Errores de interpretación / Interpretation errors

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Osteoporosis / Osteoporosis

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¿Medicinas alternativas? / Alternative medicines?

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Inhibitory role of oxytocin on TNFα expression assessed in vitro and in vivo.

AIM: Oxytocin administration to diet-induced obese (DIO) rodents, monkeys and humans decreases body weight and fat mass with concomitant improvements in glucose metabolism. Moreover, several studies show an immunomodulatory role of oxytocin in a number of settings (such as atherosclerosis, injury, sepsis). This study aims to shed some light on the effects of oxytocin on macrophage polarization and cytokine production, as well as its possible impact on these parameters in adipose tissue in DIO mice with impaired glucose metabolism. METHODS: Mouse bone marrow cells were differentiated into macrophages and treated with oxytocin. Macrophage proliferation, cytokine secretion and macrophage populations were determined. For experiments in vivo, DIO mice were treated with oxytocin for 2 weeks. Body weight and composition and glucose tolerance were subsequently followed. At the end of treatment, adipose tissue macrophage populations, plasma cytokine levels and cytokine expression in adipose tissue were determined. RESULTS: In bone marrow-derived macrophages, oxytocin induced an anti-inflammatory phenotype (decreased M1/M2 ratio). In M1-derived macrophages, oxytocin decreased TNFα secretion, with no effects on the other cytokines tested nor any effect on cytokine secretion by M2-derived macrophages. Oxytocin treatment in DIO mice in vivo led to decreased body weight accompanied by an improvement in glucose tolerance, with no changes in plasma cytokine levels. In adipose tissue, oxytocin decreased Tnfα expression without modifying the M1/M2 macrophage ratio. CONCLUSION: Oxytocin treatment decreases TNFα production both in vitro (in bone marrow-derived macrophages) and in vivo (in epididymal adipose tissue) in DIO mice. This effect may also be contributory to the observed improvement in glucose metabolism.

Las nuevas tecnologías de la información / New information technologies

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Virus Zika / Zika virus

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Avances en diagnóstico prenatal / Advances in prenatal diagnosis

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Oral anticoagulation in primary care.

Oral anticoagulant therapy is currently widespread in the population and primary care plays an important role in its control in Spain. Younger populations, such as those in prisons, often require this treatment for reasons other than atrial fibrillation, often in relation to valvular or congenital or acquired hypercoagulability situations. The possibility of obtaining the INR by portable coagulometers has allowed primary care physicians to tackle the indication of this therapy and the control of these patients in coordination with haematology services. The emergence of new therapeutic alternatives (Dabigatran, Rivaroxaban, Apixaban and Edoxaban, the so called "ACOD") has permitted the expansion of options for oral anticoagulation in some cases, since they do not require systematic monitoring of their effect and interact with far fewer drugs than their predecessors, although there are still restrictions by the health authorities on their widespread use. This article reviews the different indications of oral anticoagulant therapy according to the new recommendations as well as the clinical scenarios in which it should be used.

Anticoagulación oral en Atención Primaria / Oral anticoagulation in primary care

El tratamiento anticoagulante oral (TAO) está hoy en día ampliamente difundido en la población y en el caso de nuestro país la atención primaria juega un papel relevante en su control. La población joven, como la de los centros penitenciarios, muchas veces requiere de este tratamiento por motivos diferentes a la fibrilación auricular, muchas veces en relación con valvulopatías o situaciones de hipercoagulabilidad congénitas o adquiridas. La posibilidad de obtener mediante coagulómetros portátiles el INR de los pacientes ha permitido que los médicos de atención primaria asuman la indicación de esta terapia y el control de estos pacientes en coordinación con los servicios de hematología. La aparición de nuevas alternativas terapéuticas (Dabigatran, Rivaroxaban, Apixaban y Edoxaban, los llamados 'ACOD') ha permitido ampliar las opciones de anticoagulación oral en algunos casos, aunque todavía existen restricciones por parte de las autoridades sanitarias para su uso generalizado. No requieren monitorización sistemática de su efecto e interaccionan con muchos menos fármacos que sus predecesores. Este artículo repasa las diferentes indicaciones de la terapia anticoagulante oral de acuerdo con las nuevas recomendaciones, así como los escenarios clínicos en los que se debe utilizar (AU)

