Magnetically mediated release of ciprofloxacin from polyvinyl alcohol based superparamagnetic nanocomposites.

Polymer nanocomposites exhibiting superparamagnetic behavior have been recognized as a promising tool to achieve targeted drug delivery using external magnetic field for treating complex diseases like cancers and tumors. The present investigation attempts to design a superparamagnetic nanocomposite which could desirably deliver ciprofloxacin drug by application of varying magnetic field. In order to achieve the proposed objectives, a polymer matrix of polyvinyl alcohol-g-polymethyl methacrylate was prepared by free radical polymerization and iron oxide particles were impregnated by in situ precipitation method. The prepared nanocomposites were characterized by techniques like FTIR, electron microscopy (SEM and TEM) and XRD and magnetization studies were performed to ensure superparamagnetic behavior. The antibiotic drug ciprofloxacin was loaded onto the magnetic nanocomposites and the influence of various factors such as percent loading, chemical composition of the nanocomposite, applied magnetic field, pH of the release medium were investigated on the release profiles of the drug. The chemical integrity of the drug and its antibacterial potential were also studied. The dynamics of the release process was also examined mechanistically.

Efficient graphene-coated iron oxide (GCIO) nanoadsorbent for removal of lead and arsenic ions.

ABSTRACTThe graphene-coated iron oxide (GCIO) was used for the removal of Pb2+ and As3+ ions from aqueous solution. For the characterization of GCIO, several techniques (FTIR, XRD, EDX, SEM, TEM, TGA, DSC and vibrating sample magnetometry) were used which indicated the interaction of Pb2+ and As3+ with adsorbent. In addition, the effects of adsorbate concentration, different composition of adsorbent, temperature, pH of the solution and contact time of adsorbate-adsorbent were studied. After analysis of these experiments, it was found that GCIO offered very fast removal of Pb2+ and As3+ with small amount of GCIO (0.09 g) in 100 mg/L adsorbate solution. The maximum removal of Pb2+ ions (up to 97.62%) was achieved when 100 mg/L standard solution of metal ion was treated with GCIO for 35 min at 45°C in weak acidic medium (5 pH). The adsorption of Pb2+ ions followed Freundlich model with high correlation coefficient 0.98 R2. In case of As3+ ions, maximum removal of metal ion (up to 86.62%) was attained when 100 mg/L adsorbate solution is treated with GCIO for 25 min in slightly acidic medium (6 pH) at 25°C. The adsorption of As3+ ions followed D-R model with 0.98 R2 value. The adsorption of both metal ions (Pb2+ and As3+) follows second-order kinetic model. The high percentage removal of metal ions with little quantity of GCIO confirmed that GCIO is an excellent, effective and economic adsorbent.

Investigation on magnetically controlled delivery of doxorubicin from superparamagnetic nanocarriers of gelatin crosslinked with genipin.

Gelatin (Type B) nanoparticles were prepared by a single W/O emulsion technique and characterized by infrared (IR) spectra, transmission electron micrographs (TEM), surface potential measurements and magnetization studies. Whereas the IR spectra clearly confirmed the presence of gelatin, genipin and doxorubicin in the loaded nanoparticles, the transmission electron micrographs (TEM) image depicts smooth surface, spherical shape and non-uniform size of nanoparticles (up to 100 nm). The prepared nanoparticles were loaded with doxorubicin, a well known anticancer drug, and in vitro release dynamics of entrapped drug was investigated as a function of various experimental factors such as percent loading of the drug, chemical architecture of the nanocarriers, and pH, temperature, ionic strength and nature of the release medium in presence and absence of magnetic field. The nanoparticles were also studied for their water sorption capacity. The drug release process was analyzed kinetically using Ficks power law and a correlation was established between the quantity of released drug and swelling of the nanoparticles.

Celiac Disease in Indian Children and Adolescents with Type 1 Diabetes.

