Cardiac transcriptomic changes induced by early CKD in mice reveal novel pathways involved in the pathogenesis of Cardiorenal syndrome type 4.

Background: Cardiorenal syndrome (CRS) type 4 is prevalent among the chronic kidney disease (CKD) population, with many patients dying from cardiovascular complications. However, limited data regarding cardiac transcriptional changes induced early by CKD is available. Methods: We used a murine unilateral ureteral obstruction (UUO) model to evaluate renal damage, cardiac remodeling, and transcriptional regulation at 21 days post-surgery through histological analysis, RT-qPCR, RNA-seq, and bioinformatics. Results: UUO leads to significant kidney injury, low uremia, and pathological cardiac remodeling, evidenced by increased collagen deposition and smooth muscle alpha-actin 2 expression. RNA-seq analysis identified 76 differentially expressed genes (DEGs) in UUO hearts. Upregulated DEGs were significantly enriched in cell cycle and cell division pathways, immune responses, cardiac repair, inflammation, proliferation, oxidative stress, and apoptosis. Gene Set Enrichment Analysis further revealed mitochondrial oxidative bioenergetic pathways, autophagy, and peroxisomal pathways are downregulated in UUO hearts. Vimentin was also identified as an UUO-upregulated transcript. Conclusions: Our results emphasize the relevance of extensive transcriptional changes, mitochondrial dysfunction, homeostasis deregulation, fatty-acid metabolism alterations, and vimentin upregulation in CRS type 4 development.

Role of Incretins in Muscle Functionality, Metabolism, and Body Composition in Breast Cancer: A Metabolic Approach to Understanding This Pathology.

A poorly studied issue in women with breast cancer is the role of incretins (GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1)) in the quantity and quality of muscle mass in lean and obese individuals. The current report aims to analyze the patterns of association and the role of incretin in muscle functionality and body composition in women with cancer compared with healthy women (mammography BI-RADS I or II) to elucidate whether GIP and GLP-1 can be used to estimate the risk, in conjunction with overweight or obesity, for breast cancer. We designed a case-control study in women with a breast cancer diagnosis confirmed by biopsy in different clinical stages (CS; n = 87) and healthy women with a mastography BI-RADS I or II within the last year (n = 69). The women were grouped according to body mass index (BMI): lean (<25 kg/m2BS), overweight (≥25-<30 kg/m2BS), and obese (≥30 kg/m2BS). We found that GLP-1 and GIP levels over 18 pg/mL were associated with a risk of breast cancer (GIP OR = 36.5 and GLP-1 OR = 4.16, for the entire sample), particularly in obese women (GIP OR = 8.8 and GLP-1 OR = 6.5), and coincidentally with low muscle quality indexes, showed an association between obesity, cancer, incretin defects, and loss of muscle functionality.

Adipocytokines and Insulin Resistance: Their Role as Benign Breast Disease and Breast Cancer Risk Factors in a High-Prevalence Overweight-Obesity Group of Women over 40 Years Old.

Insulin levels, adipocytokines, and inflammatory mediators trigger benign breast disease (BBD) and breast cancer (BC). The relationship between serum adipocytokines levels, overweight-obesity, metabolic disturbs, and BC is unclear. Methods: To analyze the serum levels of the adipocytokines, insulin, and the HOMA IR in women without breast disease, with BBD or BC, and the role of these as risk factors for benign breast disease or breast cancer. Results: Adipsin values > 0.91 and visfatin levels > 1.18 ng/mL represent a risk factor to develop BBD in NBD lean women (OR = 18; and OR = 12). Data in overweight-obese women groups confirm the observation due to insulin levels > 2.6 mU/mL and HOMA IR > 0.78, with OR = 60.2 and 18, respectively; adipsin OR = 26.4, visfatin OR = 12. Breast cancer risk showed a similar behavior: Adipsin risk, adjusted by insulin and visfatin OR = 56 or HOMA IR and visfatin OR = 22.7. Conclusion: Adipose tissue is crucial for premalignant and malignant tissue transformation in women with overweight-obesity. The adipocyte−breast epithelium interaction could trigger a malignant transformation in a continuum, starting with BBD as premalignant disease, especially in overweight-obese women.

