Search

Abstract Introduction Infants born small for gestational age (SGA) have an increased risk of developing various cardiovascular complications. While many influencing factors can be adjusted or adapt over time, congenital factors also have a significant role. This study, therefore, seeks to explore the effect of perinatal factors on the left ventricular (LV) parameters in SGA infants, as assessed immediately after birth. Methods and materials This single-center prospective cohort study, conducted between 2014 and 2018, involved healthy SGA newborns born > 35 weeks’ gestation, delivered at New York-Presbyterian Brooklyn Methodist Hospital, and a gestational age (GA)-matched control group of appropriate for gestational age (AGA) infants. Data analysis was performed using multivariate linear regression in STATA. Results The study enrolled 528 neonates, 114 SGA and 414 AGA. SGA infants exhibited a mean GA of 38.05 weeks (vs. 38.54), higher male representation (69.3% vs. 51.5%), lower birth weight (BW) (2318g vs 3381g), lower Apgar scores at birth, and a higher rate of neonatal intensive care unit admission compared to AGA infants (41.2% vs.18.9%; p

In the current study, the impact of energy storage material on triangular pyramid solar still operating under constant water depth is investigated in an experimental setting. Experiments were carried out in a pyramidal solar still with various types of energy storage materials to determine their effectiveness. To increase the amount of freshwater that can be obtained from the solar still, materials such as quartz rock, mild steel, and sieved red bricks were utilized as a part of the construction of the basin material. The conventional correlation method was used to calculate the evaporative and convective heat transfer coefficients based on experimental data. It is dependent on the kind of material utilized within the basin for efficient energy storage as well as the depth of water maintained whether or not the output of fresh water improves. As a result of using 1 1/4” red bricks within the basin rather than a typical solar still, the results indicate that the utilization of thermal energy storage inside the basin increased the output of fresh water by 30 %. Additionally, the yield of fresh water obtained was found to be 3.5, 4, 4.3, and 4.2 for 14-inch quartz rock, 3/4-inch quartz rock, 1-1/4-inch red bricks, and mild steel scraps, while the yield of fresh water obtained was found to be 3.5, 4, 4.3, and 4.2 Litres/day.

The environmental friendly and renewability nature of PV Module has aroused the interest of researchers. The precise modelling of PV Module is mandatory before the installation part. However, the specific modelling is cumbersome as some parameters are not available in the manufacturer’s specifications. Predator–Prey based firefly optimization algorithm is proposed and implemented to optimize the unknown values in PV Module non-linear equations by changing the curve at various environmental conditions. The achievement of proposed technique is analysed with the flower pollination and Jaya algorithm based on the convergence curve.

Southern blotting of DNA terminal restriction fragment lengths is the gold standard for measuring mean telomere length. Analysis of the final image is a crucial step in this process, however, current techniques are cumbersome and prone to error. Here we present a simple and accurate method for analyzing telomere smears. Basic 2D gel imaging software was used to automatically subtract background, generate standard curves and calculate net intensity and MW at each position (i) along the telomere smear. Our method required no statistical software or major data manipulation and correctly classified >80% of 18 samples as having short, medium or long telomeres compared with 33–72% using other methods.

Objectives: Earlier studies have revealed high macrophage inflammatory protein-1β (MIP-1β) levels in the gingival crevicular fluid (GCF) and the serum of patients with chronic periodontitis. However, reports correlating effect of non surgical theraphy on levels of GCF and serum MIP-1βlevels are inadequate. Therefore, the present study estimates the GCF and serum MIP-1β levels in periodontal health, disease and after periodontal treatment with non surgical theraphy. Materials and Methods: Periodontal examination and collection of GCF and serum was performed for 60 subjects categorized into four groups with 20 subjects in each group: Group I (healthy); group II (gingivitis), group III (chronic periodontitis). Twelve weeks after scaling and root planing, the GCF and serum were collected from 20 patients of group III, who were considered as group IV. MIP-1β levels were estimated using the enzyme-linked immunosorbent assay. Results: MIP-1β was detected in all samples. However, the levels reduced significantly in group IV (P < 0.05). Mean MIP-1β levels in GCF and serum were the highest in group III (1.404 ng/μL,1.712 ng/μl) and the lowest in group I (0.342 ng/μl,0.465 ng/μl), and those in groups II and IV appeared between those of groups I and III. Conclusions: The GCF and serum MIP-1β levelsincreased proportionally with the progression of periodontal disease (PD) and decreased after treatment. Because MIP-1β levels in the GCF and serum correlated positively with clinical parameters, MIP-1βmay be considered a “novel biomarker” in PD progression. However, controlled longitudinal studies are required to confirm this possibility.

