Systemic inflammatory syndrome in COVID-19-SISCoV study: systematic review and meta-analysis.

BACKGROUND: There has been a recent upsurge in the cases of Multisystem inflammatory syndrome in children (MIS-C) associated with Coronavirus disease (COVID-19). We performed a systematic review and meta-analysis on the demographic profile, clinical characteristics, complications, management, and prognosis of this emerging novel entity. METHODS: Using a predefined search strategy incorporating MeSH terms and keywords, all known literature databases were searched up till 10th July 2020. The review was done in accordance with PRISMA guidelines and registered in PROSPERO (CRD4202019757). RESULTS: Of the 862 identified publications, 18 studies comprising 833 patients were included for meta-analysis. The socio-demographic profile showed male predilection (p = 0.0085) with no significant racial predisposition. A higher incidence of gastrointestinal symptoms (603/715, 84.3%), myocarditis (191/309, 61.8%), left ventricular dysfunction (190/422, 45.0%), pericardial (135/436, 31.0%) and neurological symptoms (138/602, 22.9%) was reported. Serological evidence of SARS-CoV-2 had higher sensitivity compared to rtPCR (291/800, 36.4% vs 495/752, 65.8%; p < 0.001). Coronary artery anomaly (CAA) was reported in 117/681 in 9 publications (17.2%). A total of 13 (1.6%) fatalities were reported. CONCLUSION: Clinicians need to be vigilant in identifying the constellation of these symptoms in children with clinical or epidemiologic SARS-CoV-2 infection. Early diagnosis and treatment lead to a favorable outcome. IMPACT: Key message This review analyses the demographic profile, clinical spectrum, management strategies, prognosis, and pathophysiology of MIS-C among children with SARS-CoV-2 infection. The stark differences of MIS-C from Kawasaki disease with respect to demographics and clinical spectrum is addressed. Over-reliance on rtPCR for diagnosis can miss the diagnosis of MIS-C. New addition to existing literature The first systematic review and meta-analysis of published literature on MIS-C associated with COVID-19. IMPACT: The article will serve to spread awareness among the clinicians regarding this emerging novel entity, so that diagnosis can be made early and management can be initiated promptly.

Randomised comparison of a balloon-expandable and self-expandable valve with quantitative assessment of aortic regurgitation using magnetic resonance imaging.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a safe and effective treatment for inoperable, intermediate- or high-risk patients with severe symptomatic aortic stenosis and has been associated with excellent clinical outcomes. A clinically relevant remaining problem is aortic regurgitation (AR) post-TAVI, which is associated with increased mortality. Therefore, we conducted a prospective randomised trial to assess the safety and efficacy of a first-generation self-expandable valve (SEV; CoreValve) and a third-generation balloon-expandable valve (BEV; Sapien 3) with respect to clinical outcomes and AR as determined quantitatively by magnetic resonance imaging (MRI). METHODS: The ELECT study was an investigator-initiated, single-centre trial involving patients with severe symptomatic aortic stenosis and with a clinical indication for transfemoral TAVI. Fifty-six patients were randomly assigned to the BEV or SEV group. RESULTS: AR determined quantitatively by MRI was lower in the BEV than in the SEV group [regurgitant fraction: 1.1% (0-8.0) vs 8.7% (3.0-14.8) for SEV; p = 0.01]. Secondary endpoints according to the criteria of the Second Valve Academic Research Consortium (VARC-2) showed BEV to have better early safety [0 (0%) vs 8 (30%); p = 0.002] at 30 days and a lower risk of stroke [0 (0%) vs 5 (21%); p = 0.01], major adverse cardiac and cerebrovascular events [0 (0%) vs 10 (38%); p < 0.001] or death [0 (0%) vs 5 (19%); p = 0.02] in the 1st year compared with SEV. CONCLUSIONS: The use of the latest generation of BEV was associated with less AR as quantitatively assessed by MRI. Although the use of MRI to quantify AR is not feasible in daily clinical practice, it should be considered as a surrogate endpoint for clinical outcomes in comparative studies of valves for TAVI. ClinicalTrials.gov number NCT01982032.

