KIS counteracts PTBP2 and regulates alternative exon usage in neurons.

Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here, we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.

QSAR analysis of five generations of cephalosporins to establish the structural basis of activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus.

Solving the worldwide problem of growing bacterial drug resistance will require a short-run and medium-term strategy. Structure-activity relationship (SAR) and quantitative SAR (QSAR) analyses have recently been utilized to reveal the molecular basis of the antibacterial activity and antibacterial spectrum of penicillins, the use of which is no longer solely empirical. Likewise, a more rational drug design can be achieved with cephalosporins, the largest group of ß-lactam antibiotics. The current contribution aimed to establish the molecular and physicochemical basis of the antibacterial activity of five generations of cephalosporins on methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). With SAR and QSAR analyses, the molecular portions that provide essential and additional antibacterial activity were identified. The substitutions with greater volume and polarity on the R2 side chain of the cephem nucleus increase potency on MSSA. The best effect is produced by substitutions with polar nitrogen atoms at the alpha-carbon (Cα). Substitutions with greater volume and polarity on the R1 side chain further enhance antibacterial activity. In contrast, the effect against MRSA seems to be independent of any substitution on R2 or at the Cα, while depending on the accessory portions with greater volume and polarity on R1.

Modulatory Activity of the Endocannabinoid System in the Development and Proliferation of Cells in the CNS.

The Endocannabinoid System (ECS, also known as Endocannabinoidome) plays a key role in the function of the Central Nervous System, though the participation of this system on the early development - specifically in neuroprotection and proliferation of nerve cells - has been poorly studied. Here, we collect and describe evidence regarding how cannabinoid receptors CB1R and CB2R regulate several cell markers related to proliferation. While CB1R participates in the modulation of neuronal and glial proliferation, CB2R is involved in the proliferation of glial cells. The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) exert significant effects on nerve cell proliferation. AEA generated during embryogenesis induces major effects on the differentiation of neuronal progenitor cells, whereas 2-AG participates in modulating cell migration events rather than affecting the neural proliferation rate. However, although the ECS has been demonstrated to participate in neuroprotection, more characterization on its role in neuronal and glial proliferation and differentiation is needed, especially in brain areas with recognized high neurogenesis rates. This has encouraged scientists to elucidate and propose specific mechanisms related with these cell proliferation mechanisms to better understand some neurodegenerative disorders such as Parkinson, Huntington and Alzheimer diseases, in which neuronal loss and poor neurogenesis are crucial factors for their onset and progression. In this review, we collect and present recent evidence published pointing to an active role of the ECS in the development and proliferation of nerve cells.

Advanced Diffusion MRI of the Visual System in Glaucoma: From Experimental Animal Models to Humans.

Glaucoma is a group of ophthalmologic conditions characterized by progressive retinal ganglion cell death, optic nerve degeneration, and irreversible vision loss. While intraocular pressure is the only clinically modifiable risk factor, glaucoma may continue to progress at controlled intraocular pressure, indicating other major factors in contributing to the disease mechanisms. Recent studies demonstrated the feasibility of advanced diffusion magnetic resonance imaging (dMRI) in visualizing the microstructural integrity of the visual system, opening new possibilities for non-invasive characterization of glaucomatous brain changes for guiding earlier and targeted intervention besides intraocular pressure lowering. In this review, we discuss dMRI methods currently used in visual system investigations, focusing on the eye, optic nerve, optic tract, subcortical visual brain nuclei, optic radiations, and visual cortex. We evaluate how conventional diffusion tensor imaging, higher-order diffusion kurtosis imaging, and other extended dMRI techniques can assess the neuronal and glial integrity of the visual system in both humans and experimental animal models of glaucoma, among other optic neuropathies or neurodegenerative diseases. We also compare the pros and cons of these methods against other imaging modalities. A growing body of dMRI research indicates that this modality holds promise in characterizing early glaucomatous changes in the visual system, determining the disease severity, and identifying potential neurotherapeutic targets, offering more options to slow glaucoma progression and to reduce the prevalence of this world's leading cause of irreversible but preventable blindness.

