Polymicrobial Bacterial Meningitis in a Patient with Chronic Suppurative Otitis Media: Case Report and Literature Review.

Polymicrobial meningitis is a rare entity in the adult population, especially in the antibiotic era. However, disorders such as chronic suppurative otitis media (CSOM) or even poor oral hygiene are considered risk factors for the development of such cerebral infection. We report a case of polymicrobial meningitis associated with oto-mastoiditis in a 64-year-old female patient known to have CSOM. The patient presented atypical symptoms for community-acquired meningitis, showing subacute evolution of headache, without fever or neck stiffness. The aerobe microorganisms Streptococcus anginosus and Corynebacterium spp., sensitive to beta-lactamines, and the anaerobe Prevotella spp., resistant to penicillin and metronidazole, were isolated from CSF specimens, while Proteus mirabilis and Enterococcus faecalis were identified from the ear drainage. The diversity of pathogens identified in our case led us to the hypothesis of two different sources of meningitis: otogenic and/or odontogenic. Favorable evolution was obtained after a multi-disciplinary approach, combining surgery and broad-spectrum antibiotics. In addition, we performed a literature review that highlights the low incidence of polymicrobial mixed aerobe-anaerobe meningitis.

Antibiotic Usage in the COVID-19 Intensive Care Unit of an Infectious Diseases Hospital from Nord-Eastern Romania.

Background and Objectives. The intensive care unit (ICU), especially in an infectious disease hospital, is both an area with a high consumption of antibiotics (atb) and a "reservoir" of multidrug-resistant bacteria. We proposed the analysis of antibiotic therapy practices in such a department that treated, in conditions of a pandemic wave, patients with COVID-19 and its complications. Materials and Methods. This was a retrospective transversal study of 184 COVID-19 patients treated in the ICU of a regional infectious disease hospital of Iasi, Romania, in a 3-month interval of 2020 and 2021. Results. All the included patients (Caucasians, 53% males, with a median age of 68 years, and a Charlton comorbidity index of 3) received at least one antibiotic during their stay in the ICU (43% also had antibiotics prior to hospital admission and 68% in the Infectious Diseases ward). Only 22.3% of the ICU patients had only one antibiotic. A total of 77.7% of them started with an association of two antibiotics, and 19.6% of them received more than three antibiotics. The most-used ones were linezolid (77.2%), imipenem (75.5%), and ceftriaxone (33.7%). The median atb duration was 9 days. No change in the number or type of atb prescription was seen in 2021 (compared to 2020). Only 9.8% of the patients had a microbiological confirmation of bacterial infection. A total of 38.3% of the tested patients had elevated procalcitonin levels at ICU admission. The overall fatality rate was 68.5%, with no significant differences between the two analyzed periods or the number of administered antibiotics. More than half (51.1%) of the patients developed oral candidiasis during their stay in the ICU, but only 5.4% had C. difficile colitis. Conclusion. Antibiotics were widely used in our ICU patients in the presence of a reduced microbiological confirmation of a bacterial co-infection, and were justified by other clinical or biological criteria.

Profile of Newly Diagnosed Patients with HIV Infection in North-Eastern Romania.

Background and Objectives: Human immunodeficiency virus infection and the acquired immunodeficiency syndrome (HIV/AIDS) pandemic are unquestionably the most serious public crisis of our time. Identifying, preventing, and treating HIV-associated comorbidities remains a challenge that must be addressed even in the era of antiretroviral therapy. Materials and Methods: In this study, we aimed to characterize the aspects of newly diagnosed patients with HIV/AIDS, during 2021-2022 in Northeastern Romania. We reviewed the frequency and associated comorbidities of these patients in correspondence with national and global results. Results: Our study found that of all newly diagnosed HIV cases (167 cases-74 cases in 2021 and 98 cases in 2022), 49.70% were diagnosed with HIV infection and 50.30% had AIDS. Based on sex correlated with the CD4+ T-lymphocyte level, the most affected were males, with a lower CD4+ T-lymphocyte level overall. The average HIV viral load was 944,689.55 copies/mL. Half of males had an abnormal ALT or AST (39.53% and 49.61%); as for the females, less than a quarter had an increased value of ALT or AST, respectively (18% and 26%). The most frequent co-infections were as follows: oral candidiasis (34.73% of patients), hepatitis B (17.37% of patients), and SARS-CoV-2 infection (8.38%), followed by hepatitis C (6.39%), tuberculosis (TB), syphilis, toxoplasmosis, Cryptococcus, Cytomegalovirus infections. Males were more affected than females, with a higher percentage of co-infections. The prescribed antiretroviral treatment focused on a single-pill regimen (79.04%) to ensure adherence, effectiveness, and safety. Therefore, 20.96% had been prescribed a regimen according to their comorbidities. Conclusions: Our study found a concerning rise in the incidence of HIV in 2022 compared to that in 2021 in Northeastern Romania, because of the rise in post-SARS-CoV-2 pandemic addressability. Advanced immunodeficiency and the burden of opportunistic infections characterize newly diagnosed HIV patients. The physicians should keep in mind that these patients may have more than one clinical condition at presentation.