18F-FDG PET as novel imaging biomarker for disease progression after ablation therapy in colorectal liver metastases.

PURPOSE: Recurrent disease following thermal ablation therapy is a frequently reported problem. Preoperative identification of patients with high risk of recurrent disease might enable individualized treatment based on patients' risk profile. The aim of the present work was to investigate the role of metabolic parameters derived from the pre-ablation 18F-FDG PET/CT as imaging biomarkers for recurrent disease in patients with colorectal liver metastases (CLM). METHODS: Included in this retrospective study were all consecutive patients with CLM treated with percutaneous or open thermal ablation therapy who had a pre-treatment baseline 18F-FDG PET/CT available. Multivariable cox regression for survival analysis was performed using different models for the metabolic parameters (SULpeak, SULmean, SULmax, partial volume corrected SULmean (cSULmean), and total lesion glycolysis (TLG)) corrected for tumour and procedure characteristics. The study endpoints were defined as local tumour progression free survival (LTP-FS), new intrahepatic recurrence free survival (NHR-FS) and extrahepatic recurrence free survival (EHR-FS). Clinical and imaging follow-up data was used as the reference standard. RESULTS: Fifty-four patients with 90 lesions were selected. Univariable cox regression analysis resulted in eight models. Multivariable analysis revealed that after adjusting for lesion size and the approach of the procedure, none of the metabolic parameters were associated with LTP-FS or EHR-FS. Percutaneous approach was significantly associated with a shorter LTP-FS. It was demonstrated that lower values of SULpeak, SULmax, SULmean , and cSULmean are associated with a significant better NHR-FS, independent of the lesion size and number and prior chemotherapy. CONCLUSION: We found no association between the metabolic parameters on pre-ablation 18F-FDG PET/CT and the LTP-FS. However, low values of the metabolic parameters were significantly associated with improved NHR-FS. The clinical implication of these findings might be the identification of high-risk patients who might benefit most from adjuvant or combined treatment strategies.

Rationale and design of the Edwards SAPIEN-3 periprosthetic leakage evaluation versus Medtronic CoreValve in transfemoral aortic valve implantation (ELECT) trial : A randomised comparison of balloon-expandable versus self-expanding transcatheter aortic valve prostheses.

BACKGROUND AND OBJECTIVES: Periprosthetic aortic regurgitation (PPR) after transcatheter aortic valve implantation (TAVI) remains an important issue associated with impaired long-term outcomes. The current randomised study aims to evaluate potential differences between the balloon-expandable Edwards SAPIEN-3 and the self-expanding Medtronic CoreValve system with the main focus on post-TAVI PPR by means of novel imaging endpoints, and an additional focus on other clinical endpoints. ENDPOINTS: The primary endpoint of this study is quantitative assessment of the severity of post-procedural PPR using cardiac magnetic resonance imaging. Several other novel imaging modalities (X-ray contrast angiography, echocardiography) are used as secondary imaging modalities for the assessment of PPR following TAVI. Secondary objectives of the study include clinical outcomes such as cerebral and kidney injury related to TAVI, and quality of life. METHODS AND DESIGN: The ELECT study is a single-centre, prospective, two-armed randomised controlled trial. For the purpose of this study, 108 consecutive adult patients suitable for transfemoral TAVI will be randomly allocated to receive the SAPIEN-3 (n = 54) or the CoreValve system (n = 54). DISCUSSION: The ELECT trial is the first randomised controlled trial to quantitatively compare the extent of post-TAVI PPR between the SAPIEN-3 and CoreValve. Furthermore, it will evaluate potential differences between the two prostheses with regard to mid-term clinical outcome and quality of life.

Total laparoscopic management of lesions involving liver segment 7.

