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1.  Swertisin an Anti-Diabetic Compound Facilitate Islet Neogenesis from Pancreatic Stem/Progenitor Cells via p-38 MAP Kinase-SMAD Pathway: An In-Vitro and In-Vivo Study 
PLoS ONE  2015;10(6):e0128244.
Transplanting islets serves best option for restoring lost beta cell mass and function. Small bio-chemical agents do have the potential to generate new islets mass, however lack of understanding about mechanistic action of these small molecules eventually restricts their use in cell-based therapies for diabetes. We recently reported “Swertisin” as a novel islet differentiation inducer, generating new beta cells mass more effectively. Henceforth, in the present study we attempted to investigate the molecular signals that Swertisin generate for promoting differentiation of pancreatic progenitors into islet cells. To begin with, both human pancreatic progenitors (PANC-1 cells) and primary cultured mouse intra-islet progenitor cells (mIPC) were used and tested for Swertisin induced islet neogenesis mechanism, by monitoring immunoblot profile of key transcription factors in time dependent manner. We observed Swertisin follow Activin-A mediated MEPK-TKK pathway involving role of p38 MAPK via activating Neurogenin-3 (Ngn-3) and Smad Proteins cascade. This MAP Kinase intervention in differentiation of cells was confirmed using strong pharmacological inhibitor of p38 MAPK (SB203580), which effectively abrogated this process. We further confirmed this mechanism in-vivo in partial pancreatectomised (PPx) mice model, where we could show Swertisin exerted potential increase in insulin transcript levels with persistent down-regulation of progenitor markers like Nestin, Ngn-3 and Pancreatic Duodenal Homeobox Gene-1 (PDX-1) expression, within three days post PPx. With detailed molecular investigations here in, we first time report the molecular mode of action of Swertisin for islet neogenesis mediated through MAP Kinase (MEPK-TKK) pathway involving Ngn-3 and Smad transcriptional regulation. These findings held importance for developing Swertisin as potent pharmacological drug candidate for effective and endogenous differentiation of islets in cell based therapy for diabetes.
doi:10.1371/journal.pone.0128244
PMCID: PMC4457488  PMID: 26047129
2.  Basal Expression of Pluripotency-Associated Genes Can Contribute to Stemness Property and Differentiation Potential 
Stem Cells and Development  2013;22(12):1802-1817.
Pluripotency and stemness is believed to be associated with high Oct-3/4, Nanog, and Sox-2 (ONS) expression. Similar to embryonic stem cells (ESCs), high ONS expression eventually became the measure of pluripotency in any cell. The threshold expression of ONS genes that underscores pluripotency, stemness, and differentiation potential is still unclear. Therefore, we raised a question as to whether pluripotency and stemness is a function of basal ONS gene expression. To prove this, we carried out a comparative study between basal ONS expressing NIH3T3 cells with pluripotent mouse bone marrow mesenchymal stem cells (mBMSC) and mouse ESC. Our studies on cellular, molecular, and immunological biomarkers between NIH3T3 and mBMSC demonstrated stemness property of undifferentiated NIH3T3 cells that was similar to mBMSC and somewhat close to ESC as well. In vivo teratoma formation with all three germ layer derivatives strengthen the fact that these cells in spite of basal ONS gene expression can differentiate into cells of multiple lineages without any genetic modification. Conclusively, our novel findings suggested that the phenomenon of pluripotency which imparts ability for multilineage cell differentiation is not necessarily a function of high ONS gene expression.
doi:10.1089/scd.2012.0261
PMCID: PMC3668502  PMID: 23343006
3.  A Small Molecule Swertisin from Enicostemma littorale Differentiates NIH3T3 Cells into Islet-Like Clusters and Restores Normoglycemia upon Transplantation in Diabetic Balb/c Mice 
Aim. Stem cell therapy is one of the upcoming therapies for the treatment of diabetes. Discovery of potent differentiating agents is a prerequisite for increasing islet mass. The present study is an attempt to screen the potential of novel small biomolecules for their differentiating property into pancreatic islet cells using NIH3T3, as representative of extra pancreatic stem cells/progenitors. Methods. To identify new agents that stimulate islet differentiation, we screened various compounds isolated from Enicostemma littorale using NIH3T3 cells and morphological changes were observed. Characterization was performed by semiquantitative RT-PCR, Q-PCR, immunocytochemistry, immunoblotting, and insulin secretion assay for functional response in newly generated islet-like cell clusters (ILCC). Reversal of hyperglycemia was monitored after transplanting ILCC in STZ-induced diabetic mice. Results. Among various compounds tested, swertisin, an isolated flavonoid, was the most effective in differentiating NIH3T3 into endocrine cells. Swertisin efficiently changed the morphology of NIH3T3 cells from fibroblastic to round aggregate cell cluster in huge numbers. Dithizone (DTZ) stain primarily confirmed differentiation and gene expression studies signified rapid onset of differentiation signaling cascade in swertisin-induced ILCC. Molecular imaging and immunoblotting further confirmed presence of islet specific proteins. Moreover, glucose induced insulin release (in vitro) and decreased fasting blood glucose (FBG) (in vivo) in transplanted diabetic BALB/c mice depicted functional maturity of ILCC. Insulin and glucagon expression in excised islet grafts illustrated survival and functional integrity. Conclusions. Rapid induction for islet differentiation by swertisin, a novel herbal biomolecule, provides low cost and readily available differentiating agent that can be translated as a therapeutic tool for effective treatment in diabetes.
