inflammation

Aims: Histological diagnostic criteria are used for the assessment of the degree of dysplasia and hence the risk of cancer progression for premalignant lesions. Clonal changes in the form of hyperorthokeratosis and hyperchromasia that are sharply demarcated from adjacent areas are not currently part of the criterion for dysplasia diagnosis. The objective of this study was to determine whether such clonal change should be regarded as a diagnostic feature for dysplasia. The following histological conditions were used to define such change: (1) hyperorthokeratosis; (2) hyperchromatism but no other features of dysplasia; (3) sharp margin demarcation from adjacent area by both the hyperorthokeratosis and hyperchromasia (clonal change), and (4) no prominent rete ridges, marked acanthosis or heavy inflammation. Lesions fitting these criteria were termed orthokeratotic lesions with no dysplasia. Methods: Patients from a population-based longitudinal study with more than 10 years of follow up were analyzed. Of the 214 patients with primary oral premalignant lesions, 194 had mild or moderate dysplasia (dysplasia group) and 20 fit the criteria for orthokeratotic lesions without dysplasia (orthokeratotic with no dysplasia group). The two groups were compared for their cancer risks using clinical (site and toluidine blue), histological (nuclear phenotype score), and molecular criteria (loss of heterozygosity) and by outcome (progression). Results and conclusions: The lesions from orthokeratotic with no dysplasia group showed a similar cancer risk (clinical, histological and molecular risk) and time to progression as the dysplastic lesions. We recommend that the clonal change should be included as a criterion for dysplasia diagnosis

Background: Despite remarkable progress in surgical, cardiopulmonary bypass (CPB) and anesthetic tecniques, neurocognitive damage still remains an important cause of postoperative morbidity in cardiac surgery. The aetiology of neurocognitive damage is likely to be multifocal; including macro and microemboli, cerebral hypoperfusion, inflammation and nonpulsatile flow. N-methyl-D-asparticAcid (NMDA) receptors play an important role during neurocognitive damage. Ketamine is a non-competitive antagonist to the phencyclidine site of NMDA receptor for glutamate and directly suppresses proinflammatory cytokine production. The aim of the present study was to evaluate whether ketamine has neuroprotective effects during open-heart surgery through the use of neurocognitive tests. Methods: We considered all patients aged between 58-76 years who were referred to a single cardiothoracic surgical team for elective, primary coronary revascularization. Patients were excluded from the study for the following reasons: a history of neurological, psychiatric, gastrointestinal, hepatic, renal, hematologic and clotting systems disorder and repeat procedures. Undergoing CPB were randomized 2 groups: Group1 (ketamine)(n=25) or Group2 (propofol)(n= Patients 25) In the propofol group, anesthesia was induced with 3mg/kg propofol, 1µg/kg remifentanyl, 0.1mg/kg vecuronium. Remifentanyl 0.5-1μg/kg/min was infused intravenously throughout the whole procedure. In the ketamine group, anesthesia was induced with 1-2mg/kg propofol, 1-2mg ketamin, 0.1mg/kg vecuronium. Ketamin 1mg/kg/hour was infused intravenously. Pressors, inotropic agents and antiarrhythmics were used as needed. The Mini-Mental State Examination(MMSE) was administered the day before surgery and three days later. The change in scores for MMSE was calculated for each patient and all the group. The results were compared statistically with paired simple t-test. Results: The mean age, CBP duration, lowest temperature was not statistically significant (Table1). Peroperative and postoperative blood pressures and pulse rates showed differences between groups. There were no preoperative differences between the groups on any of the mean MMSE score (Table2). The ECG monitoring revealed that most patients remained in sinus rhythm, with no difference between groups. Conclusions: We could not demonstrate that intraoperatively administered ketamine resulted in greater neuroprotective effects compared with propofol. Ketamine in combination with propofol during cardiac surgery is associated with a stable hemodynamic profile. Propofol may reduce the delivery of microemboli to the cerebral circulation by decreasing the cerebral blood flow. Propofol has a direct neuroprotective effect in vitro, although Roach et al. could not demonstrate a protective effect of propofol during open-heart surgery. Propofol enhances the antiinflammatory response to surgery by several mechanisms. This might have masked a neuroprotective effect of ketamine because propofol was administered in both groups in our study.

