bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Intravenous Erythromycin Lactobionate in Respiratory Infections
Authors: Sciacca A. Di , Durante F. , Cucchiara G. , Ingrassia A. , Mira G. , Mannone F. , Piazza R. M. Di , Frontini A. , Sangiorgi G. Barbagallo
Published: January 2017

The antibiotic erythromycin lactobionate given intravenously acts almost exclusively on Gram-positive bacteria. Even at high plasma and tissue concentrations there is an almost total absence of side-effects. It could be considered, therefore, as first choice in the treatment of patients with infectious respiratory diseases. Most of the 40 patients admitted to the present study were elderly and all had either acute or chronic and becoming acute respiratory disease. Their clinical symptoms and levels of phlogosis improved on treatment with erythromycin lactobionate without any interruption of therapy due to side-effects and toxicity. The absence of unfavourable pharmacological interactions further enhances the usefulness of the drug. In view of the excellent response to monotherapy with erythromycin lactobionate and the few groups of resistant bacteria found in those cases when it was possible to check, it was not considered necessary to investigate any synergistic association with other antibiotics. It can be concluded, therefore, that therapy with erythromycin lactobionate in patients with infective respiratory disease is favourable and patients show excellent tolerability.
Treatment of Chronic Obstructive Pulmonary Disease with Two Sustained-Release Theophylline Preparations
Authors: Giosue' S. , Bernocchi D , Parola D. , Munno R. , Mancini P.
Published: January 2017

A sustained-release theophylline preparation in capsule form was compared with standard slow-release theophylline tablets for variation in plasma theophylline concentration, effectiveness and tolerability in 30 adults with chronic broncho-obstructive pathology. They were administered every 12 h and blood samples were collected after 8 days of treatment during the steady-state period. In this double-dummy crossover study, the sequence of the two regimens (sustained-release capsules versus tablets) was selected at random. The results of this study demonstrate that plasma theophylline levels remain within the therapeutic range for both preparations. Effectiveness and tolerability of the two drugs were satisfactory.
Adequate Relief as an Endpoint in Clinical Trials in Irritable Bowel Syndrome
Authors: Mangel AW , Hahn BA , Heath AT , Northcutt AR , Kong S , Dukes GE , McSorley D
Published: January 2017

Irritable bowel syndrome is characterized by recurrent abdominal pain and altered bowel function. In designing studies to evaluate new treatments for this disease, however, it is difficult to select appropriate endpoints to reflect improvement in the range of symptoms of the syndrome. In the present study we evaluated the parameter of adequate relief of abdominal pain and discomfort, as perceived by the patients, as a key endpoint for efficacy in the treatment of patients with irritable bowel syndrome. Abdominal pain and bowel function data were collected daily from 370 patients with the disease during treatment with placebo or a novel potent 5HT3 receptor antagonist. Once every 7 days adequate relief of pain and discomfort was assessed. Quality-of-life data were collected using self-administered questionnaires. The endpoint of adequate relief was significantly ( P < 0.05) correlated with improvement in pain severity scores, percentage of pain-free days, percentage of days with urgency, improvement in stool frequency and consistency, and quality-of-life parameters. Adequate relief of pain and discomfort is significantly correlated with changes in multiple parameters associated with irritable bowel syndrome and can be used as an endpoint for assessing response to therapy in these patients.
Effects of Splenectomy on Luteal Function in Pseudopregnant Rabbits
Authors: Endo T , Kanayama K
Published: January 2017

The involvement of the immune system in changes in luteal function was evaluated in rabbits. Pseudopregnancy was induced in 10 females and the spleens (considered to be the source of macrophages) of five were excised on day 7 of pseudopregnancy, while the five controls had sham splenectomies. Subsequent changes in serum progesterone concentrations were measured as an indicator of luteal function and luteolysis. A second pseudopregnancy was induced 31 days after splenectomy. The first pseudopregnancy was prolonged and during the second pseudopregnancy the serum progesterone concentrations on days 3 and 7 were much lower in the splenectomy group than in the control group. On day 14 of the second pseudopregnancy, the serum progesterone concentration markedly decreased in the control group while it remained almost at the level of day 7 in the splenectomy group. These results suggest that splenectomy suppresses the expression of luteal function and delays luteolysis in rabbits.
Expression of p53 Protein and Prognosis in Gastric Carcinoma
Authors: Gürel S , Dolar E , Yerci Ö , Samli B , Öztürk H , Nak SG , Gülten M , Memik F
Published: January 2017

A study was carried out to assess whether p53 expression is related to tumour type, grade or pathological characteristics, or to prognosis, in gastric cancer. Immunohistochemical studies were performed to detect p53 protein in sections from 55 consecutive gastrectomy or partial gastrectomy specimens. Tumours were classified for T-stage, histopathological grade and pathological characteristics. Immunohistochemical staining detected p53 protein in 11 (19%) of the 55 specimens. There was no statistically significant difference between patients with p53 positively staining tumours and patients with p53 negatively staining tumours with regard to tumour grade, stage or pathological characteristics (lymph-node infiltration, depth of invasion, necrosis, or necrosis of vessels). Survival time was statistically significantly lower in patients with positively staining tumours (mean survival times 12.0 and 23.4 months, respectively). These results suggest that expression of p53 protein is related to poor prognosis in gastric carcinoma.
Carcinoma of the Anal Sac Glands in Ranch Mink
Authors: Hadlow W. J.
Published: January 2017

