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Hepatoprotective mechanism of Lygodium microphyllum (Cav.) R.Br. through ultrastructural signaling prevention against carbon tetrachloride (CCl4)-mediated oxidative stress

Gnanaraj C, Shah MD, Song TT, Iqbal M

Biomed Pharmacother, 2017 Aug;92:1010-1022.
PMID: 28609838 DOI: 10.1016/j.biopha.2017.06.014

Plants have been consumed in medicinal practices for centuries. Lygodium microphyllum (Cav.) R.Br. (Lygodiaceae), also known as Old World Climbing Fern, is a medicinal plant used by local communities in Sabah for skin and dysentery ailments. This study aims to test aqueous extract of L. microphyllum leaves for hepatoprotective and immunosuppressive activity in rats. Animal studies were carried out to evaluate hepatoprotection of aqueous extract of L. microphyllum at different doses (200, 400 and 600mg/kg b.w.) against carbon tetrachloride (CCl4)-mediated liver injury and histopathological alterations. Total phenolic content in aqueous extract of L. microphyllum leaves was 206.38±9.62mg gallic acid equivalent/g. The inhibitory concentration (IC50) for free radical scavenging activity of L. microphyllum was reached at a concentration of 65μg/ml.L. microphyllum was able to prevent the increase in levels of serum alanine aminotransferase, serum aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal, 8-hydroxydeoxyguanosine) and pro-inflammatory cytokines (Tumor Necrosis Factor-α, Interleukin-6, Prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations showed protective effects by L. microphyllum against CCl4-mediated oxidative stress. Hepatoprotective mechanism of L. microphyllum can be attributed to its antioxidative effects through protection of ultrastructural organelles.

Matched MeSH terms: Microscopy, Electron, Transmission
Fulltext Cellular Homeostasis and Antioxidant Response in Epithelial HT29 Cells on Titania Nanotube Arrays Surface

Smn Mydin RB, Sreekantan S, Hazan R, Farid Wajidi MF, Mat I

Oxid Med Cell Longev, 2017;2017:3708048.
PMID: 28337249 DOI: 10.1155/2017/3708048

Cell growth and proliferative activities on titania nanotube arrays (TNA) have raised alerts on genotoxicity risk. Present toxicogenomic approach focused on epithelial HT29 cells with TNA surface. Fledgling cell-TNA interaction has triggered G0/G1 cell cycle arrests and initiates DNA damage surveillance checkpoint, which possibly indicated the cellular stress stimuli. A profound gene regulation was observed to be involved in cellular growth and survival signals such as p53 and AKT expressions. Interestingly, the activation of redox regulator pathways (antioxidant defense) was observed through the cascade interactions of GADD45, MYC, CHECK1, and ATR genes. These mechanisms furnish to protect DNA during cellular division from an oxidative challenge, set in motion with XRRC5 and RAD50 genes for DNA damage and repair activities. The cell fate decision on TNA-nanoenvironment has been reported to possibly regulate proliferative activities via expression of p27 and BCL2 tumor suppressor proteins, cogent with SKP2 and BCL2 oncogenic proteins suppression. Findings suggested that epithelial HT29 cells on the surface of TNA may have a positive regulation via cell-homeostasis mechanisms: a careful circadian orchestration between cell proliferation, survival, and death. This nanomolecular knowledge could be beneficial for advanced medical applications such as in nanomedicine and nanotherapeutics.

Matched MeSH terms: Microscopy, Electron, Scanning
Effect of annealing temperature on antimicrobial and structural properties of bio-synthesized zinc oxide nanoparticles using flower extract of Anchusa italica

Azizi S, Mohamad R, Bahadoran A, Bayat S, Rahim RA, Ariff A, et al.

