eQuilibrator 3.0: a database solution for thermodynamic constant estimation.

eQuilibrator (equilibrator.weizmann.ac.il) is a database of biochemical equilibrium constants and Gibbs free energies, originally designed as a web-based interface. While the website now counts around 1,000 distinct monthly users, its design could not accommodate larger compound databases and it lacked a scalable Application Programming Interface (API) for integration into other tools developed by the systems biology community. Here, we report on the recent updates to the database as well as the addition of a new Python-based interface to eQuilibrator that adds many new features such as a 100-fold larger compound database, the ability to add novel compounds, improvements in speed and memory use, and correction for Mg2+ ion concentrations. Moreover, the new interface can compute the covariance matrix of the uncertainty between estimates, for which we show the advantages and describe the application in metabolic modelling. We foresee that these improvements will make thermodynamic modelling more accessible and facilitate the integration of eQuilibrator into other software platforms.

Estimating COVID-19 recovery time in a cohort of Italian healthcare workers who underwent surveillance swab testing.

OBJECTIVES: The COVID-19 pandemic is putting a huge strain on the provision and continuity of care. The length of sickness absence of the healthcare workers as a result of SARS-CoV-2 infection plays a pivotal role in hospital staff management. Therefore, the aim of this study was to explore the timing of COVID-19 recovery and viral clearance, and its predictive factors, in a large sample of healthcare workers. STUDY DESIGN: This is a retrospective cohort study. METHODS: The analysis was conducted on data collected during the hospital health surveillance programme for healthcare staff at the University Hospital of Verona; healthcare workers were tested for SARS-CoV-2 through RT-PCR with oronasopharyngeal swab samples. The health surveillance programme targeted healthcare workers who either had close contact with SARS-CoV-2-infected patients or were tested as part of the screening-based strategy implemented according to national and regional requirements. Recovery time was estimated from the first positive swab to two consecutive negative swabs, collected 24 h apart, using survival analysis for both right-censored and interval-censored data. Cox proportional hazard was used for multivariate analysis. RESULTS: During the health surveillance programme, 6455 healthcare workers were tested for SARS-CoV-2 and 248 (3.8%, 95% confidence interval [CI]: 3.4-4.3) reported positive results; among those who tested positive, 49% were asymptomatic, with a median age of 39.8 years, which is significantly younger than symptomatic healthcare workers (48.2 years, P < 0.001). Screening tests as part of the health surveillance programme identified 31 (12.5%) of the positive cases. Median recovery time was 24 days (95% CI: 23-26) and 21.5 days (95% CI: 15.5-30.5) in right- and interval-censoring analysis, respectively, with no association with age, sex or presence of symptoms. Overall, 63% of participants required >20 days to test negative on two consecutive swabs. Hospitalised healthcare workers (4.8%) were older and had a significantly longer recovery time compared with non-hospitalised healthcare workers in both analyses (33.5 vs 24 days, P = 0.005). CONCLUSIONS: Recovery from COVID-19 and viral clearance may take a long time, especially in individuals who are hospitalised. To detect asymptomatic cases, screening programmes for healthcare workers is recommended.

Probabilistic thermodynamic analysis of metabolic networks.

MOTIVATION: Random sampling of metabolic fluxes can provide a comprehensive description of the capabilities of a metabolic network. However, current sampling approaches do not model thermodynamics explicitly, leading to inaccurate predictions of an organism's potential or actual metabolic operations. RESULTS: We present a probabilistic framework combining thermodynamic quantities with steady-state flux constraints to analyze the properties of a metabolic network. It includes methods for probabilistic metabolic optimization and for joint sampling of thermodynamic and flux spaces. Applied to a model of Escherichia coli, we use the methods to reveal known and novel mechanisms of substrate channeling, and to accurately predict reaction directions and metabolite concentrations. Interestingly, predicted flux distributions are multimodal, leading to discrete hypotheses on E.coli's metabolic capabilities. AVAILABILITY AND IMPLEMENTATION: Python and MATLAB packages available at https://gitlab.com/csb.ethz/pta. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Rehabilitative Good Practices in the Treatment of Sarcopenia: A Narrative Review.