During a 14-year period, carcinoma of the anal sac apocrine glands was found in 52 pastel and 8 sapphire mink ( Mustela vison) kept for studies on slow viral diseases. The pastel mink varied in age from 72 to 135 months (mean age 108 months), the sapphire mink from 63 to 100 months (mean age 81 months). All but one pastel mink were females. The primary tumor varied in size from masses that caused bulges in the perineum to those that were found only after microscopic examination of the anal sac glands. Although the primary tumor grew mainly by expansion with little local infiltration, 41 of the 60 tumors had metastasized to the regional lymph nodes and sometimes also to more distant sites. The striking propensity of the carcinoma to metastasize while still small, even microscopic, often resulted in massive secondary growths, notably in the iliac lymph nodes. Hypercalcemia did not accompany the carcinoma. Its varied microscopic appearance included solid, glandular, squamous cell, and spindle or round cell components. Combinations of them formed mixed or complex histologic patterns, no doubt largely attributable to neoplastic proliferation of myoepithelial cells and squamous metaplasia of the apocrine gland epithelium. Although its cause remains obscure, the carcinoma appeared to arise from small foci of hyperplastic apocrine glands, sometimes in relation to both anal sacs. The tumor is a common and distinctive expression of neoplasia in older ranch mink.
Pathogenesis of Placentitis in the Goat Inoculated with Brucella abortus. II. Ultrastructural Studies
Authors: Anderson T. D. , Cheville N. F. , Meador V. P.
Published: January 2017

Pregnant goats were inoculated intravenously or in uterine arteries with Brucella abortus, and tissues from the uterus and placenta were examined by electron microscopy. Identification of B. abortus in placentae was with antibody-coated colloidal gold. B. abortus was first seen in phagosomes of erythrophagocytic trophoblasts and in the rough endoplasmic reticulum of chorioallantoic trophoblasts. Subsequently, trophoblast necrosis and ulceration of chorioallantoic membranes were present. Coincidently, B. abortus was present in the lumen of placental capillaries. In late stages of infection, placental vasculitis was present, and placentomal trophoblasts were separated from maternal syncytial epithelium. In lesions with vasculitis, large numbers of B. abortus were in connective tissue of chorionic villi. Within the placentome, trophoblasts that lined chorionic villi contained no intracellular bacteria and were separated from B. abortus by intact basement membranes. These results suggest that bacteremic B. abortus is endocytosed by erythrophagocytic trophoblasts and that B. abortus replicates in the rough endoplasmic reticulum of chorioallantoic trophoblasts. Replication of brucellae in trophoblastic rough endoplasmic reticulum is unique; we believe that B. abortus may utilize endoplasmic reticulum for synthesis and glycosylation of bacterial membrane proteins or that B. abortus catabolizes trophoblast secretory proteins.
Ultrastructural and Clinicopathological Studies on the Toxicity of Cationic Acrylamide-based Flocculant to Rainbow Trout
Authors: Albassam M. , Moore J. , Sharma A.
Published: January 2017

Rainbow trout (Salmo gairdneri) of two age groups were exposed to a cationic acrylamide-based flocculant at various concentrations in static bioassay chambers. At lethal concentrations the flocculant produced severe gill alterations in all fish. The principal alterations were necrosis and separation of the respiratory epithelial cells covering secondary lamellae. Many necrotic chloride cells were also seen, their apical plasma membrane was destroyed, and mitochondria were swollen with separated cristae. An influx of a large amount of fluid into the interstitial spaces caused partial or complete separation of subepithelial spaces from the covering epithelial cells and basement membranes of underlying blood vessels. Clinicopathological alterations included marked decreases in blood pH, partial pressure of oxygen, bicarbonate and plasma sodium, and chloride concentrations. Hematocrit, total protein, and blood glucose were increased. Fish exposed to sublethal concentrations had gill alterations characterized by hypercellularity and thickening of the secondary lamellae. These were due to undifferentiated cell proliferation and macrophage and lymphocyte infiltration between the covering epithelial cells and the underlying blood vessels. Macrophages and undifferentiated cells had large phagolysosomes containing cytoplasmic organelles, an indication of cell injury and increased turnover.
Spontaneous Tumors of the Meninges in Rats
Authors: Mitsumori K. , Maronpot R. R. , Boorman G. A.
Published: January 2017

Histologic brain sections from 107 rats reported to have granular cell tumors or meningiomas in 2-year carcinogenicity studies conducted by the National Toxicology Program (NTP) or the National Cancer Institute (NCI) were reexamined microscopically. There were 62 rats with granular cell tumors, 26 with benign meningiomas, and 19 with meningeal sarcomas. Granular cell tumors were compatible with previous descriptions of this tumor. Meningeal sarcomas were subclassified into nine spindle cell sarcomas and ten fibrosarcomas. Among the rats with benign meningiomas, five were typical meningiomas (three fibroblastic meningiomas, and two meningothelial meningiomas) and 21 were meningothelial meningiomas containing cells with granules identical to those in granular cell tumors. There was a transition from epithelial-like cells of the meningothelial meningiomas to granular cells in these 21 cases. Based upon anatomic location, cytomorphologic similarities, and the occurrence of transitional or mixed forms of meningothelial meningiomas and granular cell tumors, it is suggested that these two tumors are related and may both originate from a common progenitor meningothelial arachnoid cell.
Coagulation Defects of Aflatoxin Intoxicated Rabbits
Authors: Baker D. C. , Green R. A.
Published: January 2017

