Nanolipid-loaded Preyssler polyoxometalate: Synthesis, characterization and invitro inhibitory effects on HepG2 tumor cells.

Polyoxometalate-based drugs have been selected by some researchers as alternative antitumor substances with promising results in suppression of tumor growth because of low toxicity towards the human body and high activity. In this research, for the first time, nanolipid-loaded Preyssler polyoxometalate with diameters of 230-250 nm was synthesized and characterized by the Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Analysis (EDAX), Atomic Force Microscopy (AFM), and Infrared (IR) spectroscopy. The nanoliposomes were found to be nearly spherical, without any agglomeration with the Entrapment Efficiency of 53.8%. In -vitro antitumor activity of the synthesized nanoliposomes was investigated using the MTT method on HepG2 tumor cells. Our findings showed enhanced anticancer activity for the nanolipid-loaded Preyssler (NLP) compared to the Sorafenib as a commercially drug at 72 h. Selectivity of the synthesized NLP and Sorafenib for cancer cells versus primary HFF cells was obtained as 4.2 and 2.2, respectively. The IC50 value of the loaded nanoliposomes for cancer cells and normal cells was equal to 470 and 2000 µg/mL, respectively at 72 h, which was much better compared to that of the Sorafenib (7 and 16 µg/mL, respectively).

Intrathecal Administration of Nanoclusters for Protecting Neurons against Oxidative Stress in Cerebral Ischemia/Reperfusion Injury.

Oxidative stress is one of the important mechanisms in cerebral ischemia/reperfusion (I/R) injury. Antioxidants with high brain accumulation are highly desired to help prevent cerebral I/R injury. Herein, intrathecal injection of polyoxometalate (POM) nanoclusters as nano-antioxidants with preferential brain uptake were applied for neuronal protection in cerebral I/R injury. Using powerful positron emission tomography imaging, the uptake of nano-antioxidants in the brain was non-invasively and real-timely monitored. Our results demonstrated that POM nanoclusters rapidly reached the ischemic penumbra after intrathecal injection and effectively scavenged reactive oxygen species (ROS) for inhibiting oxidative stress. The infarct size was reduced, and neurological function was restored in cerebral I/R injury rat models. As a proof-of-concept, the intrathecal injection of nano-antioxidants is an excellent therapeutic strategy to ameliorate cerebral I/R injury.

Antiviral effects of a niobium-substituted heteropolytungstate on hepatitis B virus-transgenic mice.

To study the efficacy of a polyoxometalate, Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O, as an antiviral treatment in HBV transgenic mice. HBV transgenic mice were treated with Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O by intragastric administration. Adefovir and distilled water were administered as controls. Serum HBV DNA, liver HBV RNA levels were measured by quantitative RT-PCR. Serum HBsAg levels were measured by ELISA. The hepatitis B virus surface antigen (HBsAg) in liver cells was detected by immunohistochemistry (IHC). Pathological changes in the liver tissues were also observed by light and electron microscopy. Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O significantly decreased serum HBsAg and HBV DNA levels. Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O resulted in a 98% decrease in serum HBV DNA at 28 days, from 4.3 log10 copies/ml at baseline to 2.5 log10 copies/ml after treatment, and the inhibition rate of HBV DNA was higher than ADV at the same dose. The HBV replication levels in each group slightly increased at 7 days after withdrawal, but rebounded slightly more in the Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O treatment group compared to the H2 O control group (p < .05). There were no differences in HBV RNA levels. No significant differences were observed in the pathology, but there were decreased HBsAg levels in the Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O-treated group compared to the control group. The results demonstrated that Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O displayed potent anti-HBV activity in HBV transgenic mice and supported for future clinic study.

Radioluminescent nanoparticles for radiation-controlled release of drugs.