Optimization of Therapy and the Risk of Probiotic Use during Antibiotherapy in Septic Critically Ill Patients: A Narrative Review.

Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug-drug or drug-nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and/or PD results were included. Studies on patients <18 years old or with classical TDM-guided therapy were excluded. New approaches in TDM-guided therapy in septic critically ill patients based on PK and/or PD parameters are presented for cefiderocol, carbapenems, combinations beta-lactams/beta-lactamase inhibitors (piperacillin/tazobactam, ceftolozane/tazobactam, ceftazidime/avibactam), plazomicin, oxazolidinones and polymyxins. Increased midazolam toxicity in combination with fluconazole, nephrotoxic synergism between furosemide and aminoglycosides, life-threatening hypoglycemia after fluoroquinolone and insulin, prolonged muscle weakness and/or paralysis after neuromuscular blocking agents and high-dose corticosteroids combinations are of interest in critically ill patients. In the real-world practice, the use of probiotics with antibiotics is common; even data about the risk and benefits of probiotics are currently spares and inconclusive. According to current legislation, probiotic use does not require safety monitoring, but there are reports of endocarditis, meningitis, peritonitis, or pneumonia associated with probiotics in critically ill patients. In addition, probiotics are associated with risk of the spread of antimicrobial resistance. The TDM-guided method ensures a true optimization of antibiotic therapy, and particular efforts should be applied globally. In addition, multidrug and drug-nutrient interactions in critically ill patients may increase the likelihood of adverse events and risk of death; therefore, the PK and PD particularities of the critically ill patient require a multidisciplinary approach in which knowledge of clinical pharmacology is essential.

Assessment and outcome of hospitalized patients during delta variant COVID-19 pandemic: A multicenter international study.

INTRODUCTION: To date, the world has experienced four waves of the Coronavirus disease- 19 (COVID-19) pandemic. Patients infected during the era of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant were the subject of this study. The objectives were to describe their clinical manifestations, explain their laboratory and radiological findings, conclude factors contributing to clinical outcomes, and evaluate treatment protocols. METHODOLOGY: Relevant data were collected retrospectively from records of patients admitted to six referral centers in four countries. Data included sociodemographic patterns, symptoms, associated comorbidities, physical examination, laboratory and radiologic findings, treatment received, and patient outcomes. RESULTS: Data analysis identified symptomatology and variables related to acquisition and infection outcome. The most prevalent symptoms were cough (81.5%), body aches (74.1%), and fever (71.6%). Independent risk factors for mortality were age, vomiting, epigastric pain, diabetes, obesity, oxygen saturation less than 90%, leukocytosis, neutrophilia, lymphopenia, thrombocytopenia, elevated creatinine, high glucose level, lung ground glass opacities with consolidation, affection of four lobes and bilateralism. Neither d-dimer nor lactate dehydrogenase nor ferritin foretells death possibility. The efficacy of the medications used was convenient. CONCLUSIONS: Assessing the clinical features of different COVID-19 waves, identifying predictors of outcomes, and concluding the efficacy of treatment protocols provide insight into patients' responses and viral behaviors, which help in the proper diagnosis and treatment of subsequent surges.

