'Bottom-up' effects in a tritrophic plant-aphid-parasitoid system: Why being the perfect host can have its disadvantages.

In this study the host plant genotype effect on cabbage aphid, Brevicoryne brassicae (L.)(Hemiptera: Aphididae) preference and performance, the effect of aphid genotype on parasitoids performance, as well as the indirect effects of plant genotypes on aphid parasitoid performance, were tested using different population samples of the aphid and its primary endoparasitoid wasp, Diaeretiella rapae (M'Intosh) (Hymenoptera: Braconidae). Experiments were run as fully-factorial randomized block design in a greenhouse. Accordingly, host plant cultivar had significant effects on the total number of aphids and aphid-load whilst the fitness of the aphid genotypes were also influenced by plant cultivar. The effect of parasitism on cabbage aphids was significantly different between plant cultivars. Overall, the results revealed that cabbage aphid is under different selective pressures arising from both higher (parasitoid) and lower (host plant cultivar) trophic levels. The host plant cultivar had a significant effect on both aphid fitness and parasitism rate on particular aphid genotypes. This indicates that host-plant-adapted aphid species can create much context-dependency in the nature and strength of 'fitness benefits parasitism', which may in turn alter the costs and benefits of host specialization.

Characterization of the thrombin generation profile in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.

[Interrelationship between polymorphic markers of methylenetetrahydrofolate reductase gene and development of acute disturbance of brain circulation in families of patients with atrial fibrillation].

In the present work we for the first time on the clinic-genetic material revealed genetic predictors of development of acute disturbance of brain circulation (ADBC) in families of patients with atrial fibrillation (AF) namely polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Genotype CC was significantly more often found among patients with AF and ADBC compared with controls (58.1 and 35.2%, respectively, p=0.02) as well as in relatives of probands compared with the control group (59.3 and 35.2%, respectively, p=0.008). With this in relatives with revealed paroxysmal AF and ADBC we also noted presence of CC genotype. Taking into consideration the relationship obtained between polymorphysms of MTHFR gene and AF it was possible to assume that polymorphic marker CC appeared to be a predictor of ADBC in these families.

Predation drives stable coexistence ratios between red and green pea aphid morphs.

We conducted field surveys and experiments to evaluate the hypothesis that predation is an important driving factor determining the degree of coexistence between red and green morphs of the pea aphid Acyrthosiphon pisum. Theory suggests that the different colour morphs are differentially susceptible to natural enemies and selection by predation which in turn leads to variable relative abundances of red and green morphs among host plants across landscapes. Our field surveys on pea and alfalfa revealed, however, that the colour morphs tended to coexist closely in a ratio of one red to three green aphids across fields with different host plant monocultures. Experimentation involving manipulation of the relative abundances of the two colour morphs on host plants pea and alfalfa with and without predator presence revealed that red morphs had higher or same fitness (per capita reproduction) than green morphs on both pea and alfalfa only when in the proportion of one red/three green proportion. Moreover, experimentation evaluating predator efficiency revealed that red morphs are safest from predation when in a 1 : 3 ratio with green morphs. These results suggest that in addition to predation selection effects, red morphs may behaviourally choose to associate with green morphs in a narrow 1 : 3 ratio to maximize their fitness. This evidence, along with existing published data on red and green morph anti-predator behaviour indicates that a 1 : 3 red and green morph coexistence ratio is driven by a balance between predation pressure and behavioural assorting by red morphs across landscapes. In this way predators may have ecological-evolutionary consequences for traits that affect the colour morphs' proportion and tolerances to selective pressure.

Secondary MGUS after autologous hematopoietic progenitor cell transplantation in plasma cell myeloma: a matter of undetermined significance.

