Effect of vitamin E and vitamin C combination on experimental influenza virus infection

Successful antioxidant treatment of the so-called "free radical diseases" has been reported in the literature. In this study we examined the preventive effect of vitamin E and vitamin C, alone and in combination, on the damage caused by influenza virus infection (IVI). Male mice (ICR), infected with influenza virus A/2/68/(H3N2) (1.5 of LD(50)), were administered single once-daily doses of vitamin E (60 mg/kg b.w.) and vitamin C (80 mg/kg b.w.) intraperitoneally (3 days before virus inoculation). On the 5th and 7th day, respectively, after virus inoculation, animals were decapitated. Monooxygenase enzyme activity (ethylmorphine N-demethylase, amidopyrin N-demethylase, analgin N-demethylase, aniline hydroxylase, cytochrome P-450 content and NADPH-cytochrome C reductase [CCR]) was determined in liver 9000 x g supernatant. Primary and secondary products of lipid peroxidation (LPO; conjugated dienes [CD] and TBA-reactive substances) were measured in blood plasma, lung and liver 9000 x g supernatant. Vitamin E effectively restored LPO-levels increased by IVI. The effect of vitamin C was similar, but slighter. The combination (vitamin E + C) had greater effect on LPO levels than their separate administration. P-450-dependent monooxygenase activity was significantly restored and more pronounced cytochrome P-450 content and NADPH-CCR activity was noted. The preventive effect of vitamin E was stronger than the effect of vitamin C, but the combination (vitamin E + C) had the strongest effect. The superior protective effect of the combination is probably due to vitamin C's repairing effect on vitamin E's tocopheroxyl radical.     

Tick-borne encephalitis: Possibly a fatal disease in its acute stage. PCR amplification of TBE RNA from postmortem brain tissue

Summary Tick-borne encephalitis has occurred regularly in Europe since it was first diagnosed in 1931 bySchneider. The mortality rate of patients with this disease is 1–2%. Death usually occurs in the acute stage of illness. A case report of a 28-year-old patient from Slovenia, who died shortly after the onset of tick-borne encephalitis, is described. The clinical course of disease, results of serological tests, neuropathological findings and polymerase chain reaction amplification of parts of viral genome from postmortem brain tissues are presented.     

Sea snake Hydrophis cyanocinctus venom. II. Histopathological changes, induced by a myotoxic phospholipase A2 (PLA2-H1).

A toxic phospholipase A2 (PLA2-H1), isolated from the venom of the sea snake Hydrophis cyanocinctus, was tested for its ability to induce myonecrosis and histopathological changes in albino rats and mice. Induction of myonecrosis was demonstrated by their ability to release creatine kinase (CK) from damaged muscle fibers and direct histopathological examination of the injected muscles (i.m.). PLA2-H1 exhibits intense myonecrosis characterized by the changes including, necrosis and edematous appearance with cellular infiltrate, vacuolation and degenerated muscle cells with delta lesions and heavy edema in between the cells. No myoglobinuria was noted in any group of animals. The purified PLA2-H1 was also administered intraperitoneally into the experimental animals and tissue samples were taken at several time intervals. Light microscopic examination of the kidney sections revealed severe damage, evident by focal tubular necrosis, complete disquamation of epithelial lining and epithelial degeneration of tubules in all test animals. Light micrographs of liver sections after 24 h of injection shows fatty infiltration in parenchyma and squashed hepatocytes, while after 48 h, fatty vacuolation of parenchyma in a generalized pattern was observed. Furthermore, sections of the lungs of the same group of animals (48 h) show dilated bronchia and marked infiltration of inflammatory cells within alveoli. Our results suggest that the purified PLA2-H1 induced moderate myotoxicity in muscles and mild histopathological changes in other vital organs without myoglobinuria.     

Possibilities and limits of treatment in patients with thrombotic thrombocytopenic purpura

Results of treatment of 18 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Sixteen of the 18 patients (88.8%) had mental status changes, and seven of the 18 patients (38.8%) had renal impairment. One patient had a secondary type of TTP, caused by non-Hodgkin's lymphoma of the large intestine (that was diagnosed later) and was excluded from the study. Immunosuppresive therapy with steroids, plasma exchange and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in a statistically significant increase of platelet count (P = 0.00222), and a significant improvement in consciousness defined by increased GCS after 2 weeks (P = 0.00222). In two patients renal function recovered, and in one of them hemodialysis was no longer needed. This improvement in a small group of patients had no statistical significance. TTP recurred in seven patients. High doses of steroids caused serious side effects in two patients: in one patient, steroid diabetes, and in the other one, intestinal perforation.     