doi:10.1155/2013/280392
PMCID: PMC3639639  PMID: 23662125
4.  Comparative Evaluation of Löwenstein-Jensen Proportion Method, BacT/ALERT 3D System, and Enzymatic Pyrazinamidase Assay for Pyrazinamide Susceptibility Testing of Mycobacterium tuberculosis▿  
Pyrazinamide (PZA) is an important first-line antituberculosis drug because of its sterilizing activity against semidormant tubercle bacilli. In spite of its very high in vivo activity, its in vitro activity is not apparent unless an acidic environment is available, which makes PZA susceptibility testing difficult by conventional methods. The present study was, therefore, planned to assess the performance of the colorimetric BacT/ALERT 3D system and compare the results with those from conventional tests, i.e., the Löwenstein-Jensen (LJ) proportion method (pH 4.85) and Wayne's pyrazinamidase (PZase) assay, using 107 clinical isolates. The concordance among all of these tests was 89.71% after the first round of testing and reached 92.52% after resolution of the discordant results by retesting. Prolonged incubation of the PZase tube for up to 10 days was found to increase the specificity of the PZase test. The concordances between LJ proportion and BacT/ALERT 3D, LJ proportion and the PZase assay, and BacT/ALERT 3D and the PZase assay were found to be 99.06%, 93.46%, and 92.52%, respectively. Using the LJ results as the gold standard, the sensitivities of BacT/ALERT 3D and the PZase assay were 100 and 82.85%, respectively, while the specificity was 98.61% for both of the tests. The difference between the sensitivities of BacT/ALERT 3D and the PZase assay was significant (P = 0.025). The mean turnaround times for the detection of resistant and susceptible results by BacT/ALERT 3D were 8.04 and 11.32 days, respectively. While the major limitations associated with the PZase assay and the LJ proportion method are lower sensitivity in previously treated patients and a longer time requirement, respectively, the BacT/ALERT 3D system was found to be rapid, highly sensitive, and specific.
doi:10.1128/JCM.00951-06
PMCID: PMC1828947  PMID: 17093022
5.  Clinico bacteriological evaluation of surface and core microflora in chronic tonsillitis 
The present study is undertaken on 50 tonsillectomy cases to determine the correlation between surface culture swabs and tonsillar core. Tonsillar disease may stem from the bacteria within the core of the tonsil, rather than the bacteria identified on its surface. Also no consistent pattern of combinations of different pathogenic bacteria was noted. The study proves that surface culture does not reliably predict core pathogens.
doi:10.1007/BF02907664
PMCID: PMC3450963  PMID: 23120146
Core pathogens; surface culture; tonsillectomy
6.  Traumatic retropharyngeal abscess presenting with quadriparesis: A case report 
Retropharyngeal abscess is not very common in adults. If it occurs,it is usually secondary to tuberculous lesion of spine or penetrating forgein body in food passage. We describe a case of retropharyngeal abscess with quadriparesis following neck trauma.
doi:10.1007/BF03006198
PMCID: PMC3451120  PMID: 23119690
Reteropharyngeal abscess; Quadriparesis; Neck trauma
7.  A Clinical Study of Local Acriflavin in Treatment of Rhinoscleroma 
Rhinoscleroma is a chronic granulomatous disease which involves upper respiratory tract. We undertook this study to find out the antibacterial effect of local acriflavin on Klebsiella rhinoscleromatis, as well as the disease rhinoscleroma. Antibiotic effect of acriflavin was studied on one of the isolate of Klebsiella rhinoscleromatis using whatman No.1 filter paper disc soaked in 2% and 5% acriflavin solution and was found sensitive. A total of 26 cases diagnosed clinically and histopathologically were studied. These patients were treated using 1%, 2% and 5% acriflavin ointment. The cure was 33%, 67% and 100% respectively. Details of response to acriflavin therapy and its adverse effect will be discussed. It is concluded that acriflavin can be used as a good alternative to systemic therapy for rhinoscleroma. As it can be prepared and applied easily and is not a financial burden on already poor patient.
doi:10.1007/BF02996846
PMCID: PMC3451466  PMID: 23119485
Rhinoscleroma; Therapy; Acriflavin; Scleroma
8.  A Microbiological Study of Anterior Nasal Packs in Epistaxis 
Bleeding per nose is one of the comnonest ailment encountered by each and every otolaryngologvst Since hemostasis is immediate concern, anterior nasal pressure pack is put and is usually allowed to remain for 24-72 hours. Blood soaked pack and raw mucosal surface are good media for bacterial multiplication resulting in infection including sinusitis and sometimes toxic shock syndromes.
