Vitamin D alleviates cognitive dysfunction and brain damage induced by copper sulfate intake in experimental rats: focus on its combination with donepezil.

This study aimed to demonstrate the potential benefits of donepezil (DPZ) and vitamin D (Vit D) in combination to counteract the neurodegenerative disorders induced by CuSO4 intake in experimental rats. Neurodegeneration (Alzheimer-like) was induced in twenty-four male Wistar albino rats by CuSO4 supplement to drinking water (10 mg/L) for 14 weeks. AD rats were divided into four groups: untreated AD group (Cu-AD) and three treated AD groups; orally treated for 4 weeks with either DPZ (10 mg/kg/day), Vit D (500 IU/kg/day), or DPZ + Vit D starting from the 10th week of CuSO4 intake. Another six rats were used as normal control (NC) group. The hippocampal tissue content of ß-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 and the cortical content of acetylcholine (Ach), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. Cognitive function tests (Y-maze) and histopathology studies (hematoxylin and eosin and Congo red stains) and immunohistochemistry for neurofilament. Vit D supplementation alleviated CuSO4-induced memory deficits including significant reduction hippocampal BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α and cortical AChE and MDA. Vit D remarkably increased cortical Ach, TAC, and hippocampal Bcl-2. It also improved neurobehavioral and histological abnormalities. The effects attained by Vit D treatment were better than those attained by DPZ. Furthermore, Vit D boosted the therapeutic potential of DPZ in almost all AD associated behavioral and pathological changes. Vit D is suggested as a potential therapy to retard neurodegeneration.

CG Demethylation Leads to Sequence Mutations in an Anther Culture of Barley Due to the Presence of Cu, Ag Ions in the Medium and Culture Time.

During plant tissue cultures the changes affecting regenerants have a broad range of genetic and epigenetic implications. These changes can be seen at the DNA methylation and sequence variation levels. In light of the latest studies, DNA methylation change plays an essential role in determining doubled haploid (DH) regenerants. The present study focuses on exploring the relationship between DNA methylation in CG and CHG contexts, and sequence variation, mediated by microelements (CuSO4 and AgNO3) supplemented during barley anther incubation on induction medium. To estimate such a relationship, a mediation analysis was used based on the results previously obtained through metAFLP method. Here, an interaction was observed between DNA demethylation in the context of CG and the time of culture. It was also noted that the reduction in DNA methylation was associated with a total decrease in the amount of Cu and Ag ions in the induction medium. Moreover, the total increase in Cu and Ag ions increased sequence variation. The importance of the time of tissue culture in the light of the observed changes resulted from the grouping of regenerants obtained after incubation on the induction medium for 28 days. The present study demonstrated that under a relatively short time of tissue culture (28 days), the multiplication of the Cu2+ and Ag+ ion concentrations ('Cu*Ag') acts as a mediator of demethylation in CG context. Change (increase) in the demethylation in CG sequence results in the decrease of 'Cu*Ag', and that change induces sequence variation equal to the value of the indirect effect. Thus, Cu and Ag ions mediate sequence variation. It seems that the observed changes at the level of methylation and DNA sequence may accompany the transition from direct to indirect embryogenesis.

The Activation of Heat-Shock Protein After Copper(II) and/or Arsenic(III)-Induced Imbalance of Homeostasis, Inflammatory Response in Chicken Rectum.

