Preparation of cupric sulfate-based self-emulsifiable nanocomposites and their application to the photothermal therapy of colon adenocarcinoma.

Nanocomposites (NCs) of cupric sulfate monohydrate (CuSO4) were fabricated by hot-melt extrusion (HME) system equipped with twin screws. Micron-sized bulk powder of CuSO4 was dispersed in the mixture of surfactants (Span 80 and Tween 80) and hydrophilic polymer (polyethylene glycol (PEG) 6000) by HME process. Reduction of surface tension by surfactants and homogeneous dispersion in hydrophilic polymer along with HME technique were introduced to prepare CuSO4 NCs. Dispersion of CuSO4 NCs exhibited approximately 204 nm hydrodynamic size, unimodal size distribution, and positive zeta potential values. Encapsulation of CuSO4 in CuSO4 NCs and the physicochemical interactions between CuSO4 and pharmaceutical excipients were investigated by solid-state studies. Of note, CuSO4 NCs group exhibited higher antiproliferation efficacies, compared with bulk CuSO4, in Caco-2 (human adenocarcinoma) cells at 75 and 100 µg/mL CuSO4 concentrations (p < 0.05). Also, near-infrared laser irradiation to CuSO4 NCs group elevated the antiproliferation efficacies, compared with non-irradiation group, in Caco-2 cells. After intravenous injection in mice, CuSO4 NCs did not show severe in vivo toxicities. Developed CuSO4 NCs can be one of promising candidates of photothermal therapeutic agents for colon cancers.

Copper sulphate use in South African traditional medicine.

Copper (Cu) is an essential element to humans; however, exposure to elevated concentrations through occupational hazard and/or environmental means may be detrimental. This paper provides results of a cross-sectional study aimed to determine the prevalence of copper sulphate (CuSO4) use in South African traditional medicine by traditional health practitioners (THPs) and details the use thereof. A total of 201 THPs were enrolled from two main municipal areas of KwaZulu-Natal (South Africa). Information on demographic characteristics of THPs, reasons for using or not using CuSO4 as well as administration methods and age groups of recipients were collected. Of the 201 THPs interviewed, 145 (72 %) use CuSO4 for healing purposes. The use of CuSO4 was strongly associated with gender (p = 0.009) where the proportion of CuSO4 users was higher for female than male THPs. CuSO4 was reportedly administered to individuals of all ages, including infants and children. The main routes of administration were enema (n = 110; 76 %), oral (n = 40; 28 %) and use in bath (n = 40; 28 %). The reasons cited for use are diverse and included skin rashes (n = 43; 30 %), aches, pains and swelling (n = 38; 28 %) as well as sexually transmitted diseases (n = 28; 19 %). This study identified a high prevalence of THPs using CuSO4 for healing purposes. These findings support the need to regulate South African traditional medicine to safeguard the user.

Effectiveness of 5-Pyrrolidone-2-carboxylic Acid and Copper Sulfate Pentahydrate Association against Drug Resistant Staphylococcus Strains.

Bacterial resistance is an ongoing challenge for pharmacotherapy and pharmaceutical chemistry. Staphylococcus aureus is the bacterial species which makes it most difficult to treat skin and soft tissue infections and it is seen in thousands of hospitalization cases each year. Severe but often underrated infectious diseases, such as complicated nasal infections, are primarily caused by MRSA and S. epidermidis too. With the aim of studying new drugs with antimicrobial activity and effectiveness on drug resistant Staphylococcus strains, our attention in this study was drawn on the activity of a new association between two natural products: 5-pyrrolidone-2-carboxylic acid (PCA), naturally produced by certain Lactobacillus species, and copper sulfate pentahydrate (CS). The antimicrobial susceptibility test was conducted taking into account 12 different Staphylococcus strains, comprising 6 clinical isolates and 6 resistant strains. PCA 4%, w/w, and CS 0.002%, w/w, association in distilled water solution was found to have bactericidal activity against all tested strains. Antimicrobial kinetics highlighted that PCA 4%, w/w, and CS 0.002% association could reduce by 5 log10 viable bacterial counts of MRSA and oxacillin resistant S. epidennidis in less than 5 and 3 minutes respectively. Microscopic investigations suggest a cell wall targeting mechanism of action. Being very safe and highly tolerated, the natural product PCA and CS association proved to be a promising antimicrobial agent to treat Staphylococcus related infections.