Impact of transplantation on neutrophil extracellular trap formation in patients with end-stage renal disease: A single-center, prospective cohort study.

ABSTRACT: Increased neutrophil extracellular trap (NET) formation associates with high cardiovascular risk and mortality in patients with end-stage renal disease (ESRD). However, the effect of transplantation on NETs and its associated markers remains unclear. This study aimed to characterize circulating citrullinated Histone H3 (H3cit) and Peptidyl Arginase Deiminase 4 (PAD4) in ESRD patients undergoing transplantation and evaluate the ability of their neutrophils to release NETs.This prospective cohort study included 80 healthy donors and 105 ESRD patients, out of which 95 received a transplant. H3cit and PAD4 circulating concentration was determined by enzyme-linked immunosorbent assay in healthy donors and ESRD patients at the time of enrollment. An additional measurement was carried out within the first 6 months after transplant surgery. In vitro NET formation assays were performed in neutrophils isolated from healthy donors, ESRD patients, and transplant recipients.H3cit and PAD4 levels were significantly higher in ESRD patients (H3cit, 14.38 ng/mL [5.78-27.13]; PAD4, 3.22 ng/mL [1.21-6.82]) than healthy donors (H3cit, 6.45 ng/mL [3.30-11.65], P < .0001; PAD4, 2.0 ng/mL [0.90-3.18], P = .0076). H3cit, but not PAD4, increased after transplantation, with 44.2% of post-transplant patients exhibiting high levels (≥ 27.1 ng/mL). In contrast, NET release triggered by phorbol 12-myristate 13-acetate was higher in neutrophils from ESRD patients (70.0% [52.7-94.6]) than healthy donors (32.2% [24.9-54.9], P < .001) and transplant recipients (19.5% [3.5-65.7], P < .05).The restoration of renal function due to transplantation could not reduce circulating levels of H3cit and PAD4 in ESRD patients. Furthermore, circulating H3cit levels were significantly increased after transplantation. Neutrophils from transplant recipients exhibit a reduced ability to form NETs.

Hyaluronic Acid Reduces Fibrosis in a Rabbit Model of Urethral Anastomosis.

INTRODUCTION: Urethral stricture caused by fibrosis is a common medical condition, but top-line therapy for this pathology has a high recurrence rate. This study aimed to determine the efficacy of hyaluronic acid (HA) treatment in preventing the development of fibrosis in a rabbit model of urethral anastomosis. MATERIALS AND METHODS: This experimental study involved 20 rabbits. HA (0.5 mL, 25 µg/mL) was applied in the experimental group (n = 10) during an experimental urethral anastomosis, and sterile saline (0.9%) solution was applied in the control group (n = 10). Animals underwent reoperation 12 weeks later for urethral resection. Fibrosis, inflammation, and urethral diameter were measured by two blinded pathologists at the site of the anastomosis. RESULTS: The amount of inflammatory infiltrate was similar in both groups. The thicknesses of the collagen fiber band were 275.9 ± 62.3 and 373.4 ± 44.3 µm in the study and control groups (p = 0.001), respectively, and the urethral lumen diameters at the anastomosis site at follow-up were 2575 ± 167 and 2382 ± 214 µm, respectively (p = 0.04). CONCLUSION: HA treatment reduced fibrosis at the anastomosis site during this experiment; we suggest further research to corroborate its efficacy in the treatment of urethral stricture.

Opioid Preconditioning Modulates Repair Responses to Prevent Renal Ischemia-Reperfusion Injury.

