The effect of engagement in an HIV/AIDS integrated health programme on plasma HIV-1 RNA suppression among HIV-positive people who use illicit drugs: a marginal structural modelling analysis.

OBJECTIVES: HIV treatment-as-prevention campaigns emphasize early diagnosis and immediate access to care and antiretroviral therapy for HIV-positive individuals in order to increase levels of plasma HIV RNA viral load (VL) suppression. However, the possible role of harm reduction-based programmes in this objective has not yet been well evaluated. The objective of the study was to examine the relationship between being a client of the Dr. Peter Centre (DPC; an HIV/AIDS-focused adult integrated health programme) and VL suppression among highly active antiretroviral therapy (HAART)-exposed HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada. METHODS: Data were derived from the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) study, a study of a community-recruited cohort of HIV-positive PWUD. A marginal structural model using inverse probability of treatment weights was used to estimate the longitudinal relationship between being a DPC client and exhibiting a VL < 50 HIV-1 RNA copies/mL plasma. RESULTS: Between 2005 and 2014, 746 HAART-exposed participants were included in the study, of whom 269 (36.1%) reported being a DPC client at some time during the study period. A marginal structural model estimated a 1.54 greater odds of achieving VL suppression (95% confidence interval 1.20-1.99) among DPC clients. CONCLUSIONS: Our findings demonstrate that participating in an innovative HIV/AIDS-focused adult integrated health programme that provides a broad range of clinical, harm reduction, and support services may contribute to optimizing the benefits of HAART in terms of morbidity, mortality and viral transmission among PWUD, and as a result help to fulfill the goals of the treatment-as-prevention strategy.

Meaningful engagement of people living with HIV who use drugs: methodology for the design of a Peer Research Associate (PRA) hiring model.

BACKGROUND: Community-based HIV, harm reduction, and addiction research increasingly involve members of affected communities as Peer Research Associates (PRAs)-individuals with common experiences to the participant population (e.g. people who use drugs, people living with HIV [PLHIV]). However, there is a paucity of literature detailing the operationalization of PRA hiring and thus limited understanding regarding how affected communities can be meaningfully involved through low-barrier engagement in paid positions within community-based participatory research (CBPR) projects. We aim to address this gap by describing a low-threshold PRA hiring process. RESULTS: In 2012, the BC Centre for Excellence in HIV/AIDS and the Dr. Peter AIDS Foundation collaborated to develop a mixed-method CBPR project evaluating the effectiveness of the Dr. Peter Centre (DPC)-an integrative HIV care facility in Vancouver, Canada. A primary objective of the study was to assess the impact of DPC services among clients who have a history of illicit drug use. In keeping with CBPR principles, affected populations, community-based organizations, and key stakeholders guided the development and dissemination of a low-barrier PRA hiring process to meaningfully engage affected communities (e.g. PLHIV who have a history of illicit drug use) in all aspects of the research project. The hiring model was implemented in a number of stages, including (1) the establishment of a hiring team; (2) the development and dissemination of the job posting; (3) interviewing applicants; and (4) the selection of participants. The hiring model presented in this paper demonstrates the benefits of hiring vulnerable PLHIV who use drugs as PRAs in community-based research. CONCLUSIONS: The provision of low-barrier access to meaningful research employment described herein attempts to engage affected communities beyond tokenistic involvement in research. Our hiring model was successful at engaging five PRAs over a 2-year period and fostered opportunities for future paid employment or volunteer opportunities through ongoing collaboration between PRAs and a diverse range of stakeholders working in HIV/AIDS and addictions. Additionally, this model has the potential to be used across a range of studies and community-based settings interested in meaningfully engaging communities in all stages of the research process.

An integrated approach to care attracts people living with HIV who use illicit drugs in an urban centre with a concentrated HIV epidemic.