Background: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-II) has become a global pandemic disrupting public health services. Telemedicine has emerged as an important tool to deliver care during these situations. Patients receiving Vitamin K antagonists (VKA) require structured monitoring which has posed a challenge during this pandemic. We aimed to evaluate the impact of Virtual anticoagulation clinic (VAC), a Telehealth model on the quality of anticoagulation, adverse events, and patient satisfaction vis-a-vis standard Anticoagulation clinic (ACC) care.Materials and methods: A bidirectional cohort study was conducted in the Department of Cardiology, JSS Hospital, Mysore. Two hundred and twenty-eight patients in the VAC and 274 patients in the ACC fulfilling inclusion criteria were the subjects of the study. Telehealth tools like WhatsApp and telephone were used. Time in therapeutic range (TTR), Percentage of International normalized ratio in range (PINRR), and adverse events were analyzed and compared between the VAC group and the ACC group, between pre-COVID and COVID ACC groups, and between the VAC group and the same pre-COVID cohort. Patient satisfaction was assessed by a questionnaire at the end of 8 months. Descriptive statistics were used for the patient characteristics and inferential statistics for the comparisons between pre-VAC and VAC care.Results: The mean TTR was 75.4 ± 8.9% and 71.2 ± 13.4% in the VAC group and ACC group, respectively (p < 0.001). The mean PINRR was 66.7 ± 9.4% and 62.4 ± 10.9% in the VAC group and ACC group respectively, (p < 0.001). There was no significant difference in TTR between the VAC group and the same pre-COVID cohort. The TTR differential between the pre-COVID and COVID ACC groups was significant. In either group, no major adverse events were seen. The most common tools used for data exchange were WhatsApp (83%) and SMS (17%). Seventy-four percent of patients were extremely satisfied with the overall VAC care.Conclusions: Virtual anticoagulation clinic, a telehealth model can be used as an alternative option to deliver uninterrupted anticoagulation care during pandemic times.

Background: We aimed at comparing the performance of the three different sizes of AirtraqTM, when performing tracheal intubation in paediatric patients requiring general anaesthesia with endotracheal intubation. Methods: After obtaining informed count from parents, 30 infant, 30 children and 30 adolescent patients underwent tracheal intubation in K.E.M. hospital using AirtraqTM laryngoscope. All patients were intubated by an anaesthetist having at least 5 years of experience in anaesthesia. Results: The Small Airtraq performed best, with less time taken for intubation, no failed intubations, grater percentage of glottic opening score and visual analogue score for ease of use. Optimization manoeuvres were required for intubations in all the patients in infant group; with 5 failed intubations indicating intubation using infant Airtraq was more challenging. Conclusions: Proficiency in using Airtraq in adults may not always translate to successful intubations in infants. Learning curve of an airway gadget is witnessed in its different sized version.

This experimental work intensively studies the effect of nanoparticle concentration and exergy of a conventional solar still. Experimental studies were conducted with concentration ranging from 0.05 to 0.2% with Al2O3, CuO and TiO2 on conventional solar still. The results show that the effect of nanoparticles improves the yield of freshwater from conventional solar still. The water temperature of conventional solar still with different concentration of nanofluids improved by 3 and 5% for CuO, 4.2 and 6% for TiO2 and, 3 and 7% for Al2O3. Similarly, the average water temperature of conventional solar still is higher with 0.2% concentration of Al2O3 inside the basin. There is increase in the yield of freshwater about 50% for conventional solar still respectively with Al2O3 nanofluids (φ=0.2%). The maximum exergy efficiency from the system is found as 11.12% with Al2O3 nanofluid (φ=0.2%). There is a greater possibility of negative efficiency during the start of the experiment while the ambient temperature is lower than water temperature (Ta>Tw). The daily exergy efficiency increases by 20% with increase in concentration of nano-particles in fluid (Al2O3).

