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Gioacchino Li Cavoli,1 Giuseppe Mulè,2 Mario Giuseppe Vallone,3 Flavia Caputo1 1Nephrology, Dialysis and Renal Transplant Department, Civico and Di Cristina Hospital, Palermo, Italy; 2Internal Medicine, Cardiovascular and Renal Diseases Department, University of Palermo, Palermo, Italy; 3Radiology Department, Civico and Di Cristina Hospital, Palermo, Italy Abstract: Takayasu arteritis (TA) is a chronic vasculitis disease of unknown etiology. Clinically significant renal disease is relatively common, and renovascular hypertension is the major renal problem. The assessment of TA activity is usually challenging because vascular inflammation may progress to fixed vascular injury without findings of active disease. Until now, the best therapeutic options have not been identified. This review highlights the current perspectives of renal involvement in TA. Keywords: arteritis, kidney involvement, large vessel vasculitis

Abstract: Fusarium subglutinans is a maize ear rot pathogen and producer of beauvericin and other mycotoxins. This species has recently been split into two major phylogenetic within-species groups based on RFLP DNA sequence polymorphisms identified in the histone H3 and β-tubulin sequences. A Pan European collection of the fungus originating mostly from maize was subjected to phylogenetic analysis by RFLP grouping and to chemical analysis for beauvericin production. Of the 62 isolates belonging to Group 1, 48 (77%) produced from 10 to 532 µg/g of beauvericin, whereas none of the 39 Group 2 isolates synthesized detectable amounts of the mycotoxin. The association between RFLP group and beauvericin production is consistent with the existence of two reproductively isolated subgroups within F. subglutinans and indicates that the toxicological risk of isolates of F. subglutinans depends on the group with which they are affiliated. [Copyright &y& Elsevier]

The still-high mortality for lung cancer urgently requires the availability of new, noninvasive diagnostic tools for use in early diagnosis and screening programs. Recently, exhaled breath condensate (EBC) has been proposed as a useful tool to obtain biological information on lung cancer disease. This study provides, for the first time, evidence that DNA alterations already described in lung cancer are detectable in EBC from patients with non-small cell lung cancer (NSCLC) and in healthy subjects. Thirty patients with histologic evidence of NSCLC and 20 healthy subjects were enrolled in the present study. All subjects had allelotyping analysis of DNA from EBC (EBC-DNA) and from whole blood (WB-DNA) of a selected panel of five microsatellites (D3S2338, D3S1266, D3S1300, D3S1304, D3S1289) located in chromosomal region 3p. Results from healthy subjects and subjects with cancer, and from EBC and WB, were compared. In addition, the relationships with smoking habit and clinicopathologic tumor features were considered. Microsatellite alterations (MAs) were found in 53% of EBC-DNA and in 10% of WB-DNA loci investigated in patients with NSCLC (p < 10[-6]); conversely, MAs were present only in 13% of EBC-DNA and in 2% of WB-DNA informative loci in healthy subjects. In patients with NSCLC, a direct association between number of MAs detected in EBC-DNA and tobacco consumption was observed. We conclude that EBC-DNA is highly sensitive in detecting MA information unique to patients with lung cancer. Furthermore, MA information seems to be directly related with tobacco consumption, and is potentially applicable to screening and early diagnostic programs for patients with NSCLC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the relationship between insulin, the renin-aldosterone system and blood pressure in obese subjects. DESIGN AND METHODS: A cross sectional study of a group of severely obese normotensive subjects who were surgical candidates (n=39; mean BMI: 47.8±1.4) and a group of hypertensive patients (n=57; mean BMI: 28.0±0.7) twenty-nine of whom had BMI>27. All subjects were studied after 15 days on a balanced diet. Insulin, plasma renin activity and aldosterone were measured. RESULTS: Fasting insulin, plasma renin activity and aldosterone were higher in severely obese normotensive subjects than in hypertensive subjects (respectively 32.3±3.0 vs 13.1±1.0 mU/l, P=0.0001; 1.34±0.22 vs 0.88±0.12 ng/ml/h, P=0.04; 137.2±16.2 vs 87.9±12.1 pg/ml, P=0.015). Insulin was related to BMI and to aldosterone both in normotensive and in hypertensive patients. CONCLUSION: Hyperinsulinemia itself does not determine hypertension; in some people it could play a vasodilator role in opposition to the renin-aldosterone system. [ABSTRACT FROM AUTHOR]

