[Chest X-ray in patients with fever and no localizing symptoms?] / Thoraxfoto bij koorts zonder duidelijk focus?

Fever without localizing symptoms is a clinical problem that is frequently encountered on the emergency department. According to the NICE sepsis guideline, a chest X-ray should be considered in such patients. However, the evidence supporting this recommendation is limited to patients with neutropenic fever. We performed a telephone survey among the internists and residents at every Dutch hospital. Of the 141 physicians that responded, 88% considered a chest X-ray a valuable diagnostic tool and one that is indicated in patients with fever without localizing symptoms. In view of rising health costs, diagnostics should be chosen wisely. A clinical study on the diagnostic value of a chest X-ray in patients with fever without localizing symptoms is needed.

[Toxicological Evaluation of Intravenous Formulation of Rifapentine.]

Rifapentine belongs to the most potent antituberculosis drugs. Nevertheless, there are some limitations for its clinical use because of the low aqueous solubility and side effects. A technological approach to development of rifapentine intravenous formulation based on human serum albumin was described earlier and its efficacy against experimental tuberculosis was estimated. Toxicological evaluation of that water-compatible form of rifapentine revealed its low acute toxicity (LD50 340 mg/kg). Chronic toxicity tests of both the oral substance and the injectable formulation of rifapentine demonstrated similar adverse effects. However, in contrast to the conventional oral formulations, the intravenous formulation of rifapentine had no gastrointestinal toxic effects or cardiotoxicity, thus suggesting its usefulness for clinical application.

The Effect of Blood Glucose Concentration on the Error Monitoring and Processing System in Alcohol Users During Intensive Mental Activities

Background:The error monitoring and processing system (EMPS) located in the substantia nigra of the midbrain; basal ganglia and cortex of the forebrain; plays a leading role in error detection and correction. Although recent data show that alcohol disrupts the EMPS; the mechanism of alcohol's effect on this system remains unknown.Aims: To suggest a hypothesis that explains the processes and mechanism of alcohol-related disruption of EMPS. Methods:We critically examined our recent research data; as well as peer-reviewed literature on the effect of alcohol on blood glucose levels; and cognitive functions. The role of blood glucose concentration in the EMPS; including associated theories and hypothesis were also reviewed. Databases utilised were African Journals On Line; Elsevier; Science Direct; Medline from January 1940 to February 2010 . Results: Blood glucose concentration plays a vital role in the EMPS. The effect of blood glucose concentration on the EMPS is realised through the modulation of the activity of the dopaminergic system by proportional changes in the brain glucose level. Based on current literatures and the results of our recent study; here we suggest a hypothesis of alcohol-related glucose-dependent system of error monitoring and processing.The main postulate of this hypothesis holds that the disruption of EMPS by ethanol is related to disorders in glucose metabolism; which in turn may determine the dopamine level the major component of EMPS.Conclusion: Alcohol may disrupt the EMPS indirectly by affecting dopamine level through disorders in glucose homeostasis regulation

Intravenous tolerance of a nanoparticle-based formulation of doxorubicin in healthy rats.

A comparative toxicological study of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 was performed in male and female Wistar rats. The drug substance was used as a reference formulation. The formulations were injected intravenously at a therapeutic dose of 6 mg/kg administered either as a single injection or in form of four weekly injections. The animals were followed up for 4 and 40 days (single injection) or 25 and 61 days (multiple injections) for assessment of the dynamics of body weight, hematological parameters, blood biochemical parameters, and urinalysis. Pathomorphological evaluation included macroscopic evaluation and weight measurement of the internal organs. The heart, lung, spleen, testes, and liver were also subjected to the histological evaluation. The overall result of this study suggests that the surfactant-coated nanoparticle formulation of doxorubicin has a favorable toxicological profile. Specifically, this formulation displays a considerably reduced cardio- and testicular toxicity, as compared to a free drug.

Influence of the formulation on the tolerance profile of nanoparticle-bound doxorubicin in healthy rats: focus on cardio- and testicular toxicity.

