Shor- and long-term effect of a calcium channel blocker, barnidipine, on renal hemodynamics in spontaneously hypertensive, diabetic rats

Background The purpose of this study was to examine the short- and long-term effects of the calcium channel blocker, barnidipine, on renal hemodynamics and urinary albumin excretion in spontaneously hypertensive rats with streptozotocin-induced diabetes. Methods Diabetic and nondiabetic spontaneously hypertensive rats and nonhypertensive rats were treated with barnidipine or placebo (vehicle). In the short-term experiment, barnidipine was given as a single bolus injection (3 μg/kg); in the long-term experiment, barnidipine was administered orally (15 mg/kg per day) for 16 to 20 weeks. Results Renal hyperfiltration was observed in both hypertensive and nonhypertensive rats at 1 to 2 weeks after induction of diabetes, without changes in renal blood flow. Although short-term administration of barnidipine significantly decreased mean arterial pressure and renal vascular resistance, barnidipine did not affect renal blood flow or glomerular filtration rate in hypertensive, diabetic rats. At 16 to 20 weeks after induction of diabetes, renal hyperfiltration and increased urinary albumin excretion were still observed in hypertensive rats given placebo, compared to values for hypertensive nondiabetic rats given placebo. Long-term administration of barnidipine to hypertensive, diabetic rats suppressed the increase in both glomerular filtration rate and urinary albumin excretion, and reduced systolic blood pressure without any change in renal blood flow, renal vascular resistance, or filtration fraction. Conclusions These results indicate that in hypertensive, diabetic rats short-term administration of barnidipine, despite reducing renal vascular resistance, is less effective than long-term administration in restoring normal renal filtration, although long-term administration may normalize renal filtration and reduce urinary albumin excretion.     

Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats

Oxidative stress and suppressed H₂S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H₂S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n?=?6) were treated for 4?weeks either as controls or received NaHS (SHR?+?NaHS), tempol (SHR?+?Tempol), or NaHS plus tempol (SHR?+?NaHS?+?Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0?±?2 vs. 100.0?±?3?mmHg), lower plasma and urinary H₂S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p?p?2S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.     

Changes in Bone Density in Patients with Ankylosing Spondylitis: A Two-Year Follow-Up Study

The objectives of the study were to determine the 2 year rate of bone changes in patients with ankylosing spondylitis (AS) and, whether bone loss is related to physical impairment, systemic inflammation, and therapy. Consecutive outpatients fulfilling the modified New York criteria for AS were included. Baseline assessment included age, disease duration, treatment, clinical, radiologic and laboratory data. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were determined every 6 months. Persistent systemic inflammation was defined as mean ESR ≥ 28 mm/h or mean CRP ≥ 15 mg/l. Bone mineral density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry, at baseline and year 2. Statistical analysis compared the baseline and 24 month follow-up BMD data, and determined whether baseline data, and persistent systemic inflammation during the 2 years, were related to the 24 month percentage changes in BMD. Fifty-four patients (35 men, 19 women; mean age 37.3 ± 11.3 years, mean disease duration 12.4 ± 8.6 years) were included. After 2 years, BMD did not change at the lumbar spine (+0.75%± 3.5, p= 0.23), and decreased at the femoral neck (–1.6%± 4, p= 0.006). The 24 month percentage change in femoral neck BMD was related to persistent systemic inflammation, defined using ESR (mean percentage change –4.1%± 5.7 and –1.2%± 3.9 in patients with and without persistent inflammation; respectively; p= 0.007). These results suggest that persistent inflammation might be an etiologic factor of bone loss in AS. Received: 15 November 2000 / Accepted: 15 February 2001     

Neural effects of natural behavior on renal blood flow in spontaneously hypertensive rats

Background In states of stress and exercise, renal blood flow is shown to be depressed, mainly through neural mechanisms. Little is known, however, about the effects of natural or spontaneous behaviors on renal blood flow and renal sympathetic nerve activity. Methods We simultaneously measured renal sympathetic nerve activity and renal blood flow as a Doppler shift during grooming and exploring behaviors in spontaneously hypertensive rats. We also tested the effects of vasodilating drugs on changes in renal blood flow. Results Grooming behavior (n=21) increased renal sympathetic nerve activity, mean arterial pressure, and decreased renal blood flow. Percentage changes in renal sympathetic nerve activity correlated negatively with percentage changes in renal blood flow. Exploring with rearing (n=14) induced similar but larger changes in these variables. Denervation of renal nerves suppressed a reduction in renal blood flow during these behaviors. After intravenous injection of manidipine (a calcium channel blocker) or CV-11974 (an angiotensin II receptor antagonist), the behavior-induced reduction in renal blood flow was significantly smaller than that found before treatment, despite similar increases in renal sympathetic nerve activity. Conclusion Natural behaviors decrease renal blood flow in relation to the enhancement of renal sympathetic nerve activity, which is similar to the responses of the animals to stressful psychologic stimuli. Vasodilating drugs can attenuate the reduction in renal blood flow.     

Blood pressure profile in renal transplant recipients and its relation to diastolic function: tissue Doppler echocardiographic study

Hypertension is a common complication after renal transplantation and is associated with increased risk of cardiovascular disease. The aim of the current study was to investigate the diurnal blood pressure pattern and its relation to structural and functional cardiac changes in renal transplant recipients. Sixty-six stable renal transplant patients (34 female, 32 male), aged 7 to 25 years (mean 17.4 ± 4.3 years) were enrolled in this study. Cardiac function assessed by tissue Doppler echocardiography and blood pressure measurement performed using both the ambulatory and the casual method. Hypertension was demonstrated in 57% of recipients by the casual method and in 75.7% by ambulatory blood pressure monitoring (ABPM). The efficacy of BP control among patients on antihypertensive drugs was 60%. The prevalence of non-dipping was 73%. There was significant inverse correlation between systolic or diastolic day-time or night-time BP index and post-transplant duration (p < 0.001, r =−0.386), but no correlation between ABP parameters and BMI, gender, and eGFR. There was a significant relationship between all ABP parameters and left ventricular mass index (LVMI) (p = 0.025–0.007, r = 0.28–0.38). LVMI was significantly higher in hypertensive than in normotensive cases (p = 0.034). There was no difference in diastolic function between hypertensive and normotensive patients or between patients with and without left ventricular hypertrophy (LVH). In conclusion, our study showed the advantage of ABPM over the casual method of diagnosis of hypertension. LVH is common in transplant patients and is likely associated with arterial hypertension. Hypertension and LVH cannot differentiate transplant patients with diastolic malfunction.     

Skeletal Status in Children,Adolescents and Young Adults with End-Stage Renal Failure Treated with Hemo- or Peritoneal Dialysis

The skeletal status in 30 children, adolescents and young adults (18 females, 12 males) with end-stage renal failure (ESRF) aged 9-23 years (mean 15.8 ± 3.6 years) was evaluated using measurements of bone mineral density (BMD, g/cm²) at the spine and total body (TB) (Lunar DPX-L, USA), quantitative ultrasound (QUS) of the hand phalanges (DBM Sonic 1200, IGEA, Italy) and laboratory investigations (parathyroid hormone, serum total and ionized calcium, serum phosphate). Eleven subjects were treated with hemodialysis and 19 with peritoneal dialysis. The mean value of the amplitude-dependent speed of sound (Ad-SoS, m/s) measured by QUS was significantly decreased in comparison with the value obtained in a group of 686 age-matched controls (1942 ± 74 m/s vs 2050 ± 77 m/s, p<0.0001). BMD measurements were also decreased in comparison with mean values for the healthy population (Z-scores for spine −1.47, and for TB −1.53). Duration of dialysis correlated significantly with spine-BMD, TB-BMD and Ad-SoS (r=−0.37, r = −0.45, r=−0.55, respectively, p<0.05), while duration of ESRF did not have such an influence. Laboratory investigations did not correlate with skeletal parameters. Ad-SoS correlated significantly with spine-BMD (r= 0.45, p<0.05) and TB-BMD (r= 0.56, p<0.01). Both QUS and BMD values correlated significantly with Tanner stages (r ranged from 0.59 to 0.69, p<0.001) and did not increase with age except for correlation between age and TB-BMD. In conclusion, skeletal status in the population studied is strongly affected by ESRF. Both QUS and BMD measurements show an ability to express skeletal changes in a similar manner, though the QUS parameter seems to be more sensitive at revealing changes due to renal failure. Received: 12 July 2001 / Accepted: 8 November 2001     