To estimate the time trend and prevalence of celiac disease in 208 children with type 1 diabetes by retrospective case review. Tissue transglutaminase (TTG IgA) levels were done within the first six months of diagnosis and annually on follow-up. Celiac disease was diagnosed in 35 (16.8%; 3 before diagnosis, 18 at initial screening and 14 on follow-up). 14 subjects with negative TTG serology at presentation, developed celiac disease after 3.9 (2.9) years (range 1.4 - 12.6 years, 85.7% within 5 years). Celiac disease is common in Indian children and adolescents with type I diabetes, developing in most within five years of diagnosis.

Factors Associated With Cerebral Edema at Admission in Indian Children with Diabetic Ketoacidosis.

OBJECTIVE: To evaluate the time course and predictors of cerebral edema in diabetic ketoacidosis (DKA). METHODS: Review of hospital records of 107 episodes of DKA between January 2013 to March 2019. RESULTS: Cerebral edema was identified in 26 (24.3%; 22 at presentation and 4 during treatment). Cerebral edema at presentation was associated with lower (<10 mmHg) arterial carbon dioxide (OR 3.6, 95% CI 1.0,12.7; P=0.04), prior fluid treatment (OR 4.7, 95% CI 1.8,12.7; P=0.001) and new onset diabetes (OR 3.5, 95% CI 1.1,11.1; P=0.03). Prior fluid was the only significant predictor on multivariate analysis (P=0.013). Cerebral edema resulted in a longer ICU stay [4.1 (2.3) vs 1.8 (0.9) d; P<0.001]. CONCLUSIONS: Cerebral edema at admission is common in Indian children with DKA and should be suspected with severe metabolic acidosis and inappropriate prior fluid treatment.

Macrophages of diverse phenotypes drive vascularization of engineered tissues.

Macrophages are key contributors to vascularization, but the mechanisms behind their actions are not understood. Here, we show that diverse macrophage phenotypes have distinct effects on endothelial cell behavior, with resulting effects on vascularization of engineered tissues. In Transwell coculture, proinflammatory M1 macrophages caused endothelial cells to up-regulate genes associated with sprouting angiogenesis, whereas prohealing (M2a), proremodeling (M2c), and anti-inflammatory (M2f) macrophages promoted up-regulation of genes associated with pericyte cell differentiation. In 3D tissue-engineered human blood vessel networks in vitro, short-term exposure (1 day) to M1 macrophages increased vessel formation, while long-term exposure (3 days) caused regression. When human tissue-engineered blood vessel networks were implanted into athymic mice, macrophages expressing markers of both M1 and M2 phenotypes wrapped around and bridged adjacent vessels and formed vessel-like structures themselves. Last, depletion of host macrophages inhibited remodeling of engineered vessels, infiltration of host vessels, and anastomosis with host vessels.

Designing of macroporous biocompatible cryogels of PVA-haemoglobin and their water sorption study.

Macroporous polymeric materials are three-dimensional porous architectures having enormous utility in the areas of biomedical, biotechnological and separation sciences. Thus realizing the crucial role of macroporous polymeric materials in tissue engineering and allied fields the present paper discusses synthesis, characterization, and blood compatibility study of macroporous cryogels of PVA and haemoglobin. Biocompatible spongy and porous hydrogels of polyvinyl alcohol-haemoglobin have been synthesized by repeated freezing-thawing method and characterized by Infrared (FTIR), and ESEM techniques. The FTIR analysis of prepared cryogels indicated that haemoglobin was introduced into the cryogel possibly via hydrogen bonds formed amongst hydroxyl groups and amino groups present in PVA and haemoglobin, respectively. The 'cryogels' were evaluated for their water uptake potentials and influence of various factors such as chemical architecture of the spongy hydrogels, pH and temperature of the swelling bath were investigated on the degree of water sorption by the cryogels. The hydrogels were also swollen in salt solutions and various simulated biological fluids. The effect of drying temperature on its water sorption capacity was also studied. The biocompatibility of the prepared cryogels was judged by in vitro methods of blood-clot formation, percent haemolysis and protein (BSA) adsorption.

An in vitro release study of 5-fluoro-uracil (5-FU) from swellable poly-(2-hydroxyethyl methacrylate) (PHEMA) nanoparticles.

