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.

Thyroid Stem Cells But Not Differentiated Thyrocytes Are Sensitive to Slightly Increased Concentrations of Heavy Metals.

Thyroid cancer incidence is markedly increased in volcanic areas where residents are biocontaminated by chronic lifelong exposure to slightly increased metals in the environment. Metals can influence the biology of living cells by a variety of mechanisms, depending not only on the dose and length of exposure but also on the type and stage of differentiation of target cells. We explored the effect of five heavy metals (Cu, Hg, Pd, W and Zn) at nanomolar concentrations (the biocontamination level in residents of the volcanic area in Sicily where thyroid cancer is increased) on stimulating the proliferation of undifferentiated (thyrospheres) and differentiated human thyroid cells. Thyrosphere proliferation was significantly increased after exposure to each individual metal and a greater stimulating effect was observed when a mixture of the examined metals was used. No effect was seen in differentiated thyrocytes. For all metals, the dose-response curve followed a biphasic pattern that is typical of hormesis. Thyrosphere growth concerned the size rather than number, except with the metal mixture. An altered morphology was also observed in metal-treated thyrospheres. Metal-induced proliferation was due to activation of the ERK1/2 pathway, as confirmed by growth inhibition when ERK1/2 signaling was blocked. These studies show that stem/precursor thyroid cells are sensitive to small increases in environmental metal concentrations that are harmless for differentiated thyrocytes.

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.

Involvement of the Prion Protein in the Protection of the Human Bronchial Epithelial Barrier Against Oxidative Stress.

Aim: Bronchial epithelium acts as a defensive barrier against inhaled pollutants and microorganisms. This barrier is often compromised in inflammatory airway diseases that are characterized by excessive oxidative stress responses, leading to bronchial epithelial shedding, barrier failure, and increased bronchial epithelium permeability. Among proteins expressed in the junctional barrier and participating to the regulation of the response to oxidative and to environmental stresses is the cellular prion protein (PrPC). However, the role of PrPC is still unknown in the bronchial epithelium. Herein, we investigated the cellular mechanisms by which PrPC protein participates into the junctional complexes formation, regulation, and oxidative protection in human bronchial epithelium. Results: Both PrPC messenger RNA and mature protein were expressed in human epithelial bronchial cells. PrPC was localized in the apical domain and became lateral, at high degree of cell polarization, where it colocalized and interacted with adherens (E-cadherin/γ-catenin) and desmosomal (desmoglein/desmoplakin) junctional proteins. No interaction was detected with tight junction proteins. Disruption of such interactions induced the loss of the epithelial barrier. Moreover, we demonstrated that PrPC protection against copper-associated oxidative stress was involved in multiple processes, including the stability of adherens and desmosomal junctional proteins. Innovation: PrPC is a pivotal protein in the protection against oxidative stress that is associated with the degradation of adherens and desmosomal junctional proteins. Conclusion: Altogether, these results demonstrate that the loss of the integrity of the epithelial barrier by oxidative stress is attenuated by the activation of PrPC expression, where deregulation might be associated with respiratory diseases.

Analysis of 28 trace elements in the blood and serum antioxidant status in chickens under arsenic and/or copper exposure.

This study aimed to evaluate the 28 trace elements in the blood and serum antioxidant status in chickens under arsenic (As) and/or copper (Cu) exposure. A total of 200 1-day-old male Hy-Line chickens were fed either a commercial diet (C-group) or arsenic trioxide (30 mg/kg) and/or cupric sulfate (300 mg/kg) for 90 days. The 28 trace element levels in the blood were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The concentrations of As in the blood of chickens were elevated approximately 17.15-fold, 2.30-fold, and 13.37-fold in the As-group, Cu-group, and As + Cu-group, respectively, at 90 days. The concentrations of Cu did not change in the As-group and increased approximately 29.53 and 23.37% in the Cu-group and As + Cu-group, respectively, at 90 days. Moreover, As exposure caused ion profile disorders in the blood, including increased concentrations of Na, Mg, Si, K, Cr, Fe, and Se and reduced B, Ca, Ti, V, Mn, Co, Ni, Zn, Sr, and Mo. Cu exposure increased the contents of Mg, Si, Ca, Ti, V, Cr, Mn, Fe, Co, Zn, and Se and decreased the content of B, Ca, Al, Ni, and Mo. As + Cu exposure increased the contents of Mg, Si, Cr, Fe, Zn, and Se and decreased the content of B, Ca, Ti, Co, Ni, Sr, and Mo. Moreover, As and/or Cu exposure induced oxidative stress in the blood of chickens. In conclusion, the results indicated that the mixture of As and Cu caused a synergistic effect via disturbing homeostasis of trace elements and oxidative stress in the blood of chickens.

Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment.

Aspects of memory involved in cognitive mechanisms were investigated in rat after oxaliplatin (OX) chemotherapy using animal behavioural assessment of passive avoidance and social learning paradigms, which are both hippocampus-sensitive. Rodents, previously subjected to 2-week OX treatment, showed passive avoidance and social learning impairment and apoptotic processes in the hippocampus. Apoptosis rate significantly increased in cultured hippocampal cells exposed to OX at increasing doses, and this effect was dose-dependent. Ex vivo experiments showed that cell damage and apoptosis were blocked in the hippocampus from OX rats cotreated with copper sulphate (CS) which precludes OX transport inside the cell. In vivo, passive avoidance and social learning impairment could not be observed in OX rats co-administered with CS. Thus, a site of action of OX treatment on memory impairment appears to be located at the hippocampus. These findings strongly support that cellular damage induced by OX in rodent hippocampus underlies the weakening of some memory functions.

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.

Contributions of rat Ctr1 to the uptake and toxicity of copper and platinum anticancer drugs in dorsal root ganglion neurons.

Dorsal root ganglion (DRG) neurons are affected by platinum-induced neurotoxicity and neurodegenerative processes associated with disturbed copper homeostasis and transport. This study aimed to understand the role of copper transporter 1 (Ctr1) in the uptake and toxicity of copper and platinum drugs in cultured rat DRG neurons, and the functional activities of rat Ctr1 (rCtr1) as a membrane transporter of copper and platinum drugs. Heterologous expression of rCtr1 in HEK293 cells (HEK/rCtr1 cells) increased the uptake and cytotoxicity of copper, oxaliplatin, cisplatin and carboplatin, in comparison to isogenic vector-transfected control cells. Cultured rat DRG neurons endogenously expressed rCtr1 protein on their neuronal cell body plasma membranes and cytoplasm, and displayed substantial capacity for taking up copper, but were resistant to copper toxicity. The uptake of copper by both cultured rat DRG neurons and HEK/rCtr1 cells was saturable and inhibited by cold temperature, silver and zinc, consistent with it being mediated by rCtr1. Cultured rat DRG neurons accumulated platinum during their exposure to oxaliplatin and were sensitive to oxaliplatin cytotoxicity. The accumulation of platinum by both cultured rat DRG neurons and HEK/rCtr1 cells, during oxaliplatin exposure, was saturable and temperature dependent, but was inhibited by copper only in HEK/rCtr1 cells. In conclusion, rCtr1 can transport copper and platinum drugs, and sensitizes cells to their cytotoxicities. DRG neurons display substantial capacity for accumulating copper via a transport process mediated by rCtr1, but appear able to resist copper toxicity and use alternative mechanisms to take up oxaliplatin.

Histopathological changes in liver and gill epithelium of Nile tilapia, Oreochromis niloticus, exposed to waterborne copper

Nile tilapia, Oreochromis niloticus, of both sexes were reared in freshwater and exposed to 0.5, 1.0 and 2.5mg L-1 of waterborne copper for a period of 21 days. Liver and gill samples were collected after 21 days of exposure to copper and lesions were analyzed by light microscopy. The main histopathological changes observed in gills exposed to the highest concentration were edema, lifting of lamellar epithelia and an intense vasodilatation of the lamellar vascular axis. Although less frequent, lamellar fusion caused by the filamentar epithelium proliferation and some lamellar aneurisms were also found. The liver of control group exhibited a quite normal architecture, while the fish exposed to copper showed vacuolation and necrosis. These hepatic alterations were more evident in fish exposed to 1.0 and 2.5mg L-1 copper concentrations. The number of hepatocytes nucleus per mm² of hepatic tissue decreased with the increase of copper concentration. In contrast, the hepatic somatic index was high in fish exposed at 2.5mg L-1 of copper. In short, this work advance new knowledge as influence of copper in the gill and liver histology of O. niloticus and demonstrated that their effects could be observed at different concentrations.