BACKGROUND: People living with HIV (PLHIV) who are also marginalized by social and structural inequities often face barriers to accessing and adhering to HIV treatment and care. The Dr. Peter Centre (DPC) is a non-profit integrated care facility with a supervised injection room that serves PLHIV experiencing multiple barriers to social and health services in Vancouver, Canada. This study examines whether the DPC is successful in drawing in PLHIV with complex health issues, including addiction. METHODS: Using data collected by the Longitudinal Investigations into Supportive and Ancillary health services (LISA) study from July 2007 to January 2010, linked with clinical variables available through the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program, we identified DPC and non-DPC clients with a history of injection drug use. Bivariable and multivariable logistic regression analyses compared socio-demographic and clinical characteristics of DPC clients (n = 76) and non-DPC clients (n = 482) with a history of injection drug use. RESULTS: Of the 917 LISA participants included within this analysis, 100 (10.9%) reported being a DPC client, of which 76 reported a history of injection drug use. Adjusted results found that compared to non-DPC clients with a history of injection drug use, DPC-clients were more likely to be male (AOR: 4.18, 95% CI = 2.09-8.37); use supportive services daily vs. less than daily (AOR: 3.16, 95% CI = 1.79-5.61); to have been diagnosed with a mental health disorder (AOR: 2.11; 95% CI: 1.12-3.99); to have a history of interpersonal violence (AOR: 2.76; 95% CI: 1.23-6.19); and to have ever experienced ART interruption longer than 1 year (AOR: 2.39; 95% CI: 1.38-4.15). CONCLUSIONS: Our analyses suggest that the DPC operating care model engages PLHIV with complex care needs, highlighting that integrated care facilities are needed to support the multiple intersecting vulnerabilities faced by PLHIV with a history of injection drug use living within urban centres in North America and beyond.

Effects of selenium nanoparticle on the growth performance and nutritional quality in Nile Tilapia, Oreochromis niloticus.

Selenium is an important micronutrient that has antioxidant, growth potential, and reproduction enhancement abilities in various organisms. The aquaculture industry is a significant contributor towards meeting the dietary requirements of a majority of the global population, which further warrants developing novel approaches for enhancing the production of dietary fish. This study was performed to assess the growth performance of Nile tilapia (Oreochromis niloticus) fingerlings (1 gm in average weight and 2.75 cm in average length) upon nano-selenium (Se-Nps) supplementation. Nanoselenium was synthesized using high-energy ball milling (HEBM) using a 10-hour dry milling technique at 10:1 ball-to-powder ratio (BPR), size characterized by XRD and TEM, followed by mixing with basal feed in desired concentrations (0.5 mg/kg, 1 mg/kg, and 2 mg/kg) and administration to Nile tilapia fingerlings for 30 days, followed by the evaluation of growth performance parameters, fatty acid profile analysis using GC-MS, and nutritional quality index (NQI): [Thrombogenicity Index (IT), Atherogenicity Index (IA), n-3/n-6, n-6/n-3)]. Nile tilapia supplemented with 1 mg/kg Se-Nps showed improved growth performance (RGR: 1576.04%, SGR: 4.70%, and FCR: 1.91), demonstrated by higher survivability (> 95%), isometric growth (coefficient of allometry, b = 2.81), and higher weight gain compared to control (RGR: 680.41%, SGR: 3.42%, and FCR: 1.31), 0.5 mg/kg Se-Nps (RGR: 770.83%, SGR: 3.61%, and FCR: 1.18) and 2 mg/kg Se-Nps (RGR: 383.67%, SGR: 2.63%, and FCR: 1.22). The average length-weight relationship assessed as the condition factor (K) was highest in the 1 mg/kg Se-Nps group compared to others (p < 0.05). GC-MS analysis revealed that Nile tilapia supplemented with 1 mg/kg Se-Nps showed better meat quality, higher amount of n-3 fatty acids, eicosapentaenoic acid, and docosahexaenoic acid, high PUFA/SAFA ratios (1.35) and n-3/n-6 (0.33) ratios, with low atherogenicity index (0.36) and thrombogenic index (0.44), and relatively low n-6/n-3 fatty acid ratio (3.00) compared to other groups. Overall, Se-Nps supplementation at 1 mg/kg enhanced the growth performance and meat quality in Nile tilapia, and therefore could be a potential growth-promoting micronutrient for aquaculture enhancement.

Techniques to assess myocardial viability.

Assessment of myocardial viability in patients with chronic coronary artery disease or acute and sub-acute myocardial infarction is clinically important for distinguishing stunned and hibernating myocardium from irreversibly injured myocardium. Patients may benefit from revascularization when viable tissue is present in the dysfunctional area of the myocardium. Several clinical imaging modalities exist for assessment of viable myocardium which have proven useful for chronic chronic coronary artery disease are available but a reliable technique for the assessment of myocardial viability in the sub-acute situation does not exist.

