Rosmarinic acid turned α-syn oligomers into non-toxic species preserving microtubules in Raw 264.7 cells.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, and the therapeutic is focused on several approaches including the inhibition of fibril formation by small compounds, avoiding the formation of cytotoxic oligomers. Thus, we decided to explore the capacity of compounds carrying catechol moieties to inhibit the progression of α-synuclein. Overall, the compounds rosmarinic acid (1), carnosic acid (2), carnosol (3), epiisorosmanol (4), and rosmanol (5) avoid the progression of fibril formation assessed by Thiofavine T (ThT), and atomic force microscopy images showed that morphology is influenced for the actions of compounds over fibrillization. Moreover, ITC experiments showed a Kd varying from 28 to 51 µM, the ΔG showed that the reaction between compounds and α-syn is spontaneous, and ΔH is associated with an exothermic reaction, suggesting the interactions of hydrogen bonds among compounds and α-syn. Docking experiments reinforce this idea showing the intermolecular interactions are mostly hydrogen bonding within the sites 2, 9, and 3/13 of α-synuclein, and compounds 1 and 5. Thus, compound 1, rosmarinic acid, interestingly interacts better with site 9 through catechol and Lysines. In cultured Raw 264. 7 cells, the presence of compounds showed that most of them can promote cell differentiation, especially rosmarinic acid, and rosmanol, both preserving tubulin cytoskeleton. However, once we evaluated whether or not the aggregates pre-treated with compounds could prevent the disruption of microtubules of Raw 264.7 cells, only pre-treated aggregates with rosmarinic acid prevented the disruption of the cytoskeleton. Altogether, we showed that especially rosmarinic acid not only inhibits α-syn but stabilizes the remaining aggregates turning them into not-toxic to Raw 264.7 cells suggesting a main role in cell survival and antigen processing in response to external α-syn aggregates.

Voltammetric analysis of luminescent markers in gunshot residues.

Currently, SEM-EDS is used to detect gunshot residue (GSR) from the presence of Ba, Pb, and Sb in the sample. However, the development of new nontoxic ammunition (NTA) has prevented conventional metals from being found. In this work, we aim to determine the presence of an inorganic luminescent chemical marker based on rare earth in gunshot residues using the technique of squarewave voltammetry (SWV). After firing, the luminescent complex [(Eu2 Zr)(btc)3 (Hbtc)0.5 .6H2 O], which is used as a chemical marker, can be detected under a UV lamp. An aqueous solution with 0.1 mol L-1 KCl as supporting electrolyte can be easily collected on carbon paste electrode surfaces for SWV analysis A = 100 mV, f = 10 Hz, and step potential of 5 mV are required. The luminescent marker incorporated into the carbon paste electrode showed two anodic peak currents in the region of 0.4 V (vs Ag/AgCl) and at 0.75 V (vs Ag/AgCl) and also a cathodic one in 0.4 V (vs Ag/AgCl). SEM-EDS was able to analyze the same voltammetric results for conventional and nontoxic ammunition containing the luminescent marker. Therefore, voltammetry and SEM-EDS are valid for detecting the new residue marker in GSR. Despite this, the electrochemical method is still more advantageous because of its low cost and lack of expensive equipment and supplies in forensic laboratories.

Environmentally Safe Photodynamic Control of Aedes aegypti Using Sunlight-Activated Synthetic Curcumin: Photodegradation, Aquatic Ecotoxicity, and Field Trial.

This study reports curcumin as an efficient photolarvicide against Aedes aegypti larvae under natural light illumination. Larval mortality and pupal formation were monitored daily for 21 days under simulated field conditions. In a sucrose-containing formulation, a lethal time 50 (LT50) of 3 days was found using curcumin at 4.6 mg L-1. This formulation promoted no larval toxicity in the absence of illumination, and sucrose alone did not induce larval phototoxicity. The photodegradation byproducts (intermediates) of curcumin were determined and the photodegradation mechanisms proposed. Intermediates with m/z 194, 278, and 370 were found and characterized using LC-MS. The ecotoxicity of the byproducts on non-target organisms (Daphnia, fish, and green algae) indicates that the intermediates do not exhibit any destructive potential for aquatic organisms. The results of photodegradation and ecotoxicity suggest that curcumin is environmentally safe for non-target organisms and, therefore, can be considered for population control of Ae. aegypti.

