Miguel Valle - Academia.edu (original) (raw)

Papers by Miguel Valle

Journal of Cardiovascular Pharmacology, 1994

Hypertension is associated with insulin resistance and dyslipidemia in a syndrome named X. Epidem... more Hypertension is associated with insulin resistance and dyslipidemia in a syndrome named X. Epidemiologic evidence also supports a link between hyperinsulinemia and blood pressure (BP), independent of obesity and non-insulin-dependent diabetes mellitus. To assess the possible role of insulin receptors in this syndrome, we studied insulin binding by erythrocyte ghosts in patients with moderate essential hypertension with or without fasting or postglucose hyperinsulinemia. We measured plasma glucose and insulin before and at 30, 60, and 120 min after administration of 75 g glucose in 62 hypertensive patients and 20 matched normotensive controls. Both groups had comparable age (mean 45 years) and waist/hip ratios (mean 0.88). Patients undergoing antihypertensive treatment did not receive antihypertensive medication for 3 weeks. Patients with fasting or postglucose hyperglycemia were excluded from the study. Insulin binding to erythrocyte ghosts was significantly decreased (p < 0.001) to almost half the values of controls (6.5% specific binding) in both patients with hyperinsulinemic (3.2% specific binding) and those with normoinsulinemic (3.9% specific binding) hypertension. Scatchard analysis demonstrated that this was due to a lesser number of insulin receptors. These data indicate that patients with essential hypertension can show decreased erythrocyte insulin receptors without detectable hyperinsulinemia.

Journal of Hypertension, 1995

Pancreastatin, a novel peptide, is known to inhibit insulin secretion and to have a glycogenolyti... more Pancreastatin, a novel peptide, is known to inhibit insulin secretion and to have a glycogenolytic effect, and is present in many endocrine and chromaffin cells. Both the plasma insulin levels and the adrenergic activity accompanying insulin resistance have been shown to be increased in hypertensive subjects. Our working hypothesis was that pancreastatin might play a role in these pathological phenomena. We studied the plasma pancreastatin level in non-obese essential hypertensive patients in response to an intravenous glucose load. We further measured the responses to the glucose challenge of insulin, glucagon, catecholamines and free fatty acids, as well as other factors related to insulin resistance (i.e. lipoproteins and apolipoproteins). We separated the hypertensive patients into three groups according to their response to an oral glucose-tolerance test: normoinsulinaemic, hyperinsulinaemic and glucose-intolerant. Matched normotensive control subjects were also studied. Pancreastatin levels did not change in the control group after the glucose challenge. However, all hypertensive patients showed an increase in plasma pancreastatin levels after glucose loading. The normoinsulinaemic hypertensive patients also had elevated basal pancreastatin levels. The increase in pancreastatin levels was in the ranking: normoinsulinaemic > hyperinsulinaemic > glucose-intolerant. The pancreastatin: insulin ratio showed that the secretion of pancreastatin and insulin may be regulated differently. Basal free fatty acid and glucagon levels were found to be elevated both in the hyperinsulinaemic and in the glucose-intolerant group. Fasting triglycerides levels were increased in all of the hypertensive patients. Other risk factors for coronary artery disease were also found to be altered: elevated very low-density lipoprotein-cholesterol and decreased high-density lipoprotein-cholesterol, with ranking: normoinsulinaemic < hyperinsulinaemic < glucose-intolerant. These results show an increase in pancreastatin levels in hypertensive patients, suggesting that pancreastatin might play a role in the pathophysiology of essential hypertension.

European Journal of Endocrinology, 2000

Objective: A relationship between hyperinsulinemia and decreased serum sex hormone-binding globul... more Objective: A relationship between hyperinsulinemia and decreased serum sex hormone-binding globulin (SHBG) has been described in adults. We evaluated the usefulness of SHBG as an index of hyperinsulinemia and/or insulin resistance in obese children (aged 6±9 years) of both sexes and its possible in¯uence on the androgenic status. Design: We carried out a cross-sectional study of cases and controls. We studied 61 obese children (22 males, 39 females) with body mass index (BMI) superior to the 90 th percentile and a control group of age-and sex-matched non-obese children. We measured serum glucose, insulin, TSH, free thyroxine, 17b-estradiol, testosterone and SHBG. Also, we correlated these parameters with anthropometric measures. Results: The obese group presented signi®cantly elevated levels of insulin (P 0:001) and insulin/ glucose ratio (P 0:0012) compared with the control group. SHBG (P 0:0001) and testosterone (P 0:0169) levels were signi®cantly lower than those in the non-obese group. We did not ®nd any difference in the free androgen index (FAI). Fasting insulin (r À0.4512; P < 0:001), BMI (r À0.3185; P < 0:05) and testosterone (r À0.3705; P < 0:01) were inversely correlated with SHBG concentration. According to multivariate analyses, insulin was the only independent predictor factor for serum SHBG concentration in the obese group (r partial=0.1280; P 0:0171). Conclusions: In summary, at this age there is a strong relationship between insulin and SHBG. The changes in SHBG levels of the obese group did not affect FAI and, therefore, they did not cause changes in the androgenic status. Our data support the role of insulin in the regulation of serum SHBG levels.

Journal of Nutritional Biochemistry, 2002

Homocysteine has been associated with the oxidative stress in the pathogenesis of atherosclerosis... more Homocysteine has been associated with the oxidative stress in the pathogenesis of atherosclerosis. Oxidative stress caused by triglycerides and free fatty acids is known to cause insulin resistance and hyperinsulinemia. On the other hand, insulin resistance may increase homocysteine levels. Since obesity is associated with insulin resistance and hyperinsulinemia, we aimed to study the possible association of homocysteine with hyperinsulinemia in obese subjects. 20 obese male subjects (body mass index >29), aged 33–55 (mean 45 years old) were studied. A fasting blood sample was obtained for the study and the subjects undertook an oral glucose tolerance test with samples taken at 1 and 2 h after glucose. Subjects were divided in two groups according to the fasting insulin levels, < 9 μU/ml or normoinsulinemic (group 1) and >9 μU/ml or hyperinsulinemic (group 2). Glucose, insulin, homocysteine, folate, B12, total cholesterol, HDL-cholesterol and triglycerides levels were determined in fasting blood samples. In oral glucose tolerance test, glucose, insulin and homocysteine levels were measured. Hyperinsulinemic obese subjects (group 2) had higher levels of insulin and glucose at 1 h and 2 h postglucose, compared with group 1. Fasting total homocysteine and triglyceride levels were also increased in this group, whereas folate and B12 levels were similar in both groups. Fasting homocysteine significantly correlated with fasting insulin (r = 0.6, p <0.01). Homocysteine levels slightly but significantly decreased after glucose loading in normoinsulinemic but not in hyperinsulinemic obese subjects. These results show that higher homocysteine levels are observed in the hyperinsulinemic obese subjects and suggest that homocysteine could play a role in the higher risk of cardiovascular disease in obesity.

