[Pharmacodynamic Study of Racemic TJ0711 on Renal Hypertensive Rats After Long-Term Administration].
[Pharmacodynamic study of racemic TJ0711 on renal hypertensive rats after long-term administration].
Filed under: Drug and Alcohol Rehabilitation
Yao Xue Xue Bao. 2012 Aug; 47(8): 1001-5
Li RJ, Qiu J, Zhang XN, Chen J, Li G
The study is to observe the effect of racemic TJ0711 on blood pressure and heart rate as well as protection of cardiovascular system of renal hypertensive rats after long-term administration. The renal hypertensive models were established by the two-kidney, one-clip (2K1C) method in Wistar rats. Four weeks later, assigned the rats whose SBP had increased at least 4 kPa randomly into 5 groups: racemic TJ0711 10, 20 and 40 mg x kg(-1) groups, carvedilol control group, model group and sham group (n=10), ig administration once daily. The changes of BP (blood press) and HR (heart rate) before and after administration were measured by tail-cuff method weekly. Plasma samples of all animals were taken in 6-8 weeks, and plasma MDA as well as renin, angiotensin II (Ang II) and endothelin-1 (ET-1) levels were measured. Left ventricle was cut off after 9 weeks, and left ventricular weight index (LVWI) and hydroxyproline were measured. The significant decrease of the BP of TJ0711 40 mg x kg(-1) group was observed after TJ0711 ig administration for 4 weeks, and this effect remained till the end of the study. In 8th week, the systolic blood pressure values were: TJ0711 40 mg x kg(-1) group 18.93 +/- 1.82 kPa (vs 21.30 +/- 2.30 kPa, P < 0.05); 20 mg x kg(-1) group 20.68 +/- 3.29 kPa (vs 22.19 +/- 2.88 kPa). The plasma MDA level of all treated groups was significantly lower than that of model group, so were the plasma renin, Ang II and ET-1 levels (P < 0.05). LVWI and hydroxyproline content of myocardial tissue decreased to some extent, but was not significant as compared with that of model group. The study showed that TJ0711 repeated dosing could reduce BP level beginning from drug administration; besides block adrenal alpha and beta receptors to play an antihypertensive role. The sustained antihypertensive effect also related to reduce plasma vasoconstrictor substances and oxidation product MDA. These effects benefited cardiovascular protection. HubMed – drug
[Research progress in co-delivery of gene and chemotherapy drugs with cationic liposome carrier for cancer therapy].
Filed under: Drug and Alcohol Rehabilitation
Yao Xue Xue Bao. 2012 Aug; 47(8): 986-92
Chen WG, Liu YG, Wang SB, Chen AZ
Despite recent advances in conventional therapeutic approaches for cancer, the efficacy of chemotherapy for cancer is limited due to the drug resistance and toxic side effects during treatment. To overcome drug resistance, higher doses of the toxic chemotherapy drugs are frequently administered, thus leading to even severe adverse side effects, which have limited their clinical application. Cationic liposome as a novel non-viral carrier for co-delivery of gene and chemotherapy drugs in cancer gene therapy has already attracted more and more attention in recent years. Most importantly, this combined strategy can generate a significant synergistic effect, which can silence the related gene expression and increase the concentration of the intracellular chemotherapy drugs. This approach allows the use of a much lower dose of the chemotherapy drugs to achieve same therapeutic effect, which may have the potential for overcoming some major limitations of the conventional chemotherapy. In conclusion, co-delivery of gene and chemotherapy drugs with cationic liposome delivery system will play a vital role in the future and especially could be a promising clinical treatment for drug-resistant tumors.
HubMed – drug
Shiga toxin 2-induced intestinal pathology in infant rabbits is A-subunit dependent and responsive to the tyrosine kinase and potential ZAK inhibitor imatinib.
Filed under: Drug and Alcohol Rehabilitation
Front Cell Infect Microbiol. 2012; 2: 135
Stone SM, Thorpe CM, Ahluwalia A, Rogers AB, Obata F, Vozenilek A, Kolling GL, Kane AV, Magun BE, Jandhyala DM
Shiga toxin producing Escherichia coli (STEC) are a major cause of food-borne illness worldwide. However, a consensus regarding the role Shiga toxins play in the onset of diarrhea and hemorrhagic colitis (HC) is lacking. One of the obstacles to understanding the role of Shiga toxins to STEC-mediated intestinal pathology is a deficit in small animal models that perfectly mimic human disease. Infant rabbits have been previously used to study STEC and/or Shiga toxin-mediated intestinal inflammation and diarrhea. We demonstrate using infant rabbits that Shiga toxin-mediated intestinal damage requires A-subunit activity, and like the human colon, that of the infant rabbit expresses the Shiga toxin receptor Gb(3). We also demonstrate that Shiga toxin treatment of the infant rabbit results in apoptosis and activation of p38 within colonic tissues. Finally we demonstrate that the infant rabbit model may be used to test candidate therapeutics against Shiga toxin-mediated intestinal damage. While the p38 inhibitor SB203580 and the ZAK inhibitor DHP-2 were ineffective at preventing Shiga toxin-mediated damage to the colon, pretreatment of infant rabbits with the drug imatinib resulted in a decrease of Shiga toxin-mediated heterophil infiltration of the colon. Therefore, we propose that this model may be useful in elucidating mechanisms by which Shiga toxins could contribute to intestinal damage in the human.
