[Nutritional support in acute kidney injury]. / Supporto nutrizionale nel danno renale acuto.

Optimal nutritional requirements and nutrient intake composition for patients with acute kidney injury is still a partially unresolved issue. Targeting nutritional support to the actual protein and energy needs improves the clinical outcome of critically ill patients. So far, very few data are currently available on this topic in acute kidney injury. In this specific clinical condition, the risk for under- and overfeeding may be increased by factors interfering on nutrient need estimation, such as rapidly changing body weight due to fluid balance variations, nutrient losses and hidden calorie sources from renal replacement therapy. Moreover, since acute kidney injury is now considered a kidney-centered inflammatory syndrome, the renoprotective role of specific pharmaconutrients with anti-inflammatory properties remains to be fully defined. This review is aimed at discussing recently published results concerning quantitative and qualitative aspects of the nutritional approach to acute kidney injury in critically ill patients.

[Prognosis evaluation in the critically ill with acute renal failure]. / Indici prognostici nel paziente critico con insufficienza renale acuta.

Acute renal failure (ARF) is highly incident among hospitalized patients, especially in intensive care units. ARF carries an independent and significant risk for increased mortality, morbidity, and health resources usage, both in the short- and the long-term perspective. Many controversies exist concerning the epidemiological and prognostic aspects of ARF. Key problems are the lack of a widely accepted ARF definition, the poor knowledge of the pathophysiological mechanisms of complications peculiar to ARF, and the unavailability of prognostic tools able to adequately express the medical complexity of the syndrome. These aspects are fundamental with regard to ARF prevention, a strategic goal in the approach to the syndrome; therefore, they will analyzed in depth in this review.

[Sustained low-efficiency dialysis in acute renal failure]. / Terapie sostitutive renali intermittenti prolungate (SLED/EED) nell'insufficienza renale acuta in terapia intensiva.

Renal replacement therapies (RRT) are a key component of the therapeutic approach to acute renal failure (ARF) in the intensive care unit (ICU), and they are usually performed as classic Intermittent (intermittent hemodialysis) or continuous RRT (such as for example continuous venovenous hemofiltration, CVVH). No clear evidence exists on what the first-choice RRT option should be for ICU patients with ARF. Alternative strategies have been developed, under the form of intermittent prolonged RRT, with the aim of providing easy to perform, highly efficient, and less expensive RRT in the ICU. In this review we put forward the hypothesis that hybrid RRT, such as sustained low-efficiency dialysis ( sLED), could offer a valuable alternative to the currently available strategies in the critically ill with ARF.

[Artificial nutrition in acute renal failure]. / Nutrizione artificiale nell'insufficienza renale acuta.

Artificial nutrition in course of acute renal failure (ARF) is reviewed, on the basis of recent concepts on epidemiology and prognosis of the syndrome in critically ill patients. The relationships between nutritional status and ARF are evaluated, analyzing the possible role of nutritional status alterations as comorbidities and complications; pathogenetic mechanisms and consequences of hypercatabolism are described, with special regard to the peculiar metabolic derangements which are the hallmark of ARF. The effects of artificial nutrition on mortality and morbility in ARF are illustrated, along with quantitative and qualitative aspects of nutritional support (energy and protein needs, trace elements, vitamins etc). A rational approach to nutritional management of ARF patients is proposed, stressing the potential role of enteral nutrition, as well as the need for a full integration between nutritional support and renal replacement therapies.

[Antihaemostatic strategies or renal replacement therapies in acute renal failure]. / Trattamento anticoagulante per le terapie sostitutive della funzione renale (RRT) nell'insufficienza renale acuta.

Critically ill patients with acute renal failure, and especially those with sepsis, may have increased coagulation changes as well as a high incidence of hemorrhagic complications. Thus, in this clinical condition, the use of renal replacement therapies (RRT) can be frequently complicated both by high rates of extracorporeal circuit coagulation, resulting in a reduced treatment efficacy, and by increased incidence of bleeding. Heparin is the most commonly used RRT anticoagulant, even if several alternative options have been proposed, aiming at obtaining regional anticoagulation (i.e., limited to the extracorporeal circuit). This review analyses modern strategies for RRT anticoagulation and evaluates safety and efficacy parameters of each method. In this regard, no definite recommendations can be made based on the available evidence further randomised controlled trials are needed in this field, with a clear endpoint definition.

[Lead and blood pressure]. / Piombo e pressione arteriosa.