Background: Dysmenorrhea is menstrual disorder that affects about 40% - 90% of women worldwide, it is associated with oxidative stress. The current treatment of this condition is administration of non-steroidal anti-inflammatory drugs, which when frequently used, may affect organs. Objective: Assess the hepatotoxicity and nephrotoxicity side effects related to dysmenorrhea and its treatment Materials and methods: A survey (questionnaire) was designed and implemented on 689 female students of the University of Dschang. After this, and following the inclusion criteria, 191 blood samples were collected for assay of hepatotoxicity markers (transaminases, albumin), nephrotoxicity indicators (creatinine, urea, total protein) and the inflammation associated indicators. The measurements were performed on fully automated Olympus AU 400 Analyzer, using standard reagent kits. Results: Subjects with untreated dymenorrhea lasting more than five years had a significantly high level (p < 0.05) of ALT (39.47 ± 15.74 IU/L) and AST (44.37 ± 13.74 IU/L). Transaminases levels were significantly associate (p < 0.01) and positively correlate (0.251 for ALT and 0. 223 for AST) with the disease duration. Dysmenorrheic individuals on medication for more than 9 years had significantly higher ALT (25.14 ± 7.85 IU/L) and AST (35.26 ± 0.70 IU/L) levels (p < 0.05) compared to those under treatment for less than 5 years (19.37 ± 8.27 UI/L and 27.68 ± 8.56 UI/L). The use of analgesics, regardless of the duration of treatment, had normal creatinine clearance (107.44 ± 30.86 ml/min), compared to those treated with either anti-inflammatory drugs (71.56 ± 26.44 ml/min), or a combination of analgesics and anti-inflammatory drugs (81.34 ± 31.97 ml/min), which was significantly reduced (p < 0.05). Conclusion: Dysmenorrhea duration, type and duration of treatment potentially expose participants to liver and kidney disorders.

Haemophagocytosis is a dysregulated immune condition characterised by both inflammation and uncontrolled activation of macrophages and T-cells, which causes aberrant cytokine release, leading to cytokine storm [1] it can be primary or secondary, depending upon the etiology. 

Infectious bursal disease (IBD) considered as one of the major viral diseases threatening the poultry industry worldwide. The causative agent of the IBD is Infectious bursal disease virus (IBDV) which replicates in developing B lymphocytes in the bursa of Fabricius leading to its destruction and bursal inflammation. In this study, we investigated a technology to produce therapeutic recombinant antibodies against IBDV in bacteria by constructing a bacterial displayed recombinant scFv library from immunized chickens, followed by screening the scFv library by fluorescence activated cell sorting (FACS) with FITC-labeled VP2. Twelve VP2-binding scFv clones with unique sequences were obtained, with overall amino acid homology of 81.53%. The complementarity determining region (CDR) 3 in the heavy chain displayed the lowest homology, while the amino acid sequences in framework regions and CDR2 of both chains and CDR1 of the heavy chain are relatively conserved. Twelve VP2-binding scFv clones were expressed in E.coli and purified through denaturation and denaturation of inclusion bodies. Our ELISA results showed that all scFvs exhibited binding ability and specificity to VP2 and various IBDV strains. In addition, two scFvs showed significant neutralizing activity to IBDV (B-87 strain) as these scFvs inhibited cytopathic effect of chicken embryo fibroblast (DF1) caused by IBDV. In conclusion, our study provides a lead candidate for further development of therapeutic antibodies for IBDV infection.

Lung cancer is the leading cause of cancer-related deaths worldwide, and almost accounts for 20% of these deaths, however, the cure rate is less than 10% [1]. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer [1], but fewer than 15% of individuals diagnosed with NSCLC can survive for more than 5 years, which poses a great threat to the patient’s life and health [2]. Recently, the incidence of lung cancer keeps dynamically growing, but more than 75% of patients at diagnosis has appeared local development or metastasis, missing the best period of surgery. Moreover, despite surgical treatment is the optimal choice for early-stage NSCLC patients, 30%-40% of patients with NSCLC develop tumor recurrence in a short time. Therefore, improving the prognosis of patients with lung cancer and predicting the long-term survival of patients is of particular importance [3]. At present, tumor and node metastasis (TNM) staging system, clinicopathological characteristics, visceral pleural invasion and marginal status are used to predict the disease progression and overall survival of NSCLC patients. There is no index which is stable, effective, reliable and less harmful to assess prognosis, predict recurrence risk and overall survival.

