Synthesis, characterization, and antibacterial activities of a heteroscorpionate derivative platinum complex against methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus is one of the species with the greatest clinical importance and greatest impact on public health. In fact, methicillin-resistant S. aureus (MRSA) is considered a pandemic pathogen, being essential to develop effective medicines and combat its rapid spread. This study aimed to foster the translation of clinical research outcomes based on metallodrugs into clinical practice for the treatment of MRSA. Bearing in mind the promising anti-Gram-positive effect of the heteroscorpionate ligand 1,1'-(2-(4-isopropylphenyl)ethane-1,1-diyl)bis(3,5-dimethyl-1H-pyrazole) (2P), we propose the coordination of this compound to platinum as a clinical strategy with the ultimate aim of overcoming resistance in the treatment of MRSA. Therefore, the novel metallodrug 2P-Pt were synthetized, fully characterized and its antibacterial effect against the planktonic and biofilm state of S. aureus evaluated. In this sense, three different strains of S. aureus were studied, one collection strain of S. aureus sensitive to methicillin and two clinical MRSA strains. To appraise the antibacterial activity, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC) were determined. Moreover, successful outcomes on the development of biofilm in a wound-like medium were obtained. The mechanism of action for 2P-Pt was proposed by measuring the MIC and MBC with EDTA (cation mediated mechanism) and DMSO (exogenous oxidative stress mechanism). Moreover, to shed light on the plausible antistaphylococcal mechanism of this novel platinum agent, additional experiments using transmission electron microscopy were carried out. 2P-Pt inhibited the growth and eradicated the three strains evaluated in the planktonic state. Another point worth stressing is the inhibition in the growth of MRSA biofilm even in a wounded medium. The results of this work support this novel agent as a promising therapeutic alternative for preventing infections caused by MRSA.

Methacrylate Cationic Nanoparticles Activity against Different Gram-Positive Bacteria.

Nanotechnology is a developing field that has boomed in recent years due to the multiple qualities of nanoparticles (NPs), one of which is their antimicrobial capacity. We propose that NPs anchored with 2-(dimethylamino)ethyl methacrylate (DMAEMA) have antibacterial properties and could constitute an alternative tool in this field. To this end, the antimicrobial effects of three quaternised NPs anchored with DMAEMA were studied. These NPs were later copolymerized using different methylmethacrylate (MMA) concentrations to evaluate their role in the antibacterial activity shown by NPs. Clinical strains of Staphylococcus aureus, S. epidermidis, S. lugdunensis and Enterococcus faecalis were used to assess antibacterial activity. The minimal inhibitory concentration (MIC) was determined at the different concentrations of NPs to appraise antibacterial activity. The cytotoxic effects of the NPs anchored with DMAEMA were determined in NIH3T3 mouse fibroblast cultures by MTT assays. All the employed NPs were effective against the studied bacterial strains, although increasing concentrations of the MMA added during the synthesis process diminished these effects without altering toxicity in cell cultures. To conclude, more studies with other copolymers are necessary to improve the antibacterial effects of NPs anchored with DMAEMA.

Antimicrobial evaluation of quaternary ammonium polyethyleneimine nanoparticles against clinical isolates of pathogenic bacteria.

Peritonitis is a disease caused by bacterial strains that have become increasingly resistant to many antibiotics. The development of alternative therapeutic compounds is the focus of extensive research, so novel nanoparticles (NPs) with activity against antibiotic-resistant bacteria should be developed. In this study, the antibacterial activity of quaternary ammonium polyethyleneimine (QA-PEI) NPs was evaluated against Streptococcus viridans, Stenotrophomonas maltophilia and Escherichia coli. To appraise the antibacterial activity, minimal inhibitory concentration (MIC), minimal bactericidal concentration and bactericidal assays were utilised with different concentrations (1.56-100 µg/ml) of QA-PEI NPs. Moreover, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and annexin V/propidium iodide toxicity assays were performed in cell cultures. MICs for S. maltophilia and E. coli isolates were 12.5 and 25 µg/ml, respectively, whereas the MIC for S. viridans was 100 µg/ml. Furthermore, the growth curve assays revealed that these QA-PEI NPs at a concentration of 12.5 µg/ml significantly inhibited bacterial growth for the bacterial isolates studied. On the other hand, QA-PEI NPs lacked significant toxicity for cells when used at concentrations up to 50 µg/ml for 48 h. The present findings reveal the potential therapeutic value of this QA-PEI NPs as alternative antibacterial agents for peritonitis, especially against Gram-negative bacteria.

