scholarly journals Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG)

2000 ◽  
Vol 7 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Bjørn Andersen ◽  
Nicola Margiotta ◽  
Mauro Coluccia ◽  
Giovanni Natile ◽  
Einar Sletten

The single-stranded oligonucleotide 5′-d(CCTCGCTCTC) (I) was reacted with the antitumor trans platinum iminoderivative trans-[PtCl2{E-HN = C(OMe)Me}2] (trans-EE) and subsequently annealed with its complementary strand 5′-d(GAGAGCGAGG) (II). The platinated duplex was characterized by 1D and 2D proton NMR spectroscopy at 600 MHz. In agreement with previous studies by different techniques trans-EE was found to form a monofunctional adduct with the duplex involving the guanine residue. The modification by trans-EE has been found to induce only minor local distortion in the duplex geometry. Two key crosspeaks observed in the NOESY map corresponding to a close contact between G5-H8 and the methoxy and the methyl group, respectively, enabled us to dock the trans-EE complex with the duplex by geometry optimization. The results support the idea that the antitumor activity of trans-EE is related to lesion of DNA fundamentally different from that of cisplatin. Unexpectedly, the NOESY spectra indicated that at the high NaCl concentration used (0.2 M) the duplex was found to undergo slow deplatination. This was subsequently proved by HPLC. In a separate experiment on platination of the single strand in a salt free environment the HPLC analysis showed that the monofunctional adduct was not deplatinated, however, after 24 hours, additidnal minor isomers were detected.

Author(s):  
Z. Hruban ◽  
J. R. Esterly ◽  
G. Dawson ◽  
A. O. Stein

Samples of a surgical liver biopsy from a patient with lactosyl ceramidosis were fixed in paraformaldehyde and postfixed in osmium tetroxide. Hepatocytes (Figs. 1, 2) contained 0.4 to 2.1 μ inclusions (LCI) limited by a single membrane containing lucid matrix and short segments of curved, lamellated and circular membranous material (Fig. 3). Numerous LCI in large connective tissue cells were up to 11 μ in diameter (Fig. 2). Heterogeneous dense bodies (“lysosomes”) were few and irregularly distributed. Rough cisternae were dilated and contained smooth vesicles and surface invaginations. Close contact with mitochondria was rare. Stacks were small and rare. Vesicular rough reticulum and glycogen rosettes were abundant. Smooth vesicular reticulum was moderately abundant. Mitochondria were round with few cristae and rare matrical granules. Golgi complex was seen rarely (Fig. 1). Microbodies with marginal plates were usual. Multivesicular bodies were very rare. Neutral lipid was rare. Nucleoli were small and perichromatin granules were large. Small bile canaliculi had few microvilli (Fig. 1).


Author(s):  
Kenneth S. Vecchio

Shock-induced reactions (or shock synthesis) have been studied since the 1960’s but are still poorly understood, partly due to the fact that the reaction kinetics are very fast making experimental analysis of the reaction difficult. Shock synthesis is closely related to combustion synthesis, and occurs in the same systems that undergo exothermic gasless combustion reactions. The thermite reaction (Fe2O3 + 2Al -> 2Fe + Al2O3) is prototypical of this class of reactions. The effects of shock-wave passage through porous (powder) materials are complex, because intense and non-uniform plastic deformation is coupled with the shock-wave effects. Thus, the particle interiors experience primarily the effects of shock waves, while the surfaces undergo intense plastic deformation which can often result in interfacial melting. Shock synthesis of compounds from powders is triggered by the extraordinarily high energy deposition rate at the surfaces of the powders, forcing them in close contact, activating them by introducing defects, and heating them close to or even above their melting temperatures.


1969 ◽  
Vol 14 (2) ◽  
pp. 97-97
Author(s):  
CHARLES J. MCINTYRE
Keyword(s):  

1994 ◽  
Vol 07 (04) ◽  
pp. 180-182
Author(s):  
N. Gofton ◽  
Joanne Cockshutt

The AO wire passer can be used as an effective guide for passage of obstetrical saw wire for osteotomy. Use of the wire saw and passer reduces soft tissue trauma by minimizing tissue dissection, and promoting positioning of the saw in close contact with the bone.


1987 ◽  
Vol 58 (02) ◽  
pp. 786-789 ◽  
Author(s):  
O Behnke

SummaryAdhesion of rat blood platelets to native rat tail collagen fibrils was studied in the electron microscope under conditions that preserved collagen-associated proteoglycans (CAPG). The CAPG molecules were aligned in chain-like configurations that encircled the fibrils with a 65 nm period; they appeared to coat the fibrils completely and extended 60-100 nm away from the fibril. The initial platelet-fibril contact occurred between the platelet glycocalyx and the CAPG of the fibrils i.e. between two surfaces with net-negative charges. When close contact was established between the fibril surface proper and the platelet membrane, CAPG were not identified in the area of contact, and the collagen-platelet distance was reduced to a ~10-12 nm wide gap traversed by delicate links in register with fibril periodicities.


1997 ◽  
Vol 77 (03) ◽  
pp. 562-567 ◽  
Author(s):  
Takehiro Kaida ◽  
Hiroyuki Matsuno ◽  
Masayuki Niwa ◽  
Osamu Kozawa ◽  
Hideo Miyata ◽  
...  