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. The use of nanoparticles as drug delivery vehicles for anticancer therapeutics has great potential to revolutionize the future of cancer therapy. The present paper concerns both the optimizations of anticancer drug loading and its release from polymeric nanoparticles. The major aim of this study was to design poly (HEMA) nanoparticles as swelling controlled drug release system for anticancer drug. The prepared nanoparticles were characterized by Infra-Red (IR) Spectra, Particle size Analysis, and Scanning Electron Microscopy (SEM). The nanoparticles were loaded with widely used anticancer drug, 5-Fluorouracil, and controlled release of drug was investigated to observe the effects of various parameters such as percent loading of the drug, chemical architecture of the nanocarriers, pH, temperature, and nature of release media on the release profiles. The chemical stability of 5-Fluorouracil (5-FU) was also tested in phosphate buffer saline (PBS) (pH = 7.4) and release was studied in various simulated biological fluids. The prepared nanoparticles could provide a possible pathway for controlled and targeted delivery of anticancer drug, thus causing lower side effects and higher efficacy.

Nano-silver hydroxyapatite based antibacterial 3D scaffolds of gelatin/alginate/poly (vinyl alcohol) for bone tissue engineering applications.

In the present study macroporous three dimensional spongy scaffolds composed of gelatin, alginate, and poly (vinyl alcohol) were prepared by cryogelation technique and silver hydroxyapatite was reinforced into the 3 D matrix. The polymer nanocomposite materials were characterized by analytical techniques such as Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and x-ray diffraction (XRD) analysis. The nanocomposite scaffolds were studied for their porous nature, water sorption capacity, and mechanical behavior. The suitability of scaffolds for bone tissue engineering applications was judged by evaluating their antibacterial and cytotoxic nature against gram positive and gram negative bacteria, and MC3T3-E1 preosteoblast cells, respectively. The scaffolds were also studied for release of silver ions and the influence of various experimental conditions on the release profiles of silver ions was investigated.

Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium.

This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, globally available formulations, considerations of benefit of treatment, monitoring of therapy, adverse events, and long-term outcome data. Additional sections review use in transgender individuals and other pediatric endocrine related conditions. Although there have been many significant changes in GnRHa usage, there is a definite paucity of evidence-based publications to support them. Therefore, this paper is explicitly not intended to evaluate what is recommended in terms of the best use of GnRHa, based on evidence and expert opinion, but rather to describe how these drugs are used, irrespective of any qualitative evaluation. Thus, this paper should be considered a narrative review on GnRHa utilization in precocious puberty and other clinical situations. These changes are reviewed not only to point out deficiencies in the literature but also to stimulate future studies and publications in this area.

Estrogens and growth.

Estrogen plays a key role in the regulation of growth in both genders, via its stimulation of the pubertal growth spurt and mediation of epiphyseal fusion. Mouse knockout models suggest a differential effect of oestrogen receptor (ER) alpha and beta on the growth plate, with ER beta possibly being more important in regulating epiphyseal fusion. Epiphyseal fusion may also depend on growth plate senescence, which is regulated by oestrogen. While molecular mechanisms for oestrogen's actions remain unclear, local production of oestrogen may be important for growth. Aromatase inhibitors appear to be effective in improving final height outcome in short stature, however long term safety data is lacking particularly in regards to reproductive function. Future studies are required to further understand the mechanisms by which ER alpha and ER beta affect growth plate function, while longer term studies of aromatase inhibitor usage, preferably utilising animal models, are required to verify the safety of these compounds.

Designing of silk and ZnO based antibacterial and noncytotoxic bionanocomposite films and study of their mechanical and UV absorption behavior.