Enhanced external counterpulsation and CVD protection: 3D echo validation: a promising approach.

UNLABELLED: AIMS & OBJECTIVE: To evaluate the impact of enhanced external counterpulsation (EECP) on various echo variables by 3D-Echocardiography. MATERIALS AND METHODS: 60 adult patients from indoor and outdoor patient department; consisting of 16 patients with heart failure (HF) with left ventricular systolic dysfunction, 20 patients with heart failure with normal ejection fraction (HFNEF), 4 patients with prior percutaneous coronary intervention (PCI), 3 patients with prior coronary artery bypass grafting (CABG) and 17 patients with syndrome X; were subjected to Echocardiographic evaluation. The various echo variables included were left ventricular myocardial performance index (LVMPI), left ventricular mass index (LVMi), left ventricular diastolic dysfunction (LVDD), left ventricular systolic function (LVEF) and left atrial volume index (LAVi). Once randomized, patients underwent 35 hrs EECP treatment sessions, each lasting 1 hour, could be given once or twice per day. RESULTS: There was a significant reduction in the overall prolonged mean LVMPI from baseline (0.54 +/- 0.2) to post ECP treatment (0.43 +/- 0.1) in the total study population (p < 0.001). EECP treatment significantly reduced baseline grade II or grade III diastolic dysfunction and E/E' ratio > 12, but not in patients with baseline E/E' < 12, baseline normal diastolic function or grade I diastolic dysfunction. Similiarly the mean LVEF in the subset of patients with HF treatment was 30.7 +/- 3.1; post ECP the mean LVEF was increased to 36.9 +/- 3.2 which was statistically significant (p < 0.001). In the remaining patients, who had mean LVEF within normal range, there was no significant difference pre and post EECP (p value- NS). Pre EECP the mean LAVi in the total population was increased up to 33.4 +/- 5.6 ml/m2. Post EECP the mean LAVi reduced to 24.8 +/- 4.2 ml/m2, which was also statistically significant (p < 0.001). Regarding mean LVMi as well as in the patterns of LVH, there were no significant changes seen as compared to baseline. CONCLUSION: Enhanced External counterpulsation is noninvasive, non-surgical method of choice for CVD & heart failure protection. It is very useful in Single vessel or multivessel disease, heart failure, HFNEF, Post PCI or post CABG and syndrome X. It reduces LVMPI and improves global cardiac function, increases LVEF in patients with ejection fraction of less than 50%, reduces grade II or grade III diastolic dysfunction and E/E' ratio more than 12, decreases LAVi by 25.7%; thereby reducing adverse clinical events in CAD and heart failure.

Patterns of left ventricular hypertrophy in chronic kidney disease: an echocardiographic evaluation.

BACKGROUND: We evaluated the chronic kidney disease (CKD) patients having different degree of uremia for the prevalence of Left Ventricular Hypertrophy (LVH), different patterns of left Ventricular Hypertrophy by echocardiographic variables to define the most sensitive and powerful predictor of cardiovascular disease (CVD) and premature morbidity and mortality. METHODS: We used clinical and biochemical data from the prospective study done by us to evaluate "The Echocardiographic assessment of cardiac functions in patients with chronic kidney disease". The diagnosis of CKD was made on the basis of serum creatinine (sCr) concentration of more than 1.5 mg/dl, persistent and with no evidence of recovery over a period of 3 months. Glomerular filtration rate (GFR) was calculated by the Modification of Diet in Renal Disease (MDRD) equation and cut-off for CKD was taken to be < 60 ml/min/1.73 m2 as per existing guidelines. The study population consisted of a total of 75 subjects divided into three groups of 25 subjects each, all between the age of 20-65 yrs: GROUP A: Healthy normal controls (sCr < 1.5 mg/dl); GROUP B: Patients with mild to moderate CKD (sCr 1.5 - 6.0 mg/dl); GROUP C: Patients with severe CKD (sCr > 6.0 mg/dl). RESULTS: A progressive rise in prevalence of LVH was observed with the severity of kidney disease from 64% (mild/ moderate CKD group) to 96% (severe CKD group) and higher prevalence of LVH in females than males in the severe CKD group. The mean LVMI in both the groups of CKD was significantly higher than the healthy controls (76.62 +/- 10.97). Also, mean LVMI in severe CKD (139.23 +/- 17.47) patients was significantly higher than in mild/moderate CKD (114.91 +/- 15.20) patients. The prevalence of concentric remodeling in both the CKD groups was alike (20%). While that of concentric hypertrophy in severe CKD patients (68%) was significantly higher than in mild/moderate CKD group (40%) (p < 0.05), but no significant difference was observed for eccentric pattern of hypertrophy between the two CKD groups. This suggests that concentric hypertrophy is more prevalent in CKD patients. CONCLUSIONS: The mean left ventricular mass index (LVMI) showed a proportionate increase with the severity of renal failure and a progressive rise with increase in severity of disease. Patients of CKD groups revealed occurrence of concentric remodeling which is a predictor of high vulnerability for progressing into concentric and eccentric hypertrophy. Hence early medical intervention may reverse the concentric remodeling, thereby preventing the advancement to concentric or eccentric LVH.