Present study is conducted to work out bacterial flora of anterior nasal pack and effect of svstemic antibiotics in controlling it. Thirty cases of epistaxis of different etiology were included. Out of these 26 cases were positive on culture. These included Staphylococcus aureus 70%,. Pseudomonas aeruginosa twenty three percent. Klabsiella pneumonia and proteus mirabilis 3.3%, Streptococcus and Hemolyticus 3.3%. Details of type and duration of packing and its relation with organism cultured are discussed. It is concluded that the packing material should be soaked with antibiotics prior to use and should not be keep for more than 48 hours. And systemic antibiotics does not have any significant on this local infection due to packing.
doi:10.1007/BF02996844
PMCID: PMC3451490  PMID: 23119483
9.  Antileishmanial and Cytotoxic Activity of Some Highly Oxidized Abietane Diterpenoids from the Bald Cypress, Taxodium distichum 
Journal of natural products  2016;79(3):598-606.
Two new compounds, including a para-benzoquinone ring-containing abietane (1), a para-benzoquinone ring-containing 7,8-seco-abietane (2), and 14 other known highly oxidized abietane diterpenoids (3-16), were isolated from an extract prepared from the cones of Taxodium distichum, collected in central Ohio. The active subfraction from which all compounds isolated in this study were purified was tested in vivo using Leishmania donovani-infected mice, and was found to dose-dependently reduce the parasite burden in the murine livers after iv administration of this crude mixture at 5.6 and 11.1 mg/kg. The structures of 1 and 2 were established by detailed 1D- and 2D-NMR experiments, HRESIMS data, and electronic circular dichroism studies. Compounds 3 and 4 were each fully characterized spectroscopically and also isolated from a natural source for the first time. Compounds 2-16 were tested in vitro against L. donovani promastigotes and L. amazonensis intracellular amastigotes. Compound 2 was the most active against L. amazonensis amastigotes (IC50 = 1.4 μM), and 10 was the most potent against L. donovani promastigotes (IC50 = 1.6 μM). These compounds may be suggested for further studies such as in vivo experimentation either alone or in combination with other Taxodium isolates.
doi:10.1021/acs.jnatprod.5b01131
PMCID: PMC4831050  PMID: 26905523
10.  Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations 
High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products.
doi:10.1016/j.ijpharm.2016.01.031
PMCID: PMC4755808  PMID: 26784976
Abuse deterrent formulation; opioid analgesics; evaluation matrix; drug abuse; manipulation; mode of abuse; syringeability; injectability
11.  Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway* 
The Journal of Biological Chemistry  2015;290(47):28540-28558.
Background: Neurogenesis, the process of generation of new neurons, is reduced in Alzheimer disease (AD).
Results: Ethosuximide (ETH), an anticonvulsant drug, increased neurogenesis, reduced neurodegeneration, and reversed cognitive impairments in a rat model of AD-like phenotypes.
Conclusion: ETH induces neurogenesis, thus reversing AD-like phenotypes.
Significance: ETH could be used as a therapeutic molecule to enhance neurogenesis.
Neurogenesis involves generation of new neurons through finely tuned multistep processes, such as neural stem cell (NSC) proliferation, migration, differentiation, and integration into existing neuronal circuitry in the dentate gyrus of the hippocampus and subventricular zone. Adult hippocampal neurogenesis is involved in cognitive functions and altered in various neurodegenerative disorders, including Alzheimer disease (AD). Ethosuximide (ETH), an anticonvulsant drug is used for the treatment of epileptic seizures. However, the effects of ETH on adult hippocampal neurogenesis and the underlying cellular and molecular mechanism(s) are yet unexplored. Herein, we studied the effects of ETH on rat multipotent NSC proliferation and neuronal differentiation and adult hippocampal neurogenesis in an amyloid β (Aβ) toxin-induced rat model of AD-like phenotypes. ETH potently induced NSC proliferation and neuronal differentiation in the hippocampus-derived NSC in vitro. ETH enhanced NSC proliferation and neuronal differentiation and reduced Aβ toxin-mediated toxicity and neurodegeneration, leading to behavioral recovery in the rat AD model. ETH inhibited Aβ-mediated suppression of neurogenic and Akt/Wnt/β-catenin pathway gene expression in the hippocampus. ETH activated the PI3K·Akt and Wnt·β-catenin transduction pathways that are known to be involved in the regulation of neurogenesis. Inhibition of the PI3K·Akt and Wnt·β-catenin pathways effectively blocked the mitogenic and neurogenic effects of ETH. In silico molecular target prediction docking studies suggest that ETH interacts with Akt, Dkk-1, and GSK-3β. Our findings suggest that ETH stimulates NSC proliferation and differentiation in vitro and adult hippocampal neurogenesis via the PI3K·Akt and Wnt·β-catenin signaling.
doi:10.1074/jbc.M115.652586
PMCID: PMC4653709  PMID: 26420483
cell differentiation; cell proliferation; hippocampus; neural stem cell (NSC); neurodegeneration; neurodegenerative disease; neurogenesis; neuron; neuroprotection; ethosuximide
12.  Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: An Indian rural cancer centre experience 
South Asian Journal of Cancer  2016;5(2):59-62.
