Tratamiento de la osteonecrosis de los maxilares asociada a medicamentos: Enfoque médico-quirúrgico de estadios II y III

Resumen Introducción: La osteonecrosis de los maxilares asociada a medicamentos (OMAM) se define como la presencia de hueso necrótico expuesto de los maxilares en pacientes con historia de tratamiento farmacológico antirresortivo o antiangiogénico. Se describen diferentes estadios se severidad, con tratamiento conservador para estadios 0 y I, y tratamiento médico-quirúrgico para II-III. Objetivo: Describir los factores desencadenantes, opciones de tratamiento médico-quirúrgico y resultados en pacientes con OMAM estadios II-III. Material y Método: Estudio retrospectivo, descriptivo, de pacientes diagnosticados con OMAM estadios II y III que requirieron manejo médico-quirúrgico en la Red de Salud UC-Christus entre los años 2007 y 2018. Resultados: Todos los pacientes presentaron historia de tratamiento con bifosfonatos intravenosos. La mayoría de los registros de seguimiento de pacientes estuvo disponible para su análisis. El tratamiento consistió en aseo quirúrgico, decorticación y secuestrectomía. Se reportó disminución de la sintomatología con resolución parcial en la mitad de los casos y cierre completo de la exposición ósea en los restantes. Conclusión: Sugerimos que el tratamiento médico-quirúrgico en pacientes con OMAM en etapas II y III es efectivo en términos de disminución de sintomatología y control de infección. Sin embargo, es necesario realizar nuevos estudios prospectivos, con mayor cantidad de pacientes y tiempo de seguimiento.

Abstract Introduction: Medication-associated osteonecrosis of the jaws (MRONJ) is defined as the presence of exposed necrotic bone of the jaws in patients with a history of antiresorptive or antiangiogenic drug treatment. Different stages of severity are described, with conservative treatment for stages 0 and I, and medical-surgical treatment for II-III. Aim: To describe the triggers, medical-surgical treatment options and outcomes in patients with stage II-III MRONJ. Material and Method: Retrospective, descriptive study of patients diagnosed with MRONJ stages II and III that required medical-surgical management in the UC-Christus Health Network between 2007 and 2018. Results: All patients had a history of treatment with intravenous bisphosphonates. Most of the patient follow-up records were available for analysis. Treatment consisted of surgical grooming, decortication, and sequestrectomy. A decrease in symptoms was reported with partial resolution in half of the cases, and complete closure of bone exposure in the remainder. Conclusion: We suggest that medical-surgical treatment in patients with MRONJ in stages II and III is effective in terms of reducing symptoms and controlling infection. However, it is necessary to carry out new prospective studies, with a greater number of patients and follow-up time.

Prevalencia de osteonecrosis de los maxilares asociada a medicamentos en pacientes tratados con bifosfonatos intravenosos: análisis epidemiológico en Centro del Cáncer - Red de Salud UC-CHRISTUS

Resumen Introducción: La osteonecrosis de los maxilares asociada a medicamentos (OMAM) es una patología que involucra la exposición necrótica de hueso maxilar o mandibular, relacionada al uso de fármacos antirresortivos y antiangiogénicos, con una prevalencia de 0,94%-13% en pacientes oncológicos y con osteoporosis que hacen uso de ellos. Objetivo: Determinar la prevalencia de osteonecrosis de los maxilares en pacientes en tratamiento con bifosfonatos intravenosos (BFIV) en el Centro del Cáncer de la Red de Salud UC-Christus, Santiago de Chile. Material y Método: Se analizaron los datos de pacientes que recibieron tratamiento de bifosfonatos intravenoso entre marzo y septiembre de 2016, con seguimiento por los equipos tratantes. Se consideró para la extracción de datos el género, edad, diagnóstico primario, bifosfonato intravenoso utilizado, tiempo de seguimiento, presencia de metástasis óseas y diagnóstico de OMAM. Resultados: Se obtuvo una muestra de 143 pacientes, con una relación hombre:mujer de 1:2; promedio de edad de 63,2 años; 78% de ellos fueron tratados con ácido zoledrónico y un 22% con pamidronato. Del total de pacientes un 1,4% (n = 2) desarrolló OMAM. Ambos casos con diagnóstico de cáncer de mama en tratamiento con ácido zoledrónico, lo que corresponde al 1,8% de los pacientes en tratamiento con este fármaco. Conclusión: Si bien la OMAM es una patología infrecuente, esta se presenta con alta morbilidad y es de manejo complejo. La prevención y tratamiento de focos infecciosos odontogénicos de pacientes antes, durante o después del tratamiento con BFIV es fundamental para prevenir su desarrollo.