Carbonic anhydrase IX as a specific biomarker for clear cell renal cell carcinoma: comparative study of Western blot and immunohistochemistry and implications for diagnosis.

OBJECTIVE: This study aimed to evaluate the usefulness of carbonic anhydrase IX (CA-IX) expression in clear cell renal cell carcinoma (CCRCC) using two different techniques to detect protein expression. MATERIAL AND METHODS: An experimental, cross-sectional, analytical study was conducted to analyse proteins in renal tumour and healthy tissue specimens from 38 consecutive patients who underwent nephrectomy for renal cancer. CA-IX protein expression was measured by immunohistochemistry and Western blot analysis and quantified. Statistical analysis was performed with the positive and negative specific agreements and kappa coefficient. The sensitivity and specificity of both techniques were assessed. Statistical tests were conducted to analyse the association between CA-IX expression quantitation and normal prognosis factors (TNM stage and Fuhrman nuclear grade), only in CCRCC. RESULTS: The mean patient age was 65 years, 78.9% of patients were men and 57.9% of tumours were CCRCC. CA-IX protein expression was positive in 63.2% of tumours by immunohistochemistry and in 60.5% by Western blot. Both techniques detected CA-IX expression only in CCRCC and unclassifiable tumours. High concordance indices were observed for CCRCC diagnosis. Western blot and immunohistochemistry had a sensitivity of 95.5% and 100%, respectively; the specificity was 100% in both techniques. CA-IX expression quantitation did not correlate with tumour stage or Fuhrman nuclear grade. CONCLUSIONS: Immunochemistry and Western blot techniques can be used to detect abnormal CA-IX protein expression in CCRCC and to support morphology-based diagnostic techniques.

Aliskiren prevents the toxic effects of peritoneal dialysis fluids during chronic dialysis in rats.

The benefits of long-term peritoneal dialysis (PD) in patients with end-stage renal failure are short-lived due to structural and functional changes in the peritoneal membrane. In this report, we provide evidence for the in vitro and in vivo participation of the renin-angiotensin-aldosterone system (RAAS) in the signaling pathway leading to peritoneal fibrosis during PD. Exposure to high-glucose PD fluids (PDFs) increases damage and fibrosis markers in both isolated rat peritoneal mesothelial cells and in the peritoneum of rats after chronic dialysis. In both cases, the addition of the RAAS inhibitor aliskiren markedly improved damage and fibrosis markers, and prevented functional modifications in the peritoneal transport, as measured by the peritoneal equilibrium test. These data suggest that inhibition of the RAAS may be a novel way to improve the efficacy of PD by preventing inflammation and fibrosis following peritoneal exposure to high-glucose PDFs.

Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers.

The existence, diagnostic features, and the biological and clinical relevance of lymphocyte-rich classical Hodgkin's lymphoma remain controversial. A comparative marker analysis of lymphocyte-rich classical Hodgkin's lymphoma, nodular lymphocyte-predominance Hodgkin's lymphoma, and of other subtypes of classical Hodgkin's lymphoma was carried out. Markers were selected focusing on B-cell lineage and transcription program (OCT.1, OCT.2, BOB.1, BCL6, PAX-5, GCET1, KLHL6, and BLIMP1), the NF-kappaB signaling pathway (REL-B, C-REL, TRAF-1, p-50, and MUM-1) and the T-cell microenvironment (CD3, CD57, PD-1, CXCL-13, and CD10, BCL-6, CD23). Lymphocyte-rich classical Hodgkin's lymphoma cases displayed features intermediate between those of classical Hodgkin's lymphoma and nodular lymphocyte-predominance Hodgkin's lymphoma. The expression of B-cell transcription factors such as OCT.1, OCT.2, BOB.1, and BCL6 was more frequent in lymphocyte-rich classical Hodgkin's lymphoma than in classical Hodgkin's lymphoma. A follicular T-cell microenvironment was also identified in 50% of lymphocyte-rich classical Hodgkin's lymphoma cases. NF-kB markers were expressed at frequencies comparable with those observed in classical Hodgkin's lymphoma. The neoplastic cell immunophenotype and microenvironment in lymphocyte-rich classical Hodgkin's lymphoma closely mimic that which are observed in the outer zone of the germinal center, where B-cell blasts with germinal-center markers co-express CD30 and the B-cell transcription program, surrounded by follicular T-cell rosettes. Lymphocyte-rich classical Hodgkin's lymphoma seems to be characterized by a stronger expression of the B-cell transcription program by the neoplastic cells and by a follicular T-cell background, occupying an intermediate position between classical Hodgkin's lymphoma and nodular lymphocyte-predominance Hodgkin's lymphoma.