HubMed – drug
Radiation-induced changes in microcirculation and interstitial fluid pressure affecting the delivery of macromolecules and nanotherapeutics to tumors.
Filed under: Drug and Alcohol Rehabilitation
Front Oncol. 2012; 2: 165
Multhoff G, Vaupel P
The immature, chaotic microvasculature of most solid tumors can present a significant impediment to blood-borne delivery, uneven distribution, and compromised penetration of macromolecular anticancer drugs and diagnostic agents from tumor microvessels across the interstitial space to cancer cells. To reach viable tumor cells in relevant concentrations, macromolecular agents are confronted with several barriers to vascular, transvascular, and interstitial transport. Amongst those (1) heterogeneous and poor blood supply, (2) distinctly reduced or even abolished hydrostatic and oncotic pressure gradients across the microvessel wall abrogating the convective transport from the vessel lumen into the interstitial space (impairment of transvascular transport), and (3) impediment of convective transport within the interstitial compartment due to elevated interstitial fluid pressure (IFP) (resulting from hyperpermeable blood vessels coupled with non-functional lymphatics) and a dense structure of the interstitial matrix are the major mechanisms hindering drug delivery. Upon irradiation, changes in these barrier functions are inconclusive so far. Alterations in vascular transport properties following fractionated radiation up to 40 Gy are quite inconsistent in terms of direction, extent, and time course. Total doses above 45 Gy can damage tumor microvessels, additionally impeding vascular delivery. Vascular permeability for macromolecules might be enhanced up to a total dose of 45 Gy. However, this effect is counteracted/abolished by the elevated IFP in solid tumors. When assessing IFP during fractionated radiotherapy in patient tumors, inconsistent alterations have been observed, both in direction and extent. From these data it is concluded that modulations in vascular, transvascular, and interstitial transport by irradiation of solid tumors are rather unclear so far. Translation of experimental data into the clinical setting thus needs to be undertaken with especial care.
HubMed – drug
Tissue dynamics spectroscopy for phenotypic profiling of drug effects in three-dimensional culture.
Filed under: Drug and Alcohol Rehabilitation
Biomed Opt Express. 2012 Nov 1; 3(11): 2825-41
Nolte DD, An R, Turek J, Jeong K
Coherence-gated dynamic light scattering captures cellular dynamics through ultra-low-frequency (0.005-5 Hz) speckle fluctuations and Doppler shifts that encode a broad range of cellular and subcellular motions. The dynamic physiological response of tissues to applied drugs is the basis for a new type of phenotypic profiling for drug screening on multicellular tumor spheroids. Volumetrically resolved tissue-response fluctuation spectrograms act as fingerprints that are segmented through feature masks into high-dimensional feature vectors. Drug-response clustering is achieved through multidimensional scaling with simulated annealing to construct phenotypic drug profiles that cluster drugs with similar responses. Hypoxic vs. normoxic tissue responses present two distinct phenotypes with differentiated responses to environmental perturbations and to pharmacological doses.
HubMed – drug
‘The Royal Collection’ Auction Event November 11, 2012- Coach Darrell K & Mrs. Edith Royal – It is with great honor that Austin Auction Gallery will offer a selection of sports memorabilia from the private collection of Coach Darrell K and Mrs. Edith Royal. Darrell K Royal born in Hollis, Oklahoma in 1924 is a former All American football player and coach. Darrell Royal, known as “The Coach”, is the winningest coach in the University of Texas Longhorns football history, serving as head coach from 1957-1976. Mrs. Edith Royal, Darrell’s wife of over 65 years is known as The First Lady of Texas Football. Her advocacy of drug and alcohol rehabilitation has helped many people on the path to a life in sobriety. Most recently Mrs. Royal has created a fund to support Alzheimer’s disease research in Texas in her husband’s name. A portion of the proceeds from this auction will go directly to the DKR Alzheimer’s Fund. Join us November 11 in Austin Auction Gallery’s ‘Texas Legends’ Two Distinct Collections, One Amazing Auction Catalog Auction Event. Session I -‘The Theriot Collection’ is comprised of antiques and artifacts personally collected from around the world by iconic restaurateur, designer and builder Beau Theriot.! **The soundtrack of this slide show is comprised of segments of lots 619A and 621A- two unreleased personal audio files from the private collection of Coach Darrell K and Mrs. Edith Royal: Lot 619A- A CD copy of a recording of Astronaut Charles Duke describing his experiences on the Apollo 16 moon flight of April, 1972, at a ‘pickin’ party hosted by …
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