BACKGROUND: Until recently, laparoscopic resection of tumors involving segment 7 (s7) of the liver was seen as a relative contraindication. We analyzed our experiences with laparoscopic resection of tumors in s7. METHODS: Retrospective analysis of prospective database on operative and postoperative characteristics and surgical outcomes of patients in whom the intention was to remove tumors located in s7 of the liver laparoscopically. We defined two groups: those with laparoscopic metastasectomy of s7 (s7 group) and those undergoing laparoscopic right posterior sectionectomy (RPS group). RESULTS: Of 400 patients undergoing laparoscopic liver resection, 20 patients (5 %) underwent total laparoscopic resections of tumors in s7 (7 metastasectomy of s7 and 13 RPS). The type of resection was decided on the basis of tumor size and location. Median age was 70 years (range 46-82), and the indication for surgery was mainly CRLM (n = 13, 65 %) and HCC (n = 4, 20 %). There was 1 (5 %) conversion. Mean operative times were 252 min (±69) for s7 and 271 min (±102) for RPS. The mean intraoperative blood loss was 400 mL (±493) for s7 and 625 mL (±363) for RPS. A Pringle maneuver was used in 86 % of patients in s7 group and 75 % of patients in RPS group. Mean total hospital stay was 4.6 days (±2.5) in s7 and 6.9 days (±7.8) for RPS. The overall R0 resection rate was 95 % (s7 100 %, RPS 92 %). CONCLUSION: Although resection of lesions in s7 is technically demanding, a laparoscopic approach can be performed safely and effectively in experienced hands.

Outcomes of repeat laparoscopic liver resection compared to the primary resection.

BACKGROUND: Repeat laparoscopic liver resection (R-LLR) can be technically challenging. Data on this topic are scarce and many investigators would question its feasibility and outcomes. The aim of the present study was to evaluate the safety, feasibility, oncological efficiency and outcomes of R-LLR. METHODS: We reviewed a prospectively collected database of 403 patients undergoing 422 laparoscopic liver resections (LLRs) from August 2003 to August 2013. Data of 19 patients undergoing R-LLR were analyzed and compared to the primary resection (P-LLR) in these patients. Demographic and clinical data were studied. A subgroup analysis was done for minor resections. RESULTS: Twenty R-LLRs were performed in 19 patients (female 58 %; mean age: 57.5 years; age range: 23-79 years). Colorectal liver metastases (CRLM) were the commonest indication for R-LLR (60 %), followed by neuroendocrine tumor liver metastases (NETLM) (20 %) and hepatocellular carcinoma (HCC) (10 %). The majority (90 %) of resections were for malignant disease (18/20). There were three conversions (15 %), and two patients developed complications (10 %). The operative time (p = 0.005) and blood loss (p = 0.03) were both significantly greater in R-LLR compared to P-LLR, whereas length of stay (median 4 days; p = 0.30) and complications (p = 0.58) did not differ between the groups. R0 resection rates for P-LLR and R-LLR were 95 and 90 %, respectively (p = 0.73). CONCLUSIONS: Repeat LLR is safe, feasible, and can be performed with minimal morbidity. It appears to be technically more challenging than P-LLR, but without any increase in complications or length of hospital stay.

Solid lipid nanoparticles of anticancer drug andrographolide: formulation, in vitro and in vivo studies.

Diterpenoidal anti-cancer drug andrographolide (AD) was encapsulated into solid lipid nanoparticle (SLN) because of poor aqueous solubility and high lipophilicity. AD-SLNs were prepared by solvent injection method and characterized for droplet size, surface morphology, zeta potential, etc. In vitro drug release was carried out by dialysis-membrane method. A pharmacokinetic study was performed by UPLC/Q-TOF-MS method to determine the maximum plasma concentration (Cmax), area under the curve (AUC), etc. There was an improvement in Cmax and AUC of AD-SLNs when compared with AD, thereby enhancing the bioavailability of AD. The tmax was increased than that of AD suspension, indicating the sustained release pattern of AD-SLNs. The antitumor activity was carried out on Balb/c mice showing better results with AD-SLNs as compared to AD. Thus, the AD-loaded SLNs would be useful for delivering poorly water-soluble AD with enhanced bioavailability and improved antitumor activity.

