bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of Trimethoprim and Sulfametopyrazine in the Female Reproductive Tract
Authors: Preza Paulo Cesar , Moura Claudia , Filho Aguinaldo Leite , Cavallari Valeria , Nüdemberg Franklin , Piaia Francesca
Published: January 2017

A combination of trimethoprim (TMP) 250 mg and sulfametopyrazine (SMP) 200 mg (dose ratio 5:4) in capsules was administered to ten patients undergoing hysterectomy for uterine leiomyoma.

Each patient received a total of 3 of these Kelfiprim capsules: 2 capsules in a single administration 36 hours before surgery and 1 capsule 24 hours later.

TMP and SMP concentrations were analyzed in plasma and also in the ovary, Fallopian tube and uterus, removed during surgery.

The results indicated that in the reproductive organs of the female genital tract TMP reaches the same concentrations as in plasma. In contrast SMP is 3 to 3·5 times less concentrated in these tissues compared with plasma. At the TMP/SMP ratios obtained in these various organs synergism of the two compounds is reported to be particularly prominent for most bacterial strains. These findings indicate that this TMP-SMP combination may be useful in the treatment of female reproductive tract infections.
The Prevention of Wound Contamination by Skin Organisms by the Pre-Operative Application of an Iodophor Impregnated Plastic Adhesive Drape
Authors: Fairclough J A , Johnson D , Mackie I
Published: January 2017

Prior to preparing the skin for surgery, samples for bacterial growth were taken from 107 patients. The same site was sampled after preparation with povidone-iodine and at the end of surgical procedure the deep part of the wound was also sampled. This demonstrated that the wounds of 15% of patients became contaminated by organisms present on the skin prior to disinfection.

A comparison was made with a further 122 patients undergoing hip surgery in whom an iodophor impregnated plastic adhesive drape (‘Ioban’) was applied to the operation site 24 hours prior to surgery. Bacterial sampling of the wound at the end of the procedure showed that wound contamination was reduced from 15% to 1·6% by this method. When patients are to have implant surgery, the protection from contamination by skin organisms afforded by ‘Ioban’ drape is likely to prove a valuable tool in the fight to prevent infection.
A Review of Flavoxate Hydrochloride in the Treatment of Urge Incontinence
Authors: Ruffmann R.
Published: January 2017

This article provides a review of the use of flavoxate hydrochloride in the treatment of urge incontinence. It outlines the pharmacology, mode of action, toxicology and pharmacokinetic studies which have been carried out, and then reviews the clinical studies, including those involving patients with benign prostatic hypertrophy. The effects of dosages of 600–1200 mg/day are compared, particularly regarding safety and tolerability factors. Finally, alternative therapies to flavoxate hydrochloride (α-adrenergic receptor blockers, oxybutinin chloride, terodiline hydrochloride, emepronium bromide and imipramine) are summarized. The article is written in the knowledge of recent evidence which indicates that flavoxate hydrochloride exhibits only weak anticholinergic activity on receptors involved in the control of the lower urinary tract.
Inhibitory Effect of Barbiturates and Local Anaesthetics on Protein Kinase C Activation
Authors: Mikawa K. , Maekawa N. , Hoshina H. , Tanaka O. , Shirakawa J. , Goto R. , Obara H. , Kusunoki M.
Published: January 2017

A calcium- and phospholipid-dependent protein kinase C subspecies purified from rat brain was inhibited by thiamylal, thiopentone, pentobarbitone, mepivacaine and bupivacaine. This was attributed to the inhibition of the activation process rather than to direct interaction with the active site of the enzyme. It is well established that unsaturated diacylglycerol markedly increases the affinity of protein kinase C for calcium ions. Kinetic analysis suggested that pentobarbitone brought about the inhibition by competing with the diacylglycerol diolein and that mepivacaine and bupivacaine competed with the phospholipid phosphatidylserine used in the assay. The possibility exists that the effects of local anaesthetics on the function of various tissues are due, in part, to an inhibitory action on protein kinase C.
Thyroid Function and Release of Thyroid-stimulating Hormone and Prolactin from the Pituitary in Human Obesity
Authors: Scaglione R. , Averna M.R. , Dichiara M.A. , Barbagallo C.M. , Mazzola G. , Montalto G. , Licata G. , Notarbartolo A.
Published: January 2017

Thyroid function, basal serum thyroid-stimulating hormone (TSH) and prolactin concentrations, and the effects of 200 μg TSH-releasing hormone (TRH) given intravenously on TSH (ΔTSH) and prolactin (Δprolactin) were investigated in 25 euthyroid obese subjects and 20 lean controls. No significant differences in serum thyroid hormone concentrations, glucose metabolism parameters, or basal TSH and prolactin concentrations were detected between groups, but a significant ( P < 0.01) increase in ΔTSH and a significant (P < 0.01) decrease in Δprolactin were observed in obese subjects. No significant differences in basal TSH and prolactin were observed in obese men and women compared with corresponding lean controls, but Δprolactin decreased significantly ( P < 0.01) in obese men and women compared with lean controls and TSH increased significantly ( P < 0.01) in obese men and women. No correlation was found between ΔTSH or Δprolactin and body mass index. The study suggests that hyper-responsiveness of TSH and hyporesponsiveness of prolactin to TRH in obese subjects can be related to changes in the central serotoninergic system.
Acute Interstitial Pneumonia in Mink Kits: Experimental Reproduction of the Disease
Authors: Alexandersen S.
Published: January 2017

