Antimicrobial peptides as an argument for the involvement of innate immunity in psoriasis (Review).

Antimicrobial peptides (AMPs) are a group of oligopeptides found in most multicellular organisms with a capacity for rapid and nonspecific destruction of pathogens. The action of destroying pathogens is associated with a strong proinflammatory activity, stimulating the secretion of cytokines, chemokines, growth factors but also chemotaxis, the activation of dendritic cells and involving adaptive immunity also. The action of AMPs fits perfectly into the characteristics of innate immunity which makes these peptides candidates to be considered as an important element of this type of immunity. It has been shown that AMPs are involved in a number of cellular processes such as: differentiation, proliferation, maturation, thus widening the degree of involvement of these peptides in the pathogenesis of chronic inflammatory diseases. In psoriasis, AMPs act both as a pro-inflammatory and chemotaxis factor and through the cathelicidin (LL-37)/dc DNA complex as a possible autoantigen for T cells, triggering an autoimmune response, activating the Th17/IL23 axis and maintaining the inflammatory process. Thus, many arguments are accumulated to consider that innate immunity through AMPs is an important link in the pathogenesis of psoriasis. Moreover, the action of antimicrobial peptides in psoriasis is almost entirely characteristic for the general mode of action of innate immunity.

Dermatology facing autoinflammatory syndrome.

Cutaneous symptoms are characteristic for the autoinflammatory disorders (AIDs), both in the classical autoinflammatory phenotype and in most disorders included in this syndrome, but they are not specific and inconstant. Several skin disorders (pyoderma gangrenosum and pustular acne) may be encountered either isolate or associated with autoinflammatory symptoms, forming well-defined clinical entities within the autoinflammatory syndrome. The high prevalence of cutaneous manifestations is an important characteristic of AIDs. The presence of cutaneous symptoms in AIDs opens the perspective of understanding the contribution of innate immunity mechanisms involved in skin pathology. It is possible that many diseases present the alteration, in various degrees, of the innate immune mechanisms. Recently, dermatology faced two challenges connected to AIDs. The first involves the diagnosis of skin symptoms in a clinical autoinflammatory setting and the investigative approach to identify a disorder classified as AID. The second is to identify the altered mechanisms of inborn immunity among the pathogenetic mechanisms of known dermatological diseases (e.g., neutrophilic dermatoses). On the other hand, cutaneous symptoms are in certain cases regarded as a criterion to asses the efficacy of specific or non-specific therapies with monoclonal antibodies in disorders included in AIDs. Dermatology mostly benefits from the identification and knowledge of AIDs due to the role of innate immunity in skin pathogeny and also due to the large extent of clinical forms resulting from the association of skin symptoms with other disorders included in this group.

The impact of respiratory tract infections on the nutritional state of children with cystic fibrosis.

UNLABELLED: Cystic fibrosis (CF) is a life-shortening, autosomal-recessive disorder characterized by intestinal malabsorption, impaired growth and lung disease. Recurrent pulmonary infections in children with CF are often associated with nutritional deficiencies. AIM: To emphasize the effects of recurrent pulmonary infections on nutritional status in children with CF. MATERIAL AND METHODS: This retrospective study included 27 patients diagnosed with CF between 1994 and 2011 in the 3rd Pediatric Clinic of the Iasi "Saint Mary" Children's Hospital. The nutritional status was assessed according to ponderal index (PI), body mass index (BMI), Z score for weight and waist. Correlations between the age of onset of symptoms, age at diagnosis, and frequency of infectious episodes, identified bacterial agents and nutritional status were established. RESULTS: Patients aged between 3 months old and 17 years old with an average of 49.48 months +/- 9.83DS; sex ratio was 1.7:1. The patients were diagnosed late, one month to 112 months (average 41.11 months +/- 9.4DS) from the first symptoms until the moment of diagnosis. The clinical forms of CF in the study group were: predominantly respiratory manifestations in 48.14% of cases, and the mixed type, with both respiratory and digestive symptoms, in 18.52% of cases. Delayed weight and/or height gains were identified in 85.19% of cases. The etiologic agents involved in pulmonary infections were Staphylococus aureus (48.14%), Pseudomonas aeruginosa (33.33%), Stenotrophomonas maltophilia (18.51%), Haemophilus influenzae (14.8%), Klebsiella pneumoniae (11.10%), Moraxella catarrhalis (7,40%), Streptococcus pneutmoniae (7.40%), Neisseria sica (7.40%). Pulmonary infections caused by Staphylococus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia were more often associated with nutritional status abnormalities. CONCLUSIONS: In small children with CF pulmonary infections due to various causative agents cause a slow rate of growth (both weight and height). Good nutrition and adequate early treatment of pulmonary infections are beneficial for the general state of affected children and are very important in maintaining their health.