Impact of Non-Pharmacological Interventions on the Mechanisms of Atherosclerosis.

Atherosclerosis remains the leading cause of mortality and morbidity worldwide characterized by the deposition of lipids and fibrous elements in the form of atheroma plaques in vascular areas which are hemodynamically overloaded. The global burden of atherosclerotic cardiovascular disease is steadily increasing and is considered the largest known non-infectious pandemic. The management of atherosclerotic cardiovascular disease is increasing the cost of health care worldwide, which is a concern for researchers and physicians and has caused them to strive to find effective long-term strategies to improve the efficiency of treatments by managing conventional risk factors. Primary prevention of atherosclerotic cardiovascular disease is the preferred method to reduce cardiovascular risk. Fasting, a Mediterranean diet, and caloric restriction can be considered useful clinical tools. The protective impact of physical exercise over the cardiovascular system has been studied in recent years with the intention of explaining the mechanisms involved; the increase in heat shock proteins, antioxidant enzymes and regulators of cardiac myocyte proliferation concentration seem to be the molecular and biochemical shifts that are involved. Developing new therapeutic strategies such as vagus nerve stimulation, either to prevent or slow the disease's onset and progression, will surely have a profound effect on the lives of millions of people.

Seroprevalence of Anti-Hepatitis E Virus Antibodies among Patients from a Tertiary Hospital from Northeast Romania.

Background and Objectives. Being an enterically transmitted pathogen with a growing prevalence in developed countries, hepatitis E virus (HEV) infection remains an underdiagnosed disease in Eastern Europe. As far as Romania is concerned, only a few studies address this issue. Our goal was to estimate the prevalence of serum anti-HEV IgA/IgM/IgG antibodies in a group of patients admitted to the Clinical Hospital for Infectious Diseases "St. Parascheva" Iasi. Materials and Methods. The cross-sectional study consisted of enrollment of 98 patients admitted to the clinic for COVID-19 over a period of three months in 2020. Results. The median age in our study was 73 years, with an equal gender ratio and with a predominance of people from the urban environment (75%). The overall HEV antibody seroprevalence was 12.2%. The main risk factors associated with HEV infection were consumption of water from unsafe sources (58.3% HEV-positive patients vs. 26.7% HEV-negative patients, p = 0.026) and improperly cooked meat (58.3% HEV-positive patients vs. 23.2% HEV-negative patients, p = 0.01). Zoonotic transmission was an important criterion in our study, with patients reporting contact with pigs, poultry, rats, or other farms animals, but no significant differences were found between HEV antibody positive and negative groups. Conclusions. The seroprevalence rate of HEV antibodies was similar to other previous reports from our area but higher than in most European countries. The fact that HEV antibodies were detected in patients without identifiable risk factors for hepatitis E is evidence of subclinical infection as a silent threat.

Clinical significance of early IgA anti-SARS-CoV-2 antibody detection in patients from a Romanian referral COVID-19 hospital.

Controlling the spread of coronavirus disease 2019 (COVID-19) includes institute isolation, quarantine measures and appropriate clinical management, which all require effective screening, diagnostic and prognostic tools. The present study aimed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin (Ig)A detection and determine the potential association with the clinical course of COVID-19 and the levels of inflammation. In the present study, the presence of IgA and IgG SARS-CoV-2 antibodies in 75 consecutive patients with confirmed COVID-19 infection was investigated. No significant differences were found between the IgA positive and negative groups, regarding the presence of symptoms, haematological and inflammatory variables, or the presence of pneumonia. In the majority of cases, antibody detection was comparable, for example, 79.7% of patients in the IgA positive group exhibited both types of antibodies, while 80.9% of patients in the IgA negative group were also IgG negative. A total of four patients in the IgA negative group presented with anti-SARS-CoV-2 IgG antibodies. Early detection of IgA was more frequent in patients who later developed severe forms of the disease. In addition, the IgG SARS-CoV-2 antibody response was higher in patients with the severe form of the disease.

RT- PCR testing of upper respiratory tract samples for diagnosis of SARS-CoV-2: Between justification and overestimation, a multi-center international study.

