Universidad del Zulia

We provide a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide. A secondary aim was to consider the possible impact of geographic, cultural/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD. Based on the evidence reviewed, the median of prevalence estimates of autism spectrum disorders was 62/10 000. While existing estimates are variable, the evidence reviewed does not support differences in PDD prevalence by geographic region nor of a strong impact of ethnic/cultural or socioeconomic factors. However, power to detect such effects is seriously limited in existing data sets, particularly in low-income countries. While it is clear that prevalence estimates have increased over time and these vary in different neighboring and distant regions, these findings most likely represent broadening of the diagnostic concets, diagnostic switching from other developmental disabilities to PDD, service availability, and awareness of autistic spectrum disorders in both the lay and professional public. The lack of evidence from the majority of the world's population suggests a critical need for further research and capacity building in low- and middle-income countries.

BACKGROUND: Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. METHODS: To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012-2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). RESULTS: Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9-36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. CONCLUSIONS: C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

BACKGROUND: Uric acid is an independent risk factor in fructose-induced fatty liver, but whether it is a marker or a cause remains unknown. RESULTS: Hepatocytes exposed to uric acid developed mitochondrial dysfunction and increased de novo lipogenesis, and its blockade prevented fructose-induced lipogenesis. CONCLUSION: Rather than a consequence, uric acid induces fatty liver SIGNIFICANCE: Hyperuricemic people are more prone to develop fructose-induced fatty liver. Metabolic syndrome represents a collection of abnormalities that includes fatty liver, and it currently affects one-third of the United States population and has become a major health concern worldwide. Fructose intake, primarily from added sugars in soft drinks, can induce fatty liver in animals and is epidemiologically associated with nonalcoholic fatty liver disease in humans. Fructose is considered lipogenic due to its ability to generate triglycerides as a direct consequence of the metabolism of the fructose molecule. Here, we show that fructose also stimulates triglyceride synthesis via a purine-degrading pathway that is triggered from the rapid phosphorylation of fructose by fructokinase. Generated AMP enters into the purine degradation pathway through the activation of AMP deaminase resulting in uric acid production and the generation of mitochondrial oxidants. Mitochondrial oxidative stress results in the inhibition of aconitase in the Krebs cycle, resulting in the accumulation of citrate and the stimulation of ATP citrate lyase and fatty-acid synthase leading to de novo lipogeneis. These studies provide new insights into the pathogenesis of hepatic fat accumulation under normal and diseased states.

OBJECTIVES: This study presents a reliable index inspired by the total variability concept of real analysis in mathematics, called average real variability (ARV), for the prognostic significance of blood pressure variability (BPV) overcoming the pitfalls of the commonly used standard deviation (SD). BACKGROUND: Recent studies have suggested that an increase in BPV is associated with an increase in subsequent cardiovascular events/complications. However, there are other studies where the cited association was not found or was lost in the presence of other well-known risk factors. An explanation for these apparently contradictory results may be the selection of the variability index used (SD). METHODS: Ambulatory blood pressure monitoring in 312 subjects aged > or = 55 years. Logistic regression models and survival methods were used to establish the prognostic significance of awake systolic BPV: in particular, (i) the performance of ARV versus SD, and (ii) the value of BPV relative to other well-known risk factors. RESULTS: The analyses using the ARV index show a statistically significant relative risk equal to 4.548 (P = 0.006) for the group with high BPV with respect to the low BPV group (reference level); in contrast, the corresponding relative risk associated to the SD index was not statistically significant. Furthermore, ARV exhibited a similar predictive value to systolic blood pressure. CONCLUSIONS: The proposed ARV index is a more reliable representation of time series variability than SD and may be less sensitive to the relative low sampling frequency of the ambulatory blood pressure monitoring devices. The results suggest that ARV adds prognostic value to the ABPM and could prompt the use of therapeutic measures to control BPV.