Background:
Paclitaxel-platinum and optimal cytoreductive surgery are the standard of care for ovarian carcinoma. Poor socioeconomic profile and therapeutic constraints in rural India poses a therapeutic challenge.
Aim:
To evaluate outcomes of epithelial ovarian carcinoma.
Objectives:
To calculate disease-free survival (DFS), overall survival (OS), and factors affecting outcomes.
Materials and Methods:
Data of patients diagnosed as ovarian carcinoma registered between March 2009 and March 2014 were retrieved. Demographic profile, chemotherapy and response, surgery, and disease progression were collected. Patients who underwent surgery or completed three cycles of chemotherapy were selected. Kaplan–Meir survival was used to determine disease-free and OS. Log-rank test used to evaluate factors affecting outcome.
Results:
Median follow-up is 26 months. 93/102 patients (91%) underwent cytoreductive surgery, of which 37 had primary cytoreduction (40%) while 56 had interval cytoreduction. 21/93 (23%), 57/93 (61%), and 15/93 (16%) patients were operated by local surgeons, surgeons of our hospital, and trained oncosurgeons, respectively. Induction paclitaxel-platinum was used in 35/63 (56%) patients while 28/63 patients (44%) received neoadjuvant metronomic chemotherapy. Median DFS and OS are 17 and 54 months respectively while 3 year OS of 66%. Median DFS of patients operated by oncosurgeons versus local surgeons were 22 months versus 15 months (P = 0.01), OS was 54 versus 26 months (P = 0.01).40/88 (45%) patients received maintenance metronomic therapy after adjuvant chemotherapy with median of 6 months (range 2–18 months). Patients receiving metronomic maintenance had better DFS, 18 months versus 15 months (P = 0.69).
Conclusion:
Induction therapy in ovarian carcinoma helps in selecting patients for cytoreductive surgery. Outcomes are better if operated by trained oncosurgeons. Maintenance metronomic has potential to delay disease progression.
doi:10.4103/2278-330X.181627
PMCID: PMC4873697  PMID: 27275448
Advanced epithelial carcinoma ovary; metronomic maintenance; metronomic neoadjuvant
13.  Northalrugosidine is a Bisbenzyltetrahydroisoquinoline Alkaloid from Thalictrum alpinum with in Vivo Antileishmanial Activity 
Journal of natural products  2015;78(3):552-556.
Screening of a plant-derived natural product library led to the observation of in vitro antileishmanial activity by three bisbenzyltetrahydroisoquinoline alkaloids (1-3) that were purified previously from Thalictrum alpinum. A spectroscopic study of the active compounds was conducted to confirm their identities. Of the compounds tested, northalrugosidine (1) showed the most potent in vitro activity against Leishmania donovani promastigotes (0.28 μM), and the highest selectivity (29.3–fold) versus its general cytotoxicity against HT-29 human colon adenocarcinoma cells. Northalrugosidine was tested in vivo using a murine model of visceral leishmaniasis, resulting in the observation of a dose-dependent reduction to the parasitic burden in the liver and spleen without overt toxicity effects at 2.8, 5.6, and 11.1 mg/kg per animal when administered intravenously. This represents the first report of a bisbenzyltetrahydroisoquinoline alkaloid with in vivo efficacy against visceral leishmaniasis.
doi:10.1021/np501028u
PMCID: PMC4394985  PMID: 25629555
14.  Sepsis 2016 Agra, India 
Sharma, Surinder Kumar | Rohatgi, Anurag | Bajaj, Mansi | Sprung, Charles L. | Morales, Ricardo Calderon | Kasdan, Harvey | Reiter, Allon | Volker, Tobias | Meissonnier, Julien | Beloborodova, Natalia | Moroz, Viktor | Bedova, Aleksandra | Sarshor, Yulia | Osipov, Artem | Chernevskaya, Katerina | Fedotcheva, Nadezhda | Chernevskaya, Ekaterina | Beloborodova, Natalia | Imahase, Hisashi | Yamada, Kosuke C. | Sakamoto, Yuichiro | Ohta, Miho | Sakurai, Ryota | Yahata, Mayuko | Umeka, Mitsuru | Miike, Toru | Koami, Hiroyuki | Nagashima, Futoshi | Iwamura, Takashi | Inoue, Satoshi | Li, Zhifeng | Grech, Dennis | Morcillo, Patrick | Bekker, Alex | Ulloa, Luis | Mukhopadhyay, Samanwoy | Pandey, Abhay D. | Bhattacharjee, Samsiddhi | Mohapatra, Saroj K. | Wilson, Julie K. | Jadhav, Savita | Misra, Rabindra Nath | Gandham, Nageswari | Angadi, Kalpana | Vywahare, Chanda | Gupta, Neetu | Desai, Deepali | Bakochi, Anahita | Mohanty, Tirthankar | Linder, Adam | Malmström, Johan | Anand, Dimple | Bhargava, Seema | Srivastava, Lalit Mohan | Ray, Sumit | Fisher, Jane | Bentzer, Peter | Linder, Adam | da Costa, Luis Henrique Angenendt | dos Santos Júnior, Nilton Nascimentos | Catalão, Carlos Henrique Rocha | da Rocha, Maria José Alves | Focà, Alfredo | Peronace, Cinzia | Matera, Giovanni | Giancotti, Aida | Barreca, Giorgio Settimo | Quirino, Angela | Loria, Maria Teresa | Settembre, Pio | Liberto, Maria Carla | Amantea, Bruno | Hartog, Christiane | Moeller, Claudia | Fleischmann, Carolin | Thomas-Rueddel, Daniel | Vlasakov, Vlasislav | Rochwerg, Bram | Theurer, Philip | Reinhart, Konrad | Smith, Anna E. | Taylor, Sandra D. | Da Costa, Christopher | Radford, Amanda | Lee, Terry | Singer, Joel | Boyd, John | Fineberg, David | Williams, Mark | Russell, James A.