Metabolism-clinical and Experimental, 2009

The metabolic syndrome is associated with insulin resistance, a systemic low-grade inflammatory s... more The metabolic syndrome is associated with insulin resistance, a systemic low-grade inflammatory state, and endothelial dysfunction. These disorders may arise at a very early age in obese children. The aim of this study was to confirm changes in endothelial dysfunction and inflammatory biomarkers in obese prepubertal children and to evaluate the effect of body mass index (BMI) modification on these biomarkers. Biomarkers for inflammation, endothelial dysfunction, and insulin resistance were measured in obese children (47) and healthy controls (47). Baseline pretreatment levels of insulin (P = .019), homeostasis model assessment of insulin resistance (P = .004), soluble intercellular adhesion molecule (sICAM) (P = .003), and C-reactive protein (CRP) (P b .001) were significantly higher in obese children than in controls. After 9 months of treatment, obese children with lowered BMI SD score (SDS-BMI) displayed a significant decrease in insulin (P = .011), homeostasis model assessment of insulin resistance (P = .012), CRP (P = .006), and interleukin-6 (IL-6) (P = .045) levels compared with obese children with stable SDS-BMI; they also displayed a nonsignificant drop in sICAM levels. Similarly, obese children with lowered SDS-BMI displayed a decrease in CRP (P = .005) and IL-6 (P = .065) compared with baseline levels before treatment. In the total obese group, changes in SDS-BMI correlated positively with changes in CRP (P = .035), IL-6 (P = .027), and sICAM-1 (P = .038) levels. Only SDS-BMI was an independent predictive factor for CRP (P = .031), IL-6 (P = .027), and sICAM-1 (P = .033). Prepubertal obese children displayed alterations indicative of endothelial dysfunction, insulin resistance, and inflammatory state. Lowering of the SDS-BMI after 9 months of treatment was associated with an improvement in these variables compared with those in obese children with stable SDS-BMI status.

Metabolism-clinical and Experimental, 2006

Obesity is an independent risk factor for the development of cardiovascular disease frequently as... more Obesity is an independent risk factor for the development of cardiovascular disease frequently associated with hypertension, dyslipemia, diabetes, and insulin resistance. Higher homocysteine (Hcy) levels are observed in the hyperinsulinemic obese adults and suggest that Hcy could play a role in the higher risk of cardiovascular disease in obesity. We analyzed total Hcy levels in obese prepubertal children and their possible association with both metabolic syndrome and various inflammatory biomarkers and leptin. We studied 43 obese children (aged 6-9 years) and an equal number of nonobese children, paired by age and sex. The obese subjects presented significantly elevated values for insulin ( P = .003), C-reactive protein ( P = .033), and leptin ( P b .001). No significant differences were found in Hcy levels between the obese and nonobese children. However, Hcy concentration was significantly higher in the hyperinsulinemic obese children than in the normoinsulinemic group ( P = .002). Using multivariant regression analysis, in the obese group, corrected for age and sex, the homeostasis model assessment for insulin resistance ( P partial = .001) and leptin ( P partial = .02) are independent predictive factors for Hcy. In the control group, corrected for age and sex, the homeostasis model assessment for insulin resistance ( P partial = .005) and leptin ( P partial = .031) also are independent predictive factor for Hcy. Increased plasma Hcy, particularly in hyperinsulinemic obese children, may be causally involved in the pathogenesis of atherosclerosis and/or cardiovascular disease, both of which are common in obesity. D

Metabolism-clinical and Experimental, 2002

The aim of this study was to detect the presence and degree of impairment of cardiovascular disea... more The aim of this study was to detect the presence and degree of impairment of cardiovascular disease (CVD) risk factors, grouped as metabolic cardiovascular syndrome (MCS), in obese prepubertal children. We also assessed the influence of high fasting insulin levels in this pathological status. A cross-sectional study was performed on obese children based on fasting blood samples. Subjects were 61 obese children (aged 6 to 9 years) and an equal number of non-obese children paired by age and sex. The obese children presented the following characteristics in comparison to the non-obese group: significantly high levels of insulin (8.2 +/- 0.52 v 6.12 +/- 0.34 microU/mL), triglycerides (TG) (0.79 +/- 0.04 v 0.60 +/- 0.02 mmol/L), uric acid (0.24 +/- 0.005 v 0.21 +/- 0.004 mmol/L), systolic (SBP) (94.59 +/- 1.06 v 88.85 +/- 1.2 mm Hg) and diastolic (56.49 +/- 1.07 v 52.21 +/- 1.06 mm Hg) blood pressure (DBP), and low levels of high-density lipoprotein cholesterol (HDL-C) (1.30 +/- 0.04 v 1.46 +/- 0.03 mmol/L), and nonesterified fatty acids (0.407 +/- 0.02 v 0.505 +/- 0.02 mmol/L). The hyperinsulinemic obese children showed the same types of differences when compared with the normoinsulinemic group. In the obese group, having adjusted for age, waist/hip ratio (WHR), body mass index (BMI), and sex hormone-binding globulin (SHBG), insulin was an independent prediction factor for triglycerides (P =.0004), apolipoprotein A-I (Apo-AI) (P =.005), and alanine aminotransferase (ALT) (P =.029). BMI was an independent prediction factor for HDL-C (P =.001) and triglycerides (P =.027). However, insulin was an independent prediction factor in the control group for triglycerides (P =.0002) and SBP (P =.012), just as BMI was for HDL-C (P =.011) and uric acid (P =.041). We conclude that the cluster of CVD risk factors associated with MCS and intra-abdominal fat is present in obese prepubertal children. This situation seems to depend, to a large extent, on the insulin basal level. The apparent association between BMI and MCS is due to the correlation between BMI and insulin, and to the fact that insulin associates with MCS. Within the obese group, hyperinsulinemic children present the greatest impairment in the parameters considered to be constituents of MCS.