Arsenic and copper, two toxic pollutants, are powerful inducers of oxidative stress. Exposure to copper and arsenic can cause intestinal injury in cockerel. This study was carried out to investigate the effects of these two pollutants on the gastrointestinal tract of cockerels. Experimental results showed that the activity of antioxidant enzymes (catalase and glutathione peroxidase) was inhibited and the ionic balance was destroyed after exposure to copper sulfate (300 mg/kg) and/or arsenic trioxide (30 mg/kg). However, the expression of pro-inflammatory cytokines (nuclear factor kappa-B, cyclooxygenase-2, tumor necrosis factor-α, and prostaglandin E2 synthases) increased markedly. Damages to the biofilm structure and inflammatory cell infiltration were simultaneously observed during histological examination. Heat-shock proteins were also expressed in large quantities after exposure to the poisons. Collectively, exposure to arsenite and/or Cu2+ can cause rectal damage in cockerels, inducing inflammation and an imbalance in immune system responses. Sometimes, exposure to both pollutants can produce even more toxic effects. Heat-shock proteins can protect the tissue from the exotoxins but the specific mechanisms require exploration. After oral ingestion of toxins, the rectum can still be damaged, necessitating attention to the safety of poultry breeding, human food safety, and environmental protection.

Interventions for treating phosphorus burns.

BACKGROUND: Phosphorus burns are rarely encountered in usual clinical practice and occur mostly in military and industrial settings. However, these burns can be fatal, even with minimal burn area, and are often associated with prolonged hospitalisation. OBJECTIVES: To summarise the evidence of effects (beneficial and harmful) of all interventions for treating people with phosphorus burns. SEARCH METHODS: In October 2013 for this first update we searched the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library);Ovid OLDMEDLINE; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL and Conference Proceedings Citation Index - Science (CPCI-S). We did not apply any methodological filters or restrictions on the basis of study design, language, date of publication or publication status. SELECTION CRITERIA: Any comparisons of different ways of managing phosphorus burns including, but not restricted, to randomised trials. DATA COLLECTION AND ANALYSIS: We found two non-randomised comparative studies, both comparing patients treated with and without copper sulphate. MAIN RESULTS: These two comparative studies provide no evidence to support the use of copper sulphate in managing phosphorus burns. Indeed the small amount of available evidence suggests that it may be harmful. AUTHORS' CONCLUSIONS: First aid for phosphorus burns involves the common sense measures of acting promptly to remove the patient's clothes, irrigating the wound(s) with water or saline continuously, and removing phosphorus particles. There is no evidence that using copper sulphate to assist visualisation of phosphorus particles for removal is associated with better outcome, and some evidence that systemic absorption of copper sulphate may be harmful. We have so far been unable to identify any other comparisons relevant to informing other aspects of the care of patients with phosphorus burns. Future versions of this review will take account of information in articles published in languages other than English, which may contain additional evidence based on treatment comparisons.

Effect of a tea tree oil and organic acid footbath solution on digital dermatitis in dairy cows.

Copper sulfate is the industry gold standard footbath ingredient for controlling dairy cow digital dermatitis. However, when used footbath solutions are deposited on soil, high levels of copper in the soil may result, which can have toxic and negative effects on plant growth. An alternative to copper sulfate is Provita Hoofsure Endurance (Provita Eurotech Ltd., Omagh, UK), which is a biodegradable solution containing organic acids, tea tree oil, and wetting agents. The objective of this study was to quantify changes in digital dermatitis frequency when using Provita Hoofsure Endurance and copper sulfate in a split footbath in 3 commercial dairy herds. This study was conducted from January 5, 2012, to March 19, 2012, in 3 commercial Kentucky dairies with 120, 170, and 200 milking Holstein cows. None of the herds was using a footbath for digital dermatitis control before the study. Footbath solutions were delivered using a split footbath. During the study, a 3% Hoofsure Endurance solution for the left hooves and a 5% copper sulfate solution for the right hooves was used. Digital dermatitis was scored every 3wk using the M0 to M4 system, where M0=a claw free of signs of digital dermatitis; M1=a lesion <2cm that is not painful; M2=the ulcerative stage, with lesion diameter of >2cm, and painful to the touch; M3=the healing stage and covered by a scab; and M4=the chronic stage and characterized by dyskeratosis or proliferation of the surface that is generally not painful. McNemar's test statistic suggested that a statistically significant difference existed in the proportions of M1 and M2 lesions between the beginning and end of the study for both treatments. This indicates that each solution was effective in decreasing the proportion of M1 or M2 lesions from baseline to the last time point. A chi-square test calculated using PROC FREQUENCY of SAS (SAS Institute Inc., Cary, NC) indicated that no statistically significant relationship existed between the treatments among changes in digital dermatitis frequency from the baseline to the end of the study. Performance of the 2 footbath solutions was comparable throughout the study. No significant differences were observed between the copper sulfate and Provita Hoofsure Endurance.

