INNOVATIVE GROWTH IN DEVELOPING NEW METHODS FOR FORMULATING SOLID LIPID NANOPARTICLES AND MICROPARTICLES

The solid lipid nanopaticles are the colloidal drug delivery system which is spherical in shape and present in 10-1000nm particle sized range. The surfactant is used to stabilize the solid lipid nanoparticles to avoid aggregation. The Co-surfactant was used in addition to increase the micelles concentration. The optimization of surfactant concentration was used to stabilize the nanoparticles and microparticles formed and to decrease the particle size by decrease the aggregation. The manufacturing methods of the SLN are of four types, the high pressure homogenization which is further divides into two types hot homogenization method and cold homogenization method, Solvent-Diffusion evaporation method, ultrasonication method, and membrane contactor method. The non-uniform particles sizes were obtained from high pressure and ultra-sonication methods but the solvent-Diffusion Evaporation method and membrane contactor methods give uniform sized particles. But disadvantages of the later methods are the toxicity of organic solvent if not evaporates completely from the SLNs and the high cost of membrane contactor instrument is there in the formulation of SLNs. While the ultra-turrax and high pressure homogenization methods are the safest methods to use as compared to Solvent-Diffusion Evaporation method. The unpublished results have indicated that the drug release from the HPH and ultra-sonication gave highest drug release as compared to marketed conventional gel and formulation obtained by Solvent-Diffusion Evaporation method. Keywords: SLN, high pressure homogenization method, Solvent-Diffusion Evaporation method, ultrasonication method, Membrane contactor metho

PARTICLE SIZE REDUCTION OF ACECLOFENAC BY USING SURFACTANTS AND MICRONIZATION FOR NANOCARRIER ENTRAPMENT

The Aceclofenac (2-[(2, 6- dichlorophenyl) amine] phenylacetoxyacetic acid) is a Non-Steroidal Anti-Inflammatory category of drug, which is water insoluble drug of BCS class-II which has low solubility and high permeability phenomenon. The particle size reduction technique is used to solubilize the aceclofenac. The particle size of aceclofenac in bulk form is 140-200 microns. In this experiment, The 35 microns particle size was reduced in powder form from 140-200 microns by using Air jet mill and 17.08 microns size was reduced by using dynomill and 33.62 microns particle size was reduced by using Tween 80 as surfactant as considered as lowest particle size. The Labrasol and Na. CMC were also used in this experiment. The equipments used to reduce particle size of aceclofenac are ultra-Turrax (Ultra-sonication), Air jet mill and Dynomill. These all instruments used to reduce the particle size of aceclofenac are safe and not any chemical compound was added in any of the method described above. This study was used to see the uniform nature of the nano- and micro-particles entrapping the aceclofenac drug obtained by High shear homogenization, high pressure homogenization, Solvent-Diffusion evaporation and membrane contactor methods. If the particle size of aceclofenac cannot be reduced less than 14 microns then at the time of Permeation studies the same particle size will enter in Stratum corneum of Skin and entrapped in the carrier matrix. And formation of microns sized particles will obtained while preparing Solid lipid nanoparticles. Keywords: Solubilization, Particle size reduction, Air jet mill, high shear homogenizer, particle size analyzer, Dynomil

Autophagy induction by Scutellaria flavones in cancer: recent advances

In parallel with a steady rise in cancer incidence worldwide, the scientific community is increasingly focused on finding novel, safer and more efficient modalities for managing this disease. Over the past decades, natural products have been described as a significant source of new structural leads for novel drug candidates. Scutellaria root is one of the most studied natural products because of its anticancer potential. Besides just describing the cytotoxic properties of plant constituents, their molecular mechanisms of action in different cancer types are equally important. Therefore, this review article focuses on the role of the Scutellaria flavones wogonin, baicalein, baicalin, scutellarein and scutellarin in regulating the autophagic machinery in diverse cancer models, highlighting these molecules as potential lead compounds for the fight against malignant neoplasms. The knowledge that autophagy can function as a dual-edged sword, acting in both a pro- and antitumorigenic manner, further complicates the issue, revealing an amazing property of flavonoids that behave either as anti- or proautophagic agents