Metabolism-clinical and Experimental, 2000

Obesity is a major risk factor for cardiovascular disease frequently associated with hypertension... more Obesity is a major risk factor for cardiovascular disease frequently associated with hypertension, dyslipidemia, and diabetes. In recent years, alterations in the hemostatic system have been added to these dysfunctions. We analyzed some of these alterations in coagulation and fibrinolysis in obese children (6 to 9 years old) of both sexes. We studied 61 obese children (mean body mass index [BMI], 22.35 kg/m2; 95% confidence interval [CI], 21.82 to 22.87) and 70 non-obese children (mean BMI, 16.58 kg/m2; 95% CI, 16.24 to 16.93) as a control group. The obese subjects presented significantly elevated values for insulin (P < .001), tissue-plasminogen activator ([t-PA] P < .001), plasminogen activator inhibitor-1 ([PAI-1] P < .001), and fibrinogen (P < .001) with respect to the control group. We found no significant differences in the concentration of glucose and fragment 1 + 2 of prothrombin (F1 + 2). In the obese subjects, insulin, PAI-1, and F1 + 2 were positively correlated with the BMI. On the other hand, t-PA was correlated with insulin and PAI-1 but not with the BMI. Therefore, in the obese children, there was an increment of the risk factors for cardiovascular disease.

Anatomy and Embryology, 1994

The cochleo-vestibular ganglion (CVG) contains the neurons connecting the sensory epithelia of th... more The cochleo-vestibular ganglion (CVG) contains the neurons connecting the sensory epithelia of the inner ear to the cochlear and vestibular nuclei in the medulla. Expression of trkB protein-like immunoreactivity was studied in the developing CVG, using both Western blot and immunocytochemistry on tissue sections. Specific immunoreactivity was observed in the CVG from the 12th gestation day (gd) to the first postnatal week, reflecting the presence of high-affinity receptors for brain-derived neurotrophic factor (BDNF), a member of the NGF family of neurotrophins. Whole explants and dissociated cell cultures of cochlear (CG) and vestibular ganglion (VG) from mouse embryos and postnatal specimens were grown in neurotrophin-free medium to assay changes in neurite outgrowth and neuronal survival in response to the addition of physiological concentrations (0–5 ng/ml) of BDNF. Exogenous BDNF (2 ng/ml) promoted neurite outgrowth and neuronal survival in explants of both CG and VG, and the effects were stage-dependent. The onset of the response to BDNF occurred at gd 11–12. The response then reached a maximum between 14 and 18 gd and subsequently decreased, although it remained significantly present during the first postnatal week. BDNF-induced response was no longer observed in the mature cochlear and vestibular ganglion (after 30 postnatal days). The effects of BDNF on neuronal differentiation and survival were dose-dependent, starting at 0.5 ng/ml, with saturation at 2 ng/ml and half-maximal effect occurring between 1 and 1.5 ng/ml. On the basis of our results, we propose that BDNF may be physiologically involved in the control of both neuronal differentiation, and central and peripheral target-dependent neuronal death, in the CVG of embryos and early postnatal mice. BDNF may act alone or in cooperation with other neurotrophins to establish the afferent innervation of the inner ear sensory epithelium.

Mechanisms of Ageing and Development, 1995

The distribution of neurotrophin receptors (p75, trkA-, trkB-, and trkC-receptor proteins) was st... more The distribution of neurotrophin receptors (p75, trkA-, trkB-, and trkC-receptor proteins) was studied by immunohistochemistry on sections of human gastrointestinal tract mucosa from esophagus through rectum. Moreover, chromogranin A (CgA) was studied in parallel to identify endocrine cells (EC). In all of the analyzed samples there was specific immunoreactivity (IR) for trkB-receptor protein in EC, the percentage of which varied between 26 ± 0.6% for the duodenum and 78 ± 3% for the sigmoid colon. EC displaying trkC-receptor protein IR were also encountered, in some cases, in EC of the gastric fundus (9%), duodenum (12%), jejune (23%), and colon (12%); trkA-receptor protein IR was occasionally present labelling EC in the jejune (52%), ileum (25%), and sigmoid colon (18%); finally, p75 was in 21% of EC exclusively in one case in the ileum. In addition to EC, IR for all assessed antigens was also present in the submucous blood vessels. Our results provide evidence for the occurrence of neurotrophin receptor proteins in nonneuronal tissues and suggest that neurotrophins, especially that binding trkB receptor proteins, can regulate a subpopulaUon of EC cells. However, whether EC expressing different trk receptor proteins represent neurochemical subtypes of EC, and whether the identified trk receptor proteins correspond to functional receptors, remain to be elucidated.

Urologia Internationalis, 1997

The present study was undertaken to analyze the changes in neuroendocrine cells of the human pros... more The present study was undertaken to analyze the changes in neuroendocrine cells of the human prostate induced by neoplasms and the effect of hormonal treatment. Samples of human prostate (n = 47) were obtained during surgery or removal of organs for transplantation. The cases analyzed represent normal prostates (n = 4); benign prostatic hyperplasias (n = 10; prostatic carcinomas with Gleason scores of 2-4 (n = 5), 5-7 (n = 10), and 8-10 (n = 3), and prostatic carcinomas treated with hormonal therapy (n = 15). Immunohistochemistry for chromogranin A was performed, and the density of neuroendocrine cells as well as the intensity of the immunostaining within their cytoplasms were evaluated using image analysis. Neuroendocrine cells showing chromogranin A immunoreactivity were identified in all cases studied. They were localized scattered in the acini, and no differences in their morphology were observed among groups. Interestingly, chromogranin A immunoreactivity was also present in typical epithelial cells of prostatic cancer with Gleason scores ranging from 8 to 10. The density of chromogranin A immunoreactive cells was higher in neoplastic tissue with respect to the normal prostate, reaching maximal values in prostatic carcinomas with Gleason scores of 8-10 which were hormonally treated. Regarding the intensity of immunostaining in the prostatic carcinomas with Gleason scores of 8-10 only, a significant increase in relation to the other groups was found. The present results demonstrate that the neuroendocrine cells have similar morphological features and distribution in normal prostate, benign prostatic hyperplasia, and prostatic carcinoma. Their density in prostatic cancer increases following hormonal therapy and varies in relation to the tumoral degree or histological evaluation, suggesting a role of neuroendocrine cells in human prostatic cancer.

