Papers by Tiago Henriques
Kidney International, 2007
2 Kidney International o r i g i n a l a r t i c l e M Moreira-Rodrigues et al.: Cardiac remodeli... more 2 Kidney International o r i g i n a l a r t i c l e M Moreira-Rodrigues et al.: Cardiac remodeling in PAN nephrosis
Journal of Urology, 2006
For many abdominal procedures, advantages such as minimal scarring, reduced pain, and faster reco... more For many abdominal procedures, advantages such as minimal scarring, reduced pain, and faster recovery have made laparoscopy the favored approach over traditional open surgery. The most recent minimally invasive approach is natural orifice transluminal endoscopic surgery (NOTES), which limits morbidity because this surgery does not require incision. This article reviews the history, development, and current and future applications of NOTES in the field of urology.
American Journal of Physiology-heart and Circulatory Physiology, 2009
We investigated the endogenous production of apelin and the cardiac and pulmonary effects of its ... more We investigated the endogenous production of apelin and the cardiac and pulmonary effects of its chronic administration in monocrotaline (MCT)-induced pulmonary hypertension (PH). Male Wistar rats were injected with MCT (60 mg/kg sc) or vehicle (day 0). One week later, these animals were randomly treated during 17 days with pyroglutamylated apelin-13 (Pyr-AP13; 200 microg*kg(-1)*day(-1) ip) or a similar volume of saline, resulting in four groups: sham (n = 11), sham-AP (n = 11), MCT (n = 16), and MCT-AP (n = 13). On day 25, right ventricular (RV) and left ventricular (LV) hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis. When compared with sham, the MCT group presented a significant increase of RV mass (166 +/- 38%), diameter of cardiomyocyte (40 +/- 10%), myocardial fibrosis (95 +/- 20%), peak systolic pressure (99 +/- 22%), peak rate of ventricular pressure rise (dP/dt(max); 74 +/- 24%), peak rate of ventricular pressure decline (dP/dt(min); 73 +/- 19%), and time constant tau (55 +/- 16%). In these animals, RV expression of apelin (-73 +/- 10%) and its receptor APJ (-61 +/- 20%) was downregulated, whereas mRNA expression of type B natriuretic peptide (9,606 +/- 713%), angiotensinogen (191 +/- 147%), endothelin-1 (RV, 497 +/- 156%; and LV, 799 +/- 309%), plasmatic levels of apelin (104 +/- 48%), and angiotensin 1-7 (161 +/- 151%) were increased. Chronic treatment with Pyr-AP13 significantly attenuated or normalized these changes, preventing apelin-APJ mRNA downregulation and PH-induced neurohumoral activation of several vasoconstrictors, which exacerbates apelin-APJ vasodilator effects. Therefore, apelin delayed the progression of RV hypertrophy and diastolic dysfunction. Together, these observations suggest that the apelin-APJ system may play an important role in the pathophysiology of PH, representing a potential therapeutic target since it significantly attenuates RV overload and PH-induced neurohumoral activation.
Journal of Pediatric Surgery, 2002
American Journal of Respiratory Cell and Molecular Biology, 2008
Fibroblast growth factor-10 (FGF10) is a mesenchymal growth factor, involved in epithelial and me... more Fibroblast growth factor-10 (FGF10) is a mesenchymal growth factor, involved in epithelial and mesenchymal interactions during lung branching morphogenesis. In the present work, FGF10 overexpression was transiently induced in a temporally and spatially restricted manner, during the pseudoglandular or canalicular stages of rat lung development, by trans-uterine ultrasound-guided intraparenchymal microinjections of adenoviral vector encoding the rfgf10 transgene. The morphologic and histologic classification of the resulting malformations were dependent upon developmental stage and location. Overexpression of FGF10 restricted to the proximal tracheobronchial tree during the pseudoglandular phase resulted in large cysts lined by tall columnar epithelium composed primarily of Clara cells with a paucity of Type II pneumocytes, resembling bronchiolar type epithelium. In contrast, FGF10 overexpression in the distal lung parenchyma during the canalicular phase resulted in small cysts lined by cuboidal epithelial cells composed of primarily Type II pneumocytes resembling acinar epithelial differentiation. The cystic malformations induced by FGF10 overexpression appear to closely recapitulate the morphology and histology of the spectrum of human congenital cystic adenomatoid malformation (CCAM). These findings support a role for FGF10 in the induction of human CCAM and provide further mechanistic insight into the role of FGF10 in normal and abnormal lung development.