Critical Care  2016;20(Suppl 1):45.
Table of contents
P1 D-Dimer in adult patients with presumed sepsis and their clinical outcomes
Surinder Kumar Sharma, Anurag Rohatgi, Mansi Bajaj
P2 Diagnosis of infection utilizing Acellix CD64
Charles L. Sprung, Ricardo Calderon Morales, Harvey Kasdan, Allon Reiter, Tobias Volker, Julien Meissonnier
P3 High levels of phenylcarboxylic acids reflect the severity in ICU patients and affect phagocytic activity of neutrophils
Natalia Beloborodova, Viktor Moroz, Aleksandra Bedova, Yulia Sarshor, Artem Osipov, Katerina Chernevskaya
P4 The role of bacterial phenolic metabolites in mitochondrial dysfunction
Nadezhda Fedotcheva, Ekaterina Chernevskaya, Natalia Beloborodova
P5 The early diagnosis of severe sepsis and judgment of rapid transport to critical care center: better prognostic factor
Hisashi Imahase, Kosuke C Yamada, Yuichiro Sakamoto, Miho Ohta, Ryota Sakurai, Mayuko Yahata, Mitsuru Umeka, Toru Miike, Hiroyuki Koami, Futoshi Nagashima, Takashi Iwamura, Satoshi Inoue
P6 Translational neuromodulation of the immune system
Zhifeng Li, Dennis Grech, Patrick Morcillo, Alex Bekker, Luis Ulloa
P7 Pathway-level meta-analysis reveals transcriptional signature of septic shock
Samanwoy Mukhopadhyay, Abhay D Pandey, Samsiddhi Bhattacharjee, Saroj K Mohapatra
P8 Antibiotic dosing in septic patients on the critical care unit - a literature review
Julie K Wilson
P9 Pandemic of Escherichia coli clone O25: H4-ST131 producing CTX-M-15 extended spectrum- β- lactamase- as serious cause of multidrug resistance extraintestinal pathogenic E. coli infections in India
Savita Jadhav, Rabindra Nath Misra, Nageswari Gandham, Kalpana Angadi, Chanda Vywahare, Neetu Gupta, Deepali Desai
P10 Detection and characterization of meningitis using a DDA-based mass spectrometry approach
Anahita Bakochi, Tirthankar Mohanty, Adam Linder, Johan Malmström
P11 Diagnostic usefulness of lipid profile and procalcitonin in sepsis and trauma patients
Dimple Anand, Seema Bhargava, Lalit Mohan Srivastava, Sumit Ray
P12 Heparin – a novel therapeutic in sepsis?
Jane Fisher, Peter Bentzer, Adam Linder
P13 Hypothalamic impairment is associated with vasopressin deficiency during sepsis
Luis Henrique Angenendt da Costa, Nilton Nascimentos dos Santos Júnior Carlos Henrique Rocha Catalão, Maria José Alves da Rocha
P14 Presepsin (soluble CD14 subtype) is a dependable prognostic marker in critical septic patients
Alfredo Focà, Cinzia Peronace, Giovanni Matera, Aida Giancotti, Giorgio Settimo Barreca, Angela Quirino, Maria Teresa Loria, Pio Settembre, Maria Carla Liberto, Bruno Amantea
P15 Safety and efficacy of gelatin-containing solutions versus crystalloids and albumin - a systematic review with quantitative and qualitative summaries
Christiane Hartog, Christiane Hartog, Claudia Moeller, Carolin Fleischmann, Daniel Thomas-Rueddel, Vlasislav Vlasakov, Bram Rochwerg, Philip Theurer, Konrad Reinhart
P16 Immunomodulatory properties of peripheral blood mesenchymal stem cells following endotoxin stimulation in an equine model
Anna E. Smith, Sandra D. Taylor
P17 Frequency and outcome of early sepsis-associated coagulopathy
Christopher Da Costa, Amanda Radford, Terry Lee, Joel Singer, John Boyd, David Fineberg, Mark Williams, James A Russell
doi:10.1186/s13054-016-1204-x
PMCID: PMC4895252  PMID: 26996981
15.  Effect of Saliva on the Tensile Bond Strength of Different Generation Adhesive Systems: An In-Vitro Study 
Background
Newer development of bonding agents have gained a better understanding of factors affecting adhesion of interface between composite and dentin surface to improve longevity of restorations.
