Vascular function in rats with adenine-induced chronic renal failure

The aim of the present study was to characterize the function of resistance arteries, and the aorta, in rats with adenine-induced chronic renal failure (A-CRF). Sprague-Dawley rats were randomized to chow with or without adenine supplementation. After 6-10 wk, mesenteric arteries and thoracic aortas were analyzed ex vivo by wire myography. Plasma creatinine concentrations were elevated twofold at 2 wk, and eight-fold at the time of death in A-CRF animals. Ambulatory systolic and diastolic blood pressures measured by radiotelemetry were significantly elevated in A-CRF animals from week 3 and onward. At death, A-CRF animals had anemia, hyperphosphatemia, hyperparathyroidism, and elevated plasma levels of asymmetric dimethylarginine and oxidative stress markers. There were no significant differences between groups in the sensitivity, or maximal response, to ACh, sodium nitroprusside (SNP), norepinephrine, or phenylephrine in either mesenteric arteries or aortas. However, in A-CRF animals, the rate of aortic relaxation was significantly reduced following washout of KCl (both in intact and endothelium-denuded aorta) and in response to ACh and SNP. Also the rate of contraction in response to KCl was significantly reduced in A-CRF animals both in mesenteric arteries and aortas. The media of A-CRF aortas was thickened and showed focal areas of fragmented elastic lamellae and disorganized smooth muscle cells. No vascular calcifications could be detected. These results indicate that severe renal failure for a duration of less than 10 wk in this model primarily affects the aorta and mainly slows the rate of relaxation.     

Plasma adiponectin concentrations in patients with chronic renal failure: relationship with metabolic risk factors and ischemic heart disease.

AIMS: To compare plasma adiponectin levels between healthy controls and patients with chronic renal failure and to examine for a relationship between plasma adiponectin levels and ischemic heart disease as well as aortic distensibility which is an early marker of atherosclerosis. METHODS: We included 89 patients with CRF (45 on and 44 not on hemodialysis) and 70 controls in a cross-sectional study. Plasma adiponectin levels were measured by radioimmunoassay. Aortic distensibility was assessed by high-resolution ultrasonography. RESULTS: Plasma adiponectin levels were significantly almost twice as high in patients with renal failure compared to controls (9.7 +/- 1.1 vs. 5.4 +/- 0.6 microg/ml, p < 0.0001). No significant differences were found between renal patients on hemodialysis and not on hemodialysis (p = 0.71). Multivariate linear regression analysis in the renal patient group demonstrated a significant negative relationship between plasma adiponectin levels and ischemic heart disease (p = 0.02). The same analysis in the control subjects group showed a significant, negative relationship between plasma adiponectin levels and body mass index (p = 0.02) and a highly significant positive relationship with the high density lipoprotein cholesterol (p < 0.0001). In the total study population, glomerular filtration rate was the only independent predictor of plasma adiponectin concentrations. Aortic distensibility was lower in renal patients than in controls at a high level of significance (p < 0.0001). However, no significant relationship could be found between plasma adiponectin and aortic distensibility in either the controls or the renal patients. CONCLUSIONS: Plasma adiponectin levels are almost twice as high in patients with chronic renal failure in comparison with healthy controls, but not different between renal patients on and those not on hemodialysis. In addition, low plasma adiponectin levels are strongly associated with ischemic heart disease, but not with aortic distensibility in chronic renal failure.     

Duration of renal failure as risk factor for conjunctival squamous metaplasia

OBJECTIVE: To assess ocular surface changes in patients with chronic renal failure (CRF), to compare the results with the duration of illness. STUDY DESIGN: Impression cytology from 48 patients with CRF on regular hemodialysis and 16 age- and sex-matched control subjects were studied. Specimens were taken from the temporal bulbar conjunctiva using cellulose acetate filter paper. RESULTS: Among the patients with CRF who were ill for 0-10 years, 25 patients (78.1%) disclosed grade 0-1, and 7 patients (21.9%) disclosed grade 2-3 cytologic changes, whereas in those with the duration of CRF > 10 years, 9 patients (56.2%) had grade 0-1 and 7 patients (43.8%) had grade 2-3 changes. Specimens from the control group revealed 93.8% grade 0-1 and 6.2% grade 2-3 changes (p < 0.05). CONCLUSION: The ocular surfaces of patients with CRF differ significantly from those of normal individuals, and the severity of conjunctival changes is related to the duration of CRF.     

Pre-operative risk factors predict post-operative respiratory failure after liver transplantation

Objective

Post-operative pulmonary complications significantly affect patient survival rates, but there is still no conclusive evidence regarding the effect of post-operative respiratory failure after liver transplantation on patient prognosis. This study aimed to predict the risk factors for post-operative respiratory failure (PRF) after liver transplantation and the impact on short-term survival rates.

