In vitro 2,3,7,8-tetrachlorodibenzo-p-dioxin interference with the anterior pituitary hormone adrenocorticortropin

Pharmacological effects of acute treatment with venlafaxine (VEN), a clinically active antidepressant [a noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor without any affinity for neurotransmitter receptors] were studied in mice and rats. VEN inhibited the reserpine- or apomorphine-induced hypothermia and enhanced the L-5-HTP-induced head twitches in mice. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). VEN reduced the locomotor hyperactivity induced by amphetamine (AMP), apomorphine (APO) and quinpirole (QUI), as well as the APO-induced stereotypy; the stereotypy induced by AMP in rats was prolonged. VEN neither changed the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that VEN, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, VEN does not exhibit an alpha 1-adrenolytic or a cholinolytic activity (in vivo tests).     

Polyclonal antibodies from blood and cerebrospinal fluid of patients with multiple sclerosis effectively hydrolyze DNA and RNA

It is known that in the blood of patients with some autoimmune diseases catalytically active antibodies hydrolyzing proteins, DNA, and RNA may be detected. In the present work homogeneous preparations of IgG antibodies (Ab) possessing high affinity for nucleic acids (NA) were obtained for the first time from blood and cerebrospinal fluid of patients with multiple sclerosis (MS). The fraction of IgG Ab as well as its Fab fragments and isolated light chains of both kappa- and lambda-types were shown to catalyze effectively the hydrolysis of DNA and RNA. It is shown by different methods that the capability for nucleic acid hydrolysis is an intrinsic property of the polyclonal Ab. NA-hydrolyzing Ab were detected in the blood of 69 of 72 and in the cerebrospinal fluid of 5 of 5 examined MS patients, while they were not detected in the blood of any of 50 healthy donors examined. Comparison of relative rates of RNA hydrolysis and of the substrate specificity in hydrolysis of various model RNAs--cCMP, poly(U), poly(A), and poly(C)--revealed pronounced differences of MS antibodies from ribonucleases of human blood, ribonuclease A, and all earlier described abzymes. The abzymes are usually characterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS patients are the first example of autoabzymes whose specific activity in RNA hydrolysis is comparable or even higher than that of pancreatic ribonuclease A--one of the most active RNA-hydrolyzing enzymes.     

Sexual conflict and speciation

We review the significance of two forms of sexual conflict (different evolutionary interests of the two sexes) for genetic differentiation of populations and the evolution of reproductive isolation. Conflicting selection on the alleles at a single locus can occur in males and females if the sexes have different optima for a trait, and there are pleiotropic genetic correlations between the sexes for it. There will then be selection for sex limitation and hence sexual dimorphism. This sex limitation could break down in hybrids and reduce their fitness. Pleiotropic genetic correlations between the sexes could also affect the likelihood of mating in interpopulation encounters. Conflict can also occur between (sex-limited) loci that determine behaviour in males and those that determine behaviour in females. Reproductive isolation may occur by rapid coevolution of male trait and female mating preference. This would tend to generate assortative mating on secondary contact, hence promoting speciation. Sexual conflict resulting from sensory exploitation, polyspermy and the cost of mating could result in high levels of interpopulation mating. If females evolve resistance to make pre- and postmating manipulation, males from one population could be more successful with females from the other, because females would have evolved resistance to their own (but not to the allopatric) males. Between-locus sexual conflict could also occur as a result of conflict between males and females of different populations over the production of unfit hybrids. We develop models which show that females are in general selected to resist such matings and males to persist, and this could have a bearing on both the initial level of interpopulation matings and the likelihood that reinforcement will occur. In effect, selection on males usually acts to promote gene flow and to restrict premating isolation, whereas selection on females usually acts in the reverse direction. We review theoretical models relevant to resolution of this conflict. The winning role depends on a balance between the 'value of winning' and 'power' (relating to contest or armament costs): the winning role is likely to correlate with high value of winning and low costs. Sperm-ovum (or sperm-female tract) conflicts (and their plant parallels) are likely to obey the same principles. Males may typically have higher values of winning, but it is difficult to quantify 'power', and females may often be able to resist mating more cheaply than males can force it. We tentatively predict that sexual conflict will typically result in a higher rate of speciation in 'female-win' clades, that females will be responsible for premating isolation through reinforcement, and that 'female-win' populations will be less genetically diverse.     

Determination of the survival of Trypanosoma evansi in equine blood, using the microhematocrit method

The microhaematocrit (MH) technique was used to study the survival of Trypanosoma evansi in blood from two herds of naturally-infected horses. A comparison was made between samples treated with ethylenediaminetetraacetic acid and sodium citrate (alone or with 1% glucose), and sent to the laboratory packed in ice. In general, the number of samples yielding positive results by the MH technique showed the least variation during the first 24-36 h after sample collection. Survival varied with the anticoagulant used, but it declined rapidly from 48 h after collection, although live parasites were still observed in up to 10% of samples until the seventh day. On the basis of the results obtained, the authors recommend the use of sodium citrate in treating equine blood samples for the parasitological diagnosis of T. evansi.     

