scholarly journals Repurposing mechanistic insight of PDE-5 inhibitor in cancer chemoprevention through mitochondrial-oxidative stress intervention and blockade of DuCLOX signalling

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Manjari Singh ◽  
Sweta Kasna ◽  
Subhadeep Roy ◽  
Sara Aldosary ◽  
Abdulaziz S. Saeedan ◽  
...  

Abstract Background This study evaluates the anti-cancer effects of Tadalafil (potent PDE-5 inhibitor) in female albino wistar rats against n-methyl n-nitrosourea induced mammary gland carcinogenesis. Methods The animals were selected and randomly divided among four groups and each group contains six animals per group. The animal tissue and serum samples were evaluated for the presence of antioxidant parameters and the cellular morphology was studied using carminic staining, haematoxylin staining and scanning electron microscopy followed by immunoblotting analysis. Results On the grounds of hemodynamic recordings and morphology, n-methyl n-nitrosourea treated group showed distorted changes along with distorted morphological parameters. For morphological analysis, the mammary gland tissues were evaluated using scanning electron microscopy, whole mount carmine staining, haematoxylin and eosin staining. The serum samples were evaluated for the evaluation of oxidative stress markers and inflammatory markers. The level of caspase 3 and 8 were also evaluated for the estimation of apoptosis. The fatty acid profiling of mammary gland tissue was evaluated using fatty acid methyl esters formation. The mitochondrial mediated apoptosis and inflammatory markers were evaluated using immunoblotting assay. Conclusion The results confirm that Tadalafil treatment restored all the biological markers to the normal and its involvement in mitochondrial mediated death apoptosis pathway along with inhibition of inflammatory markers.

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Aliya Nur Hasanah ◽  
Firdha Senja Maelaningsih ◽  
Fadli Apriliandi ◽  
Akhmad Sabarudin

A monolithic imprinted atenolol column was constructed by in situ polymerisation using a methacrylic acid monomer and a 1 : 1 (v/v) porogen of propanol: toluene with two template: monomer: crosslinker combinations, namely, MIP 1 (1 : 4 : 20) and MIP 2 (1 : 5 : 20). Physical characterisation of the monolithic columns consisted of permeability testing, Fourier transform infrared (FTIR) testing, surface area analysis (SAA), and scanning electron microscopy (SEM). The permeability value of four monolithic columns was in the good category: MIP 1 (24.01 mD), NIP 1 (56.43 mD), MIP 2 (23.03 mD), and NIP 2 (14.47 mD). The polymerisation process of these four monolithic imprinted columns was carried out perfectly, as shown by the absence of vinyl groups (1000 cm−1 and 900 cm−1) during FTIR testing. Based on SAA testing, the pores of the four polymers were classified as mesopores. The best monolithic column was MIP 1, as seen from the intercolumn and intracolumn reproducibility values and a % RSD <2.0%. The MIP 1 column was selective towards atenolol, as seen from the selectivity factor, imprinting factor (IF), and resolution (Rs) values. The IF values of MIP 1 were atenolol (204.62), metoprolol (3.36), and propranolol (1.27). The Rs value between atenolol and the analogue compounds was 7.23. The MIP 1 column can be used for the analysis of atenolol in blood serum samples with an average percentage recovery rate of 94.88 ± 4.43%.


2019 ◽  
Author(s):  
Brandon S Jackson ◽  
Julien Nunes ◽  
Etheresia Pretorius

Abstract Background. Patients infected with the human immunodeficiency virus (HIV) are more prone to systemic inflammation and pathological clotting, and many may develop deep vein thrombosis (DVT) as a result of this dysregulated inflammatory profile. Coagulation tests are not routinely performed unless there is a specific reason. Methods. We recruited ten healthy control subjects, 35 HIV negative patients with deep vein thrombosis (HIV negative-DVT), and 13 HIV patients with DVT (HIV positive-DVT) on the primary antiretroviral therapy (ARV) regimen- Emtricitabine, Tenofovir and Efavirenz. Serum inflammatory markers, haematological results, viscoelastic properties (using thromboelastography-TEG) and scanning electron microscopy (SEM) of whole blood (WB) were used to compare the groups.Results. DVT patients (HIV positive and HIV negative) have anaemia with raised inflammatory markers which are more pronounced in HIV positive patients. HIV positive-DVT patients also have a microcytic hypochromic anaemia. DVT patients have a hypercoagulable profile on the TEG but no significant difference between HIV negative-DVT and HIV positive-DVT groups. The TEG analysis compared well and supported our ultrastructural results. Scanning electron microscopy of HIV positive-DVT patient’s red blood cells (RBCs) and platelets demonstrates inflammatory changes including abnormal cell shapes, irregular membranes and microparticle formation. All the ultrastructural changes were more prominent in the HIV positive-DVT patients. Conclusions. HIV positive patients have an increased hypercoagulability and DVT prevalence. Our results point to the importance of looking at the coagulation system function in HIV infected individuals with DVT. Parameters like haematological markers, coagulation tests (activated partial thromboplastin time and prothrombin time / International normalized ratio), thromboelastography and global clotting tests should be used as standard indicators of hypercoagulation and part of standard clinical practice.


Author(s):  
P.S. Porter ◽  
T. Aoyagi ◽  
R. Matta

Using standard techniques of scanning electron microscopy (SEM), over 1000 human hair defects have been studied. In several of the defects, the pathogenesis of the abnormality has been clarified using these techniques. It is the purpose of this paper to present several distinct morphologic abnormalities of hair and to discuss their pathogenesis as elucidated through techniques of scanning electron microscopy.