ABSTRACT: To date, rehabilitative good practices that analyze all aspects of the rehabilitation management of the patient with sarcopenia are absent in the literature. The purpose of this article is to carry out research and evaluation of the evidence, good practice, and recommendations in the literature relating to the rehabilitative treatment of disabilities associated with sarcopenia. Bibliographic research was conducted on Medline, PEDro, Cochrane Database, and Google Scholar. All articles published in the last 10 yrs were analyzed. The results of this research generated three guidelines, eight meta-analyses, five systematic reviews, a Cochrane review, 17 reviews, and seven consensus conferences. From the analysis of the literature, it seems that most of the works agree in affirming that exercise and diet supplementation are the cornerstones of rehabilitation treatment of patients with sarcopenia. The practice of an adequate lifestyle received numerous high-grade recommendations in the included guidelines. Based on the data obtained, the rehabilitation management of the patient with sarcopenia must be personalized and must include exercise and nutritional supplementation. These factors are important in increasing the autonomy of the elderly essential for safe walking without neglecting stretching exercises that are important for flexibility and balance and coordination exercises.

COVID-19 pandemic: an Italian single institution's experience and lessons learned by public health residents' workforce.

Methods: We hereby provide a systematic description of the response actions in which the public health residents' workforce was pivotal, in a large tertiary hospital. Background: The Coronavirus Disease 2019 pandemic has posed incredible challenges to healthcare workers worldwide. The residents have been affected by an almost complete upheaval of the previous setting of activities, with a near total focus on service during the peak of the emergency. In our Institution, residents in public health were extensively involved in leading activities in the management of Coronavirus Disease 2019 pandemic. Results: The key role played by residents in the response to Coronavirus Disease 2019 pandemic is highlighted by the diversity of contributions provided, from cooperation in the rearrangement of hospital paths for continuity of care, to establishing and running new services to support healthcare professionals. Overall, they constituted a workforce that turned essential in governing efficiently such a complex scenario. Conclusions: Despite the difficulties posed by the contingency and the sacrifice of many training activities, Coronavirus Disease 2019 pandemic turned out to be a unique opportunity of learning and measuring one's capabilities and limits in a context of absolute novelty and uncertainty.

Pediatric bronchoscopy: recent advances and clinical challenges.

Introduction: During the last 40 years equipment has been improved with smaller instruments and sufficient size working channels. This has ensured that bronchoscopy offers therapeutic and interventional options.Areas covered: We provide a review of recent advances and clinical challenges in pediatric bronchoscopy. This includes single-use bronchoscopes, endobronchial ultrasound, and cryoprobe. Bronchoscopy in persistent preschool wheezing and asthma is included. The indications for interventional bronchoscopy have amplified and included balloon dilatation, endoscopic intubation, the use of airway stents, whole lung lavage, closing of fistulas and air leak, as well as an update on removal of foreign bodies. Others include the use of laser and microdebrider in airway surgery. Experience with bronchoscope during the COVID-19 pandemic has been included in this review. PubMed was searched for articles on pediatric bronchoscopy, including rigid bronchoscopy as well as interventional bronchoscopy with a focus on reviewing literature in the past 5 years.Expert opinion: As the proficiency of pediatric interventional pulmonologists continues to grow more interventions are being performed. There is a scarcity of published evidence in this field. Courses for pediatric interventional bronchoscopy need to be developed. The COVID-19 experience resulted in safer bronchoscopy practice for all involved.

idtracker.ai: tracking all individuals in small or large collectives of unmarked animals.

Understanding of animal collectives is limited by the ability to track each individual. We describe an algorithm and software that extract all trajectories from video, with high identification accuracy for collectives of up to 100 individuals. idtracker.ai uses two convolutional networks: one that detects when animals touch or cross and another for animal identification. The tool is trained with a protocol that adapts to video conditions and tracking difficulty.

Integrating -omics data into genome-scale metabolic network models: principles and challenges.