Früh- und Spätergebnisse der CO2-Reservekapazitätmessungen mit transkranieller Dopplersonographie nach Karotisoperationen

Cerebral perfusion reserve may be determined by assessing changes in cerebral blood flow using vasodilators. Transcranial Doppler (TCD) may be used to measure cerebral blood flow speed in response to such stimuli. The aim of this study was to analyze cerebral vasoreactivity in patients with high-grade carotid stenosis and to determine the short- and long-term effects of desobliteration. A total of 40 patients had bilateral preoperative studies done and 24 were re-evaluated 1 year later. The preoperative vasomotor capacity using TCD with CO₂ was 57%±45. Hemodynamic reserve did not decrease significantly in the early postoperative period on the operated hemisphere, and 1 year later hemodynamic reserve had increased to to 102%±80%. Contralateral reactivity also improved. One year later patients with unilateral stenosis (n=11) presented with a restitution of reactivity to 65%±46% after initial postoperative ipsilateral decrease from 51%±35% to 48%±38%. Patients with bilateral stenoses (n=9) demonstrated an initial decrease from 70%±60% to 48%±21% and a significant rise to 115%±77% 1 year later (P=0.02). Both the significant postoperative increase in the cerebral vasomotor capacity in patients with bilateral carotid stenoses registered in both hemispheres and long-term improvement in patients with unilateral stenosis underline the effectivity of carotid desobliteration in antiembolic prophylaxis and in cerebral blood flow increase, irrespective of the symptomatology.     

Enhanced protein synthesis in the renal arteries of genetically hypertensive rats: Its possible role in causing hypertension

A study was made of the vascular protein synthesis in young, genetically hyper tensive rats, mainly in their renal arteries. Some of the rats were treated either with 3.5 mg/kg of phenoxybenzamine (POB) or with 4 mg/kg of propranolol twice daily, from 6 to 8 weeks of age. ³H-proline was injected intravenously into each rat before sacrifice to analyse thein vivo incorporation rates of tritiated proline into the vascular collagen and vascular non-collagenous proteins.Evidence has been presented that: (1) the rates of incorporation of³H-proline into collagen and non-collagenous proteins of the renal arteries in spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) were greater than those in normotensive Wistar Kyoto rats (WKY); (2) the administration of POB decreased incorporation of³H-proline into the collagen and non-collagenous proteins of the renal arteries concomitant with a reduction of blood pressure in every rat strain; (3) the administration of propranolol failed to decrease the incorporation of³H-proline into these connective tissue proteins in the renal arteries and this drug did not reduce blood pressure in every rat strain; (4) the incorporation rates of³H-proline into these protein fractions in hearts were similar in every rat strain which received any drug treatment.These results indicate that an increased synthesis of collagen and non-collagenous proteins in the renal arteries of young SHR and SHRSP rats participates in the pathogenesis of spontaneous hypertension in the early hypertensive stage.     

Improvement of left ventricular mass with antihypertensive therapy in children with hypertension

