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1.
J Org Chem ; 88(24): 17472-17478, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38014421

ABSTRACT

A novel and highly selective 5-enolexo-exo-trig aldol condensation of 6-ketoaldehydes is presented using a proline-based alkylphosphonium ion catalyst. Bulky and oxophilic phosphonium ion plays a vital role in facilitating kinetic aldenamine formation and activating keto groups for aldol addition. This innovative approach exclusively targets five-membered carbo- and heterocyclic aldehydes, involving unusual aldehydes as donors and ketones as acceptors. Especially, enolizable aryl keto aldehydes and heteroatom-embedded ketoaldehydes exclusively produced cyclized products with our new catalyst, while other catalysts provided predominantly self-aldol or decomposed products. The scope and diversity of the method demonstrated by synthesizing different carboxaldehydes, including cyclopentene, indene, dihydrofuran, benzofuran, dihydropyrrole, indole, thiofuran, dihydrothiofuran, and benzothiofurans.

2.
J Pharm Bioallied Sci ; 15(Suppl 2): S1335-S1337, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37693969

ABSTRACT

Cleidocranial dysplasia (CCD) is a rare hereditary disease of unknown etiology which was previously known as cleidocranial dysostosis. It usually follows an autosomal dominant mode of transmission with no predilection of genre or ethnic group. It is caused by a mutation of RUNX2, characterized by generalized dysplasia of the bones and teeth. Affected individuals have short stature, atypical facial features, and skeletal anomalies affecting mainly the skull and clavicle. The dental manifestations are mainly delayed exfoliation of the primary teeth and delayed eruption of the permanent teeth, with multiple impacted supernumeraries, and the absence of cellular cementum. The frequency of this disorder is 1 per million individuals. Here we report a rare case of CCD in a 23 year old female patient having most of the characteristic features of this syndrome.

3.
J Fluoresc ; 2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37721707

ABSTRACT

Natural drug functionalised silver (Ag) nanoparticles (NPs) have gained significant interest in pharmacology related applications due to their therapeutic efficiency. We have synthesised silver nanoparticle using hesperetin as a reducing and capping agent. This work aims to discuss the relevance of the hesperetin functionalised silver nanoparticles (H-AgNPs) in the field of nano-medicine. The article primarily investigates the anticancer activity of H-AgNPs and then their interactions with calf thymus DNA (ctDNA) through spectroscopic and thermodynamic techniques. The green synthesised H-AgNPs are stable, spherical in shape and size of 10 ± 3 nm average diameter. The complex formation of H-AgNPs with ctDNA was established by UV-Visible absorption, fluorescent dye displacement assay, isothermal calorimetry and viscosity measurements. The binding constants obtained from these experiments were consistently in the order of 104 Mol-1. The melting temperature analysis and FTIR measurements confirmed that the structural alterations of ctDNA by the presence of H-AgNPs are minimal. All the thermodynamic variables and the endothermic binding nature were acquired from ITC experiments. All these experimental outcomes reveal the formation of H-AgNPs-ctDNA complex, and the results consistently verify the minor groove binding mode of H-AgNPs. The binding constant and limit of detection of 1.8 µM found from the interaction studies imply the DNA detection efficiency of H-AgNPs. The cytotoxicity of H-AgNPs against A549 and L929 cell lines were determined by in vitro MTT cell viability assay and lactate dehydrogenase (LDH) assay. The cell viability and LDH enzyme release are confirmed that the H-AgNPs has high anticancer activity. Moreover, the calculated LD50 value for H-AgNPs against lung cancer cells is 118.49 µl/ml, which is a low value comparing with the value for fibroblast cells (269.35 µl/ml). In short, the results of in vitro cytotoxicity assays revealed that the synthesised nanoparticles can be considered in applications related to cancer treatments. Also, we have found that, H-AgNPs is a minor groove binder, and having high DNA detection efficiency.

