Biomarcadores pronósticos en el uso del radio-223 en pacientes con cáncer de próstata metastásico resistente a la castración / Prognostic biomarkers in the use of radium-223 in patients with metastatic castration-resistant prostate cancer

Objetivos Establecer biomarcadores basales en pacientes con cáncer de próstata metastásico resistente a la castración (CPMRC) tratados con Ra-223 que predigan una mejor supervivencia global (SG), así como valorar la toxicidad hematológica y la respuesta. Materiales y métodos Estudio retrospectivo multicéntrico en 151 pacientes con CPMRC tratados con Ra-223 entre 2013 y 2020. Se valoró la SG de acuerdo a: los niveles basales de hemoglobina (Hb), el antígeno prostático específico (PSA), la fosfatasa alcalina (FA), la escala de dolor de la OMS, el Eastern Cooperative Oncology Group (ECOG), el número de lesiones en gammagrafía ósea (GO), el uso de agentes de protección ósea y las dosis recibidas. Se determinó el grado de toxicidad hematológica y la respuesta basada en los cambios de la FA y el dolor pre y postratamiento. Resultados Mediana de SG de 24meses (IC95%: 16,5-31). En el 70% que recibieron tratamiento completo (5-6dosis) la mediana de SG fue de 34,9meses, versus 5,8 en el tratamiento incompleto (1-4dosis). La SG fue mayor en los pacientes con menor PSA, FA, Hb>13g/dl, menor número de metástasis óseas y ECOG 0-1. 52/151pacientes (34%) fallecieron durante el seguimiento. Cerca del 70% de los pacientes presentaron disminución del dolor, y el 66%, reducción de la FA. La mitad de los pacientes presentaron eventos adversos hematológicos leves, y solo el 5%, severos. Conclusiones Los pacientes con CPMRC tratados con Ra-223 que presentan biomarcadores basales como Hb>13g/ml, ECOG 0-1, PSA<20ng/ml y menor número de lesiones en GO muestran mejor SG, con un adecuado perfil de seguridad (AU)

Objectives Establish basal biomarkers in patients with bone metastatic castration-resistant prostate cancer (mCRPC) treated with Ra-223 that predicted a better overall survival (OS), assess hematology toxicity and treatment response. Materials and methods Retrospective multicenter study in 151 patients with mCRPC between 2013 and 2020. OS was assessed according to basal hemoglobin (Hb), PSA, alkaline phosphatase (AP), WHO pain scale, Eastern Cooperative Oncology Group (ECOG), number of metastatic lesions on bone scan (BS), use of protective bone agents and received. Hematological toxicities were evaluated. Treatment response was based on changes in FA and pain. Results Median OS was 24months (95%CI: 16.5-31). OS in 70% of patients who received complete Ra-223 treatment (5-6 doses) was 34.9m vs. 5.8m in patients with incomplete treatment (1-4 doses). OS was longer in patients with lower PSA and AP, Hb>13g/dL, lesser bone metastasis on GO and ECOG 0-1. 52/151 patients (34%) died during follow-up. Nearly 70% of patients experienced decrease in pain and 66% reduction on AP. Half of patients had mild hematological adverse effects and only 5% had severe. Conclusions mCRPC patients treated with Ra-223 who had Hb>13g/mL, ECOG 0-1, low AP, PSA<20ng/ml and lesser bone metastasis on BS shown a better OS with adequate safety profile (AU)

Prognostic biomarkers in the use of radium-223 in patients with metastatic castration-resistent prostate cancer.

OBJECTIVES: This study aimed to establish basal biomarkers in patients with bone metastatic castration-resistant prostate cancer (mCRPC) treated with 223Ra to predict better overall survival (OS), and assess hematologic toxicity and treatment response. MATERIALS AND METHODS: This was a retrospective multicenter study including 151 patients with mCRPC between 2013 and 2020. OS was assessed according to basal hemoglobin (Hb), prostate-specific antigen (PSA), and alkaline phosphatase (AP) values, the World Health Organization pain scale, the Eastern Cooperative Oncology Group (ECOG) performance status scale, the number of metastatic lesions on bone scintigraphy (BS), and the use of protective bone agents and the dose received. The grade of hematological toxicities was evaluated as well as treatment response based on changes in AP and pre- and post-treatment pain. RESULTS: The median OS was 24 months (95% confidence interval 16.5-31). The OS in 70% of patients who received complete (5-6 doses) versus incomplete (1-4 doses) 223Ra treatment was 34.9 vs. 5.8 months, respectively, being longer in patients with lower PSA and AP values, Hb >13 g/dl, lesser bone metastasis on bone scan and with an ECOG 0-1. 52/151 patients (34%) died during follow-up. Pain reduced in nearly 70% of patients and 66% presented a reduction in AP values. Half of the patients presented mild and 5 % severe hematological adverse effects. CONCLUSIONS: mCRPC patients treated with 223Ra with Hb values >13 g/mL, an ECOG 0-1, low AP values, PSA < 20 ng/mL and lesser bone metastasis on BS presented a better OS with an adequate safety profile.

The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE).Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated.Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Cytokine distribution in mothers and breastfed children after omega-3 LCPUFAs supplementation during the last trimester of pregnancy and the lactation period: A randomized, controlled trial.

OBJECTIVE: To determine whether maternal diet supplementation with omega-3 long chain polyunsaturated fatty acids (omega-3 LC-PUFAs) during the last trimester of pregnancy and the breastfeeding period influences the levels of inflammatory cytokines in mother and infants. MATERIAL AND METHOD: This registered, double-blind randomized study included 46 pregnant women, who were randomly allocated to either an experimental group receiving 400mL/day of a fish oil-enriched dairy drink [320mg docosahexaenoic acid (DHA) + 72mg eicoapentaenoic acid] (FO group, n = 24) or to a control group receiving 400mL/day of a non-supplemented dairy drink (CT group, n = 22), from week 28 of pregnancy until the fourth month of lactation. During the study, maternal dietary patterns were monitored by a nutritionist, who encouraged compliance with current recommendations of fatty acids intake. DHA concentrations and cytokine levels (GM-CSF, IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-α) were measured in maternal plasma at the moment of recruitment and in maternal (n = 46) and infant (n = 46) plasma at birth and 2.5 months after birth. RESULTS: Maternal plasmatic IL-4 levels were higher in FO than in CT subjects (p = 0.009). Additionally, a tendency was observed to higher IL-10 and IL-2 in the FO group. Plasmatic IL-6 however, was higher in CT mothers (p = 0.001). TNF-α was higher in CT infants at birth and 2.5 months after birth (p = 0.005). An analysis of possible relationships between DHA and the concentrations of different cytokines revealed negative correlation between maternal plasmatic IL-6 and DHA (higher plasmatic DHA corresponded to lower IL-6). CONCLUSIONS: Maternal dietary omega-3 LC-PUFAs supplementation during critical periods like pregnancy, lactation and early newborn development may influence the levels of certain inflammatory cytokines, reducing pro-inflammatory cytokines and promoting an anti-inflammatory "environment".

Goat milk consumption modulates liver divalent metal transporter 1 (DMT1) expression and serum hepcidin during Fe repletion in Fe-deficiency anemia.

Iron deficiency is the most prevalent micronutrient deficiency worldwide. In spite of the crucial role of hepatocyte divalent metal transporter 1 (DMT1) and hepcidin in Fe metabolism, to date, no studies have directly tested the role of these proteins in liver Fe metabolism during Fe repletion after induced Fe-deficiency anemia. Therefore, the aim of the current study was to assess the effect of goat or cow milk-based diets on Fe metabolism in one of the main body storage organs, the liver, during the course of Fe repletion with goat or cow milk-based diets in anemic rats. Animals were placed on a preexperimental period of 40 d, a control group receiving a normal-Fe diet and the Fe-deficient group receiving a low-Fe diet (5 mg of Fe/kg of diet). Rats were fed for 30 d with goat or cow milk-based diets with normal Fe content (45 mg of Fe/kg of diet). The hematological parameters, serum hepcidin, hepatosomatic index, liver Fe content, and liver DMT1 expression were determined. During the recovery of the anemia with milk-based diets, the restoration of liver Fe content and hematological parameters, especially with goat milk, increased the red blood cell count, favoring the oxygen supply and weight gain. Moreover, goat milk consumption potentiates liver DMT1 expression, enhancing Fe metabolism and storage. In addition, the increase in serum hepcidin in anemic rats observed in the current study also explains and supports the higher liver Fe content after supplying goat milk, because it blocks the liberation of Fe from hepatocytes, increasing its storage in liver.