BACKGROUND: It has been found that patients recovered from COVID 19 may still test Reverse Transcriptase- Polymerase Chain Reaction (RT- PCR) positive without being infectious; the reasons are unclear. The occurrence of false-negative results of RT- PCR interferes with a proper diagnosis. The objectives of that work were to determine factors associated with persistently detectable SARS-CoV-2 RNA among recovered hospitalized patients and to determine the incidence of false-negative RT-PCR results and associated factors. METHODS: Relevant data were collected from 482 COVID 19 patients hospitalized in six referral centers from four countries. RESULTS: The median duration of RT- PCR conversion to negative was 20 days. Out of 482 studied patients, 8.7% tested positive after more than four weeks and were considered prolonged convertors. Binary logistic regression analysis revealed headache as an independent risk factor for short conversion time while fever, hypertension, chronic obstructive pulmonary disease, lymphopenia, elevated erythrocyte sedimentation rate, and the number of lobes affected, and bilateralism were found to be independent risk factors for prolonged positivity. Eighteen patients had initial negative results then turned positive after 24-48 h. Associated factors and outcomes were identified. CONCLUSION: Identifying patients with a high likelihood of COVID-19 despite a negative RT-PCR is critical for effective clinical care. However, patient isolation resumption depending on positive RT-PCR despite clinical and radiological recovery is an overrating that greatly burdens the health sector.

Randomized, placebo-controlled trial of xyloglucan and gelose for the treatment of acute diarrhea in children.

BACKGROUND: Oral rehydration is the main treatment of acute diarrhea in children. This study was undertaken to evaluate the efficacy and safety of xyloglucan and gelose (agar-agar) plus oral rehydration solution (ORS) compared with placebo and ORS for reduction of acute diarrhea symptoms in children. METHODS: In a randomized, double-blind, placebo-controlled trial, children with acute gastroenteritis received xyloglucan/gelose plus ORS (n = 50) or placebo plus ORS (n = 50) for 5 days. Demographic, clinical, anthropometric and laboratory parameters were recorded and analyzed. RESULTS: Xyloglucan/gelose plus ORS reduced the total number of type 7 and 6 stools on the Bristol Stool Form scale (p = 0.040 and p = 0.015, respectively, compared to placebo plus ORS), and had a rapid onset of action, evident 6 hours post-treatment. Xyloglucan/gelose plus ORS also improved associated clinical symptoms (apathy, vomiting, flatulence, and blood in stool). compared with placebo plus ORS. Except for a generalized rash of unknown causality in a patient receiving placebo plus ORS, all other adverse events (dehydration, n = 7, cough, n = 1, exacerbation of vomiting, n = 1) were deemed unrelated to study medication. CONCLUSIONS: Xyloglucan/gelose plus ORS was effective and safe in treating acute diarrhea in children.

Neurosyphilis Masquerading as Stroke in an 84-year-old.

The case of an 84 years old woman with uncharacteristic neurologic and cognitive symptoms, suspected of ischemic stroke is presented. Following an extensive assessment in the departments of neurology and internal medicine, the unusual aetiology of stroke was identified as meningovascular neurosyphilis. The patient fully recovered after antibiotic therapy. To our knowledge, this the eldest patient with tertiary neurosyphilis reported in the literature.

Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study.

Predicting unfavorable outcome is of paramount importance in clinical decision making. Accordingly, we designed this multinational study, which provided the largest case series of tuberculous meningitis (TBM). 43 centers from 14 countries (Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria, Turkey) submitted data of microbiologically confirmed TBM patients hospitalized between 2000 and 2012. Unfavorable outcome was defined as survival with significant sequela or death. In developing our index, binary logistic regression models were constructed via 200 replicates of database by bootstrap resampling methodology. The final model was built according to the selection frequencies of variables. The severity scale included variables with arbitrary scores proportional to predictive powers of terms in the final model. The final model was internally validated by bootstrap resampling. A total of 507 patients' data were submitted among which 165 had unfavorable outcome. Eighty-six patients died while 119 had different neurological sequelae in 79 (16%) patients. The full model included 13 variables. Age, nausea, vomiting, altered consciousness, hydrocephalus, vasculitis, immunosuppression, diabetes mellitus and neurological deficit remained in the final model. Scores 1-3 were assigned to the variables in the severity scale, which included scores of 1-6. The distribution of mortality for the scores 1-6 was 3.4, 8.2, 20.6, 31, 30 and 40.1%, respectively. Altered consciousness, diabetes mellitus, immunosuppression, neurological deficits, hydrocephalus, and vasculitis predicted the unfavorable outcome in the scoring and the cumulative score provided a linear estimation of prognosis.