Abstract Introduction: Medication-related osteonecrosis of the jaw (MRONJ) is a disease involving exposition of necrotic maxillary and mandibular bone and it's related to antiresorptive and antiangiogenic drugs, with a prevalence that variates from 0,94%-13% in oncologic and osteoporosis patients treated with them. Aim: To determine the prevalence of MRONJ in patients that underwent treatment with intravenous bisphosphonates (IVBP) at Centro del Cancer de la Red de Salud UC-CHRISTUS of Santiago, Chile. Material and Method: Data from patients who received intravenous bisphosphonate treatment between March and September 2016 were analyzed, with follow-ups by their treating teams. Data extraction considered gender, age, primary diagnosis, intravenous bisphosphonate used, follow up time, bone metastases and diagnosis of MRONJ. Results: A sample of 143 patients was obtained with a men:women ratio of 1:2; an average age of 63,2 years, 78% of the patients were treated with zoledronic acid and 22% of the patients with pamidronate. From the total number of patients,1.4% (n = 2) developed MRONJ, both cases had breast cancer as primary diagnosis and in treatment with zoledronic acid, which corresponds to 1.8% of patients being treated with this drug. Conclusion: Although MRONJ is an infrequent disease, it presents high morbidity and complex management. Prevention and treatment of odontogenic infectious foci in patients before, during and after treatment with IVBP drugs is fundamental to prevent this pathology.

Correction to: Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery.

BACKGROUND: Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined. MATERIALS AND METHODS: Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, ß-oxidation, lipolysis and cysteine oxidation. RESULTS: Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery. CONCLUSIONS: These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.

[Management of facial injuries in the emergency room]. / Manejo del trauma maxilofacial en la atención de urgencia por no especialistas.

Facial injuries are cause of consultation in emergency departments. The maxillofacial region contains several structures that are vital for life. Hence, an early assessment and management of facial injuries is important to avoid their consequential complications and eventual mortality. This article is a review of the literature about the emergency clinical assessment and management of traumatic facial injuries by non-specialists.

Manejo del trauma maxilofacial en la atención de urgencia por no especialistas / Management of facial injuries in the emergency room

Facial injuries are cause of consultation in emergency departments. The maxillofacial region contains several structures that are vital for life. Hence, an early assessment and management of facial injuries is important to avoid their consequential complications and eventual mortality. This article is a review of the literature about the emergency clinical assessment and management of traumatic facial injuries by non-specialists.

Efecto de glucosa en la expresión de lipasa endotelial en células endoteliales humanas y en sujetos con diabetes mellitus tipo 2 / Glucose effect in the expression of endothelial lipase in human endothelial cells and in patients with diabetes mellitus type 2

Introducción: Lipasa endotelial (LE), enzima que modula el metabolismo de HDL, es sobre regulada porcitoquinas-inflamatorias. Diabetes mellitus tipo 2 (DM2) se ha asocia a inflamación subclínica, por lo que se plantea que estos pacientes tendrían niveles elevados de LE. El objetivo del estudio es determinar el efecto de glucosa en expresión de LE en células de cultivo y evaluar la relación entre los niveles de LE y el control glicémico en sujetos con DM2. Método: Células endoteliales humanas (HUVEC) fueron estimuladas con distintas concentraciones de glucosa(5.5, 25 y 50 mmol/L) durante 24 h, se evaluó el efecto sobre la expresión de LE. En sujetos DM2 se midieron niveles de LE, glicemia y hemoglobina glicosilada fracciónA1c (HbA1c). Se contó con un grupo control (8) para la determinación de los niveles de la enzima. LE se midió por inmunotransferencia, y los resultados fueron expresados como unidades arbitrarias(UA). Resultados: En células HUVEC la expresión de LE fue directamente proporcional a la concentración de glucosa extracelular (p < 0,05). Se evaluaron 24 sujetos diabéticos(15 mujeres y 9 hombres), edad promedio 60 ± 9,7años,que presentaron niveles de LE mayores que el grupo control(14911UA y 10250, 18UA respectivamente, p < 0,05).No se encontró relación entre glicemia, HbA1c y LE. Conclusión: En células HUVEC existe relación directa entre glucosa extracelular y LE. Los sujetos diabéticos tuvieron niveles mayores de LE que el grupo control, pero esto no se relacionó con control glicémico, lo que apunta ala existencia de otros factores que participen en el aumento de la expresión de LE (AU)

