Vascular and glomerular changes in the ageing kidney

Glomerular size, shape and number were examined in 44 human kidneys obtained at necropsy. Intrarenal vascular appearances were assessed histologically and by post-mortem angiography. The mean cross-sectional area of glomeruli varied nearly three-fold and glomerular number varied more than three-fold when kidneys from different adult subjects were compared but kidneys from the same subject resembled one another in glomerular size and number. A significant negative correlation existed in the adult between glomerular number and dimensions. Glomerular numbers in the few immature kidneys studied were similar to those in adult kidneys but glomeruli were smaller. Glomerular numbers tended to decline as age and severity of age-related vascular changes increased but correlation was poor. The possibility remains that glomerular involution in the senescent kidney occurs independently of events in the vessels. In men, but not in women, totally hyalinised glomeruli were observed more frequently with increasing age but their presence did not appear to be related to the degree of vascular change. In the senescent kidney, glomerular lobulations tended to disappear. This, together with glomerular loss, must result in a reduction in the area available for filtration. Assessments of total glomerular surface area should take account of glomerular shape and dimensions as well as numbers.     

The origin of amyloid in cerebral vessels of aged dogs

Our morphometric study of 30 dogs, mongrels, from 6.5 to 26.5 years of age, shows amyloid angiopathy in cortical and leptomeningeal vessels of all dogs older than 13.2 years of age, and the increase in the numerical density of amyloid-positive vessels correlated with age. Cluster analysis distinguished the group of six dogs (25%) to be relatively less affected, a large group of 13 animals (54%) to have moderate pathology, and five dogs (21%) to have severe amyloid angiopathy. Amyloid accumulation starts in large vessels, particularly in the tunica media of large arteries. Amyloid deposition appears to be associated with smooth muscle cells. Ultrastructural studies of samples from nine dogs are in agreement with in vitro studies suggesting that smooth muscle cells are the source of soluble amyloid beta. beta-protein polymerizes in the basal lamina of the tunica media. Muscle cells in the area of amyloid-beta accumulation degenerate and die. Thioflavin-positivity of only 24% of cortical and 66% of leptomeningeal beta-protein-positive vessels suggests that thioflavin-negative deposits contain soluble, not yet fibrillized protein and/or partially degraded and depolymerized amyloid.     

Secretion of both IL-2 and IL-4 by tumor cells results in rejection and immunity

Chronic ischemia may cause end stage renal disease, especially in older patients with atherosclerotic renal artery stenosis. Examining the pathology of the ischemic kidney is a fundamental first step toward understanding the mechanisms of this injury. In experimental renal hypoperfusion, there is evidence of a mixture of adaptive responses, tubular and endothelial cell damage and repair events. These processes are reflected in a wide spectrum of morphological changes that include atrophy, focal necrosis, epithelial regeneration, apoptosis, inflammation, interstitial fibrosis, and thrombosis. The most severe damage is seen in the outer medulla, a region with marginal oxygenation even in normal circumstances. In the usual clinical case, the effects of aging, pre-existent hypertension, and the process of atherosclerosis further complicate the pathological picture. Lesions related to these factors include arteriosclerosis, athero-emboli, various types of glomerulosclerosis, and severe tubulointerstitial damage leading to "atubular glomeruli" and regional cortical scarring (nephrosclerosis). In this article, some mechanisms determining the varied and complex pathological findings that may be observed in individual cases are outlined.     

Characterization of cytochrome P450 (CYP3A12) induction by rifampicin in dog liver

We investigated the mechanisms of renal vascular wall thickening in a rat model of N-nitro L-arginine methyl ester (L-NAME)-induced hypertension. To separate the effects of L-NAME-induced hypertension from other effects of nitric oxide (NO) inhibition, we created two models of L-NAME-induced hypertension: both had the same blood pressure level but NO inhibition was moderate in one group (group M) and severe in the other (group S). Urinary excretion of nitrates and nitrites was lower in group S than in group M. Wall thickening and lipid deposition in renal vessels were significantly greater in group S than in groups M. Simple and multiple regression analyses indicated that renal vascular wall thickening was more strongly correlated with lipid deposition than with blood pressure. The number of vessels positive for staining with Sudan black B was negatively correlated with urinary NO excretion. Expression of fibronectin and transforming growth factor-beta was greater in the Sudan black B-positive than in the Sudan black B-negative vessels, suggesting that extracellular matrix production was increased in vessels with lipid deposition. Lipid deposition and increased production of extracellular matrix may contribute to renal vascular wall thickening in L-NAME-induced hypertension. Some mechanisms independent of hypertension play important roles in vascular wall thickening induced by NO inhibition.     