The present work demonstrates a novel concept for intratumoral chemo-radio combination therapy for locally advanced solid tumors. For some locally advanced tumors, chemoradiation is currently standard of care. This combination treatment can cause acute and long term toxicity that can limit its use in older patients or those with multiple medical comorbidities. Intratumoral chemotherapy has the potential to address the problem of systemic toxicity that conventional chemotherapy suffers, and may, in our view, be a better strategy for treating certain locally advanced tumors. The present study proposes how intratumoral chemoradiation can be best implemented. The enabling concept is the use of a new chemotherapeutic formulation in which chemotherapy drugs (e.g., paclitaxel (PTX)) are co-encapsulated with radioluminecsnt nanoparticles (e.g., CaWO4 (CWO) nanoparticles (NPs)) within protective capsules formed by biocompatible/biodegradable polymers (e.g., poly(ethylene glycol)-poly(lactic acid) or PEG-PLA). This drug-loaded polymer-encapsulated radioluminescent nanoparticle system can be locally injected in solution form into the patient's tumor before the patient receives normal radiotherapy (e.g., 30-40 fractions of 2-3 Gy daily X-ray dose delivered over several weeks for locally advanced head and neck tumors). Under X-ray irradiation, the radioluminescent nanoparticles produce UV-A light that has a radio-sensitizing effect. These co-encapsulated radioluminescent nanoparticles also enable radiation-triggered release of chemo drugs from the polymer coating layer. The non-toxic nature (absence of dark toxicity) of this drug-loaded polymer-encapsulated radioluminescent nanoparticle ("PEG-PLA/CWO/PTX") formulation was confirmed by the MTT assay in cancer cell cultures. A clonogenic cell survival assay confirmed that these drug-loaded polymer-encapsulated radioluminescent nanoparticles significantly enhance the cancer cell killing effect of radiation therapy. In vivo study validated the efficacy of PEG-PLA/CWO/PTX-based intratumoral chemo-radio therapy in mouse tumor xenografts (in terms of tumor response and mouse survival). Results of a small-scale NP biodistribution (BD) study demonstrate that PEG-PLA/CWO/PTX NPs remained at the tumor sites for a long period of time (> 1 month) following direct intratumoral administration. A multi-compartmental pharmacokinetic model (with rate constants estimated from in vitro experiments) predicts that this radiation-controlled drug release technology enables significant improvements in the level and duration of drug availability within the tumor (throughout the typical length of radiation treatment, i.e., > 1 month) over conventional delivery systems (e.g., PEG-PLA micelles with no co-encapsulated CaWO4, or an organic liquid, e.g., a 50:50 mixture of Cremophor EL and ethanol, as in Taxol), while it is capable of maintaining the systemic level of the chemo drug far below the toxic threshold limit over the entire treatment period. This technology thus has the potential to offer a new therapeutic option that has not previously been available for patients excluded from conventional chemoradiation protocols.

High doses of sodium tungstate can promote mitochondrial dysfunction and oxidative stress in isolated mitochondria.

Tungstate (W) is recognized as an agent of environmental pollution and a substitute to depleted uranium. According to some preliminary studies, tungstate toxicity is related to the formation of reactive oxygen species (ROS) under abnormal pathological conditions. The kidneys and liver are the main tungstate accumulation sites and important targets of tungstate toxicity. Since the mitochondrion is the main ROS production site, we evaluated the mechanistic toxicity of tungstate in isolated mitochondria for the first time, following a two-step ultracentrifugation method. Our findings demonstrated that tungstate-induced mitochondrial dysfunction is related to the increased formation of ROS, lipid peroxidation, and potential membrane collapse, correlated with the amelioration of adenosine triphosphate and glutathione contents. The present study indicated that mitochondrial dysfunction was associated with disruptive effects on the mitochondrial respiratory chain and opening of mitochondrial permeability transition (MPT) pores, which is correlated with cytochrome c release. Our findings suggest that high concentrations of tungstate (2 mM)-favored MPT pore opening in the inner membranes of liver and kidney mitochondria of rats. Besides, the results indicated higher tungstate susceptibility in the kidneys, compared with the liver.

Recommended Drilling Parameters of Tungsten Carbide Round Drills for the Most Optimal Bone Removals in Oral Surgery.