Estudio clínico de la eficacia del «agua de 3 sulfatos» en la balanitis y la balanopostitis / Clinical study of the effectiveness of the «water of the 3 sulfates» on balanitis and balanoposthitis

Objetivos: La utilización del «agua de 3 sulfatos» (sulfato de cinc, cobre y alumínico-potásico) se cita en la literatura como un posible tratamiento para la balanitis y balanopostitis; ahora bien, no existen trabajos prospectivos que documenten su eficacia clínica. Pretendemos estudiar dicha eficacia. Material y método: Presentamos un estudio aleatorizado doble ciego sobre 50 pacientes con balanitis o balanopostitis en el que se comparan los resultados clínicos del «agua de 3 sulfatos» (30 pacientes) frente a una solución salina (20 pacientes). Los parámetros clínicos estudiados han sido: exudado, eritema, edema, escozor y prurito. Resultados: Una vez aplicados los test estadísticos, hemos observado que el «agua de 3 sulfatos» ha sido superior al suero salino en todos los parámetros clínicos estudiados, aunque las diferencias solo han sido significativas para el parámetro exudado. Conclusiones: El «agua de 3 sulfatos» se ha mostrado significativamente más eficaz que el suero fisiológico en la eliminación del exudado de las balanitis y balanopostitis agudas de nuestro estudio. La tolerabilidad de los tratamientos ha sido excelente

Objectives: Despite scientific literature mentions the application of 'water of the 3 sulfates' (copper sulphate, zinc sulphate and alum) as a treatment for acute balanitis and balanoposthitis, no clinical trials evaluating its efficacy have been found. In our study we evaluate the efficacy of this solution in acute balanitis and balanoposthitis. Material and methods: A double-blind randomized study was designed to compare the efficacy of 'water of the 3 sulfates' (intervention) with saline solution (control) in 50 patients (30 patients and 20 patients, respectively) who suffer from acute balanitis or balanoposthitis. Exudate, erythema, oedema, burning, and itching were the clinical parameters assessed. Results: for all clinical parameters assessed, the outcomes obtained with 'water of the 3 sulfates' are higher than control, although significant differences only have been found for exudate. Conclusions: in our study, the 'water of the 3 sulfates' is significantly more effective than saline solution for removing exudates in acute balanitis and balanoposthitis. Tolerability was excellent in both treatments

Clinical study of the effectiveness of the "water of the 3 sulfates" on balanitis and balanoposthitis.

OBJECTIVES: Despite scientific literature mentions the application of "water of the 3 sulfates" (copper sulphate, zinc sulphate and alum) as a treatment for acute balanitis and balanoposthitis, no clinical trials evaluating its efficacy have been found. In our study we evaluate the efficacy of this solution in acute balanitis and balanoposthitis. MATERIAL AND METHODS: A double-blind randomized study was designed to compare the efficacy of "water of the 3 sulfates" (intervention) with saline solution (control) in 50 patients (30 patients and 20 patients, respectively) who suffer from acute balanitis or balanoposthitis. Exudate, erythema, oedema, burning, and itching were the clinical parameters assessed. RESULTS: for all clinical parameters assessed, the outcomes obtained with "water of the 3 sulfates" are higher than control, although significant differences only have been found for exudate. CONCLUSIONS: in our study, the "water of the 3 sulfates" is significantly more effective than saline solution for removing exudates in acute balanitis and balanoposthitis. Tolerability was excellent in both treatments.

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.

Stryphnodendron adstringens extract associated with the hooves trimming surgical procedure for the treatment of bovine digital dermatitis.

Hoof care, lesion curettage, and application of 5 % Stryphnodendron adstringens bark extract (S. adstringens (Mart.) Coville) or 3 % copper sulfate on surgical wounds of cattle were carried out in this research. A total of 180 cattle with digital dermatitis were used. They were distributed into six groups of 30 animals each (GI, GII, GIII, GIV, GV, and GVI). In GI and GII, only the sick digit was trimmed; in GIII and GIV, both sick and healthy digits of the lesioned limb were trimmed; and in GV and GVI, all digits were trimmed. During the postoperative period, 5 % S. adstringens extract was applied in GI, GIII, and GV, and 3 % copper sulfate solution was applied in GII, GIV, and GVI. After 60 days of evaluation, the data were analyzed using the Chi-squared test (p ≤ 0.05). Both therapeutic protocols utilizing surgical curettage of the lesions were efficient for treating digital dermatitis. However, when the procedure is followed by the trimming of sick and healthy digits, the healing is optimized and a greater number of animals are rehabilitated.