Plasma cell myeloma, characterized by clonally aberrant plasma cells that produce abnormal monoclonal Igs, is the most common indication for autologous hematopoietic progenitor cell transplantation (AHPCT) in North America. We observed appearance of new monoclonal gammopathies different from the original protein in the post-AHPCT setting and termed this condition 'secondary MGUS' (monoclonal gammopathy of undetermined significance). Hence, we performed a retrospective, single institution review of serum protein electrophoresis/immunofixation electrophoresis data in 92 AHPCT recipients from the period 2000-2009. In all, 22 of 92 patients (24%) undergoing AHPCT met criteria for secondary MGUS. Contrary to previous studies, often referred to as 'abnormal protein banding,' we did not observe this condition as a favorable prognostic indicator in affected patients when compared with the control group (P=0.686). However, we did note that a subgroup of the study cohort who developed secondary MGUS after a prolonged latency (>10 months) had an improved median OS compared with the remainder of the study cohort (75 months vs 41 months, P=0.005). As there have been significant advancements in understanding the pathobiology and clinical significance of MGUS, we believe that secondary MGUS merits dedication of resources for investigation to determine its true clinical relevance, prognostic value and pathophysiology.

Effects of chitin and contact insecticide complexes on rove beetles in commercial orchards.

A five-year research project was performed to explore the potential effects of contact insecticide applications on the change of abundance and species richness of predatory rove beetles (Coleoptera: Staphylinidae) in conventionally managed orchards. Twelve blocks of nine orchards were used for this study in Central Europe. High sensitivity atomic force microscopic examination was carried out for chitin structure analyses as well as computer simulation for steric energy calculation between insecticides and chitin. The species richness of rove beetles in orchards was relatively high after insecticide application. Comparing the mean abundance before and after insecticide application, a higher value was observed before spraying with alphacypermethrin and lambda-cyhalothrin, and a lower value was observed in the cases of diflubenzuron, malathion, lufenuron, and phosalone. The species richness was higher only before chlorpyrifos-methyl application. There was a negative correlation between abundance and stability value of chitin-insecticides, persistence time, and soil absorption coefficients. Positive correlation was observed with lipo- and water solubility.

A spatially explicit model for tropical tree diversity patterns.

A simple two-parameter model resembling the classical voter model is introduced to describe macroecological properties of tropical tree communities. The parameters of the model characterize the speciation- and global-dispersion rates. Monte Carlo type computer simulations are performed on the model, investigating species abundances and the spatial distribution of individuals and species. Simulation results are critically compared with the experimental data obtained from a tree census on a 50 hectare area of the Barro Colorado Island (BCI), Panama. Fitting to only two observable quantities from the BCI data (total species number and the slope of the log-log species-area curve at the maximal area), it is possible to reproduce the full species-area curve, the relative species abundance distribution, and a more realistic spatial distribution of species.

Follow-up of the development of femoral degeneration lesions in broilers / Seguimiento del desarrollo de lesiones por degeneración en pollos de engorde

A study was carried out in the experimental facilities of FMVZ/UNESP-Botucatu, with the aim of following-up the development and the incidence of femoral degeneration (FD). A total of 305 one-day-old male broilers were housed in six pens of 5m² each. Histological analyses of femur head collected when broilers were 0, 7, 14, 21, 28, 35, and 42 days of age were carried out. At 42 days of age, 30 birds were taken to the experimental processing plant of FMVZ for leg gross examination. Ten legs per FD score where selected, and histologically analyzed to determine the most probable age at the beginning of the lesions, and to standardize femoral degeneration lesion scores. The histological results showed that cell architecture started to disorganize at 21 days of age in the resting and proliferation zones, and that angiogenesis increased, invading the joint cartilage, The gross lesion indexes due to femoral degeneration were 22.5 percent, 42.5%, and 65% at 28, 35, and 42 days of age, respectively.

