UV-radiation, apoptosis and skin

Apoptosis or programmed cell death is a key function in regulating skin development, homeostasis and tumorigenesis. The epidermis is exposed to various external stimuli and one of the most important is UV radiation. The UVA and UVB spectra differ in their biological effects and in their depth of penetration through the skin layers. UVB rays are absorbed directly by DNA which results in its damage. UVA can also cause DNA damage but primarily by the generation of reactive oxygen species. By eliminating photodamaged cells, apoptosis has an important function in the prevention of epidermal carcinogenesis. UV-induced apoptosis is a complex event involving different pathways. These include: 1. activation of the tumour suppressor gene p53; 2. triggering of cell death receptors directly by UV or by autocrine release of death ligands; 3. mitochondrial damage and cytochrome C release. The extrinsic pathway through death receptors such as fibroblast-associated, tumour necrosis factor receptor and TNF related apoptosis inducing ligand receptor activate caspase cascade. The intrinsic or mitochondrial pathway of apoptosis is regulated by the Bcl-2 family of proteins, anti-apoptotic (Bcl-2, Bcl-xl, Bcl-w) and the pro-apoptotic (Bax, Bak, Bid). The balance between the pro-apoptotic and anti-apoptotic proteins determines cell survival or death. We discuss recent findings in the molecular mechanisms of UV induced apoptosis.     

Protection against solar ultraviolet radiation in childhood

In the last decade, awareness of the harmful effects of solar ultraviolet radiation has increased. Modern lifestyles, outdoor occupations, sports and other activities make total sun avoidance impossible. Children spend more time outdoors than adults and there is compelling evidence that childhood is a particularly vulnerable time for the photocarcinogenic effects of the sun. Sun exposure among infants and pre-school age children is largely depend on the discretion of adult care providers. It is important to learn safe habits about sun-safety behaviours during the childhood. Children deserve to live and play in safe environments, and it is the responsibility of every adult to help children stay safe. Protecting children from excessive sun exposure is protection from sunburn today and other forms of sun damages, especially skin cancers, in the future.     

Henoch-Schönlein purpura complicated by appendicitis, intussusception and ureteritis

Henoch-Sch?nlein purpura (HSP) is the most common childhood systemic small-vessel vasculitis with skin, joint, gastrointestinal (GI) and renal involvement. Uncommon GI complications are intussusception, bowel perforation and rarely reported appendicitis. HSP-associated stenosing ureteritis represents a rare and potentially serious complication. We present a 5-year-old boy with severe and prolonged course of HSP and three very rare complications that occurred sequentially: appendicitis, intussusception and ureteritis. Only three days after admission, he developed clinical signs of acute appendicitis indicating surgical intervention. Histological analysis of excised appendix showed inflammation but without signs typical for vasculitis. Two weeks later, with the reccurence of HSP he again developed clinical picture of acute abdomen. Ultrasound and radiologic evaluation demonstrated ileo-ileal intussusception and the second laparotomy was undertaken. Histological analysis of the resected bowel tissue showed typical signs of leucocytoclastic vasculitis. In the fourth week of his illness, serial urinalysis showed nephritic urinary sediment indicative of renal involvement. Unexpectedly, control abdominal ultrasound demonstrated mild hydronephrosis of the left kidney, not seen on previous ultrasound evaluations. Undertaken excretory urography and computed tomography (CT) scan showed stenosis of upper/ midureter with mild dilation of upper part of the left ureter suggesting unilateral HSP-associated stenosing ureteritis. Eventually, the patient was discharged and closely followed-up for the next two years. He had no further reccurence of HSP, the urinalysis normalized after six months, while mild unilateral hydronephrosis remained unchanged. Our search of the literature did not show reports of HSP complicated by appendicitis, intussusception and ureteritis, and to our knowledge this is the first case with three different illness events that occured sequentially. We emphasize the necessity of repeated ultrasound evaluations in the course of HSR especially in cases with severe GI and renal invovement.     

Solution and solid-state studies of complexation of transition-metal cations and Al(III) by aroylhydrazones derived from nicotinic acid hydrazide

Reactions of first series transition-metal cations, Cd(II) and Al(III) with two aroylhydrazones derived from nicotinic acid hydrazide and salicylaldehyde or o-vanillin were studied at 25 °C in buffered dioxane/water 1/1 mixture (pH 5.8) by means of spectrophotometric and spectrofluorimetric titrations. The addition of Mn(II) or Cd(II) ions in hydrazone solutions had no effect on their absorption spectra whereas the addition of Ni(II) and Cr(III) immediately caused precipitation. The reaction of Zn(II) with salicylaldehyde derivative was found to be photosensitive. Relatively high conditional stability constants of 1:1 complexes of Cu(II), Zn(II) and Al(III) with both ligands were determined. Solid complexes of Cu(II), Ni(II) and Zn(II) with aroylhydrazones studied were isolated and characterized by elemental and thermogravimetric analyses, magnetic susceptibility measurements (in the case of Cu(II) and Ni(II)) and IR spectrometry.     

