Melanotropic drugs and retinal functions. II. Effects of phenothiazine and rifampicin on the sheep ERG

The acute effects of chlorpromazine, promethazine and rifampicin on the a-, b- and c-waves of the conventional electroretinogram (ERG) were studied in sheep. Iv administration of chlorpromazine and promethazine resulted in a b-wave amplitude decrease and an initial c-wave amplitude decrease, followed by cyclic amplitude changes resembling damped oscillations. Iv injections of rifampicin, however, resulted in cyclic changes of the c-wave amplitude without initial concomitant b-wave changes. The results of the present study indicate that rifampicin has a selective influence on the pigment epithelial cells, while chlorpromazine and promethazine seem to have more generalized retinal effects on both the neuroretina and the pigment epithelial cells.     

Bacillus thuringiensis subsp. konkukian (serotype H34) superinfection: case report and experimental evidence of pathogenicity in immunosuppressed mice

We present a case of severe war wounds infected by Bacillus thuringiensis serotype H34 and describe the experimental protocol used to demonstrate its ability to infect mice after cutaneous inoculation. This case is interesting because B. thuringiensis is considered to be a contaminant in laboratories and receives inadequate attention.     

Evidence for differential binding of isoniazid by Mycobacterium tuberculosis KatG and the isoniazid-resistant mutant KatG(S315T)

Isoniazid is a mainstay of antibiotic therapy for the treatment of tuberculosis, but its molecular mechanism of action is unclear. Previous investigators have hypothesized that isoniazid is a prodrug that requires in vivo activation by KatG, the catalase-peroxidase of Mycobacterium tuberculosis, and that resistance to isoniazid strongly correlates with deletions or point mutations in KatG. One such mutation, KatG(S315T), is found in approximately 50% of clinical isolates exhibiting isoniazid resistance. In this work, 1H nuclear magnetic resonance T1 relaxation measurements indicate that KatG and KatG(S315T) each bind isoniazid at a position approximately 12 A from the active site heme iron. Electron paramagnetic resonance spectroscopy revealed heterogeneous populations of high-spin ferric heme in both wild-type KatG and KatG(S315T) with the ratios of each species differing between the two enzymes. Small changes in the proportions of these high-spin species upon addition of isoniazid support the finding that isoniazid binds near the heme periphery of both enzymes. Titration of wild-type KatG with isoniazid resulted in the appearance of a "type I" substrate-induced difference spectrum analogous to those seen upon substrate binding to the cytochromes P450. The difference spectrum may result from an isoniazid-induced change in a portion of the KatG heme iron from 6- to 5-coordinate. Titration of KatG(S315T) with isoniazid failed to produce a measurable difference spectrum indicating an altered active site configuration. These results suggest that KatG(S315T) confers resistance to isoniazid through subtle changes in the isoniazid binding site.     

The characteristics of the action of high-energy lasers on kidney tissues (experimental research)

Alternative and reparative changes in renal tissue exposed to high-energy laser radiation are characterized basing on the experimental findings. It is emphasized that hemostasis and ablasticity are secured better if dissection of the renal tissue is made by a contact YAG-Nd laser versus routine laser scalpel.     

Influence of spices on the bacterial (enzyme) activity in experimental colon cancer

Using degenerate PCR primers that target evolutionarily conserved sequences in pal genes, we show that in the gymnosperm, Pinus banksiana, phenylalanine ammonia-lyase (PAL) is encoded by a multigene family of at least eight to ten loci. Five classes of pal sequence were easily distinguished among 28 clones sequenced from the products of PCR amplification of haploid genomic DNA. The dominant sequence from each class was named, yielding pal1 to pal5 loci. These genes shared 68.8% to 94.0% nucleotide identity over the 366 bp region compared. All of pal1 to pal5 were expressed in cell suspension cultures treated with a fungal elicitor and all but pal3 were expressed in differentiating xylem tissue of a mature tree. Only pall was expressed in unelicited cell cultures. While these P. banksiana genes are quite divergent, they are still more similar to each other than to any angiosperm pal gene cloned to date. For its roles in development and defense, PAL production in P. banksiana is coordinated from a large, diverse multigene family. We discuss evidence suggesting that other pines have similar pal gene family structures.     

