A Comparative Analysis of the Venom System between Two Morphotypes of the Sea Anemone Actinia equina.

The current study investigates the venom-delivery system of green and red morphotypes of the sea anemone Actinia equina to disclose its potential as a source of bioactive compounds. We compared the two morphotypes using electron and optical microscopy, proteomics, and toxicity assessment on zebrafish embryos. Specialized venom-injecting cells (nematocysts) are equally distributed and found in the tentacles of both varieties. Proteomics revealed proteins of interest in both red and green Actinia, yielding the three most abundant Gene Ontology (GO) terms related to the biological processes "proteolysis", "hemolysis in another organism" and "lipid catabolic process". Neurotoxins and cytolytic toxins similar to known cnidarian toxins like PsTX-60A and AvTX-60A, for instance, were identified in both types. Extracts from green and red anemones were toxic to zebrafish embryos, with green anemone venom appearing to be more potent. The findings highlight the presence of proteinaceous toxins in A. equina and the potential for different varieties to possess distinct bioactive compounds. Notably, pore-forming toxins are suggested for molecular probes and immunotoxins, making them valuable assets for potential biotechnological and biomedical purposes.

Dexamethasone phosphate and penetratin co-eluting contact lenses: a strategy to enhance ocular drug permeability.

Contact lenses (CLs) have been suggested as drug delivery platforms capable of increasing the drug residence time on the cornea and therefore its bioavailability. However, when targeting the posterior segment of the eye, the drug released from CLs still encounters the barrier effect of the ocular tissues, which considerably reduces the efficacy of administration. This work aims at the development of CLs able to simultaneously deliver an anti-inflammatory drug (dexamethasone sodium phosphate) and a cell-penetrating peptide (penetratin), the latter acting as a drug carrier across the tissues. Hydroxyethyl methacrylate (HEMA)-based hydrogels were functionalized with acrylic acid (AAc) and/or aminopropyl methacrylamide (APMA) to serve as CL materials with increased affinity for the drug and peptide. APMA-functionalized hydrogels sustained the dual release for 8 h, which is compatible with the wearing time of daily CLs. Hydrogels demonstrated suitable light transmittance, swelling capacity and in vitro biocompatibility. The anti-inflammatory activity of the drug was not compromised by the presence of the peptide nor by sterilization. The ocular distribution of the drug after 6 h of CL wearing was evaluated in vivo in rabbits and revealed that the amount of drug in the cornea and aqueous humor significantly increased when the drug was co-delivered with penetratin.

Comparative analysis of the jaw apparatus of three marine annelids using scanning electron microscopy: Microstructure and elemental composition.

Polychaeta are highly diversified invertebrates that inhabit marine, brackish or freshwater environments. They have acquired a unique range of adaptative features for securing food. However, the jaw apparatus may reveal not only defence and predation mechanisms, but also its relation to environmental chemistry. The present work compared the structure and chemical profile of the jaws of different estuarine Polychaeta: Nephtys hombergii (Nephtyidae), Hediste diversicolor (Nereididae) and Glycera alba (Glyceridae) using Scanning Electron Microscopy (SEM) and Scanning Electron Microscopy with Energy Dispersive X-Ray (SEM-EDX). Analyses revealed that N. hombergii possesses a muscular jawless proboscis with terminal sensorial papillae for detecting prey, whereas the G. alba proboscis exhibits four delicately sharp jaws with perforations for venom delivery and H. diversicolor bears two blunt denticulated jaws to grasp a wide variety of food items. Melanin and metals like copper provide hardness to the slender jaws of Glycera, while, in the absence of heavier metallic elements, halogens contribute to H. diversicolor jaws robustness. The more specific chemistry of the jaws of glycerids is associated with its more refined venom injection, whereas Hediste is an opportunistic omnivore and Nepthys an agile forager. Altogether, the chemistry of jaws is an adaptive feature for feeding, locomotion and even resilience to complex and often adverse chemical profiles of estuaries.

Antitumoral and Antimicrobial Activities of Block Copolymer Micelles Containing Gold Bisdithiolate Complexes.