Introduction: Endothelial Lipase (EL), enzyme that modulates HDL metabolism, is over regulated by inflammatory-cytokines. Type 2 Diabetes (DM2) has been associated with a subclinical inflammation, so it has been ruled that these patients could have high levels of EL. The objectives of the research are to determine the effect of glucose in the expression of EL in culturing cells and evaluate the relation between the levels of EL and the metabolic control in patients with DM2. Method: During 24 hours, human endothelial cells(HUVEC) were stimulated with different concentrations of glucose (5.5, 25 and 50 mmol/L), the effect was evaluated over the expression of EL. In DM2 patients levels of EL, glucose and HbA1c were measured. We had a control group (8) to determine the levels of enzyme. EL was measured by immune transference, and the results were expressed by arbitrary units(AU).Results: In HUVEC cells, the expression of EL was directly proportional extracellular glucose (p < 0.05). 24 diabetic patients were evaluated (15 females and 9 males)average age from 60 ± 9,7 years old. The studied group showed levels of EL bigger than the control group (14911AU and 10250, 18AU) respectively (p < 0.05). We found no relation between glucose, HbA1c and EL. Conclusion: In HUVEC cells there is a direct relation between extracell glucose and EL. The diabetic patients had higher levels of EL than the control group, but these was not related with glucose or HbA1c, these shows the existence of other factors that participate in the increasement of EL (AU)

[Glucose effect in the expression of endothelial lipase in human endothelial cells and in patients with diabetes mellitus type 2]. / Efecto de glucosa en la expresión de lipasa endotelial en células endoteliales humanas y en sujetos con diabetes mellitus tipo 2.

INTRODUCTION: Endothelial Lipase (EL), enzyme that modulates HDL metabolism, is overregulated by inflammatory-cytokines. Type 2 Diabetes (DM2) has been associated with a subclinical inflammation, so it has been ruled that these patients could have high levels of EL. The objectives of the research are to determine the effect of glucose in the expression of EL in culturing cells and evaluate the relation between the levels of EL and the metabolic control in patients with DM2. METHOD: During 24 hours, human endothelial cells (HUVEC) were stimulated with different concentrations of glucose (5.5, 25 and 50 mmol/L), the effect was evaluated over the expression of EL. In DM2 patients levels of EL, glucose and HbA1c were measured. We had a control group (8) to determine the levels of enzyme. EL was measured by immune transference, and the results were expressed by arbitrary units(AU). RESULTS: In HUVEC cells, the expression of EL was directly proportional extracellular glucose (p < 0.05). 24 diabetic patients were evaluated (15 females and 9 males) average age from 60 ± 9,7 years old. The studied group showed levels of EL bigger than the control group (14911AU and 10250, 18AU) respectively (p < 0.05). We found no relation between glucose, HbA1c and EL. CONCLUSION: In HUVEC cells there is a direct relation between extracell glucose and EL. The diabetic patients had higher levels of EL than the control group, but these was not related with glucose or HbA1c, these shows the existence of other factors that participate in the increasement of EL.

Extracellular regulated kinase, but not protein kinase C, is an antiapoptotic signal of insulin-like growth factor-1 on cultured cardiac myocytes.

