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OBJECTIVE: : The aim of this study was to examine the association between polymorphisms (SNP) in the tryptophan hydroxylase-2 (TPH2) gene and late-onset depression (LOD) in the Brazilian population. METHODS: : We genotyped 8 tag SNPs in the TPH2 gene in 84 outpatients with LOD and 79 individuals belonging to the comparison group to investigate an association between the TPH2 gene and LOD. RESULTS: : Our findings suggested an association between tag SNP rs4565946 heterozygous C/T (p = 0.034; [chi] = 6.7; df = 2) and decreased risk of LOD. The tag SNP rs11179000 ancestral homozygous A/A (p = 0.025; [chi] = 7.3; df = 2) and increase risk of LOD and allelic association of ancestral allele A and increase risk of LOD was demonstrated (p = 0.005; [chi] = 7.8; df = 1). CONCLUSION: : We found the statistically significant association between two tag SNPs and LOD. Our results support the hypothesis that the TPH2 gene is associated with LOD. [ABSTRACT FROM AUTHOR]

Background. The role of nitric oxide (NO) in acute renal failure (ARF) is not yet completely understood. L-Arginine (L-arg) is protective against different ARF models, while L-arg addition in isolated proximal tubules enhances hypoxia/reoxygenation (H/R) injury. The aim of this study was to evaluate the effects of L-arg on renal ischaemia. [ABSTRACT FROM PUBLISHER]

Background: Large-scale epidemics in countries with high birth rates can create a concerning scenario where pregnant people are more likely to transmit the virus. Additionally, increased international mobility has made arboviruses a growing problem for travelers. The increased risk of vertical transmission has been related to maternal viremia near delivery. Such transmission leads to severe infection of newborns and may be associated with subsequent neurological impairment including cerebral palsy. This case series provides an overview of clinical and laboratory findings in pregnant individuals with confirmed CHIKV infection as well as the clinical effects on their newborn emphasizing the severity of neonatal chikungunya., Methods: an ambispective case series enrolled newborns with confirmed exposure to CHIKV in utero or in the neonatal period., Results: during the delivery period, the transmission rate among viremic individuals was approximately 62% (18/29). Fever, irritability, rash, and poor feeding in the first week of life were critical signs of neonatal chikungunya, highlighting its severity., Conclusion: Close monitoring of healthy newborns during the first week of life is essential in areas affected by CHIKV epidemics, and in offspring of pregnant travelers who visited the outbreaks zones. This case series is intended to increase neonatologists' awareness of the possibility of mother-to-child transmission of CHIKV among newborns with a sepsis-like presentation. Prioritizing CHIKV vaccination for women of childbearing age should also be considered., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

The Brazilian Cerrado biome is rich in plant biodiversity, with fruits that have unique sensory characteristics and high nutritional quality. Among the various fruits, baru (Dipteryx alata Vog.) has attracted the attention of researchers because of its high lipid, protein, carbohydrate, fiber, and micronutrient (minerals and vitamins) contents. The present study evaluated the effects of regular consumption of baru almonds for over 60 days on the biochemical and anthropometric profiles and fecal microbiota of obese individuals. A pilot study was conducted on 15 individuals with obesity who were instructed to consume a 20-gram portion of baru almonds throughout the day. The body composition was assessed using anthropometric measurements. Blood pressure, glucose levels, lipid profile, serum insulin and iron contents, and fecal microbiota composition were determined at baseline (day 0) and after 60 days. Baru almond consumption contributed to changes in biochemical parameters, improved HDL cholesterol levels, and reduced total and LDL cholesterol levels. Some positive changes in the microbiota composition after consuming baru almonds include a decrease in the Faecalibacterium family and an increase in the Provotella genus. Therefore, ingesting baru almonds can modulate gut microbiota of individuals with obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

There is growing evidence that the gut microbiota is associated with various aspects of human health, including immune system regulation, vitamin synthesis, short-chain fatty acid production, etc. Peanuts and pistachios are foods rich in protein, unsaturated fatty acids, vitamins, polyphenols, and other dietary components that have been shown to benefit the gut microbiota. Therefore, this review aims to describe the effects of consuming peanuts and pistachios on the gut microbiota and the potential role of these microbiota in human health. This review suggests that the consumption of peanuts or pistachios can demonstrate the potential to exert a beneficial effect on the gut microbiota by promoting the growth of beneficial gut bacteria that produce, for example, short-chain fatty acids that are beneficial for human health. In the case of peanuts, in particular, the possible modulation of the microbiota is associated with an improvement in the risk factors of metabolic syndrome and the inflammatory process triggered by a high-fat diet.

Nicotiana benthamiana is an invaluable model plant and biotechnology platform with a ~3 Gb allotetraploid genome. To further improve its usefulness and versatility, we have produced high-quality chromosome-level genome assemblies, coupled with transcriptome, epigenome, microRNA and transposable element datasets, for the ubiquitously used LAB strain and a related wild accession, QLD. In addition, single nucleotide polymorphism maps have been produced for a further two laboratory strains and four wild accessions. Despite the loss of five chromosomes from the ancestral tetraploid, expansion of intergenic regions, widespread segmental allopolyploidy, advanced diploidization and evidence of recent bursts of Copia pseudovirus (Copia) mobility not seen in other Nicotiana genomes, the two subgenomes of N. benthamiana show large regions of synteny across the Solanaceae. LAB and QLD have many genetic, metabolic and phenotypic differences, including disparate RNA interference responses, but are highly interfertile and amenable to genome editing and both transient and stable transformation. The LAB/QLD combination has the potential to be as useful as the Columbia-0/Landsberg errecta partnership, utilized from the early pioneering days of Arabidopsis genomics to today., (© 2023. The Author(s).)

