Reference range for glycated haemoglobin in full term non diabetic pregnant women: a multicentric cross sectional study.

BACKGROUND: There are no large studies to define the normal value of glycated haemoglobin (HbA1c) measured in full term pregnant women measured at the time of delivery. RESEARCH DESIGN AND METHODS: The study was conducted at three government hospitals in South India. Clinical data, maternal blood sample and foetal cord blood sample were collected from women admitted for safe confinement. Mean (± SD) of HbA1c in participants with no known diabetes (gestational or pregestational) or any complications (maternal or fetal) is described, 2.5th-97.5th centile reference range was derived. RESULTS: From 3 centres, 2004 women participated in the study. Data from 1039 participants who had no history of diabetes or any maternal or fetal complication were used to determine the reference range for HbA1c at term pregnancy. The mean HbA1c in subjects devoid of diabetes and its known complications was 5.0 (± 0.39) %. The reference range for normal HbA1c at term in these women was found to be 4.3-5.9%. Maternal HbA1c at term pregnancy in non-diabetic pregnant women is associated with pre-pregnancy BMI, maternal age and 2-h plasma glucose level of 2nd trimester oral glucose tolerance test (OGTT). CONCLUSIONS: The mean HbA1c at term pregnancy in non-diabetic women admitted for safe confinement is 5.00 (± 0.39) %. An HbA1c of 5.9% or more at term should be considered abnormal and women with such a value may be kept at a close surveillance for development of diabetes.

"Innocent" arytenoid adduction asymmetry: An etiological survey.

PURPOSE: To estimate the incidence of "innocent" arytenoid adduction asymmetry (AAA) among patients presenting at a laryngology clinic, identify its association with demographic characteristics, symptomatology and various clinical/pathological conditions and thereby determine its clinical significance. METHODS: A prospective comparative observational clinical study was conducted. Group 1 included patients presenting at the Department of Laryngology, identified with a primary diagnosis and coexisting "innocent" AAA i.e., an overriding arytenoid with normal vocal fold mobility on laryngoscopy. Group 2 included an equal number of randomly selected patients fulfilling the same criteria, without AAA. Demographic and clinical details were recorded and analyzed. RESULTS: 110 cases were included in each group. The incidence of innocent AAA was 12.7%. Males were predominant in both Groups, with the gender difference significant in Group 1. Patients in Group 1 were significantly younger than in Group 2. Professional voice users, namely singers, were significantly greater in Group 1. Symptoms associated with Group 1 (i.e. AAA) were high pitch strain while singing (p = 0.01) and unilateral throat pain (p = 0.01), and the associated diagnoses were Singing Voice Dysphonia (p = 0.005), Vocal Process Granuloma (p = 0.04) and Ventricular Band Dysphonia (p = 0.047). As a definitive diagnosis was made in all patients, the presenting complaints were not attributed to AAA. Right sided preponderance of AAA was significant. Among the diagnoses with a laterality (e.g. vocal process granuloma), AAA was observed contralateral to the pathology in 70.7% and ipsilaterally in 29.3% (p = 0.0058). CONCLUSION: Innocent AAA is common among males in the 3rd-4th decades, in singers among professional voice users, and in those with the muscle tension dysphonia spectrum and vocal process granuloma, thereby suggesting that it is an acquired habit/response to greater vocal demand. The observation of AAA contralateral to laryngeal lesions, highlights its compensatory nature, attempting to optimize glottic closure.

Lipid Profile in Indian Patients With Type 2 Diabetes: The Scope for Atherosclerotic Cardiovascular Disease Risk Reduction.

OBJECTIVE: Reduction of atherosclerotic cardiovascular disease (ASCVD) risk in patients with diabetes requires proper management of lipid parameters. This study aimed to find the pattern of dyslipidemia and scope of ASCVD risk reduction in patients with diabetes by lipid management. METHODS: Clinical, biochemical, and medication profiles of all patients with diabetes attending a tertiary diabetes care hospital over a 2-year period were collected. The prevalence of various lipid abnormalities was determined after excluding patients with thyroid dysfunction and those on lipid-lowering medications. Patients were stratified according to LDL cholesterol, HDL cholesterol, and triglyceride levels, and other clinical parameters were compared among the groups. The adequacy of statin treatment was assessed based on American Diabetes Association guidelines. RESULTS: Nine hundred and seventy-one patients were included. The prevalence of hyperlipidemia was 40.0%, of whom 14.6% were newly diagnosed. The most common lipid abnormality was elevated LDL cholesterol. Higher A1C and fasting blood glucose values were found to be associated with higher LDL cholesterol levels. Twenty-seven percent of patients with indications for treatment with statins were receiving them. Of those being treated with statins, 42.6% had an LDL cholesterol level ≥100 mg/dL. CONCLUSION: In South Indian patients with type 2 diabetes and fair glycemic control, high LDL cholesterol is the predominant lipid abnormality. There remains a huge potential for ASCVD risk reduction in this population if the knowledge practice gap is addressed.