Selenium and Zinc Oxide Multinutrient Supplementation Enhanced Growth Performance in Zebra Fish by Modulating Oxidative Stress and Growth-Related Gene Expression.

Selenium and zinc are important dietary micronutrients having antimicrobial and antioxidant roles, thereby assisting in normal development, and an enhanced immune system. Supplementation of selenium and zinc for enhancing the growth performance and reproductive capacity in fish was explored in this study. Selenium nanoparticles (SeNPs) and zinc oxide nanoparticles (ZnONPs) were synthesized by high-energy ball milling (HEBM) using a 10-h dry milling technique at a 10:1 ball-to-powder ratio (BPR) and were premixed with basal feed followed by the administration to adult zebra fish (D. rerio) (2 months old) for 30 days. Growth analysis revealed that zebra fish fed with SeNPs + ZnONPs (2 mg/ kg, equimolar mixture) had significantly higher length and weight than only SeNP (2 mg/ kg) or ZnONP (2 mg/ kg) groups and control zebra fish (p < 0.05). The average length-weight relationships were assessed by estimating the condition factor (C), which was highest in the SeNP + ZnONP group (1.96), followed by a downward trend in SeNP (C = 1.15) and ZnONP (1.11) (p < 0.05). Relative gene expression of growth hormone and insulin-like growth factor-1 was significantly high in the SeNP + ZnONP group compared to other groups (p < 0.05), which indicated that combined administration of both the nanoparticles in basal feed enhanced the growth performance of zebra fish. Intracellular ROS generation was low in the combined group, followed by control, SeNP, and ZnONP groups, indicating higher concentrations of both nanoparticles, in particular, ZnONPs induced oxidative stress. Fecundity and the development of fertilized embryos were significantly high in the SeNP + ZnONP-treated zebra fish compared to only the SeNP- or ZnONP-treated group or control (p < 0.05). These findings indicated that supplementation of SeNP + ZnONP in basal feed could considerably improve the growth performance and development of zebra fish which could be exploited for enhancing aquaculture production.

Cardiological society of India document on safety measure during echo evaluation of cardiovascular disease in the time of COVID-19.

An echocardiographic investigation is one of the key modalities of diagnosis in cardiology. There has been a rising presence of cardiological comorbidities in patients positive for COVID-19. Hence, it is becoming extremely essential to look into the correct safety precautions, healthcare professionals must take while conducting an echo investigation. The decision matrix formulated for conducting an echocardiographic evaluation is based on presence or absence of cardiological comorbidity vis-à-vis positive, suspected or negative for COVID-19. The safety measures have been constructed keeping in mind the current safety precautions by WHO, CDC and MoHFW, India.

Nanoscale structure-property relations in Sm modified lead zirconate titanate.

Nanocrystalline ferroelectric Pb0.92Sm0.08(Zr0.53Ti0.47)0.98O3 with high dielectric constant has been synthesized by mechanical alloying (high energy ball milling). The ferroelectric material exhibits novel behavior when its crystallite size falls below a critical length scale of 40 nm. We observed phenomena such as significant decrease in dielectric constant and phase transition from Tetragonal to Cubic structure on reduction in crystallite size below 40 nm.

3D echocardiography: "The most powerful predictor of masked CVD in metabolic syndrome".