Co-VAN study: COVID-19 vaccine associated neurological diseases- an experience from an apex neurosciences centre and review of the literature.

BACKGROUND: Recent studies have shown various neurological adverse events associated with COVID-19 vaccine. OBJECTIVE: We aimed to retrospectively review and report the neurological diseases temporally associated with COVID-19 vaccine. METHODS: We performed a retrospective chart review of admitted patients from 1st February 2021 to 30th June 2022. A total of 4672 medical records were reviewed of which 51 cases were identified to have neurological illness temporally associated with COVID-19 vaccination. RESULTS: Out of 51 cases, 48 had probable association with COVID-19 vaccination while three had possible association. Neurological spectrum included CNS demyelination (n = 39, 76.5 %), Guillain-Barré-syndrome (n = 3, 5.9 %), stroke (n = 6, 11.8 %), encephalitis (n = 2, 3.9 %) and myositis (n = 1, 2.0 %). Female gender had a greater predisposition (F:M, 1.13:1). Neurological events were more commonly encountered after the first-dose (n = 37, 72.5%). The mean latency to onset of symptoms was 13.2 ± 10.7 days after the last dose of vaccination. COVIShield (ChAdOx1) was the most commonly administered vaccine (n = 43, 84.3 %). Majority of the cases with demyelination were seronegative (n = 23, 59.0 %) which was followed by anti-Myelin oligodendrocyte-glycoprotein associated demyelination (MOGAD) (n = 11, 28.2 %) and Neuromyelitis optica (NMOSD) (n = 5, 12.8 %). Out of 6 Stroke cases, 2 cases (33.3 %) had thrombocytopenia and coagulopathy. At discharge, 25/51 (49.0 %) of the cases had favourable outcome (mRS 0 to 1). Among six patients of stroke, only one of them had favourable outcome. CONCLUSION: In this series, we describe the wide variety of neurological syndromes temporally associated with COVID-19 vaccination. Further studies with larger sample size and longer duration of follow-up are needed to prove or disprove causality association of these syndromes with COVID-19 vaccination.

Palladium nanoparticles as emerging pollutants from motor vehicles: An in-depth review on distribution, uptake and toxicological effects in occupational and living environment.

Palladium nanoparticles (PdNPs) play an integral role in motor vehicles as the primary vehicle exhaust catalyst (VEC) for tackling environmental pollution. Automobiles equipped with Pd-based catalytic converters were introduced in the mid-1970s and ever since the demand for Pd has steadily increased due to stringent emission standards imposed in many developed and developing countries. However, at the same time, the increasing usage of Pd in VECs has led to the release of nano-sized Pd particles in the environment, thus, emerging as a new source of environmental pollution. The present reports in the literature have shown gradual increasing levels of Pd particles in different urban environmental compartments and internalization of Pd particles in living organisms such as plants, aquatic species and animals. Occupational workers and the general population living in urban areas and near major highways are the most vulnerable as they may be chronically exposed to PdNPs. Risk assessment studies have shown acute and chronic toxicity exerted by PdNPs in both in-vitro and in-vivo models but the underlying mechanism of PdNPs toxicity is still not fully understood. The review intends to provide readers with an in-depth account on the demand and supply of Pd, global distribution of PdNPs in various environmental matrices, their migration and uptake by living species and lastly, their health risks, so as to serve as a useful reference to facilitate further research and development for safe and sustainable technology.

Crafting ɣ-L-Glutamyl-l-Cysteine layered Human Serum Albumin-nanoconstructs for brain targeted delivery of ropinirole to attenuate cerebral ischemia/reperfusion injury via "3A approach".