Cryodehydration protocol to obtain high-quality permanent anatomical material.

The study of anatomy is largely dependent on cadaveric specimens to fulfill the tridimensional comprehension of each structure as well as the relationship between organs. Given the difficult access to fresh anatomical specimens, the constant renovation of samples for research and educational purposes is unsustainable, beyond the ethical issues involved. The standard technique for preserving specimens involves fixation and later immersion in formaldehyde, which enables a good result, but also presents elevated carcinogenic potential. Therefore, safe and efficient preservation methods are mandatory for anatomical practices and investigations. An accessible and inexpensive alternative for specimen preservation is cryodehydration. Cryodehydrated specimens can be kept dry, with no final odor, reducing the use and exposure to formaldehyde. The objective of this study was to propose a simplified step-by-step cryodehydration protocol to obtain high-quality anatomical specimens. Through consecutive freezing and thawing cycles, cryodehydration caused a weight reduction of 60%-70% and allowed anatomical preservation, while maintaining the main morphological aspects of cavitary and parenchymatous organs, muscles, or even full-body sections. The final specimens presented high durability and can be maintained for decades, preserving all relevant anatomical features.

Subacute and subchronic toxicity of microencapsulated pomegranate juice in rats and mice.

Pomegranate (Punica granatum L.) is a fruit used extensively in traditional medicine by ancient and modern cultures. Different parts of the tree and fruit, such as leaf, peel, pericarp, aril, seed, and juice contain considerable amounts of phenolic compounds with high antioxidant activities. To improve its storability, pomegranate juice was microencapsulated by spray drying. The present study evaluated microencapsulated pomegranate juice (MPJ) for toxic effects in Wistar rats and CD-1 mice to determine if MPJ can be considered safe for human consumption and used as a nutraceutical. No deaths or deleterious effects occurred when high doses of 5000 mg/kg were orally administered in rats for 14 days, indicating an absence of subacute toxicity. Similarly, 3000 mg/kg MPJ administered to CD-1 mice for 90 days did not show subchronic toxicity. In fact, MPJ resulted in lowered weight gain in both rats and mice. Cytotoxic and microbiological analyses of MPJ were also performed. MPJ did not cause any cytotoxicity in epithelial cell culture as tested using the Alamar blue assay. Additionally, histopathological analysis of kidney and liver corroborated the absence of toxicity in CD-1 mice. The microbial load of the MPJ was low, and no pathogenic bacteria were present. In conclusion, the results reported here show that high doses of MPJ are apparently innocuous in rats and mice for the 14 and 90 days investigated, respectively. Although preliminary, our results suggest that MPJ may be safe to ingest and may even have beneficial effects in reducing weight gain.

Manufacturing micro/nano chitosan/chondroitin sulfate curcumin-loaded hydrogel in ionic liquid: A new biomaterial effective against cancer cells.

Chitosan/chondroitin sulfate (CHT/CS) curcumin-charged hydrogels were prepared through polyelectrolytic complexation (PEC) following two methodologies (PEC-CUR and PEC-T-CUR) and were applied on apoptosis of HeLa, HT29 and PC3 cancer cells. PEC-T-CUR (ionic liquid (IL) mixed using ultraturrax homogenizer) results show to be far better than for PEC-CUR (IL mixed using magnetic stirring), with IC50 being improved 5.13 times to HeLa cancer cells (from 1675.2 to 326.7 µg mL-1). PECs produced by this methodology presented favorable characteristics, such as particle size, hydrophobicity, pH swelling. Beyond this, the IL was quantitatively recovered in both cases. CUR entrapment levels were hugely loaded into PEC at around 100%. Swelling, dissolution/degradation, and pHpzc assays showed that PECs may positively act in several environments, releasing the CUR, the CHT and CS as well. Characterization through FTIR, SEM, TEM, TGA, DSC, and WAXS confirmed CUR presence in both types of PECs, and cytotoxic studies showed the significant anticancer effects of CUR-containing PECs.

