Tumor promotion by foreign bodies (IUD)

Commercial intrauterine devices (IUDs) were cut into small fragments and implanted subcutaneously and intraperitoneally in mice initiated with 7,12-dimethylbenzanthracene (DMBA). The mice given intraperitoneal IUDs developed significantly more tumors in a shorter time than mice without the IUD. It is suggested that foreign bodies such as the IUD can promote tumors, even at a distance by a humoral mechanism such as autoantibody.     

Downregulation of angiotensin-converting enzyme by tumor necrosis factor-alpha and interleukin-1beta in cultured human endothelial cells.

Angiotensin-converting enzyme (ACE) and cytokines are considered to play an important role in the pathophysiology of cardiovascular diseases such as atherosclerosis. In the present study, the effects of the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) on ACE in cultured human umbilical vein endothelial cells (HUVECs) was studied. TNF-alpha (0.1-10 ng/ml) and IL-1beta (0.1-10 ng/ml) caused a dose- and time-dependent decrease in the amount of ACE in intact endothelial cell membranes and decreased levels of ACE mRNA. TNF-alpha and IL-1beta activated p44/42 and p38 mitogen-activated protein kinases (MAPKs) in HUVECs; this was inhibited by the specific inhibitors of these kinases, PD98059 and SB202190, respectively. Pretreatment of endothelial cells with the specific p38 MAPK inhibitor SB202190 (5 microM) or hydrocortisone (5 microM) partly reversed the suppression of ACE by TNF-alpha or IL-1beta, whereas the specific p44/42 MAPK inhibitor PD98059 (40 microM) was without effect. Vascular endothelial growth factor (1 ng/ml) caused an increase in membrane-bound ACE and ACE mRNA levels which was inhibited by pretreatment of the cells with TNF-alpha (1 ng/ml) or IL-1beta (1 ng/ml). In summary, the cytokines TNF-alpha and IL-1beta downregulated ACE in cultured human endothelial cells, which effect was probably mediated by the p38 MAPK pathway. Downregulation of ACE by TNF-alpha and IL-1beta locally in the vascular wall may be a counterbalancing mechanism in inflammatory processes such as atherosclerosis, leading to decreased production of angiotensin II and accumulation of bradykinin.     

Alcohol consumption and cardiovascular risk in hypertensives with left ventricular hypertrophy: the LIFE study

The Losartan Intervention For End point reduction in hypertension (LIFE) study showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke, and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios (HR) in 4287 and 685 participants who reported intakes of 1-7 and >8 drinks/week at baseline, respectively, with those in 4216 abstainers, adjusting for gender, age, smoking, exercise, and race. Within categories, clinical baseline characteristics, numbers randomized to losartan and atenolol, and blood pressure (BP) lowering were similar on the drug regimens. Overall BP control (<140/90 mmHg) at end of follow-up was similar in the categories. Composite end point rate was lower with 1-7 (24/1000 years; HR 0.87, P<0.05) and >8 drinks/week (26/1000 years; HR 0.80, NS) than in abstainers (27/1000 years). Myocardial infarction risk was reduced in both drinking categories (HR 0.76, P<0.05 and HR 0.29, P<0.001, respectively), while stroke risk tended to increase with >8 drinks/week (HR 1.21, NS). Composite risk was significantly reduced with losartan compared to atenolol only in abstainers (HR 0.81 95% confidence interval, CI (0.68, 0.96), P<0.05), while benefits for stroke risk reduction were similar among participants consuming 1-7 drinks/week (HR 0.73, P<0.05) and abstainers (HR 0.72, P<0.01). Despite different treatment benefits, alcohol-treatment interactions were nonsignificant. In conclusion, moderate alcohol consumption does not change the marked stroke risk reduction with losartan compared to atenolol in high-risk hypertensives. Alcohol reduces the risk of myocardial infarction, while the risk of stroke tends to increase with high intake.     

Plasma vasopressin in conscious goats after cerebroventricular infusions of angiotensins, sodium chloride, and fructose.