Background and Aims: Neuromuscular blocking agents have been one of the cornerstones of anaesthesia. With the advent of newer surgical, anaesthetic and neurological monitoring techniques, their utility in neuroanaesthesia practice seems dispensable. The aim of this prospective, comparative, randomised study was to determine whether neuromuscular blocking agents are required in patients undergoing supratentorial surgery when balanced anaesthesia with desflurane, dexmedetomidine and scalp block is used. Methods: Sixty patients with the American Society of Anesthesiologists physical status I or II, aged between 18 and 60 years were included in the study. All patients received anaesthesia including desflurane, dexmedetomidine and scalp block. The patients were randomly allocated to receive no neuromuscular blocking agent (Group A) or atracurium infusion to keep train-of-four count 2 (Group B). The two groups were compared with respect to haemodynamic stability, brain relaxation scores and recovery characteristics. Haemodynamic parameters and time taken to achieve Aldrete score >9 and other secondary outcomes were analysed using Student's t-test. Non-parametric data were analysed using the Mann–Whitney test. Results: The mean arterial pressure was comparable between the groups. The intraoperative heart rate was comparable; however, in the post-operative period, it remained higher in Group B for 30 min after extubation (P = 0.02). The brain relaxation scores were comparable among the two groups (P = 0.27). Tracheal extubation time, time taken for orientation and time required to reach Aldrete score ≥9 were comparable among the two groups. Conclusion: The present study suggests that balanced anaesthesia using desflurane, dexmedetomidine and scalp block can preclude the use of neuromuscular blocking agents in patients undergoing supratentorial surgery under intense haemodynamic monitoring.

Background Octogenarians have low physiologic reserve and may benefit more from transcatheter aortic valve replacement (TAVR) than surgical aortic valve replacement (SAVR). Methods and Results This retrospective cohort study based on the National Inpatient Sample included octogenarians who underwent TAVR or SAVR from 2012 to 2015. Crude and standardized‐morbidity‐ratio‐weighted regression models were used to compare in‐hospital outcomes. Among 19 145 TAVR and 9815 SAVR hospitalizations, TAVR patients had higher Charlson Comorbidity Index (CCI) scores (2.0 versus 0.8, P

The usage of rubber ash as a reinforcement material for aluminium composite has never been used, this work pertains to one such experimentation. In this work rubber ash and boron carbide in varying proportions to reinforce Aluminium based Hybrid functional grade metal matrix composite (FGMMC). The fabrication is done using the centrifugal casting method. The rubbish ash and B _4 C content are varied and the samples are tested to get the ratio with the optimal mechanical properties. The tensile strength of the Aluminium based Matrix Composites (AMC) seems to increase with an increase in % weight of rubber ash. Further analysis of the composite reveals that the B _4 C and rubber ash particles were evenly distributed in the AMC. This can be confirmed using SEM imaging. This work studies the usage of boron Carbide and rubber ash to reinforce the FGMMC by comparing its properties to conventional AMC’s. The mechanical properties along with the cost factor are weighed to arrive at a convincing solution.

Earlier studies have shown the implication of growth factor receptor activation in angiotensin II (Ang II)-induced hyperproliferation of aortic VSMC as well as in hyperproliferation of VSMC from spontaneously hypertensive rats (SHR). We previously showed that NPR-C specific agonist C-ANP4-23 attenuates the hyperproliferation of VSMC from SHR through the inhibition of MAP kinase, Giα protein signaling and overexpression of cell cycle proteins. The aim of the present study was to investigate if C-ANP4-23- mediated attenuation of hyperproliferation of VSMC from SHR also involves growth factor receptor activation and upstream signaling molecules. For this study, C-ANP 4-23 (10 nmole/kg body weight) was injected intraperitoneally into 2 week-old prehypertensive SHR and Wistar Kyoto (WKY) rats twice per week for 6 weeks. The blood pressure in SHR was significantly attenuated by C-ANP4-23 treatment. In addition, C-ANP4-23 treatment also attenuated the hyperproliferation of VSMC from SHR as well as the enhanced phosphorylation of EGF-R, PDGF-R, IGF-R and c-Src. Furthermore, the enhanced levels of superoxide anion, NADPH oxidase activity, and enhanced expression of Nox4,Nox1,Nox2 and P47phox in SHR compared to WKY rats was also significantly attenuated by C-ANP4-23 treatment. In addition, N-acetyl cysteine (NAC), a scavenger of O2-, inhibitors of growth factor receptors and of c-Src, all inhibited the overexpression of cell cycle proteins cyclin D1 and cdk4 in VSMC from SHR. These results suggest that in vivo treatment of SHR with C-ANP4-23 inhibits the enhanced oxidative stress, c-Src and EGF-R, PDGF-R, IGF-R activation which through the inhibition of overexpression of cell cycle proteins result in the attenuation of hyperproliferation of VSMC.

