Suitable test concentration of cobalt and concomitant reactivity to nickel and chromium: A multicentre study from the Swedish Contact Dermatitis Research Group.

BACKGROUND: In Sweden, cobalt chloride 0.5% has been included in the baseline series since the mid-1980s. A recent study from Stockholm showed that cobalt chloride 1% petrolatum (pet.) was more suitable than 0.5%. Cobalt chloride at 1.0% has been patch tested for decades in many European countries and around the world. OBJECTIVES: To study the suitability of patch testing to cobalt 1.0% vs 0.5% and to analyze the co-occurrence of allergy to cobalt, chromium, and nickel. RESULTS: Contact allergy to cobalt was shown in 90 patients (6.6%). Eighty (5.9%) patients tested positive to cobalt 1.0%. Thirty-seven of the 90 patients (41.1%) with cobalt allergy were missed by cobalt 0.5% and 10 (0.7%) were missed by cobalt 1.0% (P < .001). No case of patch test sensitization was reported. Allergy to chromium was seen in 2.6% and allergy to nickel in 13.3%. Solitary allergy to cobalt without nickel allergy was shown in 61.1% of cobalt-positive individuals. Female patients had larger proportions of positive reactions to cobalt (P = .036) and nickel (P < .001) than males. CONCLUSION: The results speak in favor of replacing cobalt chloride 0.5% with cobalt chloride 1.0% pet. in the Swedish baseline series, which will be done 2021.

Exposure to variable doses of nickel oxide nanoparticles disturbs serum biochemical parameters and oxidative stress biomarkers from vital organs of albino mice in a sex-specific manner.

INTRODUCTION: This study was designed to report the biological effect of nickel oxide nanoparticles (NiO NPs) in albino mice. MATERIAL AND METHODS: Five weeks old albino mice of both sex were intraperitoneally injected either with 20 mg (low dose) or 50 mg/mL saline/kg body weight (high dose) of NiO NPs for 14 days. Saline-treated controls were maintained in parallel. Complete blood count, selected serum biochemical parameters and oxidative stress biomarkers from vital organs were determined in all subjects. RESULTS: Male mice treated with NiO NPS had increased blood urea nitrogen, elevated superoxide dismutase (SOD) in liver elevated MDA in liver, kidney and heart and reduced catalase activity in heart and kidney. Female mice treated with NiO NPs had significantly reduced serum albumin and total proteins, SOD in lungs and elevated MDA in liver. DISCUSSION: We are reporting that intraperitoneal injections of NiO NPs for 14 days drastically affect blood serum parameters and oxidative stress biomarkers from vital organs of albino mice. CONCLUSION: Toxic effects of NiO NPs were dose and sex dependent and they were more pronounced at higher dose and in male mice.

Experience in patch testing: A 6-year retrospective review from a single academic allergy practice.

BACKGROUND: Patch testing is the "gold standard" to identify culprit allergen(s) causing allergic contact dermatitis (ACD), but there are limited studies of patch testing from allergy practice settings. OBJECTIVE: We sought to explore patch test findings in a large academic allergy practice, including patch testing results, history of atopy, location of dermatitis, and referral source. We also wanted to determine whether patch testing using an extended panel, such as the North American screening series, compared with a limited series, such as the Thin-Layer Rapid-Use Epicutaneous (T.R.U.E.) Test, increased the sensitivity. METHODS: A retrospective chart review was conducted of patients referred for patch testing over a 6-year period. RESULTS: A total of 585 patients (mean age 48.7 years, 71.6 % female) underwent patch testing over the 6-year period, of which 369 (63%) had a positive test. Of those who tested positive, 202 (55%) reported a history of atopy. The extremities were the most commonly involved site, followed by the head/neck and trunk. The 5 most common positive allergens were nickel sulfate, gold sodium thiosulfate, methylchloroisothiazolinone, thimerosal, and bacitracin. Three hundred fourteen (53.6%) patients were positive to at least 1 allergen on TRUE testing. Extended screening series identified an additional 10.8% of patients with positive tests who were negative to T.R.U.E. test allergens. CONCLUSION: Patch testing is a valuable diagnostic tool for the practicing allergist and provides early identification of culprit allergens in ACD. Performing an extended screening series such as the North American Contact Dermatitis Group (NACDG) or supplemental panel of allergens increased sensitivity when compared with a limited series.