Twenty-nine Fusarium isolates, representing three new taxa originated by Nirenberg from F. sambucinum Fuckel sensu lato, namely: F. sambucinum Fuckel sensu stricto, F. venenotum Nirenb., and F. torulosum (Berk. & Curt.) Nirenb., were tested for in vitro production of toxic secondary metabolites on autoclaved corn kernels. F. sambucinum sensu stricto was able to produce type A trichothecenes and enniatin B (EB). In particular, amongst the 14 isolates tested, 5 produced only diacetoxyscirpenol (DAS) (up to 700 µg/g); 1 produced only neosolaniol (NEOS) (250 µg/g); 2 produced T-2 toxin (T-2) + NEOS (up to 175 and 150 µg/g, respectively); 1 produced NEOS + DAS (300 and 100 µg/g, respectively); and 5 produced DAS + EB (up to 500 and 140 µg/g, respectively). All six isolates of F. venenotum were able to produce only DAS (up to 100 µg/g). F. torulosum produced no trichothecenes, but four out of nine tested isolates were able to produce EB (up to 140 µg/g). Zearalenones and type B trichothecenes were not found. The toxicity of the culture extracts towards Artemia salina L. was correlated in general with the occurrence of the above toxins, except for some F. torulosum strains. However, the lack of correlation between the amounts of toxins recovered and toxic activity observed in the Geotrichum candidum Link ex Pers. and A. salina assays suggested the presence of unknown toxic compounds. [ABSTRACT FROM AUTHOR]

Abstract: Fungal biodiversity is one of the most important contributors to the occurrence and severity of mycotoxin contamination of crop plants. Phenotypic and metabolic plasticity has enabled mycotoxigenic fungi to colonize a broad range of agriculturally important crops and to adapt to a range of environmental conditions. New mycotoxin-commodity combinations provide evidence for the ability of fungi to adapt to changing conditions and the emergence of genotypes that confer enhanced aggressiveness toward plants and/or altered mycotoxin production profiles. Perhaps the most important contributor to qualitative differences in mycotoxin production among fungi is variation in mycotoxin biosynthetic genes. Molecular genetic and biochemical analyses of toxigenic fungi have elucidated specific differences in biosynthetic genes that are responsible for intra- and inter-specific differences in mycotoxin production. For Aspergillus and Fusarium, the mycotoxigenic genera of greatest concern, variation in biosynthetic genes responsible for production of individual families of mycotoxins appears to be the result of evolutionary adaptation. Examples of such variation have been reported for: a) aflatoxin biosynthetic genes in Aspergillus flavus and Aspergillus parasiticus; b) trichothecene biosynthetic genes within and among Fusarium species; and c) fumonisin biosynthetic genes in Aspergillus and Fusarium species. Understanding the variation in these biosynthetic genes and the basis for variation in mycotoxin production is important for accurate assessment of the risks that fungi pose to food safety and for prevention of mycotoxin contamination of crops in the field and in storage. [Copyright &y& Elsevier]

Mpox is traditionally considered a zoonotic disease with endemic circulation in Africa, but the 2022-2023 outbreak reached an unprecedented high number of cases in non-endemic countries, so that it was declared a public health emergency of international concern. The reasons for this extensive global spread, characterized by sexual transmission amongst men who have sex with men (MSM), have not been fully clarified. The existence of asymptomatic carriers with viable viral shedding might be an explanation and is under-debated after retrospective studies suggested that infection without symptoms might have a prevalence of 6.5%. We aimed to prospectively assess the presence of mpox infection in asymptomatic high-risk MSM using HIV pre-exposure prophylaxis and living with HIV. We selected individuals with no signs of active infection nor suggestive symptoms in the previous 21 days. Eligible individuals collected oral and anal swabs to undergo point-of-care testing for mpox and completed a 21-days follow-up. Seventy-two individuals were enrolled, and none tested positive for mpox infection nor developed symptoms during follow-up. We selected a high-risk population with a significant history of sexual exposure, but we failed to detect any asymptomatic infection. This observation might have important consequences in terms of contact management and epidemic control.