PD-1, a follicular T-cell marker useful for recognizing nodular lymphocyte-predominant Hodgkin lymphoma.

The nodularity and presence of T-cell rosettes surrounding the neoplastic cells has been described as a defining feature of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We have explored the potential diagnostic value of a new marker (NAT105) that recognizes the antigen PD-1 in a series of 152 cases diagnosed as nodular sclerosis Hodgkin lymphoma, mixed cellularity Hodgkin lymphoma, lymphocyte-rich classic Hodgkin lymphoma, NLPHL, and T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL). All the cases were immunostained with a panel of antibodies against CD10, bcl-6, CXCL13, CD57, and PD-1 (NAT-105). The series includes a set of cases diagnosed as NLPHL with diffuse areas, and a group of borderline cases with features between those of NLPHL and T/HRBCL. Results show that PD-1 (NAT-105) is an excellent immunomarker not only of follicular T-cell rosettes in NLPHL, but also of a subset of lymphocyte-rich classic Hodgkin lymphomas. However, it is not a unique and defining feature of NLPHL. The presence of PD-1-positive (NAT-105) T-cell rosettes seems to be an additional useful feature in the differential diagnosis of NLPHL and T/HRBCL, which is normally a controversial and difficult task. The standard T/HRBCL cases lack follicular T-cell rosettes, whereas most of the borderline cases between the 2 entities have follicular T-cell rosettes, thus suggesting a closer relation with NLPHL.

Primary intraosseous carcinomas of the jaws arising within an odontogenic cyst, ameloblastoma, and de novo: report of new cases with reconstruction considerations.

Primary intraosseous carcinoma (PIOC) of the jaws has been rarely reported. The authors report 3 new cases of PIOC arising within an odontogenic cyst, ameloblastoma, and de novo origin, respectively. Surgeons should appreciate the elevated aggressiveness of this tumor despite adequate surgical treatment. The authors recommend initial aggressive surgical treatment to decrease the local recurrence rate.

Adenoma de células basales de glándula parótida. Caso clínico y revisión de la literatura / Basal cell adenoma of the parotid gland. Case report and review of the literature

El adenoma de células basales de las glándulas salivares es un tipo de adenoma monomorfo de aparición infrecuente. La localización más habitual es la superficie de la glándula parótida. Suele debutar clínicamente como una masa firme y desplazable de crecimiento lento. Histológicamente se observan células isomórficas formando nidos y trabéculas interanastomosadas, con una membrana basal prominente, separadas por un estroma laxo e hialino y ausencia de estroma mixoide o condroide. A diferencia del adenoma pleomorfo, tiende a la multicentricidad y su tasa de recurrencia después de la extirpación quirúrgica es alta. Debido a sus implicaciones pronósticas, el diagnóstico diferencial con el adenocarcinoma de células basales, el carcinoma adenoide quístico y el carcinoma de células escamosas basalioide es prioritario. Describimos un caso clínico de adenoma de células basales de la glándula parótida, realizamos una revisión de la literatura y discutimos el manejo diagnóstico y terapéutico de esta rara entidad

Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity

Basal cell adenoma of the parotid gland. Case report and review of the literature.

Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity.