Porphyrin-Loaded TyroSpheres for the Intracellular Delivery of Drugs and Photoinduced Oxidant Species.

In order to understand the intracellular delivery of drugs and to improve the cell killing efficiency of photosensitizers (PSs) used in photodynamic therapy (PDT), we prepared TyroSphere nanoparticles, which are triblock polymer [poly(ethylene glycol)--oligo(desaminotyrosyltyrosine octyl ester suberate)--poly(ethylene glycol)] aggregates, loaded with amphiphilic porphyrins with either positive (CisDiMPyP) or negative (TPPS) charges. Their physicochemical and photochemical properties were investigated, as well as the efficiency and mechanism of PDT death in a cervical cancer cell line (HeLa). The photophysical properties of both PSs were improved when loaded in the nanocarrier, with a decrease in aggregation as well as an increase in the yield of singlet oxygen generation.

Left Ventricular Diastolic Dysfunction is Associated with Renal Dysfunction, Poor Survival and Low Health Related Quality of Life in Cirrhosis.

Background: The presence of left ventricular diastolic dysfunction (LVDD) in patients with cirrhosis leads to a restriction of activities and a poor health related quality of life (HRQoL), which should be taken into consideration when treating them for liver and cardiac complications.

Aims: The prevalence, complications, predictors of HRQoL and survival in cirrhotic patients with LVDD were studied.

Methods: We report a prospective cohort study of 145 consecutive cirrhotic patients with LVDD who were evaluated for cardiac functional status at enrollment and followed up for hepatic complications, cardiac events, outcome and HRQoL using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) over a period of 2 years.

Carvedilol Combined With Ivabradine Improves Left Ventricular Diastolic Dysfunction, Clinical Progression, and Survival in Cirrhosis.

Background: Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis.

Patients And Methods: THR was defined as heart rate reduction to 55 to 65 beats per minute.

Clinico-mycological analysis and antifungal resistance pattern in human immunodeficiency virus-associated candidiasis: An Indian perspective.

Objectives: Candidiasis is a common human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome-associated opportunistic mycoses. The present study ascertained the species spectrum of strains recovered from different clinical samples from symptomatic HIV-positive individuals and determined the antifungal susceptibility profile of the isolates.

Materials And Methods: A variety of specimens were collected from 234 symptomatic HIV seropositive individuals depending on their clinical manifestations and subjected to direct microscopic examination.

Layer-by-layer assembled gold nanoshells for the intracellular delivery of miR-34a.

Introduction: MicroRNAs (miRNAs) are short noncoding RNAs whose ability to regulate the expression of multiple genes makes them potentially exciting tools to treat disease. Unfortunately, miRNAs cannot passively enter cells due to their hydrophilicity and negative charge. Here, we report the development of layer-by-layer assembled nanoshells (LbL-NS) as vehicles for efficient intracellular miRNA delivery.

Spherical Nucleic Acid Architecture Can Improve the Efficacy of Polycation-Mediated siRNA Delivery.

Clinical translation of small interfering RNA (siRNA) nanocarriers is hindered by limited knowledge regarding the parameters that regulate interactions between nanocarriers and biological systems. To address this, we investigated the influence of polycation-based nanocarrier architecture on intracellular siRNA delivery. We compared the cellular interactions of two polycation-based siRNA carriers that have similar size and surface charge but different siRNA orientation: (1) polyethylenimine-coated spherical nucleic acids (PEI-SNAs), in which polyethylenimine is wrapped around a spherical nucleic acid core containing radially oriented siRNA and (2) randomly assembled polyethylenimine-siRNA polyplexes that lack controlled architecture.

Is Antifungal Resistance a Cause for Treatment Failure in Dermatophytosis: A Study Focused on Tinea Corporis and Cruris from a Tertiary Centre?

Background: Dermatophytoses are one of the most common skin diseases that have been largely simple to treat. However, in recent years, these infections have become recalcitrant to treatment which can possibly be due to antifungal resistance.

Aim: To analyze the resistance pattern of patients with recalcitrant dermatophytoses.

The Relationship Between Uterine Artery two-dimensional Color Doppler Measurement and Pregnancy Outcome: A Prospective Observational Study.

Background: The purpose of the study was to evaluate the role of uterine blood flow parameters measured by uterine artery two-dimensional (2D)-power color doppler (PCD) ultrasound in predicting fertility outcomes in women undergoing IVF-ET cycles.

Methods: In this prospective observational study, a total of 188 infertile women who underwent IVF-ET cycles were investigated. Uterine artery 2D-PD measurements were taken during early follicular phase and on day of trigger.

Topical Delivery of Immunosuppression to Prolong Xenogeneic and Allogeneic Split-Thickness Skin Graft Survival.

Cadaveric skin allograft is the current standard of treatment for temporary coverage of large burn wounds. Porcine xenografts are viable alternatives but undergo α-1,3-galactose (Gal)-mediated hyperacute rejection and are lost by post-operative day (POD) 3 because of naturally occurring antibodies to Gal in primate recipients. Using baboons, we previously demonstrated that xenografts from GalT-KO swine (lacking Gal) provided wound coverage comparable with allografts with systemic immunosuppression.

Pulmonary aspergillosis as opportunistic mycoses in a cohort of human immunodeficiency virus-infected patients: Report from a tertiary care hospital in North India.

Objective: The incidence of pulmonary aspergillosis in human immunodeficiency virus (HIV)-infected persons is rising. This study was designed to determine the prevalence of pulmonary aspergillosis in a cohort of HIV-positive patients ( = 71) presenting with lower respiratory tract infection at a tertiary care medical center in India.

Methods: Sputum samples were collected, and potassium hydroxide mount, cultural characteristics, and lactophenol cotton blue preparations were employed to aid in the identification of species.

Cell type-specific extracellular matrix guided the differentiation of human mesenchymal stem cells in 3D polymeric scaffolds.

The tissue microenvironment has profound effects on tissue-specific regeneration. The 3-dimensional extracellular matrix (ECM) niche influences the linage-specific differentiation of stem cells in tissue. To understand how ECM guides tissue-specific regeneration, we established a series of 3D composite scaffolds containing ECMs derived from different primary cells isolated from a single animal species and assessed their impact on the differentiation of human mesenchymal stem cells (hMSCs).

Fungal Opportunistic Pneumonias in HIV/AIDS Patients: An Indian Tertiary Care Experience.

Introduction: Opportunistic pneumonias are a major cause of mortality and morbidity in Human Immunodeficiency Virus (HIV) reactive patients. Despite the significant role that fungi play in causation of this opportunistic mycoses, very few Indian studies have attempted to investigate the burden and aetiological spectrum of HIV/AIDS-associated fungal pneumonias.

Aim: To document the prevalence of fungal aetiology in HIV/AIDS-related opportunistic pneumonias in an Indian setting; and to elucidate the various fungal opportunists responsible for the same.

Development of hybrid scaffolds with natural extracellular matrix deposited within synthetic polymeric fibers.

A major challenge of tissue engineering is to generate materials that combine bioactivity with stability in a form that captures the robust nature of native tissues. Here we describe a procedure to fabricate a novel hybrid extracellular matrix (ECM)-synthetic scaffold biomaterial by cell-mediated deposition of ECM within an electrospun fiber mat. Synthetic polymer fiber mats were fabricated using poly(desamino tyrosyl-tyrosine carbonate) (PDTEC) co-spun with poly(ethylene glycol) (PEG) used as a sacrificial polymer.

Optimization of Polymer-ECM Composite Scaffolds for Tissue Engineering: Effect of Cells and Culture Conditions on Polymeric Nanofiber Mats.

The design of composite tissue scaffolds containing an extracellular matrix (ECM) and synthetic polymer fibers is a new approach to create bioactive scaffolds that can enhance cell function. Currently, studies investigating the effects of ECM-deposition and decellularization on polymer degradation are still lacking, as are data on optimizing the stability of the ECM-containing composite scaffolds during prolonged cell culture. In this study, we develop fibrous scaffolds using three polymer compositions, representing slow (E0000), medium (E0500), and fast (E1000) degrading materials, to investigate the stability, degradation, and mechanics of the scaffolds during ECM deposition and decellularization, and during the complete cellularization-decell-recell cycle.

Identification and Antifungal Susceptibility Testing of Species: A Comparison of Vitek-2 System with Conventional and Molecular Methods.

Background: Candida infection is a major cause of morbidity and mortality in immunocompromised patients; an accurate and early identification is a prerequisite need to be taken as an effective measure for the management of patients. The purpose of this study was to compare the conventional identification of Candida species with identification by Vitek-2 system and the antifungal susceptibility testing (AST) by broth microdilution method with Vitek-2 AST system.

Materials And Methods: A total of 172 isolates were subjected for identification by the conventional methods, Vitek-2 system, restriction fragment length polymorphism, and random amplified polymorphic DNA analysis.

Off-Target Effect of Sildenafil on Postsurgical Erectile Dysfunction: Alternate Pathways and Localized Delivery System.

Introduction: There is no consensus on the best oral phosphodiesterase type 5 inhibitor (PDE5I) for patients undergoing penile rehabilitation after surgical nerve injury.

Aim: To determine the mechanism of PDE5I on cultured neuronal cells and the effectiveness of local drug delivery using nanospheres (NSPs) to sites of nerve injury in a rat model of bilateral cavernous nerve injury (BCNI).

Methods: The effects of sildenafil, tadalafil, and vardenafil on cyclic adenosine monophosphate, cyclic guanosine monophosphate, and cell survival after exposure to hypoxia and HO were measured in PC12, SH-SY5Y, and NTERA-2 (NT2) cell cultures.

Spectrum of Opportunistic Fungal Infections in HIV/AIDS Patients in Tertiary Care Hospital in India.

HIV related opportunistic fungal infections (OFIs) continue to cause morbidity and mortality in HIV infected patients. The objective for this prospective study is to elucidate the prevalence and spectrum of common OFIs in HIV/AIDS patients in north India. Relevant clinical samples were collected from symptomatic HIV positive patients (n = 280) of all age groups and both sexes and subjected to direct microscopy and fungal culture.

Self-Assembly and Critical Aggregation Concentration Measurements of ABA Triblock Copolymers with Varying B Block Types: Model Development, Prediction, and Validation.

The dissipative particle dynamics (DPD) simulation technique is a coarse-grained (CG) molecular dynamics-based approach that can effectively capture the hydrodynamics of complex systems while retaining essential information about the structural properties of the molecular species. An advantageous feature of DPD is that it utilizes soft repulsive interactions between the beads, which are CG representation of groups of atoms or molecules. In this study, we used the DPD simulation technique to study the aggregation characteristics of ABA triblock copolymers in aqueous medium.

The Clinical Outcome of Post Placental Copper-T-380A Insertion with Long Placental Forceps (Kelly's Forceps) After Normal Vaginal Delivery and Cesarean Section.

Objectives: To study the efficacy safety effect on menstrual cycles, expulsion, continuation, and failure rate of post placental Copper-T-380A after vaginal and cesarean birth in a tertiary center, over the period of 1 year.

Methods: A total of 150 women who opted for insertion of Copper-T-380A within 10 min of expulsion of placenta whether delivered vaginally or by cesarean section were enrolled into study. Women having past history of ectopic pregnancy or any genital tract infection or hemorrhagic disorders, uterine anomaly, chorioamnionitis, LPV > 18 h, unresolved PPH, Hb < 8 g% were excluded from the study.

Nanoparticles and nanofibers for topical drug delivery.

This review provides the first comprehensive overview of the use of both nanoparticles and nanofibers for topical drug delivery. Researchers have explored the use of nanotechnology, specifically nanoparticles and nanofibers, as drug delivery systems for topical and transdermal applications. This approach employs increased drug concentration in the carrier, in order to increase drug flux into and through the skin.

Formulation Strategy for the Delivery of Cyclosporine A: Comparison of Two Polymeric Nanospheres.

A wide range of nanoparticles has been explored for the delivery of highly hydrophobic drugs, but very few publications provide comparative data of the performance of different nanoparticles. To address this need, this publication compares poly(lactic-co-glycolic acid) (PLGA) nanoparticles and nanospheres made from tyrosine-derived tri-block copolymers (termed TyroSpheres) for their respective performance as carriers for cyclosporine A (CSA). Using previously reported data on PLGA, we followed similar experimental protocols to evaluate the in vitro characteristics of TyroSpheres.

Copolymers of covalently crosslinked linear and branched polyethylenimines as efficient nucleic acid carriers.

The present study describes the formation of copolymers of linear and branched PEIs (25 kDa each). These polyethylenimines (bPEI and IPEI) were crosslinked with each other to obtain branched-linear (BL) PEI copolymers using epichlorohydrin as a crosslinker in two steps. First, IPEI was reacted with epichlorohydrin to form IPEI-chlorohydrin (CHL) and subsequently, bPEI was grafted onto CHL in basic medium by in situ generation of epoxy functionalities.

Enhanced efficiency of P-element mediated transgenesis in Drosophila: Microinjection of DNA complexed with nanomaterial.

The efficiency of genetic transformation technology to generate stable transgenics depends upon the successful delivery of plasmid DNA in embryonic cells. The available gene vectors facilitate efficient plasmid DNA delivery to the cellular milieu but are exposed to nuclease degradation. Recent in vitro studies suggest encapsulation of plasmid DNA with nanomaterial(s) for better protection against nucleases.

AgNOR Count and its Correlation with Colposcopy in Suspicious Cervix.

Objectives: To evaluate the correlation of AgNOR count and colposcopy in cases of suspicious cervix.

Methods: A hundred women presenting in OPD with complaints of postcoital bleeding, discharge per vaginum, pain in the lower abdomen, or intermenstrual bleeding were subjected to colposcopy. After colposcopy, a cervical biopsy was done.

Comparison of ketamine with fentanyl as co-induction in propofol anesthesia for short surgical procedures.

Background And Objective: A prospective randomized control study was conducted to compare and evaluate quality of anesthesia with ketamine or fentanyl as co-induction with propofol.

Materials And Methods: Sixty ASA I or II, 18-50 year old patients who were scheduled for minor surgeries of short duration (<30 min anticipated duration) were selected. The patients were randomly allocated to group I and group II comprising 30 patients each.