Se realizó un estudio en las instalaciones experimentales de FMVZ/UNESP-Botucatu, con el objetivo de seguir el desarrollo y la incidencia de degeneración femoral (DF) en pollos. Se utilizaron 305 polluelos de un día, machos, distribuidos en seis corrales de 5m² cada uno. Se analizaron cortes histológicos de cabezas de fémur recolectadas a los 0, 7, 14, 21, 28, 35 y 42 días de edad. A los 40 días de edad, se llevaron 30 aves al Matadero Experimental de FMVZ, para análisis macroscópico de las piernas. Se escogieron 10 muslos por escore de DF, y se analizaron histológicamente para determinar la edad más probable del inicio de la lesión y estandarizar los escores de lesión por degeneración femoral. Los resultados histológicos indicaron que a los 21 días ocurre el inicio de la desorganización celular en la zona de reposo y de proliferación, además del aumento de la angiogénesis, invadiendo el cartílago articular. Microscópicamente, el índice de lesión por degeneración femoral fue del 22.5 por ciento, 42.5% y 65% a los 28, 35 y 42 días de edad, respectivamente.

Femur mineral density of broilers with femoral degeneration fed high nutritional density diets / Densidad mineral del fémur de pollos de engorde con degeneración femoral alimentados con dietas de alta densidad nutricional

A study was carried out in the experimental facilities of FMVZ/UNESP-Botucatu, with the aim of following-up the development and the incidence of femoral degeneration (FD). A total of 305 one-day-old male broilers were housed in six pens of 5m² each. A completely randomized experimental design, with 3 treatments (T1traditional nutritional density diet; T2high nutritional density diet) of 3 replicates each was applied. Femoral head of the broilers were submitted to gross examination at 0, 7, 14, 21, 28, 35, and 42 days of aged. At 42 days of age, 60 birds (30 per treatment) were submitted to the Veterinary Hospital of FMVZ to determine bone mineral density by radiography. Birds were then sacrificed for gross examination of the legs, and FD scoring. Five legs per treatment within each FD score were submitted to computed tomography for femur head integrity and bone mineral density. Treatments did not influence FD incidence, and the first gross FD lesions appeared when birds were 28 days old. It was concluded that radiographic optical densitometry and computed tomography are efficient methods to evaluate femoral degeneration, and both techniques expressed the same profile. In addition, using radiographic optical densitometry and computed tomography, these results also allowed us to establish bone mineral density value ranges within each gross FD score. These finding may provide an excellent non-invasive tool to describe femoral degeneration.

Se realizó un estudio en las instalaciones experimentales de FMVZ/UNESP-Botucatu, con el objetivo de seguir el desarrollo y la incidencia de degeneración femoral en pollos. Se utilizaron 305 polluelos de un día, machos, distribuidos en seis corrales de 5m² cada uno. Se adoptó un delineamiento experimental totalmente al azar, con dos tratamientos de 3 repeticiones cada uno. Se alimentaron las aves del T1 con dietas con densidad nutricional convencional, mientras el T2 consistió de una dieta con alta densidad nutricional. Se realizaron análisis macroscópicos de la cabeza del fémur de aves de 0, 7, 14, 21, 28, 35 y 42 días de edad. A los 42 días de edad, se llevaron 60 aves (30 por tratamiento) al Hospital Veterinario de FMVZ, para hacer radiografías para el análisis de la densidad mineral ósea. Posteriormente, se sacrificaron los pollos para el análisis macroscópico de las piernas y se atribuyeron puntajes para DF. Se seleccionaron cinco muslos por tratamiento dentro de cada puntaje de DF, que fueron sometidas a tomografía para evaluación de la integridad y de la densidad ósea de la cabeza del fémur. Los tratamientos no tuvieron influencia en la incidencia de DF, y a partir de los 28 días de vida, las aves presentaron lesiones macroscópicas. Se estableció que la densitometría ósea y la tomografía son métodos eficaces para evaluar la DF, además que ambos expresan el mismo perfil. Por otra parte, se encontraron intervalos de valores para densidad mineral ósea obtenida por densitometría óptica radiográfica y por tomografía en función de los puntajes macroscópicos de DF. Esos hallazgos son una importante herramienta no invasiva para la caracterización de degeneración femoral.

