Effect of aging on the microstructure, hardness and chemical composition of dentin.

OBJECTIVE: Understanding the effects of biological aging on human tissues has been a topic of extensive research. With the increase in healthy seniors and quality of life that topic is becoming increasingly important. In this investigation the effects of aging on the microstructure, chemical composition and hardness of human coronal dentin was studied from a comparison of teeth within "young" and "old" age groups. METHODS: The microstructure of dentin within three regions (i.e., inner, middle and outer) was analyzed using electron and optical microscopy. The mineral-to-collagen ratio in these three regions was estimated using Raman spectroscopy and the hardness was evaluated using microindentation. RESULTS: Results showed that there were significant differences in tubule density, tubule diameter and peritubular cuff diameter with depth. Although there was no difference in tubule density and diameter of the tubules between the age groups, there was a significant difference in the occlusion ratio. A significant increase in hardness between young and old patients was found for middle and outer dentin. An increase in mineral-to-collagen ratio from inner to outer dentin was also found for both groups. In old patients, an increase in mineral content was found in outer coronal dentin as a consequence of tubule occlusion. CONCLUSIONS: An increase in occlusion ratio, hardness, and mineral content was found in the dentin of adult patients with age. This increase is most evident in the outer coronal dentin.

New insights into c-Ret signalling pathway in the enteric nervous system and its relationship with ALS.

The receptor tyrosine kinase Ret (c-Ret) transduces the glial cell line-derived neurotrophic factor (GDNF) signal, one of the neurotrophic factors related to the degeneration process or the regeneration activity of motor neurons in amyotrophic lateral sclerosis (ALS). The phosphorylation of several tyrosine residues of c-Ret seems to be altered in ALS. c-Ret is expressed in motor neurons and in the enteric nervous system (ENS) during the embryonic period. The characteristics of the ENS allow using it as model for central nervous system (CNS) study and being potentially useful for the research of human neurological diseases such as ALS. The aim of the present study was to investigate the cellular localization and quantitative evaluation of marker c-Ret in the adult human gut. To assess the nature of c-Ret positive cells, we performed colocalization with specific markers of cells that typically are located in the enteric ganglia. The colocalization of PGP9.5 and c-Ret was preferentially intense in enteric neurons with oval morphology and mostly peripherally localized in the ganglion, so we concluded that the c-Ret receptor is expressed by a specific subtype of enteric neurons in the mature human ENS of the gut. The functional significance of these c-Ret positive neurons is discussed.

Characterization of the prostaglandin E2 pathway in a rat model of esophageal adenocarcinoma.

UNLABELLED: Accumulating evidence indicates that the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays a key role in esophageal carcinogenesis. A better understanding of the pathway downstream of COX-2 may reveal novel targets for the prevention of esophageal adenocarcinoma (EAC). The objective of this study was to characterize the profile of genes involved in PGE2 metabolism and signaling in an experimental model of EAC. Esophagojejunostomy with gastric preservation was performed in wistar rats to induce gastroduodenal reflux. Rats were sacrificed 2 or 4 months after surgery. Nine non-operated rats were used to obtain normal (control) esophageal tissues. RESULTS: All rats that underwent esophagojejunostomy developed inflammation. In addition, 90% of the animals showed intestinal metaplasia; of those, 40% progressed to AC. This process was accompanied by a significant increase in esophageal PGE2 levels and the induction of both mRNA and protein levels of COX-2, COX-1, prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, and PGE2 receptors EP3, EP4 and especially EP2, which rose to particularly high levels in experimental rats. In addition, exposure to a selective COX-2 inhibitor (SC58125) or an EP1/EP2 antagonist (AH6809), but not an EP4 antagonist (AH23848B), significantly reduced cell proliferation of esophageal explants in 24 hour-organ culture experiments. Our data suggest that, in addition to COX-2, other components of the PGE2 pathway, including COX-1, may play important roles in the development of EAC induced by gastroduodenal reflux in the rat. Although it must be confirmed in vivo, the EP2 receptor may represent a promising selective target in the prevention of Barrett's associated AC.

Galactomannan from Caesalpinia spinosa induces phenotypic and functional maturation of human dendritic cells.

Plant polysaccharides present an interesting potential as immunomodulators, particularly in the induction of antitumoral responses, principally because of their molecular complexity and low in vivo toxicity. Activation of dendritic cells (DCs) could improve antitumoral responses usually diminished in cancer patients, and natural adjuvants provide a possibility of inducing this activation. Herein, we investigated the immunomodulatory activity of a neutral plant polysaccharide Galactomannan on human monocyte-derived DCs (MDDC). MDDCs were stimulated with Galactomannan (GLM) from Caesalpinia spinosa and both phenotypic and functional activities were assessed by flow cytometry and real-time PCR. The phagocytic ability of MDDCs was determined by using E-coli pHrodo particles and induction of T-lymphocyte allostimulation was determined after T-cell staining with carboxyfluorescein succinimidyl ester (CFSE). In MDDCs, purified Galactomannan induced phenotypic maturation revealed by increased expression of CD83, CD86, CD206, and HLA-DR. Functional experiments showed the loss of particulate antigen uptake in Galactomannan-stimulated DCs and increased alloantigen presentation capacity. Finally, Galactomannan increased protein and mRNA levels of pro-inflammatory cytokines including IL-1ß, IL-6, IL-8, IL-12p70, and TNF-α. These data reveal that Galactomannan obtained from Caesalpinia spinosa promotes effective activation of MDDCs. This adjuvant-like activity may have therapeutic applications in clinical settings where immune responses need boosting.

Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: Accumulating evidence suggests that cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) is involved in oesophageal adenocarcinogenesis. PGE2 exerts its biological action by binding to specific receptors (EP1, EP2, EP3 and EP4). AIM: To investigate which PGE2 receptor subtypes regulate PGE2 signals in the oesophageal adenocarcinoma sequence. METHODS: Expression was determined in oesophageal biopsies from 85 patients with oesophagitis, Barrett's metaplasia, intraepithelial neoplasia, oesophageal adenocarcinoma and normal oesophagus. Levels of mRNA and protein expression were determined by quantitative PCR, immunohistochemistry and western-blot. Expression of EP receptors was also determined in response to acid and bile exposure in the Barrett's adenocarcinoma cell line OE33. RESULTS: All four EP receptors subtypes were expressed in human oesophageal tissues. COX-2 and, especially, EP2 were increased in the Barrett's metaplasia-intraepithelial neoplasia-adenocarcinoma sequence. Expression of the EP4 receptor protein was increased in oesophageal adenocarcinoma. In contrast, expression levels of COX-1 and EP3 receptor were decreased along the sequence. No differences in EP1 expression were found. Treatment with the bile acid deoxycholate increased COX-2, EP1, EP2 and EP4 expression in OE33 cells. CONCLUSIONS: Our data suggest that in addition to COX-2, EP2 and EP4 receptors could be a selective target in the prevention and/or treatment of the Barrett's-associated adenocarcinoma.

Investigación translacional en patología digestiva: del laboratorio a la clínica y viceversa beneficiario: el paciente / No disponible

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Molecular characterization of the kinetoplastid membrane protein-11 genes from the parasite Trypanosoma rangeli.

Trypanosomatids are early divergent parasites which include several species of medical interest. Trypanosoma rangeli is not pathogenic for humans but shows a high immunological cross-reactivity with Trypanosoma cruzi, the causative agent of Chagas' disease that affects more than 17 million people throughout the world. Recent studies have suggested that T. cruzi KMP-11 antigen could be a good candidate for the induction of immunoprotective cytotoxic responses against T. cruzi natural infection. In the present paper the genes coding for the T. rangeli kinetoplastid membrane protein-11 have been characterized. The results show that the locus encoding this protein is formed by 4 gene units measuring 550 nucleotides in length, organized in tandem, and located in different chromosomes in KP1(+) and KP1(-) strains. The gene units are transcribed as a single mRNA of 530 nucleotides in length. Alignment of the T. rangeli KMP-11 deduced amino acid sequence with the homologous KMP-11 protein from T. cruzi revealed an identity of 97%. Interestingly, the T and B cell epitopes of the T. cruzi KMP-11 protein are conserved in the T. rangeli KMP-11 amino acid sequence.

Management of tracheal agenesis.

Complete tracheal agenesis is a very rare congenital anomaly that is only compatible with life in some cases with associated tracheo-oesophageal or broncho-oesophageal fistula. In most cases, concomitant congenital anomalies of the heart, digestive tract or genitourinary tract are present. It should be suspected in any neonate with a history of hydramnios, absent crying, respiratory distress and difficulty in intubation. The possibility for surgical correction or palliation rests on the extent of atresia present. We present a case of complete tracheal agenesis without tracheo nor broncho-oesophageal fistula (type II by Floyd's classification) - the diagnosis of which was prenatally suspected - and discuss the important features of the airway management of this condition.

[Silent myocardial ischemia in unstable angina and acute myocardial infarction. Prospective clinical study]. / Isquemia miocardica asintomatica en la angina inestable y en el infarto miocardico agudo. Investigacion clinica prospectiva.

To establish the prevalence and characteristics of silent myocardial ischemia in patients with unstable angina and acute myocardial infarction and its possible correlation with coronary artery lesions; two groups patients were studied, fifteen with unstable angina and fifteen with acute myocardial infarction. In all patients a continuous 24 hours ECG recording was made with a solid state microprocessor for ST variation analysis, and all underwent coronary arteriography and ventriculography, the severity of coronary heart disease was determined by Gensini scoring system and the coronary angiography morphology was studied. In 86% patients with unstable angina ischemic ST changes were found, 90% of these episodes were silent. There were 66% of the patients with acute myocardial infarction and ST ischemic changes of these 75% were silent. There was no correlation with the ischemic myocardium score index, nor with the angiographic morphology or the heart rate. Therefore it can be said that myocardial ischemia is a result not only of anatomic factors but of many others such as vasoconstriction, endothelial, myocardial, systemic and hemorheological alterations.

[Normal values in Mexico of the echocardiographic measurements of the left heart]. / Valores normales en México de las mediciones ecocardiográficas del corazón izquierdo.

The M-Mode echocardiographic measurements, according to the international criteria, were done in tracings of 274 normal subjects residents of Mexico City, in order to know the normal values in its population. One hundred and thirty one males (47.8%), and 143 females (52.2%). The age varied from 1 to 73 years, the predominant group was between the third and fifth decades of the life. The age, weight and body surface area (BSA) were correlated with measurements, better correlation was found with BSA and it was the analysis base. According to the BSA, 6 subgroups were formed, the first one of 0.5 m2; increasing 0.4 m2 for each subgroup until the last one of 2.1(2) or more. Were observed proportional amount respect to BSA of D-E mitral valve excursion, aortic root diameter, aortic excursion, aortic opening amplitude, left atrium diameter, end diastolic and end systolic diameters of left ventricle, as well as interventricular septum (IVS) and posterior wall (PW) thickness. The measures were less than the reported other countries. The mean velocity of circumferential shortening (Vcf), fractional shortening (FS) and normalized velocities (NV) showed inverse proportion to BSA. The values of Vcf and NV were similar to the previous report, but the FS and the ejection fraction were higher. The study let us to know the normal echocardiographic values for people of Mexico and the differences with respect to the altitude of this city and the body frame of its population.