There is paucity of data on the regression of left ventricular hypertrophy (LVH) in hypertensive children. This study assessed the effects of antihypertensive therapy on left ventricular mass in children with and without LVH. Medical records of hypertensive patients who had a baseline and follow-up echocardiogram (echo 1, echo 2) were reviewed. Fifteen of 22 treated patients had LVH at echo 1. Enalapril alone or combined was used in 21/22 cases. Echo 2 was performed at a mean interval of 15 ± 7 months. The LVH group showed significant decrease in systolic blood pressure z-score (SBPZ) (2.89 ± 1.61 to 1.40 ± 1.19; p = 0.01), diastolic blood pressure z-score (DBPZ) (1.44 ± 0.90 to 0.26 ± 0.82; p < 0.001), and LV mass index (LVMI) (56.2 ± 12.50 to 43.7 ± 8.30; p = 0.001), but no significant change in body mass index z-score (BMIZ) (1.79 ± 0.75 to 1.69 ± 0.69; p = 0.74). In the no-LVH group, SBPZ (3.03 ± 1.68 to 2.27 ± 1.81; p = 0.356), DBPZ (1.00 ± 0.87 to 0.63 ± 0.68; p = 0.409), BMIZ (1.08 ± 0.98 to 1.27 ± 0.89; p = 0.672), and LVMI (29.47 ± 5.51 to 33.89 ± 3.06; p = 0.374) did not change significantly. Simple linear regression demonstrated that the change in LVMI in the combined group had a significant correlation (r = 0.477; p = 0.025) with the percentage change in SBPZ. This study demonstrates that LVH in hypertensive children improves with effective blood pressure control.     

Role of intrarenal angiotensin II in glucocorticoid-induced renal vasodilation

Background. Although glucocorticoids elicit systemic hypertension, they are also demonstrated to cause marked increases in renal blood flow. The mechanism of this alteration, however, remains undetermined. Methods. Dogs were treated with dexamethasone (DEX) for 7 days, and renal, as well as systemic hemodynamic, responses to DEX were assessed. In addition, the role of intrarenal angiotensin (ANG) II in mediating the glucocorticoid-induced renal vasodilation was examined in conscious unrestrained dogs. Results. Seven-day treatment with DEX caused prominent increases in mean arterial pressure (MAP; from 80 ± 2 to 98 ± 5 mmHg) and in renal plasma flow (RPF; from 142 ± 4 to 191 ± 7 ml/min), with decreases in renal vascular resistance [RVR; from 0.26 ± 0.01 to 0.22 ± 0.01 mmHg/(ml/min)] and in the filtration fraction (FF; from 0.24 ± 0.01 to 0.20 ± 0.01). DEX treatment did not alter plasma ANG II levels, but enhanced candesartan-induced reduction in MAP. In contrast, the candesartan-induced increase in RPF (19 ± 2% increase) was completely abolished by DEX. DEX treatment markedly reduced renal tissue ANG II content (from 1.09 ± 0.07 to 0.71 ± 0.04 pg/mg tissue), which paralleled the response of renal tissue angiotensin-converting enzyme (ACE) activity (−20 ± 4%). Finally, intravenous ANG II administration caused a greater reduction in RPF during the DEX treatment period (−17 ± 2% vs −11 ± 1% in the control period). Conclusions. Glucocorticoids cause hypertension, but they also cause a paradoxical decrease in RVR and increase in RPF. The renal responses to candesartan and exogenous ANG II during DEX treatment suggest that the attenuation of intrarenal ANG-mediated vascular tone plays an important role in the altered renal hemodynamics. The decreased ANG tone is likely caused by reduced ANG II formation, resulting in part from suppressed ACE activity, but not from decreased sensitivity to ANG II. Received: November 1, 2000 / Accepted: April 5, 2001     

Continuous Loss of Bone During Chronic Immobilization: A Monozygotic Twin Study

Acute immobilization is associated with rapid loss of bone. Prevailing opinion, based on population cross-sectional data, assumes that bone mass stabilizes thereafter. In order to address whole-body and regional skeletal mass in long-term immobilization, monozygotic twins were studied, one of each twin pair having chronic spinal cord injury (SCI) of a duration ranging from 3 to 26 years. The research design consisted of the co-twin control method using 8 pairs of identical male twins (mean ± SD age, 40 ± 10 years; range 25–58 years), one of each set with SCI. The twins were compared by paired t-tests for total and regional bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry. Linear regression analyses were performed to determine the associations of age or duration of injury with the differences between twin pairs for total and regional skeletal bone values. In the SCI twins, total-body BMC was significantly reduced (22%± 9%, p<0.001), with the predominant sites of reduction for BMC and BMD being the legs (42%± 14% 35%± 10%, p<0.0001), and pelvis (50%± 10% and 29%± 9%, p<0.0001). Duration of SCI, not age, was found to be linearly related to the degree of leg bone loss in SCI twins (BMC: r ²= 0.60, p<0.05; BMD: r ²= 0.70, p<0.01). Our findings suggest that pelvic and leg bone mass continues to decline throughout the chronic phase of immobilization in the individual with SCI, and this bone loss appears to be independent of age. Received: 28 September 1998 / Accepted: 28 December 1998     