Progression to renal damage by ischemia-reperfusion injury (IRI) is the result of the dysregulation of various tissue damage repair mechanisms. Anesthetic preconditioning with opioids has been shown to be beneficial in myocardial IRI models. Our main objective was to analyze the influence of pharmacological preconditioning with opioids in renal function and expression of molecules involved in tissue repair and angiogenesis. Experimental protocol includes male rats with 45 min ischemia occluding the left renal hilum followed by 24 h of reperfusion with or without 60 min preconditioning with morphine/fentanyl. We analyzed serum creatinine and renal KIM-1 expression. We measured circulating and intrarenal VEGF. Immunohistochemistry for HIF-1 and Cathepsin D (CTD) and real-time PCR for angiogenic genes HIF-1α, VEGF, VEGF Receptor 2 (VEGF-R2), CTD, CD31 and IL-6 were performed. These molecules are considered important effectors of tissue repair responses mediated by the development of new blood vessels. We observed a decrease in acute renal injury mediated by pharmacological preconditioning with opioids. Renal function in opioid preconditioning groups was like in the sham control group. Both anesthetics modulated the expression of HIF-1, VEGF, VEGF-R2 and CD31. Preconditioning negatively regulated CTD. Opioid preconditioning decreased injury through modulation of angiogenic molecule expression. These are factors to consider when establishing strategies in pathophysiological and surgical processes.

Sex-dependent mechanisms involved in renal tolerance to ischemia-reperfusion: Role of inflammation and histone H3 citrullination.

Ischemia-reperfusion (I/R) injury, an inevitable result of kidney transplantation, triggers early inflammatory events that affect graft viability. Evidence from human transplantation and preclinical models of I/R suggests that a female hormonal environment positively influences the ability to recover from ischemic injury. However, the mechanisms behind these effects remain mostly unexplored. Here, we studied the influence of sex on pro-inflammatory mediators involved in the pathophysiology of acute I/R injury in male, female, and female ovariectomized (OVX) Wistar rats that underwent unilateral renal ischemia for 45 min, followed by 24 h of reperfusion. We found improved renal function, reduced cytokine expression, and decreased infiltration of myeloperoxidase-positive cells in females after I/R, when compared to their male and female OVX counterparts. Remarkably, citrullination of histone H3 was exacerbated in serum and renal tubules of females after I/R. In contrast, we observed lower levels of citrullinated histone H3 in male and female OVX rats in response to I/R, mostly in neutrophil extracellular traps. Our results demonstrate that female sex promotes renal I/R tolerance by attenuating pro-inflammatory mediators involved in I/R-induced damage.

Interleukin-1 Alpha Polymorphisms Are Associated With Body Mass Index in Male But Not in Female Adolescents.

BACKGROUND: The Interleukin (IL)-1 family of cytokines plays a key role in the inflammatory response. Genes coding for IL-1α, IL-1ß, and IL-1Ra are located together as a block gene known as the IL-1 cluster. This genomic region shows wide nucleotide variability, and some polymorphisms have been widely studied and associated with features related to the metabolic syndrome. METHODS: Eight polymorphisms within three genes of the IL-1 cluster, including IL1A (rs3783553, rs17561, and rs1800587), IL1B (rs1143634, rs1143627, and rs16944) and IL1RN (rs419598 and rs2234663) were genotyped in 460 Mexican adolescents. Genotype and haplotype frequencies are reported, as well as the linkage disequilibrium analysis. Genetic associations with some anthropometric and metabolic traits were evaluated. RESULTS: Allele frequencies were similar to those found in other populations, and genotype proportions were according to the Hardy-Weinberg equilibrium. Seven haplotypes were observed at frequencies ≥5%. Of the entire cluster, only the rs17561-rs1800587 and rs1143627-rs16944 pairs showed highest and significant linkage disequilibrium values. An haplotype of IL1A, rs17561T-rs1800587T, was significantly associated with increase in body mass index in males (p <0.008), whereas IL1B and IL1RN variants showed associations with insulin, and hs-CRP (p <0.05). CONCLUSIONS: Some MetS parameters seem to be influenced by variations in the IL-1 gene cluster in Mexican adolescents. These variations may confer risk for metabolic alterations from early ages, and and these risks may be different when variables such as sex are considered. Strategies leading to generate protective behaviors could be designed to take into account specific variations in the IL-1 gene cluster and biological conditions such as sex.

Ischemic Preconditioning Preserves Liver Energy Charge and Function on Hepatic Ischemia/Reperfusion Injury in Rats.

