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Metabolomic analysis methods were employed to determine biomarkers for various chronic kidney diseases (CKDs). Modern analytical methods were developed and applied successfully to find a specific metabolomic profile in urine samples from CKD and Balkan endemic nephropathy (BEN) patients. The aim was to explore a specific metabolomic profile defined by feasible/easy-to-identify molecular markers. Urine samples were collected from patients with CKDs and BEN, and from healthy subjects from endemic and nonendemic areas in Romania. Metabolomic analysis of urine samples, extracted by the liquid-liquid extraction (LLE) method, was performed by gas chromatography-mass spectrometry (GC-MS). The statistical exploration of the results was performed through a principal component analysis (PCA) evaluation. Urine samples were statistically analyzed using a classification based on six types of metabolites. Most urinary metabolites are distributed in the center of a loading plot, meaning that these compounds do not represent significant markers for BEN. One of the most frequent and higher-concentration urinary metabolites in BEN patients was p-Cresol, a phenolic compound that implies a severe injury of the renal filtration function. The presence of p-Cresol was associated with protein-bound uremic toxins, which have specific functional groups such as indole and phenyl. In prospective studies for future investigation, prevention, and disease treatment, we suggest a larger sample size, sample extraction using other methods, and analysis using other chromatography techniques coupled with mass spectrometry, which can generate a more significant data set for statistical analysis., Competing Interests: The authors declare no conflict of interest.

Two immunotoxins containing ricin A-chain, staphylococcal protein A and mouse anti-Thy 1.2 antibodies of IgG(2a,b) subclass, were prepared. The two multivalent immunotoxins of 750 and 370 kDa and molar ratio A-chain: IgG of 1:2, were used for the treatment of mice bearing ascitic EL4 lymphoma. The immunotoxin-treatment, performed intraperitoneally, was combined or not with homologous or heterologous interleukin 2. The antitumor effects expressed by increase of mice survival time (p < 0.001 as compared with nontreated animals) corresponded to a proportion of 88-90% lymphoma cell-kill by immunotoxin and 93-95% by combination treatment (immunotoxin + interleukin 2), as calculated from the relationship between the survival time of nontreated mice and the number of tumor cells inoculated.

Antibodies of the IgG class, specifically interacted with H-2 antigens of murine leukemia EL4 cells, were used to bind the ricin toxin covalently linked to protein A of Staphylococcus aureus. The toxin thus complexed, introduced in the cytoplasm by endocytosis, was able to kill the leukemic cells inoculated in animals. The interaction of immunotoxin with the leukemic cells was performed in vitro using one, two or three treatments and the cytotoxic effect on the target cells was followed up in vivo. The time interval between immunotoxin treatments was indicated by the membrane turn-over study of EL4 cells coated with specific antibodies in their monomeric form, complexed by protein A or interacted with protein A--ricin toxin conjugate. A proportion of 99.8% cells killed was obtained after three treatments.

Two immunotoxins, the ricin A chain-multivalent hybrid antibody (750 kDa) and the complex A chain-staphylococcal protein A-rabbit IgG antibody (370 kDa), were prepared. A simple method was elaborated to test the immunotoxins' efficiency in selectively killing target cells in tumor-bearing mice. The target cell (murine EL4 leukemia) was coated with a xenogenic molecule by a method conserving its ability to proliferate and kill the inoculated animals. When the challenged animals were treated with these immunotoxins, which were specific for the antigenic molecule coating the tumor cells, survival time was lengthened compared with that of untreated animals, corresponding to a proportion of over 90% cells killed. This demonstrates the efficiency of the immunotoxins and the validity of the method elaborated.

The exertion and risk factors in relation with the state of health, with the psychophysiological reactivity and with the adaptation and fatigue symptomatology were studied by means of complex psychological, psychophysiological, medical) methods in two professional groups that perform an activity implying important mental and sensorial components: monotasterers and correctors, from three polygraphic enterprises and two publishing houses, totalling 167 subjects (74 monotasterers and 93 correctors). The ergonomic work analysis demonstrated that the exertion and risk factors are conditioned both by the contents of work and by the working environment. The occupational exertion is more complex in monotasterers (mental, sensorial and physical) and predominantly sensorial (visual) in correctors. The work hazards are especially brought about by overstraining of the attention and of the visual analyser, with consequences both on the health of workers and on the quality of production. The investigation of the state of health, of the psychophysiological reactivity, as well as of the adaptation and fatigue symptomatology has detected maladjustment and fatigue phenomena, with impairments of the psychosomatic balance, more marked in monotasterers. The suggestions regarding improvement measures were directed both towards aspects of medico-psychological prophylaxis and elements of corrective ergonomics.