The cotton bollworm, Helicoverpa armigera, is a major insect pest for a wide range of agricultural crops. It causes significant yield loss through feeding damage and by increasing the crop's vulnerability to bacterial and fungal infections. Although expression of Bacillus thuringiensis (Bt) toxins in transgenic crops has been very successful in protecting against insect pests, including H. armigera, field-evolved resistance has occurred in multiple species. To manage resistant populations, new protection strategies must be continuously developed. Trans-kingdom RNA interference (TK-RNAi) is a promising method for controlling herbivorous pests. TK-RNAi is based on delivering dsRNA or hairpin RNA containing essential insect gene sequences to the feeding insect. The ingested molecules are processed by the insect's RNAi machinery and guide it to silence the target genes. Recently, TK-RNAi delivery has been enhanced by expressing the ds- or hpRNAs in the chloroplast. This compartmentalizes the duplexed RNA away from the plant's RNAi machinery, ensuring that it is delivered in an unprocessed form to the insect. Here, we report another alternative approach for delivering precursor anti-insect RNA in plants. Insect pre-microRNA (pre-miR) transcripts were modified to contain artificial microRNAs (amiRs), targeting insect genes, and expressed in transgenic Nicotiana benthamiana plants. These modified pre-miRs remained largely unprocessed in the plants, and H. armigera feeding on leaves from these plants had increased mortality, developmental abnormalities and delayed growth rates. This shows that plant-expressed insect pre-amiRs (plin-amiRs) are a new strategy of protecting plants against herbivorous insects., (© 2020 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Paraburkholderia phymatum is a highly effective microsymbiont of Mimosa spp. and has also been shown to nodulate papilionoid legumes. P. phymatum was found to be highly competitive both in a natural environment as well as under controlled test conditions and is more competitive for nodulation over other α- and β-rhizobial strains in a variety of different plant hosts. In order to elucidate the factors that make this bacterium highly competitive for legume infection, we here characterized the type VI secretion system (T6SS) clusters of P. phymatum . T6SSs have been shown to function as a contact-dependent injection system for both bacterial and eukaryotic cells. We identified two T6SS clusters in the genome, created respective mutant strains and showed that they are defective in biofilm formation and in interbacterial competition in vitro . While the T6SS mutants were as efficient as the wild-type in nodulating the non-cognate host Vigna unguiculata , the mutants were less competitive in in planta competition assays, suggesting that the T6SS is one of the factors responsible for the success of P. phymatum in infecting legumes by directly inhibiting competitors.

Objective: Circadian rhythms have been linked to psychiatric disorders such as Depression and Bipolar Disorder (BD). Given previous evidences of sleep/circadian disturbances as well as the genetic susceptibility for BD, we decided to investigate the possible link between the PERIOD3 (Per3) circadian gene and BD., Methods: This is a genetic association case (BD) vs. control study of the Per3 gene. We further subdivided our BD sample into "good sleepers" (PSQI ≤5) and "poor sleepers" (PSQI>5) according to the Pittsburgh Sleep Quality Index (PSQI) global score, and then we assessed genetic association of the Per3 gene with sleep quality in the BD group., Results: There were 209 cases and 213 controls in our sample. The GT genotype of the SNP rs707467 significantly associated with BD (χ 2 =8.80; p-value=0.01; adjusted residual=±2.6). We also found significant association of the SNP rs10462020 allele T with BD (χ 2 =5.81; p-value=0.01) as well as the genotype TT (χ 2 = 6.01; p-value=0.04; adjusted residual=±2.4)., Conclusion: In this study we demonstrated evidences of genetic association between the Per3 gene and BD. The results of association between the Per3 gene and BD in our sample may bring additional evidence to the former findings of association between the Per3 gene and BD.

Members of the genus Burkholderia (β-proteobacteria) have only recently been shown to be able to establish a nitrogen-fixing symbiosis with several legumes, which is why they are also referred to as β-rhizobia. Therefore, very little is known about the competitiveness of these species to nodulate different legume host plants. In this study, we tested the competitiveness of several Burkholderia type strains ( B. diazotrophica , B. mimosarum , B. phymatum , B. sabiae , B. symbiotica and B. tuberum ) to nodulate four legumes ( Phaseolus vulgaris , Macroptilium atropurpureum , Vigna unguiculata and Mimosa pudica ) under our closely defined growth conditions. The assessment of nodule occupancy of these species on different legume host plants revealed that B. phymatum was the most competitive strain in the three papilionoid legumes (bean, cowpea and siratro), while B. mimosarum outcompeted the other strains in mimosa. The analysis of phenotypes known to play a role in nodulation competitiveness (motility, exopolysaccharide production) and additional in vitro competition assays among β-rhizobial strains suggested that B. phymatum has the potential to be a very competitive legume symbiont.

Objective: To describe the prevalence of short stature among children of Karapotó ethnic background., Methods: Cross-sectional, population-based study that included children between 6 and 59 months of age from the Plak-Ô native village and the Terra Nova settlement, São Sebastião, Alagoas, carried out between 2008 and 2009. Short stature was evaluated by the Height/Age index, using as cutoff z score ≤-2. The prevalence of short stature was determined by comparing simple and relative frequencies. The population growth curves were compared to the WHO reference curves. Data analysis included the outcome variable: Height/Age and the predictor variables: place of residence, gender, age, anemia, birth weight, family income, maternal literacy. The chi-square test was used to compare the categorical variables, whereas the chi-square test with Yates correction was used for dichotomous variables, considering as statistically significant p-values≤0.05., Results: The prevalence of short stature was 15.6% for children from the Terra Nova settlement and 9.1% for those from Plak-Ô native village. The prevalence of short stature among the Karapotó ethnicity was 13.4%. The variables: maternal literacy, family income and low birth weight were statistically associated with short stature., Conclusions: The observed short stature prevalence rates are significant, being characterized as a public health problem. Among the associated factors, the following are noteworthy: unfavorable conditions of maternal literacy, family income and low birth weight. The planning of strategies to reverse the situation must take such factors into consideration., (Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.)

Purpose: To assess peripapillary retinal nerve fiber layer, macular ganglion cell complex, and total macular thicknesses using spectral domain optical coherence tomography on sickle cell disease patients with and without sickle retinopathy., Method: Nineteen eyes of 11 patients with hemoglobin sickle cell disease, 65 eyes of 36 patients with hemoglobin SS disease, and 48 eyes of 24 healthy subjects underwent spectral domain optical coherence tomography scanning (RTVue). Eyes of patients with sickle cell disease were classified into 3 groups according to posterior segment changes: no retinopathy (n = 64), nonproliferative retinopathy (n = 12), and proliferative retinopathy (n = 8)., Results: The central fovea in eyes with proliferative retinopathy was thickened compared with control group, sickle cell disease without retinopathy, and nonproliferative retinopathy (P = 0.004); a difference between proliferative retinopathy and sickle cell disease without retinopathy groups was still present after age adjustment (P = 0.014). Eyes with proliferative changes showed higher ganglion cell complex focal loss of volume compared with control group (P = 0.002), even after age adjustment (P = 0.004). Thinning of the nasal retinal nerve fiber layer quadrant was observed in eyes with proliferative retinopathy (P < 0.001); however, no retinal nerve fiber layer thickness difference was observed after age correction (P > 0.05)., Conclusion: Peripheral changes secondary to proliferative sickle retinopathy were associated with thinning of macular inner retinal layers and thickening of central fovea.

