, 48 h after induction of differentiation with differentiation mix, p66 Shc phosphorylation and IRS-1 amounts were reduced in those cells committed to fully differentiate. Conversely, in cells treated with insulin alone or dexamethasone alone (unable to be differentiated), p66 Shc and IRS-1 activities were maintained unaltered, compared to basal values. These observations suggest that the modifications of p66 Shc and IRS-1 in the first 48 h of 3T3-L1 conversion into adipocytes could play a role on this process, or alternatively they could represent an early cellular marker of differentiation.

The overexpression of insulin receptor makes CHO cells resistant to the action of IGF-1: role of IRS-1.

We investigated the influence of the relative abundance of insulin and IGF-1 receptors on cellular growth, by measuring the stimulation of c-fos expression and of H3-thymidine incorporation into DNA by insulin and IGF-1 in CHO cells overexpressing insulin Receptor (CHO-IR). We found that CHO-IR cells were resistant to the action of IGF-1, but were more responsive to insulin, compared to parental clone. This result suggest the presence of a limiting step, distal to the IGF-1 receptor, in the transduction pathway. To address this question we measured the IGF-1 effect on c-fos expression in CHO-IR cells, transiently transfected with the cDNA for IRS-1, the common intracellular substrate for both insulin and IGF-1 receptors (CHO-IR/IRS-1 cells). In these cells IGF-1 stimulated a 10 fold higher c-fos expression compared to CHO-IR cells. These results suggest that the abundance of IRS-1, relative to the number of insulin and IGF-1 receptors, represents a limiting step for the intracellular transduction of insulin and IGF-1 biological messages.

Linkage analysis does not support a role for glucokinase gene in the aetiology of type 2 diabetes mellitus among north western Italians.

The contribution of a 3' glucokinase gene polymorphism to the aetiology of type 2 diabetes mellitus was studied in 17 diabetic pedigrees from North-Western Italy; linkage methodology was used. A CA repeat sequence was employed as a marker and amplified by PCR. Three alleles were found: Z (195 bp), Z + 4 (199 bp) and Z + 10 (205 bp). Since in diabetic families linkage analysis gave values of LOD score between -0.000438 and 0.026, the association between GK polymorphism and type 2 diabetes could not be either excluded or accepted. Based on these data, we conclude that glucokinase polymorphism is not a major determinant of type 2 diabetes mellitus, at least in our population, but, consistent with LOD score obtained, in some pedigrees it could assume a minor role in the aetiology of this disease.

c-myc gene expression in human cells is controlled by glucose.

The c-myc oncogene is implicated in normal growth and differentiation processes. Human cell lines IM9 and HepG2 stably cultured at "low" glucose concentrations (5.5 mM) show c-myc mRNA levels 3-4 times higher than cells cultured at "high" glucose concentrations (25 nM). D-fructose (a metabolizable exose) substitutes for D-glucose in reducing c-myc expression while 3-ortho-methylglucose (a non metabolizable exose) is uneffective. c-myc expression is up-regulated (by PMA) or down-regulated (by dexamethasone and long-term exposure to FCS) in human cells cultured at "low" glucose but not in cells cultured at "high" glucose. We previously demonstrated that insulin receptor gene expression in human cell lines in enhanced by glucose. Therefore, glucose controls in an opposite way the expression of two genes important in the regulation of eukaryotic cell growth and differentiation.