J. Photochem. Photobiol. B, Biol., 2016 Aug;161:441-9.
PMID: 27318600 DOI: 10.1016/j.jphotobiol.2016.06.007

The use of nontoxic biological compounds in the synthesis of nanomaterials is an economic and eco-friendly approach. The present work was undertaken to develop zinc oxide nanoparticles (ZnO-NPs) by a green method using simple precursor from the solution consisting of zinc acetate and the flower extract of Anchusa italica (A. italica). Effect of annealing temperature on structural and antimicrobial properties was investigated. The crystalline structure of ZnO-NPs was shown using X-ray diffraction (XRD) analysis. Transmission electron microscopy (TEM) results showed that ZnO-NPs are hexagonal in shapes with mean particle size of ~8 and ~14nm at 100°C and 200°C annealing temperatures respectively. The optical band gap was increased from 3.27eV to 3.30eV with the decreasing of the particle size. The antimicrobial activity of ZnO-NPs towards Gram positive (Bacillus megaterium and Stapphylococcus aureus) and Gram negative (Escherichia coli and Salmonella typhimurium) pathogens decreased with the increasing of the heat treating temperature. In vitro cytotoxicity studies on Vero cells, a dose dependent toxicity with non-toxic effect of concentration below 142μg/mL was shown. The results indicated that A. italica is an appropriate reaction media to prepare ZnO-NPs for cosmetic and bio-medical productions.

Matched MeSH terms: Microscopy, Electron, Transmission
Fulltext Antibacterial Mode of Action of Cinnamomum verum Bark Essential Oil, Alone and in Combination with Piperacillin, Against a Multi-Drug-Resistant Escherichia coli Strain

Yap PS, Krishnan T, Chan KG, Lim SH

J Microbiol Biotechnol, 2015 Aug;25(8):1299-306.
PMID: 25381741 DOI: 10.4014/jmb.1407.07054

This study aimed to investigate the mechanism of action of the cinnamon bark essential oil (CB), when used singly and also in combination with piperacillin, for its antimicrobial and synergistic activity against beta-lactamase TEM-1 plasmid-conferred Escherichia coli J53 R1. Viable count of this combination showed a complete killing profile at 20 h and further confirmed its synergistic effect by reducing the bacteria cell numbers. Analysis on the stability of treated cultures for cell membrane permeability by CB when tested against sodium dodecyl sulfate revealed that the bacterial cell membrane was disrupted by the essential oils. Scanning electron microscopy observation and bacterial surface charge measurement also revealed that CB causes irreversible membrane damage and reduces the bacterial surface charge. In addition, bioluminescence expression of Escherichia coli [pSB1075] and E. coli [pSB401] by CB showed reduction, indicating the possibility of the presence of quorum sensing (QS) inhibitors. Gas-chromatography and mass spectrometry of the essential oil of Cinnamomum verum showed that trans-cinnamaldehyde (72.81%), benzyl alcohol (12.5%), and eugenol (6.57%) were the major components in the essential oil. From this study, CB has the potential to reverse E. coli J53 R1 resistance to piperacillin through two pathways; modification in the permeability of the outer membrane or bacterial QS inhibition.

Matched MeSH terms: Microscopy, Electron, Scanning
The influence of experimental silane primers on dentin bond strength and morphology: a laboratory and finite element analysis study

Mustafa AA, Matinlinna JP, Saidin S, Kadir MR

J Prosthet Dent, 2014 Dec;112(6):1498-506.
PMID: 24993375 DOI: 10.1016/j.prosdent.2014.05.011

STATEMENT OF PROBLEM: The inconsistency of dentin bonding affects retention and microleakage.
PURPOSE: The purpose of this laboratory and finite element analysis study was to investigate the effects on the formation of a hybrid layer of an experimental silane coupling agent containing primer solutions composed of different percentages of hydroxyethyl methacrylate.
MATERIAL AND METHODS: A total of 125 sound human premolars were restored in vitro. Simple class I cavities were formed on each tooth, followed by the application of different compositions of experimental silane primers (0%, 5%, 25%, and 50% of hydroxyethyl methacrylate), bonding agents, and dental composite resins. Bond strength tests and scanning electron microscopy analyses were performed. The laboratory experimental results were validated with finite element analysis to determine the pattern of stress distribution. Simulations were conducted by placing the restorative composite resin in a premolar tooth by imitating simple class I cavities. The laboratory and finite element analysis data were significantly different from each other, as determined by 1-way ANOVA. A post hoc analysis was conducted on the bond strength data to further clarify the effects of silane primers.
RESULTS: The strongest bond of hybrid layer (16.96 MPa) was found in the primer with 25% hydroxyethyl methacrylate, suggesting a barely visible hybrid layer barrier. The control specimens without the application of the primer and the primer specimens with no hydroxyethyl methacrylate exhibited the lowest strength values (8.30 MPa and 11.78 MPa) with intermittent and low visibility of the hybrid layer. These results were supported by finite element analysis that suggested an evenly distributed stress on the model with 25% hydroxyethyl methacrylate.
CONCLUSIONS: Different compositions of experimental silane primers affected the formation of the hybrid layer and its resulting bond strength.