Correction to: Antimicrobial Drugs Encapsulated in Fibrin Nanoparticles for Treating Microbial Infested Wounds.

In the original manuscript, the Figure 2 a-i is inadvertently repeated as Figure 2 a-ii. This mistake has been rectified and the corrected Figure 2 is presented below.

Interdisciplinary Telemedicine in the Management of Dysphagia in Head and Neck.

The study considered the feasibility and impact of interdisciplinary telemedicine discussions in the management of post-treatment dysphagia in patients with head and neck tumors. This is a retrospective analysis of patients with persistent dysphagia after treatment for head and neck pathology, at an institute in India. The cases were discussed in the telemedicine meeting conducted between host institute and a second unit in the United States. A monthly meeting was organized, using an internet-based video conference system. The ongoing swallowing problems and management were presented, and through discussions, a plan for further management was formulated and carried out. The Functional Oral Intake Scale (FOIS) was measured before and after the implementation of the plan. Twenty-six patients were discussed, out of which, 22 were head and neck malignancies. The recommendations concurred with that of the host unit in 18, differed for three and additive in five patients. The pre-treatment mean FOIS was 1.46 with a standard deviation of 0.989 and post-treatment mean improved to 3.92 with a standard deviation of 1.809 (p < 0.0001). The present study supports the success of an interdisciplinary telemedicine meeting to manage difficult cases of dysphagia in head and neck. The outcome in terms of the FOIS score improved significantly after implementing them. In addition to the direct patient benefits, the meeting helped to facilitate interdepartmental collaboration between two units treating similar sets of patients across the globe, in specialized clinical areas like dysphagia management.

CD28 Promotes Plasma Cell Survival, Sustained Antibody Responses, and BLIMP-1 Upregulation through Its Distal PYAP Proline Motif.

In health, long-lived plasma cells (LLPC) are essential for durable protective humoral immunity, and, conversely, in disease are a major source of pathogenic Abs in autoimmunity, graft rejection, and allergy. However, the molecular basis for their longevity is largely unknown. We have recently found that CD28 signaling in plasma cells (PC) is essential for sustaining Ab titers, by supporting the survival of LLPC, but not short-lived PC (SLPC). We now find that, unlike SLPC, CD28 activation in LLPC induces prosurvival downstream Vav signaling. Knockin mice with CD28 cytoplasmic tail mutations that abrogate Vav signaling (CD28-AYAA) had significantly fewer LLPC but unaffected SLPC numbers, whereas mice with mutations that abrogate PI3K signaling (CD28-Y170F) were indistinguishable from wild-type controls. This was consistent with the loss of CD28's prosurvival effect in LLPC from CD28-AYAA, but not CD28-Y170F, mice. Furthermore, the CD28 Vav motif in the B lineage was essential for the long-term maintenance of Ag-specific LLPC populations and Ab titers in vivo. Signaling downstream of the CD28 Vav motif induced previously undescribed transcriptional regulation of B lymphocyte-induced maturation protein-1, a key mediator of PC differentiation and maintenance. These findings suggest CD28 signaling in LLPC modulates the central B lymphocyte-induced maturation protein-1 transcriptional nexus involved in long-term survival and function.

Isolation and characterization of pathogenic Vibrio alginolyticus from sea cage cultured cobia (Rachycentron canadum (Linnaeus 1766)) in India.