Comparison of ethylene carbonate and formamide as components of the hybridization mixture in FISH

The protocols for in situ hybridization (ISH) techniques can vary considerably; however, they usually include denaturation and hybridization steps. Denaturing compounds are used to reduce denaturation and hybridization temperature, which keeps the proper morphology of the preparation. Formamide is the most commonly used reagent in in situ hybridization to lower the melting temperature. The substitution of toxic formamide for a non-toxic ethylene carbonate at 20 % and 50% concentration in the hybridization mixture helped obtain a high quality in situ hybridization result with two sequences characteristic for rye, JNK, and Bilby. The results after hybridization, with a duration of 90 min and 16 h, were identical when formamide or ethylene carbonate were used in the mixture. In addition, the toxic formamide was eliminated from the post-hybridization steps and specific hybridization signals for both probes were still obtained.

Comparison of ethylene carbonate and formamide as components of the hybridization mixture in FISH

The protocols for in situ hybridization (ISH) techniques can vary considerably; however, they usually include denaturation and hybridization steps. Denaturing compounds are used to reduce denaturation and hybridization temperature, which keeps the proper morphology of the preparation. Formamide is the most commonly used reagent in in situ hybridization to lower the melting temperature. The substitution of toxic formamide for a non-toxic ethylene carbonate at 20 % and 50% concentration in the hybridization mixture helped obtain a high quality in situ hybridization result with two sequences characteristic for rye, JNK, and Bilby. The results after hybridization, with a duration of 90 min and 16 h, were identical when formamide or ethylene carbonate were used in the mixture. In addition, the toxic formamide was eliminated from the post-hybridization steps and specific hybridization signals for both probes were still obtained.(AU)

Analysis of Luminescent Gunshot Residue (LGSR) on Different Types of Fabrics.

The collection of gunshot residue on fabric can be an arduous task due to the microscopic size of particles (blind collection) and sheddability of some fabrics. The introduction of luminescent markers and consequent formation of luminescent gunshot residue (LGSR) can facilitate this analysis. In this study, different fabrics were analyzed in order to verify the persistence of the LGSR on them, the possibility of collecting and analyzing particles by video spectral comparator (VSC) and SEM/EDS. Also, different colored fabrics were used as targets in order to investigate influence of fabric color on LGSR visualization. Furthermore, the influence of the fabric type in the distribution of the LGSR deposited around the projectile´s hole entrance was evaluated. The fabric sheddability did not alter collection of the particles or analysis. It was possible to observe and collect LGSR on all tested fabrics, even after the fabric had been shaken, or in colored fabrics.

Resultados a corto plazo del tratamiento con 131I en el bocio multinodular: valor adicional de la estimulación previa con rhTSH / Short-term results of treatment with 131I in multinodular goiter: additional value of previus stimulation with Recombinant human thyrotropin

