Vitamin B3 Supplementation for Optic Neuropathies: A Comprehensive Review.

Optic neuropathies, such as glaucoma, are some of the leading causes of irreversible blindness worldwide. There has been a lot of research for potential therapies that could attenuate and even reduce the impact of the pathological pathways that lead to the loss of retinal ganglion cells (RGCs). In recent years, vitamin B3 (nicotinamide) has gained some interest as a viable option for these neurodegenerative diseases due to its fundamental role in enhancing the mitochondria metabolism of the RGCs. This review focuses on elucidating the impact of vitamin B3 on retinal cells, especially when in a dysfunctional state like what happens in optic neuropathies, especially glaucoma. This review also summarizes the existing and future research on the clinical effects of vitamin B3 in these optic neuropathies, and determines appropriate recommendations regarding its dosing, efficacy, and eventual side effects.

Correlational Study of Aminopeptidase Activities between Left or Right Frontal Cortex versus the Hypothalamus, Pituitary, Adrenal Axis of Spontaneously Hypertensive Rats Treated with Hypotensive or Hypertensive Agents.

It has been suggested that the neuro-visceral integration works asymmetrically and that this asymmetry is dynamic and modifiable by physio-pathological influences. Aminopeptidases of the renin-angiotensin system (angiotensinases) have been shown to be modifiable under such conditions. This article analyzes the interactions of these angiotensinases between the left or right frontal cortex (FC) and the same enzymes in the hypothalamus (HT), pituitary (PT), adrenal (AD) axis (HPA) in control spontaneously hypertensive rats (SHR), in SHR treated with a hypotensive agent in the form of captopril (an angiotensin-converting enzyme inhibitor), and in SHR treated with a hypertensive agent in the form of the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). In the control SHR, there were significant negative correlations between the right FC with HPA and positive correlations between the left FC and HPA. In the captopril group, the predominance of negative correlations between the right FC and HPA and positive correlations between the HPA and left FC was maintained. In the L-NAME group, a radical change in all types of interactions was observed; particularly, there was an inversion in the predominance of negative correlations between the HPA and left FC. These results indicated a better balance of neuro-visceral interactions after captopril treatment and an increase in these interactions in the hypertensive animals, especially in those treated with L-NAME.

Familial component of early-onset colorectal cancer: opportunity for prevention.

BACKGROUND: Individuals with a non-syndromic family history of colorectal cancer are known to have an increased risk. There is an opportunity to prevent early-onset colorectal cancer (age less than 50 years) (EOCRC) in this population. The aim was to explore the proportion of EOCRC that is preventable due to family history of colorectal cancer. METHODS: This was a retrospective multicentre European study of patients with non-hereditary EOCRC. The impact of the European Society of Gastrointestinal Endoscopy (ESGE), U.S. Multi-Society Task Force (USMSTF), and National Comprehensive Cancer Network (NCCN) guidelines on prevention and early diagnosis was compared. Colorectal cancer was defined as potentially preventable if surveillance colonoscopy would have been performed at least 5 years before the age of diagnosis of colorectal cancer, and diagnosed early if colonoscopy was undertaken between 1 and 4 years before the diagnosis. RESULTS: Some 903 patients with EOCRC were included. Criteria for familial colorectal cancer risk in ESGE, USMSTF, and NCCN guidelines were met in 6.3, 9.4, and 30.4 per cent of patients respectively. Based on ESGE, USMSTF, and NCCN guidelines, colorectal cancer could potentially have been prevented in 41, 55, and 30.3 per cent of patients, and diagnosed earlier in 11, 14, and 21.1 per cent respectively. In ESGE guidelines, if surveillance had started 10 years before the youngest relative, there would be a significant increase in prevention (41 versus 55 per cent; P = 0.010). CONCLUSION: ESGE, USMSTF, and NCCN criteria for familial colorectal cancer were met in 6.3, 9.4, and 30.4 per cent of patients with EOCRC respectively. In these patients, early detection and/or prevention could be achieved in 52, 70, and 51.4 per cent respectively. Early and accurate identification of familial colorectal cancer risk and increase in the uptake of early colonoscopy are key to decreasing familial EOCRC.

GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases.

BACKGROUND: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies. METHODS: GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1-10; 11-15; 16-20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values. DISCUSSION: HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years. TRIAL REGISTRATION: EudraCT number: 2019-004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).

A Systematic Review of the Effectiveness of Dry Needling in Subacromial Syndrome.

Our aim was to evaluate the effectiveness of dry needling (DN) combined with conventional physiotherapy in the recovery of patients with subacromial syndrome (SAS). A search was made of the main open access health science databases. The publication date was not limited for systematic reviews but was for randomized clinical trials (RCTs), which were limited to the last five years (from 2016) in English or in Spanish. Ninety-four studies were selected. In order to assess the quality of the studies, the JADAD scale or Oxford quality scoring system was used. A total of 402 patients were analyzed in all the studies in which the application of conventional physiotherapy was compared to the DN, either in a combination or in isolation. Improvements were obtained in pain intensity (Visual Analogic Scale-VAS), Range of Movement (ROM), Pressure Pain Threshold (PPT), functionality with Disabilities of the Arm, Shoulder and Hand (DASH) and the Shoulder Pain and Disability Index (SPADI), and in the cost-benefit ratio. DN is effective and safe in reducing the pain and disability produced by SAS, with the best combination of treatment turning out to be conventional physiotherapy together with DN, obtaining more stable and longer-lasting benefits than merely applying the techniques in isolation.

The Type of Fat in the Diet Influences Regulatory Aminopeptidases of the Renin-Angiotensin System and Stress in the Hypothalamic-Pituitary-Adrenal Axis in Adult Wistar Rats.

(1) Background: Prolonged feeding with a high-fat diet (HFD) acts as a stressor by activating the functions of the hypothalamic-pituitary-adrenal gland (HPA) stress axis, accompanied of hypertension by inducing the renin-angiotensin-aldosterone system. Angiotensinases enzymes are regulatory aminopeptidases of angiotensin metabolism, which together with the dipeptidyl peptidase IV (DPP-IV), pyroglutamyl- and tyrosyl-aminopeptidase (pGluAP, TyrAP), participate in cognitive, stress, metabolic and cardiovascular functions. These functions appear to be modulated by the type of fat used in the diet. (2) Methods: To analyze a possible coordinated response of aminopeptidases, their activities were simultaneously determined in the hypothalamus, adenohypophysis and adrenal gland of adult male rats fed diets enriched with monounsaturated (standard diet (S diet) supplemented with 20% virgin olive oil; VOO diet) or saturated fatty acids (diet S supplemented with 20% butter and 0.1% cholesterol; Bch diet). Aminopeptidase activities were measured by fluorimetry using 2-Naphthylamine as substrates. (3) Results: the hypothalamus did not show differences in any of the experimental diets. In the pituitary, the Bch diet stimulated the renin-angiotensin system (RAS) by increasing certain angiotensinase activities (alanyl-, arginyl- and cystinyl-aminopeptidase) with respect to the S and VOO diets. DPP-IV activity was increased with the Bch diet, and TyrAP activity decrease with the VOO diet, having both a crucial role on stress and eating behavior. In the adrenal gland, both HFDs showed an increase in angiotensinase aspartyl-aminopeptidase. The interrelation of angiotensinases activities in the tissues were depending on the type of diet. In addition, correlations were shown between angiotensinases and aminopeptidases that regulate stress and eating behavior. (4) Conclusions: Taken together, these results support that the source of fat in the diet affects several peptidases activities in the HPA axis, which could be related to alterations in RAS, stress and feeding behavior.

Percutaneous versus Transcutaneous Electrical Stimulation of the Posterior Tibial Nerve in Idiopathic Overactive Bladder Syndrome with Urinary Incontinence in Adults: A Systematic Review.