Using a sensitive RIA, the levels of plasma arginine vasopressin (pAVP) were determined from jugular venous blood of conscious goats given cerebroventricular (c.v.) infusions of angiotensins, saralasin, NaCl, and fructose. In hydrated goats, c.v. angiotensin II (0.1--1.0 microgram) caused a dose-dependent rise of pAVP, drinking, and antidiuresis. The same responses were obtained after angiotensin III (1.8 microgram) and hypertonic NaCl (0.5 M), but the effect on water intake was less striking. [des1,2]Angiotensin II hexapeptide and isotonic NaCl (0.15 M) failed to affect these variables. In nonhydrated goats, there were no changes in drinking, diuresis, or pAVP after c.v. infusions of saralasin (5.0 microgram) and isotonic NaCl (0.15 M). Fructose (0.3 M) infusions lowered the pAVP, apparently by reducing the cerebrospinal fluid (CSF) Na+ concentration, while the renal free water clearance turned positive. Angiotensin III thus carries the minimal structural requirements for pAVP release via central nervous receptors in the goat. Lack of a saralasin effect suggests that, in the nonhydrated goat, angiotensin II may not regulate pAVP via receptors accessible to the CSF. Sodium-sensitive cells monitoring the Na+ concentration of the CSF seem to control the pAVP.     

Raised Endothelin Content in Bronchoalveolar Lavage Fluid During Lung Allograft Rejection in Pigs

Abstract

Objectives. Freedom Solo is a stentless biological aortic valve which is implanted supra-annularly with a single suture line. An increased risk of postoperative thrombocytopenia in the early postoperative period has been reported in recent studies. In our study we evaluated postoperative haemodynamic performance and thrombocyte-levels. Design. Thirty seven patients who underwent valve implantation of the Sorin Freedom Solo stentless valve were included. The haemodynamic performance of the valve was evaluated by transthoracic echocardiography postoperatively at the fourth day (mean) and after a median of 4.2 months. Results. The mean gradient (mmHg) of Freedom Solo was 7.5 at four days and 8.6 at 4.2 months. Postoperatively no patient had more than grade 1 leakage. Seven percent of the patients had a reduction of thrombocytes to less than 20% of the preoperative level. Seventy six percent had a minimum postoperative thrombocyte level less than 100*10⁹/L. The 30 days mortality in our patient material was zero. Conclusions. Implantation of the Freedom Solo valve was uncomplicated in our experience. Favourable transvalvular gradients and no significant leaks were found. In accordance with the literature, we found a high percentage of patients having a postoperative level of thrombocytes less than 100*10⁹/L after implantation of Freedom Solo.     

Plasma atrial natriuretic factor during cold-induced diuresis

Summary The purpose of this study was to evaluate the possible contribution of atrial natriuretic factor (ANF) to cold-induced diuresis. Seven healthy men, dressed in shorts, were exposed to a cold environment (+12°C) for 90 min, and also to a thermoneutral environment. Exposure to cold increased urine output and sodium excretion significantly but plasma ANF concentration remained unchanged. The increase in urinary potassium excretion during cold exposure was not significant (P=0.0636) and plasma renin activity did not change either. Exposure to cold increased mean arterial pressure significantly but it did not affect heart rate. We concluded that acute exposure to the cold environment induced a diuretic response, which was a solute diuresis in its nature. Our results did not give support to the hypothesis that ANF might be involved in the renal response to cold exposure.     

Sodium load increases renal angiotensin type 1 receptors and decreases bradykinin type 2 receptors.

The regulation of both angiotensin receptors and bradykinin receptors during sodium intake is poorly understood. We hypothesized that an altered balance between renal angiotensin type 1 (AT1) receptors and bradykinin type 2 (B2) receptors might contribute to an increase in blood pressure during periods of high-sodium intake. We studied the effects of high-sodium intake on renal AT1 receptors and B2 receptors in 5-6-week-old spontaneously hypertensive rats (SHR) receiving high-sodium chloride (6% NaCl) or mineral salts (10.5%, composition: 57% NaCl, 28% KCl, 12% MgSO4) compared to those receiving a low-sodium (NaCl 0.125%) diet for 10 weeks. Mineral salt intake was included due to its beneficial effects on blood pressure and cardiac hypertrophy. Receptor densities were measured by quantitative autoradiography. AT1 receptors were quantified using incubation with 125I-Sar1-Ile8-angiotensin II and displacement was measured with PD123319 (10 micromol/l), whereas B2 receptors were quantified using 125I-HPP-icatibant and displacement was measured with icatibant (3 micromol/l). Compared to the SHR controls, a further increase in blood pressure occurred after 2 weeks in the 6% NaCl group and after 6 weeks in the mineral salt group. AT1 receptor density increased in the renal cortex by 41% (p<0.01) in the 6% NaCl group and by 26% (p<0.05) in the mineral salt group. B2 receptor density decreased in the renal medulla by 26% (p<0.01) in the 6% NaCl group, and decreased even more i.e., by 45% (p<0.001), in the mineral salt group. It was shown that a 6% NaCl or a 10.5% mineral salt loading was capable of increasing renal AT1 receptor density and decreasing renal B2 receptor density. An altered balance between these receptors might be associated with hypertension under conditions of sodium loading.