OBJETIVO: El yodo radiactivo (131I) es una opción terapeútica segura y eficaz cuando se utiliza solo o con la estimulación previa de TSH recombinante humana (rhTSH) en el tratamiento del bocio multinodular (BMN). En espera de ensayos clínicos que determinen la dosis óptima, demuestren seguridad y confirmen la eficacia, diferentes protocolos se utilizan para aplicar la dosis de 131I. Analizamos la respuesta al tratamiento con una dosis calculada por protocolo mixto (dosis fijas y cálculo por porcentaje de captación) en pacientes con BMN toxico y no toxico en nuestro hospital, en el periodo 2010-2013. MATERIALES Y MÉTODOS: Estudio prospectivo en pacientes con BMN no quirúrgico (BMNNQ) que requerían reducción del volumen glandular y/o tratamiento del hipertiroidismo. Se evaluaron 134 pacientes, 14 cumplieron con los criterios de inclusión (13mujeres) de edad media 71.08 años. Un grupo con BMN toxico, otro grupo con BMN no toxico, un tercer grupo con BMN no toxico estimulado con 0,1 mg de rhTSH previo a la dosis. Se evaluó, función tiroidea, captación tiroidea de 99ᵐTc, volumen tiroideo y síntomas compresivos. Se siguió a los pacientes durante 12 meses. RESULTADOS: Se aplicaron dosis entre 15 y 30 mCi de 131I. Remitió el hipertiroidismo en 6 de 7 pacientes. Hubo una reducción del volumen glandular (p<0.01).Los pacientes con estímulo de 0,1 mg rhTSH, aumentaron el porcentaje de captación de 99ᵐTc a las 24 h en un 32.43±10.61 permitiendo aplicar menor dosis de 131I. La tasa de aparición de hipotiroidismo fue de 7.41 por cada 100 pacientes.mes, mayor en pacientes con BMN toxico tratados con dosis bajas (p-=0.03). Hubo una mejoría subjetiva de la clínica compresiva en todos los pacientes. No hubo eventos adversos. CONCLUSIONES: Una dosis de 131I calculada por protocolo mixto es efectiva y segura para la reducción del volumen glandular y control del hipertiroidismo asociado. La estimulación con rhTSH logra el mismo efecto con una menor dosis administrada.

OBJECTIVE: Radioactive iodine (131I) is a safe and effective therapeutic option when used alone or with prior stimulation of recombinant human Thyrotropin (rhTSH) in the treatment of multinodular goiter (MNG). In absence of clinical trials that determine the optimal dose, demonstrate safety and confirm efficacy, different protocols are used to apply the dose of 131I. We analyze the response to treatment with a dose calculated by mixed protocol (fixed doses and calculation by percentage of uptake) in patients with toxic and non-toxic MNG in our hospital, in the period 2010-2013. MATERIALS AND METHODS: Prospective study in patients with non-surgical MNG that required glandular volume reduction and / or treatment of hyperthyroidism. 134 patients were evaluated, 14 met the inclusion criteria (13 women) of average age 71.08 years. One group with toxic MNG, another group with non-toxic MNG and a third with non-toxic multinodular goiter stimulated with 0.1 mg of rhTSH prior to the dose. Patients were followed for 12 months. Upon following, we assessed Thyroid function, 99ᵐTc thyroid uptake, thyroid volume and compressive symptoms. RESULTS: Doses between 15 and 30 mCi of 131I were applied. We observed hyperthyroidism remission in 6 of 7 patients. There was a reduction in glandular volume (p <0.01) considering all patients. Patients with a stimulus of 0.1 mg rhTSH, increased the percentage of uptake of 99ᵐTc at 24 h by 32.43 ± 10.61, allowing a lower dose of 131I to be applied. The rate of onset of hypothyroidism was 7.41 per 100 patients-month, and was higher in patients with toxic MNG treated with low doses (p = 0.03). There was a subjective improvement of the compression clinic in all patients. No adverse events were observed. CONCLUSIONS: A dose of 131I calculated by a mixed protocol is effective and safe for achieving glandular volume reduction and associated hyperthyroidism control. Stimulation with rhTSH produces the same effect with a lower administered dose.

TsNTxP, a non-toxic protein from Tityus serrulatus scorpion venom, induces antinociceptive effects by suppressing glutamate release in mice.