Biological nitrogen fixation (BNF) is a tightly regulated process that is carried out by diazotrophic microorganisms. The regulatory mechanisms of BNF-related genes are well characterized in Gram-negative models, but they are poorly understood in Gram-positive bacteria. Paenibacillus riograndensis SBR5(T) is a Gram-positive, endospore-forming facultative aerobic diazotroph. Three clusters of BNF-related genes with dissimilar phylogenetic histories were identified in the P. riograndensis genome, and no regulatory genes were recognized. P. riograndensis nifH2 was considered inactive based on transcript and promoter analyses, whereas transcripts of nifH1 and anfH were induced upon nitrogen-limited conditions. The functionality of the alternative nitrogenase system was also validated by enzymatic activity analysis. Fragments upstream of the two active clusters seem to harbor primary functional promoter sequences, producing a constitutive expression pattern in Escherichia coli. Sequences upstream of the anf genes were not recognized by this heterologous host, indicating a very distinct promoter pattern. These results shed light upon the evolutionary history of nitrogen fixation genes in this Gram-positive bacterium and highlight the presence of novel regulatory elements that are yet to be described., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Prefrontal dopamine is catabolized by the catechol-O-methyltransferase (COMT) enzyme. Current evidence suggests that the val/met single nucleotide polymorphism in the COMT gene can predict the efficiency of executive cognition in humans. Individuals carrying the val allele perform more poorly because less synaptic dopamine is available., Methodology/principal Findings: We investigated the influence of the COMT polymorphism on motor performance in a task that requires different executive functions. We administered a manual aiming motor task that was performed under four different conditions of execution by 111 healthy participants. Participants were grouped according to genotype (met/met, met/val, val/val), and the motor performance among groups was compared. Overall, the results indicate that met/met carriers presented lower levels of peak velocity during the movement trajectory than the val carriers, but met/met carriers displayed higher accuracy than the val carriers., Conclusions/significance: This study found a significant association between the COMT polymorphism and manual aiming control. Few studies have investigated the genetics of motor control, and these findings indicate that individual differences in motor control require further investigation using genetic studies.

Background: Impulsivity is a multidimensional construct which has been associated with dopaminergic neurotransmission. Nonetheless, until this moment, few studies addressed the relationship between different types of impulsivity and the single nucleotide polymorphism caused by a substitution of valine (val) with methionine (met) in the 158 codon of the Catechol-o-Methyltransferase gene (COMT-val158met). The present study aimed to investigate the association between val158met COMT polymorphism and impulsive behavior measured by two neuropsychological tests., Methodology/principal Findings: We administered two neuropsychological tests, a Continuous Performance Task and the Iowa Gambling Task were applied to 195 healthy participants to characterize their levels of motor, attentional and non-planning impulsivity. Then, subjects were grouped by genotype, and their scores on impulsivity measures were compared. There were no significant differences between group scores on attentional and motor impulsivity. Those participants who were homozygous for the met allele performed worse in the Iowa Gambling Task than val/val and val/met subjects., Conclusions/significance: Our results suggest that met allele of val158met COMT polymorphism is associated with poor performance in decision-making/cognitive impulsivity task. The results reinforce the hypothesis that val and met alleles of the val158met polymorphism show functional dissociation and are related to different prefrontal processes.

Crop production may benefit from plant growth-promoting bacteria. The knowledge on bacterial communities is indispensable in agricultural systems that intend to apply beneficial bacteria to improve plant health and production of crops such as canola. In this work, the diversity of root bacterial communities associated to two different developmental phases of canola (Brassica napus L.) plants was assessed through the application of new generation sequencing technology. Total bacterial DNA was extracted from root samples from two different growth states of canola (rosette and flowering). It could be shown how bacterial communities inside the roots changed with the growing stage of the canola plants. There were differences in the abundance of the genera, family, and even the phyla identified for each sample. While in both root samples Proteobacteria was the most common phylum, at the rosette stage, the most common bacteria belonged to the family Pseudomonadaceae and the genus Pseudomonas, and in the flowering stage, the Xanthomonadaceae family and the genus Xanthomonas dominated the community. This implies in a switch in the predominant bacteria in the different developmental stages of the plant, suggesting that the plant itself interferes with the associated microbial community.

Objective: The aim of this study was to examine the association between polymorphisms (SNP) in the tryptophan hydroxylase-2 (TPH2) gene and late-onset depression (LOD) in the Brazilian population., Methods: We genotyped 8 tag SNPs in the TPH2 gene in 84 outpatients with LOD and 79 individuals belonging to the comparison group to investigate an association between the TPH2 gene and LOD., Results: Our findings suggested an association between tag SNP rs4565946 heterozygous C/T (p = 0.034; χ2 = 6.7; df = 2) and decreased risk of LOD. The tag SNP rs11179000 ancestral homozygous A/A (p = 0.025; χ2 = 7.3; df = 2) and increase risk of LOD and allelic association of ancestral allele A and increase risk of LOD was demonstrated (p = 0.005; χ2 = 7.8; df = 1)., Conclusion: We found the statistically significant association between two tag SNPs and LOD. Our results support the hypothesis that the TPH2 gene is associated with LOD.