Peptides, 2006
Ghrelin is a 28-amino-acid acylated peptide that was first isolated from the rat stomach endocrin... more Ghrelin is a 28-amino-acid acylated peptide that was first isolated from the rat stomach endocrine cells (X/A-like cells of oxyntic mucosa) . It is the endogenous ligand for the growth hormone secretagogue-receptor (GHS-R1a), a G protein-coupled receptor, found mainly in the pituitary and hypothalamus, where ghrelin exerts a strong stimulatory effect on the GH release .
Surgical Endoscopy and Other Interventional Techniques, 2007
Background: Recently there has been an increasing enthusiasm for using natural orifices translume... more Background: Recently there has been an increasing enthusiasm for using natural orifices translumenal endoscopic surgery (NOTES) to perform scarless abdominal procedures. We have previously reported the feasibility and safety of the transvesical endoscopic peritoneoscopy in a long-term survival porcine model as useful for those purposes. Herein, we report our successful experience performing transvesical and transdiaphragmatic endoscopic approach to the thoracic cavity in a long-term survival study in a porcine model. Methods: Transvesical and transdiaphragmatic endoscopic thoracoscopy was performed in six anesthetized female pigs. A 5 mm transvesical port was created on the bladder wall and an ureteroscope was advanced into the peritoneal cavity. After diaphragm inspection, we introduced through the left diaphragmatic dome a ureteroscope into the left thoracic cavity. In all animals, we performed thoracoscopy as well as peripheral lung biopsy. Animals were sacrificed by day 15 postoperatively. Results: We easily introduced a 9.8 Fr ureteroscope into the thoracic cavity that allowed us to visualize the pleural cavity and to perform simple surgical procedures such as lung biopsies without complications. There were neither respiratory distress episodes nor surgical complications to report. Postmortem examination revealed complete healing of vesical and diaphragmatic holes, whereas no signs of infection or adhesions were observed in the peritoneal or thoracic cavities. Conclusion: This study demonstrates the feasibility of transvesical thoracoscopy in porcine model. However, although this study extends the potential applications of NOTES to the thoracic cavity, new instruments and further work are needed to provide evidence that this could be translated to humans and with advantages for patients.
International Journal of Cardiology
Pulmonary hypertension (PH), increasingly recognized as a major health burden, remains underdiagn... more Pulmonary hypertension (PH), increasingly recognized as a major health burden, remains underdiagnosed due mainly to the unspecific symptoms. Pulmonary arterial hypertension (PAH) has been extensively investigated. Pathophysiological knowledge derives mostly from experimental models. Paradoxically, common non-PAH PH forms remain largely unexplored. Drugs targeting lung vascular tonus became available during the last two decades, notwithstanding the disease progresses in many patients. The aim of this review is to summarize recent advances in epidemiology, pathophysiology and management with particular focus on associated myocardial and systemic compromise and experimental therapeutic possibilities. PAH, currently viewed as a panvasculopathy, is due to a crosstalk between endothelial and smooth muscle cells, inflammatory activation and altered subcellular pathways. Cardiac cachexia and right ventricular compromise are fundamental determinants of PH prognosis. Combined vasodilator therapy is already mainstay for refractory cases, but drugs directed at these new pathophysiological pathways may constitute a significant advance.
Basic Research in Cardiology, 2009
Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocri... more Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocrine activation and intrinsic myocardial dysfunction have been described in the left ventricle (LV). In order to establish the timing of LV dysfunction development in PH and to clarify underlying molecular changes, Wistar rats were studied 4 and 6 weeks after subcutaneous injection of monocrotaline (MCT) 60 mg/kg (MCT-4, n = 11; MCT-6, n = 11) or vehicle (Ctrl-4, n = 11; Ctrl-6, n = 11). Acute single beat stepwise increases of systolic pressure were performed from baseline to isovolumetric (LVPiso). This hemodynamic stress was used to detect early changes in LV performance. Neurohumoral activation was evaluated by measuring angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) LV mRNA levels. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Extracellular matrix composition was evaluated by tenascin-C mRNA levels and interstitial collagen content. Myosin heavy chain (MHC) composition of the LV was studied by protein quantification. MCT treatment increased RV pressures and RV/LV weight ratio, without changing LV end-diastolic pressures or dimensions. Baseline LV dysfunction were present only in MCT-6 rats. Afterload elevations prolonged τ and upward-shifted end-diastolic pressure dimension relations in MCT-4 and even more in MCT-6. MHC-isoform switch, ACE upregulation and cardiomyocyte apoptosis were present in both MCT groups. Rats with severe PH develop LV dysfunction associated with ET-1 and tenascin-C overexpression. Diastolic dysfunction, however, could be elicited at earlier stages in response to hemodynamic stress, when only LV molecular changes, such as MHC isoform switch, ACE upregulation, and myocardial apoptosis were present.