Importance: Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. Objective: To evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and Participants: Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). Exposures: Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and Measures: Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). Results: Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and Relevance: In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

We, as a society, find ourselves confronted with a spectrum of potentially catastrophic and irreversible environmental problems, for which conventional approaches will not suffice in providing solutions. These problems are characterized, above all, by their unpredictability. This means that surprise is to be expected, and that sudden qualitative shifts in dynamics present serious problems for management. In general, it is difficult to detect strong signals of change early enough to motivate effective solutions, or even to develop scientific consensus on a time scale rapid enough to allow effective solution. Furthermore, such signals, even when detected, are likely to be displaced in space or sector from the source, so that the motivation for action is small. Conventional market mechanisms thus will be inadequate to address these challenges.

In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

Abstract Comprehensive assessments of species’ extinction risks have documented the extinction crisis 1 and underpinned strategies for reducing those risks 2 . Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction 3 . Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods 4–7 . Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs 6 . Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened—confirming a previous extrapolation 8 and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods—agriculture, logging, urban development and invasive species—although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles—including most species of crocodiles and turtles—require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles.

High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury. Furthermore, immune reactivity may be the driving force of hypertension in autoimmune diseases. Infiltration of immune cells, oxidative stress, and stimulation of the intrarenal angiotensin system are induced by activation of the innate and adaptive immunity. High blood pressure results from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. Imbalances between proinflammatory effector responses and anti-inflammatory responses of regulatory T cells to a large extent determine the severity of inflammation. Experimental and human studies have uncovered autoantigens (isoketal-modified proteins and heat shock protein 70) of potential clinical relevance. Further investigations on the immune reactivity in hypertension may result in the identification of new strategies for the treatment of the disease.

BACKGROUND: Dementia is becoming a major public health problem in Latin America (LA), yet epidemiological information on dementia remains scarce in this region. This study analyzes data from epidemiological studies on the prevalence of dementia in LA and compares the prevalence of dementia and its causes across countries in LA and attempts to clarify differences from those of developed regions of the world. METHODS: A database search for population studies on rates of dementia in LA was performed. Abstracts were also included in the search. Authors of the publications were invited to participate in this collaborative study by sharing missing or more recent data analysis with the group. RESULTS: Eight studies from six countries were included. The global prevalence of dementia in the elderly (> or =65 years) was 7.1% (95% CI: 6.8-7.4), mirroring the rates of developed countries. However, prevalence in relatively young subjects (65-69 years) was higher in LA studies The rate of illiteracy among the elderly was 9.3% and the prevalence of dementia in illiterates was two times higher than in literates. Alzheimer's disease was the most common cause of dementia. CONCLUSIONS: Compared with studies from developed countries, the global prevalence of dementia in LA proved similar, although a higher prevalence of dementia in relatively young subjects was evidenced, which may be related to the association between low educational level and lower cognitive reserve, causing earlier emergence of clinical signs of dementia in the LA elderly population.

Endothelial dysfunction is a characteristic feature during the renal damage induced by mild hyperuricemia. The mechanism by which uric acid reduces the bioavailability of intrarenal nitric oxide is not known. We tested the hypothesis that oxidative stress might contribute to the endothelial dysfunction and glomerular hemodynamic changes that occur with hyperuricemia. Hyperuricemia was induced in Sprague-Dawley rats by administration of the uricase inhibitor, oxonic acid (750 mg/kg per day). The superoxide scavenger, tempol (15 mg/kg per day), or placebo was administered simultaneously with the oxonic acid. All groups were evaluated throughout a 5-wk period. Kidneys were fixed by perfusion and afferent arteriole morphology, and tubulointerstitial 3-nitrotyrosine, 4-hydroxynonenal, NOX-4 subunit of renal NADPH-oxidase, and angiotensin II were quantified. Hyperuricemia induced intrarenal oxidative stress, increased expression of NOX-4 and angiotensin II, and decreased nitric oxide bioavailability, systemic hypertension, renal vasoconstriction, and afferent arteriolopathy. Tempol treatment reversed the systemic and renal alterations induced by hyperuricemia despite equivalent hyperuricemia. Moreover, because tempol prevented the development of preglomerular damage and decreased blood pressure, glomerular pressure was maintained at normal values as well. Mild hyperuricemia induced by uricase inhibition causes intrarenal oxidative stress, which contributes to the development of the systemic hypertension and the renal abnormalities induced by increased uric acid. Scavenging of the superoxide anion in this setting attenuates the adverse effects induced by hyperuricemia.

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R² > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.