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: We searched the Cochrane Wounds Group Specialised Register (searched 30 September 2011); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3); Ovid OLDMEDLINE (1947 to 1965); Ovid MEDLINE (1950 to September Week 3 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations 29 September 2011); Ovid EMBASE (1980 to 2011 Week 38); EBSCO CINAHL (1982 to 23 September 2011) and Conference Proceedings Citation Index - Science (CPCI-S) (1990 to 30 September 2011). 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.

Studies of "unsteady gait disease" of the Tibetan gazelle (Procapra picticaudata).

Clinical signs of a disease locally referred to as "unsteady gait disease" for the Tibetan gazelle (Procapra picticaudata) were observed in the Qinghai Lake watershed area, China. The objective of this study was to determine if there was a relationship between the disease and copper (Cu) deficiency. Chemical examinations showed that Cu concentrations in soil and forage samples were similar from areas where gazelles were affected and unaffected. However, concentrations of sulfur (S) and molybdenum (Mo) in the soil and forage samples from the affected area were significantly higher than those from the unaffected areas (P<0.01). Copper concentrations in samples of blood, hair, and liver from the affected gazelles were significantly lower than those in unaffected animals (P<0.01). Supplementation of CuSO(4) in affected gazelles improved their appetite and vigor. We conclude that the disorder of Tibetan gazelles was caused by Cu deficiency, attributable to the high S and Mo content in forage.

Copper sulfate prevents tyrosine hydroxylase reduced activity and motor deficits in a Parkinson's disease model in mice.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the presence of motor disturbances, derived from the striatal dopamine depletion. Previously, we reported that CuSO4 pretreatment blocked an oxidative stress marker (lipid peroxidation) and prevented the striatal dopamine depletion induced by the administration of the 1-methyl-4-phenylpiridinium (MPP+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a model of PD. OBJECTIVE: . To determine if tyrosine hydroxylase (TH), the rate-limiting synthetic enzyme of dopamine, is implicated in the neuroprotective effect of CuSO4 pretreatment, and if this neuroprotective effect is able to prevent the hypokinetic state (measured as spontaneous locomotor activity, SLA) induced by the experimental model of PD. MATERIAL AND METHODS: C57 Black/6J mice received a single dose of CuSO4 (2.5 mg/kg, i.p.) either 16 or 24 h before the administration of MPP+ (18 microg/3 microl, i.c.v.). Twenty four hours later, mice SLA was registered and animals sacrificed. Striatal L-DOPA accumulation derived from the administration of a central dopamine descarboxilase inhibitor was evaluated, a strategy considered as a reliable indirect analysis of tyrosine hydroxylase activity (THA). RESULTS: Administration of, MPP+ decreased SLA (-52%; p = 0.003) as compared to control group values, whereas those mice pretreated with CuSO4 16 h before MPP+, increased SLA by 47% as compared with control group (p = 0.015). Mice pretreated with CuSO4 24 h before MPP+, also showed a statistically significant increase in SLA (71%; p = 0.02), when compared with control group. As a consequence of MPP+ administration, THA was also reduced as compared to control group values (32%; p < 0.05). Reduction of THA was blocked when mice were pretreated with CuSO4 16 h before MPP+. Moreover, mice receiving the CuSO4 24 h before MPP+ showed a significant increase (38%; p < 0.05) in THA when compared with control group. CONCLUSION: Results suggest that preservation of THA participates in the neuroprotective effects derived from the copper supplementation, a phenomenon that avoid the hypokinetic state induced by the MPP+ experimental model of PD.

Studies of a naturally occurring sulfur-induced copper deficiency in Przewalski's gazelles.