The association of congenital pulmonary airway malformation (CPAM) with congenital heart disease is rare. We present the case of a 6-month-old child with atrial septal defect and pulmonary hypertension (PH) who presented with severe respiratory distress and hypoxia. The patient underwent right lobectomy for CPAM. With timely management, real-time monitoring, one lung ventilation, and adequate analgesia, we were able to extubate the child in the immediate postoperative period. We conclude that with meticulous planning and multidisciplinary team approach, such complex cases can be managed successfully.

Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit decreased levels of nitric oxide (NO) that may be responsible for the overexpression of Giα proteins that has been shown as a contributing factor for the pathogenesis of hypertension in SHR. The present study was undertaken to investigate if increasing the intracellular levels of NO by NO donor S-Nitroso-N-acetyl-DL-penicillamine (SNAP) could attenuate the enhanced expression of Giα proteins in VSMC from SHR and explore the underlying mechanisms responsible for this response. The expression of Giα proteins and phosphorylation of ERK1/2, growth factor receptors and c-Src was determined by Western blotting using specific antibodies. Treatment of VSMC from SHR with SNAP for 24 hrs decreased the enhanced expression of Giα-2 and Giα-3 proteins and hyperproliferation that was not reversed by 1H (1, 2, 4) oxadiazole (4, 3-a) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, however, PD98059, a MEK inhibitor restored the SNAP-induced decreased expression of Giα proteins towards control levels. In addition, the increased production of superoxide anion, NAD(P)H oxidase activity, overexpression of AT1 receptor, Nox4, p22phox and p47phox proteins, enhanced levels of TBARS and protein carbonyl, increased phosphorylation of PDGF-R, EGF-R, c-Src and ERK1/2 in VSMC from SHR were all decreased to control levels by SNAP treatment. These results suggest that NO decreased the enhanced expression of Giα-2/3 proteins and hyperproliferation of VSMC from SHR by cGMP-independent mechanism and involves ROS and ROS-mediated transactivation of EGF-R/PDGF-R and MAP kinase signaling pathways.

BackgroundWe previously showed that the levels of both Giα‐2 and Giα‐3 proteins were augmented in spontaneously hypertensive rats (SHRs) before the onset of hypertension. In addition, intraperitoneal injection of pertussis toxin, which inactivates both Giα proteins, prevented the development of hypertension in SHRs. The aim of the present study was to determine the specific contributions of Giα‐2 and Giα‐3 proteins to the development of hypertension. Methods and ResultsAntisense oligodeoxynucleotide of Giα‐2 and Giα‐3 encapsulated in PEG/DOTAP/DOPE cationic liposomes were administrated intravenously into 3‐week‐old prehypertensive SHRs and Wistar Kyoto rats, whereas the control Wistar Kyoto rats and SHRs received PBS, empty liposomes, or sense. The knockdown of Giα‐2 but not Giα‐3 protein attenuated tachycardia and prevented the development of hypertension up to age 6 weeks; thereafter, blood pressure started increasing and reached the same level as that of untreated SHRs at 9 weeks. Furthermore, Giα‐2 and Giα‐3 antisense oligodeoxynucleotide treatments significantly decreased the enhanced levels of Giα‐2 and Giα‐3 proteins, respectively, and enhanced levels of superoxide anion and NADPH oxidase activity in heart, aorta, and kidney and hyperproliferation of vascular smooth muscle cells from SHRs aged 6 weeks. In addition, antisense oligodeoxynucleotide treatment with Giα‐2 but not Giα‐3 restored enhanced inhibition of adenylyl cyclase by oxotremorine to WKY levels. ConclusionsThese results suggested that the enhanced expression of Giα‐2 but not Giα‐3 protein plays an important role in the pathogenesis of hypertension and tachycardia in SHRs.