Zinc therapy improves deleterious effects of chronic copper administration on mice testes: histopathological evaluation.

This study was set to investigate whether the adverse effects of long-term copper (Cu) consumption on testicular tissue could be prevented by zinc (Zn) administration. Forty-five mature male mice were randomly divided into one control and two treatment groups. The first treatment group received copper sulphate (Cu experimental group). The second treatment group was given combined treatment of copper sulphate and zinc sulphate (ZC experimental group). Control animals received normal saline using the same volume. Five mice from each group were sacrificed on day 14, 28 and 56 from the beginning of treatments. Left testes were removed for histopathological and histomorphometrical evaluations. Morphometrically, the diameter of seminiferous tubules and Sertoli cell nuclei, epithelial height, meiotic index and the percentage of spermatogenesis in Cu groups showed significant decrease compared to those of the control groups (P < 0.05). A partial improvement was seen in the percentage of spermatogenesis and meiotic index (P < 0.05) in ZC groups, whereas a complete recovery was observed in the rest of parameters in ZC group after 56 days compared to the control group (P > 0.05). Results showed that long-term administration of Cu leads to histological impairments of testis and zinc supplementation might offset these damaging effects.

Efficacy and tolerability assessment of a topical formulation containing copper sulfate and hypericum perforatum on patients with herpes skin lesions: a comparative, randomized controlled trial.

BACKGROUND: Topical Acyclovir has moderate efficacy on recurrent HSV symptoms, requiring repeat applications for several days. Topical Dynamiclear, which requires only a single dose application, may provide a more effective and convenient treatment option for symptomatic management of HSV. OBJECTIVES: The study assessed the comparative efficacy and tolerability of a single use, topical formulation containing copper sulfate pentahydrate and Hypericum perforatum that is marketed as Dynamiclear™ to a topical 5% Acyclovir cream standard preparation and use. METHODS: A prospective, randomized, multi-centered, comparative, open-label clinical study was conducted. A total of 149 participants between 18 and 55 years of age with active HSV-1 and HSV-2 lesions were recruited for the 14-day clinical trial. Participants were randomized into two groups: A (n=61), those receiving the Dynamiclear formulation, and B (n=59), those receiving 5% Acyclovir. Efficacy parameters were assessed via physical examination at baseline (day 1), day 2, 3, 8, and 14. Laboratory safety tests were conducted at baseline and on day 14. RESULTS: Use of the Dynamiclear formulation was found to have no significant adverse effects and was well tolerated by participants. All hematological and biochemical markers were within normal range for the Dynamiclear group. Statistically, odds for being affected by burning and stinging sensation were 1.9 times greater in the Acyclovir group in comparison to the Dynamiclear group. Similarly, the odds of being affected by symptoms of acute pain, erythema and vesiculation were 1.8, 2.4, and 4.4 times higher in the Acyclovir group in comparison to the Dynamiclear group. CONCLUSIONS: The Dynamiclear formulation was well tolerated, and efficacy was demonstrated in a number of measured parameters, which are helpful in the symptomatic management of HSV-1 and HSV-2 lesions in adult patients. Remarkably, the effects seen from this product came from a single application.

Copper sulphate burns to the hands, a complication of traditional medicine.

An 11-year-old girl of Bedouin origin presented with infected burns on the dorsum of both her hands. The burns had an unusual configuration in the form of spirals, and child abuse was suspected. The family reported that the burns had been caused by a treatment, for head aches, dispensed by a traditional healer, which involved applying a blue fluid on the hands. Chemical analysis of the implicated substance identified it as copper sulfate. The local and systemic effects of copper sulfate are reviewed as well as traditional healing methods that may lead to burn injuries. When clinicians encounter bizarre patterns of injury they must consider besides the possibility of abuse also, more unusual etiologies.