UNLABELLED: AIMS & OBJECTIVE: To evaluate the impact of the Metabolic Syndrome (MetS) on various echo variables by 3D Echocardiography. MATERIALS AND METHODS: 100 patients of MetS from indoor and outdoor patient departments were subjected to Echocardiographic and Carotid Doppler evaluation. They were divided into three groups: Group A, Group B and Group C on the basis of age <40 yrs, 40-60 yrs and >60 yrs respectively. The echo variables included left ventricular myocardial performance index (LVMPI), left ventricular mass index (LVMi), left ventricular diastolic dysfunction (LVDD), systolic function (LVEF), left atrial volume index (LAVi) and composite common carotid intima media thickness (CCIMT). RESULTS: The mean LVMPI was abnormal in all the groups and showed an increasing trend with prolonged LVMPI (> 0.4) in 74% of the total population. Prolonged LVMPI in Group A, Group B and Group C were 12.1%, 52.7% and 35.1% respectively. There was also a strong correlation between LVMPI & LVDD (p-value < 0.0001). Only 9% had systolic dysfunction (LVEF < 50%), but 68% of patients had abnormal diastolic function, of which 53% had grade I LVDD, 12% had grade II LVDD and 3% had grade III diastolic dysfunction. None of our patients had grade IV diastolic dysfunction. The mean LA Vi was normal in all the groups, but LAVi increased with worsening LVDD. The mean LVMi indexed to Body Surface Area (BSA) was normal in all the groups, but showed a statistically significant increasing trend from Group A to Group C (p-value < 0.05). Statistically significant higher LVMi values were observed for males as compared to females (p-value < 0.0001). On analysis of patients having left ventricular hypertrophy (LVH), 76% had concentric remodeling; only 11 % had concentric hypertrophy, but none had eccentric hypertrophy. Most of our patients in Group B & Group C had higher mean Composite CCIMT (0.73 +/- 0.33 & 0.84 +/- 0.42 respectively) which was statistically very significant (p-value < 0.001) CONCLUSION: Metabolic Syndrome is associated with masked cardiovascular disease (CVD) as evident by 3D Echo in this series of patients. LVMPI was an early indicator and the most robust marker of early LVDD. Impaired relaxation was highly prevalent; while LAVi was less robust predictor of LVDD in this series of patients. Concentric left ventricular remodeling was the most common pattern of LVH. Most of our series of patients had increased Composite CCIMT. Thus 3D Echocardiography has great potential and is very useful for early detection and timely therapeutic interventions in patients with subclinical CVD in MetS.

Altered electrical properties with controlled copper doping in ZnO nanoparticles infers their cytotoxicity in macrophages by ROS induction and apoptosis.

The present study reports the regulation of cytotoxicity of Cu doped ZnO nanoparticles in macrophages (RAW 264.7) due to altered physiochemical properties changes like electrical properties by controlled doping of Cu in ZnO. Cu-doped ZnO nanoparticles were prepared by High Energy Ball Milling technique (HEBM) and formed single phase Zn1-xCuxO (x = 0.0, 0.01, 0.02, 0.03) were called as pure ZnO, Cu1%, 2%, 3% respectively. Hexagonal wurtzite structure with size range of 22-26 nm was verified. FE-SEM with EDX analysis indicated the Cu doping effect on the surface morphology of ZnO. Zeta potential of Zn1-xCuxO was found to be elevated with increase in doping percentage of Cu (-36.6 mV to +18.2 mV). Dielectric constant was found to be decreased with increasing doping percentage. Increase in doping percentage enhanced cytotoxicity of Zn1-xCuxO in macrophages with LC50 of 62 µg/ml, 51 µg/ml, 40 µg/ml, 32 µg/ml. Granularity change of macrophages suggested doping influenced cellular uptake as consequence of zeta potential and dielectric properties changes. 3% Cu doped ZnO shown a higher ROS signal and apoptosis than 2% and 1% Cu doping with exhibition of ROS scavenging nature leading to apoptosis of prepared Cu doped ZnO nanoparticles. Our findings revealed mechanism of cytotoxicity of Zn1-xCuxO as a consequence of alteration in electric properties eliciting ROS scavenging leading to higher apoptosis with increasing doping percentage of Cu in ZnO.