Background: Bipolar disorder (BD) is a complex disorder where genetic factors play a major role in its etiology. Probably, no other axis I diagnosis has a co-morbidity prevalence as high as BD. Since BDNF is involved in different ways in various psychiatric disorders we hypothesized that its genetic polymorphisms could be associated with the co-morbidity phenomenon in BD., Methods: We studied 320 subjects (160 BD patients and 160 healthy controls). Genotyping was performed using made-to-order TaqMan genotyping assays (rs4923463, rs6265, rs2049045, and rs7103411). Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview 4.1., Results: No genotypic, allelic or haplotype differences were found between bipolar patients and healthy controls. Concerning exclusively the rs4923463 (G/G) there was a significant association with alcoholism (p=0.009), smoking (p=0.006) and violent suicide attempt (p=0.03). We further found that the G-G haplotype (rs4923463-rs2049045) (adjusted p=0.029) and the G-T haplotype (rs4923463-rs7103411) (adjusted p=0.029) were significantly more frequent in the group with alcoholism co-morbidity when compared with the group without this co-morbidity., Limitations: Sample size and retrospective assessment of suicide behavior and psychiatric comorbidities., Conclusions: The results obtained in our study indicate that BDNF variants may confer susceptibility to additional psychiatric diagnosis in BD., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Frequent comorbidity between panic disorder (PD) and mood disorders has been widely reported in clinical and epidemiological studies and, recently, an increasing attention has been paid to the cooccurrence of PD and bipolar disorder (BD). Several studies have shown that an imbalance of serotonin activity could be related to panic symptoms. Tryptophan hydroxylase 2 (TPH2) are plausible candidates for the association with PD. The aim of this study is to investigate a possible association between TPH2 gene polymorphisms and the PD comorbidity susceptibility.Our sample consisted of 515 patients; 274 patients with BD (subtypes I and II), including 45 patients with lifetime panic disorder comorbidity and 241 controls. These patients were genotyped for eight tagging single nucleotide polymorphisms of the gene of human TPH2. We found significant differences between patients with BD, with panic disorder comorbidity, and controls in the allelic analysis (rs4448731, P=0.0069; rs4565946, P=0.0359; rs4760820, P=0.0079; rs1487275, P=0.0439) and genotypic analysis (rs4448731, P=0.011; rs4760820, P=0.0259). We also identified significant differences between patients with BD, with and without panic disorder comorbidity in the allelic analysis (rs4448731, P=0.004; rs4565946, P=0.011; rs11179000, P=0.031; rs4760820, P=0.018; rs1487275, P=0.038; rs10879357, P=0.023) and genotypic analysis (rs4448731, P=0.004; rs4565946, P=0.010; rs4760820, P=0.023; rs10879357, P=0.052). The haplotype analysis in the group of patients with BD, with and without panic disorder comorbidity, was also significant (rs4448731-rs4565946, P=0.0190; rs4448731-rs4565946, P=0.0220; rs10506645-rs4760820, P=0.0360). Further studies are needed to replicate the positive association that we observed.

The rapid diagnosis and quantification of acute kidney injury (AKI) severity remain high clinical priorities. By combining intravital fluorescent ratiometric two-photon kidney imaging and the two-compartment pharmacokinetics model, we demonstrate that rapid quantification of glomerular filtration rate (GFR) can be achieved in physiologic and AKI rat kidney models. Using a bolus infusion of a mixture of FITC-inulin and a 500-kDa Texas Red dextran, a full spectrum of GFR values, ranging from 0.17 to 1.12 ml·min(-1)·100 g(-1), was obtained. The GFR values thus determined correlated well with values obtained by the standard 2-h inulin infusion clearance method with a Pearson's correlation coefficient of 0.85. In addition, postischemia deterioration was studied by measuring GFR using the two-photon approach during 24 h following a 45-min bilateral ischemia clamp model. The GFR was found to decline sharply during the initial 4 h followed by a nadir with little sign of rising over the ensuing 24-h period. Moreover, a FITC-labeled 5-kDa dextran was identified as having nearly identical filtration characteristics as FITC-inulin, but had markedly increased fluorescent intensity, thus minimizing the quantity needed for individual studies. The technique reported allows for very rapid GFR determinations, within 10-15 min, based on plasma clearance of a freely filtered fluorescence probe, instead of a prolonged one-compartment interstitial space reporter molecule clearance employed by other technologies.

Postpartum depression disorder (PPD) is a severe illness affecting around 15% of deliveries. Several evidences suggest that PPD is, at least, partially genetic determined. The gene encoding BDNF is a strong candidate for pathogenesis of PPD since that it has been observed decrease of serum BDNF in patients suffering from PPD. The gene encoding BDNF has a polymorphism (Val66Met) that alters the regulated protein secretion; the methionine variant being associated with insufficient secretion compared with the Valine variant. We hypothesized that BDNF gene Val66Met polymorphism could be associated with PPD. We assessed 227 subjects randomly selected who had delivery at a maternity hospital using EPDS. Differences in genotype frequency were calculated by chi (2) test. Logistic Regression Analyses was performed to verify the existence of interaction between biological, psychiatric and environmental variables and PPD. Difference between groups was tested with Student's t test. Tests were two-tailed and results significant when p < or = 0.05. No difference in BDNF genotype distribution was observed between the depressed and non-depressed women. Educational level, stress during pregnancy, bipolar disorder and anxiety was strongly associated with PPD. We were not able to show an association between BDNF polymorphisms and PPD. Further studies are necessary to both of confirm our results and improve validity of PPD diagnosis.

Bipolar disorder (BD) is a severe psychiatric illness characterized by the occurrence of elevated mood alternating with depressive episodes, having a estimated lifetime prevalence of 0.4-1.6% using DSM-IV criteria. Disturbances of the central serotonergic system has been associated with the pathophysiology of affective disorders and suicidal behavior. Tryptophan hydroxylase 2 (TPH2) which is a rate limiting enzyme in the serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. Our sample consisted of 527 subjects (303 diagnosed with bipolar disorder and 224 healthy controls) which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the whole gene of the human TPH2. Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview((R)). Single markers, genotype and haplotype association analysis did not show significant genetic association with bipolar disorder or suicidal behavior. Our findings do not support the association between diagnosis of BD or suicidal behavior and TPH2 polymorphisms.

Proximal tubule cells (PTCs), which are the primary site of kidney injury associated with ischemia or nephrotoxicity, are the site of oligonucleotide reabsorption within the kidney. We exploited this property to test the efficacy of siRNA targeted to p53, a pivotal protein in the apoptotic pathway, to prevent kidney injury. Naked synthetic siRNA to p53 injected intravenously 4 h after ischemic injury maximally protected both PTCs and kidney function. PTCs were the primary site for siRNA uptake within the kidney and body. Following glomerular filtration, endocytic uptake of Cy3-siRNA by PTCs was rapid and extensive, and significantly reduced ischemia-induced p53 upregulation. The duration of the siRNA effect in PTCs was 24 to 48 h, determined by levels of p53 mRNA and protein expression. Both Cy3 fluorescence and in situ hybridization of siRNA corroborated a short t(1/2) for siRNA. The extent of renoprotection, decrease in cellular p53 and attenuation of p53-mediated apoptosis by siRNA were dose- and time-dependent. Analysis of renal histology and apoptosis revealed improved injury scores in both cortical and corticomedullary regions. siRNA to p53 was also effective in a model of cisplatin-induced kidney injury. Taken together, these data indicate that rapid delivery of siRNA to proximal tubule cells follows intravenous administration. Targeting siRNA to p53 leads to a dose-dependent attenuation of apoptotic signaling, suggesting potential therapeutic benefit for ischemic and nephrotoxic kidney injury.