BACKGROUND: High temperatures during drilling can cause thermal osteonecrosis and abnormal wound healing. According to our best knowledge, a widely accepted recommendation for optimal drilling parameters in routine oral surgery bone removals does not exist. PURPOSE: Our aim was to investigate the correlations of different drilling parameters, including axial load and revolution speed on drilling temperatures and preparation times. MATERIALS AND METHODS: Standard, 5 mm deep cavities were drilled in 20 PCF (lb/ft3) dens polyurethane blocks with 3 mm (50PCF) cortical layer using new and worn, 3.1mm in diameter tungsten carbide round drills. Worn drills were used in 50 impacted third molar operations before. Axial loads of 3N, 10N, and 25N and speeds of 4.000-8.000-16.000-40.000 revolutions per minute (rpm) were tested. Temperature differences of drilling parameters were calculated by 1-way ANOVA, followed by Tukey's HSD post hoc tests. Time differences and differences among "optimal" and "suboptimal" groups (with the cut-off value of 3°C and 3s) were estimated by Kruskal-Wallis test with pairwise comparisons. P<0.05 was considered significant. RESULTS: The highest mean temperatures with new and worn drills were 4.64±0.53°C and 6.89±1.16°C, while drilling times varied between 0.16±0.02s and 22.77±5.45s. A 3°C and 3s cut-off value classified drillings significantly to (1) optimal [3N and 8000-16000-40000 rpm or 10N and 4000-8000-16000-40000 rpm] or suboptimal due to (2) high temperatures or (3) long preparation times. Using worn drills, the following parameters should be avoided: 3N with 4.000-8.000 rpm, 10N with 40000 rpm, and 25N at any revolutions. DISCUSSION: The study extensively mapped the drilling temperatures and preparation times of tungsten carbide round drills. Temperatures did not exceed 10°C during drillings with maximal amount of cooling, as well as the drilling parameters, which kept temperatures and preparation times in the most optimal range which were clearly established.

Novel pH responsive supramolecular hydrogels of chitosan hydrochloride and polyoxometalate: In-vitro, in-vivo and preliminary safety evaluation.

In the current study, electrostatically-driven pH responsive, supramolecular hydrogels of the trilacunary Wells-Dawson-type 15-tungsto-2-phosphate polyanion (P2W15) and chitosan hydrochloride (ChCl) were prepared, using methacrylic acid as pH responsive agent using benzoyl peroxide (BPO) as initiator. The prepared hydrogels were characterized by FT-IR, SEM, XRD and thermal analyses (TGA-DSC). The swelling and pH based P2W15 release profile of the hydrogels showed maximum swellability and release at pH 7.4. Different mathematical models were applied, showing that P2W15 release followed supercase transport-II mechanism and zero-order kinetics. The cytotoxicity results showed that free and embedded P2W15 exhibited dose-dependent cytotoxicity against cancer cell lines (MCF-7; HeLa) with minimal effects on normal cells (Vero). The developed hydrogels were administered to the rabbits for determining the pharmacokinetic behavior of the polyanion. Moreover, the developed hydrogel system as well as polyanion concentration used were also checked for its oral tolerability and safety evaluation in rabbits. The histopathological studies, serum chemistry (except blood glucose level) and hematological investigations exhibited that administered hydrogel suspension at maximal tolerable dose (4000mg/kg body weight) and polyanion concentration used (20mg) were safe from in-vivo point of view. The developed hydrogels exhibited desirable qualities of a drug delivery system that can be used for the delivery of the embedded polyanion.

Stimuli-Responsive "Cluster Bomb" for Programmed Tumor Therapy.

In this paper, mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and capped with tumor-homing/-penetrating peptide tLyP-1-modified tungsten disulfide quantum dots (WS2-HP) was designed and applied as a stimuli-responsive "Cluster Bomb" for high-performance tumor suppression. The peptide tLyP-1 on the surface can both facilitate the homing of DOX@MSN-WS2-HP to 4T1 tumor and greatly enhance the penetration of WS2-HP in tumor. The benzoic-imine bonds as the linkers between "bomblets" and "dispenser" are stable under normal physical conditions and quite labile at pH 6.8. After arriving at the mild acidic tumor microenvironment, the nanoplatform can rapidly break into two parts: (1) electropositive DOX@MSN-NH2 for efficient chemotherapy on surface tumor cells and (2) small-sized WS2-HP with improved tumor penetrating ability for near-infrared (NIR)-light-triggered photothermal therapy (PTT) among deep-seated tumor cells. Having killed the tumor cells in different depths, DOX@MSN-WS2-HP exhibited significant antitumor effect, which will find great potential in clinical trials.

Genotoxicity and acute and subchronic toxicity studies of a bioactive polyoxometalate in Wistar rats.