Evidence, even if not univocal, of increase of systolic and diastolic blood pressure for Pb doses lower than 30 microg/dl stimulated studies in the last years and opened a discussion on a possible relapse in morbility and mortality, since hypertension is an important factor of cardiovascular risk. In this study, it was possible to investigate the relationship between lead and blood pressure of 303 subjects occupationally exposed to this metal with blood-Pb between 10 and 80 microg/dl and 206 subjects belonging to the general population with blood-Pb between 0.5 and 9 microg/dl. In both groups it resulted a positive and statistically significant correlation between blood-Pb values and systolic and diastolic blood pressure values, in detail in hypertensive subjects, belonging to the not-occupationally exposed group, this effect is proportionally higher. The effect of lead on blood pressure appears therefore proved, as confirmed by previous literature, but taking into consideration three specific information. It presents itself in a large range of doses, it is quantitatively very modest, it appears more evident at low doses, thus we could hypothesize different mechanisms for different doses.

Minimal sentinel node procedure for staging early breast cancer.

AIMS AND BACKGROUND: Sentinel lymph node dissection (SLND) has recently been evaluated as a new staging technique for early breast cancer. To minimize the extent of surgery, the feasibility of eradicating primary breast lesions and the relative sentinel lymph nodes (SLN) under regional anesthesia was evaluated in this study. METHODS AND STUDY DESIGN: A selected population of 76 patients with suspected operable breast cancer and no clinically palpable lymph nodes was enrolled in the study. Intra- and perilesional administration of a radiotracer was performed. Lymphoscintigraphy was carried out to confirm the drainage pathway and locate the SLN. The following day, after inducing a nervous block induction of the ipsilateral intercostal nerves, we performed the surgical procedure with the help of a hand-held gamma-detecting probe. In case the primary lesion was diagnosed as invasive carcinoma by frozen section, the SLN and the remaining axillary lymph nodes (non-SLNs) were removed. The status of SLN and non-SLNs was compared. RESULTS: The primary breast lesion was located and excised in all cases (identification rate: 100%). Lymphoscintigraphy positively identified SLNs in 40/45 (89%) patients; in five patients no lymphatic drainage was detected. In 38 cases an average of 1.5 SLNs and 14 non-SLNs per patient were removed and pathologically analyzed; the remaining two patients showed SLNs in the internal mammary chain, which were not excised. Twenty-nine percent of the patients showed metastatic disease in the lymph nodes examined. Of all patients with affected nodes, 55% had cancer cells only in the SLN. No false negatives (skip metastases) were found. No immediate or long-term anesthesia-related complications (e.g., pleural lesions, intravascular injection) were observed. CONCLUSIONS: Our data confirm the feasibility of single radiotracer administration for both occult lesion and SLN localization as well as the usefulness of SLND in staging early breast cancer. Regional anesthesia resulted in easy management and good patient compliance. This time-saving procedure allowed the completion of the whole surgical plan, reducing the recovery time without modifying the effectiveness of surgery.

Radioguided-surgery of early breast lesions.

BACKGROUND: Radioguided-surgery has been recently proposed in patients with clinically occult breast lesions. This study aimed to evaluate the feasibility of correctly locating and eradicating, by a single intralesional injection of a radiotracer, any breast lesion and, in the case of malignancy, to perform simultaneous sentinel lymph node (SLN) biopsy procedure. PATIENTS AND METHODS: Sixty-three women with early breast lesions were enrolled: 42 were invasive carcinomas, 16 in situ ductal carcinomas (DCIS) and 5 fibroadenomas. RESULTS: Scintigraphic images clearly identified the lesions in all patients while SLN/s were evident in 88% of them. At surgery all the breast lesions were easily radiolocalized and eradicated with minimum surgical trauma and, for those patients with invasive carcinomas, the SLN technique was performed in 86% of them. No skip metastases were found. CONCLUSION: A single intralesional administration of radiotracer is an easy and reliable procedure to simultaneously locate and remove both the non-palpable breast lesion and the SLN when primary malignancy was intraoperatively confirmed.

Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats.