Gold(III) bisdithiolate complexes have been reported as potential antimicrobial and antitumoral agents. The complex [Au(cdc)2]- (cdc=cyanodithioimido carbonate) displayed antimicrobial and outstanding antitumor activity against the ovarian cancer cells A2780 and A2780cisR, which are sensitive and resistant to cisplatin, respectively. However, poor water solubility may hamper its clinical use. Block copolymer micelles (BCMs) may solubilize hydrophobic drugs, improving their bioavailability and circulation time in blood. Aiming to provide water solubility, prolonged availability, and enhanced therapeutic indexes, BCMs loaded with [Au(cdc)2]- were synthesized and characterized. The BCM-[Au(cdc)2] micelles were prepared with a loading efficiency of 64.6% and a loading content of 35.3 mg [Au(cdc)2]-/gBCM. A hydrodynamic diameter of 77.31 ± 27.00 nm and a low polydispersity index of 0.18 indicated that the micelles were homogenous and good candidates for drug delivery. Cytotoxic activity studies against A2780/A2780cisR cells showed that BCM-[Au(cdc)2] maintained relevant cytotoxic activity comparable to the cytotoxicity observed for the same concentration of gold complexes. The Au uptake in A2780 cells, determined by PIXE, was ca. 17% higher for BCMs-[Au(cdc)2] compared to [Au(cdc)2]-. The BCMs-[Au(cdc)2] presented antimicrobial activity against S. aureus Newman and C. glabrata CBS138. These results evidenced the potential of BCM-[Au(cdc)2] for drug delivery and its promising anticancer and antimicrobial activities.

The use of ultrasound and magnetic resonance imaging in the management of hidradenitis suppurativa: a narrative review.

Hidradenitis suppurativa (HS) is a chronic, inflammatory follicular skin disease that frequently affects the apocrine gland-bearing skin of the axillary, inguinal and anogenital regions. HS has a significant impact on the psychosocial health and quality of life of patients. Diagnosis of HS is typically clinical, and relies on the ability of physicians to recognize the signs of HS. However, lesions may present at the dermal and subcutaneous skin layers, which cannot be diagnosed by clinical examination alone. Further, the complexity of the clinical presentation of HS can lead to misdiagnosis and delay of diagnosis and appropriate treatment. Imaging is an important tool that can address these issues by detecting inflammatory activity and the early subclinical and dermal features of HS, and accurately characterizing lesional morphology, thereby informing on optimal therapeutic strategies. Overall, imaging is a key tool that can be used in conjunction with clinical examination to improve the management of HS by providing additional information to physicians, and thus optimize clinical decision making. In this narrative review, we provide an overview of the general role of imaging in the management of HS, and we illustrate HS-specific applications of two pertinent imaging modalities, ultrasound and magnetic resonance imaging. Finally, based on the literature, we summarize their uses in HS and provide considerations relating to standardizing the practise of ultrasound and effectively implementing the use of imaging in the management of HS.

Dental Implant Surface Decontamination and Surface Change of an Electrolytic Method versus Mechanical Approaches: A Pilot In Vitro Study.

Dental implants are the preferred fixed oral rehabilitation for replacing lost teeth. When peri-implant tissues become inflamed, the removal of plaque accumulating around the implant becomes imperative. Recently, several new strategies have been developed for this purpose, with electrolytic decontamination showing increased potential compared to traditional mechanical strategies. In this in vitro pilot study, we compare the efficacy of an electrolytic decontaminant (Galvosurge®) with an erythritol jet system (PerioFlow®) and two titanium brushes (R-Brush™ and i-Brush™) in removing Pseudomonas aeruginosa PAO1 biofilms from implants. Changes in the implant surface after each approach were also evaluated. Twenty titanium SLA implants were inoculated with P. aeruginosa and then randomly assigned to each treatment group. After treatment, decontamination efficacy was assessed by quantifying colony-forming units (log10 CFU/cm2) from each implant surface. Scanning electron microscopy was used to analyse changes in the implant surface. With the exception of R-Brush, all treatment strategies were similarly effective in removing P. aeruginosa from implants. Major surface changes were observed only in implants treated with titanium brushes. In conclusion, this pilot study suggests that electrolytic decontamination, erythritol-chlorhexidine particle jet system and i-Brush™ brushing have similar performance in removing P. aeruginosa biofilm from dental implants. Further studies are needed to evaluate the removal of more complex biofilms. Titanium brushes caused significant changes to the implant surface, the effects of which need to be evaluated.