Dominance, activity density and prey preferences of rove beetles ( Coleoptera: Staphylinidae) in conventionally treated Hungarian agro-ecosystems.

Field experiments were conducted to investigate the mechanism underlying patterns of the rove beetle populations in apple and pear orchards (1998-2002) and winter wheat (2006-2007) in Hungary following treatment with broad-spectrum insecticide. The capacity of predatory staphylinid species to feed on cereal pests was measured, with six species tested in petri dishes, in the laboratory at room temperature. Almost 23% of the Hungarian and 13% of the European staphylinid fauna are represented in the investigated agro-ecosystems. In orchards, 5236 individuals, belonging to 253 species, were collected. The most widely occurring were Omalium caesum Gravenhorst, Drusilla canaliculata (F.), Dinaraea angustula (Gyllenhal), Palporus nitidulus (F.), Xantholinus. longiventris (Olivier), X. linearis (Olivier) and Aleochara bipustulata (L.). In winter wheat, 798 individuals and 20 species were collected, the most frequent were Staphylinus caesareus Cederh, Tachyporus hypnorum (F.), Philonthus cognatus (Stephens), Aloconota gregaria (Erichson), Tachyporus chrysomelinus (L.) and T. obtusus (L.). Species composition differed by crop (apple, pear and wheat), soil composition and surrounding habitat. Species diversity was also influenced by these parameters. In wheat, one acute change in species composition was observed with the decline of Tachyporus spp., which occurred equally across all farms. The consumption rate of prey by the dominant species occurring in wheat ecosystems was relatively high; however, we did not offer any fungal food to compare with insects' prey.

Polymorphism in the IL-8 gene, but not in the TLR4 gene, increases the severity of acute pancreatitis.

BACKGROUND/AIM: Activated granulocytes and inflammatory mediators of the innate immune response play fundamental roles in the pathogenesis of acute pancreatitis. We studied whether polymorphisms of interleukin-8 (IL-8) and Toll-like receptor 4 (TLR4) genes correlate with the severity of acute pancreatitis. METHODS: Patients with acute pancreatitis (n = 92) were grouped according to the severity of the disease on the basis of the Ranson scores. Healthy blood donors (n = 200) served as controls. The IL-8 -251 gene polymorphism was analyzed by amplification-refractory mutation system; the single-nucleotide polymorphisms (Asp299Gly and Thr399Ile) of TLR4 were investigated by using a real-time polymerase chain reaction method with melting point analysis. RESULTS: The IL-8 A/T heterozygote mutant variants were detected with a significantly higher frequency among the patients with severe pancreatitis than among the healthy blood donors (60 vs. 42%; p = 0.0264, odds ratio = 2.071, 95% confidence interval = 1.101-3.896), while the frequency of the normal allelic genotype (TT) was higher among the patients with mild pancreatitis than in the group with severe pancreatitis (35 vs. 16%; p = 0.051, odds ratio = 2.917, 95% confidence interval = 1.089-7.811). There was no significant correlation between TLR4 polymorphisms and the acute pancreatitis itself, but nonsignificantly increased frequencies of Asp299Gly and Thr399Ile heterozygotes among patients with severe infected pancreatic necrosis could be observed relative to the patients with mild pancreatitis. CONCLUSIONS: Determination of the frequency of IL-8 polymorphism in acute pancreatitis may be informative and may provide further evidence concerning the role of IL-8 in the severe form of this disease. The possible role of TLR4 polymorphism in the outcome of severe acute pancreatitis requires further investigations in a larger series of patients.

