Prothymosin α1 effects,in vitro,on the antitumor activity and cytokine production of blood monocytes from colorectal tumor patients

Recent animal studies demonstrate that prothymosin α1 (ProTα) enhances the antitumor response by stimulation of mononuclear phagocyte functions. The present study was aimed at characterizing the in vitro effects by ProTα on blood monocytes from human colon cancer patients. Purified peripheral blood monocytes were studied in terms of tumor cytostatic ability and cytokine production after incubation with ProTα or interferon (rIFN-γ) and transforming growth factor-β (TGFβ), used as reference substances. SW620 colon carcinoma cells were used as tumor target cells in growth inhibition experiments. The level of baseline growth inhibitory activity of unstimulated patient's monocytes was significantly lower than that of normal monocytes. The defective antitumor activity of patient monocytes was associated with a higher production of the inhibitory monokines prostaglandin E₂ (PGE₂) and TGFβ. The stimulation of monocytes by ProTα and/or rIFN-γ elevated the average antitumor activity in all donor groups. The ProTα-induced increase was associated with a significantly higher monocytic secretion of IL-1β and TNF-α. Moreover, the concentrations of TGFβ and PGE₂ in the culture supernatants decreased significantly, when patient's monocytes were treated with ProTα and/or rIFN-γ. Additionally, ProTα enhanced the diminished antitumor activity of TGFβ-treated normal monocytes. These results suggest that ProTα selectively regulates distinct functions of blood monocytes, the effect of this cytokine varying with the parameter and donor population examined. These data provide a rational and biological endpoint for further studies with ProTα as an activator of mononuclear function in colon cancer.     

Comparative study on the effects of three insecticides (fipronil, imidacloprid, selamectin) on developmental stages of the cat flea (Ctenocephalides felis Bouché 1835): a light and electron microscopic analysis of in vivo and in vitro experiments

The effects of three insecticides (fipronil, imidacloprid and selamectin) on developmental stages of cat fleas (Ctenocephalides felis) were studied in vivo, in vitro and by means of light and electron microscopy. The results were documented by video. Adult fleas were attached to the skin of dogs that had been treated 7 days before with one of the three compounds. Furthermore, adult fleas were exposed exclusively to the hair and skin debris of such treated dogs or were placed on filter papers that had been impregnated with one of these three compounds or with the blood of treated dogs. Larval fleas were exposed to hair of treated dogs, to debris obtained by combing treated dogs, to dried blood samples of treated dogs or were placed onto filter papers impregnated with one of the three compounds. In these experiments with adult and larval fleas, it was noted that none of the three insecticides had a repellent effect on adult or larval fleas. Imidacloprid was the only compound that acted exclusively by body contact, and was apparently taken up by adult and larval fleas via the thin, non-sclerotized intersegmental membranes of the flea's body, shown when flea stages were exposed to hairs taken from dogs treated with one of the compounds or placed onto drug-impregnated filter papers. Imidacloprid killed larvae and adult fleas within 1 h, while it took at least 24 h until all adult fleas had died on fipronil- or selamectin-treated dogs, thus allowing longer feeding periods, increasing the risk of transmission of flea-derived diseases. Flea larvae covered with debris from dogs topically treated 7 days before with fipronil, imidacloprid or selamectin died, like the untreated control, within 16–28 h after exposure. This was, however, probably mainly due to a drying effect. Adult and larval fleas exposed to filter papers impregnated with the blood of treated dogs survived longer than 7 days, as did the untreated controls. All three drugs apparently acted on nerves and muscles and thus stopped motility. Received: 7 October 2000 / Accepted: 18 October 2000     

Developing mouse Sertoli cells in vitro: effects on developing ovaries in co-culture and production of anti-Müllerian hormone

Previous work in our laboratory showed that pre-Sertoli cells adopt an epithelial phenotype when cultured in the presence of reconstituted basement membrane (RBM), and so cultures were established with and without this substrate. Biological activity of isolated developing mouse Sertoli cells maintained in vitro was assessed in the current study by utilising a co-culture approach, to determine whether the cells were capable of affecting ovarian differentiation. Developing Sertoli cells isolated at embryonic day (E) 12.5 exerted a deleterious effect on E12.5 ovaries in co-culture, inducing a loss of germ cells. However, when cells were isolated a day later and co-cultured with E13.5 ovaries (after entry to meiosis has begun), germ cells survived and showed evidence of meiosis, although ovigerous cords in co-cultures were masculinized compared to those of control cultured ovaries. Thus, both stages examined showed biological effects; cultured pre-Sertoli cells explanted at E12.5 showed a negative effect on female germ cells, whereas those explanted at E13.5 masculinized ovigerous cords. The functional status of isolated developing mouse Sertoli cells in vitro was further assessed by immunocytochemistry to investigate the expression of anti-Müllerian hormone, an early product of pre-Sertoli cells. Positive immunostaining was seen in developing Sertoli cells in vitro, particularly where cells had been explanted to an RBM substrate, demonstrating that good epithelial morphology is associated with improved function. Our culture system is therefore well suited for investigating factors produced by developing Sertoli cells, their role in influencing testicular morphogenesis and their potential to perturb ovarian differentiation. We believe that this in vitro approach provides a more physiological assessment compared with the knockout mouse model, where global effects of genes with housekeeping functions can compromise overall development.     