Matched MeSH terms: Microscopy, Electron, Scanning
The impact of surface preparation on shear bond strength of metallic orthodontic brackets bonded with a resin-modified glass ionomer cement

Elnafar AA, Alam MK, Hasan R

J Orthod, 2014 Sep;41(3):201-7.
PMID: 25143559 DOI: 10.1179/1465313314Y.0000000097

The aim of this study was to assess the effects of four enamel preparation techniques on shear bond strength (SBS) of brackets bonded with a resin-modified glass ionomer cement (RMGIC). Adhesive Remnant Index (ARI) and enamel surface roughness (Ra) were also investigated after cement removal.

Matched MeSH terms: Microscopy, Electron, Scanning
Fulltext Multimeric disintegrin protein polymer fusions that target tumor vasculature

Janib SM, Gustafson JA, Minea RO, Swenson SD, Liu S, Pastuszka MK, et al.

Biomacromolecules, 2014 Jul 14;15(7):2347-58.
PMID: 24871936 DOI: 10.1021/bm401622y

Recombinant protein therapeutics have increased in number and frequency since the introduction of human insulin, 25 years ago. Presently, proteins and peptides are commonly used in the clinic. However, the incorporation of peptides into clinically approved nanomedicines has been limited. Reasons for this include the challenges of decorating pharmaceutical-grade nanoparticles with proteins by a process that is robust, scalable, and cost-effective. As an alternative to covalent bioconjugation between a protein and nanoparticle, we report that biologically active proteins may themselves mediate the formation of small multimers through steric stabilization by large protein polymers. Unlike multistep purification and bioconjugation, this approach is completed during biosynthesis. As proof-of-principle, the disintegrin protein called vicrostatin (VCN) was fused to an elastin-like polypeptide (A192). A significant fraction of fusion proteins self-assembled into multimers with a hydrodynamic radius of 15.9 nm. The A192-VCN fusion proteins compete specifically for cell-surface integrins on human umbilical vein endothelial cells (HUVECs) and two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Confocal microscopy revealed that, unlike linear RGD-containing protein polymers, the disintegrin fusion protein undergoes rapid cellular internalization. To explore their potential clinical applications, fusion proteins were characterized using small animal positron emission tomography (microPET). Passive tumor accumulation was observed for control protein polymers; however, the tumor accumulation of A192-VCN was saturable, which is consistent with integrin-mediated binding. The fusion of a protein polymer and disintegrin results in a higher intratumoral contrast compared to free VCN or A192 alone. Given the diversity of disintegrin proteins with specificity for various cell-surface integrins, disintegrin fusions are a new source of biomaterials with potential diagnostic and therapeutic applications.

Matched MeSH terms: Microscopy, Electron, Transmission
Purification of human adipose-derived stem cells from fat tissues using PLGA/silk screen hybrid membranes

Chen DC, Chen LY, Ling QD, Wu MH, Wang CT, Suresh Kumar S, et al.