Mass mortalities of cobia, Rachycentron canadum, sub-adults occurred during August 2013 in cage culture in the Gulf of Mannar, Mandapam Tamil Nadu, India. The epizootic of disease was started with typical classical clinical signs followed by acute mortality. Grossly, severe haemorrhage and congestion were observed in the gastric mucosa. The abdomen was distended with peritoneal fluid. The heart revealed haemopericardium and fibrinous pericardium. Histologically, the gastric mucosa showed severe erosion and necrosis. Haemorrhagic pericarditis and an increased size of the melano macrophage centre (MMC) in the tail kidney were other histopathological changes. Vibrio sp. was isolated from the gastric lesions and heart blood swab of moribund fishes and it was found to be virulent to the cobia fingerlings. After the challenge, the same bacterium could be re-isolated from moribund fingerlings. The 16S ribosomal RNA of the isolate was amplified and blast analysis of the sequence confirmed that the pathogen was Vibrio alginolyticus. The confirmation was also correlated with its cultural, biochemical and pathomorphological changes. This is the second report and the first incidence of epizootics with severe pathological lesions in cultured cobia in India. The study throws light on the pathology of vibriosis. By practising cage farm management measures, occurrences of infection may be prevented. SIGNIFICANCE AND IMPACT OF THE STUDY: The epizootics of vibriosis caused serious economic losses to farmers. Natural blooms of the pathogen can be prevented by sea cage management measures such as, changing the inner net of the cages, changing the location of the cages to relatively clean water (about 50 m apart) from the affected site and providing shade over the cages while the water temperature rises. Supplementation of the feed with immunostimulants and mineral mixture may be practised to improve the immune response against infection. Early diagnosis and sea cage management measures may prevent occurrences of the infection.

CD28-mediated pro-survival signaling induces chemotherapeutic resistance in multiple myeloma.

Chemotherapeutic resistance remains a significant hurdle in the treatment of multiple myeloma (MM) and is significantly mediated by interactions between MM cells and stromal cells of the bone marrow microenvironment. Despite the importance of these interactions, the specific molecules and downstream signaling components involved remain incompletely understood. We have previously shown that the prototypic T-cell costimulatory receptor CD28, which is also expressed on MM cells, is a key mediator of MM survival and apoptotic resistance. Crosslinking CD28 by agonistic antibodies or myeloid dendritic cells (DC; these express the CD28 ligands CD80/CD86) prevents apoptosis caused by chemotherapy or serum withdrawal. We now report that CD28 pro-survival signaling is dependent upon downstream activation of phosphatidyl-inositol 3-kinase/Akt, inactivation of the transcription factor FoxO3a, and decreased expression of the pro-apoptotic molecule Bim. Conversely, blocking the CD28-CD80/CD86 interaction between MM cells and DC in vitro abrogates the DC's ability to protect MM cells against chemotherapy-induced death. Consistent with these observations, in vivo blockade of CD28-CD80/CD86 in the Vk*MYC murine myeloma model sensitizes MM cells to chemotherapy and significantly reduces tumor burden. Taken together, our findings suggest that CD28 is an important mediator of MM survival during stress and can be targeted to overcome chemotherapy resistance.

Utility of Gallium-68 DOTANOC PET/CT in the localization of Tumour-induced osteomalacia.

BACKGROUND: Tumour-induced osteomalacia (TIO) is a rare disorder characterized by hypophosphataemic osteomalacia caused by small mesenchymal tumours secreting fibroblast growth factor 23 (FGF 23). The most difficult part in the management of these patients is the localization of tumours causing TIO. OBJECTIVE: We describe the utility of Gallium (Ga)-68 DOTANOC PET/CT in the localization of tumours causing TIO. PATIENTS AND METHODS: The study was conducted in a single tertiary referral university teaching hospital in India. Ten patients with TIO who underwent Ga-68 DOTANOC PET/CT from the time period 2009 to 2014 were included in this study. Their detailed clinical history, biochemical parameters, imaging modalities, surgical interventions, histopathology and outcomes were reviewed. RESULTS: Ga-68 DOTANOC PET/CT could correctly localize the tumours in TIO in 9 of the 10 cases in which it was performed. Complete resection of the tumour led to full clinical recovery in six of the ten patients; two patients who had partial resection and one patient who underwent radiofrequency ablation showed partial remission. One patient in whom Ga-68 DOTANOC PET/CT was positive in vertebral body with a low standardized uptake value (SUV) did not show up the tumour on surgery. CONCLUSIONS: We conclude that Ga-68 DOTANOC PET/CT can be used as the first imaging modality in patients diagnosed with TIO. The extremely good outcome following the resection of these small otherwise undiagnosed tumours far outweighs its cost even in resource limited settings.