Metal-ion-mediated oxidative stress in the gill homogenate of rainbow trout (Oncorhynchus mykiss): antioxidant potential of manganese, selenium, and albumin.

Human activities play a major role in toxic and carcinogenic metal pollution of the environment. This study was undertaken to evaluate the effects of copper and mercury at the 400- to 1000-microM concentration range on some biochemical markers of oxidative stress, such as lipid peroxidation (LPO), glutathione-S-transferase (GST) activity, and reduced glutathione (GSH) content in the rainbow trout gill homogenates with or without supplementation of manganese, selenium, and bovine serum albumin (BSA). The integrity of DNA was also measured to assess metal ion toxicity. The results showed that the LPO and specific activity of GST were elevated. This indicated that cell-protecting antioxidant mechanisms were overtaxed and could not prevent membrane peroxidation. Following the addition of metals, the GSH content was also significantly reduced in a concentration-dependent manner. Mercury was found to be more effective than copper. The application of antioxidants proved beneficial in inhibiting LPO, reducing GST activity, and elevating the GSH levels in the gill samples. Manganese was more effective than selenium and BSA. Surprisingly, when BSA (1.0%) was added to the gill homogenates treated with a 1000-microM concentration of metal ions, instead of alleviating malondialdehyde (MDA) generation, a drastic elevation in the MDA levels, alleviation in GST activity, and a further decrease in glutathione (GSH) levels were observed, which were most likely the result of pro-oxidant activity of BSA. The results also indicated that mercury and copper functioned as genotoxic pollutants, which altered the DNA integrity by inducing the single- and double-stranded DNA breaks in the gill cell nuclei. Collectively, toxicity of metal ions is related to the depletion of GSH content and inhibition of antioxidant enzyme GST, resulting in the propagation of LPO and DNA damage.

Impact of certain plants and synthetic molluscicides on some fresh water snails and fish.

The LC50 (78, 85 ppm) and LC90 (88, 135 ppm) of Anagalis arvensis and Calendula micrantha respectively against Biomphalaria alexandrina were higher than those of the non-target snails, Physa acuta, Planorbis planorbis, Helisoma duryi and Melanoides tuberculata. In contrast, the LC50 of Niclosamide (0.11 ppm) and Copper sulphate (CuSO4) (0.42 ppm) against B. alexandrina were lower than those of the non-target snails. The mortalities percentage among non-target snails ranged between 0.0 & 20% when sublethal concentrations of CuSO4 against B. alexandrina mixed with those of C. micrantha and between 0.0 & 40% when mixed with A. arvensis. Mortalities ranged between 0.0 & 50% when Niclosamide was mixed with each of A. arvensis and C. micrantha. A. arvensis induced 100% mortality on Oreochromis niloticus after 48 hrs exposure and after 24 hrs for Gambusia affinis. C. micrantha was non-toxic to the fish. The survival rate of O. niloticus and G. affinis after 48 hrs exposure to 0.11 ppm of Niclosamide were 83.3% & 100% respectively. These rates were 91.7% & 93.3% respectively when each of the two fish species was exposed to 0.42 ppm of CuSO4. Mixture of sub-lethal concentrations of A. arvensis against B. alexandrina and those of Niclosamide or CuSO4 at ratios 10:40 & 25:25 induced 66.6% mortalities on O. niloticus and 83.3% at 40:10. These mixtures caused 100% mortalities on G. affinis at all ratios. A. arvensis CuSO4 mixtures at 10:40 induced 83.3% & 40% mortalities on O. niloticus and G. affinis respectively and 100% mortalities on both fish species at ratios 25:25 & 40:10. A mixture of sub-lethal concentrations of C. micrantha against B. alexandrina and of Niclosamide or CuSO4 caused mortalities of O. niloticus between 0.0 & 33.3% and between 5% & 35% of G. affinis. The residue of Cu in O. niloticus were 4.69, 19.06 & 25.37 mg/1kgm fish after 24, 48 & 72 hrs exposure to LC0 of CuSO4 against B. alexandrina respectively.