Mechanistic Insight into Size-Dependent Enhanced Cytotoxicity of Industrial Antibacterial Titanium Oxide Nanoparticles on Colon Cells Because of Reactive Oxygen Species Quenching and Neutral Lipid Alteration.

This study evaluates the impact of industrially prepared TiO2 nanoparticles on the biological system by using an in vitro model of colon cancer cell lines (HCT116). Industrial synthesis of titanium oxide nanoparticles was mimicked on the lab scale by the high-energy ball milling method by milling bulk titanium oxide particles for 5, 10, and 15 h in an ambient environment. The physiochemical characterization by field emission scanning electron microscopy, dynamic light scattering, and UV-visible spectroscopy revealed alteration in the size and surface charge with respect to increase in the milling time. The size was found to be reduced to 82 ± 14, 66 ± 12, and 42 ± 10 nm in 5, 10, and 15 h milled nano TiO2 from 105 ± 12 nm of bulk TiO2, whereas the zeta potential increased along with the milling time in all biological media. Cytotoxicity and genotoxicity assays performed with HCT116 cell lines by MTT assay, oxidative stress, intracellular lipid analysis, apoptosis, and cell cycle estimation depicted cytotoxicity as a consequence of reactive oxygen species quenching and lipid accumulation, inducing significant apoptosis and genotoxic cytotoxicity. In silico analysis depicted the role of Sod1, Sod2, p53, and VLDR proteins-TiO2 hydrogen bond interaction having a key role in determining the cytotoxicity. The particles exhibited significant antibacterial activities against Escherichia coli and Salmonella typhimurium.

Molecular insights to alkaline based bio-fabrication of silver nanoparticles for inverse cytotoxicity and enhanced antibacterial activity.

High demand for silver nanoparticles due to their extensive applications in different field has raised need of eco-friendly green synthesis with determined biomedical effects. This study proposes a novel rapid controlled alkaline based green synthesis of antibacterial silver nanoparticles from Calotropis gigantea for reduced cytotoxic effects. Silver nanoparticles termed as FAg, FAg1N, and FAg5N were synthesized with the help of floral extract of Calotropis gigantea as reducing and capping agent in presence of UV light and NaOH for catalysis and were characterized for their physiochemical properties by FESEM, DLS, UV-Visible spectrophotometry and FTIR. Facile synthesized Silver nanoparticles FAg1N and FAg5N showed enhanced antibacterial effects than FAg with increased NaOH concentration. Cytotoxic effect was found to be reduced at optimized alkaline conditioned FAg1N than FAg and FAg5N. Molecular dynamics study depicted the significant role of configurational change in "Calotropin" at variable alkalinity for controlling the size and physiological properties of synthesized AgNPs. The mechanism of cytotoxicity was revealed as consequences of variability in the interaction of Sod1 and P53 proteins with AgNPs surface for oxidative stress induction and programmed cell death.

Mechanistic insight into ROS and neutral lipid alteration induced toxicity in the human model with fins (Danio rerio) by industrially synthesized titanium dioxide nanoparticles.

The toxicological impact of TiO2 nanoparticles on the environment and human health has been extensively studied in the last few decades, but the mechanistic details were unknown. In this study, we evaluated the impact of industrially prepared TiO2 nanoparticles on the biological system using zebrafish embryo as an in vivo model. The industrial synthesis of TiO2 nanoparticles was mimicked on the lab scale using the high energy ball milling (HEBM) method by milling bulk TiO2 particles for 5 h, 10 h, and 15 h in an ambient environment. The physiochemical properties were characterized by standard methods like field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), X-ray diffraction (XRD) and UV-Visible spectroscopy. In vivo cytotoxicity was assessed on zebrafish embryos by the evaluation of their mortality rate and hatching rate. Experimental and computational analysis of reactive oxygen species (ROS) induction, apoptosis, and neutral lipid alteration was done to study the effects on the cellular level of zebrafish larvae. The analysis depicted the change in size and surface charge of TiO2 nanoparticles with respect to the increase in milling time. In silico investigations revealed the significant role of ROS quenching and altered neutral lipid accumulation functionalised by the molecular interaction of respective metabolic proteins in the cytotoxicity of TiO2 nanoparticles with zebrafish embryos. The results reveal the hidden effect of industrially synthesized TiO2 nanoparticle exposure on the alteration of lipid accumulation and ROS in developing zebrafish embryos. Moreover, the assessment provided a detailed mechanistic analysis of in vivo cytotoxicity at the molecular level.

