Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To enhance the therapeutic effect of conventional TRC using intra-arterial (i.a.) DDP plus simultaneous i.v. STS, we combined the AT-II-induced hypertension method with TRC and evaluated its efficacy for a rat uterine tumor, using the simulation of intra-arterial chemotherapy for human uterine tumors. During interruption of arterial blood flow by vascular manipulations, DDP plus AT-II were injected for 10 min through the abdominal aorta in the direction of the uterus. Then STS was administered i.v. for a further 5 min and all the arterial restrictions were released. This modified TRC using AT-II showed a much higher anti-tumor effect than that seen in conventional TRC without AT-II and was free from DDP-induced renal damage. On the other hand, severe nephrotoxicity was unavoidable in the rats given the delayed i.v. administration of STS to i.a. DDP alone. The feasibility of post-administration of STS without obvious nephrotoxicity in modified TRC was explained by transient inhibition of DDP delivery to the kidney during the AT-II-induced hypertension. The loss of body weight and the decrease in the number of leukocytes after this therapy were tolerable. Modified TRC showed a higher anti-tumor effect and a lower nephrotoxicity compared with other treatments, as follows: DDP i.a. with or without AT-II; i.v. infusion of DDP alone. Such a superior anti-tumor effect of modified TRC consists of the following 2 factors: (i) the post-administration of STS leading to the delayed neutralization of DDP at the tumor site; (ii) the selective enhancement of DDP delivery to the tumor tissue during AT-II-induced hypertension.
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PMID:Therapeutic efficacy of two-route chemotherapy using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with the angiotensin-II-induced hypertension method in a rat uterine tumor. 201 Feb 32

Systemic chemotherapy using high-dose DDP and its antidote, STS, was combined with the AT-II-induced hypertension method and evaluated for efficacy against s.c. tumors in rats. After i.v. infusion of DDP plus AT-II for 5 min, STS was administered i.v. over a further 5 min. The rats treated with this combination chemotherapy showed normal levels of BUN and serum creatinine 4 days after the treatment, although most rats given i.v. STS after DDP without AT-II showed severe nephrotoxicity. The absence of obvious nephrotoxicity in AT-II-combined chemotherapy using i.v. DDP plus post-administered STS can be explained by a transient inhibition of DDP-delivery to the kidney during the AT-II-induced hypertension. The anti-tumor effect of this modified therapy, evaluated by inhibition of tumor growth, was superior to other treatments, as follows: concomitant i.v. administrations of DDP and STS; i.v. DDP, with or without AT-II. The improvement in anti-tumor effect of this combination therapy is explained by the delayed neutralization of active DDP by STS at the tumor site and the selective enhancement of DDP delivery to the tumor tissue, as produced by AT-II. Thus, systemic chemotherapy using high-dose DDP induced no obvious nephrotoxicity and improved the anti-cancer effect in the case of concomitant administration of DDP plus AT-II and the time-delayed injection of STS.
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PMID:Systemic chemotherapy in tumor-bearing rats using high-dose cis-diamminedichloroplatinum(II) with low nephrotoxicity in combination with angiotensin II and sodium thiosulfate. 233 97

"Two-route chemotherapy" (TRC) using cis-diamminedichloroplatinum(II) (DDP) and its antidote, sodium thiosulfate (STS), combined with the angiotensin II (AT-II)-induced hypertension method was evaluated for its efficacy against peritoneally disseminated tumors in rats. A bolus i.p. injection of DDP (15 mg/kg) was given 1 min after the initiation of an AT-II (16.5 micrograms/kg) i.v. infusion lasting 11 min. Immediately after the termination of the AT-II infusion, 1,580 mg/kg STS was injected i.v. over a further 5 min. This modified TRC significantly improved the antitumor effect, evaluated by survival (increase in life span, 273%), compared with that achieved with other treatments, as follows: 15 mg/kg DDP i.p. and the concomitant i.v. infusion of 1,580 mg/kg STS (conventional TRC), 153% increase in life span; 5 mg/kg DDP i.p. with or without AT-II i.v. (167% and 107% increases in life span, respectively). As an index of nephrotoxicity, blood urea nitrogen (BUN) levels seen after modified TRC (21.1 mg/dl) were as low as those observed after conventional TRC (19.1 mg/dl), despite the postadministration of STS, and were much lower than those seen after DDP alone or DDP plus AT-II (35.6 and 35.7 mg/dl, respectively). Further evaluation of the effectiveness of modified TRC using various doses of DDP gave similar results. The feasibility of the administration of STS 10 min after DDP treatment was explained by the significant inhibition of DDP delivery to the kidney during the AT-II-induced hypertension. Thus, TRC combined with AT-II has a superior therapeutic effect against peritonitis carcinomatosa induced in rats.
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PMID:"Two-route chemotherapy" using cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with angiotensin II is effective against peritoneally disseminated cancer in rats. 273 7