Twelve New Zealand white rabbits were intoxicated with aflatoxin B1. Most rabbits developed a coagulation defect near the time of death. Immediately prior to death there were significant decreases in factors V, VII, and VIII coagulant activities and fibrinogen concentration without a change in plasma fibrin(ogen) degradation product concentration, platelet number, and detectable plasma fibrin monomers. Microscopic evidence of disseminated intravascular coagulation was present in one rabbit with marked, diffuse hepatic necrosis. Terminal serum albumin concentration was significantly correlated to plasma factors V and VII activities and fibrinogen concentration. The coagulation defect of aflatoxicosis is primarily due to diminished hepatic synthesis of coagulation factors except when hepatic necrosis is severe enough to initiate intravascular coagulation and consumption of coagulation factors.
Hematology in the Regressive Phase of Bovine Psoroptic Scabies
Authors: Stromberg P. C. , Guillot F. S.
Published: January 2017

Hereford calves were infested with Psoroptes ovis. Hemograms were evaluated weekly for 7 weeks during progressively extensive dermatitis and compared to uninfested control calves. Calves were treated with ivermectin and weekly hemograms were compared for 4 weeks during regression of clinical disease. They developed extensive dermatitis and marked decreases in total white blood cells, neutrophils, and lymphocytes. Infested calves also had moderate anemia, increased plasma proteins, and increased plasma fibrinogen. Some calves developed marked eosinophilia. Within 1 week after ivermectin treatment, nearly all hematologic parameters returned or began to return to normal values, even though scabs remained on the calves at 4 weeks. Peak eosinophilia in calves which responded occurred 1 to 2 weeks after treatment. The findings indicate that most of the hematologic changes occurring with psoroptic scabies in cattle are associated with living mites and not with toxic substances in the scab on the skin surface.
Progressive Chronic Osteoarthritis in Femorotibial Joints of Partial Medial Meniscectomized Guinea Pigs
Authors: Bendele A. M.
Published: January 2017

The sequential histopathologic alterations in femorotibial joints of partial meniscectomized male and female guinea pigs were evaluated at 1, 2, 3, 6, and 12 weeks post-surgery. Foci of moderate to severe cartilage degeneration were present in the medial tibial plateau and femoral condyle of the operated leg by 1 week post-surgery. At 2 weeks post-surgery, the cartilage degeneration in the operated legs was more extensive and there was evidence of early chondrophyte formation on the medial side of either the femur or tibia in three animals. Changes were progressively more severe at 3, 6, and 12 weeks. Focal areas of minimal to mild cartilage degeneration were in the medial tibial plateau of the contralateral nonoperated leg in some animals at 3 weeks post-surgery and in all animals at 12 weeks post-surgery. Changes in the contralateral leg of meniscectomized guinea pigs have not been described previously. Since cartilage degeneration was often severe by 1 week post-surgery, the model has limited utility for testing agents designed to modify the degenerative process in the operated leg. Milder, more slowly progressive lesions in the contralateral leg may be amenable to therapeutic intervention.
Acute Ehrlichia platys Infection in the Dog
Authors: Baker D. C. , Simpson M. , Gaunt S. D. , Corstvet R. E.
Published: January 2017

Ten dogs were inoculated with Ehrlichia platys ( E. platys) from an acutely infected dog. Two dogs were necropsied on each of days 7, 14, 21, 28, and 35 post-inoculation, and tissues were collected and either fixed in formalin or frozen for light microscopic examination of lesions or E. platys antigen localization in tissues. Serum antibody titers to E. platys and serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities were also determined. The significant light microscopic findings were lymph node follicular hyperplasia and crescent-shaped hemorrhages in the splenic periarteriolar lymphoid sheaths beginning day 7 post-inoculation. There was significant megakaryocyte hyperplasia of bone marrow on days 28 and 35 post-inoculation. Ehrlichia platys antigen was in macrophages at 14 days post-inoculation which corresponded to the initial decline in platelet numbers. Initial thrombocytopenia and splenic crescent-shaped hemorrhages were temporally related, however the degree of lesion development and prominence were not related to subsequent platelet numbers.
Objectivity to order
Authors: Caryl Christian
Published: January 2017

Access is the key problem for journalists reporting on the second Chechen war, and is under tight military control
Redemption by numbers
Authors: Verney Peter
Published: January 2017

US kids are washing windows to free enslaved Sudanese children. Have the Arab slavers returned, or is this the ultimate low in child sponsorship?
La ronde
Authors: Hope Alan
Published: January 2017

Women are an inexhaustible commodity for the East European mafiosi who trade them across borders and between states
The love boat
Authors: Walter Natasha
Published: January 2017