SummaryThe antithrombotic and restenosis-preventing effects of FK633, an inhibitor of platelet aggregation via binding to the glycoprotein (GP) Ilb/IIIa receptor, were studied. IC50 value of FK633 against platelet aggregation ex vivo induced by 2.5 |iM adenosine diphosphate (ADP) was 5.4 X 10"7 M as determined using hamster platelet rich plasma. The inhibitory effect was also investigated in vivo on thrombus formation at the carotid arterial wall injured by a modified catheter. As a control, the left carotid artery was injured and the time required to develop a thrombotic occlusion (3.9 ±1.1 min, mean ± S.E.M., n = 18) was determined. Then, the right carotid artery of the same animal was injured while a continuous intravenous (i.v.) infusion of FK633 was administered at doses of 0 (saline), 0.1,0.3 or 1.0 mg/kg/h. The time to occlusion was dose-dependently prolonged. In a separate experiment, 10% of the total tPA dose (0.52 mg/kg) was injected into the injured artery as a bolus and the remaining was infused i.v. at a constant rate for 30 min. When FK633 (0.3 or 1.0 mg/kg/h) was infused together with tPA, late patency of the reperfused artery was much improved as compared with that of treatment with tPA alone. Bleeding time, measured at the end of the tPA infusion, was markedly prolonged when the higher dose of FK633 (1.0 mg/kg/h) was coadministered, however coadministration of the lower dose of FK633 (0.3 mg/kg/h) was almost without prolongation on the bleeding time, despite a significant effect on the vascular patency after thrombolysis. Next, neointima formation was evaluated 2 weeks after the vascular injury. When FK633 (0.3 mg/kg/h) was continuously infused i. v. by an implanted osmotic pump for 3,7 or 14 days after the vascular injury, the neointimal area formation was significantly suppressed in the treatment groups for 7 or 14 days. These findings suggest that FK633 inhibits platelet activation in the injured artery and improves vascular patency after thrombolysis with tPA with a concomitant suppression of neointima formation.


2020 ◽  
Vol 33 (1) ◽  
pp. 41-47
Author(s):  
Mohsena Akhter ◽  
Ishrat Bhuiyan ◽  
Zulfiqer Hossain Khan ◽  
Mahfuza Akhter ◽  
Gulam Kazem Ali Ahmad ◽  
...  

Background: Scabies is one of the most common skin diseases in our country. It is caused by the mite Sarcoptes scabiei var hominis, which is an ecto-parasite infesting the epidermis. Scabies is highly contagious. Prevalence is high in congested or densely populated areas. Individuals with close contact with an affected person should be treated with scabicidal which is available in both oral and topical formulations. The only oral but highly effective scabicidal known to date is Ivermectin. Amongst topical preparations, Permethrin 5 % cream is the treatment of choice. Objective: To evaluate the efficacy & safety of oral Ivermectin compared to topical Permethrin in the treatment of scabies. Methodology: This prospective, non-randomized study was conducted at the out-patient department of Dermatology and Venereology of Shaheed Suhrawardy Medical College & Hospital over a period of 6 months, from August 2016 to January 2017. The study population consisted of one hundred patients having scabies, enrolled according to inclusion criteria. They were divided into two groups. group A was subjected to oral Ivermectin and the group B to Permethrin 5% cream. Patients were followed up on day 7 and 14 for assessment of efficacy and safety. Result: The mean scoring with SD in group A (Ivermectin) and group B (Permethrin) were 8.26 ± 2.22 and 7.59 ± 2.01 respectively at the time of observation. The difference between the mean score of the two group is not significant (p=0.117) the mean scoring with SD in group A and group B were 4.54 ± 2.05 and 1.64 ± 1.84 respectively at 7thdays. The difference between the mean score of the two group is significant (p<0.001). The mean scoring with SD in group A and group B were 2.68± 2.35 and .36± 1.10 respectively at 14th day difference between the mean score of the group is significant (p<0.001). Conclusion: Topical application of permethrin 5% cream is more effective and safer than oral Ivermectin in the treatment of scabies. TAJ 2020; 33(1): 41-47


2020 ◽  
Vol 99 (10) ◽  

Besides the conventional extracorporeal circulation, commonly used in cardiac surgery, the methods of extracorporeal life support (ECLS) have been applied ever more frequently in thoracic surgery in recent years. The most commonly used modalities of such supports include extracorporeal membrane oxygenation (ECMO) and the Novalung interventional lung assist device (iLA). Successful application of ECLS has led to its more frequent use in general thoracic surgery, especially as a tool to treat hypercapnia and to ensure oxygenation and haemodynamic support. However, these methods are essential in lung transplant programmes; without their help, in most cases, it would not be possible to perform the transplantatioz or prevent the severe complications associated with critical primary graft dysfunction. Additionally, the extracorporeal circulation also facilitates the performing of specific surgical procedures that would not be feasible under standard conditions or would be associated with an inadequate risk. The application of extracorporeal life supports can fundamentally increase the level of resection when treating advanced intrathoracic malignancies that are in close contact with the heart and large vessels or even directly extend into them. Without the possibility of resecting such structures en bloc, together with the tumour, and, thus, achieving an R0 resection, these malignant tumours are often directly contraindicated for surgery or are operated non-radically, i.e. unsuccessfully. Complete tumour resection is the most important prognostic factor in the surgery.


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