Primary Adenoid Cystic Carcinoma of the Skin with Multiple Local Recurrences

Primary adenoid cystic carcinoma (PACC) of the skin is a rare tumor with fewer than 70 cases studied in detail in the English literature. This type of tumor shows a prolonged course and a growth pattern usually manifested by multiple local recurrences and has a low potential for distant metastases. The most important modality for primary treatment is surgical resection followed by radiotherapy. We report a woman aged 43 years at the time of diagnosis, who presented with a slow-growing nodule in the right axilla without lymph node enlargement. A wide local excision was performed, and the histology revealed an adenoid cystic carcinoma. During the next 24 years, another four local recurrences were excised (the last one in 2015) and confirmed histologically to be adenoid cystic carcinoma. The patient was given 44 Gy of radiotherapy after the second surgery in 1996. PACC of the skin is a rare tumor with insufficient data concerning the efficacy of the surgical technique and chemotherapy and radiotherapy treatment, even more so in the case of multiple recurrences. After the last recurrence, the patient was offered an active follow-up based on the long tumor-free intervals in the past and because the site of the primary tumor allowed further surgical excisions in future recurrences.Key Words: Adenoid cystic carcinoma, Cylindroma, Skin     

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Identifying the structural requirements for chromosomal aberration by incorporating molecular flexibility and metabolic activation of chemicals

Modeling the potential of chemicals to induce chromosomal damage has been hampered by the diversity of mechanisms which condition this biological effect. The direct binding of a chemical to DNA is one of the underlying mechanisms that is also responsible for bacterial mutagenicity. Disturbance of DNA synthesis due to inhibition of topoisomerases and interaction of chemicals with nuclear proteins associated with DNA (e.g., histone proteins) were identified as additional mechanisms leading to chromosomal aberrations (CA). A comparative analysis of in vitro genotoxic data for a large number of chemicals revealed that more than 80% of chemicals that elicit bacterial mutagenicity (as indicated by the Ames test) also induce CA; alternatively, only 60% of chemicals that induce CA have been found to be active in the Ames test. In agreement with this relationship, a battery of models is developed for modeling CA. It combines the Ames model for bacterial mutagenicity, which has already been derived and integrated into the Optimized Approach Based on Structural Indices Set (OASIS) tissue metabolic simulator (TIMES) platform, and a newly derived model accounting for additional mechanisms leading to CA. Both models are based on the classical concept of reactive alerts. Some of the specified alerts interact directly with DNA or nuclear proteins, whereas others are applied in a combination of two- or three-dimensional quantitative structure-activity relationship models assessing the degree of activation of the alerts from the rest of the molecules. The use of each of the alerts has been justified by a mechanistic interpretation of the interaction. In combination with a rat liver S9 metabolism simulator, the model explained the CA induced by metabolically activated chemicals that do not elicit activity in the parent form. The model can be applied in two ways: with and without metabolic activation of chemicals.     

A model of experimental acute hematogenous pyelonephritis in the rat

The OBJECTIVE of the study was to create a model of acute hematogenous pyelonephritis in the rat without causing urinary retention by ligation of the ureter. Mixed bacterial suspension containing 1.5 x 10(6) colony-forming units (CFU) of S. aureus and 3.0 x 10(6) CFU of E. coli was inoculated in the caudal vein at a dose of 0.5 ml/kg. Control animals received the same amount of saline solution. Pyelonephritis was confirmed by lab urine tests and histopathological study of the kidneys. Infected animals initially developed sepsis with a significant increase of leukocytes and C-reactive protein in the blood. Originally only bacteriuria was found in the urine of experimental animals, but later, in the course of the development of pyelonephritis (12-18 days), leucocyturia and active leukocytes (glitter cells) were also available in urine. The levels of beta-2 microglobulin in the urine of infected animals (4.02 +/- 0.04 mmol/l on day 16 and 4.18 + 0.07 mmol/l on day 18) were significantly highly increased (p <0.0001) in comparison with the value of the control group (0.088 +/- 0.005 mmol/l). In the early days the histopathological examination of the kidneys established erythrocyte stasis. Later leukocyte infiltrates were observed in the interstitial tissue around the kidney tubules, glomeruli and vascular walls, and inflammatory cell infiltration and degenerative changes were present in the epithelium of the canaliculi. Combined hematogenous infection with S. aureus and E. coli led to the development of pyelonephritis in rats. The pathology in the kidney tubules was confirmed by histopathological study and by the elevated levels of beta-2 microglobulin and the presence of active leukocytes in urine.     

Investigating the relationship between in vitro-in vivo genotoxicity: derivation of mechanistic QSAR models for in vivo liver genotoxicity and in vivo bone marrow micronucleus formation which encompass metabolism

Strategic testing as part of an integrated testing strategy (ITS) to maximize information and avoid the use of animals where possible is fast becoming the norm with the advent of new legislation such as REACH. Genotoxicity is an area where regulatory testing is clearly defined as part of ITS schemes. Under REACH, the specific information requirements depend on the tonnage manufactured or imported. Two types of test systems exist to meet these information requirements, in vivo genotoxicity assays, which take into account the whole animal, and in vitro assays, which are conducted outside the living mammalian organism using microbial or mammalian cells under appropriate culturing conditions. Clearly, with these different broad experimental categories, results for a given chemical can often differ, which presents challenges in the interpretation as well as in attempting to model the results in silico. This study attempted to compare the differences between in vitro and in vivo genotoxicity results, to rationalize these differences with plausible hypothesis in concert with available data. Two proof of concept (Q)SAR models were developed, one for in vivo genotoxicity effects in liver and a second for in vivo micronucleus formation in bone marrow. These "mechanistic models" will be of practical value in testing strategies, and both have been implemented into the TIMES software platform ( http://oasis-lmc.org ) to help predict the genotoxicity outcome of new untested chemicals.