Fructose intake from added sugars correlates with the epidemic rise in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Fructose intake also causes features of metabolic syndrome in laboratory animals and humans. The first enzyme in fructose metabolism is fructokinase, which exists as two isoforms, A and C. Here we show that fructose-induced metabolic syndrome is prevented in mice lacking both isoforms but is exacerbated in mice lacking fructokinase A. Fructokinase C is expressed primarily in liver, intestine, and kidney and has high affinity for fructose, resulting in rapid metabolism and marked ATP depletion. In contrast, fructokinase A is widely distributed, has low affinity for fructose, and has less dramatic effects on ATP levels. By reducing the amount of fructose for metabolism in the liver, fructokinase A protects against fructokinase C-mediated metabolic syndrome. These studies provide insights into the mechanisms by which fructose causes obesity and metabolic syndrome.

Excessive dietary fructose intake may have an important role in the current epidemics of fatty liver, obesity and diabetes as its intake parallels the development of these syndromes and because it can induce features of metabolic syndrome. The effects of fructose to induce fatty liver, hypertriglyceridemia and insulin resistance, however, vary dramatically among individuals. The first step in fructose metabolism is mediated by fructokinase (KHK), which phosphorylates fructose to fructose-1-phosphate; intracellular uric acid is also generated as a consequence of the transient ATP depletion that occurs during this reaction. Here we show in human hepatocytes that uric acid up-regulates KHK expression thus leading to the amplification of the lipogenic effects of fructose. Inhibition of uric acid production markedly blocked fructose-induced triglyceride accumulation in hepatocytes in vitro and in vivo. The mechanism whereby uric acid stimulates KHK expression involves the activation of the transcription factor ChREBP, which, in turn, results in the transcriptional activation of KHK by binding to a specific sequence within its promoter. Since subjects sensitive to fructose often develop phenotypes associated with hyperuricemia, uric acid may be an underlying factor in sensitizing hepatocytes to fructose metabolism during the development of fatty liver.

Recent evidence indicates that interstitial infiltration of T cells and macrophages plays a role in the pathogenesis of salt-sensitive hypertension. The present review examines this evidence and summarizes the investigations linking the renal accumulation of immune cells and oxidative stress in the development of hypertension. The mechanisms involved in the hypertensive effects of oxidant stress and tubulointerstitial inflammation, in particular intrarenal ANG II activity, are discussed, focusing on their potential for sodium retention. The possibility of autoimmune reactivity in hypertension is raised in the light of the proinflammatory and immunogenic pathways stimulated by the interrelationship between oxidant stress and inflammatory response. Finally, we present some clinical considerations derived from the recognition of this interrelationship.

BACKGROUND/AIMS: Rats with mild hyperuricemia develop systemic hypertension, interstitial renal disease, afferent arteriolopathy, and increased renin expression [Mazzali et al.: Am J Physiol 2002;6:F991-F997]. We hypothesized that hyperuricemia might also induce glomerular changes. METHODS: We reviewed renal biopsies of rats previously made hyperuricemic for 7 weeks with the uricase inhibitor, oxonic acid. Controls included normal rats and oxonic acid-treated rats administered allopurinol, benziodarone, hydrochlorothiazide, or enalapril. Glomeruli were examined for size (computer image analysis) and structure (histology). An additional group of rats were administered oxonic acid or control diet for 6 months. RESULTS: Renal biopsies showed that hyperuricemic rats had a 30% increase in glomerular tuft area (p < 0.01); these changes were prevented by allopurinol and benziodarone. Control of blood pressure with hydrochlorothiazide did not prevent the development of glomerular hypertrophy, whereas enalapril partially reduced the glomerular hypertrophy. Prolonged hyperuricemia was associated with the development of microalbuminuria (p < 0.05) and glomerulosclerosis (22 vs. 10%, p < 0.05) compared to control rats. CONCLUSIONS: Hyperuricemic rats develop glomerular hypertrophy that can be prevented in part by ACE inhibitor therapy. Prolonged hyperuricemia is associated with the development of glomerulosclerosis in the rat.