4.
Sci Rep ; 13(1): 9045, 2023 06 03.
Article in English | MEDLINE | ID: mdl-37270606

ABSTRACT

The influence of nanoparticles inside the human body and their interactions with biological macromolecules need to be explored/studied prior to specific applications. The objective of this study is to find the potential of camptothecin functionalised silver nanoparticles (CMT-AgNPs) in biomedical applications. This article primarily investigates the binding stratagem of CMT-AgNPs with calf thymus DNA (ctDNA) through a series of spectroscopic and calorimetric methods and then analyses the anticancer activity and cytotoxicity of CMT-AgNPs. The nanoparticles were synthesized using a simple one pot method and characterized using UV-Visible, fourier transform infrared (FTIR) spectroscopy, X-ray diffraction and high-resolution transmission electron microscopy (HRTEM). The average size of CMT-AgNPs is 10 ± 2 nm. A group of experimental techniques such as UV-Visible spectrophotometry, fluorescence dye displacement assay, circular dichroism (CD) and viscosity analysis unravelled the typical groove binding mode of CMT-AgNPs with ctDNA. The CD measurement evidenced the minor conformational alterations of double helical structure of ctDNA in the presence of CMT-AgNPs. The information deduced from the isothermal titration calorimetry (ITC) experiment is that the binding was exothermic and spontaneous in nature. Moreover, all the thermodynamic binding parameters were extracted from the ITC data. The binding constants obtained from UV absorption experiments, fluorescence dye displacement studies and ITC were consistently in the order of 104 Mol-1. All these results validated the formation of CMT-AgNPs-ctDNA complex and the results unambiguously confirm the typical groove binding mode of CMT-AgNPs. An exhaustive in vitro MTT assay by CMT-AgNPs and CMT against A549, HT29, HeLa and L929 cell lines revealed the capability of CMT-AgNPs as a potential anticancer agent.


Subject(s)
Lung Neoplasms , Metal Nanoparticles , Humans , Camptothecin/pharmacology , Silver/pharmacology , Silver/chemistry , Metal Nanoparticles/chemistry , Circular Dichroism , Spectroscopy, Fourier Transform Infrared , Calorimetry , DNA/metabolism , Lung Neoplasms/drug therapy , Plant Extracts/chemistry , Anti-Bacterial Agents/chemistry
5.
Am J Prev Med ; 64(2): 270-274, 2023 02.
Article in English | MEDLINE | ID: mdl-36123230

ABSTRACT

INTRODUCTION: A booster dose of messenger RNA vaccine protects against severe COVID-19 outcomes. This study examined the incidence of COVID-19 booster vaccination among active-duty U.S. military servicemembers between August 2021 and January 2022, factors associated with vaccination uptake, and trends over time. METHODS: This was a retrospective cohort study of active-duty military personnel using data from the Defense Medical Surveillance System. Participants were included if they served in the active component from August 2021 through January 2022 and were eligible to receive a COVID-19 booster dose by January 2022. Adjusted hazard ratio estimates of time to booster vaccination were calculated using Cox proportional hazards regression. RESULTS: Lower booster vaccine uptake was seen in the U.S. military (25%) than among the general U.S. population at the same time (45%). Booster vaccination increased with older age, with greater education, with higher income, among women, and among those stationed overseas; it decreased with previous COVID-19 infection and use of the Janssen vaccine. There were no significant racial or ethnic disparities in booster vaccination. CONCLUSIONS: In the absence of a compulsory vaccination policy, lower booster vaccine uptake was seen among servicemembers than among the general U.S. population, particularly among members who were younger, were male, Marines, and had a previous history of infection. Low vaccination rates not only increase the risk of acute and long-term health effects from COVID-19 among servicemembers, but they also degrade the overall readiness of the U.S. military.


Subject(s)
COVID-19 , Military Personnel , Humans , Female , Male , Retrospective Studies , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination , Educational Status
6.
Sci Rep ; 12(1): 8275, 2022 05 18.
Article in English | MEDLINE | ID: mdl-35585158