At genome scale, it is not yet possible to devise detailed kinetic models for metabolism because data on the in vivo biochemistry are too sparse. Predictive large-scale models for metabolism most commonly use the constraint-based framework, in which network structures constrain possible metabolic phenotypes at steady state. However, these models commonly leave many possibilities open, making them less predictive than desired. With increasingly available -omics data, it is appealing to increase the predictive power of constraint-based models (CBMs) through data integration. Many corresponding methods have been developed, but data integration is still a challenge and existing methods perform less well than expected. Here, we review main approaches for the integration of different types of -omics data into CBMs focussing on the methods' assumptions and limitations. We argue that key assumptions - often derived from single-enzyme kinetics - do not generally apply in the context of networks, thereby explaining current limitations. Emerging methods bridging CBMs and biochemical kinetics may allow for -omics data integration in a common framework to provide more accurate predictions.

AP2α controls the dynamic balance between miR-126&126* and miR-221&222 during melanoma progression.

Accumulating evidences have shown the association between aberrantly expressed microRNAs (miRs) and cancer, where these small regulatory RNAs appear to dictate the cell fate by regulating all the main biological processes. We demonstrated the responsibility of the circuitry connecting the oncomiR-221&222 with the tumor suppressors miR-126&126* in melanoma development and progression. According to the inverse correlation between endogenous miR-221&222 and miR-126&126*, respectively increasing or decreasing with malignancy, their enforced expression or silencing was sufficient for a reciprocal regulation. In line with the opposite roles of these miRs, protein analyses confirmed the reverse expression pattern of miR-126&126*-targeted genes that were induced by miR-221&222. Looking for a central player in this complex network, we revealed the dual regulation of AP2α, on one side directly targeted by miR-221&222 and on the other a transcriptional activator of miR-126&126*. We showed the chance of restoring miR-126&126* expression in metastatic melanoma to reduce the amount of mature intracellular heparin-binding EGF like growth factor, thus preventing promyelocytic leukemia zinc finger delocalization and maintaining its repression on miR-221&222 promoter. Thus, the low-residual quantity of these two miRs assures the release of AP2α expression, which in turn binds to and induces miR-126&126* transcription. All together these results point to an unbalanced ratio functional to melanoma malignancy between these two couples of miRs. During progression this balance gradually moves from miR-126&126* toward miR-221&222. This circuitry, besides confirming the central role of AP2α in orchestrating melanoma development and/or progression, further displays the significance of these miRs in cancer and the option of utilizing them for novel therapeutics.

Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression.

BACKGROUND: At diagnosis, identification of reliable biological indicators of prognosis to allow stratification of patients according to different risks is an important but still unresolved aspect in the treatment of Ewing sarcoma (EWS) patients. This study aimed to explore the role of miR-34A expression on prognosis of EWS patients. PATIENTS AND METHODS: Specimens from 109 patients with non-metastatic EWS treated at the Rizzoli Institute with neoadjuvant chemotherapy (protocols ISG/SSGIII, EW-1, EW-2, EW-REN2, EW-REN3, EW-PILOT) and 17 metastases were studied. Sixty-eight patients (62%) remained disease-free and 41 (38%) relapsed (median follow-up: 67 months, range 9-241 months). Expression of miR-34a and of some of its targets (cyclin D1, bcl-2, SIRT1 and YY1) was evaluated by qRT-PCR using TaqMan MicroRNA Assays and/or by immunohistochemistry on tissue microarrays from the same patients. RESULTS: High expression of miR-34a in localized tumors was significantly related to better event-free and overall survival (P = 0.004). Relevance of miR-34a was confirmed by using different calibrators (normal mesenchymal stem cells and different normal tissues). By multivariate Cox regression analysis, low miR-34a expression as well as nontotal necrosis and high levels of lactate dehydrogenase were all confirmed as independent risk factors associated with poor outcome. Expression of miR-34a was lower in metastases than in primary tumors. It inversely correlated with expression of cyclin D1 and Ki-67. CONCLUSIONS: By demonstrating its relationship with clinical outcome, we propose evaluation of miR-34a at diagnosis of EWS patients to allow early risk stratification. Validation of these results would nonetheless ultimately need a prospective assessment.

