H-ficolin (ficolin-3) concentrations and FCN3 gene polymorphism in neonates

Serum H-ficolin (ficolin-3) concentrations (n=613) and FCN3 genotypes (n=529) from a large group of neonates are presented. Both pre-term deliveries and low birthweight (independently of gestational age) were significantly associated with low H-ficolin concentrations but not with heterozygosity for the FCN3 1637delC frameshift mutation. The presence of the variant allele, however, apparently influenced the protein level. No association of FCN3 gene heterozygosity or relative functional H-ficolin insufficiency (determined as serum level ≤8.6 μg/ml) with perinatal infections was found. One premature newborn, with confirmed infection caused by Streptococcus agalactiae, was H-ficolin-deficient (FCN3 variant homozygote, no detectable protein). We present what is only the fourth case report of total H-ficolin deficiency in the world literature. This neonate was however previously found to be mannan-binding lectin (MBL) as well as MBL-associated serine protease-2 (MASP-2) deficient and also had low serum L-ficolin.     

Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system

Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads. In conclusion, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity.     

Pulmonary functional abnormalities in asymptomatic patients with systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a disease characterized by widespread fibrosis of the skin and multiple organs, including the lungs. This study was designed to evaluate pulmonary function in SSc patients without symptoms of lung involvement. METHODS: Spirometric measurements were done in 26 female SSC patients without symptoms of pulmonary involvement. RESULTS: Maximal voluntary ventilation was found to be decreased in half of the patients, and forced vital capacity was decreased in 23% of the patients. Forced expiratory flow rate was impaired in about half of the SSc patients, especially the flow at 50-75% of forced vital capacity. Peak expiratory flow rate was decreased in 77% of asymptomatic patients. CONCLUSIONS: A functional defect, mainly of the restrictive type, was observed in the majority of asymptomatic patients with SSc. Pulmonary function testing is recommended for all SSc patients.     

Bacteriophage preparation inhibition of reactive oxygen species generation by endotoxin-stimulated polymorphonuclear leukocytes

It has been known that administration of antibiotics may lead to excessive release of bacterial endotoxins and complicate clinical course of patients with Gram-negative infections. This concern may also apply to phages. Endotoxin may in turn activate neutrophils to produce reactive oxygen species (ROS) that are believed to play an important role in the pathogenesis of multiple organ dysfunction in the course of sepsis. We showed that a purified T4 phage preparation with low-endotoxin content could significantly diminish the luminol-dependent chemiluminescence (CL) of peripheral blood polymorphonuclear leukocytes (PMNs) both stimulated by lipopolysaccharides (LPSs) isolated from different Escherichia coli strains. This effect was also observed for live bacteria used for PMNs stimulation and was independent of bacterial susceptibility for T4-mediated lysis. Our data suggest, that phage-mediated inhibition of LPS- or bacteria-stimulated ROS production by PMNs may be attributed not only to phage-PMNs interactions, but also to phage-LPS interactions and bacterial lysis (in case of homologous phage). Interestingly, the T4 preparation did not influence ROS formation by PMNs stimulated with PMA. This suggests that the observed phenomena are also dependent upon the nature of activator. Bacteriophage-mediated inhibition of ROS formation by cells exposed to endotoxin provides new evidence for possible interactions between phages and mammalian cells. It helps in understanding the role of phages in our environment and may also be of important clinical significance.     

Osteoarticular manifestations of Mycobacterium tuberculosis infection

Mycobacterium tuberculosis has affected humans for much of our existence. The incidence of global tuberculosis infection continues to rise, especially in concert with HIV coinfection. Many disease processes, such as diabetes, increase the likelihood of tuberculosis infection. Tuberculosis bacteria can infect any bone, joint, tendon, or bursa; however, the most common musculoskeletal site for infection includes the spine and weight-bearing joints of the hip and knee. Many patients who present with osteoarticular tuberculosis infection will have a gradual onset of pain at the site of infection. Many patients who develop a musculoskeletal tuberculosis infection will have no evidence of a pulmonary tuberculosis infection on x-ray film and many will have very mild symptoms with the initial infection. Healthcare providers must remember that many patients who develop tuberculosis infection do not progress to active tuberculosis disease; however, the latent infection may become active with immune compromise.     

