Where are we with pre-exposure prophylaxis use in Central and Eastern Europe? Data from the Euroguidelines in Central and Eastern Europe (ECEE) Network Group.

OBJECTIVES: Pre-exposure prophylaxis (PrEP) for HIV infection is an important intervention for control of the HIV epidemic. The incidence of HIV infection is increasing in the countries of Central and Eastern Europe (CEE). Therefore, we investigated the change in PrEP use in CEE over time. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was initiated in February 2016 to compare standards of care for HIV and viral hepatitis infections in CEE. Data on access to PrEP were collected from 23 countries through online surveys in May-June 2017 (76 respondents) and in November 2018-May 2019 (28 respondents). RESULTS: About 34.2% of respondents stated that tenofovir/emtricitabine (TDF/FTC) was licensed for use in their country in 2017, and 66.7% that it was licensed for use in 2018 (P = 0.02). PrEP was recommended in national guidelines in 39.5% of responses in 2017 and 40.7% in 2018 (P = 0.378). About 70.7% of respondents were aware of "informal" PrEP use in 2017, while 66.6% were aware of this in 2018 (P = 0.698). In 2018, there were 53 centres offering PreP (the highest numbers in Poland and Romania), whereas six countries had no centres offering PreP. The estimated number of HIV-negative people on PreP in the region was 4500 in 2018. Generic TDF/FTC costs (in Euros) ranged from €10 (Romania) to €256.92 (Slovakia), while brand TDF/FTC costs ranged from €60 (Albania) to €853 (Finland). CONCLUSIONS: Although the process of licensing TDF/FTC use for PrEP has improved, this is not yet reflected in the guidelines, nor has there been a reduction in the "informal" use of PrEP. PrEP remains a rarely used preventive method in CEE countries.

HIV care in times of the COVID-19 crisis - Where are we now in Central and Eastern Europe?

INTRODUCTION: The SARS-CoV-2 pandemic has hit the European region disproportionately. Many HIV clinics share staff and logistics with infectious disease facilities, which are now on the frontline in tackling COVID-19. Therefore, this study investigated the impact of the current pandemic situation on HIV care and continuity of antiretroviral treatment (ART) supplies in CEE countries. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was established in February 2016 to review standards of care for HIV in the region. The group consists of professionals actively involved in HIV care. On March 19, 2020 we decided to review the status of HIV care sustainability in the face of the emerging SARS-CoV-2 pandemic in Europe. For this purpose, we constructed an online survey consisting of 23 questions. Respondents were recruited from ECEE members in 22 countries, based on their involvement in HIV care, and contacted via email. RESULTS: In total, 19 countries responded: Albania, Armenia, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Greece, Hungary, Lithuania, Macedonia, Poland, Republic of Moldova, Russia, Serbia, Turkey, and Ukraine. Most of the respondents were infectious disease physicians directly involved in HIV care (17/19). No country reported HIV clinic closures. HIV clinics were operating normally in only six countries (31.6%). In 11 countries (57.9%) physicians were sharing HIV and COVID-19 care duties. None of the countries expected shortage of ART in the following 2 weeks; however, five physicians expressed uncertainty about the following 2 months. At the time of providing responses, ten countries (52.6%) had HIV-positive persons under quarantine. CONCLUSIONS: A shortage of resources is evident, with an impact on HIV care inevitable. We need to prepare to operate with minimal medical resources, with the aim of securing constant supplies of ART. Non-governmental organizations should re-evaluate their earlier objectives and support efforts to ensure continuity of ART delivery.

The burden and epidemiology of community-acquired central nervous system infections: a multinational study.

Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study.

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study.

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Evaluation of treatment outcomes for Stenotrophomonas maltophilia bacteraemia.

OBJECTIVE: The goal of this study was to retrospectively collect data about treatment outcomes in patients diagnosed with Stenotrophomonas maltophilia bacteraemia over a period of 20 years and evaluate these data with respect to the efficacy of treatment options. METHODS: The setting was a 700-bed tertiary care hospital in a large urban area. Hospital databases and medical records provided information about episodes of S. maltophilia, patient characteristics and treatment outcomes. Patients with at least one positive blood culture for S. maltophilia were included in the study. Data were analysed with respect to clinical improvement and mortality ≤30 days after the onset of infection. We compared patient characteristics, laboratory values and treatments by using the Chi-square or Fisher's exact tests and the Mann-Whitney test. RESULTS: We investigated 27 patients with S. maltophilia bacteraemia. The focus of infection was a central venous catheter in 18 (67 %) cases. The 30-day mortality rate was 11 %. All patients who were treated with an antibiotic that was effective in vitro against the pathogen recovered clinically and survived ≥30 days after the onset of infection. The most frequently used antibiotic was trimethoprim-sulfamethoxazole administered alone or in combination with a fluoroquinolone. CONCLUSIONS: Despite the fact that S. maltophilia is resistant to multiple antibiotics, the prognosis for patients with S. maltophilia bacteraemia is good when they are treated with antibiotics that are effective against this pathogen in vitro.

