Probable Mechanisms Involved in Immunotoxin Mediated Capillary Leak Syndrome (CLS) and Recently Developed Countering Strategies.

Antibody-toxin fused agents or immunotoxins, are a newly engineered class of cytotoxic agents consisting of a bacterial or plant toxin moiety hooked up either to a monoclonal antibody or a specific growth factor. Nevertheless, acquiring a full potency in clinic is mostly restricted due to the Capillary leak syndrome (CLS), a serious immune provoked, life-threatening side effect, subsequent to the endothelial damage, resulting in fluid escape from the bloodstream into tissues including lungs, muscle and brain, developing organ failure and eventually death. Proposed underlying mechanisms include direct damage to endothelial cells, acute inflammation, Lymphokine-activated killer (LAK) cells engagement, alteration in cell-cell/cell-matrix connectivities and cytoskeletal dysfunction. Very poor biodistribution and heterogeneous extravasation pattern in tumor site result in accumulation of ITs close to the extravasation site, gradual toxin release and initiation of nearby endothelial cells lysis, secretion of pro-inflammatory cytokines, development of acute inflammation and engagement of Lymphokine-activated killer (LAK) cells. Intrinsic immunogenicity of applied toxin moiety is another important determinant of CLS incidence. Toxins with more intrinsic immunogenicity possess more probability for CLS development. Recently, development of new generations of antibodies and mutated toxins with conserved cytotoxicity has partly tapered risk of CLS development. Here, we describe probable mechanisms involved in CLS and introduce some of the recently applied strategies for lessening incidence of CLS as much as possible.

Virtual resonance and frequency difference generation by van der Waals interaction.

The ability to explore the interior of materials for the presence of inhomogeneities was recently demonstrated by mode synthesizing atomic force microscopy [L. Tetard, A. Passian, and T. Thundat, Nature Nanotech. 5, 105 (2009).]. Proposing a semiempirical nonlinear force, we show that difference frequency ω_ generation, regarded as the simplest synthesized mode, occurs optimally when the force is tuned to van der Waals form. From a parametric study of the probe-sample excitation, we show that the predicted ω_ oscillation agrees well with experiments. We then introduce the concept of virtual resonance to show that probe oscillations at ω_ can efficiently be enhanced.

First case of cutaneous human dirofilariosis in Slovak Republic.

Dirofilariosis is a zoonotic disease caused by several species of the genus of Dirofilaria. The causative agent initiates a dangerous canine disease reported from many parts of the globe. The parasites are transmitted by arthropods, which act either as a vector or intermediate hosts. In humans the parasites do not usually reach the adult stage but microfilaremia is absent because of mating impossibility. Human dirofilariosis is caused by D. immitis or D. repens and has been reported from many parts of the world including European countries, namely Italy, France, Spain and Greece. Sporadically, this parasitosis is detected in Central European countries such as Hungary and Switzerland. The presented paper reports the first case of human cutaneous dirofilariosis in Slovakia. The clinical manifestation was a typical subcutaneous granuloma with the adult worm in the center. The identification of Dirofilaria repens was made based on morphological appearance of the parasite. The patient 60 years old, lives in the area where in 2005 six cases of canine dirofilariosis caused by the same species were reported (Fig. 2, Ref. 16).

Predictors of inferior outcome in community acquired bacterial meningitis.

The aim of this study was to assess mortality and sequellae within cases from Nationwide survey of community acquired meningitis and identify risk factors for inferior outcome. Risk factors such as underlying disease (diabetes mellitus, cancer, trauma, neonatal age, splenectomy, alcoholism, sepsis, other infections), etiology, clinical symptoms and outcome (death, improvement and cured after modifications of ATB therapy, cured without change of therapy, cured with neurologic sequellae) were recorded and analysed with univariate analysis (chi2 or t test for trends, CDC Atlanta 2004). Analysing risk factors for inferior outcome (death or cured with neurologic sequellae), we compared patients who died or survived with neurologic sequellae to all patients with community acquired bacterial meningitis. Univariate analysis showed that trauma (p<0.05), alcohol abuse (p<0.05), diabetes, S. aureus (p<0.05) and gram-negative etiology (A. baumannii, Ps. aeruginosa or Enterobacteriaceae) (36% vs. 11,9%, p<0.05) were predicting inferior outcome. Analysing risk factors for treatment failure (death or failed but cured after change of antibiotic treatment) prior sepsis (34.1% vs. 13.9%, p<0.01) and gram-negative etiology (25% vs. 11.9%, p<0.02) were statistically significant predictors of treatment failure. Neisseria meningitis had less failures (p<0.05). Concerning infection associated mortality again diabetes mellitus (p<0.05), alcoholism (p<0.05) staphylococcal and gram-negative etiology (p<0.05) were significant predictors of death. N. meningitis had surprisingly less treatment failures (appropriate and rapid initial therapy). Neurologic sequellae were more common in patients with alcohol abuse (p<0.05), craniocerbral trauma (p<0.05) and less common in meningitis with pneumococcal etiology (p<0.05).

[Laboratory diagnosis of toxoplasmosis]. / Postupy v laboratórnej diagnostike toxoplazmózy.

Toxoplasmosis is a world-wide spread parasitosis. The disease potentially highly affects two groups of patients: foetus and immunosuppressed patients. The determination of diagnosis and therapy on the basis of a single serum examination is very important; possible on the basis of a single serum sample. In most cases, it is possible to differentiate between recent and latent infections using a combination of suitable methods, which permit us to confirm particular antibody classes. In the presented paper the authors suggest diagnostic procedures for 4 groups of patients: pregnant, neonates with suspected congenital toxoplasmosis, immunodeficient patients and immunocompetent patients. The diagnostic methods consist of a combination of basic and supplemented diagnostic methods. Each patient's serum should be tested by basic tests which include the detection of total antibodies with CFT or IFT and specific classes of IgM and IgG antibodies by ELISA. The potential activity of toxoplasma infection can be determined by supplementary methods of e.g. IgG avidity antibodies, establishment of IgA antibodies, western blotting method and monitoring of antibodies production. For each situation the authors present interpretations of suspected cases including proposals for clinicians. These procedures are suggested for practical use in laboratories of various diagnostic levels in order to help to the diagnostic procedures in a particular situation as well as for clinical evaluation of established results. (Fig. 4, Ref. 65).

[Toxoplasma gondii]. / Toxoplasma gondii.

The authors offered a general view on Toxoplasma gondii from the historical, taxonomic, biological and epidemiological point of view. They also studied the problems of pathogenesis, pathology, clinics, diagnosis, as well as therapy and prevention. (Tab. 1, Ref. 9)

[The occurrence of protozoa in the intestinal microflora of laboratory mice]. / Výskyt prvokov v crevnej mikroflóre laboratórnych mysí.

The intestinal content of 216 white SPF laboratory mice was examined for the presence of protozoa. 153 (70.8%) were found to be positive. The following protozoa species were determined: Trichomonas muris in 31.5%, Trichomonas sp. in 29.6%, Chilomastix becentourti in 18.5%, Octomitus intestinalis in 7.8%, Giardia muris in 6.9%, Spironucleus muris in 4.1%, and Entamoeba muris in 14.8%. The given species occurred in the mice either individually or, in the majority of cases, combined infections involving 2-5 species were recorded. Young mice transferred from the breeding station were but rarely colonized, and that only by a small number of protozoa. They contract infection from older animals in the animal room. (Tab. 3, Ref. 11.).