Comparison among several 99mTc antibody-labeling methods

The effects of angiotensin-converting enzyme (ACE) inhibition with perindopril on renal vascular structure were studied in control and streptozotocin diabetic male Sprague-Dawley rats after 3 weeks. After kidneys were perfusion-fixed at systolic blood pressure, morphometric analysis of vascular structural changes in the media of the renal vasculature at the cortico-medullary junction was performed. Vascular hypertrophy was present in the diabetic vessels, as assessed by an increase in medial cross-sectional area for a given lumen size. This relative increase in medial area was prevented by perindopril treatment, consistent with an antitrophic effect on diabetic kidney vessels by ACE inhibition. The diabetic kidney had an increased proportion of small vessels less than 50 microns diameter at the cortico-medullary junction, perhaps representing diabetes induced angiogenesis. This subpopulation of vessels was reduced in number after perindopril treatment. Our data support a role for increased activity of angiotensin converting enzyme as a mechanism for vascular hypertrophy, which may be involved in the pathogenesis of diabetic vasculopathy and nephropathy.     

Effect of extracranial carotid artery stenosis and other risk factors for stroke on periventricular hyperintensity

BACKGROUND AND PURPOSE: The pathogenesis of periventricular hyperintensity (PVH) is still uncertain. We investigated the relationship between PVH and risk factors for cerebrovascular diseases, especially extracranial carotid artery stenosis (ECAS). METHODS: We studied PVH and ECAS in 323 subjects between 1991 and 1994. Using 1.5-T MRI scan images, we measured PVH quantitatively at eight points and evaluated cerebral infarction. Duplex carotid sonography was performed on the carotid arteries bilaterally and used to divide the severity of ECAS into five grades. Risk factors for cerebrovascular diseases and atherosclerotic complications were assessed from the clinical history. RESULTS: Age was significantly correlated with the size of frontal and whole PVH (P < .01). Frontal PVH was significantly more severe in subjects with hypertension (P < .05). Frontal, occipital, and whole PVH were significantly more severe in subjects with a history of cerebrovascular accident (P < .01). Other risk factors and atherosclerotic complications were not correlated with PVH. There were no significant differences in the severity of PVH among the five groups of ECAS. The severity of PVH in each region was not related to ECAS. There was no significant difference in the age of patients in relation to the five grades of ECAS. However, PVH was significantly more severe in subjects with lacunar infarction or infarction of the deep border zone (P < .05). There was no relationship between PVH and cortical infarction or infarction of the cortical border zone. CONCLUSIONS: PVH correlated with age, hypertension, and past history of cerebrovascular disease but not with ECAS. PVH was significantly more severe in lacunar infarction and infarction of the deep border zone. These results suggest that small-vessel disease may underlie the pathogenesis and development of PVH.     

Renal structural-functional relationships in early diabetes mellitus

To define the earliest renal morphological changes in patients with type I diabetes, we studied renal function and morphometric analysis of renal biopsies in 59 patients with diabetes for 5-12 years and normal blood pressure, normal creatinine clearance (CCr), and negative dipstick urinary protein. Arteriolar hyalinization and intimal fibrous thickening were noted in 43%. Glomerular basement membrane thickness and fractional mesangial volume were increased in 51% and 56%, respectively. The pre-pubertal and post-pubertal years of diabetes were associated with similar degrees of renal structural changes, but during the pre-pubertal years normal urinary albumin excretion (UAE) was seen. Principal factor analysis of morphometric structural parameters yielded four clusters of variables: "glomerular size" correlated with patient age, CCr, and UAE; "peripheral capillary decrease" correlated with glycosylated hemoglobin, diastolic blood pressure, glomerular filtration rate, and UAE; "mesangial increase" correlated with UAE; and "interstitial scarring" correlated with diastolic blood pressure. This study provides unique documentation of renal structural abnormalities which precede clinically evident renal functional abnormalities and documents that these early structural abnormalities are present in the pre-pubertal years of diabetes as well as postpuberty, and are associated with each other in constellations that correspond to postulated mechanisms in diabetic nephropathy.     

Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats

The effect of the combined ETA/ETB endothelin receptor antagonist bosentan on blood pressure, vascular hypertrophy, and pathologic renal changes was investigated in a model of malignant hypertension, severe vascular hypertrophy, and enhanced vascular expression of endothelin-1, the deoxycorticosterone acetate (DOCA), and salt-treated spontaneously hypertensive rat (SHR). DOCA-salt treated SHR received 100 mg bosentan per kilogram weight per day mixed with their food. Systolic blood pressure of untreated DOCA-salt SHR rose to 241 +/- 1.5 mm Hg, whereas that of bosentan-treated rats rose to 221 +/- 5.1 mm Hg (P < .01). Cardiac and conduit artery mass were not affected by treatment. Small arteries from the coronary, renal, and mesenteric circulations showed a smaller media width and cross-sectional area of the media in rats treated with bosentan than in untreated rats. The kidneys showed the presence of fibrinoid necrosis in a high percentage of afferent arterioles and glomeruli of untreated DOCA-SHR. Some kidneys of treated rats exhibited less severe vascular hypertrophy and lesser extent of vascular or glomerular fibrinoid necrosis, but the renal injury score of bosentan-treated DOCA-SHR was only at the limit of significance from that of untreated rats (P = .06). These results suggest a role for endothelin-1 in blood pressure elevation and the severe vascular hypertrophy of small arteries of the coronary, renal, and mesenteric vasculature, but not of the heart or larger conduit vessels in the malignant hypertension that SHR develop after treatment with DOCA and salt. Although some bosentan-treated rats showed fewer renal lesions, a significant effect on renal pathology could not be unambiguously demonstrated. Further studies will be necessary to determine whether endothelin antagonists may indeed offer some degree of renal protection and have therapeutic potential in severe or malignant hypertension.     

Evaluation and treatment of urinary tract infections in children

Urinary tract infections (UTIs) are among the most common bacterial infections encountered by primary care physicians. Although UTIs do not occur with as great a frequency in children as in adults, they can be a source of significant morbidity in children. For reasons that are not yet completely understood, a minority of UTIs in children progress to renal scarring, hypertension and renal insufficiency. Clinical presentation of UTI in children may be nonspecific, and the appropriateness of certain diagnostic tests remains controversial. The diagnostic work-up should be tailored to uncover functional and structural abnormalities such as dysfunctional voiding, vesicoureteral reflux and obstructive uropathy. A more aggressive work-up, including renal cortical scintigraphy, ultrasound and voiding cystourethrography, is recommended for patients at greater risk for pyelonephritis and renal scarring, including infants less than one year of age and all children who have systemic signs of infection concomitant with a UTI. Antibiotic prophylaxis is used in patients with reflux or recurrent UTI who are at greater risk for subsequent infections and complications.     

Fluency and memory differences between ischemic vascular dementia and Alzheimer's disease.

This study compared 32 patients with ischemic vascular dementia (IVD) to 32 patients with probable Alzheimer's disease (AD) on select language and verbal memory tests. The IVD and AD patients were individually matched on the basis of age, dementia severity, years of education, and gender. The IVD patients had poorer verbal fluency, but better free recall, fewer recall intrusions, and better recognition memory than the AD patients. Relationships between the neuropsychological measures and radiological indexes of cortical and subcortical pathology were also examined. Number of infarcts, white-matter lucency, and ventricular enlargement correlated with some of the neuropsychological measures; cortical atrophy correlated with most of the measures. The findings suggest that neuropsychological deficits in IVD may be related to dysfunction of frontal-subcortical circuits, although an associated degenerative cortical process may also be involved. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Morpho-functional study of the kidney in patients with kidney disease and liver disease with magnetic resonance