A toxicological study of doxorubicin bound to poly(butyl cyanoacrylate) or human serum albumin nanoparticles coated with polysorbate 80 was performed in healthy rats. The doxorubicin formulations were injected at a therapeutic dose regimen (3 x 1.5 mg/kg with a 72 h interval), and the animals were followed up for 15 or 30 days. The overall result of this study suggests that the surfactant-coated nanoparticle formulations of doxorubicin have favorable toxicological profiles. Specifically, these formulations display a considerably reduced cardio- and testicular toxicity, as compared to a free drug.

[Fortification of antimicrobial barrier of the small intestine in newborn mice after oral administration of ascorbigen].

Ascorbigen, a natural product, is an indole derivative of L-ascorbic acid. Its effect on postnatal development and antibacterial resistance of the small intestine was studied on newborn mice. Ascorbigen was administered to 3-5-day old mice in a dose of 100 mg/kg orally every day for 7-10 days. 30 minutes before the last administration of the drug clinical isolates of Staphylococcus aureus or Escherichia coli were administered intragastrically to the young mice. The animals were killed in 24 hours and the frequency of the isolation of the microbes from the blood, spleen, kidneys and liver was developed. The oral use of the drug normalized the intestinal microflora, provided a reliable decrease of the bacteria isolation from the blood, spleen, kidneys and liver and prevented the animal death. The morphological examination showed that ascorbigen significantly increased the number and activity of the Paneth cells in the gland crypts, the goblet cells in the villi and mononuclear cells in the selfplate of the intestine mucous membrane vs. the intact control.

Potential mutagenicity, embryotoxicity, and teratogenicity of calcium ketopantoyl aminobutyrate.

We studied mutagenic, embryotoxic, and teratogenic properties of calcium ketopantoyl aminobutyrate, a preparation proposed as a new drug. Long-term oral administration of calcium ketopantoyl aminobutyrate produced no mutagenic, embryotoxic, and teratogenic effects.

Allergic and immunotoxic effects of calcium ketopantoyl aminobutyrate.

We studied the allergic and immunotoxic effects of a new promising medicinal preparation calcium ketopantoyl aminobutyrate. Calcium ketopantoyl aminobutyrate produced no negative effects on general mechanisms of humoral and cellular immunity. This preparation did not modulate the anaphylactic reaction to bovine serum, exhibited no mitostatic and lymphotoxic properties, had no effect on the delayed-type hypersensitivity response, and did not produce active cutaneous anaphylactic reaction.

[Comparative analysis of in vitro antifungal activity and in vivo acute toxicity of the nystatin analogue S44HP produced via genetic engineering].

New polyene macrolide S44HP was purified from the culture of recombinant Streptomyces noursei strain with engineered nystatin polyketide synthase. S44HP, nystatin (NYS), and amphotericin B (Amph-B) were tested against 19 clinical fungal isolates in agar diffusion assay, which demonstrated clear differences in antifungal activities of these antibiotics. Sodium deoxycholate suspensions of all three antibiotics were subjected to acute toxicity studies in vivo upon intravenous administration in mice. NYS exhibited the lowest acute toxicity in mice in these experiments, while both Amph-B and S44HP were shown to be 4 times more toxic as judged from the LD50 values. While the acute toxicity of S44HP was higher than that of Amph-B, the data analysis revealed a significantly increased LD10 to LD50 dose interval for S44HP compared to Amph-B. The data revealed structural features of polyene macrolides, which might have an impact on both the activity and toxicity profiles of these antibiotics. These results represent the first example of preclinical evaluation of an "engineered" polyene macrolide, and can be valuable for rational design of novel antifungal drugs with improved pharmacological properties.

Effect of a novel antineoplastic drug olipifat on antitumor immunity in mice.