Altered coagulation and inflammation contribute to the pathogenesis of ischemic renal injury. Thrombomodulin is a necessary factor in the anticoagulant protein C pathway and has inherent anti-inflammatory properties. We studied the effect of soluble thrombomodulin (sTM) in a hypoperfusion model of ischemic kidney injury. To markedly reduce infrarenal aortic blood flow and femoral arterial pressures, we clamped the suprarenal aorta of rats, occluding them 90%, for 60 min. Reversible acute kidney injury (AKI) occurred at 24 h in rats subjected to hypoperfusion. Histologic analysis at 24 h revealed acute tubular necrosis (ATN), and intravital two-photon microscopy showed flow abnormalities in the microvasculature and defects of endothelial permeability. Pretreatment with rat sTM markedly reduced both I-R-induced renal dysfunction and tubular histologic injury scores. sTM also significantly improved microvascular erythrocyte flow rates, reduced microvascular endothelial leukocyte rolling and attachment, and minimized endothelial permeability to infused fluorescence dextrans, assessed by intravital quantitative multiphoton microscopy. Furthermore, sTM administered 2 h after reperfusion protected against ischemia-induced renal dysfunction at 24 h and improved survival. By using an sTM variant, we also determined that the protective effects of sTM were independent of its ability to generate activated protein C. These data suggest that sTM may have therapeutic potential for ischemic AKI.

Understanding the pathogenesis of albuminuria in diabetic nephropathy is important to improve methods for early diagnosis and treatment. In this study, we addressed whether albuminuria in diabetes results from altered glomerular filtration and/or altered processing of filtered albumin by the proximal tubule. Type 1 diabetic Munich Wistar rats developed albuminuria after 12 wk of diabetes. Intravital two-photon microscopy revealed similar glomerular permeability in the diabetic and control animals, assessed using both albumin-Alexa568 and 69-kD FITC-dextran; however, diabetic animals demonstrated significantly less filtered fluorescent albumin in renal proximal tubule (PT) cells compared with control animals. We also observed increased albumin-derived urinary peptide excretion in diabetic animals, and hyperglycemia modulated this peptideuria. In conclusion, in the early stages of diabetic nephropathy, the PT plays a major role in the development of albuminuria, which may be preceded by peptideuria.

Acute ischemic kidney injury results in marked increases in local and systemic cytokine levels. IL-1alpha, IL-6, and TNF-alpha orchestrate various inflammatory reactions influencing endothelial permeability by altering cell-to-cell and cell-to-extracellular matrix attachments. To explore the role of actin and the regulatory proteins RhoA and cofilin in this process, microvascular endothelial cells (MS1) were exposed to individual cytokines or a cytokine cocktail. Within minutes, a marked, time-dependent redistribution of the actin cytoskeleton occurred with the formation of long, dense F-actin basal stress fibers. The concentration of F-actin, normalized to nuclear staining, significantly increased compared with untreated cells (up 20%, P < or = 0.05). Western blot analysis of MS1 lysates incubated with the cytokine cocktail for 4 h showed an increase in phosphorylated/inactive cofilin (up 25 +/- 15%, P < or = 0.05) and RhoA activation (up to 227 +/- 26% increase, P < or = 0.05) compared with untreated cells. Decreasing RhoA levels using small interfering RNA blocked the effect of cytokines on stress fiber organization. Treatment with Y-27632, an inhibitor of the RhoA effector p160-ROCK, decreased levels of phosphorylated cofilin and reduced stress fiber fluorescence by 22%. In cells treated with Y-27632 followed by treatment with the cytokine cocktail, stress fiber levels were similar to control cells and cofilin phosphorylation was 55% of control levels. Taken together, these studies demonstrate cytokine stimulation of RhoA, which in turn leads to cofilin phosphorylation and formation of numerous basal actin stress fibers. These results suggest cytokines signal through the Rho-ROCK pathway, but also through another pathway to affect actin dynamics.

Aminoglycoside antibiotics, although of major clinical importance in the treatment of serious Gram- negative infections and a potential therapeutic agent in the amelioration of diseases that are characterized by premature stop mutations, are associated with a high incidence of acute renal failure. With the use of HPLC techniques, the four components (congeners) of gentamicin, the most commonly used aminoglycoside, were isolated and characterized. Described here is a congener with minimal cytotoxicity in cell culture and animal studies that retained normal bactericidal properties in both Bacillus subtilis and a multidrug-resistant form of Klebsiella pneumoniae. Furthermore, in animal studies, this congener failed to induce the functional and pathologic changes that are characteristic of gentamicin nephrotoxicity that is seen with the native compound. Finally, internalization of this non-nephrotoxic component was unaltered, but the subcellular distribution was different from native gentamicin or the other three cytotoxic congeners. These studies have identified a component of the native gentamicin congener mixture that retains its bactericidal properties with minimal or no apparent nephrotoxicity.

In this work, we further analyzed an Azospirillum brasilense Sp7 mutant (Sp7::Tn5-33) showing a pleiotrophic phenotype due to a Tn5 insertion into an open reading frame of 840 bp (orf280). The deduced amino acid sequence of this region has high similarity to a family of universal stress proteins. Because the most interesting property exhibited by the Sp7::Tn5-33 mutant was an enhanced in vitro nitrogen fixation activity, we addressed the question of whether it could benefit the host plant. We found that the increased nitrogenase activity at the free-living state of the mutant bacterium was correlated with an increased production of the nitrogenase reductase protein (NifH), in amounts approximately 1.5 times higher than the wild type. The mutant strain exhibited the same level of auxin production and the same colonization pattern of wheat roots as the wild type. We also observed that Sp7::Tn5-33 increased the total plant dry weight, although the N content did not differ significantly between wheat plants inoculated with mutant or wild-type strains.