THE NEED FOR HBV GENOTYPING: A COST-EFFICIENT APPROACH.

The outcome of chronic HBV infection is variable; approximately one half of individuals transition to an inactive carrier state, 30% progress to cirrhosis, and the remainder to chronic hepatitis. Ten different HBV genotypes and many subtypes have been identified with distinct geographical distributions. Over the years, a lot of studies presented the efficiency of different genotyping methods; for this reason we aimed to present a cost efficient genotyping diagnosis algorithm of CHB infected patients, especially useful to identify those at risk of disease progression and determine optimal anti-viral therapy as useful instrument for physicians.

Surveillance, control and management of infections in intensive care units in Southern Europe, Turkey and Iran--a prospective multicenter point prevalence study.

OBJECTIVE: We aimed to compare the features of intensive care units (ICUs), their antimicrobial resistance patterns, infection control policies, and distribution of infectious diseases from central Europe to Mid-West Asia. METHODS: A cross-sectional point prevalence study was performed in 88 ICUs from 12 countries. Characteristics of ICUs, patient and antibiotic therapy data were collected with a standard form by infectious diseases specialists. RESULTS: Out of 749, 305 patients at least with one infectious disease were assessed and 254 patients were reported to have coexistent medical problems. When primary infectious diseases diagnoses of the patients were evaluated, 69 had community-acquired, 61 had healthcare-associated, and 176 had hospital-acquired infections. Pneumonia was the most frequent ICU infection seen in half of the patients. Distribution of frequent pathogens was as follows: Enteric Gram-negatives (n = 62, 28.8%), Acinetobacter spp. (n = 47, 21.9%), Pseudomonas aeruginosa (n = 29, 13.5%). Multidrug resistance profiles of the infecting microorganisms seem to have a uniform pattern throughout Southern Europe and Turkey. On the other hand, active and device-associated infection surveillance was performed in Turkey more than Iran and Southeastern Europe (p < 0.05). However, designing antibiotic treatment according to culture results was highest in Southeastern Europe (p < 0.05). The most frequently used antibiotics were carbapenems (n = 92, 30.2%), followed by anti-gram positive agents (vancomycin, teicoplanin, linezolid, daptomycin, and tigecycline; n = 79, 25.9%), beta-lactam/beta lactamase inhibitors (n = 78, 25.6%), and extended-spectrum cephalosporins (n = 73, 23.9%). CONCLUSION: ICU features appears to have similar characteristics from the infectious diseases perspective, although variability seems to exist in this large geographical area.

Viral meningitis admitted to an infectious diseases hospital: a retrospective case series.

UNLABELLED: Given its epidemic potential and development of severe forms of disease, viral meningitis (VM) is a serious public health problem. AIM: to characterize the main clinical, epidemiologic features, the etiology and treatment of VM cases admitted to the Iasi Infectious Diseases Hospital, in 2012. MATERIAL AND METHODS: We retrospectively analyzed the medical records of the patients admitted for viral meningitis at the Iasi "St. Parascheva" Infectious Diseases Hospital in the interval January 1- December 31, 2012 (98 cases). The etiologic diagnosis was made by determining the IgM/IgG antibodies against Coxsackie virus and/or West Nile virus in blood/CSF. RESULTS: There was a fourfold increase in the number of cases as compared to the average for the years 2009-2011. Most cases (73.5%) were children aged 1 to 14 years. 61.8% of patients were males, 51.7% from urban areas. The most common symptom was headache (85.7%), followed by fever (77.6%), and vomiting (66.3%). Neck stiffness was absent in 28.6% cases. In43.5% of the 39 patients serologically investigated a Coxsackie virus infection was confirmed and 1/20 was positive for West Nile virus; three varicella-zoster virus infections and one mumps infection were diagnosed clinically. 68.3% of the patients received first-line antibiotic treatment. CONCLUSIONS: The illness mainly affected children, fever and neck stiffness being sometimes absent. The etiology was known in 22.4% of cases; enter viruses being the most frequent causative agent. Most patients received antibiotic therapy. The course was favorable in all cases.