Comparison of glycaemic control in patients with Type 2 diabetes on basal insulin and fixed combination oral antidiabetic treatment: results of a pilot study.

This randomised, open-label, two-way cross-over study compared the coefficient of variance (CV) of fasting and postprandial blood glucose (FBG and PPBG) with insulin glargine (glargine) versus neutral protamine Hagedorn (NPH) insulin treatment in patients with Type 2 diabetes (T2DM). Patients (N=20) on oral antidiabetic drugs (OADs) were treated with NPH (at bedtime) or glargine (at dinnertime) for 12 weeks of each cross-over treatment period; OADs were continued. The FBG CV was calculated from self-monitored BG values and PPBG using venous blood samples, or continuous glucose monitoring system (CGMS). Both insulins provided similar improvements in glycaemic control; however, PPBG was significantly lower after a standard meal test (performed at 13:00 h the day after insulin injection) with glargine versus NPH (p=0.02). Thirteen versus 15 patients experienced >or=1 episode of hypoglycaemia with glargine versus NPH. The results suggest that glargine plus OADs is more effective in reducing PPBG fluctuations during the day than NPH plus OADs.

Gliclazide improves anti-oxidant status and nitric oxide-mediated vasodilation in Type 2 diabetes.

AIMS: To evaluate the effects of gliclazide on oxidative status and vascular response to systemic administration of L-arginine, the natural precursor of nitric oxide (NO), in Type 2 diabetic patients. METHODS: Thirty Type 2 diabetic patients received glibenclamide (n = 15) or gliclazide (n = 15) in a 12-week, randomized, observer-blinded, parallel study. Plasma lipid peroxides, total radical-trapping anti-oxidant parameter (TRAP), and blood pressure responses to an intravenous bolus of L-arginine were measured pre- and post-treatment. RESULTS: At 12 weeks, gliclazide patients had lower plasma lipid peroxides (13.3 +/- 3.8 micro mol/l vs. 19.2 +/- 4.3 micro mol/l; P = 0.0001) and higher plasma TRAP (1155.6 +/- 143.0 micro mol/l vs. 957.7 +/- 104.3 micro mol/l; P = 0.0001) than the glibenclamide patients. Gliclazide but not glibenclamide significantly reduced systolic and diastolic blood pressure (P = 0.0199 and P = 0.00199, respectively, two-way repeated measures analysis of variance) in response to intravenous L-arginine. CONCLUSIONS: Gliclazide reduces oxidative stress in Type 2 diabetic patients by improving plasma anti-oxidant status. This effect is associated with enhanced NO-mediated vasodilation.

L-arginine infusion decreases plasma total homocysteine concentrations through increased nitric oxide production and decreased oxidative status in Type II diabetic patients.

AIMS/HYPOTHESIS: Hyperhomocysteinaemia increases cardiovascular risk in Type II (non-insulin-dependent) diabetes mellitus by augmenting oxidative stress and reducing nitric oxide availability. In vitro, nitric oxide decreases homocysteine by its conversion to the vasodilative and antioxidant compound S-nitrosohomocysteine. We investigated whether or not changes in nitric oxide availability decrease homocysteine concentrations in vivo. METHODS: The study group consisted of 20 normotensive, normolipidaemic, non-atherosclerotic Type II diabetic patients in good metabolic control (16 men, 51.2+/-1.4 years) and 15 healthy subjects (12 men, 48.1+/-1.5 years). Circulating concentrations of homocysteine, nitrite+nitrate and sulphydryl groups, a marker of oxidative stress, were assessed at baseline and then 5', 10', 30' and 60' after the intravenous infusion of either L-arginine (3 g in 10 ml saline), the nitric oxide precursor, or vehicle according to a double-blind cross-over randomized protocol. RESULTS: At baseline diabetic patients showed lower plasma sulphydryl group concentrations (491.8+/-16.9 vs 551.3+/-21.0 micro mol/l, p<0.04) and nitrite+nitrate (21.4+/-0.8 vs 29.5+/-0.9 micro mol/l, p<0.0001) and higher total homocysteine concentrations (11.1+/-0.5 vs 8.3+/-0.6 micro mol/l, p<0.002) than the control subjects. After L-arginine infusion, blood pressure levels and total homocysteine concentrations ( p< or =0.05) decreased (peak at 5' and 30', respectively) whereas nitric oxide and sulphydryl group concentrations ( p< or =0.003) increased (peak at 10' and 30', respectively) in the patients and control subjects. CONCLUSION/INTERPRETATION: Acute L-arginine infusion in both Type II diabetic patients and healthy subjects decreases plasma total homocysteine concentrations, counteract oxidative stress and increases the availability of nitric oxide.