Background and Aims: Primary biliary cirrhosis (PBC) might be complicated by osteoporosis, whose etiology remains unknown but seems to be multifactorial. Prevalence rates of 30% to 60% for distal renal tubular acidosis (DRTA) have been reported in PBC patients, generally as incomplete DRTA. Although it is undisputed that a reduced bone mineral density (BMD) is the expected outcome among patients who have been suffering from longstanding chronic metabolic acidosis, it is unclear if incomplete DRTA is also associated with metabolic bone disease in PBC patients. The present study was undertaken to compare the BMD of PBC patients with and without DRTA., Methods: The BMD of 23 PBC patients (11 with DRTA and 12 without), all with normal clearance of creatinine, was assessed by dual energy radiograph absorptiometry. The diagnosis of DRTA was made if the urine pH was above 5.4 in all samples after the oral acid overload, showing tubular inability to acidify urine in the presence of test-induced systemic metabolic acidosis., Results: Densitometric signs of osteoporosis were found in 82% of DRTA cases and in 83% of patients without DRTA (difference not significant). There were no significant differences in BMD measurement, T and Z scores of patients with and without DRTA., Conclusions: The present study could not support a correlation between the presence of DRTA and the bone loss observed in PBC patients.

Ischemic-induced cell injury results in rapid duration-dependent actin-depolymerizing factor (ADF)/cofilin-mediated disruption of the apical microvilli microfilament cores. Because intestinal microvillar microfilaments are bound and stabilized in the terminal web by the actin-binding protein tropomyosin, we questioned whether a protective effect of tropomyosin localization to the terminal web of the proximal tubule microfilament cores is disrupted during ischemic injury. With tropomyosin-specific antibodies, we examined rat cortical sections under physiological conditions and following ischemic injury by confocal microscopy. In addition, Western blot analysis of cortical extracts and urine was undertaken. Our studies demonstrated the presence of tropomyosin isoforms in the proximal tubule microvillar terminal web under physiological conditions and their dissociation in response to 25 min of ischemic injury. This correlated with the excretion of tropomyosin-containing plasma membrane vesicles in urine from ischemic rats. In addition, we noted increased tropomyosin Triton X-100 solubility following ischemia in cortical extracts. These studies suggest tropomyosin binds to and stabilizes the microvillar microfilament core in the terminal web under physiological conditions. With the onset of ischemic injury, we propose that tropomyosin dissociates from the microfilament core providing access to microfilaments in the terminal web for F-actin binding, severing and depolymerizing actions of ADF/cofilin proteins.

The role of renal microvascular endothelial cell injury in the pathophysiology of ischemic acute renal failure (ARF) remains largely unknown. No consistent morphological alterations have been ascribed to the endothelium of the renal microvasculature as a result of ischemia-reperfusion injury. Therefore, the purpose of this study was to examine biochemical markers of endothelial injury and morphological changes in the renal microvascular endothelium in a rodent model of ischemic ARF. Circulating von Willebrand factor (vWF) was measured as a marker of endothelial injury. Twenty-four hours after ischemia, circulating vWF peaked at 124% over baseline values (P = 0.001). The FVB-TIE2/GFP mouse was utilized to localize morphological changes in the renal microvascular endothelium. Immediately after ischemia, there was a marked increase in F-actin aggregates in the basal and basolateral aspect of renal microvascular endothelial cells in the corticomedullary junction. After 24 h of reperfusion, the pattern of F-actin staining was more similar to that observed under physiological conditions. In addition, alterations in the integrity of the adherens junctions of the renal microvasculature, as demonstrated by loss of localization in vascular endothelial cadherin immunostaining, were observed after 24 h of reperfusion. This observation temporally correlated with the greatest extent of permeability defect in the renal microvasculature as identified using fluorescent dextrans and two-photon intravital imaging. Taken together, these findings indicate that renal vascular endothelial injury occurs in ischemic ARF and may play an important role in the pathophysiology of ischemic ARF.

Background: Zidovudine (AZT) and didanosine (ddI) are antiretroviral drugs widely used in AIDS patients. Hypokalemia and hypomagnesemia are frequently encountered in AIDS patients using AZT and/or ddI., Objective: To verify the effects of AZT and ddI on rat renal function submitted to normal diet, low potassium diet and magnesium-free diet., Methods: Glomerular filtration rate and renal hemodynamic were measured in Wistar rats submitted to a normal or a potassium-depleted diet. The animals were given AZT, ddI for 15 days. Six groups of rats were studied: normal diet, normal diet + AZT, normal diet + ddI, low K diet, low K diet + AZT and low K diet + ddI. Three additional groups of rats submitted to magnesium depletion for 15 days were also studied: magnesium-free diet, magnesium-free diet + AZT and magnesium-free diet + ddI., Results: AZT and didanosine did not modify renal function of rats on a normal diet. However, in hypokalemic rats, both drugs produced a decrease in glomerular filtration rate and in renal blood flow consequent to renal vasoconstriction and associated with alterations in tubular function (characterized by an increased fractional excretion of sodium). Hypomagnesemia induced a decrease in glomerular filtration rate and in renal blood flow only in AZT-treated rats., Conclusion: Our data suggest that hypokalemia predisposes to AZT and ddI nephrotoxicity, while hypomagnesemia predisposes only to AZT nephrotoxicity. Thus, chronic AZT and ddI administration may produce acute renal failure in AIDS patients with hypokalemia and/or hypomagnesemia. Serum K and Mg levels should be carefully monitored in these patients.

Previously, we described a direct inhibitory effect of sodium artesunate on sodium chloride transport in the thick ascending limb of Henle's loop, indicating that artesunate acts as a diuretic agent. Here we present 2 cases of falciparum malaria treated with 4 intravenous 60-mg doses of sodium artesunate. Neither diuretics nor vasoactive drugs were administered. A rise in diuresis (6 L/24 hours) was accompanied by an increase in natriuresis, and both declined at the end of the treatment. This diuretic effect has not been reported previously in patients and may modify the course of renal failure and respiratory distress syndrome, both of which complicate severe malaria.

