scholarly journals Evaluation of the Morphological Effects of TDT 067 (Terbinafine in Transfersome) and Conventional Terbinafine on Dermatophyte HyphaeIn VitroandIn Vivo

2012 ◽  
Vol 56 (5) ◽  
pp. 2530-2534 ◽  
Author(s):  
M. Ghannoum ◽  
N. Isham ◽  
W. Henry ◽  
H.-A. Kroon ◽  
S. Yurdakul

ABSTRACTTDT 067 is a novel, carrier-based dosage form of terbinafine in Transfersome (1.5%) formulated for topical delivery of terbinafine to the nail, nail bed, and surrounding tissue. We examined the effects of TDT 067 and conventional terbinafine on the morphology of dermatophytes.Trichophyton rubrumhyphae were exposed to TDT 067 or terbinafine (15 mg/ml) and examined under white light, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subungual debris from patients treated with TDT 067 in a clinical trial was also examined. Exposure ofT. rubrumhyphae to TDT 067 led to rapid and extensive ultrastructural changes. Hyphal distortion was evident as early as 4 h after exposure to TDT 067. After 24 h, there was complete disruption of hyphal structure with few intact hyphae remaining. Exposure to terbinafine resulted in morphological alterations similar to those seen with TDT 067; however, the effects of TDT 067 were more extensive, whereas a portion of hyphae remained intact after 24 h of exposure to terbinafine. Lipid droplets were observed under TEM following 30 min of exposure to TDT 067, which after 24 h had filled the intracellular space. These effects were confirmedin vivoin subungual debris from patients with onychomycosis who received topical treatment with TDT 067. The Transfersome in TDT 067 may potentiate the action of terbinafine by delivering terbinafine more effectively to its site of action inside the fungus. Ourin vivodata confirm that TDT 067 can enter fungus in the nail bed of patients with onychomycosis and exert its antifungal effects.

2015 ◽  
Vol 59 (11) ◽  
pp. 6946-6951 ◽  
Author(s):  
Bo Wang ◽  
Yufeng Jiang ◽  
Zhuo Wang ◽  
Fangfang Li ◽  
Guoqiang Xing ◽  
...  

ABSTRACTSpillage of cyst contents during surgery is the major cause of recurrences of hydatidosis, also called cystic echinococcosis (CE). Currently, many scolicidal agents are used for inactivation of the cyst contents. However, due to complications in the use of those agents, new and more-effective treatment options are urgently needed. The aim of this study was to investigate thein vitroefficacy of arsenic trioxide (ATO) againstEchinococcus granulosusprotoscolices. Protoscolices ofE. granulosuswere incubatedin vitrowith 2, 4, 6, and 8 μmol/liter ATO; viability of protoscolices was assessed daily by microscopic observation of movements and 0.1% eosin staining. A small sample from each culture was processed for scanning and transmission electron microscopy. ATO demonstrated a potent ability to kill protoscolices, suggesting that ATO may represent a new strategy in treating hydatid cyst echinococcosis. However, thein vivoefficacy and possible side effects of ATO need to be explored.


Author(s):  
H. J. Finol ◽  
M. E. Correa ◽  
L.A. Sosa ◽  
A. Márquez ◽  
N.L. Díaz

In classical oncological literature two mechanisms for tissue aggression in patients with cancer have been described. The first is the progressive invasion, infiltration and destruction of tissues surrounding primary malignant tumor or their metastases; the other includes alterations produced in remote sites that are not directly affected by any focus of disease, the so called paraneoplastic phenomenon. The non-invaded tissue which surrounds a primary malignant tumor or its metastases has been usually considered a normal tissue . In this work we describe the ultrastructural changes observed in hepatocytes located next to metastases from diverse malignant tumors.Hepatic biopsies were obtained surgically in patients with different malignant tumors which metatastized in liver. Biopsies included tumor mass, the zone of macroscopic contact between the tumor and the surrounding tissue, and the tissue adjacent to the tumor but outside the macroscopic area of infiltration. The patients (n = 5), 36–75 years old, presented different tumors including rhabdomyosarcoma, leiomyosarcoma, pancreas carcinoma, biliar duct carcinoma and colon carcinoma. Tissue samples were processed with routine techniques for transmission electron microscopy and observed in a Hitachi H-500 electron microscope.


Crystals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1131
Author(s):  
Maricela Santana ◽  
Gonzalo Montoya ◽  
Raúl Herrera ◽  
Lía Hoz ◽  
Enrique Romo ◽  
...  