Unprotected carotid artery stenting in symptomatic patients with high-grade stenosis: results and long-term follow-up in a single-center experience.

BACKGROUND AND PURPOSE: The use of cerebral protection during CAS is an extended practice. Paradoxically it is open to question because it can lead to potential embolic complications. The aim of this study was to evaluate the safety and efficacy of CASWPD in patients with severe symptomatic carotid artery stenosis. MATERIALS AND METHODS: A prospective study was performed including 210 consecutive patients (201 symptomatic and 9 asymptomatic) with carotid artery stenosis >70%. All patients were treated by CASWPD. Angiographic results and neurologic complications were recorded during the procedure and within 30 days after it. All patients underwent clinical evaluation and Doppler sonography follow-up at 3, 6, and 12 months after the procedure. RESULTS: Two hundred twenty carotid arteries were treated. The average degree of stenosis was 88.9%. The procedure was successfully completed in 212 (96.4%) arteries. After stent placement, 98.6% of arteries showed no residual stenosis or <30%. Balloon angioplasty dilation before stent placement was performed in 16% of cases. During the 30-day periprocedural period, there were 3 major complications (1.4%), including 1 disabling ischemic stroke, 1 acute stent thrombosis, and 1 MI. The last 2 patients died from these complications. At 1-year follow-up 24 (12.8%) restenoses, 2 new ipsilateral strokes, 1 contralateral stroke, and 5 deaths (2.7%) had occurred. None of these deaths were related to the initial stroke. CONCLUSIONS: In our study, unprotected stent placement in symptomatic patients with severe carotid artery stenosis has demonstrated a low incidence of complications. We believe that this is due to the reduction of maneuvering and manipulation through the stenosis and to the protective effect of the stent placement before angioplasty balloon dilation.

Olive oil and mitochondrial oxidative stress.

This review summarizes studies on the role of olive oil intake in the prevention and attenuation of mitochondrial oxidative stress derived from several situations such as ageing, physical exercise, treatment with adriamycin or intake of thermally oxidised oils. After more than fifteen years of studies on these issues, results have demonstrated that under different models of oxidative stress the regular intake of virgin olive oil as dietary fat is able to attenuate or increase free radical production at the mitochondrial level to a lower extent than when n-6 polyunsaturated oils are used. In the same way, virgin olive oil leads to better function of the mitochondrial electron transport chain.

El tartaro de los nadadores / The swimmer's tartar

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Dietary fat type and regular exercise affect mitochondrial composition and function depending on specific tissue in the rat.

Physical exercise and fatty acids have been studied in relation to mitochondrial composition and function in rat liver, heart, and skeletal muscle. Male rats were divided into two groups according to dietary fat type (virgin olive and sunflower oils). One-half of the animals from each group were subjected to a submaximal exercise for 8 weeks; the other half acted as sedentary controls. Coenzyme Q, cytochromes b, c + c1, a + a3 concentrations, and the activity of cytochrome c oxidase were determined. Regular exercise increased (P < 0.05) the concentration of the above-mentioned elements and the activity of the cytochrome c oxidase by roughly 50% in liver and skeletal muscle. In contrast, physical exercise decreased (P < 0.05) cytochrome c oxidase activity in the heart (in micromol/min/g, from 8.4+/-0.1 to 4.9+/-0.1 in virgin olive oil group and from 9.7+/-0.1 to 6.7+/-0.2 in sunflower oil animals). Dietary fat type raised the levels of coenzyme Q, cytochromes, and cytochrome c oxidase activity in skeletal muscle (P < 0.05) among the rats fed sunflower oil. In conclusion, dietary fat type, regular exercise, and the specific tissue modulate composition and function of rat mitochondria.