Organ homogenates from kits that died of interstitial pneumonia were inoculated into adult Aleutian disease virus (ADV)-negative mink and shown to contain infectious ADV. Acute interstitial pneumonia was experimentally reproduced with the organ homogenate but only by inoculation of newborn kits born from ADV-negative dams. Older kits and kits from ADV-positive dams did not develop interstitial pneumonia, but later developed the classic form of Aleutian disease. Electron microscopic examination was done on purified suspensions of defined ADV isolates and on purified organ homogenates from kits with spontaneous or experimental interstitial pneumonia. In kits from both groups a virus, morphologically resembling the defined ADV isolates, was demonstrated. Findings of intranuclear inclusion bodies and intranuclear ADV antigen in alveolar type-II cells in affected lungs and the lack of immunologically mediated lesions suggest that lung lesions result from primary viral injury to alveolar type-II cells. Experiments also showed that infection of dams with ADV before pregnancy decreased the number of kits per mated dam and infection with ADV in mid-pregnancy caused fetal death, fetal resorption, or abortion.
Orthodoxy and Dissent
Authors: Rich Vera
Published: January 2017

Soviet Sociology of Science by Linda L. Lubrano American Association for the Advancement of Slavic Studies Columbus, Ohio 1976 102pp The Phenomenon of Science — A Cybernetic Approach to Human Evolution by V. F. Turchin Columbia University Press New York 1977 $21.90 348pp
Mainlandization, the ICAC, and the Seriousness Attached by Local Politicians to Corruption in Post-1997 Hong Kong
Authors: Li Li , Lo T. Wing
Published: January 2017

To date, few studies have focused on how the public has perceived the effectiveness of the Independent Commission Against Corruption (ICAC). Furthermore, little is known about how the public has assessed the functions of the ICAC during the political-economic convergence between Hong Kong and mainland China since 1997. This study attempts to explore local politicians’ perceptions towards the ICAC in post-1997 Hong Kong. The quantitative data show that the important historical juncture of mainlandization has been politicized in Hong Kong and has deeply influenced the seriousness attached by local politicians to corruption. Moreover, a mediating path of the effect of “Conflict of Interest” on the “Perceived Seriousness of Corruption” has been found, that is, mainlandization is found to have brought about increased levels of conflict of interest among government officials, which has weakened the symbolic anti-corruption function of the ICAC and, in turn, has affected the perceived seriousness attached to corruption.
Sphingolipid Microdomains Mediate CD38 Internalization: Topography of the Endocytosis
Authors: Trubiani O. , Guarnieri S. , Orciani M. , Salvolini E. , Di Primio R.
Published: January 2017

Plasma membranes of several cell types contain specialized microdomains (or lipid rafts) enriched in sphingolipids, cholesterol, sphingomyelin, and glycosyl-phosphatidylinositol-anchored proteins. These membrane domains are characterized by detergent insolubility at low temperatures and low buoyant density. Human CD38 is the prototype of a gene family encoding surface molecules endowed with multiple functional activities. The endocytosis of the human CD38 molecule has been investigated in normal lymphocytes and in a number of leukemia- and lymphoma-derived cell lines demonstrating that internalization after CD38 ligation is a reproducible event involving only a fraction of the whole amount of the surface molecule. This study reports the results obtained by conventional, confocal, and electron microscopy on the effects induced by the engagement of the molecule with agonistic mAb, reproducing the signals mediated by its natural ligand. The results demonstrate that the endocytosis induced as consequence of CD38 ligation is preceded by a thorough rearrangement of the cell surface with formation of glycosphingolipid- and cholesterol-rich plasma membrane microdomains. These data suggest that specialized raft microdomains might be the plasma membrane structure through which CD38 translocates at intracellular level. The CD38/lipid interactions during the coated pit formation trigger a process that generate membrane curvature, considered as the first step of CD38 endocytosis. Moreover, ultrastructural studies show that early CD38+ endosomes are pleiomorphic and contain cisternal and vesicular regions. Late endosomes exhibit a complex organisation, containing uncoupled CD38-ligand multivesicular- or multilamellar-regions.
Detection of Chlamydia Pneumoniae in Atherosclerotic Coronary Arteries
Authors: Sessa R. , Di Pietro M. , Schiavoni G. , Nicoletti M. , Soda G. , Nardoni S. , Bosco D. , Santino I. , Cipriani P. , Del Piano M.
Published: January 2017

