Targeted specific inhibition of bacterial and Candida species by mesoporous Ag/Sn–SnO2 composite nanoparticles: in silico and in vitro investigation

Invasive bacterial and fungal infections have notably increased the burden on the health care system and especially in immune compromised patients. These invasive bacterial and fungal species mimic and interact with the host extracellular matrix and increase the adhesion and internalization into the host system. Further, increased resistance of traditional antibiotics/antifungal drugs led to the demand for other therapeutics and preventive measures. Presently, metallic nanoparticles have wide applications in health care sectors. The present study has been designed to evaluate the advantage of Ag/Sn–SnO₂ composite nanoparticles over the single oxide/metallic nanoparticles. By using in silico molecular docking approaches, herein we have evaluated the effects of Ag/Sn–SnO₂ nanoparticles on adhesion and invasion responsible molecular targets such as LpfD (E. coli), Als3 (C. albicans) and on virulence/resistance causing PqsR (P. aeruginosa), RstA (Bmfr) (A. baumannii), FoxA (K. pneumonia), Hsp90 and Cyp51 (C. albicans). These Ag/Sn–SnO₂ nanoparticles exhibited higher antimicrobial activities, especially against the C. albicans, which are the highest ever reported results. Further, Ag/Sn–SnO₂ NPs exhibited interaction with the heme proionate residues such as Lys143, His468, Tyr132, Arg381, Phe105, Gly465, Gly464, Ile471 and Ile304 by forming hydrogen bonds with the Arg 381 residue of lanosterol 1 4α-demethylase and increased the inhibition of the Candida strains. Additionally, the Ag/Sn–SnO₂ nanoparticles exhibited extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species followed by several molecular pathways which indicated that it can be used to eliminate the resistance to traditional antibiotics.

Mesoporous Ag/Sn–SnO₂ composite nanoparticles exhibits extraordinary inhibitory properties by targeting different proteins of bacteria and Candida species which can be used to eliminate the resistance of traditional antibiotics.     

Elevated serum receptor activator of NFκB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase (MMP)3, and ProMMP1 in patients with juvenile idiopathic arthritis

We studied the serum levels of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), pro-matrix metalloproteinase (MMP) 1, MMP3, and tissue inhibitor of metalloproteinase (TIMP) 1 in patients with juvenile idiopathic arthritis (JIA) and correlated these with different disease variables. Sera of 70 patients with JIA (ILAR 2001 criteria) and 33 age- and sex-matched controls were assayed by enzyme-linked immunosorbent assay. Nonparametric tests were used for analysis of data. The subtype distribution of the JIA patients was: enthesitis-related arthritis (ERA) 24, polyarticular 22, systemic onset 13, oligoarticular 8, and others 3. The median level of RANKL, OPG, pro-MMP1, MMP3, and TIMP-1 were elevated in JIA patients as compared to controls (p < 0.001). There was no difference in levels among different types of JIA. RANKL/OPG ratio was elevated in all subtypes of JIA. MMP3/TIMP-1 ratio correlated with measures of disease activity including swollen and tender joint count, erythrocyte sedimentation rate, and disease activity score (rS 0.28, p < 0.05). Ours is the first study to show elevated RANKL in serum of patients with JIA. Further, our data suggest that patients with ERA have similar levels to other forms of JIA. Association of the MMP3/TIMP-1 ratio with disease activity suggests that it may be a useful biomarker for follow-up.     

Haemangioma of Cheek Different Presentation and Management

Though haemangioma of cheek is not a very uncommon entity, here we are presenting a case series of four such cases of haemangioma cheek of completely different presentation. One of which is classical maxillary haemangioma and the rest of the others have different and unusual presentations. They all have different radiological features and were managed successfully by different surgical approaches without any recurrence.     