Anatomy and Embryology, 1994

This study characterizes the temporal-spatial distribution of nerve growth factor (NGF) low (p75)... more This study characterizes the temporal-spatial distribution of nerve growth factor (NGF) low (p75) and high-affinity (trkA) receptors in the facial nerve and geniculate ganglion (GG) of developing quail embryos (E-3 to E-14). We used 125I-labeled NGF (125I-NGF) to study binding dynamics in a temporal series of isolated primordia and an autoradiographic series of staged specimens to characterize the occurrence and distribution of NGF receptors in this cranial nerve and its ganglion. In addition, expression of trkA and p75 protein-like immunoreactivity in the facial nerve and GG was studied by Western blot, in order to distinguish between high- and low-affinity NGF receptors respectively. The quantitative study of binding show that isolated facial primordia ranging from E-3 to E-14 exhibit different levels of specific binding. High initial binding levels were observed on E-3 specimens, then an initial decrease on day 4 (E-4) followed by a steady increase from days E-4 to E-7. Maximum 125I-NGF binding was achieved on E-7, followed by a steady decline in binding on days 8 (E-8) and 9 (E-9), reaching near background levels on day 10 (E-10) of development and until the oldest stage assayed (E-14). Most of the cells bearing NGF receptors appeared to be nonneuronal crest-derived cells, but some placode-derived neurons and motor fibers of the VIIth cranial nerve transiently expressed the ability to bind 125I-NGF. The temporal pattern of p75 expression matches the pattern of quantitative binding of NGF, while the trkA expression is restricted to a few stages mainly E7 and E9, implying that most of the binding detected is via low-affinity receptors, except for a proportion of high-affinity receptors present at stages of maximum binding. This temporal pattern of NGF binding sites suggests that cells within the VIIth cranial nerve are responsive to and/or dependent upon NGF in vivo, so NGF may play a biological role during normal development of the facial nerve. In view of the developmental events that parallel the occurrence and type of NGF binding sites, we suggest that this role may be to modulate from earlier chemotaxis and cell proliferation to much later events, such as neuronal differentiation and neuron-glia interactions. The significance of these findings in regeneration during adult life remain to be investigated.

Molecular and Cellular Biochemistry, 2006

Responses to perturbations in the composition of the extracellular environment are crucial to mai... more Responses to perturbations in the composition of the extracellular environment are crucial to maintain cell and tissue homeostasis. In hypertonic conditions cell lines derived from kidney epithelium initiate a variety of stress responses to maintain cell viability that include activation of Mitogen Activated Protein Kinases (MAPK). We previously showed that NaCl also regulates MAPK in different tumor cell lines and we now show that when hypertonic conditions induced with NaCl and other osmolytes were used to stimulate several tumor cell lines, Glycogen Synthase Kinase 3β (GSK3β) was rapidly dephosphorylated at serine 9 and its kinase activity was increased. This response was both time- and dose-dependent, it was independent of the Akt signaling pathway and did not increase steady state levels of phosphorylation of β-catenin, although the data suggested that activated GSK3β could regulate the activity of ERK1/2.

Molecular and Cellular Biochemistry, 2006

Perturbations of the extracellular ionic content by different hypo- or hyperosmolar stimuli initi... more Perturbations of the extracellular ionic content by different hypo- or hyperosmolar stimuli initiate stress responses to maintain cell viability that include activation of Mitogen Activated Protein Kinases (MAPK) in cell lines derived from kidney epithelium. When hyperosmolar conditions induced by different salts occurred in the extracellular environment of tumor-derived cell lines, they activated the Extracellular Regulated Kinase 1/2 by increasing its phosphorylation steady-state on Thr202/Tyr204 in a time- and dose-dependent manner. It was found that Extracellular Regulated Kinase 1/2 activation is a consequence of selective phosphorylation by mitogen-activated protein kinase/ERK kinase. Changes in cell shape or in tubulin or actin cytoskeletal structure were not found, although cell growth arrest was observed as well as induction of apoptosis and modified cell migration ability that were dependent upon Extracellular Regulated Kinase 1/2 activation evidencing a critical role for the Extracellular Regulated Kinase 1/2 in mediating survival of cells in hyperosmotic conditions.

Brain Research Bulletin, 1995

The influence of aging and of treatment with the dihydropyridine Ca2+ antagonist darodipine (PY 1... more The influence of aging and of treatment with the dihydropyridine Ca2+ antagonist darodipine (PY 108-068) on the age-related microanatomical changes of rat brain were studied in male Wistar rats treated from the 18th to the 24th month of age with an oral dose of 5 mg/kg/day of darodipine. Twelve-month-old untreated rats were used as an adult reference group. A decreased number of nerve cells and of alkaline phosphatase-positive capillaries and an increased lipofuscin deposition were observed in the frontal and occipital cortex, in the hippocampus, and in the cerebellar cortex of rats of 24 months in comparison with 12-month-old animals. The number of nerve cells was higher in the occipital cortex and in the hippocampus, but not in the frontal cortex and in the cerebellar cortex, of darodipine-treated rats in comparison with age-matched untreated animals. Lipofuscin deposition is reduced in all the brain areas investigated. The density of alkaline phosphatase-reactive capillaries is also increased in the frontal and occipital cortex and in the hippocampus of aged rats treated with darodipine. The above results suggest that treatment with darodipine is able to counter some microanatomical changes occurring in the brain of aged rats and involving not only microvascular parameters. The occipital (visual) cortex and the hippocampus were the cerebral areas more sensitive to treatment with darodipine. The possible relevance of these findings is discussed.

Neuroscience Letters, 2005

Meissner corpuscles are rapidly adapting cutaneous mechanoreceptors depending for development on ... more Meissner corpuscles are rapidly adapting cutaneous mechanoreceptors depending for development on TrkB expressing sensory neurons, but it remains to be established which of the known TrkB ligands, BDNF or NT-4, is responsible of this dependence. In this study we analyze Meissner corpuscles in the digital pads of mice with target mutations in the genes encoding for either BDNF or NT-4, using immunohistochemistry and transmission-electron microscopy, and they were identified based on their morphology and expression of S100 protein. All wild-type animals as well as NT-4 −/− animals and BDNF and NT4 heterozygous animals have Meissner corpuscles that are normal in number and size. However, Meissner corpuscles are absent the BDNF −/− mice. These results suggest that BDNF is the only TrkB ligand involved in the development of Meissner corpuscles in murine glabrous skin, and it probably regulates the development of the sensory neurons that innervate Meissner corpuscles.

Page 1. ✍Corresponding author In vitro regeneration and acclimatization of plants of Turmeric (Cu... more Page 1. ✍Corresponding author In vitro regeneration and acclimatization of plants of Turmeric (Curcuma longa L.) in a hydroponic system Elsa Ventura Zapata, Guadalupe Salcedo Morales, Ana N Hernández Lauzardo, Blanca ...