Chlamydia pneumoniae has recently been associated with the development of coronary heart diseases by sero-epidemiological studies and by direct detection of the organism in atherosclerotic tissues. The aim of our study was to employ a semi-nested PCR approach to investigate the presence of C. pneumoniae in both normal and atherosclerotic coronary arteries of humans obtained at autopsy. Moreover, we have evaluated the role of infection with C. pneumoniae in relation to the extent of coronary atherosclerosis. One hundred and eighty coronary artery specimens were collected at autopsy from 60 consecutive subjects (three arterial segments from each subject). Atherosclerosis in each arterial segment was graded histologically by the Stary classification. Thirty normal coronary arteries were also taken at autopsy as control. PCR results evidenced the presence of C. pneumoniae DNA in atherosclerotic coronary arteries in 19 (31.7%) of 60 subjects examined, while none of the 30 subjects with non-atherosclerotic tissues was positive (p=0.001). Moreover, of the 180 atherosclerotic specimens examined, C. pneumoniae DNA was detected in 3.4% (2/59) of mild atherosclerotic lesions, and in 14.0% (17/121) of advanced atherosclerotic lesions (p=0.05). Our results demonstrate that the presence of C. pneumoniae DNA may be associated with the severity of coronary atherosclerosis.
HLA and Hypocomplementemia: The Disadvantage of Carrying the HLA-B35 and the Silent Alleles of the C4 Complement Component
Authors: Zorzetto M. , Ricevuti G. , Martinetti M. , Gritti D. , Gasparetto C. , De Silvestri A. , Salvaneschi L. , Cuccia M.
Published: January 2017

Hypocomplementemia is an extremely complex phenomenon: we devoted our attention to its immunogenetic basis, particularly to the HLA haplotypes involved and to the study of C4 polymorphic genes. With this in mind we analyzed a group of unrelated patients with hypocomplementemia and 15 families suffering from specific C4 deficiency. Firstly, we performed a population analysis in order to identify a statistically significant association: HLA-B35 and C4BQ0 alleles, in the total group of hypocomplementemic individuals, seem to be associated with the primary disease.

Secondly, we defined HLA haplotypes clear-cut segregation in the hypocomplementemic families and we identified the most common HLA haplotypes carrying B35 and C4 null allele associated with this condition. With the aid of correspondence analysis and the Transmission Disequilibrium Test (TDT), we measured the strength of this association. In this work, mainly through family analysis, we envisaged a potentially interesting genomic trait, within HLA, close to B locus, that seems to be involved in hypocomplementemia itself and perhaps in hypocomplementemia-related disorders.
Omeprazole Induces Apoptosis in Jurkat Cells
Authors: Scaringi L. , Cornacchione P. , Ayroldi E. , Corazzi L. , Capodicasa E. , Rossi R. , Marconi P.
Published: January 2017

We report for the first time a potent apoptotic effect of omeprazole (OM). Apoptosis was induced in Jurkat cells in a time and concentration-dependent mode. Caspase 3 and PARP were rapidly cleaved in response to OM, but apoptosis was only partially inhibited by the caspase 3 inhibitor DEVD-CHO. OM also induced an early lysosomal destabilization which increased progressively and was correlated with a parallel increase in apoptotic cells. The cysteine protease inhibitor E64d gave strong protection against apoptosis thus proving the involvement of lysosomal enzymes in OM-induced apoptosis whereas, it did not impede the caspase 3 cleavage. Instead ZVAD-fmk, a general caspase inhibitor, also able to inhibit cathepsin activity, protected cells completely from OM-induced apoptosis. It therefore seems that both caspases and cysteine cathepsins are involved in the execution stage of OM-induced apoptosis.
Novel Evidence of PLC δ2 Involvement in the Regulation of the Differential Evolution of Aneurysms
Authors: Marchisio M. , Sabatino G.M. , Albanese A. , Santavenere E. , Buonaguidi R. , Miscia S.
Published: January 2017

The biological and molecular mechanisms which are responsible for the formation and possible evolution of human aneurysms are unknown. Previous investigations have pointed to the possible involvement of inositol specific-phospholipase C (PLC) in the mechanisms related to the formation or evolution of intracranial aneurysms, but, thus far, a relationship of one or more PLC isoforms with the biological signals influencing the fate of this lesion has not been demonstrated. The aim of this study was to investigate the expression, activity and possible modification of PLC isoforms in intracranial aneurysms in patients undergoing elective surgical repair after casual identification of unruptured aneurysms, or during emergency surgical repair of ruptured aneurysms. PLC and proliferating cell nuclear antigen (PCNA) expressions were detected by immunoistochemical analysis; PLC activity was obtained by measuring its hydrolytic activity on labelled PIP2; PKC activity was measured by total kinase activity assay. Results indicated no substantial differences between controls and aneurysms, with the only exception being PLC 52 which was nearly absent in controls and ruptured aneurysms, while strongly expressed and functionally active in almost all unruptured aneurysms. In addition, its expression always correlated with the proliferation cell marker PCNA, while its specific activity always correlated to PKC activity. PLC δ2 distribution, regulation and role in human tissues are still unknown Therefore, although preliminary, these data provide a novel insight into the signalling machinery influencing the aneurismal progression.
Cross-Reactivity between IgE-Binding Proteins from Anisakis Simplex and Dermatophagoides Pteronyssinus
Authors: Bernardini R. , Mistrello G. , Novembre E. , Roncarolo D. , Zanotta S. , Lombardi E. , Cianferoni A. , Pucci N. , De Martino M. , Vierucci A.
Published: January 2017