Intermittent pneumatic compression acts synergistically with manual lymphatic drainage in complex decongestive physiotherapy for breast cancer treatment-related lymphedema.

The application of intermittent pneumatic compression (IPC) as a part of complex decongestive physiotherapy (CDP) remains controversial. The aim of this study was to investigate whether the combination of IPC with manual lymph drainage (MLD) could improve CDP treatment outcomes in women with secondary lymphedema after breast cancer treatment. A randomized study was undertaken with 13 subjects receiving MLD (60 min) and 14 receiving MLD (30 min) plus IPC (30 min) followed by standardized components of CDP including multilayered compression bandaging, physical exercise, and skin care 10 times in a 2-week-period. Efficacy of treatment was evaluated by limb volume reduction and a subjective symptom questionnaire at end of the treatment, and one and two months after beginning treatment. The two groups had similar demographic and clinical characteristics. Mean reductions in limb volumes for each group at the end of therapy, and at one and two months were 7.93% and 3.06%, 9.02% and 2.9%, and 9.62% and 3.6%, respectively (p < 0.05 from baseline for each group and also between groups at each measurement). Although a significant decrease in the subjective symptom survey was found for both groups compared to baseline, no significant difference between the groups was found at any time point. The application of IPC with MLD provides a synergistic enhancement of the effect of CDP in arm volume reduction.

ATP-induced apoptosis of thymocytes is mediated by activation of P2 X 7 receptor and involves de novo ceramide synthesis and mitochondria.

Thymocytes were reported to undergo apoptosis in the presence of extracellular ATP through the activation of the purinergic receptors P2 X 1R, P2 X 7R or both. We investigated the identity of the P2 X R and the signaling pathways involved in ATP-mediated apoptosis. Apoptosis elicited by ATP was prevented by inhibition of P2 X 7R, or in thymocytes bearing a mutated P2 X 7R, and reproduced with a P2 X 7R agonist, but not with a P2 X 1R agonist. Stimulation of thymocytes with either ATP or a P2 X 7R agonist was found to stimulate a late de novo ceramide synthesis and mitochondrial alterations. Inhibition of either processes attenuated apoptosis. Interestingly, stimulation with either ATP or a P2 X 1R agonist induced an early ceramide accumulation and a weak caspases-3/7 activation that did not lead to apoptosis. In conclusion, de novo ceramide generation and mitochondrial alterations, both resulting from P2 X 7R activation, were implicated in ATP-induced thymocyte apoptosis.

The effect of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline on cell growth, cell cycle, induction of DNA fragmentation, and activity of caspase 3 in murine leukemia L1210 cells and fibroblast NIH-3T3 cells.

Quinazolines are multitarget agents, which have broad spectrum of biological activity, and some of them are now in cancer clinical testing. 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline is a new synthetically prepared derivative, which in our previous study showed cytotoxic effects on cancer cell lines HeLa and B16. Quinazoline, at micromolar concentrations, induced morphological changes and necrosis of B16 cells, and at nanomolar concentrations it produced changes of F-actin cytoskeleton. It did not cause changes in the cell cycle, did not induce apoptotic cell death in B16 cells, did not have a mutagenic effect, and did not even behave as a typical intercalating agent. Little significant reduction of tumor volume in intramuscular transplanted B16 cells was observed. The aim of the present study was to examine the cytotoxic effect of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline on murine leukemia L1210 cells and fibroblast NIH-3T3 cells. Induction of cell morphology and cell cycle changes, induction of apoptosis and caspase 3 activity were studied. Quinazoline acted cytotoxically on both cell lines. The sensitivity of leukemia L1210 cells to the quinazoline was higher than that of fibroblast NIH-3T3. The IC(100) was 12 microM for L1210 cells and 24 microM for NIH-3T3 cells. No effect of quinazoline on the cell cycle profile of L1210 and NIH-3T3 was detected, however, quinazoline induced an increase of the sub-G(0) cell fraction, apoptotic DNA fragmentation, and apoptotic morphological changes at a concentration of 12 microM. This quinazoline concentration induced caspase 3 activity. Our results demonstrated that induction of apoptotic cell death via activation of caspase 3 contributed to the cytotoxic effects of 3-(5-nitro-2-thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c]quinazoline in murine leukemia L1210 cells.

