Embryotoxicity of chromium: Distribution in pregnant mice and effects on embryonic cells in vitro

The embryonic and fetal uptake of Na₂ ⁵¹Cr₂O₇(Cr VI) was about 10 times higher than that of ⁵¹CrCl₃(Cr III) when these two were given in the same doses i. v. to pregnant C57BL mice. On day 13 of gestation, embryonic concentrations were 12% (Cr VI) and 0.4% (Cr III) of the maternal serum concentration 1 h after injection to the mother. After injection of Cr(III) radioactivity was not detectable in embryonic structures in early gestation, when autoradiographic techniques were used. In late gestation, administration of both forms of Cr resulted in an accumulation in the calcified areas of the fetal skeleton. The radioactivity after administration of Cr(VI) may represent Cr(III) after reduction in the tissues. When added to chick limb bud mesenchymal cells in vitro, Cr(VI) inhibited chondrogenesis at a concentration of about 0.1 g/ml medium, which is around 1/10 of the embryonic concentration achieved after giving teratogenic doses to pregnant mice. Cr(III) on the other hand did not show any overt cytotoxicity even at 15 g/ml ( 500 times higher than the in vivo embryonic concentrations after teratogenic doses). Especially Cr(III) accumulated strongly in the visceral yolk sac, probably after binding to and transport by maternal serum proteins. The possibilities that Cr(III) excerts its teratogenic action by inhibiting embryotrophic nutrition is discussed.     

Clonidine antinociceptive activity: Effects of drugs influencing central monoaminergic and cholinergic mechanisms in the rat

Summary Clonidine is able to increase the threshold for vocalisation during stimulation and the threshold for vocalisation after withdrawal of stimulus (vocalisation afterdischarge). These effects of clonidine were investigated after treatment of rats with drugs influencing central monoaminergic and cholinergic mechanisms.Chlorpromazine, atropine and p-chlorophenyl-alanine increased the activity of clonidine at both thresholds while phenoxybenzamine and reserpine pretreatment increased the activity at the threshold for vocalisation only.Yohimbine decreased clonidine activity at both thresholds while 5-HTP and -methyl-p-tyrosine decreased the effects at the threshold for vocalisation afterdischarge. Naloxone did not change the activity of clonidine at either pain response studied.It is concluded from the present findings that influence from several neuronal systems modulate the antinociceptive action of clonidine.The inhibition of the medullary nociceptive response after clonidine might be connected to a decreased activity of noradrenergic neurons. Endogenous noradrenaline seems to be of minor importance in mediating this effect. It is moreover shown that decreased cholinergic receptor activity enhances clonidine antinociceptive action on both medullary and diencephalic-rhinencephalic pain responses. The possible involvement of serotonin in these functional responses after clonidine is also discussed.Data from this investigation was presented at the International Narcotic Research Club Conference, Airlie, Va. 1975.     

Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children

Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.     

Intensity modulated radiation therapy with electrons using algorithm based energy/range selection methods.

BACKGROUND AND PURPOSE: In recent years photon intensity modulated radiation therapy (IMRT) has gained attention due to its ability to improve conformity of dose distributions. A potential advantage of electron-IMRT is that the dose fall off in the depth dose curve makes it possible to modulate the dose distribution in the direction of the beam by selecting different electron energies. This paper examines the use of a computer based energy selection in combination with the IMRT technique to optimise the electron dose distribution. MATERIALS AND METHODS: One centimetre square electron beamlets ranging from 2.5 to 50 MeV were pre-calculated in water using Monte Carlo methods. A modified IMRT optimisation tool was then used to find an optimum mix of electron energies and intensities. The main principles used are illustrated in some simple geometries and tested on two clinical cases of post-operated ca. mam. RESULTS: It is clearly illustrated that the energy optimisation procedure lowers the dose to lung and heart and makes the dose in the target more homogeneous. Increasing the energy at steep gradients compensates for lack of target coverage at beam edges and steep gradients. Comparison with a clinically acceptable four segment plan indicates the advantage of the used electron IMRT technique. CONCLUSIONS: Using an intensity optimised mix of computer selected electron energies has the potential to improve electron treatments for mastectomy patients with good target coverage and reduced dose to normal tissue such as lung and heart.     