Neuropathic pain is a common type of chronic pain caused by trauma or chemotherapy. However, this type of pain is undertreated. TsNTxP is a non-toxic protein isolated from the venom of the scorpion Tityus serrulatus, and it is structurally similar to neurotoxins that interact with voltage-gated sodium channels. However, the antinociceptive properties of this protein have not been characterized. The purpose of this study was to investigate the antinociceptive effects of TsNTxP in acute and neuropathic pain models. Male and female Swiss mice (25-30 g) were exposed to different models of acute pain (tail-flick test and nociception caused by capsaicin intraplantar injection) or neuropathic pain (chronic pain syndrome induced by paclitaxel or chronic constriction injury of the sciatic nerve). Hypersensitivity to mechanical or cold stimuli were evaluated in the models of neuropathic pain. The ability of TsNTxP to alter the release of glutamate in mouse spinal cord synaptosomes was also evaluated. The results showed that TsNTxP exerted antinociceptive effects in the tail-flick test to a thermal stimulus and in the intraplantar capsaicin administration model. Furthermore, TsNTxP was non-toxic and exerted antiallodynic effects in neuropathic pain models induced by chronic constriction injury of the sciatic nerve and administration of paclitaxel. TsNTxP reduced glutamate release from mouse spinal cord synaptosomes following stimulation with potassium chloride (KCl) or capsaicin. Thus, this T. serrulatus protein may be a promising non-toxic drug for the treatment of neuropathic pain.

Silver nanoparticles enhance survival of white spot syndrome virus infected Penaeus vannamei shrimps by activation of its immunological system.

The global aquaculture has shown an impressive growth in the last decades contributing with a major part of total food fish supply. However, it also helps in the spread of diseases that in turn, causes great economic losses. The White Spot Syndrome Virus (WSSV) is one of the major viral pathogen for the shrimp aquaculture industry. Several attempts to eliminate the virus in the shrimp have been addressed without achieving a long-term effectiveness. In this work, we determine the capacity of the commercial non-toxic PVP-coated silver nanoparticles to promote the response of the immune system of WSSV-infected shrimps with or without an excess of iron ions. Our results showed that a single dose of metallic silver in the nanomolar range (111 nmol/shrimp), which is equivalent to 12 ng/mL of silver nanoparticles, produces 20% survival of treated infected shrimps. The same concentration administered in healthy shrimps do not show histological evidence of damage. The observed survival rate could be associated with the increase of almost 2-fold of LGBP expression levels compared with non-treated infected shrimps. LGBP is a key gene of shrimp immunological response and its up-regulation is most probably induced by the recognition of silver nanoparticles coating by specific pathogen-associated molecular pattern recognition proteins (PAMPs) of shrimp. Increased LGBP expression levels was observed even with a 10-fold lower dose of silver nanoparticles (1.2 ng/shrimp, 0.011 nmol of metallic silver/shrimp). The increase in LGBP expression levels was also observed even in the presence of iron ion excess, a condition that favors virus proliferation. Those results showed that a single dose of a slight amount of silver nanoparticles were capable to enhance the response of shrimp immune system without toxic effects in healthy shrimps. This response could be enhanced by administration of other doses and might represent an important alternative for the treatment of a disease that has still no cure, white spot syndrome virus.

Immunization with a nontoxic naturally occurring Clostridium perfringens alpha toxin induces neutralizing antibodies in rabbits.

Clostridium perfringens alpha toxin, encoded by plc gene, has been implicated in gas gangrene, a life threatening infection. Vaccination is considered one of the best solutions against Clostridium infections. Although studies have identified many low quality clostridial vaccines, the use of recombinant proteins has been considered a promising alternative. Previously, a naturally occurring alpha toxin isoform (αAV1b) was identified with a mutation at residue 11 (His/Tyr), which can affect its enzymatic activity. The aim of the present study was to evaluate whether the mutation in the αAV1b isoform could result in an inactive toxin and was able to induce protection against the native alpha toxin. We used recombinant protein techniques to determine whether this mutation in αAV1b could result in an inactive toxin compared to the active isoform, αZ23. Rabbits were immunized with the recombinant toxins (αAV1b and αZ23) and with native alpha toxin. αAV1b showed no enzymatic and hemolytic activities. ELISA titration assays showed a high titer of both anti-recombinant toxin (anti-rec-αAV1b and anti-rec-αZ23) antibodies against the native alpha toxin. The alpha antitoxin titer detected in the rabbits' serum pool was 24.0 IU/mL for both recombinant toxins. These results demonstrate that the inactive naturally mutated αAV1b is able to induce an immune response, and suggest it can be considered as a target for the development of a commercial vaccine against C. perfringens alpha toxin.