Life Sciences, 2006
Objective: We investigated the effects of acute volume and RV pressure overload on biventricular ... more Objective: We investigated the effects of acute volume and RV pressure overload on biventricular function and gene expression of BNP, proinflammatory cytokines (IL-6 and TNF-a), iNOS, growth factors (IGF-1, ppET-1), ACE and Ca 2+ -handling proteins (SERCA2a, phospholamban and calsequestrin). Methods: Male Wistar rats (n = 45) instrumented with pressure tip micromanometers in right (RV) and left ventricular (LV) cavities were assigned to one of three protocols: i) Acute RV pressure overload induced by pulmonary trunk banding in order to double RV peak systolic pressure, during 120 or 360 min; ii) acute volume overload induced by dextran40 infusion (5 ml/h), during 120 or 360 min; iii) Sham. RV and LV samples were collected for mRNA quantification. Results: BNP upregulation was restricted to the overloaded ventricles. TNF-a, IL-6, ppET-1, SERCA2a and phospholamban gene activation was higher in volume than in pressure overload. IGF-1 overexpression was similar in both types of overload, but was limited to the RV. TNF-a and CSQ mRNA levels were increased in the non-overloaded LV after pulmonary trunk banding. No significant changes were detected in ACE or iNOS expression. RV end-diastolic pressures positively correlated with local expression of BNP, TNF-a, IL-6, IGF-1, ppET-1 and SERCA2a, while RV peak systolic pressures correlated only with local expression of IL-6, IGF-1 and ppET-1. Conclusions: Acute cardiac overload alters myocardial gene expression profile, distinctly in volume and pressure overload. These changes correlate more closely with diastolic than with systolic load. Nonetheless, gene activation is also present in the non-overloaded LV of selectively RV overloaded hearts. D
Molecular Therapy, 2007
These authors contributed equally to this work.
Expert Opinion on Therapeutic Patents, 2007
Growth hormone secretagogues (GHS) are synthetic molecules that promote secretion of growth hormo... more Growth hormone secretagogues (GHS) are synthetic molecules that promote secretion of growth hormone by activation of the GHS receptor (GHSR). Ghrelin is the endogenous ligand of this receptor, which was isolated from gastric mucosa. This peptide is widely expressed in ...
Journal of Pediatric Surgery, 2005
Tetrasomy of the short arm of chromosome 9 constitutes a rare condition resulting in a well clini... more Tetrasomy of the short arm of chromosome 9 constitutes a rare condition resulting in a well clinically recognized syndrome. In our case, in addition to the characteristic phenotype at birth, the existence of a hernia-type Bochdalek diaphragmatic defect was found. Cytogenetic analysis revealed a nonmosaic case of an isochromosome of the entire short arm of chromosome 9 with no involvement of the heterochromatic region of the long arm: 47, XX, +i (9p). Because chromosome 9 contains several gene locus for enzymes and receptors of the retinoid pathway, this case potentially contributes to retinoid hypothesis in the etiology of congenital diaphragmatic hernia.
Journal of Urology, 2007
Recently there has been increasing enthusiasm for performing simple abdominal procedures by trans... more Recently there has been increasing enthusiasm for performing simple abdominal procedures by transgastric surgery. We previously reported the usefulness of a combined transgastric and transvesical approach to cholecystectomy. In this study we assessed the feasibility of combined transgastric and transvesical approach for performing a more complex surgical procedure, such as nephrectomy, in a porcine model. Materials and Methods: In a nonsurvival study combined transgastric and transvesical approaches were established in 6 female pigs. Under ureteroscope guidance we installed a transvesical 5 mm over tube into the peritoneal cavity and a flexible gastroscope was passed orally into the peritoneal cavity by a gastrotomy. We performed right or left nephrectomy with instruments introduced by the 2 devices that worked in the renal hilum, alternating device intervention for dissection and retraction procedures. Results: Four right and 2 left nephrectomies were performed. There were no complications during the creation of transvesical and transgastric access. In all animals we visualized the 2 kidneys. The renal vessels and ureter were reasonably individualized and ligated separately with ultrasonic scissors, which were introduced through the transvesical port. In 2 early cases mild hemorrhage occurred after ultrasonic ligation. To overcome this complication we applied clips successfully before ultrasonic ligation in the remaining animals. Thus, complete renal release and mobilization to the stomach were achieved in all animals. Conclusions: Nephrectomy by natural orifices using the combined transgastric and transvesical approach is technically feasible, although to our knowledge there is no reliable method for removing the specimen with current instruments.