Dental cementum contains unique molecules that regulate the mineralization process in vitro and in vivo, such as cementum protein 1 (CEMP1). This protein possesses amino acid sequence motifs like the human recombinant CEMP1 with biological activity. This novel cementum protein 1-derived peptide (CEMP1-p3, from the CEMP1’s N-terminal domain: (QPLPKGCAAVKAEVGIPAPH), consists of 20 amino acids. Hydroxyapatite (HA) crystals could be obtained through the combination of the amorphous precursor phase and macromolecules such as proteins and peptides. We used a simple method to synthesize peptide/hydroxyapatite nanocomposites using OCP and CEMP1-p3. The characterization of the crystals through scanning electron microscopy (SEM), powder X-ray diffraction (XRD), high--resolution transmission electron microscopy (HRTEM), and Raman spectroscopy revealed that CEMP1-p3 transformed OCP into hydroxyapatite (HA) under constant ionic strength and in a buffered solution. CEMP1-p3 binds and highly adsorbs to OCP and is a potent growth stimulator of OCP crystals. CEMP1-p3 fosters the transformation of OCP into HA crystals with crystalline planes (300) and (004) that correspond to the cell of hexagonal HA. Octacalcium phosphate crystals treated with CEMP1-p3 grown in simulated physiological buffer acquired hexagonal arrangement corresponding to HA. These findings provide new insights into the potential application of CEMP1-p3 on possible biomimetic approaches to generate materials for the repair and regeneration of mineralized tissues, or restorative materials in the orthopedic field.


1995 ◽  
Vol 23 (3) ◽  
pp. 200-206 ◽  
Author(s):  
P Carbognani ◽  
L Spaggiari ◽  
M Rusca ◽  
L Cattelani ◽  
P Solli ◽  
...  

During lung preservation, the vascular endothelium is probably the first site of damage and these lesions are considered the main limiting factor in solid-organ preservation. In the present study, the ultrastructural changes in the endothelial cells of human pulmonary artery hypothermically stored (at 4 °C) for 6 and 12 h in Euro-Collins, University of Wisconsin and Ringer-lactate solutions were compared. The arteries obtained from three patients who underwent pneumonectomy were divided into 20 segments and preserved in the three solutions mentioned. The specimens, which were fixed in osmic acid, were examined using transmission electron microscopy. Transmission electron microscopy indicated that the cells stored in the University of Wisconsin solution either for 6 or 12 h were the best preserved, while the most severely damaged cells were those stored in Euro-Collins solution, even after just 6 h. The cells stored in Ringer-lactate showed an intermediate level of damage. The data from an ultrastructural grading scale, which quantified the damage to the cytoplasm, mitochondria and nucleus, were in broad agreement with the general transmission electron microscopy observations. Analysis of variance of the grading scale data showed that there were statistically significant differences between the groups after both 6 and 12 h storage ( P < 0.05).


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Gotelli ◽  
B. Galati ◽  
D. Medan

Tapetum, orbicule, and pollen grain ontogeny inColletia paradoxaandDiscaria americanawere studied with transmission electron microscopy (TEM). The ultrastructural changes observed during the different stages of development in the tapetal cells and related to orbicule and pollen grain formation are described. The proorbicules have the appearance of lipid globule, and their formation is related to the endoplasmic reticulum of rough type (ERr). This is the first report on the presence of orbicules in the family Rhamnaceae. Pollen grains are shed at the bicellular stage.


2017 ◽  
Vol 46 (1) ◽  
pp. 47-61 ◽  
Author(s):  
Uschi M. Graham ◽  
Robert A. Yokel ◽  
Alan K. Dozier ◽  
Lawrence Drummy ◽  
Krishnamurthy Mahalingam ◽  
...  

This is the first utilization of advanced analytical electron microscopy methods, including high-resolution transmission electron microscopy, high-angle annular dark field scanning transmission electron microscopy, electron energy loss spectroscopy, and energy-dispersive X-ray spectroscopy mapping to characterize the organ-specific bioprocessing of a relatively inert nanomaterial (nanoceria). Liver and spleen samples from rats given a single intravenous infusion of nanoceria were obtained after prolonged (90 days) in vivo exposure. These advanced analytical electron microscopy methods were applied to elucidate the organ-specific cellular and subcellular fate of nanoceria after its uptake. Nanoceria is bioprocessed differently in the spleen than in the liver.


2010 ◽  
Vol 10 ◽  
pp. 879-893 ◽  
Author(s):  
Nathaniel G. N. Milton ◽  
J. Robin Harris

The diabetes-associated human islet amyloid polypeptide (IAPP) is a 37-amino-acid peptide that forms fibrilsin vitroandin vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-β (Aβ) and prion protein (PrP) fibrils. Previous studies have shown that catalase binds to Aβ fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27. This study presents a transmission electron microscopy (TEM)—based analysis of fibril formation and the binding of human erythrocyte catalase to IAPP fibrils. The results show that human IAPP 1-37, 8-37, and 20-29 peptides form fibrils with diverse and polymorphic structures. All three forms of IAPP bound catalase, and complexes of IAPP 1-37 or 8-37 with catalase were identified by immunoassay. The binding of biotinylated IAPP to catalase was high affinity with a KDof 0.77nM, and could be inhibited by either human or rat IAPP 1-37 and 8-37 forms. Fibrils formed by the PrP 118-135 peptide with a Gly-Ala-Val-Val sequence also bound catalase. These results suggest that catalase recognizes a Gly-Ala-Ile-Leu—like sequence in amyloid fibril-forming peptides. For IAPP 1-37 and 8-37, the catalase binding was primarily directed towards fibrillar rather than ribbon-like structures, suggesting differences in the accessibility of the human IAPP 24-27 Gly-Ala-Ile-Leu region. This suggests that catalase may be able to discriminate between different structural forms of IAPP fibrils. The ability of catalase to bind IAPP, Aβ, and PrP fibrils demonstrates the presence of similar accessible structural motifs that may be targets for antiamyloid therapeutic development.