Arsenic exposure and non-carcinogenic health effects.

Inorganic arsenic (iAs) exposure is a serious health problem that affects more than 140 million individuals worldwide, mainly, through contaminated drinking water. Acute iAs poisoning produces several symptoms such as nausea, vomiting, abdominal pain, and severe diarrhea, whereas prolonged iAs exposure increased the risk of several malignant disorders such as lung, urinary tract, and skin tumors. Another sensitive endpoint less described of chronic iAs exposure are the non-malignant health effects in hepatic, endocrine, renal, neurological, hematological, immune, and cardiovascular systems. The present review outlines epidemiology evidence and possible molecular mechanisms associated with iAs-toxicity in several non-carcinogenic disorders.

The elongation factor eEF1A2 controls translation and actin dynamics in dendritic spines.

Synaptic plasticity involves structural modifications in dendritic spines that are modulated by local protein synthesis and actin remodeling. Here, we investigated the molecular mechanisms that connect synaptic stimulation to these processes. We found that the phosphorylation of isoform-specific sites in eEF1A2-an essential translation elongation factor in neurons-is a key modulator of structural plasticity in dendritic spines. Expression of a nonphosphorylatable eEF1A2 mutant stimulated mRNA translation but reduced actin dynamics and spine density. By contrast, a phosphomimetic eEF1A2 mutant exhibited decreased association with F-actin and was inactive as a translation elongation factor. Activation of metabotropic glutamate receptor signaling triggered transient dissociation of eEF1A2 from its regulatory guanine exchange factor (GEF) protein in dendritic spines in a phosphorylation-dependent manner. We propose that eEF1A2 establishes a cross-talk mechanism that coordinates translation and actin dynamics during spine remodeling.

In vivo MRI evaluation of early postnatal development in normal and impaired rat eyes.

This study employed in vivo 7-T magnetic resonance imaging (MRI) to evaluate the postnatal ocular growth patterns under normal development or neonatal impairments in Sprague-Dawley rats. Using T2-weighted imaging on healthy rats from postnatal day (P) 1 (newborn) to P60 (adult), the volumes of the anterior chamber and posterior chamber (ACPC), lens, and vitreous humor increased logistically with ACPC expanding by 33-fold and the others by fivefold. Intravitreal potassium dichromate injection at P1, P7, and P14 led to T1-weighted signal enhancement in the developing retina by 188-289%. Upon unilateral hypoxic-ischemic encephalopathy at P7, monocular deprivation at P15, and monocular enucleation at P1, T2-weighted imaging of the adult rats showed decreased ocular volumes to different extents. In summary, in vivo high-field MRI allows for non-invasive evaluation of early postnatal development in the normal and impaired rat eyes. Chromium-enhanced MRI appeared effective in examining the developing retina before natural eyelid opening at P14 with relevance to lipid metabolism. The reduced ocular volumes upon neonatal visual impairments provided evidence to the emerging problems of why some impaired visual outcomes cannot be solely predicted by neurological assessments and suggested the need to look into both the eye and the brain under such conditions.

Stress granules display bistable dynamics modulated by Cdk.

Stress granules (SGs) are conserved biomolecular condensates that originate in response to many stress conditions. These membraneless organelles contain nontranslating mRNAs and a diverse subproteome, but our knowledge of their regulation and functional relevance is still incipient. Here, we describe a mutual-inhibition interplay between SGs and Cdc28, the budding yeast Cdk. Among Cdc28 interactors acting as negative modulators of Start, we have identified Whi8, an RNA-binding protein that localizes to SGs and recruits the mRNA of CLN3, the most upstream G1 cyclin, for efficient translation inhibition and Cdk inactivation under stress. However, Whi8 also contributes to recruiting Cdc28 to SGs, where it acts to promote their dissolution. As predicted by a mutual-inhibition framework, the SG constitutes a bistable system that is modulated by Cdk. Since mammalian cells display a homologous mechanism, we propose that the opposing functions of specific mRNA-binding proteins and Cdk's subjugate SG dynamics to a conserved hysteretic switch.