Maternal and fetal plasma concentrations of endothelin, lipidhydroperoxides, glutathione peroxidase and fibronectin in relation to abnormal umbilical artery velocimetry

The topoisomerase II alpha (topo II alpha) enzyme is the target for several chemotherapeutic agents, including etoposide, teniposide, mitoxantrone, and doxorubicin (topo II poisons). The enzyme also is a marker of cell proliferation. Most cases of Hodgkin's disease (HD) are responsive to combination chemotherapy regimes that include topo II poisons such as doxorubicin. Immunoperoxidase methods for detection of the topo II alpha isoenzyme are now available for use in formalin-fixed, paraffin-embedded tissues, which may provide information about the proliferative capacity and possible sensitivity of tumors to drugs that target topo II. We used a specific antibody to analyze subsets of HD for topo II alpha staining patterns. Formalin-fixed blocks from 49 cases of HD, including 20 nodular sclerosis (NS), 14 mixed-cellularity (MC), and 15 lymphocyte-predominant (LP) subtypes, were analyzed by dual staining for topo II in combination with monoclonal antibodies against Reed-Sternberg (RS) cells consisting of CD15 for the NS and MC subtypes and CD20 for LP lymphocytic and histiocytic (L & H) cells. The number of morphologically appropriate cells coexpressing the RS or L & H marker and topo II alpha was quantitated. Positive nuclear staining for topo II alpha in RS or L & H cells was seen in 100% of cases, irrespective of subtype. Coexpression of CD15 and topo II alpha was seen in 58.4% of the RS cells or mononuclear variants in NSHD cases and 68.4% in MCHD cases. No significant difference in the percentage of neoplastic cells expressing topo II alpha was found between NS and MC subtypes. Cases of LPHD showed coexpression of CD20 and topo II alpha in 84.4% of the L & H cells, a significant increase over the level of tumor cell coexpression seen in NSHD and MCHD (P < .001). Only one case was found to have a low (< 25% of tumor cell coexpression) level of topo II alpha expression. Immunohistochemical detection of a high level of topo II alpha expression in HD, irrespective of subtype, suggests a molecular explanation for the excellent response of most HD to standard combination chemotherapy, which can include topo II poisons. The LP subtype has a higher expression of topo II alpha in the neoplastic cell population than do NS or MC subtypes, perhaps indicating increased sensitivity of these tumors to topo II poisons. It may be possible to identify subsets of HD that are more or less sensitive to conventional chemotherapeutic regimes, which would help in the selection of appropriate treatment.     

Diagnosis of hyperventilation for elimination of false-positive results of physical exercise test

The study was conducted in 55 patients with cardiac pains. Electrocardiography was used successively prior to, during and following physical exercises, followed by Seldinger selective coronary angiography, and electrocardiography prior to, during and following hyperventilation tests. In 2 of 55 patients the result of the exercise test was interpreted as false-positive, since the coronary angiography demonstrated intact vessels, and during hyperventilation ECG recorded a decreased ST segment. To avoid false-positive results in patients with suspected angina pectoris the physical exercises tests can be considered positive only in cases in which hyperventilation caused no ECG changes typical for angina pectoris.     

Treatment of intestinal paresis in children

In the paper, a clinical experience with treatment of intestinal paresis in 545 children, aged from 1 day to 13 years, including 225 children operated upon for peritonitis is summarized. The authors differentiate 3 stages in the development of intestinal paresis depending on the degree of intensity of systemic and local disturbances. The employed methods of treatment in intestinal paresis were classified by the principle of their effect as 3 groups. Application of some or other method of the paresis therapy is determined by the stage of its development. In treatment of postoperative intestinal paresis a continuous peridural blockade is considered to be the method of choice. Utilization of the latter enabled the authors to reveal a number of postoperative complications: mechanic intestinal obstruction, incompetent anastomosis, etc.     

Evidence for plasmid-associated crystal toxin production in Bacillus thuringiensis subsp. israelensis

Three crystalliferous (Cry+) strains of Bacillus thuringiensis subsp. israelensis (serotype 14) that produce parasporal protein crystals toxic to dipteran larvae and several acrystalliferous (Cry-) mutants, either induced or spontaneously derived from a single Cry+ parent, were examined for the presence of covalently closed circular (CCC) DNA in attempts to correlate toxin production with the presence of a specific plasmid. The plasmid profiles of both Cry+ and Cry- variants were analyzed by both a cleared lysate- and a modified Eckhardt lysate-electrophoresis technique. All of the Cry- mutants derived from the Cry+ parental strain had lost a 4.0- to 4.4-megadalton (Mdal) plasmid. Bioassay data confirmed loss of toxin production by the Cry- variants. All three Cry+ strains, including the parent of the Cry- strains, contained CCC plasmids DNAs of the following approximate molecular weights: 4.0 to 4.4, 5.2 to 6.0, and 11.4 to 13.0 Mdal. One Cry+ strain contained an additional CCC plasmid of 6.7 to 7.2 Mdal. The plasmid patterns for several Cry- derivatives differed in other respects from the pattern for their parent strain. The various Cry+ and Cry- strains could be distinguished either by phenotypical differences in antibiotic sensitivity, crystal production, and toxicity, or by differences in their plasmid profiles.     

Muscle fiber composition and blood ammonia levels after intense exercise in humans

The relationship between fiber type composition and the increase in blood ammonia was examined following a maximal O2 consumption (VO2max) test. Muscle biopsies were taken from the middle portion of the vastus lateralis for determination of fiber type percentages. Two subject groups were selected on the basis of a high (HST) or low (LST) percentage of slow-twitch fibers and compared for blood ammonia and lactate levels after exercise at work loads of approximately 85 and 110% of VO2max. An inverse relationship was found between the percentage of slow-twitch fibers and the increase in blood ammonia. Blood ammonia increased after exercise at both 85 and 110% of VO2max. However, the increase was twofold greater for the LST group following the 110% work effort. The increases in blood ammonia and lactate were positively correlated for both groups following exercise. The results suggest that the proportion of slow-twitch fibers plays an important role in determining the magnitude of the increase in blood ammonia after intense exercise.