Journal of Cardiovascular Pharmacology, 1994

Hypertension is associated with insulin resistance and dyslipidemia in a syndrome named X. Epidem... more Hypertension is associated with insulin resistance and dyslipidemia in a syndrome named X. Epidemiologic evidence also supports a link between hyperinsulinemia and blood pressure (BP), independent of obesity and non-insulin-dependent diabetes mellitus. To assess the possible role of insulin receptors in this syndrome, we studied insulin binding by erythrocyte ghosts in patients with moderate essential hypertension with or without fasting or postglucose hyperinsulinemia. We measured plasma glucose and insulin before and at 30, 60, and 120 min after administration of 75 g glucose in 62 hypertensive patients and 20 matched normotensive controls. Both groups had comparable age (mean 45 years) and waist/hip ratios (mean 0.88). Patients undergoing antihypertensive treatment did not receive antihypertensive medication for 3 weeks. Patients with fasting or postglucose hyperglycemia were excluded from the study. Insulin binding to erythrocyte ghosts was significantly decreased (p &amp;amp;amp;amp;amp;amp;lt; 0.001) to almost half the values of controls (6.5% specific binding) in both patients with hyperinsulinemic (3.2% specific binding) and those with normoinsulinemic (3.9% specific binding) hypertension. Scatchard analysis demonstrated that this was due to a lesser number of insulin receptors. These data indicate that patients with essential hypertension can show decreased erythrocyte insulin receptors without detectable hyperinsulinemia.

Journal of Hypertension, 1995

Pancreastatin, a novel peptide, is known to inhibit insulin secretion and to have a glycogenolyti... more Pancreastatin, a novel peptide, is known to inhibit insulin secretion and to have a glycogenolytic effect, and is present in many endocrine and chromaffin cells. Both the plasma insulin levels and the adrenergic activity accompanying insulin resistance have been shown to be increased in hypertensive subjects. Our working hypothesis was that pancreastatin might play a role in these pathological phenomena. We studied the plasma pancreastatin level in non-obese essential hypertensive patients in response to an intravenous glucose load. We further measured the responses to the glucose challenge of insulin, glucagon, catecholamines and free fatty acids, as well as other factors related to insulin resistance (i.e. lipoproteins and apolipoproteins). We separated the hypertensive patients into three groups according to their response to an oral glucose-tolerance test: normoinsulinaemic, hyperinsulinaemic and glucose-intolerant. Matched normotensive control subjects were also studied. Pancreastatin levels did not change in the control group after the glucose challenge. However, all hypertensive patients showed an increase in plasma pancreastatin levels after glucose loading. The normoinsulinaemic hypertensive patients also had elevated basal pancreastatin levels. The increase in pancreastatin levels was in the ranking: normoinsulinaemic &amp;amp;amp;amp;amp;amp;gt; hyperinsulinaemic &amp;amp;amp;amp;amp;amp;gt; glucose-intolerant. The pancreastatin: insulin ratio showed that the secretion of pancreastatin and insulin may be regulated differently. Basal free fatty acid and glucagon levels were found to be elevated both in the hyperinsulinaemic and in the glucose-intolerant group. Fasting triglycerides levels were increased in all of the hypertensive patients. Other risk factors for coronary artery disease were also found to be altered: elevated very low-density lipoprotein-cholesterol and decreased high-density lipoprotein-cholesterol, with ranking: normoinsulinaemic &amp;amp;amp;amp;amp;amp;lt; hyperinsulinaemic &amp;amp;amp;amp;amp;amp;lt; glucose-intolerant. These results show an increase in pancreastatin levels in hypertensive patients, suggesting that pancreastatin might play a role in the pathophysiology of essential hypertension.

European Journal of Endocrinology, 2000

Objective: A relationship between hyperinsulinemia and decreased serum sex hormone-binding globul... more Objective: A relationship between hyperinsulinemia and decreased serum sex hormone-binding globulin (SHBG) has been described in adults. We evaluated the usefulness of SHBG as an index of hyperinsulinemia and/or insulin resistance in obese children (aged 6±9 years) of both sexes and its possible in¯uence on the androgenic status. Design: We carried out a cross-sectional study of cases and controls. We studied 61 obese children (22 males, 39 females) with body mass index (BMI) superior to the 90 th percentile and a control group of age-and sex-matched non-obese children. We measured serum glucose, insulin, TSH, free thyroxine, 17b-estradiol, testosterone and SHBG. Also, we correlated these parameters with anthropometric measures. Results: The obese group presented signi®cantly elevated levels of insulin (P 0:001) and insulin/ glucose ratio (P 0:0012) compared with the control group. SHBG (P 0:0001) and testosterone (P 0:0169) levels were signi®cantly lower than those in the non-obese group. We did not ®nd any difference in the free androgen index (FAI). Fasting insulin (r À0.4512; P < 0:001), BMI (r À0.3185; P < 0:05) and testosterone (r À0.3705; P < 0:01) were inversely correlated with SHBG concentration. According to multivariate analyses, insulin was the only independent predictor factor for serum SHBG concentration in the obese group (r partial=0.1280; P 0:0171). Conclusions: In summary, at this age there is a strong relationship between insulin and SHBG. The changes in SHBG levels of the obese group did not affect FAI and, therefore, they did not cause changes in the androgenic status. Our data support the role of insulin in the regulation of serum SHBG levels.

Journal of Nutritional Biochemistry, 2002

Homocysteine has been associated with the oxidative stress in the pathogenesis of atherosclerosis... more Homocysteine has been associated with the oxidative stress in the pathogenesis of atherosclerosis. Oxidative stress caused by triglycerides and free fatty acids is known to cause insulin resistance and hyperinsulinemia. On the other hand, insulin resistance may increase homocysteine levels. Since obesity is associated with insulin resistance and hyperinsulinemia, we aimed to study the possible association of homocysteine with hyperinsulinemia in obese subjects. 20 obese male subjects (body mass index >29), aged 33–55 (mean 45 years old) were studied. A fasting blood sample was obtained for the study and the subjects undertook an oral glucose tolerance test with samples taken at 1 and 2 h after glucose. Subjects were divided in two groups according to the fasting insulin levels, < 9 μU/ml or normoinsulinemic (group 1) and >9 μU/ml or hyperinsulinemic (group 2). Glucose, insulin, homocysteine, folate, B12, total cholesterol, HDL-cholesterol and triglycerides levels were determined in fasting blood samples. In oral glucose tolerance test, glucose, insulin and homocysteine levels were measured. Hyperinsulinemic obese subjects (group 2) had higher levels of insulin and glucose at 1 h and 2 h postglucose, compared with group 1. Fasting total homocysteine and triglyceride levels were also increased in this group, whereas folate and B12 levels were similar in both groups. Fasting homocysteine significantly correlated with fasting insulin (r = 0.6, p <0.01). Homocysteine levels slightly but significantly decreased after glucose loading in normoinsulinemic but not in hyperinsulinemic obese subjects. These results show that higher homocysteine levels are observed in the hyperinsulinemic obese subjects and suggest that homocysteine could play a role in the higher risk of cardiovascular disease in obesity.