Oral Nickel Changes of Intestinal Microflora in Mice.

Nickel, a silver-colored metal found in nature, is a common cause of allergic contact dermatitis. Nevertheless, the existence of inflammatory reaction to oral nickel exposure remains controversial. The following study investigates whether oral nickel can change the intestinal microflora in mice. A total of 20 female ICR mice were randomly divided into two groups: the oral nickel group (Group O) and the control group (Group C). Group O received water containing 400 µM NiSO4·6H2O, while group C was given pure water for 21 days. The content of nickel in the kidneys was determined by atomic absorption spectrophotometry, while the composition of bacterial community in the cecum was detected by 16S rDNA sequencing. The results were subsequently validated by real-time quantitative PCR with genus and species specific primers. Compared to Group C, significantly higher nickel levels were observed in Group O (P = 0.016); however, our data suggested that oral administration of 400 µM NiSO4·6H2O was nontoxic to the animals. (No statistical difference in body animal weight was found between Group O and Group C, before and after oral administration of nickel.) At the genus level, significantly higher relative abundance of Bacteroides (P = 0.016) and Intestinimonas (P = 0.018), and significantly lower relative abundance of Lachnospiraceae_NK4A136_group (P = 0.002) and Lachnospiraceae_UCG-001_group (P = 0.042) were observed in the oral nickel group compared to the control group. In addition, Group O had significantly lower ratio of Firmicutes/Bacteroides (P = 0.008). The results of real-time quantitative PCR further confirmed that the amplicon mass of Bacteroides and B. fragilis in the Group O was significantly higher compared to C group (P = 0.034 and P = 0.02). Oral nickel could change the intestinal microflora in mice, thus suggesting that oral nickel alters the interaction between the host and the intestinal flora.

Repeated oral dose toxicity study of nickel oxide nanoparticles in Wistar rats: a histological and biochemical perspective.

Despite the increasing use of nickel oxide (NiO) nanoparticles (NPs), limited information is available on their toxicological effects. Health consequences of 28 days repeated oral exposure to NiO NPs have not been explored thoroughly. Hence, toxicity investigations were performed after 28-day daily exposure in albino Wistar rats with NiO NPs following Organization for Economic Co-operation and Development test guideline 407. Histopathology, biochemical indices including oxidative stress and biodistribution patterns were evaluated to decipher the toxicological impact of NiO NPs. NiO NP characterization by transmission electron microscopy showed an average size of 12.9 (±3.4) nm. Histological studies depicted a prominent impact on the vital organs of the rats. A dose-dependent rise in both aminotransferase enzyme values was recorded in the homogenates of liver and kidney tissues. A significant decrease in superoxide dismutase activity and increase in catalase activity was noted. Further, a dose-dependent decrease in reduced glutathione content was recorded in rats, which suggested generation of reactive oxygen species and oxidative stress. Increase in the malondialdehyde levels was observed with an increase in the dose substantiating the antioxidant enzyme activity profiles. Biodistribution studies indicated maximum accumulation of Ni content in liver followed by kidney. Excretion of Ni was predominantly through feces and a little through renal clearance. Our study indicated that NiO NPs adversely alter the biochemical profile of the rats and cause histological damage. Further investigations are warranted to address the mechanism by which physiological path these NiO NPs exhibit their toxic nature in in vivo.

A seven-year retrospective analysis of patch test data in a cohort of patients with contact dermatitis in Sri Lanka.