Stromal cell-derived factor 1alpha increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells.

The alpha chemokine receptor CXCR4 has been shown to be expressed on human hematopoietic progenitor cells and during the megakaryocytic differentiation pathway. Stromal cell-derived factor 1 (SDF-1) is the ligand for CXCR4. In this study, the role of SDF-1alpha in megakaryocytopoiesis was investigated. CD34(+) progenitors purified from peripheral blood were grown in serum-free liquid suspension culture supplemented with thrombopoietin to obtain a virtually pure megakaryocytic progeny. In this condition, the addition of SDF-1alpha gives rise to megakaryocytes (MKs) showing an increased DNA content and a rise of lobated nuclei, as compared with untreated cells: at day 5, approximately 20% of the cells already showed the presence of more than one nuclear lobe versus fewer than 5% in the control cells; at day 12, approximately 85% of the cells were of large size and markedly polyploid, whereas approximately 60% of the control cells were polyploid, showed fewer lobes, and were a smaller size. This effect was dose-dependent and did not affect the megakaryocytic proliferation. Experiments with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 suggested a role for MAPK pathway on SDF-1alpha-induced endomitosis. Furthermore, SDF-1alpha induced a significant increase in the number of proplatelet-bearing MKs and promoted the migration of megakaryocytic cells. Treatment with SDF-1alpha caused reduction in CXCR4 abundance on the plasma membrane, seemingly owing to receptor internalization. Furthermore, the presence of SDF-1alpha did not affect the expression of megakaryocytic markers, indicating that differentiation and polyploidization are independently regulated events.

Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes: isotype restriction and polyclonality.

OBJECTIVE: To determine the isotypes and clonality of antibodies to GAD (GADA) and IA-2 (IA-2A) in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied the following consecutive series of patients who attended a diabetes center for antibodies to GADA and IA-2A: 52 newly diagnosed type 1 diabetic patients, 199 type 2 diabetic patients, 200 control patients, and a cohort of 34 nondiabetic identical twins of patients with type 1 diabetes (15 of whom developed diabetes) who were followed prospectively. RESULTS: GADA or IA-2A were detected in 37 (71%) type 1 diabetic patients compared with only 10 (5%) type 2 diabetic patients (P<0.0001). Both GAD and IA-2 antibodies, regardless of the type of diabetes, were usually subclass restricted to IgG1 and were polyclonal. IgM, IgG3, and IgE isotypes were also detected, but all isotypes of GADA and IA-2A were less prevalent than IgG1 (P<0.017 for either antibody). There was no evidence of spreading or switching of isotypes before the onset of type 1 diabetes. CONCLUSIONS: These observations suggest that the pathogenesis of antigen-specific antibodies in type 1 and type 2 diabetes is similar and probably involves a chronic nonrandom antigen-driven polyclonal B-cell activation that is consistent with a Th1-type immune response.

cis expression of the F12 human immunodeficiency virus (HIV) Nef allele transforms the highly productive NL4-3 HIV type 1 to a replication-defective strain: involvement of both Env gp41 and CD4 intracytoplasmic tails.

