Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake.

Homeostatic mechanisms stabilize neural circuit function by keeping firing rates within a set-point range, but whether this process is gated by brain state is unknown. Here, we monitored firing rate homeostasis in individual visual cortical neurons in freely behaving rats as they cycled between sleep and wake states. When neuronal firing rates were perturbed by visual deprivation, they gradually returned to a precise, cell-autonomous set point during periods of active wake, with lengthening of the wake period enhancing firing rate rebound. Unexpectedly, this resetting of neuronal firing was suppressed during sleep. This raises the possibility that memory consolidation or other sleep-dependent processes are vulnerable to interference from homeostatic plasticity mechanisms. PAPERCLIP.

Rapid and active stabilization of visual cortical firing rates across light-dark transitions.

The dynamics of neuronal firing during natural vision are poorly understood. Surprisingly, mean firing rates of neurons in primary visual cortex (V1) of freely behaving rodents are similar during prolonged periods of light and darkness, but it is unknown whether this reflects a slow adaptation to changes in natural visual input or insensitivity to rapid changes in visual drive. Here, we use chronic electrophysiology in freely behaving rats to follow individual V1 neurons across many dark-light (D-L) and light-dark (L-D) transitions. We show that, even on rapid timescales (1 s to 10 min), neuronal activity was only weakly modulated by transitions that coincided with the expected 12-/12-h L-D cycle. In contrast, a larger subset of V1 neurons consistently responded to unexpected L-D and D-L transitions, and disruption of the regular L-D cycle with 60 h of complete darkness induced a robust increase in V1 firing on reintroduction of visual input. Thus, V1 neurons fire at similar rates in the presence or absence of natural stimuli, and significant changes in activity arise only transiently in response to unexpected changes in the visual environment. Furthermore, although mean rates were similar in light and darkness, pairwise correlations were significantly stronger during natural vision, suggesting that information about natural scenes in V1 may be more strongly reflected in correlations than individual firing rates. Together, our findings show that V1 firing rates are rapidly and actively stabilized during expected changes in visual input and are remarkably stable at both short and long timescales.

Renal Decapsulation Prevents Intrinsic Renal Compartment Syndrome in Ischemia-Reperfusion-Induced Acute Kidney Injury: A Physiologic Approach.

OBJECTIVES: Acute kidney injury is a serious complication with unacceptably high mortality that lacks of specific curative treatment. Therapies focusing on the hydraulic behavior have shown promising results in preventing structural and functional renal impairment, but the underlying mechanisms remain understudied. Our goal is to assess the effects of renal decapsulation on regional hemodynamics, oxygenation, and perfusion in an ischemic acute kidney injury experimental model. METHODS: In piglets, intra renal pressure, renal tissue oxygen pressure, and dysoxia markers were measured in an ischemia-reperfusion group with intact kidney, an ischemia-reperfusion group where the kidney capsule was removed, and in a sham group. RESULTS: Decapsulated kidneys displayed an effective reduction of intra renal pressure, an increment of renal tissue oxygen pressure, and a better performance in the regional delivery, consumption, and extraction of oxygen after reperfusion, resulting in a marked attenuation of acute kidney injury progression due to reduced structural damage and improved renal function. CONCLUSIONS: Our results strongly suggest that renal decapsulation prevents the onset of an intrinsic renal compartment syndrome after ischemic acute kidney injury.

Adolescents rats engage the orbitofrontal-striatal pathway differently than adults during impulsive actions.

Adolescence is characterized by increased impulsive and risk-taking behaviors. To better understand the neural networks that subserves impulsivity in adolescents, we used a reward-guided behavioral model that quantifies age differences in impulsive actions in adult and adolescent rats of both sexes. Using chemogenetics, we identified orbitofrontal cortex (OFC) projections to the dorsomedial striatum (DMS) as a critical pathway for age-related execution of impulsive actions. Simultaneous recording of single units and local field potentials in the OFC and DMS during task performance revealed an overall muted response in adolescents during impulsive actions as well as age-specific differences in theta power and OFC-DMS functional connectivity. Collectively, these data reveal that the OFC-DMS pathway is critical for age-differences in reward-guided impulsive actions and provide a network mechanism to enhance our understanding of how adolescent and adult brains coordinate behavioral inhibition.

Acute psilocybin enhances cognitive flexibility in rats.

Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2 A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin's pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.

Acute psilocybin enhances cognitive flexibility in rats.

Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin's pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.

Differential modulation of natural killer cell cytotoxicity by 17ß-estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells.

Natural killer (NK) cells play a crucial role in cervical cancer (CC). As estrogens and prolactin (PRL) have been reported to be involved in CC, the present study attempted to elucidate the effects of both hormones on NK cells in CC. For this purpose, NKL cells, as well as CC-derived cell lines (HeLa, SiHa and C33A) and non-tumorigenic keratinocytes (HaCaT cells) were stimulated with 17ß-estradiol (E2; 10 nM), PRL (200 ng/ml), or both (E2 and PRL) for 48 h. The expression of hormone receptors (estrogen receptor α and ß, G protein-coupled estrogen receptor 1 and PRL receptor) and NK cell activating receptors [natural killer group 2D (NKG2D), natural cytotoxicity triggering receptor 3, natural cytotoxicity triggering receptor 2 and natural cytotoxicity triggering receptor 1] were measured using western blot analysis and flow cytometry, respectively. In the HeLa, SiHa, C33A and HaCaT cells stimulated with the hormones, the expression of NKG2D ligands [MHC class I polypeptide-related sequence A/B (MICA/B)] on the membrane and the soluble form of MICA was evaluated using flow cytometry and ELISA. Cytotoxicity assay was performed using GFP-transfected K562 cells as target cells. E2 reduced NKL cell-mediated cytotoxicity, while PRL exerted the opposite effect. NKL cells expressed different hormone receptor forms, of which PRL only induced a decrease in NKG2D expression compared to the untreated control NKL cells. PRL increased MICA/B expression in HeLa cells and E2 and PRL reversed this effect. However, in SiHa cells, the concurrent incubation with the two hormones decreased MICA/B expression. E2 and PRL, either alone or in combination, decreased soluble MICA secretion in all CC cell lines, while E2 solely increased soluble MICA secretion in SiHa cells. On the whole, the present study provides evidence that E2 and PRL mediate the mechanisms through which NK and CC cells mediate a cytotoxic response and these have an antagonistic effect on NK cell-mediated cytotoxicity.

Sleep Promotes Downward Firing Rate Homeostasis.

Homeostatic plasticity is hypothesized to bidirectionally regulate neuronal activity around a stable set point to compensate for learning-related plasticity, but to date only upward firing rate homeostasis (FRH) has been demonstrated in vivo. We combined chronic electrophysiology in freely behaving animals with an eye-reopening paradigm to enhance firing in primary visual cortex (V1) and found that neurons bidirectionally regulate firing rates around an individual set point. Downward FRH did not require N-methyl-D-aspartate receptor (NMDAR) signaling and was associated with homeostatic scaling down of synaptic strengths. Like upward FRH, downward FRH was gated by arousal state but in the opposite direction: it occurred during sleep, not during wake. In contrast, firing rate depression associated with Hebbian plasticity happened independently of sleep and wake. Thus, sleep and wake states temporally segregate upward and downward FRH, which might prevent interference or provide unopposed homeostatic compensation when it is needed most.

PHONI: Streamed Matching Statistics with Multi-Genome References.

Computing the matching statistics of patterns with respect to a text is a fundamental task in bioinformatics, but a formidable one when the text is a highly compressed genomic database. Bannai et al. gave an efficient solution for this case, which Rossi et al. recently implemented, but it uses two passes over the patterns and buffers a pointer for each character during the first pass. In this paper, we simplify their solution and make it streaming, at the cost of slowing it down slightly. This means that, first, we can compute the matching statistics of several long patterns (such as whole human chromosomes) in parallel while still using a reasonable amount of RAM; second, we can compute matching statistics online with low latency and thus quickly recognize when a pattern becomes incompressible relative to the database. Our code is available at https://github.com/koeppl/phoni.