[Current microbiological data on lower respiratory tract infection in cystic fibrosis. Part I: Isolated microorganisms and their clinical significance]. / Date microbiologice actuale privind infectia tractusului respirator inferior în fibroza chistica. Partea I: Microorganisme izolate si semnificatia lor clinica.

Cystic fibrosis (CF) is a disease that degrades the local defense mechanisms of the lower respiratory tract. As a result, patients develop recurrent infections that progressively deteriorates antiinfection defenses and represent the major cause of mortality. A hallmark of those infections is the diversity of microorganisms isolated from broncho-alveolar lavage or sputum. The clinical significance of isolates is different, the recognition of the role in altering of respiratory function being important in guiding antibiotic therapy. Current data support pathogenicity in CF of S. aureus, P. aeruginosa and B. cepacia complex, the latter two being considered "preterminal bacteria". S. aureus was the most common cause of mortality and morbidity in preantibiotic era. Today, life expectancy was improved with the introduction of antistaphylococcal antibiotics. Hypermutation of P. aeruginosa--the most common species isolated from patients with CF, is the essential factor in the development of multi-resistance to antibiotics. As P. aeruginosa, B. cenocepacia is a virulent species that cause infections with poor prognosis. Microorganisms with secondary role (H. influenzae, S. maltophilia, atypical Mycobacteria, Aspergillus spp) whose clinical significance has not been clarified yet, require further studies.

Current microbiological data on lower respiratory tract infection in cystic fibrosis. Part II: Recommendations for microbiological diagnosis in cystic fibrosis.

Current standards of sputum examination in respiratory infections with opportunistic bacteria cannot be applied to patients with cystic fibrosis due to their particularities. In 2010, a working group from Great Britain established standards for microbiological processing of samples from patients with cystic fibrosis. Recommendations on sample collection, transportation, storage, and processing, identification of bacterial isolates and in vitro antibiotic susceptibility are made. Also recommended is that the multidisciplinary team monitoring patients with cystic fibrosis to include a microbiologist.

[Carbapenem resistance in Klebsiella pneumoniae clinical isolates from urinary tract infections]. / Emergenta rezistentei la carbapeneme la tulpini de Klebsiella pneumoniae izolate din infectii ale tractusului urinar.

UNLABELLED: Resistance to carbapenems by KPC (Klebsiella pneumoniae carbapenemase) production in Klebsiella pneumoniae clinical isolates was first described ten years ago in the U.S.A. and recently reported in other countries. This enzyme inactivates all beta-lactam antibiotics and is associated with fluoroquinolone and aminoglycoside resistance. MATERIAL AND METHODS: We investigated the carbapenem resistance in 498 Escherichia coli and Klebsiella pneumoniae strains isolated from urinary tract infections during 2009 in the lasi "Dr. C. I. Parhon" Clinical Hospital. Antimicrobial susceptibility testing was performed according to CLSI guidelines. To detect ESBL (extended spectrum beta-lactamase) and KPC production we used phenotypic tests and molecular biology methods (PCR). RESULTS: From all tested strains, only two K. pneumoniae strains showed modified susceptibility to carbapenems. The modified Hodge test was positive for the strain resistant to ertapenem, meropenem, imipenem (KA) and negative for the strain resistant only to ertapenem (K(B)). Both KA and K(B) isolates were negative for blaKPC and blaTEM genes, but harbored blaSHV and bla(CTX-M) genes, respectively. CONCLUSIONS: We report the first carbapenem resistant K. pneumoniae strains from Northeast Romania. The resistance is not mediated by KPC-carbapenemase; the possibility of dual mechanisms through cefalosporinases production and porins loss is suggested.

[Persistent and recurrent skin infection with small-colony variant methicillin-resistant Staphylococcus aureus]. / Infectie cutanata persistenta si recurenta cu Staphylococcus aureus meticilino-rezistent, varianta cu colonii mici.