This study aims to elucidate the signaling pathway for insulin-like growth factor-1 (IGF-1) in cultured neonatal rat cardiomyocytes and particularly the role of IGF-1 in cardiac apoptosis. IGF-1 stimulated polyphosphoinositide turnover, translocation of protein kinase C (PKC) isoforms (alpha, epsilon, and delta) from the soluble to the particulate fraction, activation of phospholipid-dependent and Ca(2+)-, phospholipid-dependent PKC, and activation of the extracellular-regulated kinase (ERK). IGF-1 attenuated sorbitol-induced cardiomyocyte viability and nuclear DNA fragmentation. These antiapoptotic effects of IGF-1 were blocked by PD-098059 (an MEK inhibitor) but not by bisindolylmaleimide I (BIM, a specific PKC inhibitor). The ERK pathway may therefore be an important component in the mechanism whereby IGF-1 exerts its antiapoptotic effect on the cardiomyocyte.

Endothelial cell oxidative stress and signal transduction.

Endothelial dysfunction (ED) is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS) have been implicated as important mechanisms that contribute to ED, and ROS's may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1), tyrosine kinases (Src and Syk) and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC), we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy) and oxidized LDL (oxLDL) enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process.

Endothelial cell oxidative stress and signal transduction

Endothelial dysfunction (ED) is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS) have been implicated as important mechanisms that contribute to ED, and ROS's may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1), tyrosine kinases (Src and Syk) and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC), we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy) and oxidized LDL (oxLDL) enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process.

Plasma polyphenols and antioxidants, oxidative DNA damage and endothelial function in a diet and wine intervention study in humans.

An intervention study was performed to evaluate the influence of a Mediterranean diet, a high fat diet, and their supplementation with red wine in moderate amounts, on biochemical, physiological, and clinical parameters related to atherosclerosis and other chronic diseases. For 3 months two groups of 21 male volunteers each, received either a Mediterranean diet or a high fat diet; during the second month, red wine was added isocalorically, 240 ml/day. Participants were kept under close medical and nutritional surveillance. At days 0, 30, 60 and 90, clinical, physiological and biochemical evaluations were made. Plasma vitamin C was significantly decreased in the high fat diet group compared to the Mediterranean diet group. After wine supplementation to the Mediterranean diet, a significant 13.5% increase in plasma vitamin C was observed. Furthermore, when wine was added vitamin E decreased significantly in plasma, 15% in the high fat diet and 26% in the Mediterranean diet. Total plasma antioxidant capacity (total antioxidant reactivity) increased 28% above basal levels in the Mediterranean diet group, but not in the high fat diet group. In both groups, wine induced a marked increase in total antioxidant reactivity above basal levels, 56% and 23%, respectively. Oxidative DNA damage, detected as 8-hydroxydeoxyguanosine (8-OHdG) levels in blood leukocyte DNA, was markedly increased by the high fat diet; however, it was strongly reduced, to approximately 50% basal values, after wine supplementation, both in the high fat diet and Mediterranean diet groups. Endothelial function, evaluated noninvasively as flow-mediated vascular reactivity of the brachial artery, was suppressed by the high fat diet, and was normal after wine supplementation. These effects are attributed to oxidative stress associated with a high fat diet, and to the elevated plasma antioxidant capacity associated with wine consumption and the Mediterranean diet. The results presented support the following conclusions: a high fat diet induces oxidative stress; a diet rich in fruits and vegetables enhances antioxidant defenses; wine supplementation to a high fat or a Mediterranean diet increases plasma antioxidant capacity, decreases oxidative DNA damage, and normalizes endothelial function.

Oxidative stress and upregulation of mitochondrial biogenesis genes in mitochondrial DNA-depleted HeLa cells.