ABSTRACT

Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib. Resistance mechanisms mainly involve secondary mutations in the KIT receptor tyrosine kinase gene indicating continued dependency on the KIT signaling pathway. The fact that the type of secondary mutation confers either sensitivity or resistance towards TKIs and the notion that secondary mutations exhibit intra- and intertumoral heterogeneity complicates the optimal choice of treatment in the imatinib-resistant setting. Therefore, new strategies that target KIT independently of its underlying mutations are urgently needed. Homoharringtonine (HHT) is a first-in-class inhibitor of protein biosynthesis and is FDA-approved for the treatment of chronic myeloid leukemia (CML) that is resistant to at least two TKIs. HHT has also shown activity in KIT-mutant mastocytosis models, which are intrinsically resistant to imatinib and most other TKIs. We hypothesized that HHT could be effective in GIST through downregulation of KIT expression and subsequent decrease of KIT activation and downstream signaling. Testing several GIST cell line models, HHT led to a significant reduction in nascent protein synthesis and was highly effective in the nanomolar range in IM-sensitive and IM-resistant GIST cell lines. HHT treatment resulted in a rapid and complete abolishment of KIT expression and activation, while KIT mRNA levels were minimally affected. The response to HHT involved induction of apoptosis as well as cell cycle arrest. The antitumor activity of HHT was confirmed in a GIST xenograft model. Taken together, inhibition of protein biosynthesis is a promising strategy to overcome TKI resistance in GIST.


Subject(s)
Antineoplastic Agents , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Drug Resistance, Neoplasm/genetics , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Homoharringtonine/pharmacology , Humans , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Mutation , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-kit/metabolism
7.
Neurosurg Focus ; 52(2): E3, 2022 02.
Article in English | MEDLINE | ID: mdl-35104792

ABSTRACT

OBJECTIVE: Isocitrate dehydrogenase (IDH) mutations are found in more than 80% of low-grade gliomas and in the majority of secondary glioblastomas. IDH mutation (IDHmut) leads to aberrant production of an oncogenic metabolite that promotes epigenetic dysregulation by inducing hypermethylation to suppress transcription of various tumor suppressor genes. Hypermethylation in IDHmut gliomas leads to transcriptional repression of NKG2D ligands, especially UL16-binding protein (ULBP)-1 and ULBP-3, and subsequent evasion of natural killer (NK) cell-mediated lysis. The demethylating agent 5-aza-2'deoxycytodine (decitabine [DAC]) is a DNA methyltransferase 1 inhibitor that prevents hypermethylation and is capable of restoring NKG2D ligand expression in IDHmut gliomas to resensitize them to NK cells. Given its capacity for sustained epigenetic reprogramming, the authors hypothesized that DCA would be an effective immunotherapeutic agent in treating IDHmut gliomas in an NK cell-dependent manner by upregulating epigenetically repressed activating NKG2D ligands in IDHmut tumors. In this study, the authors sought to use a glioma stem cell, preclinical animal model to determine the efficacy of DAC in IDHmut and IDH wild-type (IDHwt) tumors, and to characterize whether the activity of DAC in gliomas is dependent on NK cell function. METHODS: Xenograft models of IDHwt and IDHmut gliomas were established in athymic-nude mice. When tumors were grossly visible and palpable, mice were treated with either DCA or dimethylsulfoxide intraperitoneally every 7 days. Tumor sizes were measured every 2 to 3 days. After the animals were euthanized, xenografts were harvested and analyzed for the following: tumor expression of NKG2D ligands, tumor susceptibility to human and murine NK cells, immunohistochemistry for NK infiltration, and tumor-infiltrating lymphocyte characterization. RESULTS: DAC significantly inhibited the growth of IDHmut xenografts in the athymic nude mice. This effect was abrogated with NK cell depletion. Ex vivo analysis of tumor cells from harvested xenografts confirmed that DAC increased NKG2D ligand ULBP-1 and ULBP-3 expressions, and enhanced susceptibility to lysis of both human and murine IDHmut glial cells with corresponding NK cells. Immunohistochemical analysis of the xenografts indicated that DCA-treated IDHmut gliomas had a greater level of NK infiltration into the tumor compared with the negative control. Finally, DCA radically altered the tumor-infiltrating lymphocyte landscape of IDHmut glioma xenografts by increasing NK cells, dendritic cells, and M1 macrophages, while decreasing suppressive monocyte infiltration. CONCLUSIONS: DCA displayed novel immunotherapeutic functions in IDHmut gliomas. This effect was critically dependent on NK cells. Additionally, DCA significantly altered the tumor immune landscape in IDHmut gliomas from suppressive to proinflammatory.