Design

The retrospective observational cohort study was conducted in a twelve-bed adult surgical intensive care unit in northern Taiwan. The medical records of 147 liver transplant patients were reviewed from September 2002 to July 2007. Sixty-two experienced post-operative respiratory failure while the remaining 85 patients did not.

Measurements and Main Results

Gender, age, etiology, disease history, pre-operative ventilator use, molecular adsorbent re-circulating system (MARS) use, source of organ transplantation, model for end-stage liver disease score (MELD) and Child-Turcotte-Pugh score calculated immediately before surgery were assessed for the two groups. The length of the intensive care unit stay, admission duration, and mortality within 30 days, 3 months, and 1 year were also evaluated. Using a logistic regression model, post-operative respiratory failure correlated with diabetes mellitus prior to liver transplantation, pre-operative impaired renal function, pre-operative ventilator use, pre-operative MARS use and deceased donor source of organ transplantation (p<0.05). Once liver transplant patients developed PRF, their length of ICU stay and admission duration were prolonged, significantly increasing their mortality and morbidity (p<0.001).

Conclusions

The predictive pre-operative risk factors significantly influenced the occurrence of post-operative respiratory failure after liver transplantation.     

Ovulation failure and double ovulation in dairy cattle: risk factors and effects

Ovulation failure and double ovulation rates were examined in 1917 inseminations performed in high-yielding dairy cows under standard commercial conditions. The ovulation rate was determined 11 days post-insemination by ultrasound detection of at least one corpus luteum in the ovaries. Analyzing the double ovulation and pregnancy rates, the study population consisted only of ovulated cows (n = 1792). Data were analyzed using logistic regression methods. A failure to ovulate was recorded in 125/1917 (6.5%) services: 82/663 (12.4%) during the warm and 43/1254 (3.4%) during the cool period. Based on the odds ratios, the risk of ovulation failure was 3.9 times higher for inseminations performed during the warm period. No significant effects of estrous synchronization, milk production and days in milk at AI, and service and lactation number on ovulation failure were found. Double ovulation was recorded in 277/1792 (15.5%) services: 146 (52.7%) unilateral double ovulations (42.5% left versus 57.5% right); 115 (41.5%) bilateral double ovulations; and 16 (5.8%) triple ovulations. Double ovulation was recorded in 72 (12.4%) and 205 (16.9%) AI during the warm and the cool period, respectively. The percentages of double ovulation for first, second and third or more lactations were 6.7, 16.6 and 25%, respectively. Double ovulation rates for early (less than 90 days), mid- (90-150 days) and late (more than 150 days) lactation periods were 13, 20.7 and 14.2%, respectively. Reaching estrus during the warm period decreased the likelihood of double ovulation by a factor of 0.86; the risk of double ovulation was lower in cows with higher milk production (a 1 kg increase in milk yield led to a 0.97-fold reduced risk of double ovulation); cows in their second and in their third or more lactations showed a likelihood of double ovulation (using the first lactation as reference) increased by factors of 3.4 and 5.6, respectively; and reaching estrus during the early and late lactation period was related to a decreased probability of double ovulation (using the mid-lactation period as reference) by factors of 0.56 and 0.84, respectively. No significant effects of synchronization and service number on the double ovulation rate were found. Pregnancy was recorded in 914/1792 (51%) services: rates of 53.5% (811/1515) were recorded for single ovulations; 37.2% (103/277) for double ovulations: 28.8% (42/146) for unilateral double ovulations; 45.2% (52/115) for bilateral double ovulations; and 56.3% (9/16) for triple ovulations. The likelihood of pregnancy diminished in cows: inseminated during the warm period (by a factor of 0.5); inseminated by one particular bull (by a factor of 0.33); with higher milk production (a 1 kg increase in milk yield decreased the probability of pregnancy by a factor of 0.98); or undergoing unilateral (by a factor of 0.31) and bilateral (by a factor of 0.64) double ovulation. Logistic regression analysis indicated no significant effects of synchronization, days in milk, lactation number and service number on pregnancy rate. Collectively, our results indicate that cows showing estrus in conditions of heat stress had a high risk of ovulation failure. The effect of milk production on double ovulation was negative, whereas lactation number was positively correlated with this factor; the highest incidence of double ovulation occurring during the mid-lactation period.     