Autism-Associated Shank3 Is Essential for Homeostatic Compensation in Rodent V1.

Mutations in Shank3 are strongly associated with autism spectrum disorders and neural circuit changes in several brain areas, but the cellular mechanisms that underlie these defects are not understood. Homeostatic forms of plasticity allow central circuits to maintain stable function during experience-dependent development, leading us to ask whether loss of Shank3 might impair homeostatic plasticity and circuit-level compensation to perturbations. We found that Shank3 loss in vitro abolished synaptic scaling and intrinsic homeostatic plasticity, deficits that could be rescued by treatment with lithium. Further, Shank3 knockout severely compromised the in vivo ability of visual cortical circuits to recover from perturbations to sensory drive. Finally, lithium treatment ameliorated a repetitive self-grooming phenotype in Shank3 knockout mice. These findings demonstrate that Shank3 loss severely impairs the ability of central circuits to harness homeostatic mechanisms to compensate for perturbations in drive, which, in turn, may render them more vulnerable to such perturbations.

Policies and health care financing issues for dialysis in Latin America: extracts from the roundtable discussion on the economics of dialysis and chronic kidney disease.

During the 2008 Congress of the International Society for Peritoneal Dialysis, academic nephrologists, nephrology societies, and government officials from Colombia, Brazil, Argentina, Chile, Central America, Ecuador, and Mexico participated in a roundtable discussion on the Economics of Dialysis and Chronic Kidney Disease in Latin America. The main focus was policy and health care financing. The roundtable promoted open discussion between policymakers and clinicians on how to find viable solutions to contain spending on treatment for end-stage renal disease into the future. A number of options were proposed, including early medical intervention (disease management programs) to slow the progression of chronic kidney disease in high-risk patients, promotion of pre-emptive renal transplantation, and use of the most cost-effective dialysis therapy that can be offered to a patient without compromising outcome. It was concluded that the burden of treating more patients in the future could be alleviated by wider utilization of peritoneal dialysis (PD). However, important changes in health care reimbursement systems and realignment of incentives in the region are required to support wider PD penetration.

Association between CAPN10 UCSNP-43 gene polymorphism and polycystic ovary syndrome in Chilean women.

BACKGROUND: Studies have suggested that the Calpain-10 gene polymorphisms may play a role in polycystic ovary syndrome (PCOS) susceptibility. Thus, the aim of the present study was to evaluate the possible association between three single nucleotide polymorphisms (SNPs) in the calpain-10 gene (UCSNPs -43, -19, and -63) and polycystic ovary syndrome (PCOS) in Chilean women. METHODS: Fifty women with PCOS (28.8+/-8.2 y) and 70 healthy women (28.6+/-8.6 y) were included in this study. Serum lipids, hormonal status, fasting glucose, oral glucose tolerance test (OGTT), insulin, HOMAIR, and uric acid levels were determined by conventional methods. The calpain-10 gene variants were detected by PCR and PCR-RFLP, respectively. RESULTS: The presence of uncommon allele (A) for the UCSNP-43 was associated with increased risk of PCOS (odds ratio=1.93, 95% CI: 1.11-3.34). The UCSNP-63 (OR=1.11, 95% CI: 0.59-2.11) and UCSNP-19 (OR=0.93, 95% CI: 0.55-1.57) were not associated to PCOS. However, the PCOS women carrying the CC genotype for UCSNP-63 exhibited higher values of total cholesterol and LDL-C (P<0.05). Similarly, control women carrying the CC genotype showed higher serum levels of triglycerides, HDL-C and uric acid (P<0.05). CONCLUSION: Our data suggest the contribution of CAPN10 UCSNP-43 gene polymorphism to PCOS in Chilean women. However, further studies with larger samples are necessary to confirm this observation.

