Engineered CRISPR-Cas12a for higher-order combinatorial chromatin perturbations.

Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting one to three genomic sites per cell. We engineer an Acidaminococcus Cas12a (AsCas12a) variant, multiplexed transcriptional interference AsCas12a (multiAsCas12a), that incorporates R1226A, a mutation that stabilizes the ribonucleoprotein-DNA complex via DNA nicking. The multiAsCas12a-KRAB fusion improves CRISPRi activity over DNase-dead AsCas12a-KRAB fusions, often rescuing the activities of lentivirally delivered CRISPR RNAs (crRNA) that are inactive when used with the latter. multiAsCas12a-KRAB supports CRISPRi using 6-plex crRNA arrays in high-throughput pooled screens. Using multiAsCas12a-KRAB, we discover enhancer elements and dissect the combinatorial function of cis-regulatory elements in human cells. These results instantiate a group testing framework for efficiently surveying numerous combinations of chromatin perturbations for biological discovery and engineering.

Higher-order combinatorial chromatin perturbations by engineered CRISPR-Cas12a for functional genomics.

Multiplexed genetic perturbations are critical for testing functional interactions among coding or non-coding genetic elements. Compared to double-stranded DNA cutting, repressive chromatin formation using CRISPR interference (CRISPRi) avoids genotoxicity and is more effective for perturbing non-coding regulatory elements in pooled assays. However, current CRISPRi pooled screening approaches are limited to targeting 1-3 genomic sites per cell. To develop a tool for higher-order ( > 3) combinatorial targeting of genomic sites with CRISPRi in functional genomics screens, we engineered an Acidaminococcus Cas12a variant -- referred to as mul tiplexed transcriptional interference AsCas12a (multiAsCas12a). multiAsCas12a incorporates a key mutation, R1226A, motivated by the hypothesis of nicking-induced stabilization of the ribonucleoprotein:DNA complex for improving CRISPRi activity. multiAsCas12a significantly outperforms prior state-of-the-art Cas12a variants in combinatorial CRISPRi targeting using high-order multiplexed arrays of lentivirally transduced CRISPR RNAs (crRNA), including in high-throughput pooled screens using 6-plex crRNA array libraries. Using multiAsCas12a CRISPRi, we discover new enhancer elements and dissect the combinatorial function of cis-regulatory elements. These results instantiate a group testing framework for efficiently surveying potentially numerous combinations of chromatin perturbations for biological discovery and engineering.

Evaluation of bone gain in horizontal ridge augmentation using titanium mesh in combination with different flap advancement techniques: a randomized clinical trial.

The aim of this study was to investigate and compare the clinical and radiographic bone gain in guided bone regeneration with titanium mesh, for four different advancement techniques: periosteal releasing incision (PRI), double flap incision (DFI), modified periosteal releasing incision (MPRI), and coronally advanced lingual flap (CALF). Forty patients with a partially edentulous mandible were allocated randomly to four study groups (PRI, DFI, MPRI, CALF; 10 patients in each). Clinical bone gain (primary outcome) and radiographic bone gain were evaluated. In addition, correlations between study variables (clinical and radiographic bone gain, flap advancement, mesh exposure area and percentage exposure, pain, and swelling) were explored. CALF exhibited the highest mean clinical bone gain (4.12 ± 1.37 mm) and PRI the lowest (2.60 ± 1.36 mm); the mean clinical bone gain differed significantly among the groups (P < 0.001). The highest mean radiographic bone gain was seen in the CALF group (3.54 ± 1.65 mm) and the lowest in the PRI group (2.06 ± 1.11 mm); the mean radiographic bone gain also differed significantly among the groups (P < 0.001). The correlation analysis revealed positive correlations between flap advancement and radiographic bone gain (P = 0.003) and between swelling and pain (P = 0.007). An inverse correlation was found between flap advancement and swelling (P = 0.049), mesh exposure area and clinical bone gain (P = 0.022), and mesh exposure percentage and clinical bone gain (P = 0.017). In summary, the highest clinical and radiographic bone gain was observed for CALF, while the lowest was observed for PRI.

Lateral ventricular liponeurocytoma: Review of literature and case illustration.