INTRODUCTION: We studied renal function and perfusion after the i.v. injection of Gd-DTPA-BMA, a nonionic paramagnetic contrast agent, to assess renal morphology and function in normal subjects, in renal insufficiency patients and in patients with hepatic failure and normal renal function. The latter were chosen because some patients with advanced hepatic failure may suffer from the hepatorenal syndrome, characterized by severe vasoconstriction in the renal cortical vessels. We investigated if dynamic MRI can detect early renal perfusion abnormalities in the patients who will eventually develop this syndrome. MATERIAL AND METHODS: Thirty MR examinations were carried out on 30 subjects after the i.v. injection of Gd-DTPA-BMA. Our series consisted of: 10 normal subjects; 10 renal insufficiency patients; 10 patients with hepatic failure and normal renal function. MR examinations were performed on a Philips ACS II scanner operating at 1.5 T. Two sequences were carried out in all cases: T1-weighted SE and T1-weighted TGE sequences after the bolus injection of .1 mmol/kg contrast agent. Renal longitudinal diameter and parenchymal thickness were measured in all cases and signal intensity time curves were always made. The signal intensity of the cortex, corticomedullary junction, medulla and pyelocaliceal system of each kidney was measured using a region of interest (ROI). The signal intensity curves were made considering quantitative parameters, including the area below the curve (ASC), the peak (P) and the time to peak (T-P). RESULTS: Longitudinal diameter and parenchymal thickness values were significantly lower in renal insufficiency patients than in normal subjects. Four phases were demonstrated after i.v. contrast agent injection in normal subjects, namely A) the cortical phase, B) the corticomedullary junction phase, C) the medullary phase, D) the pyelocaliceal phase. No signal intensity decrease in the medullary and pyelocaliceal curves was observed in renal insufficiency patients. Signal intensity curves values were lower in hepatic failure patients than in those with normal renal function. Hepatic failure patients could be divided into two groups: 5 patients had low P and ASC values and 4 had normal P and ASC values. The patients with lower P and ASC values developed the hepatorenal syndrome within a few months of the MR examination. DISCUSSION: Signal intensity decreased in the pyelocaliceal system phase in normal subjects because of the high paramagnetic contrast agent concentration. The lack of signal intensity decrease in renal insufficiency patients was caused by the reduced capability of concentrating Gd-DTPA-BMA. Lower signal intensity values in hepatic failure patients may be considered an early sign of the hepatorenal syndrome.     

Haemodynamic and renal effects of felodipine in young and elderly subjects

OBJECTIVE: To study the influence of age on renal and haemodynamic effects of the calcium antagonist felodipine. METHODS: Eight young (mean age 27 years) and eight elderly (mean age 75 years) healthy normotensive subjects were given felodipine intravenously for 120 min aiming at close to therapeutic plasma level concentration. Renal blood flow (RBF) and renal vascular resistance (RVR) was estimated from para-aminohippuric acid (PAH) clearance 51CrEDTA clearance was used to measure glomerular filtration rate (GFR) and used in the calculations of fractional excretion (FE) of electrolytes. Impedance cardiography was performed to assess stroke volume and for the calculation of cardiac output and ejection fraction. RESULTS: At the end of felodipine infusion, the concentration of felodipine was on average 10.0 nmol x l(-1) in young and 12.0 nmol x l(-1) in elderly subjects (NS). During felodipine infusion blood pressure (BP) decreased from 138/76 to 120/68 in elderly subjects. The BP in young subjects was 126/74 at basal and 125/70 after infusion of felodipine. The systemic and renal vascular resistance decreased to a similar extent in young and elderly subjects after felodipine infusion. Felodipine caused a decrease in systemic vascular resistance from 25.6 to 23.3 in elderly and from 23.8 to 21.8 in the young subjects. Mean values for RVR at baseline and during infusion of felodipine were significantly higher in the elderly (10.1-15.1) than in the young subjects (5.4-6.7). Felodipine reduced RVR by 10% in the young and by 12% in the elderly at the end of infusion. The young subjects had 31% higher GFR than the elderly subjects at the start of infusion. Felodipine infusion did not affect GFR. There were no effects on stroke volume and ejection fraction. An initial natriuretic effect was found after infusion of felodipine in the young subjects. The fractional excretion of all electrolytes tended to increase after both felodipine and placebo, more in the elderly than in the young subjects. CONCLUSION: The effects of felodipine on central and renal haemodynamics previously observed in young and middle-aged subjects also seem to exist in the elderly. Volume expansion seems to increase the excretion of electrolytes more in elderly than in young people, and therefore the effect of felodipine on natriuresis is more evident in young subjects.     