Biomaterials, 2014 May;35(14):4278-87.
PMID: 24565521 DOI: 10.1016/j.biomaterials.2014.02.004

The purification of human adipose-derived stem cells (hADSCs) from human adipose tissue cells (stromal vascular fraction) was investigated using membrane filtration through poly(lactide-co-glycolic acid)/silk screen hybrid membranes. Membrane filtration methods are attractive in regenerative medicine because they reduce the time required to purify hADSCs (i.e., less than 30 min) compared with conventional culture methods, which require 5-12 days. hADSCs expressing the mesenchymal stem cell markers CD44, CD73, and CD90 were concentrated in the permeation solution from the hybrid membranes. Expression of the surface markers CD44, CD73, and CD99 on the cells in the permeation solution from the hybrid membranes, which were obtained using 18 mL of feed solution containing 50 × 10⁴ cells, was statistically significantly higher than that of the primary adipose tissue cells, indicating that the hADSCs can be purified in the permeation solution by the membrane filtration method. Cells expressing the stem cell-associated marker CD34 could be successfully isolated in the permeation solution, whereas CD34⁺ cells could not be purified by the conventional culture method. The hADSCs in the permeation solution demonstrated a superior capacity for osteogenic differentiation based on their alkali phosphatase activity, their osterix gene expression, and the results of mineralization analysis by Alizarin Red S and von Kossa staining compared with the cells from the suspension of human adipose tissue. These results suggest that the hADSCs capable of osteogenic differentiation preferentially permeate through the hybrid membranes.

Matched MeSH terms: Microscopy, Electron, Scanning
Use of UV-vis-NIR spectroscopy to monitor label-free interaction between molecular recognition elements and erythropoietin on a gold-coated polycarbonate platform

Citartan M, Gopinath SC, Tominaga J, Chen Y, Tang TH

Talanta, 2014 Aug;126:103-9.
PMID: 24881539 DOI: 10.1016/j.talanta.2014.03.043

Label-free-based detection is pivotal for real-time monitoring of biomolecular interactions and to eliminate the need for labeling with tags that can occupy important binding sites of biomolecules. One simplest form of label-free-based detection is ultraviolet-visible-near-infrared (UV-vis-NIR) spectroscopy, which measure changes in reflectivity as a means to monitor immobilization and interaction of biomolecules with their corresponding partners. In biosensor development, the platform used for the biomolecular interaction should be suitable for different molecular recognition elements. In this study, gold (Au)-coated polycarbonate was used as a platform and as a proof-of-concept, erythropoietin (EPO), a doping substance widely abused by the athletes was used as the target. The interaction of EPO with its corresponding molecular recognition elements (anti-EPO monoclonal antibody and anti-EPO DNA aptamer) is monitored by UV-vis-NIR spectroscopy. Prior to this, to show that UV-vis-NIR spectroscopy is a suitable method for measuring biomolecular interaction, the interaction between biotin and streptavidin was demonstrated via this strategy and reflectivity of this interaction decreased by 25%. Subsequent to this, interaction of the EPO with anti-EPO monoclonal antibody and anti-EPO DNA aptamer resulted in the decrease of reflectivity by 5% and 10%, respectively. The results indicated that Au-coated polycarbonate could be an ideal biosensor platform for monitoring biomolecular interactions using UV-vis-NIR spectroscopy. A smaller version of the Au-coated polycarbonate substrates can be derived from the recent set-up, to be applied towards detecting EPO abuse among atheletes.

Matched MeSH terms: Microscopy, Electron, Scanning
Fulltext Growth inhibitory response and ultrastructural modification of oral-associated candidal reference strains (ATCC) by Piper betle L. extract