An association was found between Anisakis simplex (As) and Dermatophagoides pteronyssinus (Dp) sensitization. One recent study shows a cross-reactivity between As and Dp and tropomyosin (tr) is suspected as being one of the proteins responsible of this cross-reaction. The aim of our study was: 1) to confirm the cross-reactivity between Dp and As; 2) to determine the importance of tr in this cross reaction. SDS-PAGE analysis of Dp and As (metabolic and somatic) extracts was carried out. Then an IgE immunoblotting test using serum from a patient who had specific IgE only to Dp and As and immunoblotting inhibition experiments using Dp extract and tr as inhibitors were performed. We found that patient's serum reacted: 1) against larval As antigens with a molecular weight (mw) of 25 kilodalton (kD) and a mw > 100 kD, 2) against various metabolic As antigens with a mw > 100 kD, a mw ranging approximately from 35 to 50 kD, and a mw around 20 kD, and 3) against Dp proteins with mw between 35 and 55 kD. Preincubation of patient's serum with Dp extract caused the disappearance of reactivity against antigens with a mw > 100 kD in both larval and metabolic As extracts and against proteins with mw ranging approximately from 35 to 50 kD in the metabolic As extract. Preincubation of patient's serum with As extract caused the disappearance of reactivity against antigens with mw between 35 and 55 kD in the Dp extract. Pre-incubation of patient's serum with tr did not induce any change in the immunoblotting profile. The results show that 1) cross-reactive components between Dp and As are some proteins with a mw ranging approximately from 35 to 50 kD and with a mw > 100 kD, and 2) tr is not involved in cross-reactivity between As and Dp.
Back-Pack Mice as a Model of Renal Mesangial IgA Dimers Deposition
Authors: March A. Kennel-De , Prin-Mathieu C. , Kohler C.H. , Kolopp-Sarda M.N. , Faure G.C. , Béné M.C.
Published: January 2017

Mesangial IgA in IgA nephropathy are dimers with a J chain but no poly-Ig receptor. This molecular structure has led to the hypothesis that these IgA are issued from the lamina propria of mucosal areas, reaching the kidney by way of the peripheral blood. The availability of hybridomas producing IgA dimers provided an opportunity to test this hypothesis in a new experimental model of IgA nephropathy. Mice were injected subcutaneously (back-pack mice) or intraperitoneally with hybridoma cells secreting either monoclonal IgA dimers, or monoclonal IgA monomers. The influence of immune complex formation was also tested in both these models. Renal IgA deposition was investigated 12 days after the injection of hybridoma cells. Backpack mice developed highly vascularized subcutaneous tumors. Mesangial IgA deposits were observed only in dimeric IgA hybridoma back-pack animals. No significant staining was observed in glomeruli from animals injected with hybridoma cells producing monomeric IgA. None of the hybridomas induced mesangial deposition when injected intraperitoneally. This animal model demonstrates the capacity of circulating IgA dimers to spontaneously form mesangial deposits and contributes to confirm the involvement of abnormalities of mucosal immunity in the pathogenesis of IgA nephropathy.
Effect of Mirtazapine on Thyroid Hormones in Adult Patients with Major Depression
Authors: Gambi F. , De Berardis D. , Sepede G. , Campanella D. , Galliani N. , Carano A. , La Rovere R. , Salini G. , Penna L. , Cicconetti A. , Spinella S. , Quartesan R. , Salerno R.M. , Ferro F.M.
Published: January 2017

Hypothalamic pituitary thyroid (HPT) axis abnormalities and alterations in major depression are reported in literature. The aim of our study was to evaluate the effect of mirtazapine on thyroid hormones after 6 months of therapy in a sample of adult outpatients with Major Depression (MD). 17 adult outpatients (7 men, 10 women) with MD according to DSM-IV criteria, were included in the study. All participants had to have met criteria for a major depressive episode with a score of at least 15 on the Hamilton Depression Rating Scale (HAM-D). Fasting venous blood samples were obtained for determination of serum Thyroid Stimulating Hrmone (TSH), Free T3 (FT3) and Free T4 (FT4) concentrations both at baseline and after 6 months of therapy. HAM-D scores decreased significantly from the first day of treatment to the end of the treatment period (p<0.001) and twelve patients (70.6%) were classified as responders. A significant increase in FT3 concentrations was found between baseline and the end of treatment period (P=0.015) whereas FT4 concentrations decreased (P=0.046). No significant changes were found in TSH levels. Higher FT4 concentrations at baseline predicted higher HAM-D scorers both at baseline and at the end of the treatment period. Furthermore, higher FT3 concentrations at endpoint were found to be predictors of lower HAM-D scores. Long-term treatment with mirtazapine increases FT3 levels and decreases FT4 maybe involving the deiodination process of T4 into T3.
Glutaric Aciduria Type II: A Case Report
Authors: Domizio S. , Romanelli A. , Brindisino P. , Puglielli C. , Conte E. , Domizio R. , Sgarrella M. C. , Sabatino G.
Published: January 2017