Gqα signaling has been implicated in cardiac hypertrophy. In addition, angiotensin II (Ang II) was also shown to induce its hypertrophic effect through Gqα and PKCδ activation. We recently showed the role of enhanced expression of Gqα/PLCβ1 proteins in vascular smooth muscle cell (VSMC) hypertrophy, however, the role of PKCδ in VSMC hypertrophy in animal model is still lacking. The present study was therefore undertaken to examine the role of PKCδ and the associated signaling mechanisms in VSMC hypertrophy using 16-week-old spontaneously hypertensive rats (SHR). VSMC from 16-week-old SHR exhibited enhanced phosphorylation of PKCδ-Tyr311 and increased protein synthesis, marker of hypertrophy, as compared to WKY rats which was attenuated by rottlerin, an inhibitor of PKCδ. In addition, knocking down of PKCδ by PKCδ-siRNA also attenuated enhanced protein synthesis in VSMC from SHR. Furthermore, rottlerin attenuated the increased production of superoxide anion, NAD(P)H oxidase activity, increased expression of Gqα, phospholipase C (PLC)β1, insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) proteins in VSMC from SHR. In addition, the enhanced phosphorylation of c-Src, PKCδ-Tyr311, IGF-1R, EGFR and ERK1/2 exhibited by VSMC from SHR was also attenuated by rottlerin. These results suggest that VSMC from SHR exhibit enhanced activity of PKCδ and that PKCδ is the upstream molecule of reactive oxygen species (ROS) and contributes to the enhanced expression of Gqα and PLCβ1 proteins and resultant VSMC hypertrophy involving c-Src, growth factor receptor transactivation and MAP kinase signaling.

Context : An epidemic of chikungunya disease occurred in India during late 2005 through 2006 affecting nearly 1,400,000 people. Aim : To study the cutaneous manifestations in suspected cases of chikungunya disease. Settings and Design : Patients who attended our outpatient departments from January 2006 to September 2006 were prospectively included if they had symptoms of chikungunya disease according to the ′case definition′ of the National Institute of Communicable Diseases, Directorate General of Health Services, Government of India. The criteria were an acute illness characterized by the sudden onset of fever and several symptoms such as joint pain, headache, backache, photophobia, and eruption during an epidemic of chikungunya fever in the absence of confirmatory serological tests. Materials and Methods : A total of 115 patients (65 men and 50 women) who satisfied the above criteria were enrolled for the study. Results : An erythematous maculopapular rash subsiding without any sequelae in 3-4 days was the most common cutaneous finding in our patients. Genital ulcers distributed predominantly over the scrotum and base of the penile shaft in men and labia majora in women were the second most common manifestation. Other manifestations included tenderness/edema of hands and feet, grouped hyperpigmented macules over the nose and cheeks, fixed drug eruptions, erythema nodosum, erythema multiformae, generalized urticarial eruptions, and flare up of pre-existing psoriasis and lichen planus. Conclusions : To conclude, a plethora of cutaneous manifestations were noted in suspected cases of chikungunya disease. Genital ulcers, to the best of our knowledge, have not been reported during the earlier epidemics but have been reported by others during the present one.

Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit hyperproliferation and overexpression of cell cycle proteins. We earlier showed that small peptide fragments of cytoplasmic domain of natriuretic receptor-C (NPR-C) attenuate vasoactive peptide-induced hyperproliferation of VSMC. The present study investigated if C-ANP4-23, a specific agonist of NPR-C, could attanuate the hyperproliferation of VSMC from SHR by inhibiting the overexpression of cell cycle proteins and examine the underlying signaling pathways contributing to this inhibition. The proliferation of VSMC was determined by [(3)H] thymidine incorporation and the expression of proteins was determined by Western blotting. The hyperproliferation of VSMC from SHR and overexpression of cyclin D1,cyclin A, cyclin E, cyclin-dependent kinase 2 (cdk2), phosphorylated retinoblastoma protein (pRb), Giα proteins and enhanced phosphorylation of ERK1/2 and AKT exhibited by VSMC from SHR were attenuated by C-ANP4-23 to control levels. In addition, in vivo treatment of SHR with C-ANP4-23 also attenuated the enhanced proliferation of VSMC. Furthemore, PD98059, wortmannin and pertussis toxin, the inhibitors of MAP kinase, PI3kinase and Giα proteins respectively, also attenuated the hyperproliferation of VSMC from SHR and overexpression of cell cycle proteins to control levels. These results indicate that NPR-C activation by C-ANP4-23 attenuates the enhanced levels of cell cycle proteins through the inhibition of enhanced expression of Giα proteins and enhanced activation of MAPkinase/PI3kinase and results in the attenuation of hyperproliferation of VSMC from SHR. It may be suggested that C-ANP4-23 could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension, atherosclerosis and restenosis.