There is growing evidence that gastroesophageal disease is influenced by the esophageal microbiome, and that commensal bacteria of the oropharynx, stomach, and colon are thought to have a role in modulatiing pathogenesis. These emerging hypotheses are based on observed changes in the composition of the esophageal flora, notably, repeated observations: 1. There is an abundance of gram-positive bBacteria in the healthy esophagus. are more gram positive prevalent 2. The esophageal bacterial population becomes increasingly gram negative with disease progression. Associated with this shift to a more gram negative prevalence is an increase in the potential for the presence of antigenic lipopolysaccharide (LPS). The immunoreactivity of LPS endotoxin thought to promote susceptibility to inflammation and disease. The pathogenesis of the more common diseases of the esophagus e.g. gastroesophageal reflux disease (GERD), esophageal dysmotility (achalasia), eosinophilic esophagitis (EoE), Barrett’s esophagus (BE), and esophageal cancer, are well-established. Emerging data suggest however, that these are all characterized by an immune-mediated inflammatory cascade, propogated by a dysbiotic state. Thereby, the ability of the healthy “normative state” to protect against foreign bacteria is compromised. This dysbiosis thereby can create adverse inflammatory or immunoregulatory responses with progression of disease. In the normal healthy state, the esophageal microbiome is constituted in-part, by a multitude of gram positive bacteria, many of which produce antibacterial peptides called bacteriocins. Bacteriocins are selective and used to maintain population integrity by killing off foreign bacteria. When the “normative biome” is interrupted (e.g. antibiotics, medications, diet, environmental factors), the constitutional changes may allow a more hospitable imbalance favoring the proliferation of opportunistic pathogens. Therefore it seems rational that defining, perhaps that defining, perhaps cultivating, a protective bacterial community that could help prevent or mitigate inflammatory diseases of the esophagus. Furthermore, in conjunction with evidence demonstrating that some bacteriocins are cytotoxic or antiproliferative toward cancer cell lines, further exploration might provide a rich source of effective peptide-based drug targets. Therapeutic options targeting the microbiome, including prebiotics, probiotics, antibiotics and bacteriocins, have been studied, albeit the attributable effects on the esophagus for the most part, have been unrecognized by clinicians. This review focuses on the current knowledge of the involvement of the microbiome in esophageal diseases (most notably GERD/Barrett’s esophagus/esophageal cancer) and identifies emerging new concepts for treatment.

Acute pancreatitis is inflammation of the pancreas that may be accompanied by a systemic inflammatory response which results in impairment of the functioning of various organs, systems. Pancreatitis associated vascular complications very often cause morbidity and mortality. There are various cardiovascular complications like shock, hypovolemia, pericardial effusion, and sometimes ST–T changes in the electrocardiogram (ECG) presenting as acute myocardial infarction (AMI). Acute myocardial infarction complicating acute pancreatitis has rarely been studied and the exact process of myocardial injury still remains unclear. We here report a case of Acute Pancreatitis associated with acute myocardial Infarction.

Introduction: Forty-six per cent children have allergic rhinoconjunctivitis (Allergologica 2005). Working hypothesis: Ocular topical cyclosporine improves the quality of life for these patients. Material, methods, design: 2-year prospective study (2015-16), 40 patients with topical corticosteroids without improvement, followed 20 and 20 switched to corticosteroids cyclosporine 0.05%. Interview with Quality of Life Questionnaire in Children with rhinoconjunctivitis (PRQLQ) before and at the end of treatment. Mean age of 10.3 years with 60% male-40% female. Treatments were applied from January to March. There were 15 questions divided into two blocks. Children responded using a card with responses rated from zero (not bothered at all) to 6 (quite upset). Results: Before the 100% reported that, the itching was very bothersome. In the group of 40 children, 80% showed symptoms of epiphora and 60% showed symptoms of ocular inflammation. 100% complained of significant discomfort in rubbing their eyes, 30% did not like to take medications. Headaches affected 20%. 100% stated that they cannot play normally. 80% showed decreased concentration in class. Continuing with corticosteroids did not show statistically significant changes. Patients with cyclosporine improved the results by 3 points, with decreased itching, tearing, swelling, pain, eye rubbing, medication and headaches. In the 2nd questionnaire there was limited variation in the results related to fatigue, malaise, and irritability but with substantially improved balance of sleep, insomnia and concentration at school. Conclusion: Cyclosporine A is a cyclic polypeptide calcineurin inhibitor developed from the fungus Tolypocladium inflatum. The first dilution was 2% but it is currently used at a dilution of 0.05% and recent publications suggest nanosuspensions. Our study showed improvement in parameters related to symptoms, especially itching and lower improvement of psychological aspects, this achieves a better quality of life for children and more willingness to adhere to the treatment.