Diabetic Retinopathy: Important Biochemical Alterations and the Main Treatment Strategies.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by impaired glucose homeostasis, insulin resistance and hyperglycemia. Among its serious multisystemic complications is diabetic retinopathy (DR), which develops slowly and often insidiously. This disorder-the most common cause of vision loss in working-age adults-is characterized by functional and morphological changes in the retina. It results from the exacerbation of ischemic and inflammatory conditions prompted by alterations in the blood vessels, such as the development of leukostasis, thickening of the basement membrane, retinal neovascularization and fibrovascular tissue formation at the vitreoretinal interface. The pathogenic alterations are usually triggered at the biochemical level, involving a greater activity in 4 pathways: the polyol pathway, the hexosamine pathway, the formation of advanced glycation end-products and the activation of protein kinase C isoforms. When acting together, these pathways give rise to increased levels of reactive oxygen species and decreased levels of endogenous antioxidant agents, thus generating oxidative stress. All current therapies are aimed at the later stages of DR, and their application implies side effects. One possible strategy for preventing the complications of DM is to counteract the elevated superoxide production stemming from a high level of blood glucose. Accordingly, some treatments are under study for their capacity to reduce vascular leakage and avoid retinal ischemia, retinal neovascularization and macular edema. The present review summarizes the biochemical aspects of DR and the main approaches for treating it.

Voltage-Dependent Sodium Channel Blocker Anticonvulsants: An Approach to the Structure-Activity Relationship.

BACKGROUND: Anticonvulsants are drugs used in the treatment of seizures; their pharmacology includes promoters of brain inhibition and inhibitors of brain activity. Of the latter, voltagedependent sodium channel blockers (VGSCB) are the most widely used in therapeutics. OBJECTIVE: The study aimed at proposing the structural requirements of VGSC blockers through a quantitative structure-activity relationship analysis of drugs with proven activity. METHODS: IC50 values of anticonvulsant drugs on VGSCs were considered under similar experimental conditions; some physicochemical properties of the molecules that were correlated with their biological activity were determined in silico. RESULTS: Relationships were observed between the dipole moment, pKa, EHOMO, and MR with the biological activity, which infers that between greater polarity and basicity of the drugs, their activity as blockers will increase. Subsequently, the structural subclassification of the drugs was carried out, based on the urea derivation, the groups of which were: Group 1 (direct and bioisostere derivatives) and Group 2 (homologue and vinylogue derivatives of urea). CONCLUSION: The biological activity depends on the polarity, basicity, and electronic density of the drugs. The derivation of urea is essential, which is present in its original substituted form or a bioisosteric form. Urea can be in the form of a homologue or a vinylogue at the ends of the molecule. Aromatic substitution to the urea portion is necessary.

Differences in oral processing behavior of consumers varying in age, gender and ethnicity lead to changes in bolus properties but only to small differences in dynamic texture perception of sausages.

Consumer characteristics such as age, gender and ethnicity influence food oral processing behavior. The aim of this study was to determine the effect of age, gender and ethnicity on consumption time, bolus properties and dynamic sensory perception of sausages. Consumption time, bolus properties (saliva incorporation, particle size distribution and rheological properties) and dynamic texture perception (Temporal Dominance of Sensations, TDS) of sausages were compared between young Dutch, Caucasians (n = 21; 22 ± 2.8 years), young Chinese, Asians (n = 21; 23 ± 1.6 years), and elderly Dutch, Caucasians (n = 22; 70 ± 4.3 years). Elderly Dutch masticated the sausage 22% longer (25.6 s) than young Dutch consumers (21.0 s). Elderly Dutch produced sausage boli that were softer, more adhesive, less cohesive and contained more particles than those of young Dutch adults. Elderly females produced more adhesive and less cohesive sausage bolus than males. Young Chinese females had 75.6% longer consumption time (29.5 s) than young Dutch females (16.8 s). Young Chinese males masticated the sausages in less time (18.8 s) than young Chinese females (29.5 s). Young Chinese produced softer and less cohesive bolus with slightly smaller and more particles than young Dutch. Saliva incorporation and bolus particle size were not affected by age, gender and ethnicity. Mediation analysis revealed that the effect of consumer characteristics such as age, gender and ethnicity on bolus properties was mediated by consumption time. At the beginning and end of consumption time, dynamic texture perception of sausages was similar for all consumer groups and strongly correlated with bolus properties. Differences in dynamic texture perception between consumer groups were observed only during the middle stages of mastication with low dominance rates. We conclude that consumers differing in age, gender and ethnicity vary in oral processing time to produce bolus with textural properties optimized to their needs. Furthermore, consumption time is the underlying mechanism that explains the differences in bolus properties between the consumer groups. While variations in consumption time of sausages lead to considerable differences in bolus properties, it only leads to small differences in dynamic texture perception.