In Albania's chaotic economy, the traffic in women is a way of life
To borrow and to borrow
Authors: Sutcliffe Bob
Published: January 2017

Debt bondage doesn't affect only individuals and families: it has shackled entire nations
The real solution
Authors: Dudley Steve
Published: January 2017

Rather than tackling them at the root, the government is throwing money at Colombia's problems
A dastardly business
Authors: Mbachu Dulue
Published: January 2017

Despite protests from western governments on the conduct of the proceedings, the trials of alleged coup plotters continues in secret in Nigeria
Hostage to a male agenda
Authors: Moorehead Caroline
Published: January 2017

From Somalia to the Balkans, from Rwanda to Colombia, rape has become the ultimate weapon in the dying century's wars
Hidden histories
Authors: Butalia Urvashi
Published: January 2017

The history of the bloodstained partition of India in 1947 is well known: 12 million displaced, over one million dead. The story of tens of thousands of women killed ‘for the honour of their community’, abducted, raped, abandoned, has yet to be told
A small war you may have missed
Authors: Corley Felix
Published: January 2017

By the time Moscow took on General Dudayev and the Chechens, it had already made war on another Caucasian people. Its success against the Ingush went unremarked
Cuba redux
Authors: Newey Adam
Published: January 2017

Cuba's resurgent civil society groups are trying to spark a debate on the country's urgent economic and social problems. But breaking down the old Cold War polarities is a dangerous business. A report from Cuba compiled
Language of survival
Authors: Dorfman Ariel
Published: January 2017

What separates intolerance from violence? Is there any way of making sure that one does not turn into the other? An encounter I had over 10 years ago may provide a way into these questions, a tentative answer
Set for collision
Authors: Cronenberg David , Ballard J. G.
Published: January 2017

Even before it opened at the 1996 London Film Festival, David Cronenberg's latest film Crash, based on the novel by JG Ballard, was subjected to vitriolic abuse in the right-wing tabloids and to outraged moralising by politicians, none of whom had seen it. Preempting a British Board of Film Classification ruling, Westminster City Council banned its screening throughout London's West End cinemas. Only on 18 March did the often over-cautious director of the board, James Ferman, defy general censure and give it a clean bill of health and an 18 certificate, saying that while ‘unusual and disturbing’, the film was neither illegal nor harmful. Author and film-maker discuss the renewed furore surrounding Crash 25 years after its first publication
Involvement of Caspase-3 in the Cleavage of Terminal Transferase
Authors: Trubiani O. , Guarnieri S. , Paganelli R. , di Primio R.
Published: January 2017

To investigate the in vivo role of caspase-3 in Terminal Transferase metabolism DMSO-treated RPMI-8402, a human pre-T cell line was used. In DMSO treated samples 3H-dGTP incorporation and TdT phosphorylation occurs after 4 hours of treatment. After 8 hours cells undergo TdT proteolysis in addition to its inactivation. The cleavage of TdT into 32- and 58-KDa proteolytic fragments occurred simultaneously with the activation of Caspase-3, but preceded changes associated with the apoptotic process described after 48 hours of treatment. The Caspase-3 peptide inhibitor V, used as a specific inhibitor, prevented TdT proteolysis prolonging its activity and rescued cells from apoptosis. Our experiments suggest that TdT is a nuclear substrate for Caspase-3, the main apoptotic effector protease in many cell types, and that the cleavage of TdT represents a primary step in a signal cascade leading to pre-T cell apoptosis.
Effect of Yogurt on the Inhibition of an Intestinal Carcinoma by Increasing Cellular Apoptosis
Authors: Rachid M.M. , Gobbato N.M. , Valdéz J.C. , Vitalone H. H. , Perdigón G.
Published: January 2017

Yogurt consumption has been associated with decreased risk of colon cancer. The apoptosis induced by yogurt as a mechanism involved in the inhibition of an experimental intestinal tumor induced by 1,2 dimethylhydrazine (DMH) in BALB/c mice, has been studied. An imbalance between apoptosis and mitosis or cell proliferation is believed to underlie colon cancer development and progression. We determined the effect of yogurt feeding in the induction of apoptosis and the relationship between mitosis and apoptosis in mice injected with the carcinogen DMH and in mice injected with DMH and fed with a diet supplemented with yogurt. The percentage of mitotic and apoptotic cells was analyzed every 2 weeks from week 8 to 16. They were analyzed on histological slices from the large intestine by colchicine, or Tunel test for mitosis and apoptosis determination, respectively. An increase in the mitosis during the first 4 weeks of tumor development with apoptosis negative and severe dysphasia, was observed in animals treated with the carcinogen. In those animals that received DMH and were given yogurt, a moderate cell proliferation with a significant increase in the number of apoptotic cells was determined. The increase in the apoptotic activity was also observed in the group of animals that received only a diet supplemented with yogurt. The results suggest that yogurt would influence the balance between mitosis and apoptosis, which was modified during the carcinogenesis process, by increasing cellular apoptosis. Dietary supplementation of yogurt may play a role in modulating cell proliferation or apoptosis during the development of colorectal carcinoma.
Immediate Allergic Reactions to β-Lactams: Diagnosis and Therapy
Authors: Romano A. , Mondino C. , Viola M. , Montuschi P.
Published: January 2017