The effect of boromycin on the Ca2+ homeostasis.

A boron-containing antibiotic, boromycin (BM), was found to influence the Ca2+ homeostasis in both excitable and non-excitable cells. In non-excitable cells (human erythrocytes and leucocytes) it inhibited the resting passive 45Ca2+ transport in 10(-6)-10(-5) mol/L concentrations. In human erythrocytes, the passive 15Ca2+ transport induced by the presence of 1 mmol/L NaVO3 was inhibited by boromycin (90% inhibition) as well. The inhibitory effect of BM on the NaVO3-induced passive 45Ca2+ transport was diminished in the presence of inhibitory concentrations of nifedipine (10 micromol/L -60% inhibition) or of those of K+o (75 mmol/L -20% inhibition). On the other hand, in rat brain synaptosomes, and rat cardiomyocytes, BM stimulated the passive 45Ca2+ transport in 'resting' cells at similar concentrations. In rat cardiomyocytes the stimulation was transient. The stimulatory effect on the passive 45Ca2+ transport in rat brain synaptosomes was accompanied with the increase of cytoplasmic Ca2+ concentration measured by means of the entrapped fluorescent Ca2+ chelator fura-2. The stimulatory effect of BM was diminished when synaptosomes were pre-treated with veratridine (10 micromol/L) which itself stimulated the passive 45Ca2+ transport. At saturating concentrations of veratridine, no stimulatory effect of BM was observed. These results could be explained by the indirect interaction of BM with both Ca2+ and Na+ transport systems via transmembrane ionic gradients of monovalent cations and could be useful in determining whether the cells belong to excitable, or non-excitable cells.

Investigation of properties of the Ca2+ influx and of the Ca2+-activated K+ efflux (Gárdos effect) in vanadate-treated and ATP-depleted human red blood cells.

In this study the properties of the 45Ca2+ influx in human red blood cells (RBC) induced by NaVO3 or ATP-depletion were compared. Both NaVO3-induced and ATP-depletion-induced 45Ca2+ influxes were in the range 10(-6)-10(-5) mol Ca2+ x l(-1)cells x h(-1). The saturatability of ATP-depletion-induced 45Ca2+ influx with Ca2+ was much less pronounced than that of NaVO3-induced 45Ca2+ influx. The NaVO3-induced Ca2+ influx was sensitive to nifedipine (IC50 = 50 micromol/l) and Cu2+ (IC50 = 9 micromol/l) but these inhibitors had only a marginal effect when ATP-depletion was used as the Ca2+ influx inducer. On the other hand, polymyxin B (PXB) (1-5 mg/ml) strongly stimulated the ATP-depletion-induced 45Ca2+ influx whereas its effect on the NaVO3-induced Ca2+ influx was biphasic, with about 10% stimulation at lower PXB concentrations and an inhibition of 40% at higher concentrations. SDS-PAGE revealed that both NaVO3 and PXB induced changes in the protein phosphorylation pattern in the presence of Ca2+. NaVO3 stimulated the phosphorylation of several proteins and this effect was counteracted by PXB. The comparison of the kinetics and temperature dependencies of the Gárdos effect induced by NaVO3 and the ATP-depletion showed marked differences. The ability of NaVO3 to induce the Gárdos effect dramatically increased in ATP-depleted cells. These findings indicate that the 45Ca2+ influxes preceding the activation of the Ca2+-activated K+ efflux (Gárdos effect) stimulated by NaVO3 and by ATP-depletion, are mediated by different transport pathways. In addition, obtained results demonstrate that ATP-depletion and NaVO3-treatment exert additive action in triggering the Gárdos effect.

[Unusual manifestations of Bartonella infections]. / Bartonella-infekciók szokatlan megjelenési formái.