[Study of aerobic capacity in chronic hemodialized patients: effect of L-carnitine supplementation]. / Estudio exploratorio de la capacidad aerobia en pacientes en hemodiálisis: efecto de la suplementación con L-carnitina.

BACKGROUND AND OBJECTIVE: Chronic hemodialyzed patients have a low level of aerobic capacity, caused by the pathologies concomitant to renal insufficiency, according with a low level of physical activity. One of the factors that would contribute to this level of aerobic capacity is the L-carnitine deficit on skeletal muscle. However, the value of the supplementation of L-carnitine to improve the physical fitness has been controversial. The objective of this work was to evaluate the effect of the administration of L-carnitine on VO2 max in hemodialyzed patients. PATIENTS AND METHODS: A group of 21 patients (20-50 years old) on a program of chronic hemodialysis was studied. During 12 weeks, 13 of them received L-carnitine, 7 men and 6 women, 38.8 (9.5) years old; BMI 24.2 (2.1) Kg/m2; 8 of them received placebo, 4 men and 4 women, 35.8 (11.4) years old; BMI 24.5 (5.8) Kg/m2. RESULTS: There was an increase in VO2 peak on L-carnitine group from 16.3 (2.8) mL x Kg(-1) x min(-1) to 19.5 (3.3) mL x Kg(-1) x min(-1), and the same was seen in the placebo group (increase in VO2 peak from 14.8 (3.8) mL x Kg(-1) x min(-1) to 18.9 (4.8) mL x Kg(-1) x min(-1)). The L-carnitine and placebo groups did not show statistical differences at the end of this study (all values above p > 0.05). CONCLUSION: In this group of patients, the intravenous supplementation of L-carnitine during 12 weeks did not have an impact on the improvement of the VO2 peak.

Lesiones de cráneo en el mieloma múltiple / Skull Lesions in Multiple Myeloma

Fig A) Radiografía de cráneo en proyección lateral: se observan múltiples lesiones radiolúcidas distribuidas en todo el cráneo. B) Acercamiento donde se evidencian múltiples lesiones en sacabocado, compatibles con mieloma múltiple(AU)

Cost/Utility study of peritoneal dialysis and hemodialysis in Chile.

In Chile the reimbursement/patient/year for chronic peritoneal dialysis (PD) is US$14,654 and for chronic hemodialysis (HD) US$10,909. However, no study comparing global (direct plus indirect) costs has been performed in our country. Our research objective was to compare global costs and quality of life between the two therapies. Patients (n = 159) from five selected dialysis units in Chile [57 patients on PD (50 on automated PD) and 102 on standard HD (3 x 4 hours weekly)] were retrospectively studied. No patient had previously received the alternate therapy. Items analyzed were quality of life, customer satisfaction, direct and indirect costs, annual global costs, and cost/utility index. Mean age on HD was 54.14 +/- 16.01 years and on PD 49.76 +/- 18.88 years (p > 0.05). No differences in the distribution of diabetic patients between the therapies were found. Hemodialysis and PD groups did not have differences in the quality of life index, although there was better customer satisfaction with PD than with HD. Direct and indirect costs were calculated. We found significant differences in favor of PD in erythropoietin consumption (2.24 +/- 1.57 vials/week on HD and 1.35 +/- 0.85 vials/week on PD, p < 0.05) and working time (31.0 +/- 13.3 hours/week on HD and 38.5 +/- 12.2 hours/week on PD, p < 0.05). The quality life index (Health-Related SF-36 Health Survey) was 65.75 on HD and 66.88 on PD. Annual global costs were US$20,803 for HD and US$20,742 for PD. The cost/utility index was 3.16 for HD and 3.10 for PD. Patients on PD have an advantage related to erythropoietin consumption and working capacity compared with HD patients. Addition of related indirect costs to reimbursements gives a more accurate insight into treatment costs. Considering all these parameters, we did not find significant differences between HD and PD in quality life index, cost/utility index, or annual global cost in this Chilean end-stage renal disease population.