Genetic polymorphisms in patients with myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a family of clonal disorders characterized by dyshematopoiesis and susceptibility to acute myelogenous leukemia. Tumor necrosis factor-a (TNF-alpha) and transforming growth factor-beta (TGF-beta) are cytokines that play key roles in the pathogenesis of MDS. There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta protein, and in the -308 promoter region of TNF-alpha. The association between TNF-alpha and TGF-beta1 gene polymorphism and the susceptibility to MDS and the progression of the disease was investigated. As compared with healthy control subjects (n = 74), patients with MDS (n = 55) showed no significant deviations in genotype or allele frequencies of TNF-alpha. Similarly, there were no differences in the distribution of TNF-alpha genotypes between the MDS patients with only anemia (mild group) and those with bi- or pancytopenia (severe group). On the other hand the TT homozygosity at codon 10 in exon 1 of TGF-beta1 gene was associated with a severe degree of cytopenia [95% CI OR = 4.889, p = 0.0071]. These findings suggest that the investigated genetic polymorphisms do not predispose to the development of MDS, but that TGF-beta1 gene polymorphism may affect the disease progression.

Tumour necrosis factor-alpha and heat-shock protein 70-2 gene polymorphisms in a family with rheumatoid arthritis.

OBJECTIVES: The aim of this work was to investigate the prevalence of TNF-alpha-308 polymorphism among the 29 members of a family with RA and the association between the MHC-linked biallelic HSP70-2 gene and the TNF-alpha polymorphism. Five of the members with RA were diagnosed by using the revised 1987 ACR criteria, and 1 member suffered from SLE. METHODS: The variations in the TNF-alpha and the HSP70-2 genotypes were analyzed by PCR-RFLP, using NcoI and PstI restriction enzymes. RESULTS: Two of the 29 members were homozygotes for allele A, 18 were heterozygotes (TNF A/G) and 9 of them were homozygotes for allele G. Nineteen of the 29 were heterozygotes for HSP70-2 (A/G), 10 of them were homozygotes for the G allele, and none were homozygotes for allele A. Four of the 5 the RA patients carried the A allele for TNF-alpha all 5 were heterozygotes for HSP70-2 genotypes. CONCLUSION: The carriage of the A allele for TNF-alpha of -308 SNP in 4 of the 5 RA patients, and the high prevalence (68.0%) of TNF A allele carriers in this family confirms the important role of this candidate gene in the pathomechanism of RA, and might be of prognostic value for future clinical observations. Further, to test for association a much larger set of genetically independent patients and controls is needed.

[Herpes simplex virus and malignancies of female genital organs]. / Herpes simpleks virus i malignomi genitalnih organa zena.

INTRODUCTION: Primary herpes simplex virus (HSV) infections of female genital tract usually end with remission, while the virus remains in the organism--almost in the sacral ganglion in a latent form, protected from humoral and cellular immunity. Stress induces the virus and the result is recurrent genital infection. Frequent exacerbations damage some parts of vital cellular structures without cytolysis, but stimulate malignant transformations. MATERIAL AND METHODS: Vulvar (portio vaginalis uteri) and endometrial tumor tissue samples were analyzed for HSV by direct and indirect fluorescent antibody technique (FAT). Pre and postoperative sera samples were analyzed for presence of anti-HSV antibodies--IgM and IgG by Elisa-Enzygnost method. Acellular filtrates obtained by ultrasonic destruction of malignant tissues were used as inoculum for rabbit corneal scarification. RESULTS AND DISCUSSION: Out of 63 tissue samples, 42 were positive for HSV antigen i.e. 67.3%. According to location 50% of vulvar, 76% PVU and 65% of endometrial tissues were positive. This antigen induces production of virus specific antibodies. Two types of antigens are known: the so-called T-antigen persisting in the cell nucleus and cell-surface antigen--product of the viral genome and can be evidenced by immunofluorescence method. Anti HSV antibodies were present in 63 preoperative serum samples and belonged to IgG group, but not one to IgM, implying a long and chronic course of infection excluding acute primary. Out of 38 postoperative serums the titer of antibodies decreased in 36 evidently, but in two samples remained unchanged. Two samples of endometrial and one from PVU origin contained HSV antigen type one. In the remaining 16 samples HSV 2 antigen was present. Rabbit corneal scarification was the proof of complete infectious virus in malignant tissues. Acellular filtrate of malignant tissues served as inoculum. Corneas of examined rabbits showed a mild inflammation after 24 hours which disappeared in the next 24 hours. We could not isolate the infectious virus by rabbit corneal scarification. Instead of herpetic changes, mild inflammation was evident. This abortive, incomplete symptomatology was probably caused by nonstructural early protein, which is a product of viral genome incorporated in malignant cells. CONCLUSION: On the basis of our results, we can conclude that HSV can have, beside other factors, a very important, maybe an initial role in development of malignant changes of female genital tract, not only on vulva and PVU, but on endometrium as well. HSV I can cause genital infections and have some role in malignant changes as well as HSV 2. However, complete infective virion couldn't be isolated from malignant tissues.

