Open reduction and internal fixation of comminuted fractures of the radial head using low-profile mini-plates.

Between 1996 and 2000, we treated ten patients with severely comminuted fractures of the radial head using low-profile mini-plates. Their mean age was 42 years (24 to 71). Three fractures were Mason type III and seven were Mason-Johnston type IV. At a mean follow-up of 28.5 months (15 to 44), all fractures had united. The plates were removed in nine patients. No patient had difficulty with daily activities or symptoms of instability of the elbow. The mean range of flexion of the elbow was from 7 degrees to 135 degrees, with 74 degrees of supination and 85 degrees of pronation. According to the Broberg and Morrey functional elbow index, the mean score was 90.7 points (73 to 100), and the outcome was excellent in three patients, good in six and fair in one. These results compare favourably with those reported previously. The technique is applicable to severely comminuted fractures of the radial head which otherwise would require excision.

Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure.

OBJECTIVES: Patients with chronic renal failure are restricted to mild physical activity and tend to a lack of exercise. However, there have been few reports regarding the influence of chronic exercise on the progression of renal disease. Similarly, there are few animal models concerned with the effect of exercise training on improving renal function. Therefore, we assessed the renal effects of moderate chronic treadmill exercise in a remnant kidney model of spontaneously hypertensive rats (SHR) with chronic renal failure. We also assessed the effects of exercise and antihypertensive therapy on renal function. DESIGN AND METHODS: Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left kidney and excision of two-thirds of the right kidney. The rats were divided into four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4 weeks. RESULTS: Chronic EX significantly attenuated the increase in proteinuria (P < 0.01) and significantly protected against increases in the index of glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly decreased blood pressure (P < 0.001), and further decreased the IGS. In the stepwise multiple regression analysis, only antihypertensive drug remained in the model as a significant predictor of IGS (P < 0.0001). In contrast, exercise, antihypertensive drug and mean systolic blood pressure (weeks 1-4) remained in the model as a significant predictors of mean proteinuria (weeks 1-4) (all P < 0.0001). CONCLUSIONS: These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.

Mesoderm formation by isolated and cultivated 8-cell stage blastomeres of the teleost, Leucopsarion ptersii (shiro-uo).

Isolation of cleavage-stage blastomeres and the study of their developmental potential has been used extensively for analyzing the mechanisms of embryogenesis in vertebrates, including amphibians and echinoderms. We devised a method to isolate 8-cell stage blastomeres in the teleost, shiro-uo, by utilizing its unique cleavage pattern of the horizontal 3rd cleavage plane. Removal of all the upper blastomeres at the 8-cell stage allowed almost normal embryogenesis from the remaining lower blastomeres and yolk cell mass. Isolated upper or lower blastomeres formed vesicles and spherical bodies, which later showed morphological changes during cultivation. Mesoderm formation was detected not only in the cultivated lower blastomeres or whole blastomeres but also in the upper blastomeres isolated from the yolk cell mass at the 8-cell stage, although at a lower frequency than the lower blastomeres. These results indicated the presence of very early signaling for mesoderm induction, which is independent from the currently postulated signals from the yolk syncytial layer at later stages. This also indicated non-equivalence or differentiation of the blastomeres from the very early cleavage stage in teleost embryos.

Changes in serum hypoxanthine levels by exercise in obese subjects.