Coatings ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 496
Author(s):  
Mingyu Zhao ◽  
Guanqi Liu ◽  
Ying Li ◽  
Xiaodong Yu ◽  
Shenpo Yuan ◽  
...  

In this study, a specific Mg–Zn–RE alloy membrane with 6 wt.% zinc and 2.7 wt.% rare earth elements (Y, Gd, La and Ce) was prepared to investigate implant degradation, transport mechanism and guide bone regeneration in vivo. The Mg-membrane microstructure and precipitates were characterized by the scanning electron microscopy (SEM) and the transmission electron microscopy (TEM). The Mg-membrane degradation process and effect on osteogenesis were investigated in a critical-sized rat calvarial defect model via micro-CT examination and hard tissue slicing after 2-, 5- and 8-week implants. Then, the distribution of elements in organs after 1-, 2- and 4-weeks implantation was examined to explore their transportation routes. Results showed that two types of precipitates had formed in the Mg–membrane after a 10-h heat treatment at 175 °C: γ-phase MgZn precipitation with dissolved La, Ce and Gd, and W-phase Mg3(Y, Gd)2Zn3 precipitation rich in Y and Gd. In the degradation process of the Mg-membrane, the Mg matrix degraded first, and the rare earth-rich precipitation particles were transferred to a more stable phosphate compound. The element release rate was dependent on the precipitate type and composition. Rare earth elements may be transported mainly through the lymph system. The defects were repaired rapidly by the membranes. The Mg-membrane used in the present study showed excellent biocompatibility and enhanced bone formation in the vicinity of the implants.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 263 ◽  
Author(s):  
Maria Letizia Manca ◽  
Iris Usach ◽  
José Esteban Peris ◽  
Antonella Ibba ◽  
Germano Orrù ◽  
...  

New three-dimensionally-structured hybrid phospholipid vesicles, able to load clotrimazole in a high amount (10 mg/mL), were obtained for the first time in this work by significantly reducing the amount of water (≤10%), which was replaced with a mixture of glycerol and ethanol (≈90%). A pre-formulation study was carried out to evaluate the effect of both the composition of the hydrating medium and the concentration of the phospholipid on the physico-chemical properties of hybrid vesicles. Four different three-dimensionally-structured hybrid vesicles were selected as ideal systems for the topical application of clotrimazole. An extensive physico-chemical characterization performed using transmission electron microscopy (TEM), cryogenic transmission electron microscopy (cryo-TEM), 31P-NMR, and small-angle X-ray scattering (SAXS) displayed the formation of small, multi-, and unilamellar vesicles very close to each other, and was capable of forming a three-dimensional network, which stabilized the dispersion. Additionally, the dilution of the dispersion with water reduced the interactions between vesicles, leading to the formation of single unilamellar vesicles. The evaluation of the in vitro percutaneous delivery of clotrimazole showed an improved drug deposition in the skin strata provided by the three-dimensionally-structured vesicles with respect to the commercial cream (Canesten®) used as a reference. Hybrid vesicles were highly biocompatible and showed a significant antifungal activity in vitro, greater than the commercial cream Canesten®. The antimycotic efficacy of formulations was confirmed by the reduced proliferation of the yeast cells at the site of infection in vivo. In light of these results, clotrimazole-loaded, three-dimensionally-structured hybrid vesicles appear to be one of the most innovative and promising formulations for the treatment of candidiasis infections.


1987 ◽  
Vol 252 (4) ◽  
pp. R774-R781 ◽  
Author(s):  
P. J. Utterback ◽  
S. C. Hand

Alteration of intracellular pH (pHi) influences yolk platelet degradation during preemergence development in Artemia embryos. Cysts incubated for 10 h under conditions of aerobic development (aqueous medium equilibrated with 60% N2-40% O2, pHi greater than or equal to 7.9) exhibit a significant decrease in numbers of yolk platelets and platelet protein. In contrast, cysts incubated for 10 h under aerobic acidosis (60% CO2-40% O2, pHi = 6.8) show no significant decrease in numbers of yolk platelets or platelet protein. When subjected to alkaline conditions in vitro, yolk platelets release protein exponentially as a function of time. The process is essentially complete in 40 min. The extent of protein and lipid release from platelets increases markedly as pH of the medium is raised in increments from 6.3 to 8.0. Concomitant with these changes are reduction (50%) in platelet dry weight and reduction (21%) in platelet diameter. Transmission electron microscopy does not reveal major structural differences between isolated yolk platelets and those contained in hydrated embryos. The proton effects on platelet composition and size detected in vitro may explain in part the mechanism of platelet degradation observed during aerobic development and its suppression under conditions of acidic pHi.


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