Reduced Pulmonary Function in Patients with Spinal Osteoporotic Fractures

Vertebral deformation in spinal osteoporosis results in spinal and thoracic deformation, causing pain, disability and an overall decrease in quality of life. We sought to determine whether thoracic spinal deformation may lead to impaired pulmonary function. We studied expiratory relaxed vital capacity (VC) and forced expiratory volume in 1 s (FEV1) in 34 patients with spinal osteoporotic fractures and 51 patients with chronic low back pain (CLBP) due to reasons other than osteoporosis. Measurements of pulmonary function tests were calculated as a percentage of the normal range adjusting for age, sex, and height using the equations for normal values of the EKGS (Europ?ische Gesellschaft für Kohle und Stahl). Severity of osteoporosis was determined by calculation of the spine deformity index (SDI-total and SDI-anterior) on lateral radiographs of the spine and clinical measures of body stature (height reduction, distance from lowest ribs to iliac crest and distance from the occiput to the wall). Patients with osteoporosis had a lower vital capacity (%VC of the reference value) than patients with CLBP. The differences were more prominent (p<0.05) when the previous body height, at age 25 years, was used as reference for calculation of VC (mean ± SD: 93.6%± 15.3% in patients with osteoporosis v 105.6%± 15.1% in patients with CLBP). FEV1 was significantly (p<0.05) lower in patients with osteoporosis when previous body height was considered, in comparison with patients with CLBP (mean ± SD: 85.0%± 14.2% in patients with osteoporosis v 92.4%± 13.6% in patients with CLBP). In patients with osteoporosis VC (standardized on previous body height) was significantly negatively correlated with SDI-anterior (r=–0.4, p<0.03). Furthermore, VC standardized on previous body height showed a weak but significant negative correlation with some clinical measures of osteoporosis (height reduction vs %VC: r=–0.34, p<0.05; distance from the lowest ribs to iliac crest vs %VC: r= 0.35, p<0.04). In conclusion, we found that pulmonary function is significantly diminished in patients with spinal osteoporotic fractures as compared with CLBP patients without evidence of manifest osteoporosis. Reduction of pulmonary function is correlated significantly with clinical and radiological measures of severity of spinal deformation due to osteoporotic fractures. Received: 17 March 1997 / Accepted: 21 October 1997     

Changes in Levels of Biochemical Markers and Ultrasound Indices of Os Calcis Across the Menopausal Transition

The aim of this longitudinal study was to investigate the changes in the levels of biochemical markers and ultrasound indices of os calcis across the menopausal transition. One hundred and ten healthy women (age 35–59 years at the 1992 baseline) participated in this 4-year population-based longitudinal study. Serum intact osteocalcin (IOC), urinary pyridinoline (Pyr), urinary deoxypyridinoline (Dpyr) and ultrasound indices were measured at baseline and after 4 years. The percentage changes in biochemical markers (%DIOC, %DPyr and %DDpyr) and the percentage decreases in the ultrasound indices (%DSOS, %DBUA and %DStiffness) were calculated. The values of %DIOC and %DDpyr in the perimenopausal subgroup (−4 to−3 years since menopause) and the values of %DSOS and %DStiffness in the perimenopausal subgroup (−2 to 0 years since menopause) were significantly higher than those in other groups. Pyr was significantly correlated with %DSOS (r=−0.467, p<0.01) and %DStiffness (r = −0.330, p<0.05) and Dpyr was significantly correlated with %DSOS (r=−0.390, p<0.05), %DBUA (r=−0.353, p<0.05) and %DStiffness (r = −0.454, p<0.05), while %DIOC was significantly correlated with %DSOS (r=−0.278, p<0.05), %DBUA (r=−0.369, p<0.01) and %DStiffness (r = −0.383, p<0.01) in the peri- and postmenopausal groups. These results indicate that the increase in bone turnover occurs 4 years before menopause. However, the correlations between biochemical markers and ultrasound indices were too low to allow prediction of bone change in the individual patient. Received: 12 October 1999 / Accepted: 30 June 1999     