BACKGROUND: Cell energy during ischemia/reperfusion depends on mechanisms including adenosine diphosphate degradation, oxygen species and cytokine liberation, neutrophil infiltration, and endothelial dysfunction. Preconditioning-a brief ischemic episode that confers a state of protection against subsequent ischemia-reperfusion injury-involves NO and adenosine production, reduction in oxygen species liberation, and preservation of microcirculation. During hypoxia, constitutive NO production assures adequate oxygen delivery and reduced energy loss. The aim was to determine the role of ischemic preconditioning in the stimulation of constitutive endothelial nitric oxide (NO) production and its effect on energy charge, radical oxygen species generation, cytokine liberation, and neutrophil infiltration during reperfusion. MATERIALS AND METHODS: Rats were assigned to one of four groups depending on the preconditioning protocol: hepatic ischemia/reperfusion, or hepatic ischemia/reperfusion and ischemic preconditioning, for 5, 10, or 20 min. A portosystemic shunt was established between the portal and left jugular veins during ischemia. RESULTS: Preconditioning produced rises in plasma nitrites, but no rise in inducible nitric oxide synthase gene expression. A 5 or 10 min preconditioning period allowed for higher energy charge, bile production, and glutathione levels, with less lipoperoxide, alanine aminotransferase, tumor necrosis factor-α, and interleukin-1 production and neutrophil infiltration, compared with 20 min or control. Survival was 80% in the G10 group, 70 in G5, 10 in GC, and 0% in the G20 group. CONCLUSIONS: Ten-min liver preconditioning improves survival and prevents energy loss during hepatic ischemia/reperfusion by stimulating constitutive NO production, maintaining glutathione concentrations and reducing oxygen species and proinflammatory cytokine generation as well as neutrophil infiltration.

Metabolic and genetic markers' associations with elevated levels of alanine aminotransferase in adolescents.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in adolescents, is a feature of metabolic syndrome (MetS). Obesity and insulin resistance (IR) are risk factors for NAFLD, as well as inflammation-related genetic markers. The relationship between metabolic or inflammation-related genetic markers and alanine aminotransferase (ALT) is not fully understood. We examined the relationship of MetS, metabolic and inflammation-related genetic markers with elevated ALT in adolescents. METHODS: A total of 674 adolescents participated in a cross-sectional study in Guadalajara, Mexico. Elevated ALT (>40 IU/L), a surrogate marker of NAFLD, and MetS (International Diabetes Federation definition) were evaluated. Obesity, IR, lipids, C-reactive protein (CRP) and genetic markers (TNFA-308G>A, CRP+1444C>T, IL1RN and IL6-597/-572/-174 haplotype) were evaluated. Multivariate logistic regression was performed. RESULTS: Elevated ALT was observed in 3% and 14.1% (total and obese, respectively) of the adolescents. Obesity (odds ratio [OR], 5.86; 95% confidence interval [95% CI], 1.16-25.89), insulin (OR, 8.51; 95% CI, 2.61-27.71), IR (OR, 9.10; 95% CI, 2.82-29.38), total cholesterol (TC) (OR, 3.67; 95% CI, 1.25-10.72), low-density lipoprotein-cholesterol (LDL-C) (OR, 3.06; 95% CI, 1.06-8.33), non-high-density lipoprotein-cholesterol (HDL-C) (OR, 3.88; 95% CI, 1.27-11.90) and IL1RN (OR, 4.64; 95% CI, 1.10-19.53) were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT (OR, 4.22; 95% CI, 1.14-15.71). CONCLUSIONS: Obesity, insulin, IR, high TC, high LDL-C, high non-HDL-C and IL1RN polymorphism were associated with elevated ALT. Among males, ≥2 MetS criteria were associated with elevated ALT. There is an urgent need to reduce obesity and IR in adolescents to prevent NAFLD.

Analysis of cytokine gene polymorphisms in Mestizo and native populations from Mexico.