BACKGROUND: Percutaneous electrical stimulation and transcutaneous electrical stimulation (PTNS and TTNS) of the posterior tibial nerve are internationally recognized treatment methods that offer advantages in terms of treating patients with overactive bladder (OAB) who present with urinary incontinence (UI). This article aims to analyze the scientific evidence for the treatment of OAB with UI in adults using PTNS versus TTNS procedures in the posterior tibial nerve. METHODS: A systematic review was conducted, between February and May 2021 in the Web of Science and Scopus databases, in accordance with the PRISMA recommendations. RESULTS: The research identified 259 studies, 130 of which were selected and analyzed, with only 19 used according to the inclusion requirements established. The greatest effectiveness, in reducing UI and in other parameters of daily voiding and quality of life, was obtained by combining both techniques with other treatments, pharmacological treatments, or exercise. CONCLUSIONS: TTNS has advantages over PTNS as it is more comfortable for the patient even though there is equality of both therapies in the outcome variables. More research studies are necessary in order to obtain clear scientific evidence.

Immediate clinical benefits of combining therapeutic exercise and interferential therapy in adults with chronic neck pain: a randomized controlled trial.

BACKGROUND: Therapeutic exercise (TE) is highly recommended for the management of non-specific neck pain (NSNP) and has shown promising results combined with interferential current therapy. Yet, the clinical relevance of the pooled effect of these approaches remains uncertain. AIM: To investigate the immediate clinical effect size of combining TE and interferential therapy, compared with the isolated use of TE, in adults with chronic NSNP. DESIGN: Randomized, single-blinded, controlled, superiority trial. SETTING: Outpatients, primary care center. POPULATION: Forty-nine adults with chronic NSNP. METHODS: Participants with neck pain (grades I or II) lasting for more than 12 weeks were allocated to a TE plus interferential currents group (N.=25) or to a TE only group (N.=24). All individuals underwent treatment 5 times a week for 2 weeks. The primary outcome was current neck pain intensity (11-point Numeric Pain Rating Scale). Secondary outcomes included neck disability (Neck Disability Index) and active cervical range-of-movement (CROM device). Measurements were taken at baseline and immediately after treatment. An intention-to-treat analysis was carried out. To quantify the effect size of the interventions, the relative risk, the absolute and relative risk reduction, and the number needed to treat (NNT) were calculated. RESULTS: A significant time*group effect was found for pain intensity, disability, and neck flexion and right rotation (all, P<0.05). In the analysis for treatment benefit, the NNT was 2 (95% CI: 2 to 4, P<0.001) for neck pain and disability, and 3 (95% CI: 2 to 11, P=0.029) for neck flexion. CONCLUSIONS: Adding interferential therapy to TE is clinically more effective than TE alone to immediately improve neck pain and disability, but not active cervical range-of-movement, in adults with persistent neck pain. CLINICAL REHABILITATION IMPACT: Our results suggest that this multimodal intervention can be a useful strategy for rehabilitation of patients with NSNP. This is the first study on this topic reporting findings in terms of clinical relevance, which is key to transfer research evidence into practice.

Hypothalamic Renin-Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet.

The brain renin-angiotensin system (RAS) has been recently involved in the homeostatic regulation of energy. Our goal was to analyse the influence of a diet rich in saturated fatty acids (butter) against one enriched in monounsaturated fatty acids (olive oil) on hypothalamic RAS, and their relationship with the metabolism of fatty acids. Increases in body weight and visceral fat, together with an increase in aminopeptidase A expression and reductions in AngII and AngIV were observed in the hypothalamus of animals fed with the butter diet. In this group, a marked reduction in the expression of genes related to lipid metabolism (LPL, CD36, and CPT-1) was observed in liver and muscle. No changes were found in terms of body weight, total visceral fat and the expression of hepatic genes related to fatty acid metabolism in the olive oil diet. The expressions of LPL and CD36 were reduced in the muscles, although the decrease was lower than in the butter diet. At the same time, the fasting levels of leptin were reduced, no changes were observed in the hypothalamic expression of aminopeptidase A and decreases were noted in the levels of AngII, AngIV and AngIII. These results support that the type of dietary fat is able to modify the hypothalamic profile of RAS and the body energy balance, related to changes in lipid metabolism.

Enkephalinase activity is modified and correlates with fatty acids in frontal cortex depending on fish, olive or coconut oil used in the diet.