Oxidative stress induced by exercise and dietary fat modulates the coenzyme Q and vitamin A balance between plasma and mitochondria.

Physical exercise induces oxidative stress. Dietary fat modulates lipid composition of plasma and fatty acid profile of mitochondrial membranes. Over 8 wk, two groups of rats were fed virgin olive oil or sunflower oil as the only fat sources. Both groups were divided into 4 subgroups according to exercise: one of sedentary rats and the other three of rats subjected to different exercises on a treadmill. There was a lower concentration of vitamin A and coenzyme Q in the plasma of animals subjected to exercise compared to the sedentary animals. The concentrations of these molecules in liver and skeletal muscle mitochondria of animals exercised until exhaustion were higher than in sedentary animals. This can suggest the existence of a balance between plasma and mitochondrial membrane for these antioxidants as a response to an oxidative attack.

Virgin olive oil and coenzyme Q10 protect heart mitochondria from peroxidative damage during aging.

The mitochondrial theory of aging suggests that this phenomenon is the consequence of random somatic mutations in mitochondrial DNA, induced by long-term exposure to free radical attack. There are two potential dietary means of delaying the effects of free radicals on cellular aging, i.e., enrichment of mitochondrial membranes with monounsaturated fatty acids and supplementation with antioxidants. We have performed a preliminary study on male rats, 6 or 12 month old, fed with diets differing in the nature of the fat (virgin olive oil or sunflower oil) and/or with antioxidant supplementation (coenzyme Q10), analysing hydroperoxide and coenzyme Q9 and Q10 in heart mitochondria. Preliminary results allow us to conclude that the CoQ10 dietetic supplementation as well as the enrichment of the cellular membranes with monounsaturated fatty acids, successfully protect mitochondrial membranes from aged rats against the free radical insult.

Relative importance of the saponified and unsaponified fractions of dietary olive oil on mitochondrial lipid peroxidation in rabbit heart.

The effects of four edible oils on lipid peroxidation have been investigated in rabbit heart mitochondrial membranes. The experimental oils (olive oil from the variety "picual", washed olive oil from the variety "picual", olive oil from the variety "arbequina" and high-oleic sunflower oil) had a similar fatty-acid composition, but differed in their unsaponified fraction (polyphenols, tocopherols, and others). The lowest hydroperoxide levels were found with picual and washed picual. No differences in mitochondrial membrane thiobarbituric acid reactive substance (TBARS), alpha-tocopherol concentrations and cytosolic antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) were found, whereas the CoQ10 content correlated inversely with hydroperoxide levels in all groups. These results suggest that mitochondrial membranes with high levels of monounsaturated fatty acids generate low levels of lipid peroxidation. Moreover, the saponified fraction of the experimental diets proved more important in preventing lipid peroxidation than the unsaponified fraction. Lastly, coenzyme Q may help to prevent peroxidative stress damage in rabbit heart mitochondria.

Plasma antioxidants are strongly affected by iron-induced lipid peroxidation in rats subjected to physical exercise and different dietary fats.

Plasma is an important vehicle through which antioxidant molecules are conveyed and in which they may show different behaviors, either acting as a protective factor for oxidative damage to different blood elements or using it as a vehicle through which dietary antioxidant factors would be distributed to the body. The aim of the study was to determine the plasma level of vitamin E, coenzyme Q, uric acid and vitamin A and their relation with the cellular oxidative damage mediated by physical training and the ingestion of different fat (virgin olive and sunflower oils). Male Wistar rats were divided into 8 subgroups based on the dietary fat intake and their physical activity. Results show that both dietary fat and physical training affect susceptibility to iron-induced lipid peroxidation in plasma and the tissues that were studied. The increase of this lipid peroxidation parallels a decrease of the level of all the plasma antioxidants that were studied.

Lipid peroxidation and antioxidants in erythrocyte membranes of full-term and preterm newborns.