Rapid Novel Facile Biosynthesized Silver Nanoparticles From Bacterial Release Induce Biogenicity and Concentration Dependent In Vivo Cytotoxicity With Embryonic Zebrafish-A Mechanistic Insight.

In this study, rapid one step facile synthesis of silver nanoparticles (AgNPs) was done using culture supernatant of two Gram positive (B. thuringiensis and S. aureus) and Gram negative (E. coli and Salmonella typhimurium [STAgNP]) bacterial strains and were termed as "Bacillus thuringiensis," "Staphylococcus aureus," "Escherichia coli," and "STAgNP," respectively. Synthesized AgNPs were well characterized with the help of different standard techniques like FESEM, DLS, UV-Vis spectroscopy, and Fourier transform infrared. Mechanism of AgNPs synthesis was elucidated using in silico approach. In vivo cytotoxicity of synthesized AgNPs was assessed in embryonic Zebrafish model with the help of uptake, oxidative stress, and apoptosis induction experimental assays, and the mechanism was investigated through in silico approach at the molecular level. The result showed successful biosynthesis of 20-40 nm sized AgNPs stable with zeta potential of - 45 to - 35 mV having standard silver nanoparticles SPR peaks due to the interaction of reduced silver particles with amino acid residues of bapA proteins of the bacterial supernatant. In vivo cytotoxicity with embryonic Zebrafish was found to be dependent on biogenicity and concentration of biosynthesized AgNPs as consequence of oxidative stress induction and apoptosis due to the influential regulation of sod1 and tp53 genes clarified by pathway analysis with reference to experimental and computational results. The study suggested that cytotoxicity of biologically synthesized silver nanoparticles from bacteria depends on strain specificity with significant difference in use of Gram positive and Gram negative bacterial strains.

Altered physiochemical properties in industrially synthesized ZnO nanoparticles regulate oxidative stress; induce in vivo cytotoxicity in embryonic zebrafish by apoptosis.

This study investigates the in vivo cytotoxicity of ZnO nanoparticles synthesized at industrial scale with embryonic Zebrafish. Industrial synthesis of ZnO nanoparticles was mimicked at lab scale by high energy ball milling technique by milling bulk ZnO particles for 15 h. Synthesized 7 h and 10 h ZnO nanoparticles showed significant alteration of size, zeta potential and optical properties in comparison to Bulk ZnO. Mortality and hatching rate in Zebrafish embryos were influenced by these alterations. Size and charge dependent effect of ZnO nanoparticles exposure on physiology and development of Zebrafish embryos were evident by malfunctioned organ development and abnormal heartbeat rate. Similar dependency on quenching of ROS due to influential hydrogen bond interaction with glycine residue of Sod1 oxidative stress protein and increased apoptosis were observed in cells. The study revealed the mechanism of cytotoxicity in exposed embryonic Zebrafish as an effect of accumulation and internalization inside cells instigating to generation of hypoxic condition and interference with the normal adaptive stress regulation signaling pathways leading towards enhanced apoptosis. The study revealed hidden size and charge dependent in vivo cytotoxicity mechanism of ZnO nanoparticles in Zebrafish embryos insight of the environmental and clinical importance of attention on industrially synthesized ZnO nanoparticles.

Pentoxifylline--a new drug for the treatment of intermittent claudication.

Pentoxifylline, a xanthine analogue was evaluated for efficacy, safety and tolerance in the treatment of intermittent claudication in a pilot study. Evaluation was performed in 35 cases. 20 patients were given Pentoxifylline in doses of 1200 mg daily, and 15 patients were given placebo for a period of 8 weeks respectively. Pentoxifylline given in doses of 1200 mg was significantly more effective than the placebo in increasing both the initial and absolute claudication distance (ICD & ACD) in patients with chronic occlusive arterial disease. The subjective parameters, such as paraesthesias, muscular cramps and sensation of heaviness in the legs paralleled the course of walking parameters. These results support the hypothesis that Pentoxifylline in doses of 400 mg TDS reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD (Fontaine Stage II or Stage III). Pentoxifylline is thus regarded as a promising drug for circulatory ischaemic disorders, especially in intermittent claudication. It was well tolerated with minimal untoward effects.