OBJECTIVE: Enkephalins are neuropeptides involved in functions such as pain modulation and/ or cognitive processes. It has been reported that dietary fat modifies enkephalins in the brain. Since enkephalins are hydrolyzed by enkephalinases, the study of the influence of dietary fats, differing in their degree of saturation, on brain fatty acids content and enkephalinase activity is important to understand its regulatory role on neuropeptides under different type of diets. METHODS: We analyzed enkephalinase activity, assayed with alanine-ß-naphthylamide as sub-strate, in frontal cortex of adult male rats fed diets supplemented with fish oil, olive oil or coconut oil, which markedly differed in the saturation of their fatty acids. RESULTS: Rats fed a diet enriched with coconut oil had lower soluble enkephalinase activity than the group fed olive oil (p<0.01) and fish oil (p<0.05) whereas rats fed a diet enriched with fish oil had lower membrane-bound enkephalinase activity than the group fed with olive (p<0.001) or coconut oil (p<0.05). Significant negative correlations were observed between certain fatty acids and enkephalinase activities in the groups fed with olive and coconut oils. No correlations were observed in the group fed with fish oil. CONCLUSIONS: Dietary fat modifies enkephalinase activity in the frontal cortex depending on the degree of saturation of the used oil. It is postulated that the functions, in which enkephalins are involved, such as pain modulation or cognitive functions, may also be affected according to the type of oil used in the diet.

Neuropeptidase activity in the frontal cortex of Wistar-Kyoto and spontaneously hypertensive rats treated with vasoactive drugs: a bilateral study.

BACKGROUND AND OBJECTIVE: Hypertension can lead to mood disorders that may worsen or ameliorate depending on the type of antihypertensive prescribed. Depression is associated with modifications in basal brain asymmetry particularly that of the frontal cortex, which is involved in blood pressure control. Furthermore, different vasoactive drugs may change the brain's asymmetry in a manner that contributes to cognition status. We studied the bilateral activity of several neuropeptidases in frontal cortex as a reflect of the functional status of certain neuropeptides involved in mood. METHODS: Using arylamide derivatives as substrates, we fluorometrically analysed the activity of these enzymes in the left and right frontal cortex of control untreated Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs) and compared their activities with WKY or SHR treated with the antihypertensive drugs captopril (CAP) and propranolol (PRO) or with the hypertensive N (G)-nitro-L-arginine methyl ester. SBP was also measured in all WKY and SHR groups. RESULTS: Untreated WKY, WKY treated with CAP or PRO and SHR treated with CAP exhibited normotensive values of SBP. However, WKY treated with N (G)-nitro-L-arginine methyl ester as well as untreated SHR and SHR treated with PRO and N(G)-nitro-L-arginine methyl ester demonstrated hypertensive values of SBP. Changes in the bilateral distribution of neuropeptidases were depending on the strain, the enzyme analysed and the drug used. Normotensive WKY groups (WKY, CAP, PRO) revealed intrahemispheric correlations mainly in the left hemisphere. In contrast, WKY treated with N(G)-nitro-L-arginine methyl ester and SHR groups demonstrated intrahemispheric correlations mainly in the right hemisphere. Interhemispheric correlations were mostly observed in WKY as well as in SHR groups with antihypertensive treatments (CAP, PRO). CONCLUSION: Our results suggest specific brain bilateral patterns of neuropeptidase activities in WKY that change in SHR. This observation may be related to the cognitive disorders that have been described in these animals and that change under antihypertensive or hypertensive drug's treatments.

Hyperbaric Oxygen Therapy in Retinal Arterial Occlusion: Epidemiology, Clinical Approach, and Visual Outcomes.