Zoonotic Cryptosporidium parvum in Romanian newborn lambs (Ovis aries).

This study was undertaken to investigate the occurrence and public health significance of Cryptosporidium species/genotypes and subtypes in a newborn lambs. A total of 175 diarrheic fecal samples from lambs (younger than 21 days) were collected in seven sheep flocks located in western Romania, and were microscopically examined for the presence of Cryptosporidium oocysts after staining with modified Ziehl-Neelsen technique. Twenty-four (13.7%) fecal samples were tested Cryptosporidium positive by microscopy and were subjected for molecular characterization. All positive samples were successfully amplified through a nested polymerase chain reaction (PCR) of the small subunit (SSU) rRNA gene (18S). Cryptosporidium species were determined by restriction fragment length polymorphism (RFLP) analysis of the secondary PCR products using the conventional SspI and VspI restriction enzymes. The identified species were: Cryptosporidium parvum (20/24), C. ubiquitum (2/24) and C. xiaoi (2/24), respectively. PCR-RFLP results for C. ubiquitum and C. xiaoi isolates were confirmed by DNA sequencing. Subsequently, subtyping of seven randomly selected C. parvum isolates, based on sequence analysis of the GP60 gene, revealed the presence of five different subtypes (IIaA17G1R1, IIaA16G1R1, IIdA20G1, IIdA24G1 and IIdA22G2R1) belonging in two zoonotic subtype families (IIa and IId). These findings may suggest the potential role of the newborn lambs as a source for human cryptosporidiosis. This is the first published report about the presence of C. ubiquitum and C. xiaoi in lambs from Romania.

[Pulmonary toxoplasmosis in immunosuppressed patient]. / Toxoplasmoza pulmonara la pacientul imunodeprimat.

Pulmonary toxoplasmosis occurs mainly in immunosuppressed patients and its diagnosis mainly relies upon biological confirmation of the parasite. We present the case of a 47 years patient in medullar aplasia after induction chemotherapy for acute lymphoblastic leukemia that developed pulmonary infiltrates of parasitic origin. The diagnosis of pulmonary toxoplasmosis was established after identification of the parasite in brochioloalveolar lavage fluid (BAL) and peripheral blood. Serological tests are of limited utility in immunosuppressed patients. We used classical methods for the diagnosis of parasitosis but they are being replaced by molecular methods. Polymerase Chain Reaction (PCR) allows a highly specific and sensitive diagnosis on any sample but it cannot be performed in any center.

[Adult toxocariasis]. / Toxocaroza la adult: studiu epidemiologic privind incidenta în zona moldovei.

AIM: Epidemiological study on a statistically significant population for determining the true degree of Toxocara canis infections in the adults from Moldova, Romania. METHODS: 457 patients, 416 females and 41 males (91% and 9%, respectively) entered the study. Mean age of the investigated patients was 44.50 +/- 12.706 years, with small differences between sexes. 49.2% were from rural and 50.8% from urban areas. Data on living conditions, animals in the household, and source of drinking water were obtained through direct questioning. At present there is no definitive diagnostic method for Toxocara infection, as the actual sensitivity and specificity of serological tests cannot be determined accurately. IgG antibody titer specific for T. canis was assessed by ELISA in all study patients. RESULTS: Most infections were recorded in 2009 (51.4%), 15.3% in 2008, 17.1% in 2010 14.0% in 2011, and 2.2% (10 cases) in 2012. An IgG titer of 1/100 was found in 40.7% of the patients. Toxocariasis prevalence in our geographic area was 51.7%, without significant sex differences. However, while the percentages of negative determinations were similar for both sexes (42.5% in females and 46.3% in males), almost twice more men (9.8% vs. 4.6% women) had a 1/10 determination, while 21,4% of the women had a 1/50 determination as compared to 9,8% of the males. The source of water was not, at least in this study group, a major cause of disease in adults. The statistical results show a major and significant influence of human contact with the dog. Thus, in dog owners 1/50 and 1/100 determinations being found in equal percentages (26% of the total), while in those having both dogs and cats the 1/100 determination was the most common (40.7% of the total). CONCLUSIONS: Our data can be the basis for a nation-wide seroprevalence study and programs to eradicate this infection.