Tilápia do Nilo, Oreochromis niloticus, de ambos os sexos foram mantidas em água doce e expostas a concentrações de 0.5, 1.0 e 2.5mg L-1 de sulfato de cobre durante um período de 21 dias. Amostras de fígado e de brânquia foram coletadas após o tempo de exposição e as lesões foram analisadas por microscopia óptica. As principais alterações histopatológicas observadas nas brânquias foram edema, "lifting" do epitélio lamelar e uma intensa vasodilatação do eixo lamelar. Embora menos freqüentes, a fusão lamelar causada pela proliferação do epitélio filamentar e alguns aneurismas lamelares também foram observadas. O fígado do grupo controle exibiu uma arquitetura normal, enquanto os dos peixes expostos ao cobre apresentaram vacuolização e necrose. Estas lesões hepáticas foram mais evidentes nos peixes expostos a concentrações de cobre de 1.0 e 2.5mg L-1. O número dos núcleos dos hepatócitos / mm² de tecido hepático decresceu com o aumento da concentração de cobre. Em contraste, o índice hepatossomático foi mais elevado nos peixes expostos a 2.5mg L-1 de cobre. Em resumo, este trabalho acrescenta nova informação sobre a influência do cobre ao nível da histologia da brânquia e do fígado de O. niloticus e demonstra que os seus efeitos podem ser observados em diferentes concentrações.

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.

[Environmental hygiene and comprehensive processing of copper sulphate ore]. / Voprosy gigieny okruzhaiushchei sredy pri kompleksnoi pererabotke mednosul'fidnykh rud.

The modern comprehensive processing of copper-sulphate ores is based on using the fire, chemical and combined fire-and-hydrometallurgy processes. The existing schemes of comprehensive ore processing do not provide for a total utilization of the metallurgical cycles wastes due to the inherent technological and design shortcomings; besides, they are a source of environmental pollution. Contamination of the atmospheric air with discharge elements has unfavorable effects on the health condition of population; it worsens the natural body resistance and contributes (through the induction of chromosome aberrations) to a higher general morbidity and mortality due to malignant neoplasms. Health-improve measures are supported by modern achievements in the sphere of copper-sulphate ore processing technologies--they ensure the hygienic and ecological rational management and usage at all stages of the processing of raw materials and secondary products. Institutions of the territorial medical-and-ecological monitoring are the corner stones for ecological safety of persons residing in areas of comprehensive copper-and-sulphate ore processing.

Action of prostanoids on the emetic reflex of Suncus murinus (the house musk shrew).

Several prostanoids were investigated for a potential to induce emesis in Suncus murinus. The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent. The emetic action of U46619 (300 microg/kg, i.p.) was antagonized significantly by the TP receptor antagonist, vapiprost (P<0.05). EP (prostaglandin E(2), 17-phenyl-omega-trinor prostaglandin E(2), misoprostol and sulprostone), FP (prostaglandin F(2alpha) and fluprostenol) and IP (iloprost and cicaprost) receptor agonists failed to induce consistent emesis at doses up to 300-1000 microg/kg, i.p. Fluprostenol reduced nicotine (5 mg/kg, s.c.)-but not copper sulphate (120 mg/kg, intragastric)-induced emesis; the other inconsistently emetic prostanoids were inactive to modify drug-induced emesis. The results indicate an involvement of TP and possibly DP and FP receptors in the emetic reflex of S. murinus.

Occupational risk factors for renal cell cancer. An Italian case-control study.

AIM: To examine possible associations between occupational and environmental risk factors and renal cell cancer (RCC), a tumour with unclear aetiology and increasing incidence. METHODS: A questionnaire-based case-control study of 100 histologically verified cases of RCC and 200 controls was conducted at Parma University Hospital. The control group was enrolled from patients attending different outpatient departments and represented the same residential area as the cases. For all exposure variables under study, two levels of duration were defined: "short" and "prolonged" for less than 10 years or more, respectively. RESULTS: The highest risk estimates for RCC were found for "prolonged" exposure to organic solvents with an odds ratio (OR) of 2.2 (95% confidence interval, CI: 1.0-4.8). "Prolonged" exposures to pesticides and copper sulphate were also associated with increased risk, OR 2.0 (95% CI: 0.8-4.7) and OR 2.7 (95% CI: 1.3-5.5), respectively. CONCLUSIONS: Our data suggests an association between RCC and exposure to organic solvents, pesticides and copper sulphate. A risk gradient as a function of exposure duration was found for organic solvents (p = 0.044) and copper sulphate (p = 0.036), but not for pesticides.