Angiotensin II-induced hypertension chemotherapy proved to be more effective than conventional chemotherapy using cis-diamminedichloroplatinum (II) (DDP), when applied to an established mouse mammary carcinoma. In an attempt to improve the effectiveness, a cardiotonic such as aminophylline or trans-pi-oxocamphor was added to a solution containing angiotensin II and DDP. A remarkable improvement in therapeutic efficacy was apparent as compared to angiotensin II hypertension chemotherapy. A possible synergism between angiotensin II and the cardiotonic may result in selective delivery of the antitumor drug to the tumor tissue.
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PMID:Some cardiotonics enhance the effectiveness of angiotensin II-induced hypertension cancer chemotherapy in mice. 308 75

Angiotensin II-induced hypertension chemotherapy using cis-diamminedichloroplatinum (II) (DDP) or carboquone (CQ), and a modification of the therapy through combination with a cardiotonic, such as aminophylline (AP) and trans-pi-oxocamphor (pi OC), were compared with regard to therapeutic efficacy on an established mouse mammary carcinoma grown s.c. in syngeneic mice. The hypertension chemotherapy proved to be more effective than conventional administration with the anticancer drug alone. On the other hand, a remarkable improvement in antitumor effect without any increase in the general toxicity was more apparent in the modified hypertension chemotherapy than in angiotensin II hypertension chemotherapy. The combination therapy using DDP, AP or pi OC, but not AT-II, did not produce any increase in antitumor effect as compared to conventional administration with anticancer drug alone. The cytotoxicity of DDP against cultured HeLa cells was not enhanced by co-administration with AT-II, AP and/or pi OC. Thus, the increase in the therapeutic efficacy obtained by the modified hypertension chemotherapy may be attributable to the specific augmentation in delivery of the anticancer drug to the tumor tissue, but not to any specific enhancement in the cytotoxicity of the anticancer drug against to the tumor cells.
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PMID:[Improvement of cancer therapy by angiotensin II-induced hypertension chemotherapy]. 356 98

We described the efficacy of "two-route chemotherapy (TRC)", in which the anticancer drug, cis-diamminedichloroplatinum (II) (DDP), is injected locally, in combination with its antidote, sodium thiosulfate (STS), given systemically. First, we tested the protective effect of sulfur-containing compounds against DDP toxicity, and found STS to be the most potent antidote of DDP. On the basis of this finding, we developed TRC using DDP and STS, and applied it for liver and lung metastasis, bladder cancer, and peritoneal disseminated tumors in experimental animals, resulting in remarkable antitumor effects without serious side effects, especially nephrotoxicity. Furthermore, we obtained an optimal increase in the lifespan of rats bearing limb tumors when we tried TRC in combination with the angiotensin II (AT-II)-induced hypertension method. We also clarified that the protection of STS against DDP toxicity was mainly due to the diminution of the active platinum level in blood. We briefly reviewed the clinical trials of TRC, and discussed the improvements which still have to be made.
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PMID:[Two-route chemotherapy using the anticancer drug cis-diamminedichloroplatinum(II) and its antidote, sodium thiosulfate]. 356

A significantly lower incidence of DDS, hypotension, and impending shock was found during and after hemofiltration as compared with conventional hemodialysis. Hemofiltration, in contrast to hemodialysis, showed less decrease of circulating plasma volume, mild change in plasma osmolality without red cell swelling, better compensation of acidosis despite less uptake of acetate, more stable PCO2 during the procedure, less paradoxical acidosis in cerebrospinal fluid, and a lower urea concentration gradient between cerebrospinal fluid and plasma. These phenomena might be explained by better mass transfer between compartments bithin the body during hemofiltration. Mass transfer from the intracellular as well as the extracellular space to circulating plasma occurred more rapidly and smoothly during HF than during HD. HF is preferable to HD in patients with severe cardiovascular complications such as hypertension, as well as hypotension and cardiac failure, and in those subject to DDS during HD. Accordingly, hemofiltration therapy promises patients more comfortable and more stable treatment of chronic uremia.
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PMID:Superiority of hemofiltration to hemodialysis for treatment of chronic renal failure: comparative studies between hemofiltration and hemodialysis on dialysis disequilibrium syndrome. 739 69