PURPOSE: To evaluate the efficacy and safety of hyperbaric oxygen therapy (HBOT) in patients with acute retinal artery occlusion (RAO). Secondarily, to analyse the epidemiology and the clinical approach. METHODS: Retrospective study of 13 patients submitted to HBOT between 2013 and 2018. The analysed parameters consisted of: systemic history, time between symptoms onset and treatment, initial approach, number of HBOT sessions, complications of HBOT and best corrected visual acuity-BCVA (of the total sample, central RAO-CRAO-group, and branch RAO-BRAO group). RESULTS: Arterial hypertension was the most prevalent systemic risk factor (53.8%). Initial therapies were 100% normobaric oxygen administration, topical and oral hypotensive medication, eye massage and aspirin. CRAO was observed in 69.2% and BRAO in 30.8% of the cases, with clinically significant visual improvement (a decrease in logMAR of 0.3) in 55.5% and 75%, respectively. Time between symptoms onset and treatment had a median of 9 hours. The median number of HBOT sessions was 7, without complications. CONCLUSIONS: HBOT provide BCVA improvement in patients with RAO, when it is performed in an early time after the symptom onset. It seems to be an effective and safe therapeutic option for a pathology that still remains without approved treatment.

Light-dark influence on enkephalinase activity in hypothalamus and pituitary.

OBJECTIVES: Enkephalins functions are partly modulated by enkephalinases especially membrane-bound alanyl aminopeptidase (EC-3.4.11.2) considered as the major enkephalin-degrading enzyme in brain. The analysis of its activity in standard and non-standard light/dark conditions may help the understanding of the regulatory mechanisms of enkephalins. METHODS: Enkephalinase activity was determined fluorometrically, using an arylamide derivative as substrate, in hypothalamus and pituitary of adult male rats, in a standard 12:12 h light/dark cycle; samples were collected at 10:00 h, 13:00 h and 16:00 h of the light period (light on from 7:00 to 19:00 h) and at 22:00 h, 01:00 h and 04:00 h of the dark one (light off from 19:00 h to 07:00 h). For comparison, the enzymatic activity was also measured in the same locations at the same time-points but under constant light conditions. RESULTS: In standard light/dark conditions, the results demonstrated an opposite daily rhythm in hypothalamus and pituitary. While the highest levels of AlaAP or enkephalinase activities were measured in hypothalamus during the dark period, they were the highest in the pituitary during the light one. In contrast, the lowest levels of activity were observed in the light period in the hypothalamus whereas they were in the dark one in the pituitary. A similar pattern was observed under constant light. The differences were however higher in hypothalamus and lower, but still significant, in pituitary. CONCLUSION: These results may reflect the behaviour of the endogenous substrates of enkephalinase and consequently be involved in their functions. This observation may affect the chronotherapeutic strategies.

Divergent profile between hypothalamic and plasmatic aminopeptidase activities in WKY and SHR. Influence of beta-adrenergic blockade.

AIMS: Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) differ in their renin-angiotensin system function and sympathetic tone. The metabolism of angiotensins and vasopressin depends on the action of certain aminopeptidases whose activity may be influenced by the autonomic nervous system. Their regulation may differ between WKY and SHR in hypothalamus and plasma according to the sympathetic tone. We analyzed aminopeptidases responsible for the hydrolysis of certain angiotensins, vasopressin, cholecystokinin or enkephalins in hypothalamus and plasma of WKY and SHR in untreated controls rats and under beta-adrenoceptor blockade. Systolic blood pressure, food intake, water intake and diuresis were measured as parameters modulated by the autonomic nervous system and the above mentioned peptides. MAIN METHODS: Glutamyl-, aspartyl-, cystinyl- and alanyl-aminopeptidase activities were analyzed fluorimetrically in plasma and hypothalamus of control and propranolol-treated (100mg/kg/day administered in drinking water for 1month) WKY and SHR, using arylamide derivatives as substrates. KEY FINDINGS: An opposite response of aminopeptidases to propranolol treatment between plasma and hypothalamus was observed in either WKY and SHR. Furthermore, the behavior of aminopeptidases was inversed between WKY and SHR either in hypothalamus and plasma: while the activity increased in hypothalamus and decreased in plasma of WKY, it decreased in hypothalamus and increased in plasma of SHR. SIGNIFICANCE: These results revealed an inverse response of aminopeptidases between hypothalamus and plasma and also an opposite behavior of these enzymes between WKY and SHR in hypothalamus and plasma. These observations support the involvement of the sympathetic system in the modulation of aminopeptidase activities.