Gastric response to acute copper exposure.

Early effects of acute copper exposure consist mainly of nausea and altered gastric permeability. To assess copper effects on gastric response 30 apparently healthy volunteers underwent two controlled trials receiving a solution with (10 mg Cu/l) and without (<0.01 mg Cu/l) copper sulfate after overnight fasting, in random order. Ultrasonography was chosen to follow indirectly the gastric emptying pattern for 120 min. Measurements were expressed as z scores [z=(mean-Xi)/S.D.]. Results showed that nobody presented symptoms after drinking water without added copper while 9 subjects presented nausea after receiving the 10 mg Cu/l solution. The group receiving drinking water with 10 mg Cu/l presented greater antral areas during the first 60 min of observation. Individual and mean fitted curves for antral area, calculated and compared using the linear mixed-effects model fit by REML, showed a group effect of copper on antral area over time (L. Ratio=23.98, P<0.0001); the effect was due to delay in decreasing antral area in the copper treated group during the first hour after ingestion. No differences were found by gender or nausea. Results show a copper effect on gastric response suggesting that acute exposure to copper in water modify the first phase of gastric emptying.

The effects of hange-shashin-to on gastric function in comparison with sho-saiko-to.

The effects of "Hange-shashin-to (TJ-14)" on gastric function were examined in comparison with "Sho-saiko-to (TJ-9)". Oral treatment with TJ-14 (125-500 mg/kg) caused dose-dependent suppression of ethanol-induced gastric injury, while it did not suppress gastric lesions induced by water-immersion stress. TJ-9 (125-500 mg/kg, p.o.) suppressed both water-immersion stress-induced gastric lesions and ethanol-induced gastric injury in a dose-dependent manner. Intraduodenal administration of TJ-14 even at 500 mg/kg did not affect gastric juice secretion, while TJ-9 at 125 to 500 mg/kg dose-dependently suppressed gastric juice secretion. TJ-14 (125-500 mg/kg, p.o.) accelerated gastric emptying in normal rats and improved the delayed gastric emptying induced by BaCl2 in a dose-dependent manner, whereas such effect was not noted with TJ-9. Oral treatment with TJ-14 at 500 mg/kg significantly suppressed apomorphine-induced vomiting, but it did not affect copper sulfate-induced vomiting. These results suggest that TJ-14 exhibits an anti-ulcer action (probably based on its ability to protect the gastric mucosa), improvement of gastric emptying and an anti-emetic action. TJ-9 also showed anti-ulcer effects, probably based on its ability to suppress gastric secretion and to protect the gastric mucosa. Thus, the present study demonstrated the effectiveness of TJ-14 and TJ-9 against gastric disease, and provided basic data which explain the differences in clinical application between these two kampo medicines.

Broad spectrum antiemetic effects of CP-122,721, a tachykinin NK1 receptor antagonist, in ferrets.

The potent, selective, tachykinin NK1 receptor antagonist, CP-122,721 ([(+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2- phenylpiperidine]), at 0.01-1 mg/kg, s.c. reduced retching and vomiting elicited by loperamide, copper sulfate, ipecac syrup and cisplatin in a dose-dependent manner. ID50 values after subcutaneous administration ranged from 0.02 mg/kg (loperamide) to 0.08 mg/kg (ipecac). Oral CP-122,721 reduced cisplatin-induced emesis with an ID50 of approximately 0.08 mg/kg. The less active (2R, 3R)-enantiomer, CP-132.687, did not significantly suppress retching or vomiting induced by any of the emetogens. These data support the hypothesis that CP-122,721 blocks emesis by a specific action at tachykinin NK1 receptors. Its broad spectrum of antiemetic activity suggests a central site of action.