How addition of peach gel particles to yogurt affects oral behavior, sensory perception and liking of consumers differing in age.

Addition of particles to foods, such as fruit pieces to dairy products or vegetable pieces to soup, is a convenient approach to alter nutritional composition, appearance, perception and acceptance. The aim of this study was to investigate the effect of addition of peach gel particles to yogurt on oral behavior, sensory perception and liking of consumers differing in age. One homogeneous yogurt and seven yogurts with peach gel particles were prepared. The added peach gel particles varied in size, fracture stress, or concentration. Oral behavior of n = 62 healthy Dutch, young adults (21 ± 2 years) and n = 62 healthy Dutch elderly (70 ± 5 years) participants was characterized by video recordings. Yogurts' sensory properties and liking were scored on nine-point scales. Elderly consumed yogurts with higher number of chews and longer consumption time leading to lower eating rate than young adults. Addition of particles, regardless of characteristics, increased number of chews, consumption time, and decreased eating rate up to 60% for both consumer groups, with an average decrement of 110 g/min for young and of 63 g/min for elderly consumers. With increasing peach gel hardness and concentration, the number of chews and consumption time increased while eating rate decreased. Peach gel particle size did not affect oral behavior. Sensory perception of yogurts with added peach gel particles was similar for healthy young adult and healthy elderly. Only small differences in sensory perception were observed between the young adults and elderly for flavor attributes, crumbliness, juiciness, and perceived particle size. Similarly, minor differences in liking of a few yogurts with peach pieces were observed between both consumer groups. Thus, healthy ageing seems to affect sensory perception of semi-solid foods to a limited extent only. We conclude that changes in food texture by addition of particles can be used as a strategy to steer eating rate and potentially impact food intake of young adult and elderly consumers while maintaining or enhancing food palatability. Additionally, particle characteristics can be modified to target specific consumer groups that might differ in eating capabilities.

Effect of (-)-epicatechin on the modulation of progression markers of chronic renal damage in a 5/6 nephrectomy experimental model.

AIMS: To evaluate the effects of (-)-epicatechin (Epi) in the progression of kidney damage. MATERIAL AND METHODS: We assessed the effects of Epi [0.01-20 mg/kg of body weight/day] during 14 days, in a 5/6 nephrectomy model in mice. KEY FINDINGS: Nephrectomy-induced systolic arterial hypertension was significantly reduced in a dose dependent manner with Epi treatment. Increased serum creatinine and urea were reduced almost to normal values. The concentration of tetrahydrobiopterin (BH4), used as subrogate of endothelial dysfunction, decreased in nephrectomyzed animals, Epi treatment increased BH4 levels almost reaching normal values. The expression of angiotensin II receptor (AT1-R) and NADPH oxidase-4 (NOX-4) and 3-nitrotyrosine levels increased with nephrectomy and were reduced with Epi treatment. Renal tissue morphology in the remaining tissue was conserved with Epi treatment in a dose dependent manner. SIGNIFICANCE: Chronic kidney disease (CKD) is an independent cardiovascular risk factor associated with a mortality rate 10 to 20 times higher than that of the general population. High blood pressure, endothelial dysfunction and oxidative stress are important factors determining kidney damage progression. Findings of this study indicate that Epi is able to counteract the deleterious effects of subtotal nephrectomy and the structural and functional changes in the remnant kidney tissue, decreasing the progression of CKD. These results warrant the possibility of implement clinical trials to limit the progression of CKD in humans.