The Przewalski's gazelles in the Hudong area of the Qinghai Lake area in China were affected by an ailment characterized by pica, emaciation, dyskinesia, loss of appetite, and anemia. Concentrations of copper (Cu) in soil and forage from affected and unaffected areas were similar and within the normal range, but concentrations of sulfur (S) in soil and forage were significantly higher (P < 0.01) in affected than in unaffected areas. Concentrations of Cu in blood, hair, and liver from the affected Przewalski's gazelles were significantly lower (P < 0.01) than those in healthy animals. Affected Przewalski's gazelles showed a hypochromic microcytic anemia and a low level of ceruloplasmin. Oral administration of copper sulphate (CuSO(4)) prevented and cured the disease. We conclude that the disorder of Przewalski's gazelles was caused by secondary Cu deficiency, mainly due to high S content in forage.

Dietary copper sulfate for control of gastrointestinal nematodes in goats.

Prevalence of anthelmintic resistance in gastrointestinal nematodes (GIN) of goats has necessitated studies for alternative means of control. The objective was to determine the effectiveness of dietary copper sulfate for control of GIN in meat goats. Naturally infected buck kids received 0 (LC), 78 (MC) or 158 (HC) mg copper sulfate (CS)/kid daily mixed with concentrate supplement for 63 days. After 42 days the HC group was re-randomized into either the LC or MC treatment. In another study, naturally infected yearling does were offered trace mineral mix with and without CS and intake was estimated to be 140-200mg CS/day. Goats grazed bermudagrass pastures and were rotated among two or three pastures to minimize pasture effects. Fecal egg count (FEC) and packed cell volume (PCV) were determined every 7 days in the first experiment and 14 days in the second experiment, and goats were weighed every 28 days. On Days 49 and 56 FEC were lower in the HC-treated kids (copper by day, P<0.02), but FEC were similar on all other days in the first experiment and were similar between the two groups of does in the second experiment. Blood packed cell volume was similar among treatment groups throughout both studies. Body weight was greater in LC compared with MC or HC-supplemented kids on Days 42 and 63 (copper by day, P<0.04). Body weights of does were similar on Days 0 and 56, but were reduced in those consuming trace mineral with CS on Day 28 (copper by day, P<0.03). Dietary CS failed to control GIN in this study.

Therapeutic management of copper deficiency in buffalo heifers: impact on immune function.

To evaluate the magnitude of copper deficiency in Northern India and to examine the various haematobiochemicals, enzymes, vitamins and immune functions affected by copper deficiency, and to identify the parameters which can be of diagnostic importance in copper deficiency, a survey was conducted in 12 districts of Northern India. Significant deficiency of copper was observed in soil, fodder and serum samples of buffalo heifers. Fifty hypocuperaemic buffalo heifers were selected from these areas and were randomly divided into two groups, A and B. The heifers in group A were provided with mineral mixture containing copper sulphate and in group B without copper sulphate. Significant (p<0.01) improvement in serum ceruloplasmin level was observed within 30 days of treatment, while significant (p<0.01) improvement in monoamine oxidase and liver cytochrome oxidase was observed at the 60th day of treatment in group A animals. Significant improvement was observed in T(3) and T(4), in the animals of group A within 60 days of treatment. The values of vitamin A and E showed significant (p<0.01) improvement within 30 days of treatment. The phagocytic activity of neutrophils against Candida albicans significantly (p<0.01) improved in group A within 60 days of treatment. Similarly, significant improvement in superoxide dismutase activity in red blood cells was observed at the 30th day, and in total leukocytes and whole blood at the 60th day in group A animals. Significant improvement in liver copper level was observed at the 30th day of treatment, while in group B the liver copper was significantly (p<0.01) depleted at the 60th day of experimentation. Additional copper supplementation improved growth performance significantly in group A.

Copper deficiency in yaks on pasture in western China.

The clinical signs of a disorder in yaks (Bos grunniens), known locally as "swayback ailment," in the Qing Hai-Tibetan Plateau are described. The purpose of this study is to investigate the possibility that swayback ailment is iron (Fe)-induced copper (Cu) deficiency. The mean concentrations of Cu in soil and forage from affected areas and unaffected areas are similar and within the normal ranges. The mean concentrations of Cu in blood and hair from the affected yaks was significantly lower (P < 0.01) than that in unaffected yaks. The mean concentrations of Fe in soil and forage were significantly higher (P < 0.01) in affected than in unaffected areas. Affected yaks showed a hypochromic microcytic anemia and a low level of ceruloplasmin. Oral administration of copper sulphate prevented and cured the disease. We conclude that "swayback disorder" of yaks is caused by secondary Cu deficiency, mainly due to the high Fe content in forage.