Bionanocomposites of sericin and polyvinyl alcohol (PVA) were prepared by solution casting method and zinc oxide nanoparticles were impregnated within the polymer blend matrix through homogenous phase reaction between zinc chloride and sodium hydroxide at high temperature following an ex-situ co-precipitation method. The prepared bionanocomposites were characterized using Fourier Transform Infrared Spectroscopy, X-ray diffraction, Field Emission Scanning Electron Microscopy, Transmission Electron Microscopy and Atomic Force Microscopy techniques. The presence of characteristic groups of sericin and ZnO nanoparticles was ascertained by the FTIR spectra. XRD analysis confirmed the impregnation of ZnO nanoparticles and sericin within the PVA matrix. XRD and FESEM of the bionanocomposites provided information about their semicrystalline nature, crystallite size of the particles, and irregular rough surfaces. The TEM confirmed the size of ZnO particles to be in the nanometer range. AFM confirmed the platykurtic nature of the surface while the negative surface skewness shows the predominance of valleys over peaks suggesting for the planar nature of the surface of the bionanocomposites. UV absorption properties of bionanocomposite films were determined by UV absorption spectroscopy. UV absorption increased with increasing amount of ZnO nanoparticles in the nanocomposites. Sericin was found to absorb UV-C radiations between 200-290nm which is mainly due to aromatic amino acids like tryptophan, tyrosine and phenylalanine. The ZnO nanoparticles and sericin protein showed antimicrobial properties as evident from the inhibition zones obtained against Staphylococcus aureus and Escherichia coli. The bionanocomposite was found to be noncytotoxic which was proved by in vitro cytotoxicity test. Microhardness of bionanocomposite films increased with increase in the amount of ZnO nanoparticles in the sericin and PVA matrix.

Reverse indentation size effects in gamma irradiated blood compatible blend films of chitosan-poly (vinyl alcohol) for possible medical applications.

In the present work binary blends of polyvinyl alcohol (PVA) and chitosan (CS) were prepared by solution cast method and characterized by analytical methods like FTIR, XRD and SEM for seeking structural and morphological information. The blends were exposed to gamma radiation and evaluated for their improved mechanical strength. It was found that the tensile strength and microhardness increased after irradiation of CS-PVA films. Plastic effect due to absorption of water molecules and scissoring effect due to gamma irradiation were found to decrease the softness or increase the microhardness of the blends. Improved mechanical properties were attributed to intermolecular and intramolecular hydrogen bonds and adhesive nature of the blends also. The blends were also investigated for water intake behavior and in vitro blood compatibility property on the basis of certain in vitro tests like protein adsorption, haemolysis and blood clot formation on the un-irradiated and irradiated blend samples. The increased % swelling with time could be assigned to the fact that increasing water content facilitates the phase separation process within the blend which results in advancement in interstitial nano-void spaces which are occupied by water molecules. The blood compatibility results showed that when the amount of CS was varied from 0.5% to 2%, the amount of blood clot and percent haemolysis decreased while the protein adsorption increased with increasing CS content of the blend films.

Dissolution testing of marketed rifampicin containing fixed dose combination formulations using a new discriminative media: a post marketing retrospective study.

Currently recommended compendial dissolution methods for quality control of orally administered solid dosage forms of rifampicin containing formulations are not found to be able to forecast the in vivo performance. A recently proposed dissolution method of 0.01 N HCl at 50 rpm using paddle apparatus for screening was found to be more appropriate and able to predict the in vivo performance of those formulations. The objective of this investigation was to validate the new method of dissolution testing for solid dosage forms of rifampicin containing formulations using a basket apparatus and to compare it with the frequently recommended pharmacopeial method. In the present study the newly proposed dissolution condition (0.01 N HCl) was validated using six formulations of two, three and four drug combinations from two different manufacturers by basket method and compared with the widely recommended compendial medium. In this investigation, the appropriateness of the proposed methodology was confirmed by the dissolution results of the two FDC formulations (a two-drug and a four-drug combinations) that had previously passed the bioequivalence tests. It was found that the recommended dissolution medium of 0.01 N HCl can be used for screening of rifampicin containing formulations using both paddle and basket dissolution apparatus at 50 rpm and 100 rpm, respectively.

Genipin-modified gelatin nanocarriers as swelling controlled drug delivery system for in vitro release of cytarabine.

The aim of the present investigation was to design biocompatible gelatin nanoparticles, capable of releasing the cytarabine drug in a controllable way by regulating the extent of swelling of nanoparticles. In order to achieve the proposed objectives, gelatin (Type A, derived from acid cured tissue) was modified by crosslinking with genipin and nanoparticles of crosslinked gelatin were prepared using single water in oil (W/O) emulsion technique. The nanoparticles were characterized by techniques like FTIR, SEM, TEM, particles size analysis, and surface potential measurements. The nanoparticle chemical architecture was found to influence drug-releasing capacity. The influence of experimental conditions such as pH and simulated physiological fluids as the release medium was also investigated on the release profiles of cytarabine. It is possible to fabricate high-performance materials, by designing of controlled size gelatin nanoparticles with good biocompatible properties along with desired drug release profiles.