Age, gender, ethnicity and eating capability influence oral processing behaviour of liquid, semi-solid and solid foods differently.

Food oral processing depends on food properties and consumer characteristics. The aim of this study was to determine the effect of age, gender, ethnicity and eating capability on oral processing behaviour of liquid, semi-solid and solid foods. Oral processing behaviour of 18 commercially available foods, ranging from liquids, semi-solids to solids, was compared between Dutch, Caucasian adults (18-30 yrs), Chinese, Asian adults (18-30 yrs), Dutch, Caucasian elderly (60-80 yrs), and consumers with mild swallowing problems and/or low mastication efficiency (18-80 yrs). Participants were video recorded during food consumption and six oral processing parameters extracted. Elderly consumed all foods with lower eating rates (g/s) than young adults by increasing consumption time (s). Females consumed solid foods with lower eating rates (g/s) than males by reducing bite size (g). Chinese, Asian consumers consumed liquid and solid foods with lower eating rates (g/s) than Dutch, Caucasian consumers by reducing bites size (g). Chinese, Asian consumers consumed semi-solid foods with lower eating rates (g/s) than Dutch, Caucasian consumers by reducing bite size (g) and increasing consumption time (s). Consumers with decreased mastication efficiency or mild swallowing problems showed similar oral processing behaviour than healthy consumers, probably because reduction in eating capability was limited in the group. This demonstrates that different consumer groups adapt eating rate (g/s) in different ways by modifying bite size (g), consumption time (s) or both. To conclude, age, gender and ethnicity influence oral processing behaviour of liquid, semi-solid and solid foods differently. Understanding differences in oral processing behaviour of specific consumer groups can assist in steering sensory perception, food choice and energy intake of specific consumer groups such as the elderly.

Aplasia pura de serie roja adquirida y enfermedad renal crónica en terapia de sustitución renal tipo hemodiálisis / Acquired pure aplasia of red cells and chronic kidney disease in renal replacement therapy type hemodialysis

La aplasia pura de serie roja (APSR) adquirida es un trastorno hematopoyético poco frecuente caracterizado por anemia normocítica y normocrómica, reticulocitopenia y ausencia de precursores eritroides en la médula ósea, frecuencia que ha ido incrementando en pacientes con enfermedad renal crónica. Presentamos el caso de un varón de 38 años de edad, con hipertensión arterial sistémica, en terapia hemodialítica. En su evolución cursa con anemia aguda, tras protocolo de estudio se objetivó una aplasia pura de células eritroides por anticuerpos anti eritropoyetina, el paciente recibió bolos de ciclofosfamida, quimioprofilaxis, terapia dialítica, se suspendió la eritropoyetina, presentando buena evolución, efectuándose posteriormente el trasplante renal.

Acquired pure red cells aplasia (PRCA) is a rare hematopoietic disorder characterized by normocytic and normochromic anemia, reticulocytopenia and absence of erythroid precursors in bone marrow, frequency that has been increasing in patients with chronic kidney disease. We present the case of a 38-year-old man with systemic hypertension in hemodialysis therapy. During the course of the disease, acute anemia was observed. After a study protocol, pure erythroid cell aplasia was detected by antierythropoietin antibodies, the patient received boluses of cyclophosphamide, chemoprophylaxis, dialysis therapy, erythropoietin was suspended, with favorable evolution. Subsequently, the kidney transplant.

[Arsenic Intake: Impact in Human Nutrition and Health]. / Ingesta de arsénico: el impacto en la alimentación y la salud humana.