Gastric ectopic pancreas in magnetic resonance imaging: A review of 2 cases.

Gastric ectopic pancreas (EP) is an uncommon congenital anomaly in which pancreatic tissue with no anatomic connection to the main pancreas is found in the stomach. Gastric EP is often discovered incidentally when a nonspecific submucosal tumor is found in endoscopic studies or other imaging examinations. Tissue characterization by biopsy or fine-needle aspiration is required as endoscopic findings alone cannot exclude malignancy. The authors present 2 cases of gastric EP incidentally detected on endoscopy, which underwent further characterization by magnetic resonance imaging (MRI). In both cases, MRI showed submucosal gastric lesions, isointense to the orthotopic pancreas in all sequences, including hyperintensity on T1-weighted images. Furthermore, the lesions showed bright arterial phase enhancement, paralleling the native pancreas. MRI may provide the best non-invasive imaging method for evaluating gastric submucosal lesions. This report intends to show that EP shows a characteristic MR appearance that allows differentiation from other submucosal lesions.

Assessing in vivo and in vitro biofilm development by Streptococcus dysgalactiae subsp. dysgalactiae using a murine model of catheter-associated biofilm and human keratinocyte cell.

Streptococcus dysgalactiae subsp. dysgalactiae (SDSD) is an important agent of bovine mastitis. This infection causes an inflammatory reaction in udder tissue, being the most important disease-causing significant impact on the dairy industry. Therefore, it leads to an increase in dairy farming to meet commercial demands. As a result, there is a major impact on both the dairy industry and the environment including global warming. Recurrent mastitis is often attributed to the development of bacterial biofilms, which promote survival of sessile cells in hostile environments, and resistance to the immune system defense and antimicrobial therapy. Recently, we described the in vitro biofilm development on abiotic surfaces by bovine SDSD. In that work we integrated microbiology, imaging, and computational methods to evaluate the biofilm production capability of SDSD isolates on abiotic surfaces. Additionally, we reported that bovine SDSD can adhere and internalize human cells, including human epidermal keratinocyte (HEK) cells. We showed that the adherence and internalization rates of bovine SDSD isolates in HEK cells are higher than those of a SDSD DB49998-05 isolated from humans. In vivo, bovine SDSD can cause invasive infections leading to zebrafish morbidity and mortality. In the present work, we investigated for the first time the capability of bovine SDSD to develop biofilm in vivo using a murine animal model and ex-vivo on human HEK cells. Bovine SDSD isolates were selected based on their ability to form weak, moderate, or strong biofilms on glass surfaces. Our results showed that SDSD isolates displayed an increased ability to form biofilms on the surface of catheters implanted in mice when compared to in vitro biofilm formation on abiotic surface. A greater ability to form biofilm in vitro after animal passage was observed for the VSD45 isolate, but not for the other isolates tested. Besides that, in vitro scanning electron microscopy demonstrated that SDSD biofilm development was visible after 4 hours of SDSD adhesion to HEK cells. Cell viability tests showed an important reduction in the number of HEK cells after the formation of SDSD biofilms. In this study, the expression of genes encoding BrpA-like (biofilm regulatory protein), FbpA (fibronectin-binding protein A), HtrA (serine protease), and SagA (streptolysin S precursor) was higher for biofilm grown in vivo than in vitro, suggesting a potential role for these virulence determinants in the biofilm-development, host colonization, and SDSD infections. Taken together, these results demonstrate that SDSD can develop biofilms in vivo and on the surface of HEK cells causing important cellular damages. As SDSD infections are considered zoonotic diseases, our data contribute to a better understanding of the role of biofilm accumulation during SDSD colonization and pathogenesis not only in bovine mastitis, but they also shed some lights on the mechanisms of prosthesis-associated infection and cellulitis caused by SDSD in humans, as well.

Copper Acts Synergistically With Fluconazole in Candida glabrata by Compromising Drug Efflux, Sterol Metabolism, and Zinc Homeostasis.