Human Peritoneal Mesothelial Cell Death Induced by High-Glucose Hypertonic Solution Involves Ca2+ and Na+ Ions and Oxidative Stress with the Participation of PKC/NOX2 and PI3K/Akt Pathways.

Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.

Esclerosis lateral amiotrófica, reto diagnóstico: Presentación de un caso clínico / Amyotrophic lateral sclerosis, diagnostic challenge: Presentation of a clinical case

Resumen La esclerosis lateral amiotrófica (ELA) es una enfermedad neurológica degenerativa que afecta la vía piramidal, a lo largo de su primera y segunda motoneurona. En Estados Unidos de América, la ELA es mejor conocida como enfermedad de Lou Gehrig, en alusión al jugador de béisbol de los Yankees que murió en 1941 debido a esta patología. Etimológicamente, esclerosis significa endurecimiento y hace referencia al estado de la médula espinal en las fases avanzadas de la enfermedad. Lateral significa "al lado" y pone de manifiesto la ubicación del daño en la médula espinal. Por último, el término amiotrófica significa "sin nutrición muscular" y se refiere a la pérdida de señales que los nervios envían normalmente a los músculos. La etiología de este trastorno es desconocida, se considera esporádico en 90 a 95% de los casos y con tendencia familiar en 5%. La supervivencia al momento del diagnóstico ronda el 20% a los 3-5 años.

Abstract Amyotrophic lateral sclerosis (ALS) is a degenerative neurological disease that affects the pyramidal pathway, along its first and second motor neurons. In the United States of America, ALS is better known as Lou Gehrig's disease, alluding to the Yankees baseball player who died in 1941 from this condition. Etymologically, Sclerosis means hardening and refers to the state of the spinal cord in the advanced stages of the disease. Lateral means "to the side" and reveals the location of the spinal cord damage. Finally, the term amyotrophic means "without muscle nutrition" and refers to the loss of signals that the nerves normally send to the muscles. The etiology of this disorder is unknown, it is considered sporadic in 90-95% of cases and with a familial tendency in 5%. Survival at diagnosis is around 20% at 3-5 years.

Effectiveness of short-term physical agents treatment on macroscopic morphology in patients with plaque psoriasis / Efectividad del tratamiento a corto plazo de los agentes físicos en la morfología macroscópica de las placas de psoriasis

Psoriasis is a chronic inflammatory disease that presents skin rashes which can arise through plaques. The aim of this work was to compare the effectiveness of short-term physical agents treatment on macroscopic morphology (area and erythema) in patients with plaque psoriasis. This prospective randomized experimental study included fourteen subjects, medically diagnosed with psoriasis, with more than one plaque in the skin and voluntarily without topical treatment. All subjects completed the study that consisted of 12 treatment sessions divided in control (C), artificial balneotherapy (AB), phototherapy (PT) or balneophototherapy (BPT) groups. After session 12, there was a significant reduction of the plaque area by all treatments when compared to C group and BPT was the most effective one. However, only AB and PT presented a reduction of erythema. Regarding severity, 9 patients changed to a lower category on the PASI test, and 5 of them maintained a mild psoriasis, but lowered their score. Finally, 13 of 14 subjects improved their quality of life. The physical agents used reduced the severity of psoriasis and improved quality of life of patients after 12 sessions of treatment during a onemonth period. The BPT was the more effective in controlling psoriasis by diminishing its area and PT by attenuating the erythema.