BACKGROUND: Liponeurocytoma is an uncommon tumor of the central nervous system. It is very rare for this tumor to originate within the lateral ventricle. In the context of the rarity of this tumor entity, this review article aims to summarize the clinical, radiological, and pathological features of lateral ventricular liponeurocytoma to facilitate its diagnosis and management. METHODS: Here, we conduct a systematic literature review using the Pubmed, Scopus, and Cochrane Library database for all cases of lateral ventricular liponeurocytoma. A case illustration complements this review. RESULTS: The described cases from 1997 onward include 14 cases that have been published in full papers in the English literature. Six additional cases are reported in short English abstracts in full non-English papers, and one case was described in a central neurocytoma report. There is a definite male predominance of 70% (14 male) and a mean age of 37 years (range 24-62). Heterogenous enhancement and signals in magnetic resonant images (MRI) are the radiological characteristics. In all reported cases, the presence of lipocytes and fat vacuoles is considered the paramount histopathological feature. Total surgical resection was achieved in 80% (12 out of 15) of the cases. Only two cases (including ours) received radiation therapy. Recurrence was seen in two patients during follow-up that was treated by radiation therapy in one and surgery in the other. The proliferation index is mostly below 5% in all cases, with the Ki-67 range between<1% to 10%. CONCLUSIONS: Lateral ventricular liponeurocytoma has been treated effectively by surgical resection in a limited number of cases. The decision for radiation therapy is based on a high proliferation index and tumor recurrence.

Dietary patterns and semen quality: a systematic review and meta-analysis of observational studies.

A number of studies have examined the association between dietary patterns and semen quality, but the findings have been inconclusive. Herein, we conducted a systematic review and meta-analysis of observational studies to assess the association between dietary patterns and semen quality. PubMed, Cochrane library, Science direct, Scopus, Google Scholar, and ISI web of science databases were searched up to August 2016 for observational studies assessing the association between common dietary patterns and sperm quality markers. Data were pooled by the generic inverse variance method with random effects and expressed as mean differences with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochrane Q-statistic) and quantified (I2 -statistic). The Newcastle-Ottawa Scale assessed study quality. Six eligible studies, involving 8207 participants, were included in our systematic review and meta-analysis. The pooled mean difference of sperm concentration for the healthy dietary pattern versus unhealthy dietary pattern intake was mean difference: 0.66; 95% CI, 0.305-1.016; p < 0.001. In comparison with those who had the highest adherence to healthy dietary pattern, individuals in the lowest adherence had significantly lower level of sperm concentration. However, no significant association was seen between eating patterns and other semen quality. Healthy dietary pattern seems to be associated with elevated sperm concentration level. Further longitudinal studies are needed to clarify this relationship.

The effects of KinesioTape on the treatment of lateral epicondylitis.

STUDY DESIGN: Randomized clinical trial. INTRODUCTION: KinesioTape (KT) is a noninvasive method to treat pain and muscular dysfunction. PURPOSE: To investigate the effect of KT with and without tension on pain intensity, pain pressure threshold, grip strength and disability in individuals with lateral epicondylitis, and myofacial trigger points in forearm muscles. METHODS: Thirty women with lateral epicondylitis and myofacial trigger point in forearm muscles were randomly assigned to KT with tension and placebo (KT without tension). The treatment was provided 3 times in one week, and outcome measures were assess pre-post treatment. RESULTS: The mean score of visual analogue scale (VAS) during activity decreased significantly from 6.4 and 6 pretest to 2.53 and 4.66 posttest, respectively, for the KT with and without tension groups. The mean score of Disabilities of the Arm, Shoulder and Hand decreased significantly from 16.82 and 22.79 pretest to 8.65 and 8.29 posttest, respectively, for the KT with and without tension groups. A paired t-test revealed a significant reduction in VAS during activity and Disabilities of the Arm, Shoulder and Hand before and after treatment in both groups (P < .05). Pain pressure threshold, grip strength, and VAS using an algometer revealed no significant differences. The study showed no significant difference in variables immediately after intervention. DISCUSSION: Improvements in functional disability were superior when KT was used with tension, than obtained with a placebo-no tension application. CONCLUSION: The application of KT produces an improvement in pain intensity and upper extremity disability in subjects with LE and MTP in forearm muscles, and KT with tension was more effective than placebo group. LEVEL OF EVIDENCE: NA. TRIAL REGISTRATION NUMBER: 100-216.

Ultrasound imaging transducer motion during standing postural tasks with and without using transducer fixator.

BACKGROUND: Changes in the orientation of ultrasound (US) transducer relative to the body surface during dynamic standing tests can affect US measurements. OBJECTIVE: The purpose of the study was to evaluate ultrasound imaging transducer motion while measuring the lateral abdominal muscle thickness during standing tasks with and without using transducer fixator (TF). DESIGN: Cross-sectional experimental study. METHODS: A digital optical motion analysis system was used to assess the motions of US transducer during double-leg stance in different levels of platform stability of Biodex Balance System (BBS) (static, levels 6 and 3) with and without using TF in 45 healthy individuals. In addition, lateral abdominal muscle thickness was evaluated by US imaging. RESULTS: The results indicated that the amount of angular and linear transducer motions during static and dynamic standing tasks significantly decreased by the use of TF as compared to the conditions without TF (P < 0.001, effect size> 0.84). CONCLUSION: TF can significantly control US transducer motions within acceptable threshold limits during standing postural task. This may improve the clinical application of US imaging.

In Silico and In Vitro Evaluation of Cytotoxic Activities of Farnesiferol C and Microlobin on MCF-7, HeLa and KYSE Cell Lines.

Background: Cancer is one of the leading causes of death worldwide. Despite certain advances in cancer therapy, still there is considerable demand for developing efficient therapeutic agents. Nowadays, there is a rising interest in the use of natural-based anti-cancer drugs. In this study, the cytotoxicity of farnesiferol C and microlobin isolated from Ferula szowitsiana was investigated against MCF-7, HeLa and KYSE cancer cell lines. In addition, the mechanism of binding of these compounds to apoptotic proteins (Bax, Bak and Bcl-2) was analyzed by an in silico method. Materials and methods: We used MTT assay in order to assess the cytotoxicity of compounds against cancer cell lines. For in silico study, the AutoDock 4 was adopted. Results and discussion: According to the in vitro findings, in general, farnesiferol C showed significant cytotoxicity at higher concentrations (>50 µM) following 48 and 72 h incubation with the selected cancer cells; however, microlobin exhibited almost no activity at concentrations up to 100 µM. The in silico results revealed that both compounds could bind to Bax more efficiently rather than to Bcl-2 or Bak proteins. Conclusion: The results obtained by our preliminary in vitro and in silico studies suggest that these compounds might induce apoptosis through Bax activation; however further studies, either in vitro or in vivo are needed to clarify these activities.

Usefulness of Ki-67, Mitoses, and Tumor Size for Predicting Metastasis in Carcinoid Tumors of the Lung: A Study of 48 Cases at a Tertiary Care Centre in Canada.

Background. Evaluation of Ki-67 index in lung carcinoid tumors (LCTs) has been of interest in order to identify high risk subsets. Our objectives are (1) to evaluate the usefulness of Ki-67 index, mitoses, and tumor size in predicting metastasis and (2) to compare the Manual Conventional Method (MCM) and the Computer Assisted Image Analysis Method (CIAM) for Ki-67 calculation. Methods. We studied 48 patients with LCTs from two academic centres in Canada. For Ki-67 calculation, digital images of 5000 cells were counted using an image processing software and 2000 cells by MCM. Mitoses/10 HPF was counted. Results. We had 37 typical carcinoids (TCs) and 11 atypical carcinoids (ACs). 7/48 patients developed metastasis. There was a positive relationship between metastasis and carcinoid type (P = 0.039) and metastasis and mitoses (≥2) (P = 0.017). Although not statistically significant, the mean Ki-67 index for ACs was higher than for TCs (0.95% versus 0.72%, CIAM, P = 0.299). Similarly, although not statistically significant, the mean Ki-67 index for metastatic group (MG) was higher than for nonmetastatic group (NMG) (1.01% versus 0.71% by CIAM, P = 0.281). However when Ki-67 index data was categorized at various levels, there is suggestion of a useful cutoff (≥0.50%) to predict metastasis (P = 0.106, CIAM). A significantly higher proportion of patients with mitosis ≥2 and Ki-67 index ≥0.50% had metastasis (P = 0.033) compared to other patients. Similarly patients with tumor size ≥3 cm and Ki-67 ≥0.50% had a greater percentage of metastases than others (P = 0.039). Although there was a strong correlation between two (MCM versus CIAM) counting methods (r = 0.929, P = 0.001), overall the calculated Ki-67 index was slightly higher by MCM (range 0 to 6.4, mean 1.5) compared to CIAM (range 0 to 2.9, mean 0.75). Conclusion. This study confirms that mitoses ≥2 is a powerful predictor of metastasis in LCTs. Although this is a small sample size, there is suggestion that analysis of Ki-67 index along with mitoses and tumor size may be a useful adjunct for predicting metastasis in LCTs.

Relationship between ultrasonography and electromyography measurement of abdominal muscles when activated with and without pelvis floor muscles contraction.

AIM: The importance of the abdominal musculature in spine stability, has promoted the development of a variety of studies. Ultrasound imaging (UI) is a valuable tool which, when applied appropriately, has the potential to provide significant insight into abdominal muscle contraction. Limited studies have been taken place regarding the relationship between ultrasound measures of muscle thickening and electromyography (EMG) measures of activation. Inconsistent results, however, have been reported. Based on previous studies association between abdominal muscle activation and thickening may be affected by contraction level. The aims of this study were to measure the relationship between abdominal muscle thickness and abdominal muscles amplitude in different levels of abdominal muscles contraction. METHODS: The research was carried on with a convenience sampling at the Physical Therapy Department of University of Social Welfare and Rehabilitation Sciences. Thirty healthy participants volunteered for this study. Muscle thickness right transversus abdominis (TrA) and obliqus internus (OI) muscles in abdominal hallowing maneuvers with and without pelvic floor muscle (PFM) contraction has been measured. Additionally, surface EMG of the right TrA/IO muscles was recorded. A hardware electrical part that acts as trigger system was used to record the activities of abdominal muscles in UI and EMG synchronously. Thickness change, normalized thickness and maximum amplitude abdominal muscles were used for statistical analysis. RESULTS: Correlations between the thickness change and amplitude measures were -0.03 -- 0.38 for TrA/IO. The Correlations between the normalized thickness and amplitude measures were -0.04--0.26 for TrA/IO. CONCLUSION: There is not clear relationship between increases in abdominal muscle activation and corresponding measures of thickening during abdominal muscle contraction. Changes in thickness of deep abdominal muscle cannot be used to indicate changes in the electrical activity in this muscle.

Methyl jasmonate increases the tropane alkaloid scopolamine and reduces natural herbivory in Brugmansia suaveolens: is scopolamine responsible for plant resistance?

The tropane alkaloid (TA) scopolamine is suggested to protect Brugmansia suaveolens (Solanaceae) against herbivorous insects. To test this prediction in a natural environment, scopolamine was induced by methyl jasmonate (MJ) in potted plants which were left 10 days in the field. MJ-treated plants increased their scopolamine concentration in leaves and herbivory decreased. These findings suggest a cause-effect relationship. However, experiments in laboratory showed that scopolamine affect differently the performance of the specialist larvae of the ithomiine butterfly Placidina euryanassa (C. Felder & R. Felder) and the generalist fall armyworm Spodoptera frugiperda (J. E. Smith): the specialist that sequester this TA from B. suaveolens leaves was not negatively affected, but the generalist was. Therefore, scopolamine probably acts only against insects that are not adapted to TAs. Other compounds that are MJ elicited may also play a role in plant resistance against herbivory by generalist and specialist insects, and deserve future investigations.

A diet rich in leafy vegetable fiber improves cholesterol metabolism in high-cholesterol fed rats.

In the present study, the hypocholesterolemic effect of leaf vegetable (Jew's mallow) was studied in high-cholesterol fed rats. The animals were fed diets supplemented with cholesterol (0.25%) for 4 weeks. Leaf vegetable diet produced an important hypocholesterolemic action: it led to a significant lowering (p<0.05) of cholesterol in the plasma and liver, as well as of the atherogenic index and a significant increase (p<0.05) in cecal short chain fatty acids, with respect to the control group. Concurrently, total fecal neutral sterols in the excretion increased (p<0.05) and apparent absorption of dietary cholesterol was significantly depressed (-58%). The consumption of leaf vegetable (Jew's mallow) with a hypercholesterolemic diet improved the lipidemic profile and increased excretion of the total cholesterol end-products.

Effect of sowing depth on performance of Quercus castaneifolia seedling at different levels of canopy cover.

Due to failure of oak (Quercus castaneifolia C.A. Meyer) natural regeneration, investigation on the best acorn sowing depth of this species under different levels of canopy cover is an important consideration in the Caspian forests, north of Iran. For this purpose, a study site with north-facing slope, clay-loam soil and 260-280 m a.s.l. was chosen in a mixed oak forest. The experiment was conducted as a Complete Randomized Split Plot Design (CRSPD) and the measurements made in one growing season in nine fenced circular 1000 m2 plots with three canopy densities (25, 50 and 75%) at three soil depths (5, 10 and 15 cm). The results revealed that under all canopy densities the maximum seedling emergence occurred at 5 cm depth. The highest emergence rate was appeared in June and the lowest in October. Neither canopy density nor sowing depth did prominently reduce seedling establishment, but a high quotient of mortality likely could be attributed to rodent populations, particularly Hystrix indica. Under all canopies, ground line diameter decreased with increasing sowing depth, the biggest being at 5 cm depth. Neither canopy density nor sowing depth influenced the seedling height. It can be concluded that the best performance of Q. castaneifolia seedling occurs at 5 cm sowing depth and 25% canopy cover.