Novel effects of On-Chung-Eum,the traditional plant medicine,on cytokine production in human mononuclear cells from Behçet's

Plant medications have been used as treatment in various kinds of systemic inflammatory disorder such as Beh?et's disease (BD). We investigated the roles of On-Chung-Eum (OCE), a traditional plant medicine, in cytokine regulation of BD. The effects of OCE on cytokine production from phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Beh?et's patients and control subjects were measured by ELISA. PBMC from patients with active BD produced higher levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) compared to control. OCE significantly inhibited the production of TNF-alpha, IL-1beta and interferon-gamma (INF-gamma), compared to absence of OCE. The inhibitory effects of OCE showed in a dose-dependent manner, and OCE had better effects than immunosuppressive drug, cyclosporin A. OCE is able to effectively inhibit proinflammatory cytokines and immunoregulatory Th1 cytokine. OCE treatment for BD patients may help the improvement of symptoms through cytokine modulation.     

Evaluation of the impact of Exomite Pro™ on Varroa mite (Varroa destructor) populations and honeybee (Apis mellifera) colonies: efficacy,side effects and residues

In this research, we examined the application of thymol-based powder, directly over the top of the brood frames in colonies with different population in a 2-year study. The efficacy against mites, the side effects on bees and the contamination of honey were studied comparably to thymol-based gel treatment. In one-store colonies, thymol-based powder treatment gave average efficacy 64.5 % and did not differ significantly from thymol-based gel treatment (65.4 %). The natural mortality in control colonies was 41.4 % and the corrected efficacy (E _T) during 2 years was 39.4 and 40.9 %, respectively. In two-store bee colonies, the application of thymol-based powder on top of each hive body gave higher E _T (45,4 %) than on top of the double body hive (40.4 %), without statistically significant differences. The average concentration of thymol residues in honey 24 days after the application was 368 and 1,119 μg kg^?1 for the honey of colonies treated with thymol-based powder and thymol-base gel, respectively.     

Genetic ancestry effects on the distribution of toll-like receptors (TLRs) gene polymorphisms in a population of the Atlantic Forest,São Paulo,Brazil

The innate immune system governed by toll-like receptors (TLRs) provides the first line of defense against pathogens. Surface-localized TLR1 and TLR6 are known to detect parasite components. TLR encoding genes were shown to display signatures of recent positive selection in Europeans and might be involved in local adaptation at immune-related genes. To verify the influence of Brazilian population admixture on the distribution of polymorphisms in TLRs, we analyzed the genotype frequencies of 24 polymorphisms distributed across five TLR genes in a Southeastern Brazilian population where autochthonous cases of malaria occur in small foci of transmission. The estimation of ancestry showed mainly European ancestry (63%) followed by African ancestry (22%). Mean proportions of European ancestry differed significantly between the genotypes of the TLR1 (I602S) gene and in the TLR6 (P249S) gene. The chance of having the G allele in TLR1 gene increases as European ancestry increases as well as the chance of having the T allele in the TLR6 gene. The 602S allele is related to a ‘‘hypo-responsiveness’’ possibly explaining the high prevalence of asymptomatic malaria cases in areas of Southeastern Brazil. Our results underline the necessity to include informative ancestry markers in genetic association studies in order to avoid biased results.     