BACKGROUND: Cs2K4Na [SiW9Nb3O40] (POM93) is a novel broad-spectrum antiviral agent with high activity, high stability, and low toxicity in vitro. Most toxicity studies for POM93 have been performed in cultured cell lines rather than in animals. Like other POMs, there is a lack of evidence for in vivo toxicity limits, oral bioavailability, and therapeutic applications. METHODS: The toxic properties of POM93 were evaluated comprehensively in vivo, including the acute and subchronic oral toxicity studies and genotoxicity tests. RESULTS: The acute toxicity study showed no abnormal changes or mortality in rats treated with POM93 even at the single high dose of 5000 mg/kg body weight. In the subchronic toxicity study, regardless of the body weight, the organ weight, and the hematological parameters, similar results were observed between the control group and the experimental groups. POM93 produced mild changes in rare hematological parameters in the liver and kidneys, but did not induce the clinical symptoms of liver or kidneys injury in rats as confirmed by histopathological analysis. Moreover, neither mutagenicity nor clastogenicity was caused by POM93 treatment in vitro and in vivo. CONCLUSIONS: The present study demonstrates that the oral administration of POM93 is presumed safe and poses a low risk of potential health risks.

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water.

Tungsten is a naturally occurring, high-tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0-2000 mg STD/L in their drinking water for 28 d, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3(+) T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely affect cell-mediated immunity.

Ultrastructural Analysis of In Vivo Hypoglycemiant Effect of Two Polyoxometalates in Rats with Streptozotocin-Induced Diabetes.

Two polyoxometalates (POMs), synthesized through a self-assembling method, were used in the treatment of streptozotocin (STZ)-induced diabetic rats. One of these nanocompounds [tris(vanadyl)-substituted tungsto-antimonate(III)-anions­POM1] was previously described in the literature, whereas the second [tris-butyltin-21-tungsto-9-antimonate(III)-anions­POM2], was prepared by us based on our original formula. In rats with STZ-induced diabetes treated with POMs (up to a cumulative dose of 4 mg/kg bodyweight at the end of the treatments), statistically significant reduced levels of blood glucose were measured after 3 weeks, as compared with the diabetic control groups (DCGs). Ultrastructural analysis of pancreatic ß-cells (including the mean diameter of secretory vesicles and of their insulin granules) in the treated diabetic rats proved the POMs contribute to limitation of cellular degeneration triggered by STZ, as well as to the presence of increased amounts of insulin-containing vesicles as compared with the DCG. The two POMs also showed hepatoprotective properties when ultrastructural aspects of hepatocytes in the experimental groups of rats were studied. Based on our in vivo studies, we concluded that the two POMs tested achieved hypoglycemiant effects by preventing STZ-triggered apoptosis of pancreatic ß-cells and stimulation of insulin synthesis.

Interactions of 1D- and 2D-layered inorganic nanoparticles with fibroblasts and human mesenchymal stem cells.

AIM: This study investigates the effects of tungsten disulfide nanotubes (WSNTs) and molybdenum disulfide nanoplatelets (MSNPs) on fibroblasts (NIH-3T3) and mesenchymal stem cells (MSCs) to determine safe dosages for potential biomedical applications. MATERIALS & METHODS: Cytotoxicity of MSNPs and WSNTs (5-300 µg/ml) on NIH-3T3 and MSCs was assessed at 6, 12 or 24 h. MSC differentiation to adipocytes and osteoblasts was assessed following treatment for 24 h. RESULTS: Only NIH-3T3 cells treated with MSNPs showed dose or time dependent increase in cytotoxicity. Differentiation markers of MSCs in treated groups were unaffected compared with untreated controls. CONCLUSION: MSNPs and WSNTs at concentrations less than 50 µg/ml are potentially safe for treatment of fibroblasts or MSCs for up to 24 h.

Role of sodium tungstate as a potential antiplatelet agent.