Objective
The present study evaluated the influence of salivary contamination on the tensile bond strength of different generation adhesive systems (two-step etch-and-rinse, two-step self-etch and one-step self-etch) during different bonding stages to dentin where isolation is not maintained.
Materials and Methods
Superficial dentin surfaces of 90 extracted human molars were randomly divided into three study Groups (Group A: Two-step etch-and-rinse adhesive system; Group B: Two-step self-etch adhesive system and Group C: One-step self-etch adhesive system) according to the different generation of adhesives used. According to treatment conditions in different bonding steps, each Group was further divided into three Subgroups containing ten teeth in each. After adhesive application, resin composite blocks were built on dentin and light cured subsequently. The teeth were then stored in water for 24 hours before sending for testing of tensile bond strength by Universal Testing Machine. The collected data were then statistically analysed using one-way ANOVA and Tukey HSD test.
Results
One-step self-etch adhesive system revealed maximum mean tensile bond strength followed in descending order by Two-step self-etch adhesive system and Two-step etch-and-rinse adhesive system both in uncontaminated and saliva contaminated conditions respectively.
Conclusion
Unlike One-step self-etch adhesive system, saliva contamination could reduce tensile bond strength of the two-step self-etch and two-step etch-and-rinse adhesive system. Furthermore, the step of bonding procedures and the type of adhesive seems to be effective on the bond strength of adhesives contaminated with saliva.
doi:10.7860/JCDR/2015/13801.6251
PMCID: PMC4573047  PMID: 26393214
Aesthetic dentistry; Adhesion; Composite resin; Saliva
16.  Orthodontic Treatment Provided by General Dentists with Different Types of Appliances in Chattishgarh, India 
Objective
The study was done to determine the quantity of orthodontics and the type of appliance used for orthodontic treatment by general dentist.
Materials and Methods
A total of 410 dentists completely participated in the study. The study included questions to know the positive effects of orthodontic treatment done by general dentists and their opinions and qualities regarding the provision of treatment.
Statistical Analysis
Statistical analysis was done using SPSS version of 16.0 was used at p ≤ 0.05.
Results
One forty six (35.6%) dentists answered that they practice orthodontic treatment to their patients, of which most were providing removable appliances (39.5%). There was a significant difference between the groups toward the benefits of orthodontic treatment according to experience of service and locality. General dentist were providing this treatment mainly in the mixed dentition period i.e. 96(65.8%). Most of the participants gave positive response regarding expansion of their syllabus related to orthodontics.
Conclusion
A significant difference in response to the benefits of the treatment were seen according to experience and are of practice and most of the participants showed positive response increasing their courses in orthodontics at undergraduate level.
doi:10.7860/JCDR/2015/13666.6042
PMCID: PMC4525600  PMID: 26266210
Dentists; Fixed appliance; Removable appliances
17.  A localised soft tissue and bone enlargement in an infant mandible 
BMJ Case Reports  2013;2013:bcr2013010291.
A 4-month-old infant was referred by a paediatrician for a rapidly growing swelling on the right side of the mandible of 1.5 months duration. His medical and family history was unremarkable. Palpation divulged a firm and tender enlargement with the overlying soft tissue showing no significant alteration in colour. CT scan revealed cortical irregularity involving the ramus on the right side along with right masseter muscle hypertrophy. Routine haematological investigation yielded values within normal limits except for a raised erythrocyte sedimentation rate. Histopathological examination of the tissue submitted following an open biopsy procedure showed reactive lamellar bone and trabeculae with fibrous marrow exhibiting inflammation. The final diagnosis of infantile cortical hyperostosis was clinched based on the clinicopathological correlation. A rare reactive bone dystrophy which could pose a certain diagnostic dilemma is addressed herewith.
doi:10.1136/bcr-2013-010291
PMCID: PMC3702968  PMID: 23787824
18.  Mechanisms of cellular invasion by intracellular parasites 
doi:10.1007/s00018-013-1491-1
PMCID: PMC4107162  PMID: 24221133
Leishmaniasis; American trypanosomiasis; Chagas disease; toxoplasmosis; Malaria; Leishmania; Trypanosoma cruzi; Toxoplasma gondii; Plasmodium; invasion
19.  Liposomal resiquimod for the treatment of Leishmania donovani infection 
Objectives
The imidazoquinoline family of drugs are Toll-like receptor 7/8 agonists that have previously been used in the treatment of cutaneous leishmaniasis. Because of the hydrophobic nature of imidazoquinolines, they are traditionally not administered systemically for the treatment of visceral leishmaniasis. We formulated liposomal resiquimod, an imidazoquinoline, for the systemic treatment of visceral leishmaniasis.