S. aureus is one of the problematic bacteria, capable to develop resistance mechanisms to all antibiotics that the bacteria are naturally susceptible. A particular phenotypic mechanism, especially against the antibiotics that repressed the synthesis of the cellular wall and aminoglycosides, was evidenced in subpopulations that grows in small-colonies and represents auxotrophic mutants for hemin, menadione or thymidine. This type of strains has been isolated most frequently from patients with osteomyelitis, septic arthritis or pulmonary infections after a long period of antibiotic treatment. The authors present the case of a patient with persistent and recurrent staphylococcal infection of the peritoneal dialysis exit site, treated with different antibiotics (ciprofloxacin, vancomycin, amoxicillin and clavulanic acid, cephalexin) from witch has been isolated a small-colony strain of methicillin-resistant S. aureus. Therapeutic failure can be explain by the slow multiplication of this strain in vivo, persistence into phagocytes and the protection offered by biofilm from the surface of the catheter. Bacteriologic diagnosis in these cases is difficult because of the culture, biochemical and susceptibility testing particularities of these strains. All these may lead failure to identification small colony variants of S. aureus and mis-evaluation of the frequency of infection with these strains in patients with long-term antibiotherapy.

[Urinary tract infections in children--aspects of microbiological diagnosis]. / Infectia urinara la copil aspecte ale diagnosticului bacteriologic.

UNLABELLED: Urinary tract infection (UTI) is one of the most common bacterial infections of childhood, with the incidence range between 1-1.5% in boys and 3-8% in girls. AIM: To estimate the value of urine analysis (bacteriology and biochemistry) for diagnostic of UTI in children. MATERIAL AND METHOD: The method was to observe 700 urinary specimens collected from patients hospitalized in 4th Clinic of Pediatric Nephrology between October 2004 and February 2005, the urinalysis (UA) being performed in the Microbiology laboratory of "St. Maria" Emergency Children Hospital Iasi. The sample collection was made from the midstream urine flow, direct microscopy and standard culture were performed immediately after collection. We applied a diagnostic strategy study in order to evaluate sensitivity and specificity of UA for prediction of UTI. The data was assessed according to the Receiver Operator Characteristic Curve. RESULTS AND DISCUSSION: We analysed the relation between leukocituria and positive urine culture and we find a sensitivity equal to 56%, with CI 95% = 0.56 +/- 0.07, and a specificity equal to 10%, with CI 95% = 0.10 +/- 0.02. The likelihood of UTI with negative UA result has been calculated as a negative likelihood ratio = 4.4. If we supplement a number of culture (2-3) we have obtain a sensitivity 97% +/- 0.02%, and the predictive negative value 97% (that mean the possibility to lose UTI in just 3% cases), and a specificity 35%, with a predictive positive value 61% (that mean a decrease of possibility to over-measure UTI). CONCLUSIONS: The sensitivity of UA increase if we correlate more than leukocyturie and the significantly positive urine culture. We must to supplement a number of urine culture for increase the chance to obtain a positive diagnostic of UTI, and to exclude a possibility to over-measure UTI. Through increase a sensibility of method for diagnostic, decrease the possibility to loose and no treaty UTI with serious consequence.

Regional occurrence of plasmid-mediated carbapenem-hydrolyzing oxacillinase OXA-58 in Acinetobacter spp. in Europe.

The spread of the plasmid-mediated carbapenem-hydrolyzing oxacillinase OXA-58 was detected in Acinetobacter sp. clinical isolates from southern Europe, the Balkans, and central Turkey. It may contribute significantly to the emergence of carbapenem resistance in Acinetobacter spp., at least in this part of the world.

International spread of major clones of methicillin resistant Staphylococcus aureus: nosocomial endemicity of multi locus sequence type 239 in Saudi Arabia and Romania.

Phenotypically identified methicillin resistant Staphylococcus aureus (MRSA) strains from several hospitals in Romania and Saudi Arabia (n = 103 and 68, respectively) were confirmed to be MRSA by mecA PCR and PBP-2' based latex agglutination. Subsequently, strains were differentiated at the sub-species level using pulsed field gel electrophoresis (PFGE) of SmaI DNA macro-restriction fragments. Comparison of the PFGE fingerprints identified major clusters of strains, persistently present in the various hospitals. Endemicity of certain strains was identified, amongst others one due to a particularly methicillin resistant type in the burn wound sector of the Romanian hospital. No PFGE-based overlap was found between the Saudi and Romanian strains. However, multi locus sequence typing (MLST), performed for 20% of all strains, revealed that genuine genetic similarity was obscured by the PFGE analysis. In both the Romanian and Saudi hospitals the renowned sequence type (ST) 239 was very over-represented. This was especially apparent in Saudi Arabia, where all strains except two shared the ST 239 genotype. This clonal type has previously been identified in a variety of other countries. Despite the MLST concordance, PFGE data indicate that ST 239 diversifies while maintaining its core genome intact. ST 80, another previously but less frequently identified clone, was introduced in 2000 in the Romanian institutes and persisted over the past 3 years as a frequent cause of infections in a surgical department. The successful MRSA types can acquire prominent positions in hospitals of previously low-endemicity MRSA status.