Copper status and enzyme, hormone, vitamin and immune function in heifers.

A survey was conducted in 10 districts of Northern India to record the copper deficiency in soil, fodder and serum samples. Significant deficiency of copper was observed in soil, fodder and serum samples of heifers. The copper deficient animals were listless, showed depigmentation of skin, stiff gait and were anaemic and diahorric. The purpose of the study was to evaluate the magnitude of copper deficiency in Northern India and to examine the various haematobiochemicals, enzymes, vitamin and immune function which are affected by the deficiency of copper, so as to identify the parameters which can be of diagnostic importance in copper deficiency. Forty hypocuperemic heifers were selected from these areas and were randomly divided into two groups A and B. The heifers in group A were provided with mineral mixture containing copper sulphate and in group B without copper sulphate. Significant improvement (P<0.01) was observed in the haemoglobin (Hb), total leukocyte count (TLC) and total erythrocyte count (TEC) level at the 30th day of treatment in the animals of group A. Significant (P<0.01) improvement in serum. Ceruloplasmin (Cp) level was observed within 30 days of treatment, while significant (P<0.01) improvement in monoamine oxidase and liver cytochrome oxidase was observed at the 60th day of treatment in group A animals. Regarding hormones significant improvement was observed in T(3) and T(4), in the animals of group A within 60 days of treatment. The values of vitamin A and E showed significant (P<0.01) improvement within 30th days of treatment. The phagocytic activity of neutrophils against Candida albicans significantly (P<0.01) improved in group A within 60 days of treatment. Similarly significant improvement in superoxide dismutase activity in RBC was observed at the 30th day, and WBC and whole blood at 60th day in group A animals. Significant improvement in liver Cu level was observed at the 30th day of treatment, while in group B the liver Cu was significantly (P<0.01) depleted at the 60th day of experimentation. Additional Cu supplementation improved growth performance significantly in group A.

Therapeutic evaluation of zinc and copper supplementation in acute diarrhea in children: double blind randomized trial.

OBJECTIVE: To test the hypothesis that daily supplementation of zinc and copper mixed with the oral rehydration solution (ORS) reduces the duration and the severity of acute diarrhea in children. METHODS: In a randomized, double blind, placebo controlled trial children aged 6 months to 59 months in an urban hospital with acute diarrhea, were assigned to receive the intervention of once daily 40 mg of zinc sulfate and 5 mg of copper sulfate dissolved in a liter of standard ORS (n = 102) or placebo (50 mg of standard ORS powder) dissolved in a liter of ORS (n = 98). RESULT: The baseline characteristics in the two groups were similar. The mean survival time (days) (SE) with diarrhea was not significantly different in the treatment (4.34 (0.2)) as compared to the placebo group (4.48 (0.2)), nor was there any difference in the median time to cure. Cure was less likely with longer duration of diarrhea prior to enrollment (P < 0.001), if the time taken for rehydration was more (P = 0.001) and if intravenous fluids were used (P = 0.03) regardless of the micronutrient supplementation. The proportion of children with diarrhea > 4 days was 46% in the placebo group with an adjusted odds ratio (OR) (95% CI) of 1.19 (1.58, 0.9; P = 0.2) as compared to 39% in the supplemented group. The most important risk factor for diarrhea > 4 days was diarrheal duration prior to enrollment with OR = 6.25 (3.7, 11.1). The supplemented group however had less severity of diarrhea with a lower proportion of children requiring unscheduled intravenous fluids (OR = 0.4; 95% CI 0.05, 2.2), with weight loss (OR = 0.7; 95% CI; 0.4, 1.3), with complications (OR = 0.15; 0.01, 1.3) and had no deaths as compared to two in the placebo group. CONCLUSIONS: This study showed that the most important predictor for duration of diarrhea in children was the severity of the disease at enrollment, and, not the supplementation. There were clinical beneficial effects of supplementation on rate of any complications and mortality. A larger trial is warranted before supplementation of micronutrients mixed with ORS are recommended for management of acute diarrhea.