We report a case of a newborn with Glutaric aciduria type II. Pregnancy was complicated by polyhidramnios and fetal bradycardia. Cardiomegaly was detected by fetal echocardiography. The baby was admitted to the Neonatal Intensive Care Unit of Chieti with respiratory distress syndrome immediately after delivery. He showed head and neck edema, micrognathia, paucity of movement, pronounced hypotonia, bilateral cryptorchidism, micropenis, small hands, skin hyperelasticity and joint hypermobility. Serum and urine analysis showed a fatty acid beta-oxidation disorder. He died at 7 days of age for cardiac arrest and autopsy showed marked hepatic and cardiac vacuolisation, lipid storage myopathy and glial cells vacuolisation. Based upon these findings, we speculate that this infant may be suffering from inborn metabolic disease.
Tumor Necrosis Factor-α in Airway Secretions from Cystic Fibrosis Patients Upregulate Endothelial Adhesion Molecules and Induce Airway Epithelial Cell Apoptosis: Implications for Cystic Fibrosis Lung Disease
Authors: Mitola S. , Sorbello V. , Ponte E. , Copreni E. , Mascia C. , Bardessono M. , Goia M. , Biasi F. , Conese M. , Poli G. , Bussolino F. , De Rose V.
Published: January 2017

Airway inflammation plays a crucial role in lung damage in cystic fibrosis (CF) and is characterized by a persistent influx of neutrophils into the airways. We hypothesized that the high levels of inflammatory products that accumulate in the microenvironment of the CF lung contribute to induce the persistent neutrophil recruitment and the airway epithelial damage. Thus, we evaluated the in vitro effect of sputum sol phase (SSP) from CF patients on a) adhesion molecule expression by human microvascular endothelial cells (HMECs) and b) apoptosis of human bronchial epithelial cells (HBECs), both wild-type and CFTR-defective. SSP was obtained from 7 clinically stable adult CF patients and 8 patients with an acute exacerbation. HMECs and HBECs were cultured in the absence or presence of SSP. Cell adhesion molecule expression was assessed by flow cytometry and cell death by the detection of histone-associated DNA fragments, caspase activation, and cytochrome c release. SSP obtained from CF patients, especially at the time of an acute exacerbation, induced a) an upregulation of endothelial adhesion molecules on cultured HMECs that was associated with an increase of neutrophil adhesion to these cells, and was mediated at least in part by TNF-α and IL-1 and b) apoptosis of airway epithelial cells, mainly activated by TNF-α pathway. These results suggest that the high concentrations of inflammatory mediators in CF airways contribute both to the chronic neutrophil influx and the airway damage, and support the crucial role of early anti-inflammatory treatment in the disease.
Carbamazepine Transbuccal Delivery: The Histo-Morphological Features of Reconstituted Human Oral Epithelium and Buccal Porcine Mucosae in the Transmucosal Permeation
Authors: Campisi G. , Paderni C. , Saccone R. , Siragusa M.G. , Lo Muzio L. , Tripodo C. , Giannola L.I. , Florena A.M.
Published: January 2017

Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailability; thus the aptitude of the drug to penetrate the buccal mucosa has to be assessed by using tissue models resembling human normal mucosa. In our experience, CBZ well permeates mucosal membranes. In order to assess the efficacy of CBZ transbuccal delivery and to verify the reliability of these tissues in permeability testing before and after the passage of CBZ, the histo-morphological features of reconstituted human oral (RHO) epithelium (E) and buccal porcine mucosae were investigated. Significant histological changes due to CBZ passage were observed both in RHO-E and porcine mucosa. The main findings detected in RHO samples were cellular swellings with a signet ring-like appearance, nuclear swelling, prominent nucleoli lined against the nuclear membrane and the presence of keratohyalin granules. The most striking finding regarding porcine buccal mucosa was a cytoplasmic vacuolization, mainly involving the basal layer.
Chronic and Acute Alcohol Exposure Prevents Monocyte-Derived Dendritic Cells from Differentiating and Maturing
Authors: Buttari B. , Profumo E. , Mancinelli R. , Incani U. Cesta , Tosti M.E. , Attilia M.L. , Ceccanti M. , Riganò R.
Published: January 2017

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics' monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-α and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.
Hospitalizations for Pediatric Anaphylaxis
Authors: Calvani M. , Di Lallo D. , Polo A. , Spinelli A. , Zappalà D. , Zicari A.M.
Published: January 2017

The aim of the study is to examine the epidemiology of anaphylaxis in hospitalized children in Lazio (Central Italy) and to evaluate the incidence and case fatality rate. We also verified the concordance of diagnosis between the Emergency Department and Ordinary Hospitalizations. In order to obtain these results, we reviewed all ICD-9 codes indicative of anaphylaxis in all primary and secondary diagnoses from 2000 to 2003 in all Emergency Departments, Ordinary Hospitalizations and Day Hospitals in Lazio. We then identified 203 ICD-9 diagnoses of anaphylaxis in children aged between 0 and 17 years. Anaphylactic shock (995.0) accounted for 109 (53.7%) of cases. Food anaphylaxis (995.60 onwards) accounted for 87 (43.0%) of cases. Food anaphylaxis was more frequent in the first years of life. In fact, it decreased from 12.5/100,000 resident children/year in the first year of life to 6.1/100,000 resident children/year in the first two years of life, and less than 3/100,000 resident children/year after the seventh year (p <0.001). Only 12.5% of cases of anaphylaxis diagnosed in Ordinary Hospitalizations were subsequently diagnosed by the Emergency Department as anaphylaxis. Moreover, only 42.3% of the diagnoses of anaphylaxis made in the Emergency Department were later confirmed during Ordinary Hospitalization. In the four years of study, one child died from anaphylaxis. Thus, mortality was 0.038 cases/100,000 resident children/year. In conclusion, the incidence of hospitalization was highest in the first years of life, during which food anaphylaxis accounted for most hospitalizations. The inconsistency of diagnoses between Emergency Departments and Ordinary Hospitalizations suggests the need to increase awareness of anaphylaxis among health workers.
Dahi Containing Probiotic Lactobacillus Acidophilus and Lactobacillus Casei Has a Protective Effect against Salmonella Enteritidis Infection in Mice
Authors: Jain S. , Yadav H. , Sinha P.R. , Naito Y. , Marotta F.
Published: January 2017