Magnetic stimulation and the crossed–uncrossed difference (CUD) paradigm: selective effects in the ipsilateral and contralateral hemispheres

When a visual target is presented to one hemifield, manual responses made to the target using the ipsilateral hand (uncrossed responses) are faster than responses using the contralateral hand (crossed response), because there is no need for visuomotor information to be transferred between the hemispheres. This difference in response times is termed the crossed–uncrossed difference (CUD) and is a valuable means of estimating interhemispheric transfer time. We aimed to investigate the CUD by applying repetitive transcranial magnetic stimulation (rTMS) over the left and right occipital cortex during a lateralized target-detection task. Eleven neurologically healthy subjects, all right-handed, participated in the study. Relative to sham TMS we increased the CUD, by inhibiting the crossed latencies, but only when rTMS was applied to the hemisphere receiving visual information. These results replicate and extend previous findings and suggest the inhibitory rTMS effect under the crossed condition might be because the weak visual output is unable to activate the crossed pathway.     

Population-S benzimidazole- and tetrahydropyrimidine-resistant small strongyles in a pony herd in Kentucky (1977–1999): effects of anthelmintic treatment on the parasites as determined in critical tests

Population-S small strongyles have been studied since 1974 in central Kentucky in a closed Shetland pony breeding herd. The ponies were treated approximately every 8 weeks with cambendazole (1974–1978), oxibendazole (OBZ) (1978–1992), or pyrantel pamoate (PRT) (1992–1999). Small strongyles in the ponies have shown resistance to these compounds in field and critical tests. One purpose of this presentation was to compare different parameters for determination of effects on the small strongyle species in ponies after treatment, mainly with OBZ or PRT, from data in critical tests (n=112). Also, the objective was to report on relative changes in the composition of species of small strongyles during the period 1977 through 1999. The following entities were compared to evaluate the effect of OBZ- or PRT-treatment on the small strongyles: (1) numbers of specimens with eggs in utero—there were less gravid worms passed in the feces than recovered at necropsy for OBZ but the numbers of gravid worms were similar in both categories for PRT, (2) pre- and posttreatment counts of eggs per gram of feces (EPGs) and larvae per gram of feces (LPGs)—the reductions were greater for the counts of EPGs than LPGs for OBZ but not for PRT, and (3) pre- and posttreatment counts of EPGs versus % of worms removed—reductions of the former were greater than the latter for both compounds. As shown from data in this study, reduction of EPG counts post treatment indicated much greater drug activity than was actually demonstrated by removal of worms. One evident factor was the value of doing critical tests to verify posttreatment counts of EPGs as indicators of anthelmintic activity. Twenty-eight species of small strongyles were found. For the 20 most prevalent species in the study, two decreased, five remained unchanged, three increased and then became stationary, five increased but then decreased, and five increased progressively. Numbers of small strongyles were highest in 1987 and 1999.     

Inhibition of nitric oxide production by aminoguanidine influences the number of Trichinella spiralis parasites in infected “low responders” (C57BL/6) and “high responders” (BALB/c) mice

The influence of nitric oxide (NO) on the development of adults and larvae Trichinella spiralis was examined in two strains of mice: C57BL/6 and BALB/c. The influence of aminoguanidine (AG)-inhibitor of inducible nitric oxide synthase (iNOS) administered in the first days after T. spiralis infection (1–5 dpi) on the number of adult parasites, as well as the influence of AG administered at the beginning of muscle phase of the T. spiralis infection (16–29 dpi) on the number of muscle larvae, was studied. In mice that were treated with AG from the 1st to the 5th day post infection (dpi), the numbers of adult T. spiralis were counted in intestines at 6, 9, 15, and 20 dpi. In this experiment, the impact of AG expressed as diminution of adult worms at 9, 15, and 20 dpi in BALB/c mice. The opposite effect of AG was demonstrated in C57BL/6 mice at 6 and 9 dpi. In mice in which AG was applied from the 16th to the 29th dpi T. spiralis larvae were counted at 30, 35, and 41 dpi. This experiment demonstrated that treating mice with AG at the beginning of muscle phase of the infection inhibits the reduction of muscle larvae number in mice of both strains.     

Sedative effects of the jasmine tea odor and (R)-(−)-linalool, one of its major odor components, on autonomic nerve activity and mood states

We investigated the effects of the odor of jasmine tea on autonomic nerve activity and mood states in a total of 24 healthy volunteers. We used the odor of jasmine tea at the lowest concentration that could be detected by each subject but that did not elicit any psychological effects. R–R intervals and the POMS test were measured before and after inhalation of the odors for 5 min. Both jasmine tea and lavender odors at perceived similar intensity caused significant decreases in heart rate and significant increases in spectral integrated values at high-frequency component in comparison with the control (P < 0.05). In the POMS tests, these odors produced calm and vigorous mood states. We also examined the effects of (R)-(–)-linalool, one of its major odor components, at the same concentration as in the tea, and (S)-(+)-linalool. Only (R)-(–)-linalool elicited a significant decrease in heart rate (P < 0.05) and an increase in high-frequency component in comparison with the controls, and produced calm and vigorous mood states. Thus, the low intensity of jasmine tea odor has sedative effects on both autonomic nerve activity and mood states, and (R)-(–)-linalool, one of its components, can mimic these effects.     