Arsenic is an element that is widely distributed throughout the environment. Its compounds are mainly in the state of pentavalent and trivalent oxidation; and in inorganic and organic forms. Arsenical species vary in their degree of toxicity, with inorganic compounds being more toxic than organic and trivalent compounds more toxic than pentavalent compounds. There would be interconversion between the less toxic species and other more toxic species and the cooking and processing methods could affect it. Arsenic is a carcinogenic agent and causes multiple negative effects on human health in the short and long term. Non-occupational human exposure to arsenic occurs mainly through water and food. The regulation is variable for each country and is based on WHO standards, the Codex Alimentarius, and the European Union. Many studies focus on determining the total arsenic content but do not identify arsenical species in foods. Globally, fish and seafood, chicken, meat, rice, and seaweed have high levels of arsenic. In Peru, there are few studies on total arsenic content and arsenical species in food despite the fact that we have areas with high levels of environmental contamination. The objective of this review is to discuss exposure to arsenic through food and water intake, related regulations, toxicity, consequences on human health and main foods that contribute to its intake.

El arsénico es un elemento que se encuentra ampliamente distribuido en todo el medio ambiente. Sus compuestos se hallan principalmente en estado de oxidación pentavalente y trivalente; y en formas inorgánicas y orgánicas. Las especies arsenicales varían en su grado de toxicidad, siendo los compuestos inorgánicos más tóxicos que los orgánicos, y los compuestos trivalentes más tóxicos que los pentavalentes. Habría interconversión entre las especies menos tóxicas a otras más toxicas y los métodos de cocción y de procesamiento podrían afectarla. El arsénico es un agente carcinogénico y ocasiona múltiples efectos negativos sobre la salud humana a corto y largo plazo. La exposición humana no ocupacional al arsénico se da principalmente por agua y alimentos. La normativa es variable para cada país, y se basa en los estándares de la OMS, Codex Alimentarius y la Unión Europea. Muchos estudios se enfocan en determinar el contenido total de arsénico mas no identifican las especies arsenicales en alimentos. A nivel global, pescado y mariscos, pollo, carnes, arroz y algas marinas tienen niveles elevados de arsénico. En Perú, hay escasos estudios sobre contenido de arsénico total y especies arsenicales en alimentos a pesar que tenemos zonas con altos niveles de contaminación ambiental. El objetivo de esta revisión es discutir la exposición al arsénico a través de la ingesta de alimentos y agua, la normativa relacionada, toxicidad, consecuencias en la salud humana y principales alimentos que contribuyen a su ingesta.

Ingesta de arsénico: el impacto en la alimentación y la salud humana / Arsenic Intake: Impact in Human Nutrition and Health

RESUMEN El arsénico es un elemento que se encuentra ampliamente distribuido en todo el medio ambiente. Sus compuestos se hallan principalmente en estado de oxidación pentavalente y trivalente; y en formas inorgánicas y orgánicas. Las especies arsenicales varían en su grado de toxicidad, siendo los compuestos inorgánicos más tóxicos que los orgánicos, y los compuestos trivalentes más tóxicos que los pentavalentes. Habría interconversión entre las especies menos tóxicas a otras más toxicas y los métodos de cocción y de procesamiento podrían afectarla. El arsénico es un agente carcinogénico y ocasiona múltiples efectos negativos sobre la salud humana a corto y largo plazo. La exposición humana no ocupacional al arsénico se da principalmente por agua y alimentos. La normativa es variable para cada país, y se basa en los estándares de la OMS, Codex Alimentarius y la Unión Europea. Muchos estudios se enfocan en determinar el contenido total de arsénico mas no identifican las especies arsenicales en alimentos. A nivel global, pescado y mariscos, pollo, carnes, arroz y algas marinas tienen niveles elevados de arsénico. En Perú, hay escasos estudios sobre contenido de arsénico total y especies arsenicales en alimentos a pesar que tenemos zonas con altos niveles de contaminación ambiental. El objetivo de esta revisión es discutir la exposición al arsénico a través de la ingesta de alimentos y agua, la normativa relacionada, toxicidad, consecuencias en la salud humana y principales alimentos que contribuyen a su ingesta.