Treatment of Ischemic Stroke is inordinately challenging due to its complex aetiology and constraints in shuttling therapeutics across blood-brain barrier. Ropinirole hydrochloride (Rp), a propitious neuroprotectant with anti-oxidant, anti-inflammatory, and anti-apoptotic properties (3A) is repurposed for remedying ischemic stroke and reperfusion (I/R) injury. The drug's low bioavailability in brain however, limits its therapeutic efficacy. The current research work has reported sub-100 nm gamma-L-Glutamyl-L-Cysteine coated Human Serum Albumin nanoparticles encapsulating Rp (C-Rp-NPs) for active targeting in ischemic brain to encourage in situ activity and reduce unwanted toxicities. Confocal microscopy and brain distribution studies confirmed the enhanced targeting potentiality of optimized C-Rp-NPs. The pharmacokinetics elucidated that C-Rp-NPs could extend Rp retention in systemic circulation and escalate bioavailability compared with free Rp solution (Rp-S). Additionally, therapeutic assessment in transient middle cerebral occlusion (tMCAO) model suggested that C-Rp-NPs attenuated the progression of I/R injury with boosted therapeutic index at 1000 times less concentration compared to Rp-S via reinstating neurological and behavioral deficits, while reducing ischemic neuronal damage. Moreover, C-Rp-NPs blocked mitochondrial permeability transition pore (mtPTP), disrupted apoptotic mechanisms, curbed oxidative stress and neuroinflammation, and elevated dopamine levels post tMCAO. Thus, our work throws light on fabrication of rationally designed C-Rp-NPs with enormous clinical potential.

AI-CoV Study: Autoimmune Encephalitis Associated With COVID-19 and Its Vaccines-A Systematic Review.

BACKGROUND AND PURPOSE: Autoimmune encephalitis (AIE) following coronavirus disease 2019 (COVID-19) is an underexplored condition. This study aims to systematically review the clinico-investigational and pathophysiologic aspects of COVID-19 and its vaccines in association with AIE, and identify the factors predicting neurological severity and outcomes. METHODS: Relevant data sources were searched using appropriate search terms on January 15, 2022. Studies meeting the criteria for AIE having a temporal association with COVID-19 or its vaccines were included. RESULTS: Out of 1,894 citations, we included 61 articles comprising 88 cases: 71 of COVID-19-associated AIE, 3 of possible Bickerstaff encephalitis, and 14 of vaccine-associated AIE.There were 23 definite and 48 possible seronegative AIE cases. Anti-NMDAR (N-methyl-D-aspartate receptor; n=12, 16.9%) was the most common definite AIE. Males were more commonly affected (sex ratio=1.63) in the AIE subgroup. The neurological symptoms included alteredmental state (n=53, 74.6%), movement disorders (n=28, 39.4%), seizures (n=24, 33.8%), behavioural (n=25, 35.2%), and speech disturbances (n=17, 23.9%). The median latency to AIE diagnosis was 14 days (interquartile range=4-22 days). Female sex and ICU admission had higherrisks of sequelae, with odds ratio (OR) of 2.925 (95% confidence interval [CI]=1.005-8.516)and 3.515 (95% CI=1.160-10.650), respectively. Good immunotherapy response was seen in42/48 (87.5%) and 13/13 (100%) of COVID-19-associated and vaccine-associated AIE patients, respectively. Sequelae were reported in 22/60 (36.7%) COVID-19 associated and 10/13 (76.9%) vaccine-associated cases. CONCLUSIONS: The study has revealed diagnostic, therapeutic, and pathophysiological aspects of AIE associated with COVID-19 and its vaccines, and its differences from postinfectious AIE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021299215.

CoRe study: COVID-19 and remdesivir: An insight into the current health planning and policy.