Mechanism of the negative action of a bacterial lipopolysaccharide (pyrogenal) on the course of experimental ornithosis infection

The intravenous injection of pyrogenal into mice following their intravenous infection aggravates the course of ornithosis infection and leads to more intensive multiplication of the infective agent. After the injection of pyrogenal is discontinued a change in the course of the infectious process occurs and the infective agent is quickly eliminated from the body. This is accompanied by increased formation of specific antibodies. The negative effect of pyrogenal is due to its high toxicity for macrophages containing the colonies of the infective agent, the suppression of the reaction of neutrophil leukocytes at the sites of the destruction of infected cells and the suppression of the general reaction of the mononuclear phagocytic system. Pyrogenal does not damage lymphoid tissue and even produces an immunostimulant effect on it, but the increased immune response can be completely realized only after pyrogenal injections are stopped and the reaction of mononuclear phagocytes is restored.     

Recent progress in development of psychotropic drugs (4)--Anticonvulsants: an overview on the mechanisms of action

Conventional anticonvulsants can be classified into three types according to their mechanisms of action: (1) those which act on voltage-dependent Na+ channels such as phenytoin, (2) those which act on T-type Ca2+ channels such as ethosuximide, and (3) those which enhance GABA receptor-mediated inhibitory neurotransmission such as phenobarbital or valproate. However, recent studies on experimental models of epilepsy have suggested that the neural mechanisms underlying experimental epileptogenesis are based on: (1) increments in cellular excitability through changes in the function of Na(+)- or Ca2+ channels, (2) desinhibition or inhibition failure, and (3) enhancement of excitatory amino acid receptor-mediated excitatory neurotransmission. These findings might help us to understand the recently developed anticonvulsants and vice versa. In this review, newly developed anticonvulsants are categorized according to the neural mechanisms underlying epileptogenesis, particularly actions on excitatory and inhibitory neurotransmission.     

Effects of bacterial DNA on cytokine production by (NZB/NZW)F1 mice

Microbial DNA has multiple immune effects including the capacity to induce polyclonal B cell activation and cytokine production in normal mice. We recently described the accelerated induction of anti-DNA Abs in NZB/NZW mice immunized with Escherichia coli (EC) dsDNA; paradoxically these mice developed less renal disease than unimmunized mice or mice immunized with calf thymus DNA. We postulated that alterations in cytokine production induced by bacterial DNA may play a key role in renal protection. To determine the effect of bacterial DNA on cytokine production in NZB/NZW mice, we measured the serum cytokine levels, cell culture supernatant cytokine levels, and number of cytokine-producing splenocytes in NZB/NZW mice injected with EC DNA, calf thymus DNA, or an immune active oligonucleotide. There was a 10- to 25-fold increase in the number of cells secreting IFN-gamma compared with IL-4 in mice immunized with EC DNA. IL-12-secreting cells were also increased by bacterial DNA immunization. In parallel with the increase in IFN-gamma secreting cells, there was a significant rise in serum IFN-gamma levels in mice receiving EC DNA. These results indicate that EC DNA modulates systemic cytokine levels in NZB/NZW mice, selectively increasing IL-12 and IFN-gamma while decreasing IL-4 production. The cytokine response of NZB/NZW mice to bacterial DNA may be of significance in disease pathogenesis and relevant to the treatment of lupus-like disease.     

Influence of anthraquinones on the formation of urinary calculi in experimental animals (author''s transl)

A method is presented for the quantitation of urinary and CSF protein. In the presence of 0.10 N NaOH the peptide bonds of the protein remove and bind copper from an ion exchange resin. The resulting copper-protein complex is separated from low molecular weight substances by gel filtration and the copper in the eluted complex is determined colorimetrically with diethyldithiocarbamic acid. The method requires only 100mul of sample, has biuret specificity and uses a single prepacked column. The limit of sensitivity is 2 mg of protein per deciliter.     