The microtubule-stabilizing agents epothilones A and B and their desoxy-derivatives induce mitotic arrest and apoptosis in human prostate cancer cells.

Epothilones are a new class of natural products that bind to tubulin and prevent the depolymerization of microtubules, although they have no structural similarity to paclitaxel. Taxanes are only marginally effective in the treatment of disseminated prostate cancer, although they may have useful activity when administered in combination with estramustine. Unlike paclitaxel, epothilones are not substrates for P-glycoprotein and are active in multidrug resistant cells. Epothilones A and B (EA, EB) have recently been synthesized in toto. In this report, we examine the effects of synthetic epothilones and their desoxy derivatives, as well as paclitaxel, on prostate cancer cell lines. EB was the most active of these compounds in tissue culture (IC(50): 50-75 pM), four to ten-fold more potent than paclitaxel. EA and the desoxyderivatives of EA and EB (dEA, dEB) were also active, but less potent than EB. Each of these compounds causes mitotic block followed by apoptotic cell death. The relative potencies for cell cycle arrest and cytotoxicity directly correlate with the ability of the drugs to bind microtubules, stabilize mitotic spindles and induce the formation of interphase microtubule bundles. Therefore, synthetic epothilones are potent inhibitors of prostate cancer cell lines and work in a fashion similar to paclitaxel. Recently, we showed that farnesyl transferase inhibitors sensitize tumor cells to paclitaxel-induced mitotic arrest. We now have extended these observations to show that paclitaxel and the epothilones synergize with FTI to arrest the growth of prostate cancer cells. Moreover, this occurs in DU145, a cell line that is not particularly sensitive to the FTI. The combination of FTI and epothilone represent a new potential clinical strategy for the treatment of advanced prostatic cancer.

Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel.

The epothilones are naturally occurring, cytotoxic macrolides that function through a paclitaxel (Taxol)-like mechanism. Although structurally dissimilar, both classes of molecules lead to the arrest of cell division and eventual cell death by stabilizing cellular microtubule assemblies. The epothilones differ in their ability to retain activity against multidrug-resistant (MDR) cell lines and tumors where paclitaxel fails. In the current account, we focus on the relationship between epothilone and paclitaxel in the context of tumors with multiple drug resistance. The epothilone analogue Z-12,13-desoxyepothilone B (dEpoB) is >35,000-fold more potent than paclitaxel in inhibiting cell growth in the MDR DC-3F/ADX cell line. Various formulations, routes, and schedules of i.v. administration of dEpoB have been tested in nude mice. Slow infusion with a Cremophor-ethanol vehicle proved to be the most beneficial in increasing efficacy and decreasing toxicity. Although dEpoB performed similarly to paclitaxel in sensitive tumors xenografts (MX-1 human mammary and HT-29 colon tumor), its effects were clearly superior against MDR tumors. When dEpoB was administered to nude mice bearing our MDR human lymphoblastic T cell leukemia (CCRF-CEM/paclitaxel), dEpoB demonstrated a full curative effect. For human mammary adenocarcinoma MCF-7/Adr cells refractory to paclitaxel, dEpoB reduced the established tumors, markedly suppressed tumor growth, and surpassed other commonly used chemotherapy drugs such as adriamycin, vinblastine, and etoposide in beneficial effects.