[Epidemiologic, clinical and laboratory observations of some Streptococcus pneumoniae serotypes implicated in the evolution of asthma in children]. / Observatii epidemiologice, clinice si de laborator asupra implicarii unor serotipuri de Streptococcus pneumoniae în evolutia astmului bronsic la copii.

The Authors present the results of a multidisciplinary study carried out on a sample of 103 children comprised in a programme of vaccination against Streptococcus pneumoniae infections, in order to avoid the worsening of their asthma. In the nasopharyngeal exudate of 39 children, we detected the presence of S. pneumoniae strains of serotypes 6, 8, 14, and 19 and their absence after vaccination with PNEUMO 23. This was followed by a significant decrease in the incidence of pneumococcal infections and also by the reduction in the frequency of crises and severity of the disease.

[Acute diarrhea associated with Cyclospora cayetanensis]. / Boala diareica acuta cu Cyclospora cayetanensis.

Acute diarrhea is a major problem with high morbidity and mortality rates in developing countries, especially in children. Complex laboratory investigations are required to define the etiology because of the broad spectrum of etiological agents and the non-specific clinical signs. In the last decade, Cyclospora cayetanensis--a new acid-fast coccidian species--was pointed to be the cause of watery self-limited or prolonged diarrhea in immunocompetent and immunocompromised patients, with very good evolution after treatment with co-trimoxazole. Unlike Cryptosporidium parvum, nonsporulated Cyclospora oocysts are eliminated in feces, with no risk of human to human transmission. Cyclospora cayetanensis is widely spread, producing endemic infections, in Asia and South America and was reported to produce infections in foreign travellers in these areas and epidemic outbreaks of foodborne diarrhea. We describe the first case of acute diarrhea associated with Cyclospora cayetanensis in an immunocompetent child admitted to Iasi "Sf. Maria" Hospital.

Expanded-spectrum cephalosporin-resistant salmonella strains in Romania.

Thirteen Salmonella enterica serotype Typhimurium and one Salmonella enterica serotype Heidelberg strain resistant to expanded-spectrum cephalosporins were isolated from October 2000 to February 2001 from infants with gastroenteritis in Iasi, Romania. In all but one serotype Typhimurium isolate, resistance was due to the production of a CMY-2 cephalosporinase encoded by a nonconjugative plasmid. The remaining isolate produced an SHV-5-type beta-lactamase. Typing by pulsed-field gel electrophoresis indicated that the CMY-2-producing serotype Typhimurium isolates were related.

Tolerance to penicillin in Staphylococcus pyogenes isolated from skin infections.

The tolerance to penicillin of S. pyogenes has been mentioned in pharyngeal strains and associated by some authors with penicillin treatment failure in streptococcal angina. In this study we followed the presence of tolerance in S. pyogenes strains isolated from children hospitalized in the Clinic of Infantile Surgery and Clinic of Dermatology Iasi for skin infections. From 138 samples of pus examined we isolated 14 strains of S. pyogenes. In 7 strains we pointed out the tolerance to penicillin by both, beta-lactamase disc test and time-killing curve methods. We did not correlate to our cases the tolerance presence with penicillin treatment failure.

High levels of sFas and PBMC apoptosis before and after excision of malignant melanoma--case report.

In our study we investigated the level of apoptosis in PBMCs and the serological level of sFas (CD95/APO-1) in 22 patients with malignant melanoma (12 patients with unique cutaneous primary tumour and 10 patients with unique brain metastasis). The first determination was performed before tumour excision and the second at 6-7 months after excision. Results in patients with primary tumour in the first determination: 6 patients with over normal values in PBMCs apoptosis and 5 patients with increased values of sFas. In the second determination: apoptosis was increased in 5 patients and sFas level was increased in 4 cases. In patients with metastases in the first determination apoptosis of PBMC was increased in 7 cases and sFas in 5 cases. In the second determination apoptosis was increased in 4 cases and sFas was increased in 4 cases. Our results show that half of the investigated patients presented elevated values of PBMCs apoptosis and Fas receptor both before and 6-7 months after tumour excision. Apoptosis values for PBMCs and sFas values were with 1/4 higher than normals. There was no difference in clinical evolution of the patients with normal or increased values for studied parameters. Clinical evolution was performed for 1 year. The presence of increased values for PBMCs and sFas after tumour excision, primary or metastasis is surprising and hard to explain. It is possible that tumoral evolution induces a disregulation at PBMCs level or other cells level that persists unexpectedly, after tumour excision or apoptotic processes, in a certain level to be independent and anterior to tumour development.