Immunocompetent cells infiltrate the kidney in several models of experimental hypertension. We have previously shown that reduction of this infiltrate results in prevention of salt-sensitive hypertension induced by short-term angiotensin II infusion and nitric oxide inhibition (Quiroz Y, Pons H, Gordon KI, Rincón J, Chávez M, Parra G, Herrera-Acosta J, Gómez-Garre D, Largo R, Egido J, Johnson RJ, and Rodríguez-Iturbe B. Am J Physiol Renal Physiol 281: F38-F47, 2001; Rodríguez-Iturbe B, Pons H, Quiroz Y, Gordon K, Rincón J, Chávez M, Parra G, Herrera-Acosta J, Gómez-Garre D, Largo R, Egido J, and Johnson RJ. Kidney Int 59: 2222-2232, 2001). We therefore studied whether hypertension could be controlled in genetically hypertensive rats [spontaneously hypertensive rats (SHR)] by the administration of 20 mg x kg(-1) x day(-1) of the immunosuppressive drug mycophenolate mofetil (MMF group; n = 35). Other SHR received vehicle (n = 35), and Wistar-Kyoto rats (n = 20) were used as controls. MMF or vehicle was given in two separate 4-wk periods, separated by a 3-wk interval. Systemic hypertension was reduced to normal levels in both periods of MMF treatment in association with a reduction in lymphocyte, macrophage, and angiotensin II-positive cells infiltrating the kidney. Oxidative stress was also reduced by MMF, as indicated by a reduction in urinary malondialdehyde (MDA), renal MDA content, and superoxide-positive cells, and was highly correlated with blood pressure levels. We conclude that the renal immune infiltrate plays a major role in the hypertension in SHR.

BACKGROUND: Dengue fever, a mosquito-borne viral disease, is now the fastest spreading tropical disease globally. Previous studies indicate that climate and human behavior interact to influence dengue virus and vector (Aedes aegypti) population dynamics; however, the relative effects of these variables depends on local ecology and social context. We investigated the roles of climate and socio-ecological factors on Ae. aegypti population dynamics in Machala, a city in southern coastal Ecuador where dengue is hyper-endemic. METHODS/PRINCIPAL FINDINGS: We studied two proximate urban localities where we monitored weekly Ae. aegypti oviposition activity (Nov. 2010-June 2011), conducted seasonal pupal surveys, and surveyed household to identify dengue risk factors. The results of this study provide evidence that Ae. aegypti population dynamics are influenced by social risk factors that vary by season and lagged climate variables that vary by locality. Best-fit models to predict the presence of Ae. aegypti pupae included parameters for household water storage practices, access to piped water, the number of households per property, condition of the house and patio, and knowledge and perceptions of dengue. Rainfall and minimum temperature were significant predictors of oviposition activity, although the effect of rainfall varied by locality due to differences in types of water storage containers. CONCLUSIONS: These results indicate the potential to reduce the burden of dengue in this region by conducting focused vector control interventions that target high-risk households and containers in each season and by developing predictive models using climate and non-climate information. These findings provide the region's public health sector with key information for conducting time and location-specific vector control campaigns, and highlight the importance of local socio-ecological studies to understand dengue dynamics. See Text S1 for an executive summary in Spanish.

Evidence that was obtained in several experimental models and in strains of hypertensive rats indicates that infiltration of inflammatory cells and oxidative stress in the kidney play a role in the induction and maintenance of hypertension. Similar evidence is lacking in human hypertension, at least in part, because immunosuppressive treatment is unjustified in patients with hypertension. For addressing this issue, patients who were prescribed by their private physicians mycophenolate mofetil (MMF) for the treatment of psoriasis or rheumatoid arthritis and had, in addition, grade I essential hypertension and normal renal function were studied. Eight patients were studied before MMF was started, during MMF treatment, and 1 mo after MMF treatment had been discontinued. Other treatments and diet were unchanged in the three phases of the study. MMF therapy was associated with a significant reduction in systolic, diastolic, and mean BP. Urinary excretion of TNF-alpha was reduced progressively by MMF treatment and increased after MMF was discontinued. Reduction of urinary malondialdehyde, TNF-alpha, and RANTES excretion during MMF administration did not reach statistical significance but had a direct positive correlation with the BP levels. These data are consistent with the hypothesis that renal immune cell infiltration and oxidative stress play a role in human hypertension.