Cytokine gene polymorphisms as potential risk and protective factors in renal cell carcinoma

Serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels in the serum of 34 patients with head and neck cancer (HNC) undergoing locoregional radiotherapy (RT) were examined. The aim of the RT was definitive in 19 and postoperative adjuvant in 15 patients. Serum TNF-alpha and IL-6 levels were recorded before RT and after the completion of the fifth week of RT. The mean TNF-alpha levels before and after RT were 28.26 +/- 2.87 and 83.03 +/- 7.47, and the mean IL-6 levels were 61.56 +/- 14.32 and 122.45 +/- 30.66, respectively. The statistical analysis yielded a significant rise in TNF-alpha levels with RT in all patients (p < 0.0001) and also in IL-6 levels in patients treated with postoperative adjuvant RT (p = 0.001). Irradiation is likely to cause an acute phase response, and the cytokines studied may be used to monitor this clinically important response in further trials.     

Radiation therapy failure in prostate cancer patients: risk factors and methods of detection

Radiation therapy for clinically localized prostatic carcinoma remains one of the mainstays among therapeutic approaches; however, patients continue to fail radiation therapy at too high a rate. This article reviews the risk factors and methods of detection for prostate cancer recurrence. The relative merits of the three major pre-therapy prognostic indicators-TNM staging, Gleason score, and serum prostate-specific antigen (PSA) levels-are discussed. The use of staging and Gleason score, as well as digital rectal examination, transrectal ultrasound, and post-radiation prostate biopsies in detecting failure of radiation therapy is reviewed. Challenges relating to the use of serum PSA levels as an indicator of recurrence are examined. Finally, this article makes recommendations as to procedure for evaluating patients suspected of failing radiation therapy.     

Bcl-2 genes and growth factors in the pathology of ischaemic acute renal failure.

For the past decade, an attempt has been made by many research groups to define the roles of the growing number of Bcl-2 gene family proteins in the apoptotic process. The Bcl-2 family consists of pro-apoptotic (or cell death) and anti-apoptotic (or cell survival) genes and it is the balance in expression between these gene lineages that may determine the death or survival of a cell. The majority of studies have analysed the role/s of the Bcl-2 genes in cancer development. Equally important is their role in normal tissue development, homeostasis and non-cancer disease states. Bcl-2 is crucial for normal development in the kidney, with a deficiency in Bcl-2 producing such malformation that renal failure and death result. As a corollary, its role in renal disease states in the adult has been sought. Ischaemia is one of the most common causes of both acute and chronic renal failure. The section of the kidney that is most susceptible to ischaemic damage is the outer zone of the outer medulla. Within this zone the proximal tubules are most sensitive and often die by necrosis or desquamate. In the distal nephron, apoptosis is the more common form of cell death. Recent results from our laboratory have indicated that ischaemia-induced acute renal failure is associated with up-regulation of two anti-apoptotic Bcl-2 proteins (Bcl-2 and Bcl-XL) in the damaged distal tubule and occasional up-regulation of Bax in the proximal tubule. The distal tubule is a known reservoir for several growth factors important to renal growth and repair, such as insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF). One of the likely possibilities for the anti-cell death action of the Bcl-2 genes is that the protected distal cells may be able to produce growth factors that have a further reparative or protective role via an autocrine mechanism in the distal segment and a paracrine mechanism in the proximal cells. Both EGF and IGF-1 are also up-regulated in the surviving distal tubules and are detected in the surviving proximal tubules, where these growth factors are not usually synthesized. As a result, we have been using in vitro methods to test: (i) the relative sensitivities of renal distal and proximal epithelial cell populations to injury caused by mechanisms known to act in ischaemia-reperfusion; (ii) whether a Bcl-2 anti-apoptotic mechanism acts in these cells; and (iii) whether an autocrine and/or paracrine growth factor mechanism is initiated. The following review discusses the background to these studies as well as some of our preliminary results.     

Polyamines in renal failure

Summary. The levels of polyamines (putrescine, spermidine and spermine) and polyamine oxidase in plasma of patients with chronic renal failure were determined. The level of putrescine was increased but the level of spermine was decreased in the plasma of these patients. The patients also had increased plasma polyamine oxidase activity leading to increased degradation of spermine. As acrolein was a major toxic compound produced from spermine by polyamine oxidase, the levels of free and protein-conjugated acrolein in plasma were also measured. Acrolein levels were enhanced in plasma of patients with chronic renal failure. The accumulated acrolein found as protein conjugates was equivalent to 170 μM, which was about 5-fold higher than in plasma of normal subjects. It was found that acrolein is mainly produced by spermine oxidase in plasma. An increase in putrescine, spermine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. After patients with chronic renal failure had undergone hemodialysis, their levels of plasma polyamines, spermine oxidase and acrolein returned towards normal. It is likely that acrolein produced from spermine accumulates in the blood due to decreased excretion into urine and may function as a uremic “toxin”.