Effects of polyelectrolyte complex (PEC) on human periodontal ligament fibroblast (HPLF) function. I. Three-dimensional structure of HPLF cultured on PEC

The functional effect of activating Ca2+-permeable neuronal nicotinic acetylcholine receptors (nAChRs) on vesicle secretion was studied in PC12 cells. Single cells were patch-clamped in the whole-cell configuration and stimulated with either brief pulses of nicotine to activate the Ca2+-permeable nAChRs or with voltage steps to activate voltage-dependent Ca2+ channels. Membrane capacitance was used as a measure of vesicle secretion. Activation of nAChRs by nicotine application to cells voltage clamped at -80 mV evoked secretion. This secretion was completely abolished by nicotinic antagonists. When the cells were voltage clamped at +20 mV in the presence of Cd2+ to block voltage-activated Ca2+ channels, nicotine elicited a small amount of secretion. Most interestingly, when the nAChRs were activated coincidentally with voltage-dependent Ca2+ channels, secretion was augmented approximately twofold over the secretion elicited with voltage-dependent Ca2+ channels alone. Our data suggest that Ca2+ influx via nAChRs affects Ca2+-dependent cellular functions, including vesicle secretion. In addition to the secretion evoked by nAChR activation at hyperpolarized potentials, we demonstrate that even at depolarized potentials, nAChRs provide an important Ca2+ entry pathway underlying Ca2+-dependent cellular processes such as exocytosis.     

Influence of aminophylline and 8-(p-sulfophenyl)theophylline on the anticonvulsive action of diphenylhydantoin, phenobarbital, and valproate against maximal electroshock-induced convulsions in mice

Time variation of drinking is substantial and has an effect on aggregate estimates of consumption. In this article it is shown that because of a considerable seasonal variation in consumption (+/- 20%) a serious bias in annual consumption estimates can be expected in surveys with a limited time frame. The present study analyzes drinking data collected in the general population of the Netherlands from March 1985 through December 1985 (including Christmas and New Year's Eve). Since it was expected that sensitivity to temporal fluctuations might not be equal for different methods of measurement, several indices of consumption were compared. Although the assessed seasonal effect varies indeed across types of measurement, across male and female subsample and across types of alcoholic beverage, the general tendency is for consumption to be highest in the spring season and lowest in the autumn. Sales figures fluctuate accordingly. It is evident that the risk of biased estimates is larger the shorter the time frame of the survey. Seasonal variation was highest in the frequency domain. Furthermore, exclusion from the time frame of collective holidays, during which people drink more often and more per occasion (viz., Christmas), increases the risk of biased estimates. Even estimates of abstention, but also regular heavy drinking among women, appear to vary considerably over the three seasons in this study. The main conclusion is that results of comparisons of survey data on drinking, particularly those over time, are more or less invalid if the respective time frames of the surveys do not correspond.     

Copulatory behavior of deer mice (Peromyscus maniculatus): III. Effects on pregnancy initiation.

10 experiments defining the nature and dynamics of the responsivity pattern of female deer mice to copulatory stimulation are reported. In cycling estrus, copulation beyond the 1st ejaculatory series was critical for maximal probabilities of pregnancy. The stimulus requirements appeared elevated in older, multiparous Ss. Young Ss tested in postpartum estrus were more responsive, with a single ejaculatory series sufficient for maximal probabilities of pregnancy. Artificial vaginal-cervical stimulation triggered pseudopregnancy in Ss when given in the appropriate amount and pattern. The responsivity followed an orderly dose–response relation in Ss without extensive test experience. The dose–response relation was not an artifact of changes in responsivity within the dark phase. Ss became more responsive to artificial stimulation as a function of experience and/or age. The female "vaginal code" is seen as a critical link in successful reproduction, but one that is both sensitive to prevailing conditions for the individual female and evolutionarily labile. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Test for the efficacy of disinfectants at surfaces in test models. I. (communication:) Dependence of experimental results on the method of demonstration of surviving germs (swab and rinsing) (author's transl)