Salmonella enteritidis infection has received attention during recent years owing to its high prevalence worldwide. In the present study, the protective effect of probiotic dahi (curd) supplemented with Lactobacillus acidophilus and L. casei against Salmonella enteritidis infection in mice is investigated. Seven days pre-feeding with probiotic dahi significantly increased anti- S. enteritidis sIgA (secretary IgA) antibodies and lymphocyte proliferation in S. enteritidis infected mice. IL-2, IL-6 and IFNγ production were significantly increased in supernatant of cultured splenocytes collected from mice pre-fed with probiotic dahi, while IL-4 levels were not changed significantly. Moreover, activities of β-galactosidase and β-glucuronidase, and counts of S. enteritidis in intestine, liver and spleen were decreased, whereas total lactobacilli in faeces were increased in mice pre-fed with probiotic dahi. Pre-feeding of probiotic dahi for 7 days was more effective than 2 days pre-feeding. Thus, the results indicate that, pre-feeding with probiotic dahi ameliorated S. enteritidis infection by stimulating specific and non-specific immune response. Above all, it lowered colonization of gastrointestinal tract as well as translocation of S. enteritidis.
Selective TNF-ALPHA Gene Silencing Attenuates Apoptosis in Human Salivary Gland Epithelial Cells
Authors: Sisto M. , D'Amore M. , Scagliusi P. , Mitolo V. , Lisi S.
Published: January 2017

RNA interference (RNAi) was used in this study for selective knockdown of TNF-alpha gene expression in anti-Ro/SSA autoantibodies (Abs)-treated human salivary gland epithelial cells. Our findings reveal that selective TNF-alpha gene silencing resulted in the subsequent attenuation of the pro-apoptotic effects of anti-Ro/SSA Abs; this could have therapeutic effects in autoimmune diseases.
SHH-Dependent Knockout of HIF-1 Alpha Accelerates the Degenerative Process in Mouse Intervertebral Disc
Authors: Wu W-J. , Zhang X-K. , Zheng X-F. , Yang Y-H. , Jiang S-D. , Jiang L-S.
Published: January 2017

Hypoxia-inducible factor-1α (HIF-1α) has been reported to have an important role in the metabolism and synthesis of extracellular matrix of the nucleus pulposus cells (NPCs) and was assumed to be involved in the process of intervertebral disc degeneration. The objective of this study was to investigate the role of HIF-1α in disc degeneration in vivo using a conditional HIF-1α knockout (KO) mouse model. ShhCre transgenic mice were mated with HIF-1α fl/fl mice to generate conditional HIF-1α KO mice ( HIF-1α fl/fl- ShhCre+). Three mice of each genotype (Wide-type and HIF-1α KO) at the age of 3 days, 6, and 12 weeks were sacrificed after genotyping. Five lumbar disc samples were harvested from each mouse, with a total of 45 disc samples for each genotype. In situ hybridization and immunohistochemical analysis were used to check the efficacy of HIF-1α knockout. Histological grading of the disc degeneration was performed according to the classification system proposed by Boos et al. Picro-sirius red staining, Safranine O/fast green staining and immunohistochemical study were used to evaluate the expression of aggrecan, type-II collagen and vascular endothelial growth factor (VEGF). Histologic analysis revealed more NPC deaths and signs of degeneration in HIF-1α KO mice and the degeneration scores of HIF1-α KO mice were significantly higher than those of the Wide-type mice at the age of 6 weeks and 12 weeks. There were less expressions of aggrecan, type-II collagen and VEGF in the intervertebral discs of HIF1-α KO mice than in those of wild-type mice. Taken together, the results of our study indicated that HIF-1α is a pivotal contributor to NPC survival and the homeotasis of extracellular matrix through the HIF-1α/VEGF signaling pathway, and plays an important role in the development of disc degeneration.
Helicobacter Pylori HP(2–20) Induces Eosinophil Activation and Accumulation in Superficial Gastric Mucosa and Stimulates VEGF-α and TGF-β Release by Interacting with Formyl-Peptide Receptors
Authors: Prevete N. , Rossi F.W. , Rivellese F. , Lamacchia D. , Pelosi C. , Lobasso A. , Necchi V. , Solcia E. , Fiocca R. , Ceppa P. , Staibano S. , Mascolo M. , D'Argenio G. , Romano M. , Ricci V. , Marone G. , De Paulis A.
Published: January 2017