The authors review the cases of two patients with an atypical form of cat scratch disease. The first case exhibited ileocoecal and hepatoportal lymphadenitis, and the second case the emerging symptoms of a non-specific granulomatous process in the middle third of the right forearm, which caused a differential-diagnostic problem. Establishment of a diagnosis was possible only on the basis of the disease process and the pathological, serological and histopathological pictures of the lymphatic glands after other causes of the lymphadenopathy had been excluded. Following two weeks of antibiotic treatment, the patients were free of complaints- and symptoms. Bartonella antibody tests were performed on 5 cats living in the neighbourhood of the patients with titer determinations too in 3 cases.

The effect of azalomycin F on Ca2+ homeostasis in Trichoderma viride and Saccharomyces cerevisiae.

Azalomycin F (AMF), a macrocyclic lactone antibiotic, in concentrations of 10(-5) g/ml (10(-6) - 10(-5) mol/l) was found to stimulate both the 45Ca2+ influx and efflux in intact Trichoderma viride submerged mycelium and in cells of Saccharomyces cerevisiae without having Ca2+ ionophoric properties. AMF also inhibited ATP-dependent Ca2+ uptake in membrane fractions prepared from T. viride submerged mycelium. 45Ca2+ which had been accumulated in membrane fractions in an ATP-dependent manner was released upon addition of AMF. This release was observed in light organellar fractions (LOF) of S. cerevisiae and of T. viride submerged mycelium and, to a small extent, in heavy organellar fraction (HOF) of S. cerevisiae. No Ca2+ releasing effect of AMF was observed in HOF from T. viride submerged mycelium. In S. cerevisiae expressing Ca2+-dependent photoprotein aequorin, AMF induced transients of luminescence which reflect changes in the cytoplasmic Ca2+ concentration. The results suggest that the stimulation by AMF of the Ca2+ efflux from the mycelium (cells) could be explained by an increase of the cytoplasmic Ca2+ concentration due to the release of Ca2+ from microsomal membranes or to the stimulation of Ca2+ influx.

Serological evidence of adenovirus infection in cats.

The widespread presence of adenoviruses in various species makes it probable that infection and the carrier state also exist in cats. On the basis of these considerations, investigations were carried out to find antibodies against adenovirus in sera from different cat populations kept under different conditions. For the antibody detection, purified adenovirus was used in an indirect ELISA. To produce positive serum, SPF cats were immunized with a purified hexon preparation. Altogether 632 field sera of different origin were tested. Among field samples, adenovirus seropositivity varied between 10-26%.

Properties of uracil transport by vegetative mycelium of Trichoderma viride.

The transport of radioactively labelled uracil into submerged mycelium of T. viride was measured by means of a membrane filtration technique. It was found to be time-dependent (up to 90 min) and concentration-dependent (up to 8 mmol l-1). Its concentration dependence was biphasic and consisted from the saturatable part (at the uracil concentration below 0.2 mmol l-1) with KM = 0.08 +/- 0.02 mmol l-1 and Vmax = 1.74 +/- 0.3 nmol (mg dry wt.)-1 h-1, and from the region at higher uracil concentration which showed only a weak saturatability with the substrate. The transport measured in the saturatable part of the curve was also pH- and temperature-dependent. The optimal pH was between 5.4 and 6.4 and the optimal temperature was at 37 degrees C. The activation energy of 54 kJ mol-1 and the temperature quotient of Q10 = 2.1 could be calculated from the temperature dependence. The entry of uracil was in part inhibited by nucleobases and their analogues, nucleosides, nucleotides and amino acids. The inhibitors had similar inhibitory efficiency about 50% at 0.2 mmol l-1. 3,3',4',5-tetrachlorosalicylanilide (TCS), the uncoupling agent, significantly inhibited the uracil transport, but its inhibitory efficiency decreased upon increasing the uracil concentration. Ionophore antibiotics valinomycin and monensin also inhibited the uracil transport. Inhibitors of RNA-polymerase, rifamycin and rifampicin were without effect. The results suggest that at low uracil concentrations (below 0.2 mmol l-1), its transport is mediated by a carrier and is driven by the electrochemical potential of protons. At higher uracil concentrations, the transport may be driven by the concentration difference of uracil with the contribution of the protonmotive force. It is feasible that inhibitors of uracil transport tested exert their inhibition by the dissipation of the driving force rather than by the direct competition with the substrate-binding site.

Detection of adenovirus hexon sequence in a cat by polymerase chain reaction (short communication).