DNA is one of the prime molecules, and its stability is of utmost importance for proper functioning and existence of all living systems. Genotoxic chemicals and radiations exert adverse effects on genome stability. Ultraviolet radiation (UVR) (mainly UV-B: 280–315 nm) is one of the powerful agents that can alter the normal state of life by inducing a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers (CPDs), 6-4 photoproducts (6-4PPs), and their Dewar valence isomers as well as DNA strand breaks by interfering the genome integrity. To counteract these lesions, organisms have developed a number of highly conserved repair mechanisms such as photoreactivation, base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). Additionally, double-strand break repair (by homologous recombination and nonhomologous end joining), SOS response, cell-cycle checkpoints, and programmed cell death (apoptosis) are also operative in various organisms with the expense of specific gene products. This review deals with UV-induced alterations in DNA and its maintenance by various repair mechanisms.

Pyrethroid insecticides are very widely used in agriculture and household due to their high effectiveness and low toxicity in humans. Despite their extensive worldwide use, there are a few reports of human pyrethroid poisoning. The poisoning has a varied presentation and its symptoms overlap with those of other compounds, which can lead to misdiagnosis. We present a case of poisoning with prallethrin, a pyrethroid compound, commonly available as All-Out.

Although social networks have been examined in teams, an understanding of the consequences of team social network ties on employees' attitudes beyond team boundaries is hard to come by. Integrating insights from social networks and gestalt field theory, we examine interactive effects of centrality and density of inclusion and exclusion ties in teams on the relationship between employees' community embeddedness—connectedness with the broader social context—and turnover intentions. In a multi-source field study of 215 employees in 34 teams, we demonstrate that inclusion and exclusion centrality and team exclusion density weaken the effect of community embeddedness on turnover intention. [ABSTRACT FROM AUTHOR]

We earlier showed that angiotensin (Ang) II-induced overexpression of Gi[alpha] proteins contributes to the hyperproliferation of vascular smooth muscle cells (VSMC). In addition, the implication of the JAK2/STAT3 pathway in Ang II-induced hyperproliferation of VSMC has also been reported. However, the role of the JAK2/STAT3 pathway in Ang II-induced overexpression of Gi[alpha] proteins and hyperproliferation of VSMC remains unexplored. In the present study, we show that inhibition or knockdown of the JAK2/STAT3 pathway by a specific inhibitor 'cucurbitacin I' (CuI) or siRNAs attenuated Ang II-induced overexpression of Gi[alpha] proteins and hyperproliferation of VSMC. In addition, the enhanced expression of cell cycle proteins induced by Ang II was also attenuated by CuI. Furthermore, Ang II-induced enhanced production of the superoxide anion ([O.sub.2.sup.-]), [H.sub.2][O.sub.2], and NADPH oxidase activity, as well as the enhanced expression of NADPH oxidase subunits implicated in enhanced expression of Gi[alpha] proteins and hyperproliferation, were also attenuated by inhibition of the JAK2/STAT3 pathway. On the other hand, Ang II-induced inhibition and augmentation of the levels of nitric oxide and peroxynitrite, respectively, in VSMC were restored to control levels by CuI. In summary, our results demonstrate that Ang II through the JAK2/STAT3 pathway increases nitroxidative stress, which contributes to the overexpression of Gi[alpha] proteins and cell cycle proteins and the hyperproliferation of VSMC. Key words: angiotensin II, JAK/STAT pathway, oxidative stress, VSMC, hyperproliferation. Nous avons montre precedemment que la surexpression des proteines Gi[alpha] engendree par l'angiotensine (Ang) II contribue a l'hyperproliferation des cellules musculaires lisses vasculaires (CMLV). De plus, la participation de la voie de signalisation JAK2/STAT3 dans l'hyperproliferation des CMLV engendree par l'Ang II a ete rapporte. Cependant, le role de la voie de signalisation JAK2/STAT3 dans la surexpression des proteines Gi[alpha] et l'hyperproliferation des CMLV engendrees par l'Ang II reste a explorer. Dans la presente etude, nous montrons que l'inhibition ou la repression (<< knockdown >>) de la voie de signalisation JAK2/STAT3 par l'intermediaire de la 'cucurbitacine I' (CuI), un inhibiteur specifique, ou des siRNA permettait d'attenuer la surexpression des proteines Gi[alpha] et l'hyperproliferation des CMLV engendrees par l'Ang II. En outre, l'augmentation de l'expression des proteines du cycle cellulaire engendree par l'Ang II s'attenuait aussi avec la CuI. De surcroit, l'augmentation de la production d'anions superoxydes ([O.sub.2.sup.-]) et de [H.sub.2][O.sub.2], ainsi que de l'activite de la NADPH comme oxydase qu'amplifie l'Ang II, avec l'augmentation de l'expression des sous-unites oxydases de la NADPH jouant un role dans l'augmentation de l'expression des proteines Gi[alpha] et l'hyperproliferation etaient aussi attenuees avec l'inhibition de la voie de signalisation JAK2/STAT3. Par ailleurs, la CuI permettait de retablir au niveau des temoins l'inhibition et l'augmentation des taux d'oxyde nitrique et de peroxynitrites engendrees par l'Ang II dans les CMLV. En resume, nos resultats ont montre que, par l'intermediaire de la voie de signalisation JAK2/STAT3, l'Ang II entraine l'augmentation du stress nitroxydatif, lequel contribue a la surexpression des proteines Gi[alpha] et des proteines du cycle cellulaire, ainsi qu'a l'hyperproliferation des CMLV. [Traduit par la Redaction] Mots-cles: angiotensine II, voie de signalisation JAK/STAT, stress oxydatif, cellules musculaires lisses vasculaires, hyperproliferation., Introduction Angiotensin (Ang) II, an important component of the reninangiotensin-aldosterone system (RAS or RAAS), regulates a variety of physiological functions, including cell proliferation, migration, hypertrophy, and blood pressure through its [...]