Sulfhydryl reactive phenylarsine oxide inhibits signal transduction in NK and LAK cells: effect on zeta-chain phosphorylation and phosphatidylinositol level.

The specific role of sulfhydryl groups in cell-mediated cytotoxicity (CMC) is still unknown. Here we demonstrate that natural killer cells and lymphokine-activated killer cells, when incubated with phenylarsine oxide (PAO), an organoarsenic compound showed a dose- and time-dependent inhibition of CMC and antibody-dependent cellular cytotoxicity (ADCC). PAO interacted directly with the effector cells (EC) without affecting the target cells (TC) or EC:TC conjugate formation. The loss of cytotoxicity was not due to lack of degranulation or to inhibition of serine esterases in PAO-treated cells. However, PAO inhibited the target-induced down regulation of phosphatidylinositol (PI) level in NK cells indicating that PAO blocked the cytolytic cascade at an early stage, upstream of PI. In addition, PAO also did not affect the disulfide link of the zeta-chain dimers, implicated in signal transduction in cytotoxic lymphocytes but did cause the rapid phosphorylation of the zeta chain. Finally, the effect of PAO on CMC was competitively blocked by dithiothreitol, a dithiol, but not by beta-mercaptoethanol, a mono-thiol. Taken together, these results indicate for the first time how sulfyhydryl groups may regulate CMC and ADCC.

Successful treatment of Acanthamoeba meningitis with combination oral antimicrobials.

Acanthamoeba was implicated as the causative agent of chronic meningitis in three apparently immunocompetent children. Diagnosis was established by cerebrospinal fluid wet mount examination and culture. Two children improved rapidly with combination oral therapy composed of trimethoprim-sulfamethoxazole, rifampin and ketoconazole.

Congenital adrenal hyperplasia presenting as hematuria and acute renal faliure.

We present a neonate who presented with hematuria and acute renal failure. Classical 21 hydroxylase deficiency was diagnosed on the basis of features of salt wasting, response to treatment with corticosteroids and mineralocorticoids and a positive ACTH stimulation test. Renal vein thrombosis secondary to hemoconcentration due to salt wasting was attributed as the cause of hematuria. Follow-up revealed clinical improvement and normalization of renal parameters. This is the first report of congenital adrenal hyperplasia presenting as hematuria and renal failure to the best of our knowledge.

Patent ductus arteriosus in preterm neonates.

Failure of the ductus arteriosus to close within 48-96 hours of postnatal age results in a left to right shunt across the ductus and overloading of the pulmonary circulation. This is more likely to happen in premature neonates with respiratory distress syndrome. Deterioration in the respiratory status on day 3-4 in a ventilated neonate and unexplained metabolic acidosis may be the earliest indicators of a patent ductus arteriosus (PDA). Indomethacin is the main stay of medical management of PDA in preterm neonates. Guidelines for administration of indomethacin have been described in the protocol. Restricted fluid therapy may be beneficial in the prevention of PDA in preterm neonates. Presence of PDA in a term neonate should be investigated to rule out an underlying congenital heart disease.

Hypocalcemic heart failure masquerading as dilated cardiomyopathy.

Hypocalcemia is a rare, but reversible, cause of congestive heart failure. We report a 4-month-old boy diagnosed as dilated cardiomyopathy who had prolonged QoTc with low blood levels of calcium, normal phosphate, elevated alkaline phosphatase and findings suggestive of rickets. In view of non response to calcium and vitamin D3, a possible diagnosis of VDDR I (Vitamin D-dependent rickets) was made and he was treated with calcium and calcitriol. The serum calcium levels normalised within 10 days, along with resolution of the signs and symptoms of heart failure, near normal left ventricular function and normalisation of QoTc. Pediatricians should be aware of the association of hypocalcemia with cardiac dysfunction and should keep it as a possible reversible cause of heart failure in children.