Eosinophils participate in the immune response against Helicobacter pylori, but little is known about their role in the gastritis associated to the infection. We recently demonstrated that the Hp(2–20) peptide derived from H. pylori accelerates wound healing of gastric mucosa by interacting with N-formyl peptide receptors (FPRs) expressed on gastric epithelial cells. The aim of the present study was to investigate whether eosinophils play a role in the repair of gastric mucosa tissue during H. pylori infection. Immunohistochemistry and transmission electron microscopy were used to detect eosinophils in gastric mucosal biopsies. Eosinophil re-distribution occurred in the gastric mucosa of H. pylori-infected patients: their density did not change in the deep mucosal layer, whereas it increased in the superficial lamina propria just below the foveolar epithelium; eosinophils entered the epithelium itself as well as the lumen of foveolae located close to the area harboring bacteria, which in turn were also engulfed by eosinophils. The H. pylori-derived peptide Hp(2–20) stimulated eosinophil migration through the engagement of FPR2 and FPR3, and also induced production of VEGF-A and TGF-β, two key mediators of tissue remodeling. We also demonstrate that Hp(2–20) in vivo induced eosinophil infiltration in rat gastric mucosa after injury brought about by indomethacin. This study suggests that eosinophil infiltrate could modulate the capacity of gastric mucosa to maintain or recover its integrity thereby shedding light on the role of eosinophils in H. pylori infection.
Sarcoidosis, Cancer and Molecular Mimicry
Authors: Tchernev G. , Wollina U.
Published: January 2017

Molecular mimicry seems to be the most important factor for the heterogeneous clinical presentation and the immunopathogenesis of sarcoidosis. Molecular mimicry may occur as a result of altered activity of oncogenes. This can lead to crossed-type mediated body reactions targeting structurally similar sections or regions from the tissue homeostasis. Available data suggest that structural analogy between tissue and foreign or de novo-appearing peptides is not always reliable. Nevertheless, lack of amino acid identity between the tissue and the de novo-generated tumour antigens does not exclude the phenomenon of molecular mimicry as the major generator of sarcoidosis. There is growing evidence of the mimicry phenomena, caused not only by the similarity between the amino acids but also between the elements which connect segments in the immunological cascade and which may also be affected by external factors. Molecular mimicry may occur between two identified peptides having similar antigenic surfaces (transitory or not), in the absence of a primary homology in amino acid sequence. As far as tumour antigens are concerned, a structural analogy to the de novo-appearing tumour antigens is more likely than transitory imitation resulting from the additional interference of other physical forces. Further research should be performed to confirm, or reject, the transitory imitation thesis or hypothesis.
Evidence and Role of Autoantibodies in Chronic Rhinosinusitis with Nasal Polyps
Authors: Macri G.F. , Greco A. , Marinelli C. , Gallo A. , Fusconi M. , De Virgilio A. , De Vincentiis M.
Published: January 2017

In this study, we review our current knowledge of the autoimmune etiopathogenesis of chronic rhinosinusitis with nasal polyps including bacterial infections, viral infections and immunomediated mechanisms and to discuss pathogenesis with relevance for pharmacotherapy. Relevant publications on the etiopathogenesis and treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) from 1977 to 2013 were analyzed. The characteristic signs and symptoms include appearance of relapsing nasal polyps, with typical symptoms such as nasal obstruction, nasal discharge and, usually, loss of the sense of smell. The etiology and pathogenesis remain unknown. Proposed theories of causation include bacterial or viral infections and immunomediated mechanisms. The autoimmune aetiology of of unknown origin or failure to respond to classic pharmacological treatments with nasal and oral steroids is now suspected. At present, the nature of the antigen trigger, the exact role played by B/T cells and anti-dsDNA autoantibodies in the pathogenesis of nasal polyposis remains unclear. Corticosteroids and surgery are the first line of treatment in CRSwNP. In the case of corticosteroid treatment failure, other drugs can be used such as rituximab, belimumab or omalizumab which have demonstrated clinical efficacy in the treatment of nasal polyposis with comorbid asthma. Immunosuppressive drugs such as methotrexate, and cyclophosphamide have also been used with varying degrees of success.
Corticotropin-Releasing Hormone, Microglia and Mental Disorders
Authors: Kritas S.K. , Saggini A. , Cerulli G. , Caraffa A. , Antinolfi P. , Pantalone A. , Rosati M. , Tei M. , Speziali A. , Saggini R. , Conti P.
Published: January 2017

Microglia derive from mononuclear myeloid progenitors and are a major glial complement of the central nervous system. When microglia are activated they secrete inflammatory cytokines and toxic mediators which amplify the inflammatory response. In addition, the microglia inflammatory products are implicated in the neuronal destruction usually observed in various neurodegenerative diseases. Microglia cells express corticotropin releasing hormone (CRH) receptors, and activation of microglia by CRH releases bioactive molecules which have a biological effect in the brain and regulate several neurological diseases. CRH plays a pivotal role in stress responses and is a key mediator of the hypothalamic-pituitary-adrenocortical system. CRH is expressed in human mast cells, leading to autocrine effects and participates in inflammatory response together with neuropeptides, and stimulates mast cells. IL-33-activated mast cells release vascular endothelial growth factor in response to CRH and act synergistically to increase vascular permeability. CRH also up-regulates IL-18 expression by increasing intracellular reactive oxygen in microglia cells. Here we report the relationship between CRH, microglia and mental disorders.
Do Elevated Serum IgM Levels Have to Be Included in Probable Diagnosis Criteria of Patients with Ataxia-Telangiectasia?
Authors: Azarsiz E. , Karaca N.E. , Gunaydin N.C. , Gulez N. , Ozturk C. , Aksu G. , Genel F. , Kutukculer N.
Published: January 2017