[Combined use of left atrial transesophageal pacing and cordarone in atrial flutter]. / Sochetannoe primenenie chrezpishchevodnoi stimuliatsii levogo predserdiia i kordarona pri lechenii trepetaniia preserdii.

AIM: To investigate the effectiveness of superfrequent transesophageal left atrial stimulation (TLAS) and its combination with cordarone in management of atrial flutter (AF). MATERIALS AND METHODS: 650 patients with paroxysmal AF underwent TLAS. The paroxysm duration varied from 1 hour to 1 month. In 312 patients TLAS was performed prior to treatment with antiarrhythmic drugs (group 1), in 338 patients--after intravenous administration of cordarone (group 2). RESULTS: Superfrequent TLAS has restored sinus rhythm (SR) in 85(27.2%) and 169(50%) patients of groups 1 and 2, respectively (p < 0.001). TLAS promoted conversion of AF in atrial fibrillation (AFi) in 185(59.3%) and 159(47.1%) patients of groups 1 and 2, respectively (p < 0.01). Moreover, SR recovered 24-48 hours after TLAS in 87(27.9%) and 64(18.9%) patients of groups 1 and 2 respectively (p < 0.01). Sinus rhythm recovered in a total of 172(55.1%) and 233(69.0%) patients, AF was converted to AFi in a total of 88(31.4%) and 95(28.1%) patients (p > 0.05) of groups 1 and 2, respectively. TLAS was uneffective in 42(13.5%) and 10(2.9%) patients of groups 1 and 2, respectively. CONCLUSION: Superfrequent TLAS is a highly effective and non-invasive modality in the treatment of paroxysmal AF. It promotes recovery of SR. In some patients TLAS induces AFi which is more controllable by medication as regards the heart rate. Cordarone contributes to the response to TLAS in patients with paroxysmal AF.

[Use of transesophageal left atrial cardiac pacing for assessment of cordarone effectiveness in patients with atrioventricular tachycardia]. / Primenenie chrezpishchevodnoi stimuliatsii levogo predserdiia dlia otsenki éffektivnosti lecheniia kordaronom patsientov s atrioventrikuliarnymi takhikardiiami.

AIM: To assess by means of transesophageal left atrial pacing the effectiveness of cordarone treatment for arrhythmias caused by re-entry mechanism. MATERIALS AND METHODS: Effectiveness of cordarone treatment was estimated in 25 patients with atrioventricular nodal tachycardia (AVNT) and in 33 patients with WPW syndrome and reciprocal atrioventricular tachycardia (RAVT) with frequent paroxysms of tachycardia 1-5 times per week. Transesophageal left atrial pacing (TELAP) was performed before antiarrhythmic treatment and on cordarone treatment day 14-18. Cordarone was given for two months in common regimen (the first 10 days--600 mg/day, the next 10 days--400 mg/day and then 200 mg/day). RESULTS: The first TELAP induced paroxysmal AVNT or RAVT in all the patients. According to the results of the second TELAP, all the patients were divided into three groups. Group 1 included 28 patients in whom the second TELAP was unable to induce tachycardia. All these patients had increased effective refractory period (ERP) of AV node and/or of accessory pathway (AP) values and a decreased Wenkebach point (WP) < 150/min during the second TELAP in comparison with the first TELAP. All these patients had no spontaneous paroxysms of T during the 3-month follow-up. Group 2 included 18 patients in whom the second TELAP induced AVT lasting < 30 seconds. 16 of these patients had tachycardia with less heart rate during the second TELAP in comparison with the first TELAP, 153 + (-) 8 bpm vs 188 + (-) 10 bpm, p < 0.001, respectively. Also, in these 16 patients we found an increase of values of ERP of AV node and/or AP > 360 ms and a decrease of WP < 150 bmp. 14 of these 16 patients had no spontaneous paroxysms of AVT and 2 patients had short episodes of AVT during the 3-month follow-up with effects of vagal manoeuvers. From 2 other patients of group 2 one had short episodes of spontaneous T and one had long episodes of tachycardia with effect of verapamil i.v. Group 3 included 12 patients in whom the second TELAP induced the same AVT as the first TELAP. Values of ERP of AV node and/or AP and WP during the first and second TELAP were not different. All of these patients had long spontaneous paroxysms of AVT during cordarone treatment day 14-18. The treatment was discontinued in all patients of group 3. CONCLUSION: Cordarone is effective in prevention of AVT. Negative results in provocation of AVT during TELAP after 14-18 days of cordarone treatment is a very specific predictor of cordarone treatment effectiveness. Provocation by TELAP of short episodes of AVT with reduced heart rate and higher values of ERP of AV node and AP and lowering of WP < 150 bpm may not predict ineffectiveness of cordarone in patients with AVT. Moreover, the majority of these patients had no spontaneous episodes of AVT. Provocation by TELAP during cordarone treatment of the same AVT episodes as before cordarone treatment is a very specific predictor of cordarone effectiveness.