Variability of the nonstructural 5A protein of hepatitis C virus type 3a isolates and relation to interferon sensitivity

The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) genotype 1 is thought to interact with several cellular proteins, including the double-stranded RNA-dependent protein kinase (PKR) induced by interferon (IFN). The PKR-binding domain (PKR-BD; aa 2209-2274), including the IFN sensitivity-determining region (aa 2209-2248) and other regions, could be linked to IFN resistance. Thus, the entire NS5A sequence of 27 isolates of HCV genotype 3a was investigated in relation to the clinical response to IFN. The NS5A 3a protein presented a low variability with some specific variable regions. Differential analysis between IFN-resistant and -sensitive isolates identified 5 regions in NS5A, 2 of them inside the PKR-BD and another around the variable 3 region. However, using the yeast growth suppression assay, no interaction was found between 5 resistant NS5A 3a proteins and PKR. Some amino acid changes of the NS5A protein of genotype 3a seemed to relate to IFN resistance independently of the PKR pathway.     

Correlates of depression among heavy drinkers in Polish primary care clinics

OBJECTIVE: Depression and co-morbid substance abuse disorders are a major public health problem. Information is limited for patients attending Polish primary care clinics. This article addresses 30-day and lifetime prevalence of major depression in a heavy drinking population from 12 Polish primary care clinics. METHOD: 277 heavy drinkers were interviewed by a researcher in each clinic. Heavy drinking was defined as more than 20 drinks per week for males, or more than 13 drinks per week for females, or consumption of more than four drinks five or more times in the previous 30 days, or two or more positive replies to the CAGE questions. Criteria from the Diagnostic and Statistical Manual were used to assess lifetime and past 30-day depression. RESULTS: 35% of women and men met criteria for depression in the 30 days prior to the interview. Lifetime rates were 45% for women and 52% for men. Men and women with a CAGE score of 4 were at higher risk for both 30-day (67%, OR = 3.85 [1.47, 10.08]) and lifetime (78%, OR = 3.28 [1.12, 9.66]) depression. Recreational drug users and patients reporting symptoms of anti-social personality disorders were at increased risk for lifetime depression. Subjects reporting symptoms of a childhood conduct disorder were at higher risk for 30-day depression. CONCLUSIONS: Depression among patients with substance abuse problems is a common problem. The rates are higher than for other countries and highlight the need for Polish primary care clinicians to routinely screen for depression in patients with substance use disorders.     

Value of hyperbaric oxygen in bacterial and fungal malignant external otitis treatment

Malignant external otitis (MEO) is an invasive, morbidity, even mortality, mainly pseudomonal infection of the external auditory canal, frequently involving the base of the skull, multiple cranial nerve and the meninges. In many cases conventional therapy has been prolonged, intensive and relatively ineffective, especially in infections other than bacterial (mainly fungal). We presented theoretical principles of hyperbaric oxygen (HBO) treatment in MEO, our own experience and others’ experience in applying this treatment method. We treated eight patients with MEO applying pharmacotherapy, topical management, surgery in one case and also adjunct HBO. In six patients, infection was caused by Pseudomonas aeruginosa, in one by Staphylococcus sp. and in one by Aspergillus sp. Complete recovery was achieved in seven patients. In the patient with MEO caused by Aspergillus sp., intracranial complications developed and the patient died. Our experiences in employing HBO in bacterial-caused MEO have confirmed the role of HBO as a valuable, beneficial, supporting classical treatment method. Small number of patients with MEO, especially with non-bacterial infection, and unforeseen clinical course of disease make our experience difficult to objectivize.