Technetium-99m dimercaptosuccinic acid scintigraphy studies of renal cortical scarring and renal length

The aims of this study were to validate 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy appearances with histopathological features of scarring; to evaluate the sensitivity and specificity of 99mTc-DMSA and ultrasound for the detection of renal scarring; to compare planar, pinhole and SPECT techniques when using 99mTc-DMSA; and to compare 99mTc-DMSA and ultrasound renal length measurement. METHODS: Reflux nephropathy was induced in large white pigs using established methods. To ensure that the abnormalities detected were scars and not inflammatory changes, the pigs were not studied until 3 mo after the treated episode of acute pyelonephritis confirmed by 99mTc-DMSA. RESULTS: Twenty pigs were enrolled in the study. Eleven reached the end point, but only nine pigs (18 kidneys) were available for analysis. Thirty-four scars were identified pathologically; 24 were present macroscopically and a further 10 were seen only on microscopy. Technetium-99m-DMSA abnormalities correlated with scars histopathologically with an accuracy of 92% versus that of ultrasound, 75% (p < 0.001). Technetium-99m-DMSA more accurately identified scarring with a higher sensitivity (76% versus 29%) and specificity (98% versus 92%) than ultrasound. On the 99mTc-DMSA study, pinhole imaging had the highest accuracy (92%) when compared with planar (90%) and SPECT (87%) data. These differences were not statistically significant. Renal lengths as measured on 99mTc-DMSA more closely correlated with length measurement at pathological examination than ultrasound. Technetium-99m-DMSA measurement was, on average, 6% higher than pathology, and ultrasound was, on average, 22% lower. CONCLUSION: Technetium-99m-DMSA appears to be the preferred method for the detection of renal cortical scarring and accurate renal length measurement when compared with ultrasound examination.     

Cooperative relaxation of supercoils and periodic transcriptional initiation within polymerase batteries

OBJECTIVE: To examine quantitatively white-matter changes at different sites in patients with definite vascular dementia and Alzheimer's disease. DESIGN: Prospective clinical and neuropathological series. SETTING: University Hospital clinics (Helsinki, Finland and London, Ontario). SUBJECTS: Twenty-two patients with a clinical and neuropathological diagnosis of vascular dementia and 20 patients with Alzheimer's disease. MEASURES: The frequencies of focal white-matter lesions, arteriolosclerosis, and cerebral amyloid angiopathy were assessed. Validated ratings and cell counts were done in the subcortical U-fiber, centrum semiovale, and periventricular areas of the frontal white matter. Degrees of abnormality (none, mild, moderate, severe) were rated for spongiosis (vacuolization of white matter), état criblé (widening of perivascular spaces), myelin loss, oligodendrocyte density, axonal loss, and overall. Densities of oligodendrocytes and astrocytes (cells per square millimeter) were determined. RESULTS: Patients with vascular dementia showed focal white-matter lesions and arteriolosclerosis more often than patients with Alzheimer's disease. The patients with vascular dementia also had significantly greater spongiosis (P<.001), état criblé (P=.004), myelin loss (P<.005) and overall white-matter abnormality (P<.001). Arteriolosclerosis was found in association with spongiosis but not with état criblé. Cerebral amyloid angiopathy did not appear to be related to any of the white-matter changes in patients with either vascular dementia or Alzheimer's disease. The U-fiber area showed fewer changes, and the periventricular area tended to be most affected. CONCLUSION: In addition to focal infarcts, patients with vascular dementia showed widespread diffuse changes, including spongiosis and arteriolosclerosis, along with état criblé and myelin loss. White-matter changes in patients with Alzheimer's disease could not be related to infarction. Pathologic changes in small blood vessels are associated with diffuse white-matter changes and may have a distinct role in the genesis of vascular dementia.     

Age-related and vasomotor stimuli-induced changes in renal vascular resistance detected by Doppler ultrasound