Immunosuppressive agents may have an impact on ischemia/reperfusion (I/R) injury. The immunosuppressant mycophenolate mofetil (MMF) presents properties that can attenuate such injury. This study investigated the effects of MMF on renal I/R injury. Male Wistar rats received MMF (20 mg/kg per d) or vehicle by gavage beginning 2 d before ischemia and maintained during the entire study. Ischemic injury was induced by bilateral renal arteries occlusion for 60 min. Control rats received MMF and underwent sham operation. At days 1, 2, and 14, post-ischemia renal function was assessed and kidneys were removed for histologic and immunohistochemical studies. MMF given to nonischemic rats did not alter renal function. There was no functional protection at 24 h post-ischemia with MMF. At 2 d, post-ischemia rats pretreated with MMF presented higher inulin clearance compared with untreated rats (0.42 +/- 0.04 versus 0.15 +/- 0.02 ml/min per 100 g; P < 0.001) and attenuated renal blood flow decrease (5.23 +/- 0.28 versus 3.24 +/- 0.37 ml/min; P < 0.01). The immunostaining for intercellular adhesion molecule-1 (ICAM-1) was less intense in rats pretreated with MMF. These rats also presented an earlier decreased infiltrating macrophages/lymphocytes and cell proliferation at day 1 post-ischemia. The functional and immunohistochemical analyses performed at day 14 post-ischemia returned to values similar to controls in both groups of rats. To determine whether mycophenolic acid (MPA) could induce cytoprotection, the effects of MPA on normoxic and hypoxic/reoxygenated (H/R) isolated tubule suspensions were also investigated. MPA was not deleterious to normoxic tubules and it was not protective against H/R tubules. In conclusion, pretreatment with MMF attenuates I/R injury in rats and does not limit the recovery from ischemia. The protective effect of MMF by reducing inflammation precedes the hemodynamic changes and tubular injury.

Background: Sodium artesunate is currently used in malaria treatment. Adverse effects of this drug have not been described, probably because they cannot be differentiated from malaria-related effects., Methods: The effects on renal function of an acute infusion of sodium artesunate (12 mg/kg body weight) were studied in the rat with clearance techniques. We also evaluate the effect of sodium artesunate on chloride lumen-bath flux (Cl Jlb) in the isolated thick ascending limb of the loop of Henle (TALH) microperfused in vitro., Results: Acute infusion of artesunate to the rat decreased inulin clearance, despite an increase in renal blood flow. These effects were associated with an increase in urinary excretion of sodium, chloride, potassium, and nitric oxide metabolites (NO(2)/NO(3)). In water-loaded animals, artesunate increased sodium and water distal delivery and decreased free water clearance (C(H(2)O)) factored for sodium and water delivery. Following hypertonic NaCl infusion, artesunate decreased free water excretion (Tc(H(2)O)) corrected by clearance of osmolarity (C(Osm)). In vitro, artesunate 10(-6) and 10(-3) mol/L added to bath solution decreased chloride lumen-bath flux in isolated rabbit TALH in a dose-dependent manner, with the threshold effect at 10(-4) mol/L. This effect was completely blocked by N(G)-nitroL-arginine-metilester (L-NAME) 5 mmol/L. Artesunate 10(-4) mol/L added to the perfusion solution did not change Cl Jlb., Conclusion: These findings suggest that artesunate decreases glomerular filtration rate and increases renal blood flow and urinary excretion of Na, Cl, and K. These effects were due, at least in part, to the inhibition of Cl transport across cortical and medullary TALH, and were mediated by local production of nitric oxide, since it is associated with an increase in NO(2)/NO(3) urinary excretion and it is blocked by L-NAME in vitro.

The effects of hypercholesterolemia on ischemic renal failure were evaluated in rats subjected to 60 min of left renal artery clamping and contralateral nephrectomy. One group of rats (HC) was kept on a cholesterol-supplemented diet for 3 weeks before renal injury and compared to a group fed a regular diet (ND). Two days after renal ischemia, inulin clearance (C(in), ml/min per 100 g BW) was lower in HC-rats (0.033 +/- 0.011) than in ND-rats (0.227 +/- 0.037; P < 0.01). indicating that hypercholesterolemia potentiated renal ischemic injury. Twenty-one days after renal ischemia the C(in) of HC-rats did not differ from ND-rats, suggesting that hypercholesterolemia did not limit late recovery. Since nitric oxide production is impaired in HC, L-arginine (50 mg/kg BW i.v.) was administered immediately after ischemia. Two days after ischemia, L-arg did not protect ND-rats from ischemia, while the C(in) and renal blood flow were higher in L-arg-treated HC rats than in untreated HC rats (C(in) = 0.125 +/- 0.013 rats vs. 0.033 +/- 0.011; P < 0.001) (RBF = 3.96 +/- 0.64 vs. 2.40 +/- 0.20 ml/min per 100 g BW; P < 0.05), indicating that L-arg protects HC rats from renal ischemia. The administration of D-arginine to ND rats induced a significant decrease of the C(in) and a significant increase of FE H2O, FE Na and FE K compared to the L-arginine and not treated groups. Cultures of inner medullary collecting duct cells from ND rats were resistant to 24-h hypoxia. In contrast, IMCD cell cultures from HC rats showed higher LDH release after 24-h hypoxia than normoxic cells (69.2 +/- 3.4 vs. 30.9 +/- 3.6%, P < 0.001); 1 mM L-arg added to the medium attenuated LDH release (44.3 +/- 2.4%, P < 0.01). These data demonstrate that HC predisposes renal tubular cells to hypoxic injury and L-arg protects cells of HC.

It is well known that the radiocontrast-induced ARF depends on risk factors often associated with compromised renal circulation. Since studies have shown that endothelium-dependent vasodilation is impaired in hypercholesterolemia (HC), we studied the effect of radiocontrast (RC) administration (6 ml/kg body wt, via femoral artery) in salt-depleted rats that were kept on a normal cholesterol (NC) or HC diet (4% cholesterol and 1% cholic acid). Inulin clearance (CIn, ml/min/100 g body wt), renal blood flow (RBF; electromagnetic flowmeter, ml/min/100 g body wt), and fractional excretions of sodium, potassium and water (FENa, FEK and FEH2O, respectively), cholesterol (mg/dl), and albumin (g/dl) were measured 24 hours after radiocontrast administration. The administration of RC to HC rats (RCHC) resulted in lower values of CIn compared with NC rats (RCNC) and control rats: 0.36 +/- 0.085 versus 0.76 +/- 0.13 (RCNC; P < 0.01), versus 0.84 +/- 0.03 (control HC; P < 0.01), versus 0.87 +/- 0.06 (control NC; P < 0.01). Hypercholesterolemia per se did not alter renal function, and control HC versus control NC was not significant. Renal blood flow was significantly lower in the RCHC when compared to RCNC (4.3 +/- 0.3 vs. 6.1 +/- 0.3; P < 0.001) and to control animals (control HC 8.2 +/- 0.3; P < 0.001), and control NC 7.5 +/- 0.33 (P < 0.001). To study the role of nitric oxide (NO), HC rats were treated with an infusion of L-arginine or D-arginine (150 mg via femoral artery) in a 50 mg bolus before RC administration and the remaining dose continuously for a period of one hour. The administration of L-arginine to RCHC rats resulted in significantly higher CIn (0.86 +/- 0.1; P < 0.001) when compared to the untreated rats (RCHC). D-arginine did not show a significant difference in CIn (0.49 +/- 0.08). There was a considerable difference between D-arginine RCHC and L-arginine RCHC (P < 0.05). The RBF fall was prevented by L-arginine in RCHC (8.4 +/- 0.23 vs. 4.3 +/- 0.3; P < 0.001), but it was not prevented by D-arginine (5.1 +/- 0.57; P < 0.001). Our data suggest that hypercholesterolemia aggravates nephrotoxicity, which is attenuated by L-arginine but not by D-arginine administration, suggesting that nitric oxide plays a significant role in this model of acute renal failure.