Cyclic AMP response element (CRE) binding protein (CREB) is a nuclear transcription factor that regulates the transcription of several genes containing the CRE sites on their promoters. CREB is activated by phosphorylation on a key serine residue, Ser311, in response to a wide variety of extracellular stimuli including angiotensin II (Ang II). Ang II is an important vasoactive peptide and mitogen for vascular smooth muscle cells (VSMC) that in addition to regulating the contractile response in VSMC also plays an important role in phenotypic switch of VSMC from contractile to a synthetic state. The synthetic VSMC are known to exhibit proliferative and migratory properties due to hyperactivation of Ang II-induced signaling events. Ang II has been shown to induce CREB phosphorylation/activation and transcription of genes implicated in proliferation, growth, and migration. Here, we have highlighted some key studies that have demonstrated an important role of CREB in Ang II-mediated gene transcription, proliferation, hypertrophy, and migration of VSMC. Key words: angiotensin II, CREB, VSMC, MAPK, PKB/Akt. La proteine CREB liant le CRE (de l'anglais << cyclic AMP response element >>) constitue un facteur de transcription nucleaire qui participe a la regulation de la transcription de plusieurs genes comprenant les sites du CRE sur leurs promoteurs. La proteine CREB est activee par une phosphorylation de la Ser311, un residu serine cle, en reaction a une grande variete de stimuli extracellulaires, y compris l'angiotensine II (Ang II). L'Ang II est un peptide vasoactif et un agent mitogene important dans les cellules musculaires lisses vasculaires (CMLV) qui, en plus de participer a la regulation de la reaction contractile des CMLV, joue un role important dans la commutation phenotypique des CMLV de l'etat contractile a un etat synthetique. Il est connu que les CMLV synthetiques sont dotees de proprietes proliferatives et migratoires en raison d'evenements de signalisation engendres par l'hyperactivation de l'Ang II. Il a ete montre que l'Ang II engendre la phosphorylation et l'activation de la proteine CREB ainsi que la transcription de genes participant a la proliferation, a la croissance et a la migration. Ici, nous avons mis de l'avant certaines etudes cles, qui ont montre un role important de la proteine CREB dans la transcription de genes medies par l'Ang II ainsi que dans la proliferation l'hypertrophie et la migration des CMLV. [Traduit par la Redaction] Mots-cles : angiotensine II, CREB, CMLV, MAPK, PKB/Akt., Introduction Cyclic AMP response element binding protein (CREB) is an important transcription factor that was originally discovered as a regulator of somatostatin gene transcription in response to forskolin-induced elevation in [...]