Whether vaccination confers a protective effect against progression after hospital admission for COVID-19 remains to be elucidated. Observational study including all the patients admitted to San Paolo Hospital in Milan for COVID-19 in 2021. Previous vaccination was categorized as: none, one dose, full vaccination (two or three doses >14 days before symptoms onset). Data were collected at hospital admission, including demographic and clinical variables, age-unadjusted Charlson Comorbidity index (CCI). The highest intensity of ventilation during hospitalization was registered. The endpoints were in-hospital death (primary) and mechanical ventilation/death (secondary). Survival analysis was conducted by means of Kaplan-Meier curves and Cox regression models. Effect measure modification by age was formally tested. We included 956 patients: 151 (16%) fully vaccinated (18 also third dose), 62 (7%) one dose vaccinated, 743 (78%) unvaccinated. People fully vaccinated were older and suffering from more comorbidities than unvaccinated. By 28 days, the risk of death was of 35.9% (95%CI: 30.1−41.7) in unvaccinated, 41.5% (24.5−58.5) in one dose and 28.4% (18.2−38.5) in fully vaccinated (p = 0.63). After controlling for age, ethnicity, CCI and month of admission, fully vaccinated participants showed a risk reduction of 50% for both in-hospital death, AHR 0.50 (95%CI: 0.30−0.84) and for mechanical ventilation or death, AHR 0.49 (95%CI: 0.35−0.69) compared to unvaccinated, regardless of age (interaction p > 0.56). Fully vaccinated individuals in whom vaccine failed to keep them out of hospital, appeared to be protected against critical disease or death when compared to non-vaccinated. These data support universal COVID-19 vaccination.

Rationale: Genotype-phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but little is known about lung volume changes over time. Objectives: To investigate the evolution of static lung volumes with ultrastructural defects, gene mutations, body mass index, and specific infections in PCD. Methods: Prospective, longitudinal, single-center study in children and adults evaluated twice yearly for up to 10 years. Linear mixed-effects models were used to assess associations between ciliary morphology, genetic mutations, and clinical features. Results: A total of 122 patients had 1,096 visits. At enrollment, almost all spirometric and, especially in adults, plethysmographic parameters were significantly worse in absent inner dynein arms (IDAs), central apparatus (CA) defects, and microtubular disorganization (MTD) (IDA/CA/MTD) compared with patients with normal electron microscopy (EM) results. The mean trend increase with time for residual volume (RV) was significantly higher in IDA/CA/MTD group compared with groups with outer dynein arm defect and normal EM results. The mean trend of RV/total lung capacity in the IDA/CA/MTD group was significantly worse than in all other groups. The steepest rise in lung volumes was in CCDC39 and CCDC40, whereas hyperinflation increased less in DNAH5 and DNAH11 groups. RV/total lung capacity showed a significantly steeper rise in patients with Pseudomonas aeruginosa compared with patients with other infections or patients without infection. Conclusions: Patients with IDA/CA/MTD defects or CCDC39 and CCDC40 mutations had the greatest increase in hyperinflation, whereas those with outer dynein arm defect and normal EM results or DNAH11 and DNAH5 mutations had less severe changes. We have robustly confirmed the worse prognosis for some genetic and ultrastructural defects, which association hitherto rested solely on spirometry.