Melatonin inhibira lipidnu peroksidaciju u jetri štakora uzrokovanu benzenom

We studied the antioxidative role of melatonin against benzene toxicity in rat liver. The inhibition of mitochondrial and microsomal lipid peroxidation differed between 24-hour (single-dose), 15-day, and 30-day treatments. Inhibition of mitochondrial lipid peroxidation was the highest after the single dose of melatonin, whereas highest microsomal inhibition was recorded after 30 days of melatonin treatment. No signifi cant difference was recorded between 15-day and 30-day treatments. Cytochrome P4502E1 (CYP4502E1) activity declined after the single-dose and 15-day melatonin treatment in the benzenetreated group, but it rose again, though not signifi cantly after 30 days of treatment. Liver histopathology generally supported these fi ndings. Phenol concentration in the urine samples declined in melatonin and benzene-treated rats. Our results show that melatonin affects CYP4502E1, which is responsible for benzene metabolism. Inhibition of its metabolism correlated with lower lipid peroxidation. In conclusion, melatonin was found to be protective against lipid peroxidation induced by benzene.Istražena je antioksidacijska uloga melatonina u zaštiti protiv toksičnoga djelovanja benzena u jetri štakora. Utvrđeno je da kratkoročno odnosno dugoročnije liječenje štakora melatoninom u različitoj mjeri štiti štakore istodobno izložene benzenu. Inhibicija lipidne peroksidacije mitohondrija i mikrosoma bila je različita nakon 24 h, 15 dana, odnosno 30 dana liječenja melatoninom. Najveća inhibicija lipidne peroksidacije mitohondrija zamijećena je nakon primjene jednokratne doze melatonina, dok je najizraženija inhibicija u mikrosomima zamijećena nakon 30 dana liječenja melatoninom. Slična istraživanja pokazuju da razina glutationa (GSH) najviše raste nakon 24 h liječenja melatoninom. Nije zamijećena razlika između liječenja u trajanju od 15 odnosno 30 dana. U štakora koji su uz benzen istodobno primali i melatonin razine citokroma P4502E1 pale su nakon 24 h odnosno 15 dana izloženosti. U štakora koji su primali samo melatonin te su razine nakon 30 dana statistički neznačajno porasle u odnosu na skupinu izloženu samo benzenu. Histopatološka analiza jetre načelno je potvrdila ove nalaze. Koncentracije fenola u mokraći bile su niže u štakora koji su istodobno primali melatonin i benzen. Ovi rezultati pokazuju da melatonin utječe na citokrom P4502E1, koji je odgovoran za metabolizam benzena. Inhibira li se njegov metabolizam, smanjuje se lipidna peroksidacija. Zaključak je da melatonin štiti od lipidne peroksidacije uzrokovane benzenom

Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project)

REIPI/INCREMENT-SOT Group.[Background] Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear.[Methods] We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively.[Results] Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes.[Conclusions] Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).This work was supported by: (1) Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [RD16/0016/0001, RD16/0016/0002, REIPI RD16/0016/0008; RD16/0016/00010], co-financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligent Growth 2014-2020; (2) European Society of Clinical Microbiology and Infectious diseases Study Group for Infections in Compromised Hosts (ESGICH, grant to J.M.A.); (3) Sociedad Andaluza de Trasplante de Órgano Sólido (SATOT, grant to L.M.M.); (4) Research project PI16/01631 integrated into the Plan Estatal de I+D+I 2013-2016 and co-financed by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación and the Fondo Europeo de Desarrollo Regional (FEDER); (5) M.F.R. holds a research contract “Miguel Servet” (CP 18/00073) from ISCIII, Ministerio de Ciencia, Innovación y Universidades. The work was also supported by the following European Society of Clinical Microbiology and Infectious diseases (ESCMID) study groups: Infections in Compromised Hosts (ESGICH), Bloodstream Infections and Sepsis (ESGBIS) and Antimicrobial Resistance Surveillance (ESGARS).Peer reviewe

Genomic plasticity associated with antimicrobial resistance in Vibrio cholerae.

The Bay of Bengal is known as the epicenter for seeding several devastating cholera outbreaks across the globe. Vibrio cholerae, the etiological agent of cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and adapt them into its genome for structuring metabolic processes, developing drug resistance, and colonizing the human intestine. Antimicrobial resistance (AMR) in V. cholerae has become a global concern. However, little is known about the identity of the resistance traits, source of AMR genes, acquisition process, and stability of the genetic elements linked with resistance genes in V. cholerae Here we present details of AMR profiles of 443 V. cholerae strains isolated from the stool samples of diarrheal patients from two regions of India. We sequenced the whole genome of multidrug-resistant (MDR) and extensively drug-resistant (XDR) V. cholerae to identify AMR genes and genomic elements that harbor the resistance traits. Our genomic findings were further confirmed by proteome analysis. We also engineered the genome of V. cholerae to monitor the importance of the autonomously replicating plasmid and core genome in the resistance profile. Our findings provided insights into the genomes of recent cholera isolates and identified several acquired traits including plasmids, transposons, integrative conjugative elements (ICEs), pathogenicity islands (PIs), prophages, and gene cassettes that confer fitness to the pathogen. The knowledge generated from this study would help in better understanding of V. cholerae evolution and management of cholera disease by providing clinical guidance on preferred treatment regimens.DBT Indi

Chemoenzymatic synthesis, nanotization and anti- aspergillus activity of optically enriched fluconazole analogues

Despite recent advances in diagnostic and therapeutic advances in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogs. Anti-Aspergillus activity was observed for an optically enriched derivative, (-)-S-2-(2’ ,4’ -difluorophenyl)-1-hexyl-amino-3-(1‴,2‴,4‴) triazol-1‴-yl-propan-2-ol, which exhibits MIC values of 15.6 μg/mL and 7.8 μg/disc in microbroth dilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1000 μg/mL. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analog exhibited improved antifungal activity against Aspergillus fumigatus (MIC = 1.63 μg/mL). These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotised counterparts, exhibiting anti-Aspergillus activity may have reduced toxicity

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Some New First-Order All-Pass Realizations Using CCII

Some new first-order all-pass filters using a second-generation current conveyor are reported. Two circuits have higher input impedance than reported very recently and use a grounded capacitor. Additionally two more circuits have been reported, one of which has minimum passive and active components and has the facility of single resistance tuning. The other circuit has high input impedance and uses two current conveyors but has one passive component less than the similar circuits reported earlier