Nordin MA, Wan Harun WH, Abdul Razak F, Musa MY

Int J Oral Sci, 2014 Mar;6(1):15-21.
PMID: 24406634 DOI: 10.1038/ijos.2013.97

Candida species have been associated with the emergence of strains resistant to selected antifungal agents. Plant products have been used traditionally as alternative medicine to ease mucosal fungal infections. This study aimed to investigate the effects of Piper betle extract on the growth profile and the ultrastructure of commonly isolated oral candidal cells. The major component of P. betle was identified using liquid chromatography-mass spectrophotometry (LC-MS/MS). Seven ATCC control strains of Candida species were cultured in yeast peptone dextrose broth under four different growth environments: (i) in the absence of P. betle extract; and in the presence of P. betle extract at respective concentrations of (ii) 1 mg⋅mL(-1); (iii) 3 mg⋅mL(-1); and (iv) 6 mg⋅mL(-1). The growth inhibitory responses of the candidal cells were determined based on changes in the specific growth rates (µ). Scanning electron microscopy (SEM) was used to observe any ultrastructural alterations in the candida colonies. LC-MS/MS was performed to validate the presence of bioactive compounds in the extract. Following treatment, it was observed that the µ-values of the treated cells were significantly different than those of the untreated cells (P<0.05), indicating the fungistatic properties of the P. betle extract. The candidal population was also reduced from an average of 13.44×10(6) to 1.78×10(6) viable cell counts (CFU)⋅mL(-1). SEM examination exhibited physical damage and considerable morphological alterations of the treated cells. The compound profile from LC-MS/MS indicated the presence of hydroxybenzoic acid, chavibetol and hydroxychavicol in P. betle extract. The effects of P. betle on candida cells could potentiate its antifungal activity.

Matched MeSH terms: Microscopy, Electron, Scanning
pH dependent poly[2-(methacryloyloxyethyl)trimetylammonium chloride-co-methacrylic acid]hydrogels for enhanced targeted delivery of 5-fluorouracil in colon cancer cells

Mishra RK, Ramasamy K, Ahmad NA, Eshak Z, Majeed AB

J Mater Sci Mater Med, 2014 Apr;25(4):999-1012.
PMID: 24398912 DOI: 10.1007/s10856-013-5132-x

Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.

Matched MeSH terms: Microscopy, Electron, Scanning
Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: characterization, stability assessment and cytotoxicity

How CW, Rasedee A, Manickam S, Rosli R

Colloids Surf B Biointerfaces, 2013 Dec 1;112:393-9.
PMID: 24036474 DOI: 10.1016/j.colsurfb.2013.08.009

Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines.

Matched MeSH terms: Microscopy, Electron, Transmission
Development and characterization of lecithin stabilized glibenclamide nanocrystals for enhanced solubility and drug delivery

Kumar BS, Saraswathi R, Kumar KV, Jha SK, Venkates DP, Dhanaraj SA

Drug Deliv, 2014 May;21(3):173-84.
PMID: 24102185 DOI: 10.3109/10717544.2013.840690

Novel LNCs (lipid nanocrystals) were developed with an aim to improve the solubility, stability and targeting efficiency of the model drug glibenclamide (GLB). PEG 20000, Tween 80 and soybean lecithin were used as polymer, surfactant and complexing agent, respectively. GLB nanocrystals (NCs) were prepared by precipitation process and complexed using hot and cold melt technique. The LNCs were evaluated by drug loading, saturation solubility (SL), optical clarity, in vitro dissolution, solid state characterization, in vivo and stability analysis. LNCs exhibited a threefold increase in SL and a higher dissolution rate than GLB. The percentage dissolution efficiency was found to decrease with increase in PEG 20000. The average particle size was in the range of 155-842 nm and zeta potential values tend to increase after complexation. X-ray powder diffractometry and differential scanning calorimetry results proved the crystallinity prevailed in the samples. Spherical shaped particles (<1000 nm) with a lipid coat on the surface were observed in scanning electron microscopy analysis. Fourier transform infrared results proved the absence of interaction between drug and polymer and stability study findings proved that LNCs were stable. In vivo study findings showed a decrease in drug concentration to pancreas in male Wistar rats. It can be concluded that LNCs are could offer enhanced solubility, dissolution rate and stability for poorly water soluble drugs. The targeting efficiency of LNCs was decreased and further membrane permeability studies ought to be carried out.