Background Inflammatory bowel disease ( IBD ) is characterized by a low prevalence of traditional risk factors, an increased aortic pulse-wave velocity ( aPWV ), and an excess of cardiovascular events. We have previously hypothesized that the cardiovascular risk excess reported in these patients could be explained by chronic inflammation. Here, we tested the hypothesis that chronic inflammation is responsible for the increased aPWV previously reported in IBD patients and that anti-TNFa (anti-tumor necrosis factor-alpha) therapy reduce aPWV in these patients. Methods and Results This was a multicenter longitudinal study. We enrolled 334 patients: 82 patients with ulcerative colitis, 85 patients with Crohn disease, and 167 healthy control subjects matched for age, sex, and mean blood pressure, from 3 centers in Europe, and followed them for 4 years (range, 2.5-5.7 years). At baseline, IBD patients had higher aPWV than controls. IBD patients in remission and those treated with anti-TNFa during follow-up experienced an aortic destiffening, whereas aPWV increased in those with active disease and those treated with salicylates ( P=0.01). Disease duration ( P=0.02) was associated with aortic stiffening as was, in patients with ulcerative colitis, high-sensitivity C-reactive protein during follow-up ( P=0.02). All these results were confirmed after adjustment for major confounders. Finally, the duration of anti-TNFa therapy was not associated with the magnitude of the reduction in aPWV at the end of follow-up ( P=0.85). Conclusions Long-term anti-TNFa therapy reduces aPWV , an established surrogate measure of cardiovascular risk, in patients with IBD . This suggests that effective control of inflammation may reduce cardiovascular risk in these patients.

Background: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus., Results: We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli., Conclusions: Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.

Objective: Recent studies suggest that enlarged aortic root diameter (ARD) may predict cardiovascular events in absence of aneurysmatic alterations. Little is known about the influence of renal function on ARD. Our study was aimed to assess the relationships between glomerular filtration rate (GFR) and ARD in hypertensive subjects., Methods: We enrolled 611 hypertensive individuals (mean age: 52 ± 15 years; men 63%). ARD was measured by echocardiography at the level of Valsalva's sinuses using M-mode tracings. It was considered as absolute measure, normalized to body surface area (ARD/BSA) and indexed to height (ARD/H). GFR was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. The study population was categorized into seven groups: subjects without chronic kidney disease (no CKD) and subjects with increasing severity of CKD (1, 2, 3a, 3b, 4, 5), as proposed by the 2012 Kidney Disease: Improving Global Outcomes guidelines., Results: ARD/BSA and ARD/H showed a stepwise increase from the group with normal renal function to the groups with increasing severity of CKD. GFR correlated significantly with ARD (r = -0.17), ARD/BSA (r = -0.43) and ARD/H (r = -0.35; all P < 0.001). The associations of GFR with ARD/BSA (β = -0.26; P < 0.001) and ARD/H (β = -0.13; P = 0.01) held in linear multiple regression analyses, after adjustment for various confounding factors., Conclusion: Our study seems to suggest that a reduced renal function may adversely influence ARD. This may contribute to explain the enhanced cardiovascular risk associated with renal insufficiency.

Rationale: Our group has recently demonstrated the possibility of studying microsatellite alterations (MAs) of 3p in the DNA of exhaled breath condensate (EBC) of patients with non-small cell lung cancer (NSCLC)., Objectives: To verify whether MAs analyzed in DNA from EBC reflect a profile of alterations present in tumor tissue of NSCLC., Methods: Fifty-nine subjects undergoing histologic diagnosis for clinical suspicion of lung cancer entered the study: 41 were found to have NSCLC and 18 to have nonneoplastic diseases. All subjects underwent allelotyping on DNA from whole blood, EBC, and lung tissue removed for histologic diagnosis by analyzing a panel of five microsatellites located in chromosomal region 3p. Results obtained from DNA of the three biological sites and nonneoplastic tissues from controls were compared., Measurements and Main Results: MAs in DNA from tumor tissues and EBC of each patient with cancer presented an overlapping profile of loss of heterozygosity and microsatellite instability. An MA profile of DNA of lung tissue reflecting the DNA of EBC profile from controls was also confirmed. Smoking status was associated with the presence of MAs in patients with NSCLC and in control subjects., Conclusions: We demonstrated that MAs in DNA from EBC of patients with NSCLC are significantly more frequent than in control subjects. More interesting, the MA profile of DNA from EBC corresponds to that from lung cancer tissue of each patient with NSCLC.

The aim of the study was to cross-sectionally analyze, in a group of essential hypertension patients without diabetes mellitus, the influence of the metabolic syndrome (MS) on the stroke volume index to pulse pressure (SVi/PP) ratio, a measure of total arterial compliance. A total of 528 essential hypertension patients, aged 18 to 72 years, free from cardiovascular and renal disease (41% of whom had MS) were enrolled. All participants underwent routine blood chemistry, echocardiographic examination, and 3 blood pressure measurements at the end of echocardiographic examination. When compared with participants who did not have MS, hypertensive patients with MS exhibited lower SVi/PP ratio (0.65+/-0.22 vs 0.73+/-0.21 mm Hg; P=.0003). The independent association of MS with SVi/PP ratio (beta=0.10; P=.02) was confirmed in a multivariate regression model including age, sex, and other potential confounders as covariates. The authors' finding may help to explain the enhanced cardiovascular risk associated with MS.