[On carcinogenic effects of sulfate copper and nickel ore]. / Ob onkogennom deistvii pyli sul'fidnykh medno-nikelevykh rud.

Underground mines are places for extraction of three types of copper and nickel sulfide ores: rich, copper and incorporated--those three ones differ in mimeralogic and chemical contents. Experimental evaluation of carcinogenic effects obtained during intratracheal administration of copper and incorporated ores indicates the certain carcinogenic activity of the dust with 0.49-1.14% nickel and 1.9-5.8% copper content--therefore a unified MAC for all the stated dust types could be suggested.

The emetic and anti-emetic effects of the capsaicin analogue resiniferatoxin in Suncus murinus, the house musk shrew.

1. In SUNCUS: murinus the ultrapotent capsaicin analogue resiniferatoxin (RTX) induced an emetic response in the dose range 1 - 1000 microg kg(-1), s.c. The latency was inversely related to dose and ranged from 41.2+/-4.4 min. (1 microg kg(-1), s.c.) to 2.7+/-0.6 min. (1000 microg kg(-1), s.c.). 2. The emetic response to RTX (10 or 100 microg kg(-1), s.c.) was blocked or markedly reduced by pre-treatment with RTX (100 microg kg(-1), s.c.), 8-OH-DPAT (100 microg kg(-1), s.c.), morphine (2 mg kg(-1), s.c.), neonatal capsaicin (100 mg kg(-1), s.c.) and the NK(1) receptor antagonist CP-99,994 (10 - 20 mg kg(-1), s.c.) but not by the 5-HT(3) receptor antagonist tropisetron (200 microg kg(-1), s.c.). 3. RTX (100 microg kg(-1), s.c.) induced c-fos-like immunoreactivity in the area postrema and parts of the nucleus tractus solitarius. This pattern is consistent with the proposal that the emetic effect is mediated via one or both of these structures and an involvement of substance P is discussed. 4. RTX (10 and 100 microg kg(-1), s.c.) had broad-spectrum antiemetic effects in Suncus as indicated by its ability to block or markedly reduce the emetic response to motion (1 Hz, 4 cm lateral, 10 min.), cisplatin (20 mg kg(-1), i.p.), intragastric copper sulphate (40 mg kg(-1), p.o.), nicotine (10 mg kg(-1), s.c.) and RTX (100 microg kg(-1), s.c.) itself. 5. It is proposed that the site of the anti-emetic effect is in the nucleus tractus solitarius and mechanisms involving the modulation of substance P release are discussed. 6. The general utility of SUNCUS: for investigations of vanilloid receptors is reviewed in the light of the exquisite sensitivity of the emetic reflex in this species to resiniferatoxin.

Intoxicación aguda por plaguicidas / Acute poisoning from pesticides

Objetivo. Describir la epidemiología de la intoxicación aguda por plaguicidas (IAP) en el Hospital General O'Horán de Mérida, Yucatán, México. Material y métodos. Se revisaron los expedientes de 33 pacientes =13 años, tratados en una unidad de cuidados intensivos (UCI), entre 1994 y 1998. Se recopilaron variables demográficas y clínicas relevantes, y se aplicó estadística descriptiva. Resultados. En la población estudiada predominó el sexo masculino (82 por ciento) del medio rural (70 por ciento), y la edad media fue de 34 ñ 15.8 años. El intento de suicidio fue causa frecuente de IAP (79 por ciento), y en 33 por ciento de los casos la intoxicación se produjo por la utilización de organofosforados. La mortalidad fue de 12 por ciento. Conclusiones. La IAP fue baja entre los sujetos del medio rural, por lo que los resultados de este estudio parecen no reflejar la realidad del problema. Es importante añadir que los plaguicidas son utilizados con relativa frecuencia para el intento de suicidio.

Inhibition of emesis by tachykinin NK1 receptor antagonists in Suncus murinus (house musk shrew).