Indirect measurement of renal vascular resistance by duplex Doppler waveform analysis was evaluated in relation to aging and some pathophysiological conditions. Baseline renal resistive index (RRI) (peak systolic frequency shift - lowest diastolic frequency shift/peak systolic frequency shift) was measured in healthy controls aged 20 to 85 years by analyzing the blood flow velocity waveform of interlobar arteries. RRI changes induced by sympathetic activation (cold pressor test and handgrip test) or by fluid load were evaluated. Both repeatability and reproducibility were very good, as the intra and interoperator variations were all less than their reproducibility coefficients. RRI showed a significant increase with aging (ANOVA P < .001), particularly evident in subjects older than 50 years. Both the cold pressor test and handgrip test induced in all the subjects (n = 16) a significant increase in RRI (P < .001), from 0.59 +/- 0.04 to 0.69 +/- 0.04 (12 +/- 6%) for the cold pressor test and from 0.57 +/- 0.03 to 0.66 +/- 0.03 (15 +/- 2%) for the handgrip test. In eight subjects intravenous fluid load (0.25 mL/kg/min of 0.9% NaCl for 120 min) caused a significant decrease in RRI (P < .001), from 0.62 +/- 0.02 to 0.53 +/- 0.01 (17 +/- 2%), which was inversely related to mean blood pressure rise (r = 0.71, P < .001). These data show that pulsed wave Doppler analysis is an accurate method for an indirect evaluation of changes in renal vascular resistance induced by common vasomotor stimuli.     

Serum and plasma concentrations of clindamycin following a single intramuscular injection of clindamycin phosphate in maintenance haemodialysis patients and normal subjects

Serum levels of clindamycin bioactivity and total clindamycin were studied after single intramuscular injections of 300 mg of clindamycin phosphate in a group of 6 normal subjects and a group of 6 maintenance haemodialysis patients. The patients were studied during a non-dialysis period and then again during haemodialysis. Peak levels tended to be higher and elimination half-lives shorter in the patients than in the normal subjects. Possible reasons for these differences are discussed. There was no evidence that haemodialysis per se influenced the pharmacokinetics of clindamycin phosphate. The proportion of unhydrolysed clindamycin phosphate tended to be higher in the renal failure patients and the reason for this is not apparent. Little, if any, dosage modification is necessary in severe renal fialure although there is probably little point in exceeding a dose of 300 mg intramuscularly every 5 h even in severe infections in patients with severe renal failure. The higher peak levels in patients with advanced renal failure indicate the need for further studies with repeated doses.     

Incidence and morphology of endometrial angiopathies in mares in relationship to age and parity

The morphology of endometrial blood vessels in uterine biopsy specimens from mares of varying age and reproductive status was examined by light (n = 117) and electron microscopy (n = 13), and additionally after elastase digestion (n = 86). Inflammatory vascular alterations were observed in 20.5% of the specimens. Smaller and larger arterial and venous vessels demonstrated mild to severe degenerative lesions. Unaltered vessels were detected only in maiden mares. Vessels in older maiden mares were frequently affected by angiosclerotic changes, characterized by mild to moderate perivascular and intimal sclerosis. The incidence and severity of angiosis increased with the number of previous pregnancies and with advancing age. Changes in multiparous mares resembled the so-called "pregnancy-sclerosis" of other species, with fraying and disruption of the membrana elastica interna, medial atrophy intimal, medial and adventitial elastosis and fibrosis, and calcification processes within the media. Ultrastructural studies revealed characteristic arterial changes in post-parturient mares, namely, disruption of the membrana elastica interna, as well as activated smooth muscle cells and immature elastic fibres within the intima and inner media, suggesting a pregnancy-induced pathogenesis. Haemodynamic and hormonal alterations during pregnancy and the puerperium possibly induce active vascular remodelling. Cycles of vascular growth during pregnancy and subsequent involution post partum are thought to result in progressive degenerative vascular changes, as seen in multiparous mares. Ageing processes, chronic inflammation and short foaling intervals have to be considered as additional pathogenetic factors. Furthermore, severe angiosis was frequently combined with phlebectasia and lymphangiectasia. This may indicate a reduced ability of the vessels to adapt to the varying demands of uterine circulation, with a decrease of uterine perfusion and lymph drainage. Angiosis in older, multiparous mares might therefore be intimately related to infertility.     

Effects of intake level of a mixed diet on chewing activity and on particle size of ruminated boli, ruminal digesta fractions and faeces of steers