Novel regulation of CD80/CD86-induced phosphatidylinositol 3-kinase signaling by NOTCH1 protein in interleukin-6 and indoleamine 2,3-dioxygenase production by dendritic cells.

Dendritic cells (DC) play a critical role in modulating antigen-specific immune responses elicited by T cells via engagement of the prototypic T cell costimulatory receptor CD28 by the cognate ligands CD80/CD86, expressed on DC. Although CD28 signaling in T cell activation has been well characterized, it has only recently been shown that CD80/CD86, which have no demonstrated binding domains for signaling proteins in their cytoplasmic tails, nonetheless also transduce signals to the DC. Functionally, CD80/CD86 engagement results in DC production of the pro-inflammatory cytokine IL-6, which is necessary for full T cell activation. However, ligation of CD80/CD86 by CTLA4 also induces DC production of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), which depletes local pools of the essential amino acid tryptophan, resulting in blockade of T cell activation. Despite the significant role of CD80/CD86 in immunological processes and the seemingly opposing roles they play by producing IL-6 and IDO upon their activation, how CD80/CD86 signal remains poorly understood. We have now found that cross-linking CD80/CD86 in human DC activates the PI3K/AKT pathway. This results in phosphorylation/inactivation of its downstream target, FOXO3A, and alleviates FOXO3A-mediated suppression of IL-6 expression. A second event downstream of AKT phosphorylation is activation of the canonical NF-κB pathway, which induces IL-6 expression. In addition to these downstream pathways, we unexpectedly found that CD80/CD86-induced PI3K signaling is regulated by previously unrecognized cross-talk with NOTCH1 signaling. This cross-talk is facilitated by NOTCH-mediated up-regulation of the expression of prolyl isomerase PIN1, which in turn increases enzyme activity of casein kinase II. Subsequently, phosphatase and tensin homolog (which suppresses PI3K activity) is inactivated via phosphorylation by casein kinase II. This results in full activation of PI3K signaling upon cross-linking CD80/CD86. Similar to IL-6, we have found that CD80/CD86-induced IDO production by DC at late time points is also dependent upon the PI3K → AKT → NF-κB pathway and requires cross-talk with NOTCH signaling. These data further suggest that the same signaling pathways downstream of DC CD80/CD86 cross-linking induce early IL-6 production to enhance T cell activation, followed by later IDO production to self-limit this activation. In addition to characterizing the pathways downstream of CD80/CD86 in IL-6 and IDO production, identification of a novel cross-talk between NOTCH1 and PI3K signaling may provide new insights in other biological processes where PI3K signaling plays a major role.

Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment.

BACKGROUND: Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model. METHODS: CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC. RESULTS: The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU. CONCLUSIONS: To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo. GENERAL SIGNIFICANCE: The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases.

Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal management.

BACKGROUND: The objective of this study was to fabricate, characterize and evaluate in vitro, an injectable calcium sulfate bone cement beads loaded with an antibiotic nanoformulation, capable of delivering antibiotic locally for the treatment of periodontal disease. METHODS: Tetracycline nanoparticles (Tet NPs) were prepared using an ionic gelation method and characterized using DLS, SEM, and FTIR to determine size, morphology, stability and chemical interaction of the drug with the polymer. Further, calcium sulfate (CaSO4) control and CaSO4-Tet NP composite beads were prepared and characterized using SEM, FTIR and XRD. The drug release pattern, material properties and antibacterial activity were evaluated. In addition, protein adsorption, cytocompatibility and alkaline phosphatase activity of the CaSO4-Tet NP composite beads in comparison to the CaSO4 control were analyzed. RESULTS: Tet NPs showed a size range of 130±20nm and the entrapment efficiency calculated was 89%. The composite beads showed sustained drug release pattern. Further the drug release data was fitted into various kinetic models wherein the Higuchi model showed higher correlation value (R(2)=0.9279) as compared to other kinetic models. The composite beads showed antibacterial activity against Staphylococcus aureus and Escherichia coli. The presence of Tet NPs in the composite bead didn't alter its cytocompatibility. In addition, the composite beads enhanced the ALP activity of hPDL cells. CONCLUSIONS: The antibacterial and cytocompatible CaSO4-Tet NP composite beads could be beneficial in periodontal management to reduce the bacterial load at the infection site. GENERAL SIGNIFICANCE: Tet NPs would deliver antibiotic locally at the infection site and the calcium sulfate cement, would itself facilitate tissue regeneration.