Diurnal opposite variation between angiotensinase activities in photo-neuro-endocrine tissues of rats.

Central and peripheral renin-angiotensin systems (RASs) act in a coordinated manner for the physiologic functions regulated by neuroendocrine events. However, whereas the diurnal rhythm of peripheral circulatory and tissue RASs is well known, the circadian behaviour of their components in central photo-neuro-endocrine structures, key elements for the control of circadian rhythms, has been barely studied. In the present study, we analysed the aspartyl- (AspAP) and glutamyl-aminopeptidase (GluAP) (aminopeptidase A) activities, the angiotensinases responsible for the metabolism of Ang I to Ang 2-10 and Ang II to Ang III, respectively, in the retina, anterior hypothalamus and pituitary at different light and dark time-points of a 12:12 h light:dark cycle (7-19 h light), using arylamide derivatives as substrates. The results demonstrated that while retina and pituitary exhibited their highest levels of AspAP activity in the light period and the lowest in the dark one, the contrary occurred in the hypothalamus - the lowest levels were observed in light conditions and the highest in darkness. The outcome for GluAP showed the highest levels in the light period and the lowest in the dark one in the three tissues analysed. In conclusion, changes in angiotensinase activities throughout the daytime may cause changes of their respective substrates and derived peptides and, consequently, in their functions. This observation may have implications for the treatment of hypertension.

Facilitation of accurate and effective radiation therapy using fentanyl pectin nasal spray (FPNS) to reduce incidental breakthrough pain due to procedure positioning.

PURPOSE: To provide effective and accurate radiotherapy (RT) for advanced cancer patients who experience breakthrough pain (BP) due to positioning manoeuvres, through the use of FPNS. Secondary endpoints were the dose and time required to achieve a 50% numeric rating scale (NRS) reduction and conduction of a pharmacoeconomic analysis. PATIENTS AND METHODS: Twenty-seven advanced cancer patients with moderate-severe BP associated with routine radiotherapy procedures and manoeuvres were selected to receive FPNS. Most patients (20/27) had bone metastases. The patients showed a low Karnovsky performance status (mean 54%; range: 30-80). BP intensity was scored with the NRS before and after the procedures that triggered it. All patients were already receiving opioid baseline treatment at a total dose equivalent to 40-160mg oral morphine. Before the procedure, BP was treated with 100-400µg of FPNS. Data related to tolerance, pain relief, onset of the relief and efficient dose to allow RT to proceed were collected. RESULTS: In 26 patients the BP score was reduced by at least 50% as determined in 15.5min (range 8-35min) after fentanyl pectin intranasal administration, and pain relief started after 7min (range 3-15min); p<0.05 in both cases. The duration of pain reduction facilitated the proceeding of RT. The Mean NRS score before the procedure was 9 (95%CI: 8.6-9.4) and decreased during procedure to 3 (95%CI: 2.5-3.8). The average dose of FPNS for most patients was 100-200µg to achieve pain control, except in three patients who required progressive doses of up to 300-400µg. After receiving 300µg, one patient dropped out of the study due to severe adverse effects (nausea). Seven patients reported minor undesirable effects related to FPNS administration. CONCLUSIONS AND IMPLICATIONS: Certain necessary RT procedures in advanced cancer patients can cause severe BP episodes. A simple, safe, fast acting and strong analgesic is needed. FPNS is a rapidly absorbed opioid analgesic with a pain relief profile that would be particularly well suited for this patient population. By reducing BP, the drug enables the completion of necessary RT procedures without needless patient discomfort. When BP is attenuated, Department productivity is maintained and unnecessary delays are avoided. Further studies and clinical trials are needed to assess therapeutic FPNS dosages with a view to defining efficacy in the correct clinical context.

[NUTRIENTS AND RADIOTHERAPY; REVIEW OF THE LITERATURE]. / NUTRIENTES Y RADIOTERAPIA; REVISIÓN DE LA LITERATURA.