Olipifat is an antineoplastic drug containing pyrophosphate and a product of special lignin processing. Donor C57Bl/6J mice with syngeneic B16 melanoma received a single 5-day course of olipifat. Effect of olipifat on antitumor resistance was evaluated by local neutralization test [3]. In animals with rapid melanoma growth, splenic cells from intact donors stimulated tumor growth. Olipifat abolished this growth-stimulating effect of splenocytes. In animals with slow melanoma growth, splenocytes had no effect on the growth of melanoma or Lewis lung cancer. In this case, splenocytes from olipifat-treated donors completely arrested the growth of melanoma B16 and decelerated the growth of Lewis lung carcinoma.

Histamine-correcting drug pherofunginum and bone tissue regeneration.

It has been shown that a histamine-correcting preparation (Pherofunginum) speeds up bone tissue regeneration. Other histamine correcting preparations behave in a similar way. We conclude that the application of these preparations in traumatology may have beneficial results.

[Prolonged psychoemotional stress as an inducer of mutations in mammals and as a modifier of mutagenesis]. / Dlitel'nyi psikhoémotsional'nyi stress kak induktor mutatsii u mlekopitaiushchikh i modifikator mutageneza.

The present study was made to determine the genotoxicity of psychoemotional stress (PES) alone and its possible influence on chemical mutagenesis under combined treatment. Stress was registered by the classical parameters: 1) weights of the thymus and adrenal; 2) stomach and duodenal mucosa conditions. The unscheduled DNA synthesis (UDS) measurement in peripheral blood lymphocytes with simultaneous determination of chromosomal aberrations (CA) and micronuclei (MN) levels in bone marrow cells were applied for estimation the mutagenic activity. The results indicated that PES alone, as CP, induced UDS in peripheral blood lymphocytes. Intensity of UDS was dependent on the stress duration. The UDS kinetics in the lymphocytes from stressed mice and stressed mice treated with CP were different. PES and CP induced the similar amounts of CA in bone marrow cells. Value of CA had a comparable tendency with results of UDS. The combined effect of PES and CP in both tests was different from additive one. The effects in NM test were statistically significant only in case of combined PES and CP action. The mutagenic potency of PES and its role in the modification of environmental mutagenesis will be discussed.

[The morphological changes in the organs of the lymphoid system in the experimental infection of mice with Trichinella spiralis]. / Morfologicheskie izmeneniia v organakh limfoidnoi sistemy pri éksperimental'nom zarazhenii myshei Trichinella spiralis.

The dynamics of morphological changes in central and peripheral organs of the lymphoid system of mice experimentally invaded with Trichinella spiralis was studied. The immune response of the host was shown to have two phases including two peaks and the suppression period. The activation of the lymphoid organs was observed in earlier intestinal and muscular phases, and the suppression was noted in migration phase of invasion.

[A morphometric study of the bone marrow of mice infected with Trichinella spiralis and T. pseudospiralis]. / Morfometricheskoe issledovanie kostnogo mozga myshei, zarazhennykh Trichinella spiralis i T. pseudospiralis.

The study of cytograms of the marrow of mice with experimental T. spiralis and T. pseudospiralis invasion of 1 to 60 days revealed the marked activation of granulocytes and lymphoid cell proliferation with the much lower response of erythroid cells. The maximal response occurred at 21-35 days of invasion with subsequent diminution. In mice experimentally invaded with T. pseudospiralis the response of the marrow was less pronounced, but the period of active cell proliferation was prolonged.

[The composition of the peripheral blood in white mice infected with Trichinella spiralis and Trichinella pseudospiralis]. / Sostav perifericheskoi krovi u belykh myshei, zarazhennykh Trichinella spiralis i Trichinella pseudospiralis.

The study of the peripheral blood response in mice with an experimental T. spiralis infection from the 1 to the 60 days of the latter showed leucocytosis, lymphomonocytosis and neutropenia maximal at the 21--35 days of the infection along with hyperthrombocytosis and ESR elevation, with the subsequent declination up to the end of the supervision. In experimental P. pseudospiralis infection lymphomonocytosis and ESR levels were comparatively lower but eosinophilia was significantly higher.