Development of play fighting in kindling‐prone (FAST) and kindling‐resistant (SLOW) rats: How does the retention of phenotypic juvenility affect the complexity of play?

Rats selectively bred for susceptibility to amygdala kindling (FAST) have been shown to retain neural and behavioral features of the juvenile phase into adulthood. In contrast, rats selectively bred for resistance to amygdala kindling (SLOW) are neurobehaviorally more typically adult. The development of play fighting in male and female rats of both selected lines was studied. Given the apparent association of juvenility and play often noted in the literature for mammals in general, it was predicted that the FAST rats should be more playful and be more likely to retain the juvenile tactics of play that lead to more prolonged and complex patterns of social contact. As expected, FAST rats initiated more playful attacks and were more likely to defend against attacks than SLOW rats as both juveniles and adults. Unexpectedly, however, both selected lines exhibited patterns of defense that reduced the likelihood of complex and prolonged social contact. Importantly, the two selected lines did so by very different means. The FAST rats did so by avoiding contact whereas the SLOW rats did so by responding in an adult-typical manner that blocks contact. That is, the FAST rats exaggerated the changes typically occurring at puberty whereas the SLOW rats, at all ages, responded in a more adult manner. These data suggest that the different components of play fighting do not change uniformly with changes in the neurobehavioral underpinnings of juvenility.     

What are the effects of maternal and pre-adult environments on ageing in humans, and are there lessons from animal models?

An open issue in research on ageing is the extent to which responses to the environment during development can influence variability in life span in animals, and the health profile of the elderly in human populations. Both affluence and adversity in human societies have profound impacts on survivorship curves, and some of this effect may be traceable to effects in utero or in infancy. The Barker Hypothesis that links caloric restriction in very early life to disruptions of glucose-insulin metabolism in later life has attracted much attention, as well as some controversy, in medical circles. It is only rarely considered by evolutionary biologists working on phenotypic plasticity, or by biogerontologists studying model organisms such as C. elegans or Drosophila. One crucial mechanism by which animals can respond in an adaptive manner to adverse conditions, for example in nutrition or infection, during development is phenotypic plasticity. Here we begin with a discussion of adaptive plasticity in animals before asking what such phenomena may reveal of relevance to rates of ageing in animals, and in humans. We survey the evidence for effects on adult ageing of environmental conditions during development across mammalian and invertebrate model organisms, and ask whether evolutionary conserved mechanisms might be involved. We conclude that the Barker Hypothesis is poorly supported and argue that more work in human populations should be integrated with multi-disciplinary studies of ageing-related phenomena in experimental populations of different model species that are subjected to nutritional challenges or infections during pre-adult development.     

Comments on the article “Changing attitudes towards the care of children in hospital: a new assessment of the influence of the work of Bowlby and Robertson in the UK, 1940–1970” by Frank C.P. van der Horst and Rene van der Veer (Attachment and Human Development Vol 11, No 2, March 2009, 119–142)

The authors give an impressive list of references, but these do not reflect the situation in the UK; most of those looking after children in hospital did not write about what they did or read about what others did. Children in hospital saw little or nothing of their parents, and once they had ‘settled’ the doctors and nurses were unaware of their distress. John Bowlby's interest in maternal deprivation led him to appoint James Robertson as his research assistant, to observe responses of young children to loss of maternal care on admission to hospital. They formulated the theoretical framework of the three stages through which the children went; protest, despair, and detachment constituting a developmental interference. Robertson was so concerned when nobody would listen that in 1952 he made the film ‘A Two Year Old Goes to Hospital’, which upset children's doctors and nurses. It also probably contributed to the government setting up in 1957 a Committee chaired by Sir Harry Platt to consider the Welfare of Children in Hospital. ‘Going to Hospital with Mother’ was made by Robertson in 1958. With Dermod MacCarthy he showed the films to the Committee, who accepted the suggestions in Robertson's Memorandum which included unrestricted visiting and mothers being admitted with their young children. The Report, known as the Platt Report, was published in 1959. Robertson could then show his films publicy, campaign in the media and encourage the pressure group NAWCH (the National Association for the Welfare of Children in Hospital) who were successful in getting many of the Committee's recommendations implemented, to the benefit of all children in hospital.