To study on effect of obesity on changes in serum hypoxanthine with exercise, exercise stress testing with treadmill was performed on 7 obese subjects (body mass index [BMI], 30.6 +/- 3.2 kg/m(2)) and 16 healthy volunteers (BMI, 21.5 +/- 2.10 kg/m(2)). Expiratory gas analysis during exercise showed that peak Vo(2) was significantly lower in the obese group than in the control group (28.1 +/- 4.0 v 37.1 +/- 4.7 mL/kg/min; P <.001). Furthermore, the obese group had lower anaerobic threshold (AT) values (P <.005), respiratory quotient at AT (P =.003), and exercise capacity reserve (P =.002) than the control group. Baseline serum hypoxanthine levels were significantly higher in the obese group than in the control group (3.46 +/- 3.70 v 1.23 +/- 1.16 micromol/L; P <.05). Exercise induced a pronounced increase in serum hypoxanthine level in the obese group compared with the control group (10.65 +/- 6.81 v 43.86 +/- 4.56 micromol/L; P <.01). Serum levels of uric acid before and after load were also higher in the obese group than in the control group (404 +/- 43 v 302 +/- 77 micromol/L; P <.005). A pronounced increase in hypoxanthine with exercise may result in organ damage caused by free radicals, and intermittent training from mild intensity may be less hazardous for exercise treatment of obesity.

Effects of troglitazone and temocapril in spontaneously hypertensive rats with chronic renal failure.

OBJECTIVE: The insulin resistance state is common in humans and animals with chronic renal failure. We investigated the effects of troglitazone, an insulin sensitizer, on blood pressure and nephropathy in the remnant kidney model of spontaneously hypertensive rats (SHR). METHODS: Eight-week-old male SHR were subjected to five-sixth nephrectomy. At the age of 10 weeks, the rats were randomly allocated to groups that received troglitazone (70 mg/kg per day); the angiotensin converting enzyme inhibitor temocapril (10 mg/kg per day); troglitazone (70 mg/kg per day) plus temocapril (10 mg/kg per day), or a vehicle alone as an untreated control group. Systolic blood pressure (SBP) and urinary protein excretion were measured every 2 weeks. At the age of 22 weeks, biochemical measurements and histological examination were performed. RESULTS: Blood glucose, glycosylated hemoglobin and body weight were similar in the four groups. SBP, serum creatinine and glomerular sclerosis index were significantly reduced in all treated groups compared with those in the control group. Urinary protein excretion, glomerular volume and aortic media thickness were significantly decreased in temocapril-treated rats and troglitazone plus temocapril-treated rats compared with those in control rats. Although antihypertensive effects of troglitazone were minute compared with those of temocapril or troglitazone plus temocapril, there was no significant difference between the glomerular sclerosis indices in these three drug-treated groups. CONCLUSIONS: The results suggest that troglitazone has renoprotective effects in this rat model. These effects might be due to the inhibition of growth factors rather than to the minute hypotensive effect, although the mechanism remains to be elucidated.

Renal-protective effect of nondepressor dose of cicletanine in diabetic rats with hypertension.

We assessed the renal and cardiac benefits of cicletanine (CIC), a furopyridine derivative drug with diuretic and antihypertensive properties, in diabetic spontaneously hypertensive rats with renal impairment. Uninephrectomized streptozotocin (STZ)-diabetic spontaneously hypertensive Izmo rats (SHRIzm) (10 weeks old) were randomly assigned to receive vehicle or CIC (100 mg/kg/day, orally), and age-matched, uninephrectomized STZ diabetic Wistar-Kyoto Izmo rats (WKYIzm) were assigned to receive vehicle for up to 12 weeks. Blood pressure increased progressively in diabetic SHRIzm but not in diabetic WKYIzm. Urinary albumin excretion increased significantly in both diabetic SHRIzm and diabetic WKYIzm throughout the experiment. The antihypertensive effect of CIC was not significantly observed in diabetic SHRIzm. However, the subdepressor doses of CIC significantly decreased urinary albumin excretion, serum creatinine, and blood urea nitrogen in diabetic SHRIzm. These results were confirmed by morphological analysis of kidneys in each group of rats. The index of focal glomerular sclerosis (FGS) in diabetic SHRIzm was significantly higher than that in diabetic WKYIzm. The CIC treatment significantly and effectively protected against an increase in the index of FGS in diabetic SHRIzm. Moreover, CIC treatment significantly attenuated the increase in the heart weight to body weight ratio in diabetic SHRIzm. Treatment with CIC did not affect urinary and blood glucose concentrations at this dose. These results suggest that CIC has a renal-protective action, which is not related to improvement of diabetes or improvement of high blood pressure in diabetic rats with hypertension. The action might be due to the reduction of intraglomerular capillary pressure or protection of the renal glomerular vascular endothelial cell injury and mesangial cell injury through stimulation of PGI2 generation or elimination of free radicals, although the mechanism remains to be further investigated.