Subject(s)
Brain Neoplasms , Glioma , Animals , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Decitabine , Glioma/drug therapy , Glioma/genetics , Humans , Immunotherapy , Isocitrate Dehydrogenase/genetics , Killer Cells, Natural/metabolism , Killer Cells, Natural/pathology , Mice , Mice, Nude
8.
Oncotarget ; 13: 426-438, 2022.
Article in English | MEDLINE | ID: mdl-35198102

ABSTRACT

Suppressive effects of extracellular matrix (ECM) upon various cancers have been reported. Glioblastoma multiforme has poor prognosis and new therapies are desired. This work investigated the effects of a saline-soluble fraction of urinary bladder ECM (ECM-SF) upon glioma cells. Viability at 24 hours in 1, 5, or 10 mg/mL ECM-SF-spiked media was evaluated in primary glioma cells (0319, 1015, 1119), glioma cell lines (A172, T98G, U87MG, C6), and brain cell lines (HCN-2, HMC3). Viability universally decreased at 5 and 10 mg/mL with U87MG, HCN-2, and HCM3 being least sensitive. Apoptosis in 0319 and 1119 cells was confirmed via NucView 488. Bi-weekly intravenous injection of ECM-SF (120 mg/kg) for 10 weeks in Sprague-Dawley rats did not affect weight, temperature, complete blood count, or multi-organ histology (N = 5). Intratumoral injection of ECM-SF (10 uL of 30 mg/mL) at weeks 2-4 post C6 inoculation in Wistar rats increased median survival from 24.5 to 51 days (hazard ratio for death 0.22) and decreased average tumor volume at time of death from 349 mm3 to 90 mm3 over 10 weeks (N = 6). Mass spectrometry identified 2,562 protein species in ECM-SF, parent ECM, and originating tissue. These results demonstrate the suppressive effects of ECM on glioma and warrant further study.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Animals , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Survival , Extracellular Matrix/metabolism , Glioblastoma/pathology , Glioma/pathology , Rats , Rats, Sprague-Dawley , Rats, Wistar
9.
Cleft Palate Craniofac J ; 59(9): 1097-1106, 2022 09.
Article in English | MEDLINE | ID: mdl-34402312

ABSTRACT

OBJECTIVE: The Furlow palatoplasty is a proven procedure in the management of secondary velopharyngeal dysfunction in patients with cleft palate. But the selection of cases, the degree of clinical success, and the preoperative predictors of the same are less established. This study is an effort to retrospectively look at outcomes, in a large series of velopharyngeal dysfunction cases treated with the Furlow palatoplasty alone. DESIGN: Retrospective analysis of preoperative and postoperative speech and videofluoroscopic data. SETTING: Tertiary care center. PATIENTS/PARTICIPANTS: Ninety-two patients who were diagnosed with velopharyngeal dysfunction post primary cleft palate repair. INTERVENTIONS: Furlow palatoplasty for velopharyngeal dysfunction post primary cleft palate repair. MAIN OUTCOME MEASURES: Variables analyzed were perceptual speech parameters and, closure ratios obtained from lateral video-fluoroscopic images. RESULTS: Overall, 81.5% had postoperative improvements in their lateral video-fluoroscopic parameters, 63% improved their nasality scores, and 65.2% had improved speech intelligibility. A simple linear regression was done to predict the postoperative closure ratio. Preoperative closure ratio, hypernasality (moderate and severe), and audible nasal air emission are predictors for postoperative closure ratio. CONCLUSIONS: The Furlow palatoplasty alone led to complete resolution, or significant improvement of velopharyngeal dysfunction in a majority of patients, despite the cohort having a wide range of severity in terms of degree of dysfunction. The predictive formula will be validated in a further study.


Subject(s)
Cleft Palate , Velopharyngeal Insufficiency , Cleft Palate/complications , Cleft Palate/surgery , Humans , Palate, Soft/surgery , Retrospective Studies , Speech Intelligibility , Treatment Outcome , Velopharyngeal Insufficiency/complications , Velopharyngeal Insufficiency/surgery
10.
MSMR ; 28(7): 2-10, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-34542257