ABSTRACT Arsenic is an element that is widely distributed throughout the environment. Its compounds are mainly in the state of pentavalent and trivalent oxidation; and in inorganic and organic forms. Arsenical species vary in their degree of toxicity, with inorganic compounds being more toxic than organic and trivalent compounds more toxic than pentavalent compounds. There would be interconversion between the less toxic species and other more toxic species and the cooking and processing methods could affect it. Arsenic is a carcinogenic agent and causes multiple negative effects on human health in the short and long term. Non-occupational human exposure to arsenic occurs mainly through water and food. The regulation is variable for each country and is based on WHO standards, the Codex Alimentarius, and the European Union. Many studies focus on determining the total arsenic content but do not identify arsenical species in foods. Globally, fish and seafood, chicken, meat, rice, and seaweed have high levels of arsenic. In Peru, there are few studies on total arsenic content and arsenical species in food despite the fact that we have areas with high levels of environmental contamination. The objective of this review is to discuss exposure to arsenic through food and water intake, related regulations, toxicity, consequences on human health and main foods that contribute to its intake.

Apocynin combined with drugs as coadjuvant could be employed to prevent and/or treat the chronic kidney disease.

A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO• to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH4), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion ([Formula: see text]). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress ([Formula: see text]) and endothelial function (BH4). There were significantly lower levels of [Formula: see text] and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.

Effects of Allicin on Hypertension and Cardiac Function in Chronic Kidney Disease.

This work was performed to study the effect of allicin on hypertension and cardiac function in a rat model of CKD. The groups were control, CKD (5/6 nephrectomy), and CKD-allicin treated (CKDA) (40 mg/kg day/p.o.). Blood pressure was monitored (weekly/6 weeks). The cardiac function, vascular response to angiotensin II, oxidative stress, and heart morphometric parameters were determined. The CKD group showed hypertension and proteinuria. The coronary perfusion and left ventricular pressures were decreased in CKD group. In contrast, the vascular response to angiotensin II and expression of angiotensin II type 1 receptor (AT1R) were increased. These data were associated with the increment in morphometric parameters (weight of heart and left ventricle, heart/BW and left ventricular mass index, and wall thickness). Concurrently, the oxidative stress was increased and correlated inversely with the expression of Nrf2, Keap1, and antioxidant enzymes Nrf2-regulated. Allicin treatment attenuated hypertension and improved the renal and the cardiac dysfunctions; furthermore, it decreased the vascular reactivity to angiotensin II, AT1R overexpression, and preserved morphometric parameters. Allicin also downregulated Keap1 and increased Nrf2 expression, upregulated the antioxidant enzymes, and reduced oxidative stress. In conclusion, allicin showed an antihypertensive, nephroprotective, cardioprotective, and antioxidant effects, likely through downregulation of AT1R and Keap1 expression.

[Genes associated to cancer]. / Los genes del cáncer.

In 2010, in a cancer genes census, 291 genes were enumerated. These represent near to the 1 % of the total genes, for which there is enough biological evidence that they belong to a new genes classification, known as the cancer genes. These have been defined as the causal genes for sporadic or familiar cancer, when they mutate. The mutation types for these genes includes amplifications, point mutations, deletions, genomic rearranges, amongst others, which lead to a protein over-expression, muting, production of chimeric proteins or a de novo expression. In conjunction these genomic alterations or those of the genetic expression, when they affect specific genes which contribute to the development of cancer, are denominated as cancer genes. It is possible that the list of these alterations will grow longer due to new strategies being developed, for example, the genomic analysis.

En el año 2010, en un censo de genes del cáncer, se enumeraron 291 genes humanos que representan cerca del 1 % de los genes totales, para los cuales existe suficiente evidencia biológica de que pertenecen a una nueva clasificación de genes: los genes del cáncer. Estos se han definido como los genes causales de cáncer esporádico o cáncer familiar, cuando mutan. El tipo de mutaciones para estos genes del cáncer incluye las amplificaciones, las mutaciones puntuales, las deleciones, los rearreglos genómicos, entre otros, los cuales conducen a una sobreexpresión proteica, silenciamiento, producción de proteínas quiméricas o una expresión de novo. Cuando afectan genes específicos que contribuyen al desarrollo de un cáncer, estas alteraciones genómicas o de la expresión génica son denominadas en conjunto como genes del cáncer. Es posible que esta lista crezca más debido a las nuevas estrategias que se están desarrollando, como, por ejemplo, las de análisis genómico.