Relation between changes in serum hypoxanthine levels by exercise and daily physical activity in the elderly.

Effect of exercise at mild intensity on the serum levels of hypoxanthine was studied in eleven healthy elderly subjects. They were divided into the active and sedentary groups according to their daily physical activity. They performed exercise testing to walk for 5 minutes keeping heart rate at approximately 70% of the maximum heart rate. Mean intensity of exercise estimated according to Karvonen's formula in the active or sedentary group was 41.8 +/- 9.6% or 34.1 +/- 6.1%, respectively. In the sedentary group, the serum hypoxanthine levels at 10 minutes after completion of walk load was significantly higher than that before exercise. Changes in the serum hypoxanthine levels in the active and sedentary groups were -0.97 +/- 1.36 and 0.80 +/- 0.57 micromol/liter, respectively (p < 0.05). This result suggests that mild intensity exercise increases the serum hypoxanthine concentration in the elderly leading inactive daily life, and physical activity suppresses an increase in the serum hypoxanthine levels by mild exercise.

Renal-protective effect of non-depressor dose of cicletanine in streptozotocin diabetic rats.

OBJECTIVE: To assess the renal benefits of cicletanine (CIC) in diabetic rats with renal impairment. METHODS: Hemi-nephrectomized streptozotocin-diabetic Wistar-Kyoto Izmo rats (WKYIzm) (10 weeks old) were randomly assigned to receive vehicle or a low or high dose of CIC (30 or 100 mg/kg per day, orally) for 12 weeks. RESULTS: The blood pressure was raised slightly but not significantly in this model. An anti-hypertensive effect of CIC was not significantly observed. However, the sub-depressor doses of CIC significantly and dose-dependently decreased urinary albumin excretion. These results were confirmed by morphological analysis of kidneys in each group of rats. CIC treatment significantly and effectively protected against an increase in the percentage of focal glomerular sclerosis. CIC did not affect urinary and blood glucose concentrations at either dose. CONCLUSIONS: These results suggest that CIC has a renal-protective action, which is not related to improvement of diabetes or of high blood pressure in this model. The action might be due to the reduction of intraglomerular capillary pressure, although the mechanism remains to be further investigated.

[Effects of chronic exercise on renal function in 5/6 nephrectomized spontaneously hypertensive rats (SHR)].

We assessed the renal effects of chronic treadmill exercise in the remnant kidney model of chronic renal failure. Eight-week-old spontaneously hypertensive rats (SHR) were subjected to 5/6 nephrectomy by removal of the left kidney and infarction of two thirds of the right kidney. We performed two series of experiments. Firstly, we investigated the renal effects of chronic mild treadmill exercise in 5/6 nephrectomized SHR. The SHR were divided into 2 groups: a non-exercising group (Non-Ex) and a group conducting mild treadmill running at 20 m/min 0 degree grade for 30 min (Mild-Ex) 5 times/week for 4 weeks. Secondly, we investigated the effects of moderate or severe treadmill exercise in the rats. The SHR were divided into 3 groups: a non-exercising group (Non-Ex), a group conducting moderate treadmill running at 20 m/min 0 degree grade for 60 min (Moderate-Ex) and, a group conducting severe treadmill running at 35 m/min 0 degree grade for 60 min (Severe-Ex) 5 times/week for 4 weeks. Chronic treadmill exercise significantly attenuated the increase in proteinuria and serum total cholesterol levels intensity-dependently. These results were confirmed by morphological analysis of the kidneys. Moderate-Ex provided significantly effective protection against an increase in focal glomerular sclerosis. These results indicate that exercise did not worsen renal function and in contrast, suggest a renal-protective action in this rat model.