ABSTRACT

Long-acting reversible contraceptives (LARCs) are highly effective means of birth control that can improve service women's overall health and readiness. This report expands upon prior data and summarizes the annual prevalence (overall and by demographics) of LARC use from 2016 through 2020 among active component U.S. service women, compares LARC prevalence to the prevalence of short-acting reversible contraceptives (SARCs), and evaluates the probability of continued use of LARCs by type. LARC use increased from 21.9% to 23.9% from 2016 through 2019 while SARC use decreased from 28.3% to 24.9%. Both SARC and LARC use decreased in 2020 which may have been related to the coronavirus disease 2019 (COVID-19) pandemic. The prevalence of intrauterine devices (IUDs) was greater than implants, and IUDs also had a higher probability of continuation than implants. At 12 months, the continuation for IUDs was 81% compared to 73% for implants. At 24 months, the probabilities of continuation were 70% for IUDs and 54% for implants. Probabilities of continuation were similar across outsourced care and direct care settings. The increased use of LARCs along with their high frequency of continuation in U.S. service women may have a positive impact on overall health and readiness.


Subject(s)
Long-Acting Reversible Contraception/statistics & numerical data , Military Personnel/statistics & numerical data , Adolescent , Adult , COVID-19/epidemiology , Contraception Behavior/statistics & numerical data , Female , Humans , Intrauterine Devices/statistics & numerical data , Middle Aged , Military Personnel/psychology , Retrospective Studies , United States/epidemiology , Young Adult
11.
Cancer Gene Ther ; 28(9): 971-983, 2021 09.
Article in English | MEDLINE | ID: mdl-32759988

ABSTRACT

It has now been nearly 15 years since the last major advance in the treatment of patients with glioma. "The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity". Autophagy is primarily a survival pathway, literally self-eating, that is utilized in response to stress (such as radiation and chemotherapy), enabling clearance of effete protein aggregates and multimolecular assemblies. Promising results have been observed in patients with glioma for over a decade now when autophagy inhibition with chloroquine derivatives coupled with conventional therapy. The application of autophagy inhibitors, the role of immune cell-induced autophagy, and the potential role of novel cellular and gene therapies, should now be considered for development as part of this well-established regimen.


Subject(s)
Autophagy/immunology , Biomarkers, Tumor/metabolism , Glioblastoma/therapy , Female , Humans , Male
12.
J Oral Maxillofac Pathol ; 25(3): 553, 2021.
Article in English | MEDLINE | ID: mdl-35281163

ABSTRACT

Objectives: To estimate the awareness of hepatitis B virus (HBV) and coverage of hepatitis B vaccination among dental students enrolled in dental colleges located in Andhra Pradesh. Materials and Methods: A cross-sectional study was conducted using a prestructured questionnaire to find out the awareness of HBV and coverage of hepatitis B vaccine among dental students. Results: A total of 2780 dental students were approached to participate in the study but only 2701 (97.1%) students (M = 900, F = 1801) gave response. Out of the total 2701 students, 79.45% were aware of HBV infection and only 51.50% of the participants received hepatitis B vaccine. 20.5% have come across HBV infected patients and 59.5% are unaware of postexposure protocol. Of all, 63.9%, 21.5% and 42% felt the mode of transmission is blood, sexual contact and oral fluids, respectively. 49.12% recommended for awareness programs on risks in HBV; 56.46% suggested mandatory Hepatitis B vaccination programs in dental colleges. Conclusions: Despite the availability and accessibility of a cost-effective hepatitis B vaccine, the vaccination coverage among dental students was low. Health education needs to be improved for all health care students especially for dental students.

13.
MSMR ; 28(11): 2-8, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-35044733

ABSTRACT

The objective of this study was to assess the incidence and trends of sepsis hospitalizations in the active component U.S. military over the past decade. Between 1 January 2011 and 31 December 2020, there were 5,278 sepsis hospitalizations of any severity recorded among the active component. The overall incidence was 39.8 hospitalizations per 100,000 person-years (p-yrs). Annual incidence increased 64% from 2011 through 2019, then dropped considerably in 2020. Compared to their respective counterparts, rates were highest among female service members, the oldest and youngest age groups, and recruits. The gap in sepsis hospitalization rates between female and male service members increased over the surveillance period. Pneumonia was the most commonly co-occurring infection, followed by genitourinary infections. Among female service members, genitourinary infections were more commonly diagnosed compared to pneumonia. The most common non-infection co-occurring diagnoses were acute kidney failure and acute respiratory failure. This study demonstrates an apparent sex disparity in sepsis rates and further study is recommended to understand its cause.