Renal hemodynamic changes in children with liver cirrhosis

To assess the sensitivity of duplex Doppler ultrasonography in detecting early impairment of renal function in childhood cirrhosis, intrarenal arterial pulsatility index (PI) and resistive index (RI) were measured in 10 ascitic and 11 non-ascitic children with liver cirrhosis and normal creatinine clearance and 10 age- and sex-matched controls. PI and RI were higher in ascitic than non-ascitic children [PI 1.54±0.4 vs. 1.1±0.2 (mean ± SD), P=0.006; RI 0.76±0.07 vs. 0.68±0.07, P=0.03). Non-ascitic patients had higher PI and RI than controls (P=0.002 and 0.0001, respectively). PI was inversely correlated with creatinine clearance (r=–0.54, P=0.01). A significant positive relationship was observed between both PI and RI and Child score (r=0.47, P=0.009; r=0.45, P=0.01, respectively). However, no significant correlation was observed between PI and RI and portal hypertension. We conclude that renal vascular resistance indexes evaluated by duplex Doppler ultrasonography are increased in the non-ascitic phase of cirrhosis. Development of ascites is associated with a further increase in these indexes. The resistance indexes are best correlated with severity of hepatocellular dysfunction, assessed by Child score, but not with portal hypertension. Hence, monitoring these indexes, especially PI, is a non-invasive means of studying early renal hemodynamic alteration in childhood cirrhosis. Received: 2 September 1998 / Revised: 15 February 1999 / Accepted: 19 February 1999     

Effects of phenylephrine and ephedrine on pulmonary arterial pressure in patients with cervical or lumbar epidural anesthesia,or enflurane anesthesia

The authors studied systemic and pulmonary hemodynamic changes with ephedrine (EP) or phenylephrine (PH) when used to normalize arterial hypotension resulting from acute sympathectomy due to cervical or lumbar epidural anesthesia, or enflurane anesthesia in 52 patients. Both EP (0.2±0.05 mg·kg⁻¹) and PH (0.025±0.008 mg·kg⁻¹) produced a significant increase in pulmonary arterial pressure (PAP) with a concomitant increase in arterial pressure (AP). In the patients anesthetized with cervical epidural block and NO₂−O₂, systolic PAP increased from 22±5 to 28±8 mmHg with EP and from 23±6 to 32±10 mmHg with PH in response to approximately 30 mmHg increase of AP, and the ratio of the increment of systolic PAP to systolic AP (ΔPAP/ΔAP) was 0.15±0.08 with EP and 0.20±0.13 with PH (P<0.05); these changes did not differ significantly from those observed in the patients having lumbar epidural or enflurane-N₂O−O₂ anesthesia. The influence on cardiac output (CO) differed significantly between EP and PH; EP increased CO in all three groups (P<0.05), while PH did not elicit any significant changes in CO. A significant relationship between PAP and AP was found in patients given EP; the regression equation was ΔPAP=0.22×ΔAP−2.9 (r=0.77). The relationship in patients given PH was less significant (r=0.38). The results indicated that EP and PH elicit pulmonary hypertensive effect similarly in the patients with a high level of epidural anesthesia and that although both drugs act differently (EP mainly due to increases in the blood flow and PH solely due to its pulmonary vasconstrictive action), the increases in PAP were predictable, to some extent, from the increase of AP in anesthetized humans without predominant cardiopulmonary disorders.     