Physical and psychological improvements after phase II cardiac rehabilitation in patients with myocardial infarction.

We have designed a new 4-week hospitalized phase II cardiac rehabilitation program. The purpose of the present study is to clarify whether the physical and psychological status of patients with myocardial infarction (MI) improves after participation in our program. Twenty-nine patients (27 males, two females) with acute MI who enrolled in the 4-week hospitalized phase II rehabilitation program were assessed. All patients enrolled in this study had received coronary interventions. The rehabilitation consisted of exercise training, education and counseling. We evaluated the physical and psychological status of the patients before and just after the program, and at a 6-month follow up. The physical status was assessed by exercise tolerance measured by the peak oxygen consumption and anaerobic threshold, frequency of exercise, and serum concentrations of triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol. The psychological status was assessed by the Spielberger state-trait anxiety inventory questionnaire (STAI) and the self-rating questionnaire for depression (SRQ-D). Thirty-four patients (27 men, seven women) with MI who did not participate in our rehabilitation program served as a control group. After participation in our rehabilitation program, exercise tolerance and the serum lipid profiles of the patients were improved compared with those before rehabilitation. These parameters had improved significantly 6 months after rehabilitation. The STAI anxiety score was improved significantly and the SRQ-D depression score tended to be improved just after the rehabilitation program. Regular physical activity was continued even 6 months after the completion of the program. Our hospitalized phase II cardiac rehabilitation program improved the management of cardiac risk factors and the psychological status in patients with MI. This comprehensive program may contribute to the secondary prevention of MI as well as the recovery of physical and psychological activities.

Chronic effects of FR139317 and enalapril on renal failure rats with moderate exercise.

We assessed the renal effects of moderate treadmill exercise in the spontaneously hypertensive rats (SHR) remnant kidney model of chronic renal failure (CRF). The effects of chronic administration of a specific endothelin (ET) subtype A (ETA) receptor antagonist, FR139317 (32 mg/kg/day i.p.) and an angiotensin-converting enzyme inhibitor, enalapril (2 mg/kg/day i.p.), in combination with moderate exercise were also investigated. Eight-week-old SHR were subjected to 5/6 nephrectomy. One week after surgery the rats were divided into five groups: (a) no treadmill running; (b) moderate treadmill running, 20 m/min for 60 min (Ex) per day; (c) Ex plus FR139317; (d) Ex plus enalapril; and (e) m-Ex plus enalapril in combination with FR139317, for 4 weeks. In SHR-CRF, Ex significantly attenuated the increase in urinary protein excretion. Enalapril significantly attenuated the increase in systolic blood pressure and urinary protein excretion. FR139317 at this dose did not show any antihypertensive or renal protective effect in this model. These results suggest that moderate exercise may protect renal function in SHR CRF. They also suggest that FR139317 may not have an additional antihypertensive and renal protective effect in this exercise model.

Endothelin receptors and angiotensin II receptors in tumor tissue.

In cancer chemotherapy, selective enhancement of drug delivery to tumor tissue is essentially important for increase of chemotherapeutic effects. An attenuated vasoconstrictive response to angiotensin II (Ang II) in tumors and a marked increase in tumor blood flow were observed compared with normal tissues during systemic hypertension induced by Ang II infusion. The phenomenon was absent when hypertension was provoked by endothelin-1 (ET-1). We assessed this response to characterize ET receptor and Ang II receptor density and affinity in normal and tumor tissues. The tumor cell line LY80 was transplanted to the skin in nude rats. Four weeks later the rats were sacrificed. [125I] ET-1 and [125I Sar1, Ile8]-Ang II were used to map the receptors for ET and Ang II in rat tissues using computerized in vitro autoradiography. A moderately high density of ET receptors, (ETB > ETA) was found in tumors. The Ang II receptors were markedly reduced in tumor tissues without changes in the affinity. These results suggest that the decrease in Ang II receptors but not ET receptors in tumors may explain the hemodynamic effect of Ang II-induced hypertension and ET-induced hypertension on tumor blood flow.