Matched MeSH terms: Microscopy, Electron, Scanning
Fulltext Controlled release and angiotensin-converting enzyme inhibition properties of an antihypertensive drug based on a perindopril erbumine-layered double hydroxide nanocomposite

Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Zainal Z, Hakim MN

Int J Nanomedicine, 2012;7:2129-41.
PMID: 22619549 DOI: 10.2147/IJN.S30461

The intercalation of perindopril erbumine into Zn/Al-NO(3)-layered double hydroxide resulted in the formation of a host-guest type of material. By virtue of the ion-exchange properties of layered double hydroxide, perindopril erbumine was released in a sustained manner. Therefore, this intercalated material can be used as a controlled-release formulation.

Matched MeSH terms: Microscopy, Electron, Scanning
Construction and characterization of a Burkholderia pseudomallei wzm deletion mutant

Yuen CW, Ong EB, Mohamad S, Manaf UA, Najimudin N

J Microbiol Biotechnol, 2012 Oct;22(10):1336-42.
PMID: 23075783

In Burkholderia pseudomallei, the pathogen that causes melioidosis, the gene cluster encoding the capsular polysaccharide, is located on chromosome 1. Among the 19 capsular genes in this cluster, wzm has not been thoroughly studied. To study the function of wzm, we generated a deletion mutant and compared it with the wild-type strain. The mutant produced less biofilm in minimal media and was more sensitive to desiccation and oxidative stress compared with the wild-type strain, indicating that wzm is involved in biofilm formation and membrane integrity. Scanning electron microscopy showed that the bacterial cells of the mutant strain have more defined surfaces with indentations, whereas cells of the wild-type strain do not.

Matched MeSH terms: Microscopy, Electron, Scanning
Fulltext Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Sahib MN, Darwis Y, Peh KK, Abdulameer SA, Tan YT

Int J Nanomedicine, 2011;6:2351-66.
PMID: 22072872 DOI: 10.2147/IJN.S25363

Inhaled corticosteroids provide unique systems for local treatment of asthma or chronic obstructive pulmonary disease. However, the use of poorly soluble drugs for nebulization has been inadequate, and many patients rely on large doses to achieve optimal control of their disease. Theoretically, nanotechnology with a sustained-release formulation may provide a favorable therapeutic index. The aim of this study was to determine the feasibility of using sterically stabilized phospholipid nanomicelles of budesonide for pulmonary delivery via nebulization.

Matched MeSH terms: Microscopy, Electron, Transmission
Development of a probiotic delivery system from agrowastes, soy protein isolate, and microbial transglutaminase

Yew SE, Lim TJ, Lew LC, Bhat R, Mat-Easa A, Liong MT

J Food Sci, 2011 Apr;76(3):H108-15.
PMID: 21535834 DOI: 10.1111/j.1750-3841.2011.02107.x

Probiotic delivery system was developed via the use of microbial transglutaminase (MTG) cross-linked soy protein isolate (SPI) incorporated with agrowastes such as banana peel (BE), banana pulp (BU), and pomelo rind (PR). Inoculums of Lactobacillus bulgaricus FTDC 1511 were added to the cross-linked protein matrix. The incorporation of agrowastes had significantly (P<0.05) reduced the strength, pH value, and the lightness of the SPI gel carriers, while sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles revealed that the occurring cross-links within the SPI gel carriers were attributed to the addition of MTG. Scanning electron microscope micrographs illustrated that SPI carriers containing agrowastes have exhibited a less-dense protein matrix. All the SPI carriers possessed maximum swelling ratio at 4 to 4.5 within 15 min in simulated gastric fluid (SGF), whereas the maximum swelling ratios of SPI/BE, SPI/BU, and SPI/PR were higher compared to that of control in simulated intestinal fluid (SIF). Additionally, SPI carriers in SGF medium did not show degradation of structure, whereas a major collapse of network was observed in SIF medium, indicating controlled-release in the intestines. The addition of agrowastes into SPI carriers led to a significantly (P<0.0001) lower release of L. bulgaricus FTDC 1511 in SGF medium and a higher release in SIF medium, compared to that of the control. SPI carriers containing agrowastes may be useful transports for living probiotic cells through the stomach prior to delivery in the lower intestines.