Methods
By using lipid film hydration with extrusion, we encapsulated resiquimod in liposomes. These liposomes were then injected intravenously to treat BALB/c mice infected with Leishmania donovani.
Results
Treatment with liposomal resiquimod significantly decreased the parasite load in the liver, spleen and bone marrow. In addition, resiquimod treatment increased interferon-γ and interleukin-10 production in an antigen recall assay. Resiquimod was shown to be non-toxic in histology and in vitro culture experiments.
Conclusions
FDA-approved resiquimod, in a liposomal formulation, displays promising results in treating visceral leishmaniasis.
doi:10.1093/jac/dkt320
PMCID: PMC3861330  PMID: 23956375
drug delivery; imidazoquinoline; visceral; therapy
20.  Development and Optimization of Polymeric Self-Emulsifying Nanocapsules for Localized Drug Delivery: Design of Experiment Approach 
The Scientific World Journal  2014;2014:516069.
The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X1 (oil), X2 (polymeric emulsifier), and X3 (adsorbent), was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y1) and encapsulation efficiency (Y2) of the formulation. Polymeric nanocapsules with an average diameter of 100–180 nm and an encapsulation efficiency of 64.85 ± 0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (Cmax 200 ng/mL) that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0–2 h in upper GIT; 2–4 h in small intestine; and 4–24 h in the lower intestine). Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 μM) in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.
doi:10.1155/2014/516069
PMCID: PMC4265377  PMID: 25525620
21.  Estimation of Salivary and Serum Total Sialic Acid Levels in Periodontal Health and Disease 
Background: Chronic gingivitis and periodontitis are inflammatory diseases. An important function of host sialic acid is to regulate innate immunity. The aim of the study was to assess the concentration of Total sialic acid (TSA) in saliva and serum and also to find out their association if any, in periodontal health and disease.
Materials and Methods: A total of 90 subjects were clinically examined and distributed into three groups (n=30) according to the periodontal status namely healthy, chronic gingivitis and chronic periodontitis.Clinical measurements including probing depth, clinical attachment level, gingival index, oral hygeine index were recorded .TSA concentration was determined in saliva and serum of all subjects.
Results: In healthy group the mean salivary TSA level was 39.05mg/dl ±6.35(p<0.0001), mean serum TSA level was 49.75 mg/dl ± 4.87 (p<0.0001). In the chronic gingivitis group the mean salivary TSA level was 68.23 mg/dl ± 2.71 (p<0.0001), mean serum TSA level was 65.65 mg/dl ±3.56 (p<0.0001). In the chronic periodontitis group the mean salivary TSA was 81.33 mg/dl ±3.94 (p<0.0001), mean serum TSA level was 75.98 mg/dl ±3.58 (p<0.0001).
Conclusion:The present data indicates that salivary & serum TSA levels can differentiate between chronic periodontitis patients and normal individuals. Thus it can be used as an adjunct to diagnose, monitor response to therapy, to determine the current periodontal disease status and to assess the treatment outcomes.
doi:10.7860/JCDR/2014/9615.4800
PMCID: PMC4225966  PMID: 25386514
Chronic periodontitis; N-Acetylneuraminic acid; Saliva; Serum
22.  Influence of phase I periodontal therapy on levels of matrix metalloproteinase 1 and tissue inhibitor of metalloproteinase 1 
The Saudi Dental Journal  2014;26(4):171-175.
Background
Matrix metalloproteinase-1 (MMP-1) is a member of a family of enzymes that can degrade most extracellular matrix macromolecules. Extracellularly, MMPs are controlled by tissue inhibitors of metalloproteinases (TIMPs) and by mechanisms of pro-MMP activation. Levels of MMPs and TIMPs change during healing, inflammation, and normal tissue turnover. Herein we aimed to evaluate the levels of MMP-1 and TIMP-1 in gingival crevicular fluid (GCF) from periodontally healthy patients (control group) and chronic periodontitis patients before and after phase 1 therapy.
Methods
In this study we examined 30 patients who had chronic periodontitis with probing depth sites ⩾5 mm and a clinical attachment level (CAL) ⩾5 mm. We included 30 periodontally healthy patients as a control. Clinical measurements such as plaque (PI) and gingival (GI) indices, papillary bleeding index (PBI), probing depths (PD), and CAL were recorded both before treatment (BT) and after phase I periodontal treatment (AT). Assays for MMP-1 and TIMP-1 were performed with an enzyme-linked immunosorbent assay (ELISA) method.