BACKGROUND: Peroxynitrite (ONOO-), the product of superoxide and nitric oxide, seems to be involved in vascular alterations in hypertension. OBJECTIVES: To evaluate the effects of ONOO- on endothelium-dependent and independent aortic vascular responsiveness, oxidized/reduced glutathione balance (GSSG/GSH), malondialdehyde aortic content, and the formation of 3-nitrotyrosine (3-NT), a stable marker of ONOO-, in N-acetylcysteine (NAC)-treated normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). RESULTS: In SHR only, NAC significantly reduced heart rate and systolic, but not diastolic, blood pressure. It also improved endothelium-dependent aortic relaxation in SHR, but not after exposure to ONOO-. Endothelium-dependent and independent aortic relaxations were markedly impaired by ONOO- in both strains of rat. NAC partially protected SHR against the ONOO- -induced reduction in endothelium-independent relaxation. Aortic GSSG/GSH ratio and malondialdehyde, which were higher in SHR than in WKY rats, showed a greater increase in SHR after exposure to ONOO-. NAC decreased GSSG/GSH and malondialdehyde in both strains of rat before and after exposure to ONOO-. The 3-NT concentration, which was similar in both strains of rat under basal conditions, was greater in SHR than in WKY rats after the addition of ONOO-, with a reduction only in NAC-treated SHR. CONCLUSIONS: These findings suggest an increased vulnerability of SHR aortas to the effects of ONOO- as compared with those of WKY rats. The selective improvements produced by NAC, in systolic arterial pressure, heart rate, aortic endothelial function, ONOO- -induced impairment of endothelium-independent relaxation, aortic GSSG/GSH balance, malondialdehyde content and 3-NT formation in SHR suggest that chronic administration of NAC may have a protective effect against aortic vascular dysfunction in the SHR model of hypertension.

Norepinephrine reuptake is impaired in skeletal muscle of hypertensive rats in vivo.

Certain forms of experimental hypertension are characterized by organ-specific alterations of catecholaminergic pathways. The purpose of this study was to evaluate, in the same awake and freely moving normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) before and after the development of arterial hypertension, the norepinephrine (NE) turnover and, in particular, the neuronal NE reuptake activity that ends its effects once released from nerve terminals, in subcutaneous adipose tissue and in skeletal muscle, whose sympathetic efferents are respectively independent or dependent from baroreflexes. Plasma and tissue interstitial NE and 3,4-dihydroxyphenylethylene glycol (DHPG), its major deaminated metabolite, were measured before and after blockade of NE reuptake by tissue perfusion of desipramine through microdialysis probes. Arterial pressure and plasma NE in SHR were similar to those in WKY at 5 weeks of age but increased at 16 weeks of age. In contrast, plasma DHPG was already higher in young SHR. Basal interstitial NE and DHPG were increased in both tissues of young and old SHR compared with age-matched WKY. Desipramine induced a higher rise of interstitial NE in SHR of both ages, with a lesser increase in the skeletal muscle of old compared with young SHR. These results indicate an increased NE turnover in prehypertensive and hypertensive SHR in both baroreflex-dependent and -independent tissues, not shown by plasma NE levels in young SHR. In the skeletal muscle, where sympathetic efferents are baroreflex dependent, the reduced interstitial NE reuptake contributes to the higher availability of interstitial NE for postsynaptic effects in old SHR.

Outbreak of acute renal failure due to cefodizime-vancomycin association in a heart surgery unit.

OBJECTIVE: To describe an outbreak of acute renal failure (ARF) occurring in a group of patients undergoing open-heart surgery, simultaneously to a change in perioperative antibiotic prophylaxis. DESIGN: Case series. SETTING: A nine-bed heart surgery intensive care unit, serving a 1,300-bed University teaching hospital. PATIENTS: Thirty-two patients undergoing open-heart surgery during an 11-day period, when the preoperative surgical prophylaxis protocol had been changed from the usual antibiotic association of ceftriaxone + vancomycin to cefodizime + vancomycin. RESULTS: ARF occurred in 16 of the 32 (50%) patients exposed to the new antibiotic prophylaxis regimen; seven patients had oliguric ARF, and nine patients had an increase in serum creatinine (SCr) levels >50% over 24-48 h. In the seven patients with oliguric ARF, SCr increased from a median preoperative level of 88 micromol/l (80-115 micromol/l) to a peak value of 725 micromol/l (521-857 micromol/l) in 5 days (4-6). Eight patients out of the sixteen with ARF (50%) were diabetics, as opposed to none of the 16 patients not experiencing ARF. Renal biopsy (three patients) showed tubular dilation and necrosis, interstitial edema, and lymphomononuclear infiltrate of moderate degree. Only one patient required hemodialysis, and all recovered renal function. No other cases of unexplained ARF occurred in the unit after the original prophylaxis protocol was resumed. CONCLUSION: The simultaneous infusion of cefodizime and vancomycin may involve a high risk of substantial renal function derangement, especially in diabetics.

Doppler tissue echocardiography: myocardial wall motion velocities in essential hypertension.

AIMS: Doppler tissue echocardiography (DTE) was applied to extract the myocardial wall velocities along different planes and evaluate the left ventricular function in essential hypertension. METHODS AND RESULTS: Fifty-four hypertensives (HT) were compared to a control group of 31 normotensive (NT) subjects. The short-axis shortening and lengthening was assessed through the parasternal projections, sampling from interventricular septum and posterior wall. Through the apical projections the mitral annulus excursion was observed at four sites (anterior, posteroseptal, lateral, inferior walls) to assess the longitudinal dynamic of the heart. In each myocardial segment, peak velocity and time-velocity integral for systolic (S) and diastolic waves (E and A) were measured and their means for the long- and short-axis directions were calculated. Significant changes in hypertensives involved mainly the longitudinal motion. In diastole, the E-wave relaxation velocity was significantly decreased and the late A-wave velocity was unchanged. The E/A velocity ratio was significantly reduced. Relaxation velocity was negatively correlated to age, left ventricular mass and diastolic blood pressure. In systole, the peak S-wave shortening velocity was reduced and no association with age, left ventricular mass and blood pressure could be demonstrated. The range of segmental data produced by DTE proved useful to manufacture sensitive indices for recognition of hypertensive damage. Single DTE variables also proved slightly more sensitive than those extracted from the mitral flow pattern for the discrimination of HT patients. CONCLUSION: The presence of impaired relaxation was confirmed by DTE in a large portion of patients with hypertension and left ventricular hypertrophy. A peculiar systolic disturbance is evidenced by this technique. DTE-derived information can be used to detect early and quantify target-organ damage and its progression or regression during antihypertensive treatment.

Effect of antioxidant treatments on nitrate tolerance development in normotensive and hypertensive rats.

OBJECTIVES: To investigate the effect of chronic antioxidant treatments on the development of nitrate tolerance in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats by evaluating (i) coronary vascular reactivity, (ii) lipid peroxidation (malondialdehyde), and (iii) peroxynitrite formation (3-nitrotyrosine). METHODS: Tolerance was induced in 16-week-old male SHR and WKY, by 4 days of continuous treatment with nitroglycerin patches. Two groups were orally pre-treated (2-weeks) with antioxidants: N-acetyl-L-cysteine (NAC) or melatonin. Effects of serotonin (5-HT) and sodium nitroprusside (SNP) perfusion were tested in isolated Langendorff-perfused hearts. 3-Nitrotyrosine levels were measured in coronary sinus effluent and malondialdehyde in plasma. RESULTS: Nitrate tolerance reduced SNP-induced dilation in both strains. This alteration was differently improved by antioxidants: melatonin was effective in SHR, whereas NAC was effective in WKY. Tolerance also reduced 5-HT-mediated vasodilation in WKY, which was reversed by both antioxidants. By contrast, nitrate tolerance enhanced the vasoconstriction to 5-HT in SHR and both antioxidants prevented this response. Furthermore, tolerance was associated with higher malondialdehyde levels in both strains and with higher 3-nitrotyrosine levels in SHR. These changes were reversed by both antioxidants. CONCLUSIONS: A participation of oxidative stress was suggested during nitrate tolerance development, since antioxidants prevented the increase in lipid peroxidation and improved vascular responses to SNP and 5HT. Differential effects of antioxidants on SNP-induced vasodilation in SHR and WKY may suggest distinct mechanisms of tolerance development in hearts from hypertensive and normotensive rats. An increased peroxynitrite generation, expressed by higher 3-nitrotyrosine levels, could contribute to nitrate tolerance in the coronary circulation of SHR.

Regional sympathetic activity in pre-hypertensive phase of spontaneously hypertensive rats.