β-Lactams are the antibiotics which most frequently provoke adverse reactions mediated by specific immunological mechanisms. These reactions, classifiable as immediate or non-immediate, can be produced by the four classes of β-lactams (penicillins, cephalosporins, carbapenems and monobactams) currently available, which share a common β-lactam ring structure. Immediate reactions occur within the first hour after drug administration and are characterized by urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock. Immediate reading skin tests are the quickest and most reliable method for demonstrating the presence of β-lactam specific IgE antibodies. It is crucial to use in diagnosis the suspected β-lactams themselves, particularly cephalosporins, in addition to penicillin determinants. Serum specific IgE assays can be used as complementary tests. Negative test results should be interpreted in light of the time elapsed from the last exposure to the responsible β-lactam. In fact, both in vivo and in vitro test sensitivity is known to decrease over time. In some diagnostic work-ups, patients with a positive history and negative skin and in vitro tests with classic reagents undergo a controlled administration of the suspected β-lactam. The management of immediate allergic reactions should take into consideration their severity and type. Adrenaline is the drug of choice in the treatment of anaphylactic shock. In addition to adrenaline, corticosteroids and antihistamines should be administered. Histamine H1 receptor antagonists are the mainstay of the treatment of immediate allergic reactions such as urticaria, rhinitis and conjunctivitis.
Levels of Enzymatic Antioxidants Activities in Mononuclear Cells and Skin Reactivity to Sodium Dodecyl Sulphate
Authors: Camera E. , Lisby S. , Dell'Anna M.L. , Santucci B. , Paganelli R. , Baadsgaard O. , Picardo M.
Published: January 2017

Chemical irritants are able to produce several biological modifications of the skin, including the direct or indirect production of cytokines and reactive oxygen species leading to an inflammatory reaction. This report examines the existence of a possible correlation between the skin sensitivity to the irritant sodium dodecyl sulphate (SDS) and the activity of the enzymatic antioxidants. In twenty-three healthy subjects the evaluation of the epidermal and peripheral blood mononuclear cells (PBMCs) activities of superoxide Dismutase (SOD) and Catalase (Cat) demonstrate a significant correlation (r= 0,85 and p< 0,005 for SOD, and r= 0,87 and p< 0,0001 for Cat). Based on this result, on a further group of normal subjects (n=13) we studied the link between the threshold dose of skin reactivity to SDS and the activities of the enzymatic antioxidants in PBMCs. The degree of skin modification induced by SDS, applied at different concentrations for 24 hrs, was determined by means of Trans Epidermal Water Loss (TEWL), Erythemal Index or by Visual Score (VS). The minimal dose of the irritant capable of inducing skin modifications, was significantly correlated with SOD (r=0,77) and Cat (r=0,81) activities in PBMCs, and the modification of TEWL or EI were inversely correlated with levels of antioxidants in PBMCs (r=−0,62 for SOD and r=−0,66 for Cat). Our results indicate that the skin reactivity to irritants can be modulated by the levels of antioxidants, and suggest a possible therapeutical approach in preventing irritant contact dermatitis.
The Role of Substance P in the Cerebral Ischemia
Authors: Bruno G. , Tega F. , Bruno A. , Graf U. , Corelli F. , Molfetta R. , Barucco M.
Published: January 2017

Tackykinins are involved in the inflammatory process of a large number of diseases. The role of the tachykinins in ischemic brain injury was evaluated by the serum levels of Substance P (SP), one of the most known tachykinins and detected by a competitive enzyme immunoassay. The study was performed in 15 human females and 3 human males with typical manifestation of complete stroke (12 cases) or transient ischemic attack (6 cases). The mean SP level in the serum of patients with transient ischemic attack (0.53±0.25 ng/ml) and of patients with complete stroke (0.31±0.14 ng/ml), showed significantly higher values than in controls (0.10±0.02 ng/ml). Moreover, in transient ischemic attack, the SP values were significantly higher than in cerebral complete stroke. But SP levels, based on the timings of classification of patients (i.e. before 12 hours: 0.34±0.15 ng/ml vs. 12 to 24 hours: 0.26±0.11 ng/ml) with brain injury, did not show any significant difference. Both values anyway were significantly higher than in controls. Our original results demonstrate the SP increase during cerebral ischemia. Further studies are necessary to verify if SP has an effective physiopathological role in the neurological ischemic damage, or if it is only a concomitant phenomenon. Our data, if confirmed, will be particularly important, not only to improve the knowledge of cerebral ischemic injury, but also for diagnosis and therapeutic approaches.
Macrophage-Targeted Photodynamic Therapy: Scavenger Receptor Expression and Activation State
Authors: Liu Q. , Hamblin M. R.
Published: January 2017