Asthma is a chronic respiratory disease which characterized by recurrent airflow obstruction, wheezing, chest tightness and coughing. Management of allergic asthma especially in children, is main problem for industrial world. Immunological factors have critical role in pathogenesis of allergic asthma. Cytokines as major controller of immune system, are important in this reaction. Allergic asthma is a disease with symptoms: eosinophilic inflammation, mucus hyper secretion, airway obstruction, airways hyperresponsivness, IgE high level production, smooth muscle spasm. Cytokines have main and complicated role in pathophysiology of allergic asthma.

Bronchial asthma, is a quite common disease characterized by the chronic inflammation of the airways. It is due to the interaction of genetic with environmental factors. Currently, bronchial asthma is regarded as a public health problem, since its prevalence is constantly increasing worldwide. Common symptoms associated with asthma include repeated episodes of wheeze, dyspnoea, chest tightness and cough. Although commonly most asthmatic episodes are resolved with medical treatment, at times serious complications can deteriorate the clinical picture. Among these complications, the simultaneous spontaneous bilateral pneumothorax, the subcutaneous emphysema and the pneumomediastinum are life threatening complications.

Asthma is a complicated chronic disease of airway and airway inflammation, bronchoconstriction, cough, dyspnea and wheezing that are main symptoms of the asthma. Genetic, epigenetic and environmental agents are main factors in pathophysiology of the asthma. Direct and indirect healthcare costs and health-related quality of life in asthmatic patients require more and more attention. A main challenges of asthma control is environment and specially house and building [1].

Asthma is a chronic inflammatory disease of the airways characterized by airway inflammation, bronchial hyperresponsiveness, reversible airflow obstruction and recurrent symptoms. Patients often present with coughing, wheezing, dyspnea, and chest tightness, were they usually responds to the mainstay of treatment that relies on inhaled glucocorticoids (ICS), and long acting β2 agonist (LABA), along with leukotriene. In around 20% of the patient’s morbidity, mortality and cost of therapy increased because they fail to benefit from the existing gold standard therapy regimen. Both immunoglobulin-E (IgE), interlukin-5 (IL-5) had proven to play important major role in asthma pathogenesis. Over the past two decades biologic therapy that targeting IgE begins the era in treating severe asthma, and recently anti-IL-5, revealed major role in eosinophils maturation, activation, survival, and recruitment process of severe asthma. The different biologic therapy that is currently available in the market are supported by solid evidence from controlled randomized clinical trials, to guide the clinician on the type of patients that will benefit from the therapy, with an insight on the appropriate monitoring parameters and patient evaluation plans. This review was conducted by searching PubMed, EMBASE, and Google Scholar to identify peer-reviewed clinical trials, guidelines, and review articles published in English in the role of biologic therapy in severe asthma. The main aim from publishing this review is to summarize the current available evidence on the approved biologic therapy in treating patients with severe asthma.

Asthma is a chronic respiratory disease characterized by chronic airway inflammation. Common manifestations of asthma include wheezing, chest tightness, cough, shortness of breath. Diagnosis of asthma requires clinical documentation of respiratory symptoms, exacerbation of symptoms following exposure to triggers, as well as demonstration of expiratory airflow obstruction. Wheeze is a continuous sound, lasting longer than 0.25 s that is produced by oscillation of opposing airway walls [1,2]. Wheezing, although a typical symptom of asthma, can also be caused by other diseases. Apart from asthma, wheezing can be due to extra-thoracic upper airway obstruction, intrathoracic upper airway obstruction, lower airway obstruction. Benign multimodal goiter is a common disease, that rarely causes upper airway obstruction. Retrosternal goiter should be taken into account the differential diagnosis of upper airway obstruction [3]. The respiratory symptoms of a retrosternal goiter may be masked for years due to the slow growth of the goiter. Patients commonly complain of respiratory symptoms if tracheal diameter is narrowed more than 50% from the normal size. Respiratory symptoms may be suddenly precipitated by spontaneous or traumatically induced bleeding into the substernal goiter, as well as by tracheal infections [4]. Clinical management of this condition is really challenging. Diagnosis is also not straightforward, as clinical suspicion is needed. There are cases of retrosternal goiter mimicking asthma that remain undiagnosed for many years. Retrosternal goiter should be taken into account in the differential diagnosis of patients diagnosed as suffering from asthma, and presenting no improvement despite medical therapy. In addition, it should be taken into account that sudden gland enlargement due to hormonal changes might lead to life threatening upper airway obstruction with clinical picture similar to bronchial asthma attack [5]. In a recent very interesting case report, the authors present a case of a pregnant woman in the second trimester who presented with an acute airway obstruction due to the enlargement of a retrosternal goiter [3]. Goiters are the more common masses of the superior mediastinum [6,7]. Commonly, retrosternal goiter is due to the extension in the thorax of a cervical goiter. However, rarely, it may represent primary disease due to the growth of ectopic thyroid tissue. In addition, retrosternal goiter may develop in patient submitted to thyroidectomy due to cervical multinodular goiter [8]. Although retrosternal goiters are commonly asymptomatic, symptoms may include dyspnea, stridor, hoarseness, dysphagia, superior vena cava syndrome, transient ischemic attacks, cerebral edema, Horner’s syndrome, and thyrotoxicosis [4]. Diagnosis could be verified by neck and chest radiography, thorax CT and MRI. Chest radiography commonly shows a widened mediastinum with a superior mediastinal mass causing compression of the trachea as well as deviation of the trachea to the right. Mediastinal computed tomography reveals a mass that is extension of the thyroid gland. The presence of respiratory symptoms in a patient with retrosternal goiter is an indication for surgery. The majority of retrosternal goiters can be approached through a cervical approach [9,10].