La Psoriasis es una enfermedad inflamatoria crónica que presenta irritación cutánea que puede derivar a placas. El objetivo de este trabajo fue comparar la efectividad del tratamiento a corto plazo con agentes físicos en la morfología macroscópica (área y eritema) en pacientes con placas de psoriasis. Estudio experimental, prospectivo, randomizado. Catorce sujetos participaron con diagnóstico médico de psoriasis, con más de una placa en la piel y sin tener tratamiento tópico de forma voluntaria. Todos los sujetos completaron el estudio, el cual consistió de 12 sesiones de tratamiento dividido en grupo control (C), BA, FT y BFA. Posterior a la sesión 12, se observó una reducción significativa en toda el área de las placas que recibieron tratamiento al compararlas al grupo C y el grupo BFA fue el más efectivo. Sin embargo, solo los grupos BA y FT presentaron una reducción del eritema. Respecto a la severidad, 9 pacientes cambiaron de la baja categoría en el test de PASI y 5 de ellos se mantuvieron en el nivel medio, pero disminuyeron su puntaje. Finalmente, 13 de 14 sujetos mejoraron su calidad de vida. Los agentes físicos usados redujeron la severidad de la psoriasis y mejoraron la calidad de vida de los pacientes después de 12 sesiones de tratamiento durante el período de un mes. La BFA fue la más efectiva en controlar la psoriasis por la disminución en el área y la FT por la atenuación del eritema.

Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis.

Propolis is a polyphenol-rich resinous substance extensively used to improve health and prevent diseases. The effects of polyphenols from different sources of propolis on atherosclerotic lesions and inflammatory and angiogenic factors were investigated in LDL receptor gene (LDLr-/-) knockout mice. The animals received a cholesterol-enriched diet to induce the initial atherosclerotic lesions (IALs) or advanced atherosclerotic lesions (AALs). The IAL or AAL animals were divided into three groups, each receiving polyphenols from either the green, red or brown propolis (250 mg/kg per day) by gavage. After 4 weeks of polyphenol treatment, the animals were sacrificed and their blood was collected for lipid profile analysis. The atheromatous lesions at the aortic root were also analyzed for gene expression of inflammatory and angiogenic factors by quantitative real-time polymerase chain reaction and immunohistochemistry. All three polyphenol extracts improved the lipid profile and decreased the atherosclerotic lesion area in IAL animals. However, only polyphenols from the red propolis induced favorable changes in the lipid profiles and reduced the lesion areas in AAL mice. In IAL groups, VCAM, MCP-1, FGF, PDGF, VEGF, PECAM and MMP-9 gene expression was down-regulated, while the metalloproteinase inhibitor TIMP-1 gene was up-regulated by all polyphenol extracts. In contrast, for advanced lesions, only the polyphenols from red propolis induced the down-regulation of CD36 and the up-regulation of HO-1 and TIMP-1 when compared to polyphenols from the other two types of propolis. In conclusion, polyphenols from propolis, particularly red propolis, are able to reduce atherosclerotic lesions through mechanisms including the modulation of inflammatory and angiogenic factors.

Single nucleotide polymorphisms in ABCG5 and ABCG8 genes in Chilean subjects with polygenic hypercholesterolemia and controls.

BACKGROUND: The excretion of cholesterol from liver and intestine is regulated by ATP-binding cassette half-transporters ABCG5 and ABCG8. Polymorphisms in their genes have been related to higher levels of plasma lipids. Thus, the aim of the present study was to evaluate the possible association between the 1950C > G (ABCG5) and the 251A > G (ABCG8) polymorphisms and the presence of hypercholesterolemia (HC) in Chilean subjects. METHODS: A total of 118 non-related individuals with HC (total cholesterol, TC > or = 6.2 mmol/L) and 104 normolipidemic subjects (controls, TC < or = 5.17 mmol/L), aged 18 to 65 years old, were included in this study. The ABCG5 1950C>G and ABCG8 251A>G genotypes were assessed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The genotype distribution of the ABCG5/ABCG8 polymorphisms was in Hardy-Weinberg equilibrium in both groups. The frequency of CC homozygous genotype for ABCG5 1950C > G polymorphism was higher in HC patients than in controls (42% vs. 10%, p < 0.001). On the other hand, no significant differences for the 251A > G polymorphism of the ABCG8 gene were observed (p=NS). Nevertheless, HC subjects carrying the GG genotype for the 251A > G variant exhibited higher values of high-density lipoprotein cholesterol when compared to other genotypes (p=0.020). CONCLUSIONS: Our data showed that the ABCG5 1950C > G polymorphism is associated with HC in the studied population. Nevertheless, this study is limited by its sample size.