Macrophage-targeted photodynamic therapy (PDT) may have applications in the selective killing of cells involved in atherosclerosis, inflammation and tumor. We have previously shown that a conjugate between the photosensitizer chlorin(e6) (ce6) and maleylated bovine serum albumin (BSA-mal) gives highly selective targeting to macrophages. In this report we examine the effect of macrophage activation and scavenger receptor class A (SRA) expression on this targeting in two murine macrophage tumor cell lines (RAW264.7 and P388D1) and a control murine mammary sarcoma cell line (EMT-6). Cells were pretreated with interferon gamma (IFNγ) and/or lipopolysaccharide (LPS) followed byBSA-ce6-mal addition, and SRA expression, tumor necrosis factor alpha (TNFα) release, conjugate uptake and PDT killing were measured. Both macrophage cell lines expressed SRA and took up conjugate specifically in an SRA-dependent manner, but differences were observed in their response to activation. RAW264.7 expressed increasingly more SRA and took up increasingly more BSA-ce6-mal in response to IFNγ, LPS, and IFNγ+LPS, respectively. The PDT killing did not follow the same pattern as the uptake of the photosensitizer. The increase in uptake in the IFNγ treated cells did not lead to an increase in PDT killing, while stimulation with LPS or IFNγ+LPS resulted in a significant protection against PDT, despite a significant increase in photosensitizer uptake. P388D1 was responsive to neither IFNγ, nor to LPS, or to IFNγ+LPS with respect to SRA expression, conjugate uptake, and PDT killing. These data may have implications for the use of PDT to target physiologically undesirable macrophage subtypes implicated in disease, and on how manipulation of the activation status of the macrophage will influence the PDT effect.
Elevated 8-Isoprostane Levels in Basal Cell Carcinoma and in Uva Irradiated Skin
Authors: Belli R. , Amerio P. , Brunetti L. , Orlando G. , Toto P. , Proietto G. , Vacca M. , Tulli A.
Published: January 2017

Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2α, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2α is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2α formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model.
Abnormal Expression of Genes Associated with Development and Inflammation in the Heart of Mouse Maternal Phenylketonuria Offspring
Authors: Matalon R. , Surendran S. , McDonald J. D. , Okorodudu A. O. , Tyring S. K. , Michals-Matalon K. , Harris P.
Published: January 2017

This study descibes gene expression in the fetus hearts obtained from mouse model for Phenylketonuria. These hearts have cardiovascular disease (CVD). Therefore genes involved in CVD were examined. Several genes associated with heart development and inflammation were found to be altered. In order to investigate whether the abnormal gene expression alters transcription and translation, the levels of troponin mRNA and protein were determined. One step real time RT-PCR showed a reduction in cardiac troponin I, troponin T2 and ryanodine receptor 2. Determination of troponin I and T protein levels showed reduced levels of these proteins. Our results suggest that altered gene expression affects protein production. These changes are likely involved in the cardiovascular defects seen in the mouse.
Normalisation of High Ca 19-9 Values in Autoimmune Hepatitis after Steroidal Treatment
Authors: Montalto M. , Santoro L. , Vastola M. , Curigliano V. , Ricci R. , Vecchio F.M. , Manna R. , Gasbarrini G.
Published: January 2017

Carbohydrate 19-9 antigen (CA 19–9) is considered a specific marker of pancreatobiliary adenocarcinomas, but slight increase of its levels can be found in several non malignant diseases of the liver, such as autoimmune hepatitis. We describe a case of marked CA 19-9 elevation (up to 898.0 U/ml) in a patient with autoimmune hepatitis. Laboratory and instrumental examinations excluded malignant diseases. Immunohistochemical analysis for CA 19-9 and MIB-1, performed on liver biopsy, showed reactivity in inflammatory areas, in particular in bile ductule cells and hepatocytes in ductular metaplasia, suggesting that these cells could be involved in CA 19-9 serum levels increase. After steroids, the clinical picture improved and all the laboratory parameters normalised.
Effect of Bifidobacteriuminfantis on Interferon- γ- Induced Keratinocyte Apoptosis: A Potential Therapeutic Approach to Skin Immune Abnormalities
Authors: Cinque B. , Di Marzio L. , Della Riccia D.N. , Bizzini F. , Giuliani M. , Fanini D. , De Simone C. , Cifone M.G.
Published: January 2017

Current management of atopic dermatitis is mainly directed to the reduction of cutaneous inflammation. Since patients with atopic dermatitis show abnormalities in immunoregulation, a therapy aimed to adjust their immune function could represent an alternative approach, particularly in the severe form of the disease. Indeed, T-lymphocytes constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated T-cell induced keratinocyte apoptosis appears to be an important pathogenetic factor of the eczematous disease. In recent years, attention has been focused on the interaction between host and probiotics which may have anti-inflammatory properties and immunomodulatory activities. The aim of the present work is to investigate the effect of a selected probiotic extract, the Bifidobacterium infantis extract, on a human keratinocyte cell line (HaCaT) abnormal apoptosis induced by activated-T-lymphocyte. An in vitro model of atopic dermatitis was used to assess the ability of the probiotic extract to protect HaCaT from apoptosis induced by soluble factors (IFN-γ and CD95 ligand) released by human T-lymphocytes in vitro activated with anti-CD3/CD28 mAbs or Phytohemoagglutinin. Evidence is given that the bacterial extract treatment was able to totally prevent T lymphocyte-induced HaCaT cell apoptosis in vitro. The mechanism underlying this inhibitory effect has been suggested to depend on the ability of the bacterial extract to significantly reduce anti-CD3/CD28 mAbs and mitogen-induced T-cell proliferation, IFN-γ generation and CD95 ligand release. These preliminary results may represent an experimental basis for a potential therapeutic approach mainly targeting the skin disorders-associated immune abnormalities.
Progesterone Inhibits Mast Cell Secretion
Authors: Vasiadi M. , Kempuraj D. , Boucher W. , Kalogeromitros D. , Theoharides T.C.
Published: January 2017

Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.
Raloxifene Covalently Bonded to Titanium Implants by Interfacing with (3-Aminopropyl)-Triethoxysilane Affects Osteoblast-like Cell Gene Expression
Authors: Bambini F. , Greci L. , Memè L. , Santarelli A. , Carinci F. , Pezzetti F. , Procaccini M. , Lo Muzio L.
Published: January 2017

Since Raloxifene, a drug used in osteoporosis therapy, inhibits the osteoclast functions but not osteoblast functions, it could improve the recovery during implant surgery. This preliminary report describes a simple method to link, through a covalent bond, Raloxifene to titanium by interfacing with (3-aminopropyl)-Triethoxysilane as assessed by the IR-FT and SEM. To evaluate the biological response of osteoblast-like cells to this implant, we compared expression gene profiling of cell cultures on Raloxifene conjugated implant and normal implant by DNA microarray. By using DNA microarrays containing 19,200 genes, we identified differently expressed genes in osteoblast-like cell line (MG-63). Surface Raloxifene conjugated implants have been shown to have a relevant importance in modifying cell response. This result could be an interesting starting point for the use of an immediate functional loading of implants.
High Prevalence of Pollinosis Symptoms among the Farmers Cultivating Japanese Pears
Authors: Hayashi S. , Teranishi H. , Shimooka Y. , Yamada N.
Published: January 2017

In a district of Japanese pear cultivators, a questionnaire survey and an IgE antibody survey were conducted on the pollinosis. A high prevalence of 36.3 % of the farmers complained of pollinosis symptoms. By the IgE antibody survey, the symptoms were found to be related to the airborne pollens in the orchard.
Relationship between, Lifestyle, Mold and Sick Building Syndromes in Newly Built Dwellings in Japan
Authors: Nakayama K. , Morimoto K.
Published: January 2017

To investigate the relationships among Sick Building Syndrome (SBS) symptoms, we conducted a questionnaire and an indoor environment mold survey in a sample of newly built dwellings in Japan. The questionnaire included questions on SBS symptoms and lifestyle and a mold survey conducted in the living room of each dwelling. The odds ratios (OR) for insufficient sleep were 3.58 in males and 2.57 (weighted for SBS symptoms; W) in females, 0.38 (W) for alcohol consumption in males, and 0.10 (W) for working hours in females. The ORs for total molds were 2.90 and 2.90 (W): 2.25 (W) for Cladosporium cladosporioides, 3.60 and 7.69 (W) for Penicillium sp. in females, and 4.08 and 8.82 (W) for Alternaria alternata in males. These results suggest that the presence of Penicillium sp. in females and Alternaria alternata in males increases the risk of SBS, whereas sufficient sleep, moderate alcohol consumption for males, and fewer working hours for females might alleviate SBS symptoms.
Airborne Biological Hazards in Different PIG Fattening Systems
Authors: Diefenbach H. , Hartung E. , Sundrum A. , Lohmeyer M. , Rieger M.A.
Published: January 2017

In this research project two organic and two conventional housing systems for fattening pigs are assessed in regard to the emission of microorganisms, endotoxins and dust. The concentrations of microorganisms and endotoxins varied between the different housing systems while no distinct differences for the dust concentrations were observed. Endotoxins concentrations reached up to 14 495 EU/m3 (median) in deep litter stable, indicating the high exposure with biological agents during farm work. The differences between the stables could not be assigned to the organic or conventional kind of husbandry but to the management of the systems.
Allergenic Pollens and Spores in the Working Environment of Japanese Pear Farmers
Authors: Teranishi H. , Uchida M. , Hayashi S. , Yamada N.
Published: January 2017

Occupational allergies such as pollinosis are reported in several agricultural works in Japan. Many pollens and spores were observed in Japanese pear orchard during the artificial pollination season. By the study on daily symptoms in an allergic farmer, we confirmed that the pollinosis symptoms were most common and most severe during the artificial pollination. These results suggest that the exposure to allergenic pollens and spores induces allergic symptoms. Thus, caution should be paid for the avoidance of the exposure to these allergenic pollens and spores to prevent the allergy.
Possible Involvement of Advanced Glycation End Products in Periodontal Diseases
Authors: Pietropaoli D. , Tatone C. , D'Alessandro A.M. , Monaco A.
Published: January 2017