Degradation of organochlorine pesticides by meat starter in liquid media and fermented sausage.

The effect of meat starter on the degradation of DDT and lindane was investigated. The insignificant role of Lactobacillus plantarum in degrading p,p'-DDT and lindane presented in tryptone soya broth (TSB) and mineral salt medium (MSM) with or without 120 ppm nitrite was observed.The degradation of DDT and lindane by Micrococcus varians in TSB and MSM with or without nitrite were studied. The results indicated that DDT or lindane were degraded during the incubation period. The reduction in DDT at the end of the incubation period (15 days) was about 24.1 and 32.5% in TSB and MSM without nitrite, respectively. Corresponding values in the same media with nitrite were 37.5 and 46.4%. Regarding the reduction in lindane, it was recorded as 27.9 and 40.0% in TSB and MSM without nitrite, respectively and 38.4 and 48.4% in the same media with nitrite. The results indicated that culture media M. varians metabolized DDT mainly to DDD and lindane mainly to 2,4-, 2,5-, 2,6- and 3,4-dichlorophenol; 2,3,4- and 2,3,5-trichlorophenol; hexachlorobenzene; and pentachlorophenol. The effect of pesticides on the growth rate of meat starter was also investigated. The addition of DDT or lindane resulted in a slight decrease in counts of the strains during the initial incubation in TSB or MSM. Then the microorganisms recovered and began to grow logarithmically, but not as well as in a normal situation. The effect of fermentation stage by meat starter on DDT and lindane in fermented sausage was recorded. The results indicated that during the 72 h of fermentation, the reduction was 10 and 18% of DDT and lindane, respectively. These results confirmed that the fermentation process in meat products reduced pesticide residues and these reductions were due to the activity of meat starter.

Failure of a novel balloon-expandable gamma-emitting ((103)Pd) stent to prevent edge effects.

BACKGROUND: Balloon-expandable beta-particle-emitting ((32)P) stents inhibit within-stent neointimal hyperplasia but induce lumen narrowing beyond the stent margins, ie, the so-called "edge effects." METHODS AND RESULTS: We prospectively investigated the performance of novel stents impregnated with the gamma-emitting isotope (103)Pd, designed to reduce edge effects, in 24 rabbits. The stents had a length of 18 mm and were mounted on 20-mm-long delivery balloons for deployment. Angiograms were obtained immediately and 1 month after direct implantation of control and 1-, 2-, and 4-mCi (103)Pd stents into the iliac arteries without predilatation or postdilatation. Late lumen loss was measured with quantitative angiography. Neointimal hyperplasia and vascular remodeling were evaluated by histomorphometry. Late lumen loss was inhibited within (103)Pd stents (control 0.18 mm, 1 mCi 0.08 mm, 2 mCi 0.05 mm, and 4 mCi -0.03 mm, P<0.05 all activities versus control). Conversely, late lumen loss occurred at the edges of (103)Pd stents, correlating with areas of high balloon/artery ratios and vessel overstretch injury. Edge effects were primarily due to neointimal hyperplasia but were also caused by negative vessel remodeling at high stent activities. CONCLUSIONS: Edge effects after implantation of radioisotope stents can occur independently of the isotope chosen for stent impregnation.

Overestimation of stent delivery balloon diameters by manufacturers' compliance tables: a quantitative coronary analysis of Duet and NIR stent implantation.