Ataxia-telangiectasia (AT) is a rare multisystem, neurodegenerative genetic disorder that is characterised by progressive neurological abnormalities, oculocutaneous telangiectasias and immunodeficiency. Delay in diagnosis or misdiagnosis is probable due to its wide clinical heterogeneity in infancy. Recurrent sinopulmonary infections are often the only presenting symptom and usually patients have decreased immunoglobulins. A total 10% of patients who present with decreased serum immunoglobulin G and A and with normal or elevated immunoglobulin M levels are often misdiagnosed as hyperimmunoglobulin M syndrome. Definitive diagnosis is made if a patient with progressive cerebellar ataxia has a disease causing mutation on the ATM gene. Ataxia-telangiectasia guideline of the European Society for Immunodeficiencies defines the probable diagnosis criteria. We evaluated twenty ataxia-telangiectasia patients (mean age 13.8±4.1 years) retrospectively who were followed-up for a mean of 38.6±27.0 months. Twelve patients had a family history of consanguinity. A total of 80% patients suffered from various infections. Neoplasms occurred in three of them. Patients showed immunological abnormalities as low IgG (45%), low IgA (65%) and elevated IgM (60%) levels. CD3+CD4+ T lymphocyte frequency was low in 45% patients. The mean AFP concentration at the diagnosis was 191.9±140.1 ng/ mL and the raised IgM values did not show any statistically significant relationship with high AFP concentrations. Frequency of the elevated IgM concentrations in (60%) patients raises the concerns about thinking this finding has to be accepted as a probable diagnosis criterium.
An Incomplete Form of Childhood Behçet's Disease Treated with Infliximab
Authors: Caporuscio S. , Pranteda G. , Nisticò S. , Maucione T. , Canzoni M. , Stefani A. , Muscianese M. , Fantò M. , Sorgi M.
Published: January 2017

Behçet's disease (BD) is a multi-systemic vasculitis characterized by the possible presence of cutaneous, ocular, articular and neurological manifestations. In this report, we examine the case of a fifteen-year-old boy with an incomplete form of juvenile Behcet's disease which began with joint involvement and developed into a complete form only after several years. The patient showed a rapid response to anti-TNF-alpha (infliximab) with an improvement of mucocutaneous lesions (oral and genital ulcers, pseudofolliculitis) and arthritis.
Serine/Threonine Phosphatases: Classification, Roles and Pharmacological Regulation
Authors: Bastan R. , Eskandari N. , Sabzghabaee A.M. , Manian M.
Published: January 2017

Phosphatases are important enzymes in a variety of biochemical pathways in different cells which they catalyze opposing reactions of phosphorylation and dephosphorylation, which may modulate the function of crucial signaling proteins in different cells. This is an important mechanism in the regulation of intracellular signal transduction pathways in many cells. Phosphatases play a key role in regulating signal transduction. It is known that phosphatases are specific for cleavage of either serine-threonine or tyrosine phosphate groups. To date, numerous compounds have been identified. This paper reviews the classification, roles and pharmacological of protein serine/threonine phosphates.
Current Advances in the Understanding and Treatment of Mevalonate Kinase Deficiency
Authors: Esposito S. , Ascolese B. , Senatore L. , Bosis S. , Verrecchia E. , Cantarini L. , Rigante D.
Published: January 2017

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory metabolic disease that is caused by mutations in the MVK gene. Patients with MKD typically have an early onset in infancy. MKD is characterized by recurrent episodes of high fever, abdominal distress, diffuse joint pain, and skin rashes. In a subset of patients, MKD is also associated with elevated serum immunoglobulin D (IgD) levels (hyperimmunoglobulinemia D syndrome, HIDS). The clinical phenotype of MKD varies widely and depends on the severity of the impaired mevalonate kinase activity. Complete impairment results in the severe metabolic disease, mevalonic aciduria, while a partial deficiency results in a broad spectrum of clinical presentation, including HIDS. The precise molecular mechanisms behind the elevated serum IgD levels and inflammation that occurs in MKD remain unknown. Children who exhibit symptoms of MKD should be tested for mutations in the MKD gene. However, the complexity of MKD often results in delays in its definitive diagnosis and the outcome in adult age is not completely known. Therapeutic options for MKD are based on limited data and include non-steroidal anti-inflammatory drugs, corticosteroids, and biological agents that target specific cytokine pathways. In recent years, some studies have reported promising results for new biological drugs; however, these cases have failed to achieve satisfactory remission. Therefore, further studies are needed to understand the pathogenesis of MKD and identify innovative therapeutic tools for its management.
Role of Mast Cells in Atherosclerosis: A Classical Inflammatory Disease
Authors: Spinas E. , Kritas S.K. , Saggini A. , Mobili A. , Caraffa A. , Antinolfi P. , Pantalone A. , Tei M. , Speziali A. , Saggini R. , Conti P.
Published: January 2017

Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selectin, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process.