F12 human immunodeficiency virus type 1 (HIV-1) nef is a naturally occurring nef mutant cloned from the provirus of a nonproductive, nondefective, and interfering HIV-1 variant (F12-HIV). We have already shown that cells stably transfected with a vector expressing the F12-HIV nef allele do not downregulate CD4 receptors and, more peculiarly, become resistant to the replication of wild type (wt) HIV. In order to investigate the mechanism of action of such an HIV inhibition, the F12-HIV nef gene was expressed in the context of the NL4-3 HIV-1 infectious molecular clone by replacing the wt nef gene (NL4-3/chi). Through this experimental approach we established the following. First, NL4-3/chi and nef-defective (Deltanef) NL4-3 viral particles behave very similarly in terms of viral entry and HIV protein production during the first replicative cycle. Second, no viral particles were produced from cells infected with NL4-3/chi virions, whatever the multiplicity of infection used. The viral inhibition apparently occurs at level of viral assembling and/or release. Third, this block could not be relieved by in-trans expression of wt nef. Finally, NL4-3/chi reverts to a producer HIV strain when F12-HIV Nef is deprived of its myristoyl residue. Through a CD4 downregulation competition assay, we demonstrated that F12-HIV Nef protein potently inhibits the CD4 downregulation induced by wt Nef. Moreover, we observed a redistribution of CD4 receptors at the cell margin induced by F12-HIV Nef. These observations strongly suggest that F12-HIV Nef maintains the ability to interact with the intracytoplasmic tail of the CD4 receptor molecule. Remarkably, we distinguished the intracytoplasmic tails of Env gp41 and CD4 as, respectively, viral and cellular targets of the F12-HIV Nef-induced viral retention. For the first time, the inhibition of the viral life cycle by means of in-cis expression of a Nef mutant is here reported. Delineation of the F12-HIV Nef mechanism of action may offer additional approaches to interference with the propagation of HIV infection.

Analytical evaluation of virgin olive oil of first and second extraction.

Virgin olive oils from percolation (first extraction) have been compared with the corresponding oils from centrifugation (second extraction). The former were characterized by (i) higher contents of total phenols, o-diphenols, hydroxytyrosol, tyrosol-aglycons, tocopherols, trans-2-hexenal, total volatiles, and waxes; (ii) higher values of resistance to autoxidation and of turbidity; (iii) higher sensory scores; (iv) higher ratios of campesterol/stigmasterol, trans-2-hexenal/hexanal, and trans-2-hexenal/total volatiles; (v) lower contents of chlorophylls, pheophytins, sterols, and aliphatic and triterpene alcohols; (vi) lower alcoholic index and color indices; (vii) similar values of acidity, peroxide index, and UV (ultraviolet) spectrophotometric indices; (viii) similar percentages of saturated and unsaturated fatty acids, triglycerides, and diglycerides; and (ix) similar values of glyceridic indices. Stigmastadienes, trans-oleic, trans-linoleic, and trans-linolenic acid isomers were not detected in the two genuine oil kinds. Hence, the qualitative level of the first extraction oil was superior to the second extraction one.

Effects of insulin on in vitro vascular cell adhesion molecule-1 expression and in vivo soluble VCAM-1 release.

AIMS/HYPOTHESIS: To evaluate the effects of insulin on vascular cell adhesion molecule-1 expression by cultured human vascular endothelial cells and soluble vascular cell adhesion molecule-1 release in vivo. METHODS: Human vascular endothelial cells derived from umbilical cord veins were incubated with either insulin (from 10(-6) to 10(-9) mol/l) or tumour necrosis factor-alpha (5 ng/ml) for 6 to 24 h. Plasma soluble vascular cell adhesion molecule-1 concentrations were evaluated in 12 non-insulin-dependent diabetic patients (8 men, 4 women, mean age 47.1 +/- 7.7 years) and 12 healthy volunteers matched for age, sex and weight (7 men, 5 women, mean age 42.2 +/- 7.2 years) before and after a 2-h euglycaemic hyperinsulinaemic clamp. RESULTS: Transcriptional activities of nuclear factor-kappaB luciferase and vascular adhesion molecule-1 luciferase statistically significantly increased after incubation with tumour necrosis factor-alpha. By contrast, a slight increment of nuclear factor-kappaB luciferase (mean: 1.8 +/- 0.3 fold) but not of vascular cell adhesion molecule-1 luciferase transcriptional activities were detected in cells stimulated with insulin. Soluble vascular cell adhesion molecule-1 concentrations in cell supernatants increased after tumour necrosis factor-alpha but not insulin stimulation. In vivo, baseline plasma soluble vascular cell adhesion molecule-1 concentrations were higher (p = 0.03) in non-insulin-dependent patients (708.7 +/- 97.4 microg/l) than controls (632.1 +/- 65.2 microg/l) but were not related to fasting insulin concentrations and did not change during insulin infusion. CONCLUSION/INTERPRETATION: The increased concentrations of circulating soluble vascular cell adhesion molecule-1 indicates that the vascular endothelium is activated in non-insulin dependent diabetic patients. Our in vitro and in vivo findings show that vascular cell adhesion molecule-1 activation cannot be due to hyperinsulinaemia. [Diabetologia (1999) 42: 1235-1239]