Use of luminescent gunshot residues markers in forensic context-Part II.

Gunshot residues (GSR) are important physical evidence in firearm-related crimes. Recently developed non-toxic ammunition, however, requires a new methodology for its characterization. To overcome this drawback, the introduction of noncommercial luminescent markers in ammunition was proposed. These markers, synthesized and added to the gunpowder, presented as a versatile tool for GSR analysis, since they require UV radiation alone to visualize the luminescent GSR (LGSR). This has opened up new perspectives for understanding GSR behavior at a crime scene. This work aims to expand previous studies performed with the luminescent markers in forensic contexts, exploring four different important aspects related to GSR behavior. Using LGSR amount/dispersion and a series of blind tests with marked ammunition, we tried to (1) identify the shooter position; (2) estimate the shooting distance; (3) evaluate the influence of the pistol type on the LGSR distribution on the shooter's hands and guns; and (4) study the transference of LGSR by a chain of handshaking. For this purpose, a portable UV lamp (λ=254nm) and/or techniques such as video spectral comparator (VSC) and scanning electron microscopy with energy dispersive X-ray analysis (SEM/EDS) were used to visualize and analyze the residues. As a result, the observation of the LGSR enabled accurate determination of the shooter position and the firing distance without any chemicals. Besides, the LGSR were visualized on different kinds of pistols, regardless of firing mechanism. And finally, this study evidenced transference of residues from shaking hands with the shooter, which should be carefully considered when interpreting the results of a GSR analysis.

Pollen morphology of four species of Jatropha (Euphorbiaceae), including toxic varieties, in Northwestern Mexico / Morfología del polen de cuatro especies de Jatropha (Euphorbiaceae), incluyendo variedades tóxicas, en el noroeste de México

AbstractJatropha curcas is a native Mexican plant, distributed in the forests of coastal regions; it has shown potential for the production of biofuel, and its raw protein can be used as animal feed. Nevertheless, its current varieties have low yield and production variability, as it is in domestication period. The knowledge of the pollen grains is fundamental for studies of Jatropha reproductive biology and breeding for genetic improvement to generate new hybrids and improve fruit and seed yield. This study compared pollen morphology of four Jatropha species, which include two varieties of J. curcas (one toxic from India and one non-toxic from Mexico), and two varieties of wild J. cinerea (Sinaloa and Baja California Sur); additionally, pollen was collected from wild J. platyphylla (Sinaloa) and J. vernicosa (Baja California Sur) to characterize them palynologically. We used a scanning electron microscope to describe the size and shape of pollen grains. Pollen grains were observed spheroidal. The diameter of the varieties of toxic and non-toxic J. curcas and that of J. platyphylla were 58 ± 2.3, 54 ± 1.7, and 51 ± 2.4 µm, respectively; the number of clavae was 84 ± 10, 108 ± 15, and 180 ± 15.5, respectively. Pollen grains of J.cinerea (Sinaloa) had a diameter of 50 ± 1.7 µm and 220 ± 14 clavae by area; J. cinerea (Baja California Sur) had a diameter of 45 ± 1.9 µm and 195 ± 14.7 clavae. Pollen grains of J. vernicosa had a diameter of 46 ± 2.1 µm and 231 ± 25.6 clavae. The ornamentation of the exine showed clava with capita gemma shaped for varieties of J.curcas species and clavum shaped for J. platyphylla, J. cinerea and J. vernicosa species. The studied varieties have a cross-linked endexine and ectexine intectate. Luminal bacules were observed in the reticular space of J. curcas varieties while none were present in the varieties of J. cinerea, J. platyphylla, and J. vernicosa.