For the testing of disinfectants at surfaces, the germs having survived at the surface are demonstrated by means of swabs according to the guide-lines of the Deutsche Gesellschaft fur Hygiene und Mikrobiologie (DGHM): after the period of exposure to the disinfectant, the surfaces were rubbed off with a damp swab, and the frictional surface of the swab was plated out on nutrient agar. The effectiveness of this technique was compared with the effectiveness of a rinsing method in a test model. In the rinsing process, the objects to be tested for surviving germs were shaken together with a suspension and with glass beads. Then the content of germs in the suspension was quantitatively determined by means of dilution tests and pour plates. The findings were evaluated according to the guide-lines for evaluation of the DGHM (less than or equal to 10 surviving germs = adequate efficacy). For the findings obtained by rinsing, the average number of surviving germs was also determined. For maldehyde solutions were used as disinfectants for the test models (time of exposure: 4 hours; temperature 22 to 25 degrees C). These disinfecting experiments were performed on raw smoothed as well as on varnished beech-wood. The experimental results showed that the criterion "less than or equal to X surviving germs" in itself does not mean clear evidence of the efficacy of a disinfectant. The one and only decisive criterion is the frequency of the statement that a certain disinfectant or a corresponding dilution of this disinfectant has shown adequate efficacy. Therefore, one single test according to the guide-lines of the DGHM is insufficient. The frequency of the finding "adequate efficacy" is not only dependent on the concentration of the disinfectant but also on the technique used for the demonstration of surviving germs. The swab method (according to the guide-lines of the DGHM) occasionally resulted in the finding "adequate efficacy" already if 10(4) to 10(5) surviving germs were demonstrable by the rinsing method. The range of formaldehyde concentrations for which the finding of adequate efficacy were present with a frequency between 20% (minimum) and 80% (maximum) amounted to 0.2-0.5% (varnished surface) and 1.1-2.5% (raw surface), respectively for the swab method. The respective figures for the rinsing method were 0.8-1.3% and 4.8-6.5%, respectively. When using the swab method, there is a slower increase in the efficacy of the disinfectant with concentration as compared with the rinsing method. The rinsing method is, therefore, more representative of the efficacy of a disinfectant than the swab method. On account of the results of this study, it is recommended for model experiments to recover the surviving germs quantitatively by the rinsing method and to determine their number.     

Effects of diet on the lipid composition of Echinostoma caproni (Trematoda) in ICR mice

High-performance thin-layer chromatography (HPTLC) was used to determine neutral lipids and phospholipids in the intestinal trematode Echinostoma caproni from experimentally infected ICR mice fed a high-fat diet (hen's egg yolk) as compared with worms from mice fed a standard laboratory diet. Worms were removed from the hosts at 2, 3, and 4 weeks postinfection (p.i.). Analysis by TLC-densitometry showed significantly greater amounts of triacylglycerols and free sterols at 2, 3, and 4 weeks p.i. in worms from mice on the high-fat diet as compared with worms from mice on the standard laboratory diet. Significantly greater amounts of phosphatidylcholine and phosphatidylethanolamine were found in worms from mice on the high-fat diet as compared with worms from those on the standard diet at 2 weeks p.i. but not at 3 and 4 weeks p.i. The results of this study suggest that the host diet influences the lipid content of E. caproni adults.     

Comparison of the immunosuppressive efficacy of 6-mercaptopurine, azathioprine, cyclophosphamide and 036.5122 (Asta) on the primary and secondary immune response of mice to sheep erythrocytes

Two alkylating (cyclophosphamide and 036.5122 Asta) and two antiproliferative agents (6-mercaptopurine and azathioprine) have been compared for their immuno-suppressive potency on the primary and secondary humoral immune response of mice. If equitoxic dosages of the respective drugs are compared, the alkylating agents proved to be of much higher immunosuppressive potency than the antiproliferative agents. In non toxic dosages alkylating agents were able to completely inhibit a primary or secondary immune response, whilst a similar effect with antiproliferative drugs could not be obtained even within toxic dose ranges. Induction of immunological tolerance was possible only by use of the alkylating agents. The significance of these comparative studies is discussed in view of the frequent use of the tested drugs in clinical immunosuppression.     

Use of pharmacologic immunosuppression to augment the specific unresponsiveness (tolerance) to skin allografts induced by donor-specific bone marrow in antilymphocyte serum-treated mice: the unique effect of sirolimus

Tolerance produced with ALS treatment, DSBM, and sirolimus involves multiple mechanisms of a specific and nonspecific nature. In eventual clinical application for tolerance induction, sirolimus (rapamycin) has great potential for augmenting the tolerogenicity of the ALS/BM regimen.