BACKGROUND: Patch testing with a baseline series is a common tool employed when the sensitizing agent in contact dermatitis is unclear. However, for Asian countries, there are no locally validated baseline series to utilize in screening. METHODS: We completed a retrospective analysis of all patients that had undergone patch testing with the European Baseline series, Shoe Series or Comprehensive International Baseline series, over 7 years from 2012 to 2018 in a tertiary care reference dermatology clinic in Sri Lanka to evaluate the suitability of these investigations to identify causes for contact dermatitis in the local study population. RESULTS: Out of 438 patients tested, 239 (54.8%) reacted to at least one substance in the series. The Shoe Series was significantly more likely to yield a positive result than the European Baseline Series (70.2% vs 46.9%, p < 0.05). The top three sensitizers identified by all series were nickel sulfate (16%, 70/438), p-phenylenediamine (12.3%, 54/438) and 2-mercaptobenzothiazole or mercapto mix (10.5%, 46/438). CONCLUSION: Shoe series has a comparatively high yield in the local population compared to European Baseline series. Since little less than half of the study population did not have any reactivity to any of the allergens tested it is important to develop or modify and validate a locally relevant, more suitable baseline series which is based on the Shoe Series in Sri Lanka. This is further evidence for the continuously changing nature of allergens in the environment and the need to modify existing patch testing standards accordingly.

Short contact with nickel causes allergic contact dermatitis: an experimental study.

BACKGROUND: Knowledge about the required duration of exposure for elicitation of allergic nickel dermatitis in nickel-allergic individuals is limited. However, it often has been proposed that short skin contact is safe. OBJECTIVES: To examine whether repeated skin contact with nickel over short time periods (3 × 10 min) can elicit allergic nickel dermatitis. METHODS: Sixteen nickel-allergic adults and 10 controls were exposed to, respectively, nickel- and aluminium-containing discs on each volar forearm and on each earlobe for 3 × 10 min. One arm was pretreated for 24 h with sodium lauryl sulfate (SLS) 0·5% under occlusion before exposure. One aluminium and one nickel exposure site were clinically evaluated, and blood flow was measured with laser Doppler flowmetry at day 2 and day 4. RESULTS: Ten of 16 (63%) nickel-allergic participants developed allergic nickel dermatitis on SLS-pretreated arm skin and three of 16 (19%) developed it on normal skin on the earlobe. On the SLS-pretreated arms of nickel-allergic participants, blood flow increased significantly more on the nickel-exposed skin than on the aluminium-exposed skin on days 2 and 4. No change in clinical reactivity or blood flow was found on normal forearm skin in nickel-allergic participants or on any skin in controls. CONCLUSIONS: This experimental study showed that relatively short repeated skin contact (3 × 10 min) with metallic nickel elicits allergic nickel dermatitis in irritated skin and at sites with previous dermatitis. The results support the restrictions in current nickel regulation.

Biochemical alterations induced by nickel oxide nanoparticles in female Wistar albino rats after acute oral exposure.

CONTEXT: Nickel oxide (NiO) nanoparticles (NPs) with appropriate surface chemistry have been widely used for their potential new applications in biomedical industry. Increased usage of these NPs enhances the chance of exposure of personnel involved in the work place. OBJECTIVE: This study was designed to assess the ability of NiO NPs to cause biochemical alterations post-acute oral exposure in female Wistar rats. MATERIALS AND METHODS: Rats were administered with 125, 250, and 500 mg/kg doses of NiO NPs for haematological, biochemical, and histopathological studies. Biodistribution patterns of NiO NPs in female Wistar rats were also monitored. RESULTS: NiO NPs caused significant (p < 0.01) inhibition of RBC and brain AchE of treated rats at the high dose. Activation of the hepatotoxicity marker enzymes, aminotransferases, was recorded in serum and liver, whereas inhibition was observed in kidney. The activity of antioxidant enzymes was also altered by NiO NPs in a dose-dependent manner and found to be significant at the high dose of exposure. CONCLUSIONS: This study revealed that exposure to nanosized NiO particles at acute doses may cause adverse changes in animal biochemical profiles. Further, the in vivo studies on toxicity evaluation help in biomonitoring of the potential contaminants.

Does clinical testing support the current guidance definition of prolonged contact for nickel allergy?