The Bloom's syndrome helicase (BLM) interacts physically and functionally with p12, the smallest subunit of human DNA polymerase delta

Bloom's syndrome (BS) is a cancer predisposition disorder caused by mutation of the BLM gene, encoding a member of the RecQ helicase family. Although the phenotype of BS cells is suggestive of a role for BLM in repair of stalled or damaged replication forks, thus far there has been no direct evidence that BLM associates with any of the three human replicative DNA polymerases. Here, we show that BLM interacts specifically in vitro and in vivo with p12, the smallest subunit of human POL δ (hPOL δ). The hPOL δ enzyme, as well as the isolated p12 subunit, stimulates the DNA helicase activity of BLM. Conversely, BLM stimulates hPOL δ strand displacement activity. Our results provide the first functional link between BLM and the replicative machinery in human cells, and suggest that BLM might be recruited to sites of disrupted replication through an interaction with hPOL δ. Finally, our data also define a novel role for the poorly characterized p12 subunit of hPOL δ.     

Calcium-dependent antibacterial activity of donkey’s milk against <Emphasis Type="Italic">Salmonella</Emphasis>

The aim of this study was to examine the antibacterial activity of raw donkey’s milk (DM) against Salmonella Enteritidis and Salmonella Typhimurium as well as to determine the dependence of this antibacterial activity on calcium, lysozyme and lactoferrin content. Antibacterial assays were conducted in DM artificially contaminated with these Salmonella serotypes and then incubated at 38 °C for 8 hours. Calcium concentration was found to have a strong influence on the antibacterial activity of the contaminated DM samples supplemented with CaCl₂ and EDTA. The antibacterial activity of DM against the tested Salmonella strains was observed to be strongly calcium dependent, with the addition of CaCl₂ to DM samples improving its antibacterial potential against both pathogens. Salmonella Enteritidis appeared to be less sensitive to the antimicrobial agents in DM than S. Typhimurium. One explanation is the calcium-dependant antibacterial activity of DM is attributable to the calcium-binding ability of its lysozyme. Lysozyme may be the main antibacterial agent, most probably via a nonenzymatic mode of action against tested Salmonella strains.     

Effect of Selenium Pre-treatment on Antioxidative Enzymes and Lipid Peroxidation in Cd-exposed Suckling Rats

Since there are no data about the protective role of selenium (Se) against cadmium (Cd)-induced oxidative damage in early life, we studied the effect of Se supplementation on antioxidative enzyme activity and lipid peroxidation (through thiobarbituric acid reactive substances; TBARS) in suckling Wistar rats exposed to Cd. Treated animals received either Se alone for 9 days (8 μmol, i.e., 0.6 mg Se as Na₂SeO₃ kg⁻¹ b.w., daily, orally; Se group), Cd alone for 5 days (8 μmol, i.e., 0.9 mg Cd as CdCl₂ kg⁻¹ b.w., daily, orally; Cd group), or pre-treatment with Se for 4 days and then co-treatment with Cd for the following 5 days (Se + Cd group). Our results showed that selenium supplementation, with and without Cd, increased SOD activity in the brain and kidney, but not in the liver and GSH-Px activity across all tissues compared to control rats receiving distilled water. Relative to the Cd group, Se + Cd group had higher kidney and brain SOD and GSH-Px activity (but not the liver), while in the liver caused increased and in the brain decreased TBARS level. These results suggest that Se stimulates antioxidative enzymes in immature kidney and brain of Cd-exposed rats and could protect against oxidative damage.     

The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia

The eotaxin chemokines have been implicated in allergen-induced eosinophil responses in the lung. However, the individual and combined contribution of each of the individual eotaxins is not well defined. We aimed to examine the consequences of genetically ablating eotaxin-1 or eotaxin-2 alone, eotaxin-1 and eotaxin-2 together, and CCR3. Mice carrying targeted deletions of these individual or combined genes were subjected to an OVA-induced experimental asthma model. Analysis of airway (luminal) eosinophilia revealed a dominant role for eotaxin-2 and a synergistic reduction in eotaxin-1/2 double-deficient (DKO) and CCR3-deficient mice. Examination of pulmonary tissue eosinophilia revealed a modest role for individually ablated eotaxin-1 or eotaxin-2. However, eotaxin-1/2 DKO mice had a marked decrease in tissue eosinophilia approaching the low levels seen in CCR3-deficient mice. Notably, the organized accumulation of eosinophils in the peribronchial and perivascular regions of allergen-challenged wild-type mice was lost in eotaxin-1/2 DKO and CCR3-deficient mice. Mechanistic analysis revealed distinct expression of eotaxin-2 in bronchoalveolar lavage fluid cells consistent with macrophages. Taken together, these results provide definitive evidence for a fundamental role of the eotaxin/CCR3 pathway in eosinophil recruitment in experimental asthma. These results imply that successful blockade of Ag-induced pulmonary eosinophilia will require antagonism of multiple CCR3 ligands.