Evaluation of downstaging in the detection of cervical neoplasia in Kolkata,India

Unaided visual inspection or "downstaging" has been suggested as a potential alternative method for cervical cancer screening in developing countries. Our study was designed to evaluate the accuracy of downstaging to detect cervical neoplasia in a low-resource setting. A total of 6,399 women aged 30-64 years were screened with downstaging by trained nonmedical health workers. Two thresholds were used to define positive downstaging: "low threshold" when any visible abnormality on the cervix was considered positive and "high threshold" when selected abnormalities such as bleeding on touch, bleeding erosion, hypertrophied oedematous cervix, congested stippled cervix and growth or ulcer constituted the positive test. All women underwent a colposcopy examination. Biopsies were directed when colposcopy revealed abnormal lesions. True disease status was defined as histologically proven moderate dysplasia and worse lesions. Since all the participants received a diagnostic (reference) investigation (biopsy and/or colposcopy), sensitivity, specificity and predictive values were estimated directly. Low- and high-threshold downstaging were positive in 1,585 (24.8%) and 460 (7.2%) women, respectively. The sensitivities of low- and high-threshold downstaging to detect high-grade precursors and invasive cancers were 48.9% and 31.9%, respectively. The specificities were 75.8% and 93.3%, respectively. These results indicate that downstaging is not suitable as an independent primary screening modality for cervical neoplasia.     

Proton magnetic resonance spectroscopy of the thalamus in patients with chronic neuropathic pain after spinal cord injury

BACKGROUND AND PURPOSE: Spinal cord injury (SCI) results in a number of consequences; one of the most difficult to manage is chronic neuropathic pain. Thus, defining the potential neural and biochemical changes associated with chronic pain after SCI is important because this may lead to development of new treatment strategies. Prior studies have looked at the thalamus, because it is a major sensory relay station. The purpose of our study was to define alterations in metabolites due to injury-induced functional changes in thalamic nuclei by using single-voxel stimulated echo acquisition mode MR spectroscopy. METHODS: Twenty-six men were recruited: 16 patients with SCI and paraplegia (seven with pain, nine without pain) and 10 healthy control subjects. Pain was evaluated in an interview, which included the collection of information concerning the location, quality, and intensity of pain, carefully identifing the dysesthetic neuropathic pain often seen in SCI. Localized single-voxel (8-cm(3) volume) proton spectra were acquired from the left and right thalami. RESULTS: The concentration of N-acetyl (NA) was negatively correlated with pain intensity (r = -0.678), and the t test showed that NA was significantly different between patients with pain and patients without pain (P =.006). Myo-inositol was positively correlated with pain intensity (r = 0.520); difference between patients with pain and those without pain was almost significant (P =.06). CONCLUSION: The observed differences in metabolites in SCI patients with and pain and in those without pain suggest anatomic, functional, and biochemical changes in the thalamic region.     

Structural Requirements for Interaction with the Oligopeptide Transporter in Caco-2 Cells

Pharmaceutical Research -     

Removable high intensity iridium-192 brain implants

A preclinical evaluation of the technical details and dosimetry for temporary high intensity ¹⁹²Ir brain implants is presented. The canine brain was used for this quality assurance study in which direct in vivo dose measurements were done by thermoluminescent dosimetry (TLD rods). Precise and reproducible positioning of the TLD rods and ¹⁹²Ir ribbons were assured by simple accessories which can be utilized in the clinical situation. The neurosurgical procedure for this non-routine interstitial implant of the brain, suitability of type and size of afterloading cannulas and facility for firmly anchoring them to the scalp, and comparison of measured doses with computer-predicted values are details assured by the canine study. Agreement between the in vivo determination and computer-generated doses was consistently in the range 2–5%. Data derived from this preclinical evaluation are currently used in both stereotactic and non-stereotactic brain implants at our institution.Details are presented for the implant procedure, dose measurements and brachytherapy planning for multiple ribbons. The latter incorporates direct interaction on computed tomography (CT) images for a hypothetical patient case.