Desoxyepothilone B: an efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone B.

A new class of 16-membered macrolides, the epothilones (Epos), has been synthesized and evaluated for antitumor potential in vitro and in vivo. Recent studies in these and other laboratories showed that epothilones and paclitaxel (paclitaxel) share similar mechanisms of action in stabilizing microtubule arrays as indicated by binding-displacement studies, substitution for paclitaxel in paclitaxel-dependent cell growth, and electron microscopic examinations. The present study examined cell growth-inhibitory effects in two rodent and three human tumor cell lines and their drug-resistant sublines. Although paclitaxel showed as much as 1, 970-fold cross-resistance to the sublines resistant to paclitaxel, adriamycin, vinblastine, or actinomycin D, most epothilones exhibit little or no cross-resistance. In multidrug-resistant CCRF-CEM/VBL100 cells, IC50 values for EpoA (1), EpoB (2), desoxyEpoA (3) (dEpoA), desoxyEpoB (4) (dEpoB), and paclitaxel were 0.02, 0.002, 0.012, 0.017, and 4.14 microM, respectively. In vivo studies, using i.p. administration, indicated that the parent, EpoB, was highly toxic to mice and showed little therapeutic effect when compared with a lead compound, dEpoB. More significantly, dEpoB (25-40 mg/kg, Q2Dx5, i.p.) showed far superior therapeutic effects and lower toxicity than paclitaxel, doxorubicin, camptothecin, or vinblastine (at maximal tolerated doses) in parallel experiments. For mammary adenocarcinoma xenografts resistant to adriamycin, MCF-7/Adr, superior therapeutic effects were obtained with dEpoB compared with paclitaxel when i.p. regimens were used. For ovarian adenocarcinoma xenografts, SK-OV-3, dEpoB (i.p.), and paclitaxel (i. v.) gave similar therapeutic effects. In nude mice bearing a human mammary carcinoma xenograft (MX-1), marked tumor regression and cures were obtained with dEpoB.

Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones.

An important class of cellular proteins, which includes members of the p21ras family, undergoes posttranslational farnesylation, a modification required for their partition to membranes. Specific farnesyl transferase inhibitors (FTIs) have been developed that selectively inhibit the processing of these proteins. FTIs have been shown to be potent inhibitors of tumor cell growth in cell culture and in murine models and at doses that cause little toxicity to the animal. These data suggest that these drugs might be useful therapeutic agents. We now report that, when FTI is combined with some cytotoxic antineoplastic drugs, the effects on tumor cells are additive. No interference is noted. Furthermore, FTI and agents that prevent microtubule depolymerization, such as taxol or epothilones, act synergistically to inhibit cell growth. FTI causes increased sensitivity to induction of metaphase block by these agents, suggesting that a farnesylated protein may regulate the mitotic check point. The findings imply that FTI may be a useful agent for the treatment of tumors with wild-type ras that are sensitive to taxanes.