It has long been recognized that arterial hypertension is often a part of a larger constellation of anthropometric and metabolic abnormalities that includes abdominal (or visceral) obesity, a characteristic dyslipidemia (low high-density lipoprotein cholesterol and high triglycerides), glucose intolerance, insulin-resistance and hyperuricemia. These traits occur simultaneously to a greater degree than would be expected by chance alone, supporting the existence of a discrete disorder that, over the years, has been defined by a variety of terms, including plurimetabolic syndrome, the deadly quartet, dysmetabolic syndrome, insulin resistance syndrome, cardiometabolic syndrome and more recently metabolic syndrome (MS). In last years some scientific organizations proposed working definitions for MS. Among these definitions, the one suggested by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII) is the simplest and the most commonly applied. The MS is extremely common worldwide. This high prevalence is of considerable concern because accumulating evidences suggest that the MS, even without type 2 diabetes, carries an increased risk for cardiovascular and renal events. Recently it has been demonstrated that the adverse prognostic impact of MS may also be extended to hypertensive patients. Some recent studies reported an increased prevalence of left ventricular hypertrophy, diastolic dysfunction, early carotid atherosclerosis, impaired aortic distensibility, hypertensive retinopathy and microalbuminuria in hypertensive patients with MS when compared to those without it. The increased occurrence of these early signs of subclinical target organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular and renal outcomes, may partially explain the association of the MS with a higher cardiovascular and renal risk.

Fusarium verticillioides is considered to be the main source of fumonisins, a group of toxins that contaminate commodities and result in chronic and acute diseases affecting humans and animals. The detection and control of this species is crucial to prevent fumonisins from entering the food chain. The objective of the present research was to develop a specific, sensitive, and robust PCR assay to detect F. verticillioides strains using two pairs of specific primers for F. verticillioides, which have been designed on the basis of the intergenic spacer region of the rDNA units. The first pair of primers was F. verticillioides species specific, whereas the second pair of primers detected fumonisin-producing F. verticillioides strains. This second pair of primers allowed for the discrimination between the major group of F. verticillioides strains, fumonisin-producing strains that are mainly associated with crops, and a minor group of strains, non-fumonisin-producing strains that are associated with bananas. Fifty-four strains of F. verticillioides from different geographical regions and hosts were tested using both sets of primers. Sixteen additional Fusarium species were examined. The specificity of the primer sequences provides the basis for a simple, rapid, accurate, and sensitive detection and identification method of this fungal species that represents a risk for human and animal health.

Background: Arterial hypertension is an important cause of end-stage renal failure. Insulin has been shown to modify glomerular hemodynamics in hypertensive subjects. The aim of this work, therefore, was to observe the relationships between renal hemodynamics and insulin resistance in arterial hypertension., Methods: Sixty-two non-diabetic hypertensive patients and 25 healthy normal subjects were studied. Renal plasma flow and the glomerular filtration fraction were determined by renoscintigraphy and the insulin sensitivity by an oral glucose test., Results: Renal plasma flow in hypertensive subjects was lower than expected and was related to pressure values, whereas the mean glomerular filtration rates were not different in the two groups. In most patients the filtration fraction was higher than expected. A lower glomerular filtration rate and lower filtration fraction were found in patients with higher insulin resistance., Conclusions: The progressive decrease of glomerular function in subjects with hypertension is linked with insulin-resistance.