The aim of our study was to assess frequency of death from myocardial infarction in patients (pts) treated for small cell lung cancer (SCLC). 33 out of 845 patients treated for SCLC died from myocardial infarction. All patients were smokers. In 6 patients coexisted hypertension, in 2--diabetes and in 5--obesity. Eight patients have had cardiac disease in anamnesis. All patients were treated with one or more number of cardiotoxic drugs as DDP, VCR or VBL, E, MTX and ADR which are able to cause ischemic heart disease or myocardial infarction. Sixteen out of 33 patients have had radiotherapy of lung tumour. Death from myocardial infarction occurred from 0.5 up till 98.5 months from the beginning of start treatment. Eighteen men died from myocardial infarction in the first year of treatment. Risk of death from myocardial infarction was 15 times greater in men with SCLC than in men of the polish population at the same age and at the same time.
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PMID:[Myocardial infarction as a cause of death in patients treated for small cell lung cancer]. 1080 90

The main problem in the replacement of pathological segments of the aorta with vascular prostheses consists of matching the fluid admittance of the host artery and the graft. This mismatch results from the different compliance between natural and prosthetic vessels and from the plastic dilatation of the prosthesis diameter that occurs after implantation. An experimental procedure was set up for evaluating the mechanical properties of aortic vascular prostheses. An MTS 858 MiniBionix testing machine was equipped with a purposely designed testing apparatus, which allows loading a ring-shaped prosthesis specimen with forces that can be related easily to the transmural pressure acting on the prostheses in vivo. The reference pressure waveforms are simulated from a lumped parameter model of the cardiovascular system. Preliminary tests on 3 different (woven, warp knitted, and carbon-coated warp knitted fabric) aortic prostheses point out a good reproducibility of the results. The fabric strongly affects the circumferential elasticity and the dimensional stability of the graft. Simulation of hypertension promotes larger diameter dilatation and reduction in compliance. Agreement between in vitro and clinical diameter measurements has been assessed for 8 prosthesis samples and found to be adequate. This method is thus a potentially useful means for preclinical evaluation of compliance of vascular prostheses for the purpose of matching to native vessels.
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PMID:An in vitro methodology for evaluating the mechanical properties of aortic vascular prostheses. 1207 15

Renal failure is a frequent and costly complication of many chronic diseases, including diabetes and hypertension. One common feature of renal failure is glomerulosclerosis, the pathobiology of which is unclear. To help elucidate this, we generated a mouse strain carrying the missense mutation Wt1 R394W, which predisposes humans to glomerulosclerosis and early-onset renal failure (Denys-Drash syndrome [DDS]). Kidney development was normal in Wt1(+/R394W) heterozygotes. However, by 4 months of age 100% of male heterozygotes displayed proteinuria and glomerulosclerosis characteristic of DDS patients. This phenotype was observed in an MF1 background but not in a mixed B6/129 background, suggestive of the action of a strain-specific modifying gene(s). WT1 encodes a nuclear transcription factor, and the R394W mutation is known to impair this function. Therefore, to investigate the mechanism of Wt1 R394W-induced renal failure, the expression of genes whose deletion leads to glomerulosclerosis (NPHS1, NPHS2, and CD2AP) was quantitated. In mutant kidneys, NPHS1 and NPHS2 were only moderately downregulated (25 to 30%) at birth but not at 2 or 4 months. Expression of CD2AP was not changed at birth but was significantly upregulated at 2 and 4 months. Podocalyxin was downregulated by 20% in newborn kidneys but not in kidneys at later ages. Two other genes implicated in glomerulosclerosis, TGFB1 and IGF1, were upregulated at 2 months and at 2 and 4 months, respectively. It is not clear whether the significant alterations in gene expression are a cause or a consequence of the disease process. However, the data do suggest that Wt1 R394W-induced glomerulosclerosis may be independent of downregulation of the genes for NPHS1, NPHS2, CD2AP, and podocalyxin and may involve other genes yet to be implicated in renal failure. The Wt1(R394W) mouse recapitulates the pathology and disease progression observed in patients carrying the same mutation, and the mutation is completely penetrant in male animals. Thus, it will be a powerful and biologically relevant model for investigating the pathobiology of the earliest events in glomerulosclerosis.
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PMID:The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure characteristic of human Denys-Drash syndrome. 1550 92


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