Author(s):  
P.J. Dailey

The structure of insect salivary glands has been extensively investigated during the past decade; however, none have attempted scanning electron microscopy (SEM) in ultrastructural examinations of these secretory organs. This study correlates fine structure by means of SEM cryofractography with that of thin-sectioned epoxy embedded material observed by means of transmission electron microscopy (TEM).Salivary glands of Gromphadorhina portentosa were excised and immediately submerged in cold (4°C) paraformaldehyde-glutaraldehyde fixative1 for 2 hr, washed and post-fixed in 1 per cent 0s04 in phosphosphate buffer (4°C for 2 hr). After ethanolic dehydration half of the samples were embedded in Epon 812 for TEM and half cryofractured and subsequently critical point dried for SEM. Dried specimens were mounted on aluminum stubs and coated with approximately 150 Å of gold in a cold sputtering apparatus.Figure 1 shows a cryofractured plane through a salivary acinus revealing topographical relief of secretory vesicles.


Author(s):  
Nakazo Watari ◽  
Yasuaki Hotta ◽  
Yoshio Mabuchi

It is very useful if we can observe the identical cell elements within the same sections by light microscopy (LM), transmission electron microscopy (TEM) and/or scanning electron microscopy (SEM) sequentially, because, the cell fine structure can not be indicated by LM, while the color is; on the other hand, the cell fine structure can be very easily observed by EM, although its color properties may not. However, there is one problem in that LM requires thick sections of over 1 μm, while EM needs very thin sections of under 100 nm. Recently, we have developed a new method to observe the same cell elements within the same plastic sections using both light and transmission (conventional or high-voltage) electron microscopes.In this paper, we have developed two new observation methods for the identical cell elements within the same sections, both plastic-embedded and paraffin-embedded, using light microscopy, transmission electron microscopy and/or scanning electron microscopy (Fig. 1).


Author(s):  
Ronald H. Bradley ◽  
R. S. Berk ◽  
L. D. Hazlett

The nude mouse is a hairless mutant (homozygous for the mutation nude, nu/nu), which is born lacking a thymus and possesses a severe defect in cellular immunity. Spontaneous unilateral cataractous lesions were noted (during ocular examination using a stereomicroscope at 40X) in 14 of a series of 60 animals (20%). This transmission and scanning microscopic study characterizes the morphology of this cataract and contrasts these data with normal nude mouse lens.All animals were sacrificed by an ether overdose. Eyes were enucleated and immersed in a mixed fixative (1% osmium tetroxide and 6% glutaraldehyde in Sorenson's phosphate buffer pH 7.4 at 0-4°C) for 3 hours, dehydrated in graded ethanols and embedded in Epon-Araldite for transmission microscopy. Specimens for scanning electron microscopy were fixed similarly, dehydrated in graded ethanols, then to graded changes of Freon 113 and ethanol to 100% Freon 113 and critically point dried in a Bomar critical point dryer using Freon 13 as the transition fluid.


Author(s):  
Jane A. Westfall ◽  
S. Yamataka ◽  
Paul D. Enos

Scanning electron microscopy (SEM) provides three dimensional details of external surface structures and supplements ultrastructural information provided by transmission electron microscopy (TEM). Animals composed of watery jellylike tissues such as hydras and other coelenterates have not been considered suitable for SEM studies because of the difficulty in preserving such organisms in a normal state. This study demonstrates 1) the successful use of SEM on such tissue, and 2) the unique arrangement of batteries of nematocysts within large epitheliomuscular cells on tentacles of Hydra littoralis.Whole specimens of Hydra were prepared for SEM (Figs. 1 and 2) by the fix, freeze-dry, coat technique of Small and Màrszalek. The specimens were fixed in osmium tetroxide and mercuric chloride, freeze-dried in vacuo on a prechilled 1 Kg brass block, and coated with gold-palladium. Tissues for TEM (Figs. 3 and 4) were fixed in glutaraldehyde followed by osmium tetroxide. Scanning micrographs were taken on a Cambridge Stereoscan Mark II A microscope at 10 KV and transmission micrographs were taken on an RCA EMU 3G microscope (Fig. 3) or on a Hitachi HU 11B microscope (Fig. 4).


Author(s):  
J.N. Ramsey ◽  
D.P. Cameron ◽  
F.W. Schneider

As computer components become smaller the analytical methods used to examine them and the material handling techniques must become more sensitive, and more sophisticated. We have used microbulldozing and microchiseling in conjunction with scanning electron microscopy, replica electron microscopy, and microprobe analysis for studying actual and potential problems with developmental and pilot line devices. Foreign matter, corrosion, etc, in specific locations are mechanically loosened from their substrates and removed by “extraction replication,” and examined in the appropriate instrument. The mechanical loosening is done in a controlled manner by using a microhardness tester—we use the attachment designed for our Reichert metallograph. The working tool is a pyramid shaped diamond (a Knoop indenter) which can be pushed into the specimen with a controlled pressure and in a specific location.


Author(s):  
Yasushi Kokubo ◽  
Hirotami Koike ◽  
Teruo Someya

One of the advantages of scanning electron microscopy is the capability for processing the image contrast, i.e., the image processing technique. Crewe et al were the first to apply this technique to a field emission scanning microscope and show images of individual atoms. They obtained a contrast which depended exclusively on the atomic numbers of specimen elements (Zcontrast), by displaying the images treated with the intensity ratio of elastically scattered to inelastically scattered electrons. The elastic scattering electrons were extracted by a solid detector and inelastic scattering electrons by an energy analyzer. We noted, however, that there is a possibility of the same contrast being obtained only by using an annular-type solid detector consisting of multiple concentric detector elements.


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