Results
All clinical parameters were significantly reduced at the post-therapy visit. MMP-1 levels were significantly higher in patients BT than the controls; however, the patients AT were not statistically different than the controls. TIMP-1 levels in patients BT were significantly lower than in the controls and significantly lower than patients AT. We observed a significant positive correlation between GCF volume and MMP-1 levels. Furthermore, TIMP-1 levels were significantly negatively correlated with both GCF volume and all clinical parameters.
Conclusions
We observed that as the extent of periodontal destruction increases, MMP-1 concentration increases and TIMP-1 concentration decreases in GCF. When chronic periodontitis patients were treated by scaling and root planing (SRP), the average MMP-1 concentrations decreased and TIMP-1 concentrations increased in GCF.
doi:10.1016/j.sdentj.2014.05.003
PMCID: PMC4223804  PMID: 25382950
MMP-1; TIMP-1; Chronic periodontitis; Gingival crevicular fluid
23.  Development and Validation of a HPLC Method for Dissolution and Stability Assay of Liquid-Filled Cyclosporine Capsule Drug Products 
AAPS PharmSciTech  2013;14(3):959-967.
To assay the dissolution samples of a drug product from several sources, a simple but broadly applicable analytical method is always desired. For the liquid-filled cyclosporine capsules, while analyzing the dissolution samples, the current compendial and literature HPLC methods have been found to be inadequate to provide satisfactory separation of the drug and the excipient peaks. Accordingly, a suitable isocratic reverse-phase HPLC method was developed for the analysis of dissolution samples of liquid-filled cyclosporine capsules. The method successfully separated the cyclosporine peak from the interfering chromatographic peaks of the excipients. The method was validated according to the ICH and FDA guidelines. Specificity, selectivity, linearity, accuracy, precision, and robustness were established over 3 days as part of method validation. Additionally, the degradation kinetics of cyclosporine in dissolution media was determined. Cyclosporine degradation followed a zero-order kinetics in the dissolution media with the respective rate constants of −3.5, −1.5, and −0.3%/h at 37°C, 25°C, and 10°C.
doi:10.1208/s12249-013-9983-8
PMCID: PMC3755155  PMID: 23761263
cyclosporine; degradation; dissolution; HPLC; liquid-filled capsules
24.  Electrospray Encapsulation of Toll-Like Receptor Agonist Resiquimod in Polymer Microparticles for the Treatment of Visceral Leishmaniasis 
Molecular pharmaceutics  2013;10(3):10.1021/mp3005098.
Leishmaniasis is a disease caused by the intracellular protozoan, Leishmania. A current treatment for cutaneous leishmaniasis involves the delivery of imidazoquinolines via a topical cream. However, there are no parenteral formulations of imidazoquinolines for the most deadly version of the disease, visceral leishmaniasis. This work investigates the use of electrospray to encapsulate the imidazoquinoline adjuvant resiquimod in acid sensitive microparticles composed of acetalated dextran (Ac-DEX) or Ac-DEX/Tween blends. The particles were characterized and tested both in vitro and in vivo. Solutions of Ac-DEX and resiquimod in ethanol were electrosprayed to generate approximately 2 µm Ac-DEX particles containing resiquimod with an encapsulation efficiency of 85%. To prevent particle aggregation, blends of Ac-DEX with Tween 20 and Tween 80 were investigated. Tween 80 was then blended with the Ac-DEX at ~10% (w/w) of total polymer and particles containing resiquimod were formed via electrospray with encapsulation efficiencies between 40% and 60%. In vitro release profiles of resiquimod from Ac-DEX/Tween 80 particles exhibited the acid-sensitive nature of Ac-DEX, with 100% drug release after 8 h at pH 5 (phagosomal pH) and after 48 h at pH 7.4 (physiological pH). Treatment with Ac-DEX/Tween 80 particles elicited significantly greater immune response in RAW macrophages over free drug. When injected intravenously into mice inoculated with Leishmania, parasite load reduced significantly in the bone marrow compared to blank particles and phosphate-buffered saline controls. Overall, electrospray appears to offer an elegant, scalable way to encapsulate adjuvant into an acid sensitive delivery vehicle for use in treating visceral leishmaniasis.
doi:10.1021/mp3005098
PMCID: PMC3857017  PMID: 23320733
electrospray; drug delivery; immune adjuvant; subunit vaccine; Leishmania
25.  Mechanisms of Immune Evasion in Leishmaniasis 
Diseases caused by Leishmania present a worldwide problem, and current therapeutic approaches are unable to achieve a sterile cure. Leishmania is able to persist in host cells by evading or exploiting host immune mechanisms. A thorough understanding of these mechanisms could lead to better strategies for effective management of Leishmania infections. Current research has focused on parasite modification of host cell signaling pathways, entry into phagocytic cells, and modulation of cytokine and chemokine profiles that alter immune cell activation and trafficking to sites of infection. Immuno-therapeutic approaches that target these mechanisms of immune evasion by Leishmania offer promising areas for preclinical and clinical research.
doi:10.1016/B978-0-12-407679-2.00005-3
PMCID: PMC3697132  PMID: 23415155

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