The synergistic combinations of drugs are promising strategies to boost the effectiveness of current antifungals and thus prevent the emergence of resistance. In this work, we show that copper and the antifungal fluconazole act synergistically against Candida glabrata, an opportunistic pathogenic yeast intrinsically tolerant to fluconazole. Analyses of the transcriptomic profile of C. glabrata after the combination of copper and fluconazole showed that the expression of the multidrug transporter gene CDR1 was decreased, suggesting that fluconazole efflux could be affected. In agreement, we observed that copper inhibits the transactivation of Pdr1, the transcription regulator of multidrug transporters and leads to the intracellular accumulation of fluconazole. Copper also decreases the transcriptional induction of ergosterol biosynthesis (ERG) genes by fluconazole, which culminates in the accumulation of toxic sterols. Co-treatment of cells with copper and fluconazole should affect the function of proteins located in the plasma membrane, as several ultrastructural alterations, including irregular cell wall and plasma membrane and loss of cell wall integrity, were observed. Finally, we show that the combination of copper and fluconazole downregulates the expression of the gene encoding the zinc-responsive transcription regulator Zap1, which possibly, together with the membrane transporters malfunction, generates zinc depletion. Supplementation with zinc reverts the toxic effect of combining copper with fluconazole, underscoring the importance of this metal in the observed synergistic effect. Overall, this work, while unveiling the molecular basis that supports the use of copper to enhance the effectiveness of fluconazole, paves the way for the development of new metal-based antifungal strategies.

Dose Rate Effects on the Selective Radiosensitization of Prostate Cells by GRPR-Targeted Gold Nanoparticles.

For a while, gold nanoparticles (AuNPs) have been recognized as potential radiosensitizers in cancer radiation therapy, mainly due to their physical properties, making them appealing for medical applications. Nevertheless, the performance of AuNPs as radiosensitizers still raises important questions that need further investigation. Searching for selective prostate (PCa) radiosensitizing agents, we studied the radiosensitization capability of the target-specific AuNP-BBN in cancer versus non-cancerous prostate cells, including the evaluation of dose rate effects in comparison with non-targeted counterparts (AuNP-TDOTA). PCa cells were found to exhibit increased AuNP uptake when compared to non-tumoral ones, leading to a significant loss of cellular proliferation ability and complex DNA damage, evidenced by the occurrence of multiple micronucleus per binucleated cell, in the case of PC3 cells irradiated with 2 Gy of γ-rays, after incubation with AuNP-BBN. Remarkably, the treatment of the PC3 cells with AuNP-BBN led to a much stronger influence of the dose rate on the cellular survival upon γ-photon irradiation, as well as on their genomic instability. Overall, AuNP-BBN emerged in this study as a very promising nanotool for the efficient and selective radiosensitization of human prostate cancer PC3 cells, therefore deserving further preclinical evaluation in adequate animal models for prostate cancer radiotherapy.

Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells.

As Yondelis joins the ranks of approved anti-cancer drugs, the benefit from exploring the oceans' biodiversity becomes clear. From marine toxins, relevant bioproducts can be obtained due to their potential to interfere with specific pathways. We explored the cytotoxicity of toxin-bearing secretions of the polychaete Eulalia onto a battery of normal and cancer human cell lines and discovered that the cocktail of proteins is more toxic towards an ovarian cancer cell line (A2780). The secretions' main proteins were identified by proteomics and transcriptomics: 14-3-3 protein, Hsp70, Rab3, Arylsulfatase B and serine protease, the latter two being known toxins. This mixture of toxins induces cell-cycle arrest at G2/M phase after 3h exposure in A2780 cells and extrinsic programmed cell death. These findings indicate that partial re-activation of the G2/M checkpoint, which is inactivated in many cancer cells, can be partly reversed by the toxic mixture. Protein-protein interaction networks partake in two cytotoxic effects: cell-cycle arrest with a link to RAB3C and RAF1; and lytic activity of arylsulfatases. The discovery of both mechanisms indicates that venomous mixtures may affect proliferating cells in a specific manner, highlighting the cocktails' potential in the fine-tuning of anti-cancer therapeutics targeting cell cycle and protein homeostasis.