BACKGROUND: The European Chemical Agency (ECHA) definition of prolonged contact was introduced in 2014 and has not been evaluated clinically. OBJECTIVES: To assess whether nickel-sensitized individuals react on patch testing with high nickel-releasing metal discs for short and repetitive periods. MATERIALS AND METHODS: We patch tested 45 nickel-sensitized individuals double-blind with 2 different types of high nickel-releasing discs for 10, 30 and 60 minutes on 3 occasions over a period of 2 weeks, and for 1 longer period. Discs were tested for nickel release. RESULTS: Nickel release from both discs significantly exceeded the 0.5 µg Ni/cm2 /week limit of the EU REACH nickel restriction. However, only 1 individual tested had a largely dose-dependent allergic reaction. CONCLUSIONS: The majority of nickel-allergic subjects did not react to nickel discs after 2 hours or after repetitive exposures of up to 30 minutes on 3 occasions over a period of 2 weeks. The length of time needed to cause nickel allergic contact dermatitis in most nickel-allergic individuals is longer than the ECHA guidance definition. Longer test times are needed to define the time required to cause dermatitis in most nickel-allergic individuals. As a limitation, the test conditions did not adequately assess real-life factors such as friction, which is relevant for some uses of nickel.

Investigation into the pulmonary inflammopathology of exposure to nickel oxide nanoparticles in mice.

We investigated the effects of nickel oxide nanoparticles (NiONPs) on the pulmonary inflammopathology. NiONPs were intratracheally installed into mice, and lung injury and inflammation were evaluated between 1 and 28 days. NiONPs caused significant increases in LDH, total protein, and IL-6 and a decrease in IL-10 in the BALF and increases in 8-OHdG and caspase-3 in lung tissues at 24 h. Airway inflammation was present in a dose-dependent manner from the upper to lower airways at 24 h of exposure as analyzed by SPECT. Lung parenchyma inflammation and small airway inflammation were observed by CT after NiONP exposure. 8-OHdG in lung tissues had increased with formation of fibrosis at 28 days. Focal adhesion was the most important pathways identified at 24 h as determined by protemics, whereas glutathione metabolism was the most important identified at 28 days. Our results demonstrated the pulmonary inflammopathology caused by NiONPs based on image-to-biochemical approaches.

Quality aspects of ex vivo root canal treatments done by undergraduate dental students using four different endodontic treatment systems.

OBJECTIVE: To evaluate factors associated with treatment quality of ex vivo root canal treatments performed by undergraduate dental students using different endodontic treatment systems. MATERIAL AND METHODS: Four students performed root canal treatment on 80 extracted human teeth using four endodontic treatment systems in designated treatment order following a Latin square design. Lateral seal and length of root canal fillings was radiographically assessed; for lateral seal, a graded visual scale was used. Treatment time was measured separately for access preparation, biomechanical root canal preparation, obturation and for the total procedure. Mishaps were registered. An ANOVA mirroring the Latin square design was performed. RESULTS: Use of machine-driven nickel-titanium systems resulted in overall better quality scores for lateral seal than use of the manual stainless-steel system. Among systems with machine-driven files, scores did not significantly differ. Use of machine-driven instruments resulted in shorter treatment time than manual instrumentation. Machine-driven systems with few files achieved shorter treatment times. With increasing number of treatments, root canal-filling quality increased, treatment time decreased; a learning curve was plotted. No root canal shaping file separated. CONCLUSIONS: The use of endodontic treatment systems with machine-driven files led to higher quality lateral seal compared to the manual system. The three contemporary machine-driven systems delivered comparable results regarding quality of root canal fillings; they were safe to use and provided a more efficient workflow than the manual technique. Increasing experience had a positive impact on the quality of root canal fillings while treatment time decreased.

Nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex can inhibit Ehrlich solid tumor growth in mice: A potential new antitumor drug.