PURPOSE: Platelet inhibition is a key strategy in the management of atherothrombosis. However, the large variability in response to current strategies leads to the search for alternative inhibitors. The antiplatelet effect of the inorganic salt sodium tungstate (Na2O4W), a protein tyrosine phosphatase 1B (PTP1B) inhibitor, has been investigated in this study. METHODS: Wild-type (WT) and PTP1B knockout (PTP1B(-/-)) mice were treated for 1 week with Na2O4W to study platelet function with the platelet function analyzer PFA-100, a cone-and-plate analyzer, a flat perfusion chamber, and thrombus formation in vivo. Human blood aliquots were incubated with Na2O4W for 1 hour to measure platelet function using the PFA-100 and the annular perfusion chamber. Aggregometry and thromboelastometry were also performed. RESULTS: In WT mice, Na2O4W treatment prolonged closure times in the PFA-100 and decreased the surface covered (%SC) by platelets on collagen. Thrombi formed in a thrombosis mice model were smaller in animals treated with Na2O4W (4.6±0.7 mg vs 8.9±0.7 mg; P<0.001). Results with Na2O4W were similar to those in untreated PTP1B(-)/(-) mice (5.0±0.3 mg). Treatment of the PTP1B(-)/(-) mice with Na2O4W modified only slightly this response. In human blood, a dose-dependent effect was observed. At 200 µM, closure times in the PFA-100 were prolonged. On denuded vessels, %SC and thrombi formation (%T) decreased with Na2O4W. Neither the aggregating response nor the viscoelastic clot properties were affected. CONCLUSION: Na2O4W decreases consistently the hemostatic capacity of platelets, inhibiting their adhesive and cohesive properties under flow conditions in mice and in human blood, resulting in smaller thrombi. Although Na2O4W may be acting on platelet PTP1B, other potential targets should not be disregarded.

Sodium tungstate induced neurological alterations in rat brain regions and their response to antioxidants.

Tungsten, recognized recently as an environmental contaminant, is being used in arms and ammunitions as substitute to depleted uranium. We studied the effects of sodium tungstate on oxidative stress, few selected neurological variables like acetylcholinesterase, biogenic amines in rat brain regions (cerebral cortex, hippocampus and cerebellum) and their prevention following co-administration of N-acetylcysteine (NAC), naringenin and quercetin. Animals were sub-chronically exposed to sodium tungstate (100 ppm in drinking water) and orally co-supplemented with different antioxidants (0.30 mM) for three months. Sodium tungstate significantly decreased the activity of acetylcholinesterase, dopamine, nor-epinephrine and 5-hydroxytryptamine levels while it increased monoamine oxidase activity in different brain regions. Tungstate exposure produced a significant increase in biochemical variables indicative of oxidative stress while, neurological alterations were more pronounced in the cerebral cortex compared to other regions. Co-administration of NAC and flavonoids with sodium tungstate significantly restored glutathione, prevented changes in the brain biogenic amines, reactive oxygen species (ROS) and TBARS levels in the different brain regions. The protection was more prominent in the animals co-administered with NAC. We can thus conclude that sodium tungstate induced brain oxidative stress and the alterations in some neurological variables can effectively be reduced by co-supplementation of NAC.

Subchronic Oral Toxicity of Sodium Tungstate in Sprague-Dawley Rats.

The subchronic toxicity of sodium tungstate dihydrate aqueous solution in male and female Sprague-Dawley rats was evaluated by daily oral gavage of 0, 10, 75, 125, or 200 mg/kg/d for 90 days. Measured parameters included food consumption, body weight measurements, hematology, clinical chemistry, and histopathological changes. There was a significant decrease in food consumption and body weight gain in males at 200 mg/kg/d from days 77 to 90; however, there was no effect in food consumption and body weights in females. There were no changes in the hematological and clinical parameters studied. Histopathological changes were seen in kidney of male and female and epididymis of male rats. Histopathological changes were observed in the kidneys of male and female rats dosed at 125 or 200 mg/k/d consisting of mild to severe cortical tubule basophilia in 2 high-dose groups. Histological changes in epididymides included intraluminal hypospermia with cell debris in the 200 mg/kg/d dosed male rats. Histopathological changes were observed in the glandular stomach including inflammation and metaplasia in the high-dose groups (125 or 200 mg/kg/d) of both sexes of rats. Based on histopathology effects seen in the kidneys, the lowest observable adverse effect level was 125 mg/kg/d and the no observable adverse effect level was 75 mg/kg/d in both sexes of rats for oral subchronic toxicity.

Gold-nanoparticle-based multifunctional amyloid-ß inhibitor against Alzheimer's disease.