Oral anticoagulant therapy is currently widespread in the population and primary care plays an important role in its control in Spain. Younger populations, such as those in prisons, often require this treatment for reasons other than atrial fibrillation, often in relation to valvular or congenital or acquired hypercoagulability situations. The possibility of obtaining the INR by portable coagulometers has allowed primary care physicians to tackle the indication of this therapy and the control of these patients in coordination with haematology services. The emergence of new therapeutic alternatives (Dabigatran, Rivaroxaban, Apixaban and Edoxaban, the so called 'ACOD') has permitted the expansion of options for oral anticoagulation in some cases, since they do not require systematic monitoring of their effect and interact with far fewer drugs than their predecessors, although there are still restrictions by the health authorities on their widespread use. This article reviews the different indications of oral anticoagulant therapy according to the new recommendations as well as the clinical scenarios in which it should be used (AU)

The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice.

AIMS/HYPOTHESIS: Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function. METHODS: Rkip1 (also known as Pebp1) knockout (Rkip1 (-/-)) mice were characterised in terms of pancreatic and glucose homeostasis, including morphological and functional analysis. Glucose tolerance and insulin sensitivity were examined, followed by assessment of glucose-induced insulin secretion in isolated islets and beta cell mass quantification through morphometry. Further characterisation included determination of endocrine and exocrine proliferation, apoptosis, MAPK activation and whole genome gene expression assays. Capacity to reverse a diabetic phenotype was assessed in adult Rkip1 (-/-) mice after streptozotocin treatment. RESULTS: Rkip1 (-/-) mice exhibit a moderately larger pancreas and increased beta cell mass and pancreatic insulin content, which correlate with an overall improvement in whole body glucose tolerance. This phenotype is established in young postnatal stages and involves enhanced cellular proliferation without significant alterations in cell death. Importantly, adult Rkip1 (-/-) mice exhibit rapid reversal of streptozotocin-induced diabetes compared with control mice. CONCLUSIONS/INTERPRETATION: These data implicate RKIP1 in the regulation of pancreatic growth and beta cell expansion, thus revealing RKIP1 as a potential pharmacological target to promote beta cell regeneration.

Glucose and fructose as functional modulators of overall dog, but not boar sperm function.

The main aim of the present work was to test the effects of glucose and fructose on the phosphorylation levels of proteins linked to the control of overall sperm function in two species with very different metabolic characteristics, dog and boar. Incubation of dog spermatozoa with 10mM glucose increased serine phosphorylation of proteins related to cell cycle and signal transduction including cyclins B and E, Cdk2, Cdk6, Cdc6, PYK2, c-kit, Raf-1, TRK and several protein phosphatases. Incubation of dog spermatozoa with 10mM fructose decreased serine phosphorylation levels of cyclins B and D3, Cdk1/Cdc2, Cdk2, Cdk6, Akt, PI3 kinase, ERK-1 and protein kinase C. Incubation of boar spermatozoa with glucose or fructose did not modify any of the phosphorylation patterns studied. Given that one important difference between dog and boar spermatozoa is the presence of glucokinase (GK) in dog but not in boar, GK-transfected COS7 cells were incubated with either 10mM glucose or 10mM fructose. Incubation of GK-transfected cells with fructose decreased serine phosphorylation of cyclin A, ERK-2 and Hsp-70. In contrast, incubation of control COS7 cells with fructose increased serine phosphorylation of Cdk6, Cdk1/Cdc2, protein kinase C and Hsp-70. Incubation with glucose did not induce any significant effect. Our results indicate that monosaccharides act as signalling compounds in dog spermatozoa after ejaculation through changes in the phosphorylation levels of specific proteins. One of the factors that may be related to the action of sugars is the equilibrium of the total sperm hexokinase activity, in which the presence or absence of GK appears to be relevant.