Subject(s)
Military Personnel , Sepsis , Female , Hospitalization , Humans , Incidence , Male , Population Surveillance , Sepsis/epidemiology , United States/epidemiology
14.
Indian J Plast Surg ; 52(2): 201-208, 2019 May.
Article in English | MEDLINE | ID: mdl-31602136

ABSTRACT

Introduction Timing of cleft palate repair and the method of speech outcome measurement in children with cleft lip and palate are much debated topics. The associated problems and quality of life in these children depend on the timing of the surgery. Aim The aim of this study was to investigate the velopharyngeal (VP) function and resonance parameters in children following early cleft palate repair. Method A total of 25 Kannada-speaking children with early repaired cleft palate were subjected to speech assessment and videofluoroscopic assessment. Perceptual speech parameters measured were severity of hypernasality and presence of nasal air emission. Videofluoroscopy was interpreted in terms of closure ratios to predict the severity of VP dysfunction. Results The analysis of videofluoroscopic images indicated that 48% of children had complete VP closure and 52% had perceptually normal resonance. A good correlation was found between the closure ratio and hypernasality. Conclusion Understanding the perceptual speech parameters and their structural correlates for outcome measurement will give better evidence for refining the existing treatment protocols. Data on a larger population are warranted for establishing predictors of optimum speech outcome.

15.
Elife ; 72018 12 18.
Article in English | MEDLINE | ID: mdl-30561326

ABSTRACT

Approximately, 30% of embryonic stem cells (ESCs) die after exiting self-renewal, but regulators of this process are not well known. Yap1 is a Hippo pathway transcriptional effector that plays numerous roles in development and cancer. However, its functions in ESC differentiation remain poorly characterized. We first reveal that ESCs lacking Yap1 experience massive cell death upon the exit from self-renewal. We subsequently show that Yap1 contextually protects differentiating, but not self-renewing, ESC from hyperactivation of the apoptotic cascade. Mechanistically, Yap1 strongly activates anti-apoptotic genes via cis-regulatory elements while mildly suppressing pro-apoptotic genes, which moderates the level of mitochondrial priming that occurs during differentiation. Individually modulating the expression of single apoptosis-related genes targeted by Yap1 is sufficient to augment or hinder survival during differentiation. Our demonstration of the context-dependent pro-survival functions of Yap1 during ESC differentiation contributes to our understanding of the balance between survival and death during cell fate changes.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Apoptosis/genetics , Cell Differentiation/genetics , Mouse Embryonic Stem Cells/metabolism , Phosphoproteins/genetics , Adaptor Proteins, Signal Transducing/metabolism , Animals , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Caspases/metabolism , Cell Cycle Proteins , Cell Line , Cell Self Renewal , Gene Expression , Gene Knockout Techniques , Mice , Mitochondria/genetics , Mitochondria/metabolism , Mouse Embryonic Stem Cells/cytology , Mutation , Phosphoproteins/metabolism , YAP-Signaling Proteins
16.
Int J Biol Macromol ; 110: 2-6, 2018 Apr 15.
Article in English | MEDLINE | ID: mdl-29355638

ABSTRACT

Intracellular infections are tricky to treat, the reason being the poor penetration of antibiotics/antimycotics into the microbial niche (host cell). Macrophages are primary targets of facultative and obligate intracellular bacteria/fungi to be abused as host cells. The need for drugs with better intracellular penetration led to the development of endocytosable drug carriers, which can cross the cell membrane of the host cells (macrophages) by imitating the entry path of the pathogens. Therefore, the drugs can be targeted to macrophages ensuring enhanced therapeutic effect. This review discusses the exploitation of various nanocarriers for targeted delivery of drugs to the macrophages in the last two decades.