Although manufacturers' compliance tables of stent delivery balloons indicate the diameter of the balloon at a given inflation pressure, it is unclear whether these data correlate with in vivo true intracoronary balloon diameters (TBDs). The TBDs of two new-generation balloon-expandable stent delivery systems (Duet and NIR) were measured by quantitative coronary analysis (QCA) in 100 consecutive patients. The manufacturers' stated balloon diameter (BD) of the stent delivery systems overestimated the TBD in 94% +/- 4% of patients receiving both Duet or NIR stent implantations. In only 6% of the patients, the TBD matched the manufacturers' stated balloon diameter. There was no underestimation of TBDs by both manufacturers' compliance tables. The Duet tables overestimated TBDs by 14% +/- 8% (range, 1%-36%), the NIR tables by 18% +/- 8% (range, 1%-41%), P < 0.05, Duet vs. NIR, respectively. When the manufacturers' data were corrected for the differences in reporting data from in vitro tests, i.e., balloon compliance data with or without the stent, the degree of overestimation of diameters was similar for Duet and NIR stent delivery balloons (14% +/- 8% vs. 13% +/- 7%, Duet vs. NIR; P = NS). Manufacturers' compliance tables of both the Duet and NIR stent delivery balloon systems significantly overestimate the true intracoronary balloon diameter. The manufacturers' of stent delivery balloons should clearly state on the box, if balloon compliance data were derived from in vitro bench testing, which phantoms were used for compliance analysis, and that the tables may overestimate the true intracoronary balloon diameter. The findings of the present study have important clinical implications with respect to performing coronary stent implantation with precision.

Heavy metal contents in Egyptian meat and the role of detergent washing on their levels.

Pollution of the environment with heavy metals is a serious problem, which is recognized in most countries of the world. Metals accumulate in the liver, and particularly in the kidneys. The present study provides information about the concentrations of metals in animal organs from both rural and industrial areas. It was surprising that the Pb, Cd, Zn, Cu, Mn and Fe contents in muscle, liver, kidney, heart and spleen in industrial areas were higher than in the same organs of rural areas. Lead concentrations in bovine liver and kidney, in buffalo, elk, sheep and goat kidneys as well as Cd in elk liver and kidneys were higher in the present study than the recommended values. The effect of washing for bovine muscle, liver and kidney using tap water and other detergent solutions on the metals was studied. Washing by only tap water was less effective than the other detergent. The results indicate the efficient role of washing by acidic detergent in the reduction of Pb, Cd and Zn from naturally contaminated meat compared with neutral and alkaline detergent.

Functional ultrastructure of the midgut of the fire ant Solenopsis saevissima Forel 1904 (Formicidae: Myrmicinae).

Solenopsis saevissima has a midgut composed of columnar, regenerative, and goblet cells. The midgut epithelium was covered by a basal lamina. Outside the basal lamina, layers of inner oblique, circular, and outer longitudinal muscles were present. Columnar cells showed a basal plasma membrane containing numerous folds, mitochondria, and the nucleus. Rough endoplasmic reticulum, Golgi bodies, membrane bounded vacuoles, and spherocrystals were found in this region. The apical plasma membrane was constituted by microvilli, which were above a region rich in mitochondria. Regenerative cells were found in groups lying by the basal lamina. Goblet cells were associated with an ion-transporting mechanism between the haemolymph and the midgut epithelium. These cells were lying by the midgut lumen and large microvilli were evident, but the cytoplasmic features were similar to the columnar cells.

Nitric oxide diminishes apoptosis and p53 gene expression after renal ischemia and reperfusion injury.

BACKGROUND: The role of nitric oxide in the ischemic injury of the kidney is still controversial. The aim of this study was to reevaluate the beneficial effect of exogenous nitric oxide and define its effects as regulator of gene p53 expression and apoptosis in the ischemic renal injury. METHODS: Sprague-Dawley rats were subjected to 75 min of renal warm ischemia and contralateral nephrectomy. The animals were divided into six groups (n=6 per group): Two sham groups at 4 and 24 hr, two ischemic control (IC) at same times and two treated groups (Na-NP), studied at same intervals, where sodium nitroprusside (5 mg/kg) was given 15 min before reperfusion. The parameters evaluated included: serum creatinine, blood urea nitrogen, neutrophil infiltration determined by myeloperoxidase, gene p53 expression determined by reverse transcriptase polymerase chain reaction, apoptosis determined by peroxidase in situ technique and light histology. RESULTS: There were significant improvements in serum creatinine and blood urea nitrogen at 24 hr in the NA-NP group when compared with the IC group (P<0.05). Myeloperoxidase levels were higher in the IC when evaluated against the Na-NP groups. Na-NP exhibited a downregulating effect in the expression of gene p53 when compared to the IC group. Apoptosis was more evident in the IC group and had moderately increased histological damage when compared to the Na-NP group. CONCLUSIONS: Nitric oxide demonstrated a protective effect in the ischemic injury of the kidney and exerted an antiapoptotic action dowregulating the expression of gene p53.