Periodontal diseases are considered as multifactorial conditions initiated by infection with pathogenic bacteria, promoted by inflammation and immune response against bacteria and modified by different environmental and genetic factors. Recently, interest in periodontal diseases has been increasing due to the awareness that the hyperinflammatory status associated with this disorder could impose a significant increase of reactive oxygen species (ROS) relevant to numerous systemic diseases driven by a pro-oxidant profile. A highly complex interplay occurs between oxidative stress and AGEs (Advanced Glycation End products), a group of heterogeneous compounds that form constantly under physiologic conditions, although their rate of formation is markedly increased in hyperglycemia and oxidizing conditions. Starting from the most relevant hypotheses on the pathogenesis of periodontal diseases, the present review outlines their relationship with oxidative stress and inflammation response in order to make a critical evaluation of the potential role of AGEs in periodontal deterioration. Although direct evidence for the presence of AGEs in the periodontal ligament is still lacking, valuable approaches based on the use of periodontal cells along with genetic and biochemical studies in animal models and chronic periodontal patients support a potential role for protein glycation in the aetiology and severity of this disease. Following a review of the current literature, the present study highlights the need for further investigation on the presence of AGEs in the periodontal ligament as a means for the comprehension of the pathogenic mechanisms underlying periodontal diseases in order to develop prevention and treatment modalities for this dysfunction.
Role of Etanercept in the Treatment of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome: Personal Experience and Review of the Literature
Authors: Cantarini L. , Rigante D. , Lucherini O.M. , Cimaz R. , Pasini F. Laghi , Baldari C.T. , Benucci M. , Simonini G. , Di Sabatino V. , Brizi M.G. , Galeazzi M.
Published: January 2017

Tumor necrosis factor-α receptor (TNFRl)—associated periodic syndrome (TRAPS) is the most common autosomal-dominant autoinflammatory condition and is caused by mutations in the TNFRSF1A gene. TRAPS is characterized by recurrent attacks of fever typically lasting from 1 to 3 weeks; in addition to fever, common clinical features include mainly periorbital oedema, conjunctivitis, a migratory erythematous plaque simulating erysipela with underlying myalgia, and arthritis or arthralgia; serosal membrane inflammation is also possible. The identification of TNFRSF1A mutations as the genetic cause of TRAPS coincided with the wider use of biological agents in medicine and raised the possibility that blocking TNF could potentially represent the primary therapeutic goal in TRAPS, thus disclosing new treatment choices for this complex disease. In the past few years, isolated reports and case-series have been published suggesting that inhibition of TNF-α might represent a promising therapeutic approach in TRAPS. We present here our experience with etanercept in the treatment of patients affected with TRAPS, and we also add a review of the literature.
IL-31 a TH2 Cytokine Involved in Immunity and Inflammation
Authors: Castellani M.L. , Felaco P. , Galzio R.J. , Tripodi D. , Toniato E. , De Lutiis M.A. , Fulcheri M. , Caraffa A. , Antinolfi P. , Tetè S. , Felaco M. , Conti F. , Pandolfi F. , Theoharides T.C. , Shaik-Dasthagirisaheb Y.B.
Published: January 2017

Cytokines are immunal regulatory proteins, however they also play a relevant role in inflammatory diseases. IL-31 is a newly discovered cytokine expressed primarily in TH2 cells, introduced by activated CD4+ T cells. IL-31 is capable of inducing chemokines and other cytokines in several inflammatory diseases via its surface receptor. This cytokine is also produced by mast cells and mast cell line, suggesting a role in allergic diseases. In this editorial we revisit the biological role of IL-31 in immunity and inflammation.
Divergent and Synergistic Regulation of Matrix Metalloprotease Production by Cytokines in Combination with C-C Chemokines
Authors: Richardson V.J.
Published: January 2017

The chemotactic effects of chemokines on cells has long been known, but it is now clear that chemokines also have much broader activities and are also involved in a number of disease pathologies, such as rheumatoid arthritis, cancer metastasis and other inflammatory processes. This study investigates the effects of four C-C chemokines, CCL2, CCL3, CCL4 and CCL5 either alone or in the presence of two regulatory cytokines TNF-α and TGF-β and their effect on secretion of two matrix metalloproteases MMP, MMP-2 and MMP-9, and the expression of one membrane bound MMP, MMP-14, by a monocytic human cell line, MonoMac6. All four C-C chemokines were shown to be chemotactic, but only CCL2 and CCL4 had any significant stimulatory effect on MMP-9 and MMP-2, respectively. Both TNF-α and TGF-β were found to divergently enhance MMP-9 and MMP-2 secretion respectively, with stimulation indexes of two and five respectively. Simultaneous treatment with TNF-α and chemokine resulted in up to a fifteen-fold stimulation of MMP-9 secretion and treatment with TGF-β and chemokine resulted in up to a fifteen-fold stimulation of MMP-2 secretion, while TNF-α in combination with CCL4 stimulated MMP-14 expression five-fold. Chemokine receptor expression was also investigated using a calcium-sensitive dye and FACS analysis. CCL2, CCL3, and CCL5 all resulted in a detectable enhancement of cytoplasmic Ca2+concentration. CCL4 was unable to activate Ca2+ mobilization, despite the presence of CCR5, the receptor for CCL4. There appeared to be no correlation between MMP production and chemotaxis. The strong synergy between chemokines and cytokines and the enhanced production of MMP may signify the differential regulatory mechanisms of the two cytokines and chemokines in disease pathology.