Endocrinology, 2008
The pathogenesis of pulmonary hypertension (PH) includes an inflammatory response. Thymulin, a zi... more The pathogenesis of pulmonary hypertension (PH) includes an inflammatory response. Thymulin, a zinc-dependent thymic hormone, has important immunobiological effects by inhibiting various pro-inflammatory cytokines and chemokines. We investigated morphological and hemodynamic effects of thymulin administration in a rat model of monocrotaline (MCT)-induced PH, as well as, the pattern of pro-inflammatory cytokines gene expression and the intracellular pathways involved. Adult Wistar rats received an injection of MCT (60 mg/kg, sc) or an equal volume of saline. One day after, the animals randomly received during three weeks an injection of saline, vehicle (zinc+carboxymethyl cellulose) or thymulin (100 ng/kg, sc, qd). At days 23-25, the animals were anesthetized for hemodynamic recordings, whereas and heart and lungs were collected for morphometric and molecular analysis. Thymulin prevented morphological, hemodynamic, and inflammatory cardiopulmonary profile characteristic of MCT-induced PH, whereas part of these effects were also observed in MCT-treated animals injected with the thymulin's vehicle containing zinc. The pulmonary thymulin effect was likely mediated through suppression of p38 pathway.
Gastrointestinal Endoscopy, 2007
Background: An isolated transgastric port has some limitations in performing transluminal endosco... more Background: An isolated transgastric port has some limitations in performing transluminal endoscopic cholecystectomy. However, transvesical access to the peritoneal cavity has recently been reported to be feasible and safe.
Journal of Comparative Physiology B-biochemical Systemic and Environmental Physiology, 2003
This study investigated potential differences on load dependence of relaxation rate and diastolic... more This study investigated potential differences on load dependence of relaxation rate and diastolic function between Oryctolagus cuniculus and Ratus norvegicus, which have constitutive differences in the mechanisms involved in myocardial inactivation. Load dependence of relaxation rate and diastolic function were evaluated with the response of left ventricular time constant τ and diastolic pressure-dimension relation to beat-to-beat aortic constrictions in open-chest rabbits and rats. Afterload levels were normalized, being expressed as a percentage of peak isovolumetric pressure (relative load). In control heartbeats, relaxation rate and diastolic function were similar in the two animal species. They presented, however, distinct responses to afterload elevations. In rabbits, time constant decreased ~7% and diastolic pressure-dimension relation remained unchanged when afterload was elevated to a relative load of 73–76%. Above this afterload level, a significant deceleration of relaxation rate (increase of time constant) and an upward shift of diastolic pressure-dimension relation were observed. In rats, afterload elevations accelerated pressure fall up to a relative load of 97–100% and no afterload-induced shift of the diastolic pressure-dimension relation was observed. This study provides, therefore, evidence that Oryctolagus cuniculus has lower afterload reserve of myocardial relaxation and diastolic function than Ratus norvegicus.
Physiological Measurement, 2008
The objective of this study was the assessment of heart-rate (HR) dynamics with linear and nonlin... more The objective of this study was the assessment of heart-rate (HR) dynamics with linear and nonlinear methods during episodes of mechanical ventilation and acute anoxia in rats. Namely, to assess whether linear and nonlinear HR analysis was able to discriminate acute anoxia from baseline in rats and if this was consistent with human foetal and adult studies. Five HR segments of 1 min duration, during baseline recording, mechanical ventilation and first, second and third minutes of induced acute anoxia, were analysed in ten adult Wistar rats. Linear time and frequency domain and nonlinear methods were used, namely mean HR (mHR), long-term irregularity (LTI), interval index (II), low frequency (LF) and high frequency (HF), approximate entropy (ApEn) and sample entropy (SampEn). New parameters for the entropy indices are proposed for the analysis of rats' HR. Bootstrap percentile confidence intervals and nonparametric statistical tests were used in the evaluation of the differences between segments. During mechanical ventilation a clear spectral band was detectable at the ventilation rate, but mHR, II and the 'new' entropy indices were the only significantly changed indices. In the transition from baseline-mechanical-ventilation to mechanical-ventilationinduced anoxia, a statistically significant decrease of mHR, II and entropy indices was observed, clearly discriminating these two instances, whereas most linear indices increased. With continued anoxia, most linear indices decreased significantly, whereas entropy remained stably low. These results are consistent with other foetal human and non-human studies and evidence that the rat model may be used for further research on linear and nonlinear analysis of heart-rate dynamics. The transition from baseline to acute anoxia was encompassed by 0967-3334/08/091133+11$30.00 © 2008 Institute of Physics and Engineering in Medicine Printed in the UK 1133 1134 H Gonçalves et al
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Papers by Tiago Henriques