The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass biomarker.

AIMS/HYPOTHESIS: Transmembrane protein 27 (TMEM27) is a membrane protein cleaved and shed by pancreatic beta cells that has been proposed as a beta cell mass biomarker. Despite reports of its possible role in insulin exocytosis and cell proliferation, its function in beta cells remains controversial. We aimed to characterise the function of TMEM27 in islets and its potential use as a beta cell mass biomarker. METHODS: To determine TMEM27 function, we studied TMEM27 gene expression and localisation in human healthy and diabetic islets, the correlation of its expression with cell cycle and insulin secretion genes in human islets, its expression in tungstate-treated rats, and the effects of its overproduction on insulin secretion and proliferation in a beta cell line and islets. To elucidate its utility as a beta cell mass biomarker, we studied TMEM27 cleavage in a beta cell line, islets and primary proximal tubular cells. RESULTS: TMEM27 mRNA levels in islets are lower in diabetic donors than in controls. Its gene expression correlates with that of insulin and SNAPIN in human islets. TMEM27 expression is downregulated in islets of tungstate-treated rats, which exhibit decreased insulin secretion and increased proliferation. TMEM27 overproduction in a beta cell line and islets significantly enhanced glucose-induced insulin secretion, with modest or no effects on proliferation. Finally, TMEM27 is cleaved and shed by renal proximal tubular cells and pancreatic islets. CONCLUSIONS/INTERPRETATION: Our data support a role for TMEM27 in glucose-induced insulin secretion but not in cell proliferation. The finding that its cleavage is not specific to beta cells challenges the current support for its use as a potential beta cell mass biomarker.

Fertility and histology after rabbit ovarian wedge resection with CO2 laser or electrocautery using posterior reconstruction with nylon or polyglactin sutures.

In an experimental study in rabbits, the CO2 laser and electrocautery were compared in performing microsurgical ovarian wedge resection; polyglactin and nylon sutures were compared for ovarian reconstruction. Histologic reaction, adhesion formation, and functional parameters (number of corpora lutea, number of pregnancies, nidation index) were evaluated 30 and 90 days postoperatively. Thirty days after surgery, the tissue inflammatory response was very similar in the four groups; fibrosis was not detected. Significant reductions (P less than 0.01) were found for the experimental (operated right ovary) vs. the control (unoperated left ovary) groups when comparing the number of corpora lutea and the number of pregnancies. No significant differences in the nidation index were demonstrated. Adhesion formation was not different between any of the experimental procedures; adhesions were not detected in the control ovaries. At 90 days, the polyglactin suture was entirely absorbed and no inflammatory reaction persisted. Minimal giant cell infiltration was found around the nylon suture. The histologic differences between the two sutures were statistically significant (P less than 0.02). No fibrosis was observed. The functional parameters did not reveal statistically significant differences between the two sutures.

Serial measurements of a plasma prostacyclin inhibitor in a patient with recurrent abortions and lupus anticoagulant; a case report.

Defective plasmatic stimulation of prostacyclin (PGI2) production by vascular cells has been described in patients with lupus anticoagulant (LAC). A young woman with recurrent abortions, LAC and evidence for deficient PGI2 production was studied. Serial measurements of a plasma PGI2 inhibitor, LAC and anticardiolipin antibodies (ACA) have been performed before and throughout her fourth pregnancy. Antenatal care and treatment with prednisone and heparin started at 10 weeks gestation. The plasma of our patient continued to inhibit PGI2 production by vascular cells despite treatment. The presence of inhibitor(s) of PGI2 release was confirmed by mixing the patient's plasma with normal plasma. In addition, an IgM lupus anticoagulant fraction (but not the IgG fraction) interfered with the release of arachidonic acid in human endothelial cells induced by thrombin. Despite prednisone and heparin treatment we did not find a complete correction of the LAC activity and the ACA (IgM type) still remained positive before the detection of a fetal death at 26 weeks. The placenta showed abundant infarcts and areas of ischaemic necrosis. We suggest that the defect in vascular PGI2 release could compromise fetal outcome.