INTRODUCTION: nutrition is an important influence on treatments and quality of life of cancer patients. The relationship between different nutritional components and radiotherapy is today a topic of growing interest. OBJECTIVE: to evaluate the influence of macro and micronutrients on tolerance and effectiveness of radiotherapy and their role in modulating chronic toxicity. MATERIALS AND METHODS: we performed a research of the published literature by consulting the MEDLINE database and Cochrane Library online between 1995 and 2015, relevant publications based on impact factor were selected. Data from the analyzed studies were exposed in sections by type of nutrient. RESULTS: most of the studies showed common features: small sample sizes, high heterogeneity, underpowered results and few prospective randomized studies. In the section of fiber, its use in prophylaxis and treatment of radiation enteritis has been successfully evaluated in some studies, although evidence of its recommendation is still weak. Omega 3 and omega 6 fatty acids have a high metabolic potential, however the evidence regarding this benefit is limited to observational studies in certain tumors. Among the amino acids, glutamine is the most studied, and controversial results of its effect on mucositis, esophagitis and radiation enteritis were found. Vitamins and minerals are a heterogeneous group of substances that showed potential benefit due to their antioxidant activity and their supposed protector effect against toxicity secondary to radiotherapy. Ketogenic diets are beginning to be clinically studied after promising preclinical results. CONCLUSIONS: the analyzed studies show controversial or inconclusive results regarding the influence of nutrients in the radiotherapy. It has been not found Sorong evidence about their role in patients receiving ionizing radiation. Well-designed, prospective and randomized studies are needed to establish recommendations.

Introducción: la nutrición ejerce una importante influencia sobre los tratamientos y la calidad de vida del paciente oncológico. En la actualidad, la relación de los distintos componentes nutricionales con el tratamiento radioterápico es un tema de creciente interés. Objetivos: evaluar la posible influencia de los macro y micronutrientes sobre la tolerancia y eficacia del tratamiento radioterápico, así como su papel en la modulación de la toxicidad crónica. Material y métodos: se ha realizado una revisión bibliográfica consultando las bases de datos MEDLINE y Biblioteca Cochrane online entre los años 2000 y 2015, seleccionando los trabajos más relevantes según factor de impacto. Los datos obtenidos de los estudios analizados se han expuesto por apartados según el tipo de nutriente. Resultados: la mayoría de los estudios analizados presentan características comunes: pequeños tamaños muestrales, alta heterogeneidad en estudios de un mismo tema, escaso poder estadístico, pocos estudios prospectivos y aleatorizados. En el apartado de la fibra, su empleo como profilaxis y tratamiento de la enteritis rádica ha sido evaluado con resultados satisfactorios en algunos estudios, aunque la evidencia de su recomendación es todavía débil. Los ácidos grasos omega­3 y omega­6 tienen una gran potencialidad metabólica, aunque la evidencia de su beneficio se limita a estudios observacionales en determinados tumores. Entre los aminoácidos, la glutamina es el más estudiado, con resultados contradictorios en el aporte de beneficio en la mucositis oral, la esofagitis y la enteritis rádica. Las vitaminas y minerales constituyen un grupo heterogéneo de sustancias con beneficio potencial por su actividad antioxidante y su posible efecto protector, disminuyendo la toxicidad producida por la radioterapia. Las dietas cetogénicas están comenzando a estudiarse clínicamente después de los prometedores resultados preclínicos. Conclusiones: los estudios analizados muestran resultados contradictorios o poco concluyentes respecto a la influencia de los nutrientes en el tratamiento radioterápico. No se pueden establecer en la actualidadrecomen daciones claras sobre su papel. Son necesarios estudios prospectivos y aleatorizados, bien diseñados, para poder establecer recomendaciones.

Influence of extra virgin olive oil on blood pressure and kidney angiotensinase activities in spontaneously hypertensive rats.