Adenoviral nucleic acid was detected by polymerase chain reaction (PCR) in pharyngeal and rectal swab samples of a cat seropositive for adenovirus and suffering from transient hepatic failure. The samples were taken at a one-year interval, and both faecal samples as well as the second pharyngeal sample were positive in PCR performed with general adenovirus primers. The size of the amplified products corresponded to that of the positive control. The identity of the amplicons was also confirmed by DNA sequencing. The 301 bp long hexon gene fragment was very similar to but distinguishable from the corresponding hexon sequence of human adenovirus type 2. This result suggests the possibility of persistent carrier status and shedding of adenovirus in cats.

[Determination of 23 elements in lady's thistle (Silybum marianum L. Gaertner)]. / A máriatövis (Silybum marianum L. Gaertner) elemtartami vizsgálatai.

23 elements (Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Li, Mg, Mn, Mo, Na, P, Pb, S, Ti, V, Zn) were measured in lady's thistle (Silybum marianum L.) herba and fructus by ICP-AES technique after digestion in teflon vessels. This is the first report about the content of these elements in the plant originated from Hungary. This measurements is important in view of plant physiology and pharmacology. Significant amounts of aluminium and iron were measured in lady's thistle herba. In the course of tea making, the relative concentration of some elements decreases because of the poor solubility of the compounds of these elements. The low concentration of these elements in teas in favourable in pharmacological aspect. No significant differences were found in boron, calcium, potassium and magnesium concentrations of lady's thistle fructus samples of different origin.

[Local treatment of rheumatic diseases with propolis compounds]. / Mozgásszervi betegségek helyi kezelése propolisz készítményekkel.

The authors conducted a single blind, placebo controlled local therapy trial on a total of 190 patients involving the use of materials (i) topically and (ii) by iontophoresis for pain and/or inflammation of the organs of movement. The materials used comprised of the following: (i) purified propolis and propolis saturated with antiinflammatory trace metal elements and (ii) propolis saturated with trace metal elements and poplar bud ointment saturated with trace metal elements also. Both methods of application using all the three preparations significantly improved symptoms. The preparations saturated with metallic ions were more effective. The mild effect of the placebo treatment is explained by the treatment procedure itself. Side effects were not observed.

[Cytochrome P-450: structure, function, induction and practical significance]. / Citokróm P-450 enzimek: szerkezet, aktivitás, indukció és gyakorlati jelentöségek.

The liver contains a series of microsomal hemoproteins, called cytochromes P-450 which are mixed-function oxygenases involved in the metabolic oxygenation of diverse xenobiotic chemicals (drugs, pesticides, etc.). This enzyme system converts lipophilic foreign compounds into more water soluble products, thereby facilitating their elimination from the body. In general, cytochrome P-450-catalyzed oxidation results in detoxification, however the cytochromes P-450 can also convert certain xenobiotics to more toxic or carcinogenic products. Many of the individual isoenzyme forms of cytochrome P-450 are inducible by a wide variety of chemicals. After induction the concentration of total cytochrome P-450 in liver microsomes and the activity of different cytochrome P-450 forms increase. Elevated levels of cytochrome P-450 are the result of multiple mechanisms. Increased transcription of P-450 genes is a major mechanism of cytochrome P-450 induction. Higher levels of specific mRNAs are detectable soon after treatment with either "phenobarbital-like" or polycyclic aromatic compounds. Although increased transcription plays some role in the induction of cytochromes P-450 by other inducers like pregnenolone-16 alpha-carbonitrile (PCN)/glucocorticoids and "ethanol-type" compounds, post-transcriptional events are also very important. Cytochrome P-450 induction can be achieved by message stabilization and enhanced transport of mRNA from the nucleus to the cytoplasm that also increase the specific mRNA levels at the site of protein synthesis. Elevated cytochrome P-450 levels may also result from protein stabilization. Stabilization of cytochrome P-450 protein and/or mRNA are the main processes of induction by PCN/glucocorticoids and ethanol-type inducers. Although these mechanisms exist, they do not seem to be important in the induction by "phenobarbital-like" and "3-methylcholanthrene-like" inducers. The fact that induction is produced by a large variety of xenobiotics and is mediated by multiple mechanisms suggests that cytochrome P-450 system can provide increased protection for organisms in potentially hostile chemical environment. Since cytochrome P-450 induction is a characteristic response to chemicals for various living organisms ranging from microorganisms to man, it seems to be an adaptive mechanism for organisms to increase the chance for survival.