Background: Endothelial cell damage occurs during vasculitic processes in vivo. With the alteration of the endothelium, exposure to basement membrane components may occur with induction of humoral immunity., Methods: In the present study, we evaluated the prevalence of antibodies against the basement membrane antigen laminin (LMN) in patients with ANCA-associated systemic vasculitis (AASV), pathologic controls (systemic lupus erythematosus, mixed cryoglobulinaemia, Henoch-Schönlein purpura, primary glomerulonephritis) and normal individuals., Results: By ELISA, 21.6% of AASV (16/74) and 10% of pathologic controls (3/30), but only one of the normal controls (2. 8%) had these antibodies (P=0.02). When AASV patients were divided into two groups according to diagnosis and ANCA antigen specificity, antibodies to LMN were found in 27.5% of MPO-ANCA positive microscopic polyangiitis patients (11/40) vs. only 14.7% of PR3-ANCA positive Wegener granulomatosis patients (5/34). There was no correlation between the presence or titre of anti-LMN antibodies and the main clinical and laboratory parameters., Conclusion: These results indicate that basement membrane antigens may become immunogenic in patients with AASV, especially in those with MPO-ANCA positivity. These antibodies are most likely the result of endothelial damage secondary to the initial inflammatory process but may well perpetuate further vascular damage in some patients.

Previous evidence has demonstrated a relationship between growth factors and cardiovascular diseases. This study was aimed at evaluating levels of some endothelium-derived growth factors, and their relationship with microalbuminuria (MAU), in essential hypertension. Ninety-nine mild-moderate essential hypertensives (EH) and 25 healthy controls were studied. All patients underwent 24-h blood pressure monitoring, serum endothelin-1 (ET-1), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), and 24-h MAU assays. Later, EH were divided into two subsets consisting of microalbuminurics (MAU >11 microg/min) and nonmicroalbuminurics (MAU <11 microg/min). In microalbuminuric EH, circulating ET-1, bFGF, and PDGF were significantly higher than in nonmicroalbuminurics (P < .0001, P < .0001, P < .005, respectively) or in controls. In the group of 99 EH, significant positive correlations of MAU with both ET-1 and bFGF (r = 0.35, P < .001, and r = 0.34, P < .001, respectively) were found. ET-1 and bFGF correlated significantly (r = 0.31, P < .002). Circulating bFGF also correlated significantly with MAU in the microalbuminuric EH subset (r = 0.49, P < .01). Our results show that in microalbuminuric EH circulating levels of certain growth factors are increased. In human essential hypertension these factors are linked with MAU, an early cardiovascular and renal damage marker.

The stimulation of autocrine and paracrine factors such as basic fibroblast- (bFGF) and platelet-derived (PDGF) growth factors mediates many of the growth-promoting actions of angiotensin II. The aim of this study was to evaluate the effect of chronic AT1-receptor blockade on plasma endothelin-1 (ET-1) and growth factors levels, and on left ventricular mass, in essential hypertension (EH). The study population consisted of 16 patients with mild-moderate EH, and 25 normotensive controls. In the EH patients under basal conditions, and after 3 and 6 months of chronic therapy with Losartan 50 mg/day, we measured serum levels of ET-1, bFGF and PDGF, and tumor necrosis factor (TNF). At the same time, all patients underwent 24-h ambulatory blood pressure monitoring and an echocardiographic evaluation to measure the thickness of the posterior wall (PWT) of the left ventricle and of the interventricular septum (IVS). The healthy controls underwent the same analyses, under basal conditions, at baseline and after 3 and 6 months of observation. In the EH patients, after 3 months of AT1-receptor blockade bFGF was reduced from 13.6 +/- 0.7 to 10.9 +/- 0.7 pg/mL (P < .004), and both TNF and PDGF were significantly decreased (P < .006 and P < .007, respectively). After 6 months of therapy, ET-1 was significantly diminished in comparison with baseline (6.9 +/- 0.8 v 5.5 +/- 0.1 fmol/mL; P < .05), and the reduction in the levels of growth factors were even more significant than at 3 months of treatment. Both PWT and IVS were significantly changed after 6 months of therapy with losartan after basal evaluation (P < .05, respectively). Systolic and diastolic 24-h blood pressures declined significantly after 3 and 6 months of therapy with losartan (P < .01, respectively). It seems likely that the inhibition of the action of angiotensin II by the specific AT1-receptor blockade, by reducing circulating levels of ET-1 and those of some growth factors, may offer an advantage regarding the effect on hypertensive cardiovascular changes in human hypertension.