OBJECTIVES: To determine whether the well-known genetic structure of the Mexican population observed with other multiallelic markers can be detected by analyzing functional polymorphisms of cytokine and other inflammatory-response-related genes. METHODS: A total of 834 Mestizo individuals from five Mexican cities and 92 Lacandonians - an Amerindian group from southeastern Mexico - were genotyped for 14 polymorphisms in the CRP, IL10, IL6, TGFB1, TNFA, LTA, ICAM1 IFNG, and IL1RN genes. Allele and haplotype frequencies were used for genetic structure analysis using F-statistics pairwise distances and multidimensional scaling plot. Ancestry analysis was performed, as well. RESULTS: Significant interpopulational differences at the allele and haplotype frequency level were observed, mainly between Northern (Guadalajara, Monterrey, and Culiacan) and Southern (Tierra Blanca and Puebla) Mexican populations. Also, low but significant substructure was detected between some populations from these two broad regions. Interestingly, both Lacandonian populations were highly differentiated from each other and with respect to Mestizos. Consistent with previous data, Amerindian ancestry in the Southern Mexican groups was higher compared to Northern ones. CONCLUSIONS: The Mexican population exhibits regional differences in functional polymorphisms of inflammatory-response genes, as observed for other genetic markers. This information constitutes a reference for epidemiological studies that include these genetic markers to assess the susceptibility of the Mexican population to several immune-response-related diseases, such as diabetes, obesity, and renal disease, which have been shown to be common in the Mexican population but with prevalence differences within this country.

Fibrinogen and thrombin concentrations are critical for fibrin glue adherence in rat high-risk colon anastomoses.

OBJECTIVE: Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats. METHODS: Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g) treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal) or high-risk (ischemic) end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL) or low (40 mg/mL) concentrations and thrombin at high (1000 IU/mL) or low (500 IU/mL) concentrations. RESULTS: Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis. CONCLUSIONS: Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery.

Nitric oxide in the commissural nucleus tractus solitarii regulates carotid chemoreception hyperglycemic reflex and c-Fos expression.

Carotid body chemoreceptors function as glucose sensors and contribute to glucose homeostasis. The nucleus tractus solitarii (NTS) is the first central nervous system (CNS) nuclei for processing of information arising in the carotid body. Here, we microinjected a nitric oxide (NO) donor sodium nitroprusside (SNP), an NO-independent activator of the soluble guanylyl cyclase (sGC) (YC1) or an NO-synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (L-NAME) into the commissural NTS (cNTS) before carotid chemoreceptor anoxic stimulation and measured arterial glucose and the expression of Fos-like immunoreactivity (Fos-ir). Male Wistar rats (250-300 g) were anesthetized, and the carotid sinus was vascularly isolated. Either artificial cerebrospinal fluid (aCSF), SNP, YC1 or L-NAME were stereotaxically injected into the cNTS. The SNP and YC1 infused into the cNTS before carotid chemoreceptor stimulation (SNP-2 and YC1-2 groups) similarly increased arterial glucose compared to the aCSF-2 group. By contrast, infusion of L-NAME into the cNTS before carotid chemoreceptor stimulation (L-NAME-2 group) decreased arterial glucose concentration. The number of cNTS Fos-ir neurons, determined in all the groups studied except for YC1 groups, significantly increased in SNP-2 rat when compared to the aCSF-2 or SNP-2 groups. Our findings demonstrate that NO signaling, and the correlative activation of groups of cNTS neurons, plays key roles in the hyperglycemic reflex initiated by carotid chemoreceptor stimulation.

Interleukin-6 polymorphisms are associated with obesity and hyperglycemia in Mexican adolescents.