Metabolism-clinical and Experimental, 2009

The metabolic syndrome is associated with insulin resistance, a systemic low-grade inflammatory s... more The metabolic syndrome is associated with insulin resistance, a systemic low-grade inflammatory state, and endothelial dysfunction. These disorders may arise at a very early age in obese children. The aim of this study was to confirm changes in endothelial dysfunction and inflammatory biomarkers in obese prepubertal children and to evaluate the effect of body mass index (BMI) modification on these biomarkers. Biomarkers for inflammation, endothelial dysfunction, and insulin resistance were measured in obese children (47) and healthy controls (47). Baseline pretreatment levels of insulin (P = .019), homeostasis model assessment of insulin resistance (P = .004), soluble intercellular adhesion molecule (sICAM) (P = .003), and C-reactive protein (CRP) (P b .001) were significantly higher in obese children than in controls. After 9 months of treatment, obese children with lowered BMI SD score (SDS-BMI) displayed a significant decrease in insulin (P = .011), homeostasis model assessment of insulin resistance (P = .012), CRP (P = .006), and interleukin-6 (IL-6) (P = .045) levels compared with obese children with stable SDS-BMI; they also displayed a nonsignificant drop in sICAM levels. Similarly, obese children with lowered SDS-BMI displayed a decrease in CRP (P = .005) and IL-6 (P = .065) compared with baseline levels before treatment. In the total obese group, changes in SDS-BMI correlated positively with changes in CRP (P = .035), IL-6 (P = .027), and sICAM-1 (P = .038) levels. Only SDS-BMI was an independent predictive factor for CRP (P = .031), IL-6 (P = .027), and sICAM-1 (P = .033). Prepubertal obese children displayed alterations indicative of endothelial dysfunction, insulin resistance, and inflammatory state. Lowering of the SDS-BMI after 9 months of treatment was associated with an improvement in these variables compared with those in obese children with stable SDS-BMI status.

Metabolism-clinical and Experimental, 2006

Obesity is an independent risk factor for the development of cardiovascular disease frequently as... more Obesity is an independent risk factor for the development of cardiovascular disease frequently associated with hypertension, dyslipemia, diabetes, and insulin resistance. Higher homocysteine (Hcy) levels are observed in the hyperinsulinemic obese adults and suggest that Hcy could play a role in the higher risk of cardiovascular disease in obesity. We analyzed total Hcy levels in obese prepubertal children and their possible association with both metabolic syndrome and various inflammatory biomarkers and leptin. We studied 43 obese children (aged 6-9 years) and an equal number of nonobese children, paired by age and sex. The obese subjects presented significantly elevated values for insulin ( P = .003), C-reactive protein ( P = .033), and leptin ( P b .001). No significant differences were found in Hcy levels between the obese and nonobese children. However, Hcy concentration was significantly higher in the hyperinsulinemic obese children than in the normoinsulinemic group ( P = .002). Using multivariant regression analysis, in the obese group, corrected for age and sex, the homeostasis model assessment for insulin resistance ( P partial = .001) and leptin ( P partial = .02) are independent predictive factors for Hcy. In the control group, corrected for age and sex, the homeostasis model assessment for insulin resistance ( P partial = .005) and leptin ( P partial = .031) also are independent predictive factor for Hcy. Increased plasma Hcy, particularly in hyperinsulinemic obese children, may be causally involved in the pathogenesis of atherosclerosis and/or cardiovascular disease, both of which are common in obesity. D

Metabolism-clinical and Experimental, 2002

The aim of this study was to detect the presence and degree of impairment of cardiovascular disea... more The aim of this study was to detect the presence and degree of impairment of cardiovascular disease (CVD) risk factors, grouped as metabolic cardiovascular syndrome (MCS), in obese prepubertal children. We also assessed the influence of high fasting insulin levels in this pathological status. A cross-sectional study was performed on obese children based on fasting blood samples. Subjects were 61 obese children (aged 6 to 9 years) and an equal number of non-obese children paired by age and sex. The obese children presented the following characteristics in comparison to the non-obese group: significantly high levels of insulin (8.2 +/- 0.52 v 6.12 +/- 0.34 microU/mL), triglycerides (TG) (0.79 +/- 0.04 v 0.60 +/- 0.02 mmol/L), uric acid (0.24 +/- 0.005 v 0.21 +/- 0.004 mmol/L), systolic (SBP) (94.59 +/- 1.06 v 88.85 +/- 1.2 mm Hg) and diastolic (56.49 +/- 1.07 v 52.21 +/- 1.06 mm Hg) blood pressure (DBP), and low levels of high-density lipoprotein cholesterol (HDL-C) (1.30 +/- 0.04 v 1.46 +/- 0.03 mmol/L), and nonesterified fatty acids (0.407 +/- 0.02 v 0.505 +/- 0.02 mmol/L). The hyperinsulinemic obese children showed the same types of differences when compared with the normoinsulinemic group. In the obese group, having adjusted for age, waist/hip ratio (WHR), body mass index (BMI), and sex hormone-binding globulin (SHBG), insulin was an independent prediction factor for triglycerides (P =.0004), apolipoprotein A-I (Apo-AI) (P =.005), and alanine aminotransferase (ALT) (P =.029). BMI was an independent prediction factor for HDL-C (P =.001) and triglycerides (P =.027). However, insulin was an independent prediction factor in the control group for triglycerides (P =.0002) and SBP (P =.012), just as BMI was for HDL-C (P =.011) and uric acid (P =.041). We conclude that the cluster of CVD risk factors associated with MCS and intra-abdominal fat is present in obese prepubertal children. This situation seems to depend, to a large extent, on the insulin basal level. The apparent association between BMI and MCS is due to the correlation between BMI and insulin, and to the fact that insulin associates with MCS. Within the obese group, hyperinsulinemic children present the greatest impairment in the parameters considered to be constituents of MCS.