Introduction: The ongoing coronavirus disease-2019 (COVID-19) pandemic has witnessed rampant use of the repurposed drug, remdesivir, despite its conflicting evidence and rapidly changing guidelines. Methods: A cross-sectional, country-wide, questionnaire-based, electronic survey was conducted among the healthcare professionals involved in COVID-19 management from April 18 to May 18, 2021. Results: Out of 231 responses, 185 were included. Significantly, greater knowledge of trials was reported by the frontline healthcare professionals compared to those who are not involved in COVID-19 care. Medicine practitioners and pulmonologists expressed greater willingness to continue remdesivir (Odds ratio (OR) 5.329, 95% Confidence interval (CI) 2.31-12.291 and 5.063, 95% CI 1.414-18.129, respectively). The rationale attributed was personal experience, current guidelines, non-availability of any alternate antiviral drug, expert recommendations, and local hospital policy either alone (20%, 8.1%, 5.9%, 2.7%, and 2.2%, respectively) or in combination (46.5%, 39.5%, 29.2%, 21.1%, and 15.7%, respectively). Awareness of evidence and knowledge of landmark studies made no statistically significant impact on clinical decision-making. Improved clinical outcomes were reported by 10/22 (45.4%) practitioners who used remdesivir for unconventional indications. Conclusion: The study throws critical insights into the current perspectives of doctors on remdesivir in clinical management and its potential impact on current health planning strategies.

Predictive Parameters in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan for Unresectable Liver Metastases from Uveal Melanoma: A Retrospective Pooled Analysis.

PURPOSE: The aim of this study was to identify positive predictors for survival in uveal melanoma (UM) patients treated with percutaneous hepatic perfusion with melphalan (M-PHP), by retrospectively pooling data from three centers. MATERIALS AND METHODS: Retrospective analysis including patients ([Formula: see text] 18 years) treated with M-PHP between February 2014 and December 2019 for unresectable liver-dominant or liver-only metastases from UM. Predictors for OS were assessed using uni- and multivariate analyses. Other study outcome measures were response rate, progression-free survival (PFS), liver progression-free survival (LPFS), overall survival (OS) and complications according to CTCAEv5.0. RESULTS: In total, 101 patients (47.5% males; median age 59.0 years) completed a minimum of one M-PHP. At a median follow-up time of 15.0 months, complete response (CR), partial response (PR), stable disease (SD) and progressive disease were seen in five (5.0%), 55 (54.5%), 30 (29.7%) and 11 (10.9%) patients, respectively, leading to a 89.1% disease control rate. Median PFS, LPFS and OS were 9.0, 11.0 and 20.0 months, respectively. Survival analyses stratified for radiological response demonstrated significant improved survival in patients with CR or PR and SD category. Treatment of the primary tumor with radiotherapy, ≥ 2 M-PHP and lactate dehydrogenase (LDH) < 248 U/L were correlated with improved OS. Thirty-day mortality was 1.1% (n = 2). Most common complication was hematological toxicity (self-limiting in most cases). CONCLUSION: M-PHP is safe and effective in patients with UM liver metastases. Achieving CR, PR or SD is associated with improved survival. Primary tumor treatment with radiotherapy, normal baseline LDH and > 1 M-PHP cycles are associated with improved OS.

Bio-engineered palladium nanoparticles: model for risk assessment study of automotive particulate pollution on macrophage cell lines.

The surge in vehicular activity in densely populated areas has led to an increased concentration of airborne palladium nanoparticles (PdNPs) in the environment. Recent toxicity data have indicated that PdNPs exhibit adverse effects in in vitro and in vivo models, however, their effect on the immune system is not fully understood. Therefore, in the present study, we aimed to evaluate possible toxic effects of bio-engineered palladium nanoparticles on the murine macrophage cell line (J774). Here we prepared palladium nanoparticles using aqueous leaf extract of Parthenium hysterophorus and characterized them by UV-Vis spectroscopy, XRD, FT-IR spectroscopy, HR-TEM, EDX, SEM and zeta potential. Toxicity parameters such as cell viability, cell membrane integrity, induction of apoptosis and ROS production were assessed on J774 cell lines. Spherical palladium nanoparticles of mean size ∼4 nm, when subjected to time and dose-dependent cytotoxicity assay, showed cell viability was >95% at lower doses (25, 200 µg mL-1) and <50% at higher doses of palladium nanoparticles (400, 500 µg mL-1) after 24 hours of incubation. We also observed cell membrane injury at higher doses by lactate dehydrogenase assay. The induction of apoptosis observed was moderate. H2DCFDA assay revealed visible cell damage which could be due to modest levels of ROS generation. The detection of Pd in the road-dust samples of New Delhi using inductively coupled plasma-mass spectroscopy (ICP-MS) technique was also investigated.