BACKGROUND AND AIMS: Interleukin-6 is an inflammatory response mediator used as a metabolic marker of obesity. Polymorphisms IL6 -597C>A, -572G>C, and -174G>C modify the production of this protein. The associations between these haplotypes and obesity or metabolic markers have not been studied in adolescents, so an analysis of these associations was performed. METHODS: The cross-sectional study included 745 apparently healthy 14- to 19-year-old adolescents. Obesity, serum glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-C), and high-sensitivity C-reactive protein (hs-CRP) were evaluated, and IL6 -597G>A, -572G>C and -174G>C polymorphisms determined. The associations were analyzed using multivariate logistic regression models. RESULTS: The allele frequencies were 0.15 for -597A and -174C and 0.30 for -572C. Genotypes were in Hardy-Weinberg equilibrium. IL-6(-597/-572/-174) haplotypes GGG, GCG, and AGC comprised 99.74% of the total haplotypes. The associations were significant between genotype GCG/GCG and hyperglycemia (OR = 2.86, 95% CI = 1.02-7.97); between GCG/GCG and high hs-CRP (OR = 6.17, 95% CI = 1.13-33.77); between AGC/AGC and obesity (OR = 4.42, 95% CI = 1.40-14.01); and between GGG/GCG and low HDL-C (OR = 1.53, 95% CI = 1.03-2.28). CONCLUSIONS: Genotypes of the IL6(-597/-572/-174) polymorphisms are associated with metabolic risk factors in Mexican adolescents.

Alternate method for hybrid Fontan completion.

A Fontan completion with a hybrid approach was performed on a 27-month-old girl with a univentricular heart. A large covered stent was placed between the inferior vena cava and the cavopulmonary anastomosis through a pericardial patch in the intracardiac fenestrated tunnel, circumventing the need for an occluder device for baffle closure. The child's progress has been good and she displays normal growth and acceptable clinical, ultrasonographic, and laboratory results.

Pig heart preservation with antegrade intracellular crystalloid versus antegrade/retrograde miniplegia.

Both histidine-tryptophan-ketoglutarate (HTK) solution and Braile miniplegia are commercially available and used with high success. The objective of this work was to compare the effects of both strategies in an animal model. Twelve pigs were divided into control, HTK, or Braile groups using a model of controlled global cardiac ischemia/reperfusion under cardiopulmonary bypass with 1 hour heart ischemia followed by 2 hour reperfusion. No significant differences were found over time or between groups for heart rate, arrhythmia, number of defibrillations required, blood gases, myocardial lactate production, myocardial oxygen consumption, nor coronary flow index. The Braile strategy was associated with a lower 120 minute postreperfusion coronary vascular resistance with higher water content, leukocyte infiltration, and oxidative damage compared with controls. Drainage of HTK solution to the venous return was followed by higher potassium and lower sodium blood concentrations. One-hour heart preservation with HTK or Braile systems followed by 2 hour reperfusion both allow for acceptable preservation of the healthy pig myocardium. Maneuvers such as leukocyte filtration or hemofiltration may further improve these conditions.

Nitric oxide infused in the solitary tract nucleus blocks brain glucose retention induced by carotid chemoreceptor stimulation.

Previous work has shown that the carotid body glomus cells can function as glucose sensors. The activation of these chemoreceptors, and of its afferent nucleus in the brainstem (solitary tract nucleus - STn), induces rapid changes in blood glucose levels and brain glucose retention. Nitric oxide (NO) in STn has been suggested to play a key role in the processing of baroreceptor signaling initiated in the carotid sinus. However, the relationship between changes in NO in STn and carotid body induced glycemic changes has not been studied. Here we investigated in anesthetized rats how changes in brain glucose retention, induced by the local stimulation of carotid body chemoreceptors with sodium cyanide (NaCN), were affected by modulation of NO levels in STn. We found that NO donor sodium nitroprusside (SNP) micro-injected into STn completely blocked the brain glucose retention reflex induced by NaCN chemoreceptor stimulation. In contrast, NOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) increased brain glucose retention reflex compared to controls or to SNP rats. Interestingly, carotid body stimulation doubled the expression of nNOS in STn, but had no effect in iNOS. NO in STn could function to terminate brain glucose retention induced by carotid body stimulation. The work indicates that NO and STn play key roles in the regulation of brain glucose retention.

Concomitant effects of nitric oxide and carotid chemoreceptor stimulation on brain glucose in normoglycemic and hyperglycemic rats.