Metabolism-clinical and Experimental, 2000

Obesity is a major risk factor for cardiovascular disease frequently associated with hypertension... more Obesity is a major risk factor for cardiovascular disease frequently associated with hypertension, dyslipidemia, and diabetes. In recent years, alterations in the hemostatic system have been added to these dysfunctions. We analyzed some of these alterations in coagulation and fibrinolysis in obese children (6 to 9 years old) of both sexes. We studied 61 obese children (mean body mass index [BMI], 22.35 kg/m2; 95% confidence interval [CI], 21.82 to 22.87) and 70 non-obese children (mean BMI, 16.58 kg/m2; 95% CI, 16.24 to 16.93) as a control group. The obese subjects presented significantly elevated values for insulin (P < .001), tissue-plasminogen activator ([t-PA] P < .001), plasminogen activator inhibitor-1 ([PAI-1] P < .001), and fibrinogen (P < .001) with respect to the control group. We found no significant differences in the concentration of glucose and fragment 1 + 2 of prothrombin (F1 + 2). In the obese subjects, insulin, PAI-1, and F1 + 2 were positively correlated with the BMI. On the other hand, t-PA was correlated with insulin and PAI-1 but not with the BMI. Therefore, in the obese children, there was an increment of the risk factors for cardiovascular disease.

Anatomy and Embryology, 1994

The cochleo-vestibular ganglion (CVG) contains the neurons connecting the sensory epithelia of th... more The cochleo-vestibular ganglion (CVG) contains the neurons connecting the sensory epithelia of the inner ear to the cochlear and vestibular nuclei in the medulla. Expression of trkB protein-like immunoreactivity was studied in the developing CVG, using both Western blot and immunocytochemistry on tissue sections. Specific immunoreactivity was observed in the CVG from the 12th gestation day (gd) to the first postnatal week, reflecting the presence of high-affinity receptors for brain-derived neurotrophic factor (BDNF), a member of the NGF family of neurotrophins. Whole explants and dissociated cell cultures of cochlear (CG) and vestibular ganglion (VG) from mouse embryos and postnatal specimens were grown in neurotrophin-free medium to assay changes in neurite outgrowth and neuronal survival in response to the addition of physiological concentrations (0–5 ng/ml) of BDNF. Exogenous BDNF (2 ng/ml) promoted neurite outgrowth and neuronal survival in explants of both CG and VG, and the effects were stage-dependent. The onset of the response to BDNF occurred at gd 11–12. The response then reached a maximum between 14 and 18 gd and subsequently decreased, although it remained significantly present during the first postnatal week. BDNF-induced response was no longer observed in the mature cochlear and vestibular ganglion (after 30 postnatal days). The effects of BDNF on neuronal differentiation and survival were dose-dependent, starting at 0.5 ng/ml, with saturation at 2 ng/ml and half-maximal effect occurring between 1 and 1.5 ng/ml. On the basis of our results, we propose that BDNF may be physiologically involved in the control of both neuronal differentiation, and central and peripheral target-dependent neuronal death, in the CVG of embryos and early postnatal mice. BDNF may act alone or in cooperation with other neurotrophins to establish the afferent innervation of the inner ear sensory epithelium.

Mechanisms of Ageing and Development, 1995

The distribution of neurotrophin receptors (p75, trkA-, trkB-, and trkC-receptor proteins) was st... more The distribution of neurotrophin receptors (p75, trkA-, trkB-, and trkC-receptor proteins) was studied by immunohistochemistry on sections of human gastrointestinal tract mucosa from esophagus through rectum. Moreover, chromogranin A (CgA) was studied in parallel to identify endocrine cells (EC). In all of the analyzed samples there was specific immunoreactivity (IR) for trkB-receptor protein in EC, the percentage of which varied between 26 ± 0.6% for the duodenum and 78 ± 3% for the sigmoid colon. EC displaying trkC-receptor protein IR were also encountered, in some cases, in EC of the gastric fundus (9%), duodenum (12%), jejune (23%), and colon (12%); trkA-receptor protein IR was occasionally present labelling EC in the jejune (52%), ileum (25%), and sigmoid colon (18%); finally, p75 was in 21% of EC exclusively in one case in the ileum. In addition to EC, IR for all assessed antigens was also present in the submucous blood vessels. Our results provide evidence for the occurrence of neurotrophin receptor proteins in nonneuronal tissues and suggest that neurotrophins, especially that binding trkB receptor proteins, can regulate a subpopulaUon of EC cells. However, whether EC expressing different trk receptor proteins represent neurochemical subtypes of EC, and whether the identified trk receptor proteins correspond to functional receptors, remain to be elucidated.

Urologia Internationalis, 1997

The present study was undertaken to analyze the changes in neuroendocrine cells of the human pros... more The present study was undertaken to analyze the changes in neuroendocrine cells of the human prostate induced by neoplasms and the effect of hormonal treatment. Samples of human prostate (n = 47) were obtained during surgery or removal of organs for transplantation. The cases analyzed represent normal prostates (n = 4); benign prostatic hyperplasias (n = 10; prostatic carcinomas with Gleason scores of 2-4 (n = 5), 5-7 (n = 10), and 8-10 (n = 3), and prostatic carcinomas treated with hormonal therapy (n = 15). Immunohistochemistry for chromogranin A was performed, and the density of neuroendocrine cells as well as the intensity of the immunostaining within their cytoplasms were evaluated using image analysis. Neuroendocrine cells showing chromogranin A immunoreactivity were identified in all cases studied. They were localized scattered in the acini, and no differences in their morphology were observed among groups. Interestingly, chromogranin A immunoreactivity was also present in typical epithelial cells of prostatic cancer with Gleason scores ranging from 8 to 10. The density of chromogranin A immunoreactive cells was higher in neoplastic tissue with respect to the normal prostate, reaching maximal values in prostatic carcinomas with Gleason scores of 8-10 which were hormonally treated. Regarding the intensity of immunostaining in the prostatic carcinomas with Gleason scores of 8-10 only, a significant increase in relation to the other groups was found. The present results demonstrate that the neuroendocrine cells have similar morphological features and distribution in normal prostate, benign prostatic hyperplasia, and prostatic carcinoma. Their density in prostatic cancer increases following hormonal therapy and varies in relation to the tumoral degree or histological evaluation, suggesting a role of neuroendocrine cells in human prostatic cancer.