Targeted delivery of thermoresponsive polymeric nanoparticle-encapsulated lycopene: in vitro anticancer activity and chemopreventive effect on murine skin inflammation and tumorigenesis.

Naturally occurring lycopene has been reported for its chemopreventive and chemotherapeutic efficiency in various cancers, but its exceptional lipophilicity, poor aqueous solubility, instability, and consequently poor bioavailability limit its usage as a chemopreventive and chemotherapeutic agent. The present study aimed to synthesize co-polymeric nanoparticle-encapsulated formulations of commercial lycopene (NLY) and extracted lycopene (NLX) and evaluate their in vitro anticancer activity and inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin inflammation and tumorigenesis in Swiss albino mice. To prepare the nanoparticle-encapsulated formulations of lycopene, thermosensitive PNIPAAM-PEG-based co-polymeric nanoparticles were synthesized and characterized by FTIR spectroscopy, NMR spectroscopy, DLS, and TEM. Nanolycopene, unlike free lycopene, could be readily dispersed in aqueous media. Nanolycopene demonstrated stronger antioxidant activity and comparable in vitro anticancer efficacy to free lycopene against the melanoma cell line B16. Furthermore, nanolycopene showed comparable reduction of TPA-induced skin edema, expression of COX-2, and oxidative stress response. Additionally, it showed significant inhibition of tumor promotion. It also altered Bax and Bcl2 expressions, which led to the induction of apoptosis. The results also supported that the extracted lycopene-encapsulated nanoparticles may be a good alternative to the expensive commercial lycopene for cancer treatment.

Enhancement of the cancer inhibitory effect of the bioactive food component resveratrol by nanoparticle based delivery.

Naturally occurring bioactive food components such as dietary polyphenols have shown many beneficial biological activities due to their good antioxidant properties. Among them significant attention has been given to resveratrol (RV) in recent years as it plays a promising role in cancer prevention. It has demonstrated anti-proliferative effects, as well as the ability to inhibit the initiation and progression of induced cancer in a wide variety of tumor models. However, the benefits of its therapeutic effects were found to be limited due to its poor pharmacokinetic properties such as poor aqueous solubility, instability and extensive first pass metabolism. To overcome these limitations, the present study aimed to synthesize thermosensitive copolymeric nanoparticle encapsulated formulations of resveratrol-nanoresveratrol (NRV) and evaluate their in vitro anticancer activity and inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin inflammation and tumorigenesis in Swiss albino mice. For this purpose PNIPAAM-PEG based thermosensitive copolymeric nanoparticles were synthesized followed by the encapsulation of RV in their hydrophobic core. This enhanced the therapeutic bioavailability of resveratrol. Nanoresveratrol demonstrated stronger antioxidant activity and comparable anticancer efficacy to free resveratrol. Nanoparticles were characterized by IR, NMR, DLS and TEM. The best results were obtained with NRV at significantly lower doses. NRV demonstrated better in vitro anticancer activity against melanoma cell line B16. It showed comparable reduction of TPA induced skin edema, hyperplasia and oxidative stress response. In the promotion phase, a significant reduction was found in tumor incidence and tumor burden in mice pre-treated with NRV. Moreover, at all doses NRV altered Bax and Bcl2 expressions which lead to the induction of apoptosis.

Combinatorial drug delivery strategy employing nano-curcumin and nano-MiADMSA for the treatment of arsenic intoxication in mouse.