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease caused by mutation(s) in the Mediterranean fever (MEFV, pyrinmarenostrin) gene [1,2]. FMF is characterized by recurrent fever crises combined with serosal, synovial, or cutaneous inflammation and, in some individuals, by the eventual development, in the long-term, of systemic amyloidosis [3,4]. FMF mainly affects peoples living along eastern Mediterranean Sea (Turks, Sephardic Jews, Armenians) and it is not a rare disease in other Mediterranean areas such as Greeks, Italians and Iranians [4,6]. Until now, more than 304 sequence variants have been recorded [6]. In Italy M694V, V726A, M680I, M694I and E148Q are the most frequent FMF-associated mutations [7]. Here, we describe a recent case of mild FMF, characterized by all the clinical manifestations indicative of FMF described in the literature, according to Tei-Hashomer criteria [4] and by the analysis of MEFV gene, characterized by polymorphism c1588-69G>A. This is in agreement with previous our observations in a wider sample collected in the years. We are training to define the relations among gene mutations and clinical forms of FMF.

Treatment of various inflammatory processes, including acute pneumonia(АP), over the past decades is identical and does not reflect the specifics of a particular disease. The basis of such treatment is «antibiotics alone». The need for additional therapeutic efforts is realized by the use of General therapeutic techniques, regardless of the diagnosis. This does not take into account the important fact that the localization of inflammation not only determines its clinical picture,but,above all,the mechanisms of influence on other organs and systems of the body.

Disruptions in Maternal-infant Bonding are shown to be the mediating variable between maternal distress and the subsequent expression of childhood asthma. When the mothers’ bonding is repaired, their children’s asthmatic symptoms diminish or remit. This study evaluated 16 asthmatic children before and after their mothers were treated with Bonding Therapy. Fourteen improved on 11 measures, including reduction in the STEP classification system and medication use. Thirteen children were able to stop all medications. Surprisingly, all mothers scores on the Beck Depression Inventory improved through Bonding Therapy, suggesting that impaired bonding can lead to maternal depression or even Postpartum Depression. The link between bonding disruptions and airway inflammation are discussed. Bonding Therapy is described.

Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR. Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness.

Modern AP concepts are focused exclusively on the infectious nature of the disease and the presence of certain pathogens. This belief determines the principles of treatment, the lack of effectiveness of which remains a concern of health professionals. The article presents a fragment of the study devoted to the etiology of АP. 994 children aged 4 months to 14 years with various forms of so-called community-acquired pneumonia were examined and treated. Bacteriological examination of the material from the inflammation zone was carried out in 542 patients. Experiments on modeling АP and its pleural complications were performed on 44 animals. The obtained results and critical analysis of the literature data and scientific facts allow us to consider bacteria only as one of the etiological elements of АP, which is not mandatory in all cases of the disease. Scientifically based revision of existing ideas about the causes and mechanisms of AP development leads to the need for a radical change in the principles of treatment and is a strategic direction in solving the problem.

The article presents the results of x-ray anatomical studies of 56 whole lung preparations, which were carried out immediately after the autopsy of children who died from АP. In 47 cases it was carried out the contrast of the vessels and in 9 cases the bronchial tree. The results allowed to clarify some details of the pathogenesis of АP and were additional arguments in support of the new doctrine of the disease.