Matched MeSH terms: Microscopy, Electron, Scanning
Lack of hepato- and nephrotoxicity induced by antifungal drug voriconazole in laboratory rats

Somchit N, Chung JH, Yaacob A, Ahmad Z, Zakaria ZA, Kadir AA

Drug Chem Toxicol, 2012 Jul;35(3):304-9.
PMID: 22288423 DOI: 10.3109/01480545.2011.614619

Voriconazole is a new, potent broad-spectrum triazole systemic antifungal drug, a second-generation azole antifungal that is increasing in popularity, especially for the treatment of invasive aspergillosis and fluconazole-resistant invasive Candida infections. However, it is also known to induce hepatotoxicity clinically. The aim of this study was to investigate the hepatotoxicity and nephrotoxicity potential of voriconazole in vivo in rats. Forty rats were treated intraperitoneally with voriconazole as single (0, 10, l00, and 200 mg/kg) or repeated (0, 10, 50, and l00 mg/kg per day for 14 days) doses. Venous blood was collected for the repeated-dose group on days 1 and 14. Rats were sacrificed 24 hours after the last dose. Body weight, liver weight, and kidney weight of rats were recorded. Livers and kidneys samples were taken for histological and transmission electron microscopy (TEM) analysis. Results revealed that voriconazole had no effects on serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphotase, gamma glutamyl transpeptidase, blood urea nitrogen, and creatinine for both the single- and repeated-dose groups. However, histologically, in the repeated 50- and 100-mg/kg voriconazole-treated rats, mild focal inflammation was observed. Under TEM, only small changes in the 100 mg/kg/day group were revealed. These results collectively demonstrated that voriconazole did not induce significant hepatotoxicity and nephrotoxicity, even at very high doses.

Matched MeSH terms: Microscopy, Electron, Transmission
Biologic interaction of three-dimensional periodontal fibroblast spheroids with collagen-based and synthetic membranes

Berahim Z, Moharamzadeh K, Rawlinson A, Jowett AK

J. Periodontol., 2011 May;82(5):790-7.
PMID: 21080786 DOI: 10.1902/jop.2010.100533

Cell-based therapy using autologous cells has been suggested as a potential approach for periodontal tissue regeneration. Spheroid systems are a form of three-dimensional cell culture that promotes cell matrix interaction, which could recapitulate the aspect of cell homeostasis in vivo. The aim of this study is to assess the interaction of periodontal fibroblast spheroids with synthetic and collagen-based membranes that have been used in guided tissue regeneration.

Matched MeSH terms: Microscopy, Electron, Scanning
Design of in situ dispersible and calcium cross-linked alginate pellets as intestinal-specific drug carrier by melt pelletization technique

Nurulaini H, Wong TW

J Pharm Sci, 2011 Jun;100(6):2248-57.
PMID: 21213311 DOI: 10.1002/jps.22459

Conventional alginate pellets underwent rapid drug dissolution and loss of multiparticulate characteristics such as aggregation in acidic medium, thereby promoting oral dose dumping. This study aimed to design sustained-release dispersible alginate pellets through rapid in situ matrix dispersion and cross-linking by calcium salts during dissolution. Pellets made of alginate and calcium salts were prepared using a solvent-free melt pelletization technique that prevented reaction between processing materials during agglomeration and allowed such a reaction to occur only in dissolution phase. Drug release was remarkably retarded in acidic medium when pellets were formulated with water-soluble calcium acetate instead of acid-soluble calcium carbonate. Different from calcium salt-free and calcium carbonate-loaded matrices that aggregated or underwent gradual erosion, rapid in situ solvation of calcium acetate in pellets during dissolution resulted in burst of gas bubbles, fast pellet breakup, and dispersion. The dispersed fragments, though exhibiting a larger specific surface area for drug dissolution than intact matrix, were rapidly cross-linked by Ca(2+) from calcium acetate and had drug release retarded till a change in medium pH from 1.2 to 6.8. Being dispersible and pH-dependent in drug dissolution, these pellets are useful as multiparticulate intestinal-specific drug carrier without exhibiting dose dumping tendency of a "single-unit-like" system via pellet aggregation.

Matched MeSH terms: Microscopy, Electron, Scanning

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