Pre-pubertal induction of experimental diabetes protects against early renal macrophage infiltration

The present study was undertaken to identify whether the age at induction of experimental diabetes modifies macrophage infiltration in the kidney. Renal macrophage infiltration was studied 10 days after the induction of experimental diabetes in 4-week-old pre-pubertal and 12-week-old adult male rats of normotensive [Wistar-Kyoto (WKY) rats] and hypertensive (spontaneously hypertensive rats, SHRs) background. Renal macrophage infiltration was evaluated by immunohistochemistry for ED1. Plasma glucose levels were similar in all diabetic groups. Adult SHRs were hypertensive, and induction of diabetes did not alter blood pressure (BP) in any group. Induction of diabetes in pre-pubertal rats did not induce macrophage infiltration in the kidney. However, in adult rats, tubulointerstitial macrophage infiltration was increased in both WKY (22.86 ± 3.93 vs 7.86 ± 2.16 per high-power field, P < 0.001) and SHR (26.41 ± 5.91 vs 11.48 ± 1.23, P < 0.001) groups after induction of diabetes. Glomerular macrophage infiltration was also increased after induction of diabetes in the adult WKY group (1.83 ± 0.50 vs 1.16 ± 0.26 per glomerular cross section, P = 0.029), which was not significant in the adult SHRs (2.52 ± 0.34 vs 1.95 ± 0.35). We conclude that the pre-pubertal induction of diabetes apparently protects against early renal macrophage infiltration, while the induction of diabetes in adults induces exaggerated macrophage infiltration in the kidney.     

Influence of anthropometric parameters and biochemical markers of bone metabolism on quantitative ultrasound of bone in the institutionalized elderly

The assessment of bone quality by quantitative ultrasound (QUS), a transportable and relatively cheap method, shows some correlations with bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) and with fracture risk. To examine its correlation with bone metabolism in a population of institutionalized elderly people known to be at high risk for vitamin D deficiency and secondary hyperparathyroidism, QUS of the calcaneus and biochemical parameters were measured in 264 women aged 85±7 (SD) years and in 103 men aged 81±8 years living in 19 nursing homes. Vitamin D deficiency was frequent in this population: 41.9% of the women and 31.4% of the men had a serum 25-hydroxyvitamin (25OHD) level below the 2.5th percentile level of 3276 normal Swiss adults (6.2 μg/l or 15.5 mmol/l). Hyperparathyroidism was less frequent: serum parathyroid hormone (PTH) levels were above the 97.5th percentile level of normal adults (70 pg/l) in 18.9% of women and 9.8% of men. In women, QUS data correlated significantly with age (r=−0.297), body mass index (BMI) (r=0.403), calcium (r=0.220), PTH (r=−0.296), 25OHD (r=0.298) and alkaline phosphatase (AP) (r=−0.170) for broadband ultrasound attenuation (BUA), and with age (r=−0.195), BMI (r=0.208), PTH (r=−0.174), 25OHD (r=0.140) and AP (r=−0.130) for speed of sound (SOS). In men, ultrasound data correlated with BMI (r=0.326), calcium (r=0.199), 25OHD (r=0.258) and AP (r=−0.311) for BUA, and with AP (r=−0.196) for SOS. In women, but not in men because of their smaller number, a multivariate analysis was performed to examine relationships between age, BMI, biochemical markers and QUS. Age, BMI, PTH and phosphate explained 30% of the variance of BUA and 10% for SOS. In conclusion, QUS of bone evaluates characteristics of bone that are influenced, at least partially, by age, BMI and the secondary hyperparathyroidism due to vitamin D deficiency. Part of this work was presented at the 17th Annual Meeting of the American Society of Bone and Mineral Research in Baltimore, MA, USA, September 1995.     

Randomized, Double-masked, 2-year Comparison of Tibolone with 17β-Estradiol and Norethindrone Acetate in Preventing Postmenopausal Bone Loss