No association between immunohistochemical expression of p53, c-erbB-2, Ki-67, estrogen and progesterone receptors in female papillary thyroid cancer and ionizing radiation

An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation.     

Effects of phencyclidine on acoustic startle and prepulse inhibition in neuronal nitric oxide synthase deficient mice.

Prepulse inhibition of acoustic startle is a behavioural response, which is used to estimate sensorimotor gating deficits in schizophrenia. Recent studies show that several behavioural effects of the psychotomimetic drug, phencyclidine (PCP), in rodents are blocked by nitric oxide synthase (NOS) inhibitors suggesting that NO plays an important role in the pharmacological effects of PCP. The present study was conducted to examine the effects of PCP on prepulse inhibition in neuronal NOS (nNOS) deficient mice. PCP treatment caused a significant and dose-related increase in prepulse inhibition in nNOS-/- mice whereas prepulse inhibition was not significantly affected in +/+ and +/- mice. Basal prepulse inhibition level did not differ significantly between the groups. Furthermore, PCP caused a dose-related decrease in startle response reactivity in +/+ mice but did not significantly affect this measure in +/- and -/- mice. Basal startle response level did not differ between +/+ and +/- but was significantly lower in -/- mice. It is concluded that nNOS plays a role in the NO-sensitive effects of PCP.     

Gene–environment interactions in the aetiology of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease that displays a multitude of symptoms and a vast array of autoantibodies. The disease course may vary substantially between patients. The current understanding of SLE aetiology includes environmental factors acting on a genetically prone individual during an undetermined time period resulting in autoimmunity and finally surpassing that individual's disease threshold. Genetic differences and environmental factors may interact specifically in the pathogenetic processes and may influence disease development and modify the disease course. Identification of these factors and their interactions in the pathogenesis of SLE is vital in understanding the disease and may contribute to identify new treatment targets and perhaps also aid in disease prevention. However, there are several problems that need to be overcome, such as the protracted time frame of environmental influence, time dependent epigenetic alterations and the possibility that different pathogenetic pathways may result in a similar disease phenotype. This is mirrored by the relatively few studies that suggest specific gene-environment interactions. These include an association between SLE diagnosis and glutathion S-transferase gene variants combined with occupational sun exposure as well as variants of the N-acetyl transferase gene in combination with either aromatic amine exposure or hydralazine. With increased knowledge on SLE pathogenesis, the role of environmental factors and their genetic interactions may be further elucidated.     

High salivary secretory IgA antibody levels are associated with less late‐onset wheezing in IgE‐sensitized infants

To cite this article: Sandin A, Björkstén B, Böttcher MF, Englund E, Jenmalm MC, Bråbäck L. High salivary secretory IgA antibody levels are associated with less late‐onset wheezing in IgE‐sensitized infants. Pediatr Allergy Immunol 2011; 22 : 477–481. Low levels of secretory IgA (SIgA) and transient IgA deficiency have been associated with an increased risk for allergy, but data are conflicting. The aim was to assess the relationship between salivary SIgA antibody levels at 1 yr and wheezing at age four in a birth cohort, in particular the possible protective role of salivary SIgA in sensitized children. Saliva samples were obtained from all children (n = 67) with a positive skin prick test (SPT) at 1 yr and 212 children with a negative SPT. In all, 200 of these children responded to questionnaires at 4 yrs and 183 were skin prick tested at that age. The levels of salivary SIgA and salivary IgA antibodies to the most common food allergen egg and inhalant allergen cat were analyzed by ELISA. Serum was analyzed for IgE antibodies to egg and cat. Development of late‐onset wheezing was associated with low SIgA levels in children with positive SPT to at least one allergen both at 1 and 4 yrs of age (p = 0.04), as well as in children with circulating IgE antibodies to egg or cat at 1 yr (p = 0.02). None of nine persistently sensitized children with SIgA levels in the upper quartile developed wheezing, when compared to 10/20 children with lower levels (p = 0.01). Older siblings, more than three infections during infancy, at least one smoking parent, and male gender, were all associated with SIgA in the upper quartile. In conclusion, high levels of SIgA antibodies in sensitized infants were associated with significantly less late‐onset wheezing, supporting a protective role against development of asthmatic symptoms. Recurrent infections and other factors supporting an increased microbial pressure during infancy were associated with high levels of salivary SIgA.