Urinary levels of endocrine-disrupting chemicals, including bisphenols, bisphenol A diglycidyl ethers, benzophenones, parabens, and triclosan in obese and non-obese Indian children.

Obesity has been recognized as a major global public health concern. In particular, childhood obesity is a major risk factor for other health issues, such as type 2 diabetes, in later stages of life. A few earlier studies have associated exposure to endocrine-disrupting chemicals (EDCs) with childhood obesity. There is limited information, however, on exposure to EDCs and childhood obesity in India. In this study, urinary levels of 26 EDCs were determined in 49 obese and 27 non-obese Indian children. Eleven EDCs, including 2,2-bis(4-hydroxyphenyl)propane (BPA), 4,4'-sulfonyldiphenol (BPS), methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), 4-hydroxybenzoic acid (4-HB), 3,4-dihydroxybenzoic acid (3,4-DHB), triclosan (TCS), benzophenone-3 (BP3), bisphenol A diglycidyl ether (BADGE), and bisphenol A bis(2,3-dihydroxypropyl) glycidyl ether (BADGE·2H2O) were found in >70% of urine samples. No significant associations were found between childhood obesity and most target chemicals studied, except for 3,4-DHB, which showed a significant positive association. Urinary concentrations of 3,4-DHB were higher in obese children than in non-obese children, independent of age, sex, family income, parent education, physical activity, and urinary creatinine. Urinary concentrations of several EDCs were higher in Indian children than the concentrations reported for children in the USA and China. To our knowledge, this is the first study to report urinary concentrations of several EDCs in Indian children.

Optimization, equilibrium, kinetic, thermodynamic and desorption studies on the sorption of Cu(II) from an aqueous solution using marine green algae: Halimeda gracilis.

The aptitude of marine green algae Helimeda gracilis for sorption of Cu(II) ions from an aqueous solution was studied in batch experiments. The effect of relevant parameters such as function of pH, sorbent dosage, agitation speed and contact time was evaluated by using Response surface methodology (RSM). A maximum percentage removal of Cu (II) by Halimeda gracilis occurs at pH-4.49, sorbent dosage-1.98g/L, agitation speed-119.43rpm and contact time-60.21min. Further, the sorbent was characterized by using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning electron microscope (SEM) analysis. Experimental data were analyzed in terms of pseudo-first order, pseudo-second order, intraparticle diffusion, power function and elovich kinetic models. The results showed that the sorption process of Cu(II) ions followed well pseudo-second order kinetics. The sorption data of Cu(II) ions at 308.15K are fitted to Langmuir, Freundlich, Dubinin-Radushkevich (D-R), Temkin, Sips and Toth isotherms. Sorption of Cu(II) onto marine green algae Helimeda gracilis followed the Langmuir and Toth isotherm models (R(2)=0.998 and R(2)=0.999) with the maximum sorption capacity of 38.46 and 38.07mg/g. The calculated thermodynamic parameters such as ΔG°, ΔH° and ΔS° showed that the sorption of Cu(II) ions onto Helimeda gracilis biomass was feasible, spontaneous and endothermic. Desorption study shows that the sorbent could be regenerated using 0.2M HCl solution, with up to 89% recovery.

KLF9 is a novel transcriptional regulator of bortezomib- and LBH589-induced apoptosis in multiple myeloma cells.

Bortezomib, a therapeutic agent for multiple myeloma (MM) and mantle cell lymphoma, suppresses proteosomal degradation leading to substantial changes in cellular transcriptional programs and ultimately resulting in apoptosis. Transcriptional regulators required for bortezomib-induced apoptosis in MM cells are largely unknown. Using gene expression profiling, we identified 36 transcription factors that displayed altered expression in MM cells treated with bortezomib. Analysis of a publically available database identified Kruppel-like family factor 9 (KLF9) as the only transcription factor with significantly higher basal expression in MM cells from patients who responded to bortezomib compared with nonresponders. We demonstrated that KLF9 in cultured MM cells was up-regulated by bortezomib; however, it was not through the induction of endoplasmic reticulum stress. Instead, KLF9 levels correlated with bortezomib-dependent inhibition of histone deacetylases (HDAC) and were increased by the HDAC inhibitor LBH589 (panobinostat). Furthermore, bortezomib induced binding of endogenous KLF9 to the promoter of the proapoptotic gene NOXA. Importantly, KLF9 knockdown impaired NOXA up-regulation and apoptosis caused by bortezomib, LBH589, or a combination of theses drugs, whereas KLF9 overexpression induced apoptosis that was partially NOXA-dependent. Our data identify KLF9 as a novel and potentially clinically relevant transcriptional regulator of drug-induced apoptosis in MM cells.