In the rat cortical taste area (CTA), we recorded 31 pairs of taste neurons and seven pairs of taste and non-taste neurons, with single or double electrodes. By using a cross-correlogram (CCG) in a stationary state, we examined the functional interaction between neurons of the pairs while activating them by taste stimulation. Though only 14.3% of the taste and non-taste neuron pairs were correlated, 54.8% of the taste neuron pairs showed correlated activities, 41.9% of them showing common inputs, including one with an additional excitatory connection. The remainder (12.9%) showed excitatory connections with a time lag of 1-3 ms. When pairs were recorded using single or double electrodes with an intertip distance of < 50 microns in a dorsoventral direction, a larger fraction had correlated activities than when the intertip distance was > 50 microns. Whereas pairs of neurons showed correlated activities in area DI whatever the vertical intertip distance was, most of the pairs having correlated activities in area GI were found within 50 microns of the vertical intertip distance. The taste profiles of common inputs to the pair were estimated on the basis of peak at time 0 in CCGs for various taste stimuli. The efficacy contribution of the source to target neurons tended to be larger when both had the same best stimulus. This tendency held true for pairs showing excitatory connections. Interlayer excitatory connections were also evident. It is concluded that a functional column with a diameter of 50 microns may present in the CTA in rats, and that information flow is larger between pairs of neurons with the same best stimulus.     

Renal vascular responses to angiotensin II in conscious spontaneously hypertensive and normotensive rats

It has been postulated that exaggerated renal sensitivity to angiotensin II may be involved in the development and maintenance of hypertension in the spontaneously hypertensive rat (SHR). The purpose of this study was to compare the renal vascular responses to short-term angiotensin II infusions (50 ng/kg/min, i.v.) in conscious SHRs and Wistar-Kyoto (WKY) rats. Renal cortical blood flow was measured in conscious rats by using quantitative renal perfusion imaging by magnetic resonance, and blood pressure was measured by an indwelling carotid catheter attached to a digital blood pressure analyzer. Renal vascular responses to angiotensin II were similar in control SHRs and WKY rats. Pretreatment with captopril to block endogenous production of angiotensin II significantly augmented the renal vascular response to exogenous angiotensin II in the SHRs but not in the WKY rats. The renal vascular responses to angiotensin II were significantly greater in captopril-pretreated SHRs than in WKY rats (cortical blood flow decreased by 1.66 +/- 0.13 ml/min/g cortex in WKY rats compared with 2.15 +/- 0.14 ml/min/g cortex in SHR; cortical vascular resistance increased by 10.5 +/- 1.4 mm Hg/ml/min/g cortex in WKY rats compared with 15.6 +/- 1.7 mm Hg/ml/min/g cortex in SHRs). Responses to angiotensin II were completely blocked in both strains by pretreatment with the angiotensin II AT1-receptor antagonist losartan. Results from this study in conscious rats confirm previous findings in anesthetized rats that (a) the short-term pressor and renal vascular responses to angiotensin II are mediated by the AT1 receptor in both SHRs and WKY rats, and (b) the renal vascular responses to angiotensin II are enhanced in SHRs compared with WKY rats when endogenous production of angiotensin II is inhibited by captopril pretreatment.     

Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis)

Insulin neuritis, or painful neuropathy following rapid improvement in glycaemic control, is well recognised but its aetiology is unclear. An understanding of the processes involved in the genesis of acute painful neuropathy of rapid glycaemic control may give an insight into the early pathogenetic factors leading to diabetic nerve damage in general. We have identified five subjects with insulin neuritis including one who developed severe autonomic neuropathy following treatment with insulin. Subjects underwent: 1) assessment of neuropathic symptom and deficit scores; 2) quantitative sensory and electrophysiological studies and 3) sural nerve epineurial vessel photography and fluorescein angiography in vivo. The sural nerve photographs were independently graded by an ophthalmologist. All subjects with insulin neuritis presented with severe sensory symptoms but clinical examination and electrophysiological tests were normal except in the subject with the severe autonomic neuropathy in whom all the tests were abnormal. On nerve photography, there was an abundance of epineurial nutrient vessels although these showed severe abnormalities including arteriolar attenuation, tortuosity and arterio-venous shunting in all subjects. Proliferating neural 'new vessels' which bear striking similarities to those found in the retina and that were more leaky to fluorescein than normal vessels, were observed in three subjects. Venous distension and/or tortuosity was also observed in three subjects and this was most marked in the subject with severe autonomic neuropathy. This study shows that epineurial nutrient vessel anatomy is abnormal in subjects with acute painful neuropathy of rapid glycaemic control, a condition previously thought to be purely metabolic in origin. The presence of epineurial arterio-venous shunting and a fine network of vessels resembling the new vessels of the retina, may lead to a 'steal' effect rendering the endoneurium ischaemic. This process may be important in the genesis of neuropathic pain, and further supports the importance of vascular factors in the pathogenesis of diabetic neuropathy.