The chief chemotherapeutic drug, cisplatin had common bad effects such as nephrotoxicity, ototoxicity and bone marrow depression. This led us to develop a new potential anticancer drug based on nickel metal ion that may be less toxic. Nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex cytoprotective effect, superoxide dismutase (SOD)-like activity and anticancer activities were studied. In vitro, the complex showed SOD-like activity of 86.62%. It was capable to kill 90.2% of Ehrlich ascites carcinoma (EAC) cells and to protect 92.48% of human RBCs. In vivo, the complex lowered the tumor burden markedly in a concentration-dependent manner. Noticeably, solid tumor growth was suppressed; tumor volume and weight were reduced and mice life span was lengthened. The hematological indices were improved, catalase activity was re-elevated and malondialdehyde (MDA) level was reversed towards normal. Nucleic acids, cholesterol, triglycerides, liver enzymes, urea and creatinine contents were reduced to near normal ranges. Glutathione (GSH), SOD, albumin and total protein levels were increased. In conclusion, our results revealed that the complex has the ability to suppress Ehrlich solid tumor growth in mice with minimal side effects. This may possibly via its redox activity. Surprisingly, nickel complex antitumor activities were more potent than those of cisplatin.

Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure.

T cell mediated hypersensitivity to nickel (Ni2+) is one of the most common causes of allergic contact dermatitis. Ni2+ sensitization may also contribute to the failure of Ni2+ containing joint implants, and revision to non-Ni2+ containing hardware can be costly and debilitating. Previously, we identified Ni2+ mimotope peptides, which are reactive to a CD4+ T cell clone, ANi2.3 (Vα1, Vß17), isolated from a Ni2+ hypersensitive patient with contact dermatitis. This T cell is restricted to the major histocompatibility complex class II (MHCII) molecule, Human Leukocyte Antigen (HLA)-DR52c (DRA, DRB3*0301). However, it is not known if Ni2+ induced T cell responses in sensitized joint replacement failure patients are similar to subjects with Ni2+ induced contact dermatitis. Here, we generated DR52c/Ni2+ mimotope tetramers, and used them to test if the same Ni2+ T cell activation mechanism could be generalized to Ni2+ sensitized patients with associated joint implant failure. We confirmed the specificity of these tetramers by staining of ANi2.3T cell transfectomas. The DR52c/Ni2+ mimotope tetramer detected Ni2+ reactive CD4+ T cells in the peripheral blood mononuclear cells (PBMC) of patients identified as Ni2+ sensitized by patch testing and a positive Ni2+ LPT. When HLA-typed by a DR52 specific antibody, three out of four patients were DR52 positive. In one patient, Ni2+ stimulation induced the expansion of Vß17 positive CD4+ T cells from 0.8% to 13.3%. We found that the percentage of DR52 positivity and Vß17 usage in Ni2+ sensitized joint failure patients are similar to Ni sensitized skin allergy patients. Ni2+ independent mimotope tetramers may be a useful tool to identify the Ni2+ reactive CD4+ T cells.

Kinetics and dissolution of intratracheally administered nickel oxide nanomaterials in rats.

BACKGROUND: The toxicokinetics of nanomaterials are an important factor in toxicity, which may be affected by slow clearance and/or distribution in the body. METHODS: Four types of nickel oxide (NiO) nanoparticles were single-administered intratracheally to male F344 rats at three doses of 0.67-6.0 mg/kg body weight. The rats were sacrificed under anesthesia and the lung, thoracic lymph nodes, bronchoalveolar lavage fluid, liver, and other organs were sampled for Ni burden measurement 3, 28, and 91 days post-administration; Ni excretion was measured 6 and 24 h after administration. Solubility of NiO nanoparticles was determined using artificial lysosomal fluid, artificial interstitial fluid, hydrogen peroxide solution, pure water, and saline. In addition, macrophage migration to trachea and phagosome-lysosome-fusion rate constants were estimated using pulmonary clearance and dissolution rate constants. RESULTS: The wire-like NiO nanoparticles were 100% dissolved by 24 h when mixed with artificial lysosomal fluid (dissolution rate coefficient: 0.18/h); spherical NiO nanoparticles were 12% and 35% dissolved after 216 h when mixed with artificial lysosomal fluid (1.4 × 10-3 and 4.9 × 10-3/h). The largest irregular-shaped NiO nanoparticles hardly dissolved in any solution, including artificial lysosomal fluid (7.8 × 10-5/h). Pulmonary clearance rate constants, estimated using a one-compartment model, were much higher for the NiO nanoparticles with a wire-shape (0.069-0.078/day) than for the spherical and irregular-shaped NiO nanoparticles (0-0.012/day). Pulmonary clearance rate constants of the largest irregular-shaped NiO nanoparticles showed an inverse correlation with dose. Translocation of NiO from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner for three spherical and irregular-shaped NiO nanoparticles, but not for the wire-like NiO nanoparticles. Thirty-five percent of the wire-like NiO nanoparticles were excreted in the first 24 h after administration; excretion was 0.33-3.6% in that time frame for the spherical and irregular-shaped NiO nanoparticles. CONCLUSION: These findings suggest that nanomaterial solubility differences can result in variations in their pulmonary clearance. Nanoparticles with moderate lysosomal solubility may induce persistent pulmonary inflammation.