Anatomy and Embryology, 1994

This study characterizes the temporal-spatial distribution of nerve growth factor (NGF) low (p75)... more This study characterizes the temporal-spatial distribution of nerve growth factor (NGF) low (p75) and high-affinity (trkA) receptors in the facial nerve and geniculate ganglion (GG) of developing quail embryos (E-3 to E-14). We used 125I-labeled NGF (125I-NGF) to study binding dynamics in a temporal series of isolated primordia and an autoradiographic series of staged specimens to characterize the occurrence and distribution of NGF receptors in this cranial nerve and its ganglion. In addition, expression of trkA and p75 protein-like immunoreactivity in the facial nerve and GG was studied by Western blot, in order to distinguish between high- and low-affinity NGF receptors respectively. The quantitative study of binding show that isolated facial primordia ranging from E-3 to E-14 exhibit different levels of specific binding. High initial binding levels were observed on E-3 specimens, then an initial decrease on day 4 (E-4) followed by a steady increase from days E-4 to E-7. Maximum 125I-NGF binding was achieved on E-7, followed by a steady decline in binding on days 8 (E-8) and 9 (E-9), reaching near background levels on day 10 (E-10) of development and until the oldest stage assayed (E-14). Most of the cells bearing NGF receptors appeared to be nonneuronal crest-derived cells, but some placode-derived neurons and motor fibers of the VIIth cranial nerve transiently expressed the ability to bind 125I-NGF. The temporal pattern of p75 expression matches the pattern of quantitative binding of NGF, while the trkA expression is restricted to a few stages mainly E7 and E9, implying that most of the binding detected is via low-affinity receptors, except for a proportion of high-affinity receptors present at stages of maximum binding. This temporal pattern of NGF binding sites suggests that cells within the VIIth cranial nerve are responsive to and/or dependent upon NGF in vivo, so NGF may play a biological role during normal development of the facial nerve. In view of the developmental events that parallel the occurrence and type of NGF binding sites, we suggest that this role may be to modulate from earlier chemotaxis and cell proliferation to much later events, such as neuronal differentiation and neuron-glia interactions. The significance of these findings in regeneration during adult life remain to be investigated.

Molecular and Cellular Biochemistry, 2006

Responses to perturbations in the composition of the extracellular environment are crucial to mai... more Responses to perturbations in the composition of the extracellular environment are crucial to maintain cell and tissue homeostasis. In hypertonic conditions cell lines derived from kidney epithelium initiate a variety of stress responses to maintain cell viability that include activation of Mitogen Activated Protein Kinases (MAPK). We previously showed that NaCl also regulates MAPK in different tumor cell lines and we now show that when hypertonic conditions induced with NaCl and other osmolytes were used to stimulate several tumor cell lines, Glycogen Synthase Kinase 3β (GSK3β) was rapidly dephosphorylated at serine 9 and its kinase activity was increased. This response was both time- and dose-dependent, it was independent of the Akt signaling pathway and did not increase steady state levels of phosphorylation of β-catenin, although the data suggested that activated GSK3β could regulate the activity of ERK1/2.

Molecular and Cellular Biochemistry, 2006

Perturbations of the extracellular ionic content by different hypo- or hyperosmolar stimuli initi... more Perturbations of the extracellular ionic content by different hypo- or hyperosmolar stimuli initiate stress responses to maintain cell viability that include activation of Mitogen Activated Protein Kinases (MAPK) in cell lines derived from kidney epithelium. When hyperosmolar conditions induced by different salts occurred in the extracellular environment of tumor-derived cell lines, they activated the Extracellular Regulated Kinase 1/2 by increasing its phosphorylation steady-state on Thr202/Tyr204 in a time- and dose-dependent manner. It was found that Extracellular Regulated Kinase 1/2 activation is a consequence of selective phosphorylation by mitogen-activated protein kinase/ERK kinase. Changes in cell shape or in tubulin or actin cytoskeletal structure were not found, although cell growth arrest was observed as well as induction of apoptosis and modified cell migration ability that were dependent upon Extracellular Regulated Kinase 1/2 activation evidencing a critical role for the Extracellular Regulated Kinase 1/2 in mediating survival of cells in hyperosmotic conditions.

Brain Research Bulletin, 1995

The influence of aging and of treatment with the dihydropyridine Ca2+ antagonist darodipine (PY 1... more The influence of aging and of treatment with the dihydropyridine Ca2+ antagonist darodipine (PY 108-068) on the age-related microanatomical changes of rat brain were studied in male Wistar rats treated from the 18th to the 24th month of age with an oral dose of 5 mg/kg/day of darodipine. Twelve-month-old untreated rats were used as an adult reference group. A decreased number of nerve cells and of alkaline phosphatase-positive capillaries and an increased lipofuscin deposition were observed in the frontal and occipital cortex, in the hippocampus, and in the cerebellar cortex of rats of 24 months in comparison with 12-month-old animals. The number of nerve cells was higher in the occipital cortex and in the hippocampus, but not in the frontal cortex and in the cerebellar cortex, of darodipine-treated rats in comparison with age-matched untreated animals. Lipofuscin deposition is reduced in all the brain areas investigated. The density of alkaline phosphatase-reactive capillaries is also increased in the frontal and occipital cortex and in the hippocampus of aged rats treated with darodipine. The above results suggest that treatment with darodipine is able to counter some microanatomical changes occurring in the brain of aged rats and involving not only microvascular parameters. The occipital (visual) cortex and the hippocampus were the cerebral areas more sensitive to treatment with darodipine. The possible relevance of these findings is discussed.

Neuroscience Letters, 2005

Meissner corpuscles are rapidly adapting cutaneous mechanoreceptors depending for development on ... more Meissner corpuscles are rapidly adapting cutaneous mechanoreceptors depending for development on TrkB expressing sensory neurons, but it remains to be established which of the known TrkB ligands, BDNF or NT-4, is responsible of this dependence. In this study we analyze Meissner corpuscles in the digital pads of mice with target mutations in the genes encoding for either BDNF or NT-4, using immunohistochemistry and transmission-electron microscopy, and they were identified based on their morphology and expression of S100 protein. All wild-type animals as well as NT-4 −/− animals and BDNF and NT4 heterozygous animals have Meissner corpuscles that are normal in number and size. However, Meissner corpuscles are absent the BDNF −/− mice. These results suggest that BDNF is the only TrkB ligand involved in the development of Meissner corpuscles in murine glabrous skin, and it probably regulates the development of the sensory neurons that innervate Meissner corpuscles.

Page 1. ✍Corresponding author In vitro regeneration and acclimatization of plants of Turmeric (Cu... more Page 1. ✍Corresponding author In vitro regeneration and acclimatization of plants of Turmeric (Curcuma longa L.) in a hydroponic system Elsa Ventura Zapata, Guadalupe Salcedo Morales, Ana N Hernández Lauzardo, Blanca ...