ResumenJatropha curcas es nativa de México, y se distribuye en los bosques de las regiones costeras; las plantas han mostrado potencial para la producción de biodiesel, y la proteína cruda puede utilizarse para alimentación animal. Sin embargo, sus variedades actuales tienen bajo rendimiento y variabilidad en la producción, por estar en periodo de domesticación. El conocimiento de los granos de polen es fundamental para el estudio de la biología reproductiva de Jatropha y mejoramiento genético para generar nuevos híbridos y mejorar el rendimiento de frutos y semillas. Este estudio compara la morfología del polen de cuatro especies de Jatropha, que incluyen dos variedades de J. curcas, (una tóxica de India y una no tóxica de México) y dos variedades silvestres de J. cinerea (Sinaloa y Baja California Sur), por último, se obtuvo polen de J. platyphylla (Sinaloa) y J. vernicosa (Baja California Sur) silvestres para caracterizarlos palinológicamente. Para describir el tamaño y la forma de los granos de polen, se utilizó un microscopio electrónico de barrido. Los granos de polen tienen forma esferoidal. El diámetro de las variedades de J. curcas tóxica y no tóxica, y J. platyphylla fueron 58 ± 2.3, 54 ± 1.7, y 51 ± 2.4 micras, respectivamente; el número de clavas fue de 84 ± 10, 108 ± 15 y 180 ± 15.5, respectivamente. Los granos de polen de J. cinerea (Sinaloa) tienen un diámetro de 50 ± 1.7 micras y 220 ± 14 clavas por zona; J. cinerea (Baja California Sur) tiene un diámetro de 45 ± 1.9 micras y 195 ± 14.7 clavas. Los granos de polen de J. vernicosa tienen un diámetro de 46 ± 2.1 micras y 231 ± 25.6 clavas. La ornamentación de la exina mostró clavas con cápita en forma de gema y pequeños báculos en el lumen para ambas J. curcas y en forma de clavum para J. cinerea, J. platyphylla y J. vernicosa y no presentan báculos en el lumen. Las variedades estudiadas tienen una endexina reticulada y ectexina intectada.

Which Is the Ideal Treatment for Benign Diffuse and Multinodular Non-Toxic Goiters?

Patients with large benign goiters often present local compressive symptoms that require surgical treatment, including dysphagia, neck tightness, and airway obstruction. In contrast, patients with such goiters who remain asymptomatic may be observed after exclusion of malignancy. The use of levothyroxine (LT4) to reduce the volume of the goiter is still a controversial treatment for large goiters, and the optimal surgical procedure for multinodular goiter is still debatable. Radioiodine is a safe and effective treatment option when used alone or in combination with recombinant human TSH. This review discusses current therapeutic options to treat diffuse and multinodular non-toxic benign goiters.

A universal polysaccharide conjugated vaccine against O111 E. coli.

E. coli O111 strains are responsible for outbreaks of blood diarrhea and hemolytic uremic syndrome throughout the world. Because of their phenotypic variability, the development of a vaccine against these strains which targets an antigen that is common to all of them is quite a challenge. Previous results have indicated, however, that O111 LPS is such a candidate, but its toxicity makes LPS forbidden for human use. To overcome this problem, O111 polysaccharides were conjugated either to cytochrome C or to EtxB (a recombinant B subunit of LT) as carrier proteins. The O111-cytochrome C conjugate was incorporated in silica SBA-15 nanoparticles and administered subcutaneously in rabbits, while the O111-EtxB conjugate was incorporated in Vaxcine(TM), an oil-based delivery system, and administered orally in mice. The results showed that one year post-vaccination, the conjugate incorporated in silica SBA-15 generated antibodies in rabbits able to inhibit the adhesion of all categories of O111 E. coli to epithelial cells. Importantly, mice immunized orally with the O111-EtxB conjugate in Vaxcine(TM) generated systemic and mucosal humoral responses against all categories of O111 E. coli as well as antibodies able to inhibit the toxic effect of LT in vitro. In summary, the results obtained by using 2 different approaches indicate that a vaccine that targets the O111 antigen has the potential to prevent diarrhea induced by O111 E. coli strains regardless their mechanism of virulence. They also suggest that a conjugated vaccine that uses EtxB as a carrier protein has potential to combat diarrhea induced by ETEC.