Targeting amyloid-ß (Aß)-induced complex neurotoxicity has received considerable attention in the therapeutic and preventive treatment of Alzheimer's disease (AD). The complex pathogenesis of AD suggests that it requires comprehensive treatment, and drugs with multiple functions against AD are more desirable. Herein, AuNPs@POMD-pep (AuNPs: gold nanoparticles, POMD: polyoxometalate with Wells-Dawson structure, pep: peptide) were designed as a novel multifunctional Aß inhibitor. AuNPs@POMD-pep shows synergistic effects in inhibiting Aß aggregation, dissociating Aß fibrils and decreasing Aß-mediated peroxidase activity and Aß-induced cytotoxicity. By taking advantage of AuNPs as vehicles that can cross the blood-brain barrier (BBB), AuNPs@POMD-pep can cross the BBB and thus overcome the drawbacks of small-molecule anti-AD drugs. Thus, this work provides new insights into the design and synthesis of inorganic nanoparticles as multifunctional therapeutic agents for treatment of AD.

Studies on some fish parasites of public health importance in the southern area of Saudi Arabia / Estudos sobre alguns parasitas de peixes com importância para a saúde pública na região sul da Arábia Saudita

The present study was the first attempt to survey the diversity of fish zoonotic parasites in the southern region of Saudi Arabia, particularly the Najran area, from October 2012 to October 2013. Approximately 163 fish representing seven species (two of freshwater fish and five of marine fish) were examined for fish-borne trematode metacercariae using the compression technique, and for zoonotic nematode larvae. Adult flukes were obtained from cats experimentally infected with the metacercariae on day 25 post-infection The prevalence of each parasite species was recorded. The parasites found belonged to two taxa: Digenea (Heterophyes heterophyes and Haplorchis pumilio) in muscle tissue; and nematodes (larvae of Capillaria sp.) in the digestive tract. The morphological characteristics of the fish-borne trematode metacercariae and their experimentally obtained adults were described. This is the first report of these parasites in fish in Saudi Arabia. Moreover, Myripristis murdjan presented higher prevalence of Capillaria sp. infection (22.7%), while Haplorchis pumilio was the dominant metacercarial species (7.9%). Although the number of documented cases continues to increase, the overall risk of human infection is slight. The increasing exploitation of the marine environment by humans and the tendency to reduce cooking times when preparing seafood products both increase the chances of becoming infected with these parasites. Furthermore, our results indicate that certain fish production systems are at risk of presenting fish zoonotic parasites, and that control approaches will benefit from understanding these risk factors.

O presente estudo representa a primeira tentativa para investigar a diversidade dos parasitas zoonóticos em peixes na Região Sul da Arábia Saudita, em particular na área de Najran, de outubro de 2012 a outubro de 2013. Aproximadamente, 163 peixes representando sete espécies (duas de água doce e cinco marinhas) foram examinados para as metacercária, dos trematódeos de peixes, usando-se a técnica de compressão e para as larvas de nematoides. Os trematódeos adultos foram obtidos em gatos experimentalmente infectados com metacercárias no 25° dia após a infecção. A prevalência de cada espécie parasita foi registrada. Os parasitas encontrados pertenciam a dois taxa: Digenea (Heterophyes heterophyes e Haplorchis pumilio) no tecido muscular; e nematoides (larvas de Capillaria sp.) no trato digestivo. As características morfológicas das metacercárias dos trematódeos de peixes e dos adultos experimentalmente obtidos são descritas. Esse é o primeiro relato desses parasitas em peixes da Arábia Saudita. Além desses, Myripristis murdjan apresentou alta prevalência de infecção por Capillaria sp. (22,7%), enquanto Haplorchis pumilio foi a espécie de metacercárias dominante (7,9%). Embora o número de casos documentados continue a aumentar, o risco global de infecção humana é pequeno. A exploração crescente do ambiente marinho pelos seres humanos e a tendência de redução do processo de cozimento no preparo de alimentos oriundos do mar aumentam as chances de infecção por esses parasitas. Os resultados deste estudo também indicam que certos sistemas de produção de pescados estão em risco de apresentar parasitas zoonóticos, e que o seu controle trará benefícios na compreensão destes fatores de risco.