In vitro and in vivo biological evaluation of O-carboxymethyl chitosan encapsulated metformin nanoparticles for pancreatic cancer therapy.

PURPOSE: In vitro anticancer effect and in vivo biodistribution and biocompatibility of metformin encapsulated O-Carboxymethyl chitosan nanoparticles were evaluated for its application as pancreatic cancer therapy. METHODS: In vitro studies such as cell migration assay, clonogenic assay, cell cycle analysis and qRT-PCR analysis were done in pancreatic cancer cells (MiaPaCa-2) treated with O-CMC-metformin NPs for evaluating its anticancer potential. In vivo biodistribution studies were carried out by NIR imaging of O-CMC-metformin NPs after tagging it with ICG. In vivo biocompatibility of the NPs was assessed by histopathology analysis of organs from mice administered with the NPs. RESULTS: In vitro cell migration assay showed marginal effect of NPs on migration property of pancreatic cancer cells (MiaPaCa-2). In vitro clonogenic assay established that the O-CMC-metformin NPs reduced colony formation ability of the cancer cells. While cell cycle analysis showed that the O-CMC-metformin NPs had only minor effect on progression of cell cycle in the cancer cells. qRT-PCR analysis exhibited reduced mRNA expression of p21, vanin 1 and MMP9 in pancreatic cancer cells treated with the nanoparticles. In vivo NIR imaging study showed normal biodistribution pattern of the intravenously injected O-CMC-metformin NPs suggesting normal clearance rate of nanoparticles and no adverse toxicity to the organs. CONCLUSIONS: The biocompatible O-CMC-metformin NPs with anticancer potential and capability for normal biodistribution can be beneficial for the treatment of pancreatic cancer.

Antimicrobial drugs encapsulated in fibrin nanoparticles for treating microbial infested wounds.

PURPOSE: In vitro evaluation of antibacterial and antifungal drugs encapsulated fibrin nanoparticles to prove their potential prospect of using these nanocomponent for effective treatment of microbial infested wounds. METHODS: Surfactant-free oil-in-water emulsification-diffusion method was adopted to encapsulate 1 mg/ml each of antimicrobial drugs (Ciprofloxacin and Fluconazole) in 4 ml of aqueous fibrinogen suspension and subsequent thrombin mediated cross linking to synthesize drug loaded fibrin nanoparticles. RESULTS: Ciprofloxacin loaded fibrin nanoparticles (CFNPs) showed size range of 253 ± 6 nm whereas that of Fluconazole loaded fibrin nanoparticles (FFNPs) was 260 ± 10 nm. Physico chemical characterizations revealed the firm integration of antimicrobial drugs within fibrin nanoparticles. Drug release studies performed at physiological pH 7.4 showed a release of 16% ciprofloxacin and 8% of fluconazole while as the release of ciprofloxacin at alkaline pH 8.5, was 48% and that of fluconazole was 37%. The antimicrobial activity evaluations of both drug loaded systems independently showed good antibacterial activity against Escherichia coli (E.coli), Staphylococcus aureus (S. aureus) and antifungal activity against Candida albicans (C. albicans). The in vitro toxicity of the prepared drug loaded nanoparticles were further analyzed using Human dermal fibroblast cells (HDF) and showed adequate cell viability. CONCLUSION: The efficacies of both CFNPs and FFNPs for sustained delivery of encapsulated anti microbial drugs were evaluated in vitro suggesting its potential use for treating microbial infested wounds (diabetic foot ulcer).

Carbohydrate-based nanogels as drug and gene delivery systems.

Nanogels are hydrogels with nanometer-scale three-dimensional networks of physically or chemically cross-linked chains. Nanogels have attracted much interest in recent years for various biomedical applications such as drug delivery systems and bioimaging owing to their specific properties of size tunability and intrinsic hydrophilic surfaces. Nanogels are generally classified either as natural polymer-based or synthetic polymer-based nanogels. Natural polymer-based nanogels are considered better candidates for drug delivery than synthetic polymer-based nanogels. This review summarizes the role of natural polymer-based nanogels, especially carbohydrate-based nanogels as drug and gene delivery systems.