Imbalances in central and peripheral sympathetic nervous system (SNS) activity have been observed in essential and experimental hypertension. This study was carried out in order to evaluate SNS activity in two distinct tissue types of spontaneously hypertensive rats (SHR), compared to Wistar-Kyoto normotensive (WKY) rats, in the pre-hypertensive phase (4-5 weeks of age). Interstitial concentrations of norepinephrine (NE) and other catecholamines were measured by microdialysis in striated muscle, whose tone is controlled by baroreflexes, and in the subcutaneous adipose tissue where sympathetic output mainly controls metabolism. Two groups of SHR and WKY male rats were studied, aged 4-5 weeks, with a mean body weight of 92 and 86 g respectively. Systolic blood pressure (SBP, tail-cuff) values were 113 mm Hg (SD +/- 6.2) in SHR and 108 mm Hg (SD +/- 7.3) in WKY rats (p=0.28,t test). Two microdialysis probes were positioned in the subcutaneous fatty tissue and in the striated muscle of the parascapular region and perfused with Ringers' solution. The dialysate was collected every thirty minutes for 3 hours and analyzed in HPLC-ED to determine the content of NE and other catecholamines. Interstitial levels of NE were higher in SH than in WKY rats in both tissues. Mean NE values from subcutaneous adipose tissue in 4-5 week-old SHR were 1162 +/- 193 pg/ml compared to 496 + 188 pg/ml in WKY rats (p<0.001, t test). Muscle tissue NE levels in SHR were 1241 +/- 337 pg/ml vs. 521 +/- 138 pg/ml in WKY rats (p<0.001, t test). Plasma NE concentrations (279 +/- 61 pg/ml in SHR vs 246 + 69 pg/ml in WKY P = 0.65, t test) were not significantly different between the two strains at this young age. These findings suggest SNS hyperactivity in young SHR, though still normotensive, possibly dissociated from regional components of regulation (baroreceptor control in striated muscle and metabolic control in subcutaneous adipose tissue).

[Continuous veno-venous hemofiltration in acute renal insufficiency and heart failure]. / Emofiltrazione veno-venosa continua nell'insufficienza renale acuta associata ad insufficienza cardiaca.

The application of intermittent renal replacement therapies in critically ill patients with both acute renal failure and heart failure is often associated with circulatory instability and refractory hypotension. We have evaluated the efficacy and safety of a continuous technique (continuous veno-venous hemofiltration-CVVH) in 7 patients (1 male, 6 females, mean age 77 +/- 4 years) referred to our intermediate care unit for oliguria, acute renal failure and NYHA functional class IV, CVVH was performed by a peristaltic pump with blood flow at 200 ml/min, controlled ultrafiltration production rate (25 ml/min), minute to minute microprocessor controlled fluid balance system, biocompatible filters, low-dose prostacyclin for the extracorporeal circuit maintenance. Non invasive evaluation of cardiac function was performed by Doppler echocardiography. A total of 673 hours of CVVH were performed, with a mean extracorporeal circuit duration of 96 +/- 26 hours/patient (range 15-134). Daily urea clearance was 32 +/- 21. A mean body weight decrease of 10% was obtained (body weight before-CVVH 64.5 +/- 6 kg vs end-CVVH 58.5 +/- 5 kg, p < 0.01, paired data Student's test) without any hemodynamic worsening; metabolic control was adequate (urea before-CVVH 251 +/- 73 mg% vs end-CVVH 117 +/- 18 mg%, p < 0.01). Hospital survival was 42% (3/7 patients). In patients with acute renal failure and severe heart failure, CVVH allows an easy control of both fluid balance and acid-base equilibrium, along with the maintenance of acceptable hemodynamic stability.

Use of Fourier shape descriptors to improve the reproducibility of echographic measurements of arterial intima-media thickness.

BACKGROUND: A major source of error in the longitudinal assessment of the intima-media thickness (IMT) is the difficulty in retrieving the same echographic view of the vessel. OBJECTIVE: To present a method for increasing the reproducibility of IMT measurements by ultrasound in large arteries. METHOD: The Fourier descriptor is a well-known means of describing an object's shape. By means of the discrete Fourier transform (DFT), the shape was represented in a frequency domain; the computational advantages of the DFT then permitted a measure of unlikeness between different shapes (the 'distance' measure; DM) to be defined and used as a criterion for reproducing the contour. When the sonographer compared successive images of a complex vascular segment, like the carotid bifurcation, the identity of the echographic cut was deduced from the identity of the vessel's contour. The best match of the baseline image was the view that minimized the contour DM. RESULTS: Preliminary studies in the carotid artery bifurcations of eight subjects showed that the DM responds to systematic variations in the ultrasound interrogation angle and reveals minimal changes in transducer position. Duplicate scans of 12 subjects were performed by three sonographers with different strategies for acquisition of the same images: a low DM was associated with a low difference in pairs of IMT measurements. Data were classified into two groups (normal or borderline vessels with a pooled mean IMT of 0.62 mm and overtly thickened segments with a pooled mean IMT of 1.31 mm). When minimization of the DM was the criterion for the acquisition of replicate scans, the mean absolute difference of paired data for the mean IMT of the distal common carotid artery was 0.03 +/- 0.02 mm for the first group and 0.06 +/- 0.03 mm for the second group. This is a significant reduction in comparison with non-quantitative alternative criteria for image reproduction. For the maximum IMT of the same segments the mean absolute differences were 0.07 +/- 0.03 and 0.13 +/- 0.06 mm in the first and second groups, respectively. CONCLUSION: This method can be applied to the serial assessment of single atherosclerotic segments. The computational time is negligible. By reducing the scatter in sequential IMT data, longitudinal investigations (e.g. of the results of antihypertensive therapy) with shorter durations and smaller sample groups may be rendered feasible.