Nephrotoxicity is the major adverse effect of conventional amphotericin B (AMB/D), often limiting administration of full dosage. The new liposomal amphotericin B seems to be less toxic. The new liposomal amphotericin B seems to be less toxic. In this study, it is proposed that solubilizing the standard AMB/D preparation with 10% lipid emulsion will attenuate nephrotoxicity. Rats were injected with either AMB/D (Fungizone), AMB, AMB/D plus lipid emulsion (AMB/D/LE), or sodium deoxycholate (D). Renal function studies were performed on day 5. To assess a direct tubular toxic effect, isolated rat proximal tubule suspensions and inner medullary collecting duct cells in culture were exposed to AMB/D, AMB, AMB/D/LE, liposomal amphotericin B, and D for 60 min in normoxia. Lactate dehydrogenase (LDH) release was assessed as an index of cell injury. Creatinine clearance (ml/min per 100 g) averaged 0.79 +/- 0.04 in control rats, 0.29 +/- 0.09 in AMB rats (P < 0.001 versus control), 0.38 +/- 0.04 in AMB/D rats, 0.46 +/- 0.05 in D rats, and 0.78 +/- 0.03 in AMB/LE rats. Renal blood flow (ml/min per 100 g) was 3.45 +/- 0.31 in control, 1.29 +/- 0.28 in AMB, 1.42 +/- 0.23 in AMB/D, 3.03 +/- 0.39 in D, and 2.71 +/- 0.21 in AMB/D/LE rats. The fractional excretion of potassium (%) was 27.3 +/- 1.18 in control rats, 61.6 +/- 7.00 in AMB/D rats, 58.4 +/- 15.32 in AMB rats, and 37.9 +/- 2.06 in AMB/D/LE rats. LDH release (%) in proximal tubules incubated with AMB/D and D was 43.6 +/- 3.39 and 58.6 +/- 4.20, respectively. Addition of lipid emulsion decreased LDH release: 21.6 +/- 1.22 for AMB/D/LE and 26.4 +/- 3.03 for deoxycholate plus lipid emulsion. AMB did not demonstrate any toxic effect in proximal tubule suspensions. D was not toxic to inner medullary collecting duct cells at 0.16 mg/ml, whereas D at a higher dose and AMB induced a significant LDH release. Addition of lipid emulsion did not affect the antifungal activity as assessed by the Etest method. In conclusion, an alternative way of administering standard AMB with reduced nephrotoxicity is proposed.

The renal effects of acyclovir (100 mg/kg body weight i.p. for 7 days) were studied in rats. All animals became polyuric and presented an increase in blood urea nitrogen and fractional excretion of sodium and potassium. During hypotonic saline infusion, the acyclovir-treated rats showed higher distal fractional delivery compared to normal rats (27.8 +/- 4.7 vs. 11.3 +/- 0.9%, p less than 0.01) and a lower ratio of free-water clearance to distal sodium delivery (33.5 +/- 7.8 vs. 57.2 +/- 3.9%, p less than 0.02). Following hypertonic saline infusion, the ratio of osmolar to inulin clearance was higher in acyclovir rats (47.8 +/- 7.4%) than in normal rats (27.0 +/- 4.8%), whereas the ratio of free-water reabsorption to osmolar clearance was lower in the acyclovir rats (13.6 +/- 4.6 vs. 38.2 +/- 3.2%, p less than 0.01). These findings suggest an effect of acyclovir on the proximal tubule, thick ascending limb and/or inner medullary collecting duct (IMCD). In vitro measurements of 3H2O permeability of perfused IMCD of normal rats showed that vasopressin (50 microU/ml) added to the bath increased the diffusional water permeability (43.4 +/- 4.8 vs. 105.6 +/- 9.1 x 10(-5) cm/s), while in acyclovir rats, the control value (58.8 +/- 9.1 x 10(-5) cm/s) did not increase significantly in the presence of vasopressin (71.3 +/- 13.6 x 10(-5) cm/s). These results suggest that high doses of acyclovir produce azotemia and an abnormal function of the proximal tubule and thick ascending limb associated with resistance to vasopressin of the IMCD.

The effects of chronic dietary protein restriction on ischemic renal failure were evaluated in rats subjected to 90 min of bilateral renal clamping. The rats were kept on either 20% casein (regular) diet or casein-free (protein-free) diet 10 days before and 21 days after renal injury. Rats on regular protein diet showed higher levels of BUN and serum creatinine and had a lower inulin clearance (microliter/min/100 g BW) than animals on protein-free diet (289 +/- 34 vs 582 +/- 103, p less than 0.05) 2 days after ischemia. However, the inulin clearance measured 21 days following ischemia was significantly higher in rats on regular diet (1468 +/- 181) than those maintained on protein-free diet after ischemia (560 +/- 167). When unilateral 90 min ischemia was performed in rats on regular diet, the postischemic kidneys showed an incomplete recovery of the inulin clearance (226 +/- 35) compared to the contralateral kidney (900 +/- 116), 21 days after ischemia; whereas in rats on a protein-free diet the inulin clearance averaged 106 +/- 17 in the postischemic kidney and 345 +/- 41 in the right kidney. When left renal ischemia and contralateral nephrectomy were performed, the inulin clearance was 1149 +/- 74 in rats on regular diet and 534 +/- 60 in rats on protein-free diet, 21 days following renal insult. These results suggest that protein restriction can play a protective role against renal ischemia in an initial phase, but it limits the late recovery from ischemia. The presence of a normal contralateral kidney inhibits the functional recovery of the postischemic kidney and a contralateral nephrectomy produces a compensatory functional hypertrophy of the postischemic kidney, even in rats on a protein-free diet.