Operational scores in the diagnosis of chronic hepatitis. A semi-quantitative assessment.

Starting from the quantification of the specific lesions for chronic hepatitis B and C, our study focused on (i) the correspondence between the necroinflammatory activity and the fibrosis stage ascertained through the Ishak scoring system, (ii) the classification overlaps and differences of Ishak vs. METAVIR score. The study group consisted of 202 cases with chronic hepatitis B and 751 cases with chronic hepatitis C, diagnosed based on liver biopsies. The fragments of hepatic tissue were routinely processed and stained with Hematoxylin-Eosin, trichrome Szekely, Gordon-Sweet silver impregnation, and Periodic Acid-Schiff. A semiquantitative evaluation was performed using the Ishak (for hepatitis B and C) and the METAVIR (for hepatitis C) scoring systems. Our results revealed that the comparison between hepatitis B and C, based on the necroinflammatory activity and fibrosis, is able to offer through the numeric values of the Ishak scoring system accurate proofs, which support the aggressivity of hepatitis C, because it develops fibrosis more quickly, even on the background of mild necroinflammatory activity. Also, our data showed that the necroinflammatory activity and the fibrosis are not processes which progress in a consistent pattern. The application of the METAVIR scoring system for the cases with chronic hepatitis C confirmed that there is not a direct correlation between necroinflammation and fibrosis. The Ishak scoring system provides through the wide range of numeric values attributed for the evaluation of necroinflammatory activity and fibrosis far more precise criteria for the appraisal of the degree of damage to the hepatic parenchyma at the time of the diagnosis. Supplementary, the METAVIR scoring system allows for the hepatitis C an assessment of the entire histologic activity, including the interface hepatitis and the associated lobular necrosis components. The scoring systems have unavoidably strengths and weaknesses, but the choice of a specific one must reflect the consensus between the pathologists and the clinicians, relying on their experience.

Positive regulation of NADPH oxidase 5 by proinflammatory-related mechanisms in human aortic smooth muscle cells.

NADPH oxidase Nox5 subtype expression is significantly increased in vascular smooth muscle cells (SMCs) underlying fibro-lipid atherosclerotic lesions. The mechanisms that up-regulate Nox5 are not understood. Consequently, we characterized the promoter of the human Nox5 gene and investigated the role of various proinflammatory transcription factors in the regulation of Nox5 in human aortic SMCs. The Nox5 promoter was cloned in the pGL3 basic reporter vector. Functional analysis was done employing 5' deletion mutants to identify the sequences necessary to effect high levels of expression in SMCs. Transcriptional initiation site was detected by rapid amplification of the 5'-cDNA ends. In silico analysis indicated the existence of typical NF-kB, AP-1, and STAT1/STAT3 sites. Transient overexpression of p65/NF-kB, c-Jun/AP-1, or STAT1/STAT3 increased significantly the Nox5 promoter activity. Chromatin immunoprecipitation demonstrated the physical interaction of c-Jun/AP-1 and STAT1/STAT3 proteins with the Nox5 promoter. Lucigenin-enhanced chemiluminescence, real-time PCR, and Western blot assays showed that pharmacological inhibition and the silencing of p65/NF-kB, c-Jun/AP-1, or STAT1/STAT3 reduced significantly the interferon γ-induced Ca(2+)-dependent Nox activity and Nox5 expression. Up-regulated Nox5 correlated with increases in intracellular Ca(2+), an essential condition for Nox5 activity. NF-kB, AP-1, and STAT1/STAT3 are important regulators of Nox5 in SMCs by either direct or indirect mechanisms. Overexpressed Nox5 may generate free radicals in excess, further contributing to SMCs dysfunction in atherosclerosis.