The anti-emetic potential of CP-122,721 ((+)-2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl)amino-2-phenylpi peridine), CP-99,994 ((+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), CP-100,263 ((-)-(2R,3R)-3-(2-methoxybenzylamino)-2-phenylpiperidine), RP 67580 ((3R, 7aR)-7,7-diphenyl-2-[1-imino-2-(2-methoxyphenyl)ethyl] po-hydroisoindol-4-one), FK 888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-in-dole-3-yl)carbonyl-L-propyl] -N-methyl-N-phenylmethyl-1-3-(2-naphthyl)-alaninamide) and GR 82334 ([D-Pro9[spiro-g-lactam]Leu10]-physalaemin-(1-11)) was investigated to inhibit nicotine (5 mg/kg, s.c.)-, copper sulphate pentahydrate (120 mg/kg, intragastric)- and motion (4 cm horizontal displacement at 1 Hz for 5 min)-induced emesis in Suncus murinus. A 30 min intraperitoneal pre-treatment with CP-122,721, CP-99,994, RP 67580 and FK 888 significantly (P < 0.05) antagonized nicotine-induced emesis with ID50 values of 2.1, 2.3, 13.5 and 19.2 mg/kg, respectively CP-100,263, the less active enantiomer of CP-99,994, was inactive at doses up to 10 mg/kg. Infusion of GR 82334, CP-122,721, CP-99,994 and FK 888 into the dorsal vagal complex of the hindbrain also antagonized nicotine-induced emesis yielding ID50 values of 1.1, 3.0, 3.3 and 58.0 microg/dorsal vagal complex, respectively RP 67580 and CP-100,263 were inactive. RP 67580 and FK 888 failed to antagonize copper sulphate-induced emesis but CP-122,721 and CP-99,994 were active yielding ID50 values of 2.2 and 3.0 mg/kg, i.p., respectively. CP-99,994 also completely prevented motion-induced emesis at 10 mg/kg, i.p. (P < 0.05) and RP 67580 produced a significant reduction of motion-induced emesis at 10 mg/kg, i.p. (P < 0.05). These studies provide evidence of a central site of action of tachykinin NK1 receptor antagonists to inhibit nicotine-induced emesis in S. murinus and confirm the broad profile of inhibitory action. The rank order of potency of the antagonists following the intra-dorsal vagal complex administration suggests that the S. murinus tachykinin NK1 receptor has a unique pharmacological profile.

[The use of copper sulfate in the treatment of esophageal cancer]. / Primenenie sul'fata medi v lechenii raka pishchevoda.

The authors have developed and approbated a methodology involving the use of copper sulphate as a radio sensitizer. The methods permit the enhancement of the immediate efficiency of treatment up to the level comparative with the best results of radiosensibilization at the expense of cytostatic agents. The incidence of complete regression of the tumor came up to 43.3%, partial one to 53.3%, stabilization to 3.3%. The advantages of the use of copper sulphate include low toxicity, practical availability, and exceptional cheapness, which facts suggest superiority of the proposed methods to other methodologies.

Estudio morfológico y morfométrico del epitelio lingual de fetos de ratas intoxicadas con cobre durante la preñez / Morphologic and morphometric study of the tongue epithelium of rat fetuses after copper intoxication during pregnancy

En ratas grávidas se estudiaron los efectos de la administración intravenosa de sulfato de cobre (4 mg/kg de peso) sobre la estructura del epitelio de la mucosa lingual de sus fetos. Los exámenes histopatológicos y morfométrico revelaron, en los animales del grupo intoxicado, un epitelio más delgado debido, principalmente, a la ausencia de los estratos granuloso y córneo en las regiones dorsal posterior y ventral de la mucosa lingual

Antiemetic effects of morphine on motion- and drug-induced emesis in Suncus murinus.

Emetic and antiemetic effects of morphine were investigated in Suncus murinus. Subcutaneous (up to 30 mg/kg) or intracerebroventricular administration (50 micrograms) of morphine failed to cause emesis. However, pretreatment with morphine (s.c.) prevented the emesis induced by nicotine (10 mg/kg, i.p.), copper sulfate (40 mg/kg, p.o.), cisplatin (20 mg/kg, i.p.) and motion stimulus. These results suggest that morphine has only antiemetic potency and may block a common mechanism for the emetic reflex of suncus, because the antiemetic effects of the drug were exerted irrespective of the stimulus.