Evaluation of various filling techniques in distal canals of mandibular molars instrumented with different single-file nickel-titanium systems.

BACKGROUND AND AIMS: The aim of this study was to evaluate the quality of various filling techniques in distal canals of mandibular molars instrumented with different single-file nickel-titanium (NiTi) systems. MATERIALS AND METHODS: A total of 150 distal roots of mandibular molar teeth were randomly assigned into three main groups and instrumented by using Reciproc (VDW, Munich, Germany), WaveOne (Dentsply Tulsa, Tulsa, OK, USA), or One Shape (MicroMega, Besancon, France) NiTi file systems. The roots were then treated using one of five filling techniques: (1) Matched-single-cone, (2) cold lateral compaction with matched gutta-percha (GP) cone, (3) Thermafil filling, (4) System B/Obtura II, and (5) lateral compaction with standardized GP cones. The roots were then sectioned at three levels (coronal, middle, and apical). Photographs were acquired under a stereomicroscope, and the percentage of GP-filled areas (PGFAs), percentage of sealer-filled areas (PSFAs), and voids were measured using the ImageJ software. Comparisons between groups were applied using Student's t-test or one-way ANOVA for normally distributed data. The Mann-Whitney U-test or Kruskal-Wallis test was used when variables were not normally distributed. RESULTS: Canals filled with the System B/Obtura showed the highest PGFA and lowest PSFA, whereas those filled with matched-single-cone showed the highest PSFA and lowest PGFA (P < 0.05). The cold lateral compaction with matched GP cone group, lateral compaction group, and Thermafil filling group showed no statistically significant differences in PSFA and PGFA (P > 0.05). CONCLUSIONS: System B/Obtura technique appears to be the best technique to properly fill root canals, whereas the matched-single-cone technique in oval-shaped distal canals of mandibular molars was inadequate.

Indium oxide (In2O3) nanoparticles induce progressive lung injury distinct from lung injuries by copper oxide (CuO) and nickel oxide (NiO) nanoparticles.

Indium is an essential element in the manufacture of liquid crystal displays and other electronic devices, and several forms of indium compounds have been developed, including nanopowders, films, nanowires, and indium metal complexes. Although there are several reports on lung injury caused by indium-containing compounds, the toxicity of nanoscale indium oxide (In2O3) particles has not been reported. Here, we compared lung injury induced by a single exposure to In2O3 nanoparticles (NPs) to that caused by benchmark high-toxicity nickel oxide (NiO) and copper oxide (CuO) NPs. In2O3 NPs at doses of 7.5, 30, and 90 cm(2)/rat (50, 200, and 600 µg/rat) were administered to 6-week-old female Wistar rats via pharyngeal aspiration, and lung inflammation was evaluated 1, 3, 14, and 28 days after treatment. Neutrophilic inflammation was observed on day 1 and worsened until day 28, and severe pulmonary alveolar proteinosis (PAP) was observed on post-aspiration days 14 and 28. In contrast, pharyngeal aspiration of NiO NPs showed severe neutrophilic inflammation on day 1 and lymphocytic inflammation with PAP on day 28. Pharyngeal aspiration of CuO NPs showed severe neutrophilic inflammation on day 1, but symptoms were completely resolved after 14 days and no PAP was observed. The dose of In2O3 NPs that produced progressive neutrophilic inflammation and PAP was much less than the doses of other toxic particles that produced this effect, including crystalline silica and NiO NPs. These results suggest that occupational exposure to In2O3 NPs can cause severe lung injury.