Conservative treatment of intrapartum fetal acidosis with a betamimetic agent.

553 cases of intrapartum fetal acidosis (pH less than 7.25) were treated with a betamimetic agent (ritodrine 250-300 micrograms/min). In 403 cases (72.8%), an improvement of fetal pH greater than 0.05 pH U was observed. Improvement was comparable in cases where the cause of fetal distress was abnormal uterine activity and in those where this was not the cause. Indeed, the recovery rate was the same, independent of the percentage of uterine activity inhibition. The neonatal condition was better in the pH recovered versus not recovered group. We suggest that conservative treatment of fetal distress with betamimetic drugs is a reasonable measure for improvement of fetal and neonatal condition.

Long-term hospitalization and beta-mimetic therapy in the treatment of intrauterine growth retardation of unknown etiology.

A group of 98 third trimester pregnant women whose ultrasonographic studies raised the suspicion of intrauterine fetal growth retardation was studied. The patients were randomly assigned to two groups: Group A (Treatment group: 44 patients) and Group B (Control group: 54 patients). All patients were admitted to the hospital upon diagnosis for baseline evaluation. Those in Group A remained in the hospital until delivery (mean stay 15 +/- 5 days) and received treatment with 10 mg/t.i.d. of p.o. ritodrine. Group B patients were discharged after an average stay of 7 +/- 3 days. This group was not treated with ritodrine, and they were seen weekly in an outpatient setting. The prevalence of low-birth-weight infants for their gestational age was 47.73% in the treatment group and 40.74% in the control group. Of the deliveries in the treatment group, 40.9% were induced (half for fetal indications). In the control group 35.18% of the induced labors was (47.35% for fetal indications). Of the cases in the treatment group 18.18% were delivered by cesarean section, of which 62.5% were performed for fetal distress. The control group showed similar figures: 16.66% cesarean sections with 77.7% of them done for fetal distress. We observed an incidence of 20.45% of acute fetal distress in the study group against 12.96% in the control group. Such a difference is not statistically significant. The group under study demonstrated a rate of 6.82% pathological pH value in the umbilical artery, while the rate of abnormal values in the control group was 18.52%. In both groups, the greatest percentage of acidotic pH was observed in patients with IGR.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal transplantation during pregnancy--a case report.

A case of renal transplantation during the 12th week of pregnancy is presented. An episode of rejection 6 days after surgery was treated satisfactorily. At the 18th week, the patient showed a mild hypertension which was treated by hidralazine. At the 30th week a fetal pyelouretheral stenosis with celiciar dilatation was diagnosed and the mother had another rejection episode. At the 33rd week a cesarean section was performed after a pathological NST. Neonatal and maternal developmental courses were good.

Effects of a cyproterone-containing oral contraceptive on hormonal levels in polycystic ovarian disease.

The management of polycystic ovarian disease in women not desiring pregnancy is controversial. To avoid the progressive androgenic effects on peripheral target organs, some advocate the use of oral contraceptives. This study reports the effects of a preparation with 50 micrograms ethinyl estradiol and 2 mg cyproterone acetate on gonadotropins, prolactin, testosterone, sex hormone binding globulin (SHBG), androstenedione, and calculated free testosterone index before and after six months of treatment. Gonadotropins, testosterone, and androstenedione levels decreased, prolactin did not change, and sex hormone binding globulin increased as the result of the treatment. This led to a net decrease in the calculated free testosterone.