The signaling mechanism through which deficitary mitochondrial function would activate nuclear genes required for mitochondrial biogenesis, has not been established. To explore the hypothesis that reactive oxygen species (ROS), a mitochondrial product, constitute part of the mitochondria-nuclei signaling pathway, we obtained HeLa cells depleted of mitochondrial DNA (rho0 cells) through exposure to ethidium bromide. We found evidences of oxidative stress in rho0 cells, employing a fluorescent probe and measuring NF-kappaB activation. Nuclear Respiratory Factor-1 (NRF-1) and Mitochondrial Transcription Factor A (Tfam) mRNA were measured by RT-PCR. For both transcription factors, rho0 cells revealed significantly higher levels of mRNA. These results support several hypothesis: that endogenous ROS enhance the expression of nuclear mitochondrial biogenesis genes NRF-1 and Tfam; that DNA deprived mitochondria lead to cellular oxidative stress, probably because of incomplete biogenesis of the mitochondrial electron transport chain, and consequently, that ROS are part of a mitochondria-nuclei regulatory signaling pathway.

Effect of inhibitors of signal transduction on IGF-1-induced protein synthesis associated with hypertrophy in cultured neonatal rat ventricular myocytes.

IGF-1 increased 2-fold protein synthesis in cardiac myocytes. Genistein, whether added during preincubation or with IGF-1 at the start of incubation, significantly inhibited the IGF-1-induced stimulation of protein synthesis, autophosphorylation of the beta-subunit of IGF-1 receptor and inhibition of ERK. When added 1 or 6 h after IGF-1, however, genistein was without effect. IGF-1-stimulated protein synthesis was also significantly inhibited by PD-098059, staurosporine, and rapamycin, but not by wortmannin, in cardiac myocytes. Some inhibitors produced a reduction in cell size. Activation of the ERK cascade by IGF-1 may be responsible for some of the features associated with cardiac myocyte hypertrophy.

Insulin-like growth factor-I rapidly activates multiple signal transduction pathways in cultured rat cardiac myocytes.

In response to insulin-like growth factor-I (IGF-I), neonatal rat cardiac myocytes exhibit a hypertrophic response. The elucidation of the IGF-I signal transduction system in these cells remains unknown. We show here that cardiac myocytes present a single class of high affinity receptors (12,446 +/- 3,669 binding sites/cell) with a dissociation constant of 0.36 +/- 0.10 nM. Two different beta-subunits of IGF-I receptor were detected, and their autophosphorylation was followed by increases in the phosphotyrosine content of extracellular signal-regulated kinases (ERKs), insulin receptor substrate 1, phospholipase C-gamma1, and phosphatidylinositol 3-kinase. IGF-I transiently activates c-Raf in cultured neonatal cardiac myocytes, whereas A-raf is activated much less than c-Raf. Two peaks of ERK activity (ERK1 and ERK2) were resolved in cardiac myocytes treated with IGF-I by fast protein liquid chromatography, both being stimulated by IGF-I (with EC50 values for the stimulation of ERK1 and ERK2 by IGF-I of 0.10 and 0. 12 nM, respectively). Maximal activation of ERK2 (12-fold) and ERK1 (8.3-fold) activities was attained after a 5-min exposure to IGF-I. Maximal activation of p90 S6 kinase by IGF-I was achieved after 10 min, and then the activity decreased slowly. Interestingly, IGF-I stimulates incorporation of [3H]phenylalanine (1.6-fold) without any effect on [3H]thymidine incorporation. These data suggest that IGF-I activates multiple signal transduction pathways in cardiac myocytes some of which may be relevant to the hypertrophic response of the heart.

Cyclic AMP-dependent protein kinase and mechanical heart function in ventricular hypertrophy induced by pressure overload or secondary to myocardial infarction.