[The relationship between regional sympathetic activity and the onset of arterial hypertension in spontaneously hypertensive rats]. / Relazione fra attività simpatica distrettuale e sviluppo di ipertensione arteriosa in ratti spontaneamente ipertesi.

Several studies on spontaneously hypertensive rats (SHR) have demonstrated increased activity of the sympathetic nervous system (SNS). Using microdialysis, we have observed a greater release of norepinephrine (NE) into the interstitia of striated muscle, than that observed in control Wistar-Kyoto (WKY) rats in the prehypertensive phase. We confirmed these results in the subcutaneous adipose tissue where the sympathetic output controls metabolism. This study was carried out in order to evaluate SNS activity in two district tissue types conducted during both the prehypertensive phase (4-5 weeks of age) and the established hypertensive phase (15-16 weeks of age). Interstitial concentrations of NE were measured by microdialysis in striated muscle and subcutaneous adipose tissue. Two groups of rats were studied. Each group was made up of 8 subjects, SHR and WKY, males of 4-5 weeks of age with a mean body weight of 80 and 75 g respectively. Arterial systolic pressure (tail-cuff) values were 106 mmHg (standard deviation +/-8.2) in SHR and 101 mmHg (standard deviation +/-6.9) in WKY rats (NS). Two microdialysis probes were positioned in the subcutaneous fatty tissue and in the striated muscle of the parascapular region and perfused with Ringers' solution. The dialysate was collected every 30 min for 150 min and analyzed in high-performance liquid chromatography-every day. The content of NE and other catecholamines was determined. The same animals in both groups were reevaluated at 15-16 weeks of age. The mean body weight at this time was 246 g for the SHR and 289 g for the WKY rats. Arterial systolic pressure was 161 mmHg (standard deviation +/-13.3) and 108 mmHg (standard deviation +/-15.6) respectively (p < 0.01, Student's t test). Interstitial levels of NE were higher in SHR than in WKY rats in both tissues examined in the prehypertensive phase and in the established hypertensive phase. Mean NE values from subcutaneous adipose tissue in 4-5 week-old SHR were 1362.1 +/- 181.3 pg/ml compared to 479.0 +/- 162.3 pg/ml in WKY rats (p < 0.001, Student's t test). Muscle tissue NE levels in SHR were 1292.7 +/- 319.1 vs 536.3 +/- 146.7 pg/ml in WKY rats (p < 0.001, Student's t test). Values from the same rats at 15-16 weeks of age were 1405.0 +/- 148.3 pg/ml in SHR compared to 501.6 +/- 131.2 pg/ml in fatty tissue from WKY rats and 1893.7 +/- 214.6 vs 502.0 +/- 118.8 pg/ml in muscle tissue from the respective groups (p < 0.001, Student's t test). Significant differences (p < 0.01, Student's t test) were also observed in mean NE values in striated muscle tissue during the developing phase of hypertension. These findings document SNS hyperactivity in SHR when compared to WKY normotensive controls. This increase in SNS activity was observed in both the prehypertensive phase and in the established hypertensive phase indicating a complete disassociation from regional components of regulation (baroreceptor control and metabolic control), at least in the prehypertensive phase. These results may suggest as alteration in primitive sympathetic central outflow. Higher interstitial NE concentrations in the muscle tissue from SHR during the hypertensive phase compared to levels of young animals that are still normotensive, reveal an interesting pathophysiological aspect for the development of arterial hypertension.

FIV induced encephalopathy: early brain lesions in the absence of viral replication in monocyte/macrophages. A pathogenetic model.

FIV induced encephalopathy represents a model for the study of the neuropathogenesis of AIDS. It has yet to be determined whether massive viral replication is a prerequisite for the development of early brain lesions. Using a drug delivery system developed by us, we have shown that early encephalic lesions appear in FIV infected subjects even when viral transport within the brain has been markedly reduced or blocked.