Cardiac angiotensin converting enzyme and endothelin receptor in rats with chronic myocardial infarction.

To ascertain the pathophysiological roles of the renin-angiotensin system and endothelin in heart failure and cardiac hypertrophy, we assessed changes in cardiac angiotensin converting enzyme (ACE) and endothelin-1 (ET-1) receptor using rats in which myocardial infarction was induced by left coronary ligation. The animals were decapitated 1 or 8 months after the operation. Cardiac ACE and ET-1 receptor were quantified by computerized in vitro autoradiography using 125I-MK351A (a lisinopril derivative) and 125I-ET-1. One month after myocardial infarction, cardiac weight and plasma atrial natriuretic peptide had increased in rats with infarction, compared to sham-operated controls, indicating the presence of chronic left ventricular dysfunction, although exchangeable body sodium and plasma renin activity were unchanged. Cardiac ACE increased markedly in the infarcted area and moderately in hypertrophied myocardium without any change in affinity compared to sham-operated rats. On the other hand, there was no change in cardiac ET-1 receptors in infarcted rats. The same results were found even at 8 months after myocardial infarction. The present study indicates that cardiac ACE may participate in tissue repair at the site of myocardial infarction and may also play a role in the pathophysiology of cardiac hypertrophy in rats with chronic heart failure. However, the present results do not reveal whether ET-1 receptor participates in the pathophysiology of cardiac hypertrophy in this model.

Plasma enzymic changes in insulin-induced hypoglycemia in experimental rabbits.

In order to elucidate the effects of hypoglycemia on cardiac and skeletal muscle, plasma activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) were assessed in rabbits with hypoglycemia induced by i.v. injection of insulin. After hypoglycemia lasting for more than 30 min, the plasma levels of ALT, AST and LDH rose significantly in 4 out of 5 rabbits reaching a peak at 24 hr. The plasma activity of CK rose remarkably and reached a peak at 6 hr after insulin injection in all rabbits. These results suggest prolonged hypoglycemia may cause myocardial and/or skeletal muscle damage, which can be ascertained by measuring plasma activities of the related enzymes.

Kinin and angiotensin II receptor antagonists in rats with chronic renal failure: chronic effects on cardio- and renoprotection of angiotensin converting enzyme inhibitors.

OBJECTIVE: To assess the potential of the kallikrein-kinin and renin-angiotensin systems in mediating the cardio- and renoprotective effects of angiotensin converting enzyme (ACE) inhibitors in rats with chronic renal failure. MATERIALS AND METHODS: Spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats subjected to five-sixths nephrectomy were randomly assigned to treatment with vehicle, a kinin antagonist (Hoe 140) or an ACE inhibitor (cilazapril) or both drugs, intraperitoneally via osmotic minipumps for 4 weeks. In addition, the effects of a chronic infusion of a specific angiotensin receptor antagonist (losartan) alone or in combination with an ACE inhibitor (enalapril) were also investigated in nephrectomized SHR for 2 weeks. RESULTS: In nephrectomized SHR and WKY rats, cilazapril alone significantly reduced systolic blood pressure, urinary protein excretion, heart weight and serum creatinine. In nephrectomized SHR, Hoe 140 alone or cilazapril in combination with Hoe 140 (7 or 70 mu g/kg per day) induced no changes in these parameters, other than those associated with the effects of cilazapril alone. In nephrectomized WKY rats, cilazapril in combination with Hoe 140 (70 mu g/kg per day) slightly, but not significantly, attenuated the antihypertensive effect of cilazapril but did not affect the other parameters. These results were confirmed by morphological analysis of kidneys. All the drug regimens provided effective protection against an increase in focal glomerular sclerosis. Enalapril did not modify the antihypertensive and renoprotective effects of losartan in nephrectomized SHR. CONCLUSIONS: The present results indicate that the kallikrein-kinin system might not be a major factor in the cardio- and renoprotective effects of ACE inhibitors in rats with chronic renal failure.