The role of cyclic AMP-dependent protein kinase (PKA) and systolic function during the development of left ventricular hypertrophy (LVH) still remain uncertain. The aim of this work is to study PkA activity and mechanical heart function in two experimental heart hypertrophy models: specifically, one induced by pressure overload (Goldblatt model: two kidneys, one clamped, Gb); and another secondary to myocardial infarction (MI) generated by ligation of the left coronary artery. Hypertension in the Gb group becomes evident by the third and fourth week after surgery without any significant change in the corresponding sham group. The myocardial infarction group did not show any change in systolic pressure. Different degrees of LVH for the two experimental models were observed. Relative cardiac mass (RCM) and relative ventricular mass (RVM) increased 23 and 16%, respectively, above the sham-operated rats in MI group (P < 0.05). For the pressure overload model, the increase values were 42 and 44%, respectively (P < 0.05). Left ventricular hypertrophy was also evaluated through quantitative changes in cardiac beta-myosin heavy chain which agreed with morphometric studies in Goldblatt rats. Ventricular PKA activity did not show any significant difference with respect to the sham-operated group after induction of pressure overload. For the MI model, ventricular PKA activity changed only at day 7 post-infarction with a 289% increase above the sham-operated group (P < 0.05). The absence of activation of ventricular PKA after constriction of renal artery or myocardial infarction was also corroborated by the patterns of PKA-dependent phosphorylated proteins. While force-generating capacity was increased, there was no change in ventricular PKA activity, indicating that there is no relation between this enzyme and systolic stress-strain regression lines in either pressure overload or myocardial infarction conditions. Cyclic AMP-dependent protein kinase activity had no relation with development of cardiac hypertrophy in the two experimental models of LVH. These findings contribute to the hypothesis for a multifactorial interaction of different intracellular biochemical and molecular mechanisms in the genesis of cardiac hypertrophy.

Changes in protein kinase C activity, subcellular distribution and protein phosphorylation during the lactogenic cycle in the rat mammary tissue.

Direct and indirect evidence emphasizes the participation of classical protein kinase C (cPKC) in the development and function of the mammary gland. This work shows that there are changes not only in total cPKC activity during the lactogenic cycle, but also in the relative amounts of the soluble and particulate cPKC activities and that the time-course of these two events are not the same. The time-course of translocation from the cytoplasm to the plasma membrane suggests that the soluble and particulate forms of the enzyme may be associated with growth and differentiation of the tissue, respectively. Phosphorylation patterns also show characteristic and significant differences throughout the development of the gland. These results suggest that both total mammary cPKC activity and its subcellular forms change in accordance with the proliferative and differentiative stages of the mammary gland, and that the enzyme translocation occurs during the transition from pregnancy to lactation.

Changes in beta-adrenergic receptors of rat heart and adipocytes during volume-overload induced cardiac hypertrophy.

Modification of cardiac beta-adrenergic receptors (beta-AR), resulting from the stimulation of the sympathetic nervous system, is one of the most important factors in the generation of cardiac hypertrophy and heart failure. In this research, we propose the utilization of adipocytes as an alternative to the use of predominantly beta 2-AR subtype containing circulating lymphocytes for the convenient assessment of cardiac failure in the experimentally, volume-overload induced heart hypertrophy in rats. Using this model, we measured beta-AR both in the heart and adipocytes of male rats 2, 7, 21 and 56 days after creating an aorta-cava fistula. Whereas an increase (58%) in cardiac beta-AR density from day 7 to 21 was followed by a decrease in this measurement (30%) on day 56 [changes expressed as percentage of controls; no significant changes in beta-AR affinity (Kd) were recorded at any of the time interval studied], adipocytes beta-AR density showed a progressive increase starting on day 21 (87%) which continued until the end (131%) of the study period. This lack of correlation of the beta-AR population in both tissues supports the need for a specific evaluation of the beta 1-AR subtype in the heart and adipocyte in order to evaluate the usefulness of adipocyte cells as an alternative to assess cardiac failure.

[Evaluation of the effect of enalapril, a converting enzyme inhibitor, on lymphocytic beta-adrenergic receptors of patients with chronic cardiac insufficiency]. / Evaluación del efecto de enalapril, inhibidor de la enzima conversiva, en los receptores betaadrenérgicos de linfocitos de pacientes con insuficiencia cardíaca crónica.

We have previously corroborated that lymphocyte beta-adrenergic receptor density is significantly reduced in patients with chronic heart failure. It is well known that angiotensin converting enzyme inhibitors normalize the function of sympathetic nervous system. We have assessed the effect of enalapril on lymphocyte beta-adrenergic receptor system from patients with chronic heart failure (n = 14) using a random, cross and double blind protocol. Our results show that the improvement in clinical score and ventricular function were not related with changes in the number and affinity of beta-adrenergic receptor nor cyclic AMP content in lymphocytes obtained from these patients.