Spiro-ß-lactam BSS-730A Displays Potent Activity against HIV and Plasmodium.

The high burden of malaria and HIV/AIDS prevents economic and social progress in developing countries. A continuing need exists for development of novel drugs and treatment regimens for both diseases in order to address the tolerability and long-term safety concerns associated with current treatment options and the emergence of drug resistance. We describe new spiro-ß-lactam derivatives with potent (nM) activity against HIV and Plasmodium and no activity against bacteria and yeast. The best performing molecule of the series, BSS-730A, inhibited both HIV-1 and HIV-2 replication with an IC50 of 13 ± 9.59 nM and P. berghei hepatic infection with an IC50 of 0.55 ± 0.14 µM with a clear impact on parasite development. BSS-730A was also active against the erythrocytic stages of P. falciparum, with an estimated IC50 of 0.43 ± 0.04 µM. Time-of-addition studies showed that BSS-730A potentially affects all stages of the HIV replicative cycle, suggesting a complex mechanism of action. BSS-730A was active against multidrug-resistant HIV isolates, with a median 2.4-fold higher IC50 relative to control isolates. BSS-730A was equally active against R5 and X4 HIV isolates and displayed strong synergism with the entry inhibitor AMD3100. BSS-730A is a promising candidate for development as a potential therapeutic and/or prophylactic agent against HIV and Plasmodium.

Esophageal Dilatation as a Predictor of Systemic Sclerosis in Patients with Interstitial Lung Disease.

OBJECTIVE: To determine the predictive value of esophageal dilatation as observed in high-resolution computed tomography (HRCT) for the diagnosis of systemic sclerosis (SSc) in patients with interstitial lung disease (ILD). METHODS: Our sample consisted of patients diagnosed with SSc and proven interstitial lung involvement with available HRCT exams (n = 20). Individuals with other forms of rheumatic ILD were included as a control group (n = 20). Two blinded radiologists independently reviewed the images for the presence of esophageal dilatation, measured at 3 different levels. Interobserver agreement was tested with Lin's concordance correlation coefficient (CCC). Independent t-test was used to compare maximum esophageal diameters between groups. Friedman's test was used to evaluate differences between the 3-level measurements. Receiver operating characteristic analysis was performed. RESULTS: There was a substantial correlation between both readers (CCC = 0.9802-0.9919). Esophageal dilatation was significantly associated with SSc (P = .0012). The optimal calculated cut-off value to differentiate SSc from other ILDs was 18.5 mm (sensitivity and specificity of 70 and 90%, respectively; area under the curve 0.819), measured 1 cm above the diaphragmatic hiatus. CONCLUSION: HRCT may have a discriminative role in the presence of both ILD and esophageal dilatation for the diagnosis of SSc. Our results suggest that a cut-off value for the esophageal diameter of 18.5 mm might propose the diagnosis of SSc with reasonable confidence.

Imaging evaluation of the liver in oncology patients: A comparison of techniques.

The liver is commonly affected by metastatic disease. Therefore, it is essential to detect and characterize liver metastases, assuming that patient management and prognosis rely on it. The imaging techniques that allow non-invasive assessment of liver metastases include ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)/CT, and PET/MRI. In this paper, we review the imaging findings of liver metastases, focusing on each imaging modality's advantages and potential limitations. We also assess the importance of different imaging modalities for the management, follow-up, and therapy response of liver metastases. To date, both CT and MRI are the most appropriate imaging methods for initial lesion detection, follow-up, and assessment of treatment response. Multiparametric MRI is frequently used as a problem-solving technique for liver lesions and has evolved substantially over the past decade, including hardware and software developments and specific intravenous contrast agents. Several studies have shown that MRI performs better in small-sized metastases and moderate to severe liver steatosis cases. Although state-of-the-art MRI shows a greater sensitivity for detecting and characterizing liver metastases, CT remains the chosen method. We also present the controversial subject of the "economic implication" to use CT over MRI.

Size-Dependent Biological Activities of Fluorescent Organosilane-Modified Zinc Oxide Nanoparticles.