Subject(s)
Drug Delivery Systems/methods , Endocytosis , Infections/drug therapy , Macrophages/metabolism , Animals , Drug Delivery Systems/trends , Humans , Infections/metabolism
17.
Int J Biol Macromol ; 110: 140-149, 2018 Apr 15.
Article in English | MEDLINE | ID: mdl-29169943

ABSTRACT

Intercellular Candida glabrata infections are difficult to treat due to poor penetration of drugs into the fungal niche. Delivering amphotericin B (Amp B) into the macrophages where the pathogen inhabits is an effective solution. We are studying the macrophage targeting proficiency of É©-carrageenan for the delivery of Amp B using gelatin A nanoparticles (GNPs). The choice of gelatin A was the outcome of in silico inspections where the amino functionalized polymer having the best docking score with Amp B was selected. We prepared a sustained release formulation of amp B loaded carboxymethyl É©-carrageenan conjugated gelatin nanoparticles (CMC-Amp B-GNPs) with size 343±12nm and -25±5.3mV zeta potential. The formulations were found to be stable, biocompatible and non-haemolytic. Flow cytometry analysis showed 3 fold higher uptake of CMC-GNPs compared to the GNPs by RAW 264.7 cells. CMC-Amp B-GNPs showed enhanced antifungal activity than bare Amp B and Amp B-GNPs.


Subject(s)
Amphotericin B , Candida glabrata/metabolism , Candidiasis/drug therapy , Carrageenan , Gelatin , Macrophages/metabolism , Nanoparticles , Amphotericin B/chemistry , Amphotericin B/pharmacology , Animals , Candidiasis/metabolism , Candidiasis/microbiology , Candidiasis/pathology , Carrageenan/chemistry , Carrageenan/pharmacology , Drug Delivery Systems , Gelatin/chemistry , Gelatin/pharmacology , Macrophages/microbiology , Macrophages/pathology , Mice , Nanoparticles/chemistry , Nanoparticles/therapeutic use , RAW 264.7 Cells
18.
Carbohydr Polym ; 177: 67-76, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-28962797

ABSTRACT

We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery.


Subject(s)
Anti-Bacterial Agents/chemistry , Chitin/chemistry , Drug Carriers/chemistry , Drug Delivery Systems , Models, Molecular , Nanoparticles/chemistry , Drug Liberation , Molecular Docking Simulation , Particle Size
19.
Indian J Clin Biochem ; 31(4): 463-7, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27605745

ABSTRACT

The total proteins in human urine have been compared by sulfosalicylic acid, sulfosalicylic acid with sodium sulphate and trichloroacetic acid methods with pyrogallol red molybdate method as there are no studies found quantifying imprecision and bias components. Fresh urine of 36 patients was analyzed by four methods. Imprecision and inaccuracy were determined by repeated analysis and method comparison studies using correlation plots, Bland and Altman, and Passing and Bablok regression analyses respectively. The coefficient of variation was 5.07 % for pyrogallol red molybdate; 6.84 % for sulfosalicylic acid; 3.97 % for sulfosalicylic acid with sodium sulphate and 5.93 % for trichloroacetic acid methods. Bland and Altman analysis showed a bias of 5.8, 1.7 and -5.4 for pyrogallol red molybdate versus sulfosalicylic acid, sulfosalicylic acid with sodium sulphate and trichloroacetic acid methods respectively. Passing and Bablok regression revealed a constant bias for pyrogallol red molybdate versus all turbidimetric methods but a proportional bias only with trichloroacetic acid method. Sulfosalicylic acid with sodium sulphate method is preferred to sulfosalicylic acid and trichloroacetic acid methods.

20.
J Int Oral Health ; 7(5): 49-52, 2015 May.
Article in English | MEDLINE | ID: mdl-26028903

ABSTRACT

BACKGROUND: Age estimation is an important factor in establishing the identity of a person. Among various techniques, dental age estimation is helpful in estimating the age in children above 16 years of age. Determination of age using developmental stages of teeth is more useful than using tooth eruption. MATERIALS AND METHODS: A total of 550 orthopantomographs of 248 males and 302 females aged between 15 and 22 years were taken and evaluated by Demirjian's tooth mineralization stages. Statistical assessment was done using logistic regression analysis. RESULTS: Complete apical closure of third molars was observed at the age of 20.4 years in 50% of males. Gender is also thought to influence mineralization and males showed early apical closure than females. Mean value testing is also done but showed influence of high and lower end age groups on age estimation. CONCLUSION: Finally, we conclude that, though the exact age of a person cannot be determined, the Demirjian's stage at which 18 years of age is attained can be found out.

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