Detección temprana de cáncer de mama y cervicouterino en localidades con concentración de población indígena en Morelos / Early detection of breast and cervical cancer among indigenous communities in Morelos, Mexico

Objetivo. Analizar la percepción de mujeres y proveedores de salud sobre cuándo y cómo realizar acciones para la detección temprana del cáncer de mama y cervicouterino en localidades de Morelos con presencia de población indígena. Material y métodos. Se entrevistó a 10 proveedores de salud y 58 usuarias en unidades médicas del primer nivel de atención de cinco localidades; luego se analizó la información con base en el paradigma de la teoría fundamentada. Resultados. El personal de salud está deficientemente familiarizado con los lineamientos oficiales para la detección de cáncer cervicouterino y de mama. Pocos practican sus labores bajo una perspectiva de sensibilización intercultural. Las usuarias tienen nociones imprecisas o equivocadas de las acciones de detección. Conclusiones. La necesidad de capacitación con apego a las normas es evidente. Urge asumir un abordaje con pertinencia cultural que permita la comunicación eficiente y alfabetización en salud para la detección oportuna de estos dos cánceres.

Objective. To analyze the perception in relation to when and how to perform actions for the early detection of breast and cervical cancer among women and health care providers in communities with a high percentage of indigenous population in Morelos, Mexico. Materials and methods. Ten health providers and 58 women users of health services were interviewed which have a first level of attention in five communities. The analysis was developed under the approach of the Grounded Theory. Results. Providers are poorly informed about current regulations and specific clinical indications for the detection of cervical and breast cancer. Few propitiate health literacy under intercultural sensitization. The users have imprecise or wrong notions of the early detection. Conclusions. The need for training in adherence to norms is evident. It is urgent to assume a culturally relevant approach to enable efficient communication and promote health literacy for early detection of these two cancers.

Tungstate promotes ß-cell survival in Irs2-/- mice.

Pancreatic ß-cells play a central role in type 2 diabetes (T2D) development, which is characterized by the progressive decline of the functional ß-cell mass that is associated mainly with increased ß-cell apoptosis. Thus, understanding how to enhance survival of ß-cells is key for the management of T2D. The insulin receptor substrate-2 (IRS-2) protein is pivotal in mediating the insulin/IGF signaling pathway in ß-cells. In fact, IRS-2 is critically required for ß-cell compensation in conditions of increased insulin demand and for ß-cell survival. Tungstate is a powerful antidiabetic agent that has been shown to promote ß-cell recovery in toxin-induced diabetic rodent models. In this study, we investigated whether tungstate could prevent the onset of diabetes in a scenario of dysregulated insulin/IGF signaling and massive ß-cell death. To this end, we treated mice deficient in IRS2 (Irs2(-/-)), which exhibit severe ß-cell loss, with tungstate for 3 wk. Tungstate normalized glucose tolerance in Irs2(-/-) mice in correlation with increased ß-cell mass, increased ß-cell replication, and a striking threefold reduction in ß-cell apoptosis. Islets from treated Irs2(-/-) exhibited increased phosphorylated Erk1/2. Interestingly, tungstate repressed apoptosis-related genes in Irs2(-/-) islets in vitro, and ERK1/2 blockade abolished some of these effects. Gene expression profiling showed evidence of a broad impact of tungstate on cell death pathways in islets from Irs2(-/-) mice, consistent with reduced apoptotic rates. Our results support the finding that ß-cell death can be arrested in the absence of IRS2 and that therapies aimed at reversing ß-cell mass decline are potential strategies to prevent the progression to T2D.

Use of pectin-thorium (IV) tungstomolybdate nanocomposite for photocatalytic degradation of methylene blue.

Pectin-thorium (IV) tungstomolybdate (Pc/TWM) nanocomposite was prepared by mixing biopolymer pectin with its inorganic counterpart thorium (IV) tungstomolybdate (TWM) using the sol-gel method. The nanocomposite was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). Distribution coefficient, thermal stability, pH titrations, elution and concentration behaviour were investigated to explore the ion exchange behaviour of nanocomposite material. Pc/TWM exhibited higher ion exchange capacity (1.10 mequiv/g) than its inorganic counterpart (0.62 mequiv/g). The Pc/TWM nanocomposite ion exchanger was thermally stable as it retained 59% of its ion exchange capacity upto 400°C. The pH titrations study revealed the bifunctional nature of Pc/TWM. In order to explore the environmental applicability of the Pc/TWM nanocomposite material, its antibacterial and photocatalytic activities was investigated. 76% of methylene blue dye was photocatalytically degraded after five hours exposure. It also totally inhibited Escherichia coli at 400 µg/ml concentration of Pc/TWM nanocomposite.