Surface modification of zinc oxide nanoparticles (ZnO NPs) is a strategy to tune their biocompatibility. Herein we report on the synthesis of a series of fluorescent ZnO NPs modified with 2-10% (3-glycidyloxypropyl)trimethoxysilane (GPTMS) to investigate the fluorescence properties and to explore their applications in microbiology and biomedicine. The obtained ZnO NPs were characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM) and Fourier transform infrared spectroscopy (FTIR). Size reduction occurred from ca. 13 nm in unmodified ZnO to 3-4 nm in silane-modified samples and fluorescence spectra showed size-dependent variation of the photoemission bands' intensity. The antibacterial and cytotoxic activities were investigated on Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, and in ovarian (A2780) and prostate (PC3) cancer cells by tetrazolium/formazan-based methods. The antibacterial effect was higher for E. coli than S. aureus, while the cytotoxic activity was similar for both cancer cells and varied with the particle size. Cell death by apoptosis, and/or necrosis versus autophagy, were explored by flow cytometry using an Annexin V based-method and transmission electron microscopy (TEM). The main mechanism of ZnO NPs toxicity may involve the generation of reactive oxygen species (ROS) and the induction of apoptosis or autophagy. This work revealed the potential utility of GPTMS-modified ZnO NPs in the treatment of bacterial infection and cancer.

Extruded Bioreactor Perfusion Culture Supports the Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells in 3D Porous Poly(ɛ-Caprolactone) Scaffolds.

Novel bioengineering strategies for the ex vivo fabrication of native-like tissue-engineered cartilage are crucial for the translation of these approaches to clinically manage highly prevalent and debilitating joint diseases. Bioreactors that provide different biophysical stimuli have been used in tissue engineering approaches aimed at enhancing the quality of the cartilage tissue generated. However, such systems are often highly complex, expensive, and not very versatile. In the current study, a novel, cost-effective, and customizable perfusion bioreactor totally fabricated by additive manufacturing (AM) is proposed for the study of the effect of fluid flow on the chondrogenic differentiation of human bone-marrow mesenchymal stem/stromal cells (hBMSCs) in 3D porous poly(ɛ-caprolactone) (PCL) scaffolds. hBMSCs are first seeded and grown on PCL scaffolds and hBMSC-PCL constructs are then transferred to 3D-extruded bioreactors for continuous perfusion culture under chondrogenic inductive conditions. Perfused constructs show similar cell metabolic activity and significantly higher sulfated glycosaminoglycan production (≈1.8-fold) in comparison to their non-perfused counterparts. Importantly, perfusion bioreactor culture significantly promoted the expression of chondrogenic marker genes while downregulating hypertrophy. This work highlights the potential of customizable AM platforms for the development of novel personalized repair strategies and more reliable in vitro models with a wide range of applications.

Exploring the cytotoxic activity of new phenanthroline salicylaldimine Zn(II) complexes.

Zinc(II) complexes bearing N-salicylideneglycinate (Sal-Gly) and 1,10-phenanthroline (phen) or phenanthroline derivatives [NN = 5-chloro-1,10-phenanthroline, 5-amine-1,10-phenanthroline (amphen), 4,7-diphenyl-1,10-phenanthroline (Bphen) and 5,6-epoxy-5,6-dihydro-1,10-phenanthroline] are synthesized. Complexes formulated as [Zn(NN)2(H2O)2]2+(NN = phen and amphen), are also prepared. The cytotoxicity of the compounds is evaluated towards a panel of human cancer cells: ovarian (A2780), breast (MCF7) and cervical (HeLa), as well as non-tumoral V79 fibroblasts. All compounds display higher cytotoxicity than cisplatin (IC50 = 22.5 ±â€¯5.0 µM) towards ovarian cells, showing IC50values in the low micromolar range. Overall, all compounds show higher selectivity for the A2780 cells than for the non-tumoral cells and higher selectivity indexes (IC50(V79)/IC50(A2780) than cisplatin. [Zn(Sal-Gly)(NN)(H2O)] complexes induce caspase-dependent apoptosis in A2780 cells, except [Zn(Sal-Gly)(Bphen)(H2O)], one of the most cytotoxic of the series. The cellular uptake in the ovarian cells analyzed by Inductively Coupled Plasma mass spectrometry indicates different Zn distribution profiles. Transmission electronic microscopy shows mitochondria alterations and apoptotic features consistent with caspase activation; cells incubated with [Zn(Sal-Gly)(amphen)(H2O)] present additional nuclear membrane alterations in agreement with significant association with the nucleus. The increase of reactive oxygen species and lipid peroxidation forms could be related to apoptosis induction. [Zn(NN)2(H2O)2]2+complexes have high ability to bind DNA through intercalation/groove binding, and circular dichroism data suggests that the main type of species that interact with DNA is [Zn(NN)]2+. Studies varying the % of fetal bovine serum (1-15%) in cell media show that albumin binding decreases the complex activity, indicating that distinct speciation of Zn- and phen-containing species in cell media may affect the cytotoxicity.