High plasma renin activity is combined with elevated urinary albumin excretion in essential hypertensive patients.

BACKGROUND: Several studies suggest that the hyperactivity of the circulating renin-angiotensin system might favor the progression of renal disease in essential hypertension. To elucidate this aspect, we investigated the relationship between plasma renin activity (PRA) and the urinary albumin excretion rate (UAER), an early marker of hypertension-related renal changes, in human essential hypertension. METHODS: Ninety nonobese, nondiabetic, nonhyperlipidemic patients with mild-to-moderate essential hypertension (67 males, 23 females; mean age 51.4 +/- 6.2 years) were divided into low renin (LR), normal renin (NR), and high renin (HR) subgroups according to individual PRA while they were on a constant NaCl intake (120 mmol NaCl/day). The UAER was assessed during the same NaCl intake. RESULTS: Data showed significantly higher UAER (31.3 +/- 12.9 microg/min) in HR (N = 30) than NR (N = 30, 22.7 +/- 14.4 microg/min, P < 0.02) and LR patients (N = 30, 21.7 +/- 10.8 microg/min, P < 0. 01). CONCLUSIONS: Our study demonstrates that the UAER is elevated in HR essential hypertensive patients, suggesting that high PRA accelerates the onset of early renal changes in human essential hypertension.

Early upregulation of endothelial adhesion molecules in obese hypertensive men.

Upregulation of endothelial adhesion molecules is the earliest step of atherogenesis. Whether obesity induces endothelial adhesin upregulation is unknown. To address this topic, circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and von Willebrand factor (vWF) concentrations were evaluated in 22 obese hypertensive (51.4+/-4.6 years [mean+/-SD age]), 19 obese normotensive (50.6+/-3.8 years), 18 nonobese hypertensive (52.3+/-3.9 years), and 16 nonobese normotensive (52. 4+/-3.5 years) men without other risk factors or overt atherosclerosis. All measurements were repeated in the obese subgroups after weight loss induced by 12 weeks of caloric restriction. Basal circulating VCAM-1 levels were similar between the 2 obese groups but were higher (P<0.0001) than in the 2 nonobese groups. No differences were found between nonobese hypertensives and normotensives. Serum low density lipoprotein cholesterol was weakly correlated with plasma soluble VCAM-1 levels in pooled, obese subjects (r=0.362, P=0.02). Plasma soluble adhesin and vWF concentrations decreased significantly after weight loss in obese hypertensives (VCAM-1 P=0.03, ICAM-1 P=0.004, E-selectin P<0.0001, and vWF P=0.003) and normotensives (VCAM-1 P=0.04, ICAM-1 P=0.003, E-selectin P<0.0001, and vWF P<0.0001). Body mass index was correlated with plasma E-selectin concentrations at baseline and after weight loss in obese hypertensives (r=0.501, P=0.018 and r=0. 466, P=0.03, respectively) and obese normotensives (r=0.523, P=0.021 and r=0.460, P=0.05, respectively). In conclusion, our data show that obesity per se induces early endothelial activation in hypertensive and normotensive men. Weight loss counteracted endothelial activation in both obese hypertensive and normotensive men.