Chelation therapy is the mainstream treatment for heavy metal poisoning. Apart from this, therapy using antioxidant/herbal extracts are the other strategies now commonly being tried for the treatment. We have previously reported individual beneficial efficacy of nanoparticle mediated administration of an antioxidant like 'curcumin' and an arsenic chelator 'monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)' for the treatment of arsenic toxicity compared to bulk drugs. The present paper investigates our hypothesis that a combination drug delivery therapy employing two nanosystems, a chelator and a strong antioxidant, may produce more pronounced therapeutic effects compared to individual effects in the treatment of arsenic toxicity. An in-vivo study was conducted wherein arsenic as sodium arsenite (100 ppm) was administered in drinking water for 5 months to Swiss albino mice. This was followed by a treatment protocol comprising of curcumin encapsulated chitosan nanoparticles (nano-curcumin, 15 mg/kg, orally for 1 month) either alone or in combination with MiADMSA encapsulated polymeric nanoparticles (nano-MiADMSA, 50 mg/kg for last 5 days) to evaluate the therapeutic potential of the combination treatment. Our results demonstrated that co-treatment with nano-curcumin and nano-MiADMSA provided beneficial effects in a synergistic way on the adverse changes in oxidative stress parameters and metal status induced by arsenic.

Polymeric nanoparticles as a platform for permeability enhancement of class III drug amikacin.

Amikacin (A), a water soluble aminoglycoside antibiotic is commercially available for intravenous administration only. Present investigation is aimed at the development of poly-lactic-co-glycolic acid (PLGA) nanoparticles (A-NPs).1 for oral permeability enhancement of amikacin. The pharmaceutical attributes of the A-NPs revealed particle size, 260.3 ±â€¯2.05 nm, zeta potential, -12.9 ±â€¯1.12 mV and drug content, 40.10 ±â€¯1.87 µg/mg with spherical shape and smooth surface. In vitro antibacterial studies showed that the A-NPs were active against P. aeruginosa, K. pneumoniae and E. coli. The permeation study across rat ileum showed 2.6-fold improvement in Papp for A-NPs than A-S2 This increase in permeability is due to the uptake of nanoparticles by Peyer's patches of intestinal epithelium and endocytic uptake via enterocytes. Flow cytometric analysis demonstrated 2.2-fold higher uptake of Rh B-NPs3 than Rh B-S4 and elucidated the dominance of enterocytes mediated endocytosis of nanoparticles. Furthermore, stability data collected as per ICH guidelines for three months under accelerated conditions had shown that the A-NPs were stable. The purported drug delivery system hence, seems a promising tool to replace successfully the current intravenous therapy and is used to support relevant patient compliance thereby, adding value to the "patient care at home".

Portal vein ligation versus portal vein embolization for induction of hypertrophy of the future liver remnant: A systematic review and meta-analysis.

An important risk of major hepatic resection is postoperative liver failure, which is directly related to insufficient future liver remnant (FLR). Portal vein embolization (PVE) and portal vein ligation (PVL) can minimize this risk by inducing hypertrophy of the FLR. The aim of this systematic review and meta-analysis was to compare the efficacy and safety of PVE and PVL for FLR hypertrophy. A systematic search was conducted on the17th of January 2017. The methodological quality of the studies was assessed using the Oxford Critical Appraisal Skills Program for cohort studies. The primary endpoint was the relative rate of hypertrophy of the FLR. Number of cancelled hepatic resection and postoperative morbidity and mortality were secondary endpoints. For meta-analysis, the pooled hypertrophy rate was calculated for each intervention. The literature search identified 21 eligible studies with 1953 PVE and 123 PVL patients. All studies were included in the meta-analysis. No significant differences were found regarding the rate of FLR hypertrophy (PVE 43.2%, PVL 38.5%, p = 0.39). The number of cancelled hepatic resections due to inadequate hypertrophy was significantly lower after PVL (p = 0.002). No differences were found in post-intervention mortality and morbidity. This meta-analysis demonstrated no significant differences in safety and rate of FLR hypertrophy between PVE and PVL. PVE should be considered as the preferred strategy, since it is a minimally invasive procedure. However, during a two-stage procedure, PVL can be performed with expected comparable outcome as PVE.