Antitumour and Toxicity Evaluation of a Ru(II)-Cyclopentadienyl Complex in a Prostate Cancer Model by Imaging Tools.

BACKGROUND: Ruthenium complexes have been extensively investigated for their prospective value as alternatives to cisplatin. Recently, we reported the in vitro anticancer properties of a family of organometallic ruthenium( II)-cyclopentadienyl complexes and have explored their mechanism of action. OBJECTIVE: The purpose of this study was to evaluate the in vivo antitumour efficacy and toxicity of one of these Ru(II) compounds, [RuCp(mTPPMSNa)(2,2'-bipy)][CF3SO2] (TM85) which displayed an interesting spectrum of activity against several cancer cells. METHODS: Studies to assess the antitumour activity and toxicity were performed in a metastatic prostate (PC3) mice model using ICP-MS, nuclear microscopy, elemental analysis and Transmission Electron Microscopy (TEM). RESULTS: TM85 showed low systemic toxicity but no significant tumour reduction, when administered at tolerated dose (20mg/kg) over 10 days. Ru was mainly retained in the liver and less in kidneys, with low accumulation in tumour. Increased bilirubin levels, anomalous Ca and Fe concentrations in liver and mitochondria alterations were indicative of liver injury. The hepatotoxicity observed was less severe than that of cisplatin and no nephrotoxicity was found. CONCLUSION: Under the experimental conditions of this study, TM85 is less toxic than cisplatin, induces similar tumour reduction and avoids the formation of metastatic foci. No renal toxicity was observed by the analysis of creatinine levels and the effective renal plasma flow by 99mTc-MAG3 clearance. Hence, it can be considered a valuable compound for further studies in the field of Ru-based anticancer drugs.

Mineralization of Sialoliths Investigated by Ex Vivo and In Vivo X-ray Computed Tomography.

The fraction of organic matter present affects the fragmentation behavior of sialoliths; thus, pretherapeutic information on the degree of mineralization is relevant for a correct selection of lithotripsy procedures. This work proposes a methodology for in vivo characterization of salivary calculi in the pretherapeutic context. Sialoliths were characterized in detail by X-ray computed microtomography (µCT) in combination with atomic emission spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Correlative analysis of the same specimens was performed by in vivo and ex vivo helical computed tomography (HCT) and ex vivo µCT. The mineral matter in the sialoliths consisted essentially of apatite (89 vol%) and whitlockite (11 vol%) with average density of 1.8 g/cm3. In hydrated conditions, the mineral mass prevailed with 53 ± 13 wt%, whereas the organic matter, with a density of 1.2 g/cm3, occupied 65 ± 10% of the sialoliths' volume. A quantitative relation between sialoliths mineral density and X-ray attenuation is proposed for both HCT and µCT.

Infectious and Inflammatory Diseases of the Urinary Tract: Role of MR Imaging.

Urinary tract infection (UTI) is among the most common of bacterial infections. Imaging studies are only required in cases of complicated UTIs. Ultrasound remains the first-line imaging method; however, CT is the gold standard for evaluation of UTIs. MR imaging's improved contrast resolution and absence of ionizing radiation may recommend its use for assessment of lower UTIs. Furthermore, MR imaging performs with diagnostic accuracy at least similar to CT in complicated UTIs, except for the identification of calculi and emphysematous pyelonephritis. In this article, the role of MR imaging for the evaluation of infectious and inflammatory disease processes of the urinary tract is reviewed.