High-fat diets are associated with the development of cardiovascular diseases. The efficacy of the current strategies of treatment is still not entirely satisfactory, and new approaches are being considered. To analyze the beneficial effects of extra virgin olive oil as a major component of the Mediterranean diet, we studied systolic blood pressure and angiotensinase activities, since this enzyme is involved in the metabolism of angiotensins, in the kidney of hypertensive rats fed during 12 weeks with a diet enriched with extra virgin olive oil compared with a standard diet. As a reflex of oxidative stress, 8-isoprostanes and nitric oxide were quantified in urine. Results demonstrated a progressive increase in systolic blood pressure until the end of the feeding period in both groups. However, this increase was delayed in the extra virgin olive oil group until week six, with the systolic blood pressure being always lower in this group. Nitric oxide and 8-isoprostanes were lower in the extra virgin olive oil group. While we can deduce a higher formation of angiotensin 2-10 in the renal cortex, a higher availability of angiotensin II may be presumed in the renal medulla of animals fed an extra virgin olive oil diet than in animals fed a standard diet. Our results support the beneficial influence of extra virgin olive oil on cardiovascular function and suggest that the Mediterranean diet may be beneficial in itself but it may also be an effective tool in the treatment of hypertension.

Brain, heart and kidney correlate for the control of blood pressure and water balance: role of angiotensinases.

The renin-angiotensin system (RAS) plays a major role in the control of blood pressure (BP) and water balance by coordinating brain, heart and kidney functions, connected with each other by hormonal and neural mechanisms through the autonomic nervous system (ANS). RAS function may be monitored by the study of the enzymes (angiotensinases) involved in the metabolism of its active peptides. In order to study the relationship between the brain-heart-kidney axis and the control of BP and water balance, we analyzed the correlation of angiotensinase activities, assayed as arylamidase activities, between hypothalamus, left ventricle, renal cortex and renal medulla, collected from Wistar-Kyoto and spontaneously hypertensive rats, treated or not treated with L-NAME [N(G)-nitro-L-arginine methyl ester]. This compound not only inhibits the formation of nitric oxide but also disrupts the normal function of the ANS activating the sympathetic nervous system (SNS) to increase BP. In addition, to assess the influence of the SNS, we studied the effect of its blockade by treatment of both strains with propranolol. The present results support the notion that RAS function of the brain-heart-kidney axis, as reflected by the activities of angiotensinases, is reciprocally connected by afferent and efferent mechanisms between these locations, presumably through the ANS. These results reveal new aspects of neuroendocrine regulation possibly involving the ANS.

Dietary fatty acid composition affects aminopeptidase activities in the testes of mice.

The autocrine/paracrine control mechanisms of local factors, such as the renin-angiotensin system and the thyrotropin-releasing hormone (TRH), seem to play a relevant role in testicular physiology. It has been proposed that dietary fat composition influences male reproductive function modifying the cholesterol-phospholipid composition of testicular plasma membranes. Modifications in the composition and physical properties of the membranes may lead to alterations in the activities of membrane-bound (M-B) enzymes. We have previously demonstrated that cholesterol and steroid hormones affect aminopeptidase (AP) activities. Dietary fatty acids with different degrees of saturation modified AP activities in the serum of mice and an olive oil supplemented diet influenced the AP activities in the testes of mice. We hypothesized that the modification of dietary fat composition may affect angiotensin- [glutamyl-AP (GluAP), aspartyl-AP (AspAP)] and TRH- [pyroglutamyl-AP (pGluAP)] degrading activities in the testis. In this study, we investigated the effect of diets supplemented with sunflower oil (SFO), fish oil (FO), olive oil (OO), lard (L) or coconut oil (CO) on soluble (Sol) and M-B GluAP, AspAP and pGluAP in mice testis, using arylamides as substrates. Sol GluAP activity did not show differences among groups. However, Sol AspAP and Sol pGluAP progressively decreased with the degree of saturation of the fatty acid used in the diet. In contrast, M-B GluAP progressively increased with the degree of saturation of the fatty acid used in the diet. For M-B AspAP activity, mice fed diets containing FO showed significantly higher levels than those fed diets containing SFO, OO and L but not those containing CO. For M-B pGluAP activity, the highest levels were observed for mice fed diets containing FO and OO. The present data suggest that the type of fat used in the diet may influence the autocrine/paracrine functions of locally synthesized angiotensin peptides and TRH in the testis, and consequently may be important in male reproductive functions.