The most probable factor connecting premature infant problems such as retinopathy, intraventricular hemorrhage and chronic lung disease appears to be the excessive production of oxygen free radicals which can occur as a consequence of oxygen therapy. The aim of our investigation was to elucidate the possible correlations between lipid peroxidation, in this study measured as hydroperoxides production, and antioxidant concentrations in erythrocyte membranes of both full term and preterm infants. Hydroperoxide concentrations were found to be high, especially in premature infants, in erythrocyte membranes at birth and in the initial days of life. The erythrocyte membranes were also found to contain low levels and/or low activities of antioxidant defense mechanisms which was more evident in premature newborns where alpha-tochopherol levels were significantly lower in comparison to full term infant levels. Furthermore, when premature infants undergo oxygen therapy these effects were exacerbated. These results demonstrate that at birth, particularly in the premature newborn, the degree of oxidative stress outweighs the antioxidant defense mechanisms.

Dietary intake and anthropometric measures in a Spanish students group.

Two four-day diet records were used to estimate usual energy and nutrient intake, eating patterns (habits) and contribution of meals to total energy intake, in a group of 92 biology students from the Granada University. At the same time, a series of anthropometric measures was taken from each subject (weight, height, skin pleats and arm measurement). Comparison of real intakes with those recommended was carried out using the 1980 Spanish recommendations and the 1992 European Community recommendations. For men (n = 42) mean intakes for most nutrients were similar to the recommended levels and the proportion with intakes of vitamins and minerals below 80% of the recommended intakes was also minimal. Among women (n = 50) mean intake of zinc was below 80% of the Spanish recommendation. However, there was a wide range of intakes of minerals and vitamins within both groups; therefore, we found a high percentage of subjects with intakes of some vitamins or minerals below 80% of the recommended intakes. Finally, anthropometric measures showed normal body weight, height, and body composition among the students.

[Posterior cortical dementia]. / Demencia cortical posterior.

Two patients, aged 59 and 73 years, presented with the clinical syndrome of Posterior Cortical Dementia (PCD). Follow-up during 3 and 11 years confirmed the progressive nature of the disorder. Posterior cerebral impairment was seen on SPECT studies. Neuroimaging studies showed an early dilatation of the right occipital ventricular horn which predominated over the cortical atrophy. This kind of cerebral atrophy could identify a subset of PCD cases that may be unrelated to Alzheimer's disease.

[Clinical and ultrasonographic data in ectopic pregnancy]. / Datos clínicos y ultrasonográficos asociados al diasgnóstico de embarazo ectópico.

In order to evaluate the clinical and sonographic findings in 60 patients with ectopic pregnancy confirmed at laparotomy, we carried out a prospective study at the Hospital de Gineco-Obstetricia del Centro Médico León, Instituto Mexicano del Seguro Social. The patients were 28.17 years old, average. The ectopic pregnancy was more common in multiparous women (80%) than in nuliparous ones. The obstetric risk factors more frequent were abortion (26.6%) and use of intrauterine device (23.3%). The clinical sign reported most common was pelvic pain, referred in 48 patients (80%). Hemodynamic changes were detected in 21.6% of the cases. The ultrasound findings were seen in most of the patients and heterogeneous adnexal mass was observed in 91.6% of them, moreover intraperitoneal fluid was reported in 61.6% of the patients with ectopic pregnancy. The heterogeneous adnexal mass had a direct relationship with the diagnosis of ectopic pregnancy and had a correlation coefficient value R = 0.99 (P < 0.01). The ultrasonographic findings seen with transvaginal technique were similar than those obtained through transabdominal procedure. We conclude that ultrasonography has a definite role in improving the diagnosis of ectopic pregnancy.

Cluster tic syndrome.

Cluster tic syndrome (CTS) is a disorder characterized by three types of pain attacks. One resembles trigeminal neuralgia, the second resembles cluster headache, and the third is mixed, starting as a neuralgic pain immediately followed by a homolateral headache accompanied by autonomic signs. This type of attack is pathognomonic for CTS. The three pain types can all be provoked. CTS appears between ages 20 and 70 and may be either episodic or chronic; medical treatment is poor.

Cluster-tic syndrome and basilar artery ectasia: a case report.

A 54-year-old patient presented with two types of pain. The first was similar to trigeminal neuralgia and the second was similar to cluster headache. Clinical diagnosis was cluster-tic syndrome. Neuro-imaging studies disclosed an ectatic basilar artery. The significance of this finding is difficult to ascertain.