Apoptotic mechanisms of N1-acetylacetone, N4-4-methoxy-salicylidene-thiosemicarbazide chelating with Nickel(II) on HL60 leukemia cells.

Thiosemicarbozone complexes that have a broad spectrum of biological activity are formed as a result of condensation reaction between thiosemicarbazide [H2N(C=S)-NH-NH2] and carbonyl-containing compounds. A new Nickel(II) complexes with N1-acetylacetone, N4-4-methoxy-salicylidene-thiosemicarbazidato ligand was synthesized and characterized. We studied the antileukemic activity of the Ni(II) thiosemicarbazone compound and assessed their potential for drug development. Specifically, the effects of this Ni(II) thiosemicarbazone compound on intracellular signal nodes and apoptotic pathways were investigated. According to our results, the Ni(II) thiosemicarbazone compound has apoptotic activity against HL60 cells. Moreover, while Ni(II) thiosemicarbazone compound significantly increased levels of p53 and cleaved caspase-3 proteins, it decreased level of Phospho-Akt1 protein in HL60 cells. The Ni(II) thiosemicarbazone compound could induce HL60 cell apoptosis through inhibiting of PI3K/Akt pathway. These results showed that Ni(II) thiosemicarbozone compound might be an antileukemic agent.

Neuronal effects of a nickel-piperazine/NO donor complex in rodents.

In the brain, NO is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also importantly involved in many neuronal functions and innumerable roles of NO in many brain related disorders including epilepsy, schizophrenia, drug addiction, anxiety, major depression, have been postulated. The present study aimed to explore the neuronal role exerted by the metal-nonoate compound Ni(PipNONO)Cl, a novel NO donor whose vascular protective effects have been recently demonstrated. Ni(PipNONO)Cl showed antidepressant-like properties in the tail suspension test and antiamnesic activity in the passive avoidance test in the absence of any hypernociceptive response to a mechanical stimulus. These effects were related to the NO-releasing properties of the compound within the central nervous system as demonstrated by the increase of iNOS levels in the brain, spinal cord and dura mater. The modulation of neuronal functions appeared after acute and repeated treatment, showing the lack of any tolerance to neuronal effects. At the dose used (10 mg/kg i.p.), Ni(PipNONO)Cl did not induce any visible sign of toxicity and experiments were performed in the absence of locomotor impairments. In addition to the NO-related neuronal activities of Ni(PipNONO)Cl, the decomposition control compound Ni(Pip)Cl2 showed anxiogenic-like and procognitive effects. The present findings showed neuronal modulatory activity of Ni(PipNONO)Cl through a NO-mediated mechanism. The activities of the decomposition compound Ni(Pip)Cl2 attributed to Ni(PipNONO)Cl the capability to modulate additional neuronal functions independently from NO releasing properties extending and improving the therapeutic perspectives of the NO donor.

Short and frequent skin contact with nickel.

BACKGROUND: The existing EU nickel restriction does not sufficiently protect the population from skin exposure to nickel. Better understanding is needed of the extent to which short and frequent contact with nickel-releasing items contributes to nickel deposition on skin. OBJECTIVES: To quantify nickel skin exposure from short and frequent contact with nickel-releasing materials. MATERIALS/METHODS: Sequences of short contact events were assessed in (i) touch tests for measurement of nickel skin dose, (ii) wipe tests to similarly quantify the nickel release during a touch, and (iii) immersion tests in artificial sweat, for nickel-containing alloys and pure nickel. RESULTS: Nickel skin doses from a single touch were 0.024-4.7 µg/cm(2) for all materials. Touching or wiping five untouched surfaces resulted in more accumulated nickel than five repeated touches of the same surface. The released amounts of nickel were generally lower at immersion, but increased with the number of repeated immersion periods. CONCLUSIONS: Nickel skin doses were quantified after one single touch for all study materials. Touch tests, and potentially wipe tests as a proxy for skin dose measurements, are preferred to immersion tests for the assessment of short and frequent skin contact with nickel.