BACKGROUND AND AIMS: Carotid body (CB) sinus perfusion with different glucose concentrations modifies arterial glucose concentration and brain glucose retention, thereby changing the brain's threshold to hypoxia. Because nitric oxide (NO) modulates hypoxic chemoreception, we investigated the relationship between NO- and CB-receptor pathways on arterial glucose and brain arteriovenous (a-v) glucose difference after hypoxic stimulation under hyperglycemic conditions. METHODS: Normoglycemic and streptozotocin (STZ, 50 mg/kg i.p.)-induced hyperglycemic Sprague Dawley rats were infused with the NO donor, sodium nitroprusside (SNP), or the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) into the circulatory isolated carotid sinus after (30 sec) local anoxic CB chemoreceptor stimulation with sodium cyanide (NaCN). RESULTS: L-NAME abolished the hyperglycemia and the increase in brain a-v glucose concentration difference induced by CB chemoreceptor stimulation in normoglycemic rats, whereas the same treatment in hyperglycemic rats did not change the glucose variables studied. However, SNP infused under the same conditions induced a bigger rise in arterial glucose and brain a-v glucose concentration difference only in normoglycemic rats, when compared with the results obtained in sham-2-control rats. CB stimulation plus SNP treatment also resulted in an increase in nitrite levels in cephalic venous blood in normoglycemic, but not in hyperglycemic, rats. CONCLUSIONS: We showed a clear concomitant effect of SNP infusion into local CB circulation and anoxic cyanide stimulation, enhancing hyperglycemia and brain a-v glucose concentration difference. Importantly, at high glucose levels, nitrergic drugs did not modify glucose variables when compared with the corresponding sham controls.

Contribution of TNF-308A and CCL2-2518A to carotid intima-media thickness in obese mexican children and adolescents.

BACKGROUND: Although commonly used in adults to detect early atherosclerosis, the value of the carotid intima-media thickness (CIMT) in children and adolescents is not clear. This marker has an inheritable component that supports the notion of a genetic influence. Among the genes studied as candidates for atherosclerosis development are those for chemokines, cytokines, and adhesion molecules because of their participation in atheroma formation through monocyte recruitment and migration. METHODS: We analyzed the relationship between CIMT and functional polymorphic variants in the genes for chemokines and proinflammatory cytokines associated with cardiovascular events in adults in lean and obese but otherwise healthy 6- to 19-year-old subjects. RESULTS: In the obese group, systolic blood pressure correlated negatively (r =-0.332; p = 0.008) and the TNF-308A allele correlated positively (r = 0.262; p = 0.040) with CIMT. The mean CIMT was higher in obese individuals with the TNF-308A allele than in those with TNF-308G allele (p = 0.041). In a multiple regression model for the total population, an increase in CIMT was explained by body mass index, systolic and diastolic blood pressure, and the TNF-308A and CCL2-2518A alleles (r(2) = 0.321; p = 0.022). CONCLUSIONS: This study contributes to the understanding of the pathophysiology of atherosclerosis and suggests that genetic markers of an increased inflammatory response and its deleterious effects are already present in obese children and adolescents.

[Larrea tridentata. Effect on a non-metabolic model of urolithiasis in rats]. / Larrea tridentata en urofitiasls. Efecto en un modelo no metabólico en ratas.

OBJECTIVE: To evaluate the effect of L. tridentata infusion on the development of urinary calculi in a non-metabolic model. METHODS: Male Wistar rats were divided into two groups (n = 10 each). The experimental group received 1 mL of oral L. tridentata infusion three times daily for 95 days. Control group received 1 mL tap water. Five days after initiating treatment, urolithiasis was induced inserting a series of 15 knots of 5-0 chromic catgut into the urinary bladder. Measurements included body weight and water intake, complete blood counts, glucose, BUN, creatinine, bacterial culture, and weight of urinary stones and sands. RESULTS: No statistically significant differences were found between groups for any variable. CONCLUSIONS: An infusion of L. tridentata was not effective in the prevention of urolith formation in the suture-induced rat model. It produced no alterations in body weight gain, blood counts, or water intake. Future work is needed to completely rule out any effect of the plant on urolith formation.