In this 2-year, randomized study, we compared the efficacy and tolerability of tibolone 2.5 mg (n= 75), tibolone 1.25 mg (n= 76) and estradiol 2 mg plus norethindrone acetate 1 mg (E₂/NETA; n= 74) for preventing bone loss in postmenopausal women. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry, and bone remodeling markers were assessed every 6 months. Side-effects were assessed quarterly. After 24 months, the mean increase (± SD) in lumbar spine BMD from baseline was 3.6%± 2.9%, 1.9%± 3.5% and 6.8%± 4.5% in the tibolone 2.5 mg, tibolone 1.25 mg and E₂/NETA groups, respectively. All pairwise differences were significant. The proportion of responders (women with a change from baseline in lumbar spine BMD of ≥−2% after 2 years) was 95.7%, 89.0% and 98.5% with tibolone 2.5 mg, tibolone 1.25 mg and E₂/NETA, respectively. Similar results were obtained for femoral BMD, although the difference between tibolone 2.5 mg and E₂/NETA was not significant at 24 months. Decreases in bone remodeling markers were similar in the three groups. Vaginal bleeding was more common in the E₂/NETA group (33.8%) than with tibolone 2.5 mg (12.0%) or tibolone 1.25 mg (9.2%), as was breast pain (23.0%, 2.7% and 2.6%, respectively). Each treatment effectively prevented bone loss. Overall, tolerability of tibolone was better than with E₂/NETA, because of less frequent vaginal bleeding and breast pain. This may promote long-term adherence. Received: 6 July 2001 / Accepted: 3 October 2001     

Elucidating the relationship between cardiac preload and renal perfusion under pneumoperitoneum

Introduction Pneumoperitoneum is associated with a well-described decrease in renal blood flow, but it remains unclear whether a decrease in cardiac preload is responsible. Our aim was to characterize the relationship between cardiac preload and renal perfusion during pneumoperitoneum. Methods Eleven pigs were submitted to three 30 minute study periods: 1) Baseline (n=11): no interventions, 2) Pneumoperitoneum (n=11): 12 mmHg CO2 pneumoperitoneum, 3) Preload Reduction: pneumoperitoneum and nitroglycerin infusion (n=8); or pneumoperitoneum and hemorrhage to a mean arterial pressure (MAP) of 40 mmHg (n=3). Echocardiographic measurements of left ventricular end-diastolic diameter (LVEDD) were used as an index of preload. Renal cortical perfusion (RCP) was measured using laser doppler flowmetry. Results LVEDD decreased from 4.2 ± 0.5 to 4.1 ± 0.6 cm (p=0.02) with pneumoperitoneum and then to 4.0 ± 0.5 cm (p=0.03) with the addition of nitroglycerin. There was no statistically significant change in RCP with pneumoperitoneum (33.5 ± 8.4 to 28.5 ± 8.4 ml/min/100g tissue, p=0.2), but it decreased to 18.5 ± 11.3 ml/min/100g tissue (p=0.001) with the addition of nitroglycerin. The correlation between RCP and LVEDD was weak (0.35, p=0.003), whereas correlation between RCP and MAP was superior (R=0.59, p<0.0001). Conclusions While decreasing preload under extreme lab conditions also decreases RCP, simply creating a pneumoperitoneum of 12 mmHg does not. The decrease in renal blood flow associated with pneumoperitoneum is likely not solely a function of preload.     

Relationship of glomerular filtration rate and serum CK activity after resistance exercise in women

The aim of study was to assess the correlation between the changes in serum CK activity after a resistance exercise and renal function measured by glomerular filtration rate (eGFR). Twenty-nine trained women (32 ± 10 years; 157 ± 4 cm; 58.8 ± 6.4 kg) performed a resistance exercise session with 17 exercises with 3 × 12 repetitions in a circuit training fashion. Subjects provided blood samples prior to exercise session (PRE), and at 24, 48, and 72 h following exercise session for creatine kinase (CK) and creatinine. 24-Urine samples were collected before and 72 h after exercises. eGFR was obtained by the three most recommended methods (MDRD; MCQE; Cockcroft-Gault). After the exercise session, serum CK activity increase up 1.68 times (P < 0.01). Serum creatinine increased 25.5% (P = 0.0000) while urinary creatinine decreased on average 6.4% (P = 0.0422). eGFR decreased in all formulas: MDRD by 21.5%, MCQE by 14.2%, and C-G by 17% (all with P < 0.01). Ccr also decreased (−22.9%, P < 0.01). The index of correlation was significant for MDRD (r = −0.924; P < 0.01), C-G (r = −0.884; P < 0.01), and MQCE (r = −0.644; P < 0.05). In conclusion, we observed a significant negative correlation between CK activity and the eGFR indices of renal function.